Draft report to applicants
National Industrial Chemicals Notification and
Assessment Scheme
Trichloroethylene
________________________________________
Priority Existing Chemical
Assessment Report No. 8
March 2000
Number 8
?Commonwealth of Australia 2000
ISBN 0 642 42202 8
This work is copyright. Apart from any use permitted under the Copyright Act 1968, no
part may be reproduced by any process without prior written permission from AusInfo.
Requests and inquiries concerning reproduction and rights should be addressed to the
Manager, Legislative Services, AusInfo, GPO Box 84, Canberra, ACT 2601.
ii Priority Existing Chemical Number 8
Preface
This assessment was carried out under the National Industrial Chemicals Notification and
Assessment Scheme (NICNAS). This Scheme was established by the Industrial
Chemicals (Notification and Assessment) Act 1989 (the Act), which came into operation
on 17 July 1990.
The principal aim of NICNAS is to aid in the protection of people at work, the public and
the environment from the harmful effects of industrial chemicals.
NICNAS assessments are carried out in conjunction with Environment Australia (EA)
and the Therapeutic Goods Administration (TGA), which carry out the environmental and
public health assessments, respectively.
NICNAS has two major programs: the assessment of the health and environmental effects
of new industrial chemicals prior to importation or manufacture; and the other focussing
on the assessment of chemicals already in use in Australia in response to specific
concerns about their health/or environmental effects.
There is an established mechanism within NICNAS for prioritising and assessing the
many thousands of existing chemicals in use in Australia. Chemicals selected for
assessment are referred to as Priority Existing Chemicals (PECs).
This PEC report has been prepared by the Director (Chemicals Notification and
Assessment) in accordance with the Act. Under the Act manufacturers and importers of
PECs are required to apply for assessment. Applicants for assessment are given a draft
copy of the report and 28 days to advise the Director of any errors. Following the
correction of any errors, the Director provides applicants and other interested parties with
a copy of the draft assessment report for consideration. This is a period of public
comment lasting for 28 days during which requests for variation of the report may be
made. Where variations are requested the Director's decision concerning each request is
made available to each respondent and to other interested parties (for a further period of
28 days). Notices in relation to public comment and decisions made appear in the
Commonwealth Chemical Gazette.
The draft trichloroethylene report was published in May 1998. Dow Chemical (Australia)
Ltd and Orica Australia Pty Ltd submitted applications to vary the draft report with
reference to the carcinogenicity and mutagenicity classification in the report. Following
the Director's decision concerning these requests on 14 July 1998, Orica Australia Pty
Ltd and Dow Chemical (Australia) Ltd lodged appeals with the Administrative Appeals
Tribunal (AAT) to review the Director's decision. Orica Australia Pty Ltd withdrew their
application before the hearing. The AAT hearing was held in Melbourne from 3-9
November 1999. Additional unpublished studies provided by applicants and articles
published since preparation of the draft report were considered by the Tribunal.
Appendix 5 contains a list of these article and studies. The Tribunal's decision was
handed down on 31 December 1999 affirming all the decisions of the Director. The
Tribunal's decision is reproduced in full in Appendix 6.
In accordance with the Act, publication of this report revokes the declaration of this
chemical as a PEC, therefore manufacturers and importers wishing to introduce this
iii
Trichloroethylene
chemical in the future need not apply for assessment. However, manufacturers and
importers need to be aware of their duty to provide any new information to NICNAS, as
required under section 64 of the Act.
For the purposes of Section 78(1) of the Act, copies of Assessment Reports for New and
Existing Chemical assessments may be inspected by the public at the Library, NOHSC,
92-94 Parramatta Road, Camperdown, Sydney, NSW 2050 (between 10 am and 12 noon
and 2 pm and 4 pm each weekday). Summary Reports are published in the
Commonwealth Chemical Gazette, which are also available to the public at the above
address.
Copies of this and other PEC reports are available from NICNAS either by using the
prescribed application form at the back of this report, or directly from the following
address:
GPO Box 58
Sydney
NSW 2001
AUSTRALIA
Tel: +61 (02) 9577 9437
Fax: +61 (02) 9577 9465 or +61 (02) 9577 9465 9244
Other information about NICNAS (also available on request) includes:
? NICNAS Service Charter;
? information sheets on NICNAS Company Registration;
? information sheets on Priority Existing Chemical and New Chemical assessment
programs;
? subscription details for the NICNAS Handbook for Notifiers; and
? subscription details for the Commonwealth Chemical Gazette.
Information on NICNAS, together with other information on the management of
workplace chemicals can be found on the NOHSC Web site:
http://www.nohsc.gov.au/nicnas
iv Priority Existing Chemical Number 8
Abstract
Trichloroethylene has been assessed as a Priority Existing Chemical under the National
Industrial Chemicals Notification and Assessment Scheme. Trichloroethylene is a
chlorinated solvent used mainly in metal cleaning. The most common form of metal
cleaning using trichloroethylene is vapour degreasing, while cold cleaning, such as
dipping and wiping, occurs to a lesser extent. Trichloroethylene is either used as a
solvent neat or as an ingredient of products such as adhesives, electrical equipment
cleaners, waterproofing agents, paint strippers and carpet shampoos. Most of these
products are used for industrial purposes, although some are available for consumer use.
Exposure to trichloroethylene is mainly by inhalation, with skin contact significant in
some cases, particularly cold cleaning. In a comprehensive NICNAS survey conducted in
industry to investigate current uses, exposure levels, control technologies and
environmental exposure, there was little evidence of routine exposure monitoring.
Consequently, a special project was commissioned to undertake atmospheric and
biological monitoring of workers using trichloroethylene as a neat solvent in cold
cleaning and in products for various purposes. From the study and other exposure data, it
was concluded that exposure to trichloroethylene vapours could be high during vapour
degreasing and cold cleaning.
Trichloroethylene is absorbed via inhalational, dermal and oral routes, with the most
significant uptake being through inhalation of the vapour. Absorbed trichloroethylene is
distributed throughout the body and is deposited mainly in adipose tissue and liver. It
readily crosses the placental and blood brain barriers. The liver is the primary site of
metabolism. The major metabolites are trichloroethanol, trichloroacetic acid and
trichloroethanol glucuronide. Other minor metabolites that have been identified are
chloral hydrate, monochloroacetic acid, dichloroacetic acid and N-acetyl dichlorovinyl
cysteine. A second pathway identified in humans and animals is conjugation with
glutathione with the formation of dichlorovinyl cysteine in the kidneys. The major part of
the absorbed trichloroethylene is excreted in urine as metabolites while a small amount is
exhaled unchanged.
There are some species differences in the metabolism of trichloroethylene. The rate of
metabolism of trichloroethylene to trichloroacetic acid in mice is more rapid than in rats.
Saturation of the oxidative pathway has also been reported in rats at 200 to 500 mg/kg
while in mice saturation is only seen at 2000 mg/kg. Saturation in humans has been
predicted by physiologically based pharmacokinetic (PBPK) models to occur at 2000
mg/kg.
The predominant effect of acute exposure to trichloroethylene in humans is CNS
depression. It is a skin and eye irritant but not a skin or respiratory sensitiser. The critical
effect on repeated exposure is kidney toxicity, with an inhalational No Observed Adverse
Effect Level (NOAEL) of 100 ppm observed in a two year study. Other affected systems
are the lungs, nervous system and hearing. In animal reproductive toxicity studies,
adverse effects were only observed at maternally toxic doses.
v
Trichloroethylene
Trichloroethylene is weakly mutagenic in vitro. In the presence of metabolic activation,
trichloroethylene tested positive in several bacterial and fungal gene mutation assays.
Trichloroethylene also tested positive in a mouse lymphoma gene mutation assay, and
unscheduled DNA synthesis (UDS) was reported in several studies. In somatic cell
studies in vivo, both positive and negative results were obtained in micronucleus tests,
with negative results obtained in studies for chromosome aberrations, sister chromatid
exchange and UDS. Trichloroethylene induced DNA single strand breaks in the liver of
rats and mice in one study, and in mice liver and kidneys in a second study. A mouse
spot test was equivocal, however, a preliminary test for pink-eyed unstable mutation was
clearly positive. In germ cell assays, dominant lethal tests were either negative or
inconclusive. Studies in occupationally-exposed groups of workers were inconclusive.
However, a study of somatic mutations in the von Hippel-Lindau gene in tissue from
renal cancer patients reported that trichloroethylene acts on the gene. Further work is
underway in Europe to confirm the effects of trichloroethylene on the VHL gene.
Trichloroethylene has been shown to induce tumours in mouse liver and lung and rat
kidney and testis with all but the rat kidney tumours considered not relevant to humans.
Peroxisomal proliferation is thought to be the mechanism of liver tumour formation and
this has not been seen in humans. Lung tumours in mice are related to the accumulation
of chloral hydrate in the Clara cells of the lung. Testicular tumours were observed only in
one strain of rats with a high incidence in the control group. These tumours are rare in
men and are often associated with peroxisomal proliferators. A number of
epidemiological studies have investigated the carcinogenic potential of trichloroethylene.
Most studies that were large enough to detect an effect individually did not show any
association between cancer and occupational exposure to trichloroethylene. However two
other studies, with some weaknesses in their conduct, indicated an apparent association
between cancer and occupational exposure to trichloroethylene. The kidney tumours are
thought to be related to the metabolism of trichloroethylene and are considered to be of
concern to humans. The mechanism by which trichloroethylene causes rat kidney
cytotoxicity is uncertain and is currently under investigation. It has been proposed that
the likely mechanism of kidney tumours in rats is repeated cytotoxicity and regeneration.
Some workers have postulated that kidney toxicity is due to formic acid while others have
attributed it to the metabolite dichlorovinyl cysteine. Dichlorovinyl cysteine has been
identified in the urine of workers exposed to trichloroethylene.
Based on the assessment of health effects, trichloroethylene meets the Approved Criteria
for Classifying Hazardous Substances for classification as a skin and eye irritant (risk
phrases R36/38 - irritating to eyes and skin), mutagen category 3 (R40(M3) Possible risk
of irreversible effects, mutagen category 3) and carcinogen category 2 (R45 - May cause
cancer).
The occupational risk assessment found that during formulation of products the risk of
kidney effects is considered to be minimal. However, there is a concern during vapour
degreasing as workers may be exposed to high vapour concentrations for prolonged
periods. Use of trichloroethylene in cold cleaning is of concern as workers may be
exposed to the vapour as well as absorption of liquid through the skin. Use of
trichloroethylene products usually involves work activities of short duration. However
there is a concern if workers are exposed on a prolonged basis to products containing high
concentrations of trichloroethylene, especially if they are used as aerosols.
vi Priority Existing Chemical Number 8
It is recommended that greater research and development be directed to substitute
processes and non-hazardous substances because of concern that workers may be
exposed to high trichloroethylene concentrations during vapour degreasing and cold
cleaning.
To control worker exposure during vapour degreasing it is recommended that the vapour
degreasing tank conform to the requirements of the Australian Standard AS 2661 - 1983
(Standards Association of Australia, 1983). This standard also describes the safety
requirements for the operation of a vapour degreaser plant.
Use of trichloroethylene in cold cleaning is not supported by this assessment, and a phase
out period of two years is recommended. The use of trichloroethylene may be
unnecessary and/or excessive for some processes. Alternative processes and the
substitutes available for some of the uses should be used. During the period where
alternatives are being identified, for other uses, appropriate engineering controls such as
local exhaust ventilation must be used to minimise exposure. Use of trichloroethylene
products in an aerosol form is not supported by this assessment. Local exhaust
ventilation will help to minimise exposure of workers to trichloroethylene during use of
other products.
Gross deficiencies were noted in the MSDS and labels provided for assessment and it is
recommended that suppliers amend these in accordance with regulatory requirements.
The deficiencies and the recommendations to rectify them are detailed in the full report.
Trichloroethylene is not expected to present a risk to public health provided consumer
products containing trichloroethylene are labelled in accordance with the requirements of
the Standard for the Uniform Scheduling of Drugs and Poisons and the label instructions
are followed.
The risk to the environment is expected to be low in Australia. Based on the available
data it is predicted that trichloroethylene will not occur at concentrations potentially
harmful to the aquatic environment or the atmosphere. There is no manufacture of
trichloroethylene in Australia, and measures for handling and storing bulk
trichloroethylene are in place, therefore except in the case of a major spill, contamination
of groundwater is unlikely.
vii
Trichloroethylene
Contents
PREFACE iii
ABSTRACT v
ACRONYMS AND ABBREVIATIONS xv
INTRODUCTION 1
1.
1.1 Declaration 1
1.2 Purpose of assessment 1
1.3 Data collection 1
2. BACKGROUND 4
2.1 History 4
2.2 International perspective 4
2.2.1 United States 4
2.2.2 European Union 6
2.3 Australian perspective 7
3. APPLICANTS 8
4. CHEMICAL IDENTITY 9
5. PHYSICAL AND CHEMICAL PROPERTIES 10
5.1 Physico-chemical properties 10
5.2 Decomposition products 10
5.3 Reactivity 11
5.4 Additives and impurities 11
6. METHODS OF DETECTION AND ANALYSIS 13
6.1 Atmospheric monitoring 13
6.2 Biological monitoring 13
6.2.1 Estimation of trichloroethylene 13
6.2.2 Estimation of trichloroacetic acid and trichloroethanol 15
7. USE, MANUFACTURE AND IMPORTATION 17
7.1 Manufacture and importation 17
7.2 Uses 17
7.2.1 Trichloroethylene 17
7.2.2 Products containing trichloroethylene 19
viii Priority Existing Chemical Number 8
7.3 Other information on uses 21
8. OCCUPATIONAL EXPOSURE 22
8.1 Routes of exposure 22
8.2 Methodology for estimating exposure 22
8.3 Importation and repacking 23
8.3.1 Importation of trichloroethylene 23
8.3.2 Repacking 24
8.3.3 Importation of products 24
8.3.4 Monitoring data for bulk storage, transfer and repacking 24
8.3.5 Summary of exposure during importation and repacking 25
8.4 Formulation 25
8.4.1 Atmospheric monitoring and health surveillance 27
8.4.2 Summary of exposure during formulation 27
8.5 Vapour degreasing 27
8.5.1 Numbers of workers potentially exposed 27
8.5.2 Potential frequency and duration of exposure 27
8.5.3 Types of vapour degreasers 28
8.5.4 Cleaning and maintenance of vapour degreasers 29
8.5.5 Potential sources of exposure 30
8.5.6 Atmospheric monitoring 31
8.5.7 Summary of exposure during vapour degreasing 34
8.6 Cold cleaning 35
8.6.1 Potential exposure during cold cleaning 36
8.6.2 Atmospheric monitoring 40
8.6.3 Summary of exposure during cold cleaning 42
8.7 Trichloroethylene products 42
8.7.1 Adhesives 42
8.7.2 Other products 44
8.7.3 Atmospheric monitoring during use of products 44
8.7.4 Potential for exposure during use of products 47
8.8 Recycling 47
8.8.1 Recycling process 48
8.8.2 Monitoring during recycling 48
8.8.3 Potential sources of exposure 49
9. TOXICOKINETICS AND METABOLISM 50
9.1 Absorption 50
9.2 Distribution 50
9.3 Metabolism 50
ix
Trichloroethylene
9.4 Excretion 54
10. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST
SYSTEMS 56
10.1 Acute toxicity 56
10.2 Irritation and corrosivity 57
10.2.1 Skin 57
10.2.2 Eye 57
10.3 Sensitisation 57
10.4 Repeated dose toxicity 57
10.5 Immunotoxicity 62
10.6 Reproductive toxicity 62
10.6.1 Fertility 62
10.6.2 Developmental toxicity 62
10.7 Genotoxicity 66
10.7.1 In vitro tests 66
10.7.2 In vivo tests 67
10.7.3 Trichloroethylene metabolites 76
10.8 Carcinogenicity 77
10.8.1 Hepatic tumours 81
10.8.2 Lung tumours 82
10.8.3 Kidney tumours 84
10.8.4 Testicular tumours 85
11. HUMAN HEALTH EFFECTS 86
11.1 Acute toxicity 86
11.1.1 Inhalation 86
11.1.2 Oral 87
11.2 Irritation and corrosivity 88
11.2 Irritation and corrosivity 89
11.2 Irritation and corrosivity 90
11.2 Irritation and corrosivity 91
11.2.1 Skin 91
11.2.2 Eye 91
11.3 Sensitisation 91
11.4 Repeated dose toxicity 91
11.4.1 Oral 100
11.5 Reproductive toxicity 100
11.5.1 Fertility 100
11.5.2 Developmental toxicity 100
x Priority Existing Chemical Number 8
11.6 Genotoxicity 101
11.7 Carcinogenicity 101
11.7.1 Cohort studies 102
11.7.2 Case-control studies 105
12. HAZARD CLASSIFICATION 106
12.1 Physicochemical hazards 106
12.2 Kinetics and metabolism 106
12.3 Health hazards 107
12.3.1 Acute effects 107
12.3.2 Irritant effects 107
12.3.3 Sensitisation 108
12.3.4 Effects after repeated or prolonged exposure 108
12.3.5 Reproductive effects 109
12.3.6 Genotoxicity 109
12.3.7 Carcinogenicity 110
13. OCCUPATIONAL RISK CHARACTERISATION 115
13.1 Methodology 115
13.2 Critical health effects 116
13.2.1 Acute effects 116
13.2.2 Effects due to repeated exposure 116
13.3 Occupational health and safety risks of trichloroethylene 116
13.3.1 Risks from physicochemical hazards 116
13.3.2 Margin of exposure 117
13.3.3 Uncertainties in risk characterisation 119
13.3.4 Uncertainties in risk characterisation of
trichloroethylene 119
13.3.5 Risk during formulation 120
13.3.6 Risk during vapour degreasing 120
13.3.7 Risk during cold cleaning 121
13.3.8 Risk during use of trichloroethylene products 122
13.3.9 Areas of concern 123
14. RISK MANAGEMENT 124
14.1 Control measures 124
14.1.1 Elimination 124
14.1.2 Substitution 125
14.1.3 Isolation 125
14.1.4 Engineering controls 126
xi
Trichloroethylene
14.1.5 Safe work practices 128
14.1.6 Personal protective equipment 129
14.2 Emergency procedures 130
14.3 Hazard communication 133
14.3.1 Assessment of Material Safety Data Sheets 133
14.3.2 Assessment of labels 137
14.3.3 Education and training 142
14.4 Monitoring and regulatory controls 143
14.4.1 Atmospheric monitoring 143
14.4.2 Exposure standard 143
14.4.3 Biological exposure index 145
14.4.4 Health surveillance 145
15. PUBLIC HEALTH ASSESSMENT 146
15.1 Public exposure 146
15.2 Public health risk assessment 146
15.3 Conclusions 147
16. ENVIRONMENTAL ASSESSMENT 148
16.1 Introduction 148
16.2 Environmental exposure 148
16.2.1 Releases 148
16.2.2 Levels in Australian media 150
16.2.3 Fate 150
16.2.4 Summary 153
16.3 Environmental effects 153
16.3.1 Aquatic organisms 153
16.4 Environmental hazards 155
16.5 Conclusions 157
17. OVERALL CONCLUSIONS AND RECOMMENDATIONS 158
17.1 Hazard classification 158
17.2 Control measures 161
17.2.1 Elimination 161
17.2.2 Substitution 161
17.2.3 Engineering controls 162
17.2.4 Safe work practices 163
17.2.5 Personal protective equipment 164
17.3 Hazard communication 165
17.3.1 MSDS 165
xii Priority Existing Chemical Number 8
17.3.2 Labels 165
17.3.3 Training and education 167
17.4 Exposure standard 167
17.5 Public health protection 168
17.6 Environmental protection 168
17.7 Further studies 168
18. SECONDARY NOTIFICATION 170
APPENDICES
Appendix 1 Occupational exposure calculations 171
Appendix 2 Sample Material Safety Data Sheet 177
Appendix 3 Trichlorethylene survey questionnaire 182
Appendix 4 Approved criteria for classifying hazardous substances 190
Appendix 5 Additional material considered by the Administrative Appeals
Tribunal: Unpublished studies and published articles available
after preparation of the draft report. 199
Appendix 6 Administrative Appeals Tribunal's Decision and Reasons
for Decision re:Dow Chemical (Australia) Limited
(Applicant) and Director, Chemicals Notification and
Assessment (Respondent), 1999. 201
REFERENCES 235
LIST OF FIGURES
Figure 1 - Annual chlorinated solvents production (Wolf & Chestnutt, 1987) 5
Figure 2 - Use of chlorinated solvents in Sweden 1970-1992 (KEMI, 1995) 6
Figure 3 - Open-topped manual vapour degreaser 29
Figure 4 - Metabolic pathways of trichloroethylene (Adapted from ATSDR (1993)) 52
Figure 5- Metabolism of trichlorethylene via glutathione conjugation
53
(From: (United Kingdom, 1996))
LIST OF TABLES
Table 1 -Trichloroethylene imported into Australia 7
Table 2 - Chemical identity of trichloroethylene 9
Table 3 - Physico-chemical properties of trichloroethylene 10
Table 4 - Analytical methods for determining trichloroethylene in air (ATSDR, 1995) 14
Table 5 - Trichloroethylene products identified by applicants and notified by
respondents to a NICNAS industry survey 20
Table 6 - Atmospheric monitoring results (TWA) at bulk storage facilities 25
xiii
Trichloroethylene
Table 7 - Total body burden from inhalation and dermal exposure 27
Table 8 - Distribution of potential exposure 28
Table 9 - Results of air sampling of vapour degreasers by WorkCover Authority
of NSW: 1984-1995 31
Table 10 - Results of HSE short-term air sampling of 100 vapour degreasers
(Robinson, updated January 1996) 33
Table 11 - Results of air sampling of 4 worksites by NIOSH 34
Table 12 - Trichloroethylene vapour degreasing exposures - Dow Chemical
Company (USA) 34
Table 13 - Details provided to NICNAS industry survey by respondents using
cold cleaning processes 37
Table 14 - Work activity and control measures 39
Table 15 - Atmospheric and biological monitoring results during use in cold cleaning 41
Table 16 - Total body burden from inhalation and dermal exposure 42
Table 17 - Work scenarios in adhesive application 43
Table 18 - Use information on products containing trichloroethylene 45
Table 19 -Atmospheric and biological monitoring data during use of
trichloroethylene products 46
Table 20 - Combined inhalational and dermal exposure during use of
trichloroethylene products 47
Table 21- LC50 and LD50 values for trichloroethylene 56
Table 22 - Repeated dose toxicity 59
Table 23 - Effects on fertility and development in animals 63
Table 24 - Genotoxicity of trichloroethylene in vitro 70
Table 25 - Genotoxicity of trichloroethylene in vivo 73
Table 26 - Carcinogenicity studies in animals 78
Table 27 - Acute inhalation toxicity of trichloroethylene 88
Table 28 - Repeated dose toxicity in humans 92
Table 29 - Characteristics of major cohort studies of people occupationally
exposed to trichloroethylene (Adopted from Weiss (1996)) 103
Table 30 - Margins of Exposure (MOE) 118
Table 31 - Uncertainties in risk characterisation 119
Table 32 - Ratings for glove materials for protection against trichloroethylene
by various information sources 132
Table 33 - Findings of MSDS Assessment 134
Table 34 - Compliance with the Labelling Code 139
Table 35 - Results of assessment of three labels for compliance with the SUSDP. 143
Table 36 - Occupational exposure limits 144
Table 37 - Estimates of daily release of trichloroethylene (TCE) Australia wide. 150
Table 38 - Selected highest toxicity values of trichloroethylene to the aquatic
compartment. 155
xiv Priority Existing Chemical Number 8
Acronyms and Abbreviations
ABS Australian Bureau of Statistics
ACGIH American Conference of Governmental Industrial Hygienists
ACS Australian Customs Service
ADG Code Australian Code for the Transport of Dangerous Goods by Road and Rail
ALT alanine aminotransaminase
AS Australian Standard
AST apartate aminotransamine
ATSDR US Agency for Toxic Substances and Disease Registry
BEI biological exposure index
CAS Chemical Abstracts Service
CFC chlorofluorocarbons
CNS central nervous system
cm centimeter
DNA deoxyribonucleicacid
EA Environment Australia
EC European Commision
EC50 concentration at which 50% of the test population are affected
ECD electron capture detection
ECG electrocardiograph
ECETOC European Center for Ecotoxicology and Toxicology of Chemicals
EEG electroencephalograph
EU European Union
FID flame ionisation detection
GC gas chromatography
h hour
HECD Hall's electrolytic conductivity detection
HRGC high resolution gas chromatography
HSE Health and Safety Executive (UK)
IARC International Agency for Research on Cancer
IPCS International Program on Chemical Safety
LC50 median lethal concentration
LD50 median lethal dose
LOAEL lowest observable adverse effect level
LOEC lowest observed effect concentration
MAK "Maximale Arbeitsplatz-Konzentration' (maximum workplace
concentration)
min minute
xv
Trichloroethylene
MOE margin of exposure
MS mass spectrometry
MSDS Material Safety Data Sheet
NICNAS National Industrial Chemicals Notification and Assessment Scheme
NIOSH National Institute for Occupational Safety and Health (US)
NOAEL no observed adverse effect level
NOEC no observed effect concentration
NOHSC National Occupational Health and Safety Commission
NSW New South Wales
NTP National Toxicology Program (US)
NZS New Zealand Standard
OSHA Occupational Safety and Health Administration (US)
PBL peripheral blood leucocytes
PCE polychromatic erythrocytes
PEC predicted environmental concentration
PPE personal protective equipment
ppm parts per million
ppt parts per trillion
PVC polyvinyl chloride
RR risk ratio
SCE sister chromatid exchange
SIAM SIDS Initial Assessment Meeting
SIAR SIDS Initial Assessment Report
SIDS Screening Information Data Set
SIR standardised incidence rate
SMR standardised mortality rate
STEL short term exposure limit
SUSDP Standard for the Uniform Scheduling of Drugs and Poisons
TCA trichloroacetic acid
TCOH trichloroethanol
TGA Therapeutic Goods Administration
TLV threshold limit value
TWA time weighted average
UDS unscheduled DNA synthesis
礸 microgram
VHL von Hippel-Lindau
WA Western Australia
xvi Priority Existing Chemical Number 8
1. Introduction
1.1 Declaration
Trichloroethylene (CAS No 79-01-6) was declared a Priority Existing Chemical
under the Industrial Chemicals (Notification and Assessment) Act 1989 (the Act)
(Cwlth) by the Minister for Industrial Relations, by notice in the Chemical
Gazette of 4 April 1995.
The grounds for declaring trichloroethylene a Priority Existing Chemical were:
? wide use as an industrial solvent with occupational and public exposure to a
wide range of products containing the chemical;
? concerns that trichloroethylene may be used as a substitute for 1,1,1-
trichloroethane after its phase out by the end of 1995, thereby increasing
human and environmental exposure;
? exposure to trichloroethylene may give rise to adverse health effects;
? the differences of opinion regarding the carcinogenic status of the chemical.
1.2 Purpose of assessment
The purpose of this assessment is to:
? characterise current and potential occupational, public and environmental
exposure to trichloroethylene;
? characterise the human health hazards and environmental effects/impact and
in particular clarify the carcinogenic status of trichloroethylene;
? assess current risk management measures for trichloroethylene including
occupational exposure standards and other current standards and guidelines;
? to make recommendations on control measures for the management of the
risks to occupational/public health and appropriate hazard communication
measures;
? to make recommendations on control measures for the management of
environmental hazards along with information on disposal and waste
management.
1.3 Data collection
In accordance with the Act manufacturers and importers of trichloroethylene who
wished to continue manufacturing or importing trichloroethylene, whilst it was a
Priority Existing Chemical were required to apply for assessment and supply
information. Information for the assessment was also received from end users,
formulators, unions and from a comprehensive literature search. Concurrent with
this report has been the preparation of an initial Screening Information Data Set
(SIDS) assessment report (SIAR) by the UK Health and Safety Executive (the
UK SIAR). The UK draft SIAR was reviewed at the 4th OECD SIDS Initial
1
Trichloroethylene
Assessment Meeting (SIAM) and accepted with changes. Australia had the
opportunity to review the report before finalisation as a member of the OECD.
To enhance the efficiency of the National Industrial Chemical Notification and
Assessment Scheme (NICNAS) assessment the review of health effects on
experimental animals and humans has been based on the UK SIAR. A number of
relevant reviews were used to assess the mutagenic and carcinogenic potential of
trichloroethylene. Information on mode of use and exposure was also obtained
through a number of site visits. The Canadian Environmental Protection Act and
German BUA Reports on trichloroethylene were used as the basis of the
environmental fate and environmental toxicity review.
The additional data sources that were utilised are as discussed below:
Australian Bureau of Statistics (ABS)
Quantities of trichloroethylene imported in to Australia from 1988 -1997 were
obtained from the ABS.
Australian Customs Services (ACS)
The import of trichloroethylene into Australia was monitored through
information provided by the Australian Customs Service (ACS). Data on the
importers and amounts imported into the country were obtained from the ACS.
Data supplied by applicants
Applicants supplied the following data:
? quantity of trichloroethylene imported;
? quantity of products containing trichloroethylene imported;
? uses of the chemical and products containing the chemical;
? information on recycling of trichloroethylene;
? MSDS and labels
? list of end users
No unpublished data on health or environmental effects of trichloroethylene were
provided by applicants.
Surveys
All the applicants on-sell the imported trichloroethylene or trichloroethylene
products and do not use the chemical and were unable to provide any data on
occupational exposure during use of the chemical. NICNAS therefore conducted
a survey to investigate the use processes, exposure levels, control technologies
and environmental exposure to trichloroethylene.
Survey 1 Survey of users of trichloroethylene
A survey was undertaken by NICNAS in 1995 to obtain information on the use of
trichloroethylene in Australia, to assist in the assessment of occupational and
environmental exposure.
2 Priority Existing Chemical Number 8
Survey 2 Atmospheric monitoring survey
Twenty-six companies identified from the user survey as conducting atmospheric
monitoring were followed up with a questionnaire to obtain more detailed
monitoring data. Results of 37 samples from 9 worksites were provided in
response to the monitoring survey. In addition, monitoring data were also
obtained from one bulk storage site and one recycler of trichloroethylene.
Atmospheric Monitoring Project
No atmospheric monitoring data was obtained for use of trichloroethylene in cold
cleaning or during use of trichloroethylene products. A project was therefore
specially commissioned to an external consultant to undertake atmospheric and
biological monitoring of workers using trichloroethylene products for various
purposes and neat trichloroethylene in cold degreasing.
Workplaces were identified and contacted by NICNAS. Seven workplaces were
willing to participate, with one workplace using both neat trichloroethylene and a
trichloroethylene product. The number of workers involved at each workplace
depended on the work available. Atmospheric monitoring included personal
monitoring and was conducted in accordance with Australian Standard AS 2986
and the samples were analysed by gas chromatography. Biological monitoring
included estimation of trichloroacetic acid in urine and analysis of the urine
samples by a method developed at the WorkCover Laboratories at Thornleigh.
3
Trichloroethylene
2. Background
2.1 History
Trichloroethylene was first prepared in 1864 by Fischer by the reduction of
hexachloroethane with hydrogen. Commercial production of trichloroethylene in
Europe started in 1908 and in the USA in the 1920s. In the past, as is today,
trichloroethylene has mainly been used as a liquid or vapour degreasing solvent
in the metal fabricating industry.
International and national concern about the environmental and health and safety
implications of chlorinated solvents has resulted in a number of regulations and
controls that have impacted on the use of trichloroethylene.
2.2 International perspective
In general, there has been a continuing decline in demand for trichloroethylene
over the years. New growth is possible in future due to concerns with some of
the alternatives for trichloroethylene, for example the phasing out of 1,1,1-
trichloroethane at the end of 1995 under the Montreal Protocol. Overseas, new
growth in use has also been seen because of its use as a precursor in the
manufacture of chlorofluorocarbons (CFC) alternatives such as HFC-134a or
HCFC-123 (Anon, 1995). However, conversely, increasing trends in the
recovery and recycling of trichloroethylene may reduce production of
trichloroethylene. Such circumstances could introduce new sources of potential
exposure.
2.2.1 United States
Severe restrictions by the US government in the use and emission of
trichloroethylene led to a decrease in demand for trichloroethylene (Wolf &
Chestnutt, 1987). The restrictions were as follows:
? In 1968, Los Angeles County adopted Rule 66 which limited emissions of
trichloroethylene.
? By 1972, several other states enacted legislation similar to L.A. County's
Rule 66. The original US Clean Air Act (1970) which regulated emissions of
chlorinated solvents like trichloroethylene led to the chemical's replacement
with 1,1,1-trichloroethane by many users (Shelley et al., 1993).
? In 1974 conversion from trichloroethylene to 1,1,1-trichloroethane proceeded
rapidly in solvent and degreasing applications to comply with air pollution
standards.
? By 1975, industry agreed that trichloroethylene was photoreactive and
Federal and local governments severely restricted the use and emission of
trichloroethylene in vapour degreasing plants in many areas of the country to
reduce air pollution.
4 Priority Existing Chemical Number 8
? In 1977, the US Environmental Protection Agency's recommended policy on
the control of volatile organic compounds was announced and
trichloroethylene was listed as photochemically reactive.
Another event that contributed to the decline in demand was a "Memorandum of
alert" issued on trichloroethylene by the US National Cancer Institute in April
1975. Preliminary findings in bioassays of the solvent indicated that it had
carcinogenic effects in mice. The alert resulted in a push for replacement by
"safer" solvents such as tetrachloroethylene (perchloroethylene) and 1,1,1-
trichloroethane.
The findings of photoreactivity and potential carcinogenicity of trichloroethylene
led to a decline in production. For example, in the USA the demand for
trichloroethylene dropped from 244,939 tons (540 million pounds) in 1971 to
only 68,038 tons (150 million pounds) in 1990. Refer to Figure 1.
Figure 1 - Annual chlorinated solvents production (Wolf & Chestnutt, 1987)
+
perchloroethylene methylene chloride
trichloroethylene methyl chloroform
x CF113
5
Trichloroethylene
2.2.2 European Union
The decline in use in the US has also been seen in other countries. For example,
in the European Union (EU) the use of trichloroethylene has declined by over
50% since the mid-1970s (United Kingdom, 1996). The EU has rules limiting
discharges to watercourses. Germany has introduced rules on the use of
chlorinated solvents for degreasing, dry cleaning and extraction, designed to
achieve substantial reductions in emissions. There are also regulations in Austria
and Switzerland banning certain solvent applications.
More recently, in 1991 Sweden issued an Ordinance which banned the sale,
transfer or use of chemical products containing trichloroethylene, methylene
chloride, or tetrachloroethylene. The bans came into force with respect to
consumer use on 1 January 1993 and with respect to professional use (with the
exception of tetrachloroethylene which was not included in this ban) from 1
January 1996. The decision to ban was based on the hazards to health posed by
these compounds and the fact that they were being used in very large quantities.
Factors taken into account when banning trichloroethylene were the volatility of
the chemical and the assessment that a limitation or control on trichloroethylene
was not enough to ensure people were not exposed. The fact that
trichloroethylene use was widespread among small companies, and that
knowledge on how to protect people from exposure differed, were factors taken
into consideration. In addition, it was considered that a ban would contribute to
development of less harmful substances or techniques. The National Chemicals
Inspectorate may issue regulations on exemptions and grant exemptions in
individual cases, for instance, trichloroethylene may still be used for research and
development and analysis purposes. (European Chemical News, 1995; KEMI,
1995; Cederberg, 1996).
6 Priority Existing Chemical Number 8
2.3 Australian perspective
Trichloroethylene was manufactured in Australia for approximately 30 years
from the early 1950s to the early 1980s. At present, the Australian market
demand for trichloroethylene is entirely met by imports of the chemical.
Trichloroethylene is used widely in both large and small industries mainly as a
degreasing agent.
It is likely that the use of trichloroethylene in Australia has followed the trend
seen in the US and worldwide. Information suggests that several years ago many
users changed from using trichloroethylene to 1,1,1-trichloroethane due to the
potential carcinogenicity of trichloroethylene. Import data obtained from the
ABS show an increase in trichloroethylene imports from 1994 to 1996. This
could probably be attributed to the phase out of 1,1,1-trichloroethane and
substitution with trichloroethylene. Table 1 shows amounts of trichloroethylene
imported from 1988 to 1997.
Table 1 -Trichloroethylene imported into Australia
Year Amounts (tonnes)
1988 3090
1989 2098
1990 1924
1991 2235
1992 2168
1993 1988
1994 2101
1995 2873
1996 3015
1997 2709
Australia has adopted the Montreal Protocol leading to the phasing out of 1,1,1-
trichloroethane. It is therefore likely that trichloroethylene will replace the
chemical for some of its uses, resulting in an increase in demand. This may be
balanced by increasing trends to recycle trichloroethylene.
7
Trichloroethylene
3. Applicants
Ajax Chemicals Ltd Elf Atochem Australia Pty Ltd
9 Short St 893 Princes Highway
Auburn NSW 2128 Springvale VIC 3171
Albright & Wilson Specialities Pty Ltd Merck Pty Ltd
313 Middleborough Road 207 Colchester Road
Box Hill VIC 3128 Kilsyth VIC 3137
Orica Australia Pty Ltd
Beltreco Limited
1 Nicholson St
382 Victoria Road
Melbourne VIC 3000
Malaga WA 6062
Beltreco Pacific Pty Ltd Rema Tip Top Australia Pty Ltd
93 Colebard Street West 11/350 Edgar Street
Archerfield Qld 4108 Bankstown NSW 2200
Campbell Brothers Ltd Solvents Australia Pty Ltd
7-11 Burr Court 77 Bassett Street
Laverton Nth VIC 3026 Mona Vale NSW 2103
Consolidated Chemical Co. Specialty Trading Pty Ltd
52-62 Waterview Close 2 Lanyon Street
Hampton Park VIC 3176 Dandenong VIC 3175
Dow Chemical (Aust) Ltd
Kororoit Creek Road
Altona VIC 3018
8 Priority Existing Chemical Number 8
4. Chemical Identity
Table 2 - Chemical identity of trichloroethylene
Chemical Name: Trichloroethylene
Synonyms: 1,1,2-Trichloroethylene
1,1-Dichloro-2-chloroethylene
Ethylene trichloride
Acetylene trichloride
Ethinyl trichloride
Trichloroethene
Trade Names: Altene D6
Altene D1
NEU-TRI* Solvent
Specialene
Trineu
C2HCl3
Molecular Formula:
H Cl
C=C
Structural Formula:
Cl Cl
Chemical Abstracts Service (CAS) Number: 79-01-6
EINECS Number: 2011674
*Trademark of The Dow Chemical Company
9
Trichloroethylene
5. Physical and Chemical
Properties
5.1 Physico-chemical properties
Physico-chemical properties of trichloroethylene are shown in table 3.
Table 3 - Physico-chemical properties of trichloroethylene
Property Value Reference
Physical state clear, colourless or blue HSDB,1998
mobile liquid
Odour ethereal, chloroform-like HSDB,1998
Odour threshold 100 ppm ATSDR,
1993
Molecular weight 131.40 HSDB,1998
Boiling point 86.7癈 ATSDR,1993
Melting point -86.5癈 UK SIAR,1996
Surface tension 0.0293 N/m HSDB,1998
Density at 20癈 1.465 g/ml HSDB,1994
Vapour density 4.53 HSDB,1994
Vapour pressure at 20癈 7.7 kPa HSDB,1994
Water solubility at 20癈 1.07 g/L ATSDR,1993
Flash point None ATSDR,1993
Autoignition temperature 410癈 UK SIAR, 1996
Flammability limits at 25癈 8.0-10.5% in air ATSDR,1993
Decomposition temperature > 125癈 NIOSH,1973
Partition coefficients
Log Kow 2.42 ATSDR,1993
Log Koc 2.03-2.66 ATSDR,1993
Conversion factors ATSDR,1993
3
Air at 20癈 1 mg/m = 0.18 ppm
1 ppm = 5.46 mg/m3
Water 1 ppm (w/v) = 1 mg/L
1 ml/m3 = 1.465 mg/L
5.2 Decomposition products
Trichloroethylene decomposes under a number of environmental conditions,
including:
? in the presence of oxygen and ultraviolet light it undergoes auto-oxidation
with the formation of acidic products such as hydrogen chloride;
10 Priority Existing Chemical Number 8
? at high temperatures it decomposes to form phosgene and hydrogen chloride;
and
? in the presence of moisture, dichloroacetic acid and hydrochloric acid are
formed. These products are highly corrosive and react with many metals.
Other decomposition products formed are carbon monoxide, trichloroethylene
ozonides and trichloroethylene epoxide.
5.3 Reactivity
In contact with finely divided or hot metals, such as magnesium and aluminium at
very high temperatures (300-600癈) it decomposes readily to form phosgene and
hydrogen chloride. Such conditions are seen in the vicinity of arc welding and
degreasing operations. Aluminium is more reactive than magnesium.
In the presence of strong alkalis such as sodium hydroxide, dichloroacetylene,
which is explosive and flammable, is formed.
5.4 Additives and impurities
Trichloroethylene undergoes auto-oxidation in air at higher temperatures and on
exposure to ultraviolet radiation. To prevent this, stabilisers and inhibitors are
added to the commercial grades. Epichlorohydrin was one of the stabilisers used
in the past but its use has been discontinued as it was found to be carcinogenic.
Mixed amines are now used as stabilisers. Mixed amines and butylene oxide act
as acid acceptors when solvent degradation leads to formation of hydrogen
chloride.
Trichloroethylene is available in a variety of commercial grades that are made up
of approximately 99% trichloroethylene with impurities and stabilisers forming
the remainder.
Additives may include the following:
Butanone
1,2-Butylene oxide
Diisopropylamine
Ethyl acetate
Epoxybutane
Glycidyl ether
Isopropyl acetate
1-Methylpyrrole
2-Methyl-3-butin-2-ol
Thymol
Triethylamine
Trimethyloxirane
11
Trichloroethylene
2,2,4-trimethylpentene
2,4-di-tertbutylphenol
12 Priority Existing Chemical Number 8
6. Methods of Detection and
Analysis
6.1 Atmospheric monitoring
The most common analytical techniques for trichloroethylene in air are gas
chromatography (GC) combined with either flame ionisation detection (FID),
electron capture detection (ECD) or Hall's electrolytic conductivity detection
(HECD). Gas chromatography with mass spectrometry (MS) is used for
identification of the chemical.
Air samples are collected by adsorption on to activated charcoal or Tenax-GC.
Trichloroethylene may be extracted either thermally or with a solvent such as
carbon disulfide.
In the standard NIOSH method, trichloroethylene is collected by adsorption on
activated charcoal. It is then extracted with carbon disulfide and an aliquot is
analysed by GC/FID. The estimated limit of detection for this method is 0.01 mg
per sample (National Institute for Occupational Safety and Health (NIOSH),
1994).
Table 4 gives details of commonly used analytical methods.
6.2 Biological monitoring
Several methods are available for measuring and testing for trichloroethylene in
biological media. Samples may be analysed for the presence of trichloroethylene
or its metabolites, trichloroethanol and trichloroacetic acid. Trichloroethylene
may be estimated in exhaled air or blood while its metabolites are estimated in
blood or urine. The main analytical method used is gas chromatography
combined with electron capture detection (ECD).
The headspace gas chromatographic method allows simultaneous measurements
of trichloroethylene, trichloroacetic acid and trichloroethanol. In headspace
analysis, the gaseous layer above the sample is injected in to a gas chromatograph
either directly or following preconcentration prior to injection on to the GC
column.
6.2.1 Estimation of trichloroethylene
Expired air analyses
Several methods have been described for analysis of trichloroethylene in expired
air. Methods used include preconcentration on Tenax-GC cartridges followed by
thermal desorption either directly onto the gas chromatograph column for
separation and detection or to a cryogenic trap connected to the gas
chromatograph.
13
Trichloroethylene
14 Priority Existing Chemical Number 8
Results of studies in human volunteers indicate that the concentration of
trichloroethylene in expired alveolar air collected during exposure is an indication
of current atmospheric concentration, while estimation 16 h after the end of
exposure reflects the average airborne exposure during the preceding day
(Kimmerle & Eben, 1973; Stewart et al., 1974a; Fernandez et al., 1975; Monster
et al., 1979). Measurements of trichloroacetic acid and trichloroethanol are non-
specific indicators of exposure to trichloroethylene as they can be metabolites of
other chlorine containing hydrocarbons.
American Conference of Governmental Industrial Hygienists (ACGIH) has
recommended monitoring of trichloroethylene in end-exhaled air as a
confirmatory test when the origin of trichloroacetic acid and trichloroethanol is
doubtful.
Blood analyses
The most common method used to analyse trichloroethylene in blood is
headspace analysis, followed by GC or GC/MS. Sensitivity is in the low-ppb
range (2-20 ppb) (ATSDR, 1993).
6.2.2 Estimation of trichloroacetic acid and trichloroethanol
Urine analyses
Trichloroacetic acid in urine is an indicator of exposure by all routes.
Measurements at the end of the shift and at the end of the work week are
considered appropriate to measure recent exposure and cumulative effect,
respectively. Trichloroethylene is converted to trichloroacetic acid and samples
taken at the end of the shift reflect recent exposure. However, trichloroacetic acid
is tightly and extensively bound to plasma proteins and has a half-life in blood of
70-100 h. Repeated exposure causes trichloroacetic acid to accumulate in blood
with the metabolite being excreted very slowly. Trichloroacetic acid levels are
not influenced by timing of exposure and sampling as very little fluctuation in
concentration occurs because of the long elimination half-life.
ACGIH recommends a biological exposure index (BEI) of 10 mg/g of creatinine.
This provides the same degree of protection as a TLV of 50 ppm. There is a
linear correlation between trichloroethylene levels in breathing zone air and
urinary levels of the metabolites, total trichloro-compounds, trichloroethanol and
trichloroacetic acid in men and women (Inoue et al., 1989). Measurements of
trichloroacetic acid in urine may be much higher than indicated by atmospheric
monitoring if dermal exposure to liquid trichloroethylene occurs.
There are significant racial and ethnic differences in the production of
trichloroacetic acid. Deficiency of alcohol dehydrogenase and aldehyde
dehydrogenase is more common in non-Caucasians and can lead to an
underestimation of exposure and an increase in risk to workers. Alcohol intake
and disulfiram treatment also, partly inhibit production of trichloroacetic acid.
15
Trichloroethylene
Total trichloro-compounds (TTC) index in urine reflects the sum of
trichloroacetic acid (TCA) and free and conjugated trichloroethanol expressed as
trichloroacetic acid. Sampling time is critical for this index because of the short
elimination half-life of trichloroethanol. ACGIH recommends collection at the
end of the shift after 4 consecutive days of exposure. A TTC concentration of
300 mg/g of creatinine in urine provides the same degree of protection as
inhalation exposure at the ACGIH TLV of 50 ppm.
Blood analyses
Free trichloroethanol (TCOH) in blood index is an indicator of recent exposure
(day of sampling). The sampling time is critical and a method without the
hydrolysis of TCOH conjugates must be used as the BEI is for the free form.
Hydrolysis would result in conversion of some conjugated trichloroethanol to the
free form giving false results. The timing is critical as trichloroethanol in blood
rises rapidly during exposure and starts declining shortly after exposure. A BEI
of 4 mg/L (27 祄ol/L of SI units) of free TCOH is recommended by ACGIH for
specimens collected at the end of the shift after at least 2 consecutive days
exposure. Alcohol intake may result in lower trichloroethanol levels and lead to
an underestimation of exposure. The test is nonspecific as trichloroethanol is a
metabolite of other chlorine containing ethanes and ethylenes.
16 Priority Existing Chemical Number 8
7. Use, Manufacture and
Importation
7.1 Manufacture and importation
Trichloroethylene is not manufactured in Australia. Approximately 3000 tonnes
of trichloroethylene are imported annually into Australia from France, USA and
UK. It is imported in drums and in bulk. Trichloroethylene is also imported as
an ingredient in formulated products. From information provided by applicants,
it is estimated that approximately 125 tonnes of trichloroethylene is imported in
formulated products annually, in a total of 20 products.
Trichloroethylene is recycled in Australia. Recycling occurs by either distillation
at the work site or off-site recycling companies. More than 185 tonnes of
trichloroethylene is recycled and reused each year.
Data supplied by the Australian Bureau of Statistics indicates a trend towards
increasing amounts being imported commencing from 1995 (see Section 2).
7.2 Uses
No published data on the uses of trichloroethylene in Australia were available.
Therefore a survey of the industry was conducted in order to identify the uses (the
NICNAS industry survey). A total of 310 questionnaires were mailed to
companies and organisations selected from customer lists provided by applicants.
Users of trichloroethylene were selected on the basis of the industry involved to
ensure representation of a wide range of industries using trichloroethylene. The
same questionnaire was also sent to applicants and recyclers. The questionnaire
comprised of separate sections for formulators, resellers and end users of
trichloroethylene and trichloroethylene products (Appendix 3) and also sought
information on Material Safety Data Sheets (MSDS) and labels. One hundred and
fifteen responses were received, representing a response rate of 37%. The total
number of customers identified by applicants was 457, therefore the response
represents approximately 25% of the total number of organisations that buy
trichloroethylene directly from importers. The information below is based on
data gathered from this survey. The data is considered representative but not
complete.
7.2.1 Trichloroethylene
The major use for trichloroethylene in Australia is metal cleaning. Metal
cleaning occurs during the manufacture, maintenance and repair of articles in a
wide range of industries. Trichloroethylene is an effective cleaning agent for
many organic materials as it has a low latent heat of vaporisation and is
nonflammable.
17
Trichloroethylene
Industries using trichloroethylene
The NICNAS industry survey identified the following industries using
trichloroethylene:
? Metal forming/Machining (50%)
? Powdercoating (10%)
? Automotive (10%)
? Aerospace (6%)
? Electrical (6%)
? Chemical Processing (2%)
? Rubber products manufacture (2%)
? Telecommunications (1%)
? Paint (1%)
? Oil refining (1%)
? Gas production and manufacture (1%)
? Locomotive (1%)
? Lubricants manufacture (1%)
? Manufacture (unspecified) (4%)
? Other (4%)
In the final stages of the assessment NICNAS was advised that trichloroethylene
is also used in the Textile Clothing and Footwear Industry as a cleaning agent.
Small amounts of trichloroethylene are also used in the asphalt industry to
dissolve bitumen in the laboratory analysis of aggregate in asphalt.
Vapour degreasing
Vapour degreasing was the most common use of trichloroethylene among
respondents to the NICNAS survey. Seventy seven percent of respondents
(89/115) were end users of trichloroethylene, and of these, 75 percent (67/89)
used trichloroethylene for vapour degreasing. Overseas studies have also
reported that vapour degreasing is the most common use of trichloroethylene
(IPCS, 1985; United Kingdom, 1996).
Vapour degreasing is a process used in many industries to clean metal
components. Most commonly it is used to remove oil, grease, and/or metallic
swarf from metal components prior to surface coating, assembly or repair
operations, machining, inspection, or end use of the component. Vapour
degreasing is also used to remove polishing compounds, paints, metallic oxides,
and mineral soils.
Vapour degreasing involves the heating of a quantity of solvent in a tank to
boiling point. Condensing coils located on the inside perimeter of the tank
control the height to which the solvent vapours rise, creating a `vapour zone' into
which metal components to be degreased are lowered. Vapour condenses on the
cold components, dissolving surface oils and greases. The contaminated
condensate drains into the boiling liquid below. This cleaning action continues
18 Priority Existing Chemical Number 8
until the temperature of the components being degreased reaches the temperature
of the vapour, at which point condensation ceases. The components are then
lifted above the vapour zone and held in a freeboard area for cooling and
evaporation of any remaining solvent, and then removed from the degreaser at a
controlled rate to avoid lifting vapour out of the degreaser. Vapour degreasers
can incorporate spraying and/or immersion in boiling solvent as part of the
cleaning process.
Trichloroethylene is one of several solvents that can be used for vapour
degreasing. Other solvents used include tetrachloroethylene, methylene chloride,
and 1,1,2-trichloro-1,2,2-trifluoroethane. The manufacture of 1,1,1-
trichloroethane, another solvent commonly used in vapour degreasing, ceased in
January 1996 in accordance with the Montreal Protocol, and importation of
existing stocks is strictly regulated under the Ozone Protection Act 1989. It is
possible that the use of trichloroethylene in vapour degreasing may increase due
to the phase out of 1,1,1-trichloroethane.
Cold cleaning
Cold cleaning refers to the process of cleaning by dipping or soaking articles in a
cleaning liquid, or spraying, brushing, or wiping the cleaner onto articles at
temperatures below boiling point. Twenty nine percent of end users (26/89) of
trichloroethylene responding to the NICNAS industry survey reported using
trichloroethylene in cold cleaning processes. This proportion of use of
trichloroethylene in cold cleaning activities is higher than that reported in
overseas studies.
Cold cleaning activities mentioned in the NICNAS survey included immersion in
tanks, drums, or other containers, ultrasonic cleaning, and spraying, brushing and
wiping. In ultrasonic cleaning, a transducer mounted on the bottom or side of a
tank containing solvent creates vibrations which cause the rapid expansion and
contraction of microscopic bubbles in the solvent, resulting in a scrubbing action
on parts that are immersed in the tank. Ultrasonic agitation can be employed in
hot or cold immersion cleaning, and is sometimes incorporated into vapour
degreasing systems.
7.2.2 Products containing trichloroethylene
Several categories of products containing trichloroethylene have been identified
as being in use in Australia from information supplied by applicants and from the
NICNAS survey. They are:
? adhesives
? electrical equipment cleaning solvents
? metal degreasing solvents
? waterproofing agents
? paint strippers
? carpet shampoos
? tyre cleaning product
19
Trichloroethylene
Details on the number of products identified in each product category, the range
of concentrations of trichloroethylene within each category, and the total
estimated amount of trichloroethylene used in the products are summarised in
Table 5.
It is expected that there are more products containing trichloroethylene
formulated in Australia which have not been identified. Regarding imported
products, it is not possible to identify products containing trichloroethylene from
customs data, and so it is possible that more products containing trichloroethylene
are being imported.
Table 5 - Trichloroethylene products identified by applicants and notified by
respondents to a NICNAS industry survey
Product Type Number Percentage Approx.
of TCE (range) amount TCE
products used
annually
(tonnes)
Adhesives ?imported 18 20 - >90 105
Adhesives - formulated in 3 10 - 88 6.5
Australia
Electrical equipment cleaning 8 13 - >60 93
solvents
Metal degreasing solvents 7 <10 - 65 53
Waterproofing agents 璱mported 1 90 0.2
Waterproofing agents - 3 60 - 70 5.4
formulated in Australia
Paint strippers 3 0.05 - 8 1.5
Carpet shampoos 2 3 0.2
Tyre cleaning product - imported 1 >90 18
TOTAL 46 0.05 - >90 282.9
Adhesives
Solvents are used in adhesives to lower the viscosity and increase the wetting of
the adherent/substrate. Many industrial adhesives comprise polymer blends,
organic compounds and mineral fillers dissolved in solvent (such as
trichloroethylene). They are used in bonding natural and synthetic rubber to
metal and other rigid substrates, plastics, and fabrics. Other adhesives bond
plastics, rubber and fabric, and bond polyurethane coatings to metal or to natural
or synthetic rubber. Some are two-part adhesive systems, which are mixed just
prior to use. Further dilution of the mixtures with solvents including
trichloroethylene may also occur prior to application. Trichloroethylene is often
used where a solvent of low flammability with the desired drying time is
required.
The majority of the imported adhesives containing trichloroethylene are used for
rubber repair and rubber lining in the mining and automotive industries. Uses
include the hot or cold vulcanisation of patches to tyres, and sealing tyre inner
20 Priority Existing Chemical Number 8
linings after buffing; and the lining of tanks with rubber and repair of rubber
belting. Two products, used in cold vulcanisation repair of tyres, are available to
the public. Approximately 5 tonnes of trichloroethylene per year are used in
these two products in total.
7.3 Other information on uses
Trichloroethylene is used overseas as a precursor in the manufacture of CFC
alternatives such as HFC-134a or HCFC-123. However, trichloroethylene is not
used as a feed stock for other chemicals in Australia.
In the past, trichloroethylene has been used in Australia as an anaesthetic agent,
in dry cleaning, in correction fluids and as a solvent in pesticide formulations.
These uses apparently no longer occur.
It has come to the attention of NICNAS that trichloroethylene is being considered
for use in scouring wool.
21
Trichloroethylene
8. Occupational Exposure
8.1 Routes of exposure
Occupational exposure to trichloroethylene may occur during transport, storage,
formulation or use of the chemical, during the solvent re-cycling process or
during disposal (ie of contaminated solvent). Workers may be exposed to
trichloroethylene by the inhalation and dermal routes.
Trichloroethylene is a volatile liquid at room temperature. Inhalation of
trichloroethylene may occur through exposure to vapour emitted by liquid or
mixtures containing trichloroethylene, or by exposure to aerosols. Activities such
as heating or agitation of the liquid will increase the emission of vapours and the
likelihood of exposure.
Dermal absorption of trichloroethylene may occur through contact with the liquid
form. Contact with vapour condensate, or with aerosols from sprayed products or
mixtures containing trichloroethylene, are also potential sources of dermal
exposure.
8.2 Methodology for estimating exposure
Good quality measured data for various work scenarios is preferable in the
assessment of occupational exposure. If monitoring data is limited, then
modelling can be used with standard formulae to estimate exposure. In the
assessment of trichloroethylene measured data was limited and standard formulae
were used to estimate exposure.
The exposure estimates in this assessment are considered to be "feasible" worst
case estimates, as they describe high-end or maximum exposures in feasible, not
unrealistic situations. The estimates are not intended to be representative of
extreme or unusual use scenarios which are unlikely to occur in the workplace.
However, it is likely that the majority of occupational exposures will be below
these estimates.
The formulae used to calculate exposures are detailed in Appendix 1. The
constants in the formulae such as body weight and inhalation rate were those
used in international assessments.
Estimates for exposure to vapour did not include dermal uptake of vapour as
dermal absorption of vapour is considered to be negligible (see section 9).
22 Priority Existing Chemical Number 8
8.3 Importation and repacking
8.3.1 Importation of trichloroethylene
Drums
Trichloroethylene is imported in 205 L sealed steel drums and is generally
transported to distributors or direct to end-users without being opened. Exposure
during transportation and storage of drums is unlikely except in case of accidents
such as leakage from damaged drums.
Bulk storage facilities
Trichloroethylene is also imported in bulk containers to Port Botany in NSW and
to Coode Island in Victoria. Bulk trichloroethylene is pumped by shoreline from
tanks on board ships to on-shore bulk tanks. From here it is transferred to road
tankers and drums (205L) and transported to a warehouse site, where it is stored
prior to distribution. Occasionally trichloroethylene is transported directly to the
end-user from the bulk storage facility.
Worker activities include connection and disconnection of shore and wharf lines,
and a process called `pigging' in which a polyurethane foam sponge is placed at
one end of a line and propelled by nitrogen through the line (for up to one
kilometre) in order to clean and dry it. The sponge is collected from the other
end of the line by an operator who places it in a bucket of water. Other activities
include filling of road tankers and drums, cleaning of bulk storage tanks, and
maintenance work on pumps and piping.
A continuously operating automatic carbon absorption vapour extraction system
draws air from around hose connections at tanker and drum filling stations, and
openings on bulk storage tanks, through piping to a central carbon bed adsorption
unit. The air is drawn through the carbon and out an emission stack. The carbon
is regularly desorbed of trapped chemical by high pressure steam. Vapour
condensate is collected and disposed of through waste collection agencies.
Filling of tankers is controlled by a mass flow meter. Tanker filling station areas
have an underground collection area in case of accidental spillage. Drums are
filled using a specially designed device that uses a mass flow meter to pre-set the
volume. This system involves a moveable filling handle that minimises manual
handling of drums. More traditional filling stations employing scales are also
used for drum filling. Drums are double capped. Drum filling station areas are
bunded. Cloth gloves are supplied for use during filling.
A full face organic canister mask or breathing apparatus is worn in situations
where it is believed a potential for high exposure exists, such as during `pigging'
and dipping bulk storage tanks to measure levels. Special work permits issued by
management are required before cleaning of bulk storage tanks, and confined
space work procedures are followed.
A total of 39 workers are employed at the two sites. Filling and monitoring of
bulk tanks typically engages workers for 4-5 hours, 4-6 times a year. Similarly,
filling of drums occurs for about 4 hours, 6 times a year. Filling of road tankers
23
Trichloroethylene
is typically undertaken 150 times a year, with filling taking approximately 10-20
minutes.
Due to enclosure of the transfer process and other control measures in place, the
potential for inhalation exposure is considered low. The potential for dermal
exposure during tanker and drum filling is low due to the use of mass flow
meters. Handling of shorelines and the sponges used for cleaning them may pose
a potential for dermal exposure through splashes.
In the exceptional circumstance of imported trichloroethylene being
contaminated, it is sent to a recycling plant. Information provided suggests this
happens rarely.
8.3.2 Repacking
One importer of trichloroethylene and some distributors repack trichloroethylene
from drums into smaller containers prior to distribution to end-users. The
importer stated that decanting is conducted using a filling hose and controls in
place include air extraction systems in the packing area, and the wearing of
personal protective equipment. Ten workers are employed on both repacking and
formulation tasks for 1 to 4 hours a day, 25 days a year.
The repacking process presents a potential for both inhalational and dermal
exposure through vapour emitted during the transfer process and accidental spills
and splashes. The extent of exposure will depend on factors such as the method
of transfer, amount of time spent on the task, and type of controls in place.
Little information was available to determine whether distributors also repack and
if they do, the methods used for repacking. Limited data indicates that repacking
generally involves one to two workers, on an intermittent basis.
8.3.3 Importation of products
Products are onsold by importers, and information provided indicates products
are not repacked in Australia. Exposure during importation would be expected
only in the case of accidental spills/leaks of product.
8.3.4 Monitoring data for bulk storage, transfer and repacking
Atmospheric monitoring results from the Port Botany (3 samples during ship to
shore transfer) and Coode Island (60 samples during various activities) bulk
storage sites were made available. The results are shown in Table 6. Both area
and personal breathing zone sampling were conducted using passive dosimeters
over full shift periods. All exposure levels were below 1 ppm with the exception
of one sample taken during `pigging' and connection and disconnection of wharf
lines (3.2 ppm) and 3 samples taken during drum filling (2.0 - 2.4 ppm)
No monitoring data were available for worksites engaged in repacking
trichloroethylene or handling trichloroethylene products.
24 Priority Existing Chemical Number 8
Table 6 - Atmospheric monitoring results (TWA) at bulk storage
facilities
Activity Area/Tasks Type of No. of Duration TCE (ppm)
Monitoring Samples of
sampling
(hours)
Ship to shore Site boundary A 15 7.5 0.01 - 0.28
transfer
Top of tank A 3 9 - 11.5 0.01 - 0.05
Exchanger pit A 2 9 0.06 - 0.06
Pigging & P 2 8 - 12 0.8 - 3.2
connection lines
Transfer P 3 10 0.05 - 0.07
General duties P 4 8.5 - 10 0.05 - 0.42
Truck Loading gantry A 8 7.5 - 8.5 0.01 - 0.26
Loading
" P 12 " 0.01 - 0.08
Site boundary A 4 8 0.01 - 0.01
Office duties P 2 8.5 0.06, 0.06
Drum filling Drum fill P 2 7.5 - 11 2.0, 2.4
building
" A 1 " 2.2
General Site boundary A 4 7.5 0.27 - 0.31
operations General duties P 1 7.5 0.05
TCE = trichloroethylene
A = area monitoring
P = personal monitoring
8.3.5 Summary of exposure during importation and repacking
The potential for exposure to trichloroethylene during importation is likely to be
low as transfer and storage of bulk trichloroethylene is an enclosed process, the
process occurs intermittently and precautions have been taken to minimise
exposure. The atmospheric monitoring data provided indicate low exposure via
inhalation with all except four readings being <1 ppm. The maximum TWA
reading obtained was 3.2 ppm during pigging and connection and disconnection
of wharf lines. Dermal exposure is expected to be minimal if care is taken to
avoid splashes during "pigging".
Very little information was provided on repacking. No monitoring appears to
have been carried out. However, the limited data indicates that repacking is an
infrequent process. Exposure during handling of trichloroethylene products is
expected to be very low.
8.4 Formulation
Processes commonly operating in the formulation of products containing
trichloroethylene include transferring ingredients to mixing vessels from drums or
from bulk storage tanks, cold blending the ingredients in mixing vessels, and
filling containers from mixing vessels. Formulation of aerosol products may
25
Trichloroethylene
include production processes such as automated filling of cans with line operators
packing cans from the assembly line.
Twenty seven individual products containing trichloroethylene and formulated in
Australia by 11 companies, were identified by the NICNAS survey. Information
on formulation, including engineering controls and personal protective equipment
were provided by nine of the companies. Two formulators use closed pipelines to
transfer trichloroethylene from a bulk storage tank to mixing vessels, with
metered pumps to control flow rate. One formulator uses a gravity feed hose and
a drum trolley to decant trichloroethylene from a drum into 20 L containers
containing the other ingredients of the mixture. Closed mixing vessels are used
by four formulators while five use open mixing vessels. Two of the formulated
products are aerosols.
Approximately 30 workers are involved in formulation of these products.
Typically, 1 to 4 process workers are employed on the task for short periods,
several times a year. There is a wide variation in the time spent in formulating
products ranging from 1-8 hours a day for 4-60 days per year.
Four of the worksites have no mechanical ventilation controls, four have some
type of air extraction system in place, one uses a fan. Use of personal protective
equipment varies, with all workplaces using gloves and most using safety glasses
and overalls. Where specified, gloves are described as impervious, chemical or
solvent resistant, or nitrile. A twin cartridge mask is used in one workplace.
Empty drums at the nine sites for which information was provided were disposed
of through sale to drum recyclers.
Formulation of trichloroethylene products is conducted at room temperature and
is a batch process. There is the potential for inhalation exposure to vapour and
incidental dermal exposure through splashes etc. Exposure may occur during
transfer to the mixing tank, the mixing process and filling of containers with the
product.
The potential exposure of workers to trichloroethylene during formulation is
likely to vary as the control measures used by the formulators are variable. When
trichloroethylene is added to the mixing tanks through closed pipelines with
metered pumps to control flow rate the exposure is likely to be low. However,
exposure is likely to be high at worksites having an open mixing process with no
mechanical ventilation controls.
There is also the potential for worker exposure during the filling procedure. The
frequency and duration of exposure is likely to be greater during the filling
procedure when the mixed product is transferred to containers. The NICNAS
survey contained an open-ended question asking for a description of the
formulation process, however, no information was provided on the filling
process. One site visit was made to a formulator of an electrical equipment
solvent. After blending, the mixture was decanted into drums and 20 L cans. For
filling the cans, an operator stood at a filling and weighing station, with the can
on a weigh bench at waist level. A lever was pulled and the mixture flowed from
a tap connected to the mixing vessel into the can, from a distance of about 7.5
cms. When the can was full, the lever was lifted, and the can turned around for
capping. It was observed that the tap leaked slightly. The worker wore eye
goggles. No gloves or other protective clothing was worn.
26 Priority Existing Chemical Number 8
8.4.1 Atmospheric monitoring and health surveillance
Responses to the NICNAS survey indicated that air monitoring had been
conducted at only one of the nine worksites. The results were not provided.
Health surveillance in the form of annual liver function tests was performed at
one of the worksites, however these results were also not provided.
8.4.2 Summary of exposure during formulation
As no monitoring data from Australian formulators of trichloroethylene products
were available, standard formulae were used to estimate exposure (Appendix 1).
Inhalation exposure was estimated for three atmospheric levels of
trichloroethylene 10, 30 and 50 ppm (the same levels used for vapour
degreasing). Duration of exposure was for 4 h a day, 30 days per year.
No dermal exposure data for trichloroethylene were available, hence estimates for
exposure to liquid were calculated according to the formula described in
Appendix 1. Concentration ranges for the various formulated products were
<10%, 10-80%, 10->60%, 60-70%, and 60->90%. The concentration selected for
dermal exposure estimate was 90%.
Inhalation exposure was considered to be continuous and dermal exposure
incidental (ie 1% of the total time). Estimates for total body burden (mg/kg/day)
from inhalation and dermal exposure are provided in Table 7.
Table 7 - Total body burden from inhalation and dermal exposure
Exposure estimate
(mg/kg/day)
Inhalation
10 ppm (54.6 mg/m3) 0.26
30 ppm (163.8 mg/m3) 0.76
50 ppm (273 mg/m3) 1.26
Dermal
90% 0.013
8.5 Vapour degreasing
8.5.1 Numbers of workers potentially exposed
From the survey it is known that there are at least 75 vapour degreaser units
involving over 1,000 people in operation in Australia (this figure includes 500
employees of an aerospace company, estimated to be exposed on an intermittent
basis). Due to the relatively low response to the survey (37%), it is likely that the
number of vapour degreasers in operation and the number of people operating
vapour degreasers are much higher.
8.5.2 Potential frequency and duration of exposure
The survey indicated that the majority of workplaces have one vapour degreaser,
and employ 1-3 workers on vapour degreasing tasks. Adequate information on
the duration and frequency of work on vapour degreasing tasks was provided by
27
Trichloroethylene
61/67 respondents. Details were provided for a total of 766 workers. Table 8
shows the number of workers involved in vapour degreasing and the duration of
exposure. The 500 aerospace workers, employed on vapour degreasing tasks on
an "occasional, intermittent" basis, are included in the lowest potential exposure
category.
Table 8 - Distribution of potential exposure
Days per year Hours per day
0.25-2 >2-4 >4-8 >8-12
509 3 7
1-20
9 3
21-50
3 8 1.5
51-100
15 6 2
101-150
3 5 2
151-200
43 8 38 1
201-250
35 7.5 51 6
>250
The survey indicates that the most common scenario is working for between 15
minutes to 2 hours, for up to 20 days a year. If the aerospace company
employees are excluded, the most common scenario is working > 4-8 hours a day,
for more than 200 days a year (33%). The next most common scenario is
working for up to 2 hours a day for more than 200 days a year (29%). A small
proportion of workers (2%) worked extended shifts for more than 250 days a
year.
8.5.3 Types of vapour degreasers
Australian Standard AS 2661 - Vapour Degreasing Plant - Design, Installation
and Operation - Safety Requirements (Standards Association of Australia, 1983)
describes the requirements for safe design and operation of vapour degreasers.
Information from the NICNAS industry survey and site visits (7) carried out in
1995-96 indicated that the types of vapour degreasers in operation in Australia
range from small to medium sized manually operated open-topped degreasers to
semi-automated plants with platform lifts that lower and raise work containers
according to preset cleaning times, to large fully automated end loading
degreasers with conveyor monorails that carry the work baskets through the tank.
Some vapour degreasers incorporate liquid as well as vapour stages, with
components being dipped into boiling solvent and/or sprayed with liquid solvent
prior to rinsing and drying through vapour condensation. The length of time of
cleaning cycles varies according to the type of degreaser and the articles being
degreased, however an average cycle lasts around 30 minutes. Figure 3 illustrates
the common features of an open-topped manual vapour degreaser.
28 Priority Existing Chemical Number 8
Figure 3 - Open-topped manual vapour degreaser
Open-topped top loading degreasers loaded by hoist or manually were the most
common type of degreaser described in the survey (49/67). Lids of various types
(sliding or lift out/hinged) are sometimes fitted on open-topped top loading
degreasers, however information indicated that use of lids appears to be
infrequent, and they are sometimes put on only at night or when the degreaser is
not in use.
The remainder of the vapour degreasers (18/67) were described as closed or
partially closed systems. Some of these incorporated dipping and spraying
cycles. One was a 15 station conveyor system with five cycles: hot liquid dip,
hot liquid spray, cold liquid, cold liquid spray, vapour rinsing. Three degreasers
were operated inside sealed `clean rooms'. Two very large installations using
11,000 and 12,000L of solvent respectively were also identified.
The survey indicated that addition of trichloroethylene to degreasers is mainly
from drums. Only a few respondents (4/67) mentioned addition of
trichloroethylene through closed pipelines from bulk storage tanks.
8.5.4 Cleaning and maintenance of vapour degreasers
Vapour degreasers require periodic cleaning to remove sludge and contaminated
solvent from the sump area. The frequency of cleaning will vary according to
factors such as the volume of work being processed and the nature and amount of
contaminants. The boiling point of trichloroethylene rises as it becomes
contaminated and so temperature is commonly used to determine the degree of
contamination and hence when to clean a degreaser. Another method used to
29
Trichloroethylene
determine when to clean is the measurement of specific gravity, which falls as the
temperature rises.
Information from industries in Australia on clean-out procedures indicated a wide
variation in the frequency of cleaning ranging from once a year to twice a week.
The cleaning process involves removal of the solvent via distillation or discharge
from the sump, usually into drums. Doors usually situated at the bottom of the
sump are opened and sludge raked out and transferred to drums. In one case an
electric hoist was used to tilt a small degreasing tank to a 45 degree angle in order
to allow raking out of the sludge. Raking out is usually done from outside the
degreaser, however entry of workers into a degreasing tank sometimes occurs.
Some companies employ contractors to clean degreasing tanks. Information from
one contracting company indicated that the usual method employed was to pump
out solvent into drums; use high pressure water spray to clean the sides of the
tank and scrape solidified material into drums. This company follows confined
space procedures when entry into tanks is required. A team of at least 3 and
usually 4 workers certified to work in confined spaces work together in cleaning
the tanks.
8.5.5 Potential sources of exposure
Routine operation
Routine operation of a vapour degreaser will result in some emission of vapour
and consequent potential for exposure. Two main sources of emissions are
air/solvent vapour interface losses and workload related losses. Air
solvent/vapour interface losses occur by diffusion of solvent vapour from the
vapour zone into the air and convection due to heating of the freeboard.
Workload losses occur through turbulence and consequent displacement of
vapour into the air caused by work routines such as lowering/lifting of baskets,
and through dragout of vapour or liquid solvent trapped in work pieces (Radian
Corporation, 1990).
During shutdown of the degreaser, vapour can be emitted through evaporation of
hot liquid solvent from the sump and its diffusion into the air. After cooling,
vapour emissions may continue as a result of evaporation from the liquid surface.
During start-up of the degreaser, solvent-laden air can be pushed out of the
degreaser as a consequence of the heating of the sump area and creation of a
vapour zone.
Filling or topping up the degreasing plant may result in exposure from vapour
surges, for instance, as may occur if cold solvent is added to hot solvent or if the
solvent is poured in instead of being pumped or fed through gravity feed hoses so
that the solvent enters the tank below the existing liquid level in the sump.
Leaks from pipe connections or cracks are another potential source of exposure.
Technical service personnel involved in installing, modifying or maintaining
plant equipment may be exposed to trichloroethylene when performing these
tasks.
Maintenance
30 Priority Existing Chemical Number 8
During cleanout of degreasers there is high potential for exposure. Draining off
solvent into drums, opening sludge doors and raking out sludge into containers
and refilling the tank will expose workers to vapour and the possibility of
accidental skin splashes. Draining off hot solvent may increase exposure to
fumes and may lead to fire. A high potential for exposure is presented by entry
into the tank for cleaning and strict procedures for working in confined spaces
should be followed (see section 14).
The treatment of plant which has become acidic, as described in Appendix A in
the Australian Standard AS 2661 - Vapour Degreasing Plant - Design, Installation
and Operation - Safety (Standards Association of Australia, 1983), presents a
potential for exposure similar to that involved with clean-out of degreasers.
8.5.6 Atmospheric monitoring
Australian data
WorkCover Authority of NSW
The WorkCover Authority of NSW provided air monitoring data for
trichloroethylene from sampling conducted at twelve worksites between 1984 and
1995. The monitoring was carried out by WorkCover inspectors. Requests by
the company was the reason for six of the visits, requests by unions were the
reason for two visits, and the remainder of the visits were initiated by the
WorkCover Authority. A total of 23 samples were taken at or around vapour
degreasing tanks. Results ranged from `not detectable' to 194 ppm. Nine of the
17 personal samples were above 50 ppm, with five over 100 ppm. Seven of the
11 worksites at which personal monitoring was conducted had at least one
personal monitoring result above 50 ppm. The duration of monitoring was not
specified for 11 samples while the monitoring duration was 4 h or more for the
rest of the samples. One of the 6 area samples was greater than 50 ppm. No data
was provided on the work practices at the workplaces. The distribution of results
in concentration ranges are shown in Table 9.
Table 9 - Results of air sampling of vapour degreasers by WorkCover
Authority of NSW: 1984-1995
Concentration ranges Number of samples
(ppm) Personal samples (17) Area samples (6)
0 - 25 6 4
>25 - 50 2 1
>50 - 100 4
>100 - 200 5 1
NICNAS survey results
Very little monitoring data for Australian workplaces was provided considering
the scale of use of trichloroethylene. A total of 26 organisations out of the 115
respondents to the NICNAS industry survey indicated that air monitoring had
been conducted at their workplaces. These 26 organisations were followed up
31
Trichloroethylene
with a further questionnaire aimed at gathering details of their monitoring data.
Thirty-seven samples from 9 worksites were provided. The majority of samples
were area sampling around the vapour degreaser while in operation. Samples
were taken between 1987 to 1995. All except one sample were below 50 ppm.
One result was 145 ppm, taken at 15 cm above the top of a degreaser while the
degreaser was at idle (boiling). The range of the other samples was `not
detectable' to 27 ppm. The air monitoring survey indicated that monitoring is
generally conducted on an ad hoc basis, not as part of a routine monitoring
program. Monitoring was generally conducted on specific occasions such as
following modification to a degreaser, following complaints of fumes after
installation of a new plant, or as a one-off reading to ensure that standards were
being met.
Other monitoring data
Data from air monitoring for trichloroethylene conducted by the School of Public
Health and Tropical Medicine of Sydney University at one worksite in 1977 was
made available. Eighteen grab samples of up to 20 seconds were taken in the
breathing zone of a vapour degreaser operator, around the vapour degreaser, and
in a pit under the degreaser. Several high readings (125 ppm to >700 ppm) in the
operators breathing zone were obtained when the operator was lowering and
pulling up baskets manually, and a reading of >700 ppm was obtained when the
operator was spraying objects with his head over the edge of the tank. Removing
articles from the tank using a hoist after leaving them suspended to dry also gave
high readings (400 ppm to >700 ppm). The lack of rim ventilation and placement
of the degreaser in an area exposed to draughts were factors contributing to the
high readings, according to the author of the study.
Overseas monitoring data
United Kingdom
Personal sampling at 37 locations was conducted by Shipman and Whim in
England in the late 1970s. Of the 306 samples (8 h TWAs), 94% were less than
50 ppm and 96% were less than 100 ppm (Shipman & Whim, 1980). More recent
monitoring by HSE inspectors conducted between 1984 and 1994, show that of
25 personal samples (8 h TWAs), 96% were <30 ppm and all were less than 50
ppm (United Kingdom, 1996).
In 1994 a survey of vapour degreasing operations was carried out by the UK
Health and Safety Executive (Robinson, updated January 1996). Air sampling
using Drager tubes was undertaken at 100 of 120 vapour degreasing plants using
trichloroethylene. At most sites, samples were taken at four positions around the
degreaser. Of the 120 degreasing plants, 111 were open-topped and manually
loaded. Many of these tanks had covers, however it was unclear how many used
these covers during degreasing.
A total of 379 grab samples were taken and the results, broken up into 50 ppm
ranges, are shown in table 10 below. Of the 379 samples, 155 (41%) were above
50 ppm and 54 (14%) were above 200 ppm. It was also noted that where high
results were obtained, generally some obvious deficiency in the maintenance or
operating procedures was found which could account for the results. These
32 Priority Existing Chemical Number 8
included draughts, high hoist speeds (ie >3 m/min), blocked rim ventilation, and
freeboards less than 75% of the width of the plant.
Table 10 - Results of HSE short-term air sampling of 100 vapour degreasers
(Robinson, Updated January 1996)
Concentration ranges No. of samples No. of sites with at least
(ppm) one reading in the range
0 - 50 224 88
>50 - 100 67 41
>100 - 150 25 18
>150 - 200 9 8
>200 15 13
>250 39 25
Limited data is available from the HSE for air monitoring during the cleaning of
degreasing baths where the operator does not enter the degreasing bath. Five
samples were taken during 1994/95, with results ranging from 9-350 ppm (2
samples were above 150 ppm). The sampling duration was 18 minutes. (United
Kingdom, 1996)
United States
Air monitoring data for trichloroethylene from sampling conducted at four
worksites using vapour degreasers are available from reports of investigations
carried out by the Hazard Evaluation and Technical Assistance Branch of
NIOSH. This Branch is responsible for investigating possible health hazards in
the workplace and investigations are carried out following a request from
employers or employees.
Exposure data taken at the four manufacturing sites between 1989 -1991 is
presented in Table 11. In three cases, health effects were reported in the request
to investigate. Effects reported in two cases were headache, dizziness, nausea,
sleepiness/fatigue, upper respiratory tract irritation, and skin rash (one site).
Effects reported in the third case were cancers, breathing problems, kidney
problems and watery eyes. The sites investigated included a large industrial
complex with 4 conveyor fed degreasers; a manufacturer operating a conveyor
fed liquid-vapour immersion degreaser; a manufacturer operating an open-topped
degreaser; and a company operating an open-topped degreaser and an ultrasonic
degreaser. At the latter site, a further source of potential trichloroethylene
exposure was the use of a spray lacquer containing trichloroethylene. Sampling
was done over 8 h obtaining a TWA for the entire shift. (National Institute for
Occupational Safety and Health (NIOSH), 1989a; 1989b; 1990; 1991).
The highest readings were three short-term (10-24 minutes) personal samples
taken at one worksite while the worker was engaged in servicing a liquid-vapour
conveyor-fed degreaser.
Table 11 - Results of air sampling of 4 worksites by NIOSH
Concentration ranges Number of samples
33
Trichloroethylene
(ppm) Personal samples (37) Area samples (18)
TWA STEL TWA STEL
0 - 25 12 12
>25 - 50 22 4
>50 - 100 1 1
>100 - 200 3
A project, tracking exposure profiles of chlorinated solvents in various industries
was conducted as part of the Dow Chemical Company's Product Stewardship
Program during 1994 - 1995 in the United States. Personal sampling (61
samples) was carried out using organic vapour monitoring badges. The average
concentration of trichloroethylene for all vapour degreasing measurements was
28.4 ppm. The results are shown in Table 12, grouped and analysed according to
the different ventilation conditions of the worksites sampled (Skory Consulting
Inc. & Skory, 1995)
Table 12 - Trichloroethylene vapour degreasing exposures - Dow Chemical
Company (USA)
conc. (ppm)
Ventilation
Deviation
Standard
Average
Sample
Median
Mode Number of Results
Size
<50 50-100 >100
ppm ppm ppm
40.2 27.7 40.6 5 3 2 0
Enclosed
system
14.8 5.1 23.0 24 23 3 0
Local exhaust
38.7 17.9 40.9 30 20 6 4
General
6.0 6.0 2.4 2
Spray booth
8.5.7 Summary of exposure during vapour degreasing
Inhalation and dermal exposures to trichloroethylene are likely during use of the
chemical in vapour degreasing. Emission of vapours from open-topped tanks
may lead to inhalation exposure. Inhalation exposure may also occur during
manual loading of metal parts to be degreased. Dermal exposure to liquid
trichloroethylene may occur during filling of tanks with trichloroethylene or
during handling of hollow degreased parts that may contain trapped liquid
trichloroethylene or during spills.
A variety of control measures may be incorporated in degreasing tanks to reduce
emissions. A survey of degreasing operations carried out by the Health and
Safety Executive in U.K.(1996) has shown that emission is likely to be < 30 ppm
in tanks fitted with the appropriate control measures such as rim ventilation,
adequate freeboard zone, condensing coils etc and where good work practices are
followed. Some older tanks do not have all the appropriate controls resulting in
high short-term emissions (Robinson, Updated January 1996). According to
34 Priority Existing Chemical Number 8
information obtained from the NICNAS survey most workplaces have open-
topped tanks and those equipped with lids are generally only covered at night.
At least 1000 people, excluding aerospace workers, are involved in vapour
degreasing in Australia either on a regular or intermittent basis. The most
common exposure scenario was 4-8 h a day for more than 200 days a year.
Atmospheric monitoring is not conducted on a regular basis by most users during
vapour degreasing in Australia. Very limited atmospheric monitoring data was
provided by users with the data relating to grab samples and no time weighted
average results being provided. Short-term measurements have been high in
some cases especially during manual loading and unloading of parts. The
monitoring data provided by WorkCover did not state the time period over which
the monitoring was done making it difficult to determine if they were time
weighted average or grab samples. Based on the the U.K. data of Shipman and
Whim (1980) exposure during vapour degreasing in this assessment were
estimated for three scenarios at 10, 30 (results recorded at most workplaces) and
50 ppm.
Dermal exposure to liquid trichloroethylene was assumed to be incidental. The
estimates for total body burden (mg/kg/day) from inhalation and dermal exposure
were 3.5 mg/kg/day for 10 ppm, 10.2 mg/kg/day for 30 ppm and 16.9 mg/kg/day
for 50 ppm. Details of the exposure estimates for vapour degreasing are given in
Appendix 1.
8.6 Cold cleaning
Cold cleaning refers to the process of cleaning by dipping or soaking articles in a
cleaning liquid, or spraying, brushing, or wiping the cleaning liquid onto articles
at temperatures below boiling point. Processes may be manual, such as in wipe
cleaning, or semi- or fully automated, such as in some in-line cleaning systems in
which parts carried by conveyor lines are dipped into one or more tanks of
solvent. Immersion cleaning can involve manual, mechanical or ultrasonic
agitation of the solvent in the tank.
The NICNAS industry survey identified 26 companies in Australia using
trichloroethylene in various cold cleaning processes. This represented 29% of the
total number of respondents who are end users of trichloroethylene. The most
common type of cleaning described was immersion in tubs or tanks (15/26
companies). In most cases this was combined with manual scrubbing of the
articles using paint brushes and/or some form of agitation of the liquid solvent
such as swirling. One respondent used an ultrasonic system. Manual wipe
cleaning was the second most common form of cold cleaning (7/26 companies),
and spraying was mentioned by one company. One company uses
trichloroethylene for regular daily flushing of polyurethane mixing chambers to
prevent gelling of mixture in the machine.
Some companies use cold cleaning processes only occasionally, however others
use cold cleaning processes on a regular or semi-regular basis, as part of a normal
work routine. Details of the industry, type of activity, number of workers,
duration and frequency of employment on cold cleaning tasks, and personal
protective equipment, where provided by respondents, are given in Table 13. The
survey results indicate that there is a great variability in cold cleaning processes.
35
Trichloroethylene
8.6.1 Potential exposure during cold cleaning
Immersion cleaning
Exposure to trichloroethylene from immersion cleaning processes may occur
from inhalation of vapour or skin contact with liquid solvent during the transfer
of solvent from bulk storage tanks, drums or other containers into soak tanks,
during immersion and washing of the articles, and handling of articles after
washing. The use of open containers to transport solvent to soak tanks and
agitation of the solvent in the soak tank, via brushing for instance, presents an
increased potential for inhalational exposure and for dermal exposure from
accidental splashes and spills. The design of immersion tanks will affect the
potential for exposure, with open tanks presenting an increased potential for
inhalational and dermal exposure compared with closed tanks or enclosed
automated systems.
Wipe cleaning
In the case of wipe cleaning, inhalational and dermal exposure may occur during
the transfer of solvent from drums or containers onto the cloth and during surface
cleaning using the cloth. The use of open containers for dipping cloths increases
the potential for inhalational exposure and for dermal exposure from accidental
splashes and spills.
Spray cleaning
Spray cleaning using trichloroethylene presents an increased potential for
exposure from inhalation of spray mist or vapour and skin contact with spray
mist.
Table 14 shows the work activity and control measures obtained from the
workplaces as part of a project undertaken by WorkCover for NICNAS.
36 Priority Existing Chemical Number 8
37
Trichloroethylene
38 Priority Existing Chemical Number 8
39
Trichloroethylene
8.6.2 Atmospheric monitoring
Australian data (atmospheric and biological monitoring)
No monitoring data were provided by applicants for cold cleaning activities using
trichloroethylene.
Atmospheric and biological monitoring was conducted by WorkCover, as part of
a project commissioned by NICNAS, at workplaces using trichloroethylene for
cold cleaning. The monitoring was carried out on a half shift basis as most of the
jobs were continuous throughout the day. At two workplaces trichloroethylene
use occurred for only half a day. In these cases the monitoring results were
converted to give an eight hour TWA (by halving the results). The cold cleaning
activities ranged from dip cleaning to combined dip cleaning and rag wiping to
rag wiping alone and are described in Table 14. Atmospheric monitoring was
carried out in accordance with Australian Standard AS 2986 "Workplace
Atmospheres - Organic Vapour Sampling by Solid Adsorption Techniques".
Biological monitoring involved estimation of urinary trichloroacetic acid with
urine samples being collected at the end of shift at the end of the work week.
Table 15 shows the air monitoring results and the urinary trichloroacetic acid
levels obtained during this study.
Overseas data
Some atmospheric monitoring of cold metal cleaning operations using
trichloroethylene has been carried out in the United States as part of a larger long-
term analysis of exposure profiles for chlorinated hydrocarbons conducted for the
Dow Chemical Company Product Stewardship Program (Skory Consulting Inc. &
Skory, 1995). Monitoring was carried out using organic vapour monitors
attached to the collars of employees during their work day and during the time
they are exposed to trichloroethylene. The overall average concentration of 9
samples was 68.4 ppm. Of these, 5/9 were less than 50 ppm, 1/9 was between 50
to 100 ppm and 3/9 were > 100 ppm.
40 Priority Existing Chemical Number 8
41
Trichloroethylene
8.6.3 Summary of exposure during cold cleaning
Inhalation and dermal exposure can occur during cold cleaning. Situations in
which dermal contact might occur include immersion and brushing of articles in
soak tanks, handling of work pieces that are not thoroughly drained of
trichloroethylene and handling of cloths and rags used in cold cleaning. There is a
potential for accidental splashes during the work process involving
trichloroethylene such as transfer of solvent from or to drums or other vessels.
Monitoring data from the cold cleaning project was used to estimate exposure.
Exposure was estimated for 120 days/yr and 200 days/yr as these were the
common scenarios encountered in the workplaces monitored. Inhalation
exposure was considered to be continuous and dermal exposure was assumed for
5% of the total time. At two of the workplaces the job was continuous
throughout the day while at the other two places exposure was for half a day
only. Information obtained from the NICNAS survey indicated that in 3 of 21
workplaces trichloroethylene was used for cold cleaning during the entire shift (8
h). Inhalation exposure was therefore estimated for 8 h/day, 200 days in a year
and 120 days in a year. The estimated exposures may be an overestimation for
those workplaces involved in this activity for only a few hours of the shift. The
temperature during monitoring at the various sites varied from 11.4 癈 to 19.5癈.
It is expected that in summer with high temperatures exposures are likely to be
high. Estimates for the total body burden (mg/kg/day) from inhalation and
dermal exposures are provided in Table 16.
Table 16 - Total body burden from inhalation and dermal exposure
Exposure estimate
(mg/kg/day)
200 days/yr 120 days/yr
Inhalation
0.4 ppm (2.18 mg/m3) 0.13 0.079
3.8 ppm (20.75 mg/m3) 1.27 0.76
68.3 ppm (372.92 22.77 13.66
mg/m3)
0.9 ppm (4.91 mg/m3) 0.29 0.179
7.5 ppm (40.95 mg/m3) 2.5 1.5
1.0 0.60
Dermal
8.7 Trichloroethylene products
The NICNAS industry survey identified 46 products containing trichloroethylene
in use in Australia, including adhesives, electrical equipment cleaning solvents,
metal degreasing solvents, waterproofing agents, paintstrippers, and carpet
shampoos. Some data on uses of these products were obtained from the NICNAS
industry survey and some were obtained from labels and technical bulletins.
8.7.1 Adhesives
Adhesives are applied by brushing, dipping, roller coating or spraying. They may
be diluted prior to application with trichloroethylene, xylene, toluene, methyl
42 Priority Existing Chemical Number 8
ethyl ketone, methyl isobutyl ketone, or other solvents, depending on the type of
adhesive and processing methods employed by the individual users of the
adhesives. Stirring and agitation of adhesive solutions prior to application is
usually done to ensure dispersed solids are uniformly suspended. In some two-
part systems, the parts are mixed prior to application. Pre-weighing of
ingredients can occur if less than the full amounts are used.
Methods for applying adhesives described in technical bulletins provided by
companies for some of the products in use include applying the adhesive to one
or both surfaces to be joined, air drying the coated parts at room temperature for
15 minutes to 2 hours, or in hot drying ovens or tunnels (up to 149篊) for a
shorter period, followed by contact bonding and curing.
Six products used for the repair of rubber tyres were identified. They contain <60
to >90% trichloroethylene. They are used variously for hot and cold
vulcanisation of patches to tyres, cleaning rubber prior to vulcanisation and for
sealing tyre inner linings after buffing. No information was available on methods
of application except for the rubber cleaning product, which is rubbed into the
surface with a linen cloth prior to repair using adhesive products. This product is
comprised of >90% trichloroethylene.
Some information on work scenarios involving the use of adhesives was obtained
from the NICNAS industry survey. The scenarios are outlined in Table 17.
Table 17: Work scenarios in adhesive application
Application Wor- Duration Freq. Engineering PPE
kers (h/day) Controls
2 8-10 6 Extracted Rubber gloves,
Brush paint
days/week spray booth safety glasses,
metal
half-face masks
substrates
(particles and
carbon filter),
safety boots
Dilute & spray 3 2 10 Spray booth Knitted polyester
metal surfaces days/month gloves, vapour
mask
Gloves, boots,
20 1-8 250 Open area
Apply rubber
masks, protective
days/year Fans in drying
adhesive by
clothing
tunnel
brush or mop
onto metal or
rubber substrate
15 8 340 Vented work Gloves, mask,
Hand paint
days/year bench glasses
metal inserts
Gloves, mask,
1 0.5 218 Fume
Mix with curing
goggles
days/year extraction
agent, use in
system
manufacture of
automotive trim
Glue wood to 4 3 240 Natural Gloves
back of sinks days/year ventilation
43
Trichloroethylene
8.7.2 Other products
No end users of other products containing trichloroethylene responded to the
industry survey, however some information on possible work scenarios was
obtained from labels and technical bulletins, and from information supplied by
some formulators of the products (one electrical solvent formulator, one paint
stripper formulator and one formulator of waterproofing products) (see table 18).
8.7.3 Atmospheric monitoring during use of products
Australian data
The NICNAS monitoring project referred to earlier in the section also included
atmospheric and biological monitoring of workplaces using products containing
trichloroethylene. The results are summarised in Table 19.
The results of one personal sample taken by WorkCover in 1984 at a worksite
using natural ventilation during adhesive spraying was made available. The
result was 1.15 ppm. The monitoring duration was not specified.
Overseas data
Atmospheric monitoring data from a US automotive factory using
trichloroethylene containing adhesives in the manufacture of fibrous and non-
fibrous glass headliners were available. The adhesives were used in a cold
lamination process to bond paper to foam core or fabric to cardboard core. After
bonding, the cores were cold rolled, stacked to air dry and cut by a hot wire.
Four area samples for trichloroethylene were collected with a sampling time of 5-
6 hours. Concentrations ranged from 2.7 to 21.4 ppm, with the highest
concentration recorded in the area where adhesive was used to coat paper with
fabric.
44 Priority Existing Chemical Number 8
45
Trichloroethylene
46 Priority Existing Chemical Number 8
8.7.4 Potential for exposure during use of products
Procedures which present a potential for inhalational exposure include transfer of
solutions into containers in preparation for use, including pre-weighing and
mixing or dilution of ingredient, and application of the products. Any agitation
or heating of solutions, such as may occur in adhesive preparation and in dip
cleaning, will increase vapour emission and the potential for exposure. Spraying
may increase inhalational exposure through the release of spray mist into the air.
Drying of film adhesives, which is accomplished by the evaporation of solvent,
and heating processes used for contact bonding and curing, will release solvent
into the air, and increase the potential for exposure.
Accidental spills or splashes during transfer or application of the products present
a potential for dermal exposure when open containers are used to hold products.
Use of brushes to apply products poses a risk of splattering or dripping of the
solution onto skin. Cloths used to apply solutions will present a potential for
dermal exposure if they come into contact with the skin. Mixing and agitation
increase the potential for dermal exposure. In addition, spraying of products
containing trichloroethylene presents a potential for dermal absorption of spray
droplets.
The total exposure during use of trichloroethylene products was estimated from
the monitoring data obtained in the NICNAS project and is shown in Table 20.
Table 20 - Combined inhalational and dermal exposure during use of
trichloroethylene products
Concentration - activity Exposure estimate
(mg/kg/day)
mg/m3
ppm
35% product - spray painting
0.7 3.82 0.3
4.8 26.21 1.67
20% product - rag wiping
3.8 20.75 1.31
4.1 22.38 1.64
90% product - brushing on
2.5 13.65 1.01
8.8 Recycling
The majority of vapour degreaser users recycle trichloroethylene either through
on-site stills or off-site recyclers. From information provided by industry more
than 185 tonnes of trichloroethylene in total is recycled each year at three solvent
recycling plants. Other companies are known to recycle trichloroethylene,
however the amounts recycled are not known. One importer and one major
distributor of trichloroethylene provide recycling services to customers. The
importer supplies drums to customers to hold drummed off waste. The waste is
transported to a recycling plant, and recovered trichloroethylene is bought back
from the recycling company. The other company has its own recycling plant and
47
Trichloroethylene
since 1988 has offered a recycling service to its customers as part of its product
stewardship, which includes dissemination of literature (company manual on
chlorinated solvents; MSDS; and information on exposure standards, relevant
Australian Standards, and a vapour degreasing handbook); analysis of
trichloroethylene samples to determine degree of contamination or identify the
sources of possible problems with the vapour degreaser; and collection of
contaminated trichloroethylene for recycling.
Some vapour degreasers incorporate stills that operate concurrently with the
vapour degreaser, collecting waste oils as the contaminated solvent passes
through. Twenty-one percent of respondents to the NICNAS industry survey
who used trichloroethylene in vapour degreasers indicated that they operated such
stills. Waste oil and trichloroethylene mixtures collected in stills is sent to a
solvent recycler. Regardless of whether vapour degreasers had stills or not, the
majority of respondents sent solvent to recyclers.
8.8.1 Recycling process
Two site visits were made to solvent recycling plants. One plant operates three
distillation units 24 hours a day, 5 days a week and recycles trichloroethylene in
batches in an enclosed system. Contents of drums are pumped into one of three
enclosed distillation stills, and distillate is siphoned into covered, but not fully
enclosed 200 L drums. There was no bunding around the distillation units.
Distillate is checked for specific gravity, acid acceptance value and clarity. The
facility is open roofed providing natural ventilation and ventilation fans run 24
hours a day. Operators wear personal protective equipment consisting of Proban
overalls and hood, glasses, gloves and respirator (when cleaning out stills). Stills
are cleaned out by opening doors at the bottom of the unit and raking out sludge
into containers.
At the other site, the contents of each drum are tested prior to recycling to check
the contents. Four 200 L drums are placed on a pallet in front of one of three
distillation stills and contents sucked out by vacuum pressure through steel pipes.
The distillation units are situated in an open workplace with natural ventilation.
Distillate drains from the still into smaller pipes leading to an enclosed vessel.
There is no bunding around the stills or collection vessel. Contents of the vessel
are analysed and appropriate amounts of stabiliser added. Drums are filled from
the vessel. Two operators are employed at the site. Drum filling takes about ten
minutes a day and operators wear gloves and organic vapour respirators.
8.8.2 Monitoring during recycling
Air monitoring is conducted at one site, however no test results for
trichloroethylene were made available. At another site air monitoring using
Drager tubes for grab samples is done occasionally, but not on a regular basis.
No results were made available.
No overseas monitoring data during recycling was available.
48 Priority Existing Chemical Number 8
8.8.3 Potential sources of exposure
During the recycling process, transfer of contaminated solvent from drums into
distillation units and of distillate into drums is a potential source of exposure
through inhalation of vapour. Cleaning sludge out of stills presents a potential
source of high exposure from inhalation of vapour. Accidental spills and
splashes present a further potential of inhalation and dermal exposure.
Exposure during recycling is likely to be low as it involves a closed process.
49
Trichloroethylene
9. Toxicokinetics and Metabolism
Numerous reviews of trichloroethylene that have been conducted include
toxicokinetics of the chemical. This section is taken mainly from the UK SIAR
and IARC (1995).
9.1 Absorption
Trichloroethylene is a low molecular weight, nonpolar, highly lipophilic
compound. It is absorbed readily and rapidly by inhalation, oral and dermal
routes in humans and animals. Skin absorption of the vapour is negligible
(Lauwerys & Hoet, 1993; Goeptar et al., 1995). In humans, between 28 to 80%
of the trichloroethylene in inspired air is taken up by the lungs (Monster et al.,
1979) with a high initial rate of uptake. Uptake is dependent on the rate of
respiration and the trichloroethylene concentration in the inspired air. Increased
workload increases the uptake of trichloroethylene in humans (Monster et al.,
1979). After inhalation, 40 to 70% of the absorbed dose is metabolised.
In mice, the dermal absorption rate was reported to be 7.82 礸/cm2/min on
application of 0.5 ml of pure trichloroethylene in a closed cell to the clipped
abdominal skin of mice for 15 mins (Tsuruta, 1978). The dermal absorption rate
was also investigated in hairless female guinea pigs immersed in low (0.02 - 0.1
ppm) or high (100 ppm) concentrations of trichloroethylene in aqueous solution
for 70 mins. The uptake rate was found to be approximately 5.4 礸/cm2/min for
both the high and low concentrations (Bogen et al., 1992).
9.2 Distribution
Absorbed trichloroethylene is distributed rapidly throughout the body and, in
humans, the major sites of deposition appear to be body fat and liver (McConnell
et al., 1975). It readily crosses the blood:brain and placental barriers.
Trichloroethylene was detected in the blood of babies at birth after the mothers
had received trichloroethylene anaesthesia (Laham, 1970). The blood:air
partition coefficient in humans is 15 (Monster et al., 1979) and the fat:blood
partition coefficient is about 700 (Steward et al., 1973; Sherwood, 1976), leading
to deposition of trichloroethylene in adipose tissue. Trichloroethylene is stored in
the adipose tissue for about 40 h with detectable levels even after 70 h (Fernandez
et al., 1977).
9.3 Metabolism
Metabolism of trichloroethylene is rapid with common pathways in animals and
humans. Liver is the main site of trichloroethylene metabolism in animals, with
lesser metabolism in extra-hepatic organs such as the kidneys and bronchi.
Several studies have suggested that the metabolites are responsible for
trichloroethylene toxicity (Bruckner et al., 1989; Davidson & Beliles, 1991). The
principal metabolites in humans are trichloroethanol, trichloroethanol glucuronide
and trichloroacetic acid. Other minor metabolites that have been identified in
50 Priority Existing Chemical Number 8
urine are chloral hydrate, chloroform, monochloroacetic acid, dichloroacetic acid,
N-(hydroxyacetyl)-aminoethanol and N-acetyl dichlorovinyl cysteine following
exposure of humans to trichloroethylene. Most of these metabolites have been
identified in experimental animals.
In the major metabolic pathways, trichloroethylene is metabolised by cytochrome
P-450, possibly P4502E1, to a transient epoxide (trichloroethylene oxide) which
may undergo intramolecular rearrangement in two different ways. One pathway
leads to chloral which is hydrolysed to chloral hydrate. A recent study (Green et
al., 1997) has demonstrated that the specific enzyme responsible for
transformation of trichloroethylene to chloral hydrate is cytochrome P4502E1.
Chloral hydrate is converted by alcohol dehydrogenase or chloral hydrate
dehydrogenase to form trichloroethanol and trichloroacetic acid which are
eliminated in the urine. Trichloroethanol is excreted either in the free form or
conjugated with glucuronide (Miller & Guengerich, 1983). The other pathway
leads to the formation of dichloroacetyl chloride which then forms dichloroacetic
acid (Dekant et al., 1984; Green & Prout, 1985) or trichloroethylene oxide may
hydrolyse to form formic acid, glyoxylic acid and carbon dioxide (Dekant et al.,
1984; Green & Prout, 1985). The main metabolic pathways of trichloroethylene
are shown in Figure 4.
Another minor pathway in rats, mice and humans is conjugation of
trichloroethylene in the liver with glutathione by glutathione-S transferase
(Figure 5). Both the 1,2-dichloro and the 2,2-dichloro isomers of dichlorovinyl
glutathione are found in the liver. The dichlorovinyl glutathione is transported to
the kidneys where it is transformed into a cysteine compound, dichlorovinyl
cysteine. Dichlorovinyl cysteine is concentrated in the proximal tubule cells.
This compound is metabolised either by N-acetyl transferase to the mercapturic
acid which is excreted in the urine or by -lyase to form a thiol. The thiol is an
unstable, highly reactive intermediate forming a thioketene which can react with
cellular nucleophiles. Both the isomers 1,2-dichlorovinylcysteine and to a lesser
extent 2,2-dichlorovinylcysteine are substrates for -lyase. The glutathione
metabolites were detected in the urine of volunteers exposed to 40, 80 and 160
ppm for 6 h. These metabolites were excreted slowly with considerable amounts
detected in the urine 48 h after the end of exposure (Bernauer et al., 1996). The
ratio of the two isomers of N-acetyl-S-(dichlorovinyl)-L-cysteine,1,2- and 2,2-
excreted in urine is different in rats and humans (Bernauer et al., 1996). The
proportion of the two isomers are similar in human urine while rats excrete more
of the 2,2- isomer. The 1,2- dichlorovinylcysteine is a better substrate for renal
- lyase than the 2,2- isomer. Bioactivation of the 1,2- isomer may lead to the
formation of chlorothioketene and the 2,2- isomer to the less cytotoxic
thioaldehyde (Commandeur et al., 1991).
51
Trichloroethylene
52 Priority Existing Chemical Number 8
Figure 5- Metabolism of trichlorethylene via glutathione conjugation
(From: (United Kingdom, 1996))
Trichloroethylene
glutathione-S-transferase
S-1,2-dichlorovinyl glutathione
S-1,2-dichlorovinyl cysteine
N-acetyl transferase
-lyase (activation)
(deactivation) Acylase
N-acetyl dichlorovinyl Chlorothioketene
cysteine Thioacyl chloride
mercapturates
53
Trichloroethylene
Trichloroethylene metabolism has been shown to be saturable at lower doses in
rats than in mice. In rats, metabolic saturation occurs after administration of 200-
500 mg/kg trichloroethylene orally while in mice saturation is only seen at 2000
mg/kg of oral trichloroethylene or at inhalation doses of 2000 ppm (Stott et al.,
1982; Buben & O'Flaherty, 1985; Prout et al., 1985). After administration of
2000 mg/kg, 78% of the dose in rats was exhaled as unchanged trichloroethylene
but only 14% in mice (Prout et al., 1985). There is no evidence that the
metabolic pathway is saturable in humans, however, the exposure levels used in
human studies were considerably lower (maximum 380 ppm) than those used in
animal studies. Saturation of metabolism in humans has been predicted at
relatively high concentrations (2000 ppm) by mathematical models (Feingold &
Holaday, 1977).
The rate of biotransformation of trichloroethylene in mice is much higher than in
rats and blood levels of trichloroethanol and trichloroacetic acid were 4 and 6
times higher than those in rats (Fisher et al., 1991).
A number of commonly used drugs or chemicals are able to modify the
metabolism of trichloroethylene. Phenobarbitone is an inducer of some forms of
cytochrome P-450 and has been shown to stimulate the metabolism and binding
of trichloroethylene. Ethanol has a dual effect on the metabolism of
trichloroethylene in rats. At low doses it inhibits the metabolism of
trichloroethylene giving rise to high blood levels (Jakobson et al., 1986). High
doses of ethanol, however, enhance the metabolism of trichloroethylene to
trichloroacetic acid (Kaneko et al., 1994). Other substances competitively
inhibiting the metabolism of trichloroethylene are 1,1,1-trichloroethane
(Savolainen, 1981), tetrachloroethylene, isopropanol, pyrazole and
tetraethylthiuram disulfide (Jakobson et al., 1986).
9.4 Excretion
Trichloroethylene, following oral or inhalation exposure, is mainly excreted in
the urine as trichloroethanol and trichloroacetic acid in animals and humans. In
humans, about 48 to 85% of inhaled trichloroethylene is excreted as metabolites
by urinary excretion and approximately 8% in the faeces. About 10 to 28% of
trichloroethylene is exhaled unchanged in the breath. Small amounts of
trichloroethanol are also excreted in the breath while trichloroacetic acid has been
identified in bile.
The elimination kinetics of trichloroethanol and trichloroacetic acid differ in
humans. Studies in volunteers have shown that during inhalation exposure to
trichloroethylene, trichloroethanol levels in blood rise steadily with no plateau
being reached within a 6 h exposure period. Trichloroethanol is excreted rapidly
once exposure to trichloroethylene stops and most of the trichloroethanol is
excreted in the urine within 24 h. Some accumulation of trichloroethanol occurs
with repeated exposure but elimination is rapid once exposure ceases. The half-
life of trichloroethanol in human blood is approximately 10-12 h (Ertle et al.,
1972; Muller et al., 1972; Muller et al., 1974).
54 Priority Existing Chemical Number 8
Trichloroacetic acid is tightly and extensively bound to plasma proteins in
humans and has a half-life in blood of 70-100 h. Repeated exposure causes
trichloroacetic acid to accumulate in blood with the metabolite being excreted
very slowly once exposure has ceased.
The levels of trichloroethylene and its metabolites trichloroacetic acid and
trichloroethanol were measured in blood and urine of a worker following acute
poisoning, to investigate the kinetics of trichloroethylene (Yoshida et al, 1996).
Accidental ingestion of trichloroethylene had occurred as a result of a fall into a
reservoir bath during maintenance. The worker had been in the bath for 3 to 5
mins and was in deep coma with chemical burns and pneumonia on admission.
Trichloroethylene was detected in urine for the first two days (43.4 mg/day on the
first day and 13.3 mg/day on the second day) suggesting that it may be directly
excreted in urine prior to metabolism. Trichloroethylene levels in blood fell
rapidly and biphasically. Trichloroethanol levels however, increased for up to 4
days after ingestion and then decreased biphasically with a half life of 53 h in the
rapid phase and 269 h in the slow phase. This elimination pattern and the half-
life of trichloroethanol observed in blood, differed from previous studies in
volunteers following inhalation exposure (Nomiyama, 1971; Monster et al.,
1976). In these studies, inhalation of trichloroethylene resulted in maximum
trichloroethanol concentration in blood immediately after inhalation followed by
an exponential decrease with a half-life of 10 to 15 h. The difference in the study
by Yoshida et al (1996) is attributed by the authors to delayed formation of
trichloroethanol from trichloroethylene stored in adipose tissue.
Yoshida et al (1996) also observed that trichloroethanol and trichloroacetic acid
were excreted in urine bi-phasically with the amount of trichloroethanol excreted
being twice that of trichloroacetic acid for the first two days. Subsequently the
ratio of trichloroethanol to trichloroacetic acid excretion became approximately
1:2. The excretion of trichloroacetic acid is slow in humans because of protein
binding.
Some studies have reported sex differences in the urinary excretion of
trichloroethylene metabolites. The urinary levels of trichloro compounds and
trichloroethanol were significantly higher in men than in women workers exposed
to trichloroethylene while the urinary levels of trichloroacetic acid did not differ
between the two sexes (Inoue et al., 1989). However, one study reported that
urinary trichloroacetic acid levels were greater in women than in men within 24 h
of exposure (Nomiyama & Nomiyama, 1971).
Physiologically based pharmacokinetic (PBPK) models predict that humans have
a lower rate of metabolism than mice but higher than rats (Allen & Fisher, 1993).
A PBPK model used to predict the differences in body weight, fat content and sex
found that women and obese people would be expected to have lower
concentrations but longer residence times of blood trichloroethylene because of
their higher fat content.
55
Trichloroethylene
10. Effects on Experimental
Animals and in vitro Test
Systems
Numerous reviews of the health effects of trichloroethylene have been conducted.
No additional toxicity data was provided by applicants. For the genotoxicity and
carcinogenicity endpoints a different approach was taken acknowledging the
contentious interpretation of many of the available studies. For these endpoints
individual studies which were in contention were reviewed together with views of
other authorities.
10.1 Acute toxicity
Trichloroethylene has low acute toxicity by all routes of exposure. The LC50 and
LD50 values in various animals are shown in Table 21. The lowest LC50 in rats is
4800 ppm for 4 h and 5857ppm in mice following 6 h exposure.
Table 21- LC50 and LD50 values for trichloroethylene
Route Species LC50\LD50 Reference
Inhalation rat 26000 ppm (1 h) (Vernot et al., 1977)
Inhalation rat 4800 ppm (4 h) (Adams et al., 1951)
Inhalation rat 12000 ppm (4 h) (Siegal et al., 1971)
Inhalation rat 5918 ppm (6 h) (Bonnet et al., 1980)
Inhalation mouse 8450 ppm (4 h) (Friberg et al., 1953)
Inhalation mouse 5857 ppm (6 h) (Gradiski et al., 1978)
Oral rat 5400-7200 mg/kg (in water) (Smyth et al., 1969)
Oral mouse 2900 mg/kg b.w (in water) (Aviado et al., 1976)
Oral rat 5600 mg/kg b.w (in corn oil) (National Cancer Institute
(NCI), 1976)
Oral mouse 10000 mg/kg b.w. (in corn oil) (National Cancer Institute
(NCI), 1976)
Dermal rabbits 29000 mg/kg b.w. (occluded) (Smyth et al., 1962)
(Smyth et al., 1969)
Dermal rabbits > 20000 mg/kg b.w. (semi- (Kinkead & Wolfe, 1980)
occlusive)
The major acute toxic effects in animals are consistent with the findings in
humans. The main signs of acute toxicity in rats and mice were those of CNS
depression such as stupor and poor coordination and respiratory failure. Irritation
of the eyes and respiratory tract were also reported. Effects on the liver, indicated
by transient increases in serum ALT and AST, were reported following oral
administration.
56 Priority Existing Chemical Number 8
Species specific toxicity has been noted since pulmonary toxicity has been
observed in mice but not in rats. A dose dependent increase in the number of
vacuolated Clara cells was seen in mice following single inhalation exposures
between 20 and 2000 ppm of trichloroethylene for 6 h. At higher dose levels
pyknosis and focal loss of bronchiolar epithelium were observed. Other cell
types were not affected (Odum et al., 1992).
10.2 Irritation and corrosivity
10.2.1 Skin
Several studies in animals, guinea pigs and rabbits, using occluded and non
occluded dressing indicate that trichloroethylene is irritating to the skin. (Smyth
et al., 1969; Duprat et al., 1976; Wahlberg, 1984; Anderson et al., 1986).
10.2.2 Eye
Animal studies provide limited information on eye irritation. No animal tests
complying with standard protocols for detecting eye effects of trichloroethylene
have been reported. Two studies reported corneal abrasions and necrosis of the
cornea following instillation of trichloroethylene into rabbit eyes (Smyth et al.,
1969; Duprat et al., 1976).
10.3 Sensitisation
No skin or respiratory sensitisation studies have been conducted in animals.
10.4 Repeated dose toxicity
Many repeated dose studies (inhalation and oral) have been conducted in a range
of species. The results of the major studies are summarised in Table 22.
The main toxic effects following repeated exposure of animals by the inhalation
and oral route are on the liver and kidneys. Adverse effects were also seen on
hearing, the lungs and the nervous system following inhalation exposure. Studies
reported animals surviving repeated inhalation exposure to between 1000 and
7000 ppm for 90 days.
No Observed Adverse Effect Levels (NOAEL) have been identified for effects of
trichloroethylene on the various systems in animals. The kidneys appear to be the
most sensitive organs in animals. Kidney effects were observed in male rats
following inhalation, and in both rats and mice in both sexes after oral exposure.
In a 2-year inhalation study using rats, meganucleocytosis of the renal tubules
was reported at 300 ppm (LOAEL) in male rats with no effects being seen at 100
ppm (0.55mg/L) (NOAEL) (Maltoni et al., 1988). Meganucleocytosis was also
reported in an oral study at 250 mg/kg bw/day in rats with a NOAEL of 50 mg/kg
bw/day (Maltoni et al., 1986). In mice, renal cytomegaly was observed in both
sexes following oral administration of 1000 mg/kg bw/day for 2 years (US
National Toxicology Program NTP, 1990)
57
Trichloroethylene
Trichloroethylene-induced liver effects have been reported in mice and rats, with
mice being more sensitive than rats. Increased liver weight, AST and ALT levels
and cytochrome P-450 activities have been noted. At very high doses
centrilobular cell enlargement and necrosis have been observed following
inhalation and oral exposure. Peroxisome proliferation has been observed in the
mouse liver but not in rats. NOAELs identified for liver effects are 200 ppm
(inhalation) in both rats and rabbits (Adams et al., 1951) and 375 mg/kg/day and
500 mg/kg/day (oral) for mice and rats respectively.
Evidence of neurotoxicity, such as increased activity and ototoxicity was also
reported in animals. Simultaneous exposure to two solvents, styrene and
trichloroethylene did not produce a greater hearing loss than from exposure to
either solvent alone (Rebert et al., 1993).
Pulmonary toxicity was reported in mice following repeated inhalation exposure
to 450 ppm trichloroethylene for two weeks. Vacuolation of Clara cells was
observed following exposure on the first day, however the lungs returned to
normal after 4 or 5 consecutive exposures. The Clara cell lesions were observed
again after a 2-day break from exposure to trichloroethylene. It is likely that
restoration of the non-ciliated cells occurs (Odum et al, 1992).
58 Priority Existing Chemical Number 8
59
Trichloroethylene
60 Priority Existing Chemical Number 8
61
Trichloroethylene
10.5 Immunotoxicity
Immunotoxic effects of trichloroethylene have been assessed in mice.
Impairment of the cell mediated immune response to sheep erythrocytes was
reported in mice given doses of 24 or 240 mg/kg by gavage daily for 14 days. No
effects were observed on the humoral immune response (Tucker et al., 1982).
Mice exposed to trichloroethylene in drinking water at doses of 18 - 800 mg/kg
for 6 months have exhibited depressed cell and humoral mediated immune
response. In mice exposed by gavage to 24 or 240 mg/kg for 14 days, a
significant inhibition of cell mediated immunity was noted in males (Sanders et
al., 1982).
10.6 Reproductive toxicity
10.6.1 Fertility
Short-term inhalation exposure of mice resulted in sperm abnormalities with no
effects being seen in rats. Sperm morphology was affected in mice at 2000 ppm
in short-term studies with a NOAEL of 200 ppm (Land et al., 1981). These
findings are not consistent with the results of long-term oral exposure. Long term
oral exposure studies indicate that effects on fertility (reduced sperm motility) are
seen in animals only at doses that produce general toxicity. The LOAEL for
fertility effects was 750 mg/kg/day in mice and 150 mg/kg/day in rats while the
NOAEL for fertility effects was 350 mg/kg/day in mice and 75 mg/kg/day in rats
(US National Toxicology Program, 1990).
Table 23 summarises the studies carried out to assess effects on fertility and
developmental toxicity of trichloroethylene.
10.6.2 Developmental toxicity
Several developmental studies have been conducted according to conventional
test guidelines. No clear evidence of developmental toxicity was reported in any
of these studies. The UK SIAR has described three studies from the same
laboratory that suggest maternal exposure to trichloroethylene in drinking water
in rats at doses ranging from 28-110 mg/kg/day produce increased locomotor
activity, a decrease in the 2-deoxyglucose uptake by the brain and a decrease in
the number of myelinated fibres in one region of the brain (Taylor et al., 1985;
Noland-Gerbac et al., 1986; Isaacson & Taylor, 1989). The significance of these
findings is not clear but they are of concern as the findings indicate a potential for
trichloroethylene to induce developmental neurotoxicity.
62 Priority Existing Chemical Number 8
63
Trichloroethylene
64 Priority Existing Chemical Number 8
65
Trichloroethylene
10.7 Genotoxicity
Trichloroethylene has been investigated in a number of in vitro and in vivo test
systems. The genotoxicity of trichloroethylene has been reviewed extensively by
IARC (1995); Fahrig et al (1995) and by the UK in the UK SIAR (1996). The
description below is based mainly on the UK SIAR. Data on the genotoxic
effects of trichloroethylene metabolites are from IARC (1995). Three published
studies (Fahrig, 1977 ; Duprat & Gradiski, 1980; Kligerman et al., 1994 ) have
been assessed in this report as the interpretation of the results of these three
studies differed in the above reviews. Two published articles describing tests
conducted in mice and indicative of point mutation were reviewed during this
assessment: a mouse spot test and mouse pink-eyed unstable mutation.
10.7.1 In vitro tests
Genotoxicity studies for trichloroethylene are summarised in Table 24. Briefly
reported studies are not included in the table.
Bacterial tests
Trichloroethylene used industrially is stabilised to prevent auto-oxidation.
Epichlorohydrin was one of the stabilisers used but its use has been discontinued
as it was found to be carcinogenic. Mixed amines are now used as stabilisers.
Early mutagenicity studies using trichloroethylene stabilised by epichlorohydrin
and 1,2-epoxybutane reported positive results in S. typhimurium assays either
with or without an exogenous metabolising system. These epoxide stabilisers in
vapour form, when tested alone, in S. typhimurium strains TA1535 and TA100
were also found to be mutagenic in low concentrations (McGregor et al., 1989).
It is therefore difficult to interpret genotoxicity studies with trichloroethylene
containing these stabilisers.
Epoxide-free trichloroethylene vapour in three studies did not induce mutations in
various strains of S. typhimurium in the presence or absence of an exogenous
metabolising system. Three studies reported positive results in the presence of a
metabolising system. In a further three briefly reported studies trichloroethylene
produced positive responses according to the authors (Riccio et al., 1983; Milman
et al., 1988; Warner et al., 1988). The study by Crebelli et al (1982) reported a
small dose-related statistically significant increase in the number of revertants per
plate that was reproducible in nine experiments. There was no increase in the
number of revertants in the absence of metabolic activation.
Trichloroethylene liquid (purity >99.9%) was not mutagenic in various strains of
S. typhimurium in the presence or absence of an exogenous metabolising system
with toxicity seen at the highest concentration tested (Henschler et al., 1977;
Mortelmans et al., 1986).
Analytical grade trichloroethylene induced arg+ reverse mutations but not
forward mutations or gal+ or nad+ reversions in E. coli (Greim et al., 1975).
66 Priority Existing Chemical Number 8
Fungal tests
Epoxide-free trichloroethylene was tested in Schizosaccharomyces pombe and
various strains of Saccharomyces cerevisiae either in the presence or absence of
an exogenous metabolising system. In most of these assays, trichloroethylene
tested positive. Of the positive studies, the increase in colonies of
Saccharomyces cerevisiae strain D61.M in one study was thought to be due to
"respiratory deficiency" (Whittaker et al., 1990) in the UK SIAR, and a dose-
related increase in the number of colonies seen with strain D61.M in the second
(Koch et al., 1988) was considered by the authors to indicate aneuploidy. In two
other studies positive results were only seen at concentrations toxic to the cells
(Shahin & Von Borstel, 1977; Callen et al., 1980). No information on the
presence or absence of stabilisers was provided in any of the studies.
Mammalian cells
Three mouse lymphoma L5178Y/TK+/- mutation tests reported positive results in
the presence of metabolic activation provided by rat liver S9 fraction. Of these,
two (Caspary et al., 1988; Myhr & Caspary, 1991) are reported to be further
reports of the experiment described by NTP (1988). Another positive experiment
was only available as an abstract (Rudd et al., 1983). The assays were negative in
the absence of S9.
Trichloroethylene tested negative in two in vitro chromosomal aberration tests
and in a sister chromatid exchange (SCE) assay whilst the results were equivocal
in another SCE assay. Trichloroethylene did not induce unscheduled DNA
synthesis (UDS) in rat hepatocytes as assessed by autoradiography. Assays using
scintillation counting techniques have reported positive results (Table 24). One
SCE test was considered equivocal as the frequencies in the exposed cells were
within the background range of negative controls.
10.7.2 In vivo tests
In vivo assays conducted to assess genotoxicity of trichloroethylene are
summarised in Table 25.
Host-mediated assays
A host-mediated assay using mice (National Institute for Occupational Safety and
Health (NIOSH), 1980) did not provide any conclusive evidence of the mutagenic
activity of trichloroethylene (purity >99.9%) in S. typhimurium strain TA98, as
an appropriate response was not observed in the positive control group.
A host-mediated assay was conducted by Bronzetti et al (1978) and showed an
increased number of mutants in cultures from the liver and kidneys but not from
the lungs. Groups of 3 to 4 mice were treated with an oral dose of 400 mg/kg of
trichloroethylene followed by instillation of yeast cultures. Some groups
received additional oral exposure to 150 mg/kg/day prior to instillation. The
animals received 22 administrations of trichloroethylene over a 4 week period.
The purity of trichloroethylene was not specified in either of these studies.
67
Trichloroethylene
Micronucleus tests
Four micronucleus tests were reported in the U.K. SIAR. Of these, one was
reported to be negative (Shelby et al., 1993) and a positive study (Sbrana et al.,
1985) was only reported to be available as an abstract. The other two studies
(Duprat & Gradiski, 1980; Kligerman et al., 1994) have been reviewed as part of
this assessment.
Kligerman et al (1994) exposed rats and mice to a single 6 h exposure by
inhalation of 0, 5, 50, 500 or 5000 ppm of reagent grade trichloroethylene. The
only significant effect seen was a dose-related increase in micronuclei in rat bone
marrow polychromatic erythrocytes (PCEs). At 5000 ppm the increase was
approximately four-fold and was reproducible. Animals in the 5000 ppm group
displayed signs of toxicity such as tremors and paralysis. Evidence of
cytotoxicity was also observed at this level with a significant reduction in the
percentage of PCEs in bone marrow. The authors state that their findings of
micronucleus induction without the presence of chromosomal aberrations and the
large size of the micronuclei may be indicative of spindle effects such as
aneuploidy. No statistically significant cytogenetic changes were seen in mice
similarly exposed. Groups of rats were also exposed for 6 h/day for 4 days to 0,
5, 50 or 500 ppm of trichloroethylene. The number of micronuclei in bone
marrow PCEs was comparable to the 1-day study. However, the number of
micronuclei in the concurrent control in the 4-day study was unusually high and
hence the results were not statistically different from the control. There was no
increase in micronucleated peripheral blood leukocytes (PBL) with single or
repeated exposures.
A dose-related increase in the number of micronucleated PCEs in mice was also
reported by Duprat and Gradiski (1980) with analytical grade trichloroethylene.
Groups of 10 CD1 strain mice were treated orally with trichloroethylene
dispersed in a vehicle at doses of 3000, 2250, 1500, 1125, 750 and 375 mg/kg.
The study also included an untreated control group (20 animals), a vehicle group
(0.5 ml/20 gms of a 10% gum arabic solution) and a positive control group (100
mg/kg of cyclophosphamide). The mice were treated with two single doses
separated by 24 h and were killed 16 h later and bone marrow smears examined.
However the significance of this study is limited by the uncertainties of the
scoring method used (micronuclei, including microbodies appearing to be of
nuclear origin) and the unusually high frequency of micronucleated PCEs in the
control group. The micronucleus frequency in the untreated and vehicle control
groups also differed significantly from each other.
Chromosomal aberrations and sister chromatid exchange
According to the UK SIAR, trichloroethylene did not induce chromosomal
aberrations or sister chromatid exchange in 2 assays each.
Tests for UDS, DNA binding and damage
Induction of unscheduled DNA synthesis was also reported to be negative in two
assays. The SIAR also reported 6 tests investigating DNA interaction in rats and
mice. Of these, 3 were positive and 3 negative.
68 Priority Existing Chemical Number 8
DNA interactions
Trichloroethylene induced DNA single strand breaks in two studies. DNA
binding could not be demonstrated in vivo in the tissues of mice in one study or in
the liver of rats in another study. However, a low level of interaction with DNA
of rat and mouse liver, kidney, lungs and stomach was reported by Mazullo et al
(1992).
Germ cell assays
Trichloroethylene did not increase the frequency of micronuclei in spermatids in
mice following inhalation exposure nor induce dominant lethal mutations in mice
or in rats.
Mouse spot test
In a mouse spot test the number of offspring with spots presumed to result from
somatic mutation were 2 of 145 at 140 mg/kg and 2 of 51 at 350 mg/kg after a
single intra-peritoneal dose of trichloroethylene (99.5%). In the pooled negative
control group 1 of 794 had genetically relevant spots (Fahrig, 1977). The
survival of offspring in the treated groups was low compared with the control.
The results are considered to be equivocal because of the unusually low
frequency of spots in the control group.
Mouse pink-eyed unstable mutation
Highest purity grade trichloroethylene in corn oil was administered intra-
peritoneally to mice homozygous for pink eyed dilution (C57BL/6J pun/pun ) at a
dose of 200 mg/kg, 10.5 days postconception. The mice were observed for the
frequency of spontaneous and chemical-induced spots. A positive response was
noted. Spontaneous frequency varied between 4 and 11 %. Control animals
injected with corn oil alone had a spotting frequency of 3.9% while
trichloroethylene caused 32% spotting. Trichloroethylene caused sedation in the
female adult mice because of its anaesthetic effect. The litter size was also
reduced in the trichloroethylene treated group. The pun mutation causes a
dilution of the pigment in coat colour and eye colour and reversion of the pun
mutation is scorable as black spots on the dilute coat (Schiestl et al., 1997). A
positive response was noted in this preliminary study.
69
Trichloroethylene
70 Priority Existing Chemical Number 8
71
Trichloroethylene
72 Priority Existing Chemical Number 8
73
Trichloroethylene
74 Priority Existing Chemical Number 8
75
Trichloroethylene
10.7.3 Trichloroethylene metabolites
Trichloroethylene metabolites may be responsible for cytotoxicity in the liver and
extrahepatic organs and therefore the mutagenic effects of these metabolites need to
be considered. Data on trichloroethylene metabolites in this report were obtained
from IARC (1995) and the original studies and articles have not been sighted. Data
reported for dichlorovinyl cysteine is a summary of data reported in the
Documentation for the MAK evaluation of trichloroethylene.
Chloral hydrate
Chloral hydrate is mutagenic only in S. typhimurium strains TA100 (Haworth et al.,
1983) and TA 104 (Ni et al., 1994). It did not induce reverse mutations in S.
cerevisiae. However, induction of gene conversion in the absence of metabolic
activation was observed (Bronzetti et al., 1984). Chloral hydrate induced somatic
mutations in Drosophila melanogaster in a wing-spot test (Zordan et al., 1994).
Chloral hydrate did not induce single strand breaks in rat hepatocytes in vitro.
Frequency of micronuclei was increased in Chinese hamster cell lines. In mammalian
cell cultures chloral hydrate induced genetic effects such as chromosomal aberrations
(Degrassi & Tanzarella, 1988; Furnus & et al., 1990), aneuploidy (Furnus & et al.,
1990; Vagnarelli et al., 1990; Natarajan, 1993; Sbrana et al., 1993) and micronuclei
(Degrassi & Tanzarella, 1988; Migliore & Nieri, 1991; Bonatti & et al., 1992; Lynch
& Parry, 1993).
Chloral hydrate did not induce chromosomal aberrations in vivo in rat (Leuschner &
Leuschner, 1991) or mouse (Xu & Adler, 1990) bone marrow cells or in mouse
spermatocytes (Russo & Levis, 1992a.). Conflicting results were observed in
micronucleus tests using mouse bone marrow cells. Weakly positive results were
obtained in some experiments (Gudi & et al., 1992; Russo & Levis, 1992a.; Russo &
Levis, 1992b.; Leopardi & et al., 1993) while negative results were reported by others
(Bruce & Heddle, 1979; Adler & et al., 1991; Leuschner & Leuschner, 1991).
Chloral hydrate induced aneuploidies in mouse spermatocytes (Russo et al., 1984;
Liang & Pacchierotti, 1988; Miller & Adler, 1992) but not in mouse oocytes (Mailhes
& et al., 1988.; Mailhes et al., 1993).
Trichloroacetic acid
Trichloroacetic acid is not mutagenic to S. typhimurium strains in the presence or
absence of metabolic activation (Shirasu et al., 1976; Waskell, 1978; Nestmann et al.,
1980; Rapson et al., 1980, Moriya, 1983; Moriya et al., 1983; DeMarini et al., 1994).
It did not induce DNA strand breaks in mammalian cells in vitro. DNA strand breaks
were not observed in the livers of rats or mice (Chang et al., 1992). Chromosomal
aberrations were not induced in human lymphocytes in vitro (Mackay et al., 1995).
Trichloroacetic acid induced micronuclei and chromosomal aberrations in bone
marrow cells and abnormal sperm morphology in Swiss mice in vivo (Bhunya &
Behera, 1987). However, no micronucleus induction was observed in another study
when a 10-fold higher dose was used in a different strain of mouse (Mackay et al.,
1995).
76 Priority Existing Chemical Number 8
Dichloroacetic acid
Dichloroacetic acid was mutagenic to S. typhimurium TA98 (Herbert et al., 1980) and
TA100 (DeMarini et al., 1994) while other studies have reported negative results with
TA1535, TA1537, TA1538 and TA100 (Herbert et al., 1980). Dichloroacetic acid
did not induce single strand breaks in mammalian cells in vitro in the absence of an
activating system (Chang et al., 1992). The in vivo results were conflicting with
DNA strand breaks observed in mouse and rat hepatic cells pretreated with
dichloroacetate but no effects after a single dose of 500 mg/kg and after repeated
dosing (Nelson & Bull, 1988). No effects on DNA were observed in mouse
hepatocytes, splenocytes, epithelial cells from stomach and duodenum and in rat
hepatic cells following repeated dosing (Chang et al., 1992).
Dichlorovinyl cysteine
Dichlorovinyl cysteine was mutagenic in S. typhimurium in the presence of rat kidney
S9 (Dekant et al., 1986). The 1,2-isomer and its mercapturic acid were more potent
mutagens than 2,2-dichlorovinyl cysteine and its mercapturic acid (Commandeur et
al., 1991). The mutagenic activity of 1,2-dichlorovinyl cysteine was inhibited by
inhibition of -lyase activity (Vamvakas et al., 1988a). 1,2-dichlorovinyl cysteine
induced an increase in DNA repair in cultured kidney cells (Vamvakas et al., 1989b).
10.8 Carcinogenicity
A number of long term animal studies (in hamsters and various strains of rats and
mice) by the oral and inhalation routes have demonstrated that trichloroethylene is
carcinogenic in rats and mice. Details of the carcinogenicity studies in animals are
shown in Table 26.
77
Trichloroethylene
78 Priority Existing Chemical Number 8
79
Trichloroethylene
80 Priority Existing Chemical Number 8
10.8.1 Hepatic tumours
In the mouse, trichloroethylene induced hepatocellular tumours by oral and inhalation
routes in Swiss and B6C3F1 strains (Maltoni et al., 1986) but not in NMRI or Ha:ICR
strains (Henschler et al., 1984). The tumours were observed at oral doses of 1000
mg/kg and above and by inhalation at 600 ppm but not at 300 ppm (Maltoni et al.,
1986). HA:ICR strains were also tested dermally for tumour initiating properties with
negative results.
Trichloroethylene has been shown to induce peroxisome proliferation in mice but not
in rats (Elcombe, 1985 and Goldsworthy, 1987). Hepatic peroxisome proliferation
has therefore been proposed as the primary mechanism for eliciting hepatocellular
tumours. Peroxisomal proliferation has also been proposed as a mechanism for
hepatic tumours for several other chemicals eg tetrachloroethylene (Ashby et al.,
1994) and HCFC-123 (National Industrial Chemicals Notification and Assessment
Scheme (NICNAS), 1996)
There is growing evidence, as shown below, indicating that liver tumours in mice are
due to the major metabolite, trichloroacetic acid. Evidence indicates that:
? Oral administration of trichloroacetic acid produced similar levels of peroxisome
proliferation in mice and rats (Elcombe, 1985 ; Goldsworthy & Popp, 1987;
Watson et al., 1993).
? The inability of trichloroethylene to induce peroxisomal proliferation in rats is
believed to be related to saturation of metabolism of trichloroethylene to
trichloroacetic acid. Saturation of metabolism occurs at much lower levels in rats
than in mice (Prout et al., 1985). Hence greater amounts of the metabolites
trichloroacetic acid and dichloroacetic acid are produced in mice as compared to
rats. It has been postulated that a threshold exists for peroxisome proliferation
and mice produce sufficient trichloroacetic acid to exceed this threshold but rats
do not. Oxidative stress associated with peroxisome proliferation in mice may be
responsible for development of hepatic tumours (Reddy & Rao, 1992).
Trichloroethylene metabolites, trichloroacetic acid and dichloroacetic acid, have been
demonstrated to be tumourigenic in certain strains of mice (Herren-Freund et al.,
1987; Bull et al., 1990). Limited data suggest that mice are more sensitive to the
effects of dichloroacetic acid than rats.
Peroxisomal proliferation is considered to be species specific (ECETOC, 1992;
Purchase et al., 1994) with humans being relatively insensitive. Human hepatocytes
metabolise trichloroethylene to trichloroacetic acid at a slower rate than rats and a
much slower rate than mice (Elcombe, 1985; Knadle et al., 1990). In vitro studies
have shown that trichloroacetic acid does not induce peroxisome proliferation in
human hepatocytes (Elcombe, 1985).
The other potential mechanism for carcinogenicity of trichloroethylene investigated
in rats and mice include effects on hepatic DNA synthesis and mitosis. There may be
some species differences in DNA synthesis and cell division between rats and mice
(Stott et al., 1982; Elcombe, 1985; Mirsalis et al., 1985; Dees & Travis, 1993). The
extent to which DNA synthesis is increased in rats given trichloroethylene is
conflicting. There are also some indications of species differences in the extent to
which mice and rats undergo DNA synthesis in response to trichloroacetic acid
(Sanchez & Bull, 1990; Watson et al., 1993).
81
Trichloroethylene
The effects of the other metabolites of trichloroethylene have been investigated in an
attempt to clarify their role in carcinogenicity. There is some evidence to indicate
that dichloroacetic acid may have a different mechanism of action compared to
trichloroacetic acid. Dichloroacetic acid induces peroxisome proliferation in mice but
at doses much higher than those inducing liver tumours (DeAngelo et al., 1989;
Daniel et al., 1992). Administration of dichloroacetic acid in drinking water to male
B6C3F1 mice for 52 weeks produced severe cytomegaly and glycogen accumulation
throughout the liver (Bull et al., 1990). In rats hepatocyte enlargement was less
marked with localised glycogen accumulation.
Conflicting data are available on the levels of dichloroacetic acid produced following
trichloroethylene administration. One study has shown that mice metabolise
trichloroethylene to dichloroacetic acid to a greater extent than rats (Larson & Bull,
1992) while others have shown that mice and rats produce similar amounts of
dichloroacetic acid (Dekant et al., 1984); (Green & Prout, 1985).
The effects of dichloroacetic acid on human liver are not known. Formation of
dichloroacetic acid is probably a minor pathway in humans as in rats.
Chloral hydrate and monochloroacetic acid, other metabolites of trichloroethylene,
have not been adequately investigated for their liver effects in experimental animals.
There are limited data in animals regarding liver carcinogenicity of chloral hydrate.
Chloral hydrate administered to B6C3F1 mice (1g/L, 166 mg/kg) for 104 weeks
resulted in hepatocellular carcinomas in 2/5 animals killed at 60 weeks. No
carcinomas were detected in the control group. Of those killed at 104 weeks, 11/24
treated and 2/20 controls had hepatocellular carcinomas. Hepatocellular adenomas
were seen in 7/24 treated mice and 3/20 controls. Non-neoplastic changes were also
reported in the animals (Daniel et al., 1992).
The role of these metabolites in the tumourigenic effect of trichloroethylene is unclear
based on the limited data available.
10.8.2 Lung tumours
Pulmonary toxicity specific to the Clara cells was observed in mice given single or
repeated doses of trichloroethylene by the inhalation or intra-peritoneal route. No
effects were seen in rats (Forkert et al., 1985; Forkert & Birch, 1989; Villaschi et al.,
1991; Odum et al., 1992). Lung tumours were seen in some strains only, with female
Ha:ICR mice, male Swiss mice and female B6C3F1 mice of both sexes being
affected, while no tumours were seen in female Swiss mice, NMRI mice of either sex
or in hamsters. Lung tumours occurred at exposure levels of 150 ppm and above of
trichloroethylene (Fukuda et al., 1983).
In vitro studies on Clara cells from mice have shown that the major metabolite
formed in these cells is chloral hydrate (Odum et al., 1992). The Clara cells are
unable to metabolise chloral hydrate further leading to accumulation of the metabolite
within these cells. Inhalation exposure of female CD-1 mice to 100 ppm of chloral
hydrate produces lung toxicity.
It is thought that chloral hydrate is responsible for the pulmonary toxicity though the
exact mechanism is not yet known. Regeneration and repair of the damaged Clara
cells occurs (Villaschi et al., 1991). Lung tumours may result from repeated damage
and regeneration. Chloral hydrate has also been shown to be mutagenic and other
mechanisms may also be involved.
82 Priority Existing Chemical Number 8
Inhalation exposure to a single dose of 100 ppm trichloroethanol for 6 h or 500 ppm
for 2 h or 200 or 500 mg/kg trichloroacetic acid administered intraperitoneally failed
to produce any lung toxicity. Oral administration of trichloroethylene or chloral
hydrate does not result in lung tumours as the compounds would undergo
metabolism before reaching the Clara cells. Inhalation exposure results in direct
contact of Clara cells with trichloroethylene with metabolism of the chemical to
chloral hydrate by the cytochrome P-450 in the cells.
Changes in the Clara cells of mice exposed to chloral hydrate by inhalation were
more severe, with alveolar necrosis and epithelial desquamation. In addition, in
trichloroethanol treated mice only few animals were affected at 100 or 500 ppm with
minimal lesions and no vacuolation. The metabolite chloral hydrate has been
implicated in lung toxicity as Clara cells are able to metabolise trichloroethylene to
chloral hydrate but have a low ability to metabolise chloral hydrate to
trichloroethanol. Cytochrome P-450 activities were found to be reduced in a dose
dependent manner in Clara cells from lungs of trichloroethylene exposed mice. The
activities of glutathione S-transferases were not affected. The lowest observable
adverse effect level was 20 ppm for 6 h.
Metabolism of trichloroethylene has also been investigated in isolated rat and guinea
pig lungs (Dalbey & Bingham, 1978). Trichloroethanol and trichloroacetic acid were
detected in the perfusate in both species but not chloral hydrate. This suggests that
rat and guinea pig lungs are able to further metabolise the chloral hydrate formed to
trichloroethanol and trichloroacetic acid (United Kingdom, 1996)
Human lung tissue is capable of xenobiotic metabolism (Benford & Bridges, 1986)
but very few studies have been conducted using human lung tissue. The Clara cells
found in human lung tissue are few in number and lack smooth endoplasmic
reticulum suggesting less cytochrome P450 activity. The Clara cells in humans are
localised in specific regions of the airways. It is not clear which cells in human lungs
are capable of metabolising chemicals and the extent to which trichloroethylene is
metabolised in human lung.
A recent study has investigated the metabolic processes for trichloroethylene in rat
and human lungs. Green et al (1997b) measured the formation of chloral hydtrate
from trichloroethylene in liver and lung microsomal fractions from mice, rats and
humans. The liver samples in these three species were found to metabolise
trichloroethylene to significant extents. The chloral levels however, were twenty
times higher in mouse lung microsomal incubations than in rat lung microsomes and
could not be detected in human lung incubations. Rat lung cytosol was found to be
most active in metabolising chloral to trichloroethanol in this study, followed by
mouse lung and then human lung. Conjugation of trichloroethanol with glucuronic
acid catalysed by UDP-glucuronosyl-transferase was low in mouse lung (rate 0.03
nmol/min/ mg protein) and was not detectable in human lung. Immunolocalisation
showed that mouse lung contains high levels of cytochrome P4502E1 heavily
localised in the Clara cells. The number of Clara cells in the rat lung was smaller and
the concentration of P452E1 was less than the mouse lung. Cytochrome P4502E1
could not be detected in sections of the human lung. Enzyme protein levels were
quantified and were found to be consistent with the results of immunolocalisation.
83
Trichloroethylene
10.8.3 Kidney tumours
Kidney tubular adenomas along with meganucleocytosis were seen in rats exposed to
600 ppm by inhalation but not at 300 ppm (Maltoni et al., 1986). No increases in any
tumour types were reported in inhalational rat studies by Henschler et al (1980) and
Fukuda et al (1983). Kidney tubule meganucleocytosis was observed in rats following
administration of 250 mg/kg/day orally (Maltoni et al., 1986). Oral exposure of rats
at 500 mg/kg/day and 1000 mg/kg/day produced kidney tumours (US National
Toxicology Program (NTP), 1988). Kidney tumours were also observed in male rats
in a subsequent NTP study at 500 and 1000 mg/kg/day (US National Toxicology
Program (NTP), 1990). The US NTP considered these studies as inadequate due to
insufficient survival and significant non-tumour pathology. Despite this conclusion
the findings of the two studies are consistent with each other (UK Report, 1996) and
with studies conducted by Maltoni et al (1986) following oral administration and
inhalation exposure.
Some chemically-induced renal tumours in rats have been attributed to binding of the
chemical or its metabolite to -2?globulin. In this mechanism, binding of the
chemical to the male rat-specific protein -2?globulin, results in accumulation in the
form of protein hyaline droplets in kidney tubule cells. Overload of the chemically
associated protein in the cells results in increased cell death and increased
regenerative cell replication. Studies have shown that hyaline droplet accumulation is
unlikely to be responsible for kidney toxicity with trichloroethylene in rats
(Goldsworthy & Popp, 1987 ; Green et al., 1990).
Renal cytotoxicity was observed in rodent studies with trichloroethylene at
concentrations or doses that did not cause renal tumours. Renal tumours were
observed in rats, only in the presence of cytotoxicity at very high concentrations of
trichloroethylene. It has been proposed that a likely mechanism of renal tumours seen
in rats exposed to trichloroethylene is repeated cytotoxicity and regeneration (United
Kingdom, 1996).
The mechanism by which trichloroethylene causes rat kidney cytotoxicity is still
unclear. It has been postulated that cytotoxicity could be due to formation of the
metabolite dichlorovinyl cysteine (Henschler 1995). Dichlorovinyl cysteine has been
identified in the urine of workers exposed to 50 ppm of trichloroethylene. Renal
tumours have been reported in one two studies in workers exposed occupationally to
high levels of trichloroethylene. However, three other well conducted
epidemiological studies failed to show an association between occupational exposure
to trichloroethylene and renal cancer under the conditions of exposure in these
studies. These are discussed in detail in section 11.7.
A recent study by Green et al (1997a) has assessed quantitatively the metabolic
pathway leading to the formation of dichlorovinyl cysteine in rats in vivo and in rats,
mice and humans in vitro (Green et al, 1997a). The in vitro studies have shown that
the rate of conjugation of trichloroethylene with glutathione is higher in the mouse
(2.5 pmol/min/mg protein) than in the rat (1.6 pmol/min/mg protein) and is very low
in human liver (0.02-0.37 pmol/min/mg protein). The lyase activity in rat kidney
was found to be ten-fold greater than in the mouse and the metabolic clearance
through this pathway was found to be greater in rat kidney than in human kidney. In
vivo studies have shown that the mouse is more sensitive to the nephrotoxic effects of
DCVC than rats.
84 Priority Existing Chemical Number 8
Green (1997) have postulated an alternative mechanism for the renal toxicity of
trichloroethylene. Rats administered trichloroethylene, trichloroethanol and
trichloroacetic acid excreted high levels of formic acid. This was also observed in
mice exposed to trichloroethylene, though the amount of formic acid was lower than
in rats. The authors have postulated that formic acid excretion may be responsible for
renal toxicity. Formic acid is not a metabolite of trichloroethylene and the source of
formic acid needs to be studied further.
The mechanism of renal toxicity is being investigated further by several workers.
Renal toxicity in rats is considered to be of concern to human health until the
mechanism is elucidated.
10.8.4 Testicular tumours
A dose related and significant increase in the incidence of Leydig cell tumours was
reported in Sprague Dawley rats following inhalation exposure to trichloroethylene
for 8 weeks to 0, 100, 300 or 600 ppm (Maltoni et al., 1986). The number of affected
animals ranged from 4% in controls to 24% in the 600 ppm group (Maltoni et al.,
1986).
Following gavage administration of trichloroethylene to four strains of rats, ACI,
August, Marshall and Osborne-Mendel strains, an increased incidence of Leydig cell
tumours was observed in Marshall rats receiving 1000 mg/kg/day (67%) as compared
to control (35%) and vehicle control (37%) (US National Toxicology Program NTP,
1988). An increased incidence was not seen in the other strains. The Leydig cell
tumours were not considered to be associated with trichloroethylene because of the
high incidence seen in controls and the absence of tumour induction in the other
strains.
Benign Leydig cell tumours are common in aging rats and are associated with senile
endocrine disturbances. The spontaneous incidence varies in the different strains.
The spontaneous incidence rate for testicular tumours, at NCI, in Sprague Dawley rats
is 4.2%. No historical control data were available for Marshall rats. However,
Leydig cell tumours are rare in men and constitute <3% of all testicular neoplasms
(Mostofi & Price, 1973). Leydig cell tumours are often associated with peroxisome
proliferators and therefore their relevance to humans is questionable.
85
Trichloroethylene
11. Human Health Effects
A number of reviews have been published on the health effects of trichloroethylene.
This section summarises data from the published reviews and is based mainly on the
UK SIAR (United Kingdom, 1996). Articles published recently, that is, since
completion of the SIDS report, have been assessed. No unpublished studies were
provided for assessment.
11.1 Acute toxicity
Data are available from studies in volunteers, accident reports and from use as an
anaesthetic.
11.1.1 Inhalation
The predominant effect of acute inhalation exposure of humans to trichloroethylene is
CNS depression. At very high doses trichloroethylene causes narcosis and has been
used as an anaesthetic for short operations at concentrations of 5000 to 10,000 ppm.
Generally, there were no adverse effects after the patients had recovered from
anaesthesia. Cardiac arrhythmias have been reported during use as an anaesthetic.
Cranial neuropathies specially involving the trigeminal nerve have also been
observed. The trigeminal palsies were believed to be due to dichloroacetylene, a
decomposition product of trichloroethylene.
Death has been reported following accidental exposure to high levels of
trichloroethylene at work. Death was thought to be due to ventricular fibrillation
resulting from sensitisation of the heart by trichloroethylene to endogenous
catecholamines. Loss of sensation in the trunk and lower extremities and extensive
sensory loss over face with numbness have been reported following accidental
exposure to high concentrations of trichloroethylene. Loss of consciousness for
varying periods has been observed in workers with exposure to high levels (2800
ppm). Workers have also reported symptoms of CNS depression such as dizziness,
lethargy, headache and vertigo. Other effects seen following accidental exposure to
high levels were raised serum aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels, hypercalcaemia and hyperglobulinaemia. Kidney
damage was reported in one worker with acute renal failure following exposure
(David et al., 1989).
Several studies in volunteers under controlled conditions have reported acute effects
of trichloroethylene on CNS functions at 500 ppm and above. Dizziness, lethargy
and lightheadedness have been noted by volunteers. Exposure to 1000 ppm for 2 h
resulted in marked changes in performance of a range of tests. These changes were
potentiated with exposure to alcohol. No significant signs of CNS depression have
been noted at 300 ppm. Some subjective effects such as dizziness and lethargy were
reported at lower doses (27 ppm) by volunteers in one study (Nomiyama &
Nomiyama, 1971). No significant changes were seen in flicker fusion frequency and
two-point discrimination. "Irritant effects" have been reported in this study at 27
ppm, however these effects were not reported in other studies following higher
exposures. The results of this study were not considered for NOAEL as only three
subjects were involved and the symptoms reported were subjective. Another study
(Salvini et al., 1971) indicated that impairment of performance can be induced by
86 Priority Existing Chemical Number 8
exposures to 130 ppm of trichloroethylene. This is in contrast to the effects seen in
other studies. However the UK SIAR states that actual data was not given and only a
statistical analysis of the results was given. This study involved six subjects and was
not included when considering a NOAEL for acute effects.
From case reports, the no effect level for single inhalation exposure of humans to
trichloroethylene is around 300 ppm and is similar to that in animals.
Acute effects of trichloroethylene following accidental exposure and in volunteers
under controlled conditions are summarised in Table 27.
11.1.2 Oral
CNS effects are the main effects observed following acute oral ingestion of
trichloroethylene. Ingestion of <20 ml (450 mg/kg) has reportedly caused headache
and slight confusion, while with doses of >50 ml (1100 mg/kg) CNS and cardiac
effects (tachycardia and ventricular systoles) have been reported. Death due to
ventricular fibrillation after ingestion of 50 ml has been reported, but recovery has
been observed even after ingestion of up to 200 ml of trichloroethylene (around 4500
mg/kg body weight).
Two recently published articles reporting accidental and suicidal ingestion
respectively of high doses of trichloroethylene have been reviewed during this
assessment. No new data on low dose ingestion was available.
Accidental oral ingestion of approximately 29 gms of trichloroethylene by a 58 year
old man following a fall into a reservoir bath resulted in disturbed consciousness and
markedly oedematous pharynx and larynx. Laboratory examinations showed slightly
elevated serum AST and ALT levels but kidney functions were normal. The man
also developed respiratory insufficiency, chemical pneumonia and chemical burns to
30% of his body surface. The CNS functions returned to normal by 5 weeks and the
man was discharged after 44 days (Yoshida et al., 1996).
Ingestion of 70 ml trichloroethylene by a 17 yr old male in a suicide attempt resulted
in tremor, general motor restlessness and sinus tachycardia. The person lost
consciousness 5 h after poisoning. The highest concentration of trichloroethylene in
blood was 4 mg/L and was detected 13 h after ingestion. The metabolites by the
oxidative and glutathione pathways were quantified in urine. N-acetyl-S-1,2-
dichlorovinyl-L-cysteine excretion increased continuously with a maximum (1.25
nmol/mg creatinine) seen 5 days after poisoning. Several low molecular weight
proteins were also detected in the urine 5 days after poisoning indicating renal tubular
damage (Bruning et al., 1996a).
87
Trichloroethylene
11.2
88 Priority Existing Chemical Number 8
89
Trichloroethylene
90 Priority Existing Chemical Number 8
Irritation and corrosivity
11.2.1 Skin
In humans, trichloroethylene is irritating to the skin after both single and repeated
exposures. Studies in volunteers and case reports of workers exposed to the chemical
have described erythema, burning sensation of the skin (Sato & Nakajima, 1978),
rashes and dermatitis. Repeated dermal contact with trichloroethylene causes
defatting of the skin with roughening and erythema (Irish, 1963). Chemical burns to
about 30% of the total body surface was reported in a man who had accidentally
fallen into a reservoir bath during a degreasing operation (Yoshida et al., 1996).
11.2.2 Eye
Limited human data are available on the eye irritant effects of trichloroethylene.
Ophthalmodynia (pain in the eyes) was reported in a worker following an accident
that resulted in his face, shoulders and chest being bathed in trichloroethylene
(Nakajima et al., 1987). Direct eye contact with the chemical has been reported to
cause burning and irritation of the corneal epithelium. Burning and tearing of the
eyes has been reported following acute occupational exposure to trichloroethylene
(Kostrzewski et al., 1993). Studies carried out in volunteers to investigate
performance in behavioural tests have also reported irritation of eyes (Salvini et al.,
1971; Nomiyama & Nomiyama, 1977).
11.3 Sensitisation
There have been a few reports of apparent skin sensitisation in humans. In one case
report, a male worker developed severe dermal effects including skin lesions,
erythroderma with oedematous face and eyes due to delayed hypersensitivity to
trichloroethylene. Hypersensitivity in this worker was also detected to the metabolite
trichloroethanol but not to trichloroacetic acid (Nakayama et al., 1988). In another
report, similar reactions were described in a female worker who developed
erythematous lesions when challenged twice with trichloroethylene during
asymptomatic periods (Conde-Salazar et al., 1983). These cases are thought to be
idiosyncratic reactions to trichloroethylene as the number of cases is very small for
such a widely used chemical.
There have been no reports of respiratory sensitisation in humans.
11.4 Repeated dose toxicity
This section is based primarily on the UK SIAR. Numerous repeated dose toxicity
studies in volunteers and occupationally exposed individuals have been published. A
number of health surveys have been carried out in occupationally exposed workers
but they have several limitations. These studies have little information on the
atmospheric concentrations of trichloroethylene, concomitant exposure to other
chemicals and some do not have a control group for comparison or have not taken
confounding factors into account. Toxicity of trichloroethylene following repeated
exposures is summarised in Table 28.
91
Trichloroethylene
92 Priority Existing Chemical Number 8
93
Trichloroethylene
94 Priority Existing Chemical Number 8
95
Trichloroethylene
96 Priority Existing Chemical Number 8
97
Trichloroethylene
98 Priority Existing Chemical Number 8
Subjective symptoms of CNS disturbances have been reported in most of these
studies. Most common symptoms include fatigue, dizziness, vertigo, headaches and
memory loss and impaired ability to concentrate. Skin and eye irritation have also
been reported. A high incidence of CNS effects and hearing defects were noted in
some workers.
Some studies have mainly investigated the liver effects of trichloroethylene.
Evidence of liver damage has been reported in some studies while liver changes were
not seen in other studies Workers exposed to trichloroethylene developed
hepatomegaly, changes in serum hepatic enzyme levels (ALT, AST and aldolase) and
abnormalities in liver function tests such as thymol turbidity and cephalin-cholesterol
tests. Raised serum bilirubin levels and gamma globulins were noted in one study.
Increased serum beta- and gamma- globulins and some abnormalities in the cephalin
flocculation test were reported in workers regularly exposed to trichloroethylene
(Guyotjeannin & Van Steenkiste, 1958). The hepatic effects seen in all these studies
could not be definitively attributed to trichloroethylene as trichloroethylene exposure
levels were not noted and similar changes are associated with alcohol ingestion.
In a recent correspondence to the editors of a journal, Bruning et al (1996b) has
reported renal tubular damage in patients who had been diagnosed with renal cell
carcinoma and had undergone nephrectomy. Seventeen patients had been exposed to
high concentrations of trichloroethylene over many years and were later diagnosed
with renal cell cancer. All these patients reported that prenarcotic symptoms such as
feeling of drunkenness, dizziness, headache and drowsiness had occurred frequently
during occupational exposure to trichloroethylene. Duration of exposure was 15
years with a mean latency period of 30.4 years. The frequency of pathologic protein
excretion patterns in these patients were compared with 35 renal cell cancer patients
(controls) from a large urological clinic. SDS PAGE (SDS polyacrylamide gradient
electrophoresis) was used to separate and differentiate between different pathological
protein patterns in the excreted urine. This method allows a high-resolution
separation between 20 different urinary proteins according to molecular size and thus
helps to differentiate between different pathological protein patterns excreted in urine
indicating tubular, glomerular or mixed renal damage. Protein excretion patterns
indicating tubular damage in the remaining kidney was identified in all the 17
exposed patients (6 severe tubular damage, 6 moderate damage, 2 minor and 3 mixed
glomerular/tubular damage). Of the control patients 18 of the 35 showed normal
protein excretion patterns with 12 controls showing tubular damage, 4 mixed
glomerular/tubular damage and 1 with glomerular damage. One of these controls had
been occupationally exposed to tetrachloroethylene. The others had no history of
being occupationally exposed to potentially nephrotoxic substances. A lower
prevalence of tubular damage was found among the non-exposed group of renal cell
cancer patients than patients who had been occupationally exposed to
trichloroethylene. This data, though limited, cannot be dismissed especially in the
light of renal toxicity findings in rodents.
Alcohol intolerance has been reported in some workers who consumed alcohol during
exposure to trichloroethylene and in single and repeated dose volunteer studies. This
presented as transient flushing of the face, shoulders and neck due to vasodilatation of
the superficial vessels. This condition is commonly known as "degreasers' flush".
Competitive inhibition of acetaldehyde dehydrogenase resulting in accumulation of
acetaldehyde in blood is thought to be the underlying mechanism.
99
Trichloroethylene
Effects of trichloroethylene on the cardiovascular system have been investigated in a
number of studies. Abnormalities in cardiac rhythm such as ventricular extra-systoles
and tachycardia, have been reported.
The UK SIAR has described reports of other effects of trichloroethylene. Stevens-
Johnson syndrome, an autoimmune disease, has been reported in some workers
exposed to trichloroethylene by inhalation and also the dermal route (Phoon et al.,
1984). Scleroderma has also been observed in some workers exposed to
trichloroethylene (Flindt-Hansen & Isager, 1987). Stevens-Johnson syndrome and
scleroderma may be idiosyncratic reactions to trichloroethylene, however more
evidence is needed before any conclusions can be drawn.
11.4.1 Oral
The UK SIAR includes two studies on the effects of trichloroethylene following oral
exposure. In the first study the effects of trichloroethylene were evaluated four
months after contamination of drinking water by a spill from a trichloroethylene plant
placing thirteen residents potentially at high risk. The concentration of
trichloroethylene in the water consumed by the residents was not known, but
concentrations in drinking water wells ranged up to 1000 ppb. No symptoms of
toxicity were reported by any of the residents. Measurable levels of trichloroethylene
metabolites were detected in the urine of two residents but one used trichloroethylene
at work and the other had not consumed the contaminated well water and did not
work with trichloroethylene (Landrigan & Kominsky, 1987). This study did not
provide any useful data as exposure levels could not be determined.
In the second study the residual neurological effects following past exposure to
trichloroethylene in drinking water (up to 256 ppb) have been studied (Feldman et al.,
1994). Blink reflex latency and neurological assessments were carried out in a group
of 28 people. A significant difference in conduction latency was seen between
control and exposed groups indicating subclinical changes in the 5th cranial nerve.
However, other chlorinated solvents were also detected in the contaminated water
indicating simultaneous exposure to other chemicals.
11.5 Reproductive toxicity
11.5.1 Fertility
The UK SIAR indicated that fertility effects of trichloroethylene have not been
investigated in humans. The report cited isolated cases of reduced potency and
decreased libido among male workers (Bardodej & Vyskocil, 1956; El Ghawabi et
al., 1973) and increased incidence of menstrual disorders in exposed females
(Bardodej & Vyskocil, 1956; Zielinski, 1973)
11.5.2 Developmental toxicity
According to the UK SIAR few studies have investigated possible links between
effects on pregnancy and exposure to trichloroethylene. The report states that the
studies in humans are of limited use as exposure data were not quantified. An
association between trichloroethylene exposure and abortions or congenital
malformations has not been reported in any of the studies (Tola et al., 1980; Taskinen
et al., 1989; Goldberg et al., 1990; Lindbohm et al., 1990).
100 Priority Existing Chemical Number 8
11.6 Genotoxicity
A recently published article by Bruning et al (1997) analysed tumour tissues for
somatic mutations within the von Hippel-Lindau (VHL) gene, from 23 patients with
renal cell cancer and prolonged occupational exposures to high levels of
trichloroethylene. The VHL gene was reported to be a specific target in
trichloroethylene induced renal cell cancer with a high mutation frequency (100%) at
the VHL gene in the trichloroethylene exposed cases. In the trichloroethylene
unexposed group the mutation frequency for renal cell cancers was 33-55% (Bruning
et al., 1997). The VHL gene has been isolated and found to be a tumour suppressor
gene (Latif et al., 1993). Renal cell cancers may develop as a result of somatic
mutation in the VHL tumour suppressor gene. The findings of this report are
preliminary as all the VHL genes had not been confirmed by sequencing. Limitations
of this study include exposure not being determined precisely for each individual,
cases not selected from a well-defined study base and controls were not selected from
the same base. Further work is underway in Europe to confirm the effects of
trichloroethylene on the VHL gene.
The UK SIAR states that several other studies conducted in occupationally exposed
groups are considered to be inconclusive. Sister chromatid exchange (SCE) in
peripheral blood lymphocytes was investigated in workers exposed to
trichloroethylene. Frequency of SCE was found to be slightly increased in the
exposed group in one study (Gu et al., 1981). However this study did not account for
potential confounding factors, had a small group size and exposure was not stated
adequately. Nagaya et al (1989) did not observe any difference in the frequency of
SCE between trichloroethylene exposed (average concentration 30 ppm) and control
groups.
The frequency of SCE in a group of workers exposed to trichloroethylene (Seiji et al.,
1990) was investigated by taking gender and smoking habits into account. Breathing
zone concentrations were between 10 and 50 ppm. The frequency of SCE was
statistically significantly greater in male exposed smokers than in age-matched
controls. No differences were seen between the control and exposed groups among
females and male non smokers. The group sizes were small in this study and no
conclusions can be drawn.
In a chromosomal aberration study in lymphocytes of a group of 15 trichloroethylene
exposed workers, the number of metaphases with gaps was significantly greater when
compared with 669 (unmatched) controls (Rasmussen et al., 1988). The increases
were primarily in three workers who had the highest exposures as determined from
urinary trichloroethylene levels. The urinary trichloroacetate values were not stated.
Potential confounders such as smoking were not considered. In the same study,
sperm counts and the frequencies of sperm with two fluorescent Y bodies - indicating
presence of two Y-chromosomes - were not significantly different in the control and
exposed groups.
11.7 Carcinogenicity
A number of cohort and case-control studies have been conducted in occupationally
exposed populations to investigate the carcinogenicity of trichloroethylene. This
report only includes a discussion of the most relevant studies. Other studies have not
been described here because of a number of limitations such as small numbers of
subjects, short follow-up periods, exposure to more than one chemical and lack of
characterisation of exposures. Readers are referred to IARC (1995) for a detailed
description of the other studies.
101
Trichloroethylene
11.7.1 Cohort studies
The major cohort studies are those by Axelson et al (1994), Spirtas et al (1991)
updated by Blair et al (1998), and Antilla et al (1995). These are detailed further in
Table 29. The study by Henschler et al (1995) reported as a retrospective cohort has
been included in table 29 as it is a recent study and provides limited data of an
association between trichloroethylene exposure and human renal cancer. The study by
Garabrant et al (1988) has not been included as a number of chemicals were used at
the company with only 37% of the workers being exposed to trichloroethylene. The
follow-up period was only 15.8 years and it is unlikely that cancers with a long
latency period would have been detected in this study.
In the cohort investigated by Axelson et al (1994) no significant increases in cancer
mortality or morbidity were observed. Mortality was analysed in worker subgroups
categorised according to urinary trichloroacetic acid levels (<49, 50 to 99 or >100
mg/L) and exposure time (< or > 2 years). The two lowest exposure groups had low
cancer mortality.
However in the > 100 mg/L group, the standardised mortality ratio (SMR) for cancer
was slightly increased. In males, some excess of cancers of the liver, larynx, prostate
and of non-Hodgkins lymphoma were observed but the excess of liver and prostate
cancers and lymphomas were in the low exposure group. A statistically significant
increase was seen for malignant skin tumours in men (standardised incidence ratio
SIR 2.36, 95% confidence interval 1.02 - 4.65). This increase, however, was in the
low exposure group. The overall female cancer morbidity was slightly higher than
expected (SIR 1.32, CI 0.53 - 3.79) among women with < 2 years exposure. Half of
these cases had tumours of the breast or genital organs and the other cancers were in
the gastrointestinal tract. There were no cases of skin or liver cancers, lymphoma or
leukaemia among women.
102 Priority Existing Chemical Number 8
103
Trichloroethylene
An epidemiological study was conducted in a group of workers at an aircraft
maintenance facility in Utah (Spirtas et al., 1991). A number of chemicals were used
at the facility, such as chlorinated hydrocarbons (including trichloroethylene),
aromatic hydrocarbons (such as toluene and xylene) and some alcohols. Exposure
indices were calculated based on job, frequency of exposure, frequency of peak
exposure and duration of exposure. Mortality from all causes was significantly less
than expected for both men and women. There were no statistically significant
excesses for cancer deaths in general or for specific kinds of cancer.
Blair et al (1998) followed up the cohort of 14457 aircraft maintenance workers
previously reported by Spirtas et al (1991). Workers exposed to trichloroethylene
showed non-significant excesses for Hodgkin's lymphoma (RR 2.0), cancers of the
oesophagus (RR 5.6), colon (RR 1.4), primary liver (RR 1.7), breast (RR 1.8), cervix
(RR 1.8), kidney (RR 1.6) and bone (RR 2.1). The findings in this study did not
show a strong association between trichloroethylene exposure and any cancers. The
associations were not significant or dose related and not consistent between men and
women. This study included a large cohort of workers with a follow up period of
about 40 years enabling detection of cancers with a long latency period. However
workers were exposed to a number of chemicals and it was not possible to evaluate
risks from individual chemicals.
Antilla et al (1995) divided the total cohort into sub-groups, on the basis of the
observation period, into 0-9, 10-19 or more than 20 years. The average urinary
trichloroacetic acid levels were 8.3 mg/L in women and 6.3 mg/L in men. The mean
latency period was 18 years. Risk of cervical cancer was significantly increased for
the study cohort , with higher numbers in the shortest follow-up group (0-9 yrs).
There was a significantly increased incidence of cancer in general (SIR 2.98 95% CI
1.20 - 6.13 ) in the group with the follow-up of > 20 yrs. There was a significant
increase in the incidence of tumours of the liver (SIR 6.1; 95% CI 1.3 - 18), prostate
(SIR 3.56; 95% CI 1.5 - 7.0), stomach (SIR 3.0; 95% CI 1.2 - 6.1) and
lymphohaematopoietic system (SIR 3.0; 95% CI 1.2 - 6.1) in the group with a follow
up of > 20 yrs.
Henschler et al (1995) reported a study of renal cancer in workers exposed to
trichloroethylene at a cardboard manufacturing factory. Physical examination of the
workers included abdominal sonography and causes of death were obtained from
hospital records. Tumour diagnosis date was the date of surgery and renal tumours
were verified by histopathological examination. Air concentrations of
trichloroethylene or metabolites in urine were not available. Information indicates
that the workers in the cohort were exposed to high concentrations of
trichloroethylene over long periods of time. The average period of exposure was 18
years and the average observation period was 30 years. The incidence of renal cancer
in the cohort was compared directly with the incidence in the control group and with
data of the cancer registries of Denmark and German Democratic Republic.
Five cases of renal cancer were diagnosed by the close of the study and two
additional cases were diagnosed later giving a total of seven cases in the cohort. No
renal cancer was observed in the control group. A statistically significant increase in
incidence of renal cancer was obtained compared with cancer registry of Denmark
(SIR of 7.97; 95% CI 2.6 - 19) and German Democratic Republic (SIR of 9.66; 95%
CI 3.1 - 23). This study has been criticised for a number of reasons. IARC (1995)
have noted that the study may have been initiated after observing a cluster of cancer
cases. Others have also noted that the study was a cluster study and that physician
104 Priority Existing Chemical Number 8
and hospital records should not be compared with general population mortality rates
(Bloemen & Tomenson, 1995; Swaen, 1995). Though this study appears to be a
cluster investigation rather than a retrospective cohort the findings of this study raise
concern of an association between high trichloroethylene exposure and renal cancer.
Mortality at a plant in the US using trichloroethylene as a degreasing agent was
investigated in a study by Shindell and Ulrich (1985). Persons working for more than
three months from 1957 to 1983 were included in the study. No data on exposure
levels were available. Overall mortality (SMR for white males 0.79) and cancer
mortality (SMR for white males 0.62) were found to be less than expected.
11.7.2 Case-control studies
Several case-control studies have been conducted, however many are of limited use.
Studies which provide useful information are discussed below.
A case-control study including 59 nephrectomised patients has been described by
Vamvakas et al (cited in Deutsche Forschungsgemeinschaft, 1996). The study
included all patients who had been diagnosed with renal cell tumours at
histopathology after nephrectomy between December 1987 and May 1992. The
control group included 84 traffic accident patients treated in the same clinic.
Abdominal ultrasonography was used to exclude renal tumours in the control group.
Exposure evaluation was carried out by questionnaires and personal interviews.
Information was also obtained from physicians and occupational hygienists. Of the
nephrectomy cases, 20 had been exposed to trichloroethylene and none to
tetrachloroethylene. Five from the control group had been exposed to
trichloroethylene and 2 to tetrachloroethylene. The average exposure period for the
cases was 19 years. A highly significant odds ratio of 13.42 (95% CI 3.50 - 51.39)
was obtained for the combined exposure to trichloroethylene and tetrachloroethylene.
However, no exposure to tetrachloroethylene had been reported in the
nephrectomised patients. Factors such as age, sex, smoking habits, blood pressure
and consumption of diuretics were allowed for by logistic regression. The significant
odds ratio is suggestive of an association between trichloroethylene exposure and
renal cell carcinomas. The nephrectomised patients were classified into high,
medium or low level exposures on the basis of duration, frequency of exposure and
the workplace description. Eight patients with renal tumours were in the high
exposure group, 10 in the medium and 2 in the low. Of the controls, 2 were in the
high exposure group, 3 in the medium and 2 in the low exposure group. Only a
summary of this study was available during the Priority Existing Chemical
assessment. The data are therefore limited and do not allow an in depth assessment of
the quality of the study.
Several other case-control studies have investigated the carcinogenic effects of
trichloroethylene. Trichloroethylene exposure was not found to be a risk factor for
astrocytic brain tumours (Heineman & et al., 1994). The incidence of liver cancer
was investigated in people exposed to trichloroethylene in separate studies (Novotna
et al., 1979; Paddle, 1983). None of the liver cancer cases identified were found to be
occupationally exposed to trichloroethylene. These two studies only looked at one
type of cancer and included limited numbers. A high odds ratio (7.4) was found for
dry cleaners exposed to trichloroethylene in a case-control study investigating risk
factors for colon cancer (Fredrickson et al., 1989). The odds ratios were not
significantly increased for all dry cleaners or for all exposed to trichloroethylene.
This study does not provide sufficient evidence of a causal association between
trichloroethylene and colon cancer in dry cleaners because of the small number of
exposed people.
105
Trichloroethylene
12. Hazard Classification
Data on physicochemical hazards, toxicokinetics and health hazards in humans and
animals are integrated in this chapter. The potential hazards to human health from
exposure to trichloroethylene can then be characterised and the appropriate
classification determined.
Workplace substances are classified as hazardous to health if they meet the NOHSC
Approved Criteria for Classifying Hazardous Substances (the Approved Criteria)
(National Occupational Health and Safety Commission (NOHSC), 1994) and
hazardous in terms of physicochemical properties if they satisfy the definitions in the
Australian Code for the Transport of Dangerous Goods by Road and Rail (ADG
Code) (Federal Office of Road Safety, 1998)
Trichloroethylene is currently included in the List of Designated Hazardous
Substances (National Occupational Health and Safety Commission (NOHSC), 1994)
as a carcinogen category 3.
For transport by road and rail, substances are classified as dangerous goods according
to the criteria in the ADG Code, for example the criteria for corrosivity, acute toxicity
and physicochemical properties such as flammability.
12.1 Physicochemical hazards
Trichloroethylene is non-flammable and non-explosive under normal conditions of
use. It is moderately volatile with a vapour pressure of 7.7 kPa. It is relatively stable
but at high temperatures, as seen in the vicinity of arc welding and degreasing
operations, it may decompose to hydrochloric acid, phosgene and other compounds.
In contact with hot metals, such as magnesium and aluminium at very high
temperatures (300-600癈) it decomposes readily to form phosgene and hydrogen
chloride.
Classification
Trichloroethylene does not meet the ADG Code criteria for any classes pertaining to
physicochemical properties.
12.2 Kinetics and metabolism
In humans, trichloroethylene is absorbed via inhalational, dermal and oral routes,
with the most significant uptake being through inhalation of the vapour. Dermal
absorption of the vapour is negligible, however, some absorption of liquid occurs
through the skin. Absorbed trichloroethylene is distributed throughout the body and
is deposited mainly in adipose tissue and liver. Metabolism of trichloroethylene is
mainly via the oxidative pathway with the major metabolites being trichlorethanol,
trichloroacetic acid and trichloroethanol glucuronide. A minor metabolite, N-acetyl
dichlorovinyl cysteine, has been identified in animal and human urine and is formed
via conjugation with glutathione.
The metabolism and excretion of trichloroethylene in animals is similar to humans,
however there are some species differences in the metabolism of trichloroethylene.
The rate of metabolism of trichloroethylene to trichloroacetic acid in mice is more
106 Priority Existing Chemical Number 8
rapid than in rats. Saturation of the oxidative pathway has also been reported in rats
at 200 to 500 mg/kg while in mice saturation is only seen at 2000 mg/kg. Saturation
in humans has not been seen at doses up to 380 ppm and has been predicted by PBPK
models to occur at 2000 mg/kg.
12.3 Health hazards
12.3.1 Acute effects
Trichloroethylene has low acute toxicity by all routes of exposure. In acute studies,
the oral LD50 in rats ranged from 5400 to 7200 mg/kg, inhalational LC50 (4h) in rats
was 4800 ppm (4 h) and dermal LD50 in rabbits was > 20000 mg/kg.
The acute effects of trichloroethylene reported in animals are consistent with the
findings in humans. The predominant effect of acute exposure of humans to
trichloroethylene is CNS depression. At very high doses trichloroethylene causes
narcosis. Other symptoms of CNS depression such as dizziness, light headedness and
lethargy have also been reported in volunteers. Changes in ECG were reported in one
study at 100 ppm. However this was seen in only one subject and the ECG returned
to normal after some time. The NOAEL for acute CNS effects in humans is 300 ppm.
Several deaths have been reported in workers following occupational exposure to
very high levels of trichloroethylene. Ventricular fibrillation, due to sensitisation of
the heart to endogenous catecholamines, has been reported as the cause of death in
some of these cases.
The acute toxicity in animals is generally similar to humans. An exception is the
acute pulmonary toxicity seen as vacuolation of Clara cells in mice at exposures of 20
ppm. This is related to the metabolism of trichloroethylene in mice.
Classification
Trichloroethylene does not meet the Approved Criteria (National Occupational
Health and Safety Commission (NOHSC), 1994) for classification on the basis of
acute lethal effects by oral, dermal or inhalation exposure. The ADG Code lists
trichloroethylene as Class 6.1. The LD50 for the oral and dermal routes and the LC50
for the inhalation route for trichloroethylene were below the cut-off for classification
as `harmful' under the ADG Code. It is therefore likely that trichloroethylene was
classified as acutely toxic based on human experience.
12.3.2 Irritant effects
Studies in human volunteers and reports of workers exposed to trichloroethylene have
indicated that trichloroethylene caused burning sensation of the skin, erythema,
rashes and dermatitis. Prolonged contact can cause defatting of the skin. Studies in
guinea pigs and rabbits also indicate that trichloroethylene is a skin irritant.
Direct eye contact with the chemical in humans has been reported to cause burning
and irritation of the corneal epithelium. Volunteers have reported irritation of eyes
during investigation of behavioural performance following exposure to
trichloroethylene. Two studies in rabbits reported conjunctivitis, corneal abrasions
and necrosis after instillation of trichloroethylene into the eyes.
107
Trichloroethylene
Classification
From human evidence and results of the animal studies, trichloroethylene meets the
Approved Criteria for classification as a skin irritant (R38 - Irritating to skin) and an
eye irritant (R36 - Irritating to eye).
12.3.3 Sensitisation
A small number of cases of apparent skin sensitisation have been reported in humans.
Due to the small number of cases for such a widely used chemical, it is thought that
these were idiosyncratic reactions and not due to sensitisation. No skin sensitisation
studies have been conducted in animals. No studies have investigated the potential of
trichloroethylene as a respiratory sensitiser.
Classification
Trichloroethylene does not meet the Approved Criteria for classification as a
sensitiser.
12.3.4 Effects after repeated or prolonged exposure
Several health surveys have been carried out in workers occupationally exposed to
trichloroethylene. These surveys are however limited due to lack of information on
atmospheric trichloroethylene levels, exposure to other chemicals and potential
confounding factors. Most of the studies reported CNS effects such as dizziness,
headaches, memory loss, inability to concentrate and skin and eye irritation. Liver
effects of trichloroethylene have been investigated in some studies. No consistent
evidence of liver damage is available as some studies reported hepatomegaly and
changes in blood chemistry while no effects were reported in other studies. A limited
number of studies included tests for the potential neurotoxicity of trichloroethylene in
occupational cohorts. These studies provided no evidence of significant effects on
EEG patterns or nerve conduction velocity. ECG was affected in one out of ten
subjects in one study. However, the ECG returned to normal after a few days. Data
on renal effects of trichloroethylene in humans is limited. Severe renal tubular
damage and tubular-glomerular damage have been reported in workers with long-
term occupational exposure to high levels of trichloroethylene.
The toxic effects identified from repeated inhalational exposure to trichloroethylene
in animal studies were liver, kidneys, CNS, lungs and hearing effects. The kidneys
appear to be the most sensitive organs in animals. Kidney effects were observed in
rats following inhalation and oral exposure and in mice following oral exposure. In a
2-year inhalation study using rats, meganucleocytosis of the renal tubules was
reported at 300 ppm (LOAEL) with no effects being seen at 100 ppm (0.55mg/L)
(NOAEL). Meganucleocytosis was also reported in an oral study at 250 mg/kg/day
in rats with a NOAEL of 50 mg/kg/day. In mice, renal cytomegaly was observed in
both sexes following oral administration of 1000 mg/kg/day for 2 years.
Trichloroethylene liver effects have been reported in mice and rats with inhalational
NOAELs of 200 ppm (1.1 mg/L) in rats and rabbits, and oral NOAELs of 375 and
500 mg/kg/day in mice and rats respectively.
Classification
Trichloroethylene does not meet the Approved Criteria for classification on the basis
of severe effects after prolonged or repeated exposure.
108 Priority Existing Chemical Number 8
According to the Approved Criteria a substance is classified as harmful where
damage to health is likely to be caused by repeated or prolonged exposure by the
following routes and dose ranges:
? oral, rat: 50 mg/kg/day
? inhalation, rat: 0.25 mg/L 6 h/day
The lowest NOAELs following exposure to trichloroethylene by the inhalation and
oral routes are 100 ppm (0.55 mg/L) and 50 mg/kg/day respectively. These values
are higher than the cut offs in the Approved Criteria for classification as harmful.
12.3.5 Reproductive effects
Reproductive effects of trichloroethylene have not been adequately investigated in
humans. No developmental toxicity has been reported in humans.
Reproductive effects following oral administration have been well investigated in
animals. Oral administration resulted in reduced sperm motility and slight reductions
in neonatal bodyweight and survival in mice at doses at which general toxic effects
were produced. In rats there was a reduction in the number of litters born and in the
litter size. General toxic effects were also observed at these levels.
Several developmental studies have been conducted in animals. In inhalation studies
on rats, mice and rabbits no clear evidence of developmental toxicity was reported at
doses up to 1800 ppm. A series of oral studies from one laboratory suggest that
trichloroethylene may induce developmental neurotoxicity following maternal
exposure.
Classification
Trichloroethylene does not meet the Approved Criteria for teratogenicity nor the EC
Criteria (European Commission Directive 93/21/EEC, 1993 27 April,) for effects on
fertility or developmental toxicity as animal studies do not provide any evidence of
fertility or developmental effects.
12.3.6 Genotoxicity
Trichloroethylene has been investigated for its mutagenic potential in a wide range of
standard in vitro and in vivo assays. Many studies have been conducted using
epoxide stabilised trichloroethylene, however these studies have not been considered
in this hazard assessment, due to the known mutagenicity of epoxides.
Trichloroethylene in the vapour state tested positive in several bacterial assays using
Salmonella typhimurium in the presence of metabolic activation. In several fungal
studies, trichloroethylene tested positive to Saccharomyces cerevisiae, also in the
presence of metabolic activation. Trichloroethylene also tested positive in a mouse
lymphoma gene mutation assay and induction of unscheduled DNA synthesis (UDS)
was reported in several studies. On this evidence, trichloroethylene can be regarded
as weakly mutagenic in vitro.
In a host-mediated gene mutation assay in mice, trichloroethylene tested positive to S.
cerevisiae in the kidneys and liver but not the lungs
109
Trichloroethylene
In somatic cell studies in vivo, both positive and negative results were obtained in rat
and mouse micronucleus tests, with some doubts about two of the studies with
positive results. Negative results were obtained in rat and mouse studies for
chromosomal aberrations, sister chromatid exchange and UDS, however,
trichloroethylene induced DNA single strand breaks in the liver of rats and mice in
one study, and in mouse liver and kidneys in a second study. A mouse spot test was
equivocal, however, a preliminary test for mouse pink-eyed unstable mutation was
clearly positive. In germ cell assays, dominant lethal tests were either negative or
inconclusive.
Studies conducted in occupationally exposed groups have been considered to be
inconclusive. These studies had limitations such as small group size and potential
confounders not being considered. A study investigating somatic mutations in the
von Hippel-Lindau (VHL) gene obtained from tumour tissue of patients with renal
cell cancer reported that trichloroethylene specifically acts on the VHL gene which
has been identified as a renal tumour suppressor gene. It is possible that renal cell
cancers following trichloroethylene exposure develop with somatic mutation of the
tumour suppressor gene being one of the events. The findings of this report are
preliminary as all the VHL genes had not been confirmed by sequencing. Limitations
of this study include exposure not being determined precisely for each individual,
cases not selected from a well-defined study base and controls were not selected for
the same base. Further work is underway in Europe to confirm the effects of
trichloroethylene on the VHL gene.
Classification
Trichloroethylene meets the Approved Criteria for classification as a category 3
mutagen (R40M3) on the basis of
? positive results in a variety of tests in somatic cells in vivo, described above;
and, supported by:
? the study of mutations in VHL tumour suppressor gene;
? positive results from a number of in vitro mutagenicity assays; and,
? mutagenicity of known metabolites.
According to the Approved Criteria category 3 are those substances which cause
concern for humans owing to possible mutagenic effects, but in respect of which
available information does not satisfactorily demonstrate heritable genetic damage
(Appendix 4).
12.3.7 Carcinogenicity
A number of epidemiological studies have investigated the carcinogenic potential of
trichloroethylene. Most cohort studies, including those by Axelson et al (1994) and
Spirtas et al (1991) which were large enough to detect an effect, individually did not
show any association between cancer and occupational exposure to trichloroethylene.
However, the cohort study by Anttila et al (1995) provided limited evidence of an
association between exposure to trichloroethylene and cancer. Occupational
exposures in the cohort studies of Axelson et al (1994) and Anttila et al (1995) were
to low levels of trichloroethylene, approximately 20 to 30 ppm.
110 Priority Existing Chemical Number 8
A high incidence of renal cancer in workers from a cardboard factory was reported by
Henschler et al (1995) following exposure to high levels of trichloroethylene for long
periods. This study appears to be a cluster investigation and has some weaknesses.
The findings of this study are supported by a case control study by Vamvakas et al
(cited in Deutsche Forchungsgemeinschaft, 1996) who have demonstrated an
association between renal cell carcinomas and occupational exposure to
trichloroethylene. The findings of these two studies are limited by weaknesses in the
design of the studies, however they cannot be dismissed.
In animals trichloroethylene induces tumours at several sites and in different species.
Tumours have been seen in mouse liver and lung and rat kidney and testis.
Studies have shown that mouse liver tumours are likely to be due to peroxisome
proliferation induced by the metabolite trichloroacetic acid. Trichloroacetic acid does
not induce peroxisome proliferation in human hepatocytes.
Mouse lung tumours are also thought to be related to the metabolism of
trichloroethylene. Green et al (1997) have demonstrated that chloral hydrate levels
were twenty times higher in mouse lung microsomal incubates than in rat lung
microsomes and could not be detected in human lung incubates. Rat lung cytosol was
found to be most active in metabolising chloral hydrate to trichloroethanol in this
study, followed by mouse lung and then human lung. This study provides evidence
that accumulation of chloral hydrate is unlikely to occur in human lung.
Testicular tumours were observed only in one strain of rats with a high incidence in
the control group. These tumours are rare in men and are often associated with
peroxisomal proliferators.
Renal cytotoxicity was observed in rodent studies with trichloroethylene at
concentrations or doses that did not cause renal tumours. Renal tumours were
observed in rats, only in the presence of cytotoxicity at very high concentrations of
trichloroethylene. It has been proposed that a likely mechanism of renal tumours seen
in rats exposed to trichloroethylene is repeated cytotoxicity and regeneration (United
Kingdom, 1996).
The mechanism by which trichloroethylene causes rat kidney cytotoxicity is still
unclear. It has been postulated that cytotoxicity could be due to formation of the
metabolite dichlorovinyl cysteine (Henschler 1995). Dichlorovinyl cysteine has been
identified in the urine of workers exposed to 50 ppm of trichloroethylene. Renal
tumours have been reported in one study in workers exposed occupationally to high
levels of trichloroethylene. However, other well conducted epidemiological studies
failed to show an association between occupational exposure to trichloroethylene and
renal cancer under the conditions of exposure in these studies.
A recent study has assessed quantitatively the metabolic pathway leading to the
formation of dichlorovinyl cysteine in rats in vivo and in rats, mice and humans in
vitro (Green et al, 1997a). The in vitro studies have shown that the rate of conjugation
of trichloroethylene with glutathione is higher in the mouse (2.5 pmol/min/mg
protein) than in the rat (1.6 pmol/min/mg protein) and is very low in human liver
(0.02-0.37 pmol/min/mg protein). The lyase activity in rat kidney was found to be
ten-fold greater than in the mouse and the metabolic clearance through this pathway
was found to be greater in rat kidney than in human kidney. In vivo studies have
shown that the mouse is more sensitive to the nephrotoxic effects of DCVC than rats.
111
Trichloroethylene
Green (1997) have postulated an alternative mechanism for the renal toxicity of
trichloroethylene. Rats administered trichloroethylene, trichloroethanol and
trichloroacetic acid excreted high levels of formic acid. This was also observed in
mice exposed to trichloroethylene, though the amount of formic acid was lower than
in rats. Formic acid excretion may be responsible for renal toxicity. Formic acid is
not a metabolite of trichloroethylene and the source of formic acid needs to be studied
further.
The mechanism of renal toxicity is being investigated further by several workers.
Renal toxicity in rats is considered to be of concern to human health until the
mechanism is elucidated.
Classification
Trichloroethylene meets the Approved Criteria for classification as a Carcinogen
Category 2 (National Occupational Health and Safety Commission (NOHSC), 1994),
that is, a substance regarded as if it is carcinogenic to humans, on the basis of the
occurrence of tumours in experimental animals and limited evidence in workers.
Thus the available data provides suspicions of carcinogenic potential in humans
(R45).
Review of carcinogenicity data by other countries/agencies
The carcinogen classification categories adopted by the various countries/agencies are
similar. There are five major categories. Most countries/agencies have the first three
categories listed below and several have all five categories. Although the
classifications are similar, the reader is referred to the relevant country/agency
classification system for further information on the criteria and basis for inclusion of
a chemical into the various categories.
The five categories in the classification of carcinogens include:
? known human carcinogen;
? probable human carcinogen;
? possible human carcinogen;
? not a human carcinogen and
? insufficient information to classify.
The carcinogenicity of trichloroethylene has been reviewed recently by a number of
countries and agencies principally with a view to classification. A brief description
of the outcome of the reviews and the classification adopted by the countries/agencies
is provided below.
IARC
IARC (International Agency for Research on Cancer) (IARC, 1995) considered three
cohort studies to be relevant for the evaluation of trichloroethylene. Meta-analysis of
the three studies (Spirtas et al., 1991; Axelson et al., 1994 and Anttila, 1995) by
IARC indicated an excess relative risk for cancer of the liver and biliary tract (23
observed cases whereas 12.7 expected) and non-Hodgkin's lymphoma (27 observed
and 18.9 expected). Results for liver cancer were given separately in the study by
Anttila et al (1995) and for the maintenance workers in the study by Spirtas et al
(1995). A total of 7 cases were observed whereas 4 were expected.
112 Priority Existing Chemical Number 8
On the basis of these findings and the induction of tumours in animals at sites other
than the liver, IARC concluded that trichloroethylene is probably carcinogenic to
humans (Group 2A), that is limited evidence in humans and sufficient evidence in
experimental animals.
Germany
The Commission for the Investigation of Health Hazards of Chemical Compounds in
the Work Area (1996) considered that the study by Henschler et al (1995) indicates
an increased incidence of renal tumours in workers exposed to high concentrations of
trichloroethylene. The Commission states that the findings of this study were
confirmed by a recent case control study carried out by Vamvakas et al (cited in
Deutsche Forschungsmeinschaft, 1996) suggesting an association between renal cell
tumours and exposure to trichloroethylene. The tumours were histopathologically
similar to those found in rats. In addition, the metabolic pathway postulated to be
responsible for nephrocarcinogenicity has been found to be similar in rats and
humans (Bernauer et al., 1996).
On the basis of these three findings ie increased incidence of renal cell tumours in
exposed workers, nephrocarcinogenicity in rats and the molecular mechanism of renal
toxicity, trichloroethylene is classified by the Commission in category IIIA1, ie
compound capable of inducing malignant tumours as shown by experience with
humans.
UK HSE
The HSE (United Kingdom, 1996) consider that the majority of epidemiological
studies, including the studies by Axelson et al (1994) and Spirtas et al (1991) that
had substantial power to detect an effect, did not show any evidence of an association
between trichloroethylene exposure and increased incidence of cancer. However,
they noted that there is limited evidence of an increased risk of liver cancer in one
cohort study (Anttila et al., 1995) and of renal cancer in another study (Henschler et
al., 1995). These two studies indicate that trichloroethylene has some carcinogenic
potential.
HSE have concluded that the liver tumours in mice are due to peroxisomal
proliferation and are of no relevance to humans but that there is no evidence to
indicate that the mechanism of induction of kidney tumours in rats and lung tumours
in mice is not applicable to humans.
On the basis of the uncertainties of the epidemiological data and the tumours in
animals, the HSE have proposed that trichloroethylene be classified as a category 3
carcinogen, ie a substance which causes concern for humans owing to possible
carcinogenic effects, but in respect of which the available information is not adequate
to make a satisfactory assessment.
Canada
The Canadian Priority Substances List Assessment (Government of Canada, 1993),
conducted by Environment Canada and Health Canada, in accordance with the
Canadian Environmental Protection Act (CEPA), states that an association between
exposure to trichloroethylene and the development of any specific type of tumour has
not been consistently observed in the epidemiological studies, including those by
Spirtas et al (1991); Axelson et al (1984); Tola et al (1980) and Shindell and Ulrich
(1980).
113
Trichloroethylene
The Canadian report concluded that the increased incidence of hepatic tumours in
mice appears to be induced by a mechanism not relevant to humans and that the
relevance of renal tumours in male rats to humans is unclear. The most pertinent
results in assessing the carcinogenicity of trichloroethylene are the pulmonary
tumours in mice reported by Maltoni et al (1986, 1988) and Fukuda et al (1983) and
the increases in testicular tumours in rats (Maltoni et al., 1986; Maltoni et al., 1988;
US National Toxicology Program NTP, 1988). Trichloroethylene also appears to be
weakly genotoxic in in vitro and in vivo assays.
The Canadian report categorised trichloroethylene in Group II, ie probably
carcinogenic to humans.
ECETOC
ECETOC (European Centre for Ecotoxicology and Toxicology of Chemicals) (1994)
state that five cohort epidemiological studies of populations occupationally exposed
to trichloroethylene have shown no association between occurrence of cancer and
exposure to trichloroethylene. The studies referred to are Spirtas et al (1991);
Axelson et al (1994); Tola et al (1980) and Shindell and Ulrich (1980) and Wong and
Morgan (1990).
ECETOC noted that animal studies have shown liver and lung tumours in mice and
kidney tumours in rats. The mechanisms in these cases are linked to species specific
metabolism of trichloroethylene or to biochemical responses which are specific to
rodents. These tumours are therefore considered to be of no relevance to humans.
ECETOC concluded that trichloroethylene does not present a carcinogenic hazard to
man.
ACGIH
ACGIH (1992) found no evidence in six epidemiological studies to suggest that an
association between trichloroethylene exposure and increased cancer in humans. The
six studies considered were Spirtas et al (1991); Axelson et al (1978); Tola et al
(1980) and Shindell and Ulrich (1980) Paddle (1983) and Novotna et al (1979).
ACGIH concluded that the hepatocellular tumours in mice (National Cancer Institute
(NCI), 1976) occur via a nongenetic mechanism following liver injury. No
carcinogenic effects were seen in animals in other studies either orally (Maltoni &
Maioli, 1977) or by dermal application (Van Duuren et al., 1979).
ACGIH categorised trichloroethylene in Group A5, ie not suspected as a human
carcinogen.
114 Priority Existing Chemical Number 8
13. Occupational Risk
Characterisation
Occupational risk characterisation combines the results of the hazard and
occupational exposure assessments to determine the potential risks of adverse health
effects in workers exposed to trichloroethylene.
13.1 Methodology
The methodology used to characterise risk to human health from exposure to
trichloroethylene in this report is the margin of exposure approach. This approach is
commonly used in international assessments (OECD, 1993; UK Government, 1993,
July; European Commission, 1994)
The following steps are used for risk characterisation of critical effects caused by
repeated or prolonged exposure:
1. Identification of the critical health effect(s).
2. If appropriate and available, then identification of the most reliable
NOAEL for the critical effect(s).
3. Estimation of the human dose (EHD)
4. Comparison of the NOAEL with the estimated human dose to give a
margin of exposure, that is:
margin of exposure = NOAEL
estimated human dose (EHD)
5. Characterisation of risk by judging whether the margin of exposure
indicates a concern.
Margin of exposure (MOE) is an indication of the magnitude by which the NOAEL
exceeds estimated human exposure (EHD). Characterisation of risk requires
consideration of a number of parameters such as the completeness and quality of the
database (including exposure data), nature and severity of the effects, interspecies and
intraspecies variability and characteristics of the human population exposed when
judging whether the MOE indicates that exposure to the substance is of concern.
For acute effects, the risk characterisation process considers likely exposure patterns
to assess whether single exposures are high enough to indicate a health concern.
115
Trichloroethylene
13.2 Critical health effects
13.2.1 Acute effects
The main adverse effect observed following acute exposure to trichloroethylene is
CNS depression. The NOAEL for CNS depression in humans is about 300 ppm for
exposure of about 8 h. Exposure to high doses causes narcosis and recovery is
generally complete. Symptoms of CNS depression such as lightheadedness, dizziness
and lethargy have been reported in workers.
Trichloroethylene is considered to be a skin and eye irritant.
13.2.2 Effects due to repeated exposure
Severe renal tubular damage and tubular-glomerular damage have been observed in
workers with long-term occupational exposure to trichloroethylene. However, the
data is insufficient to identify a NOAEL as exposures were not known.
The toxic effects identified from repeated inhalational exposure to trichloroethylene
in animal studies were liver, kidneys, CNS, lungs and hearing effects. The kidneys
appear to be the most sensitive organs in animals hence the critical effect is kidney
toxicity. In a 2-year inhalation study using rats, meganucleocytosis of the renal
tubules was reported at 300 ppm (LOAEL) with no effects being seen at 100 ppm
(NOAEL). Five rats in the highest exposure group (600 ppm) had renal tubular
adenocarcinomas (Maltoni et al., 1986).
Long term carcinogenicity studies in animals by the inhalation and oral routes
indicate that trichloroethylene is carcinogenic in rats and mice. The principal tumour
sites are the liver and the lungs in mice and the kidneys in rats.
Renal adenocarcinomas have been reported in rats following gavage and inhalation
exposure. Rat kidney tumours are thought to be due to persistent cytotoxicity and
regeneration. Epidemiological studies, one cohort and one case control, have
indicated an association between prolonged occupational exposure to high levels of
trichloroethylene and kidney tumours.
The main route of exposure is inhalation, with dermal exposure occurring to a lesser
extent. There is no dermal NOAEL available. The inhalation NOAEL chosen for
risk characterisation is the NOAEL for kidney effects in rats of 100 ppm (546
mg/m3). Assuming 100% absorption, an average rat weight of 215g and a respiratory
rate of 0.16 m3/day, this represents an absorbed dose of :
546 mg/m3 x 0.16 m3/day 7h = 118.5 mg/kg/day
0.215 x 24 h
13.3 Occupational health and safety risks of trichloroethylene
13.3.1 Risks from physicochemical hazards
Trichloroethylene is non-flammable and non-explosive under normal conditions of
use. Its flammability limits in air are 8.0 to 10.5 and the chemical is flammable when
exposed to a high energy source. At workplaces using old degreaser tanks with
inadequate engineering controls, vapours may accumulate increasing the risk of
flammability.
116 Priority Existing Chemical Number 8
Trichloroethylene is relatively stable but at high temperatures may decompose to
hydrochloric acid, phosgene and other compounds. Such conditions are seen in the
vicinity of arc welding and degreasing operations.
In the presence of strong alkalis like sodium hydroxide, dichloroacetylene is formed
which is explosive and flammable.
13.3.2 Margin of exposure
Margins of exposure (MOE) were calculated for the critical health effect, renal
toxicity, for the various occupational scenarios.
Margin of exposure = 118 mg/kg/day
estimated human dose (EHD) in mg/kg/day
The EHD for each scenario is given in Appendix 1, with the summary in Chapter 8.
The NOAEL for the critical effect, renal toxicity, is 118 mg/kg/day (100 ppm) based
on a 2-year inhalation rat study. The estimated MOE for each scenario is given in
Table 30.
117
Trichloroethylene
118 Priority Existing Chemical Number 8
13.3.3 Uncertainties in risk characterisation
In any risk assessment process, uncertainties arise due to assumptions made during
the process because of inadequate information. Uncertainties inherent in the
assessment of health risk of a chemical are listed in Table 31.
Table 31 ?Uncertainties in risk characterisation
Specific concern
Area of uncertainty
Inadequate information Lack of representative atmospheric
exposure data
Lack of dermal exposure data
Assumptions in assessment process Assumption of a linear correlation between
estimated human dose and variables such
as atmospheric concentration and
exposure time
Assumptions in rate and extent of dermal
absorption of vapours and liquid
Use of standard constants for breathing
rate, body weight and bioavailability
Experimental conditions Selection of doses used in the critical
study
Variability in results between laboratories
Amount and quality of the available toxicity
data
These uncertainties need to be considered when discussing the implications of any
margin of exposure, and in particular when deciding if an estimated exposure is of
concern.
13.3.4 Uncertainties in risk characterisation of trichloroethylene
For the critical effect, renal toxicity, an inhalational NOAEL of 100 ppm was
identified from the animal data with the LOAEL being 300 ppm. Renal
adenocarcinomas were observed at 600 ppm. The actual NOAEL may be anywhere
between 100 and 300 ppm.
Renal effects are thought to be related to the metabolism of trichloroethylene by the
reductive pathway. In humans, as in rats, the mercapturates formed are only minor
excretory products but are excreted slowly from the kidney. These metabolites have
been identified in human urine even at low levels of exposure. The ratio of the two
isomers N-acetyl-S-(dichlorovinyl) -L-cysteine excreted in urine is different in rats
and humans. In humans the proportion of the two isomers are the same. However, in
rats excretion of 2,2 isomer is 3 to 4 fold higher than the 1,2 isomer. Uncertainty
exists as to whether small amounts of these metabolites are sufficient to cause renal
toxicity or the metabolites need to exceed a certain threshold for appearance of renal
toxicity.
119
Trichloroethylene
The skin absorption rate used to estimate dermal exposure introduces an element of
uncertainty in the assessment as no data on the skin permeability rate for
trichloroethylene in humans was available in the open literature. The skin absorption
rate used (0.32 mg/cm2/h) was derived from experiments in hairless guinea pigs. The
dermal absorption rate in mice was reported as 0.47 mg/cm2/h in one study while the
theoretical model of Fiserova-Bergerova predicts that for dermal absorption of
trichloroethylene, the predicted flux is 0.27 mg/cm2/h (Fiserova-Bergerova & Pierce,
1989). The skin absorption rate in guinea pigs was used to estimate dermal exposure
as the rate in guinea pigs in general is closer to the rate in humans compared to mice.
These above uncertainties are likely to have a similar impact on MOE for all
scenarios. Uncertainties such as lack of exposure data (inhalational and dermal) and
extent and duration of skin absorption will have varying degrees of impact on the risk
assessment. These will be discussed for each scenario.
13.3.5 Risk during formulation
Acute effects
No atmospheric monitoring data were available for formulation of products
containing trichloroethylene. There is a range of processes, with some being open
and others closed. Certain stages of the formulation process such as manual filling of
the mixing vessels from drums or bulk storage sites and emptying of the tank into
containers could result in high peak inhalation exposures and dermal contact.
In a well-controlled, enclosed process, acute exposures are likely to be low. There is
a risk of irritant effects during formulation when mixing in open systems, during
maintenance work or during clean-up of spills.
Adverse effects due to repeated exposure
No atmospheric monitoring data were available for formulation of products
containing trichloroethylene. According to the data provided for assessment,
formulation is a batch process occurring approximately 1 to 2 h a day for 1 to 60 days
a year and this has been taken into account in the formulae used to estimate exposure.
The MOE for inhalation exposure was estimated for 3 atmospheric concentrations,
10, 30 and 50 ppm and were found to be 474, 158 and 95 respectively. For combined
exposure (inhalation and dermal) during formulation of a product containing 90%
trichloroethylene the MOE for the 3 scenarios were 456, 156 and 94. In estimating
dermal exposure, contact with liquid trichloroethylene was assumed to be incidental
as skin contact is expected to be infrequent during formulation.
The MOE calculated indicate that the risk of kidney effects is considered to be
minimal during formulation.
13.3.6 Risk during vapour degreasing
Acute effects
The atmospheric monitoring data available for assessment consisted of short- term
measurements or instantaneous readings indicating peak concentrations of
trichloroethylene, with all readings well below the NOAEL of 300 ppm for CNS
effects. If it is assumed that the results are representative of vapour degreasing in
Australia, then the risk of CNS effects is low. However a reading of 145 ppm was
reported 15 cms above a degreaser, indicating that a worker involved in manually
120 Priority Existing Chemical Number 8
lowering or lifting workloads from the degreaser could be exposed to high vapour
concentrations with some risk of CNS effects.
As trichloroethylene vapour is irritant to the eyes, exposure to vapours during
degreasing operations may lead to a risk of eye irritation. Trichloroethylene liquid is
a skin and eye irritant, so any splashes or spills present a risk of irritation.
Adverse effects due to repeated exposure
The atmospheric monitoring data provided by end-users during assessment were
inadequate as most of the data was limited and consisted of grab samples and not
TWA measurements. However, there is sufficient UK monitoring data available for
vapour degreasing. The mode of use of trichloroethylene in vapour degreasing in the
U.K. is similar to that in Australia and the U.K. monitoring data was used to estimate
worker exposure. Monitoring by HSE inspectors between 1984 and 1994 showed
that of 25 personal samples (8 h TWAs), 96% were <30 ppm and all were less than 50
ppm (United Kingdom, 1996). Based on this data exposure was estimated for 3
scenarios, 10, 30 and 50 ppm. The combined MOE for both inhalation and dermal
exposure for the three scenarios were 34, 12 and 7 respectively. The severity of the
renal toxicity, with higher doses causing tumours in animals, suggests the need for a
high margin of safety. The MOE at all the levels calculated for vapour degreasing are
of concern.
Inhalational values may be overestimated to some extent as most workers are
involved in other activities in addition to vapour degreasing. However in some
workplaces workers are involved in only operating the degreasers. Poor work
practices and working conditions such as poor ventilation or lack of proper protective
equipment may lead to increased exposure. Some of the commonly reported
examples of poor work practice in the literature included workers ignoring the
recommended speed for lowering and raising workloads from the degreaser and not
holding the workload in the freeboard zone for a sufficient time.
Exposure during vapour degreasing is mainly to vapours. Dermal absorption of
trichloroethylene vapour is negligible resulting in minimal absorption through the
skin. Dermal exposure to the liquid during vapour degreasing is considered to be
incidental and may occur during activities such as filling degreaser with
trichloroethylene or handling of the degreased parts containing trapped liquid
chemical. More frequent dermal exposure will lower the MOE.
13.3.7 Risk during cold cleaning
Information obtained from industry indicates that 29% of the respondents use
trichloroethylene in cold cleaning of metal parts. Common types of cleaning include
immersion in tubs or tanks along with spraying or brushing of the metal parts.
Manual wipe cleaning was another common method. Atmospheric monitoring has not
been carried out at workplaces using trichloroethylene for cold cleaning.
Margins of exposure were estimated for exposure durations of 120 days/yr and 200
days/yr using the atmpspheric monitoring data obtained in the NICNAS cold cleaning
project. Dermal exposure was assumed to occur for 5% of the shift. Estimated MOE
for combined exposures (inhalation and dermal) for the various activities for 200
days/yr were 105 for dip cleaning, 91 - 34 for combined dip cleaning and rag wiping
and 52 - 5 for rag wiping alone and for 120 days/year were 174 for dip cleaning, 152
- 56 for combined dip cleaning and rag wiping and 87 - 8 for rag wiping alone.
121
Trichloroethylene
Other monitoring data available for assessment was available from Dow Chemical
Company Product Stewardship Program, which focussed on the exposure profiles
encountered during use of trichloroethylene in vapour degreasing and cold cleaning
operations. For the average concentration obtained in this program (68.4 ppm), the
estimated combined MOE (inhalational+dermal) was 4.4.
Some of the MOE calculated for rag wiping and dip cleaning combined with rag
wiping (ie MOE < 50) indicate that there is a concern in these situations.
Dermal exposure may occur as cold cleaning involves immersion of metal parts in
tubs or tanks accompanied by scrubbing or brushing of the immersed parts leading to
agitation of trichloroethylene liquid with loss of vapour to the atmosphere and
splashes and spills of the chemical. Dermal exposure may be higher where cold
cleaning involves immersion of the hands into the tub or tank during scrubbing. High
dermal and inhalation exposure is associated with manual wipe cleaning, where
trichloroethylene is applied on a rag and used to clean surfaces. In many workplaces
no engineering controls are in place during cold cleaning and, in one of the places
interviewed, the gloves used during manual wipe did not offer any protection against
trichloroethylene.
13.3.8 Risk during use of trichloroethylene products
Trichloroethylene is an ingredient in various products such as adhesives, electrical
equipment cleaning solvents, metal degreasing solvents, waterproofing,
paintstrippers, carpet shampoos and tyre repair products. Most of these products are
for industrial use with some products identified for consumer use (tyre repair, paint
stripper, aerosol waterproofing agent and component cleaner). Most of these
products contain <60% trichloroethylene except for one tyre repair product and
electrical equipment cleaning solvent. Very little information was provided on the
use of trichloroethylene products. Due to the range of products and conditions and
duration of use it is difficult to estimate exposure for all scenarios. The methods of
use of these products are described in Chapter 8.
Acute adverse effects such as headache, dizziness and irritability have been reported
by some workers using a degreasing product indicating exposure to high
concentrations of trichloroethylene. The product was sprayed onto a cloth and used
for wipe cleaning metal rods during the entire shift. Products used in spray form
present a greater risk of exposure as the small aerosol particles are likely to be readily
absorbed through the lungs and skin.
Some data was obtained on use of adhesives containing trichloroethylene. An
atmospheric concentration of 1.15 ppm was detected in an adhesive spraying area
with good natural ventilation. Concentrations of up to 21.4 ppm over a sampling time
of 5-6 h were recorded in a US automotive factory using trichloroethylene containing
adhesives.
As part of the project commissioned by NICNAS, WorkCover monitored atmospheric
levels of trichloroethylene and urinary levels of trichloroacetic acid in workers using
trichloroethylene products. Concentration of trichloroethylene in the products varied
from spray painting (35% and 25%) to rag wiping for surface cleaning (20%) to
brushing on the product (90%). Atmospheric levels monitored varied from 0.7 ppm
to 4.8 ppm (spray painting); 3.8 ppm to 4.1 ppm (rag wiping); 2.5 ppm (brush
application). Assuming incidental dermal exposure, the estimated margins of safety
varied from 69 to 395 (spray painting) to 85 to 90 (rag wiping) to 117 (brush
application). The MOE were estimated for an 8 h exposure and would be higher at
places using the products for shorter periods.
122 Priority Existing Chemical Number 8
13.3.9 Areas of concern
The risk assessment has indicated that there may be health concerns for workers
exposed to trichloroethylene in some workplaces.
The limited short term exposure data available indicate that there may be a risk of
acute CNS effects during certain stages of vapour degreasing when high exposure to
trichloroethylene vapours may occur. Acute effects are also likely during use of
trichloroethylene in cold cleaning for 8 h shifts in places with poor ventilation and
during use of trichloroethylene products, especially in the form of aerosols. Although
it is not possible to determine how representative monitoring data was in the
NICNAS project for cold cleaning and trichloroethylene products, there is cause for
concern as anecdotal evidence of dizziness, headache and irritability during these uses
have been obtained during the assessment.
Estimates of MOE for repeated exposure indicated that there is little risk of adverse
health effects during formulation, however there was concern for workers repeatedly
exposed to trichloroethylene during vapour degreasing and cold cleaning, particularly
from inhalation exposure. Dermal exposure was minor during vapour degreasing,
however, as the risk of skin contact during cold cleaning is greater, the contribution
by dermal exposure towards the risk of adverse health effects during cold cleaning
may be significant.
In addition, while estimating human exposure in this assessment an average male
weight of 70 kg was used. This may not be applicable to the majority of the
population in sections of the metal industry and the textile and footwear industry
which have a high proportion of female employees who are likely to be < 70 kg. The
MOE would therefore be lower for these persons.
123
Trichloroethylene
14. Risk Management
The key elements in the management of health and safety risks from exposure to
hazardous substances include:
? control measures;
? hazard communication;
? atmospheric monitoring;
? regulatory controls; and
? emergency procedures.
An assessment of the measures currently employed and/or recommended to reduce
occupational health risks associated with the use of trichloroethylene and
trichloroethylene containing products is included in this chapter. MSDS and labels
supplied by the importers and formulators are also assessed here.
14.1 Control measures
According to the National Model Regulations for the Control of Workplace
Hazardous Substances, exposure to hazardous substances should be prevented, or
where that is not practicable, controlled to minimise risks to health. A National Code
of Practice for the Control of Workplace Hazardous Substances, lists the hierarchy of
control measures, in priority order, that should be implemented to eliminate or
minimise exposure to hazardous substances. These are:
? elimination;
? substitution;
? isolation;
? engineering controls;
? safe work practices; and
? personal protective equipment.
14.1.1 Elimination
Elimination means the elimination of chemicals from a process, such as using a
physical process instead of a chemical process in cleaning.
A review of the manufacturing process by end-users may show that it is not necessary
to use a chemical. For example, the requirements in a cleaning process may have
changed due to improved materials or methods of production or a slight modification
of the process may eliminate cleaning completely. Changing the work process can
avoid components becoming soiled in the first place or reduce the level of soil,
making cleaning easier.
Physical processes (Metal Finishing Association, 1996) that are effective for cleaning
some types of soils from metals include:
? shot and vapour blasting;
? dry-ice blasting;
? steam cleaning; and
124 Priority Existing Chemical Number 8
? ultraviolet or vacuum-thermal treatment
Hot aqueous cleaning for removing oils and grease is being used to clean metal parts
at one workplace, instead of trichloroethylene.
14.1.2 Substitution
Substitution includes substituting a less hazardous substance, the same substance in a
less hazardous form or the same substance in a less hazardous process.
A trichloroethylene substitute being used at one workplace for cleaning metal parts is
sodium carbonate along with wetting agents applied at high temperature and pressure
for removing heavy oils.
Alternatives to trichloroethylene in metal cleaning include aqueous and semi-aqueous
systems and emulsion cleaning (Radian Corporation, 1990). Other aliphatic and
aromatic organic solvents are also potential substitutes.
The aqueous systems involve parts being cleaned in a bath containing 5-10%
surfactant or solvent, and being allowed to dry. The advantages of water-based
processes are the absence of solvent emissions and generally lower material costs.
Disadvantages are that the energy requirements may possibly be higher since the
work may have to be dried after cleaning and rinse waters may need to be treated
before discharge or reuse.
Semi-aqueous systems use solvents such as terpenes, dibasic esters and glycol ethers
at 100% strength, or as a 50% emulsion followed by rinsing with water. These can be
used to remove heavy oils and greases. The disadvantages are similar to those of
aqueous cleaning such as the possible need for drying and appropriate effluent
treatment.
A number of solvent blends are available for cold immersion and manual cleaning
(United Nations Environment Programme Industry and Environment Programme
Activity Centre (UNEPIE/PAC), 1992). These include mixtures of aliphatic and
aromatic hydrocarbons (naphtha, toluene, xylene) and oxygenated solvents (ketones,
esters and alcohols). Cold immersion in these blends removes heavy grease and other
industrial contaminants. However, these alternatives are also likely to have adverse
health effects.
Users need to evaluate the technical issues, cost, health and safety and environmental
effects of each option when considering substitution of trichloroethylene. In
particular, if replacement of trichloroethylene with another substance is considered,
the human health and environmental effects and hazards of the substitute need to be
considered to ensure that trichloroethylene is not being replaced by a more hazardous
substance.
It should be noted that reverse substitution, that is, trichloroethylene replacing 1,1,1-
trichloroethane, appears to be occurring with the phasing out of 1,1,1-trichloroethane
under the Montreal Protocol. Current users of 1,1,1-trichloroethane should consider
all available alternatives.
14.1.3 Isolation
Isolation involves separation of the process from people by distance or the use of
barriers to prevent exposure.
125
Trichloroethylene
During importation of trichloroethylene transfer of bulk trichloroethylene from ships
to on-shore bulk tanks is largely isolated by means of dedicated pipe-lines. At two
vapour degreasing sites, the vapour degreasing bath was isolated in a sealed, enclosed
room.
14.1.4 Engineering controls
Engineering controls are plant or processes which minimise the generation and
release of hazardous substances. They include enclosure or partial enclosure, local
exhaust ventilation and automation of processes.
Bulk storage and transport
Engineering controls in use during bulk storage and transport include:
? automatic carbon adsorption vapour extraction system at a bulk storage site. This
system draws air around hose connections at tanker and drum filling stations.
? mass flow meters for filling of tankers and drums to preset the volume and avoid
overfilling.
? bunding of drum filling stations.
Formulation
The types of control measures used in formulation processes in Australia vary greatly,
such as, the extent of enclosure of the process and type of ventilation.
Best practice to be followed during formulation is total enclosure of the process,
including transfer of trichloroethylene to the mixing vessel through enclosed pipes.
At the very least, the mixing vessel should be tightly closed during mixing and also
when not in use and emptying of the mixing vessel into smaller containers should be
through closed pipelines. Exhaust ventilation installed above the mixing tank ensures
that the vapours are drawn away from the work area. Atmospheric monitoring at
regular intervals ensures that the control measures are adequate to prevent exposure.
Vapour degreasing
The two main criteria of a well-controlled vapour degreasing operation are a good
machine design and proper operating practices. A machine correctly sized for the
work that is to be done minimises dissipation of trichloroethylene vapours into the
working area and prevents release of large amounts of vapour to the workroom air.
Vapour degreasers vary in the degree of automation and closure of the plant. Some
vapour degreasers are small to medium sized open-topped degreasers that are
manually operated. Other degreasers vary from semi-automated plants with platform
lifts that lower and lift work containers to large fully automated degreasers with
conveyorised monorails that carry the work baskets through the tank.
The engineering controls that are currently in place at worksites and identified during
this assessment include: fume extraction, rim ventilation, condensing coils, condenser
water jacket, temperature control system, rolling or sliding tank cover, overhead
crane/hoist, and adequate freeboard. Several workplaces stated that the degreaser
tank was of "approved" design which was interpreted during assessment as
conforming to the requirements of the Australian Standard AS 2661 (Standards
Association of Australia, 1983).
126 Priority Existing Chemical Number 8
The above standard, prepared by the Standards Association of Australia, includes
safety requirements for design, construction, installation, and operation of a degreaser
plant. The emission control measures indicated in AS 2661 include:
? adequately sized tank to prevent spillage or dissipation of solvent;
? suitably sized freeboard zone to prevent vapour turbulence, with a freeboard ratio
of not less than 0.75;
? an exhaust if provided in open tanks to be incorporated along the top edge of the
tank;
? a thermal cutout in the boiling sump liquors to protect against overheating of
solvent;
? a thermal cutout in the freeboard zone above the condensing coils to protect
against vapour emission from the tank;
? temperature indicator for sensing the temperature of the boiling sump;
? close fitting sliding or rolling covers below the rim ventilation slot. Hinged
covers tend to draw the vapours out by a piston effect leading to solvent loss and
exposure of the worker while flat covers slide horizontally off the machine and
reduce the disturbance to the vapour layer;
? low temperature coolant such as water or refrigerant to be used to maintain
vapour level in degreasing plant to a safe level;
? an overhead lifting device operating at a controlled rate not exceeding 3 m/min.
Mechanical parts handling system reduce emissions by moving parts into and out
of the machine at appropriate rates and eliminate the excess losses caused by
manual operation. Another advantage of a mechanical transport system is that the
operator works farther away from the degreasing tank. In manual operations, a
person will be near the tank frequently and may have to bend over the top of the
cleaner to lower or extract parts.
A carbon adsorption system is an additional control technique that can be used with a
lip exhaust ventilation system. In this system the diffusing solvent vapours and the
vapours evaporating from clean parts pass through the exhaust ducts to an activated
carbon bed. The solvent molecules are adsorbed onto the activated carbon from the
stream before discharging to the atmosphere. When the carbon becomes saturated
with solvent the bed is desorbed to remove the solvent from the carbon. The
solvent/stream mixture is then condensed and passed through a water separator, and
the recovered solvent is returned to the tank.
Cold cleaning
Trichloroethylene is used for cold cleaning in a variety of ways in Australia (see
Chapter 8). Based on the limited data obtained from the NICNAS survey, it would
appear that there are few engineering controls in place during use of trichloroethylene
in cold cleaning. Use of a fume cupboard or portable fan or local exhaust ventilation
was stated by some workplaces. In one workplace where cold cleaning involved
immersing parts in a tank containing trichloroethylene the tank was provided with a
cover to minimise dissipation of the solvent into the atmosphere. Most places using
the chemical in cold cleaning stated that it was done in an area with good natural
ventilation.
The project commissioned by NICNAS indicated that no engineering controls are in
place during use of trichloroethylene in cold cleaning.
127
Trichloroethylene
Local exhaust ventilation is extremely important during cold cleaning as large
amounts of trichloroethylene could be lost to the atmosphere during this process.
Proper positioning of the local exhaust ventilation is important to prevent passage of
solvent through the workers breathing zone.
Use of trichloroethylene products
A number of products containing trichloroethylene are in use in Australia, the most
common being its use in adhesives. Although little information was available for the
assessment of application of adhesives, it does indicate that ventilation provided is
extremely variable. From the data available for assessment it appears that application
of adhesives involving painting and spraying is generally carried out in spray booths.
Control measures identified during use of other trichloroethylene products vary from
extraction ventilation to fume cupboards to vented table.
14.1.5 Safe work practices
Safe work practices have an important role in reducing solvent emissions and
therefore solvent consumption. Information obtained during the assessment indicates
that the safe work practices followed at some of the work sites are:
? adherence to the manufacturer's instructions of starting up, operating and closing
down of vapour degreasing tanks;
? holding workload in the degreasing zone for some time before drawing out to
allow adequate draining/drying time;
? loading the parts to be degreased into the basket at an angle to facilitate draining
of the solvent. Improper loading of parts can lead to trapping of solvent in the
parts with evaporation into the atmosphere.
? regular checks of the sump temperature indicator to determine changing of
solvent.
Other safe work practices that may be followed to reduce solvent loss are:
? avoid overloading of the tank. A general recommendation is that workloads not
exceed more than 50% of the total interface area;
? baskets, racks or hangers used to hold the metal parts for degreasing should not
be made of porous materials as they will absorb trichloroethylene and remove it
from the degreaser;
? if sprays are used to assist in cleaning, spraying should be done below the vapour
layer; spraying at a downward angle also helps to reduce emissions;
? slow speed for entry and exit of workloads. Increasing the speed of entry of
workload displaces the solvent out of the tank while rapid extraction of parts
leads to solvent vapour being pulled out of the tank;
? solvent soaked rags and swabs should be disposed of in closed metal bins;
? topping up of the tank with the solvent should not be done when the degreaser is
hot. Trichloroethylene should be pumped in at a low level with the cooling water
system and the rim ventilation operational. Adding solvent from the top while
the plant is hot can lead to high worker exposure. Regular checks should be
made of the solvent levels;
? placement of vapour degreaser tanks away from sources of direct draughts such
as open windows or doorways or a fan as this is likely to lift vapour over the
freeboard of the tank into the surrounding work areas;
128 Priority Existing Chemical Number 8
? installation of the tank in a well ventilated area so that any vapour that may be
dragged out with the work will be quickly removed;
? location of the tank away from naked flames and welding operations as
trichloroethylene decomposes at high temperatures to phosgene, hydrochloric
acid and chlorine.
? The Australian Standard AS 2865 (1995) "Safe working in a confined space"
(Standards Australia, 1995) should be strictly adhered to for entry into and work
in a confined space.
? Regular and frequent cleaning of degreasers avoids the baking of contamination
on to internal walls. AS 2661 (Standards Association of Australia, 1983)includes
the safe work practices to be adopted during maintenance and cleaning of a
vapour degreasing plant.
14.1.6 Personal protective equipment
Personal protective equipment (PPE) is used to minimise exposure to or contact with
chemicals. PPE should be used in conjunction with other engineering controls and
not as a replacement. Where other control measures are not practicable or adequate to
control exposure then PPE should be used. Exposure to trichloroethylene is mainly
by inhalation and skin contact and the PPE selected should protect the worker against
exposure by these routes.
Dermal exposure may be prevented by use of protective gloves. It is important to
select gloves that are resistant to the chemical exposed. Information provided for
assessment indicates that gloves are generally provided at most workplaces.
However, most of the workplaces did not specify the type of gloves used. Types of
gloves specified by some end users were nitrile, rubber and viton gloves.
Recommendations on types of glove to use with particular chemicals are provided by
many glove manufacturers, and a number of books and databases. Recommendations
are usually based on tests of degradation, that is, changes in physical properties of
gloves following contact with the chemical such as swelling or hardening, and
permeation, that is, the movement of the chemical through the material at a molecular
level. Two common measures of permeation are breakthrough time and permeation
rate. It should be noted that test results from gloves made of the same generic
material can differ due to differences in manufacture, and so test data relating to
specific glove brands may be preferable to test data relating only to material type.
Recommendations based on these types of tests should provide a starting point only
for the selection of gloves, and in choosing gloves, regard should always be had for
the particular work activities for which the glove is to be used. The glove with the
highest breakthrough time and lowest permeation rate may not always be necessary.
Factors that need to be considered in conjunction with test data include:
? duration, frequency and degree of chemical exposure;
? the degree of physical stresses that will be applied;
? the temperature of the chemical (heat may change the permeation rate of the
chemical through the glove);
? in the case of formulations, the degree of protection that the glove provides for
other ingredients, and possible synergistic effects;
? the likelihood of the glove coming into contact with water or other chemicals that
may effect the glove's performance against the chemical for which it is
recommended.
129
Trichloroethylene
No work processes involving long periods of immersion of hands in trichloroethylene
were identified, however some work processes presented the possibility of
intermittent or occasional contact with liquid trichloroethylene (hot and/or cold) or
trichloroethylene products. This information suggests that gloves with ratings that
indicate protection against intermittent exposure, as opposed to total immersion, may
be acceptable in most workplaces.
A comparison of the ratings provided by some primary sources for gloves made from
various types of material as summarised in table 32 shows a general agreement on
materials that are not recommended, or considered to provide poor protection against
trichloroethylene. However, there is greater variability about the types of gloves
which are recommended. Materials recommended by one or more sources include
PE/EVAL, PE/EVAL/PE, Silvershield, chlorobutyl, chloroprene rubber, and teflon.
The materials not recommended include butyl, chlorinated polyethylene (CPE),
neoprene, polyethylene (PE), and nitrile/PVC. Materials over which there are
different recommendations are: natural rubber, PVC and nitrile, which are
recommended in the Australian Standard but not recommended by other sources; and
PVA and viton, which are rated as poor by the ACGIH, but recommended by other
sources. It can be seen that materials unanimously not recommended by sources
included some materials that were recommended by some MSDS, i.e neoprene and
polyethylene. PVC, nitrile and natural rubber were also recommended on some
MSDS, although the majority of the sources recommended that they not be used.
A survey of six retail outlets for protective gloves in Sydney and Melbourne found
that PVA gloves were the glove usually recommended for protection against
trichloroethylene. Prices quoted for one brand varied from $37 to $44. Two outlets
mentioned that PVA breaks down easily in the presence of water. Viton gloves were
recommended by one outlet, with price quoted at $314 per pair. One outlet
recommended PVC gloves for jobs involving low level of exposure, quoting a price
of $2 a pair. This survey highlights the practical aspect of choosing gloves, and the
role of manufacturers and suppliers in making available appropriate gloves and
information.
For formulated products gloves should be selected on the basis of the component with
the shortest breakthrough time.
Protective gloves are to be used when contact of skin with trichloroethylene is likely,
such as during loading and unloading of work parts from the vapour degreaser, during
cold cleaning, clean up of spills or during other work processes when splashes are
likely.
Covering of arms and legs is useful during handling trichloroethylene and overalls or
long sleeved shirts and trousers may be used.
Respiratory protection is not required in most situations. However a face mask with
organic vapour cartridge should be worn when exposures are likely to be high, such
as during clean up of large spills.
The NICNAS industry survey indicated that if entry into a degreasing tank was
necessitated for cleaning, workers were provided with self-contained breathing
apparatus.
14.2 Emergency procedures
Information on emergency procedures was not submitted for assessment.
130 Priority Existing Chemical Number 8
Written procedures for workers for handling spills and other emergencies during
formulation and use of trichloroethylene is good practice. Procedures to be followed
during clean up of spills and first aid procedures should be recorded on the MSDS.
Trichloroethylene is listed in the Australian Code for the Transport and Handling of
Dangerous Goods (ADG Code) which provides guidelines for handling emergencies
during transport (Federal Office of Road Safety, 1998).
131
Trichloroethylene
132 Priority Existing Chemical Number 8
14.3 Hazard communication
14.3.1 Assessment of Material Safety Data Sheets
Introduction
MSDS are the primary sources of information for the safe handling of chemical
substances. Under the National Model Regulations for the Control of Workplace
Hazardous Substances (the National Model Regs.) (National Occupational Health and
Safety Commission (NOHSC), 1994) and corresponding State and Territory
legislation, suppliers are required to provide MSDS to their customers for all
hazardous substances. Employers must ensure that MSDS for any hazardous
substance used in the workplace is readily accessible to employees with potential for
exposure to the substance.
Trichloroethylene is currently on the List of Designated Hazardous Substances
(National Occupational Health and Safety Commission (NOHSC), 1994) as a
hazardous substance in concentrations at or above 1%. During assessment of MSDS
in this report comparisons are made with the current listing and classifications. Seven
MSDS for trichloroethylene (>99%) and 46 MSDS for trichloroethylene-containing
products were submitted and assessed for compliance with the National Code of
Practice for the Preparation of Material Safety Data Sheets (the MSDS Code)
(National Occupational Health and Safety Commission (NOHSC), 1994). The 46
products contain >1% trichloroethylene (range 10% - >90%) and are therefore
considered hazardous substances. Most products contain high concentrations of
trichloroethylene, with almost one half (20) containing >60% trichloroethylene (see
table 3 in chapter 7 for more information on concentration of trichloroethylene in
products). An MSDS for one other product, a paint stripper, was also submitted but
not included in the assessment as it contained 0.05% trichloroethylene.
The MSDS were divided into two groups, ie MSDS for trichloroethylene (>99%) and
products containing trichloroethylene, for assessment. The assessment focussed on
the adequacy of the information provided in relation to the following core elements of
an MSDS: product identification; health hazard information; precautions for use; safe
handling information; and contact point. Information considered most important in
each of these sections was identified and checked for inclusion. The presence of an
emergency telephone number and a statement of hazardous nature as required under
the MSDS Code were also checked. The statement of hazardous nature required to be
on MSDS for all hazardous substances is: `Hazardous according to criteria of
Worksafe Australia'. The findings of the MSDS assessment are given in Table 33.
A sample MSDS for trichloroethylene, prepared in accordance with the MSDS Code,
is provided in this report as Appendix 2. The sample MSDS, prepared from
information obtained for the assessment of trichloroethylene is for guidance purposes
only. Under the National Model Regulations, manufacturers and importers have the
responsibility to compile their own MSDS and ensure that the information is up-to-
date and accurate.
133
Trichloroethylene
Table 33 - Findings of MSDS Assessment
Trichloroethylene (>99%) Trichloroethylene products
Information Number Comments Number Comments
MSDS MSDS
Total 7 46
Statement of Hazardous 3/7 9/46
Nature
Emergency telephone no. 4/7 28/46
Product Identification*
Indicated major use(s) 6/7 (The same MSDS 37/46
was missing all of
UN Number, ADG Class, 6/7 these) N/C
Hazchem Code
Poison Schedule 6/7 27/46
Ingredient concentrations
Exact proportion or range 5/7 44/46
Stabilisers present 5/7 3 did not disclose N/A
name of stabiliser
Physical description/ properties 6/7 N/C
Health Hazard Information
Acute effects
Irritant to upper respiratory 7/7 37/46
tract
Headache 4/7 42/46
6/7 40/46
CNS depression symptoms
such as dizziness, confusion,
narcosis
Unconsciousness/Death 7/7 33/46
Cardiac effects 4/7 10/46
Nausea/Vomiting 4/7 35/46
44/46
Eye irritant/corneal 7/7 2 stated that
damage corneal damage is
unlikely
Skin irritant 7/7 43/46
Defatting of skin 7/7 39/46
27/46 One other stated `not
Absorption through skin 3/7 2 other MSDS
absorbed rapidly'
stated that it was
not readily
absorbed through
the skin
Chronic effects
CNS disturbance or 6/7 21/46
symptoms of
Hearing loss 2/7 0/46
Liver damage 6/7 23/46
Kidney damage 5/7 21/46
20/46 4 mentioned NOHSC
Carcinogenicity 6/7 2 mentioned that it
Class 3 classification; 10
was listed by
referred to the IARC
NOHSC as a Class
classification Group 3
3 carcinogen; 3
(now outdated); 6 others
mentioned IARC
mentioned
classification Group
carcinogenicity in mice.
3 (now outdated);
2 others (not included in
one mentioned
these 20) stated there
positive response in
were no long-term data
mice.
and `probably not
carcinogenic'
First Aid Statements*
6/7 36/46
If poisoning occurs, contact a
doctor of Poisons Information
Centre.
134 Priority Existing Chemical Number 8
Table 33 - Findings of MSDS Assessment (cont.)
Trichloroethylene (>99%) Trichloroethylene products
30/46 8 had instruction to
If swallowed, do NOT induce 4/7 2 others had
induce vomiting. 6
vomiting. Give a glass of water. contrary instructions
additional warned of
to induce vomiting
dangers of aspiration
and had instruction to
leave decision to doctor.
12/46 8 others said to give
Avoid giving milk or oils 2/7 2 others had
milk, 1 had conflicting
contrary instructions
instructions about giving
to give milk
of milk.
Avoid giving alcohol 2/7 21/46
7/7 45/46
If skin contact occurs, remove
contaminated clothing and
wash skin thoroughly.
7/7 46/46
Remove from contaminated
area. Apply artificial
respiration if not breathing
7/7 46/46
If in eyes, hold eyes open,
flood with water for at least 15
minutes and see a doctor.
Advice to doctor
7/7 9/46 17 did not have an
Avoid sympathomimetic
`advice to doctor' section
Amines
Precautions for Use
ACGIH and OSHA were
34/46
Correct value for TWA and 7/7 ACGIH was quoted
quoted as the source on
TWA
STEL exposure standard as the source in 3
12 MSDS. 5 gave TWA
19/46
cases.
for mixture; 2 said no
STEL
TLV established; 1 gave
TWA of 100 ppm without
saying for what chemical
Adequate ventilation 7/7 41/46
Local exhaust ventilation 6/7 31/46
Reference to AS 2661 0/7 N/A
Gloves (non specific) 2/7 12/46
- Nitrile or Fluorocarbon 1/7
- PVC 2/7 4/46
- PVC or Rubber 2/7
- Neoprene or Viton 4/46
- Neoprene, nitrile or 6/46
rubber
- Natural rubber 1/46
- PVA 10/46
- PVA, PE, or Viton 3/46
- PVA, PVC or Viton 1/46
- Viton 2/46
Eye protection 6/7 41/46
Respirator 6/7 (Specific types 40/46
mentioned)
7/7 46/46
Safe Handling Information
Contact Point
Title 3/7 22/46
Telephone number 6/7 26/46
N/C Information on UN Number, ADG Class, Hazchem Code, and the physical
description/properties section for mixtures were not checked as the information would vary
according to the ingredients.
N/A not applicable
* First Aid Statements as recommended by SUSDP for substances containing trichloroethylene.
135
Trichloroethylene
Discussion of findings
Amongst both groups of MSDS, the Safe Handling Information section provided
adequate information. Information considered important for this section was
reference to appropriate conditions of storage, storage/transport incompatibilities,
spills/disposal instructions, mention that fumes could evolve, and
recommendations for fire fighters (see sample MSDS for details). However,
deficiencies were noted in other sections, including:
? omission of a Statement of Hazardous Nature
? in the case of one MSDS for trichloroethylene, omission of several elements
in the product identification section - major uses, UN Number, ADG Code,
Hazchem Code and Poison Schedule.
? omission of information on use of products.
? in the acute health effects section, omission of information on skin absorption
and cardiac effects; also nausea, headache, irritation to the upper respiratory
tract, CNS symptoms, including unconsciousness, and skin defatting
? in the MSDS for products, omission of information on chronic health effects
? inappropriate first aid instruction to induce vomiting if ingested
? inappropriate first aid instruction to give milk if ingested
? omission of first aid instructions to avoid giving oils, milk or alcohol
? omission of Australian exposure standard for trichloroethylene or citing of
the ACGIH or other overseas exposure standards instead of the Australian
exposure standard.
Of the points listed above, the omission on one trichloroethylene MSDS of most
product identification information is of concern. The UN Number, ADG class,
Hazchem code and Poisons Schedule classifications contain information relating
to hazard identification and emergency response and are important for safe
handling.
In the health hazard section, inclusion of the fact that trichloroethylene is
absorbed through the skin is especially important, as it highlights the need to
avoid skin contact, such as through engineering controls, safe work practices or
personal protective equipment. Cardiac effects was another significant health
effect omitted on many of the MSDS, and is the reason that a statement on
avoidance of sympathomimetic drugs is recommended for inclusion in the advice
to doctor section. Many MSDS contained neither a reference to cardiac effects or
a recommendation to avoid sympathomimetic drugs (17 did not have an `advice
to doctor' section at all).
With regard to first aid instructions, it was noted that instructions contrary to the
recommended SUSDP instruction (c), that is, do NOT induce vomiting, were
given on three MSDS for trichloroethylene and eight MSDS for mixtures.
Vomiting creates a risk of aspiration of trichloroethylene into the lungs and while
the presence of other poisons in mixtures may justify an instruction to induce
vomiting, where the dangers of aspiration of trichloroethylene have been weighed
against the dangers of ingestion of another poison, this was not the case in the
cases examined in this survey.
136 Priority Existing Chemical Number 8
Another significant omission in many MSDS was the Australian exposure
standard for trichloroethylene, which should be listed in MSDS for mixtures as
well as trichloroethylene. Listing of overseas exposure standards is allowed
under the MSDS Code only where an Australian standard does not exist. A
number of MSDS listed the ACGIH standard, which happens to be the same
value as the Australian standard, or no standard at all.
Some information on carcinogenicity was provided in six of the seven MSDS for
trichloroethylene and 20 of the MSDS for products. The variation in the
information provided reflects the current uncertainty regarding its carcinogenic
classification.
The need for adequate ventilation and local exhaust ventilation were mentioned in
most MSDS, however none of the MSDS for trichloroethylene contained
recommendations on engineering controls specific to the use of trichloroethylene
in vapour degreasers, such as a reference to the Australian Standard 2661:Vapour
degreasing plant - design, installation and operation - safety requirements
(Standards Association of Australia, 1983). Under the MSDS Code,
recommendations for engineering controls in the `precautions for use' section
should reflect the intended uses and common applications of the chemical.
Vapour degreasing is a major use of trichloroethylene, reflected in the fact that
four of the six MSDS for trichloroethylene specifically mention vapour
degreasing in the `use' subsection, while the two others that contained a `use'
subsection referred to metal degreasing.
The MSDS Code requires that if special requirements for gloves exist to prevent
skin exposure, they should be clearly stated. For instance, `protective gloves'
may not be sufficient in some cases. The assessment of MSDS for
trichloroethylene and trichloroethylene-containing products indicated wide
variation in the type of glove recommended for use. Types recommended
included: nitrile or fluorocarbon (1); PVC (5); PVC or rubber (2); neoprene or
viton (4); neoprene, nitrile or rubber (6); natural rubber (1); PVA, PE, or viton
(3); PVA, PVC or viton (1); viton (2); PVA (10). Some MSDS (14)
recommended the use of gloves but did not specify a type of glove that should be
used, while three MSDS did not mention the use of gloves at all.
14.3.2 Assessment of labels
Introduction
Labels for trichloroethylene and trichloroethylene-containing products were
assessed for compliance with the requirements of the National Code of Practice
for the Labelling of Workplace Substances (the Labelling Code) (National
Occupational Health and Safety Commission (NOHSC), 1994) and the Standard
for the Uniform Scheduling of Drugs and Poisons (the SUSDP) (Australian
Health Ministers' Advisory Council, 1997).
Trichloroethylene is listed in schedule 6 of SUSDP, except when used
therapeutically in which case it is listed in schedule 4. Labelling of domestic end-
use products should comply with the SUSDP labelling requirements.
137
Trichloroethylene
Substances which are covered by the SUSDP but which are packed and sold
solely for industrial use should comply only with the Labelling Code. Products
used industrially and domestically need to comply with both codes, ie the SUSDP
along with additional labelling information in accordance with the Labelling
Code.
A total of 44 labels were assessed, comprising of 8 for (>95%) trichloroethylene
and 36 for trichloroethylene-containing products. Forty one labels, including the
eight for trichloroethylene, were for industrial products. They were screened
solely for compliance with the Labelling Code. One label was for a consumer
product available to the general public and was screened only for compliance
with the SUSDP. Two other products were available to the public but could be
expected to be used in the workplace, so they were screened for compliance with
both the SUSDP and the Labelling Code.
1) Industrial products - compliance with the Labelling Code
Hazardous substances used in the workplace should be labelled in accordance
with the Labelling Code. According to the current List of Designated Hazardous
Substances (National Occupational Health and Safety Commission (NOHSC),
1994) industrial substances containing 1% of trichloroethylene are hazardous.
Current risk and safety phrases are:
? R40 Possible risk of irreversible effects
? R36 Irritating to eyes
? R38 Irritating to skin
Current safety phrases are:
? S23 Do not breathe gas/fumes/vapour spray
? S36/37 Wear suitable protective clothing and gloves
Other requirements are: the presence of the signal word POISON; product name;
details of the amount of trichloroethylene present (exact amounts or ranges);
instructions on the control of leaks, spills or fires; the name and address in
Australia of the supplier and a telephone number where advice can be obtained; a
reference to the MSDS and first aid instructions. The ADG dangerous goods
class label (6.1) and UN Number (1710) for trichloroethylene are also required
under the Labelling Code. Until recently, trichloroethylene was classed as 6.1(b)
and the class label was `Harmful - Stow Away From Foods'. In December 1994,
the UN Committee of Experts on Dangerous Goods decided to eliminate this
class label and replace it with the skull and cross bones diamond, with the word
`Toxic'. The most recent edition of the ADG (Federal Office of Road Safety,
1998) has picked up these changes. Either were considered acceptable for the
purposes of this assessment.
The products intended solely for industrial use all contained >1%
trichloroethylene and the labels (33) were examined for compliance with the
requirements listed above. The results are presented in table 34. Compliance with
some other requirements of the Labelling Code, such as directions for use were
not examined in this assessment.
138 Priority Existing Chemical Number 8
Table 34 - Compliance with the Labelling Code
Requirement prior to this assessment Trichloroethylen Products
e (8) (33)
R40 2/8 13/33
R36 0/8 7/33
R38 0/8 7/33
S23* 8/8 28/33
S36/37 3/8 12/33
- S37 only 3/8 3/33
POISON 7/8 12/33
product name 8/8 33/33
disclosure of ingredient (trichloroethylene) 8/8 29/33
statement of strength (of trichloroethylene) 5/8 10/33
emergency instructions 2/8 7/33
supplier details 8/8 16/33
telephone number 5/8 14/33
reference to MSDS 2/8 9/33
ADG Code (6.1 or 6.1b) 5/8 n/a
UN Number (1710) 8/8 n/a
First aid statements (or equivalent phrases)
a. If poisoning occurs, contact a doctor or 6/8 32/33
Poisons Information Centre.
c. If swallowed, do NOT induce vomiting. Give 6/8 12/33
a glass of water.
d. Avoid giving milk or oils. 5/8 9/33
e. Avoid giving alcohol. 5/8 9/33
f. If skin contact occurs, remove contaminated 6/8 18/33
clothing and wash skin thoroughly.
g. Remove from contaminated area. Apply 6/8 17/33
artificial respiration if not breathing.
s. If in eyes, hold eyes open, flood with water 6/8 20/33
for at least 15 minutes and see a doctor.
*equivalent phrases such as the SUSDP safety phrase `Avoid breathing dust (or)
vapour (or) spray mist' were considered adequate.
n/a=not applicable
Summary
Labels for trichloroethylene:
The majority of labels contained safety phrases S23 and S37, the signal word
POISON, ingredient disclosure and statement of strength, UN Number, and ADG
goods class label. One of the labels had the wrong ADG class label, 6.1(a), and
two had no class label. No labels contained risk phrase R36 or R38, and most did
not contain risk phrase R40, safety phrase S36, emergency procedures, or
reference to the MSDS. Two labels did not have any first aid instructions.
Labels for products:
The majority of labels contained safety phrase S23 and disclosed the presence of
trichloroethylene in the mixture, but did not disclose the proportion of
139
Trichloroethylene
trichloroethylene present. Few contained risk phrases R36, R38 or R40, safety
phrase S36/37, emergency procedure instructions, or reference to the MSDS.
Less than half contained the signal word POISON. In addition, only 16 gave an
Australian supplier's name. First aid instructions relating to ingestion (phrases
`c', `d' and `e') were present on less than half of the labels. Five labels, however,
contained the SUSDP first aid statement `b' "If swallowed and if more than 15
minutes from a hospital induce vomiting, preferably using Ipecac Syrup APF".
This phrase is contrary to that recommended by the SUSDP for trichloroethylene,
and an analysis of the other ingredients in these four mixtures against SUSDP
requirements did not appear to justify the over-ruling of phrase `a'.
2) Domestic products - compliance with SUSDP
Three of the labels provided were for products available to the public and should
be labelled according to SUSDP requirements. The SUSDP requires that where
the concentration of trichloroethylene in a product is 71.5 g/L or 71.5g/kg or
more, the product should display the following safety directions and warning
statement:
? SD1 Avoid contact with eyes
? SD4 Avoid contact with skin
? SD5 Wear protective gloves when mixing or using
? SD8 Avoid breathing dust (or) vapour (or) spray mist
? SD9 Use only in well ventilated area
? WS12 Vapour is harmful to health on prolonged exposure
Products containing less then 71.5 g/L or 71.5 g/kg need only contain statement
`a'.
Some other elements required to be present on labels for all products containing
trichloroethylene (regardless of strength) are: the approved name
`trichloroethylene' and a statement of the quantity or strength; the signal words
and phrases POISON; NOT TO BE TAKEN; KEEP OUT OF REACH OF
CHILDREN; the name of the manufacture or distributor or the brand name or
trade name used exclusively by the manufacturer or distributor. The three labels
were checked for compliance with these requirements. Labels were also checked
for the presence of first aid instructions recommended by the SUSDP for
substances containing trichloroethylene. The results are presented in Table 35.
140 Priority Existing Chemical Number 8
Table 35 -Results of assessment of three labels for compliance
with the SUSDP.
Requirements prior to this Label 1 Label 2 Label 3
assessment
SD1 No No No
SD4 No No No
SD5 No Equivalent Equivalent
SD8 No Equivalent Equivalent
SD9 No No No
WS12 No No No
Approved name No Yes Yes
Statement of strength No No No
POISON No No No
NOT TO BE TAKEN No No No
KEEP OUT OF REACH OF CHILDREN Yes No No
Name of manufacturer/distributor or Yes No No
brand/trade name
First Aid Instructions
a. If poisoning occurs, contact a doctor Yes Equivalent Equivalent
or
Poisons Information Centre. No No No
c. If swallowed, do NOT induce vomiting.
Give a glass of water. No No No
d. Avoid giving milk or oils. No No No
e. Avoid giving alcohol. No No No
f. If skin contact occurs, remove
contaminated clothing and wash skin
thoroughly. No No No
g. Remove from contaminated area. No No No
Apply artificial respiration if not
breathing. No No No
s. If in eyes, hold eyes open, flood with
water for at least 15 minutes and see a
doctor.
Summary
All three labels demonstrated very poor compliance with the SUSDP. Label 1 is
for a product used only for domestic purposes and contains over 60%
trichloroethylene. Labels 2 and 3 were for products used both industrially and
domestically and contained <60% and >90% trichloroethylene respectively.
Labels 2 and 3 are required to comply with the Labelling Code as well as the
SUSDP, and so they were checked for the additional elements required according
to the Labelling Code. It was found that the labels contained risk phrase R40, but
not risk phrases R36 or R38. They contained appropriate safety phrases (S23,
36/37), however they were lacking in emergency instructions, contact telephone
number, and reference to the MSDS.
Discussion of findings
Deficiencies common to labels for pure trichloroethylene and mixtures used
industrially were:
141
Trichloroethylene
? omission of a risk phrase warning of irreversible effects (R40);
? omission of a risk phrase regarding irritation to eyes (R36);
? omission of a risk phrase regarding irritation to skin (R38);
? omission of a safety instruction regarding the wearing of protective clothing
(S36); and
? omission of emergency procedures for clean-up of spills, leaks or fires.
In addition, labels for the mixtures had the following deficiencies:
? omission of safety instruction regarding the wearing of gloves (S37);
? omission of the signal word POISON; and
? omission of details of the amount of trichloroethylene in the mixture.
Compliance with the SUSDP in the case of three products used domestically was
very poor, with most requirements not present.
14.3.3 Education and training
Guidelines for the induction and training of workers exposed to hazardous
substances are provided in the National Commission's National Model
Regulations for the Control of Workplace Hazardous Substances, (the Model
Regulations) (National Occupational Health and Safety Commission (NOHSC),
1994). Under these regulations employers are obliged to provide training and
education to workers handling hazardous substances.
The Model Regulations stipulate that training and induction should be appropriate
for the workers concerned. It is important that each workplace implement a
program that is suitably designed to accommodate the needs of different workers.
Training should be given to the workers at induction and repeated at regular
intervals to reinforce the information. Training and education needs for workers
should be reviewed on a regular basis.
For trichloroethylene, the training program should address:
? acute and potential chronic health effects of trichloroethylene;
? skin absorption potential and skin effects of trichloroethylene following
prolonged exposure;
? explanation of MSDS and labelling of trichloroethylene and trichloroethylene
products; and
? use and maintenance of personal protective equipment.
In addition, training for workers involved in vapour degreasing should include:
? basic plant operation, covering start up procedures, checking cut outs, cooling
and solvent condition, loading, unloading and jigging work and delays in the
freeboard zone;
? procedures to be followed during cleaning of degreasing tanks, particularly
regarding procedures for working in confined spaces when entering the tank
is required.
142 Priority Existing Chemical Number 8
Information obtained for assessment indicates that very few places have written
instructions or formal training for workers. Most of the worksites provide "on the
job" training where the supervisor trains the new employee in the various
activities involved. Only one of the six workplaces visited had a training manual
and operating procedures and the training was repeated every 12 months.
Most importers of trichloroethylene provide technical bulletins which give
information about the specifications of trichloroethylene, it's physical properties
and uses. One importer provides a Product Stewardship Manual for chlorinated
solvents to end users. The manual includes information on precautions for the
safe handling, storage and use of chlorinated solvents including trichloroethylene.
It also includes information on safe work practices to be followed while operating
a degreaser and cleaning of a degreasing tank. These bulletins and manuals may
be used as aids to draw up training programs that would be useful to workers.
14.4 Monitoring and regulatory controls
14.4.1 Atmospheric monitoring
Atmospheric monitoring is not conducted on a regular basis at workplaces in
Australia using trichloroethylene. No monitoring data were available for
worksites engaged in repacking or formulating. Some workplaces conduct air
monitoring on an ad hoc basis during vapour degreasing. The reasons for
conducting monitoring varied from a need to establish base-line monitoring
results following modifications to the degreaser and complaints of solvent fumes
following installation of a new plant to need to improve employee safety.
Under the National Commission's National Model Regulations for the Control of
Workplace Hazardous Substances (National Occupational Health and Safety
Commission (NOHSC), 1994), employers need to carry out an assessment of the
workplace for all hazardous substances, with methodology for the assessment
provided in the Guidance Note for the Assessment of Health Risks Arising from
the Use of Hazardous Substances in the Workplace (National Occupational
Health and Safety Commission (NOHSC), 1994). When the assessment indicates
that the risk of inhalation exposure is significant, atmospheric monitoring should
be conducted to measure trichloroethylene concentrations in the workplace.
Monitoring provides an indication of the effectiveness of the control measures in
place and whether there is a need to improve measures to reduce worker
exposure. Atmospheric monitoring should be repeated if any changes are made
to the process or equipment.
Analytical methods for the measurement of trichloroethylene in air are detailed in
Chapter 6.
14.4.2 Exposure standard
The current Australian occupational exposure standard for trichloroethylene,
reviewed in 1990, is 50 ppm (8 h TWA) with a short term exposure limit (STEL)
for 15 min. of 200 ppm. The National Occupational Health and Safety
Commission's Exposure Standards Expert Working Group concluded in 1990
that studies of industrial situations reported subjective symptoms, such as mild
143
Trichloroethylene
irritation, headache and dizziness at 50 ppm while controlled laboratory studies
reported anaesthetic effects may begin to occur at about 100 ppm and would be
mildly felt at 200 ppm. The STEL is recommended on the basis that it is low
enough to protect against early anaesthetic effects. The documentation states that
these levels should provide a safety margin for preventing other health effects
such as liver toxicity.
Table 36 lists the exposure standards in various countries.
The hazard assessment indicates that:
? the critical effect is renal toxicity;
? the inhalation NOAEL for renal toxicity is 100 ppm and the LOAEL is 300
ppm (these values do not incorporate any safety factor);
? a classification of carcinogen Category 2 is appropriate;
? a classification of mutagen Category 3 is appropriate; and
? trichloroethylene is absorbed through the skin.
Table 36 - Occupational exposure limits
Country TWA STEL Year
adopted
Australia 50ppm 200 ppm for 15 min 1990
Canada
Ontario 50 ppm 200 ppm 1995
British 50 ppm 150 ppm for 15 min 1991
Colombia
France 75 ppm 200 ppm
Germany 50 ppm 250 ppm with a
C maximum duration of 30
min/shift occurring
maximally twice per
work shift.
Netherlands 35 ppm 190 ppm 1992
New Zealand 50 ppm 200 ppm for 15 min 1994
Sweden 10 ppm 25 ppm for 15 min 1993
U.K. 100 ppm, skin notation 150 ppm for 10 min 1993
USA
ACGIH 50 ppm 100 ppm 1992
NIOSH 25 ppm
OSHA 50 ppm 200 ppm 1993
Note: C=pregnancy group C (no reason to fear risk of damage to the developing embryo when
adhering to MAK or BAT values)
144 Priority Existing Chemical Number 8
14.4.3 Biological exposure index
Biological monitoring is the assessment of exposure through measurement of the
chemical or its metabolites in biological specimens. Estimations of
trichloroacetic acid and trichloroethanol in urine and blood are recommended by
ACGIH (ACGIH, 1992) and Germany (Deutsche Forschungsgemeinschaft, 1996)
for biological monitoring of exposure to trichloroethylene. These are non-
specific indicators of exposure to trichloroethylene as they can be metabolites of
other chlorinated ethanes and ethylenes. Methods available for biological
monitoring of trichloroethylene are detailed in Chapter 6 of the report.
The following biological exposure indices to determine exposure to
trichloroethylene have been recommended by ACGIH and Germany.
Germany (1991): Trichloroethanol in blood 5 mg/L at end of exposure
or end of shift.
Trichloroacetic acid in urine 100 mg/L at end of
exposure or end of shift.
ACGIH: Trichloroacetic acid in urine 100 mg/g creatinine at the
(1991-1992) end of shift at the end of the workweek, as an indicator
of integrated weekly exposure to trichloroethylene.
Trichloroacetic acid and trichloroethanol in urine 300
mg/g creatinine with sampling time end of shift at end of
workweek, as an indicator of integrated exposure to
trichloroethylene.
Free trichloroethanol in blood 4 mg/L at end of shift at
end of workweek, as an indicator of recent exposure.
14.4.4 Health surveillance
Health surveillance is not routinely conducted for workers exposed to
trichloroethylene.
Trichloroethylene was reviewed by the National Commission's Expert Working
Group on Health Surveillance in 1993. It was decided not to include
trichloroethylene in Schedule 3 (substances requiring health surveillance) of the
National Model Regulations for the Control of Hazardous Substances (1994) as
atmospheric monitoring was considered adequate to assess worker exposure and
thus health surveillance was not warranted. There is therefore no formal
requirement for health surveillance programs for workers.
Under the National Commission's National Model Regulations for the Control of
Hazardous Substances (1994) health surveillance is required for employees
where the workplace assessment has shown that there is a likelihood of an
identifiable disease or health effect occurring under the particular conditions of
work following exposure to a hazardous substance. The employer is responsible
for providing health surveillance.
145
Trichloroethylene
15. Public Health Assessment
15.1 Public exposure
The NICNAS industry survey revealed that half the users of trichloroethylene
were engaged in metal forming/machining, while a further third of the users were
powdercoating, automotive, aerospace or electrical industries. There is low
potential for public exposure to trichloroethylene during industrial use.
When used in an industrial setting, most trichloroethylene which does not
evaporate during use is recycled by distillation, although small amounts of
trichloroethylene in tank washings may be discharged to sewerage as trade waste.
No public exposure is anticipated from these activities. In domestic use, the
principal fate of the solvent would be evaporation, although some
trichloroethylene may be discharged to sewerage.
Several products containing trichloroethylene were identified as being available
to the public. They comprise two tyre repair products (containing 60 and 90%
trichloroethylene; total sales volume 5 tonnes/yr), a paint stripper (8%
trichloroethylene, sales of 12 tonnes/yr), a component cleaner (100%
trichloroethylene; sales of 1.2 tonnes/yr) and an aerosol waterproofing agent
(containing 70% trichloroethylene, sales of 4 tonnes/yr).
Directions for use were provided for the waterproofing aerosol spray, which is
applied to camping gear, outdoor clothing, ski wear, umbrellas and curtains at the
rate of 400 mL/5m2 fabric. Users of this product would be exposed to
trichloroethylene by inhalation, especially when applying it indoors, with some
potential for dermal exposure. Although no details were provided for the tyre
repair products, component cleaner and paint remover, a similar pattern of
exposure may also be inferred for these products.
15.2 Public health risk assessment
Notwithstanding the large annual import volume of trichloroethylene, the
majority of the solvent is used in industrial processes which would result in
negligible exposure of the public. Similarly, negligible public exposure is
anticipated from activities involving the recycling of trichloroethylene, or
disposal of wastes containing the solvent.
There is potential for exposure of persons using consumer products containing
trichloroethylene, which comprise two tyre repair products, a paint stripper, a
component cleaner and an aerosol waterproofing agent. Exposure would occur
primarily by inhalation, with some dermal exposure possible. Given the nature of
the products, significant airborne concentrations of trichloroethylene could be
achieved if they were used in a poorly ventilated area. However, the pattern of
public exposure would be discontinuous, even among persons who use multiple
products containing trichloroethylene. Provided appropriate precautions are
observed trichloroethylene is unlikely to cause health effects in humans similar to
146 Priority Existing Chemical Number 8
those observed in experimental animals or among persons having prolonged
occupational exposure to trichloroethylene.
Significant short-term exposure of the public could occur after a transport
accident, given the high vapour pressure of the chemical. In such circumstances,
prompt isolation of the spill site could be required to minimise the risk to the
public. However, accidental spills involving the public are expected to be
extremely rare events.
15.3 Conclusions
Trichloroethylene is not expected to present a significant hazard to public health
provided that consumer products containing trichloroethylene are labelled in
accordance with the requirements of the Standard for the Uniform Scheduling of
Drugs and Poisons (Australian Health Ministers' Advisory Council, 1997) and the
instructions on the labels strictly adhered to. There are no objections to the
continued use of trichloroethylene in the intended applications, subject to these
provisions.
147
Trichloroethylene
16. Environmental Assessment
16.1 Introduction
In discussions with the applicants, it was agreed that in view of the published
reviews available on trichloroethylene, only new unpublished data needed to be
provided on environmental fate and toxicity. In the event, no new data were
provided, and this report relies heavily on two available assessment reports, one
from Canada (Government of Canada, 1993), and one from the UK (United
Kingdom, 1996).
At room temperature, trichloroethylene is a volatile, non-viscous liquid. It has a
higher density and lower surface tension than water. In environmental terms,
trichloroethylene is relatively soluble in water. With Log Kow being greater that
2, there is a moderate potential for the chemical to bioaccumulate (Government of
Canada, 1993). However, because of the high volatility of trichloroethylene, the
majority of chemical released would be expected to partition to the atmosphere,
with only negligible amounts partitioning to the water compartment, and very
little (0.01%) to soil (see fugacity modelling section 16.2.3). The chemical is
considered to be surface active (by EEC definition, a chemical has surface
activity when the surface tension is less than 60 mN/m).
16.2 Environmental exposure
16.2.1 Releases
It has been estimated that western European emissions to air due to end-use
(degreasing, adhesives etc.) of trichloroethylene is 60% of total consumption
(ECSA, 1990). The fate of the remaining trichloroethylene is not clear from this
document. It may be incinerated or released into other environmental media, and
it is also possible that it may be recycled. Most uses of trichloroethylene are
dispersive. For the purposes of this assessment, it will be assumed that the total
annual releases to the Australian environment of trichloroethylene will be close to
the net quantity of trichloroethylene consumed.
In Australia, emissions of trichloroethylene may arise during bulk handling,
formulation of trichloroethylene products and from end use. Trichloroethylene
imported in drums is generally transported direct to distributors or end-users, and
except in the case of accidental spillage, no release is likely to occur.
Bulk handling
Imports of bulk trichloroethylene need to be pumped by shoreline from tanks on
board ships to on-shore bulk tanks. It is then transferred into road tankers and
drums, and transported to storage facilities. There is the potential for release
during transfers of trichloroethylene from ship tanks to land tanks, road tankers
and drums. Vapour emissions from openings on bulk storage tanks and from
filling operations at tanker and drum filling stations are controlled by a
148 Priority Existing Chemical Number 8
continuously operating automatic carbon absorption vapour extraction system
that draws air from around hose connections through piping to a central carbon
bed absorption unit.
No information was obtained from the NICNAS industry survey of release during
handling of trichloroethylene. The Environmental assessment section on
trichloroethylene in the UK SIAR (United Kingdom, 1996) has given worst case
emission factors of 0.4% to air and <0.00025% to water from European sources.
Assuming similar figures for Australian conditions, with 300 days per year when
trichloroethylene is handled, on a continental scale around 0.025 kg per day will
be released to water, and 40 kg per day to air.
Reformulation
Reformulation of trichloroethylene into trichloroethylene products is not
extensive in Australia. Around 9 companies reformulate products, and consume a
total of about 222 tonnes per year. Formulation generally involves manual
addition of trichloroethylene through pouring or pumping to mixing vessels from
drums, cold blending in mixing vessels and packing off from vessels to
containers. Due to the relatively simple operations involved in formulation,
release would be marginal and would be expected to be confined to vapour being
released at hose connections or during pouring from drums.
End use
Vapour degreasing is the major use of trichloroethylene in Australia. Companies
responding to the NICNAS survey indicated that the amount of trichloroethylene
lost to the atmosphere ranges from <1% to 100%. For the environmental
assessment section on trichloroethylene in the UK SIAR (United Kingdom,
1996), a figure of 70% release through degreasing operations was used, for which
90% was expected to go to air, and 10% to water. Adopting these figures, release
of trichloroethylene during use as a metal degreaser could be as high as 1,680
tonnes per year. With 300 days handling per year, this equates to a continental
release of 5,040 kg per day to air, and 560 kg per day to water.
Other uses, such as general solvent, hand application and boil dipping could have
a release of up to 100% depending on individual systems. With around 600
tonnes per year going to other uses, all of which is potentially released to the
environment, a further continental release of trichloroethylene of around 1800 kg
per day to air, and 200 kg per day to water could occur.
These release levels are summarised in Table 37 below.
149
Trichloroethylene
Table 37 - Estimates of daily release of trichloroethylene (TCE) Australia
wide.
Situation Daily Estimate of TCE Release to Release to
quantity release Air Water
(kg/day) (kg/day) (kg/day)
Handling of 10,000 0.4% 40 0.025
imported TCE
Vapour 8,000 70% 5,040 560
degreasing
Other uses 2,000 100% 1,800 200
TOTAL 6,880 760
16.2.2 Levels in Australian media
Studies of groundwater contamination around the ICI Botany site at Botany Bay
have registered up to 190 ppm trichloroethylene around the former
trichloroethylene production plant, and up to 360 ppm in surficial sediments in
the same area. Other readings taken from the site, but away from the old
trichloroethylene plant area, show much lower readings. In 1982 the NSW State
Pollution Control Commission (now EPA NSW) collected groundwater samples
from four bores in the north end of the ICI Botany site. Two of these bores had
trichloroethylene present at 5 ppm and 2 ppm, while it was below detection levels
in the other two bores (Woodward-Clyde, 1995).
Investigations by individual states of Australia revealed limited data. The
Australian Capital Territory monitors trichloroethylene in effluent both upstream
and downstream of the Lower Molonglo Sewage Treatment Plant. To date, it has
been measured in November 1995 and February 1996. On both occasions the
concentration was below detection in all three samples (<80 礸/L in November,
and <0.1 礸/L in February). In January 1996, Sydney Water compiled a risk
assessment which included monitoring data for trichloroethylene (among other
chemicals) in 10 coastal sewage treatment plants. In all plants, readings were
below the detection limit of 10 礸/L.
16.2.3 Fate
As previously stated in the introduction, it was agreed with applicants that only
recent unpublished data should be provided in view of the literature reviews
available. No environmental fate data were provided and the following
discussion on environmental fate of trichloroethylene is largely paraphrased from
the Canadian Priority Substances List Assessment Report on Trichloroethylene
(Government of Canada, 1993) with some interpretation for the local situation.
The fate of trichloroethylene released to the environment is influenced by
transport processes, including volatilisation, diffusion and advection, and by
transformation processes, including photo-oxidation and biodegradation.
The level 1 Fugacity Model (as modelled by ASTER, (U.S. Environmental
Protection Agency (USEPA), 1996)) indicates that at equilibrium, 99.64% of
150 Priority Existing Chemical Number 8
trichloroethylene will partition to the atmosphere, 0.35% will partition to water
with the remainder (0.01%) partitioning to soil.
Atmospheric fate
The majority of trichloroethylene is released to the atmosphere, where it may
react with photochemically produced hydroxyl radicals to produce phosgene,
dichloroacetyl chloride, formyl chloride and other degradation products.
Trichloroethylene does not readily undergo chemical oxidation or hydrolysis in
the atmosphere, and direct photolysis is a minor transformation process. The
estimated half-life of trichloroethylene in the atmosphere varies with latitude,
season and concentration of hydroxyl radicals. In Canada, the calculated half-
lives range from 1 day in the south during summer months to several months in
the far north during winter months. Due to the generally warmer conditions in
Australia, half-lives of trichloroethylene in the atmosphere would be expected to
be at the shorter end of the scale. The relatively short atmospheric half-life
generally precludes long-range transport of trichloroethylene and transfer into the
stratosphere. Under certain conditions (eg high winds, cloud cover),
trichloroethylene will undergo short and medium range atmospheric transport.
Trichloroethylene is decomposed in the troposphere (lower atmosphere) and is
not considered to be a significant contributor to either greenhouse warming or
stratospheric ozone depletion (CEFIC, 1986).
Aquatic fate
Contamination of water arises from misuse, improper waste disposal, inadequate
effluent water treatment or incidental spillage caused by improper handling and
storage. The presence of chlorinated solvents in the hydrosphere has been widely
reported, and it has been confirmed that the main contamination has come from
improper waste disposal and spillage (ECSA, 1990). Since trichloroethylene is
denser than water and moderately water-soluble, concentrated or continuous
small discharges to surface and groundwater can lead to the formation of
"puddles". These puddles can represent a chronic source of trichloroethylene
contamination of surface and ground water.
Volatility
Trichloroethylene discharged to surface water can volatilise rapidly from the top
layers, with rates varying according to temperature, water movement and depth,
air movement and other factors. The estimated volatilisation half-lives in shallow
ponds, lakes and running waters are less than 12 days. The measured
volatilisation half-lives for trichloroethylene in experimental marine ecosystems
range from 13 to 28 days.
Other tests have found much shorter half-lives. Geyer et al (1985), determined
the half-life in an aqueous solution at 20癈 to be 18 hours/m depth of solution,
while Dilling (1975) found that the half-life for a stirred water body (initial
trichloroethylene concentration of 1 mg/L) was between 19 and 24 minutes
(United Kingdom, 1996).
151
Trichloroethylene
Degradation
In an aerobic degradation study in seawater, 80% of trichloroethylene was
degraded in 8 days. Photooxidation and hydrolysis are not significant
degradation processes for trichloroethylene in surface waters.
Trichloroethylene does not partition to aquatic sediments to any appreciable
degree, except in sediments with a high organic content. Trichloroethylene may
biodegrade to carbon dioxide in sediment. In one study, methane-utilising
bacteria isolated from sediment reduced the concentration of trichloroethylene
from 630 礸/L to 200 礸/L in 4 days at 20癈.
Soil/groundwater
The majority of trichloroethylene released onto soil surfaces will volatilise to the
atmosphere. Trichloroethylene present in subsurface soil may be transported by
diffusion, advection or dispersion of the pure liquid, as a solute in water, or by
gaseous diffusion throughout the spaces within porous soils. As a result,
trichloroethylene can penetrate the soil and contaminate groundwater.
Trichloroethylene partitions to soil particles of high organic content. Information
on the importance of biodegradation in removing trichloroethylene from
subsurface soil is limited. In one study, no degradation of trichloroethylene by
anaerobic soil microorganisms was detected after 16 weeks; however, aerobic
biodegradation has been demonstrated following artificial nutrient enrichment
and induction. In some subsurface soils, sorption and desorption of
trichloroethylene is slow. Thus, subsurface liquid trichloroethylene may continue
to contaminate groundwater aquifers and soils long after sources have been
eliminated.
In groundwater, biodegradation may be the most important transformation
process for trichloroethylene, although it is usually slow, with half-lives ranging
from months to years, depending on ambient conditions and enhanced
remediation measures. The major products resulting from biodegradation of
trichloroethylene in groundwater are dichloroethylene, chloroethane and vinyl
chloride. High concentrations are frequently observed in contaminated
groundwater where volatilisation and biodegradation are limited, where there are
point sources or where releases are small but continuous over time. Relatively
constant concentrations can therefore exist for decades.
This is demonstrated by the deep and shallow groundwater at the ICI Botany site
in NSW containing trichloroethylene as a result of manufacturing operations on
that site which ceased in 1976. The highest levels of trichloroethylene are found
in sediments (up to 360 ppm) and shallow groundwater (up to 190 ppm) in the
immediate vicinity of the old production plant. Much lower levels of
trichloroethylene have been detected in groundwater (2-5 ppm) and soil (27
ppm), away from the old production plant (Woodward-Clyde, 1995).
Bioaccumulation
Based on its low n-octanol/water partition coefficient and the results of field
studies, trichloroethylene is unlikely to bioaccumulate significantly in aquatic
biota and piscivorous birds. Measured bioaccumulation factors ranged from <3
152 Priority Existing Chemical Number 8
for muscle tissues of marine and freshwater birds to approximately 100 for fish
livers.
16.2.4 Summary
Trichloroethylene will predominantly enter the environment as release to the
atmosphere. The level 1 Fugacity Model indicates that, at equilibrium, 99.64% of
trichloroethylene will partition to the atmosphere, 0.35% will partition to water,
and 0.01% will partition to sediment. Due to the high water solubility, and
relatively small partition co-efficient, trichloroethylene which doesn't partition to
the atmosphere would be expected to be mobile, and largely remain in solution.
Degradation of trichloroethylene is expected to be in the order of days in the
atmosphere and in the aquatic compartment. However, slow degradation of
trichloroethylene in groundwater is likely. In the atmosphere, trichloroethylene
reacts with photochemically produced hydroxyl radicals, and degradation is faster
in warmer atmospheric conditions.
Bioaccumulation of trichloroethylene is unlikely to occur.
16.3 Environmental effects
As stated previously, it was agreed with applicants that only recent unpublished
data should be provided in view of the literature reviews available. No new
ecotoxicological data were provided, and the following discussion comes from a
selection of available literature.
16.3.1 Aquatic organisms
The following ecotoxicological study results have been summarised from the UK
SIAR (United Kingdom, 1996). The discussion in this section is also based on
this reference, except where indicated.
Micro-organisms
Literature values for toxicity of trichloroethylene to microorganisms give a 24 h
E(I)C50 value range from 115 mg/L to 960 mg/L, although an IC50 of 13 mg/L has
been measured for a methanogenic bacteria. Toxicity thresholds for
microorganisms range from 65 to 1200 mg/L.
Algae and aquatic plants
Trichloroethylene has been shown to both inhibit and stimulate the growth of
algae and aquatic plants, depending on species and trichloroethylene
concentration. EC50 values for aquatic plants and algae range from 8 mg/L to 150
mg/L.
Aquatic invertebrates
Toxicity tests for trichloroethylene with aquatic invertebrates have been carried
out, although many of the results are based on nominal concentrations. 48h
L(E)C50 values range from 2.2 mg/L to 132 mg/L. To overcome volatility, two
static tests have been carried out on Daphnia magna and Mysidopsis bahia
153
Trichloroethylene
(mysid shrimp) using sealed containers. These gave a 48h EC50 of 7.8 mg/L and
96h EC50 of 14 mg/L.
A natural pond field experiment in 1981 (conducted in Germany) observed
complete mortality of Daphnia magna in two test ponds within 3 days after
exposure to an initial concentration of 110 mg/L, a concentration much higher
than might be expected, except in a major accident situation. Approximately
70% mortality was observed after 3 days at an initial concentration of 25 mg/L
(the half-life of trichloroethylene in these experiments was 2.7 days). At the end
of the 43 day observation period, the daphnid population had recovered.
However, species richness and abundance of phytoplankton remained severely
depressed at the end of the observation period following exposure to 25 mg/L.
The results of subsequent field studies in natural pond communities indicate that
similar effects occur following continuous exposure to lower concentrations of
trichloroethylene for longer periods of time. For example, exposure to 1.0 to 1.5
mg/L trichloroethylene for 11 weeks caused reductions of up to 70% in the
population of Daphnia pulex (Government of Canada, 1993).
Fish
The toxicity of trichloroethylene to various fish species has been measured with
LC50 values ranging from 16 mg/L to 213 mg/L. Several of the tests are flow-
through tests and the lowest result from these tests is the 96 h LC50 for Jordanella
floridae (American flagfish) of 28.3 mg/L. Chronic toxicity tests on this species
have been carried out and the No Observed Effect Concentration (NOEC) was
5.76 mg/L.
Based on these results, trichloroethylene can be described as practically non-toxic
to microorganisms; moderately to practically non-toxic to aquatic plants, algae
and aquatic invertebrates; and slightly to practically non-toxic to fish.
154 Priority Existing Chemical Number 8
Table 38 - Selected highest toxicity values of trichloroethylene to the
aquatic compartment.
Species Conditions Result (ppm)
Microorganisms
EC50 260
Activated Sludge OECD Guideline 209, activated sludge
respiration inhibition test (S)
Pseudomonas putida 16 h, inhibition of cell multiplication (S; NC) LOEC=65
Aquatic plants/algae
Microcystis aeruginosa 8 d growth rate LOEC=63
(Blue green algae)
Phaeodactylum EC50=8
Photosynthesis
tricornutum (Marine
diatom)
Scenedesmus EC10 46-61
96 h, inhibition of cell multiplication
subspicatus
Selenastrum 96 h, growth rate NOEC 175
capricornutum (Green
algae)
Aquatic invertebrates
Daphnia magna 48 h, EPA-660/3-75-009, age <24 h. (S; NC) EC50=18
NOEC=2.2
Daphnia magna 48 h, age 4-6 days. (S) EC50 =7.8
Mysidopsis bahia (Mysid 96 h, (S; MC) EC50=14
shrimp)
Fish
Limanda limanda LC50=16
96 h (F; NC)
(Flatfish dab)
Oncorhynchus mykiss LC50=42
48 h (S; NC)
(Rainbow trout)
Pimephales promelas 48 h (S; NC) LC50=32-56
(Fathead minnow)
S= Static test; F= Flow through test; NC= Nominal concentration; MC= Measured
concentration.
16.4 Environmental hazards
Through the NICNAS industry survey it is apparent that, a large proportion of
end users of trichloroethylene have their waste trichloroethylene disposed of via a
solvent recycler. Precise figures are not available, however, and as a worst case
scenario, it will be assumed that all trichloroethylene is lost to the environment,
with 90% evaporation to the atmosphere, and 10% discharged to the sewer
system.
155
Trichloroethylene
Formulae from the EC Technical Guidance Document (European Commission, )
have been used to predict an environmental concentration for trichloroethylene in
Australian receiving waters.
The percentage of trichloroethylene in the STP being lost to the atmosphere is
91%, based on the SIMPLETREAT model, calculated by the UK in the SIAR
(United Kingdom, 1996). Therefore, the value of P in the following equations is
0.91.
PEC local(water) = Ceff/(1+Kp(susp).csusp).D
Where:
PEC local(water) predicted environmental concentration (g/L)
=
Ceff = concentration of the chemical in the sewage
treatment plant (g/L)
Kp(susp) = Suspended matter-water adsorption coefficient
(L/kg)
cs u s p = Concentration of suspended matter in receiving
waters (L/kg)
D = Dilution factor.
Ce f f = W.(100-P)/100.Q
Where:
W = emission rate (kg/day)
Q = volume of waste water.
P = percentage removal in the sewage treatment
plant
K p(susp) = a.Focsusp.Kow
Where:
Focsusp = Fraction organic carbon in suspended matter.
Kow = Octanol-water partition coefficient
Assumptions:
1) All trichloroethylene imported into Australia is released
to the environment.
2) 90% is released to the atmosphere, with 10% to
water. All release to water is via the sewage
treatment plant.
3) 300 days per year of trichloroethylene handling,
meaning a daily release of 10 tonnes.
4) In the absence of data, 40% use of trichloroethylene
will be assumed to occur in the Sydney metropolitan
area, equating to a release of 4 tonnes per day. Of
this, 400 kg will be sent to the sewer, which has a flow
of 250 ml per day.
Values:
c susp = 15 mg/L (default value)
D = 10
W = 400 kg/day
Q = 250 ML/day
156 Priority Existing Chemical Number 8
P = 91%
Focsusp = 0.1 (European Commission, 1994)
Kow = 195
a = 0.411 (European Commission, 1994)
Using the above formulae, data and assumptions, the predicted environmental
concentration in receiving waters is 14.4 礸/L (ppb).
These calculations represent a worst case scenario, and assume no degradation of
trichloroethylene by microorganisms in the STP or in receiving waters. The
estimates give a predicted environmental concentration two orders of magnitude
below the lowest toxic level for aquatic organisms being a 48h EC50 = 7.8 ppm
for Daphnia magna. Thus a low aquatic hazard may be concluded.
Because of the relatively short half-life in the atmosphere, trichloroethylene is
thought to make only a minor contribution to global warming. It is unlikely to
reach the stratosphere, and so is not likely to have an effect on stratospheric
ozone. It will not make a significant contribution to photochemical ozone
formation. However, the breakdown product, dichloracetyl chloride, may have
an adverse effect on stratospheric ozone due to its long half-life (United
Kingdom, 1996).
16.5 Conclusions
Based on available data for Australia, it can be predicted that trichloroethylene
will not occur at concentrations potentially harmful to the aquatic environment or
the atmosphere. If groundwater contamination occurs it would be of concern.
There is no manufacture of trichloroethylene in Australia and measures for
handling and storing bulk trichloroethylene are such that, except in the case of a
major spill, future contamination of groundwater is unlikely.
157
Trichloroethylene
17. Overall Conclusions and
Recommendations
17.1 Hazard classification
The recommended classification is based on the following data:
Skin and eye irritant
Results of studies in human volunteers and reports of workers exposed to
trichloroethylene have indicated that trichloroethylene caused burning sensation
of the skin with redness and rashes and burning and irritation of the corneal
epithelium. Studies in animals, not conducted according to accepted test
guidelines, reported skin irritation and corneal abrasions. Based on human
evidence and results of animal studies trichloroethylene meets the classification
for skin and eye irritation.
Mutagenicity
Positive results in tests in somatic cells in vivo such as:
? single strand breaks in rat and mouse liver, kidney, lungs and stomach
(Nelson & Bull 1988, Walles 1986);
? increased number of mutants in cultures from liver and kidneys but not from
lungs in a host-mediated assay in mice (Bronzetti et al (1978);
? positive pink eyed unstable mutation test in mice (Schiestl et al, 1997)
Supported by:
? mutations in VHL tumour suppressor gene in renal cancer cases (Bruning et
al, 1997);
? weak in vitro mutagen; and
? mutagenicity of known metabolites.
Some of the studies have limitations (Schiestl et al, 1997; Bruning et al, 1997)
and these have been noted in the report. However, looking at the overall data, the
results of these studies raise concern regarding possible mutagenic effects of
trichloroethylene.
Carcinogenicity
Currently available data in animals and humans, as follows:
? Well conducted epidemiological studies (Axelson et al, 1994; Spirtas et al,
1991 updated by Blair et al, 1998) have shown no association between
exposure to trichloroethylene and renal cancer under the conditions of these
studies.
158 Priority Existing Chemical Number 8
? However another well conducted study (Antilla et al, 1995) provided limited
evidence of an association between cancer and trichloroethylene exposure.
? Studies by Henschler et al (1995) and Vamvakas et al (Deutsche
Forschungsgemeinschaft, 1996) have indicated an association between renal
cancer in workers exposed to trichloroethylene.
? Bruning et al (1997) in a preliminary study demonstrated that
trichloroethylene caused somatic mutations of the VHL tumour supressor
gene in renal cancer cases and concluded that a linkage existed between
exposure to trichloroethylene and somatic mutation of the VHL gene.
? Bruning et al (1996b) also reported renal tubular damage in patients who had
been diagnosed with renal cell carcinoma and had undergone nephrectomy.
? Kidney tumours observed in rats along with cytotoxicity.
Although it is noted that some of the the human studies provide limited data and
have several methodological weaknesses, the findings in humans are supported
by evidence in experimental animals, with tumours observed at the same site and
the mechanism yet to be elucidated. Renal cytotoxicity has been observed in rats,
however the mechanism is not clear.
Overall, for mutagenicity and carcinogenicity, the pattern of results observed is
consistent with a chemical which is a weak mutagen and a weak carcinogen.
Overseas consideration and expected new data
The European Union (EU) is also considering the classification of
trichloroethylene. The EU Specialised Experts Group considered the mutagenic
and carcinogenic potential of trichloroethylene at their meeting in June 1997.
For mutagenicity the Group considered that:
? trichloroethylene was an in vitro mutagen;
? the results from the in vivo studies were however, less clear;
? based on the current data trichloroethylene could not be classified as a
Category 3 mutagen.
? further data was required to clarify in vivo mutagenic potential. As
trichloroethylene was under the Existing Substances Risk Assessment
Regulations (ESR) where additional studies can be requested, the Specialised
Experts recommended that the Kligerman micronucleus study be repeated
with some modifications. This was subsequently agreed by the superior EU
body as the basis on which the EU will determine whether to classify
trichloroethylene as a category 3 mutagen (a positive result to result in
classification). The EU also noted other data in generation.
For carcinogenicity, a majority of the Specialised Experts recommended that:
? trichloroethylene be classified as carcinogen category 2; R45 on the basis of
clear data in one animal species (rat) with supportive evidence from
epidemiology and genotoxicity studies;
159
Trichloroethylene
? the mechanisms of action, particularly for the liver and kidney tumours,
needed to be further elucidated to show that these tumours were not of
relevance to humans.
The Specialised Experts recommended that as the genotoxicity of
trichloroethylene was still in doubt it should be treated as a genotoxic carcinogen
until proven otherwise and thresholds should not be anticipated to exist for cancer
effects.
The above reflects the EU status as advised to NICNAS at the time of preparing
this report. EU consideration of trichloroethylene has not been finalised.
During the final stages of preparation of this report, one applicant advised that
additional laboratory work relevant to the question of mutagenicity and renal
effects was expected to be completed by September 1998 (Dow Chemical,
personal communication).
Recommendation on classification
Considering the available information and that further data are being generated,
the following recommendations are made to the National Occupational Health
and Safety Commission.
Recommendation 1:
The recommended classification for trichloroethylene based on the hazard
assessment of currently available data and in accordance with the National
Commission's Approved Criteria for Classifying Hazardous Substances
(National Occupational Health and Safety Commission (NOHSC), 1994) is:
Skin and eye irritant (Risk phrase R36/38 Irritating to eyes and skin);
Mutagen - category 3, ie substances which cause concern for humans
owing to possible mutagenic effects, but in respect of which available
information does not satifactorily demonstrate heritable genetic damage
(Risk phrase R40 (M3) May cause heritable genetic effect);
Carcinogen - category 2, ie substances regarded as if they are
carcinogenic to humans (Risk phrase R45 May cause cancer).
Products or mixtures containing 0.1% or more of trichloroethylene should also be
classified as hazardous.
Recommendation 2:
The draft report was completed in May 1998 and included the following
Recommendation:
On the basis that further data relevant to the classification is expected to be
available prior to the end of 1998, it is recommended that the NOHSC Hazardous
Substances Sub Committee consider the timing of their adoption of the revised
classification into the Designated List of Hazardous Substances to allow this
additional information to be considered. Any period allowed for consideration of
further data should be limited. Such data would require secondary notification
and assessment by NICNAS.
160 Priority Existing Chemical Number 8
The hearing by the Administrative Appeals Tribunal was held in November
1999 and all the data available up to the hearing was considered by the AAT.
The above recommendation should therefore be disregarded.
Risk Phrase R65 ?Harmful: May cause lung damage if swallowed. The draft
Approved Criteria for Classifying Hazardous Substances ?Revised Edition
(1998) includes a new risk phrase R65 ?Harmful: May cause lung damage if
swallowed. This risk phrase applies to aliphatic, alicyclic and aromatic
hydrocarbons in total concentrations equal to or greater than 10% satisfying
certain criteria. From the data currently available to NICNAS it is not possible to
consider the applicability of this risk phrase for trichloroethylene.
Recommendation 3:
Any information relating to the criteria needs to be provided under the secondary
notification provision of the Industrial Chemical (Notification and Assessment)
Act 1989 (section 18).
17.2 Control measures
Trichloroethylene is a hazardous substance with carcinogenic and irritancy
potential. In accordance with the National Commission's National Code of
Practice for the Control of Workplace Hazardous Substances (National
Occupational Health and Safety Commission (NOHSC), 1994) exposure to
hazardous substances should be prevented and where this is not practicable
control measures should be implemented to minimise risks to health. Control
measures should be implemented in accordance with the hierarchy of controls
which is a list of control measures, in priority order, that can be used to eliminate
or minimise exposure to hazardous substances. In some circumstances it may be
appropriate to use two or more control measures to reduce exposure to as low a
level as is practicable.
Trichloroethylene can be absorbed through the lungs and skin and control
measures should minimise exposure through these routes.
17.2.1 Elimination
In the hierarchy of control measures elimination is the first option to be
considered to minimise health risks. Elimination is the removal of all chemicals
from the process. For example, elimination may occur through a modification of
the manufacturing process of the metal parts removing the need for cleaning.
17.2.2 Substitution
Where elimination of chemicals from the process is not practicable, substitution
with a less hazardous substance or method of application should be considered.
Recommendation 4:
It is recommended that greater research and development be directed to substitute
processes and non-hazardous substances.
161
Trichloroethylene
Other Uses
A number of alternative options are now available. Endusers should review their
processes and the alternatives available before replacing trichloroethylene in the
process.
Cold Cleaning
Most manufacturers do not support the use of trichloroethylene in cold cleaning.
This assessment confirms this use is associated with a high and unacceptable risk.
Recommendation 5
It is therefore recommended that trichloroethylene not be used in cold cleaning,
with this use phased out over a period of two years.
Information on solvent substitution is available on the Internet, for example, the
Solvent Alternatives Guide (SAGE) and the Hazardous Substances Solvent
Substitution Data System (HSSDS).
Products in aerosol form
Recommendation 6:
It is recommended that trichloroethylene not be used in industrial aerosol product
form, due to the high and unacceptable risk identified in this assessment.
17.2.3 Engineering controls
Formulation
Recommendation 7:
It is recommended that all stages of the formulation process, transfer, mixing and
packaging, be enclosed. Transfer of trichloroethylene to the mixing tank and
emptying of the tank into containers through closed pipelines will minimise
emission of vapours. It is recommended that local extraction ventilation be
installed above the mixing tank to remove any fugitive emissions. The area
around the mixing tank should be bunded to contain any large spills.
Vapour degreasing
Recommendation 8:
To control worker exposure during vapour degreasing it is recommended that the
vapour degreasing tank must conform to the requirements of the Australian
Standard AS 2661 - 1983 (Standards Association of Australia, 1983).
Based on past experiences, the following engineering controls have been
identified as important.
162 Priority Existing Chemical Number 8
ENGINEERING CONTROLS
? Local exhaust ventilation. The exhaust ventilation should be
installed to prevent any agitation of the solvent surface or vapours
which will result in vapour being drawn out of the tank;
? Modification of old degreaser tanks (including rim ventilation) to
include the controls recommended in AS 2661 - 1983 as they limit
emission into the environment and therefore worker exposure. This
would also reduce solvent requirement because of reduced loss
resulting in economic benefit
? fitting of roller or sliding doors below the rim ventilation to prevent
escape of vapours into the atmosphere. Covers should be used
when the tank is in use and when idling; and
? use of an overhead lifting device to immerse and remove parts at a
controlled rate. This eliminates excess loss and also keeps the
operator away from the degreaser
Cold cleaning
Use of trichloroethylene in cold cleaning is not supported by this assessment.
Appropriate engineering controls such as local exhaust ventilation must be used
to minimise exposure, while use is phased out.
Trichloroethylene products
Use of industrial trichloroethylene products in aerosol form is not supported by
this assessment. Local exhaust ventilation will help to minimise exposure of
workers to other trichloroethylene products.
17.2.4 Safe work practices
Recommendation 9:
Safe work practices are critical in keeping solvent emissions to a minimum. Safe
practices that help to minimise emissions are detailed below and must be
followed.
163
Trichloroethylene
SAFE WORK PRACTICES
? location of the degreaser tank (it should be located away from
draughts such as open windows or doors) (Standards Association
of Australia, 1983);
? keeping tanks closed when in use and idling (Standards
Association of Australia, 1983);
? minimising turbulence during lowering of the workload into the
tank by reducing the rate of introduction (Standards Association of
Australia, 1983);
? proper placement of the parts to be degreased in the basket thus
avoiding solvent collecting in the parts;
? sufficient time in the freeboard zone to allow adequate
draining/drying time (Standards Association of Australia, 1983);
? routine equipment inspections to locate leaks or any other
problems (Standards Association of Australia, 1983);
? avoiding splashes or spills during solvent filling, draining or
transfer operations;
? prompt clean up of spills;
? All ignition sources should be eliminated in areas where high
concentrations of vapour may accumulate;
? frequent cleaning of the tank to prevent buildup of caked material
at the bottom (Standards Association of Australia, 1983). Regular
maintenance will reduce the need for entry into the tank during
cleaning;
? the requirements of AS 2865-1995 "Safe Working in a Confined
Space" (Standards Australia, 1995) should be conformed to if entry
into a tank is necessitated for cleaning purposes. A number of
fatalities have been reported when people have entered tanks to
clean them.
17.2.5 Personal protective equipment
Personal protective equipment (PPE) is used to minimise exposure or contact to
chemicals. PPE should be used in conjunction with other engineering controls
and not as a replacement.
Protective gloves help to prevent dermal exposure to trichloroethylene. It is
important to select gloves that are resistant to the chemical exposed and are
appropriate for the duration of exposure. If swelling of the gloves occurs they
should be discarded.
164 Priority Existing Chemical Number 8
Recommendation 10 :
It is recommended that when selecting gloves the manufacturers and suppliers
information be used as gloves made of the same generic material can differ due to
differences in manufacture. For formulated products, gloves should be selected
on the basis of the component with the shortest breakthrough time. Protective
gloves should be used when skin contact with trichloroethylene is likely, such as
during loading and unloading of work parts from the vapour degreaser, during
cold cleaning, clean up of spills or during other work processes where splashes
are likely.
Protective clothing which includes protection of the arms, legs and feet should be
worn where exposure of trichloroethylene may occur. Eye protection is
recommended when vapours may be generated or when splashing may occur.
Personal protective equipment should be in accordance with the relevant
Australian standards.
If cleaning of degreaser tanks involves entry into the tank respiratory protection is
required. A suitable supplied-air respiratory protective device complying with
AS/NZS1716 (Standards Australia & Standards New Zealand, 1994) should be
worn.
17.3 Hazard communication
Trichloroethylene is a hazardous chemical and employers are obliged to provide
employees with MSDS, training on the proper use of trichloroethylene and
information on the health hazards of the chemical and ensure that all containers
used at work are adequately labelled.
17.3.1 MSDS
Recommendation 11:
It is recommended that suppliers significantly improve and amend their MSDS
where necessary in order to rectify deficiencies identified in the assessment.
17.3.2 Labels
A large number of deficiencies were identified in the labels provided for
assessment.
Consumer Products
The labels on products available for domestic use did not comply with the
requirements of the SUSDP, (Australian Health Ministers' Advisory Council,
1997) which is a legal requirement under State and Territory legislation.
Recommendation 12:
It is recommended that suppliers review their labels as a matter of urgency and
comply with the requirements of SUSDP:
Safety directions
165
Trichloroethylene
? SD1 Avoid contact with eyes
? SD4 Avoid contact with skin
? SD5 Wear protective gloves when mixing or using
? SD8 Avoid breathing dust (or) vapour (or) spray mist
? SD9 Use only in well ventilated area
? WS12 Vapour is harmful to health on prolonged exposure
First aid instructions
? If poisoning occurs contact a doctor or Poisons Information Centre.
? If swallowed do not induce vomiting. Give a glass of water.
? Avoid giving milk or oils.
? Avoid giving alcohol.
? If skin contact occurs, remove contaminated clothing and wash skin
thoroughly.
? Remove from contaminated area. Apply artificial respiration if not breathing.
? If in eyes, hold eyes open, flood with water for at least 15 mins and see a
doctor.
In addition other elements that are required to be on the label are:
? the signal word POISON;
? phrases KEEP OUT OF REACH OF CHILDREN; NOT TO BE TAKEN;
and
? percentage of trichloroethylene in the product.
Industrial Products
Substances used industrially need to comply with the requirements of the
NOHSC National Code of Practice for the Labelling of Workplace Substances
(National Occupational Health and Safety Commission (NOHSC), 1994).
Recommendation13:
It is therefore recommended that, where necessary, labels of industrial products
be amended to include:
? risk phrases
? safety phrases
? emergency procedures;
? details of the amount of trichloroethylene present (exact amount or ranges);
and
? reference to MSDS.
Products or mixtures containing 0.1% or more of trichloroethylene should be
classified as hazardous and labelled in accordance with the Labelling Code.
166 Priority Existing Chemical Number 8
17.3.3 Training and education
Recommendation 14:
Workers potentially exposed to trichloroethylene should be provided with
training in the safe handling of the chemical. Workers should be aware of the
health hazards of the chemical.
For trichloroethylene, the training program should address those aspects detailed
below.
CONTENT OF TRAINING PROGRAMS
? acute health effects of trichloroethylene;
? chronic health effects of trichloroethylene;
? skin absorption potential and skin effects of trichloroethylene
following prolonged exposure;
? explanation of MSDS and labelling of trichloroethylene and
trichloroethylene products; and
? use and maintenance of personal protective equipment.
In addition, training for workers involved in vapour degreasing should include
? basic plant operation, covering start up procedures, checking cut
outs, cooling and solvent condition, loading, unloading and jigging
work and delays in the freeboard zone;
? procedures to be followed during cleaning of degreasing tanks; and
? procedures to be followed during clean up of spills.
Training should be given to the workers at induction and repeated at regular
intervals to reinforce the information. Training and education needs for workers
should be reviewed on a regular basis. Guidelines for the induction and training
of workers are provided in the NOHSC National Model Regulations and Code of
Practice for the Control of Hazardous Substances (NOHSC, 1994)
17.4 Exposure standard
Recommendation 15:
It is recommended to NOHSC that the present occupational exposure standard for
trichloroethylene of 50 ppm TWA be reviewed noting:
? the critical effect is renal toxicity;
? the inhalation NOAEL for renal toxicity is 100 ppm, the LOAEL is 300 ppm.
These values do not include a margin of exposure (uncertainty factor);
? a classification of carcinogen Category 2 has been recommended;
? a classification of mutagen Category 3 has been recommended; and
167
Trichloroethylene
? trichloroethylene is readily absorbed through the skin.
? recent monitoring data indicate that exposures around the current
occupational exposure standard (TWA) or even higher are occurring at
workplaces; and
? the monitoring data included and other relevant information included in this
assessment report.
17.5 Public health protection
Trichloroethylene is not expected to present a significant hazard to public health
provided that consumer products containing trichloroethylene are labelled in
accordance with the requirements of the Standard for the Uniform Scheduling of
Drugs and Poisons (Australian Health Ministers' Advisory Council, 1997) and the
instructions on the labels strictly adhered to (See Section 17.3.2).
During preparation of this report, it was noted that the lowest oral LD50 value for
trichloroethylene in rats is 4900 mg/kg bw (IPCS (International Programme on
Chemical Safety), 1985).
Recommendation 16:
It is therefore recommended that the T-value for trichloroethylene in Appendix E
Part 2 of the SUSDP, be revised from 715 to 490.
There are no objections to the continued use of trichloroethylene in the indicated
applications, subject to the above provisions.
If the conditions of use are varied, greater exposure of the public to the product
may occur. In such circumstances, further information may be required to assess
the hazards to public health.
17.6 Environmental protection
Recommendation 17:
Solvents such as trichloroethylene should not be allowed to contaminate either
surface water or ground water. The residue obtained following distillation of the
used solvent, in the form of a highly concentrated final waste, should be disposed
of by a licensed contractor.
17.7 Further studies
There is a large body of literature on trichloroethylene, however, some gaps
identified in the database for trichloroethylene are:
? the mechanism of action of carcinogenicity in kidneys (to elucidate the
relevance of these tumours to humans);
? methodical studies with `pure' trichloroethylene in systems that detect a point
mutation end point;
? information to estimate the skin absorption rate of trichloroethylene in
humans (to provide a better estimate of skin absorption);
168 Priority Existing Chemical Number 8
? information relating metabolism of trichloroethylene in humans to that in rats
and mice (to determine the most appropriate model for humans. Differences
in metabolism across species may account for the different outcomes in
cancer studies in rats and mice. Additionally saturation of metabolism at
high doses is postulated to occur in humans but sufficient data is lacking);
and
? studies on the developmental neurotoxicity of trichloroethylene in animals (as
a series of oral studies from a laboratory have indicated that trichloroethylene
may produce developmental neurotoxicity);
? data on the fate and persistence of trichloroethylene released into Australian
groundwater, sediments and subsurface soils, including any sites
contaminated with this substance, other than Orica Botany, would enable a
more complete evaluation of the potential environmental hazard of
trichloroethylene in Australia.
169
Trichloroethylene
18. Secondary Notification
Under section 65 of the Act, the secondary notification of a chemical may be
required if there has been a change in circumstances which warrants a
reassessment of any of the hazards of the chemical.
In the case of trichloroethylene, a secondary notification may be required if
significant new information about its health and/or environmental effects
becomes available, for example new data on the mutagenic or reproductive
effects of trichloroethylene.
Notification will also be required if trichloroethylene is used in wool scouring or
any other new use resulting in a significant increase in the quantities imported
into Australia.
170 Priority Existing Chemical Number 8
APPENDIX 1
OCCUPATIONAL EXPOSURE CALCULATIONS
1. Formulae for exposure calculations
A total internal dose, (D) that is an estimated human dose, is the sum of the doses
resulting from absorption of vapours (Dv) and dermal absorption of liquid (Ddl).
D = Dv + Ddl
Vapour absorption (Dv) comprises of inhalation absorption across the lungs (Div) plus
dermal absorption of vapours (Ddv).
Dv = Div + Ddv
However, as dermal absorption of trichloroethylene vapour is negligible, only inhalation
absorption is considered in this assessment. Therefore, for trichloroethylene D = Div + Ddl
Exposure to vapours
The dose arising from the inhalation of vapours (Div) is as follows:
Div in=C識譋譈 mg/kg/day
BW
C=concentration of substance in air (mg/m3)
Where
R=inhalation rate (m3/h)
E=exposure duration = h/day days/yr
365 days/yr
B=bioavailability of vapours across the lungs (1=100%)
BW=average body weight of worker (kg)
Bioavailability (B) is the proportion of inhaled substance absorbed through the lungs.
After inhalation of trichloroethylene, 40 to 70% of the administered dose is metabolised
with the rest being exhaled (IARC, 1995). The default value used often in international
assessments is 0.75 (75%) and as the values for trichlorethylene are similar, a value of
0.75 was used for this assessment.
For consistency with international assessments, a value of 1.3 m3/h was used for the
inhalation rate (R) for occupational exposure during light work activities (OECD, 1993;
European Commission, 1994) and a value of 70 kg was used for body weight (BW).
The exposure duration (E), that workers may be potentially exposed to trichloroethylene,
during the various activities were obtained from responses to questionnaires.
171
Trichloroethylene
Exposure to liquid
The daily total dose from liquid exposure (Ddl) is calculated as follows:
Ddl = W x S x A x E x F mg/kg/day
BW
W = weight fraction of substance in product, eg., 0.1 for a 10% solution
S = skin absorption rate (mg/cm2/h)
A = skin surface area exposed (cm2)
E = exposure duration = h/day x days/yr
365 days/yr
F = skin contact time (as fraction of exposure duration, e.g. 0.2 for 20% of time).
BW = average body weight of worker (kg)
For skin absorption rate, no human data either in vivo or in vitro using human tissue were
available. The skin absorption rate (0.32 mg/cm2/h) used in the calculations was derived
from an experiment in hairless guinea pigs (Bogen et al, 1992)(see Section 9).
For skin surface area (A) standard area estimates for the adult male include the following
standard US EPA values (in cm2):
arms 2280
upper arms 1430
forearms 1140
hands 840
head 1180
For calculation purposes, dermal exposure was considered to reasonably consist of no
more than exposure to both hands (840 cm2) or a hand and a forearm (990 cm2). For
consistency, a value of 1000 cm2 was considered appropriate for dermal exposure
estimates.
Liquid trichloroethylene can be in contact with the skin for various fractions (F) of the
exposure duration (E) so skin contact can be extensive, intermittent or incidental.
Extensive dermal exposure is taken as continuous contact (F=1) with the skin. Taking
into account assumptions made in the UK EASE* (Estimation and Assessment of
Substance Exposure) model for dermal exposure, intermittent exposure is taken as being
skin contact for 20% of the time (F=2), and incidental exposure as skin contact for 1% of
the time (F=0.01).
* The EASE model is the second version of the knowledge based electronic system in
development by the UK Health and Safety Executive (HSE), and was formerly called
EES (Exposure Expert System).
172 Priority Existing Chemical Number 8
2. Calculations for various scenarios
2.1 Formulation
Exposure to vapours
Dv = C mg/m3 x 1.3 m3/h x 0.75 x (E h/day x days/yr)
70 kg x 365
Exposure time (E) during the formulation process was assumed to be 4 h/day, 30 days/yr
from the information provided in the NICNAS survey.
Dermal exposure to liquid
Skin contact is assumed to be incidental (F=0.01)
Area of skin exposed assumed to be a hand and forearm (1000cm2)
Ddl = W x 0.32 mg/cm2/h x 1000 cm2 x 4 h x 30 days x 0.01
70 365 days
Concentration ranges for formulated products were <10%, 10-80%, 10->60% and 60-
90%. Dermal exposure estimates were based on formulation of products containing 90%
trichloroethylene (W = 0.9)
Combined inhalational and dermal exposure
The combined inhalational and dermal exposure estimates for formulation for the various
scenarios are tabled below.
Table 1 - Combined inhalational and dermal exposure during
formulation of product containing 90% trichloroethylene
C Daily dose (mg/kg/day)
mg/m3 Dv Ddl Dv+Ddl
ppm
10 54.6 0.25 0.013 0.26
30 163.8 0.75 0.013 0.76
50 273 1.25 0.013 1.26
C = concentration of trichloroethylene in air (mg/m3)
Dv = dose resulting from absorption of vapours
Ddl = dose resulting from dermal absorption of liquid
173
Trichloroethylene
2.2 Vapour degreasing
The combined inhalational and dermal uptakes for exposures during vapour degreasing
were calculated as for formulation except that exposure time (E) was assumed to be 8
h/day for 200 days/yr. The equations used for inhalation and dermal exposure were:
Dv = C mg/m3 x 1.3 m3/h x 0.75 x (8 h/day x 200 days/yr)
70 kg x 365
Ddl = W x 0.32 mg/cm2/h x 1000 cm2 x 8 h/day x 200 days x 0.01
70 365 days
W = 1 as 100% trichloroethylene is used.
Table 2 - Combined inhalational and dermal exposure during
vapour degreasing
C Daily dose (mg/kg/day)
mg/m3
ppm Dv Ddl Dv+Ddl
10 54.6 3.3 0.2 3.5
30 163.8 10.0 0.2 10.2
50 273 16.7 0.2 16.9
C = Concentration of trichloroethylene in air (mg/m3)
E = duration of exposure (h/day)
Dv = Dose resulting from inhalation absorption of vapours
Ddl = Dose resulting from dermal absorption of liquid
2.3 Cold cleaning
The combined inhalational and dermal uptakes for exposures during cold cleaning were
calculated as for vapour degreasing with exposure time (E) being 8 h/day for 200 days/yr
as these were the scenarios encountered in the project commissioned by NICNAS.
Dermal exposure was assumed for 5% of the total time. The equations used for inhalation
and dermal exposure were:
Dv = C mg/m3 x 1.3 m3/h x 0.75 x (8 h/day x 200 days/yr)
70 kg x 365
Ddl = W x 0.32 mg/cm2/h x 1000 cm2 x 8 h/day x 200 days x 0.01
70 365 days
W = 1 as 100% trichloroethylene is used.
174 Priority Existing Chemical Number 8
Table 3 - Combined inhalational and dermal exposure during cold
cleaning for 8 h/day, 200 days/yr
C Daily dose (mg/kg/day)
mg/m3
ppm Dv Ddl Dv+Ddl
0.4 2.18 dip cleaning 0.13 1.0 1.13
3.8 20.75 rag wiping 1.27 1.0 2.47
68.3 372.92 rag wiping 22.77 1.0 23.97
0.9 4.91 dip cleaning 0.29 1.0 1.29
and rag wiping
7.5 40.95 dip cleaning 2.5 1.0 3.5
and rag wiping
C = Concentration of trichloroethylene in air (mg/m3)
E = duration of exposure (h/day)
Dv = Dose resulting from inhalation absorption of vapours
Ddl = Dose resulting from dermal absorption of liquid
Exposure during cold cleaning was also estimated for a scenario of 120 days/yr as the
industry survey indicated that at some worksites trichloroethylene is used 2-3 days/week.
Table 4 -Combined inhalational and dermal exposure during cold cleaning for 8
h/day, 120 days/yr
C Daily dose (mg/kg/day)
mg/m3
ppm Dv Ddl Dv+Ddl
0.4 2.18 dip cleaning 0.079 0.60 0.68
3.8 20.75 rag wiping 0.76 0. 60 1.36
68.3 372.92 rag wiping 13.66 0. 60 14.26
0.9 4.91 dip cleaning 0.179 0. 60 0.78
and rag wiping
7.5 40.95 dip cleaning 1.5 0. 60 2.1
and rag wiping
2.4 Trichloroethylene products
The combined inhalational and dermal uptakes for exposures during use of
trichloroethylene products were calculated as for vapour degreasing with exposure time
(E) being 8 h/day for 200 days/yr as these were the scenarios encountered in the project
commissioned by NICNAS. The equations used for inhalation and dermal exposure
were:
Dv = C mg/m3 x 1.3 m3/h x 0.75 x (8 h/day x 200 days/yr)
70 kg x 365
Ddl = W x 0.32 mg/cm2/h x 1000 cm2 x 8 h/day x 200 days x 0.01
70 365 days
W varied depending on the concentration of trichloroethylene in the products used at the
various sites.
175
Trichloroethylene
Table 5 - Combined inhalational and dermal exposure during use of
trichloroethylene products
C Daily dose (mg/kg/day)
mg/m3
ppm Dv Ddl Dv+Ddl
35% product spray painting
0.7 3.82 0.23 0.07 0.3
4.8 26.21 1.6 0.07 1.67
20% product rag wiping
3.8 20.75 1.27 0.04 1.31
4.1 22.38 1.6 0.04 1.64
90% product brushing on
2.5 13.65 0.83 0.18 1.01
C = Concentration of trichloroethylene in air (mg/m3)
E = duration of exposure (h/day)
Dv = Dose resulting from inhalation absorption of vapours
Ddl = Dose resulting from dermal absorption of liquid
176 Priority Existing Chemical Number 8
APPENDIX 2
SAMPLE MATERIAL SAFETY DATA SHEET
Page x of Total y
Date of Issue
Trichloroethylene is considered hazardous according to the criteria of
Worksafe Australia
COMPANY DETAILS
Company Name:
Address:
Telephone Number:
Emergency Telephone Number:
Telex and Fax Numbers:
IDENTIFICATION
Chemical Name: Trichloroethylene
Other Names: 1,1,2-Trichloroethylene
1,1-Dichloro-2-chloroethylene
Ethylene trichloride
Acetylene trichloride
Ethinyl trichloride
Manufacturer's Product Code:
UN Number: 1710
Dangerous Goods Class: 6.1 Toxic
Subsidiary Risk: None
Hazchem Code: 2Z
Poisons Schedule Number: 6
Packaging Group: III
Use: As a solvent mainly in degreasing operations.
177
Trichloroethylene
Page x of Total y
Date of Issue
PHYSICAL DESCRIPTION/PROPERTIES
Appearance: clear colourless liquid
Odour: chloroform like odour
Boiling Point: 86.7癈
Vapour Pressure: 77 hPa
Density: 1.465 g/mL
Flashpoint: Not relevant
Flammability Limits: 8.0-10.5% at 25癈
Solubility in Water: 1.07 g/L at 20癈
OTHER PROPERTIES
Reactivity: in contact with hot metals, such as magnesium and aluminium at
very high temperatures (300-600癈) it decomposes readily to form
phosgene and hydrogen chloride. Such conditions are seen in areas
where arc welding occurs next to degreasing operations.
Aluminium is more reactive than magnesium.
in the presence of strong alkalis such as sodium hydroxide,
dichloroacetylene is formed which is explosive and flammable.
Autoignition Temperature: 410癈
Decomposition Temperature: >125癈
INGREDIENTS
Chemical Entity CAS Number Proportion
Trichloroethylene 79-01-6
178 Priority Existing Chemical Number 8
Page x of Total y
Date of issue
HEALTH HAZARD INFORMATION
HEALTH EFFECTS
Acute
Inhalation: Vapour is irritant to the upper respiratory tract. Inhalation of
vapour can result in headache, dizziness and confusion with high doses causing
narcosis. Exposure to high doses may cause irregular heart beats.
Swallowed: Swallowing may cause nausea, vomiting, headache and confusion.
Ingestion of larger volumes (>50 ml) can cause central nervous system depression
and effects on the heart. The main cardiac effects are increase in heart rate and
irregular heartbeats.
Eye: Irritant to the eyes. Liquid and vapour can produce corneal damage.
Skin: Severe skin irritant. Repeated skin exposure can cause defatting of the
skin and reddening. Liquid can be absorbed through the skin.
Chronic
Repeated exposure can cause central nervous system disturbances such as vertigo,
dizziness, headaches, memory loss and impaired ability to concentrate.
Hearing loss, liver and kidney damage have been reported in rats.
Repeated or prolonged exposure in animals caused liver and lung tumours in mice
and kidney tumours in rats.
FIRST AID
Inhaled: Remove person from exposure - avoid becoming a casualty.
Remove contaminated clothing and loosen remaining clothing.
Allow patient to assume most comfortable position and keep warm.
If breathing stops artificial respiration to be given by trained
personnel. Keep at rest until fully recovered. Seek medical advice.
Eye: Immediately irrigate with copious quantities of water for at least 15
minutes. Eyelids to be held open. Seek immediate medical
assistance.
Skin: Wash contaminated skin with plenty of water. Remove
contaminated clothing and wash before re-use. Seek medical
assistance if irritation persists.
Swallowed: Rinse mouth with water. Give water to drink, avoid giving milk,
oils or alcohol. Do not induce vomiting. If person is losing
consciousness do not give anything by mouth. Seek immediate
medical assistance.
179
Trichloroethylene
Page x of Total y
Date of Issue
ADVICE TO DOCTOR
Treat symptomatically. Avoid sympathomimetic amines as they may cause
cardiac arrhythmias.
PRECAUTIONS FOR USE
Exposure Standards: Trichloroethylene 50 ppm TWA
200 ppm STEL (Short Term
Exposure Limit)
Engineering Controls
Adequate ventilation should be provided to maintain air concentrations below
exposure standard.
When opening/decanting/transferring trichloroethylene local exhaust ventilation
should be used.
When used as a vapour degreaser the degreasing bath should comply with the
requirements of Australian Standard AS 2661 (Standards Association of Australia,
1983).
Personal Protection
Avoid eye and skin contact and inhalation of vapours.
Protective overalls conforming to Australian Standard AS 3765.1 (Standards
Australia & Standards New Zealand, 1990) should be worn.
If splashes are likely to occur during use safety goggles conforming to Australian
Standard AS/NZS 1337 - 1992 (Standards Australia & Standards New Zealand,
1992) should be worn.
Appropriate gloves should be worn if contact with liquid trichloroethylene is
likely.
If inhalation exposure is likely, e.g. during cleanup of spills, a respirator fitted
with a gas filter such as type A (organic vapour) should be worn during use of
trichloroethylene.
If working in a confined space or in poorly ventilated areas an air-line respirator
should be worn. Respiratory protective equipment should be in accordance with
AS/NZS 1715 (Standards Australia & Standards New Zealand, 1994) and
AS/NZS 1716 (Standards Australia & Standards New Zealand, 1994).
Flammability
Trichloroethylene is not flammable under normal conditions of use. Vapour
concentrations between 12.5% -90% v/v between 30-82癈 may ignite in contact
with high temperature heat sources. The vapour may ignite above 25癈 if mixed
with pure oxygen.
180 Priority Existing Chemical Number 8
Page x of Total y
Date of issue:
SAFE HANDLING INFORMATION
Storage and Transport
Store in a cool, dry, well ventilated area away from direct sunlight or ignition
sources. Containers should be kept closed at all times. Store away from alkalis.
Correct Shipping Name: Trichloroethylene
UN No: 1710 Packaging Group III
ADG Code: Classified as a dangerous good for the purpose of transport, Class 6.1
(toxic).
Should not be transported or stored with explosives, nitromethane, fire risk
substances of Class 5, cyanides and acids or foodstuffs and foodstuff empties.
Spills And Disposal
Contain spills using an absorbent (soil, sand or other inert material). Collect and
seal in labelled containers for disposal. Wear appropriate personal protective
equipment to prevent skin and eye contamination and to prevent inhalation.
Prevent contamination of drains and waterways. Local environment protection
authority or emergency services should be advised if contamination of sewers or
waterways occurs.
Fire/Explosion Hazard
Not combustible. Evolves highly toxic fumes such as hydrogen chloride and
phosgene at high temperatures. Fire fighters should wear full protective
equipment including self-contained breathing apparatus. Evacuation of people
from the neighbourhood should be considered if necessary. For fires, water fog or
fine water spray may be appropriate.
OTHER INFORMATION
Toxicological Information
4-h LC50 in rats is 12000 ppm and 8450 ppm in mice.
Oral LD50 varies from 5400 to 7200 mg/kg in rats.
Oral LD50 in mice is 2900 mg/kg.
Ecological Information
96 h LC50 (Flatfish dab): 16 ppm
48 h LC50 (Rainbow trout) 42 ppm
48 h LC50 (Fathead minnow) 32-56 ppm
CONTACT POINT
Title
Telephone Number
181
Trichloroethylene
APPENDIX 3
TRICHLOROETHYLENE (TCE) QUESTIONNAIRE
Company Information
Company name:
Company address:
Contact name:
Position:
Telephone: Fax:
Date:
Part A: Use Information
Please tick applicable boxes
TCE Quantity TCE Quantity
L/ month products L/mth
A1. Do you
import
buy from Australian
source
A2. Do you:
on sell
formulate
use
182 Priority Existing Chemical Number 8
Part B: Questions for resellers of TCE or products containing TCE.
If you on sell (distribute) TCE or products containing TCE please
provide the following details. Otherwise go to Part C of the
questionnaire.
B1. Please give details.
Annual
Product % Typical end use Avail to
sales
Name TCE public?
volume
Yes/No
Please supply copies of MSDS for these products where available
B2. If you repackage TCE or TCE products before sale briefly describe
the process.
B3. What industry sectors do you sell to?
Automotive Aerospace
Electrical Telecommunications
Metal forming/Machining Chemical processing
Printing Paint
Other (please specify)
183
Trichloroethylene
If you repackage TCE or TCE products please go to Part E of the
questionnaire.
Part C: Questions for Formulators
If you formulate products containing TCE, please answer the
following questions. Otherwise go to Part D of the questionnaire.
C1. Do you purchase products in : Bulk
Drums
C2. Please provide the following details for products you formulate:
Avail. to Annual
Product Typical end uses % Product
public? sales
Name TCE resold
Yes/No volume.
Yes/No
Please supply copies of the MSDS and labels.
C3. Briefly describe your formulating process.
If you do not use TCE products, please go to Part E of the
questionnaire
184 Priority Existing Chemical Number 8
Part D: Questions for end users
D1 Please indicate the type of industry in which you operate:
Automotive Aerospace
Electrical Telecommunications
Metal forming/Machining Chemical processing
Printing
Other (please specify)
D2. Do you purchase products in : Bulk
Drums
D3. Do you use TCE in any of these processes:
Vapour degreasing
Boil dip
Aerosol manufacture
Hand application eg surface cleaning
Cold ultrasonic cleaning
General solvent e.g. cleaning of small parts
Other (specify)
D4. Please specify the temperature of your process if above the
ambient temperature: 癈.
D5. Briefly describe how you use TCE/TCE products
185
Trichloroethylene
Part E: Workplace Exposure
Questions for formulators, end users and on sellers (distributors)
involved in repackaging TCE before sale.
E1. Are the processes you employ:
Open
Partially closed (eg covered tanks, trichloroethylene added
by workers manually to tanks)
Closed (fully sealed process including automated addition of
trichloroethylene to tanks)
Other (please specify)
E2. Please describe the skill level, number and activities of workers
using TCE or TCE products.
Classification/ Num- Description of Work H/day Days/yr
skill level ber
186 Priority Existing Chemical Number 8
E3. Please describe the engineering controls that are in place to reduce
exposure of workers to TCE.
Process/Activity Engineering Controls Year installed
E4. Please list the personal protective equipment used by workers.
Process/Activity Personal Protective Equipment
187
Trichloroethylene
E5. Has atmospheric monitoring been conducted to determine levels of
TCE in the workplace?
E6. Are you aware of any adverse health effects experienced by
workers after exposure to trichloroethylene? If so please describe.
Part F: Environmental Effects
Questions for all respondents
F1. Please estimate the percentage of trichloroethylene lost to the
atmosphere from your process or during use.
Process or end use % lost to atmosphere
F2. Are you aware of any discharges of TCE to land or water? If so,
please give details.
188 Priority Existing Chemical Number 8
F3. Do you actively recycle or otherwise recover TCE for re-use? If so,
how much and please describe process.
F4. What forms of trichloroethylene waste do you generate?
None Soiled rags
Sludge Contaminated solvent
Other (please describe)
F5. What methods do you use to dispose trichloroethylene waste?
Blending with other products and re-use
Evaporation to atmosphere
Licensed discharges
Incineration eg boiler fuel
Send to solvent recycler
Waste collection
Other (please specify)
F6. How much trichloroethylene waste is disposed of monthly (total of
all above methods)? litres/month.
F7. Please indicate how you handle empty containers.
Rinse and/or re-use Return to supplier
Sell to drum recycler Send to landfill
Other (please specify)
Thank you for responding to the questionnaire
189
Trichloroethylene
APPENDIX 4
APPROVED CRITERIA FOR CLASSIFYING HAZARDOUS
SUBSTANCES
CARCINOGENIC SUBSTANCES
4.76 Substances are determined to be hazardous due to carcinogenic
effects if they fall into one of the following categories:
Category 1 Substances known to be carcinogenic to humans.
Category 2 Substances which should be regarded as if they are
carcinogenic to humans.
Category 3 Substances which cause concern for humans owing to
possible carcinogenic effects but in respect of which the
available information is not adequate for making a
satisfactory assessment.
EXPLANATORY NOTES REGARDING THE
CATEGORISATION OF CARCINOGENIC SUBSTANCES
4.77 The placing of a substance into Category 1 is done on the basis of
epidemiological data; placing into Categories 2 and 3 is based
primarily on animal experiments.
CATEGORY 1
4.78 Substances are determined to be hazardous and classified as
Toxic (T) and assigned risk phrase R45 or R49 in accordance with
the criteria given below.
R45 MAY CAUSE CANCER
R49 MAY CAUSE CANCER BY INHALATION2
2
For substances which present a carcinogenic risk only when inhaled, for example, dust,
vapour or fumes (and where other routes of exposure, for example, by swallowing or in
contact with the skin do not present any carcinogenic risk) the specific risk phrase R49
should be used.
190 Priority Existing Chemical Number 8
4.79 A substance is included in Category 1 if there is sufficient evidence
to establish a causal association between human exposure and the
development of cancer on the basis of epidemiological data. The
existence of a causal relationship would be any of the following:
? an increased incidence of one or more cancer types in an exposed
population in comparison with a non-exposed population,
? evidence of dose-time-response relationships, that is, an increased
cancer incidence associated with higher exposure levels or with
increasing exposure duration,
? an association between exposure and increased risk observed in
more than one study,
? demonstration of a decline in risk after reduction of exposure, and
? specificity of any association, defined as an increased occurrence
of cancer at one target organ or of one morphological type.
CATEGORY 2
4.80 Substances are determined to be hazardous and classified as
Toxic (T) and assigned risk phrase R45 or R49 in accordance
with the criteria given below.
R45 MAY CAUSE CANCER
R49 MAY CAUSE CANCER BY INHALATION2
4.81 A substance is included in Category 2 if there is sufficient
evidence, on the basis of appropriate long term animal studies or
other relevant information, to provide a strong presumption that
human exposure to that substance may result in the development of
cancer.
4.82 For classification as a Category 2 carcinogen either positive results
in two animal species should be available or clear positive
evidence in one species, together with supporting evidence such as
genotoxicity dam, metabolic or biochemical studies, induction of
benign tumours, structural relationship with other known
2
For substances which present a carcinogenic risk only when inhaled, for example, dust, vapour or fumes
(and where other routes of exposure, for example, by swallowing or in contact with the skin do not present
any carcinogenic risk) the specific risk phrase R49 should be used.
191
Trichloroethylene
carcinogens, or data from epidemiological studies suggesting an
association.
4.83 Human data providing suspicions of carcinogenic potential may
warrant a Category 2 classification irrespective of the nature of
any animal data. Increased confidence in the credibility of a causal
relationship would be provided by evidence of carcinogenicity in
animals and/or of genotoxic potential in short term screening tests.
CATEGORY 3
4.84 Substances are determined to be hazardous and classified as
Harmful (Xn) and assigned risk phrase R40 in accordance with the
criteria given below.
R40 POSSIBLE RISK OF IRREVERSIBLE EFFECTS
4.85 A substance is included in Category 3 if there is some evidence
from appropriate animal studies that human exposure can result in
the development of cancer, but this evidence is insufficient to place
the substance in Category 2.
Category 3 actually comprises 2 sub-categories
(a) substances which are well investigated but for which the
evidence of a tumour-inducing effect is insufficient for
classification in Category 2. Additional experiments would
not be expected to yield further relevant information with
respect to classification;
(b) substances which are insufficiently investigated. The
available data are inadequate, but they raise concern for
humans. This classification is provisional; further
experiments are necessary before a final decision can be
made.
4.86 For a distinction between Categories 2 and 3 the arguments listed
below are relevant which reduce the significance of experimental
tumour induction in view of possible human exposure. These
192 Priority Existing Chemical Number 8
arguments especially in combination, would lead in most cases to
classification in Category 3, even though tumours have been
induced in animals:
? carcinogenic effects only at very high dose levels exceeding the
'maximal tolerated dose'. The maximal tolerated dose is
characterised by toxic effects which, although not yet reducing
lifespan, go along with physical changes such as about 10%
retardation in weight gain,
? appearance of tumours, especially at high dose levels, only in
particular organs of certain species known to be susceptible to a
high spontaneous tumour formation,
? appearance of tumours, only at the site of application, in very
sensitive test systems (eg intraperitoneal, or subcutaneous
application of certain locally active compounds), if the particular
target is not relevant to humans,
? lack of genotoxicity in short-term tests in vivo and in vitro,
? existence of a secondary mechanism of action with the implication
of a practical threshold above a certain dose level (eg hormonal
effects on target organs or on mechanisms of physiological
regulation, chronic stimulation of cell proliferation),
? existence of a species-specific mechanism of tumour formation (eg
by specific metabolic pathways) irrelevant for humans.
NO CARCINOGEN CLASSIFICATION
4.87 For a distinction between Category 3 and no classification
arguments are relevant which exclude a concern for humans:
? a substance should not be classified in any of the categories if the
mechanism(s) of experimental tumour formation is/are clearly
identified, with good evidence that such mechanism(s) cannot be
extrapolated to humans for each tumour,
? if the only available tumour data are liver tumours in certain
sensitive strains of mice, without any other supplementary
evidence, the substance may not be classified in any of the
categories,
? particular attention should be paid to cases where the only
available tumour data are the occurrence of neoplasms at sites and
193
Trichloroethylene
in strains where they are well known to occur spontaneously with a
high incidence.
MUTAGENIC SUBSTANCES
4.88 Substances are determined to be hazardous due to mutagenic
effects if they fall into one of the following categories:
Category 1 Substances known to be mutagenic to humans.
Category 2 Substances which should be regarded as if they are
mutagenic to humans.
Category 3 Substances which cause concern for humans owing to
possible mutagenic effects, but in respect of which
available information does not satisfactorily demonstrate
heritable genetic damage.
EXPLANATORY NOTES REGARDING THE
CATEGORISATION OF MUTAGENIC SUBSTANCES
4.89 A mutation is a permanent change in the amount or structure of the
genetic material in an organism, resulting in a change of the
phenotypic characteristics of the organism. The alterations, may
involve a single gene, a block of DNA, or a whole chromosome.
Effects involving single genes may be a consequence of effects on
single DNA bases (point mutations) or of large changes, including
deletions, within the gene. Effects on whole chromosomes may
involve structural or numerical changes. A mutation in the germ
cells in sexually reproducing organisms may be transmitted to the
offspring. A mutagen is an agent that gives rise to an enhanced
occurrence of mutations.
4.90 It should be noted that substances are classified as mutagens with
specific reference to inherited genetic damage. However, the type
of results leading to classification of chemicals in Category 3:
'induction of genetically relevant events in somatic cells', is
generally also regarded as an alert for possible carcinogenic
activity.
4.91 Method development for mutagenicity testing is an ongoing
process. For many new tests no standardised protocols and
evaluation criteria are presently available. For the evaluation of
mutagenicity data the quality of the test performance and the
degree of validation of the test method have to be considered.
194 Priority Existing Chemical Number 8
CATEGORY 1
4.92 Substances are determined to be hazardous and classified as
Toxic (T) and assigned risk phrase R46 in accordance with the
criteria given below.
R46 MAY CAUSE HERITABLE GENETIC DAMAGE
4.93 A substance is included in Category I if there is sufficient evidence
to establish a causal relationship between human exposure to a
substance and heritable genetic damage.
4.94 To place a substance in Category 1, positive evidence from human
mutation epidemiology studies will be needed. Examples of such
substances are not known to date. It is recognised that it is
extremely difficult to obtain reliable information from studies on
the incidence of mutations in human populations, or on possible
increases in their frequencies.
CATEGORY 2
4.95 Substances are determined to be hazardous and classified as
Toxic (T) and assigned risk phrase R46 in accordance with the
criteria given below.
R46 MAY CAUSE HERITABLE GENETIC DAMAGE
4.96 A substance is included in Category 2 if there is sufficient
evidence to provide a strong presumption that human exposure to
the substance may result in the development of heritable genetic
damage, generally on the basis of appropriate animal studies and
other relevant information.
4.97 To place a substance in Category 2, positive results are needed
from assays showing
(a) mutagenic effects, or
(b) other cellular interactions relevant to mutagenicity, in germ
cells of mammals in vivo, or
(c) mutagenic effects in somatic cells of mammals in vivo in
combination with clear evidence that the substance or a
relevant metabolite reaches the germ cells.
195
Trichloroethylene
4.98 With respect to placement in Category 2, at present the following
methods are appropriate:
(a) in vivo germ cell mutagenicity assays:
? specific locus mutation test,
? heritable translocation test,
? dominant lethal mutation test.
These assays actually demonstrate the appearance of affected progeny or a
defect in the developing embryo.
(b) in vivo assays showing relevant interaction with germ cells
(usually DNA):
? assays for chromosomal abnormalities, as detected by
cytogenetic analysis, including aneuploidy caused by
malsegregation of chromosomes,
? test for sister chromatid exchanges (SCEs),
? test for unscheduled DNA synthesis (UDS),
? assay of (covalent) binding of mutagen to germ cell
? DNA,
? assaying other kinds of DNA damage.
These assays provide evidence of a more or less indirect nature. Positive
results in these assays would normally be supported by positive results
from in vivo somatic cell mutagenicity assays, in mammals or in humans
(see under Category 3).
(c) in vivo assays showing mutagenic effects in somatic cells of
mammals (see sub section 4.98(a)), in combination with
toxicokinetic methods, or other methodologies capable of
demonstrating that the compound or a relevant metabolite
reaches the germ cells.
For paragraphs 4.98(b) and 4.98 (c), positive results from host- mediated
assays or the demonstration of unequivocal effects in in vitro assays can be
considered as supporting evidence.
CATEGORY 3
4.99 Substances are determined to be hazardous and classified as
Harmful (Xn) and assigned risk phrase R40 in accordance with the
criteria given below.
196 Priority Existing Chemical Number 8
R40 POSSIBLE RISK OF IRREVERSIBLE EFFECTS
4.100 A substance is included in Category 3 if there is evidence from
appropriate mutagenicity studies, of concern that human exposure
can result in the development of heritable genetic damage, but that
this evidence is insufficient to place the substance in Category 2.
4.101 To place a substance in Category 3, positive results are needed in
assays showing
(a) mutagenic effects, or
(b) other cellular interaction relevant to mutagenicity, in
somatic cells in mammals in vivo.
The latter especially would normally be supported by positive results from
in vitro mutagenicity assays.
4.102 For effects in somatic cells in vivo at present the following methods
are appropriate:
(a) in vivo somatic cell mutagenicity assays:
? bone marrow micronucleus test or metaphase analysis,
? metaphase analysis of peripheral lymphocytes,
? mouse coat colour spot test.
(b) in vivo somatic cell DNA interaction assays:
? test for SCEs in somatic cells,
? test for UDS in somatic cells,
? assay for the (covalent) binding of mutagen to somatic
cell DNA,
? assay for DNA damage, for example, by alkaline
elution, in somatic cells.
4.103 Substances showing positive results only in one or more in vitro
mutagenicity assays should normally not be classified. Their
further investigation using in vivo assays, however, is strongly
indicated. In exceptional cases, for example, for a substance
showing pronounced responses in several in vitro assays, for which
no relevant in vivo data are available, and which shows
197
Trichloroethylene
resemblance to known mutagens/carcinogens, classification in
Category 3 could be considered.
198 Priority Existing Chemical Number 8
APPENDIX 5
Additional material considered by the Administrative Appeals
Tribunal: Unpublished studies and published articles available
after preparation of the draft report.
Blair A, Hartge P, Stewart PA, et al (1998) Mortality and cancer incidence of aircraft
maintenance workers exposed to trichloroethylene and other organic solvents and
chemicals: extended follow up. Occup Environ Medicine, 55: 161-171
Boice JD, Marano DE et al. (1999) Mortality among aircraft manufacturing workers.
Occup Environ Med, 56: 581-597.
Brauch H, Weirich G et al. (1999) Trichloroethylene exposure and specific somatic
mutations inpatients with renal cell carcinoma. Journal of the National Cancer Institute,
9(10): 954-961.
Bruning T, Sundberg, AGM et al (1999) Glutathione transferase alpha as a marker for
tubular damage after trichloroethylene exposure. Arch Toxicol, 73:246-254.
Clay P (1999) Trichloroethylene and S-(1,2-dichlorovinylcysteine): in vivo COMET and
UDS assays in the rat kidney. Zeneca Central Toxicology Laboratory Report No.
CTL/R/2976. First supplement to CTL/T/2976.
Clay P (1998) Trichloroethylene and S-(1,2-dichlorovinylcysteine): in vivo COMET and
UDS assays in the rat kidney. Zeneca Central Toxicology Laboratory Report No.
CTL/R/2976.
Dekant W and Henschler D (1999) Organ-specific carcinogenicity of haloalkenes
mediated by glutathione conjugation. J Cancer Res Clin Oncol, 125: 174-181.
Green T, Dow J, Ellis M.K. et al (1997) The role of glutathione conjugation in the
development of kidney tumours in rats exposed to trichloroethylene. Chemico-Biolgical
Interactions 105: 99-117
Green T. (1997) Formic acid excretion in rats and mice exposed to trichloroethylene.
Report No: CTL/R/1312, Central Toxicology Laboratory, Cheshire UK.
Green and Dow (1999) Trichloroethylene induced vitamin B12 and folate deficiency
leads to increased formic acid excretion in the rat. Report No: CTL/R/1431, Central
Toxicology Laboratory, Cheshire, UK.
Green T, Dow J, Foster JR et al (1999) Trichloroethanol: Long-term drinking water study
in the Fischer rat. Interim report at one year. Report No: CTL/R/1312, Central
Toxicology Laboratory, Cheshire UK.
Green LC and Lash TL (1999) Re: "Renal cell cancer correlated with occupational
exposure to trichloroethylene". J Cancer Res Clin Oncol, 125: 430-432.
Green T (1998) Analysis of urine samples from humans occupationally exposed to
trichloroethylene. Zeneca Central Toxicology Laboratory Report No. CTL/R/1364.
199
Trichloroethylene
Griffin JM, Lipscomb JC et al. (1998) Covalent binding of trichloroethylene to proteins in
human and rat hepatocytes. Toxicology Letters, 95: 173-181.
Halmes NC, Samokyszyn VM et al. (1997) Covalent binding and inhibition of
cytochrome P4502E1 by trichloroethylene. Xenobiotica 27(1): 101-110.
Hayashi M, Ueda T et al. (1998) Development of genotoxicity assay system that use
aquatic organisms. Mutagen Research, 399: 125-133.
Kautianen A, Vogel JS et al. (1997) Dose-dependent binding of trichloroethylene to
hepatic DNA and protein at low doses in mice. Chemico-Biological Interactions, 106:
109-121.
Lash LH, Lipscomb JC (1999) Glutathione conjugation of trichloroethylene in human
liver and kidney: kinetics and individual variation. Drug Metabolism and Disposition,
27(3): 351-359.
Lash LH, Putt DA et al. (1999) Identification of S-(1,2-dichlorovinyl) glutathione in the
blood of human volunteers exposed to trichloroethylene. Journal of Toxicology and
Environmental Health, Part A, 56: 1-21.
McLaughlin JK & Blot WJ (1997) A critical review of epidemiology studies of
trichloroethylene and perchloroethylene and risk of renal-cell cancer. Int. Arch. Occup.
Environ. Health, 70: 222-231.
Morgan RW, Kelsh MA et al. (1998) Mortality of aerospace workers exposed to
trichloroethylene. Epidemiology, 9(4): 424-431.
Ritz B (1999) Cancer mortality among workers exposed to chemicals during uranium
processing. J Occup. Med., 41;14:556-566.
Robbiano L, Mereto E et al. (1998) Increased frequency of micronucleated kidney cells in
rats exposed to halogenated anaesthetics. Mutation Research, 413: 1-6.
Sujatha TV and Hegde MJ (1998) C-mitotic effects of trichloroethylene (TCE) on bone
marrow cells of mice. Mutation Research, 413: 151-158.
Terracini B and Parker VH (1965) A pathological study on the toxicity of S-
dichlorovinyl-L-cystine. Food Cosmet Toxicol 3: 67-74.
Vamvakas S, Bruning, T et al. (1998) Renal cell cancer correlated with occupational
exposure to trichloroethylene. J Cancer Res Clin Oncol, 124: 374-382.
200 Priority Existing Chemical Number 8
APPENDIX 6
DECISION AND REASONS FOR DECISION [1999] AATA 1023
ADMINISTRATIVE APPEALS TRIBUNAL )
) No V1998/955
General ADMINISTRATIVE DIVISION ) )
Re Dow Chemical (Australia) Limited
Applicant
And Director, Chemicals Notification and Assessment
Respondent
DECISION
Tribunal Deputy President A M Blow OAM, QC.,
Professor G A R Johnston AM, FRACI, FTSE
Miss E A Shanahan
Date 31 December 1999
Place Melbourne
Decision The decisions under review are affirmed.
[Sgd A M Blow]
Deputy President
CATCHWORDS
Health Law ?industrial chemicals ?classification of a "priority existing chemical"
?trichloroethylene 璫arcinogenicity and mutagenicity.
Industrial Chemicals (Notofication and Assessment) Act 1989 ?ss.60E(5),
102(1)(b)
Melbourne Pathology Pty Limited v Minister for Human Services and Health
(1996) 40 ALD 565
Friends of Hinchinbrook Society Inc v Minister for Environment (1997) 69FCR 28.
REASONS FOR DECISION
31 December 1999 Deputy President A M Blow OAM, QC.,
Professsor G A R Johnston AM, FRACI, FTSE
Miss E A Shanahan
1. This is an application pursuant to s.102(1)(b) of the Industrial
Chemicals (Notification and Assessment) Act 1989 ("the
201
Trichloroethylene
Act"). The applicant is seeking the review of a series of
decisions made by the respondent on 14 July 1998 under
s.60E(5) of the Act whereby she refused to vary a draft report in
a number of respects. The draft report relates to a chemical
called trichloroethylene. The decisions under review relate to
passages in the draft report concerning the carcinogenicity and
mutagenicity of trichloroethylene.
2. The objects of the Act are set out in s.3 thereof, which reads as
follows:-
"(3) The object of this Act is to provide for a national system of notification
and assessment of industrial chemicals for the purposes of:
(a) aiding in the protection of the Australian people and the
environment by finding out the risks to occupational health and
safety, to public health and to the environment that could be
associated with the importation, manufacture or use of the
chemicals; and
(b) providing information, and making recommendations, about the
chemicals to Commonwealth, State and Territory bodies with
responsibilities for the regulation of industrial chemicals; and
(c) giving effect to Australia's obligations under international
agreements relating to the regulation of chemicals; and
(d) collecting statistics in relation to the chemicals;
being a system under which information about the properties and effects
of the chemicals is obtained from importers and manufacturers of the
chemicals."
3. On 4 April 1995 the Minister for Industrial Relations published a
notice in the Chemical Gazette under s.51 of the Act declaring
trichloroethylene a priority existing chemical. On 16 June 1995 ICI
Australia Operations Pty Limited applied under s.55(2) of the Act for the
assessment of trichloroethylene. On 19 June 1995 the applicant made a
similar application. When such an application is made, s.57(1) of the Act
obliges the respondent to cause the relevant chemical to be assessed,
and to cause a report to be prepared. That sub-section reads as follows:-
"Where the Director receives an application or applications for the
assessment of a priority existing chemical, he or she must cause the
chemical to be assessed in accordance with section 60A and a report of
the assessment to be prepared."
4. The Act makes provision for the assessment process and the
preparation of a draft assessment report in ss.60A, 60B and 60C, which
read as follows:-
"60A Nature of assessment
(1) The officer preparing the report of the preliminary assessment of a
priority existing chemical must determine the significance, for the
making of a determination described in subsection (2) in relation to
that chemical, of each of the matters required to be taken into
account by the notice declaring the chemical as a priority existing
chemical.
202 Priority Existing Chemical Number 8
(2) The officer preparing the report of the full assessment of a priority
existing chemical must determine the risk (if any) of adverse health
effects, safety effects or adverse environmental effects that could
be caused by:
(a) importation of the chemical (if it is proposed to import the
chemical); or
(b) manufacture of the chemical (if it is proposed to
manufacture the chemical in Australia); or
(c) the use, storage, handling or disposal of the chemical.
(3) In making a determination under subsection (1) or (2), the officer
must take into account the matters required to be taken into
account by the notice declaring the chemical as a priority existing
chemical.
60B Contents of assessment reports
(1) An assessment report (whether it is a draft assessment report
made under section 60C or a final assessment report made under
section 60F) must include a summary of health, safety and
environmental matters considered in the assessment and such
recommendations as may reasonably be made in relation to each
of the following matters:
(a) the content of a Material Safety Data Sheet in respect of the
chemical;
(b) the precautions and restrictions to be observed during the
importation, manufacture, handling, storage, use of
disposal of the chemical to protect persons exposed to the
chemical;
(c) controls to limit emissions of the chemical into the
environment, including permissible concentrations in
emissions of the chemical into the air or water from a
manufacturing plant or other facility;
(d) the packaging, labelling, handling or storage of the
chemical;
(e) the measures to be employed in emergencies involving the
chemical to minimise hazard to persons and damage to the
environment;
(f) the uses of the chemical;
(g) the means of disposal of the chemical;
(h) the circumstances (if any) in which secondary notification of
the chemical is required;
(i) any prescribed matter.
(2) The assessment report (whether draft or final) must not contain
exempt information.
60C Draft assessment report
On completing an assessment of a priority existing chemical, the Director
must cause a draft report of the assessment to be prepared."
5. The draft report was completed by 13 March 1998. On that day a
copy of the draft report was sent to the applicant with a notice under
s.60D(1)(b) of the Act asking the applicant to notify the respondent of any
errors in it. Some non-controversial corrections were made as a result.
Once that stage is reached, s.60E of the Act provides for interested parties
203
Trichloroethylene
to request the respondent to make variations to the draft report. The
relevant provisions in that section read as follows:-
"60E Variation of draft assessment report
(1) Within 56 days of giving the draft assessment report to each
applicant, the Director must:
(a) give a copy of the draft report with any corrections to each
applicant and to any person who has provided information
for the assessment in response to a notice under section
58; and
(b) publish a notice in the Chemical Gazette:
(i) describing the matters contained in the draft report;
and
(ii) stating that the draft report has been given to each
applicant and person who provided information
under section 58; and
(iii) describing how a person may obtain a copy of the
draft report; and
(iv) describing how a person may ask the Director to
vary the draft report.
(2) Within 28 days of the publication of the notice under subsection
(1), a person may request the Director, in the approved form, to
vary the draft report.
(3) The Director must make a decision about the variation within 56
days after the publication of the notice under subsection (1).
(4) The Director must decide to vary the draft report as requested if he
or she is satisfied that the report, varied as requested, would be
correct.
(5) The Director must decide to refuse to vary the draft report as
requested if he or she is not satisfied that the report, varied as
requested, would be correct."
6. A notice was published in the Chemical Gazette on 5 May 1998
pursuant to s.60E(1)(b). The applicant faxed to the respondent a request
dated 1 June 1998 seeking a number of variations to the draft report.
Three other requests under s.60E were also sent to the respondent. On
24 July 1998 the respondent made a series of decisions in relation to each
of the four requests she had received. She made a separate decision in
relation to each variation that had been requested to the draft report ?br>
either a decision under s.60E(4) making a requested variation, or a
decision under s.60E(5) refusing to make a requested variation. Some of
the variations requested by the other parties were made under s.60E(4).
The applicant has applied to this Tribunal in respect of the requests made
by it all of which were refused by respondent under s.60E(5).
7. In March 1994 the National Occupational Health and Safety
Commission published a booklet entitled "Approved Criteria for Classifying
Hazardous Substances [NOHSC:1008 (1994)]". Although she was under
no legal obligation to do so, the respondent in her draft report assessed
trichloroethylene by reference to the Approved Criteria as published in
March 1994. A fresh edition of the Approved Criteria has been published
in 1999. That document constitutes a standard declared by the
Commission under s.38(1) of the National Occupational Health and
204 Priority Existing Chemical Number 8
Safety Commission Act 1985. It is common ground that, in reviewing
the respondent's decisions as to the draft report, we should apply the 1999
edition of the Approved Criteria. The relevant passages in the 1999
edition do not vary significantly from those in the March 1994 edition.
8. Generally speaking the Approved Criteria are intended to be the
same in substance as the criteria used by the European Communities in
their legislation for classifying dangerous substances. Appendix 3 to the
Approved Criteria lists a series of "risk phrases" relevant to different types
of health effects. These have been taken from an EEC Council Directive.
The following risk phrases are relevant in this case:
"R40 Possible risk of irreversible effects."
"R45 May cause cancer."`
"R46 May cause heritable genetic damage"
"R49 May cause cancer by inhalation."
9. Chapter 3 of the Approved Criteria sets out how those criteria are to
be applied. It contains the following paragraphs that are relevant to this
case:
"3.4 Classifying the substance will involve finding and putting together
all the available information on the substance and assessing this
information against the criteria. This process will identify the
health hazards of the substances and appropriate risk phrases to
be used.
...
3.10 If evidence is available to show that in practice the toxic effect of a
substance on humans is, or is likely to be, different from that
suggested by the results of animal testing, then the substance
should be classified according to its toxicity in humans.
3.11 If only some information is available for the substance, then the
health effects criteria and other suitable information should be
applied as far as possible to classify the substance. ...
3.12 The classification for a substance may need to be revised
periodically as new information about that substance becomes
available."
10. Chapter 4 of the Approved Criteria, entitled "Health Effects Criteria",
contains the following provisions relevant to this case:
"4.1 The criteria in this chapter are those used by the European
3
Communities in EC Council Directive 67/548/EC for classifying
dangerous substances based on their hazards to health. These
criteria take into account both short and long term health effects,
and are applicable to both pure substances and mixtures.
...
4.4 For the purposes of classification, health effects are subdivided
into:
...
?carcinogenic effects (R40, R45, R49);
?mutagenic effects (R40, R46);
...
A substance may have more than one health effect.
205
Trichloroethylene
Criteria for classification and choice of risk phrases for
ingredients and mixtures.
...
4.9 For specific effects on health (carcinogenicity, mutagenicity
and reproductive toxicity) the criteria in paragraphs 4.76 to
4.133 are to be used.
...
CARCINOGENIC SUBSTANCES
4.76 Substances are determined to be hazardous due to
carcinogenic effects if they fall into one of the following
categories:
Category 1 Substances known to be carcinogenic to
humans.
Category 2 Substances which should be regarded as if
they are carcinogenic to humans.
Category 3 Substances which cause concern for
humans owing to possible carcinogenic
effects but in respect of which the available
information is not adequate for making a
satisfactory assessment.
EXPLANATORY NOTES REGARDING THE
CATEGORISATION OF CARCINOGENIC
SUBSTANCES
4.77 The placing of a substance into Category 1 is done on the
basis of epidemiological data; placing into Categories 2
and 3 is based primarily on animal experiments.
...
CATEGORY 2
4.80 Substances are determined to be hazardous and classified
as Toxic (T) and assigned risk phrase R45 or R49 in
accordance with the criteria given below.
R45 MAY CAUSE CANCER
R49 MAY CAUSE CANCER BY INHALATION2
2
For substances which present a carcinogenic risk only when inhaled, for
example, dust, vapour or fumes (and where other routes of exposure, for
example, by swallowing or in contact with the skin do not present any
carcinogenic risk) the specific risk phrase R49 should be used.
4.81 A substance is included in Category 2 if there is sufficient
evidence, on the basis of appropriate long term animal
studies or other relevant information, to provide a strong
presumption that human exposure to that substance may
result in the development of cancer.
4.82 For classification as a Category 2 carcinogen either
positive results in two animal species should be available
or clear positive evidence in one species, together with
supporting evidence such as genotoxicity data, metabolic
or biochemical studies, induction of benign tumours,
structural relationship with other known carcinogens, or
data from epidemiological studies suggesting an
association.
206 Priority Existing Chemical Number 8
4.83 Human data providing suspicions of carcinogenic potential
may warrant a Category 2 classification irrespective of the
nature of any animal data. Increased confidence in the
credibility of a causal relationship would be provided by
evidence of carcinogenicity in animals and/or of genotoxic
potential in short term screening tests.
CATEGORY 3
4.84 Substances are determined to be hazardous and
classified as Harmful (Xn) and assigned risk phrase R40 in
accordance with the criteria given below.
R40 POSSIBLE RISK OF IRREVERSIBLE EFFECTS
4.85 A substance is included in Category 3 if there is some
evidence from appropriate animal studies that human
exposure can result in the development of cancer, but this
evidence is insufficient to place the substance in Category 2.
Category 3 actually comprises 2 sub-categories
(a) substances which are well investigated but for
which the evidence of a tumour-inducing effect is
insufficient for classification in Category 2.
Additional experiments would not be expected to
yield further relevant information with respect to
classification;
(b) substances which are insufficiently investigated.
The available data are inadequate, but they raise
concern for humans. This classification is
provisional; further experiments are necessary
before a final decision can be made.
4.86 For a distinction between Categories 2 and 3 the
arguments listed below are relevant which reduce the
significance of experimental tumour induction in view of
possible human exposure. These arguments especially in
combination, would lead in most cases to classification in
Category 3, even though tumours have been induced in
animals:
?carcinogenic effect only at very high dose levels
exceeding the `maximal tolerated dose'. The maximal
tolerated does is characterised by toxic effects which,
although not yet reducing lifespan, go along with
physical changes such as about 10% retardation in
weight gain,
?appearance of tumours, especially at high dose levels,
only in particular organs of certain species known to be
susceptible to a high spontaneous tumour formation,
?appearance of tumours, only at the site of application,
in very sensitive test systems (eg intraperitoneal, or
subcutaneous application of certain locally active
compounds), if the particular target is not relevant to
humans,
?lack of genotoxicity in short-term tests in vivo and in
vitro,
?existence of a secondary mechanism of action with the
implication of a practical threshold above a certain dose
207
Trichloroethylene
level (eg hormonal effects on target organs or on
mechanisms of physiological regulation, chronic
stimulation of cell proliferation),
? existence of a species-specific mechanism of tumour
formation (eg by specific metabolic pathways) irrelevant
for humans.
...
MUTAGENIC SUBSTANCES
4.88 Substances are determined to be hazardous due to
mutagenic effects if they fall into one of the
following categories:
Category 1 Substances known to be mutagenic to
humans.
Category 2 Substances which should be regarded as if
they are mutagenic to humans.
Category 3 Substances which cause concern for
humans owing to possible mutagenic
effects, but in respect of which available
information does not satisfactorily
demonstrate heritable genetic damage.
EXPLANATORY NOTES REGARDING THE
CATEGORISATION OF MUTAGENIC SUBSTANCES
4.89 A mutation is a permanent change in the amount or
structure of the genetic material in an organism,
resulting in a change of the phenotypic
characteristics of the organism. The alterations,
may involve a single gene, a block of DNA, or a
whole chromosome. Effects involving single genes
may be a consequence of effects on single DNA
bases (point mutations) or of large changes,
including deletions, within the gene. Effects on
whole chromosomes may involve structural or
numerical changes. A mutation in the germ cells in
sexually reproducing organisms may be transmitted
to the offspring. A mutagen is an agent that gives
rise to an enhanced occurrence of mutations.
4.90 It should be noted that substances are classified as
mutagens with specific reference to inherited
genetic damage. However, the type of results
leading to classification of chemicals in Category 3:
'induction of genetically relevant events in somatic
cells', is generally also regarded as an alert for
possible carcinogenic activity.
4.91 Method development for mutagenicity testing is an
ongoing process. For many new tests no
standardised protocols and evaluation criteria are
presently available. For the evaluation of
mutagenicity data the quality of the test
performance and the degree of validation of the test
method have to be considered.
...
CATEGORY 3
208 Priority Existing Chemical Number 8
4.99 Substances are determined to be hazardous and
classified as Harmful (Xn) and assigned risk phrase
R40 in accordance with the criteria given below.
R40 POSSIBLE RISK OF IRREVERSIBLE EFFECTS
4.100 A substance is included in Category 3 if there is
evidence from appropriate mutagenicity studies, of
concern that human exposure can result in the
development of heritable genetic damage, but that
this evidence is insufficient to place the substance in
Category 2.
4.101 To place a substance in Category 3, positive results
are needed in assays showing
(a) mutagenic effects, or
(b) other cellular interaction relevant to
mutagenicity, in somatic cells in mammals
in vivo.
The latter especially would normally be
supported by positive results from in vitro
mutagenicity assays.
4.102 For effects in somatic cells in vivo at present the
following methods are appropriate:
(a) in vivo somatic cell mutagenicity assays:
? bone marrow micronucleus test or
metaphase analysis,
? metaphase analysis of peripheral
lymphocytes,
? mouse coat colour spot test.
(b) in vivo somatic cell DNA interaction assays:
?test for SCEs in somatic cells,
?test for UDS in somatic cells,
?assay for the (covalent) binding of
mutagen to somatic cell DNA,
?assay for DNA damage, for example, by
alkaline elution, in somatic cells.
4.103 Substances showing positive results only in one or
more in vitro mutagenicity assays should normally
not be classified. Their further investigation using in
vivo assays, however, is strongly indicated. In
exceptional cases, for example, for a substance
showing pronounced responses in several in vitro
assays, for which no relevant in vivo data are
available, and which shows resemblance to known
mutagens/carcinogens, classification in Category 3
could be considered.
11. In the draft report, the respondent concluded that trichloroethylene
should be classified as a "mutagen category 3 (R40(M3) Possible risk of
irreversible effects, mutagen category 3) and carcinogen category 2 (R45-
May cause cancer)". The applicant contends that trichloroethylene should
have been categorised as a category 3 carcinogen (not category 2), and
that it should not have been classified as a mutagen at all.
209
Trichloroethylene
12. In reviewing the respondent's decisions in relation to the draft report
by reference to the Approved Criteria, we are bearing in mind that, whilst
those criteria do not have the force of law for our purposes, they are
intended to be adopted by State and Territory occupational health and
safety legislation, and thus have been drafted with the intention that for
certain purposes they should have the force of law. However the criteria
are addressed to practical people skilled in their particular trades and
industries, and should be construed in the light of practical considerations,
rather than being treated like an Act of Parliament: Melbourne Pathology
Pty Limited v Minister for Human Services and Health (1996) 40 ALD
565 at 580-581.
13. Counsel for the respondent submitted that we should take into
account the "precautionary principle" that was discussed by Sackville J in
Friends of Hinchinbrook Society Inc v Minister for Environment
(1997) 69 FCR 28 at 78-80. In simplistic terms, that principle requires that
a cautious approach be taken when there is a threat of harm and scientific
uncertainty. That is a principle of common sense, rather than a rule of
law. It is a very relevant principle in this case. But it would be a mistake
if, out of an abundance of caution, we were to give trichloroethylene a
carcinogenicity classification or a mutangenicity classification otherwise
than in accordance with the Approved Criteria.
CARCINOGENESIS
14. The Applicant accepts that trichloroethylene is a category 3
carcinogenic substance, i.e. that it is a substance which causes concern
for humans owing to possible carcinogenic effects but in respect of which
the available information is not adequate for making a satisfactory
assessment.
15. The Applicant rejects the Respondent's proposal to classify
trichloroethylene as a category 2 carcinogenic substance, i.e. that it is a
substance which should be regarded as if it is carcinogenic to humans.
16. The Approved Criteria (para 4.77) states that the placing of a
substance into Categories 2 and 3 is based primarily on animal
experiments.
Rat kidney tumours: animal studies
17. Counsel for the Applicant maintains that 'the only relevant animal
studies are the rat kidney tumour studies (Transcript 391/30).
18. Counsel for the Respondent maintains that there is 'clear positive
evidence that TCI produces renal tubular cell tumours in rats' (Transcript
387/14) and that the mice lung and liver cancers can be discounted but
not ignored (Respondent's Submissions in Reply, para 14).
210 Priority Existing Chemical Number 8
19. The full list of animal studies considered by the Director of NICNAS is
given in Table 26 of Exhibit A8, the marked up draft report on
trichloroethylene at pages 89-92.
20. The key studies of rat kidney tumours are: the US National
Toxicology Program studies NTP 1988 (Exhibit A1 Vol 2.2 Tab 24) and
NTP 1990 (Exhibit A1 Vol 2.2 Tab 20), and Maltoni et al. 1988 (T6 Vol 4
Tab 36; this is the full study of Maltoni et al., 1986 listed in Exhibit A8,
Table 26).
21. As pointed out by Counsel for the Respondent (Transcript 387/16)
the best evidence that trichloroethylene produces kidney tumours in rats
comes from the Applicant's expert witness, Dr Green.
22. Dr Green in exhibit A12 stated 'in some of the lifetime studies a low
incidence of kidney cancer has been observed in male rats. The
instances in the national toxicology program studies and Maltoni, these
tumours have rarely achieved statistical significance but have
nevertheless been considered treatment related because of the rarity of
renal cancer in rats.'
23. Further, in his oral evidence Dr Green stated 'In all of these studies
you see kidney damage, then you see a very low incidence of kidney
cancer. If you look at the individual bioassays, and whether they are
statistically significant, whether they are adequate, inadequate or not,
many of those bioassays will fail, but at the end of the day there is a clear
correlation between kidney damage and a low incidence of cancer.' He
answered 'That's correct, yes' to the question 'And the clear correlation
that you have referred to was supported by the existence of cases of
kidney cancer in multiple strains and in studies which administer TCI by
both the oral route and the inhalation route. Is that correct?' (Transcript
91/15)
24. Counsel for the Applicant maintained that there is 'some weak
evidence on the rat kidney tumours, because the rat kidney tumours were
only observed at toxic doses or doses above the maximum tolerated
dose'. (Transcript 392/13)
25. The maximum tolerated dose was not exceeded in the Maltoni et al.,
1988 study (T6 Vol 4 Tab 36) as indicated by Counsel for the Respondent
(Respondent's Submissions in Reply, para 15).
26. The maximum tolerated dose may have been exceeded in the two
NTP studies at 500 and 1000 mg/kg/day given that the final mean body
weight of the trichloroethylene treated animals was approximately 10%
less than that of the control animals. Dr McConnell pointed out that this
difference was due to the trichlorethylene treated animals failing to keep
up with the control animals in gaining body weight after some 15 weeks.
(Transcript 142/20).
211
Trichloroethylene
27. The lack of weight gain in the animals treated with trichloroethylene is
consistent with kidney damage. Nonetheless, as stated above kidney
tumours are rare in rats and thus highly likely to be treatment related as
acknowledged by the Applicant's witness, Dr Green, as noted above.
28. In exhibit R9 (Report of Carcinogens Sub-committee 1997),
trichloroethylene is listed as 'reasonably anticipated to be a human
carcinogen'. Dr McConnell explained that what the US NTP did with this
report on carcinogens 'is to look at the totality of the data, much like you're
doing here, and they would take the same studies that they previously, the
National Toxicology Program has said are inadequate, but then they would
look at the totality of all these studies together with the totality of other
information, exactly as you're doing, and to form this opinion that whether
this material has potential or can be reasonably anticipated to be a human
carcinogen.' (Transcript 144/3)
29. Dr McConnell explained further that the US only have 2 categories of
carcinogen. He stated 'In a sense, they put our categories 2 and 3 into
reasonably anticipated to be a human carcinogen '. (Transcript 144/19)
Rat kidney tumours: precursor lesions
30. Dr McConnell (former Chair, Science Advisory Panel of the US
Environmental Protection Agency), showed the Tribunal colour slides of
tissue sections (Exhibit R13) from the US National Toxicology Program
(NTP) studies into kidney damage in rats exposed to trichlorethylene. Dr
McConnell interpreted these slides as clearly showing precursor lesions.
He stated 'If I had not seen the precursor lesions in those rat studies, I
would have not - because the incidence was so low, I would have thought
that this could have been a spurious observation, the kidney tumours, but
with the presence of the precursor lesion this strengthened my view that
these kidney tumours were, indeed, related to exposure to TCI.'
(Transcript 103/13)
31. Dr McConnell provided a plausible explanation for the mode of kidney
tumour production by trichloroethylene: 'a progression from toxicity to
hyperplasia to neoplasia and benign-neoplasia and finally malignant
neoplasia'. (Transcript 103/5). The precursor lesions that he described in
the slides from the NTP study were a marker of this progression - 'We
think that if you see precursor lesions in the same organ that you have the
carcinogenic response, then that carcinogenic response has more
significance'. (Transcript 103/6) Dr Green also gave 'considerable weight'
to the finding of precursor lesions. (Transcript 91/2)
32. The Tribunal was satisfied that Dr McConnell's progression
mechanism from precursor lesions to malignant neoplasia was a
reasonable explanation of the mode of action of trichloroethylene
producing the observed rat kidney tumours.
Rat kidney tumours: mechanism(s) of production
212 Priority Existing Chemical Number 8
33. The Tribunal then went on to consider the detailed mechanism(s)
whereby trichloroethylene produced kidney tumours in rats.
34. Evidence was presented to the Tribunal on how trichloroethylene
produced kidney tumours in rats. Did the kidney tumours result from
cytotoxicity and subsequent regeneration, or from genotoxicity?
35. The Applicant's position was that 'so far as carcinogenicity is
concerned is that it is accepted by all the experts that the cause of the rat
kidney tumours is cytotoxicity and regeneration, It was accepted by both
Dr Green and Dr McConnell that there was no genotoxic effect which
produced the tumours observed.' (Transcript 392/5)
36. The Respondent's Submission in Reply (para 19) maintained "There
is no inconsistency between cytotoxicity and regeneration on the one hand
and mutation of the VHL (tumour suppressor) gene on the other. Indeed,
mutation of the VHL gene may be an explanation for the appearance of
neoplasia in the regeneration. '
37. At issue is the mechanism(s) by which trichloroethylene may have
produced kidney tumours. In exhibit R11 (The 1995 ASCEPT Toxicology
Workshop on 'Health-Based Risk Assessment of Contaminated Land:
Focus on Carcinogens' ), Dr Iain Purchase (Zeneca UK) points out that
'many chemicals found to produce cancer in animals do not interact
directly with DNA but have an indirect, non-genotoxic mechanism of
action' (Page 7), while Dr Jim Fitzgerald (South Australian Health
Commission) states 'in reality it is difficult to prove that a carcinogen is
really non-genotoxic, and here mechanistic understanding is very
important' (Page 13).
38. Three possible mechanisms for the production of kidney tumours
were put before the Tribunal: (1) the DCVC pathway, referring to the
trichloroethylene metabolite S-(dichlorovinyl)-cysteine; (2) the formic acid
pathway, referring to the increased production of formic acid as a result
ingestion of trichloroethylene; and (3) the mutation of the tumour
suppressor gene, VHL, a mechanism arising from molecular biological
studies on humans exposed to trichloroethylene in the workplace.
39. These three mechanisms (and other possible mechanisms) are not
mutually exclusive and each could contribute to the production of kidney
tumours.
The DCVC pathway
40. Dr Green provided evidence (A9) on the metabolism of
trichlorethylene. Most (80-90%) of ingested trichloroethylene is exhaled,
the remainder being metabolised and excreted in the urine (Transcript
95/25). The major metabolic pathway involves metabolism by cytochrome
P-450 to trichloroacetic acid. A minor pathway involving glutathione S-
213
Trichloroethylene
transferase leads to the production of DCVC. The DCVC pathway was
estimated to represent less than 0.005% of the injected dose of
trichloroethylene.
41. Dr McConnell, when asked had he come across any other chemical
that produces similar precursor lesions to trichloroethylene, stated 'the
chemical that comes to mind is this DCVC'. (Transcript 106/26). However,
Dr McConnell agreed that he knew 'of no evidence from your appraisal of
any of the literature which demonstrates that dichlorovinylcysteine has an
effect on or produces rat kidney tumours'. (Transcript 112/26)
42. From this and other evidence present, the Tribunal considered that
the DCVC pathway was unlikely to be of major significance in the
production of rat kidney tumours by trichloroethylene, although it cannot
be completely excluded.
The formic acid pathway
43. Dr Green and his colleagues (Exhibit A13 - Green, Dow, Foster and
Hext, Formic acid excretion in rats exposed to trichloroethylene: a possible
explanation for renal toxicity in long-term studies, Toxicology, 1998, 127,
39-47) discovered that rats exposed to trichloroethylene excrete large
amounts of formic acid, a chemical associated with kidney damage in a
number of species.
44. Formic acid is not a metabolite of trichloroethylene. It is a chemical
normally present in mammals who use it to make amino acids and
components of DNA. It is not normally excreted in the urine in any
significant amount. Dr Green and his colleagues found that the
trichlorethylene metabolites, trichloroethanol and trichloroacetic acid inhibit
the enzyme methionine synthetase, which is involved in the methionine
salvage pathway. This results in a reduction in the production of
tetrahydrofolate by some 50%, which in turn leads to the reduced
utilisation of formic acid normally used to make N-formyl tetrahydrofolate.
The net result is greatly increased excretion of formic acid in the urine. Dr
Green described this for the Tribunal using exhibit A9(3).
45. Increased levels of formic acid in the urine are a possible explanation
for the kidney damage in rats following long-term administration of
trichloroethylene. Dr Green considered that this mechanism could explain
the tubular hyperplasia seen in the kidneys of rats dosed for 12 months
with trichloroethanol in their drinking water (Exhibit A9(8)).
46. Dr McConnell, however, found that there was no evidence that
formic acid duplicated the histopathology of the kidney tumours produced
by trichloroethylene, stating 'I think the formic acid hypothesis becomes
suspect with regard to its causation of the tumours in the rats'. (Transcript
107/30).
47. Dr Green and his colleagues (Exhibit A13) acknowledge that 'Renal
214 Priority Existing Chemical Number 8
toxicity is not normally reported following exposure to chemicals such as
methanol and formaldehyde which are metabolised to formic acid. .......
However, the clearance of formic acid produced metabolically from these
chemicals is rapid and markedly different from the high and sustained
formic acid exposure which is seen in trichloroethylene treated rats.'
48. The Tribunal considered that the formic acid pathway provided a
mechanistic hypothesis regarding the causation of kidney tumours in rats
by trichloroethylene that merited further investigation.
Folates, methylation and the methionine salvage pathway
49. Other possible mechanisms arise out of the finding by Green and his
colleagues that metabolites of trichloroethylene inhibit the methionine
salvage pathway.
50. Dr Green was asked about metabolic changes resulting from
inhibition of methionine synthetase in addition to the increased excretion of
formic acid. (Transcript 96/10). He noted that there was a build up of
methyl-tetrahydrofolate in plasma and considered that there may be a
reduction in methionine levels although they had not measured this. He
had previously drawn attention to a 50% reduction in the levels of
tetrahydrofolate. (Exhibit A9(3))
51. Dr Green was asked about any association between folates and
cancer. He noted that there are chemotherapeutic drugs that act on folate
metabolism but that these acted higher up the metabolic pathway between
folate and dihydrofolate, or between dihydrofolate and tetrahydrofolate.
(Transcript 97/3)
52. Subsequent to the hearing, the Tribunal was able to find an extensive
literature on folate and methionine deficiencies and cancer, including lack
of DNA methylation. For example, Kim et al. (Kim, Pogribny, Basnakian,
Miller, Selhub, James and Mason, Folate deficiency in rats induces DNA
strand breaks and hypomethylation within the p53 tumour suppressor
gene, American Journal of Clinical Nutrition, 1996, 65, 46-52) found that
folate deficiency induced DNA strand breaks both at the genomic level and
within specific sequences of the p53 tumour suppressor gene. Diets
deficient in methyl donors such as folate and methionine are known to
lead to carcinogenesis (Henning and Swendseid, The role of folate,
choline, and methionine in carcinogenesis induced by methyl-deficient
diets, Advances in Experimental Medicine and Biology, 1996, 399, 143-
155). Such dietary deficiencies are known to increase spontaneous and
chemically induced carcinogenesis (Rogers, Methyl donors in the diet and
responses to chemical carcinogens. American Journal of Clinical Nutrition,
1995, 61(3 Suppl), 659S-665S).
53. The substantially increased excretion of formic acid (a one-carbon
acid) demonstrated by Green et al in rats receiving trichloroethylene is
considered highly likely to result in a significant metabolic deficit of one-
215
Trichloroethylene
carbon fragments for methylation. This could lead to reduced methylation
of DNA and RNA, hyperplasia, increased peroxidative damage and altered
carcinogen or promoter metabolism (as discussed in Rogers, 1995).
54. Clearly the consequences of disruption of the methionine salvage
pathway by metabolites of trichloroethylene are not limited to the
increased urinary secretion of formic acid. A number of possible
mechanisms exist that could result in the kidney tumours produced by
trichloroethylene, other than by formic acid. These mechanisms can be
tested experimentally.
55. These other possible mechanisms leading to kidney tumours are at
least as plausible as the formic acid pathway but no evidence regarding
them was presented to the Tribunal.
Rat kidney tumours: cytotoxicity and regeneration and/or
genotoxicity?
56. Genotoxicity is a key factor in the classification of chemicals as
carcinogens and is a critical issue in the classification of trichloroethylene.
57. Dr Green (Exhibit A2) in his expert witness statement stated
'Although there is evidence in some tests of weak genotoxicity, particularly
chromosomal effects, the mechanistic studies described above suggest
that the tumours seen in rats and mice develop without genotoxicity'.
58. On the balance of evidence, the Tribunal was not convinced that any
of the studies ruled out genotoxic components in the progression from
precursor lesions to the production of the rat kidney tumours.
59. Indeed, given the definitive evidence from the human studies of
effects on tumour suppressor genes, together with the rat metabolic
evidence of disruption of the methionine salvage pathway and changes to
levels of methionine and folate derivatives, the Tribunal was aware of
highly plausible molecular mechanisms for trichloroethylene induced
tumours involving genotoxicity.
Carcinogenesis supporting evidence
60. As listed in the Outline of Respondent's Submissions at 3.2.2.,
supporting evidence for carcinogenesis resulting from trichloroethylene
exposure comes from the findings of identical precursor lesions in the
mouse and rat kidney, and the findings of short-term repeat dose studies
in rats and mice showing kidney as the target organ of toxicity.
61. Kidney damage was the major consequence of a suicide attempt by
a 17-year-old male who attempted suicide by drinking approximately 70 ml
of trichloroethylene (Br黱ing et al., 1998; exhibit A10).
62. Substantially more cases of tubular damage were found in kidney cell
216 Priority Existing Chemical Number 8
carcinoma patients who had been exposed to high levels of
trichloroethylene over many years than among kidney cell carcinoma
patients who had not been exposed to trichloroethylene (Br黱ing et al.,
1996; T6 Vol 3 Tab 10). This supports the hypothesis that chronic tubular
damage may be regarded as a necessary precondition for trichlorethylene
to produce kidney carcinomas.
63. Elevated incidence ratios for kidney cancer in workers exposed to
trichloroethylene in three of seven retrospective cohort studies as
tabulated by Counsel for the Respondent in Exhibit R10. This is
consistent with the possibility of a causal connection between
trichloroethylene exposure and the incidence of kidney carcinomas.
64. The study reporting an increased incidence of kidney tumours in a
cohort of cardboard workers in Germany exposed to trichloroethylene by
Henschler, Vamvakas, Lammert, Dekant, Kraus, Thomas and Ulm
(Archives of Toxicology, 1995, 69, 291-299; T6, Vol 3, Tab 30) was the
subject of much discussion at the hearing.
65. It was clear that the study by Henschler et al. (1995) was not a
retrospective cohort study as claimed but a cluster study and that it should
carry lesser weight than if it had been a retrospective cohort study.
66. The study of Henschler et al. (1995) was the subject of two letters to
the editor of Archives of Toxicology, and a reply from Henschler et al.,
published together in the same issue of Archives of Toxicology: Swaen
(Archives of Toxicology,. 1995, 70, 127-128; T6, Vol 4, Tab 51), Bloeman
and Tomenson (Archives of Toxicology, 1995, 70, 129-130; T6, Vol 3, Tab
7) and Henschler et al. (Archives of Toxicology, 1995, 70, 131-133; T6,
Vol 3, Tab 29).
67. In their reply statement Henschler et al. (Archives of Toxicology,
1995, 70, 131-133; T6, Vol 3, Tab 29) make the following statement about
the letters of Swaen, and Bloeman and Tomenson: 'The letters are the
final manifestation of vigorous efforts of a group of scientists employed in
or engaged by industrial companies to prevent our study from being
published and acknowledged, put forward on any accessible level, even at
times violating the integrity which normally governs relations among
scientists'.
68. Henschler et al. have not withdrawn their results or retracted the
conclusions that they drew from their results, other than conceding that
theirs was a cluster study.
69. Counsel for the Applicant questioned the value of Henschler's
conclusions as Henschler, on his own admission was not an
epidemiologist. It was noted, however, that three of the seven authors on
the Henschler et al., 1995 paper and reply gave their addresses as the
Institute for Medical Statistics and Epidemiology at the Munich Technical
University.
217
Trichloroethylene
70. Henschler and his colleagues followed up their cohort-study with a
hospital based case control study claimed to demonstrate an association
of kidney cancer with long-term exposure to trichloroethylene (Vamvakas,
Br黱ing, Thomasson, Lammert, Baum黮ler, Bolt, Dekant, Birner,
Henschler and Ulm, Renal cell cancer correlated with occupational
exposure to trichloroethene, Journal of Cancer Research and Clinical
Oncology, 1998, 124, 374-382; Exhibit A1, Vol 3, Tab 6).
71. The studies of Henschler et al. (1995) and Vamvakas et al. (1998)
were the subject of criticism at the hearing by witnesses Dr Swaen and
Professor Sim.
72. Counsel for the Respondent stated in the Respondent's Submissions
in Reply (para 21) that the Director's case does not rest upon the studies
by Henschler et al. (1995) and Vamvakas et al. (1998) and that it was
common ground that the studies should be given little weight.
The tumour suppressor gene mechanism
73. Clear-cell renal carcinoma is one of the few human tumours known to
evolve from mutations of a specific gene, the von Hippel-Lindau (VHL)
tumour suppressor gene. Specific somatic mutations in this gene have
been described in humans exposed to trichloroethylene in the workplace
(Exhibit A1 Vol 4.1 Tab 1); Brauch, Weirich, Hornauer, St鰎kel, W鰄l and
Br黱ing, Trichloroethylene exposure and specific somatic mutations in
patients with renal cell carcinoma, Journal of the National Cancer Institute,
1999, 91, 854-861).
74. This study is the full publication following up from the short
communication by Br黱ing, Weirich, Hornauer, H鰈er and Brauch, Renal
cell carcinomas in trichloroethylene (TRI) exposed persons are associated
with somatic mutations in the von Hippel-Lindau (VHL) tumour
suppression gene, Archives of Toxicology, 1997, 71, 332-335 (T6 Vol 3
Tab 9). The Br黱ing et al. (1997) study concluded 'In addition to the
available epidemiological studies the results are now further proof for
human renal carcinogenicity induced by high occupational exposure to
TRI'.
75. Brauch et al. (1999) found somatic mutations in the VHL gene in 75%
of trichloroethylene-exposed patients. The mutations were frequently
multiple and there was an association between the number of mutations
and the severity of the trichloroethylene exposure.
76. Further, they observed a 'specific mutational hot spot at VHL
nucleotide 454' in the renal cell carcinomas of 39% of the patients
exposed to trichloroethylene. This mutation was neither detected in any of
the renal cell carcinomas (RCCs) from patients without trichlorethylene
exposure nor in any of the healthy subjects.
218 Priority Existing Chemical Number 8
77. Brauch et al. (1999) concluded 'Our findings of unique and frequent
VHL: mutations in RCCs of TRI-exposed patients present, to our
knowledge, the first molecular evidence between exposure to a defined
carcinogen, gene damage, and kidney cancer'.
78. The Tribunal heard evidence regarding the detailed methodology of
the Brauch et al. (1999) study, none of which detracted from the overall
conclusions of the authors. Indeed the evidence was that this study had
been very well carried out.
79. The Tribunal regarded the Brauch et al. (1999) findings as definitive
evidence providing a molecular basis, i.e. mutation of the VHL tumour
suppressor gene, for the kidney tumours produced in humans exposed to
trichloroethylene.
Category 3 carcinogenic substances
80. The Applicant accepts that trichloroethylene is a Category 3
carcinogen but disputes that there is sufficient evidence to place it in
Category 2.
81. Paragraph 4.85 of the Approved Criteria states that Category 3
actually comprises 2 sub-categories: (a) substances which are well
investigated but for which the evidence of a tumour-inducing effect is
insufficient for classification in Category 2. Additional experiments would
not be expected to yield further relevant information with respect to
classification; (b) substances which are insufficiently investigated. The
available data are inadequate, but they raise concern for humans. This
classification is provisional; further experiments are necessary before a
final decision can be made.
82. Weighing the evidence before it, the Tribunal considers there is more
than sufficient evidence to place trichloroethylene in Category 2.
83. Paragraph 4.86 of the Approved Criteria states: For a distinction
between Categories 2 and 3 the arguments listed below are relevant
which reduce the significance of experimental tumour induction in view of
possible human exposure. The arguments especially in combination,
would lead in most cases to classification in category 3, even though
tumours have been induced in animals. Each of the dot points that follow
this statement will be discussed in turn.
84. 'carcinogenic effect only at very high dose levels exceeding the
'maximum tolerated dose'. The maximal tolerated dose is characterised
by toxic effects which, although not yet reducing lifespan, go along with
physical changes such as about 10% retardation in weight gain.,' The
evidence is that kidney tumours and precursor lesions have been reported
in rats at doses of trichloroethylene below the maximum tolerated doses.
85. 'appearance of tumours, especially at high dose levels, only in
219
Trichloroethylene
particular organs of certain species known to be susceptible to a high
spontaneous tumour formation.,' Rat kidney tumours of the type produced
by trichloroethylene are relatively rare.
86. 'appearance of tumours, only at the site of application, in very
sensitive test systems (eg intraperitoneal, or subcutaneous application of
certain locally active compounds), if the particular target is not relevant to
humans,' The tumours induced by trichloroethylene in rat kidney are
remote from the site of application and they are regarded as being
relevant to humans given the epidemiological evidence of an association
between trichloroethylene exposure and kidney tumours in humans.
87. 'lack of genotoxicity in short-term tests in vivo and in vitro,' The
genotoxicity of trichloroethylene is still under investigation but highly
plausible mechanisms for genotoxicity exist, i.e. mutations in tumour
suppressor genes in humans exposed to trichloroethylene.
88. 'existence of a secondary mechanism of action with the implication of
a practical threshold above certain dose level (eg hormonal effects on
target organs or on mechanisms of physiological regulation, chronic
stimulation of cell proliferation.' Trichloroethylene is known to disrupt
metabolism resulting in the increased excretion of formic acid (a
secondary mechanism yet to be linked to tumour production) and
disruption of methionine and folate biochemistry (possible genotoxic
mechanisms yet to be thoroughly investigated).
89. 'existence of a species-specific mechanism of tumour formation (eg
by specific metabolic pathways irrelevant to humans.' There is no
evidence that trichloroethylene produces rat kidney tumours by
mechanism(s) irrelevant to humans.
Category 2 carcinogenic substances
90. In order to be categorised as a Category 2 carcinogenic substance,
the evidence regarding trichloroethylene must satisfy paragraph 4.80 in
the Approved Criteria, i.e. Substances are determined to be hazardous
and classified as Toxic (T) and assigned risk phrase R45 or R49 in
accordance with the criteria given below.
91. The criteria referred to in paragraph 4.80 are specified in paragraphs
4.81, 4.82 and 4.83. The evidence pertaining to each of these paragraphs
will be discussed in turn.
92. Paragraph 4.81 states: A substance is included in category 2 if there
is sufficient evidence on the basis of appropriate long term animal studies
or other relevant information, to provide a strong presumption that human
exposure to that substance may result in the development of cancer.
93. Taking into account the submissions before it on the interpretation of
the key phases 'sufficient evidence', 'strong presumption' and 'may result',
220 Priority Existing Chemical Number 8
the Tribunal finds that there is more than sufficient evidence on the basis
of the long term studies in rats to provide a strong presumption that human
exposure to trichloroethylene may result in the development of kidney
cancer.
94. Paragraph 4.82 states: For classification as a Category 2 carcinogen
either positive results in two animal species should be available or clear
positive evidence in one species, together with supporting evidence such
as genotoxicity data, metabolic or biochemical studies, induction of benign
tumours, structural relationship with other known carcinogens, or data
from epidemiological studies suggesting as association.
95. Taking a weight of evidence approach on all of the evidence before it,
the Tribunal concludes that there is clear positive evidence that
trichloroethylene produces kidney tumours in rats by two different routes of
long term exposure (oral and inhalation) in different strains of rats and in
different test laboratories.
96. Taking a weight of evidence approach on all of the evidence before it,
the Tribunal concludes that there is, at the very least, supporting evidence
that trichloroethylene produces anatomical, metabolic and biochemical
changes in rats consistent with the production of kidney tumours.
97. Taking a weight of evidence approach on all of the evidence before it,
the Tribunal concludes that there is, at the very least, supporting evidence
from epidemiological studies that there is an association between
exposure to trichloroethylene and kidney tumours in humans.
98. Paragraph 4.83 states: Human data providing suspicions of
carcinogenic potential may warrant a Category 2 classification irrespective
of the nature of any animal data. Increased confidence in the credibility of
a causal relationship by evidence of carcinogenicity in animals and/or of
genotoxic potential in short term screening tests.
99. The Tribunal concludes that the finding of specific mutations in a
tumour suppressor gene in kidney carcinoma cells from humans exposed
to trichloroethylene but not in kidney carcinoma cells from humans not
exposed to trichloroethylene is most certainly 'human data providing
suspicions of carcinogenic potential' and provides a plausible causal
genotoxic mechanism for such trichloroethylene associated cancers.
Category 1 carcinogenic substances
100. Paragraph 4.77 of the Approved Criteria states: The placing of a
substance into category 1 is done on the basis of epidemiological data;
101. Paragraph 4.79 states: A substance is included in Category 1 if there
is sufficient evidence to establish a causal relationship between human
exposure and the development of cancer on the basis of epidemiological
data.
221
Trichloroethylene
102. The Tribunal considers that there is not yet sufficient evidence from
epidemiological studies that to establish a causal relationship, as distinct
from an association, between exposure to trichloroethylene and kidney
tumours in humans.
103. Further, the Tribunal considers that, based on current findings on
tumour suppressor genes, a molecular biological approach to the
epidemiological studies based on analysing disorders in specific genes
could provide data sufficient to warrant a Category 1 carcinogen status in
the future for trichloroethylene.
Trichloroethylene as a Category 2 carcinogenic substance
104. On the above basis the Tribunal finds that trichloroethylene should be
categorised as a Category 2 carcinogenic substance.
MUTAGENICITY & TRICHLOROETHYLENE (TCE)
105. The Director, in her draft report, notified in the Chemical Gazette on
5 May 1998, recommended that TCE be categorised as a category 3 R40
mutagen. In response to an application for variation in the draft decision
requested by Dow Chemicals, among others, the Director notified her
decision on the variations in the Chemical Gazette on 4 August 1998,
having advised the applicants of her decision by mail on 24 July 1998.
The categorisation of TCE remained that of category 3.
106. In reaching both decisions the Director considered the criteria
entitled "Approved criteria for classifying hazardous substances" made
pursuant to the Industrial Chemical (Notification and Assessment) Act
1989. In addition, she reviewed all relevant scientific data published to the
date of her decision and the European Union Specialised Expert Group's
considerations regarding the mutagenic and carcinogenic potential of TCE
discussed at their meeting in June 1997.
107. The approved criteria in regard to mutagenic substances state:
"MUTAGENIC SUBSTANCES
4.88 Substances are determined to be hazardous due to mutagenic
effects if they fall into one of the following categories:
Category 1 Substances known to be mutagenic to humans.
Category 2 Substances which should be regarded as if they are
mutagenic to humans.
Category 3 Substances which cause concern for humans owing to
possible mutagenic effects, but in respect of which
available information does not satisfactorily demonstrate
heritable genetic damages.
EXPLANATORY NOTES REGARDING THE CATEGORISATION OF
MUTAGENIC SUBSTANCES
4.89 A mutation is a permanent change in the amount or structure of the
genetic material in an organism, resulting in a change of the
222 Priority Existing Chemical Number 8
phenotypic characteristics of the organism. The alterations may
involve a single gene, a block of DNA, or a whole chromosome.
Effects involving single genes may be a consequence of effects on
single DNA bases (point mutations) or of large changes including
deletions, within the gene. Effects on whole chromosomes may
involve structural or numerical changes. A mutation in the germ
cells in sexually reproducing organisms may be transmitted to the
offspring. A mutagen is an agent that gives rise to an enhanced
occurrence of mutations.
4.90 It should be noted that substances are classified as mutagens with
specific reference to inherited genetic damage. However, the type
of results leading to classification of chemicals in Category 3:
'induction of genetically relevant events in somatic cells', is
generally also regarded as an alert for possible carcinogenic
activity.
4.91 Method development for mutagenicity testing is an ongoing process.
For many new tests no standardised protocols and evaluation
criteria are presently available. For the evaluation of mutagenicity
data the quality of the test performance and the degree of validation
of the test method have to be considered."
108. The applicant, Dow Chemical, argues that TCE should not be
categorised as a mutagen and that the Director's finding that it is a
Category 3 R40 mutagen is incorrect.
"CATEGORY 3
4.99 Substances are determined to be hazardous and classified as
Harmful (Xn) and assigned risk phrase R40 in accordance with
the criteria given below.
R40 POSSIBLE RISK OF IRREVERSIBLE EFFECTS
4.100 A substance is included in Category 3 if there is evidence from
appropriate mutagenicity studies, of concern that human
exposure can result in the development of heritable genetic
damage, but that this evidence is insufficient to place the
substance in Category 2.
4.101 To place a substance in Category 3, positive results are needed
in assays showing
mutagenic effects, or
other cellular interaction relevant to mutagenicity, in somatic cells
in mammals in vivo.
The latter especially would normally be supported by positive results from
in vitro mutagenicity assays.
4.102 For effects in somatic cells in vivo at present the following
methods are appropriate
(a) in vivo somatic cell mutagenicity assays:
?bone marrow micronucleus test or metaphase
analysis,
?metaphase analysis of peripheral lymphocytes,
?mouse coat colour spot test.
(b) in vivo somatic cell DNA interaction assays:
?test for Sister Chromatid Exchanges (SCEs) in
somatic cells,
?test for Unscheduled DNA Synthesis (UDS) in
somatic cells,
223
Trichloroethylene
? assay for the (covalent) binding of mutagen to
somatic cell DNA,
?assay for DNA damage, for example, by alkaline
elution, in somatic cells.
4.103 Substances showing positive results only n one or more in vitro
mutagenicity assays should normally not be classified. Their
further investigation using in vivo assays, however, is strongly
indicated. In exceptional cases, for example, for a substance
showing pronounced responses in several in vitro assays, for
which no relevant in vivo data are available, and which shows
resemblance to known mutagens/carcinogens, classification in
Category 3 could be considered."
109. In addition to the T documents containing the Director's Draft
Report, and including her reply to the requests for variation, and all the
scientific reports upon which the Director based her recommendations, the
Tribunal received into evidence the witness statements of Dr B.M. Elliott
(Ex. A6) and Dr Elliott's witness statement in reply (Ex. A7), and the
witness statement of Professor Donald MacPhee (Ex. R5); Professor
MacPhee's review of the Director's report (Ex.R5B), Professor MacPhee's
witness statement in reply (R6), and several scientific papers addressing
the subject of mutagenicity of TCE published since the Director's report
was released. Dr Elliott gave expert witness evidence to the Tribunal on
behalf of the applicant and Professor MacPhee on behalf of the
respondent.
110. The applicant's argument is based primarily on the failure of the
Director to critically survey the existing scientific data as of 5 May 1998
and the weight given to the negative and positive study results in reaching
her decision. The applicant contends that had these matters been
addressed correctly and the criteria interpreted more rigidly, TCI would not
be categorised as a mutagen. (Applicant's request at p130 of report and
17.1 at p183.)
111. The term genotoxicity appears to be a generic term embracing
cytotoxic cellular damage, changes leading to carcinogenesis be they
based on cytotoxicity or mutagenesis, and mutagenicity.
IN VITRO STUDIES
112. In her report, the Director dealt with the in vitro studies assessing
the presence or absence of mutations in TCE-exposed bacteria, fungi,
mouse lymphoma cells and the evidence for DNA damage as shown by
chromosomal aberration, SCE's and UDS's in rat hepatocytes. A
summary of these results is provided in Table 24 of her report (at p6),
which shows 13 positive results and 11 negative results. The Director
concluded that TCE was a weak in vitro mutagen. Both Dr Elliott for the
applicant and Professor MacPhee for the respondent agreed with the
Director's conclusion and that such positive results could only be
supportive evidence (4.101 of the criteria).
224 Priority Existing Chemical Number 8
IN VIVO STUDIES
113. Item 4.101 of the approved criteria states that to place a substance
as a category 3, positive results are needed in assays showing (a)
mutagenic effects or, (b) other cellular interaction relevant to mutagenicity,
in somatic cells in mammals in vivo. Item 4.102 of the criteria delineates a
somatic cell interaction/DNA damage methods considered appropriate.
114. The studies considered by the Director and whether or not they
were positive or negative are summarised in Table 25 of the Director's
report (at p83). Whilst noting the limitations of some of the studies and, in
particular, Schiestl et al (1977) and Bruning et al (1997), the Director
concluded that the overall data raised concern about possible mutagenic
effects of TCE.
115. The majority of tests in common usage measure DNA damage as
an end point. The Tribunal notes that DNA damage does not equate with
mutagenic effects, but are a pointer to potential mutagenicity (MacPhee,
R5, p7). The Director considered in some detail the report of the
micronucleus tests performed by Kligerman et al in rats and mice exposed
to inhalation of various doses of TCE. This study reported a dose related
increase in micronuclei in rat bone marrow polychromatic erythrocytes. At
doses of 5000 ppm the increase was four-fold and was reproducible.
There was associated evidence of cytotoxicity in the erythrocytes in bone
marrow. No significant changes were seen in mice similarly exposed.
Rats exposed for six hours per day for four days did not exhibit an
increase in micronuclei although, as the Director pointed out, the
concurrent control group had an unusually high number of micronuclei
(Kligerman et al (1994) Inhalation studies of the genotixicity of
trichloroethylene to rodents. Mutat Res, 322: 87-96). Whilst the Director
viewed this study as a positive result, she expressed reservations
regarding the four day inhalation group. A dose related increase in
micronucleated polychromatic erythrocytes in mice was reported by Duprat
& Gradiski (Duprat P & Gradiski D (1980) Cytogenetic effect of
trichloroethylene in the mouse as evaluated by the micronucleus test.
ITRCS Med Sci, 8:182). She expressed doubts as to the significance of
the study resulting from uncertainties of the scoring method used and the
unusually high frequency of micronucleated PCEs in the control group.
116. The Director also considered the results of TCE intra-peritoneal
administration to pink-eyed unstable mutation mice (C57BL-6JPUN/PUN)
as reported by Robert H. Schiestl et al in 1997 (Carcinogens induce
reversion of the mouse pink-eyed unstable mutation. Proc Natl Acad Sci,
94:4576-4581). In this study a positive response was noted with a spotting
frequency of 32% in the offspring of mice subjected to intra-peritoneal
trichloroethylene whereas the corn oil alone control group had a spotting
frequency of 3.9%. The Director noted that this was a preliminary study,
but raised concern regarding mutagenic effects of TCE.
117. In the section of her report entitled Human Health Effects (p99) the
225
Trichloroethylene
Director dealt with a short communication by Bruning et al with the Editor
of the journal Archives Toxicology 1997 (Thomas Bruning et al Arch
Toxicol 1997 71:332-335). This report dealt with observed increased
incidence of renal cell carcinoma in persons with prolonged high exposure
to TCE. It compared this test group with an unexposed control group and
measured somatic mutations of the von Hippel Lindau (VHL) tumour
suppressor gene. Mutations in the VHL suppressor gene are known to be
a feature of renal cell carcinoma. Bruning had previously reported TCE
associated tubular damage preceding and perhaps enhancing the
nephrocarcinogenic effect. This nephrocarcinogenic effect had been
attributed to the TRE metabolyte dichlorovinylcysteine (DCVC). Somatic
VHL mutations had been known to be a common molecular event in renal
cell carcinoma from 1994. Bruning reported aberrations of the VHL gene
in all 23 renal cell carcinoma patients who had had lengthy and high
exposure to TCE. The control group of non-TCE exposed patients with
renal cell carcinoma showed 33% to 55% incidence of VHL mutations in
various studies. The Director regarded the Bruning report as being
supportive evidence raising concern regarding possible mutagenic effects
of TCE.
118. The Director did not have available to her more recent studies
placed in evidence before this Tribunal, and addressed in their witness
statements and oral evidence by Dr Elliott and Professor MacPhee. These
reports were six in number and are entitled as follows:
? T.V. Sujatha, M.J. Hegde - C-Mytotic Effects of Trichloroethylene
(TCE) on Bone Marrow Cells of Mice. Mutation Research 413 (1998)
151-158. In this study the authors concluded that preliminary results
indicated that TCE is capable of inducing C-mytotic effects in mice
bone marrow cells which is suggestive of its aneuploidy induction
potential.
? Luigi Robbiano et al. Increased frequency of micronucleated kidney
cells in rats exposed to halogenated anaesthetics. Mutation Research
413 (1998) 1-6. This study reported a potential genotoxic activity of
halogenated anaesthetics (including trichloroethylene) for the rat
kidney.
? Clay (Study Director) Report No. CTL/T/2976. Trichloroethylene and
S-1,2-Dichlorovinylcysteine: In vivo comet and UDS assays in the rat
kidney dated 29 September 1998; and First Supplement to CTL-T-
2976 Trichloroethylene and S-1,2-Dichlorovinylcysteine: in vivo comet
and UDS assays in the rat kidney dated 4 February 1999. Both of
these studies from The Central Toxicology Laboratory at Alderley Park,
Macclesfield, Cheshire, United Kingdom, were interpreted as showing
no evidence of DNA damage in rats exposed to DCVC or TCE.
? George R. Douglas et al. Evidence for the lack of base change and
small deletion mutation induction by trichloroethylene in lacZ transgenic
mice. Environmental and Molecular Mutagenesis 34:190-194 (1999).
This study was report as showing that TCE did not induce base change
or small deletion mutations in transgenic mice.
? Brauch, H. et al. Trichloroethylene exposure and specific somatic
226 Priority Existing Chemical Number 8
mutations in patients with renal cell carcinoma. Journal of the National
Cancer Institute. Vol. 91, No. 10, May 19, 1999. This report from the
Bruning group was a more detailed study of their preliminary report of
1997. They reported an incidence of VHL mutations of 75% in TRE
exposed patients with renal cell carcinoma. Mutations were frequently
multiple and an association was observed between the number of
mutations and the severity of TRE exposure. They identified specific
mutational hotspot at VHL nucleotide 454 in 39% of the exposed renal
cell carcinoma group. A nucleotide of 454 mutation was not detected
in any of the renal cell carcinoma patients without TRE exposure, nor in
any healthy subjects.
119. Dr Barry Elliott, a scientist within the AstraZeneca Central
Toxicology Laboratory in Macclesfield gave expert evidence on behalf of
the applicant. He addressed the overlap between cytotoxicity and
mutagenicity in many of the assays considered by the Director in her
report. He addressed the problem of the assays which rely on DNA
damage such as single strand break assays and micronucleus assays.
Comet assays fall into the same group. He expressed concern for the
results in those studies wherein TCE was delivered by the intraperitoneal
route and in a corn oil carrier. He was of the opinion that the use of the
intraperitoneal route could result in local deposition of TCE in close
proximity to major organs, such as the liver and the uterus. This was
particularly relevant to the Schiestl study. Dr Elliott felt that the
intraperitoneal route injection of TCE in corn oil may be deposited near the
uterus and preferentially absorbed through the uterine wall. This may
result in local cytotoxicity and may contribute to the results of less than
expected number of live offspring. He also questioned the adequacy of
the control group in the Schiestl study and the frequency of spontaneous
mutations in this group. He did not believe the observed threefold
increase in frequency of spotting was necessarily a positive result, and
also questioned the dose range used in the experiment. Dr Elliott pointed
out that the European Committee on Mutagenicity of Chemicals and Food
Consumer Products and the Environment had recommended that no
weight should be attached to the Schiestl investigation in view of the
limited study design, given negative findings reported in a mouse spot test
by a separate research group. Dr Elliott's major criticisms of Schiestl's
work are related to the design of the experiment, the dose level selection,
the causes of death in utero of the foetuses and was of the opinion that
trichloroethylene had not been identified in this study as the relevant agent
resulting in increased frequency of spotting.
120. Dr Elliott did not address the findings of Kligerman in either his
witness statement or examination-in-chief. In cross-examination Mr
Gageler questioned Dr Elliott as to why he thought the Kligerman study
had not been repeated in relation to TCE, as recommended by the
European Commission's group of specialised experts in the field of
mutagenicity, in 1997. Dr Elliott indicated that the cost of a bone marrow
micronucleus assay would be of the order of K10,000 to repeat the
experiment of Kligerman which was positive for TCE association with DNA
227
Trichloroethylene
damage as measured by bone marrow micronucleus assay.
121. Dr Elliott addressed the results of the Bruning paper of 1997, both in
his witness statement and in oral evidence before the Tribunal. He was of
the opinion that the Bruning study was well conducted, but that they had
simply shown that the DNA from the VHL suppressor gene from these
patients ran atypically on a gel. Questioned as to the appropriateness of
the control population and the general lack of knowledge of the control
population, he stated there was no evidence that TCE was causally
associated with VHL suppressor gene mutations (Transcript, p271). In
cross-examination by Mr Gageler, Dr Elliott agreed that whatever the form
of mutation it can only occur if the target cell remains alive (Transcript
p280). Dr Elliott agreed that the results in the Schiestl study were
statistically significant and that there had not been any published criticism
of this particular paper. He reiterated that his basic criticisms of the study
related to the dose level and the route of administration, and also the
conclusion reached that the statically significant increase in frequency
spotting was due to TCE having induced mutations in the offspring.
122. In relation to the Bruning and Brauch studies, Dr Elliott did not
question the methodology used in these studies but questioned the
interpretation of the results of the studies. He noted the high spontaneous
mutation rate in the control renal cell carcinoma patient group (60%). He
also expressed concern as to detailing of the control group based on age,
sex, smoking history and other parameters. The paper states that these
factors were taken into consideration, but does not in fact state the
incidence of such parameters as smoking nor the method of selection of
the control group other than that they all had renal cell carcinomas. Dr
Elliott agreed that the 454 mutation incidents showed a clear dose
response according to the severity of exposure. There is also a clear dose
response in terms of the number of mutations. He agreed that these were
statistically significant.
123. In reply to a question posed by the Tribunal, Dr Elliott stated that he
had no experimental evidence of local absorption of chemicals such as
TCE into the uterus. Dr Elliott agreed that TCE was rapidly absorbed from
all tissues and distributed to other organs by circulation. Also in response
to questioning by the Tribunal Dr Elliott agreed that the Brauch paper
revealed that in 52% of mutations in the VHL suppressor gene, the
mutation was located in exon one, 20% in exon two and 28% in exon
three. Dr Elliott agreed that the nucleotide 454 mutations located in exon
one were of significance in the TCE exposed renal cell carcinoma patient
group. He retained concern regarding the selection and analysis of the
control population, but agreed that the control population showed a zero
incidence of nucleotides 454 mutation and a zero incidence of multiple
mutations. Dr Elliott concluded that his interpretation was such that the
association of the mutations in the VHL gene to any particular causative
agent was, at the present time, unknown (transcript 299). Dr Elliott agreed
that the results of the Brauch studies would generate further research and
follow up experimentation in numerous laboratories.
228 Priority Existing Chemical Number 8
124. Professor MacPhee in his witness statement and in oral evidence
provided a useful (for the Tribunal's understanding) dissertation upon the
differences between genotoxicity and mutagenity. He emphasised that
mutagenicity is a property of a physical agent which changed the DNA in
living organisms in live cells and live tissues and in live animals. This
change is heritable. (Transcript p304). As a corollary to this statement,
cytotoxicity and cell death cannot result in mutagenic changes. He also
pointed out that while there are thousands of chemical mutants the
mechanism of mutagenesis is limited to a change in four bases in the DNA
molecule and two deletions in the DNA molecule.
125. In his statement "A report on the mutagenicity evaluation of the
trichloroethylene (TCE)", Professor MacPhee addressed the results of
Schiestl (1997) and concluded that TCE is capable of generating
mutations in the somatic cells of mice and that the bulk of the mutations
produced are extended deletions. In oral evidence he confirmed that the
Schiestl study was a test for mutagenicity. He found this study of
particular interest in that the pink eyed unstable mutation in the mouse
(PUN) is a deletion mutation and thus the presence of an increased
frequency of spotting in the offspring of such mice exposed to TCE must
result from a back mutation. This study, he said, was clearly positive for a
number of known mutagens, including the chemical TCE. Professor
MacPhee found Dr Elliott's criticism regarding the use of a dose level
considered too high to be essentially irrelevant. A toxic dose level would
have killed the melanocytes, negating the appearance of blacker spots in
the offspring. In addition, he found the route of administration of no
particular relevance when the results were positive in the skin cells of the
offspring of the mice to which the material had been administered,
regardless of the route of administration. Despite Dr Elliott's criticism with
respect to the number of viable offspring from the exposed mice, Professor
MacPhee felt there was essentially no difference in that there were 51
control offspring and 41 exposed offspring.
126. With respect to the Bruning study (1997), Professor MacPhee felt
the conclusions drawn were modest and reasonable (Ex. R5, p8, para 4).
His only criticism related to the conclusion drawn that VHL suppressor
gene mutations were more frequent in renal carcinoma patients
occupationally exposed to TCE than in renal tumour patients who had not
been exposed, were not specific for TCE to this gene as they had not
studied any other genes or sequences. Professor MacPhee regarded the
Bruning study as an attempt to delineate whether or not there is a
signature DNA change or DNA fingerprint which would allow them or their
colleagues or future investigators to distinguish between those renal
tumour patients who had TCE induced kidney tumours and those who
probably did not have TCE induced kidney tumours (Transcript, p307).
He saw this as an attempt to develop a diagnostic test , presumably for
workers' compensation purposes or the equivalent. In their efforts to find a
DNA fingerprint they had in their subsequent report (Brauch et al 1999)
demonstrated the presence of double and triple mutations in TCE exposed
229
Trichloroethylene
renal cancer patients. This mutation has been shown to reside in
nucleotide 454. Professor MacPhee was of the opinion that the control
group chosen in the Brauch and Bruning experiments was the best that
could be achieved, given that the control group by definition must be
persons with renal cell carcinomas and no history of TCE exposure.
127. In cross-examination, Professor MacPhee agreed that the VHL
gene mutation could be caused by a number of different events or
chemicals, that mutations whatever the mutagen have a final common
pathway of either base changes or deletion of DNA material and that a
comparative sequence analysis would not provide a specific pattern for
any mutagen. He was of the opinion that the Brauch data did link TCE
with the observed increased incidence of mutations.
128. In cross-examination by Mr Beach, Professor MacPhee dealt with
Dr Elliott's criticism of the control in the Schiestl study. He did not agree
with the criticism and found the Schiestl results statistically significant. He
felt the only control group to be considered was that reported
contemporaneously with the study group. He did not consider the
possibility of local toxicity of TCE injected intraperitoneally to be relevant,
given that the target organ was the offspring of the PUN mice. Professor
MacPhee also stated that TCE can induce a weak aneugenic effect in the
mouse and that he interpreted Dr Elliott's oral evidence as agreeing with
that statement.
129. There then followed what was termed a "hot tub" session in which
Dr Elliott and Professor MacPhee discussed various aspects of the
scientific reports before the Tribunal, and answered questions submitted
by both members of counsel and the Tribunal. First, Dr Elliott addressed
the question of whether or not he had stated that TCE was aneugenic.
This comment was made with regard to the results of the study of Sujatha
and Hegde. Dr Elliott concluded that the findings are consistent in the
parameters examined with TCI acting on the cellular protein architecture
and inducing changes in the protein spindle apparatus resulting in an
aneugenic effect. This, he stated, was his opinion of the study's results
but he did not agree with the interpretation.
130. Discussion ensued regarding the Kligerman study and the Duprat
and Gradiski studies in relation to micronucleus assay. This discussion
was not of assistance to the Tribunal. It related primarily to dosage levels
and frequency of administration and the conflicting results in the single and
repeated TCE exposures in rats. Dr Elliott concluded that in his view there
is no way that TCE is clearly or reproducibly showing an increase in
aneugenicity, chromosomal damage or even any reproducible positive
result in this assay type (Transcript p334).
131. Professor MacPhee argued that it is not scientifically appropriate to
balance positive results with other negative results (transcript, p346). At
page 347 of the Transcript Professor MacPhee states: You have to pay
more attention to positive results when you are concerned about human
230 Priority Existing Chemical Number 8
safety. Professor MacPhee directed a question to Dr Elliott regarding the
interpretation of positive results in light of other negative results, asking
"what would your next experimental step be?" Dr Elliott's reply was that
you would do a further set of appropriate experimental studies. (Transcript
p347). Dr Elliott was not aware of any further investigations along these
lines.
132. In response to questioning from Mr Beach for the applicant,
Professor MacPhee opined that micronucleus studies indicated that some
positive results needed further investigation. He discussed the Brauch
results and the high incidence of spontaneous mutations in patients with
renal cell carcinoma in the VHL suppressor gene. The highest incidence
placed on this spontaneous mutation was 60%. The significance of 100%
mutation rate in renal cell carcinoma patients exposed to TCE was
debated at some length (Transcript p360-363).
133. In answer to a question posed by the Tribunal, Professor MacPhee
agreed that the VHL suppressor gene was a marker of renal cell
carcinoma, but Dr Elliott felt that this summation of the VHL gene presence
blunted specific conclusions being drawn. The Tribunal then asked
whether these incidences blunted or magnified the results, to which
Professor MacPhee replied that magnifying is as good as any word.
(transcript p363). Dr Elliott disagreed with the term magnified and felt that
the observation of 100% VHL suppressor gene mutation result was
blunted by the existence of a 60% VHL suppressor gene mutation result in
the control group.
134. The Tribunal asked questions regarding the methodology of the
scientific investigations and the types of experimental animals used,
particularly in the Kligerman experiments. Dr Elliott assured the Tribunal
that these were standard numbers and certainly the same numbers were
used in his own laboratory.
135. Again in answer to a question from the Tribunal, Dr Elliott agreed
that any mutations had the potential to be carcinogenic as well as non-
carcinogenic; Professor MacPhee agreed with this. On that basis, the
Tribunal suggested that any evidence to support a mutation leading to
neoplasia should be treated with extreme caution from a regulatory sense.
Professor MacPhee essentially agreed with this statement.
136 The Tribunal had the advantage, compared to the Director at the
time of her draft report, of several more recent scientific reports regarding
mutagenicity of TCE. The Bruning and Brauch reports lend a great deal of
weight to the Director's concern that TCE is possibly mutagenic. In
particular the Brauch study has identified the point mutation of the VHL
suppressor gene at nucleotide 484. This point mutation was found only in
renal carcinoma patients exposed to TCE. The full significance of this
finding will be subject to further scientific investigation but prima facie
appears to be a finding of major scientific significance. The Tribunal finds
that the Director's recommendations that trichloroethylene be categorised
231
Trichloroethylene
as a Category 3 R40 (3 mutagen) is correct and the decision under review
with respect to mutagenicity is affirmed.
Conclusion
137. The applicant sought four changes to the draft report in its letter of 1
June 1988 (T5, pp 215-217). The first requested change related to page
130 of the draft report, which dealt with the classification of
trichloroethylene in relation to genotoxicity. The applicant wished the draft
report to say that trichloroethylene did not meet the Approved Criteria for
classification as a Category 3 (R40-M3) substance. We have decided
that it did meet the Approved Criteria for such a classification after
reviewing the evidence as to mutagenicity above. The decision under
review in relation to that requested change must be affirmed.
138. The second requested change related to page 131 of the draft
report, which dealt with the classification of trichloroethylene as a Category
2 carcinogen. The applicant sought the substitution of a paragraph saying
that trichloroethylene met the approved criteria for classification as
Category 3 carcinogen, and shortly stating the basis for such a conclusion.
For the reasons we have stated, we believe that the paragraph which the
applicant wanted changed was entirely appropriate, and that the
respondent's decision as to the second requested change should be
affirmed. The challenged paragraph read as follows:-
"Trichloroethylene meets the Approved Criteria for classification as a
Carcinogen Category 2 (National Occupational Health and Safety
Commission (NOHSC), 1994), that is, a substance regarded as if it is
carcinogenic to humans, on the basis of the occurrence of tumours in
experimental animals and limited evidence in workers. Thus the available
data provides suspicions of carcinogenic potential in humans (R45)."
139. The third requested change concerned the last paragraph of section
17.1 on page 184 of the draft report. The original version reads as
follows:
"The European Union is currently considering the classification of
trichloroethylene. Any new information that becomes available as a result
of this consideration should be considered in order to determine whether
the above classification remains valid."
The applicant requested that it be changed to read as follows:
"The European Union is currently considering the classification of
trichloroethylene with respect to carcinogenicity and mutagenicity. Until
the results of research studies clearly indicate a different classification is
appropriate it is recommended that the current hazard classification
Carcinogen: Category 3 R40(3) be maintained."
140. We have rejected the applicant's contentions as to the
carcinogenicity classification of trichloroethylene. We think there is a
232 Priority Existing Chemical Number 8
significant chance that the European Union's consideration of the
classification of the chemical may reveal or highlight new information in
relation to carcinogenicity, and that the challenged paragraph in the draft
report is therefore quite appropriate. We have therefore decided to affirm
the third decision under review.
141. The fourth request by the applicant for a change to the draft report
sought the inclusion in the abstract on page 2 thereof of a paragraph in the
same terms as the last one we have quoted. As we have reached a
contrary conclusion as to the appropriate carcinogenicity category, and
see no need to refer to the European Union's current consideration of the
appropriate classification of trichloroethylene as to carcinogenicity and
mutagenicity in the abstract, we have decided to affirm the fourth decision
under review, namely the decision not to include such a paragraph in the
abstract.
142. Thus we have decided to affirm all four of the decisions under
review. We considered whether it would be more appropriate to set aside
the decisions under review and remit the matter to the respondent with
recommendations that the draft report be changed to incorporate
references to material we have referred to that was published after the
draft report was written, and to the studies referred to in paragraph 52
above. Whilst the inclusion of such references in the draft report would
have been desirable, we think it preferable to do all we can to ensure that
this litigation is brought to an end, and that the process of reclassifying
trichloroethylene is completed as soon as possible. We have therefore
decided that it is preferable simply to affirm the decisions under review.
I certify that the 142 preceding paragraphs are a
true copy of the reasons for the decision herein of
Deputy President A M Blow OAM, QC., Professor
G A R Johnston AM, FRACI, FTSE, Miss E A
Shanahan
Signed:
....................................................................
.................
Personal Assistant
Date/s of Hearing 3,4,5,8,9, November 1999
Date of Decision 31 December 1999
Counsel for the Applicant Mr J Beach
Solicitors for Applicant Arthur Robinson & Hedderwicks
Counsel for the Respondent Mr S Gageler
Solicitor for the Respondent Australian Government Solicitor
233
Trichloroethylene
REFERENCES
ACGIH (1992) Threshold limit values for chemical substances and physical agents and
biological exposure indices. Cincinnati, Ohio, American Conference of Governmental
Industrial Hygienists.
Adams EM, Spencer HC, Rowe VK, et al. (1951) Vapor toxicity of trichloroethylene
determined by experiments on laboratory animals. Arch Ind Hyg Occup Med, 4: 469-481.
Adler I & et al. (1991) Mouse micronucleus test with known and suspect spindle
poisons:results from two laboratories. Mutagenesis, 6: 47-53.
Allen BC & Fisher JW (1993) Pharmacokinetic modeling of trichloroethylene and
trichloroacetic acid in humans. Risk Anal, 13: 71-86.
Anderson A (1957) Health dangers in industry from exposure to trichloroethylene. Acta
Med Scand, 157(Suppl 323): 7-220.
Anderson C, Sundberg K & Groth O (1986) Animal model for assessment of skin
irritancy. Contact Dermatitis, 15: 143-151.
Anon (1995) Chemical profile: trichloroethylene. Chemical Marketing Reporter(February
6).
Ansell Edmont Industrial (1990) Ansell Edmont chemical resistance guide (5th Ed).
Anttila A, Pukkala E, Sallmen M, et al. (1995) Cancer incidence among Finnish workers
exposed to halogenated hydrocarbons. Journal of Occupational and Environmental
Medicine, 37(7): 797-806.
Arai H, Nomiyama H, Saito K, et al. (1988) Health effects of high concentration of TCE
exposure for 12 weeks in rats. Sangko-Igaku, 30: 410-411.
Ashby J, Brady A, Elcombe CR, et al. (1994) Mechanistically-based human assessment
of peroxisome proliferator induced hepatocarcinogenesis. Human and Experimental
Toxicology, 13(Supplement 2).
ATSDR (1993) Toxicological profile for trichloroethylene. Atlanta, Georgia, Agency for
Toxic Substances and Disesase Registry.
ATSDR (1995) Toxicological profile for trichloroethylene. Atlanta, Georgia, Agency for
Toxic Substances and Disease Registry.
Australian Health Ministers' Advisory Council (1997) Standard for the Uniform
Scheduling of Drugs and Poisons No. 12. Canberra, Australian Government Publishing
Service.
Aviado D, Zakhari S, Simaan J, et al. (1976) Methyl chloroform and trichloroethylene in
the environment, Cleveland CRC Press.
234 Priority Existing Chemical Number 8
Axelson O,Anderson K, et al. (1978) A cohort study on trichloroethylene exposure and
cancer mortality. Journal of Occupational Medicine, 20: 194-196
Axelson O, Selden A, Andersson K, et al. (1994) Updated and expanded Swedish cohort
study on trichloroethylene and cancer risk. JOM, 36(5): 556-562.
Axelson O, Selden A, Andersson K, et al. (1994) Updated and expanded Swedish cohort
study on trichloroethylene and cancer risk. JOM, 36(5): 556-562.
Baden J, Kelley M, Mazze R, et al. (1979) Mutagenicity of inhalation anaesthetics:
trichloroethylene, divinyl ether, nitrous oxide and cyclopropane. Br J Anaesth, 15: 417-
421.
Bardodej Z & Vyskocil J (1956) The problem of trichloroethylene in occupational
medicine. AMA Arch Ind Health, 13: 581-592.
Bartsch H, Malaveille C, Barbin A, et al. (1979) Mutagenic and alkylating metabolites of
halo-ethylenes, chlorobutadienes and dichlorobutenes produced by rodent or human liver
tissues. Arch Toxicol, 41: 249-277.
Benford DJ & Bridges JW (1986) Xenobiotic metabolism in the lung. In: J. Bridges and
L. Chasseaud ed. Progress in drug metabolism. Taylor and Francis Ltd, , 9: 53-94.
Bernauer U, Birner G, Dekant W, et al. (1996) Biotransformation of trichloroethene:
dose-dependent excretion of 2,2,2-trichloro-metabolites and mercapturicm acids in rats
and humans after inhalation. Archives of Toxicology, 70: 338-346.
Best (1994) Calender guide to chemical-resistant Best gloves (2nd ed).
Bhunya SP & Behera BC (1987) Relative genotoxicity of trichloroacetic acid (TCA) as
revealed by different cytogenetic assays: bone marrow chromosome aberration,
micronucleus and sperm-head abnormality in the mouse. Mutat Res, 188: 215-221.
Blair A, Hartge P, Stewart PA, McAdams M, et al. (1998) Mortality and cancer incidence
of aircraft maintenance workers exposed to trichloroethylene and other organic solvents
and chemicals: extended follow up.Occu Environ Med,
55: 161-171
Bloemen LJ & Tomenson J (1995) Increased incidence of renal cell tumours in a cohort
of cardboard workers exposed to trichloroethylene. Arch Toxicol, 70: 129-130.
Bogen KT, Colston BW & Machiccio LK (1992) Dermal absorption of dilute aqueous
chloroform, trichloroethylene and tetrachloroethylene in hairless guinea pigs. Fund. Appl.
Toxicol, 18(30-39).
Bonatti S et al. (1992) The analysis of 10 potential spindle poisons for their ability to
induce CREST-positive micronuclei in human diploid fibroblasts. Mutagenesis, 7: 111-
114.
Bonnet P, Francin JM, Gradiski D, et al. (1980) Determination de al concentration
lethale50des principaux hydrocarbures aliphatiques chlores chez le rat. Arch Mal Prof,
41: 317-321.
235
Trichloroethylene
Bronzetti G, Corsi C, Cundari E, et al. (1984) Comparative genetic activity in vitro and in
vivo of 1,1-dichloroethylene, cis-and trans-1,2-dichloroethylene, trichloroethylene and
perchloroethylene. Acta Oncol, 5: 221-224.
Bronzetti G, Zeiger E & Frezza D (1978) Genetic activity of trichloroethylene in yeast. J
Environ Pathol Toxicol, 1: 411-418.
Bruce WR & Heddle JA (1979) The mutagenic activity of 61 agents as determined by the
micronucleus, Salmonella and sperm abnormality assays. Can J Genet Cytol, 21: 319-334.
Bruckner JV, Davis BD & Blancato JN (1989) Metabolism, toxicity and carcinogenicity
of trichloroethylene. Crit Rev in Toxicol, 20(1): 31-50.
Bruning T, Golka K, Makropoulos V, et al. (1996b) Preexistence of chronic tubular
damage in cases of renal cell cancer after long and high exposure to trichloroethylene.
Archives of Toxicology, 70: 259-260.
Bruning T, Vamvakas S, Makropoulos V, et al. (1996a) A case of acute intoxication by
trichloroethene: Clinical symptoms, toxicokinetics and renal damage. Arch Pharmacol,
353(Suppl R109).
Bruning T, Weirich G, Hornauer MA, et al. (1997) Renal cell carcinomas in
trichloroethene (TRI) exposed persons are associated with somatic mutations in the von
Hippel-Lindau (VHL) tumour suppressor gene. Arch Toxicol, 71: 332-335.
Buben JA & O'Flaherty EJ (1985) Delineation of the role of metabolism in the in the
hepatotoxicity of trichloroethylene and perchloroethylene: a dose-effect study. Toxicol
Appl Pharmacol, 78: 105-122.
Bull RJ, Sanchez IM, Nelson MA, et al. (1990) Liver tumour induction in B6C3F1 mice
by dichloroacetate and trichloroacetate. Toxicology, 63: 341-358.
Callen DF, Wolf CR & Philpot RM (1980) Cytochrome P-450 mediated genetic activity
and cytotoxicity of seven halogenated aliphatic hydrocarbons in Saccharomyces
cerevisiae. Mutat Res, 77: 55-63.
Capellini A & Grisler R (1958) Liver function in workers constantly exposed to
trichloroethylene. Med Lav, 49: 167-172.
Caspary WJ, Langenbach R, Penman BW, et al. (1988) The mutagenic activity of selected
compounds at the TK locus: rodent vs human cells. Mutation Research, 196: 61-81.
Cederberg I (1996). Personal communication.
CEFIC (1986) The occurrence of chlorinated solvents in the environment. Chemistry and
Industry, 24: 861-869.
Cerna M & Kypenova H (1977) Mugagenic activity of chloroethylenes analysed by
screening system tests. Mutat Res, 26: 214-215.
Chang LW, Daniel FB & DeAngelo AB (1992) Analysis of DNA strand breaks induced
in rodent liver in vivo, hepatocytes in primary culture, and a human cell line by
chlorinated acetic acids and chlorinated acetaldehydes. Environ Mol Mutag, 20: 277-288.
236 Priority Existing Chemical Number 8
Commandeur JNM, Boogaard J, Mulder GJ, et al. (1991) Mutagenicity and cytotoxicity
of two regioisomeric mercapturic acids and cysteine S-conjugates of trichloroethylene.
Arch Toxicol, 65: 373-380.
Conde-Salazar L, Guimarciens D, Romero LV, et al. (1983) Subcorneal pustular eruption
and erythema from occupational exposure to trichloroethylene. Contact Dermatitis, 19:
235-237.
Costa AK & Ivanetich KM (1984) Chlorinated ethylenes:their metabolism and effect on
DNA repair in rat hepatocytes. Carcinogenesis, 5: 1629-1636.
Cotter LH (1950) Trichloroethylene poisoning. Arch Ind Hyg Occup Med, 1: 319-322.
Crebelli R, Bignami M, Conti L, et al. (1982) Mutagenicity of trichloroethylene in
Salmonella typhimurium TA 100. Ann Ist Super Sanita, 18: 117-122.
Crebelli R, Conti G, Conti L, et al. (1985) Mutagenicity of trichloroethylene,
trichloroethanol and chloral hydrate in Aspergillus nidulans. Mutat Res, 155: 105-111.
Dalbey W & Bingham E (1978) Metabolism of trichloroethylene by the isolated perfused
lung. Toxicol Appl Pharmacol, 43: 267-277.
Daniel FB, DeAngelo AB, Stober JA, et al. (1992) Hepatocarcinogenicity of chloral
hydrate, 2-chloroacetaldehyde and dichloroacetic acid in the male B6C3F1 mouse. Fund
Appl Toxicol, 19: 159-168.
David NJ, Wolman R, Milne FJ, et al. (1989) Acute renal failure due to trichloroethylene
poisoning. Br J Ind Med, 46: 347-349.
Davidson IWF & Beliles RP (1991) Consideration of the target organ toxicity of
trichloroethylene in terms of metabolite toxicity and pharmacokinetics. Drug Metab Rev,
23: 493-599.
De Rosa E, Saia B & Bet E (1971) Epidemiological investigations on workers exposed to
trichlorethylene in a tannery. Lav Um, 23: 240-248.
DeAngelo AB, Daniel FB, McMillan L, et al. (1989) Species and strain sensitivity to the
induction of peroxisome proliferation by chloroacetic acid. Toxicol Appl Pharmacol, 101:
285-298.
Dees C & Travis C (1993) The mitogenic potential of trichloroethylne in B6C3F1 mice.
Toxicol Lett, 69: 129-137.
Degrassi F & Tanzarella C (1988) Immunofluorescent staining of kinetochores in
micronuclei: a new assay for the detection of aneuploidy. Mutat Res, 203: 339-345.
Dekant W, Metzler M & Henschler D (1984) Novel metabolites of trichloroethylene
through dechlorination reactions in rats, mice and humans. Biochem Pharmacol, 33:
2021-2027.
Dekant W, Vamvakas S & Berthold K (1986) Bacterial (-lyase mediated cleavage and
mutagenicity of cysteine conjugates derived from the nephrocarcinogenic alkenes
trichloroethylene, tetrachloroethylene and hexachorobutadiene. Chem Biol Interact, 60:
31-45.
237
Trichloroethylene
DeMarini DM, Perry E & Shelton ML (1994) Dichloroacetic acid and related
compounds: induction of prophage in E. Coli and mutagenicity and mutation spectra in
Salmonella TA100. Mutagenesis, 9: 429-437.
Deutsche Forschungsgemeinschaft (1996) Maximum concentrations at the workplace and
biological tolerance values for working materials. Report No 31. Weiheim, VCH.
Dimitrova M, Usheva G & Pavlova S (1974) The work environment's influence on the
cardiovascular system. Polycardiographic investigations in workers exposed to
trichloroethylene. Int Arch Arbeitsmed, 32: 145-148.
Dorfmueller MA, Henne SP, York RG, et al. (1979) Evaluation of teratogenicity and
behavioural toxicity with inhalation exposure of maternal rats to trichloroethylene.
Toxicology, 14: 153-166.
Douglas et al. (1995) as cited in UK SIAR (1996).
Dow Chemical Company (1993) Neurotoxicological examination of rats exposed to
trichloroethylene vapor for 13 weeks . The Dow Chemical Company, Health and
Environmental Sciences, The Toxicology Research Laboratory, Midland, MI.
Duprat P, Delsaut L & Gradiski D (1976) Irritant potency of the principle chlorinated
aliphatic solvents on the skin and ocular mucous membranes of rabbits. Eur J Toxicol, 3:
171-177.
Duprat P & Gradiski D (1980) Cytogenetic effect of trichloroethylene in the mouse as
evaluated by the micronucleus test. IRCS Med Sci, 8: 182.
ECETOC (1992) Hepatic peroxisome proliferation. Brussels, European Centre for
Ecotoxicology and Toxicology of Chemicals.
ECSA (1990) A comparison of cleaning methods. Aqueous and chlorinated solvents.
Brussels, European Chlorinated Solvent Association.
El Ghawabi SM, Mansoor MB & El Gamel M (1973) Chronic trichloroethylene exposure.
J Egypt Med Assoc, 56: 11-12.
Elcombe CR (1985) Species differences in carcinogenicity and peroxisome proliferation
due to trichloroethylene. A biochemical human hazard assessment. Arch Toxicol (Suppl
8): 6-17.
Elcombe CR, Rose MS & Pratt IS (1985) Biochemical, histological and ultrastructural
changes in rat and mouse liver following administration of trichloroethylene. Possible
relevance to species differences in hepatocarcinogenicity. Toxicol Appl Pharmacol, 79:
365-376.
Ertle T, Henschler D, Muller G, et al. (1972) Metabolism of trichloroethylene in man. I.
The significance of trichloroethylene in long-term exposure conditions. Arch Toxicol, 29:
171-188.
Ettema JH & Zielhuis RL (1975) Effect of alcohol, carbon monoxide and
trichloroethylene inhalation on mental capacity. Int Arch Occup Environ Health, 35: 117-
132.
238 Priority Existing Chemical Number 8
European Chemical News (1995) Swedes suggest tax to prevent perc use. (6-12 March):
21.
European Commission (1994) Technical Guidance Documents in support of the
Commission Regulation (EC) No 1488/94 on Risk Assessment for Existing Substances in
Accordance with Council Regulation (EEC) No 793/93. Luxembourg, European
Commission.
European Commission Directive 93/21/EEC (1993 27 April,) Adapting to technical
progress for the 18th time Council Directive 67/548/EEC on the approximation of the
laws, regulations and administrative provisions relating classification, packaging and
labelling of dangerous substances.
Fahrig R (1977) The mammalian spot test (Fellfleckentest) with mice. Arch Toxicol, 38:
87-98.
Fahrig R, Madle S, Baumann H (1995) Genetic toxicity of trichloroethylene (TCE).
Mutation Research, 340: 1-36
Federal Office of Road Safety (1998) Australian Code for the Transport of Dangerous
Goods by Road and Rail (6th ed.). Canberra, Australian Government Publishing Service.
Feingold A & Holaday DA (1977) The pharmacokinetics of metabolism of inhalation
anaesthetics. Br J.Anaesth, 49: 155-162.
Feldman RG (1970) Facial nerve latency studies in man. Effects of trichloroethylene
exposure. Electromyography, 10: 93-100.
Feldman RG, White RF, Eriator II, et al. (1994) Neurotoxic effects of trichloroethylene in
drinking water. In: R. Isaacson and K. Jensen ed. The vulnerable brain and environmental
risks: vol 3: Toxins in air and water. Plenum Press, New York.
Fernandez JG, Droz PO, Humbert BE, et al. (1977) Trichloroethylene exposure:
simulation of uptake, excretion and metabolism using a mathematical model. British
Journal of Industrial Medicine, 34: 43-55.
Fernandez JG, Humbert BE, Droz PO, et al. (1975) Exposition au trichloroethylene.
Bilan de l'absorption, de l'excretion et du metabolisme chez des sujets humains. Arch Mal
Prof, 36: 397 (as cited in Lauwerys 1993).
Fiserova-Bergerova V & Pierce JT (1989) Biological monitoring V: dermal absorption.
Appl Ind Hyg, 4(8): F-14-F21.
Fisher JW, Gargas ML & Allen BC (1991) Physiologically based pharmacokinetic
modeling with trichloroethylene and its metabolite, trichloroacetic acid, in the rat and
mouse. Toxicol Appl Pharmacol, 109: 183-195.
Flindt-Hansen H & Isager H (1987) Scleroderma after occupational exposure to
trichloroethylene and trichloroethane. Acta Derma Venereologica, 67: 263-264.
Fonzi S, Focardi L & Raddi R (1967) Trichloroethylene as a hepatotoxic substance.
Experimental study in chronic poisoning. Lav Um (Suppl 12), 29: 94-110.
239
Trichloroethylene
Forkert PG & Birch DW (1989) Pulmonary toxicity of trichloroethylene in mice.
Covalent binding and morphological manifestations. Drug Metab Dispos, 17: 106-113.
Forkert PG, Sylvestre PL & Poland JS (1985) Lung injury induced by trichloroethylene.
Toxicology, 34: 143-160.
Forsberg K & Mansdorf S.Z (1993) Quick selection guide to chemical protective clothing
(2nd ed), Van Nostrand Reinhold, NY.
Fredrickson M, Bengtsson N-O, Hardell L, et al. (1989) Colon cancer, physical activity
and occupational exposures. A case control study. Cancer, 63: 1838-1842.
Friberg L, Kylin B & Nystrom A (1953) Toxicities of trichloroethylene and
tetrachloroethylene and Fujiwara's pyridine-alkali reaction. Acta Pharmacol Toxicol, 9:
303-312.
Fukuda K, Takemoto K & Tsurata H (1983) Inhalation carcinogenicity of
trichloroethylene in mice and rats. Ind Health, 21: 243-254.
Furnus C et al. (1990) The induction of aneuploidy in cultured Chinese hamster cells by
propionaldehyde and chloral hydrate. Mutagenesis, 5: 323-326.
Galloway SM, Armstrong MJ, Reuben C, et al. (1987) Chromosome aberrations and
sister chromatid exchanges in Chinese hamster ovary cells: evaluation of 108 chemicals.
Environ Mol Mutagen (Suppl 10), 10: 1-175.
Garabrant DH, Held J, Langholz B, et al. (1998) Mortality of aircraft workers in Southern
California. American Journal of Industrial Medicine, 13: 683-693
Geyer H, Politzki G, Freitag D (1984) Prediction of ecotoxicological behaviour of
chemicals: relationship between n-octanol/water partition coefficient and bioaccumulation
of organic chemicals by alga Chlorella. Chemosphere,13: 269-284 as cited in the UK
SIAR (1996).
Goeptar AR, Commandeur JNM, van Ommen B, et al. (1995) Metabolism and kinetics of
trichloroethylene in relation to toxicity and carcinogenicity. Relevance of the mercapturic
acid pathway. Chem Res Toxicol, 8: 3-21.
Goldberg ME, Lebowitz MD, Graver EJ, et al. (1990) An association of human
congenital cardiac malformations and drinking water contaminants. J Am Coll Cardiac,
16: 155-164.
Goldsworthy TL & Popp JA (1987) Chlorinated hydrocarbon induced peroxisomal
enzyme activity in relation to species and organ carcinogenicity. Toxicol Appl
Pharmacol, 89: 234-244.
Government of Canada (1993) Priority Substances List Assessment Report:
Trichloroethylene. Ottawa, Canada, Canada Communication Group.
Gradiski D, Bonnet P, Raoult G, et al. (1978) A comparison of acute pulmonary toxicity
of the main chlorinated aliphatic solvents. Arch Mal Prof, 39: 249-257.
Graovac-Leposavic L, Milosavlfevic Z & Ilic V (1964) Liver function in workers
exposed to trichloroethylene. Arh Hig Rada, 15: 93-97.
240 Priority Existing Chemical Number 8
Green T (1997) Central Toxicology Laboratory, Formic Acid excretion in rats and mice
exposed to trichloroethylene, Report no CTL/R/1312, Cheshire, United Kingdom.
Green T, Dow J, Ellis MK, Foster JR et al (1997a) The role of glutathione conjugation in
the development of kidney tumours in rats ecposed to trichloroethylene: Chemico-
Biologocal Interactions, 105: 99-117.
99-117.
Green T, Mainwaring GW & Foster JR (1997b) Trichloroethylene-induced moude lung
tumours: Studies of the mode of action and comparisons between tissues. Fundamental
and Applied Toxicology, 37: 125-130.
Green T, Odum J, Nash JA, et al. (1990) Trichloroethylene induced rat kidney tumours:
the mechanisms involved and their relevance to humans. Zeneca CTL Report No.
CTL/R/1037 (as cited in UK SIAR, 1996).
Green T & Prout MS (1985) Species differences in response to trichloroethylene. II.
Biotransformation in rats and mice. Toxicol Appl Pharmacol, 79: 410-411.
Greim H, Bonse G, Radwan Z, et al. (1975) Mutagenicity in vitro and potential
carcinogenicity of chlorinated ethylenes as a function of metabolic oxirane formation.
Biochem Pharmacol, 24: 2013-2017.
Gu ZW, Sele B, Jalbert P, et al. (1981) Induction of sister chromatid exchanges by
trichloroethylene and its metabolites. Toxicol Eur Res, 3: 63-67.
Gudi R & et al. (1992) Assessment of the in vivo aneuploidy/micronucleus assay in bone
marrow cells with 16 chemicals. Environ Molec Mutag, 20: 106-116.
Gun RT, Grygorcewicz C & Nettelbeck TJ (1978) Choice reaction time in workers using
trichloroethylene. Med J Aust, 1: 535-536.
Guyotjeannin C & Van Steenkiste J (1958) Action of trichloroethylene on serum proteins
and lipids. Study of 18 employees working in a contaminated atmosphere. Arch Mal
Prof, 19: 489-494.
Haworth S, Lawlor T, Mortelmans K, et al. (1983) Salmonella mutagenicity test results
for 250 chemicals. Environ Mutagen (Suppl. 1): 3-142.
Hazardous Substances Data Base (HSDB) (1994) Trichloroethyene
Healy TEJ, Poole TR, Hooper A, (1982) Rat fetal development and maternal exposure to
trichloroethylene 100 ppm, Br J Anaesth,54: 337-341 as cited in the ATSDR (1993).
Heineman E & et al. (1994) Occupational exposure to chlorinated aliphatic hydrocarbons
and risk of astrocytic brain cancer. American Journal of Industrial Medicine, 26: 155-169.
Henschler D, Eder E, Neudecker T, et al. (1977) Carcinogenicity of trichloroethylene.
Fact or artifact? Arch Toxicol, 37: 233-236.
Henschler D, Elsasser HM, Romen W, et al. (1984) Carcinogenicity study of
trichloethylene with and without epoxide stabilisers, in mice. J Cancer Res Clin Oncol,
104: 149-156.
241
Trichloroethylene
Henschler D, Romen W, Elsasser HM, et al. (1980) Carcinogenicity study of of
trichloroethylene by long term inhalation in 3 animal species. Arch Toxicol, 43: 237-248.
Henschler D, Vamvakas S, Lammert M, et al. (1995) Increased incidence of renal cell
tumors in a cohort of cardboard workers exposed to trichloroethene. Arch Toxicol, 69:
291-299.
Herbert V, Gerdner A & Colman N (1980) Mutagenicity of dichloroacetate, an ingredient
of some formulations of pangamic acid (trade-named
vitamin B15). Am J Clin Nutr, 33: 1179-1182.
Herren-Freund SL, Pereira MA, Khoury MD, et al. (1987) The carcinogenicity of
trichloroethylene and its metabolites, trichloroacetic acid and dichloroacetic acid, in
mouse liver. Toxicol Appl Pharmacol, 90: 183-189.
IARC (1995) Dry cleaning, some chlorinated solvents and other industrial chemicals. In:
ed. IARC monographs on the evaluation of carcinogenic risks to humans. International
Agency for Research on Cancer, Lyon, 63: 75-158.
Inoue O, Seiji K, Kawai T, et al. (1989) Relationship between vapor exposure and urinary
metabolite excretion among workers exposed to trichloroethylene. Am J Ind Med, 15:
103-110.
IPCS (International Programme on Chemical Safety) (1985) Trichloroethylene:
Environmental Health Criteria 50. Geneva, World Health Organisation.
Irish DD (1963) Aliphatic hydrocarbon solvents. In: F. Patty ed. Industrial Hygiene and
Toxicology. Interscience, New York, : 1309-1313.
Isaacson LG & Taylor DH (1989) Maternal exposure to 1,1,2-trichloroethylene affects
myelin in the hippocampal formation of the developing rat. Brain Res, 488: 403-407.
Jakobson I, Holmberg B & Ekner A (1986) Venous blood levels of inhaled
trichloroethylene in female rats and changes induced by interacting agents. Acta
Pharmacol Toxicol, 59: 135-143.
Kaneko T, Wang PY & Sato A (1994) Enzymes induced by ethanol differently affect the
pharmacokinetics of trichloroethylene and 1,1,1 trichloroethane. Occup Environ Med, 51:
113-119.
Keinfeld M & Tabershaw IR (1954) Trichloroethylene toxicity - report of 5 fatal cases.
AMA Arch Ind Hyg Occup Med, 10: 134-141.
KEMI (1995) Chlorine and chlorine compounds. Use, occurrence and risks - the need for
action. Solna, The Swedish National Chemicals Inspectorate.
Kimmerle G & Eben A (1973) Metabolism, excretion and toxicology of trichloroethylene
after inhalation. 2. Experimental human exposure. Arch Toxicol, 30: 127.
Kinkead ER & Wolfe RE (1980) Dermal toxicity of various compounds to female rabbits.
Single oral toxicity of various organic compounds. J Am Coll Toxicol, 2: 712-713.
242 Priority Existing Chemical Number 8
Kjellstrand P, Holmquist B, Alm P, et al. (1983a) Trichloroethylene: further studies of the
effects on body and organ weights and plasma butyrylcholinesterase activity in mice.
Acta Pharmacol Toxicol Copenh, 53: 375-384.
Kjellstrand P, Holmquist B, Mandahl N, et al. (1983b) Effects of continuous
trichloroethylene inhalation on different strains of mice. Acta Pharmacol Toxicol Copenh,
53: 369-374.
Kjellstrand P, Kanje M, Mansson L, et al. (1981) Trichloroethylene: effects on body and
organ weights in mice, rats and gerbils. Toxicology, 21: 105-115.
Kligerman AD, Bryant MF, Doerr CL, et al. (1994) Inhalation studies of the genotoxicity
of trichloroethylene to rodents. Mutat Res, 322: 87-96.
Knadle SA, Green CE, Baugh M, et al. (1990) Trichloroethylene biotransformation in
human and rat primary hepatocytes. Toxicol in Vitro, 4: 537-541.
Koch R, Schlegelmich R & Wolf HU (1988) Genetic effects of chlorinated ethylenes in
the yeast Saccharomyces cerevisiae. Mutat Res, 206: 209-216.
Konietzko H, Elster I, Bengsath A, et al. (1975) EEG variation with controlled exposure
to trichloroethylene. Int Arch Occup Environ Health, 35: 257-264.
Konietzko H & Reill G (1980) The effect of trichloroethylene on some serum enzymes
and on the cytoenzymological activity in leucocytes and on the acid base equilibrium. Int
Arch Occup Environ Health, 47: 61-67.
Kostrzewski P, Jakubowski M & Kolacinski Z (1993) Kinetics of trichloroethylene
elimination from venous blood after acute inhalation poisoning. J Toxicol Clin Toxicol,
31: 353-363.
Krost KJ, Pellizzari ED, Walburn SG, et al. 1982. Collection and analysis of hazardous
organic emissions. Anal Chem, 54: 810-817 as cited in ATSDR (1993).
Kylin B, Axell K, Samuel HE, et al. (1967) Effect of inhaled trichloroethylene on the
CNS as measured by optokinetic nystagmus. Arch Environ Health, 15: 48-52.
Laham S (1970) Studies on placental transfer:trichloroethylene. Ind Med Surg, 39: 46-49.
Land PC, Owen EL & Linde HW (1981) Morphologic changes in mouse spermatoza after
exposure to inhalational anesthetics during early spermatogenesis. Anesthesiology, 54:
53-56.
Landrigan PJ & Kominsky JR (1987) Common source community and industrial
exposure to trichloroethylene. Arch Environ Health, 42: 327-332.
Larson JL & Bull RJ (1992) Species differences in the metabolism of trichloroethylene to
the carcinogenic metabolites trichloroacetate and
dichloroacetate. Toxicol Appl Pharmacol, 115: 278-285.
Latif F, Tory K, Gnarra J, et al. (1993) Identification of the von Hippel-lindau disease
tumour suppressor gene. Science, 260: 1317-1320.
243
Trichloroethylene
Lauwerys RR & Hoet P (1993) Industrial chemical exposure. Guidelines for biological
monitoring. Ann Arbor, Lewis Publishers.
Leopardi P et al. (1993) In vivo studies on chemically induced aneuploidy in mouse
somatic and germinal cells. Mutat Res, 287: 119-130.
Leuschner J & Leuschner F (1991) Evaluation of the mutagencicity of chloral hydrate in
vitro and in vivo. Arzneim-Forsch/Drug Res, 41: 1101-1103.
Liang JC & Pacchierotti F (1988) Cytogenic investigations of chemically-induced
aneuploidy in mouse spermatocytes. Mutat Res, 201: 325-335.
Lilis R, Stanescu D, Muica N, et al. (1969) Chronic effects of trichloroethylene exposure.
Med Lav, 60: 595-601.
Lindbohm ML, Taskinen H, Sallmen M, et al. (1990) Spontaneous abortions among
women exposed to organic solvents. Am J Ind Med, 17: 449-463.
Little AD (1990) Guidelines for the selection of chemical protective clothing, Vol I and II
(3rd ed), ACGIH, Cincinnati, Ohio.
Loprieno N & Abbondandolo A (1980) Comparative mutagenic evaluation of some
industrial compounds. In: K. Norpoth and R. Garner ed. Short-term test systems for
detecting carcinogens. Springer, Berlin, : 333-356.
Lynch AM & Parry JM (1993) The cytochalasin-B micronucleus/kinetochore assay in
vitro: studies with 10 suspected aneugens. Mutat Res, 287: 71-86.
Mackay J, Fox V, Griffiths K, et al. (1995) Trichloroacetic acid: investigation into the
mechanism of chromosomal damage in the in vitro human lymphocyte cytogenetic assay
and the mouse bone marrow micronucleus test. Carcinogenesis, 16(5): 1127-1133.
Mailhes J et al. (1988.) Analysis of mouse metaphase II oocytes as an assay for
chemically induced aneuploidy. Mutat Res, 198: 145-152.
Mailhes JB, Aardema MJ & Marchetti F (1993) Investigation of aneuploidy induction in
mouse oocytes following exposure to vinblastine-sulfate, pyrimethamine, diethylstlbestrol
diphosphate, or chloral hydrate. Environ Mol Mutag, 22: 107-114.
Makide Y, Tominaga T, Rowland FS. 1979. [ Gas Chromatographic analysis of
halogenated hydrocarbons in air over Japan.] Chemistry Letters
(Chemicals Society of Japan), 4:355-358.(Japanese) as cited in ATSDR (1993).
Maltoni C, Lefemine G, Cotti G, et al. (1988) Long term carcinogenicity bioassays on
trichloroethylene administered by inhalation to Sprague-Dawley rats and Swiss mice and
B6C3F1 mice. Ann New York Acad Sci, 534: 316-342.
Maltoni C, Leffermine G & Cotti G (1986) Experimental research on trichloroethylene
carcinogenesis. In: C. Maltoni and M. Mehlman ed. . Princeton Scientific, Princeton, NJ,
: 1-393.
Maltoni C & Maioli P (1977) Long term bioassay of carcinogenicity of trichloroethylene:
preliminary results. Osp Vita, 4: 108-110.
244 Priority Existing Chemical Number 8
Manson JM, Murphy M, Richdale N, et al. (1984) Effects of oral exposure to
trichloroethylene on female reproductive function. Toxicology, 32: 229-242.
245
Trichloroethylene
Mazzullo M, Bartoli S, Bonora B, et al. (1992) In vivo and in vitro interaction of
trichloroethylene with macromolecules from various organs or rat and mouse. Res
Commun Chem Pathol Pharmacol, 76: 192-208.
McConnell G, Ferguson DM & Pearson CR (1975) Chlorinated hydrocarbons and the
environment. Endeavour, 34: 13-18.
McGregor DB, Reynolds DM & Zeiger E (1989) Conditions affecting the mutagenicity of
trichloroethylene in Salmonella. Environ Mol Mutagen, 13: 197 - 202.
Metal Finishing Association (1996) Vapour Degreasing. U.K, Environmental Technology
Best Practice Programme.
Migliore L & Nieri M (1991) Evaluation of twelve potential aneuploidogenic chemicals
by the in vitro human lymphocyte micronucleus assay. Toxicol in vitro, 5: 325-336.
Miller BM & Adler ID (1992) Aneuploidy induction in mouse spermatocytes.
Mutagenesis, 7: 69-76.
Miller RE & Guengerich FP (1983) Metabolism of trichloroethylene in isolated
hepatocytes, microsomes and reconstituted enzyme systems containing cytochrome P-
450. Cancer Res, 43: 1145-1152.
Milman HA, Story DL, Riccio ES, et al. (1988) Rat liver foci and in vitro assays to detect
initiating and promoting effects of chlorinated ethanes and ethylenes. New York, New
York Academy of Sciences.
Mirsalis JC, Tyson CK, Loh EN, et al. (1985) Induction of hepatic cell proliferation and
unscheduled DNA synthesis in mouse hepatocytes following in vivo treatment.
Carcinogenesis, 6: 1521-1524.
Mirsalis JC, Tyson CK, Steinmetz KL, et al. (1989) Measurement of unscheduled DNA
synthesis and S-phase synthesis in rodent hepatocytes following in-vivo treatment: testing
of 24 compounds. Environ Mol Mutat, 14: 155-164.
Monster AC, Boersma G & Duba WC (1976) Pharmacokinetics of trichloroethylene in
volunteers, influence of workload and exposure concentration. Int Arch of Occup Environ
Health, 38: 87-102.
Monster AC, Boersma G & Duba WC (1979) Kinetics of Trichloroethylene in Repeated
Exposure of Volunteers. Int Archives of Occup Environ Health, 42: 283-292.
Morgan RW, Kelsh MA et al. (1998) Mortality of aerospace workers exposed to
trichloroethylene. Epidemiology, 9(4): 424-431.
Moriya M, Ohta T, Watanabe K, et al. (1983) Further mutagenicity studies on pesticides
in bacterial reversion assay systems. Mutat Res, 116: 185-216.
Mortelmans K, Haworth S, Lawlor T, et al. (1986) Salmonella mutagenicity tests. II.
Results from the testing of 270 chemicals. Environ Mutagen, 8: 1-119.
246 Priority Existing Chemical Number 8
Mostofi FK & Price EB (1973) Tumours of the testes; Leydig cell tumours. In: ed.
Tumours of the male genital system Fascicle 8. Armed Forces Institute of Pathology, , :
86-89.
Muller G, Spassovski M & Henschler D (1972) Trichloroethylene exposure and
trichloroethylene metabolites in urine and blood. Arch Toxicol, 29: 335-340.
Muller G, Spassovski M & Henschler D (1974) Metabolism of trichloroethylene in man.
II. Pharmacokinetics of metabolites. Arch Toxicol, 32: 283-295.
Myhr C & Caspary W (1991) Chemical mutagenesis at the thymidine kinase locus in
L5178Y mouse lymphoma cells: results of 31 coded compounds in the National
Toxicology Program. Environmental and Molecular Mutagenesis, 18: 51-83.
Nagaya T, Ishikawa N, et al (1989) Sister chromatid exchanges in lymphocytes of
workers exposed to trichloroethylene. Mutat Res, 222: 279-282
Nakaaki K, Onishi N, Iida H, et al. (1973) An experimental study on the effect of
exposure to trichloroethylene vapour in man. J Sci Labour, 41: 449-463.
Nakajima T, Okino T, Kurasawa K, et al. (1987) A case of chemical burn, bradycardia,
extrasystolic arrhythmia and unconciousness from accidental trichloroethylene exposure.
Jpn J Ind Health, 29: 72-73.
Nakayama H, Kobayashi M, Takahashi M, et al. (1988) Generalized eruption with severe
liver dysfunction associated with occupational exposure to trichloroethylene. Contact
Dermatitis, 19: 48-51.
Natarajan AT (1993) An overview of the results of testing of known or suspected
aneugens using mammalian cellls in vitro. Mutat Res, 287: 113-118.
National Cancer Institute (NCI) (1976) Cancer bioassay of trichloroethylene. (National
Cancer Institute Carcinogenesis Technical Report Series No 2 - Publication No.76-802),
National Cancer Institute.
National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (1996)
Priority Existing Chemical No.4: HCFC-123. Canberra, AGPS.
National Institute for Occupational Safety and Health (NIOSH) (1980) Teratogenic -
mutagenic risk of workplace contaminants: trichloroethylene, perchloroethylene, and
carbon disulphide, Contract No. 210-77-0047.
National Institute for Occupational Safety and Health (NIOSH) (1987) NIOSH manual of
analytical methods. Third edition. Second supplement. Cincinnati, OH: U.S Department
of Health and Human Services, Public Health Service, Centers for Disease control and
Prevention, NIOSH publication no. 87-117,1003-1-1003-6 as cited in the ATSDR (1993).
National Institute for Occupational Safety and Health (NIOSH) (1989a) Health Hazard
Evaluation Report No. HETA 86-380-1957, York International Corporation,
Madisonville, Kentucky. Cincinnati, OHIO, NIOSH.
National Institute for Occupational Safety and Health (NIOSH) (1989b) Health Hazard
Evaluation Report HETA 88-082-1971, Jostens Incorporated, Princeton, Illinois.
Cincinnati, OHIO, NIOSH.
247
Trichloroethylene
National Institute for Occupational Safety and Health (NIOSH) (1990) Health Hazard
Evaluation Report HETA 90-223-2211, Thomson Consumer Electronics, Marion,
Indiana. Cincinnati, OHIO, NIOSH.
National Institute for Occupational Safety and Health (NIOSH) (1991) Health Hazard
Evaluation Report No. HETA-90-344-2159, A.W. Cash Valve Manufacturing Operation,
Decatur, Illinois. Cincinatti, OHIO, NIOSH.
National Institute for Occupational Safety and Health (NIOSH) (1994) NIOSH Manual of
Analytical Methods. Cincinnati, OHIO, NIOSH.
National Occupational Health and Safety Commission (NOHSC) (1999) Approved
Criteria for Classifying Hazardous Substances. Canberra, Australian Government
Publishing Service.
National Occupational Health and Safety Commission (NOHSC) (1994) Control of
Workplace Hazardous Substances. Canberra, Australian Government Publishing Service.
National Occupational Health and Safety Commission (NOHSC) (1994) Guidance Note
for the Assessment of Health Risks Arising from the use of Hazardous Substances in the
Workplace. Canberra, Australian Government Publishing Service.
National Occupational Health and Safety Commission (NOHSC) (1999) List of
Designated Hazardous Substances. Sydney, NOHSC.
National Occupational Health and Safety Commission (NOHSC) (1994) National Code of
Practice for the Labelling of Workplace Substances. Canberra, Australian Government
Publishing Service.
National Occupational Health and Safety Commission (NOHSC) (1994) National Code of
Practice for the Preparation of Material Safety Data Sheets. Canberra, Australian
Government Publishing Service.
Nelson JL & Zenick H (1986) The effect of trichloroethylene on male sexual behaviour:
possible opoid role. Neurobehav Toxicol Teratol, 8: 441-445.
Nelson MA & Bull RJ (1988) Induction of strand breaks in DNA by trichloroethylene
and metabolites in rat and mouse liver in vivo. Toxicol Appl Pharmacol, 94: 45-54.
Nestmann ER, Chu I, Kowbel DJ, et al. (1980) Short-lived mutagen in Salmonella
produced by reaction of trichloroacetic acid and dimethyl sulphoxide. Can J Genet Cytol,
22: 35-40.
Ni Y-C, Wong T-Y, Kadlubar FF, et al. (1994) Hepatic metabolism of chloral hydrate to
free radical(s) and induction of lipid peroxidation. Biochem Biophys Res Comm, 204:
937-943.
Noland-Gerbac EA, Pfohl RJ, Taylor DH, et al. (1986) 2-Deoxyglucose uptake in the
developing rat brain upon pre- and postnatal exposure to trichloroethylene.
Neurotoxicology, 7: 157-164.
Nomiyama K (1971) Estimation of trichloroethylene exposure by biological material. Int
Arch Arbeitsmed, 27: 281-292.
248 Priority Existing Chemical Number 8
Nomiyama K & Nomiyama H (1971) Metabolism of trichloroethylene in human. Sex
differences in urinary excretion of trichloroacetic acid and trichloroethanol. Int Arch
Arbeitsmed, 28: 37-48.
Nomiyama K & Nomiyama H (1977) Dose-response relationship for trichloroethylene in
man. Int Arch Occup Environ Health, 39: 237-248.
Nomura S (1962) Health hazard in workers exposed to trichloroethylene vapour. I.
Trichloroethylene poisoning in an electroplating plant. Kumamoto Med J, 15: 29-37.
Novotna E, David A & Malek B (1979) An epidemiological study of the hepatic tumour
incidence in persons working with trichloroethylene. 1. The negative result of
retrospective investigation in persons with primary liver cancer. Prac Lek, 31: 121-123.
Odum J, Foster JR & Green T (1992) A mechanism for the development of Clara cell
lesions in the mouse lung after exposure to trichloroethylene. Chem Biol Interactions, 83:
135-153.
OECD (1993) Occupational and consumer exposure assessments (OECD Environment
Monographs No. 70). Paris, France, OECD.
Paddle GM (1983) Incidince of liver cancer and trichloroethylene manufacture: joint
study by industry and a cancer register. British Medical Journal, 286: 846.
Parchman LG & Magee N (1982) Metabolism of 14C-trichloroethylene to 14CO2 and
interaction of a metabolite with liver DNA in rats and mice. J Toxicol Environ Health, 9:
797-813.
Pennarola R, Lamanna P & Castellino N (1966) Pathological findings in experimental
trichloroethylene. Folia Med, 49: 853-864.
Perocco P & Prodi G (1981) DNA damage by haloalkanes in human lymphocytes
cultured in vitro. Cancer Lett, 13: 213-218.
Phoon WH, Chan MOY, Rajan VS, et al. (1984) Stevens-Johnson syndrome associated
with occupational exposure to trichloroethylene. Contact Dermatitis, 10: 270-276.
Prendergast JA, Jones RA, Jenkins LJ, et al. (1967) Effects on experimental animals of
long term inhalation of trichloroethylene, carbon tetrachloride, 1,1,1- trichloroethane,
dichlorodifluoromethane, and 1,1-dichloroethylene. Toxicol Appl Pharmacol, 10: 270-
289.
Prout MS, Provan WM & Green T (1985) Species differences in response to
trichloroethylene. I . Pharmacokinetics in rats and mice. Toxicology and Applied
Pharmacology, 79: 389-400.
Purchase IFH, Ashby J, Brady A, et al. (1994) Mechanistically-based human assessment
of peroxisome proliferator-induced hepatocarcinogenesis. Human and Exp Toxicol,
13(2).
Radian Corporation (1990) Halogenated solvent cleaners. Emission control technologies
and cost analyses. New Jersey, Noyes Data Corporation.
249
Trichloroethylene
Rapson WH, Nazar MA & Butsky VV (1980) Mutagenicity produced by aqueous
chlorination of organic compounds. Bull Environ Contam Toxicol, 24: 590-596.
Rasmussen K, Brogen CH & Sabroe S (1993) Subclinical affection of liver and kidney
function and solvent exposure. Int Arch Occup Environ Health, 64: 445-448.
Rasmussen RA,. Harsch DE, Sweany PH, et al. 1977. Determination of atmospheric
halocarbons by a temperature-programmed gas chromatographic freezeout concentration
method. J Air Pollut Control Assoc, 27: 579-581 as cited in ATSDR (1993)
Rasmussen K, Sabroe S, Wohlert M, et al. (1988) A genotoxic study of metal workers
exposed to trichloroethylene. Sperm parameters and chromosome aberrations in
lymphocytes. Int Arch Occup Environ Health, 60: 419-423.
Rebert CS, Boyes WK, Pryor GT, et al. (1993) Combined effects of solvents on the rats
auditory system: styrene and trichloroethylene. Int J Psychophysiol, 14: 49-59.
Reddy JK & Rao MS (1992) Peroxisome proliferation and hepatocarcinogenesis. In: H.
Vainio, P. Magee, D. McGregor and A. McMichael ed. Mechanisms of Carcinogenesis in
Risk Identification, IARC Publication No. 116. IARC, Lyon, : 225-235.
Riccio E, Griffin A & Mortelmans K (1983) A comparative mutagenicity study of volatile
halogenated hydrocarbons using different metabolic activation systems. Environ
Mutagen, 5: 472.
Robinson BJ (Updated January 1996) A survey of degreasing operations, 1994.
Birmingham, Health and Safety Executive.
Rossi AM, Migliore L, Barale R, et al. (1983) In vivo and in vitro mutagenicity studies of
a possible carcinogen, trichloroethylene, and its two stabilizers, epichlorohydrin and 1,2-
epoxybutane. Teratogen Carcinogen Mutagen, 3: 75-87.
Rudd CJ, Mitchell AD & Spalding J (1983) L5178Y mouse lymphoma cell mutagenesis
assay of coded chemicals incorporating analyses of the colony size distributions. Environ
Mutagen, 5: 419.
Ruijten MWMM, Verbeck MM & Salle HJA (1991) Nerve function in workers with
long-term exposure to trichloroethene. Br J Ind Med, 48: 87-92.
Russo A & Levis AG (1992a.) Further evidence for the aneuploidogenic properties of
chelating agents: induction of micronuclei in mouse male germ cells by EDTA. Environ
Mol Mutag, 19: 125-131.
Russo A & Levis AG (1992b.) Detection of aneuploidy in male germ cells of mice by
means of a meiotic micronucleus assay. Mutat Res(281): 187-.
Russo A, Pacchierotti F & Metalli P (1984) Nondisjunction induced in mouse
spematogenesis by chloral hydrate, a metabolite of trichloroethylene. Environ
Mutagen(6,): 695-703,.
Sagawa K, Nishitani H, Kawai H, et al. (1973) Transverse lesions of the spinal cord after
accidental exposure to trichloroethylene. Int Arch Arbeitsmed, 31: 257-264.
250 Priority Existing Chemical Number 8
Salvini M, Binaschi S & Riva M (1971) Evaluation of the psychophysiological functions
of humans exposed to trichloroethylene. Br J Ind Med, 28: 293-295.
Sanchez IM & Bull RJ (1990) Early induction of reparative hyperplasia in the liver of
B6C3F1 mice treated with dichloroacetate and trichloroacetate. Toxicology, 64: 33-46.
Sanders VM, Tucker AN, White K, et al. (1982) Humoral and cell-mediated immune
status in mice exposed to trichloroethylene in the drinking water. Toxicol Appl
Pharmacol, 62: 385-368.
Sato A & Nakajima T (1978) Differences following skin or inhalation exposure in the
absorption and excretion kinetics of trichloroethylene and toluene. Br J Ind Med, 35: 43-
49.
Savolainen H (1981) Pharmacokinetics, pharmacodynamics and aspects of neurotoxic
effects of four inhaled aliphatic chlorohydrocarbon solvents as relevant in man. Eur J
Drug Metab Pharmacokinet, 6: 85-90.
Sbrana I, Di Sibio A, Lomi A, et al. (1993) C-Mitosis and numerical chromosome
aberration analyses in human lymphocytes: 10 known or suspected spindle poisons. Mutat
Res, 287: 57-70.
Sbrana I, Lascialfari D & Loprieno N (1985) TCE induces micronuclei but not
choromosomal aberrations in mouse bone marrow cells. IV ICEM, Stockholm: 163.
Schiestl RH, Aubrecht J, Khogali F, et al. (1997) Carcinogens induce reversion of the
mouse pink-eyed unstable mutation. Proc Natl Acad Sci, 94: 4576-4581.
Schwetz BA, Leong BKJ & Gehring PJ (1975) The effect of maternally inhaled
trichloroethylene, perchloroethylene, methyl chloroform and methylene chloride on
embryonal and fetal development in mice and rats. Toxicol Appl Pharmacol, 32: 84-96.
Seiji K, Jin C, Watanabe T, et al. (1990) Sister chromatid exchanges in peripheral
lymphocytes of workers exposed to benzene, trichloroethylene or tetrachloroethylene,
with reference to smoking habits. Int Arch Occup Environ Health, 62: 171-176.
Shahin MM & Von Borstel RC (1977) Mutagenic and lethal effects of (-benzene
hexachloride, dibutyl phthalate and trichloroethylene in Saccharomyces cerevisiae. Mutat
Res, 48: 173-180.
Shelby MD, Erexson GL, Hook GL, et al. (1993) Evaluation of a 3-exposure mouse bone
marrow micronucleus protocol. Results with 49 chemicals. Environ Mol Mutagen, 21:
160-179.
Shelley S, Moore S & Ondrey J (1993) New life for old solvents. Chemical
Engineering(June): 63-65.
Sherwood RJ (1976) Ostwald solubility coefficients of some industrially important
substances. Br J Ind Med, 33: 106-107.
Shimada T, Swanson AF, Leber P, et al. (1985) Activities of chlorinated ethane and
ethylene compounds in the Salmonella/rat. Microsome mutagenesis and rat
hepatocyte/DNA repair assays under vapour phase exposure conditions. Cell Biol
Toxicol, 1: 159-179.
251
Trichloroethylene
Shindell S & Ulrich S (1985) A cohort study of employees of a manufacturing plant using
trichloroethylene. Journal of Occupational Medicine, 27(8):577-579.
Shipman AJ & Whim BP (1980) Occupational exposure to trichloroethylene in metal
cleaning process and to tetrachloroethylene in the drycleaning industry in the U.K. Ann
Occup Hyg, 23: 197-204.
Shirasu Y, Moriya M, Kato K, et al. (1976) Mutagenicity screening of pesticides in the
microbial system. Mutat Res, 40: 19-30.
Siegal J, Jones RA, Coon RA, et al. (1971) Effects on experimental animals of acute,
repeated, and continuous inhalation exposures to dichloroactylene mixtures. Toxicol Appl
Pharmacol, 18: 168-174.
Skory Consulting Inc. & Skory LK (1995) Trichloroethylene solvent vapor exposure
profile in metal cleaning; Organic vapor monitor (dosimeters) data analysis. Midland, MI.
Slacik-Erben R, Roll R, Franke G, et al. (1980) Trichloroethylene vapours do not produce
dominant lethal mutations in male mice. Arch Toxicol, 45: 37-44.
Smith GF (1970) The investigation of the mental effect of trichloroethylene. Ergonomics,
13: 580-586.
Smyth HF, Carpanter CP, Weil CS, et al. (1962) Range finding toxicity data: List VI. Am
Ind Hyd Assoc J, 23: 95-107.
Smyth HF, Carpenter CP, Weil CS, et al. (1969) Range finding toxicity data: List VII.
Am Ind Hyg Assoc J, 30: 470-476.
Spirtas R, Stewart PA, Lee JS, et al. (1991) Retrospective cohort mortality study of
workers at an aircraft maintenance facility. I Epidemiological results. British Journal of
Industrial Medicine, 48: 515-530.
Standards Association of Australia (1978) AS2161 - 1978: Industrial safety gloves and
mittens, SAA, North Sydney.
Standards Association of Australia (1983) AS 2661 Vapour Degreasing Plant - Design,
Installation and Operation - Safety Requirements. North Sydney, Standards Association
of Australia.
Standards Australia (1995) AS 2865: Safe working in a confined space. Homebush,
NSW, Standards Australia.
Standards Australia & Standards New Zealand (1990) AS 3765.1: Clothing for protection
against hazardous chemicals: Part 1: Protection against general or specific chemicals.
Homebush, NSW, Standards Australia.
Standards Australia & Standards New Zealand (1992) AS/NZS 1337: Eye protectors for
industrial applications. Homebush, NSW, Standards Australia.
Standards Australia & Standards New Zealand (1994) AS/NZS 1715: Selection, use and
maintenance of respiratory protective devices. Homebush, NSW, Standards Australia.
252 Priority Existing Chemical Number 8
Standards Australia & Standards New Zealand (1994) AS/NZS 1716: Respiratory
protective devices. Homebush, NSW, Standards Association of Australia.
Steward A, Allott PR, Cowles AL, et al. (1973) Solubility coefficients for inhaled
anaesthetics for water, oil and biological media. Br J Anaesthesiol, 45: 282-293.
Stewart RD, Hake CL, LeBurn AJ, et al. (1974a) Biological standards for the industrial
worker by breath analysis: trichloroethylene, NIOSH Research Report, Publication No.
74-133.
Stewart RD, Hake CL & Peterson JE (1974b) Degreasers' flush : dermal response to
trichloroethylene and ethanol. Arch Environ Health, 29: 1-5.
Stopps GJ & McLaughlin M (1967) Psychophysiological testing of human subjects
exposed to solvent vapours. Am Ind Hyg Assoc J, 28: 43-50.
Stott WT, Quast JF & Watanabe PG (1982) The pharmacokinetics and macromolecular
interactions of trichloroethylene in mice and rats. Toxicol Appl Pharmacol, 62: 137-151.
Swaen GMH (1995) Increased incidence of renal cell tumours in a cohort of cardboard
workers exposed to trichloroethylene. Arch Toxicol, 70: 127-128.
Szulc-Kuberska J (1972) Selected issues on chronic industrial trichloroethylene
intoxication. Folia Med Lodz, 16: 67-90.
Takamatsu M (1962) Health hazards of workers exposed to trichloroethylene vapour. II.
Exposure to trichloroethylene degreasing operations in a communicating machine factory.
Kumamoto Med J, 15: 43-54.
Taskinen H, Anttila A, Lindbohm ML, et al. (1989) Spontaneous abortions and congenital
malformations among the wives of men occupationally exposed to organic solvents.
Scand J Work Environ Health, 15: 342-352.
Taylor DH, Lagory KE, Zaccaro DJ, et al. (1985) Effect of trichloroethylene on the
exploratory and locomotor activity of rats exposed during development. Sci Total
Environ, 47: 415-420.
Tola S, Vilhunen R, Jarvinen E, et al. (1980) A cohort study on workers exposed to
trichloroethylene. Journal of Occupational Medicine, 22: 737-740.
Tolot F, Viallier J, Roullet A, et al. (1964) Hepatic toxicity of trichloroethylene. Arch
Mal Prof, 25: 9-15.
Triebig G, Reichenbach T & Flugel KA (1978) Biochemical examinations and
measurements of the conduction velocity in persons chronically exposed to
trichloroethylene. Int Arch Occup Environ Health, 42: 31-40.
Triebig G, Shaller KH, Erzigkeit H, et al. (1977a) Biochemical investigation and
psychological studies of persons exposed to trichloroethylene with regard to non-exposed
individuals. Int Arch Occup Environ Health, 38: 149-162.
Triebig G, Trautner P, Weltle D, et al. (1982) Investigations on neurotoxicity of chemical
substances at the workplace. III. Determination of the motor and sensory nerve
253
Trichloroethylene
conduction velocity in persons occupationally exposed to trichloroethylene. Int Arch
Occup Environ Health, 51: 25-34.
Tsuruta H (1978) Percutaneous absorption of trichloroethylene in mice. Ind Health, 16:
145-148.
Tucker AN, Sanders VM, Barnes DW, et al. (1982) Toxicology of trichloroethylene in
the mouse. Toxicol Appl Pharmacol, 62: 351-357.
U.S. Environmental Protection Agency (USEPA) (1996) Aster Database . National
Health and Environmental Effects Research Laboratory, Duluth, Min.
UK Government (1993, July) Risk assessment of existing substances-Guidance produced
by a UK Government /Industry Working Group.
United Kingdom (1996) SIDS Initial Assessment Report on Trichloroethylene.
United Nations Environment Programme Industry and Environment Programme Activity
Centre (UNEPIE/PAC) (1992) Protecting the ozone layer: Solvents, coatings and
adhesives.
US National Toxicology Program (NTP) (1986) Toxicology and carcinogenesis studies of
trichloroethylene in Fischer-344/N rats and B6C3F1 mice. NC, NTP, Research Triangle
Park.
US National Toxicology Program NTP (1988) NTP technical report on the toxicology
and carcinogenesis studies of trichloroethylene in four strains of rats. TR 273. NC, NTP,
Research Triangle Park.
US National Toxicology Program NTP (1990) Carcinogenesis studies of
trichloroethylene (without epichlorohydrin) (CAS No 79-01-6) in Fischer-344/N rats and
B6C3F1 mice (gavage studies). Research Triangle Park, NC, NTP.
Vagnarelli P, De Sario A & De Carli L (1990) Aneuploidy induced by chloral hydrate
detected in human lymphocytes with the Y 97 probe. Mutagenesis, 5: 591-592.
Vamvakas S, Bruning, T et al. (1996) Renal cell cancer correlated with occupational
exposure to trichloroethylene, as cited in Deutsche Forschungsgemeinschaft (1996)
Maximum concentrations at the workplace and biological tolerance values for working
materials. Report No 31. Weiheim, VCH
Vamvakas S, Dekant W & Henschler D (1989b) Assessment of unscheduled DNA
synthesis in a cultured line of renal epithelial cells exposed to cysteine S-conjugates of
haloalkenes and haloalkanes. Mutat Res, 222: 329-335.
Vamvakas S, Elfarra AA, Dekant W, et al. (1988a) Mutagenicity of amino acid and
glutathione S-conjugates in the Ames test. Mutat Res, 206: 83-90.
Van Duuren BL, Goldschmidt BM, Loewengart G, et al. (1979) Carcinogenicity of
halogenated olefinic and aliphatic hydrocarbons in mice. J. Natl Cancer Inst, 63: 1433-
1439.
Vernon RJ & Ferguson RK (1969) Effects of trichloroethylene on visual motor
performance. Arch Environ Health, 18: 894-900.
254 Priority Existing Chemical Number 8
Vernot EH, MacEwen JD, Haun CC, et al. (1977) Actue toxicity and skin corrosion data
for some organic and inorganic compounds and aqueous solutions. Toxocol Appl
Pharmacol, 42: 417-423.
Villaschi S, Giovanetti A, Lombardi CC, et al. (1991) Damage and repair of mouse
bronchial epithelium following acute inhalation of trichloroethylene. Exp Lung Research,
15: 601-614.
Wahlberg JE (1984) Edema inducing effects of solvents following topical administration.
Derm Benf Unwelt, 32: 91-94.
Wallace LA, Pellizzari ED, Hartwell TD, et al. 1986. Total exposure assessment
methodology (TEAM) study: Personal exposure, indoor-outdoor relationships, and breath
levels of volatile organic compounds in New Jersey. Environment International, 12: 369-
387 as cited in ATSDR (1993).
Walles SAS (1986) Induction of single-strand breaks in DNA of mice buy
trichloroethylene and tetrachloroethylene. Toxicol Lett, 31: 31-35.
Warner JR, Hughes TJ & Claxton LD (1988) Mutagenicity of 16 volatile organic
chemicals in a vaporization technique with Salmonella typhimurium TA 100. Environ
Mol Mutagen, 11: 111-112.
Waskell L (1978) A study of the mutagenicity of anaesthetics and their metabolites.
Mutat Res, 57: 141-153.
Watson SC, Foster JR & Elcombe CR (1993) Trichloroacetic acid: species differences in
the stimulation of hepatic DNA synthesis. Human Exp Toxicol, 4: 1-5.
Weiss NS (1996) Cancer in relation to occupational exposure to trichloroethylene.
Occupational and Environmental Medicine, 53:1-5
Wernisch M, Paya K & Palasser A (1991) Cardiac arrest after inhalation of shoemakers
glue. Wien Med Wochenschr, 141: 71-74.
White AE, Takehisa S, Eger EI, et al. (1979) Sister chromatid exchanges induced by
inhaled anaesthetics. Anaesthesiology, 50: 426-430.
Whittaker SG, Zimmerman FK, Dicus B, et al. (1990) Detection of induced mitotic
chromosome loss in Saccharomyces cerevisiae - an interlaboratory assessment of 12
chemicals. Mutat Res, 241: 225-242.
Windemuller FJB & Ettema JH (1978) Effect of combined exposure to trichloroethylene
and alcohol on mental capacity. Int Arch Occup Environ Health, 41: 77-85.
Wolf K & Chestnutt TW (1987) Chlorinated solvents: Market interactions and regulation.
Journal of Hazardous Materials, 15: 137-161.
Woodward-Clyde (1995) 4432 Groundwater Stage 2 Survey ICI Botany Contract C6
Overview Report Parts A-D .
Xu W & Adler I-D (1990) Clastogenic effects of known and suspect spindle poisons
studied by chromosome analysis in mouse bone marrow cells. Mutagenesis, 5: 371-374.
255
Trichloroethylene
Yoshida M, Fukabori S, Hara K, et al. (1996) Concentrations of trichloroethylene and its
metabolites in blood and urine after acute poisoning by ingestion. Hum Exp Toxicol,
15(3): 254-258.
Zenick H, Blackburn K, Hope E, et al. (1984) Effects of trichloroethylene exposure on
male reproductive functions in rats. Toxicology, 31: 237-250.
Zielinski A (1973) General health state of women professionally exposed to
trichloroethylene (Tri) vapours. Med Pr, 24: 263-271.
Zordan M, Osti M, Pesce M, et al. (1994) Chloral hydrate is recombinogenic in the wing
spot test in Drosophila melanogaster. Mutat Res, 322: 111-116.
256 Priority Existing Chemical Number 8
257
Trichloroethylene
258 Priority Existing Chemical Number 8
|