FULL PUBLIC REPORT
2-butoxyethanol
PRIORITY EXISTING CHEMICAL
NUMBER 6
OCTOBER 1996
AUSTRALIAN GOVERNMENT PUBLISHING SERVICE
CANBERRA
2-butoxyethanol i
Commonwealth of Australia 1996
ISBN 0 644 45141 6
This work is copyright. Apart from any use as permitted under the Copyright Act 1986, no
part may be produced by any process without prior written permission from the Australian
Government Publishing Service. Requests and inquiries concerning reproduction and
rights should be addressed to the Manager, Commonwealth Information Services,
Australian Government Publishing Service, GPO Box 84, Canberra ACT 2601.
Priority Existing Chemical Number 6
ii
Preface
This assessment is made under the National Industrial Chemicals Notification and
Assessment Scheme (NICNAS). This Scheme was established by the Commonwealth
Industrial Chemicals (Notification and Assessment) Act 1989 (the Act), which came into
operation on 17 July 1990.
The principal aim of NICNAS is to help protect people and the environment from the
harmful effects of industrial chemicals by finding out the risks to occupational health and
safety, to public health and the environment.
NICNAS has two major parts: one focussing on the risks associated with new chemicals
before importation or manufacture; and another focussing on existing industrial chemicals
already in use in Australia. As there are many thousands of existing industrial chemicals
in Australia, NICNAS has a mechanism of prioritising assessments by declaring certain
existing chemicals to be Priority Existing Chemicals (PECs). This report provides the full
public report of a PEC assessment. A summary report is also publicly available and has
been published in the Commonwealth Chemical Gazette.
NICNAS is administered by Worksafe Australia. Assessments under NICNAS are done in
conjunction with the Environment Protection Agency and Department of Health and
Family Services.
This assessment report has been prepared by the Director Chemicals Notification and
Assessment in accordance with the Act. This report has not been subject to tripartite
consultation or endorsement by the National Occupational Health and Safety Commission.
Copies of the full public report can be purchased from Commonwealth Government
Bookshops.
In accordance with Section 40 of the Act, a person may apply to the Director for variation
of this full public report using the approved form by 29 October 1996. A fee must be paid
with the application.
On publication of the Summary Report in the Chemical Gazette of 1 October 1996, the
chemical will no longer be a Priority Existing Chemical in accordance with Section 62 of
the Act.
For the purposes of subsection 78(1) of the Act, copies of full public reports may be
inspected by the public at the Library, Worksafe Australia, 92-94 Parramatta Road,
Camperdown, NSW 2050, between 10 a.m. and 12 noon and 2 p.m. and 4 p.m. each
weekday except on public holidays.
A pamphlet giving further details of the PEC program and approved forms to apply for
variation of this report are available from Worksafe Australia. Please contact the
Chemical Assessment Division at the address shown below.
GPO Box 58
SYDNEY NSW 2001
AUSTRALIA
or
92 Parramatta Road
CAMPERDOWN NSW 2050
AUSTRALIA
Telephone: +61 (02) 9577 9421
Fax: +61 (02) 9577 9465.
2-butoxyethanol iii
Abstract
2-Butoxyethanol is a glycol ether which is used in over 430 cleaning products in Australia.
Cleaning products containing 2-butoxyethanol are used in a large number of industries in
Australia and by a large number of people. In the contract cleaning industry alone, it is
estimated that there are approximately 65,000 cleaners. Many of the products are
available for sale to the public. Cleaning products which may contain 2-butoxyethanol
include general surface cleaners, floor strippers, window cleaners, spot cleaners, rust
removers and ink and resin removers.
The use of cleaning products containing 2-butoxyethanol has caused concern due to the
high potential for occupational and public exposure, reports of adverse health effects in
some workers (for example, irritation of the eyes, nose and throat) and the established
t o x i c i t y of related glycol ethers, (for example, the reproductive toxicity of 2-
methoxyethanol and 2-ethoxyethanol).
2-Butoxyethanol is well absorbed via the inhalational, dermal and oral routes. It is widely
distributed throughout the body and efficiently metabolised to 2-butoxyacetic acid (BAA),
which is rapidly excreted in urine. Studies in humans and animals have shown that the
metabolic pathways are similar.
The critical health effect from animal studies is haemolysis of the blood cells (rat NOAEL
24.6 ppm), with other effects such as liver and kidney damage being secondary to
haemolysis. The severity of the effect, caused mainly by BAA, differs markedly between
species, with rats and mice the most sensitive, rabbits less sensitive, and then guinea pigs.
Humans appear to be the least sensitive from the results of in vitro studies and in vivo
inhalational studies. Haemolytic effects in humans have been observed after the deliberate
ingestion of large doses. No haemolytic effects have been confirmed with occupational
exposure.
The reproductive effects observed with related glycol ethers, 2-methoxyethanol and 2-
ethoxyethanol, have not been demonstrated with 2-butoxyethanol. In animal reproductive
toxicity studies, adverse effects were observed only at doses which were severely toxic to
the adults. Similarly, no evidence of teratogenicity was observed with 2-butoxyethanol.
Immunotoxicity studies in animals were negative and studies indicate 2-butoxyethanol is
probably not genotoxic.
The critical health effects from acute exposure to 2-butoxyethanol are eye and respiratory
irritation. In controlled studies in humans, eye and respiratory irritation occurred at 113
ppm, with headache and nausea at 100 ppm. Human evidence indicates that 2-
butoxyethanol may be slightly irritating to the skin on repeated exposure. It is not a skin
sensitiser.
Based on the assessment of health effects, 2-butoxyethanol should be classified in
accordance with the Approved Criteria for Workplace Hazardous Substances as `Harmful
by inhalation, in contact with skin, and if swallowed' (risk phrases R20/21/22), `Irritating
to respiratory system' (R37), and `Irritating to the eyes' (R36).
The occupational risk assessment found that, for most work situations, the atmospheric
concentration of 2-butoxyethanol is unlikely to be high enough to cause irritation, but
where vapours and/or aerosols are generated, for example, during spray use or when heat
is applied, irritant effects and possibly headache and nausea may be experienced. The
assessment found that skin absorption can occur in the absence of irritation and may
contribute significantly to the total dose absorbed. The assessment found that the risk of
haemolysis in workers employed in the manufacture, formulation or use of cleaning
Priority Existing Chemical Number 6
iv
products containing 2-butoxyethanol in Australia is minimal. However, there is a concern
where workers are exposed on a prolonged basis (particularly dermal exposure) to high
concentrations of 2-butoxyethanol (30% and more).
The risk to human health can be determined by an assessment of the workplace. Areas of
concern identified in the risk assessment include spray use, use of heat, and prolonged
dermal exposure to cleaning solutions or products containing high concentrations of 2-
butoxyethanol (30% or more). In these situations, it is recommended that consideration be
given to substituting 2-butoxyethanol with safer alternatives which have been thoroughly
tested and demonstrated to have a lower toxicity, irritancy and potential for skin
absorption in humans. At the very least, the 2-butoxyethanol content in cleaning products
should be reduced to concentrations where the risk to human health is minimal. It is also
recommended that suppliers and end-users review their methods of application, for
example, by replacing spray use with use as a liquid stream.
Due to the low concentration of 2-butoxyethanol in most domestic cleaning products and
their intermittent use by the public, the public health risk is expected to be minimal.
In an assessment of MSDS and labels submitted by formulators, deficiencies were noted in
several areas. It is therefore recommended that suppliers review their MSDS and labels in
accordance with regulatory requirements and recommendations in this report. For MSDS,
more specific information about 2-butoxyethanol is required. For labels, the appropriate
risk phrases for products used industrially are required, together with a better indication of
the hazards of spray use and precautions for handling. Accordingly, it is recommended
that the safety phrase `Do not breathe vapour or spray' be on the label for products which
may be used in spray form in the workplace.
The risk to the environment is expected to be low as 2-butoxyethanol is readily
biodegradable and is of low toxicity to aquatic organisms. However, it should not be
disposed of to landfill as it may leach to groundwater due to its expected high mobility in
soil and low adsorption potential.
2-butoxyethanol v
Contents
PREFACE iii
ABSTRACT iv
ABBREVIATIONS xi
1. INTRODUCTION 1
2. BACKGROUND 2
2.1 The glycol ethers 2
2.2 The international perspective 2
2.3 The Australian perspective 3
3. APPLICANTS 5
4. CHEMICAL IDENTITY AND COMPOSITION 6
4.1 Chemical name 6
4.2 Other names 6
4.3 Molecular and structural formula 6
4.4 Trade names 6
4.5 Chemical composition 7
5. PHYSICAL AND CHEMICAL PROPERTIES 8
5.1 Physical state 8
5.2 Physical and chemical properties 8
6. METHODS OF DETECTION AND ANALYSIS 10
6.1 Identification 10
6.2 Determination of 2-butoxyethanol in air 10
6.2.1 Sampling 10
6.2.2 NIOSH method 1403 (NIOSH 1990) 10
6.2.3 OSHA method 83 (NIOSH 1990) 10
6.3 Determination of 2-butoxyacetic acid in urine 10
6.4 Determination of 2-butoxyethanol and 2-butoxyacetic
acid in blood 11
7. USE 12
7.1 Import and production 12
7.2 Uses of 2-butoxyethanol 12
7.3 Types of cleaning products 12
7.4 Methods of applying cleaning products 14
7.5 Formulation of cleaning products 14
8. OCCUPATIONAL EXPOSURE 16
8.1 Routes of exposure 16
8.2 Methodology 16
8.2.1 Monitoring data 17
8.2.2 Exposure duration and atmospheric
concentration 18
Priority Existing Chemical Number 6
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8.3 Exposure during manufacture of 2-butoxyethanol 21
8.4 Exposure during formulation of cleaning products 21
8.4.1 Potential for exposure 21
8.4.2 Exposure to vapour during formulation 22
8.4.3 Exposure to liquid during formulation 23
8.4.4 Combined dermal and inhalational exposure during
formulation 23
8.5 Exposure during use of cleaning products 24
8.5.1 Potential for exposure 24
8.5.2 Exposure to vapour during cleaning 26
8.5.3 Exposure to liquid during cleaning 26
8.5.4 Combined dermal and inhalational exposure
during cleaning 27
8.6 Conclusions 27
9. KINETICS AND METABOLISM 32
9.1 General 32
9.2 Absorption 32
9.2.1 Animal studies 32
9.2.2 In vitro studies 33
9.2.3 Human studies 34
9.3 Distribution 35
9.4 Metabolism 36
9.5 Elimination and excretion 38
9.6 Pharmacokinetic models 38
9.7 Summary 39
10. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO
TEST SYSTEMS 40
10.1 General 40
10.2 Acute toxicity 40
10.2.1 Oral 40
10.2.2 Dermal 41
10.2.3 Inhalation 42
10.2.4 Intraperitoneal injection 42
10.2.5 Intravenous injection 43
` 10.2.6 Summary 43
10.3 Irritation 43
10.3.1 Skin irritation 43
10.3.2 Eye irritation 44
10.3.3 Respiratory irritation 44
10.3.4 Summary 44
10.4 Sensitisation 44
10.5 Immunotoxicity 45
2-butoxyethanol vii
10.5.1 Effect on the proliferation of guinea pig
lymphocytes in vitro 45
10.5.2 Other studies 45
10.6 Repeated dose toxicity 45
10.6.1 Oral 45
10.6.2 Dermal 47
10.6.3 Inhalational 48
10.6.4 Summary 50
10.7 Haematological studies 51
10.7.1 Early studies 51
10.7.2 Gavage study in Sprague-Dawley rats 51
10.7.3 Other in vivo studies (published) 52
10.7.4 In vitro studies in various species (published) 53
10.7.5 Summary of haematological studies 54
10.8 Reproductive toxicity 54
10.8.1 General 54
10.8.2 Two-generation NTP study in mice 54
10.8.3 Other studies 55
10.8.4 Developmental toxicity/teratogenicity studies 56
10.8.5 Summary 58
10.9 Genotoxicity 58
10.9.1 In vitro assays 58
10.9.2 In vivo studies 59
10.9.3 Summary of data on genotoxicity 60
10.10 Carcinogenicity 60
10.11 Summary of toxicological data 60
11. HUMAN HEALTH EFFECTS 63
11.1 Case reports 63
11.2 Controlled studies 63
11.2.1 Inhalational 63
11.2.2 Dermal 64
11.3 Occupational studies 64
11.4 Other information 64
11.5 Summary 65
12. HAZARD ASSESSMENT AND CLASSIFICATION 66
12.1 Physicochemical hazards 66
12.2 Kinetics and metabolism 66
12.3 Health hazards 66
12.3.1 Acute effects 66
12.3.2 Irritant effects 67
12.3.3 Sensitisation 67
12.3.4 Immunotoxicity 68
12.3.5 Effects after repeated or prolonged exposure 68
Priority Existing Chemical Number 6
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12.3.6 Reproductive effects 71
12.3.7 Genotoxicity 71
12.3.8 Carcinogenicity 71
12.4 Classification summary 71
12.5 Comparison of glycol ethers 73
13. RISK CHARACTERISATION (OCCUPATIONAL) 75
13.1 Methodology 75
13.2 Critical health effects 75
13.2.1 Acute effects 75
13.2.2 Effects of repeated exposure 76
13.3 Occupational health and safety risks 76
13.3.1 Risk from physicochemical hazards 76
13.3.2 Margin of safety 76
13.3.3 Uncertainties in the risk characterisation 77
13.3.4 Risk during manufacture of 2-butoxyethanol 78
13.3.5 Risk during formulation of cleaning products 78
13.3.6 Risk during use of cleaning products 80
13.4 Areas of concern 82
14. RISK MANAGEMENT 83
14.1 Control measures 83
14.1.1 Elimination 83
14.1.2 Substitution 84
14.1.3 Isolation 84
14.1.4 Engineering controls 84
14.1.5 Administrative controls 85
14.1.6 Safe work practices 85
14.1.7 Personal protective equipment 86
14.2 Emergency procedures 87
14.3 Hazard communication 87
14.3.1 Assessment of Material Safety Data Sheets 87
14.3.2 Assessment of labels 91
14.3.3 Education and training 95
14.4 Monitoring and regulatory controls 97
14.4.1 Exposure standard 97
14.4.2 Atmospheric monitoring 98
14.4.3 Health surveillance 98
15. PUBLIC HEALTH ASSESSMENT 101
15.1 Exposure 101
15.2 Health effects 101
15.3 Health risk to the public 101
16. ENVIRONMENTAL ASSESSMENT 102
16.1 Environmental exposure 102
16.1.1 Release 102
2-butoxyethanol ix
16.1.2 Fate 102
16.1.3 Summary 104
16.2 Environmental effects 104
16.2.1 Summary 105
16.3 Environmental risk 105
17. RECOMMENDATIONS 106
17.1 Classification 106
17.1.1 NOHSC hazard classification 106
17.1.2 SUSDP listing 106
17.1.3 Dangerous goods classification 106
17.2 Control measures 106
17.2.1 Elimination 107
17.2.2 Substitution 107
17.2.3 Engineering controls 107
17.2.4 Safe work practices 117
17.2.5 Personal protective equipment 108
17.3 Hazard communication 108
17.3.1 MSDS 108
17.3.2 Labels 109
17.3.3 Training and education 109
17.4 Exposure standard 110
17.5 Biological monitoring and biological exposure index 110
17.6 Disposal 110
17.7 Health hazards 111
17.7.1 Case reports 111
17.7.2 Further testing 111
18. SECONDARY NOTIFICATION 112
APPENDICES
Appendix 1 Cleaning products containing 2-butoxyethanol 113
Appendix 2 Questionnaire 131
Appendix 3 Occupational exposure calculations 132
Appendix 4 Other information submitted to NICNAS 137
Appendix 5 ABSA Structured training program for cleaners 139
Appendix 6 Sample Material Safety Data Sheet 140
REFERENCES 146
GLOSSARY 159
Priority Existing Chemical Number 6
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Abbreviations
ABSA Australian Building Services Association
ACGIH American Conference of Governmental Industrial Hygienists
ADG Australian Code for the Transport of Dangerous Goods by Road and
Rail
ADH alcohol dehydrogenase
AICS Australian Inventory of Chemical Substances
ALDH aldehyde dehydrogenase
AQUIRE Aquatic Toxicity Information Retrieval database (US EPA)
ASTER Assessment Tools for the Evaluation of Risk database (US EPA)
ATP adenosine triphosphate
BAA 2-butoxyacetic acid
BAA-GLN N-butoxyacetylglutamine
BAL 2- butoxyacetaldehyde
BAT "Biologischer Arbeitsstoff-Toleranz-Wert"
(biological tolerance value for occupational exposures)
2-BE 2-butoxyethanol
BEG 2-butoxyethanol glucuronide
BEI biological exposure index
BES 2-butoxyethanol sulfate
BOD biochemical oxygen demand
CAS Chemical Abstracts Service
CHO Chinese hamster ovary
CMA Chemical Manufacturers Association (USA)
CNS central nervous system
carbon dioxide
CO2
Con A concanavalin A
cP centipoise
median effective concentration
EC50
ECETOC European Centre for Ecotoxicology and Toxicology of Chemicals
EEC European Economic Community
EG ethylene glycol
EINECS European Inventory of Existing Commercial Chemical Substances
GC gas chromatography
GC-MS gas chromatography-mass spectrometry
gd gestational day
Hgb haemoglobin
hPa hectopascal
HPLC high performance liquid chromatography
HPV high production volume
2-butoxyethanol xi
HSE Health and Safety Executive (UK)
ISO International Standards Organisation
IUPAC International Union for Pure and Applied Chemistry
median lethal concentration
LC50
median lethal dose
LD50
LOAEL lowest observable adverse effect level
MAK "Maximale Arbeitsplatz-Konzentration " (maximum workplace
concentration)
MATC maximum acceptable toxicant concentration
MCH mean corpuscular (or cell) haemoglobin
MCHC mean corpuscular (or cell) haemoglobin concentration
MCV mean corpuscular (or cell) volume
MDA malonylaldehyde
2
mg/cm /h milligrams per square centimetre per hour
mg/kg bw milligrams per kilogram body weight
mN/m millinewtons per metre
MSDS Material Safety Data Sheet
NIOSH National Institute for Occupational Safety and Health (USA)
nm nanometer
NOAEL no observable adverse effect level
NOEL no observable effect level
NOHSC National Occupational Health and Safety Commission
NTP National Toxicology Program (USA)
OECD Organisation for Economic Cooperation and Development
OSHA Occupational Safety and Health Administration (USA)
PBPK physiologically-based pharmacokinetic
PFB pentafluorobenzyl
PFBB pentafluorobenzylbromide
PHA phytohaemagglutinin
ppb parts per billion
PPE personal protective equipment
ppm parts per million
QSAR Quantitative Structure Activity Relationship
RBC red blood cell
concentration which causes a 50% decrease in respiratory rate
RD50
SCE sister chromatid exchange
SIAR SIDS Initial Assessment Report
SIDS Screening Information Data Set
STEL short-term exposure limit
SUSDP Standard for the Uniform Scheduling of Drugs and Poisons
TNP-LPS trinitrophenyl-lipopolysaccharide
TWA time-weighted average
Priority Existing Chemical Number 6
xii
UDS unscheduled DNA synthesis
祄ol micromole
US EPA Environmental Protection Agency of the USA
2-butoxyethanol xiii
Priority Existing Chemical Number 6
xiv
1. Introduction
The chemical 2-butoxyethanol (CAS no. 111-76-2) was declared by the Minister for
Industrial Relations as a priority existing chemical (PEC) under the Industrial Chemicals
(Notification and Assessment) Act 1989 (Cwlth) (the Act) by notice in the Chemical
Gazette of 5 April 1994. The declaration was specific for the use of 2-butoxyethanol in
cleaning products.
The declaration was made on the basis that there were reasonable grounds for believing
that the formulation, handling and use of cleaning products containing 2-butoxyethanol
may give rise to a risk of adverse health effects. In summary, these grounds were:
?the high potential for occupational and public exposure due to the wide use in Australia
of cleaning products containing 2-butoxyethanol;
?concern about the known and potential health hazards of 2-butoxyethanol given the
high potential exposure; and
?reported adverse health effects in workers using cleaning products containing 2-
butoxyethanol.
In accordance with the Act, manufacturers and importers of 2-butoxyethanol for its use in
cleaning products, and importers of cleaning products containing 2-butoxyethanol, applied
for the assessment of 2-butoxyethanol as a PEC. Information for the assessment was
received from manufacturers (in Australia and overseas), importers, formulators, end-
users, State and Territory departments, other interested persons, and from a comprehensive
literature search. A questionnaire was sent to formulators to obtain Material Safety Data
Sheets and labels for many of the cleaning products and to obtain information about the
formulation process and worker exposure.
2-butoxyethanol 1
2. Background
2.1 The glycol ethers
2-Butoxyethanol belongs to a group of chemicals known as glycol ethers, which are
compounds formed by reacting an alcohol with an alkyl oxide such as ethylene or
propylene oxide. 2-Butoxyethanol is one of the monoalkyl ethers, which have the general
formula R-O-R'-OH, where R is an alkyl group, for example, methyl (CH3), and R' is -
CH2CH2- for the ethylene glycol monoalkyl ethers and -CH2CH2CH2- for the propylene
glycol monoalkyl ethers. A list of typical glycol ethers is provided in Table 1 showing
structural similarities and differences.
The glycol ethers are liquids which are miscible with water and most organic solvents, so
they are widely used as solvents and in cleaners, paints and inks. A number of glycol
ethers are manufactured and used in Australia.
2.2 The international perspective
There has been widespread concern over the health effects of the glycol ethers for some
time. Health effects caused by some members of the glycol ether group include
haematotoxicity, testicular degeneration, developmental effects and immunological
effects. However, it has become increasingly evident from published studies and reports
that the type and severity of health effects of members of this group of chemicals vary
considerably, and so increasingly the health issues of the individual members of the group
are being studied.
Concerns about the health effects of the glycol ethers have led to a number of reports
being published overseas and several comparative investigations into members of the
group. In the US, the EPA conducted a review (US EPA 1993) of the human health
effects of the glycol ethers. In Europe, the European Centre for Ecotoxicology and
Toxicology of Chemicals (ECETOC) (1982; 1985; 1995) and the UK Health and Safety
Executive (HSE) (1985) published reports on the health effects of the glycol ethers.
More recently, the health effects of the individual members have been studied. ECETOC
(1994) and the US National Institute for Occupational Health and Safety (NIOSH) (1990)
have published criteria documents which have focussed on the setting of an occupational
exposure standard for 2-butoxyethanol and the HSE has recently drafted a similar report.
The US Cosmetic, Toiletry and Fragrance Association (1994) published a safety
assessment for the use of 2-butoxyethanol in cosmetics.
In the USA, the introduction of regulatory controls on the glycol ethers by the EPA led to
the formation of an Ethylene Glycol Ethers Panel by the Chemical Manufacturers
Association (CMA). The association has sponsored testing to further investigate the health
effects of the glycol ethers.
2-Butoxyethanol is listed under Phase 4 of the Organisation for Economic Co-operation
and Development (OECD) High Production Volume (HPV) program. The primary aim of
the HPV program is to investigate the hazards of chemicals produced internationally in
large volumes. As a member of the OECD, Australia has agreed to assess 2-butoxyethanol
in the HPV program. Data in this PEC report will form the basis of the Screening
Information Data Set (SIDS) required under the program. Following the incorporation of
exposure data from other OECD member countries, a SIDS Initial Assessment Report
(SIAR) will be completed and reviewed internationally. It is expected that this report will
cover all uses of 2-butoxyethanol, not just the use in cleaning products.
Priority Existing Chemical Number 6
2
In Europe, it has been reported that cleaning agents available to the public now usually
contain 2-(2-butoxyethoxy)ethanol (2-BEE), which has a lower vapour pressure and skin
absorption rate than 2-butoxyethanol. Consequently, in 1994, more than 16000 tonnes of
2-BEE were used in public sector cleaning agents compared with approximately 1000
tonnes of 2-butoxyethanol. In Germany, it has been reported that the trend is towards the
use of glycol ethers without a primary hydroxy group, for example, the 1-alkoxy-2-
propanols.
2.3 The Australian perspective
In Australia, widespread concern by employee and public interest organisations over the
use of cleaning products containing 2-butoxyethanol has persisted in recent years. In
particular, concern has been expressed about the use of these products in schools.
In Australia, 2-butoxyethanol is imported by several companies and manufactured by ICI
Australia. Most cleaning products containing 2-butoxyethanol are formulated in this
country, and a relatively small number are imported.
This report focuses on the use of 2-butoxyethanol in cleaning products in Australia
because of the specific concerns raised in this context. The report includes an assessment
of the exposure and risks to workers, the public and the environment of 2-butoxyethanol
from this use. However, information in the report, for example, the assessment of health
effects data and other hazards, is also relevant for the other uses of 2-butoxyethanol, and
the methodology used in the risk assessment is expected to have application in other uses.
2-butoxyethanol 3
Table 1 - Typical Glycol Ethers
Class Name Alkyl Group(s) Structural Formula CAS No.
Ethylene Glycol Ethers:
Monoalkyl 2-Methoxyethanol methyl CH3-O-CH2-CH2-OH 109-86-4
C2H5-O-CH2-CH2-OH 110-80-5
2-Ethoxyethanol ethyl
C4H9-O-CH2-CH2-OH 111-76-2
2-Butoxyethanol butyl
C6H5-O-CH2-CH2-OH 122-99-6
2-Phenoxyethanol phenyl
CH3-O-CH2-CH2-O-CH3 110-71-4
1,2-Dimethoxyethane methyl
CH3-(O-CH2-CH2)2-OH 111-77-3
Dialkyl 2,(2-Methoxyethoxy)ethanol methyl, ethyl
2-(2-n-Butoxyethoxy)ethanol ethyl, butyl C4H9-(O-CH2-CH2)2-OH 112-34-5
CH3-(O-CH2-CH2)2-O-CH3 111-96-6
Bis(2-methoxyethyl)ether methyl, ethyl
Trialkyl 2-[2-(2-Ethoxyethoxy)ethoxy]ethanol C2H5-(O-CH2-CH2)3-OH CH3- 112-50-5 112-
ethyl, ethyl, ethyl
(O-CH2-CH2)3-O-CH3 49-2
methyl, ethyl, ethyl
2,5,8,11-Tetraoxadodecane
Propylene Glycol Ethers:
Monoalkyl 1-Ethoxy-2-propanol ethyl CH3-CH(OH)-CH2-O-C2H5 1569-02-4
CH3-CH(OH)-CH2-O-(CH2)3-CH3 5131-66-8
1-Butoxy-2-propanol butyl
CH3-CH(O-CH3)-CH2-OH 1589-47-5
2-Methoxypropanol-1 methyl
Dialkyl (2-Methoxymethylethoxy)-propano (2- methyl, propyl CH3-(O-C3H6)2-OH C2H5- 34590-94-8
Ethoxy-methylethoxy)-propanol l ethyl, propyl (O-C3H6)2-OH 300025-38-8
Trialkyl [2-(2-Methoxymethylethoxy)methylethoxy]- propanol methyl, propyl, propyl CH3-(O-C3H6)3-OH 25498-49-1
Priority Existing Chemical Number 6
4
3. Applicants
Amway of Australia Pty Ltd
46 Carrington Rd, Castle Hill, NSW 2154
Ecolab Pty Ltd
6 Hudson Ave, Castle Hill, NSW 2154
ICI Australia Operations Pty Ltd
1 Nicholson St, Melbourne, Vic 3000
S C Johnson Pty Ltd
160 Epping Rd, Lane Cove, NSW 2066
3M Australia Pty Ltd
950 Pacific Highway, Pymble, NSW, 2073
Redox Chemicals Pty Ltd
30-32 Redfern St, Wetherill Park, NSW 2164
Swift and Company Ltd
85 Egerton St, Silverwater, NSW 2128
Union Carbide Chemicals (Australia) Pty Ltd
Suite 1, 1st floor, 1-7 Jordan St, Gladesville, NSW 2111
Whiteley Chemicals Australia Pty Ltd
82-84 Ivy St, Chippendale, NSW 2008.
2-butoxyethanol 5
4. Chemical identity and composition
4.1 Chemical name
2-Butoxyethanol is listed on the Australian Inventory of Chemical Substances (AICS) as
Ethanol, 2-butoxy-.
The Chemical Abstracts Service (CAS) registry number is 111-76-2.
Its IUPAC name is Ethylene glycol butyl ether.
The EINECS number is 203-905-0. The EEC classification number is 603-014-00-0.
4.2 Other names
?Butoxyethanol
?n-Butoxyethanol
?2-Butoxy-1-ethanol
?Butyl ethoxol
?O-Butyl ethylene glycol
?Butyl glycol
?Butyl monoether glycol
?EGBE
?Ethylene glycol butyl ether
?Ethylene glycol n-butyl ether
?Ethylene glycol monobutyl ether
?Ethylene glycol mono-n-butyl ether
?Glycol butyl ether
?Glycol monobutyl ether
?Monobutyl glycol ether
?3-Oxa-1-heptanol
4.3 Molecular and structural formula
The molecular formula is C6H14O2..
The molecular weight is 118.2.
The structural formula is CH3CH2CH2CH2OCH2CH2OH.
4.4 Trade names
2-Butoxyethanol is known commercially under the following trade names:
?Butyl Cellosolve?br>
?Butyl Icinol?br>
?Butyl Oxitol?br>
?Dowanol EB?br>
?Ektasolve EB?br>
?Gafcol EB?br>
Priority Existing Chemical Number 6
6
?Glycol ether EB?br>
?Jeffersol EB?br>
?Poly-Solv EB?
The known trade names of cleaning products in Australia which contain 2-butoxyethanol
are listed in Appendix 1. The list was compiled from responses to a questionnaire sent to
formulators in late 1994. It is not intended to be a comprehensive listing.
4.5 Chemical composition
When 2-butoxyethanol is manufactured from ethylene oxide and n-butanol, other glycol
ethers such as the di- and triethylene glycol ethers are produced. Consequently,
commercial 2-butoxyethanol may contain small concentrations of other glycol ethers, n-
butanol and ethylene glycol.
A stabiliser, 2,6-bis(1,1-dimethylethyl)-4-methylphenol, can be added at approximately
0.01% to prevent the formation of peroxides.
For the composition of cleaning products containing 2-butoxyethanol, see section 7.5.
2-butoxyethanol 7
5. Physical and chemical properties
5.1 Physical state
2-Butoxyethanol is a colourless liquid with an unpleasant odour. The odour threshold is
0.10 ppm (NIOSH 1990).
Conversion factor (for vapour): 1ppm = 4.9 mg/m3 (20癈, 1014 hPa).
5.2 Physical and chemical properties
Table 2 - Physical and Chemical Properties
Property Value Reference
o
Freezing point - 77 C (NIOSH 1990)
o
Boiling point 170.8 C (NIOSH 1990)
Density (20oC) 0.90 g/mL (EUCLID 1994)
o
Vapour density (20 C) 4.91 g/L (ECETOC 1994)
Relative vapour density (air = 1) 4.1 (NIOSH 1990)
o
Vapour pressure (25 C) 1.17 hPa (ECETOC 1994)
62oC (NIOSH 1990)
Flash point (closed cup)
o
230-245 C (EUCLID 1994)
Autoignition temperature
Flammability limits 1.10 - 12.7% (NIOSH 1990)
Explosive properties not explosive (EUCLID 1994)
Water solubility miscible (NIOSH 1990)
Partition coefficient (log Pow) 0.81 (EUCLID 1994)
Adsorption coefficient (Koc) 67 (calculated) (Howard 1993)
o
Viscosity (25 C) 6.4 cP (EUCLID 1994)
Surface tension (25oC) 27.4 mN/m (EUCLID 1994)
o
Refractive index (25 C) 1.422 (Dow 1990)
Hydrolysis:
2-Butoxyethanol is unlikely to hydrolyse as alcohols and ethers are generally resistant to
hydrolysis (Howard et al 1993).
Adsorption/desorption:
A Koc of 67 indicates that 2-butoxyethanol will not partition into organic matter contained
in sediments and suspended solids, and should be highly mobile in soil (Howard et al
1993).
Surface tension:
2-Butoxyethanol is surface active, thereby increasing its adsorption potential.
Priority Existing Chemical Number 6
8
2-Butoxyethanol is soluble in water and most organic solvents. It undergoes reactions
typical of glycol ethers (Dow Chemical 1990), viz.:
?oxidation to 2-butoxyacetic acid (BAA);
?acetal formation when reacted with aldehydes under acidic conditions;
?ester formation when reacted with a carboxylic acid, for example, acetic acid, in the
presence of a strong acid;
?phosphate and sulfate esters when reacted with phosphoric and sulfuric acids
respectively; and
?dehydrogenation in the presence of copper at high temperatures.
2-butoxyethanol 9
6. Methods of detection and analysis
6.1 Identification
2-Butoxyethanol can be characterised using nuclear magnetic resonance spectroscopy
(NMR), infra-red spectroscopy (IR) and mass spectroscopy (MS).
6.2 Determination of 2-butoxyethanol in air
6.2.1 Sampling
In standard methods for the determination of 2-butoxyethanol in air, such as personal
monitoring, activated charcoal (coconut shell type) is usually used as the adsorbent. Most
methods use a sampling pump to draw air onto the charcoal held in a tube, with a flow rate
in the range 10-100 mL/min. The use of a 3M diffusion sampling badge to collect the
sample has been reported (Sakai et al 1993).
6.2.2 NIOSH method 1403
This method (NIOSH 1990) is widely used for determining 2-butoxyethanol in air.
Samples are collected in solid sorbent tubes containing coconut shell charcoal at a flow
rate of 10-50 mL/min and desorbed with 5% methanol in methylene chloride. The
resultant solution is analysed by gas chromatography using flame ionisation detection.
The estimated limit of detection is 0.01 to 0.02 mg.
Multidimensional gas chromatography-mass spectrometry (GC-MS) has been used to
improve the detection limit of the method to 5-7 礸 per sample (Kennedy et al 1990).
6.2.3 OSHA method 83
This standard method (NIOSH 1990) is very similar to the NIOSH method. The
recommended air volume and sampling rate for 8-hr TWA samples is 48 L at 0.1 L/min
and for short term samples is 15 L collected at 1.0 L/min (15-min samples). The detection
limit for a 48 L sample is 31 ppb.
6.3 Determination of 2-butoxyacetic acid in urine
Most of the methods for the determination of 2-butoxyacetic acid (BAA) in urine
i n c o r p o r a t e pH adjustment, solvent extraction, derivatisation, and then gas
chromatography (GC) or high performance liquid chromatography (HPLC).
In the method recommended by NIOSH (1990) the sample is adjusted to pH 7, a small
amount of water is added, and the samples are freeze-dried at -60oC overnight. BAA is
then derivatised with 2,3,4,5,6-pentafluorobenzylbromide (PFBB) and a methylene
chloride solution of the PFB ester is analysed gas chromatographically. The limit of
detection is 0.03 mg/L (Groeseneken et al 1989).
In another GC method reported (Sakai et al 1993), BAA is extracted with a mixture of
d i c h l o r o m e t h a n e and isopropyl alcohol and then derivatised with trimethylsilyl-
diazomethane. The esterified acids are analysed by GC using a flame ionisation detector
and a capillary column. Analytical recovery of BAA added to urine from 15 control
subjects was 99% ?.8%. The detection limit for BAA is 0.01 mg/L. This method has
been recently upgraded to measure both BAA and the conjugated metabolites in urine
(Sakai et al 1994). The conjugates are hydrolysed by acidifying the sample with
concentrated hydrochloric acid and boiling the mixture for one hour.
BAA has also been analysed by an HPLC method which enables the simultaneous
quantification of the amino acid conjugate N-butoxyacetylglutamine (BAA-GLN)
Priority Existing Chemical Number 6
10
(Rettenmeier et al 1993). Gas chromotography is not considered suitable for the
determination of BAA-GLN as it is unstable at the temperatures required for eluting the
corresponding methyl or trimethylsilyl derivatives from the GC column. Urine samples
are acidified and then extracted with ethyl acetate, followed by the addition of 4-
nitrobenzylbromide (in ether and acetonitrile) for derivatisation. Gradient elution HPLC is
then conducted with water/acetonitrile as mobile phase on a 5祄 Hypersil/ODS column
with UV detection at 260 nm.
In a recently reported variation of this method, BAA was analysed by gradient elution
HPLC on a 礏ondapak column using 0.1M ammonium acetate and acetonitrile as the
mobile phase, with UV detection at 255 nm (Corley et al 1994).
6.4 Determination of 2-butoxyethanol and 2-butoxyacetic acid in blood
In general, the methods for BAA in blood are variations of the methods used for the
analysis of BAA in urine.
The simultaneous ion-pair extraction and derivatisation of BAA with PFBB has been
reported (Johanson and Johnssen 1991). Analysis is carried out by GC using electron
capture detection.
It has been recently reported that 2-butoxyethanol and BAA in rat and human blood can be
analysed using capillary gas chromatography linked to a mass spectrometer (GC-MS)
(Bormett et al 1995). 2-Butoxyethanol and BAA are measured as the pentafluorobenzoyl
and PFB derivatives respectively, with the quantitation limit 16-18 ng/g for both 2-
butoxyethanol and BAA.
2-butoxyethanol 11
7. Use
7.1 Import and production
Approximately 700 tonnes of 2-butoxyethanol were imported into Australia during the
1993-1994 financial year from a number of countries including the Netherlands, Russia,
Belgium, Singapore, Sweden, Germany and the USA. In addition, a number of cleaning
products containing 2-butoxyethanol were imported into Australia.
2-Butoxyethanol is one of a number of glycol ethers manufactured in Australia by ICI
Australia Operations Pty Ltd at their plant at Matraville NSW. Approximately 2000
tonnes of 2-butoxyethanol per year are manufactured.
At Matraville, 2-butoxyethanol is synthesised from the reaction of ethylene oxide and n-
butanol. A number of glycol ethers are produced in the reaction, for example, the ethers of
di- and triethylene glycol, so the various entities must be separated by distillation. The
process, which is carried out in a sealed system, is continuous, with a production campaign
usually lasting about 1-2 weeks. Other glycol ethers are synthesised at the plant from
other alcohols and from propylene oxide.
2-Butoxyethanol is packed off into 205L drums, intermediate bulk containers (IBCs), or
loaded directly into road tankers.
7.2 Uses of 2-butoxyethanol
2-Butoxyethanol is used in many different applications. The main use is in paints and
surface coatings, followed by its use in cleaning products and then inks. Other products in
Australia which contain 2-butoxyethanol include acrylic resin formulations, asphalt release
agents, firefighting foam, leather protectors, oil spill dispersants and photographic strip
solutions.
In international databases, 2-butoxyethanol is also listed as a solvent for greases, oils,
dyestuffs and nitrocellulose resins and enamels. It has been used as an ingredient in
agricultural chemicals, cosmetics and brake oils, and as a raw material in the production of
acetate esters and phthalate and stearate plasticisers.
To identify the use and exposure pattern of cleaning products containing 2-butoxyethanol
in Australia, and obtain MSDS and labels of the products, a questionnaire was sent in late
1994 to prospective formulators (see Appendix 2). From responses to the questionnaire,
82 formulators and 434 products were identified (see Appendix 1). It is estimated that
approximately 1000 tonnes of 2-butoxyethanol per year are used in the formulation of
cleaning products. No later survey was conducted to ascertain whether the cleaning
products identified in the response to the questionnaire in 1994 had been reformulated.
7.3 Types of cleaning products
Analysis of the uses of the 434 cleaning products identified during the assessment revealed
a wide variety of applications (as stated on the Material Safety Data Sheet and/or the label
for each product). The main uses are tabled below.
Priority Existing Chemical Number 6
12
Table 3 - Main Types of Cleaning Products
Use Number % of total 2-BE concentration (%)
min. max.
surface cleaner 214 49 0.57 71
floor stripper 49 11 <1 30.5
47 11 <1 40
glass/window
cleaner
carpet cleaner 40 9 <1 10-30
laundry detergent 15 4 <1.5 10-30
rust remover 11 3 <10 30-60
oven cleaner 11 2 <1 10-30
ink/resin remover 9 2 1 10 - 93
others 38 9 <10 94
For many of the products, the exact percentage of 2-butoxyethanol is not known as MSDS
and/or labels were not submitted or, in some cases, only a concentration range was
indicated on the MSDS. From the information submitted, most products had a
concentration of 2-butoxyethanol of less than 10% (Table 4).
Table 4 - Concentration of 2-Butoxyethanol in Cleaning Products
2-BE Concentration Number of Products % of Total
< 10% 297 68%
10-30% 59 14%
30-60% 6 1%
10-60% 7 2%
> 60% 5 1%
unknown 60 14%
Many of the products classed as surface cleaners were actually multi-purpose cleaners
which could be used in a variety of applications such as floor and wall cleaning, floor
stripping, oven cleaning, grease trap cleaning, engine degreasing, vehicle washing and
laundry pre-spraying. A number of products could be used in hot or cold water pressure
cleaning machines.
Among the surface cleaners were a number of single purpose surface cleaning products.
These included aircraft exterior cleaners, boat cleaners, upholstery cleaners, travel wax
cleaners for new vehicles, a grease trap cleaner, a decarboniser and an abbatoir hook
cleaner.
Other types of cleaning products notified (`Others' in Table 3 above) included aluminium
cleaner/brighteners, electrical cleaning solvents, bathroom cleaners and disinfectants, toilet
cleaner/deodorants, combined cleaner/phosphate powders, a detergent for the removal of
fats and greasy soils from apples, a detergent for the removal of sooty mould from citrus
fruit, a hand cleaner, a fuel system cleaner, a cleaner of cylinders used in a silicone coating
process, a harvester spindle cleaner, a glass and bottlewashing detergent, and an exhaust
scrubber tank cleaner on underground mining locomotives.
2-butoxyethanol 13
7.4 Methods of applying cleaning products
Cleaning products work by wetting the surface, penetrating the soil or stain, lifting and
removing the soil or stain, and holding the foreign material in suspension so that the
surface can be rinsed or wiped.
Cleaning products are generally applied by one of the following methods:
?washing with liquid cleaner, for example, with a cloth or sponge, and wiping the
surface;
?spraying the surface and then wiping;
?applying liquid cleaner by mop or brush;
?applying the cleaner as a liquid stream, for example, using a wash or squeeze bottle;
?applying the cleaning solution by machine, for example, in hot and cold water pressure
cleaners, including steam and foam cleaning; or
?soaking in liquid cleaner.
In most cases, the cleaning product as marketed needs to be diluted with water prior to
application. The dilution factor, which is often on the label, depends on the type of
surface to be cleaned, the soil loading, and the type and method of application. For
example, in degreasing and oven cleaning a dilution factor up to 1:5 is often used; as a
spray for floor and wall cleaning dilution ranges from 1:10 to 1:30, and as a wash for
delicate surfaces dilution ranges from 1:20 to 1:100.
A large proportion of the cleaning products are used in spray form. From the information
supplied by formulators, at least 163 products are used in spray form, with spraying listed
as the major method of application for 73 products. Twelve of these products are sold as
pressurised aerosol containers or trigger packs.
For a number of products, end-users are directed (on the label) to use hot water (up to
80oC) for dilution. In some applications, for example, oven cleaning, end-users are often
advised (on the label) to apply the cleaning solution to a warm surface, for example,
heated up to 65oC.
7.5 Formulation of cleaning products
The glycol ethers are common ingredients in cleaning products as they have a hydrophobic
group to dissolve the grease or organic component of the soil or stain and a hydrophilic
group to dissolve the water-soluble component. Most cleaning products also contain up to
5% surfactant, with other chemicals such as acids, alcohols and/or thickeners added to
give the formulation its desired characteristics. For example, oven cleaners contain alkali,
rust removers contain phosphoric acid and window cleaners contain ammonia. In most
cases, cleaning products containing 2-butoxyethanol are aqueous solutions but some
cleaners, for example, electrical cleaners and some carpet spotters, are hydrocarbon-based,
and some window cleaners are ethanol-based.
Cleaning products are formulated by stirring the ingredients for 1-4 hours in a mixing
tank, usually stainless steel and ranging in size from approximately 150-250,000L.
Mixing usually takes place at room temperature and 2-butoxyethanol is generally the last,
or one of the last, ingredients to be added to the mixer. It can be added directly to the
mixing vessel from a 205L drum or it can be added to the mixer via a manifold and
metering system from a drum or storage vessel. Smaller quantities are often pre-weighed
into smaller drums or buckets before addition to the mixer.
Product is packed off into containers ranging in size from <1L (generally plastic
containers) to 205L (drums). The containers are filled either by gravity feed from the
Priority Existing Chemical Number 6
14
mixing vessel or by pneumatic filling. The larger packs are distributed to repackagers and
to the larger cleaning companies.
2-butoxyethanol 15
8. Occupational exposure
8.1 Routes of exposure
The major routes of exposure to 2-butoxyethanol are inhalation and skin absorption. 2-
Butoxyethanol is a liquid which is miscible with water. It is readily absorbed through the
skin, including absorption from aqueous solution, and in vapour and aerosol form.
Inhalation of 2-butoxyethanol may occur by exposure to vapours emitted from liquid 2-
butoxyethanol or solutions containing the chemical, or by exposure to aerosols, for
example, during the spray use of cleaning products. As 2-butoxyethanol has a relatively
low volatility, emission of vapours is likely to be low. Conditions which may lead to
increased generation of vapours and/or aerosols include heating and mechanical mixing.
Therefore the total exposure of workers to 2-butoxyethanol must take into account the
inhalational uptake of vapours and aerosols and the dermal absorption of 2-butoxyethanol
in liquid, vapour and aerosol form.
8.2 Methodology
In an assessment of occupational exposure, it is preferable to use good quality measured
data, representative of the various work scenarios. When such data is unavailable or
inadequate, then modelling can be used, with standard formulae often used to estimate
exposure. Such estimates are often used in preliminary risk assessments to identify areas
of concern which may be followed up using a more in depth assessment approach after
obtaining more representative exposure data. This was the approach needed in this
assessment of 2-butoxyethanol as measured data was limited, particularly for dermal
exposure.
The estimates generated in this exposure assessment are considered to be `feasible' worst-
case estimates, as they describe high end or maximum exposures in `feasible but not
unrealistic' situations. The estimates are not intended to account for extreme or unusual
use scenarios which are unlikely to occur in the workplace. The vast majority of
occupational exposures are expected to be well below these estimates.
The formulae used to calculate exposures are detailed in Appendix 3. The constants used
in the formulae, for example, inhalation rate and body weight, were consistent with those
used in international assessments. The rationale behind the values used for some
parameters in the formulae, for example, skin absorption and skin surface area, is detailed
in Appendix 3.
In general, the critical health effect, haemolysis, is observed as a transient effect in animal
studies. In repeated dose studies, haematological effects were more evident in animals
during the first days of exposure, and generally full recovery from these effects was
observed later in the studies. Also, 2-butoxyethanol is not bioaccumulative (see subsection
12.3.5). Therefore, occupational exposure estimates were calculated for daily exposure
(up to 8 hours) rather than for long-term average exposure.
Inhalational exposure was estimated using atmospheric monitoring data, mainly from
overseas, and included extrapolation of the data in some instances. Estimates for exposure
to vapour included the dermal uptake of vapour, which was estimated using data from
PBPK modelling and the results of recent studies in volunteers, which showed that the
dermal absorption of vapours comprises approximately 20% of the total absorption of
vapours (see sections 9.2 and 9.6). As inhalational exposure estimates were based on
Priority Existing Chemical Number 6
16
actual monitoring data, which included data for spray use, the estimates incorporated
inhalational exposure to aerosols.
The dermal absorption of liquid 2-butoxyethanol was estimated using the skin absorption
rate obtained from toxicokinetic studies (see section 9.2). Liquid exposure estimates
incorporated dermal exposure to aerosols.
8.2.1 Monitoring data
The monitoring data available for 2-butoxyethanol are described below and summarised in
Table 5. Included are the results of local and overseas atmospheric monitoring and the
results of biological monitoring (for the major metabolite, 2-butoxyacetic acid, BAA). In
several of the studies, 2-butoxyethanol was being used in spray form.
Very few reports on the monitoring of workers and workplaces in Australia for 2-
butoxyethanol are available. Only the following results were available:
?Regular personal and area TWA air monitoring is conducted at the manufacturing plant
at Matraville, NSW. All 2-butoxyethanol results have been reported to be less than 2
ppm (9.8 mg/m3).
?In a survey of four cleaners at three schools in the Coffs Harbour area in NSW (Rhyder
1992), 2-butoxyethanol concentrations were below the limit of detection for both
personal monitoring (0.7 ppm; 3.4 mg/m3) and TWA area monitoring (0.2 ppm; 1.0
mg/m3). The cleaners were using a 1:4 dilution of a surface cleaner containing 1% 2-
butoxyethanol and were applying the solution in both liquid and spray form during
their work period at each school. One cleaner was monitored during dilution of the 1%
concentrate. The area monitoring was conducted in the classroom at 1-1.5 hours after
application of the cleaning solution.
?In a survey of apprentice spray painters in Sydney (Winder and Turner 1992) where 8
apprentices were exposed to a mixture of solvents which included 2-butoxyethanol, the
mean TWA 2-butoxyethanol concentration was 0.4 ppm (2.0 mg/m3).
Some overseas monitoring data are available in the open literature and in NIOSH health
hazard evaluation (HETA) reports. Little data are available for formulation, with no data
available for exposure during the formulation of cleaning products containing 2-
butoxyethanol. In a study of 12 workers in a varnish production plant (Angerer et al
1990), the concentration of 2-butoxyethanol in the varnish is not stated, nor is it stated
whether the cleaning solutions used by the workers during their shift contained 2-
butoxyethanol.
In the most comprehensive monitoring study available for workers exposed to 2-
butoxyethanol during cleaning operations, the exposure of 23 workers (in France) using
window cleaners was evaluated (Vincent 1993). The study comprised four groups of
workers cleaning cars and two groups of office cleaners, with the results detailed in Table
5. The cleaning solutions were being applied in spray form. A poor correlation existed
between 2-butoxyethanol atmospheric concentrations and BAA in urine (post-shift),
possibly due to high skin absorption as most of the workers did not wear gloves. The
highest BAA concentrations were obtained for a group of car cleaners who generally wore
gloves but, due to the warm conditions, wore short-sleeved shirts. For the office cleaners
in the study, BAA was detected in only three of the 32 post-shift urine samples. Pre-shift
BAA concentrations were generally < 10 mg/g creatinine, however, an isolated reading of
99 mg/g and a few readings of approximately 30 mg/g were obtained for car cleaners.
2-butoxyethanol 17
8.2.2 Exposure duration and atmospheric concentration
A number of different work scenarios were considered in estimating exposure during the
formulation and use of cleaning products containing 2-butoxyethanol. The modelled
estimates of worker exposure are considered to be feasible worst-case estimates as they
describe high end or maximum exposures in `feasible but not unrealistic' situations.
The principal variables in the exposure estimates are the duration of exposure, the
concentration of 2-butoxyethanol in air (for inhalational exposure) and concentration of 2-
butoxyethanol in solution (for dermal exposure). The rationale behind the values used for
these parameters in the various scenarios is discussed in the following relevant sections on
exposure during formulation and cleaning (sections 8.4 and 8.5).
The calculations for the exposure estimates discussed in the following sections are detailed
and tabled in Appendix 3.
Priority Existing Chemical Number 6
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Table 5 - Monitoring Results
Worker type No. of 2-BE conc. ppm 2-BE in air * BAA in urine ** Comments Reference
workers (in product) range mean range mean
Cleaning:
Window cleaners 23 A number of measurements for each worker. (Vincent 1993)
Cleaning cars
0.8-5h exposure, no gloves worn.
- group A 2 14.4% <0.1-1.2 0.5 9-178+
0.3-4h exposure, no gloves worn.
- group B 6 21.2% <0.1-2.8 0.84 <2-132+
+
0.7-2h exposure, no gloves worn.
- group C 3 5.7% <0.1 <2-37
5.3h exposure, short sleeves, gloves worn.
- group D 2 21.2% 2.9-7.3 4.9 40-371+
Office cleaners
15 min. exposure, no gloves worn.
- group A 8 9.8% <0.3-0.7 0.32 <2-3.3+
+
15 min. exposure, no gloves worn.
- group B 2 0.9% <0.3 <2
Printing press operators 2 <0.15-0.53 Cleaning printing press rollers (Kaiser 1990)
Print machine operators at food plant 5 10-50% 1.7-9.7 5.2 Cleaning of print machines using hydrocarbon-based (Salisbury and
wash solvent containing 2-BE. Bennett 1987)
Silk screener at fishing rod factory 1 3-5 4 (Apol 1986)
Exposure to cleaning solvents (containing 2-BE) in spray
form. Poor ventilation.
Cleaner at food plant 1 0.3% 1.6 Mechanical floor scrubbing. Sampling only during (Apol and Johnson
operation (95 min.). Gloves, overalls, boots worn. 1979)
Hospital cleaners 4 <0.2 2-BE in window cleaner applied as spray. Sampling over (Apol and Cone
whole shift. Gloves worn. 1983)
School cleaners (Coffs Harbour NSW) 4 0.25% <0.7 Concentrations below the detection limit. Cleaning (Rhyder, 1992)
solution applied in liquid and spray form.
<0.2 (A)
Formulation:
10.5#
Varnish production workers 12 <0.1-8.1 1.1 0.6-30# For individual results no correlation between 2-BE in air (Angerer et al,
and BAA in urine. 1990)
19
2-butoxyethanol
Worker type No. of 2-BE conc. ppm 2-BE in air * BAA in urine ** Comments Reference
workers (in product) range mean range mean
12 <0.1-1.4 0.6 <0.2-61# 8.2# Later monitoring of same group of workers. (Sohnlein et al
1993)
Manufacture:
Matraville plant (Sydney NSW) 100% <0.1 Enclosed process. Maximum (area) reading obtained
during maintenance.
<0.1-1.8 (A)
USA plant 100% <0.1 Enclosed process. Maximum (area) reading obtained (Clapp et al 1984)
during drum filling. Local exhaust ventilation in place.
nd-1.7 (A)
Other uses:
Apprentice spray painters (Sydney 8 0.4 Exposed to mixture of solvents including 2-BE. (Winder and Turner,
NSW) 1992)
(Sakai et al, 1993)
70 0-9.9+ Exposure to solvents containing 2-BE. BAA control
Workers in printing & electrical
averaged 0.08 mg/g.
industries
3.9+
- sub-group 9 0.4-0.8 0.64 1.3-9.9+
Parquet floor makers 9 up to 71 5.0 Exposed to wide variety of organic solvents, including 2- (Denkhaus et al
BE. 1986)
Silkscreeners 26 100% 13-36 25 Open spray troughs and wash table areas without (Kullman 1987)
ventilation or protective equipment, therefore high
results.
23-169 63 (A)
Silkscreeners 16 up to 45% 6.8 Survey of a number of screen printing shops. (Baker et al 1985)
Spray painters 5 up to 55% 2.6 Individual results not available.
Note: * 2-Butoxyethanol (2-BE) results are time-weighted average (TWA) values. ** BAA in urine results are expressed as reported in the literature - mg/g creatinine or mg/L urine.
+ #
All 2-BE results are for personal monitoring unless otherwise indicated (A = area monitoring). nd = not detectable BAA as mg/g creatinine BAA as mg/L urine
Priority Existing Chemical Number 6
20
8.3 Exposure during manufacture of 2-butoxyethanol
2-Butoxyethanol is manufactured by ICI Australia at Matraville in NSW. The process is
enclosed and 2-butoxyethanol is stored in sealed tanks which are bunded to contain any
spills.
Precautions are taken to minimise exposure during the transfer of 2-butoxyethanol to
tankers and drums. Tankers are loaded via a mass flow meter to control the filling process
so that problems such as overfilling and spillage are avoided. In drum filling, local
exhaust ventilation is provided and butyl rubber gloves are worn by the operators to
prevent skin contact in case of spillage.
Atmospheric monitoring is regularly conducted in the plant area for 2-butoxyethanol.
Personal monitoring results for 2-butoxyethanol are generally <0.1 ppm (< 0.5 mg/m3) for
both STEL and TWA measurements. The highest monitoring results have been obtained
during maintenance activities, where a TWA result of 1.8 ppm (8.8 mg/m3) has been
recorded in area monitoring. Therefore, inhalational exposure during manufacture is low.
These results for inhalational exposure during manufacture are supported by monitoring
data available for a US plant (Clapp et al, 1984). For a similar process, where the
manufacturing operation is also enclosed, the highest results were obtained during drum
filling, with a TWA result of 1.7 ppm (8.3 mg/m3 ) obtained in area monitoring. The
highest personal monitoring reading was 0.1 ppm (0.5 mg/m3). During drum filling, local
exhaust ventilation was in place to minimise inhalational exposure in case of spills.
Due to the enclosure of the process and control measures taken to minimise skin contact,
for example, during transfer to tankers, dermal exposure at the Matraville plant is
incidental and therefore likely to be low. The main source of potential exposure is during
maintenance activities. Purging of plant and equipment is standard practice on site.
However, maintenance personnel are provided with butyl rubber gloves and long-sleeved
overalls, so exposure is not expected to be significant. Incidental dermal exposure to liquid
2-butoxyethanol was calculated to be 0.2 mg/kg/day (see Appendix 3).
Taking 1.8 ppm (8.8 mg/m3) as a maximum air concentration, the combined dermal and
inhalational exposure would not be expected to exceed 1.4 mg/kg/day. From this
assessment, the exposure of workers to 2-butoxyethanol during manufacture in Australia is
low.
8.4 Exposure during formulation of cleaning products
8.4.1 Potential for exposure
In Australia, approximately 1000 tonnes of 2-butoxyethanol are formulated into cleaning
products each year. During the assessment, 82 companies were identified, some producing
cleaning products at more than one site, with at least 200 workers involved in formulation.
Duration of exposure
From responses to a questionnaire sent to formulators, workers are potentially exposed to
2-butoxyethanol for an average of 3 hours/week (range 0.1-20). For most formulators, 2-
butoxyethanol is an ingredient in only some of their products, so exposure is not
continuous on a daily or weekly basis. From 74 responses to the questionnaire, the
distribution for potential exposure duration was as follows:
2-butoxyethanol 21
number %
less than 1 hour/week 30 41
1 hour 11 15
2 hours 11 14
3-4 hours 8 11
5-8 hours 6 8
greater than 8 hours 8 11
Exposure scenarios
During the formulation of cleaning products, workers may be exposed to 2-butoxyethanol
during pre-weighing before mixing, during transfer to the mixing tank, during mixing and
during the filling of containers with product. The whole operation is carried out at room
temperature.
The potential exposure of workers to 2-butoxyethanol during mixing is variable as the
process may be enclosed or relatively open. When the transfer of 2-butoxyethanol to the
mixing vessel is carried out in a sealed system, potential exposure will be minimal.
However, when the operator adds the raw materials directly by drum to the mixing tank,
exposure may be greater due to possible splashing and vapour and/or aerosol generation.
Information obtained from the questionnaire indicated that a number of formulators use
the latter procedure and that approximately 50% of formulators carry out mixing in open
top tanks, with greater potential for exposure.
There is potential for worker exposure during the product filling operation. While workers
are potentially exposed to 2-butoxyethanol in a more dilute form than during pre-weighing
and transfer to mixing tanks, the frequency and duration of exposure may be greater. The
design of the filling operation will influence exposure. For example, if the packing line is
enclosed at the point of filling, then inhalational exposure will be reduced. If filling is an
automatic operation with containers pneumatically filled, then exposure is likely to be
lower.
As operators are generally involved in both mixing and filling, the estimates of exposure
are for the formulation process as a whole. Considering the process and the tasks during
formulation where exposure may occur, inhalational exposure is assumed to be continuous
and dermal exposure intermittent for the purpose of calculating exposures.
Product concentrations for exposure estimates
For many of the cleaning products, a concentration range was available rather than the
exact concentration of 2-butoxyethanol (see section 7.3). On the MSDS, the ranges
commonly used are < 10%, 10-30%, 30-60%, and > 60%, so the concentrations selected
for the exposure estimates were 10, 30 and 60%. Moreover, 10% is the concentration cut-
off for 2-butoxyethanol for listing as a poison under the SUSDP (see section 12.4). Of the
c l e a n i n g products surveyed in this report (section 7.3), 68% contain <10% 2-
butoxyethanol, with only 3-4% containing >30%, of which 1% contain > 60% 2-
butoxyethanol.
8.4.2 Exposure to vapour during formulation
The use of atmospheric concentrations for the estimation of worker exposure to 2-
butoxyethanol vapours and aerosols during formulation is hampered by lack of data. No
atmospheric monitoring results were available for the formulation of cleaning products
containing 2-butoxyethanol.
Priority Existing Chemical Number 6
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Taking into account the air monitoring data set out in Table 5 for cleaning activities using
high concentrations of 2-butoxyethanol (Vincent 1993; Salisbury and Bennett 1987), and
noting the potential exposure to 100% 2-butoxyethanol (during pre-weighing and transfer),
the atmospheric concentration during the formulation of a product containing 30-60% 2-
butoxyethanol would not be expected to exceed 10 ppm (49 mg/m3) TWA. This
assumption is supported to some extent by the only data available for formulation, albeit
formulation of varnishes containing 2-butoxyethanol (Angerer et al 1990; Sohnlein 1993).
The maximum TWA air concentration for workers in the varnish production plant was 8.1
ppm (39.7 mg/m3), although the 2-butoxyethanol content in the product(s) was not stated.
Atmospheric concentrations up to 1.2 ppm (5.9 mg/m3) TWA have been reported during
use of a 10-14% cleaning product (Vincent 1993). Taking into account that exposure to
the product is less likely during formulation than during cleaning, but that some potential
e x p o s u r e to 100% 2-butoxyethanol exists, atmospheric concentration during the
formulation of a product containing 10% 2-butoxyethanol would not be expected to
exceed 2 ppm (9.8 mg/m3).
As vapour estimates are based on monitoring data, they would also account for exposure to
aerosols.
Exposure estimates
Assuming that the exposure to 2-butoxyethanol during formulation may occur on a single
day each week (see Duration of exposure above), exposure estimates have been calculated
for 3 hours and 8 hours exposure on a single day. The calculations are detailed in
Appendix 3, section 2.2.
For the various scenarios, the estimates for exposure to 2-butoxyethanol vapours varied
from 0.5 mg/kg/day (for 3 hours exposure during the formulation of a product containing
10% 2-butoxyethanol) to 6.8 mg/kg/day (for 8 hours exposure during the formulation of a
product containing 60% 2-butoxyethanol) [see Appendix 3, Table 1].
8.4.3 Exposure to liquid during formulation
As little data were available for dermal exposure to 2-butoxyethanol, with no data
available for dermal exposure to liquid during formulation, exposures were estimated
using the formulae in Appendix 3. Skin contact was assumed to be intermittent (contact
for 20% of the work period).
As the generation of aerosols is expected to be infrequent during formulation, the
contribution to total dose from dermal absorption of aerosols is expected to be minor.
For the various scenarios, the estimates for exposure to liquid 2-butoxyethanol varied from
0.2 mg/kg/day (for 3 hours exposure during the formulation of a product containing 10%
2-butoxyethanol) to 2.7 mg/kg/day (for 8 hours exposure during the formulation of a
product containing 60% 2-butoxyethanol) [see Appendix 3, Table 1].
8.4.4 Combined dermal and inhalational exposure during formulation
For the various scenarios, the combined inhalational and dermal estimates for exposure to
2-butoxyethanol varied from 0.7 mg/kg/day (for 3 hours exposure during the formulation
of a product containing 10% 2-butoxyethanol) to 9.5 mg/kg/day (for 8 hours exposure
during the formulation of a product containing 60% 2-butoxyethanol) [see Appendix 3,
Table 1].
The estimates are likely to be over-estimates for most work situations as they assume
continuous inhalational exposure over the full work period and skin contact with the liquid
formulation for 20% of the time. In practice, inhalational exposure is likely to be
considerably lower in some plants, for example, where there is good ventilation and the
transfer system is enclosed, and skin contact may be minimal, for example, by use of
2-butoxyethanol 23
control measures such as automatic filling and suitable protective clothing. For air
monitoring in particular, the data indicates that typical atmospheric concentrations of 2-
butoxyethanol are likely to be significantly below the maximum values used in these
estimates.
Given that only 3-4% of formulations contain > 30% 2-butoxyethanol, exposure of the
majority of workers in formulation would not be expected to exceed 8.2 mg/kg/day.
However, given that approximately 70% of formulators spend less than the average of 3
hours per week on the production of cleaning products containing 2-butoxyethanol, and
that approximately 70% of cleaning products contain < 10% 2-butoxyethanol, the
exposure of most formulation workers in Australia would not be expected to exceed 1.0
mg/kg/day.
8.5 Exposure during use of cleaning products
8.5.1 Potential for exposure
Due to the large number of cleaning products containing 2-butoxyethanol, a large number
of workers may be exposed to the chemical. The main groups of workers who handle
cleaning products containing 2-butoxyethanol include:
? carpet cleaners;
? contract cleaners;
? food process workers;
? hospital and nursing home workers;
? hospitality industry workers;
? householders;
? laundry cleaners and workers;
? mechanics;
? metal workers;
? school and office cleaners; and
? window cleaners.
Other workers who may use cleaning products containing 2-butoxyethanol include
abbatoir workers, bottling plant workers, brewery workers, builders, chemical process
workers, fishermen, leather workers, machine operators, miners, printers, oil rig workers,
painters, panel beaters and transport workers.
The largest user-group is in the contract cleaning industry, where products containing 2-
butoxyethanol are used widely. In Australia, it is estimated that there are at least 5400
contract cleaning companies, employing approximately 65,000 cleaners. In a survey of the
occupational and health performance of the cleaning services industry (Foley 1995), it was
estimated that approximately 80% of the cleaners worked part-time, with 25 hours
estimated as their average working week. The above estimates do not include other large
groups of workers such as liquor and hospitality workers, mechanics and house cleaners.
E x p o s u r e to 2-butoxyethanol during cleaning will be extremely variable, due to
differences in frequency and duration, strength of solution used, method of application and
precautions taken during use.
Priority Existing Chemical Number 6
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Dilution of cleaning products
The strength of solution used in the cleaning process is generally low as the product is
usually diluted substantially before use, for example, most surface cleaners specify a
dilution ratio in the range 1:3 to 1:100, depending on the application and the soil loading.
A large proportion (68%) of cleaning products contain less than 10% 2-butoxyethanol, so
the final strength of solution is often less than 1%. In a random survey of 20 general
surface cleaning products containing < 10% 2-butoxyethanol, the dilution ratio ranged
from 1:1 to 1:250, with most ratios in the 1:5 to 1:100 range. Some typical examples
were:
?neat to 1:5 degreasing, cleaning ovens and equipment;
?1:3 stripping floor wax;
?1:10 cleaning hard surfaces with a heavy soil loading;
?1:20 washing floors;
?1:40 high volume foam cleaner;
?1:100 light duty general cleaning;
?1:160 pressure washing and steam cleaning.
Some products are sold as high level concentrates (> 50% 2-butoxyethanol) which must be
diluted with large volumes of water before use. In some cases, products are diluted with
h o t water (up to 80癈). A list of cleaning products with their 2-butoxyethanol
concentration can be found in Appendix 1.
Exposure during dilution
Dilution is often carried out daily at the beginning of the shift. While the dilution
procedure is usually of short duration, the potential exposure may be greater due to use of
higher concentrations of 2-butoxyethanol and the possibility of splashing. Higher
exposures may also occur if the product is diluted with hot water as vapour concentrations
may be higher and skin absorption facilitated. If dilution is carried out in a confined space
or poorly ventilated area, exposure may be increased.
Exposure during application of cleaning solution
A number of different methods are used to apply the cleaning solution, for example,
washing, wiping, mopping and spraying. Approximately half of the cleaning products are
used in spray form, and a small number (12) are marketed in aerosol spray cans or trigger
packs. This method of application will potentially increase both dermal and inhalational
exposure as the atmospheric concentration of 2-butoxyethanol will be higher and dermal
contact will be increased. The potential for exposure may also be increased where heat is
applied during cleaning, for example, cleaning ovens and hot-plates.
Duration of exposure
For the calculation of exposure estimates, daily exposure times of 5 and 8 hours were
used. As stated above, the average weekly working time in Australia for the largest group
potentially exposed, contract cleaners, is 25 hours (average 5 h/day) as most work part-
time (e.g. school and office cleaners).
As cleaners could possibly use cleaning products containing 2-butoxyethanol for the
complete shift, for example, washing cars or cleaning floors, exposure was regarded as
continuous for the purposes of calculating exposure estimates.
2-butoxyethanol 25
Product concentrations for exposure estimates
As the product is diluted substantially in most cases before use as a cleaning solution,
often to strengths well below 1% 2-butoxyethanol, the concentrations selected for the
calculation of exposure estimates were 0.1% as well as 1, 10, and 30%.
8.5.2 Exposure to vapour during cleaning
In the only local data available for cleaning operations, school cleaners using a solution
containing approximately 0.25% 2-butoxyethanol were monitored, with the atmospheric
concentrations below the detection limit of 0.7 ppm (3.4 mg/m3). As this data did not
cover the range of 2-butoxyethanol concentrations that may be used during cleaning,
overseas monitoring data were considered to be more suitable for the calculation of
e x p o s u r e estimates for cleaning solutions containing higher concentrations of 2-
butoxyethanol.
In the monitoring data available (see Table 5), TWA air concentrations up to 9.7 ppm
(47.5 mg/m3) were obtained for print machine operators using a cleaning solvent
containing 10-50% 2-butoxyethanol (Salisbury and Bennett 1987) and up to 7.3 ppm (35.8
mg/m3) for workers cleaning car windows with a 21.2% solution applied as a spray
(Vincent 1993). Based on this data, the 2-butoxyethanol air concentration selected for
worst-case estimates for a 30% cleaning solution was 10 ppm (49 mg/m3) TWA.
For cleaning solutions containing < 1% 2-butoxyethanol, the atmospheric concentrations
were generally below the limit of detection, however, a personal monitoring reading of 1.6
ppm (7.8 mg/m3) was obtained during floor scrubbing with a 0.3% solution (Apol and
Johnson 1979). Consequently, an air concentration of 2 ppm (9.8 mg/m3) was selected for
0.1 and 1% cleaning solutions.
The only results available for a solution approximating 10% are < 2 ppm, however, based
on the readings available for 0.3% and 21.2% solutions (Vincent 1993; Apol and Johnson
1979), a 2-butoxyethanol air concentration of 4 ppm (19.6 mg/m3) was selected for
exposure estimates for a 10% solution.
Exposure estimates
For the various scenarios, the estimates for exposure to 2-butoxyethanol vapours varied
from 0.9 mg/kg/day (for 5 hours exposure during the use of a solution containing 0.1% 2-
butoxyethanol) to 6.8 mg/kg/day (for 8 hours exposure during the use of a solution
containing 30% 2-butoxyethanol). The calculations for the estimates are detailed in
Appendix 3, Table 2.
8.5.3 Exposure to liquid during cleaning
As little data were available for dermal exposure to 2-butoxyethanol, exposures were
estimated using the formulae in Appendix 3. The calculations for the estimates are
detailed in Appendix 3, section 2.3.
Where cleaning solutions are applied in liquid or spray form, a skin surface area of 1000
cm2 was considered to be reasonable when estimating dermal exposure to 2-butoxyethanol
in liquid or aerosol form, taking into account that the duration of exposure is taken to be
continuous throughout the work shift.
For the various scenarios, the estimates for exposure to liquid 2-butoxyethanol varied from
0.01 mg/kg/day (for 5 hours exposure during the use of a solution containing 0.1% 2-
butoxyethanol) to 6.9 mg/kg/day (for 8 hours exposure during the use of a solution
containing 30% 2-butoxyethanol) [see Appendix 3, Table 2].
Priority Existing Chemical Number 6
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8.5.4 Combined dermal and inhalational exposure during cleaning
For the various scenarios, the combined inhalational and dermal daily dose estimates for
exposure to 2-butoxyethanol varied from 0.9 mg/kg/day (for 5 hours exposure during the
use of a solution containing 0.1% 2-butoxyethanol) to 13.7 mg/kg/day (for 8 hours
exposure during the use of a solution containing 30% 2-butoxyethanol) [see Appendix 3,
Table 2].
These estimates are likely to be over-estimates of exposure in most work situations as they
assume continuous skin contact with the cleaning solution and exposure to vapour over the
full 5 or 8 hour period. In practice, some protective clothing may be worn and methods
may be in place to minimise skin contact. Also, in many cleaning operations, use of 2-
butoxyethanol cleaning products is more likely to be intermittent than continuous. In
addition, good ventilation may be available.
Given that approximately 70% of cleaning products contain < 10% 2-butoxyethanol, and
that most are diluted to a working strength below 1%, the combined exposure for most
cleaners would not be expected to exceed 1.6 mg/kg/day. Moreover, many cleaners work
part-time, particularly in the contract cleaning industry, so exposure of most part-time
cleaners would not be expected to exceed 1.0 mg/kg/day.
8.6 Conclusions
Workers may be exposed to 2-butoxyethanol during its manufacture and during the
formulation and use of cleaning products containing the chemical. Exposure may be
short-term, for example, during spray application of a cleaning solution, or prolonged, for
example, washing cars throughout a shift.
For 2-butoxyethanol in cleaning products, good quality monitoring data were limited,
particularly for formulation. The atmospheric monitoring data available are TWA
measurements, although some short-term monitoring, for example, 15 minutes, was
conducted during specific cleaning operations. Very little data for dermal exposure were
available. Using the available data as much as possible, estimates considered to be
`feasible' worst-case estimates were calculated for the exposure of workers to 2-
butoxyethanol during manufacture, formulation and cleaning (see Appendix 3). The
exposure estimates are summarised in Table 6. Typical estimates are for the exposure of
the majority of workers to 2-butoxyethanol.
Table 6 - Summary of Exposure Estimates (mg/kg/day)
Exposure estimates - worst-case Exposure estimates - typical
manufacture 1.4 <1
formulation 9.5 unknown
cleaning 13.7 <1
Note: For formulation, scenarios for products containing up to 60% 2-butoxyethanol were considered. For
cleaning, scenarios for products containing up to 30% 2- butoxyethanol were considered. The typical
exposure estimate for cleaning assumes that most cleaning solutions contain < 1% 2-butoxyethanol.
Estimates should be recalculated for scenarios not accounted for in this exposure
assessment, for example, 12-hour shifts, very heavy workload (elevated respiratory rate)
and extensive dermal exposure (skin surface area exposed greater than 1,000 cm2).
Exposures higher than usual may also result during the use of heat and/or the use of non-
aqueous cleaning solvents. It should also be noted that in some circumstances dermal
exposure may be facilitated, for example when skin is damaged or when products are
diluted with hot water.
2-butoxyethanol 27
EXAMPLES OF USE OF CLEANING SOLUTIONS
CONTAINING 2-BUTOXYETHANOL
Examples of use of cleaning solutions containing 2-butoxyethanol: photo 1 - Spraying
and wiping
Examples of use of cleaning solutions containing 2-butoxyethanol: photo 2 - Carpet
cleaning
Priority Existing Chemical Number 6
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Examples of use of cleaning solutions containing 2-butoxyethanol: photo 3 - Floor
cleaning by machine
Examples of use of cleaning solutions containing 2-butoxyethanol: photo 4 - Dilution
of cleaning solution
2-butoxyethanol 29
Examples of use of cleaning solutions containing 2-butoxyethanol: photo 5 - Mopping
floor
Examples of use of cleaning solutions containing 2-butoxyethanol: photo 6 - Floor
and surface cleaning
Priority Existing Chemical Number 6
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2-Butoxyethanol is manufactured at only one plant in Australia. The process is enclosed
and regular air monitoring is conducted. Exposure is low, with worker exposures not
expected to exceed 1.4 mg/kg/day. This estimate is based on data for non-routine
operations such as maintenance and drum filling. As the manufacturing process is
enclosed, exposure during routine process work would be much lower. Due to the nature
of the process and the control measures in place at the plant, typical exposures are
expected to be well below the exposure estimates.
Worker exposure to 2-butoxyethanol during formulation is expected to be quite variable
due to differences in process conditions (for example, whether the process is enclosed or
relatively open) and the duration of exposure (for example, some formulators produce
cleaning products containing 2-butoxyethanol infrequently or in small quantities). From
the assessment of exposure, exposures are not expected to exceed 9.5 mg/kg/day, however,
for most formulation workers, exposures would be much lower at 1.0 mg/kg/day. Due to
the lack of measured data for formulation, and the variation in engineering controls, it is
not feasible to quote typical exposures. Exposures in plants where the process is enclosed
are expected to be much lower than the exposure estimates.
A large number of cleaning products containing 2-butoxyethanol are marketed in
Australia, with thousands of workers potentially exposed to the chemical. Worker
exposure varies considerably due to factors such as the type of work, method of
application, exposure time and concentration of 2-butoxyethanol in the cleaning solution.
Exposure, particularly inhalational exposure, will be increased during spray application or
during other operations which may generate vapours or aerosols. From the assessment of
exposure, exposures are not expected to exceed 13.7 mg/kg/day, however, for most
workers using cleaning products, exposures would be 1.6 mg/kg/day. Using the average
atmospheric levels available from monitoring data (see Table 5), typical exposures during
the use of most cleaning solutions containing (<1%) 2-butoxyethanol would be less than 1
mg/kg/day.
The exposure assessment has shown that the dermal exposure component of total worker
exposure to 2-butoxyethanol may contribute up to 50% of the total exposure (inhalation
plus dermal), especially with prolonged (5-8 hours) use of cleaning products containing
10% or more 2-butoxyethanol.
2-butoxyethanol 31
9. Kinetics and metabolism
9.1 General
The toxicokinetics of 2-butoxyethanol have been well investigated in laboratory animals,
particularly the F344 rat, and some studies have been conducted on human volunteers.
The results of many of the studies have been reported in the open literature, including
summaries by ECETOC (1994) and Johanson (1988).
In order to optimise the extrapolation of data from one species to another, pharmacokinetic
models have been developed.
9.2 Absorption
9.2.1 Animal studies
Dermal
A number of studies have been conducted in experimental animals to measure the
absorption rate of 2-butoxyethanol through the skin, including measurements using various
strengths of aqueous solution.
In a study in male and female Wistar rats (Bartnik et al 1987), 200 mg/kg of radiolabelled
2-butoxyethanol (undiluted) was applied to the skin under a perforated glass capsule for
48h. Of the applied dose, 29% was absorbed in males within 48h and 25% in females.
The maximum radioactivity in blood and plasma occurred after 2h. As the study was
conducted under nonocclusive conditions, some 2-butoxyethanol may have evaporated.
In an occlusive study in ten female guinea pigs using undiluted 2-butoxyethanol (Johanson
and Fermstrom 1986), the mean absorption rate obtained was 1.77 mg/cm2/h (range 0.35-
3.3), measured by analysing blood samples at intervals up to 2h after application. In a
later study by the same authors using aqueous solutions of 2-butoxyethanol (5-80%) and
undiluted 2-butoxyethanol (Johanson and Fernstrom 1988), higher absorption rates were
obtained for the aqueous solutions (range 0.52-0.73 mg/cm2/h) than for the undiluted
chemical (0.27 mg/cm2/h). Only 2 guinea pigs per concentration were used (except for
40% solution - 4 animals). Following this initial exposure, all animals (14) were then
exposed to 100% 2-butoxyethanol for 2h and a mean uptake rate of 0.94 mg/cm2/h (range
0.45-2.9) was obtained.
Although the mean absorption rates varied between studies and the individual rates varied
within a study, it was clearly demonstrated that 2-butoxyethanol is significantly absorbed
through the skin of the guinea pig, that uptake is rapid, and that absorption is high from
aqueous solution.
Inhalational
In a study in male Sprague-Dawley rats (Johanson 1994), the mean uptake rate for
continuous exposure to 20 or 100 ppm of 2-butoxyethanol for periods up to 12 days was
1.53 mg/h (3.5 mg/kg/h) and 7.73 mg/h (17.8 mg/kg/h) respectively. The rate was
independent of duration of exposure. No clinical signs of toxicity were observed during
exposure. By interpolation, the absorption rate for 25 ppm would be 4.4 mg/kg/h.
Priority Existing Chemical Number 6
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9.2.2 In vitro studies
A number of in vitro studies have been conducted in skin samples from various species,
including human tissue, to measure the skin absorption of 2-butoxyethanol.
A series of tests was conducted using both undiluted 2-butoxyethanol and lower strength
aqueous solutions (Bartnik et al 1987). The results are tabled below.
Table 7 - In Vitro Skin Absorption of 2-Butoxyethanol
% of Dose Absorbed/ Absorption Rate (mg/cm2/h)
Species Concentration Dose*
2
(mg/cm ) 16 hours
(2-BE %) 1hour 6hours
% rate % rate % rate
Rat 100 5.4 19.4 1.05 66.7 0.60 94.3 0.32
10 0.60 62.7 0.38 80.9 0.081 85.1 0.032
0.10 43.3 0.043
3.5 0.21 45.6 0.096 79.0 0.028 88.4 0.012
Pig 100 5.4 11.2 0.10
10 0.60 21.1 0.13 36.9 0.037
0.10 17.7 0.018
3.5 0.21 47.5 0.017
Human 10 0.10 17.3 0.017
* applied dose expressed in terms of 2-butoxyethanol weight
The results indicated that absorption through rat skin is high and rapid. Absorption
through pig and human skin was lower but significant. The % dose absorbed from
aqueous solutions was higher than for undiluted 2-butoxyethanol, but the applied dose was
much lower. The effects on the rate of skin absorption of 2-butoxyethanol by two
ingredients typical of those normally used in cleaning product formulations were also
evaluated (separately) in rat and pig skin. The addition of 5% of isopropanol and 5%
linear sodium dodecylbenzene sulfate to 3.5% and 10% aqueous 2-butoxyethanol solutions
did not significantly affect the skin absorption rate of 2-butoxyethanol.
In human skin tissue measurements, undiluted 2-butoxyethanol was allowed to permeate
for 8 hours across a hydrated section of abdominal membrane held in a glass diffusion cell.
Dugard et al (1984) obtained a mean absorption rate of 0.20 mg/cm2/h (range 0.14-0.35).
The unpublished data (Scott and Mawdsley 1982) were available for assessment. Barber et
al (1991) obtained a higher rate of 1.19 mg/cm2/h (range 0.57-1.91) for tests in which the
damage ratio was acceptable. [Note that the damage ratio is the ratio of permeability
constants before and after exposure, with a high ratio indicative of irreversible damage to
the skin specimen. In four of Barber's results, the damage ratio was regarded as being
unacceptably high (range 6-13), whereas the corresponding range in Dugard's experiments
was 0.8-3.3.] As the series of tests by Barber et al was characterised by wide variability in
the results, including a wide variation in the damage ratios of the skin specimens used, the
reliability of the study is questionable.
Dugard compared the absorption rates of a number of different glycol ethers and other
solvents, with the results summarised in Table 8 (Dugard et al 1982, 1984).
2-butoxyethanol 33
Table 8 - In Vitro Skin Absorption Rates of Glycol Ethers and Other Solvents
Chemical Rate
(mg/cm2/h)
2-methoxyethanol 2.82
2-ethoxyethanol 0.80
2-butoxyethanol 0.20
2-(2-methoxyethoxy) ethanol 0.21
2-(2-ethoxyethoxy) ethanol 0.125
2-(2-butoxyethoxy) ethanol 0.035
1-methoxypropan-2-ol 1.17
2-ethoxyethyl acetate 0.80
toluene 0.70
aniline 0.66
chlorobenzene 1.1
The results showed that the absorption rates of the lower homologues, 2-methoxyethanol
and 2-ethoxyethanol, were considerably higher than that of 2-butoxyethanol. The
absorption rates of the diethylene glycol ethers were considerably lower than the
corresponding monoethylene ether.
9.2.3 Human studies
In a human study (Johanson et al 1988), five male volunteers were exposed to 2-
butoxyethanol by immersing four fingers of one hand in the chemical (undiluted) for 2h.
None of the volunteers was occupationally exposed to solvents and all were non-smokers
and consumed little or no alcohol. The mean dermal absorption rate (geometric mean)
from 12 measurements was 0.142 mg/cm2/h, with the individual results quite variable
(range 0.05 - 0.68 mg/cm2/h). The uptake rate was about 5-10 times lower than that
obtained for guinea pigs, but similar to the human in vitro result obtained by Dugard et al
and consistent with general findings that the permeability of guinea pig skin is greater than
human skin. For most of the measurements in the study, there was little or no delay in
detecting 2-butoxyethanol in the bloodstream, with the concentration in blood continuing
to increase after exposure in most cases, possibly due to a depot effect. The effect of 2-
butoxyethanol on the skin of the volunteers was not severe, with visible changes including
decreased finger volume and skinfold thickness and a wrinkled appearance which was
most obvious at 2-4h after exposure.
In a study carried out in an inhalational chamber (Johanson et al 1986), seven male
volunteers were exposed to 20 ppm of 2-butoxyethanol for 2h during light exercise at 50
watts (mean breathing rate 22.6 L/min. or 1.36 m3/h). By analysing expired air samples at
regular intervals during the study, the mean respiratory absorption rate was estimated as
71.6 mg/h (range 54.7-97.1), equivalent to 57.3% of the inspired amount. The uptake was
rapid and remained relatively constant during exposure. No adverse health effects were
experienced by the volunteers during the experiment.
In a later study by the same authors (Johanson and Boman 1991), the absorption rate of 2-
butoxyethanol vapours was measured by exposing 4 male volunteers to 50 ppm for 2h,
firstly by inhalation (mouth only), and then by skin only (the volunteers wore shorts and
an air respirator). The absorption rates were calculated by measuring the 2-butoxyethanol
concentration in blood sampled from the fingers, using the finger-prick method, at regular
intervals during exposure. The effect of raised temperature and relative humidity was
measured by repeating the experiment at least two weeks later. At ambient temperature
(23oC), the inhalational absorption rate was 70.2 mg/h (range 58.9-78.1) whereas the
Priority Existing Chemical Number 6
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dermal absorption rate was 227 mg/h (range 61.8-348). The results suggest that dermal
uptake accounts for approximately 75% of the total uptake during whole-body exposure to
2-butoxyethanol vapours. The average absorption rates at raised temperature and humidity
were higher, although the difference was not statistically significant; breathing rates were
slightly higher but heart rates were about the same. The respiratory absorption rate was
similar to that obtained in the earlier inhalational study conducted at a lower concentration
(20 ppm) (Johanson et al 1986) probably due to the lower mean breathing rate (8.8 L/min.)
compared with the increased respiration (during light exercise at 50 watts) in the earlier
experiment. This result indicated that respiratory uptake is increased under a workload.
In a recent repeat of this study in another laboratory (Corley et al 1995), where six male
volunteers exposed one arm to 50 ppm 2-butoxyethanol for two hours, the dermal
absorption of vapours was no more than 21% of the total uptake. Blood was sampled from
the exposed arm using the finger-prick method and from the unexposed arm using a
catheter. The results indicated that sampling via the finger-prick method was not
representative of systemic blood concentrations of 2-butoxyethanol. Full details of this
study were not available.
In an inhalational study in male volunteers (Van Vlem 1987), reported by NIOSH (1990),
67-78% of the inspired amount was absorbed during exposure to 12.6 or 25.2 ppm, either
at rest or during light exercise at 30 watts. The volunteers wore face masks during the four
hour exposure. The mean absorption rate for the 25.2 ppm test at rest was 31 mg/h; the
breathing rate was not stated. At 12.6 ppm, the mean respiratory uptake rate at rest was
15.5 mg/h, but under a 30 watts workload, it was 33 mg/h.
9.3 Distribution
Animal studies have shown that 2-butoxyethanol is rapidly distributed to all tissues via the
blood stream.
In a gavage study (Ghanayem et al 1987(b)) in F344 rats treated with a single dose of 125
or 500 mg/kg of 14C-labelled 2-butoxyethanol, 14 C radioactivity was detected in the
following tissues at 48h after dosing: liver, kidney, spleen, lung, heart, forestomach,
glandular stomach, skin, testes, muscle, blood and fat, with the highest levels in the
forestomach, then the liver, kidneys, spleen and glandular stomach.
In a dermal study in male Wistar rats (Bartnik et al 1987), 14C-labelled 2-butoxyethanol
was distributed widely to all tissues, with the greatest level of radioactivity in the spleen
and thymus, followed by the liver.
In an inhalational study (Johanson 1994), male Sprague-Dawley rats were continuously
exposed to 20 or 100 ppm 2-butoxyethanol for 12 days. The mean concentrations of 2-
butoxyethanol and the principal metabolite BAA in tissues are tabled below.
2-butoxyethanol 35
Table 9 - Distribution of 2-Butoxyethanol and 2-Butoxyacetic acid in the Rat after
Exposure to 20 ppm or 100 ppm 2-Butoxyethanol
2-Butoxyethanol 2-Butoxyacetic acid
at 20 ppm at 100 ppm at 20 ppm at 100 ppm
Blood (祄ol/L) 15.1 72.3 41.0 179
Muscle (祄ol/kg) 9.1 30.4 9.3 36.2
Testis (祄ol/kg) 3.9 2.6 14.1 26.7
Liver (祄ol/kg) 10.8 83.8 16.4 85.2
9.4 Metabolism
The metabolism of 2-butoxyethanol has been thoroughly studied in experimental animals,
particularly in the rat, and the results are well documented in the open literature (ECETOC
1994). The major metabolite identified in both animals and humans is BAA. The main
pathways for the metabolism of 2-butoxyethanol in the rat are presented in Figure 1 (from
Medinsky et al 1990).
Early metabolism studies in animals indicated that the main metabolic pathway was
oxidation of 2-butoxyethanol by the alcohol and aldehyde deydrogenase enzymes to BAA
via the aldehyde, 2-butoxyacetaldehyde (BAL). It was postulated (Ghanayem et al 1987
(c)) that minor degradation of BAA to CO2 occurred by cleavage of the ether bond,
oxidation to butyric acid and entry into fatty acid catabolism. In one of the gavage studies
conducted under the NTP, the administration of 2-butoxyethanol in young (4-5 weeks) and
adult (9-13 weeks) rats resulted in higher proportions of BAA and 14CO2 in the younger
rats, probably due to more complete metabolism.
Later studies have supported this pathway and also the alternative metabolic pathways
proposed by Medinsky et al (see Figure 1), which included O-dealkylation of 2-
butoxyethanol to ethylene glycol and some further breakdown to CO2. In later dermal and
inhalational studies in the F344 rat, the same metabolites were identified. The inhalational
study indicated that there was a relationship between exposure concentration and the
metabolic route. Higher relative concentrations of BAA and ethylene glycol were
obtained at the lower vapour concentrations, and higher 2-butoxyethanol glucuronide
(BEG) at the high doses, possibly due to saturation of the pathways leading to BAA and
ethylene glycol (EG).
In a recent gavage study in the F344 rat (Corley et al 1994), BAA was again the major
metabolite in urine (approx. 65% of 14C-2-butoxyethanol at dose of 126 mg/kg), with
approximate concentrations of 15% and 4% of BEG and ethylene glycol respectively.
In an unpublished in vitro study conducted with a number of glycol ethers (Calhoun and
Miller 1983), the results indicated that 2-butoxyethanol was a relatively good substrate for
alcohol dehydrogenase.
A number of studies in volunteers indicate that 2-butoxyethanol is efficiently metabolised
in humans. In the inhalational study where seven male volunteers were exposed to 20 ppm
2-butoxyethanol for two hours (Johanson et al 1986), 41% of the absorbed dose was
excreted as BAA in the urine in 24 hours and only 0.03% as 2-butoxyethanol. In reports
(NIOSH 1990) of inhalational studies by Van Vlem (1987), 13-27% of the absorbed dose
was excreted as BAA in urine and less than 1% eliminated as 2-butoxyethanol.
A monitoring study of lacquerers exposed to 2-butoxyethanol showed that the amino acid
c o n j u g a t e of BAA, N-butoxyacetylglutamine, is an important metabolite of 2-
butoxyethanol in humans (Rettenmeier et al 1993). The metabolite has not been observed
in animal studies.
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Figure 1 - Proposed Metabolic Scheme of 2-Butoxyethanol in Rats
[Adapted from Medinsky et al 1990]
CO2
carboligase oxidase dehydrogenase
CH3CH2CH2CH2OH HOCH2CH2OH
(Butanol)
dealkylase
CH3CH2CH2CH2CH2CH2O -Gluc CH3CH2CH2CH2OCH2CH2OSO3H
(BEG) (BES)
Glucuronyl
Sulfotransferase
transeferase
CH3CH2CH2CH2OCH2CH2OH
(2-BE)
ADH (alcohol dehydrogenase)
CH3CH2CH2CH2OCH2CHO
(BAL)
aldehyde dehydrogenase
CH3CH2CH2CH2OCH2CO2H
(BAA)
dealkyl dehydrogenase
CO2
Note: See Abbreviations at beginning of report.
2-butoxyethanol 37
9.5 Elimination and excretion
Numerous studies in experimental animals have shown that the major metabolite 2-
butoxyacetic acid (BAA) is rapidly excreted in urine after exposure to 2-butoxyethanol.
In a recent inhalation study in Sprague-Dawley rats (Johanson 1994), a total blood
clearance of 2-butoxyethanol of approximately 2.6 L/h/kg was measured. The value was
independent of vapour concentration (20 and 100 ppm) and was relatively constant
throughout the 12 days of continuous exposure. The mean renal clearance values for BAA
were 0.49 L/h/kg (mean excretion rate 0.98 mg/h) for 20 ppm, and 0.58 L/h/kg (5.3 mg/h)
for 100 ppm.
In a study of the elimination kinetics of 2-butoxyethanol in perfused rat liver (Johanson
1988), the hepatic blood clearance of 2-butoxyethanol was reported as approximately 2.0
L/h/kg. The elimination rate was clearly dependent on concentration. The addition of
0.1% ethanol drastically reduced the elimination rate, supporting the hypothesis that 2-
butoxyethanol is normally oxidised by alcohol dehydrogenase in the liver. This effect of
ethanol on the elimination of 2-butoxyethanol from blood was also observed in a study in
female Sprague-Dawley rats (Romer et al 1985).
In a 2-hour inhalational study in human volunteers (Johanson et al 1986), the mean
elimination half-life of 2-butoxyethanol in the blood was 40 min., with a total blood
clearance of 1.2 L/min. and a steady-state volume of distribution of 54 L. The
concentration and excretion rate of BAA in urine was variable between subjects, with the
respective maxima attained after 5-12h and 2-10h. The mean elimination half-life for
BAA in urine after exposure was 5.8h.
In a dermal study in human volunteers (Johanson et al 1988), the half-life obtained for the
elimination of 2-butoxyethanol from blood was longer (approx. 80 min.), possibly due to a
depot effect in the skin. The BAA concentration in urine reached a maximum at about 3h
after exposure, with a mean half-life of 3.1h. A wide variation in results existed between
subjects in the study.
9.6 Pharmacokinetic models
Physiologically-based pharmacokinetic (PBPK) models link information about the
toxicokinetics and physicochemical properties of a chemical to the effects of the
physiological and biochemical processes. They enable data to be extrapolated across
species and similar chemicals to be compared within a species. A number of different
models have been proposed for 2-butoxyethanol to enable the extrapolation of the effects
observed in one species to another, in particular the effects in the rat to humans. Johanson
(1986) proposed a PBPK model for the inhalation of 2-butoxyethanol in humans, but
recent developments of the model by Shyr et al (1993) and Corley et al (1994) have
incorporated more data, including that from rat studies and other routes of exposure.
The Corley model is a dual 2-butoxyethanol-BAA model developed to incorporate more
physiological and biochemical information on BAA, the principal metabolite of 2-
butoxyethanol. The model also incorporates the other metabolic pathways identified in
metabolism studies (see section 9.4 above). In validation work against a wide variety of
test results, including data from rat and human studies and data from different exposure
routes, values predicted by the model generally agreed well with experimental data.
However, the model predicts a much lower dermal uptake of 2-butoxyethanol vapours than
the results obtained in a human study (Johanson and Boman 1991) where the dermal
uptake of vapours constituted approximately 75% of the total amount absorbed. From
simulations of the data conducted on the assumption that the blood sampled (from the
fingers) was venous blood (drained from the skin) rather than arterial blood, the Corley et
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al (1994) PBPK model predicted that the dermal uptake was much lower at 21% of the
total amount absorbed.
Aspects of the model are discussed further in chapters 12, Hazard Assessment and
Classification and 13, Risk Characterisation.
9.7 Summary
2-Butoxyethanol is well absorbed in all species via the inhalational, oral and dermal
routes. Studies have shown that 2-butoxyethanol is rapidly absorbed through the skin.
Dermal absorption rates from controlled human studies (mean 0.14 mg/cm2/h, range 0.05 -
0.68 mg/cm2/h) and in in vitro human skin specimens (mean 0.2 mg/cm2/h; range 0.14 -
0.35 mg/cm2/h) indicate that the dermal absorption rate is most likely of the order of 0.2
mg/cm2/h. Higher results were obtained in one in vitro study, however, the results were
questionable.
Studies in guinea pigs and in vitro studies in various species, including humans, showed
that 2-butoxyethanol is readily absorbed through the skin from aqueous solution. The
guinea pig study indicated that the absorption rate may be higher for aqueous solution than
for undiluted 2-butoxyethanol, but there were some inconsistent results within the study.
In vitro studies indicated a higher percentage absorbed from diluted solutions than
undiluted 2-butoxyethanol, but the rate of absorption was lower for aqueous solution. As
skin absorption rate is an important determinant in human risk assessment, additional work
is needed to clarify the effect of water on absorption rate. In vivo studies have shown that,
in experimental animals and humans, dermal absorption can occur in the absence of local
effects such as irritation.
An absorption study in volunteers exposed to 2-butoxyethanol vapours indicated that the
dermal uptake was approximately 75% of the absorbed dose during whole-body exposure.
However, a recent study in volunteers indicated that 75% is likely to be an overestimate
due to the inappropriate methodology for blood sampling. This study and predictions from
Corley et al's PBPK model indicated that the dermal absorption of vapours is more likely
20% of the dose, which is more consistent with the generally-accepted assumption that
dermal uptake of vapours is lower compared with respiratory uptake. The data
demonstrated the significant contribution of skin absorption to total body uptake during
whole-body exposure to vapours.
Inhalational studies in volunteers at rest and under light exercise showed that the
respiratory absorption rate of 2-butoxyethanol was considerably higher under a workload.
Following absorption, 2-butoxyethanol is distributed to all parts of the body. It is
efficiently metabolised, mainly to BAA, which is formed by oxidation by alcohol/-
aldehyde dehydrogenase. Smaller amounts of the glucuronide and sulfate conjugates and
ethylene glycol can be formed by other metabolic pathways. In humans, the amino acid
conjugate, N-butoxyacetylglutamine, has also been detected in urine, and suggests an
additional detoxification pathway in humans. The metabolites of 2-butoxyethanol are
rapidly excreted in urine, with BAA elimination half-lives of 3.1 and 5.8h being obtained
in human studies. Studies in animals and humans indicate that the metabolic pathways are
similar, although the main detailed studies have only been in the male F344 rat. In human
studies, wide variations in absorption and excretion rates between subjects have been
found.
2-butoxyethanol 39
10. Effects on experimental
animals and in vitro test systems
10.1 General
A number of reviews of the health effects of 2-butoxyethanol have been published in
recent years. These have included:
?ECETOC Technical Report No.64 (August 1995);
?ECETOC Special Report No.7 (April 1994);
?Chapter 31 of Patty's Industrial Hygiene and Toxicology, 4th edition, by Gingell et al
(1994);
?the USA Cosmetics Ingredient Review (Cosmetic, Toiletry and Fragrance Association
1994);
?the NIOSH Criteria for a Recommended Standard for occupational exposure to 2-
butoxyethanol and its acetate (September 1990);
?`Toxicokinetics of 2-butoxyethanol' by Johanson (1988);
?HSE Toxicity Review no.10 (1985).
This chapter will summarise data covered by other reviews of the health effects of 2-
butoxyethanol, and will report on the assessment of unpublished studies and more recently
published work.
10.2 Acute toxicity
10.2.1 Oral
The oral LD50 has been determined in a variety of species, with the range of values cited in
the open literature (ECETOC 1994; Gingell et al 1994) as follows:
sex LD50 (mg/kg)
species
rat male 560-3000
female 530-2800
mouse male 1230
guinea pig 950-1400
rabbit male 320-370
Effects observed in animals included congestion and haemorrhage of the lungs, mottled
liver, kidney congestion and haemoglobinuria. Clinical observations included narcosis,
breathing difficulty, rough haircoat and general lethargy.
A number of unpublished oral rat studies were assessed, with the LD50 values tabled
below.
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sex LD50 Observed effects Reference
(mg/kg)
male 1746 Haemoglobinuria (Eastman Kodak
1981(a))
male 2410 Breathing difficulty, bloody saliva; (Bushy Run Research
Centre 1980(c))
liver, kidney and adrenal
d i s c o l o u r a t i o n ; distended stomach,
intestinal blood
female (Carreon 1981)
1000- Clinical observations include perineal
2000 staining, rough hair coat, lethargy,
respiratory distress, necrosis of tails.
These values were within the range of published oral LD50 values for the rat. The signs of
toxicity were similar to those reported in published data.
In a recent guinea pig study (Shepard 1994 (a)), 5 animals/sex/dose were fed 500, 1000 or
2000 mg/kg 2-butoxyethanol by gavage and the LD50 was calculated to be 1414 mg/kg.
Clinical signs indicating that 2-butoxyethanol was irritating to the stomach were confirmed
at necropsy, with necrosis and haemorrhage in the gastric mucosa observed. No signs of
haematotoxicity were seen in the study.
10.2.2 Dermal
The dermal LD50 has been determined in the rabbit and the guinea pig, with the range of
values cited in the open literature ( ECETOC 1994) for the rabbit being 100-610 mg/kg.
L D 50 values obtained for the guinea pig were 210 and 270 mg/kg for intact and abraded
skin respectively (Roudabush et al 1965).
Where information was available, early deaths were due to narcosis or respiratory failure,
and later deaths to kidney damage. Effects observed at necropsy in rabbit studies included
severe congestion of the kidneys, spleen, liver and lungs. Haemoglobinuria was noted in
the rabbits and, in a study by Carpenter (1956), an increased osmotic fragility of red blood
cells was observed at 500 mg/kg one hour after a 3 minute contact period. In a study in
female rabbits (Duprat and Gradiski 1979), haemoglobinuric nephrosis was noted in all
animals which died, and kidney lesions were observed in surviving animals above 90
mg/kg.
The LD50 values obtained in unpublished studies in the rabbit were as follows: male 567
mg/kg, female 636 mg/kg (Bushy Run 1980(c) and (b)). These values are consistent with
rabbit LD50s reported in the open literature (see above). Summaries only of both studies
were available. Four animals at two doses only were used. The effects observed at
necropsy were similar to those seen in other acute studies, viz. discoloured liver, kidneys,
adrenals and intestines, and bloated stomach. Haemoglobinuria was observed in animals
at both doses. Nystagmus was seen in two high dose females some hours after exposure.
In a comparative study of nine glycol ethers in male New Zealand white rabbits (Eastman
Kodak 1981 (b)), an LD50 of 435 mg/kg was obtained for 2-butoxyethanol. The protocol
was similar to OECD TG402. The effects observed at necropsy included discoloured
(dark) kidneys and stomach, pale liver, and haemoglobinuria. In the study, members of
the mono-ethylene glycol ethers were more toxic than the corresponding members of the
diethylene glycol ethers and, for both groups, toxicity increased with molecular weight. In
the same study, it was noted in skin irritation tests that some guinea pigs survived a dose
of 4.5 g/kg for 24 hours (see subsection 10.3.1, Skin Irritation).
2-butoxyethanol 41
In a recent guinea pig study (Shepard 1994 (b)), no deaths were recorded at the single limit
dose of 2000 mg/kg. No clinical signs of toxicity were observed during the study and no
effects on organs were noted at necropsy.
There appears to be a wide variability in the dermal LD50 values for guinea pigs. The LD50
value of the Shephard study (1994(b)) is approximately ten-fold higher than the LD50
obtained by Roudabush et al (1965) but is more consistent with the data from an Eastman
Kodak (1981(b)) study in which some animals survived doses of 4.5 g/kg. The Roudabush
study was conducted in accordance with standard US testing protocol of the time, however
the methodology differs in some aspects from OECD Guideline 402, such as choice of
treatment site and degree of occlusion. Based on this information, the results of the
Roudabush study are considered questionable.
10.2.3 Inhalation
The inhalational LC5 0 has been determined in a variety of species, with the following
values cited in the open literature ( ECETOC 1994):
species sex LC50 in ppm (mg/L) Duration
exposure
rat male 486 (2.41) 4 hours
female 450 (2.21) 4 hours
mouse 700 (3.4) 7 hours
guinea pig 1300 (6.4) 7 hours
The main effects observed were spleen and kidney damage and haemoglobinuria. In
range-finding inhalational studies by Carpenter (1956), increased osmotic fragility of red
blood cells was noted in female rats exposed to 62 ppm (0.30 mg/L) for four hours, with
older rats more susceptible to this effect than young rats.
The full study for the four-hour LC5 0 rat study cited above (Snellings and Evancheck
1980) was available for assessment and the experimental details have been well reported in
the literature. During exposure, a loss of co-ordination, breathing difficulty and blood
around the urogenital area were observed at the two highest doses, 523 and 867 ppm. Tail
lesions and a marked decrease in body weight were noted in survivors at 523 ppm. Gross
pathology of the animals that died revealed enlarged, discoloured kidneys and blood in the
urine. No significant gross lesions were observed in survivors at necropsy.
In a range-finding study in six guinea pigs (Carpenter 1956), the animals were exposed to
a single dose of concentrated vapour (approx. 930 ppm or 4.5 mg/L 2-butoxyethanol) for
four hours. One animal died and no haemoglobinuria was observed.
In a recent guinea pig study (Nachreiner 1994), no mortality or clinical signs of toxicity
resulted when male and female animals were exposed (whole body) to 633 or 691 ppm 2-
butoxyethanol respectively (3.1 or 3.4 mg/L), but the duration of exposure was 1 hour
instead of the usual 4 hours.
10.2.4 Intraperitoneal injection
The rat LD50 by intraperitoneal injection cited in the open literature (Carpenter 1956) is
550 mg/kg.
In an unpublished study, the comparative LD50s in female Sprague-Dawley rats were
determined for two brands of 2-butoxyethanol, n-Butyl Oxitol?and Dowanol EB?(Norris
and Pernell 1972). Groups of four animals/dose were injected with a single dose of 200,
252, 316, 398 or 500 mg/kg body weight. The respective LD50 values for n-Butyl Oxitol?br>
and Dowanol EB?were 252 mg/kg (confidence limits 203-312) and 317 mg/kg (241-417).
Haemoglobinuria and a bloody nasal discharge were observed in all animals. In surviving
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animals at the two highest doses, tremors were noted at 22 hours after injection. Body
weight gains seemed normal in surviving animals after the two-week post-exposure
period, but there were no controls in the study.
10.2.5 Intravenous injection
A number of intravenous injection studies were conducted by Carpenter (1956), with an
LD50 for the rat of 340-380 mg/kg, for the mouse 1100 mg/kg, and for the rabbit 280-500
mg/kg. It was reported that 2-butoxyethanol solutions greater than 3% resulted in
haemolysis of red blood cells in the rat when administered intravenously.
10.2.6 Summary
2-Butoxyethanol has a moderate acute toxicity by all exposure routes in a variety of
species. The acute dermal toxicity indicates significant absorption through the skin.
Narcosis and respiratory distress are the main causes of death, and congestion and damage
to the kidneys, liver, lungs and spleen are often observed at necropsy. Haemoglobinuria,
due to haemolysis of the red blood cells, has been reported in most acute studies.
10.3 Irritation
10.3.1 Skin irritation
Few reports of skin irritation studies are available in the open literature. 2-Butoxyethanol
is generally reported as a mild to moderate skin irritant in the rabbit (ECETOC 1994;
Gingell et al 1994; Tyler 1984) but, due to lack of test detail and protocol deficiencies, the
results do not clearly establish its skin irritant potential.
In a recently published study in New Zealand albino rabbits (Zissu 1995), the skin
irritancy of five glycol ethers and their acetates was determined using the EEC method
(similar to OECD Test Guideline 404). Individual data were not reported for the three
animals used per substance in the study, but 2-butoxyethanol and isopropoxyethanol were
described as `irritant', and 2-methoxyethanol, 2-ethoxyethanol, 1-methoxy-2-propanol and
all the acetates were described as `non-irritant'.
Several unpublished rabbit studies with undiluted 2-butoxyethanol were available for
assessment.
In a study (Rohm and Hass 1983) conducted by a method similar to OECD TG 404, 0.5
mL of 2-butoxyethanol was applied to the clipped intact skin of six male New Zealand
White rabbits for four hours under a patch. Skin reactions were scored at five hours (one
hour after patch removal), one day, three days and seven days. The results were variable,
with severe and persistent erythema with eschar and severe oedema observed in three
rabbits and very slight oedema and erythema observed in the others. No oedema was
observed in any rabbit after 7 days. Under the conditions of the study, 2-butoxyethanol
was irritating to the skin of rabbits.
In a study in five rabbits little or no irritation was observed, but only 0.01 mL was
administered and the skin was uncovered during exposure (Bushy Run Research Centre,
1980(c)).
In a study in one rabbit, 0.5 mL was applied to the clipped intact skin under an occlusive
wrap for a series of ten applications over 14 days (Carreon 1981). Slight erythema
resulted immediately, with slight oedema after the seventh application. No firm
conclusion can be drawn from this study on a single rabbit.
In a comparative study of nine glycol ethers in rabbits and guinea pigs (Eastman Kodak
1981(b)), undiluted material was applied under an occlusive dressing for 24 hours at the
dose where enough animals survived to make an evaluation. 2-Butoxyethanol was
reported to be a moderate irritant in the rabbit (dose of 0.3 g/kg bw), and a strong irritant
2-butoxyethanol 43
in the guinea pig (at higher dose of 4.5 g/kg bw). The methyl, ethyl and propyl
monoethylene glycol ethers, their corresponding diethylene glycol ethers, and diethylene
glycol monobutyl ether were reported to be slight irritants in both species, while ethylene
glycol mono-2-ethylhexyl ether was reported as a moderate irritant.
10.3.2 Eye irritation
The information available in the open literature indicates that 2-butoxyethanol is an eye
irritant (Jacobs 1992; Kennah et al 1989). This was confirmed in the assessment of the
following two unpublished rabbit studies.
In a study in five rabbits, 0.005 mL of undiluted 2-butoxyethanol caused severe corneal
injury and iritis, 0.5 mL of a 15% aqueous solution caused moderate corneal injury, and no
effects were observed with 0.5 mL of a 5% solution (Bushy Run 1980(c)). An internal
protocol was used and individual results for each animal were not reported.
In a study in a single rabbit, the instillation of 0.1 mL of undiluted 2-butoxyethanol
resulted in severe conjunctivitis, iritis and corneal opacity, with irritation still obvious 21
days after exposure (Carreon 1981).
10.3.3 Respiratory irritation
In an Alarie test in male mice, the RD50 (concentration which produces a 50% decrease in
respiratory rate) for 2-butoxyethanol was estimated to be 2825 ppm (Kane et al 1980).
The animals were exposed to vapour concentrations up to approximately 1100 ppm, so the
value was obtained by extrapolation. Under the conditions of the test, 2-butoxyethanol
was a weak irritant to the upper respiratory tract.
10.3.4 Summary
In liquid form, 2-butoxyethanol is a severe eye irritant. The evidence for skin irritation is
less clear, with a number of studies producing variable results. In the best quality study,
the skin reactions were variable between animals. On balance, 2-butoxyethanol is a mild
to moderate skin irritant in test animals. 2-Butoxyethanol was a weak irritant to the upper
respiratory tract in an Alarie test in male mice.
10.4 Sensitisation
An unpublished Magnusson and Kligman guinea pig maximisation study (Unilever
Research 1989), was available for assessment to determine the skin sensitising potential of
2-butoxyethanol. In the induction phase, a group of six male and four female animals was
treated intradermally with 0.5% 2-butoxyethanol in 0.9% saline, followed by dermal
application of a 25% solution (in 0.9% saline) seven days later under an occlusive wrap.
The animals were challenged twice with 10% 2-butoxyethanol, firstly at 13 days after
induction, and then a week later. Under the conditions of the study, 2-butoxyethanol was
not a skin sensitiser. Some minor deviations from OECD test guidelines were apparent in
the assessment, but overall the study was of good quality. A vehicle control group of four
animals /sex was used in the study. In a preliminary occluded patch irritation test designed
to determine dose levels for the main study, 25% 2-butoxyethanol was irritating to the skin
and a 10% solution was non-irritating.
In a recently published Magnusson and Kligman guinea pig study (Zissu 1995) none of the
g l y c o l ethers tested, 2-butoxyethanol, 2-methoxyethanol, 2-ethoxyethanol and
isopropoxyethanol, was a skin sensitiser.
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10.5 Immunotoxicity
10.5.1 Effect on the proliferation of guinea pig lymphocytes in vitro
An unpublished in vitro proliferation study was available for assessment using 2-
butoxyethanol and its main metabolite 2-butoxyacetic acid (BAA) (Crevel et al 1990).
Earlier studies in male rats (Bartnik et al 1987; Ghanayem et al 1987(b); Grant et al 1985)
had identified the thymus and spleen as potential target organs.
Cultured lymphoid cells from the guinea pig were exposed (in medium) for 48 hours to 2-
butoxyethanol or BAA in the presence of a mitogen (phytohaemagglutinin (PHA) at 2.5-
10 礸/mL or concanavalin A (Con A) at 5-20 礸/mL) or an antigen (tuberculin at 25-100
礸/mL). After preliminary lymphocyte toxicity tests, the 2-butoxyethanol doses for the
main study were set at 0.4, 2.0 and 10mM and the BAA doses set at 0.2, 1.0 and 5.0mM.
Control cells were treated with the same doses of mitogen or antigen without exposure to
2-butoxyethanol or BAA.
For 2-butoxyethanol, no significant effects on lymphocyte proliferation were observed at
0.4 and 2.0mM apart from slight reductions at the two highest PHA doses. At the
cytotoxic dose of 10mM, a significant reduction in proliferative capacity resulted,
particularly for PHA and tuberculin. No significant effects were observed for 2-
butoxyacetic acid at any dose tested.
10.5.2 Other studies
In a drinking water study in Sprague-Dawley rats, the immune system was a sensitive
target for 2-methoxyethanol but not for 2-butoxyethanol (Exon et al 1991). The immune
function parameters measured included natural killer cell cytotoxic response, specific
antibody production, and splenocyte production of interferon and interleukin-2.
In a gavage study in male Fischer 344 rats, 2-butoxyethanol and 2-ethoxyethanol had no
effect on the immune response, as measured by the antibody response to trinitrophenyl-
lipopolysaccharide (TNP-LPS) (Smialowicz et al 1992). In contrast, 2-methoxyethanol
suppressed the response to TNP-LPS.
10.6 Repeated dose toxicity
10.6.1 Oral
NTP studies in rats and mice
A series of drinking water studies were conducted in F344/N rats and B6C3F1 mice under
the National Toxicology Program (NTP) in the USA (NTP 1993). The target doses in the
two-week studies were 100, 150, 250, 400 and 650 mg/kg/day, and for the 13-week studies
750, 1500, 3000, 4500 and 6000 ppm daily. The main results of the studies are tabled
below with the mean actual doses. Haematological effects were studied in detail only in
the 13-week rat study.
The 13-week drinking water study in rats focussed on the haematological effects of 2-
butoxyethanol. Haematology parameters were measured at one, three and 13 weeks, with
anaemia present in females at all doses and in the males at the three highest doses. The
detailed haematological results were as follows:
?decreased red blood cell count in females at all doses, and in males at higher doses;
?reduced haemoglobin concentration at the higher doses;
?increased mean cell volume (MCV) and mean cell haemoglobin (MCH) at the higher
doses (most severe at week one);
?decreased platelet count at higher doses at weeks three and 13 (more obvious in
females);
2-butoxyethanol 45
?marked increase in leucocyte count at the two highest doses (week one only);
?increased reticulocyte count at the higher doses (week one only); and
?mildly increased bone marrow cellularity at the two highest doses.
These results indicate that the haemolytic effects are related to erythrocyte toxicity and not
bone marrow toxicity.
Table 10 - NTP Repeated Dose Oral Studies
Species Duration Dose and Results
Rat (5m,5f) 2-week m: 0, 73, 108, 174, 242, 346 mg/kg/d
f: 0, 77, 102, 152, 203, 265 mg/kg/d
? reduced body weight gain at high dose (f)
? slight decrease in thymus weight at high dose (f)
? dose-related reduction in water consumption
Rat (10m,10f) 13-week m: 0, 69, 129, 281, 367, 452 mg/kg/d
f: 0, 82, 151, 304, 363, 470 mg/kg/d
? reduced final body weight at 2 highest doses
? anaemia - m: mild, at 281 mg/kg/d and above; f: mild to moderate, at all
doses
? reduced thymus weight at high dose in m & f and also at 367 mg/kg/d in
males
? atrophy of uterus at 2 highest doses
? histopathology - lesions of the liver (hepato-cellular degeneration at 2
highest doses), spleen and bone marrow (hyperplasia at 2 highest doses)
Mouse (5m,5f) 2-week m: 0, 93, 148, 210, 370, 627 mg/kg/d
f: 0, 150, 237, 406, 673, 1364 mg/kg/d
? dehydration (m & f ) at 2 highest doses
? decreased thymus weight (m) at 370, 627 mg/kg/d
13-week m: 0, 118, 223, 553, 676, 694 mg/kg/d
Mouse
(10m,10f)
f: 0, 185, 370, 676, 861, 1306 mg/kg/d
? reduced body weight gain at 3 highest doses
? no treatment-related gross or microscopic lesions
(Note: m = male, f = female)
In the two-week rat study, the only tissues examined microscopically were the testis and
epididymis from the lower dose groups and controls; no adverse effects were observed.
No microscopic evaluation of tissues was conducted in the two-week mouse study.
In the 13-week rat study, no significant adverse effects on the reproductive organs and
glands were observed in animals treated with 2-butoxyethanol. The size of the uterus was
reduced in female rats at the two highest doses, with thickening of the muscular wall and
uterine mucosa observed, but this was probably an effect secondary to the significant
reduction in body weight gain at these two doses. Concurrent studies with 2-methoxy- and
2-ethoxyethanol resulted in testicular atrophy in the male rats. Additional reproductive
tissue evaluations were conducted on ten animals/dose for the three highest doses and the
controls. Relative testis weights were normal, and the slight reductions in epididymis
weight at the two highest doses were consistent with body weight reductions at these
doses. A small but statistically significant reduction in sperm concentration was observed
at all three doses but the reduction was not dose-dependent and there were no other
Priority Existing Chemical Number 6
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changes in sperm morphology parameters. In oestrous cycle measurements at the three
doses, the total cycle length was not significantly changed but there were differences in the
length of the various stages of the cycle.
In the corresponding 13-week study in male and female mice, no adverse effects on
reproductive organs or fertility parameters were observed with 2-butoxyethanol, but
testicular degeneration was observed with both 2-methoxy- and 2-ethoxyethanol. In
additional reproductive tissue evaluations conducted in the 13-week study on ten
animals/dose at the three highest doses, slight decreases in sperm motility and testis weight
were noted, but the changes were not dose-dependent and not regarded as biologically
significant.
Under the conditions of the 13-week studies, the NOAEL for haematological effects in
male rats was 129 mg/kg/day, but the corresponding NOAEL for females was not reached
as slight anaemia was observed at the lowest dose (LOAEL 82 mg/kg/day). No significant
adverse effects were observed in the corresponding mouse study but no haematology was
conducted.
Six-week oral study in male rats
A six-week gavage study in male rats was conducted by administering 2-butoxyethanol on
5 days/week to groups of ten male CD rats at the following doses: 0, 222, 443 or 885
mg/kg body weight (Krasavage 1983). The study has been comprehensively reported in
the open literature (Krasavage 1986).
Three animals died in the study, two at 885 mg/kg and one at 443 mg/kg. The main toxic
effect was on the red blood cell, with a dose-dependent decrease in haemoglobin
concentration and red blood cell count and a decrease in mean corpuscular haemoglobin
concentration (MCHC) at the two higher doses. There was a dose-dependent increase in
MCH at all doses and in MCV at the two higher doses. Haemoglobinuria was observed in
animals at all doses, particularly at the two higher doses, and particularly after the first two
days. Other significant effects observed included increased absolute spleen weight at the
two higher doses and increased relative liver weight at all doses. No adverse effects were
observed on the testes, thymus, white blood cells or bone marrow.
Under the conditions of the study, no NOAEL could be established. The LOAEL for
haematotoxicity was 222 mg/kg/day.
10.6.2 Dermal
Nine-day repeated dermal application in rabbits
The repeated dose dermal toxicity of 2-butoxyethanol was evaluated by application to the
skin of New Zealand White rabbits on nine days over an 11-day period, followed by a 14-
day observation period (Bushy Run 1980(b)). A summary of the study has been reported
in the open literature (Tyler 1984), and the full study was available for assessment.
In a preliminary study, a dose of 0.625 mL/day 2-butoxyethanol (approx. 225 mg/kg/day)
was applied under an occlusive wrap to the backs of four male and two female rabbits for
six hours on nine days. Local dermal necrosis was observed in all animals by the fourth
day. Histologic examination of the kidneys at necropsy revealed changes consistent with
the late stages of haemoglobinuric nephrosis.
In the definitive study, five rabbits/sex/dose were similarly treated with 1 mL/day of
undiluted 2-butoxyethanol or 5%, 25% or 50% aqueous solutions. A similar group of
controls was treated with distilled water. At necropsy, only the kidneys were examined
microscopically. The main results are tabled below.
2-butoxyethanol 47
% 2-BE Dose Results
(mg/kg/day)
?Severe necrosis on all animals and accompanied by
100 360
oedema and erythema by day six;
?Haemoglobinuria on day two;
?Haematologic changes including reduced
haemoglobin and red blood cell count, and
increased MCH;
?Reduced body weight in females;
?Thickening of the skin in males;
?Colour change of the kidneys in 3/5 females.
?Necrosis on 1/5 males and 4/5 females;
50 180
?Haemoglobinuria in one female on day five, in all
animals by day nine.
?Erythema.
25 90
?Slight erythema.
5 18
Severe necrosis at the higher doses may have increased the rate of skin absorption.
Haematological parameters returned to normal by the end of the 14-day post-exposure
observation period.
90-Day dermal toxicity study in rabbits
Based on the results of the 9-day study (Bushy Run Research Centre 1980(b)), see 10.6.2
above) the subchronic dermal toxicity of 2-butoxyethanol and aqueous dilutions of the
chemical was evaluated by application to the skin of New Zealand White rabbits for six
hours a day, five days a week over 13 weeks (WIL Research Laboratories 1983). A
summary of the study has been reported in the open literature (Tyler 1984), and the full
study was available for assessment. Ten rabbits/sex/dose were similarly treated with 1
mL/day of 2.8%, 14.3% or 42.8% aqueous solutions, equivalent to 10, 50 and 150 mg/kg
body weight respectively. A similar group of controls was treated with distilled water.
Haematological and clinical chemistry parameters were measured at weeks 4 and 12
during the study and a comprehensive histopathological examination was conducted on all
animals at necropsy. There were no significant findings so, under the conditions of the
study, the NOAEL was 150 mg/kg.
Slight erythema was noted intermittently in all animals, including the controls, at and
around the dosed area.
10.6.3 Inhalational
Nine-day inhalational rat study
In a nine-day dynamic inhalational study (Longo and Dodd 1981), groups of eight male
and eight female Fischer 344 rats were exposed (whole body) to 2-butoxyethanol vapours
at 0, 20, 86 or 245 ppm. A second group of animals (8m,7f) exposed to 245 ppm and a
second control group (8m, 8f) were observed for 14 days after exposure to test the
reversibility of any treatment-related changes. The procedure used was similar to that of
OECD Test Guideline 412. The study has been summarised in the open literature (Dodd
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et al 1983), and the full study was available for assessment. The main results were as
follows:
Results
Dose (ppm)
245 Marked haematological effects;
Haemoglobinuria in males and females after first 2 exposures only;
Relative increase in liver weight;
Discolouration of lungs, respiratory difficulty;
Body weight decrease, recoverable after post-exposure period;
Abnormal righting reflex in one female, and no pupil response in
another.
86 Less marked haematological effects;
Relative increase in liver weight (females only).
20 No significant effects.
The dose-related changes in blood parameters were the most significant results of the
study. Haematological effects included decreases in erythrocyte count, haemoglobin and
MCHC, and increases in MCV, nucleated red blood cells, reticulocytes and, in males only,
lymphocytes. A significant recovery was observed after 14 days in the satellite group
exposed to 245 ppm, but the decrease in erythrocyte count and the increases in MCV and
haemoglobin were still apparent. At necropsy, no treatment-related macroscopic changes
were observed.
90-Day inhalational rat study
In a 90-day inhalational study (Snellings et al 1981), groups of 16 male and 16 female
Fischer 344 rats were exposed (whole body) to 2-butoxyethanol vapours at 0, 5.0, 24.6 or
77.0 ppm. Ten animals/sex/dose were exposed for six hours/day for 13 weeks (five
days/week), while the other six rats/sex/dose were sacrificed after six weeks for blood
analysis. The procedure was similar to OECD Test Guideline 413. The study has been
summarised in the open literature (Dodd et al 1983), and the full study was available for
assessment.
The main findings of the study were the haematological effects observed in the rats
exposed to 77 ppm, particularly the females. The haematological effects were much less
marked at 13 weeks. These effects were as follows:
?Six weeks exposure: Statistically significant decreases in haemoglobin, red blood cell
(RBC) count (f) and haematocrit (f); increase in MCH (f).
?13 weeks: Statistically significant decrease in RBC count (m,f) and increase in MCH
(f); small but not statistically significant decreases in haemoglobin and haematocrit,
and increase in white blood cells (m).
There was no sign of blood in the urine, and the nervous system changes noted at higher
doses in the nine-day study (see 10.6.3 above) were not observed in this study. No effect
on red blood cell osmotic fragility was observed. At necropsy, no significant gross or
microscopic lesions were observed, and there were no significant effects on the lungs,
liver, kidney or testes. Under the conditions of the study, the NOAEL was 24.6 ppm.
Four-day studies in rats, guinea pigs and dogs
In an unpublished study, two male Beagle dogs, six male guinea pigs and eight male rats
were exposed to 57-58 ppm of 2-butoxyethanol vapours for seven hours/day over four
consecutive days (Norris and Pernell 1972). The study was intended as a preliminary
2-butoxyethanol 49
study only and no controls were used. One guinea pig died of respiratory failure during
the study but there were no other deaths and no significant clinical observations. At
necropsy on the guinea pigs and rats two weeks after exposure, no treatment-related gross
pathological changes were observed.
The results of a similar unpublished study were incorporated into the report of the above
study. The animals were exposed to 100 ppm of a competitor's brand of 2-butoxyethanol
for seven hours/day for four days. Haemoglobinuria was observed in the rats after the first
exposure only, female guinea pigs died after the second day, and one of the dogs displayed
unusual behaviour after the second exposure. Full experimental details of both studies
were not available.
Other studies
In a series of studies reported by Carpenter (1956), rats, mice, guinea pigs, dogs and
monkeys were exposed to 2-butoxyethanol vapours at concentrations up to 494 ppm for
periods up to 90 days. Haemoglobinuria and/or increased red blood cell fragility were
observed in all species except the guinea pig, with the animals generally returning to
normal overnight after exposure ceased. Increased relative liver and kidney weights were
noted at 107 ppm and above in the rats and increased relative kidney weight at 203 ppm
and above in guinea pigs. In preliminary range-finding tests in rats, the older animals were
more susceptible to the haemolytic effects. Haematological observations in the studies are
listed in Table 11 in section 10.7.1.
In a behavioural study of nine industrial solvents, female rats were exposed by inhalation
to 50, 100, 200 or 400 ppm 2-butoxyethanol for four hours/day, five days/week for ten
exposure days (Golberg et al 1964). Behavioural effects were measured using a
conditioned avoidance-escape test. No effect on growth-rate or behavioural performance
occurred but transient haemoglobinuria was observed at 200 and 400 ppm.
10.6.4 Summary
The main effect seen in repeated dose studies by all exposure routes is anaemia due to
haemolysis of the red blood cells. Haemolytic effects included decreased RBC count and
haematocrit, decreased MCHC and increased MCV and RBC osmotic fragility.
Several studies demonstrated that the haematological effects caused by repeated exposure
to low doses of 2-butoxyethanol were transient, occurring only during the first days of
exposure (Dodd 1983, Carpenter 1956, Werner 1943). There is some evidence of
haemopoiesis occurring, such as spleen hyperplasia, as a response to the haemolytic
effects.
The repeated dose studies indicated that there are species differences in the susceptibility
to the haemolytic effects of 2-butoxyethanol. Rats appear to be the most sensitive species
in these animal studies.
Results from the 13-week oral study (NTP 1993) and 90-day inhalation study (Snellings et
al, 1981) suggest that female rats may be more sensitive to the haemolytic effects of 2-
butoxyethanol.
In some studies, adverse effects on the liver, kidney, spleen and/or thymus were observed
at dose levels at or above haematotoxic levels, but these effects are generally regarded as
being secondary to haemolysis.
In the 13-week NTP studies, no significant adverse effects on reproductive organs were
observed in rats and mice. Slight effects on fertility parameters (slight reduction in sperm
concentration and differences in length of stages of oestrous cycle) were noted in rats at
haematotoxic levels but no adverse effects on fertility were noted in mice. The results of
reproductive toxicity studies are discussed further in section 10.8.
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10.7 Haematological studies
10.7.1 Early studies
In early studies by Werner (Werner et al 1943) and Carpenter (1956) in a variety of
species, haemoglobinuria was observed in animals exposed to 2-butoxyethanol in both
acute and repeated dose studies. The effect was transient as the animals tended to recover
overnight between exposures and, in the repeated dose studies, haemoglobinuria was
generally seen only after the first few exposures. Some species were more affected than
others, for example, haemoglobinuria was observed in rats and mice exposed to 200 ppm
2-butoxyethanol for seven hours, but not in guinea pigs exposed to 665 ppm for eight
hours. Haemolysis of the red blood cells was shown to occur, and in vitro tests in a
number of species (Carpenter 1956) indicated that the major metabolite, BAA, was more
haemolytic than 2-butoxyethanol.
In inhalational studies to compare the haemolytic effect of 2-butoxyethanol in humans and
rats (Carpenter 1956), an increased RBC fragility was observed when three female rats
were exposed to 195 ppm over two periods of four hours, and again when six rats were
exposed to 113 ppm for four hours (see section 11.2.1 in Human Health Effects).
Results of the main studies by Carpenter (1956) are tabled below.
Table 11 - Haematological Effects in Studies by Carpenter et al
Species Dose Effect
rat (f) 62 ppm/4h Increased osmotic fragility
rabbit (m,f) 125, 197 ppm/7h Increased osmotic fragility
guinea pig (m) 665 ppm/8h No effect
rat (m,f) 54-432 ppm/7h, 30d Increased osmotic fragility (all doses)
Haemoglobinuria (203 ppm and above, first two
exposures only)
mouse (m) 112-400 ppm/7h, Increased osmotic fragility (all doses)
30,60,90d
Haemoglobinuria (200 ppm, first exposure only; 400
ppm, first three exposures only)
monkey (m,f) 100 ppm/7h, 90d 210 Transient increase in osmotic fragility
ppm/7h, 30d Transient increase in osmotic fragility
guinea pig (m,f) 54-494 ppm/7h, 30d No effect
Note: (m) = male, (f) = female
10.7.2 Gavage study in Sprague-Dawley rats
An investigation of the biophysical and biochemical mechanisms of the haemolysis
induced by 2-butoxyethanol was conducted in a gavage study in male Sprague-Dawley
rats (Kurantsin-Mills and Lessin 1990). The animals were given a single dose of 2-
butoxyethanol (in water) at 0, 50, 100, 250 or 500 mg/kg body weight, and blood was
sampled after 0.5, two and four hours for testing. The full study was obtained for
assessment. The main results of the study were as follows:
?The following changes in red blood cell parameters occurred:
?a significant dose and time-related increase in MCV;
?a significant dose-related decrease in MCHC;
?slight increases (without dose-dependence) in haematocrit, haemoglobin density
width and red cell density width;
2-butoxyethanol 51
?slight decreases (without dose-dependence) in haemoglobin and red blood cell
count.
?Haemoglobin was detected in the plasma and urine of exposed rats, but the
concentrations in plasma were low (<5%) compared to total blood.
?The shape of the red blood cells changed in that they swelled to become spherocytic.
?The median density of red blood cells decreased with dose, consistent with swelling of
the cells. The effect was apparent at all time intervals, particularly at 4 hours for the
two highest doses.
?Mean adenosine triphosphate (ATP) levels in the red cells from exposed rats were
slightly higher than levels in controls, especially for rats dosed at 100-500 mg/kg, but
the changes were not statistically significant.
?The lack of any increase in malonylaldehyde (MDA) concentration in blood cells
indicated that no increase in lipid peroxidation of the red cell membrane occurred.
Haemolysis can be caused by the peroxidation of unsaturated fatty acids in the
membrane of red cells, indicated by the formation of carbonyl compounds such as
MDA. In the experiment, MDA levels fell by about 50%, irrespective of the dose,
indicating an arrest of the auto-oxidative processes in the red cells by 2-butoxyethanol
and/or a metabolite.
?The viscosity of plasma and whole blood from exposed rats was higher than for
controls, but the effect was more marked at 50 and 100 mg/kg. The lack of a dose-
viscosity relationship was attributed by the authors to shear-induced haemolysis at the
higher doses. In a cell deformability test conducted under standard conditions, the red
cells from treated rats were more rigid than control rat cells.
In light of the results obtained from other studies, most of the findings were expected,
although the ATP depletion reported in in vitro studies in blood cells from Fischer 344
rats, which indicated that ATP depletion preceded the haemolysis caused by BAA, was not
observed (Ghanayem 1989). In some areas, the study report was lacking in experimental
detail, for example, numbers of animals used, and identification of dose and time interval
for some parts of the experiment.
10.7.3 Other in vivo studies (published)
In a gavage study, F344 rats were administered a single dose of 2-butoxyethanol, the
major metabolite BAA or the intermediate 2-butoxyacetaldehyde (Ghanayem et al
1987(c)). By selectively inhibiting the activity of the enzymes ADH and ALDH with
pyrazole and cyanamide respectively, it was confirmed that BAA was the primary
haemolytic agent.
The effect of age on the toxicity and metabolism of 2-butoxyethanol was examined in a
gavage study in F344 rats (Ghanayem et al 1987(a)). Both haematotoxicity and the
secondary liver and kidney effects were more severe in the older animals (9-13 weeks)
than the younger ones (4-5 weeks).
In gavage studies in rats and guinea pigs, the animals were administered a single dose of
250 mg/kg/d (Ghanayem and Sullivan 1993). Increases in MCV and haematocrit and
decreases in red cell count and haemoglobin concentration were observed for the rats, but
no significant changes in these parameters were noted in the guinea pigs.
In a gavage study in male F344 rats, the animals were dosed at 0, 500 or 1000 mg/kg bw
for four consecutive days (Grant et al 1985). At both doses, haematological changes were
observed, including reduced red blood cell count, haematocrit and haemoglobin and
increased MCV and MCH. The changes were reversible although, for the high-dose
group, the MCV and MCH were still slightly raised after 22 days.
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10.7.4 In vitro studies in various species (published)
In vitro studies in a variety of species have confirmed that the main metabolite of 2-
butoxyethanol, BAA, is the primary haemolytic agent and that there are significant
differences in haemolytic activity between species. In studies in human and rat red blood
cells (Bartnik et al 1987), 2-butoxyethanol caused haemolysis of rat cells at 175-200 mM
and of human cells at 225 mM (for 60 min. incubation). For the same incubation time,
BAA caused total haemolysis of rat cells at 7.5 mM and no haemolysis of human cells
(maximum concentration 15 mM). For an incubation time of 180 min., BAA caused total
haemolysis of rat cells at 3.75 mM and no haemolysis of human cells at the maximum
concentration of 15 mM.
In a study in red blood cells from human, rat, dog and rabbit blood, BAA lysed rat cells at
0.05% but cells from the other species were stable up to the maximum concentration of
2% BAA (Hext 1985).
In NTP and other in vitro studies in rat red blood cells, BAA was shown to cause swelling
of the cells, seen as increased mean cell volume (MCV) and haematocrit, prior to
haemolysis (Ghanayem et al 1990; Udden and Patton 1994). In a comparative study in rat
and human red blood cells, haemolysis was observed in rat cells exposed for four hours to
BAA at the lowest dose (0.5 mM) (Ghanayem 1989). No effects were observed in human
cells exposed to 2 mM BAA for four hours, but slight swelling of the cells was noted at 4
mM, and slight but significant haemolysis was observed at 8 mM BAA.
Subsequent NTP studies (Ghanayem and Sullivan 1993) confirmed the effect of BAA in
vitro in mice (at 1 mM BAA), in rats and the yellow baboon at 2 mM (rats not tested at 1
mM), but no significant effect was observed in the red blood cells of guinea pigs, dogs,
cats, domestic pigs and humans after exposure to 2 mM BAA for four hours. Rabbit and
hamster cells swelled at 2 mM, but no haemolysis occurred.
In a recent study, red blood cells from humans and Fischer 344 rats were treated with BAA
(Udden and Patton 1994). On exposure to 2 mM for four hours, the rat cells exhibited
significant haemolysis, preceded by a large decrease in red cell deformability (noted at one
hour); whereas no haemolysis or change in deformability occurred in human cells. On
exposure to 0.2 mM for six hours, the rat cells exhibited very slight haemolysis and a
significant decrease in red cell deformability (noted at four hours).
Following the results of this study (Udden and Patton 1994), the haemolytic resistance of
red blood cells from potentially susceptible humans was studied (Udden 1994). The red
cells from nine healthy younger adults (5m,4f), nine aged persons (5m,4f), 7 patients with
sickle cell disease and three persons with hereditary spherocytosis were treated with 2 mM
BAA for four hours. Haemolysis in treated cells was higher than controls for aged adults,
but the difference was not statistically significant. The deformability of red cells from
persons with sickle cell disease or hereditary spherocytosis was reduced, but BAA had no
added effect. No other haemolytic or morphological changes were observed.
An in vitro study on several haemopoietic cell lines, either growth-factor-dependent or
leukaemic, in mouse, rat and human species concluded that 2-butoxyethanol was a
haemopoietic toxin (Ruchaud 1992). However, doubts were publicly raised about the
results of the study and the purity of the reagents used. Subsequent experiments repeated
by the same laboratory with high grade reagents could not reproduce the original findings.
The authors have since publicly withdrawn all conclusions of the study (Boiron et al
1984).
2-butoxyethanol 53
10.7.5 Summary of haematological studies
Several in vivo and in vitro studies have been conducted to specifically investigate the
haemolytic effects of 2-butoxyethanol. In vivo and in vitro studies have demonstrated that
the metabolite BAA is the primary haemolytic agent.
The in vitro studies have confirmed that, as observed in in vivo studies, there are
significant differences in the susceptibility of various species to the haematotoxicity of 2-
butoxyethanol. Red blood cells of rats and mice are the most susceptible, then rabbits and
baboons, with dogs, humans, guinea pigs, cats and pigs least susceptible to the haemolytic
effects of BAA. In vitro, human red blood cells were at least 10 times less sensitive than
rat cells to the haemolytic effects of BAA.
In vitro studies confirmed that haemolysis is preceded by swelling, decreased cell
deformability and increased osmotic fragility of red blood cells. This suggests that pre-
haemolytic changes are due to changes in the cell membrane.
Haematotoxicity in rats appears to be age-related, with the effects more severe in older
rats. In vitro studies with erythrocytes of humans with congenital haemolytic disorders
and the elderly did not demonstrate an increased sensitivity to BAA.
10.8 Reproductive toxicity
10.8.1 General
Due to the known reproductive toxicity of two of the lower molecular weight glycol
ethers, 2-methoxyethanol and 2-ethoxyethanol, a number of studies of good quality have
been conducted to estimate the reproductive toxicity of 2-butoxyethanol. The results from
animal studies in a variety of species by all routes of exposure show that both 2-
methoxyethanol and 2-ethoxyethanol are toxic to the sperm of male animals and cause
damage to the testes. Animal studies show that 2-methoxyethanol and, to a lesser extent 2-
ethoxyethanol, are teratogenic in a wide variety of species.
Most of the studies carried out with 2-butoxyethanol have been reported in the open
literature.
Reproductive toxicity includes the adverse effects on the reproductive ability or capacity
of adult males and females and on the growth and development of the offspring
(developmental toxicity). Developmental toxicity includes toxicity from conception to
sexual maturity, including toxicity to the embryo and foetus. Teratogenicity is the ability
to cause structural and functional malformations during embryo development and is
therefore a part of developmental toxicity.
10.8.2 Two-generation NTP study in mice
The fertility and reproductive effects of 2-butoxyethanol in drinking water were
investigated in mice using the NTP continuous breeding protocol (CBP). The study
comprised a continuous breeding phase, a crossover mating trial and a final offspring (F1)
assessment phase (Morrisey et al 1989; Heindel 1990).
Male and female Swiss CD-1 mice received 0, 0.5, 1.0 or 2.0% 2-butoxyethanol
(equivalent to daily intakes of 0, 720, 1340 and 2050 mg/kg bw) in their drinking water
during a continuous breeding phase with a seven-day pre-mating period and a 98-day
cohabitation period. During the cohabitation period, deaths occurred in the female mice:
13/20 in 2% group, 6/20 in 1% dose group, 1/20 in 0.5% dose group and 1/40 in control
group. The average body weights in the female 2% dose group were consistently lower
than the controls. In the male mice, no deaths occurred but weight loss (1-2% of initial
body weight) in the two highest doses and reduced weight gain were noted. Reduced fluid
consumption was observed at all dose levels in both sexes. The numbers of fertile pairs
from the surviving pairs were 38/39, 19/19, 13/14 and 5/7 at 0, 0.5, 1.0 and 2.0% dose
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levels, respectively. Significant reduction in reproductive performance occurred at 1 and
2% dose levels as indicated by dose-related decrease in litter sizes, pup viability and live
pup weight. A significant reduction (5%) of live pup weight was also observed in the
0.5% dose group without other significant effects.
At the completion of the continuous breeding phase, the F0 breeding pairs were separated
and housed individually and exposure to 2-butoxyethanol continued. When the last litter
was weaned, F0 males and females from the 1% dose group were mated with male and
female control animals in a one-week crossover mating study to determine any sex-related
reproductive effects of 2-butoxyethanol. Exposure to 2-butoxyethanol was discontinued
during the one-week mating period and then reintroduced at 1% dose level (estimated
daily intake 1830 mg/kg bw). Control males and females were also mated for comparative
purposes. The proportion of successful copulations from the breeding pairs was similar in
all groups. However, the number of fertile females was significantly reduced in the group
where treated females were mated with control males. Male and female mice from the 1%
dose group had significantly lower body weights and increased relative kidney weights.
At necropsy, a significant increase in relative liver weight was also observed in the
females. No significant differences were observed between the control and treated animals
for the weights of reproductive organs, sperm motility, morphology and oestrous cycle
length and frequency. In the only histopathological examination carried out on the treated
females, no treatment related kidneys lesions were observed. The results suggest that the
fertility effects were primarily due to effects on the female mice.
A final phase was conducted to assess the fertility and reproductive effects of 2-
butoxyethanol in second generation (F1) pups. The pups selected were those born after the
CBP and when the maternal animals were individually housed. As there were insufficient
pups in the 1 and 2% dose groups, only the pups from the 0.5% dose group were used.
The F1 generation pups were nursed, weaned and reared to sexual maturity. After weaning,
the mice received 0.5% 2-butoxyethanol in their drinking water (estimated daily intake
950 mg/kg bw). At 74 ?10 days of age, the F1 animals from different litters were mated.
The animals were necropsied after delivery. No significant fertility and reproductive
effects were observed in the F1 animals as indicated by the proportions of successful
copulation and fertile females, litter size, pup viability and live pup weights. Similarly, no
treatment-related changes in the weights of reproductive organs, sperm motility,
morphology and the oestrous cycle length and frequency were noted. However, a
significant increase in relative kidney weight in the females and a significant increase in
relative liver weight in both the males and females were observed.
In summary, significant adverse reproductive effects were observed only at very high dose
levels (1340 mg/kg and above) which also caused severe maternal toxicity, including
death. Under the conditions of the study, the NOAEL for reproductive toxicity of 2-
butoxyethanol can be taken as 720 mg/kg/day as only a very slight decrease in pup weight
was observed at this dose.
10.8.3 Other studies
In a 60-day stop-exposure study conducted in association with the 13-week NTP study
(NTP 1993), 30 male rats per dose consumed 0, 124, 234 or 443 mg/kg/day in drinking
water. After exposure to 2-butoxyethanol for 60 days, testis and epididymis weights were
normal, and no microscopic lesions were noted [NOAEL 443 mg/kg/day]. On the other
hand, testicular degeneration was observed with 2-methoxy- and 2-ethoxyethanol. In the
main 13-week study, minor changes in sperm concentration and oestrous cycle were noted
with 2-butoxyethanol (see 10.6.1).
To study the reproductive toxicity of a number of ethylene glycol alkyl ethers, groups of 5
male JCL-ICR mice per dose were administered (by gavage) the ether at doses up to 2000
2-butoxyethanol 55
mg/kg/day for five weeks (Nagano et al 1984). Testicular atrophy was observed for 2-
methoxyethanol and 2-ethoxyethanol, but not for 2-butoxyethanol.
In a 21-day drinking water study in Sprague-Dawley rats, testicular atrophy and necrosis
and reduced numbers of spermatogenic cells were observed in males exposed to 486
mg/kg/day of 2-methoxyethanol, but no adverse effect on fertility parameters was seen in
males exposed to 506 mg/kg/day of 2-butoxyethanol (Exon et al 1991).
In a four-day gavage study in male F344 rats, severe testicular atrophy was observed in the
animals fed 2-methoxyethanol at 500 mg/kg but no significant effect on the testis was
noted in animals fed 2-butoxyethanol at the same dose (Grant et al 1985).
In a fertility study in male Wistar rats (Foster et al 1987), the administration (by gavage) of
a single dose of 2-butoxyacetic acid (BAA) did not result in any testicular damage at the
lowest dose of 174 mg/kg. In an in vitro test, BAA did not produce any changes in
testicular cell populations at 5mM. Simultaneous testing with the acids of methoxyethanol
and ethoxyethanol resulted in significant spermatocyte cell loss and damage in vivo and in
vitro.
10.8.4 Developmental toxicity/teratogenicity studies
Oral
In an NTP gavage study (Sleet et al 1989) in Fischer 344 rats, groups of 27-33 animals
were dosed with 2-butoxyethanol (in distilled water) during the critical periods of
cardiovascular development, with dosage set at 0, 30, 100 or 200 mg/kg/day on gestational
days (gd) 9 to 11 (group 1) or at 0, 30, 100 or 300 mg/kg/day on gd 11 to 13 (group 2).
Except for the restricted exposure time, the procedure was similar to that of OECD Test
Guideline 414, and the study satisfied quality assurance requirements.
Dose-related changes in haematological parameters were observed in the dams of both
groups at the two highest doses (100 and 200 mg/kg or 100 and 300 mg/kg). The effects
were more obvious in the early days after dosing and the effects included decreases in red
blood cell count, haemoglobin, haematocrit and MCHC, and increases in MCV, MCH,
reticulocytes and white blood cell count. Other signs of toxicity in the dams included
dose-related reductions in body weight gain and food and water consumption. The relative
spleen weights were increased at 100 and 200/300 mg/kg, relative kidney weights were
increased at 200/300 mg/kg and relative liver weights at 200/300 mg/kg. The NOAEL for
maternal toxicity was 30 mg/kg/day.
An increase in non-viable and adversely-affected implants, post-implantation loss and
resorptions per litter resulted in the animals at 200 mg/kg/day (group 1 only). In the
foetus, a decreased platelet count was noted at 300 mg/kg/day (group 2 only). No foetal
malformations, and in particular no cardiovascular malformations, were observed at any
dose.
In a gavage study in pregnant CD-1 mice, 2-butoxyethanol was administered at 0-2000
mg/kg/day during gestational days (gd) 8-14 (Wier et al 1987). Mortality resulted at 1500
mg/kg and signs of toxicity (haemolysis) were apparent at 650 mg/kg [NOAEL for
maternal toxicity 350 mg/kg/day]. An increased number of resorptions and a reduced
number of viable foetuses were observed at 1000 and 1500 mg/kg [NOAEL for embryo-
and foetotoxicity 650 mg/kg/day]. In a post-natal study, where the dams were treated with
650 or 1000 mg/kg on gd 8-14, no significant effects on pup growth or survival resulted.
In a simultaneous study with 2-ethoxyethanol, developmental toxicity was apparent at
doses below maternal toxicity levels.
In a gavage screening test conducted in groups of 50 pregnant CD-1 mice (Schuler et al
1984), including controls, 2-butoxyethanol was maternally toxic at the only dose used,
1180 mg/kg, but no significant changes in offspring resulted.
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Dermal
In a study in pregnant Sprague-Dawley rats, 0.12 mL (approx. 1760 mg/kg bw) of
undiluted 2-butoxyethanol was applied to the skin four times on one day after early tests
with 0.35 mL had resulted in mortality (Hardin et al 1984). Haemoglobinuria was
observed at the higher dose, but not with 0.12 mL. No embryotoxic, foetotoxic or
teratogenic effects resulted. Simultaneous testing with 0.25 mL of 2-ethoxyethanol
confirmed its embryotoxic, foetotoxic and teratogenic effects observed in earlier studies.
Inhalational
Studies by Tyl (Bushy Run 1984) in pregnant Fischer 344 rats and New Zealand White
rabbits have been comprehensively reported in the open literature (Tyl et al 1984). The
animals were exposed to target concentrations of 0, 25, 50, 100 or 200 ppm [0, 0.12, 0.25,
0.49 or 0.98 mg/L] for 6h/day on gd 6-15 for the rat and gd 6-18 for the rabbit. In the rat,
haematological effects, increased relative spleen weight and reduced body weight gain
were observed in the dams at and above 100 ppm [NOAEL for maternal toxicity 50 ppm].
2-Butoxyethanol was embryotoxic and foetotoxic only at maternally toxic doses [NOAEL
for developmental toxicity 50 ppm].
In the rabbit study by Tyl, exposure to 2-butoxyethanol resulted in mortality, increased
number of abortions, and reduced uterus and body weight at the highest dose, 200 ppm
[NOAEL for maternal toxicity 100 ppm]. No significant dose-dependent haematological
changes were observed. 2-Butoxyethanol was not foetotoxic at any dose [NOAEL for
foetotoxicity 200 ppm] but a significantly lower number of total and viable implants per
litter were noted at the maternally toxic dose [NOAEL for embryotoxicity 100 ppm]. No
signs of teratogenicity were observed at any dose for either species [NOAEL for
teratogenicity in the rat and rabbit 200 ppm].
In a study in Sprague-Dawley rats, the animals were exposed to 150 or 200 ppm for 7h/day
over gd 7-15 (Nelson et al 1984). Haemoglobinuria was noted (on the first day only) in
the dams at both doses, but no evidence of embryotoxicity, foetotoxicity or teratogenicity
was observed. Simultaneous testing with 2-methoxyethanol indicated that the chemical
was embryotoxic, foetotoxic and teratogenic at the lowest dose tested, 50 ppm.
Subcutaneous injection
An unpublished study of the effects of 2-butoxyethanol on the pregnancy of the CD rat by
subcutaneous injection was available for assessment (Tesh 1976). Groups of rats were
injected subcutaneously with aqueous solutions of 2-butoxyethanol to determine the
teratogenicity of the chemical. In the first of two preliminary studies to set the dose range,
non-pregnant rats received a single injection with 225-1350 mg/kg; 80% of the high dose
animals died, haemoglobinuria was observed and general poor condition of the rats
resulted. In the second preliminary study, no effects were observed when a similar group
of rats received repeated injections at 23-90 mg/kg/day. Experimental details for the
preliminary studies were not available.
In the main study, conducted in accordance with OECD test guideline 414, groups of 20
pregnant CD rats received 0, 45, 90 or 180 mg/kg/day as an aqueous solution on gd 6-15.
No mortality resulted and haemoglobinuria and body weight loss were observed in the
medium and high dose dams after the first two injections only. No significant pathological
findings were noted at necropsy. Pre-implantation loss increased in the medium and high
dose dams compared with the controls, but the values were within the laboratory's normal
range. Other parameters were normal. In the foetuses, a slight increase in rib effects and a
dose-dependent increase in incomplete ossification of cranial bones were observed, but
such changes are considered as variations and not malformations (Working and Mattison
1993).
2-butoxyethanol 57
Under the conditions of the study, pre-implantation loss occurred in dams at maternally
toxic doses and there were no treatment related signs of teratogenicity.
10.8.5 Summary
In a two-generation reproductive toxicity study, fertility was reduced in mice only at very
high doses (> 1000 mg/kg) which were severely toxic to the adults. In comparative studies
with glycol ethers, 2-butoxyethanol did not cause testicular degeneration. Lower
molecular weight homologues, 2-methoxyethanol and 2-ethoxyethanol, both caused
testicular degeneration in these studies.
No significant adverse effects on reproductive organs were observed in rats and mice in
the 13-week drinking water studies (NTP 1993). Slight effects on fertility parameters
were observed in rats at haematotoxic levels.
In other reproductive studies, developmental effects were observed only at maternally
toxic doses. No evidence of teratogenicity was observed in any studies, again in contrast
to 2-methoxyethanol and 2-ethoxyethanol.
10.9 Genotoxicity
10.9.1 In vitro assays
Three-test battery of studies
The full studies of a battery of tests designed to evaluate the genotoxicity of 2-
butoxyethanol were available for assessment (Bushy Run 1980(a)).
In a Chinese hamster ovary (CHO) cell point mutation assay, 2-butoxyethanol did not
significantly increase the frequency of mutations with or without S9 metabolic activation.
The cells were exposed for five hours at doses in the range 140-9000 礸/mL. At the
highest dose, 2-butoxyethanol was cytotoxic with S9, but non-toxic without S9.
In a sister chromatid exchange (SCE) assay, 2-butoxyethanol did not induce SCEs in CHO
cells with and without S9 at the doses used in the assay, 63-2250 礸/mL.
In an Unscheduled DNA Synthesis (UDS) assay, rat liver cells were treated with 2-
butoxyethanol in the dose range 0.9-900 礸/mL for two hours in the presence of tritiated
thymidine. In the determination of UDS activity by measurement of radioactivity in liver
cell nuclei, a statistically significant induction of UDS was observed at the two lowest
doses, with the maximum effect at 9 礸/mL. The effect was confirmed by analysis of the
radioactivity in DNA isolated from the rat cell nuclei, although the maximum effect was
seen at 0.9 礸/mL. This assay should be regarded as inconclusive as there was no clear
dose-related response and various experimental problems occurred during the study, for
example, failure of the positive control in the first of two tests, and discrepancies in
radioactivity measurements.
NTP sponsored assays
The results of a series of genotoxicity studies conducted under NTP have been reported
(NTP 1993), with much of the experimental detail included.
In a Salmonella typhimurium mutation test, 2-butoxyethanol was negative with and
without S9 metabolic activation in the strains TA100, 1535, 1537, 97 and 98 at doses up to
1000 礸/plate. The two lower molecular weight homologues, 2-methoxy- and 2-
ethoxyethanol, were also negative in this assay.
In assays in CHO cells, 2-butoxyethanol induced cell cycle delay but did not induce SCEs
or chromosomal aberrations with and without S9 at concentrations up to 5000 礸/mL.
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Reverse mutation assay on 18% 2-butoxyethanol
In a reverse mutation assay conducted on the 3M product T-3722, which contains 18% 2-
butoxyethanol, tests with the Salmonella typhimurium strains TA1538, 1537, 1535, 100
and 98 were negative with and without S9 at doses up to 5000 礸/plate (SRI International
1985). Other components in the product included isopropyl alcohols (18%) and a
fluorochemical salt (27%). The study was conducted in accordance with OECD Test
Guideline 471.
Other in vitro studies
I n a gene mutation assay, 2-butoxyethanol and its intermediate metabolite, 2-
butoxyacetaldehyde, were not mutagenic to CHO-AS52 cells at concentrations up to 0.1%
v/v (7.6 mM) and 0.2% v/v respectively (Chiewchanwit and Au 1995).
It was recently reported that 2-butoxyethanol gave positive results with Salmonella
typhimurium strain TA97a at high concentrations (2.2 mg/plate), with and without S9, but
it was negative to the strains TA98, TA100 and TA102 (Hoflack et al 1995). The
metabolite BAA and the intermediate metabolite BAL were negative to all strains.
Given that 2-butoxyethanol had previously tested negative to the Salmonella typhimurium
strain TA97 (see above), the result for the structurally similar strain TA 97a was
considered unexpected by some workers, so a similar study was conducted in the USA by
the CMA (Gollapudi et al 1995). In the repeat assay, 2-butoxyethanol tested negative to
the TA97a strain at concentrations up to 10 mg/plate, with and without S9 metabolic
activation. In the study, the Salmonella typhimurium strain TA100 and the Escherichia
c o l i strain WP2uvrA also tested negative under similar conditions. The study was
conducted in accordance with standard protocols.
In studies in human lymphocytes in vitro, 2-butoxyethanol induced SCEs in the cells at
2000 and 3000 ppm, however, a negative response was recorded in a test for chromosomal
aberrations at similar concentrations (Villalabos-Petrini et al 1989). The assays were
conducted without metabolic activation or positive controls, therefore no firm conclusions
can be drawn.
A series of short-term in vitro tests (Elias et al, 1996) were carried out with 2-
butoxyethanol and its metabolites BAL and BAA in order to detect gene mutations at the
HPRT locus in V79 cells; SCEs in V79 cells; chromosomal aberrations in V79 cells and
human lymphocytes; micronuclei (MN) in vitro in V79 cells; aneugenic effects in V79
cells; morphological transformation of Syrian hamster embryo (SHE) cells; inhibition of
intercellular communication between V79 cells.
The results demonstrated that in V79 cells 2-butoxyethanol induced gene mutations and
was a weak inducer of SCEs at high doses and aneuploidy at very high doses. 2-
Butoxyethanol enhanced the clastogenic effect of methyl methanesulfonate at high doses
and at non-cytotoxic doses it induced a dose-dependent inhibitory effect on intercellular
communication in the V79 cell system.
10.9.2 In vivo studies
In a mouse bone marrow micronucleus test (Elias et al, 1996), there was no induction of
micronucleated polychromatic erythrocytes (MPE) following administration of a single
intraperitoneal injection of 2-butoxyethanol (doses from 150-1000 mg/kg) or BAA (50-
200 mg/kg) at non-toxic to toxic dose ranges. At least 1000 polychromatic erythrocytes
per animal were scored. A significant decrease in the ratio of polychromatic erythrocytes
( P C E ) to normochromatic erythrocytes (NCE) was seen with BAA but not 2-
butoxyethanol, indicating that BAA was more toxic to erythropoiesis.
No DNA binding in liver, brain, kidney, spleen and testis was seen in rats or mice
(measured using 32P postlabelling) following exposure to 2-butoxyethanol (Keith et al,
2-butoxyethanol 59
1996). An acute dose, 120 mg/kg 2-butoxyethanol was administered to rats (3 treated and
3 control animals), which were killed 24 hours later. Transgenic mice carrying ras
oncogenes (8 to 24 animals per group) were administered 1500 mg/kg 2-butoxyethanol
subcutaneously over 2 weeks (approximately 120 mg/kg/day) and killed at between 5 and
120 days. The transgenic mice killed after 120 days were also examined for tumour
formation and no statistical difference from controls was observed.
10.9.3 Summary of data on genotoxicity
2-Butoxyethanol has tested negative in a wide variety of well-conducted in vitro assays,
including mutation, chromosomal aberration and DNA effect assays. These assays were
generally conducted at both cytotoxic and non-cytotoxic doses. 2-Butoxyethanol was a
weakly positive inducer of gene mutations, SCEs and aneuploidy in V79 cells at high
doses. 2-Butoxyethanol was negative in an in vivo mouse micronucleus assay.
Based on the available information, 2-butoxyethanol is probably not genotoxic.
10.10 Carcinogenicity
No studies were available. The NTP commenced a 2-year inhalation study in rats and
mice in 1993. 2-Butoxyethanol was originally selected for study along with other glycol
ethers because of its high production volume and human exposure, and known acute
toxicity.
The International Agency for Research on Cancer (IARC) has had the glycol ethers listed
for review since 1993, but no fixed schedule has been set for the work.
10.11 Summary of toxicological data
Table 12 summarises results of all assessed studies, including critical effects together with
NOAELs or LOAELs (where established).
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Table 12 - Summary of Toxicological Data
Study Type Species Result Section
Acute toxicity
oral rat LD50 530-3000 mg/kg 10.2.1
LD50 1230 mg/kg
mouse (m)
LD50 950-1414 mg/kg
guinea pig
LD50 320-370 mg/kg
rabbit
LD50 100-610 mg/kg 10.2.2
dermal rabbit
LD50 210->2000 mg/kg
guinea pig
LC50 (4h) 486, 450 ppm 10.2.3
inhalation rat (m,f)
LC50 (7h) 700 ppm
mouse
LC50 (7h) 1300 ppm
guinea pig
LD50 252-317 mg/kg 10.2.4
intraperitoneal rat
Irritation
skin rabbit irritant 10.3.1
guinea pig irritant
eye rabbit severe irritant 10.3.2
Sensitisation
skin guinea pig non-sensitising 10.4
Immunotoxicity
10.5.1
guinea pig (in no significant effect on proliferation
vitro) of lymphocytes
Repeated dose
9-day/2-week
dermal rabbit haematotoxicity (NOAEL 90 10.6.2
mg/kg/d)
inhalation rat haematotoxicity (NOAEL 20 ppm) 10.6.3
6-week
oral (gav) rat (m) 10.6.1
haematotoxicity (LOAEL 222
mg/kg/d)
90-day/13-week
oral (dr/w) rat (m) 10.6.1
haematotoxicity (NOAEL 129
mg/kg/d)
rat (f) haematotoxicity (LOAEL 82 10.6.1
mg/kg/d)
dermal rabbit haematotoxicity (NOAEL 150 10.6.2
mg/kg/d)
inhalation rat haematotoxicity (NOAEL 24.6 ppm) 10.6.3
Reproductive toxicity
oral (dr/w) rat (m) no effect on testis/epididymus 10.8.3
mouse 10.8.2
effects only at maternally toxic doses
(1340 mg/kg bw and above)
Developmental
oral (gav) rat 10.8.4
effects only at maternally toxic doses
(100 mg/kg/day and above)
dermal rat no effects 10.8.4
inhalation rat effects only at maternally toxic doses 10.8.4
(100 ppm and above)
rabbit 10.8.4
effects only at maternally toxic dose
(200 ppm)
subcutaneous rat no significant effects 10.8.4
Genotoxicity
2-butoxyethanol 61
In vitro
mutation S. typhimurium negative 10.9.1
E. coli negative 10.9.1
CHO negative 10.9.1
V79 positive at high doses 10.9.1
SCE CHO negative 10.9.1
V79 weakly positive at high doses 10.9.1
CHO negative 10.9.1
chromosomal aberrations CHO negative 10.9.1
UDS rat inconclusive 10.9.1
micronuclei V79 negative 10.9.1
aneuploidy V79 positive at very high doses 10.9.1
In vivo
micronuclei mouse bone negative 10.9.2
marrow
DNA binding rat, mouse negative 10.9.2
Note:m = male; f = female; dr/w = drinking water; gav = gavage.
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11. Human health effects
11.1 Case reports
A number of cases of poisoning by ingestion of formulations containing 2-butoxyethanol
have been reported in the literature. The results are summarised as follows:
?Deliberate ingestion of 250-500 mL of window cleaner containing 12% 2-
butoxyethanol (dose 30-60g 2-butoxyethanol) resulted in deep coma, metabolic
acidosis, hypokalaemia, a rise in serum creatinine level and oxalate crystals in the
urine. Haemoglobinuria was observed between the third and sixth days (Rambourg-
Schepens et al 1988).
?Deliberate ingestion of about 500 mL of window cleaner containing 12.7% 2-
butoxyethanol (dose approx. 60g) and 3.2% ethanol resulted in coma, hypotension and
metabolic acidosis. A decrease in haemoglobin was noted on the second day and
haemoglobinuria occurred. The main metabolite of 2-butoxyethanol, BAA, was
detected in urine but no oxaluria was observed (Gijsenbergh et al 1989).
?Deliberate ingestion of 500 mL of household cleaner containing 9.1% 2-butoxyethanol
(dose approx. 45g) and 2.5% ethanol resulted in severe respiratory distress, coma,
shock and metabolic acidosis. No haematologic effects were observed (Bauer et al
1992).
?Deliberate ingestion of cleaning product containing 22% 2-butoxyethanol resulted in
symptoms consistent with metabolic acidosis. No signs of haemolysis were apparent.
The estimated dose was 80-106 g 2-butoxyethanol, equivalent to 1.1-1.5 g/kg bw. In a
repeat of the incident two weeks later, similar symptoms were observed (Gualtieri
1995).
?24 cases of ingestion by children (aged 7 months to 9 years) of window/glass cleaners
containing 2-butoxyethanol (range 0.5-9.9%) were retrospectively evaluated. Most of
the quantities swallowed were small, but one child ingested 30 mL of cleaner
containing <10% 2-butoxyethanol and another 300 mL of an 8% solution. No signs of
haemolysis, metabolic acidosis or CNS depression were observed in any case (Dean et
al 1992).
One case of haemolysis in a cleaner exposed to 2-butoxyethanol has been reported in the
literature (Pesticide and Toxic Chemical News 1993). It is alleged that a carpet cleaner
using a solution containing an unknown concentration of 2-butoxyethanol experienced
dizziness, blurred vision and red urine towards the end of his eight hour shift a number of
times. Some uncertainties surround the case, including lack of exposure details and lack
of verification by medical professionals. The US EPA took no action in response to the
incident, nor have they been able to find any similar incidents involving 2-butoxyethanol.
11.2 Controlled studies
11.2.1 Inhalational
Three experiments were conducted by Carpenter (1956) on human volunteers, with the
results reported in the open literature. The main results of the three tests were as follows:
?When two men were exposed to 113 ppm for four hours, no effect on RBC fragility
was observed. The men suffered nasal and eye irritation, nasal discharge and a nasty
taste in the mouth. At 4-6 hours after exposure, one man was still unwell.
2-butoxyethanol 63
?When two men and one woman were exposed to 195 ppm for two four-hour periods,
the RBC fragility was unaffected. BAA was excreted in the urine of the woman and
one male, but only a trace was detected in the second male. Symptoms included
irritation of the eyes, nose and throat, unpleasant taste, and headache.
?When two men and two women were exposed to 100 ppm for eight hours, BAA was
excreted in all volunteers and no RBC fragility was observed. Symptoms noted were
headache and nausea.
In studies in volunteers exposed to 20 or 50 ppm for two hours (Johanson et al 1986;
Johanson and Boman 1991), it was demonstrated that 2-butoxyethanol vapours were
rapidly absorbed into the bloodstream (see 9.2.3). No adverse health effects were
reported.
11.2.2 Dermal
In a study in five volunteers carried out by immersing two or four fingers in undiluted 2-
butoxyethanol for two hours (Johanson et al 1988), the results of urine analysis for BAA
indicated that the chemical is rapidly absorbed through the skin. The fingers of the
volunteers became stiff and wrinkled but no signs of irritation were observed.
The skin sensitisation potential of 2-butoxyethanol was evaluated in a repeated insult patch
test carried out on 200 volunteers (TKL Research 1992). The results have recently been
reported in the open literature (Greenspan et al 1995). In the induction phase, 0.2 mL of a
10% aqueous solution was applied under a patch for 24 hours to the backs of the subjects
for a total of nine times over a three-week period. The sites were evaluated for skin
reaction after each application. A slight redness (without swelling) was observed in four
subjects after the first application but, by the eighth application, 40 subjects exhibited
slight erythema and in another 14, erythema was more definite. The challenge phase was
conducted two weeks later, with 10% 2-butoxyethanol applied to previously unexposed
sites, with slight erythema noted in only seven subjects after 48 hours and 12 subjects after
72 hours. Under the conditions of the study, 2-butoxyethanol was not a skin sensitiser.
11.3 Occupational studies
In a silkscreening operation in Virginia, USA, workers exposed to undiluted 2-
butoxyethanol reported irritation and discomfort (Kullman 1987). In the subsequent
inspection of the workplace, atmospheric concentrations of 2-butoxyethanol in the range
13-169 ppm were obtained.
No epidemiological studies were available. In France, studies in workers exposed to
glycol ethers, including 2-butoxyethanol, are underway to identify any adverse health
effects, including haematotoxicity, associated with exposure.
11.4 Other information
Information was obtained from one of the formulators about cleaners using floor strippers
containing high levels of 2-butoxyethanol. The effects noted included eye irritation and
drowsiness when the ventilation was poor. Some reddening of the skin and contact
dermatitis occurred when the proper safety gloves were not worn.
In New South Wales, several school cleaners reported eye and throat irritation, headache
and nausea while using cleaning products solutions, including products containing 2-
butoxyethanol. In most cases, the solutions were being used in spray form. Skin irritation
was reported by two of the 12 cleaners who responded to a call for information.
Information was also received from cleaners previously exposed to 2-butoxyethanol
during their work, which included floor stripping and heavy duty cleaning. Symptoms
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reported by the cleaners included eye and respiratory irritation, headache, nausea,
sleepiness, dizziness and confusion. One worker reported anaemia as a result of exposure.
Individual details of the above cases are summarised in Appendix 4. No monitoring of the
cleaners or the workplace was conducted and no medical examination or follow-up of the
cleaners was carried out as part of the assessment.
11.5 Summary
Exposure to 2-butoxyethanol vapours may result in irritation of the eyes, nose and throat,
headache and nausea. In liquid form (including aqueous solution), 2-butoxyethanol is
readily absorbed through the skin, and the results of controlled studies in volunteers have
indicated that 2-butoxyethanol vapours are also absorbed via the skin. A few cases of skin
irritation have been reported by cleaners using products containing 2-butoxyethanol, but
controlled studies in volunteers with 2-butoxyethanol have resulted in slight or no skin
irritation. In a patch test in volunteers, 2-butoxyethanol was not a skin sensitiser but slight
skin irritation was observed after several applications.
Haemoglobinuria has been observed in humans who have ingested large quantities (30-
60g) of 2-butoxyethanol. The ingestion of large quantities of 2-butoxyethanol may also
result in severe respiratory difficulty, shock and coma. One unsubstantiated case of
haemolysis in a worker exposed to cleaning solutions containing 2-butoxyethanol has been
reported in the literature.
2-butoxyethanol 65
12. Hazard assessment and
classification
This chapter integrates data on physicochemical hazards, kinetics and metabolism, and
health hazards identified from human studies and from experimental animal and in vitro
testing. The potential hazards to human health from exposure to 2-butoxyethanol can then
be characterised and the appropriate hazard classification determined.
Workplace substances are classified as hazardous to health if they meet the NOHSC
A p p r o v e d Criteria for Classifying Hazardous Substances (the Approved Criteria)
(NOHSC 1994(a)), 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 1992).
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.
The classification recommended for 2-butoxyethanol is incorporated in the following
assessment of health and physicochemical hazards.
12.1 Physicochemical hazards
2-Butoxyethanol is a liquid of low volatility with a flash point of 62oC.
Classification:
2-Butoxyethanol does not meet the ADG Code criteria for any classes pertaining to
physicochemical properties, for example, flammability, oxidising properties.
12.2 Kinetics and metabolism
The results of animal and human studies show that 2-butoxyethanol is readily absorbed by
all routes. Studies also indicate that 2-butoxyethanol is readily absorbed through the skin
from aqueous solution and that skin absorption of vapours may occur. In animal studies
conducted by all routes of exposure, 2-butoxyethanol is rapidly distributed to all tissues
via the bloodstream. Studies indicate that it is qualitatively metabolised in a similar
manner in both animals and humans, the main metabolite being 2-butoxyacetic acid
(BAA), which is rapidly excreted in the urine. In humans, significant amounts of the BAA
glutamine conjugate have also been measured in urine following exposure to 2-
butoxyethanol and suggest an additional detoxification pathway in humans (see chapter 9,
Kinetics and Metabolism).
12.3 Health hazards
12.3.1 Acute effects
In animal studies, 2-butoxyethanol can be lethal in all species tested by all exposure
routes, with the main cause of death being narcosis or respiratory distress. In acute
studies, oral LD50 in rats ranged from 530 to 3000 mg/kg, dermal LD50 in rabbits ranged
from 100-610 mg/kg and inhalational LC50 in rats ranged from 2.2 to 2.4 mg/L (4h).
No deaths have been reported from cases of deliberate and accidental ingestion of 2-
butoxyethanol in humans, but some of the victims lapsed into coma and experienced
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symptoms such as metabolic acidosis, shock and respiratory distress. Haemoglobinuria
was observed in two cases (at the higher doses). In humans, headache and nausea have
also been reported.
Classification:
From the LD50 and LC50 values obtained from animal testing, 2-butoxyethanol meets the
Approved Criteria for classification as `harmful' by inhalation (risk phrase R20), skin
contact (R21) and ingestion (R22).
From the results of human case reports and acute toxicity testing in animals, 2-
butoxyethanol does not meet the Approved Criteria for classification for non-lethal
irreversible effects after a single exposure.
For classification under the ADG Code, the human data are insufficient for classification
purposes so, on the basis of animal data for acute dermal and inhalational toxicity (LD50
and LC5 0 values), 2-butoxyethanol meets the criteria for classification as a Class 6.1
substance in Packaging Group III (see section 12.4 for further information).
12.3.2 Irritant effects
A number of skin irritation studies in experimental animal studies provided variable
results. On balance, 2-butoxyethanol was irritating to the skin of rabbits. On the other
hand, studies in human volunteers resulted in slight or no irritation. Isolated cases of skin
reddening and dermatitis have been reported in workers using cleaning products on a
regular basis, however, as the products contain many ingredients, the irritant effects cannot
be solely attributed to 2-butoxyethanol. In general, occupational case studies have not
identified skin irritancy as a significant effect in exposed persons.
2-Butoxyethanol has been shown to be a severe eye irritant in both animals and humans.
Occupational case reports have identified respiratory irritation as a potential health effect
in humans. In controlled human studies (Carpenter 1956), nose and throat irritation was
observed at 113 ppm but not at 100 or 50 ppm. In an Alarie test in male mice, 2-
butoxyethanol was a weak sensory irritant (Kane et al 1980).
Classification:
From human evidence and the results of animal studies, 2-butoxyethanol meets the
Approved Criteria for classification as an `eye irritant' (risk phrase R36).
From human evidence in both controlled studies and occupational case reports, 2-
butoxyethanol meets the Approved Criteria for classification as a `respiratory irritant'
(R37).
Primarily on the basis of human evidence from controlled studies in volunteers and
occupational case reports, and noting the variable results obtained in animal studies, 2-
butoxyethanol does not meet the Approved Criteria for classification as a skin irritant.
12.3.3 Sensitisation
Skin sensitisation studies in animals and humans have been negative. There is no evidence
that 2-butoxyethanol is a respiratory sensitiser.
2-butoxyethanol 67
Classification:
From the results of human and animal studies, 2-butoxyethanol does not meet the
Approved Criteria for classification as a sensitiser.
12.3.4 Immunotoxicity
Studies in rats and in vitro studies in guinea pig lymphocytes did not reveal any significant
effect on the immune response. There have been no reports of any effect of 2-
butoxyethanol on the immune system of humans.
12.3.5 Effects after repeated or prolonged exposure
Haemolytic effects
The main effect observed in both acute and repeated-dose animal toxicity studies is
haemolysis of the red blood cells. The principal agent of haemolysis is the major
metabolite of 2-butoxyethanol, 2-butoxyacetic acid (BAA). In general, the haematological
effects observed at lower doses in repeated-dose studies were transient in nature as they
tended to be noticeable during the first few days of exposure only. This feature is
attributed to the replacement of older more susceptible red blood cells with younger more
resistant cells. Several studies have shown that haemolysis is preceded by an increased
osmotic fragility or swelling of the red blood cell, indicating an effect by BAA on the cell
membrane, that is, erythrocyte toxicity. There is also limited evidence to show that the
haemolytic effects are not related to bone marrow toxicity.
Most animal studies have been conducted in the F344 rat. From inhalational studies in the
rat, the NOAEL obtained for haematological effects in a 90-day study was 24.6 ppm.
Assuming 100% absorption, an average rat weight of 215g, and a respiratory rate of 0.16
m3/day (NIOSH 1990), this represents an absorbed dose of:
121 mg/m3 x 0.16 m3/day x 6h = 22.5 mg/kg/day.
0.215 kg x 24h
In a nine-day study by the same laboratory, the NOAEL obtained for haematological
effects was similar at 20 ppm (Longo and Dodd 1981).
In a 90-day dermal study in rabbits, the NOAEL for all effects was 150 mg/kg/day, the
highest dose tested (WIL Research Laboratories 1983). In a 90-day drinking water study
in rats, the NOAEL for haematological effects in males was 129 mg/kg/day but, in
females, a NOAEL was not obtained (LOAEL 82 mg/kg/day) (NTP 1993).
Therefore, the lowest reliable NOAEL from animal studies is 24.6 ppm (121 mg/m3) in the
rat.
Numerous in vivo and in vitro studies have demonstrated a considerable variance between
species in susceptibility to the haemolytic effect of 2-butoxyethanol, with rats and mice the
most susceptible, rabbits less susceptible, and guinea pigs and humans the least
susceptible. The effect has been well characterised in the rat, with consistent results
obtained by different laboratories.
To highlight the differences in effect between species, particularly the rat and humans, the
results of key in vivo (inhalational) and in vitro haematological studies are tabled below.
The studies were designed to measure haemolysis and prehaemolytic effects such as
swelling and changes in osmotic fragility.
Several in vitro studies have demonstrated that human red blood cells are at least ten times
less sensitive to haemolysis by BAA than rat cells.
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Table 13 - Summary of In Vivo Haematological Studies (Inhalational)
Study Species Dose/Duration Haemolytic Effect
Carpenter (1956) rat 62 ppm/4h Increased RBC fragility
54-432 ppm/7h, Increased fragility (all doses)
30d Haemoglobinuria (> 203 ppm)
113 ppm/4h Increased fragility
mouse 112-400 ppm/7h, Increased fragility (all doses)
30-90d Haemoglobinuria (> 200 ppm)
rabbit 125, 197 ppm/7h Increased fragility (both doses)
guinea pig 665 ppm/8h No effect
human 113 ppm/4h No effect
195 ppm/8h No effect
rat 20 ppm/6h, 9d No effect
Longo and Dodd
(1981)
86 ppm/6h, 9d Haemolysis
Snellings (1981) rat 25 ppm/6h, 90d No effect
77 ppm/6h, 90d Haemolysis
Johanson (1994) rat 20 ppm/12d No haemolysis
100 ppm/12d No haemolysis
Table 14 - Summary of In Vitro Haematological Studies
Study Species Exposure Duration Dose (mM BAA) Effect
Bartnik (1987) rat 1h 7.5 Haemolysis
human 1h 15 No effect
rat 3h 3.75 Haemolysis
human 3h 5 No effect
Ghanayem (1989) rat 4h 0.5 Haemolysis
human 4h 2 No effect
4 Slight swelling
8 Slight haemolysis
rat 4h 2 Haemolysis
Ghanayem and
Sullivan(1993)
rabbit 2 Swelling
human 2 No effect
Udden and Patton rat 6h 0.2 Slight haemolysis
(1994) preceded by swelling
4h 2 Significant haemolysis
preceded by swelling
Haemolytic effects have been reported in humans in two cases following ingestion of large
amounts of cleaning solution containing 30-60g of 2-butoxyethanol. No confirmed cases
of haematotoxicity have been reported in persons exposed to 2-butoxyethanol in an
occupational setting. There has been one unconfirmed report of a carpet cleaner having
red urine following exposure to 2-butoxyethanol. In three controlled studies in volunteers,
exposure to 100-195 ppm 2-butoxyethanol for 4-8h did not alter the osmotic fragility of
red blood cells (see Table 13 and sections 11.1 and 11.2).
2-butoxyethanol 69
Animal studies indicated that younger rats were less susceptible to the haemolytic effects
of 2-butoxyethanol than older ones (see section 10.7). However, an in vitro study showed
that the red blood cells from aged persons and young adults were not significantly affected
in the presence of 2 mM BAA (Udden 1994). The study also indicated that the red blood
cells of persons with hereditary blood disorders (sickle cell anaemia and spherocytosis),
individuals who are likely to be more susceptible to haemolysis, were not significantly
affected in the presence of 2 mM BAA (see 10.7.4).
Toxicokinetic studies have shown that, in rats and humans, 2-butoxyethanol is readily
absorbed via inhalation and dermal routes (and oral route in rats) and widely distributed in
the rat following absorption. Evidence indicates that the dermal absorption rate in humans
for 2-butoxyethanol is approximately 0.2 mg/cm2/h, although there appears to be a high
degree of interindividual variation. Studies have demonstrated that 2-butoxyethanol is
extensively and rapidly metabolised by a similar oxidative pathway in rats and humans,
with BAA the major metabolite. The major route of elimination is in the urine, with the
major metabolite BAA being rapidly excreted in both species. It has been shown that
human interindividual rates of elimination vary (Johanson et al 1986; 1988). Conjugation
of BAA with glutamine in humans may provide an additional detoxification pathway.
In summary, the evidence from controlled and case studies in humans, in vitro studies in
animal and human red blood cells, in vivo studies in animals and toxicokinetic data
indicates that humans are less sensitive to the haemolytic effect of 2-butoxyethanol than
rats, and there is some in vitro evidence to indicate that they may be considerably less
sensitive.
T h i s conclusion is supported by the physiologically-based pharmacokinetic model
developed by Corley et al (1994), which successfully estimated the disposition of 2-
butoxyethanol and BAA under a variety of exposure scenarios. Based on data from
absorption studies indicating that 2-butoxyethanol was more readily absorbed from
aqueous solution (see Chapter 9, Kinetics and Metabolism), and assuming that 10% of
body area was exposed (approximately 2000 cm2), Corley et al's model predicted as a
worst-case scenario that the skin absorption of undiluted 2-butoxyethanol over 6h would
lead to a BAA blood concentration of 0.37 mM, and that absorption of a 40% solution
would result in 1.3 mM BAA. These values are below the BAA concentration (2 mM) at
which no haemolysis was observed in human in vitro measurements and well below the
concentration at which haemolysis has been observed in human cells in vitro (8 mM
BAA).
Other effects from repeated or prolonged exposure
In repeated dose studies in animals, changes to the liver, kidney, spleen and thymus
occurred in some cases, but these effects were seen at or above haematotoxic doses and are
generally regarded as being secondary to haemolysis. The NOAEL for liver degeneration
in a 13-week oral rat study was 281 mg/kg/day (NTP 1993). The NOAEL for all effects in
a 90-day dermal study in rabbits was 150 mg/kg/day (WIL Research Laboratories 1983).
Severe effects in humans from repeated or prolonged exposure have not been reported in
the literature.
Classification:
The lowest reliable NOAEL from repeated (inhalation) exposure to 2-butoxyethanol is
24.6 ppm (0.12 mg/L). The haematotoxic effects observed at lower doses in animal
studies are transient in nature, with affected animals recovering from these effects after the
first few exposures. Severe secondary effects were observed in animals only at high
doses. Therefore, 2-butoxyethanol does not meet the Approved Criteria for classification
on the basis of severe effects after prolonged or repeated exposure.
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12.3.6 Reproductive effects
No reports of reproductive effects in humans have been reported in the literature.
The reproductive effects of 2-butoxyethanol have been widely studied in animals by all
routes of exposure, with the results indicating that 2-butoxyethanol does not affect fertility
or developmental toxicity below doses which are severely toxic to the adults.
No evidence of teratogenicity was observed in any of the studies.
Classification:
From the results of animal studies, 2-butoxyethanol does not meet the Approved Criteria
for teratogenicity nor the EC criteria for developmental toxicity and fertility effects
(Commission of the European Communities 1993).
12.3.7 Genotoxicity
2-Butoxyethanol has tested negative in a wide range of well-conducted in vitro assays,
including gene mutation, chromosomal aberration and DNA effect assays. Weakly
positive responses in gene mutation, SCE and aneuploidy assays with V79 cells have been
observed with very high doses of 2-butoxyethanol in one study.
2-Butoxyethanol was negative in an in vivo mouse micronuclei assay.
Classification:
From the results of in vitro studies, 2-butoxyethanol does not meet the Approved Criteria
for mutagenicity.
12.3.8 Carcinogenicity
No 2-year carcinogenicity studies were available. An NTP study is underway.
Classification:
Due to the lack of data, 2-butoxyethanol cannot be classified for carcinogenicity.
12.4 Classification summary
Approved Criteria for Classifying Hazardous Substances
Under the Approved Criteria, the appropriate classification for 2-butoxyethanol is:
?R20/21/22 Harmful by inhalation, in contact with skin, and if swallowed
?R36 Irritating to eyes.
?R37 Irritating to respiratory system.
This is the same as currently specified on the List of Designated Hazardous Substances
(the List) except for the risk phrase R36. The concentration cut-offs on the List for 2-
butoxyethanol are 12.5% for R20/21/22 and 20% for R37. A cut-off of 20% would also
apply for R36. Due to its acute toxicity, a concentration cut-off of 12.5%, lower than the
usual 25% cut-off for R20/21/22, was considered appropriate by the EEC.
Poisons Schedule
2-Butoxyethanol itself is not listed on the Poisons Schedule (SUSDP), but it falls within
the scope of ethylene glycol monoalkyl ethers, which are listed on Schedule 6 for
preparations containing more than 10% glycol ether. Schedule 6 entries are `poisons that
must be available to the public but are of a more hazardous or poisonous nature than those
classified in Schedule 5'. As the health effects of ethylene glycol monoalkyl ethers vary
considerably, a separate listing for 2-butoxyethanol on the Poisons Schedule would be
more appropriate.
2-butoxyethanol 71
Dangerous goods classification
The results of this assessment indicate that 2-butoxyethanol meets the criteria in the ADG
Code for Class 6.1(b) substances, Packaging Group III (as currently listed in the fifth
edition of the Code). However, 2-butoxyethanol was delisted by the UN Committee of
Experts on the Transport of Dangerous Goods at its November 1994 meeting (United
Nations 1995). The relevant Australian authority (the Competent Authorities Sub-
Committee to the Advisory Committee on the Transport of Dangerous Goods) has
endorsed the decision by recommending that 2-butoxyethanol should not be listed in the
next edition of the ADG Code. In the meantime, the authority has issued a generic
exemption for the movement of 2-butoxyethanol throughout Australia, provided that it is
not marked as a dangerous good (Federal Office of Road Safety 1995).
The criteria for assigning substances to Dangerous Goods Class 6.1 are outlined in section
2.3.9 of the ADG Code (5th edition; Federal Office of Road Safety 1992). Toxic
substances are assigned to Class 6.1 on the basis of human experience or, in the absence of
human experience, data obtained from animal experiments. The criteria state that account
should be taken of human experience in instances of accidental poisoning and of special
properties possessed by the substance. For liquid substances assigned on the basis of data
from animal experiments, the criteria are tabled in Table 2.2 in the ADG Code, viz.:
?oral LD50 (rat) < 500 mg/kg
?dermal LD50 (rabbit) < 1000 mg/kg
?inhalational LC50 (rat) < 10 mg/L (one hour) or 5 mg/L (4h).
Initially, it was proposed to the UN that 2-butoxyethanol be reclassified, to class 9
(Miscellaneous), rather than be delisted. The proposal was based on the following
argument:
?case reports of accidental poisoning in children did not result in medical emergencies,
and three attempted suicides were unsuccessful;
?rat and mouse data are not relevant to human toxicity because the main effect in rats
and mice, haemolysis of the red blood cells, is not seen in some other species including
humans and guinea-pigs;
?acute toxicity data for the guinea-pig were outside the Dangerous Goods Code criteria
for a class 6.1 substance, viz.
LD50 (oral) 1400 mg/kg (criterion 500 mg/kg)
LD50 (dermal) >2000 mg/kg (1000 mg/kg)
LC50 (inhalation) >3.9 mg/L (10 mg/L); and
?2-butoxyethanol should be in class 9 because it may cause irritation and nausea.
The human experience alone is considered insufficient for classification purposes. In four
cases of poisoning by ingestion, where the amount of 2-butoxyethanol swallowed ranged
from 30 to 106g, the victims survived, but only after lapsing into coma and experiencing
symptoms such as respiratory distress, metabolic acidosis and shock. In two of the four
cases, haemoglobinuria was observed. In case reports of children swallowing small
amounts of cleaning products containing 2-butoxyethanol, no adverse effects were
observed.
The animal data relevant to the ADG criteria are:
?oral LD50 (rat) 530-3000 mg/kg
?dermal LD50 (rabbit) 100-610 mg/kg
?inhalational LC50 (rat) 2.2-2.4 mg/L (4h).
In consideration of the animal data for acute toxicity, the results of this assessment indicate
that 2-butoxyethanol meets the criteria for dermal toxicity (rabbit LD50) and inhalational
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toxicity (rat LC50). As noted in the UN proposal to delist 2-butoxyethanol, there is a view
held by some that the rat and mouse data, including acute toxicity data, are not relevant to
humans. This assessment has found that humans are less sensitive to the haemolytic
effects seen in rats following repeated exposure, and therefore the rat is not the most
appropriate animal model for repeated exposure. However, in acute studies in animals the
main cause of death appears to be narcosis or respiratory distress. Therefore, the results for
acute toxicity studies in rats and mice should be considered in the classification for 2-
butoxyethanol under the ADG Code.
Conclusion
The classification of 2-butoxyethanol outlined above highlights the difficulties created by
the existence of different schemes with different criteria. At present, 2-butoxyethanol is a
hazardous substance in the workplace at concentrations above 12.5%, it is a poisonous
substance to the public at concentrations above 10%, but under the ADG Code, it is not a
dangerous good. All classifications have been made on the basis of the health effects.
Also, 2-butoxyethanol is classified as `harmful' by all 3 routes under the EC regulations
and the Approved Criteria. The criteria for inhalational toxicity under the Approved
Criteria are the same as under the ADG Code (5 mg/L, 4 hours). The delisting of 2-
butoxyethanol has created an inconsistency between the two classification systems.
This problem reinforces the need for harmonised classification systems, and at least the
need for consistency in criteria between the different systems.
12.5 Comparison of glycol ethers
Due to the widespread use of ethylene glycol ethers and some concern about the adverse
health effects of some members of the group, a number of reviews of the health effects of
the ethylene glycol ethers as a class have been conducted in recent years (see section 2.2).
Comparative studies have been conducted for many of the toxicological endpoints, for
example, repeated dose and genotoxicity studies in NTP Technical Report No.26 (NTP
1993).
From the reviews, it is evident that although the ethylene glycol ethers share some
toxicological properties, individual members differ for other properties. The following
conclusions have been made about the ethylene glycol ethers as a class:
?They are absorbed through the skin, however, in general, the absorption rate decreases
with increasing molecular weight;
?Their acute toxicity is low to moderate (with animal LD5 0 and LC5 0 values for 2-
butoxyethanol generally lower than for other ethylene glycol ethers);
?The reproductive and developmental toxicity decreases with increasing alkyl chain
length. Only some ethylene glycol ethers, for example, the short chain compounds 2-
methoxyethanol and 2-ethoxyethanol, have been shown to be reproductive and
developmental toxicants. 2-Butoxyethanol does not exhibit this property;
?Some cause haemolytic effects in animals, for example, 2-butoxyethanol, but others
have been shown not to cause these effects;
?They are in general slight irritants;
?They do not appear to be sensitisers;
?They do not appear to be genotoxic.
2-butoxyethanol 73
Comparison of the health effects of glycol ethers should be treated with some caution as
many members of the class have not been tested extensively.
In 1993, the US EPA reviewed the human health effects of the glycol ethers (US EPA
1993). In trying to redefine the glycol ethers on their list of toxic substances, the EPA
stated that high molecular weight glycol ethers (surfactants) are of low concern for human
health and do not meet their toxicity criteria. They also concluded that, while the toxic
effects of the glycol ethers varied considerably in type and severity and that human health
effects generally decreased with an increase in molecular weight, there was insufficient
data at present to establish a size or molecular weight to indicate which other glycol ethers
are of low concern.
2-Butoxyethanol exhibits some of the general characteristics of ethylene glycol ethers.
However, animal data have demonstrated that 2-butoxyethanol is more acutely toxic than
most glycol ethers, is readily absorbed through the skin, does not cause reproductive and
developmental effects, but does cause haemolysis in some species. Humans appear to be
less sensitive than most animal species to the haemolytic effects of 2-butoxyethanol.
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13. Risk characterisation
(occupational)
In this section, the results of the hazard and occupational exposure assessments have been
integrated to characterise the risk of adverse health effects in workers exposed to 2-
butoxyethanol.
13.1 Methodology
The risk to human health from exposure to 2-butoxyethanol has been characterised by
using methodology commonly used in international assessments (UK Govt 1993; OECD
1993; European Commission 1994).
For critical effects caused by repeated or prolonged exposure, the risk characterisation is
made using the following procedure:
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. Where appropriate, comparison of the NOAEL with the estimated human dose
to give a margin of safety, that is:
margin of safety = NOAEL
estimated human dose (EHD)
4. Characterisation of risk, by judging whether the margin of safety indicates
a concern.
The process of characterising risk requires the consideration of a number of parameters,
including the human population exposed, the nature and severity of the effect, interspecies
and intraspecies variability, and completeness and quality of the database (including
exposure data).
For acute effects, the risk characterisation process considers likely exposure patterns to
assess whether single exposures are high enough to indicate a health concern.
13.2 Critical health effects
13.2.1 Acute effects
The critical effects identified for acute inhalational exposure to 2-butoxyethanol are
irritation of the eyes and respiratory system. In controlled studies, nasal and eye irritation
was reported in humans after exposure to 113 ppm but not after exposure to 20, 50 or 100
ppm. Eye and throat irritation have been reported in workers using cleaning products
containing 2-butoxyethanol but the atmospheric concentrations of 2-butoxyethanol and
other ingredients were not known.
Headache and nausea have been reported in controlled studies at 100 ppm and above and
b y cleaners using cleaning products which have included those containing 2-
butoxyethanol.
Haemoglobinuria was reported in animals in acute toxicity studies by all exposure routes,
however, haemolytic effects have only been observed in humans after the ingestion of
2-butoxyethanol 75
large doses (30-60g) 2-butoxyethanol. The haemolytic effects of 2-butoxyethanol are
discussed further in the next subsection.
13.2.2 Effects of repeated exposure
No long-term studies of human populations were available in the scientific literature.
In animal studies, the critical effect of 2-butoxyethanol is haemolysis of the red blood
cells. Other systemic effects such as liver damage are generally regarded as secondary to
haemolysis. The lowest reliable NOAEL for haematotoxicity in a 90-day inhalation rat
study is 24.6 ppm for the rat (Snellings et al 1981), which is equivalent to a daily dose of
22.5 mg/kg/day (see 12.3.5).
Consideration of the haemolytic effect of 2-butoxyethanol in animals indicates that the
effect is more of an acute effect than a chronic effect. In repeated dose studies, the effect
is transient at low doses, with haematological effects generally noticeable only during the
first few days of exposure. The NOAEL for a 9-day inhalational rat study, 20 ppm (Longo
and Dodd 1981), is similar to the 90-day NOAEL.
As discussed in section 12.3.5, there is sufficient evidence from controlled and case
studies in humans, animal in vivo studies, and in vitro studies in animals and human cells
to conclude that humans are less sensitive to the haemolytic effect of 2-butoxyethanol than
rats. This conclusion is supported by predictions from Corley et al's PBPK model (1994).
Animal studies indicated that older rats were more susceptible to haemolysis than younger
ones, however, at the concentrations tested, human in vitro studies did not confirm this in
humans (Udden 1994). The in vitro studies also indicated that the red blood cells of
persons with some hereditary blood disorders (sickle cell anaemia and spherocytosis) were
not significantly affected under the study conditions.
13.3 Occupational health and safety risks
13.3.1 Risk from physicochemical hazards
2-Butoxyethanol is a combustible liquid with flammability limits 1.1-12.7%. However, as
2-butoxyethanol has a low volatility, the risk of fire is low and the risk of explosion
minimal. Most cleaning products are aqueous, so there will be no fire risk during their use
and little risk during formulation. However, a small number are hydrocarbon or alcohol-
based so, for these products, there may be some risk of fire.
2-Butoxyethanol undergoes the reactions typical of glycol ethers, for example, reaction
with oxidising agents and alkalis. However, in the formulation and use of cleaning
products containing the chemical, the risk of harm to health or safety due to chemical
reaction is very low.
13.3.2 Margin of safety
The margin of safety (MOS) provides a measure of the likelihood that a particular adverse
health effect will occur under the conditions of exposure. As the MOS increases, the risk
of the adverse health effect occurring decreases. The MOS is normally used for repeated
dose systemic effects, where an animal NOAEL can be established.
Historically, the MOS was used to compare therapeutically effective drug doses with doses
which caused adverse health effects. More recently, the MOS process has been used to
establish acceptable human exposures such as acceptable daily intakes (ADIs) for food
additives and in setting occupational exposure limits. In these processes, the animal
NOAEL is divided by uncertainty (safety or modifying) factors which take into account
the human population exposed, the nature and severity of the effect, inter- and intraspecies
differences, and uncertainties in the process, for example, the exposure database. A safety
factor of 100 is often used in setting ADIs. It is generally recommended, however, that
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default safety factors wherever possible be replaced by those supported by experimental or
epidemiological data.
The approach in this assessment has been to follow international practice and compare the
estimated human dose (EHD) with the animal NOAEL. It is generally considered that
when the EHD is greater than the NOAEL, the substance is of concern regarding the
human population exposed. Where the EHD is less than the NOAEL, consideration of the
MOS is required in deciding whether exposure to the substance is a concern. Expert
judgment is required to weigh up these considerations on a case by case basis, taking into
account the human population exposed, the nature and severity of the effect, the inter- and
intraspecies variability, and the completeness and quality of the database.
For the critical health effect, haemolysis, the margins of safety (MOS) were calculated for
the various estimated human dose exposure scenarios using the formula given in section
13.1, viz.:
margin of safety = 22.5 mg/kg/day
estimated human dose (EHD) in mg/kg/day
The EHD for each scenario is given in Appendix 3, with the summary in chapter 8,
Occupational Exposure. The MOS for each scenario is tabled below.
Table 15 - Margins of Safety
Concentration of 2-BE Margin of safety
Manufacture 8 hours/day
100% 2-butoxyethanol 16
Formulation
3 hours/day 8 hours/day
10% 2-butoxyethanol 32 11.8
30% 2-butoxyethanol 7.3 2.7
60% 2-butoxyethanol 6.3 2.4
Cleaning
5 hours/day 8 hours/day
0.1% 2-butoxyethanol 25 16
1% 2-butoxyethanol 22.5 14
10% 2-butoxyethanol 7.3 4.5
30% 2-butoxyethanol 2.6 1.6
In the context of characterising the risks during manufacture of 2-butoxyethanol and the
formulation and use of cleaning products containing the chemical, the MOS are discussed
below in 13.3.4, 13.3.5 and 13.3.6.
13.3.3 Uncertainties in the risk characterisation
Uncertainties arise in any risk assessment process due to matters such as inadequate
information, assumptions made during the process, and variability in experimental
conditions. Examples of uncertainties inherent in the assessment of health risk for 2-
butoxyethanol are listed below in Table 16. These uncertainties need to be kept in mind
when discussing the implications of any margin of safety, particularly when deciding if a
calculated exposure is of concern. Given that the risk characterisation in this assessment
2-butoxyethanol 77
simply aims at identifying scenarios of possible concern, it is not considered necessary to
carry out a quantitative uncertainty analysis.
Table 16 - Uncertainties in Risk Characterisation
Area of uncertainty Specific concerns
Inadequate information Lack of representative exposure data.
Lack of dermal exposure data.
Inadequate data to differentiate between the various methods of application during
cleaning.
Assumptions in assessment Assumption of a linear correlation between estimated human dose and variables
process 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.
Precision and accuracy of constants and variables used in the assessment, for
example atmospheric monitoring data.
13.3.4 Risk during manufacture of 2-butoxyethanol
The manufacture of 2-butoxyethanol is an enclosed process so typical worker exposure is
very low. Single exposures may occur during activities such as plant maintenance and
drum filling, however, as the highest inhalational exposure reported is low (1.8 ppm
TWA) and effective control measures are in place, the risk of irritant effects is low. The
calculated MOS (for haemolytic effects) is 16, with a high degree of confidence in the
estimate due to sufficient reliable data. Therefore the risk of haemolytic effects in workers
exposed to 2-butoxyethanol during manufacture is minimal.
13.3.5 Risk during formulation of cleaning products
Acute effects
The determination of the risk of acute adverse health effects such as eye and respiratory
irritation, headache and nausea during formulation was hampered by lack of data.
Firstly, no atmospheric monitoring data were available for the formulation of cleaning
products containing 2-butoxyethanol. In particular, short-term measurements which may
have provided some insight into peak 2-butoxyethanol concentrations during specific
operations were not available. As a result, values available for varnish production and
cleaning operations were used in the exposure calculations for formulation. This may lead
to overestimates as inhalational exposure during formulation would be expected to be
lower than during cleaning, due to the less dispersive use of 2-butoxyethanol during
formulation.
In addition, information obtained from formulators indicated that there was a wide
variation in process conditions, for example, some plants have the filling operation
enclosed whereas others have an open system.
Vapour concentrations from single exposures are unlikely to be high enough to result in
respiratory or eye irritation under routine operating conditions where the process is well-
controlled, for example, transfer to the mixing tank is sealed or the filling station on the
packing line is enclosed. However, approximately 50% of formulators use open tanks and,
in some cases, 2-butoxyethanol is added directly to the tank from a drum above the tank,
and splashing may occur. The filling operation may also be open.
In the absence of definitive inhalational exposure data during formulation, it is considered
that there is a risk of acute effects during some operations in open plant systems and other
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work situations where aerosols may be generated or where high vapour concentrations
may occur, for example, during the handling of spills, during maintenance, or if heat is
applied.
Haemolysis
The risk of haemolysis from exposure is very dependent on factors such as the severity of
the effect in humans, the duration of exposure during a work shift, and the concentration of
2-butoxyethanol in the products formulated. MOS ranging from 2.4 to 32 were calculated
for the various exposure scenarios (see Table 15). MOS for the various individual
operations during formulation, for example, adding 2-butoxyethanol to the mixing tank,
were not estimated as most operators perform a variety of tasks during a normal work
period. The scenarios with the lowest MOS are those concerned with exposure during the
formulation of cleaning products containing a high concentration of 2-butoxyethanol. For
the higher concentrations of 2-butoxyethanol in formulations (30-60%), the MOS was 2-3,
however, only 3-4% of formulations contain > 30% 2-butoxyethanol. Approximately 70%
contain < 10% 2-butoxyethanol; in these circumstances, the MOS was 11.8 for an 8-hour
scenario. Also, the exposure duration for approximately 70% of formulation workers is
less than 3 hours/week, so the MOS for many work situations is > 7.3 and for most
situations > 32.
In assessing the risk of haemolysis in formulation workers exposed to 2-butoxyethanol, the
MOS for each scenario needs to be considered in conjunction with parameters such as
severity of the effect, intra- and interspecies differences and uncertainties in the risk
assessment process.
A number of uncertainties were inherent in the assessment of risk from exposure to 2-
butoxyethanol during formulation (see Table 16). In particular, the exposure assessment
for formulation was hampered by lack of data for both inhalational and dermal exposure.
Inhalational exposure may have been overestimated as a consequence of assuming
exposure to vapours is continuous and of selecting values from air monitoring data for
cleaning operations. During formulation, use of 2-butoxyethanol is less dispersive when
compared with cleaning, and exposure to vapours is likely to be more sporadic. Similarly,
the assumed skin contact time of 20% of exposure duration (intermittent exposure) and
skin surface exposed (a hand and a forearm) are also likely to be overestimations as direct
handling of 2-butoxyethanol during formulation is likely to be occasional, evaporation of
2-butoxyethanol may occur, and skin protective equipment such as gloves may be worn.
There is a degree of uncertainty regarding the rate of skin absorption. By using the rate of
0.2 mg/cm2/h (see Appendix 3) dermal exposure may have underestimated. In vitro and in
vivo studies indicate that skin permeability to 2-butoxyethanol differs considerably
between subjects (see chapter 9, Kinetics and Metabolism) . If for example, the estimates
are recalculated using the highest skin absorption rate (0.68 mg/cm2/h) observed in human
volunteers (Johanson et al 1988), the estimates of dermal exposure would be 3 to 4 times
higher. The impact on total exposure and the MOS would not be as great. The smallest
MOS would be 2.0 and 1.4 for 8 hour exposure during formulation of 30% and 60% 2-
butoxyethanol products, respectively.
Variability between subjects was also observed in inhalational absorption studies, so some
degree of uncertainty exists for the value used for bioavailability in vapour exposure
estimates. Similarly, the proportion of 2-butoxyethanol vapours dermally absorbed would
be expected to vary between subjects. Also, higher absorption under a workload may
result in a slight underestimate in the daily dose.
Importantly, when considering species differences, humans are less susceptible than rats to
the critical effect of 2-butoxyethanol, haemolysis. In addition, this effect is considered to
be transient at lower doses. Therefore, considering the range of MOS calculated, the
2-butoxyethanol 79
uncertainties involved, and the species difference, the risk of haemolytic effects in workers
exposed to 2-butoxyethanol during formulation is considered to be minimal.
Other ingredients
Many of the cleaning products which contain 2-butoxyethanol also contain other
hazardous ingredients, for example, rust removers may contain phosphoric acid. As the
overall health risk to workers may be increased by the presence of the other ingredients,
formulators need to consider all ingredients when assessing the health risk of cleaning
products containing 2-butoxyethanol.
13.3.6 Risk during use of cleaning products
Acute effects
The determination of the risk of acute adverse health effects such as eye and respiratory
irritation, headache and nausea during formulation was hampered by a shortage of data.
Some atmospheric monitoring data was available for the use of cleaning solutions
containing 2-butoxyethanol, however, TWA measurements were made rather than peak
measurements during specific cleaning operations. There are a number of different
methods of applying cleaning solutions, for example, mopping, scrubbing, and spraying,
and a wide variety of working conditions.
Cleaning products containing 2-butoxyethanol are often used in workplaces where control
measures are poor, for example, proper ventilation and protective equipment may not be
used during use in schools, offices, workshops and homes. Moreover, supervision in the
use of the products may be only occasional, for example, contract cleaners working by
themselves or in small groups, and specific training in the proper use of the products and
associated protective measures may be inadequate. In Australia, most of the reports of
adverse health effects such as eye and respiratory irritation, headache and nausea have
originated from workers such as school and office cleaners.
Many of the cleaning products are deliberately used in spray form. The resultant periodic
generation of aerosols leads to a greater risk of respiratory and eye irritant effects,
particularly in workplaces with little or no effective ventilation. Most of the reports of
irritation, headache and nausea in cleaners have been associated with the use of cleaning
products in spray form.
Vapour concentrations from single exposures are unlikely to be high enough to result in
respiratory or eye irritation under most routine operating conditions where the cleaning
operation is well-controlled, for example, when dilute solutions are used with good
ventilation. However, irritant effects and/or headache and nausea may be experienced in
work situations where aerosols are generated or where high vapour concentrations occur,
for example, during spray use, if heat is applied, or during the use of cleaning solutions
containing high concentrations of 2-butoxyethanol. Most cleaning products are diluted
before use, however, in some work situations, the product is used neat or diluted only
marginally, for example, degreasing, oven cleaning, floor stripping (see section 8.5).
Similarly, irritant effects may arise during the dilution of solutions as aerosols may be
generated during mixing, particularly if dilution is carried out in confined spaces without
adequate ventilation. The application of heat, either during dilution or use, and the
incidence of spills and maintenance work may also increase the risk of acute effects. It is
important to note that skin absorption can and does occur in the absence of local effects
such as irritation.
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Haemolysis
The risk of haemolysis in workers using cleaning solutions is very dependent on factors
such as the severity of the effect in humans, the duration of exposure, and the
concentration of 2-butoxyethanol in the cleaning products used. MOS ranging from 1.6 to
25 were calculated for the various exposure scenarios (see Table 15).
The lowest MOS for 8-hour use of a cleaning solution 30% 2-butoxyethanol is 1.6, so the
work situations of greatest concern occur when cleaning solutions containing high
concentrations are used, often undiluted, for long periods, for example, floor stripping,
washing cars.
Approximately 70% of cleaning products contain < 10% 2-butoxyethanol. For the use of
cleaning solutions containing 10% 2-butoxyethanol (undiluted) over 8 hours, the MOS is
4.5. However, most cleaning solutions are diluted substantially before use to a working
strength below 1%; the MOS for this scenario is 14 for 8 hours exposure.
In the cleaning services industry, most cleaners work part-time, with the average working
day 5 hours; the respective MOS for these scenarios for exposure to 1% and 10% solutions
are 22.5 and 7.3. A large proportion of school and office cleaners work part-time and
information indicates that they use dilute solutions, generally containing < 1% 2-
butoxyethanol. As the typical daily dose for a worker using cleaning products containing
2-butoxyethanol over 8 hours was > 1.6 mg/kg/day, the MOS for such a scenario would be
> 14. For a typical part-time work scenario (5 hours exposure), the MOS is > 22.5.
A number of uncertainties exist in the assessment of risk from exposure to 2-
butoxyethanol during cleaning operations (see Table 16). In particular, the exposure
assessment was hampered by the lack of data, especially dermal exposure data.
Inhalational exposure may have been overestimated as a consequence of selecting
maximum values from air monitoring studies. Similarly, dermal exposure may have been
overestimated by assuming worker exposure to be continuous, and not allowing for other
factors that might limit exposure, such as evaporation of 2-butoxyethanol from skin
surface and the use of protective gloves.
There is a degree of uncertainty regarding the rate of skin absorption. By using the rate of
0.2 mg/cm2/h (see Appendix 3), dermal exposure may have been underestimated. If for
example, the estimates are recalculated using the highest skin absorption rate (0.68
mg/cm2/h) observed in human volunteers (Johanson et al 1988), the estimates of dermal
exposure would be 3 to 4 times higher. The impact on total exposure and the MOS would
not be as great. The smallest MOS would be 1.2 and 0.74 for 5 and 8 hour exposure
during use of cleaning solutions containing 30% 2-butoxyethanol respectively, and 2.1 for
8 hour exposure to 10% solutions.
Other uncertainties inherent in the process included the influence of workload and the
variability in working conditions. Some cleaning operations are carried out under a
workload higher than normal, for example, washing cars, and may lead to increased
absorption. Poor working conditions, for example, poor ventilation or lack of proper
protective equipment, may also lead to increased absorption.
Importantly, when considering species differences, humans are less susceptible than rats to
the critical effect of 2-butoxyethanol, haemolysis. In addition, this effect is considered to
be transient at lower doses. Therefore, considering the uncertainties involved, and the
species difference, the risk of haemolytic effects in workers exposed to 2-butoxyethanol
during cleaning for the various scenarios considered, that is, use of cleaning solutions
containing less than 30% 2-butoxyethanol, is considered to be minimal.
Exposure estimates for use of cleaning solutions containing 30% 2-butoxyethanol indicate
that there is a concern in situations where there is prolonged exposure, particularly dermal
exposure, to solutions containing high concentrations (30% or more) of 2-butoxyethanol.
2-butoxyethanol 81
Other ingredients
As for formulators, employers of cleaners and other workers carrying out cleaning
operations using solutions containing 2-butoxyethanol also need to consider the health risk
posed by other ingredients in cleaning solutions when assessing the overall health risk as
other ingredients may increase the risk.
13.4 Areas of concern
From the risk assessment, there may be concern for the health of workers in some work
situations where exposure to 2-butoxyethanol may occur. Although little short-term
exposure data were available, sufficient information was available to conclude that there
may be a risk of eye and respiratory irritant effects, headache and nausea when high
vapour and/or aerosol concentrations of 2-butoxyethanol occur during acute exposures.
As 2-butoxyethanol is relatively non-volatile, these situations will most likely occur only
during the deliberate volatilisation of 2-butoxyethanol, for example, spraying or heating,
or when work practices are poor, for example, poor ventilation. Consequently, there is
concern for the health of workers, in relation to the irritant effects and headache and
nausea, in the following situations:
?use of products in spray form without adequate ventilation;
?use of heat during dilution or application without adequate ventilation;
?generation of aerosols;
?handling of spills if the proper procedures are not followed; and
?maintenance when the proper precautions are not taken.
From the risk assessment, it is unlikely that these effects will occur during manufacture,
but they may arise during formulation and cleaning.
Characterisation of the risk of the critical adverse health effect, haemolysis, in workers
potentially exposed to 2-butoxyethanol was hampered by a number of uncertainties in the
risk assessment process, particularly the lack of exposure data (especially dermal
exposure). A number of assumptions were needed to enable an assessment of risk,
however, for the scenarios considered, it is considered that the risk of haemolysis in
workers is minimal.
Based on the risk assessment of cleaning solutions containing 30% 2-butoxyethanol, there
is a concern in situations where there is prolonged exposure (particularly dermal exposure)
to solutions containing 30% or more of 2-butoxyethanol.
Although short-term repeated dose studies (up to 13 weeks exposure) provide some
information, it should be noted that the chronic effects of 2-butoxyethanol are largely
unknown. An NTP 2-year study in rats and mice is currently underway and will provide
some information on chronic effects of 2-butoxyethanol.
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14. Risk management
The risks to occupational health and safety posed by the manufacture of 2-butoxyethanol
and its formulation and use in cleaning products were identified and evaluated in the
previous chapter, Risk Characterisation. Areas of concern, that is, where the risk to
human health may be unacceptable, were established. This chapter focuses on the
management of those risks, with emphasis on the areas of concern. In general, many of
the strategies are applicable to other uses of 2-butoxyethanol and to the management of
potential risks to the environment and to the health and safety of the public at large.
The key elements of risk management described in this chapter for 2-butoxyethanol
include:
?control measures;
?hazard communication, including training and education;
?monitoring; and
?regulatory controls.
This chapter includes an assessment of the strategies currently employed and/or
recommended to manage health and safety risks associated with the formulation and use of
cleaning products containing 2-butoxyethanol. It includes an assessment of the MSDS and
labels submitted by formulators in response to the questionnaire sent to them during the
assessment period, and a review of the regulatory controls currently in place for 2-
butoxyethanol.
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, adequately controlled so as to minimise risks to health. A National Code of
Practice for the Control of Workplace Hazardous Substances provides further guidance in
the from of a hierarchy of controls, which should be considered to assist with this control,
namely:
?elimination;
?substitution;
?isolation;
?engineering controls;
?administrative controls;
?safe work practices; and
?personal protective equipment.
In relation to 2-butoxyethanol, particular care needs to be given to control measures to
minimise inhalational and dermal exposure.
14.1.1 Elimination
Elimination means the elimination of chemicals from a process, such as the use of a
physical process instead of a chemical process in cleaning. Elimination should be the first
option considered when minimising risks to health. However, in situations where it is
considered that a chemical process for cleaning is necessary then the second control option
to be considered is substitution.
2-butoxyethanol 83
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. Substitutes for 2-
butoxyethanol need to be thoroughly tested and, in general, they should demonstrate a
lower toxicity, irritancy and potential for skin absorption in humans.
Information on solvent substitution is available on the Internet, for example, the Solvent
Alternatives Guide (SAGE) and the Hazardous Solvent Substitution Data System
(HSSDS).
In some workplaces, the application of cleaning products in spray form has been
substituted with a procedure less likely to generate vapours or aerosols, for example,
applying the solution as a liquid stream onto the surface to be cleaned.
14.1.3 Isolation
The manufacture of 2-butoxyethanol is an enclosed process operated from a remote
control room so, during normal operation, workers are isolated from contact with 2-
butoxyethanol. Similarly, 2-butoxyethanol is transferred to road tankers and sealed
storage vessels via an enclosed system.
In some formulation plants, the process has been enclosed to a large extent to minimise
exposure. In some plants, 2-butoxyethanol is transferred via a manifold into the bottom of
the mixing tank filled with water, with the tank covered during mixing. For the filling and
packing operation, some formulators have enclosed the packing line at the point of filling
to minimise exposure and contain spills. In other cases, the filling process has been
automated to isolate workers from the process.
In the end-use of cleaning products containing 2-butoxyethanol, there is far less scope for
isolation of the worker as most of the products are applied in an open environment, for
example, cleaning offices, homes and schoolrooms. In a few cases, the work area is
enclosed, for example, the use of a spray booth or fume cupboard during the cleaning of
machinery parts in a workshop.
14.1.4 Engineering controls
At the 2-butoxyethanol manufacturing plant, local exhaust ventilation has been installed to
minimise exposure during the drumming-off of 2-butoxyethanol from storage tanks. In the
filling of road tankers, a mass flow meter has been installed to prevent overfilling and
therefore spillage.
In the formulation and end-use of cleaning products containing 2-butoxyethanol, good
ventilation is often used to minimise inhalational exposure to 2-butoxyethanol. This may
consist of local exhaust ventilation, dilution ventilation or the use of portable fans.
Several formulators indicated that exhaust fans were installed above the mixing tanks to
take any vapours away from the mixing area. In some cases, formulators have added
scrubbers to the exhaust system to prevent the escape of 2-butoxyethanol and other
contaminants to the atmosphere. On the filling line, some formulators indicated that they
had local exhaust ventilation at the point of filling to extract 2-butoxyethanol vapours
away from operators on the line. Good mechanical dilution ventilation is required in all
work areas in the formulation process and, in at least one plant, the ability to increase the
flow rate (number of changes per hour) in the event of spills has been provided.
Ventilation needs to be provided in accordance with the relevant Australian standards, in
particular AS 1668.2-1991 (Standards Australia 1991).
In the transfer of 2-butoxyethanol to the mixing tank during formulation, mass flow meters
can be installed to prevent over-filling and the consequent spillage. In at least one
formulation plant, the mixing tank and filling areas have been bunded so that any spills are
confined.
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In the end-use of cleaning products, the ventilation provided in workplaces is extremely
variable. In some applications, such as the use of a metal cleaning product in a mechanical
w o r k s h o p , effective local exhaust ventilation is provided to minimise exposure,
particularly if the product is used in spray form. Good general mechanical ventilation is
provided in many workplaces, for example, offices and some factories, to ensure an
adequate air flow in the vicinity of the worker. However, in a large proportion of work
situations, effective mechanical ventilation is not provided or switched on as the work is
conducted outside normal working hours and/or in workplaces such as schools and homes
not equipped with air-conditioning. Portable fans have been used in some work situations
where general mechanical ventilation is not available, for example, in school classrooms,
but great care is required in the positioning of the fans to ensure that vapours and aerosols
are directed away from exposed persons. Simple measures such as open doors and
windows have been shown to be helpful in reducing exposure.
As splashing and vapour and aerosol generation may occur during the dilution of cleaning
products before use, exposure to 2-butoxyethanol is likely to be lower where good
ventilation has been provided. Where available, the use of local exhaust ventilation for
dilution work is even more effective.
The design of containers used for dispensing the cleaning products is important in
minimising skin and inhalational exposure. For example, in order to reduce skin contact
during the application of cleaning solutions in liquid form, liquid stream containers such as
plastic wash bottles are being used by some cleaners to direct the cleaning solution onto
the surface instead of pouring the solution on to a cloth or rag. To reduce inhalational
exposure during spray use, the nozzles of spray applicators for cleaning solutions are often
designed to ensure that the spray droplets are not too fine.
14.1.5 Administrative controls
To reduce exposure to 2-butoxyethanol, at least one formulator has introduced job
rotation, where the operators are rotated from one part of the plant to another, with each
operator spending 2-4 hours per shift in a work area with potential exposure to 2-
butoxyethanol.
The prohibition of entry to an area which has just been cleaned or treated with a cleaning
product containing 2-butoxyethanol has also been used as a means of reducing exposure.
For example, in NSW schools, entry to classrooms is restricted until one hour after
cleaning.
14.1.6 Safe work practices
Appropriate safe work practices which have been used during the formulation, handling
and use of cleaning products containing 2-butoxyethanol include the following:
?minimising spray use;
?if spray is used, spray away from the breathing zone;
?prevention of aerosol generation during mixing and end-use (in spray use, nozzles
which produce a fine spray are not suitable);
?addition of 2-butoxyethanol as the last (or near last) ingredient during the mixing
process in formulation;
?prevention of splashing, particularly during formulation and dilution;
?avoidance of heat, for example, during mixing in formulation, during dilution of
cleaning product before application, and during end-use;
?storage of cleaning solutions in cool, well-ventilated areas;
?proper labelling of containers, including containers used for application of cleaning
solution;
2-butoxyethanol 85
?keeping lids on mixing tanks and caps on cleaning solution containers when not in use
(to prevent evaporation, splashing and spillage);
?containment of spills during handling, for example, by carrying out dilution in a sink or
bunded area;
?prompt clean-up of spills;
?proper cleaning of drums and other containers;
?proper disposal of contaminated containers and equipment no longer required;
?use of proper size funnels in dilution work to prevent spillage and skin contact;
?laundering of contaminated clothing;
?good housekeeping; and
?high standard of personal hygiene.
14.1.7 Personal protective equipment
Where other control measures are not practicable or adequate to control exposure, personal
protective equipment is generally used. As 2-butoxyethanol is readily absorbed through
the skin, the prevention of skin contact is particularly important.
Protective gloves are generally provided but some are not suitable for solutions containing
2-butoxyethanol. In a survey of different glove materials using the GlovES database, butyl
rubber and nitrile rubber were identified as being the most suitable for handling 2-
butoxyethanol (Keith et al 1990). NIOSH have also reported that butyl rubber has good
resistance to 2-butoxyethanol (NIOSH 1990). In selecting suitable gloves for use with
cleaning products, other ingredients in the solutions may need to be considered, for
example, high caustic or acid strength.
Covering of the arms and legs is good practice during the handling and use of cleaning
products containing 2-butoxyethanol, for example, overalls or long-sleeved shirts and
trousers. In formulation plants, overalls are often worn to protect the arms and legs. In
some cases, for example, in the handling of large quantities of undiluted or highly
concentrated solutions of 2-butoxyethanol, a butyl or nitrile rubber apron is often used to
reduce the risk of skin absorption in case of spills or splashing.
Similarly, socks and covered footwear provide good protection for the feet. In an
industrial environment where larger quantities of cleaning product may be handled, or
where corrosive substances such as sodium hydroxide may be present (for example, during
formulation) safety shoes or boots are often worn to provide greater protection.
For eye protection, chemical safety goggles are generally provided when handling large
quantities of solution, for example, during filling or emptying drums. In some cases (for
example, when splashing may occur) a face-shield has been found to be more suitable. In
general, protective eyewear is not worn during cleaning. In some cases, safety spectacles
are worn (for example, during spray application or if splashing may occur).
Respiratory protection is not normally required during the formulation or use of cleaning
products containing 2-butoxyethanol. In response to the questionnaire, a number of
formulators indicated that they provided half-face respirators for their workers, but they
generally elected not to wear them as they experienced no discomfort from vapours during
normal operations. However, in certain work situations, for example, during the cleanup
of large spills, a respirator was worn to reduce exposure. A half-face mask with organic
vapour cartridge has been found to be suitable.
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14.2 Emergency procedures
In the formulation of cleaning products, the availability of an emergency response plan to
deal with unexpected releases of 2-butoxyethanol such as large spills is good practice.
Standard emergency procedures are good policy wherever undiluted 2-butoxyethanol or
large amounts of concentrated cleaning solution containing the chemical are handled so
that exposure is minimised and action to remedy the situation can be taken swiftly.
14.3 Hazard communication
14.3.1 Assessment of Material Safety Data Sheets
Introduction
MSDS are the primary sources of the information needed to handle chemical substances
safely. Under the National Model Regulations for the Control of Workplace Hazardous
Substances (NOHSC 1994(c)) and corresponding State and Territory legislation, suppliers
are obliged to provide MSDS to their customers for all hazardous substances.
In 1994, prospective formulators of cleaning products containing 2-butoxyethanol were
requested to reply to a questionnaire and to send a copy of the MSDS and label for each of
these products (see section 7.2). The responses to the questionnaire identified 82
formulators and 434 cleaning products containing 2-butoxyethanol (see Appendix 1) and
409 MSDS were submitted. A representative sample was assessed, with the specific
objective to qualitatively assess the MSDS in terms of compliance with the National Code
of Practice for the Preparation of Material Safety Data Sheets (MSDS Code) (NOHSC
1994 (d)) and the SUSDP with regard to the provision of adequate information about 2-
butoxyethanol. In particular, specific health effects data and safe handling precautions
were assessed.
At the time of the survey in 1994, no State or Territory had enacted their legislation for
workplace hazardous substances and the revised MSDS Code and Approved Criteria had
only been published earlier that year. As a considerable time has elapsed since receipt of
the MSDS (late 1994), a random re-sample of MSDS took place in April 1996.
Methodology
A number of approaches have been used to assess MSDS (Lewis et al 1993; Kolp et al
1995). In this assessment, a qualitative evaluation method similar to that proposed by
Lewis was used, whereby information in the MSDS was assessed according to the MSDS
Code in the four specific information sections: product and ingredient identification, health
hazard information, precautions for use and safe handling information.
2-Butoxyethanol is currently on the List of Designated Hazardous Substances (the List) as
a hazardous substance with a concentration cut-off level of 12.5%. On the SUSDP, it falls
within the scope of `ethylene glycol monoalkyl ethers', which are listed on Schedule 6 for
preparations containing more than 10% glycol ether. Therefore, for the purposes of this
MSDS review, the products were divided into two groups, those containing 10% 2-
butoxyethanol, and those containing <10% 2-butoxyethanol, to broadly distinguish
`hazardous' products for 2-butoxyethanol from those which did not meet the criteria for
being `hazardous'.
MSDS for all 83 products identified as containing 10% 2-butoxyethanol were assessed.
Of these 83 products, four contained >60% 2-butoxyethanol, five had 30-60%, 56 had 10-
<30%, and 18 MSDS listed concentrations which did not fit into these specific proportion
ranges. Of the remaining 326 products with MSDS, 64 containing <10% 2-butoxyethanol
were selected in a way that covered various formulations and all companies. As a result, a
total of 147 MSDS were assessed.
2-butoxyethanol 87
Of 16 companies contacted in the random sample in April 1996, six had not made changes,
nine had made changes to some or all of their MSDS and one company no longer used 2-
butoxyethanol. In general, the changes were minor. Where appropriate, comment on the
changes has been incorporated into the following subsection.
Results and discussion
The results of the assessment are summarised in Table 17.
Table 17 - Findings of MSDS Assessment (1994 Survey)
Aspect > 10% 2-BE < 10% 2-BE
number % number %
Total 83 64
Ingredient- (2-BE concentration)
exact 2-BE concentration stated 17 20 5 8
no 2-BE concentration stated 2 2 5 8
correct proportion ranges used 48 58 40 78
incorrect proportion ranges used 16 19 4 6
Use
major uses indicated 72 87 61 95
spray use indicated 5 6 12 19
Hazard classification
statement of hazardous nature 1 1 3 5
SUSDP designation 60 72 n. a.
Health effects stated
skin absorption 21 25 7 11
eye irritation 70 84 53 83
skin irritation 63 76 50 78
nose/throat irritation 61 73 10 16
headache/nausea 35 42 21 33
data on chronic effects 16 19 2 3
Exposure standard
correct value stated 46 55 30 47
skin notation mentioned 14 17 13 20
Engineering controls recommended
`adequate' ventilation 58 70 41 64
`local' ventilation 19 23 7 11
Personal protection recommended
gloves (non-specific) 65 78 51 80
butyl or nitrile rubber gloves 4 5 1 2
respirator 19 23 10 16
respirator during spray use 11 13 13 20
Safe handling statements
skin protection for handling spills 2 2 4 6
Emergency telephone no. stated 28 34 27 42
Note: n. a. = not applicable; 2-BE = 2-butoxyethanol
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General information
Approximately 90% of the MSDS assessed were in the format recommended in the MSDS
Code. Several MSDS, all from one company, did not provide appropriate company details
such as Australian address or telephone number. In general, all MSDS stated the company
telephone number, but only 37% indicated the specific emergency telephone number.
For the purpose of hazard identification, the MSDS Code now specifies that a `statement
of hazardous nature' be included in the introductory section of a MSDS. The `statement of
hazardous nature' should contain one of the following phrases:
?`Hazardous according to criteria of Worksafe Australia'; or
?`Not classified as hazardous according to criteria of Worksafe Australia'.
The former statement should be used on MSDS for all workplace products containing
12.5% 2-butoxyethanol. However, it was found on the MSDS of only one of the 83
products containing 10% 2-butoxyethanol. Of the 64 products containing <10% 2-
butoxyethanol, only three were found to have a statement of hazardous nature. Hence
97% of the total MSDS assessed did not contain any statement of hazardous nature. This
omission could be explained by the fact that this statement has only been a requirement in
the MSDS Code since March 1994, and that, at the time of the survey, the hazardous
substances regulations were not in force in the State and Territory jurisdictions. The 1996
re-sample of MSDS indicated that approximately 50% of MSDS had incorporated a
statement of hazardous nature since the original survey.
Product and ingredient identification
The MSDS Code allows specific proportion ranges, namely <10%, 10-<30%, 30-60% and
>60%, to be used when stating ingredient concentration so that commercial confidentiality
of a formulation can be protected. Of the 147 MSDS assessed, 20% of products
containing 10% 2-butoxyethanol and 8% of those containing <10% 2-butoxyethanol
disclosed the exact concentration of the chemical; this more specific information may
often assist end-users in determining the hazards of the product. The allowable proportion
ranges were used in 58% and 78% of the products containing 10% and <10% 2-
butoxyethanol respectively. Non-standard proportion ranges, for example, 10-60%, <60%,
were used in 19% of the products containing 10% 2-butoxyethanol.
In addition to the `statement of hazardous nature', the hazardous nature of a product can
also be identified from the SUSDP, where any consumer product containing >10% 2-
butoxyethanol should be designated as a schedule 6 poison. Approximately 50% of the
products containing 10% 2-butoxyethanol had this designation on the MSDS.
The `Use' subsection is another important feature of a MSDS. Major uses were stated in
87% and 95% of products containing 10% and <10% 2-butoxyethanol, respectively. The
method of application, however, was not generally stated. Despite spray application being
indicated on many labels, use of the product in spray form was mentioned in only 12%
(17/147) of the MSDS. As spray use may increase the exposure to 2-butoxyethanol, it is
important to indicate `spray use' on the MSDS where applicable so that proper control
measures can be implemented during use of the product. The discrepancy between MSDS
and labels in this respect is noteworthy (see 14.3.2.).
In the re-sample of MSDS in April 1996, some of the MSDS which had been updated
contained less information about the ingredients than on the original MSDS, for example,
no identification or CAS number of ingredients, including 2-butoxyethanol. This occurred
only for some products not classified as hazardous.
2-butoxyethanol 89
Health hazard information
Based on the health hazard assessment in this report, this section of the MSDS should
include the following information about 2-butoxyethanol:
?acute effects (in humans)
?eye and respiratory irritation;
?degreasing action on skin;
?possibility of headache and nausea;
?coma and breathing difficulties after ingestion of large doses.
?chronic effects- effects on blood, kidney and liver observed in animal tests.
?ready absorption through skin.
O n l y 25% of the MSDS for products containing >10% 2-butoxyethanol provided
information on the skin absorption property. Eye irritation was stated in 84% of these
MSDS and nose and throat irritation in 73%.
Skin irritation was mentioned in 76% of MSDS. 2-Butoxyethanol appears to be only a
slight skin irritant in humans, but reddening and degreasing of the skin may occur and
contact dermatitis may result after repeated or prolonged exposure. The presence of strong
skin irritants such as sodium hydroxide and phosphoric acid in many of the cleaning
products may bias the results for this part of the assessment.
Headache and nausea were stated in 42% of the MSDS for products containing >10% 2-
butoxyethanol. Breathing difficulties and coma, which have been observed after the
ingestion of high doses of 2-butoxyethanol, were not indicated in any of these MSDS. The
effects of 2-butoxyethanol on blood, kidney and liver were stated in the `chronic effects'
subsection in 19% of these MSDS.
Clearly defined first aid instructions with standard statements are available for all
scheduled poisons listed in the SUSDP. As 2-butoxyethanol at concentrations >10% is
listed as a schedule 6 poison in the SUSDP (under ethylene glycol monoalkyl ethers),
standard first aid instructions are available and were used in the `first aid' subsection of all
the MSDS in this assessment.
Precautions for use
According to the MSDS Code, the Australian exposure standard should be used on the
MSDS where allocated. The Australian exposure standard for 2-butoxyethanol is 25 ppm
TWA (121 mg/m3) with a `skin' notation (NOHSC 1995). The numerical value was stated
as an Australian (or Worksafe) exposure standard on 52% of the total 147 MSDS, and as
an ACGIH `TLV' (also 25 ppm TWA) on 13% of the MSDS. The `skin' notation was
mentioned on only 18% of MSDS. The remainder had no exposure standard at all.
T h e MSDS Code specifies that `engineering controls' and `personal protection'
subsections should address the hazards identified for the substance. Under engineering
controls, guidance that good dilution ventilation be maintained was considered adequate.
A sole instruction to avoid breathing the vapour, found on a number of MSDS, was
considered inadequate.
For personal protection, all MSDS recommended wearing eye protective equipment, that
is, goggles or safety glasses, and 82% recommended the wearing of gloves. Butyl and
nitrile rubber gloves are considered the most suitable type of gloves for handling 2-
butoxyethanol but were specified in only 3% of the MSDS. A respirator was also
recommended in about 20% of the MSDS. The use of respirators may be an over-cautious
measure when using cleaning products containing 2-butoxyethanol as the only hazardous
substance, especially for those products containing <10% 2-butoxyethanol. However, it
may be appropriate in some situations where the product is applied in spray form, where
Priority Existing Chemical Number 6
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heat may be applied, or during the clean-up of large spills. It may also be appropriate for
products containing other respiratory irritants, for example, sodium hydroxide, where
caustic mists may be generated.
Safe handling information
In general, all cleaning products containing 2-butoxyethanol should be stored in cool, well
ventilated areas. About 56% of the 147 MSDS provided some information on the storage
and transport of products containing 2-butoxyethanol. However, over 95% of the MSDS
did not indicate the need for skin protection when containing or cleaning up spills.
Summary
The assessment indicated that a high percentage of the MSDS conformed to the format
recommended in the MSDS Code. With respect to the content of the MSDS, a number of
deficiencies were noted:
?no `statement of hazardous nature';
?correct proportion ranges not used for ingredients;
?no indication of spray use in the `use' section when applicable;
?poor indication that 2-butoxyethanol is readily absorbed through the skin;
?lack of information on the effects of prolonged or repeated exposure;
?poor indication of the most suitable types of gloves for handling 2-butoxyethanol;
?lack of information on the need for skin protection when dealing with spills; and
?the full Australian exposure standard not stated.
T h e most serious deficiencies were those related to the ready absorption of 2-
butoxyethanol through the skin from solution. Skin protection is most important in all
work situations, particularly during non-routine situations such as the cleanup of spills.
Proper indication of the exposure standard, particularly the `skin' notation, was poor.
The assessment of MSDS was not altered significantly by the re-sample of MSDS in April
1996. The only major change noted was inclusion of a statement of hazardous nature on a
large number of updated MSDS.
It was evident from the response to the questionnaire that most formulators had adopted
the policy of preparing MSDS for products whether they were classified as hazardous or
not. On examination of the re-sampled MSDS, it was noted that, unfortunately, some
suppliers had reduced the amount of information on MSDS for non-hazardous products.
A sample MSDS for 2-butoxyethanol, prepared in accordance with the MSDS Code, is
provided in this report as Appendix 6. The sample MSDS, prepared from information
obtained for the assessment of 2-butoxyethanol, 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.
14.3.2 Assessment of labels
Introduction
In 1994, information was received on 434 cleaning products containing 2-butoxyethanol.
Labels were supplied for 389 of these products. They were assessed for compliance with
some of the labelling requirements of the SUSDP (Australian Health Ministers Advisory
Council 1995) and the National Code of Practice for the Labelling of Workplace
Substances (the Labelling Code) (NOHSC 1994(e)). They were assessed in particular for
those requirements relating to safety directions/phrases and risk phrases and ingredient
statements relating to 2-butoxyethanol. In addition, labels which specified spraying as a
method of application were examined for the presence of any safety statements related to
inhalation of vapour or provision of ventilation.
2-butoxyethanol 91
In this assessment of labels, other mandatory requirements of labels were not analysed, for
e x a m p l e , directions for use, first aid procedures and information on emergency
procedures.
Products for domestic end-use are covered by the SUSDP and need to comply with
SUSDP labelling requirements. Under the SUSDP, products containing >10% 2-
butoxyethanol are schedule 6 poisons and must be labelled accordingly. After 1993,
industrial products were exempted from the SUSDP and should comply with the Labelling
Code. Products containing > 12.5% 2- butoxyethanol should be labelled in accordance
with the Labelling Code. Products used industrially and domestically need to comply with
both codes. For the purposes of this section, `hazardous' means `containing >10% 2-
butoxyethanol'. The requirements are as follows in Table 18.
Table 18 - Labelling Requirements
>10% >12.5% >20%
R20/21/22 R20/21/22, R37, R36*
Labelling code - risk
phrases
SUSDP safety directions SD1,4,8 SD1,4,8 SD1,4,8
Note: * R36 recommended in health hazard assessment (see subsection 12.3.2).
Key:
R20/21/22 Harmful by inhalation, in contact with skin and if swallowed
R37 Irritating to respiratory system
R36 Irritating to eyes
S24/25 Avoid contact with skin and eyes
SD1 Avoid contact with eyes
SD4 Avoid contact with skin
SD8 Avoid breathing dust (or) vapour (or) spray mist.
Under the Labelling Code, information on safe storage, handling and personal protection
should be provided on the label by the use of suitable safety phrases. For 2-butoxyethanol,
S24/25 are designated on the List as suitable safety phrases, however, others may be used
where appropriate. There are no concentration cut-offs specified for safety phrases.
Note that the safety phrases S24 and S25 are the same as SUSDP safety directions SD4
and SD1 respectively.
From information on labels and responses to the questionnaire submitted by the 82
formulators identified during this assessment, 59 indicated that their products were used
primarily as workplace substances in industries such as contract cleaning, hospitality, meat
processing, automotive, and the metals industries. Only eight formulators indicated that
their products were primarily for the domestic market. Most of the labels identified uses
for the product that had potential industrial application as well as domestic application,
such as floor stripping, carpet cleaning, window cleaning, engine degreasing, vehicle
c l e a n i n g , oven cleaning, cleaning of food preparation areas and equipment, and
disinfection of washrooms.
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Compliance with SUSDP
Safety directions
Of the 389 labels, 61 (16%) were for products which contained >10% 2-butoxyethanol.
Of the 61 labels, 35 (57%) had all three designated safety directions, 10 (16%) had two of
the three (SD1 and SD4), 3 (5%) had one (2 had SD1, one had SD8), while 13 (21%) had
none. That is, only 35 of the labels (57%) included a warning of the inhalational hazard
(SD8).
Ingredient statements
Labels were checked for compliance with section 2 of the SUSDP, which states that
immediate wrappers containing a poison shall be conspicuously labelled with the approved
name of the poison and a statement of the quantity or the strength of the poison. Section 5
of the SUSDP states that, in respect of a liquid poison in a liquid preparation, the statement
should be expressed as mass or volume of the poison per stated volume of the preparation.
The labels were checked for statements concerning the presence and concentration of 2-
butoxyethanol or ethylene glycol monoalkyl ether.
Of the 61 labels for hazardous products, 36 (59%) had a statement detailing the exact
concentration of 2-butoxyethanol, 6 (10%) had a statement indicating the presence of 2-
butoxyethanol without indicating the concentration, and 19 (31%) had no ingredient
statement. On 9 of the labels, the generic term `ethylene glycol monoalkyl ether' was used
instead of `2-butoxyethanol' or `ethylene glycol monobutyl ether'.
Compliance with the National Code of Practice for the Labelling of
Workplace Substances (the Labelling Code)
From information on labels and from formulators in their response to the questionnaire, all
products containing >10% 2-butoxyethanol could be used industrially. The cut-off for 2-
butoxyethanol as a hazardous ingredient in workplace substances is slightly different than
in the SUSDP (12.5% rather than 10%) but, for convenience, all labels for products
containing >10% 2-butoxyethanol (61) were assessed for their compliance with the
designated risk and safety phrases (or equivalent statements) (see Table 18). Findings
included the following:
?None of the 61 labels contained the risk phrase R20 (Harmful by inhalation), however
35 labels (57%) had the safety phrase S23 (Do not breathe gas/fumes/vapour/spray) or
the equivalent SUSDP safety direction SD8 (Avoid breathing vapour (or) spray mist);
?None contained the risk phrase R21 (Harmful in contact with skin), however 48 (79%)
had the safety phrase S24, which is the same as SUSDP safety direction SD4 (Avoid
contact with skin); and
?None contained the risk phrase R22 (Harmful if swallowed), where there is no
equivalent SUSDP safety direction.
Summarising, none of the labels contained the risk phrases for acute toxicity (R20/21/22).
Of the 61 products containing >10% 2-butoxyethanol, at least 20 products and possibly
another 20 contained >20% 2-butoxyethanol, which is the concentration cut-off for the
risk phrases R37 (Irritating to respiratory system) and R36 (Irritating to eyes). Findings
for the incidence on labels of risk and safety phrases relating to eye and respiratory
irritation included the following:
?None contained R37, but 35 of the 61 labels (57%) had the safety phrase S23 (Do not
breathe gas/fumes/vapour/spray) or the equivalent SUSDP safety direction SD8 (Avoid
breathing vapour (or) spray mist); and
?Only two (3%) had R36 (Irritating to eyes), but 48 (79%) had the safety phrase S25
(Avoid contact with eyes), which is the same as SUSDP safety direction SD1.
2-butoxyethanol 93
Summarising, many labels did not provide proper indication of the irritant effects of 2-
butoxyethanol.
The 61 labels for hazardous products were also checked for any statements relating to use
of gloves or provision of ventilation. Suitable safety phrases in the Worksafe labelling
system for workplace substances are:
?S36/37 Wear suitable protective clothing and gloves
?S51 Use only in well ventilated areas.
These safety phrases are relevant due to the ready skin absorption of 2-butoxyethanol, and
the frequent use of cleaning products in spray form. It was found that only six labels
(10%) contained S36/37 (or an equivalent statement), and only 14 (23%) contained S51
(or an equivalent statement).
Labels for spray products
The spraying of products containing 2-butoxyethanol increases the potential for exposure
to the chemical as the atmospheric concentration of 2-butoxyethanol may be increased due
to aerosol generation. A separate assessment of safety statements on the labels of these
products was undertaken in order to determine whether, as a group, any extra emphasis
was given to the increased risk associated with spraying.
Of the 389 labels, 163 identified spraying as a method of application. Of these, 73 listed
spraying as the only or the major method of application. General purpose surface cleaners
and glass/window cleaners were the most represented groups of products amongst the
spray products.
Of the 163 labels, 19 were for products containing >10% 2-butoxyethanol. Of these, eight
contained a safety phrase (or safety direction) warning against breathing of vapour (S23),
five contained a safety phrase (or safety direction) concerning ventilation (S51), and one
had both. Of the 144 labels for spray-use products containing <10% 2-butoxyethanol, 21
contained S23, seven contained S51, and three had both. Overall, only 45 (28%) of the
labels for spray products had one or more of safety phrases S23 or S51 (or equivalent
safety directions SD8, SD9 or SD10).
For spray use, a comparison was carried out between labels and MSDS for the products
surveyed in the MSDS assessment (see 14.3.1), with the results as tabled below for
products containing >10% 2-butoxyethanol and those with <10%.
The analysis found that where spray use was indicated on the label of a product, it was
rarely mentioned on the MSDS.
Table 19 - Indication of Spray Use on MSDS and Labels
>10% 2-BE <10% 2-BE
number % number %
Number of MSDS assessed 85 63
Spray use indicated on label but not MSDS 17 20 17 27
Spray use indicated on MSDS but not label 1 1 2 3
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Summary
Most cleaning products containing 2-butoxyethanol are used industrially but, at the time of
the survey in 1994, most companies had not yet updated their labels to meet the
requirements of the relatively new Labelling Code. Thus a large proportion of the
products were still labelled according to SUSDP requirements. However, many of the
labels for products containing >10% 2-butoxyethanol did not comply fully with SUSDP
requirements. Few of the labels fulfilled the requirements of the Labelling Code, in
particular, the assigning of risk phrases which may cover hazards not addressed by the
designated SUSDP safety directions (for example, acute toxicity). As no label contained
the risk phrase R22 (Harmful if swallowed), it can be assumed that no products containing
>12.5% 2-butoxyethanol complied fully with the requirements of the Labelling Code for
products that could reasonably be expected to be used in the workplace.
Other deficiencies in the labels included the following:
?Lack of warning of inhalational hazard for 43% of products containing >10% 2-
butoxyethanol;
?Omission of the ingredient statement on 31% of products containing >10% 2-
butoxyethanol; and
?Indication of presence of 2-butoxyethanol in the formulation but omission of the
concentration on 10% of products containing >10% 2-butoxyethanol.
Due to the increased health risk from spray use and the need for good ventilation and skin
protection, it would be advisable if more labels contained safety phrases (or safety
directions) to cover the following:
?Warning of inhalational hazard for all products which may be used in spray form;
?Need for the use of gloves for skin protection; and
?Need for good ventilation, particularly when products are used in spray form.
As only certain requirements were analysed in this assessment, no comment can be made
on compliance with other mandatory requirements, such as first aid and emergency
procedures. All labels should be checked against the full requirements of the SUSDP or
Labelling Code.
14.3.3 Education and training
U n d e r the National Model Regulations for the Control of Workplace Hazardous
S u b s t a n c e s , employers are obliged to provide training and education for workers
potentially exposed to hazardous substances, and their supervisors. In accordance with the
regulations, the program must address those areas where there may be a risk to health and
safety.
The key elements of an adequate induction and training program are listed in section 10.3
of the National Code of Practice for the Control of Workplace Hazardous Substances. For
2-butoxyethanol, the program should address those risks identified under section 13.4 of
this report. Specifically, matters which need to be addressed include:
?the health effects of 2-butoxyethanol;
?the skin absorption potential of 2-butoxyethanol, including the fact that it can be
absorbed without skin irritation, and that absorption may be greater when the skin is
cracked or damaged;
?explanation of MSDS and labels of cleaning products used;
?instruction in the proper handling and use of cleaning solutions containing 2-
butoxyethanol, including information about the additional risks posed by spray use and
the use of heat; and
2-butoxyethanol 95
?the specific protective equipment to be worn.
The Model Regulations stipulate that training and induction should be appropriate for the
workers concerned. The contract cleaning industry in particular comprises many workers
from a non-English speaking background, so the program should be suitably designed to
accommodate their needs. For example, visual training methods may be more suitable
than oral instruction and a fact sheet in another language may be more appropriate than a
complex MSDS in English.
In accordance with standard risk management practice, training and education needs for
workers should be reviewed on a regular basis.
In Australia, some programs have been instituted to train and educate suppliers,
supervisors and workers who may manufacture, supply or use cleaning products
containing 2-butoxyethanol. For most of the cleaning products, there are a number of
steps between the manufacture and importation of 2-butoxyethanol and final use of the
product. For example, the manufacturer may sell 2-butoxyethanol to a formulator who
may sell the cleaning product to a reseller who may then sell the product on to the final
employer. Education and training are beneficial at all steps in the process to ensure that
the proper information about the safe use of the cleaning products is passed on to the
employees using the product.
As sole manufacturer of 2-butoxyethanol in Australia, ICI Australia has conducted
Detergency Seminars for their customers and other interested parties, for example, union
and industry association representatives. The seminars have included information about
the health and environmental effects of the glycol ethers and 2-butoxyethanol in particular.
In some cases, formulators have comprehensive education programs in place for
employees. For example, S C Johnson Pty Ltd has an active hazard communication
program run by a special committee (separate from the OHS committee) which organises
regular training in chemical safety matters, reviews MSDS and conducts safety audits.
The program incorporates a written manual which has information about labelling and
MSDS and instructions for the safe handling of chemicals on the plant.
Some formulators also provide for each of their products a technical bulletin which gives
more detailed information than an MSDS about the technical aspects of the product, such
as information about the uses, methods of application and any special features of the
product.
The Australian Building Services Association (ABSA) has set up a number of training
courses for contract cleaning managers and supervisors and the cleaners themselves. The
structured training program for cleaners (see Appendix 5) can be used `in-house', for
example, by the qualified trainers of contract cleaning companies. ABSA also has audio
visual safety training programs available for use, and conducts seminars and workshops
for members on a variety of topics including occupational health and safety and
environmental issues.
In NSW, the relevant union, the LHMU - Miscellaneous Workers Division, has recently
developed a system of competency-based training with industry and government
representatives for workers in the contract cleaning industry.
At Worksafe Australia, an Occupational Health and Safety Management Resource Kit for
the Contract Cleaning Industry has been prepared as part of the organisation's Best
Practice program for industry (NOHSC 1996). The kit, compiled in consultation with
industry, unions and government, is available for companies in the contract cleaning
industry. The resource kit is suitable for use by formulators of cleaning products.
Under its Responsible Care program, the Plastics and Chemical Industry Association
(PACIA) has established a Code of Practice for Product Stewardship, which commits
members to addressing health and safety issues arising at any stage of the life cycle of the
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product. The program is supported by other members of the chemical industry such as the
Australian Chemical Specialties Manufacturers Association (ACSMA). As a means
towards fulfilling this commitment, suppliers need to make MSDS and other health and
safety information freely available to persons involved in the handling of these products at
any stage of the product's life cycle (for example, formulators, distributors and
downstream customers).
14.4 Monitoring and regulatory controls
14.4.1 Exposure standard
The current occupational exposure standard for 2-butoxyethanol in Australia is 25 ppm
TWA with a `skin' notation and was adopted from the ACGIH. The ACGIH criteria
d o c u m e n t a t i o n was issued in 1991. Other occupational exposure limits for 2-
butoxyethanol are in Table 20 below.
The current exposure standard is based on the haemolytic effects observed in experimental
animals. This assessment has concluded that in animal studies, the lowest NOAEL for
haemolytic effects is 25 ppm, based on a Dodd et al (1983) 90-day rat inhalational study.
This is the same study on which the current exposure standard is based.
No explicit numerical uncertainty factors appear to have been applied to the NOAEL
which has been used as the basis of the current exposure standard. This can be justified as
humans are less susceptible than rats to the heamolytic effects of 2-butoxyethanol. This
conclusion is based a range of data, including type and severity of the effect, intra- and
interspecies differences. The haemolytic effects are considered to be acute and transient.
Data indicate that the effect is due to changes to the red blood cell membrane and not bone
marrow toxicity. In vitro and in vivo studies have demonstrated that there are species
differences in susceptibility to the effect, with humans less sensitive than rats. For
example, in humans exposed to 195 ppm, osmotic fragility (a pre-haemolytic effect) was
not found. In addition, in vitro studies indicate that human red blood cells are at least 10
times less sensitive than rat red blood cells to haemolytic effects of BAA (the major
metabolite of 2-butoxyethanol and primary haemolytic agent). Therefore, while no
explicit factors have been included, there is an implicit uncertainty factor built into the
NOAEL and the current exposure standard is considered adequate with respect to
haemolytic effects.
Sweden has based their exposure limit primarily on other effects such as irritation and
headaches. The Swedish documentation states that these effects have been reported in
Swedish workplaces at the previous TLV of 20 ppm. These effects were reported in
humans in controlled studies at exposure levels of 100 ppm and above. Workers in
Australia (Appendix 4) have also reported these effects when using solutions containing <
10% 2-butoxyethanol, however the atmospheric levels are unknown. However, in
controlled studies by Johanson (Johanson et al 1986; Johanson and Boman 1991), no
adverse effects were reported when volunteers were exposed to 20 or 50 ppm for 2 hours.
NOHSC should review the occupational exposure standard for 2-butoxyethanol and
consider what the basis of the standard should be and use this assessment to prepare
updated Australian documentation.
It should be noted that air monitoring may not provide an accurate estimate of total
exposure in situations where significant dermal exposure occurs.
2-butoxyethanol 97
Table 20 - Occupational Exposure Limits
Country Exposure Limit
Belgium 25 ppm TWA (skin)
Denmark 25 ppm TWA (skin)
Finland 25 ppm TWA (skin)
France 25 ppm TWA (skin)
Germany (1990) 20 ppm TWA, 40 ppm STEL (skin), C
Italy 25 ppm TWA (skin)
Japan 50 ppm TWA (skin)
Netherlands 20 ppm TWA, 40 ppm STEL (skin)
New Zealand 25 ppm TWA (skin)
Norway 20 ppm TWA
10 ppm TWA+, 20 ppm STEL (skin)
Sweden
United Kingdom (HSE, 1991) 25 ppm TWA (skin)
USA - ACGIH (1987) 25 ppm TWA (skin)
- NIOSH (1990) 5 ppm TWA*
- OSHA 50 ppm TWA (skin)
Note: C = Pregnancy group C (no reason to fear risk of damage to the developing embryo when adhering
to MAK or BAT values).
+ Based primarily on `subjective effects of irritation, headache and tiredness'.
* Based on NOAEL of 50 ppm (Tyl et al 1984) and uncertainty factor of 10 for intraspecies
differences.
14.4.2 Atmospheric monitoring
U n d e r the National Model Regulations for the Control of Workplace Hazardous
Substances (NOHSC 1994 (c)), 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 (NOHSC 1994(f)). When the assessment indicates that the
risk of inhalational exposure is significant, atmospheric monitoring should be conducted to
m e a s u r e 2-butoxyethanol concentrations in the workplace as a precursor to the
introduction of proper control measures to reduce exposure. Monitoring should also be
conducted at a later stage to ensure that the measures are effectively controlling
atmospheric levels.
Analytical methods for the measurement of 2-butoxyethanol in air are detailed in Chapter
6, Methods of Detection and Analysis.
14.4.3 Health surveillance
From information obtained during the assessment, health surveillance is not routinely
conducted for workers exposed to 2-butoxyethanol. From published reports in the
literature, biological monitoring has been conducted in some work situations (outside
Australia) in order to estimate the combined inhalational and dermal exposure to 2-
butoxyethanol (see Table 5 in chapter 8, Occupational Exposure). Under the National
Model Regulations for the Control of Workplace Hazardous Substances (NOHSC 1994
(c)), 2-butoxyethanol is not on Schedule 3 (the list of hazardous substances for which
health surveillance is required).
Priority Existing Chemical Number 6
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NOHSC characterise biological monitoring as a form of health surveillance and has
established a number of points to consider in deciding whether health surveillance is
required, viz.:
?Is the substance hazardous to health?
?Is there evidence that the substance is injuring the health of workers, or is there reason
to suspect that this could be so, under the anticipated conditions of use?
?Is atmospheric monitoring, without health surveillance, sufficient to evaluate exposure
to the substance?
?Are health surveillance techniques available for the substance?
?Would health surveillance be beneficial to those at risk?
?Are the health surveillance methods likely to be acceptable to those at risk?
?Are the health surveillance methods practically and ethically acceptable?
2-Butoxyethanol is a hazardous substance. While there is no evidence of haemolytic
effects in workers during its use, there is evidence of acute effects including eye and
respiratory irritation, headache and nausea in some work situations involving the use of
cleaning products. As dermal exposure may be significant, and 2-butoxyethanol is readily
absorbed through the skin, atmospheric monitoring is not sufficient to evaluate total
exposure. While biological monitoring methods are available to estimate total exposure,
the benefits of health surveillance to those at risk are considered low. Considerations of
whether health surveillance would be acceptable to those at risk, or whether it would be
practically or ethically acceptable, are outside the scope of this assessment.
Although routine health surveillance is not recommended, the dermal exposure of workers
in Australia is largely unknown. To estimate the health risk to workers, modelling was
conducted in this assessment (see chapter 8, Occupational Exposure). To assist in the
development of risk management strategies for the various work scenarios, a study of
workers in the cleaning industry, including biological and atmospheric monitoring, should
be conducted to more accurately estimate dermal exposure. The merits of biological
monitoring for 2-butoxyethanol are discussed below.
Biological monitoring
Skin contact is one of the main routes of exposure to 2-butoxyethanol and toxicokinetic
studies in humans and animals have shown that skin absorption is significant. In vitro
studies have shown that the skin absorption rate may be higher from aqueous solution, and
controlled studies in volunteers have indicated that 2-butoxyethanol vapours can also be
absorbed via the skin (see section 9.2). For these reasons, atmospheric monitoring may
not provide a realistic indication of total exposure when significant dermal exposure
occurs.
Some biological monitoring of workers has been carried out overseas to estimate total
exposure, with measurements centred around the determination of BAA in urine at the end
o f the working shift (see Table 5 in chapter 8, Occupational Exposure). In a
comprehensive study (Vincent 1993), urinary BAA levels up to 371 mg/g creatinine were
obtained for car cleaners using a window cleaner containing 21.2% 2-butoxyethanol (for
5.3 hours). (Based on experimental data, the exposure standard of 25 ppm is equivalent to
approximately 250 mg BAA/g creatinine (NIOSH 1990)). The cleaners wore gloves, but
short-sleeved shirts were worn. In common with the results of other studies, urinary BAA
r e s u l t s in this study did not correlate well with atmospheric 2-butoxyethanol
concentrations.
No country or organisation has set a biological exposure index (BEI) based on biological
monitoring for 2-butoxyethanol. The ACGIH in the USA are in the process of setting a
BEI for 2-butoxyethanol, and some regulatory authorities have recommended that a BEI
2-butoxyethanol 99
be set for 2-butoxyethanol (NIOSH 1990). Biological monitoring has also been
recommended in a number of scientific papers (Johanson et al 1986; Rettenmeier et al
1993; Sakai et al 1993; Vincent 1993) as a means of more accurately estimating total
exposure of individuals to 2-butoxyethanol. The main reasons given for conducting
biological monitoring of workers exposed to 2-butoxyethanol have included the following:
?dermal exposure is greater than inhalational exposure in many work situations;
?atmospheric monitoring results do not correlate well with biological monitoring results,
so use of the former alone may not give an accurate measure of worker exposure;
?a suitable marker, BAA, is available; and
?biological monitoring more accurately reflects total uptake over a work shift, and takes
factors such as workload into account (see subsection 9.2.3).
In biological monitoring conducted to assess total exposure to 2-butoxyethanol, BAA is a
suitable marker for the following reasons:
?BAA is not normally found in the urine of humans, but it is found in appreciable
quantities in the urine of persons exposed to 2-butoxyethanol;
?BAA has an elimination half-life in humans of three to six hours, so it provides a good
indicator of exposure over a normal working shift;
?BAA is the primary haemolytic agent, so its concentration may more accurately reflect
potential toxicity; and
?reliable analytical methods for the determination of BAA in urine are available (see
section 6.3).
The main argument against using the determination of BAA in urine in biological
monitoring for 2-butoxyethanol is the variation in results between individuals exposed to
the same amount of 2-butoxyethanol. This is believed to be due to variations in dermal
u p t a k e , perhaps due to variations in skin thickness and permeability, and more
significantly, to variation in excretion rates. In addition, the presence of conjugated BAA
in humans raises the question as to whether the amount of BAA in urine is an accurate
reflection of the full extent of BAA exposure (Rettenmeier et al 1993).
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15. Public health assessment
15.1 Exposure
The public is unlikely to be exposed to 2-butoxyethanol during its importation,
manufacture or formulation into cleaning products in Australia. The manufacturing
process is enclosed and unused product is recycled into the process. Small amounts of 2-
butoxyethanol may be lost in spills or maintenance. Cleaning products containing 2-
butoxyethanol are produced by mixing the components at room temperature in open or
covered containers, with minor losses to the atmosphere due to the low vapour pressure of
the chemical. Small losses of 2-butoxyethanol may occur in aqueous rinses from mixing
containers, which may be disposed into the sewer system.
The public may be exposed to 2-butoxyethanol in a large number of domestic, and some
trade formulations, for example, floor strippers. Exposure is mainly by dermal contact,
and also by inhalation of vapours.
15.2 Health effects
The health effects of 2-butoxyethanol are described in chapter 10, Effects on Animals and
In Vitro Test Systems and chapter 11, Human Health Effects.
15.3 Health risk to the public
In light of the low concentration of 2-butoxyethanol in most domestic cleaning products
containing the chemical and the intermittent use of such products by the public, and
provided that normal precautions are taken to avoid skin, eye and inhalational contact, the
public health risk posed by cleaning products containing 2-butoxyethanol is expected to be
minimal.
2-butoxyethanol 101
16. Environmental assessment
16.1 Environmental exposure
16.1.1 Release
During the synthesis of 2-butoxyethanol at ICI's Matraville plant, release to air is low, due
to enclosure of the process and the low volatility of the chemical. Release to water will
occur when flushing spills to drain with copious amounts of water. Release to soil is
unlikely as the plant is confined to paved areas. Non-purified material or mixed product is
recycled back into the process, so there is virtually no disposal of waste product other than
through spills or maintenance. Drums used to transport 2-butoxyethanol are usually
recycled.
At formulation plants, mixing tanks are often covered and 2-butoxyethanol is usually
added last to the mixture, so there is little opportunity for escape of 2-butoxyethanol
vapours to atmosphere. In the filling process, 2-butoxyethanol apparently acts as a foam
suppressant, further reducing the risk of escape of vapour and liquid.
At one formulation plant visited, any spills in the production area are contained and
flushed to drain. Washings are neutralised and filtered before discharge to sewer, but any
2-butoxyethanol would pass straight through. To cater for any spills outside the
production area (for example, during storage) spill control stations are set up at the site
boundaries. Empty drums are cleaned and sent to drum reconditioners. 2-Butoxyethanol
loss was estimated as being minimal.
The predominant practice among product formulators is the disposal of tank rinsings from
the cleaning of blending tanks to sewer. For cleaning products, it is estimated that
approximately 0.1% of 2-butoxyethanol is lost to the sewer. In the responses to the
questionnaire sent to formulators, the vapour emissions from open blending tanks were
reported as being low.
Disposal practices for waste 2-butoxyethanol mentioned in the various MSDS for cleaning
products include incineration and burying, presumably in landfills.
When surfaces have been cleaned and washed down and any cleaning equipment rinsed
off, the resulting wash water containing 2-butoxyethanol is likely to be disposed to sewer.
16.1.2 Fate
2-Butoxyethanol will enter the environment via effluent at formulation sites and via wash
water from cleaning operations using the formulated products. The latter is the
predominant pathway. Biodegradation studies indicate that 2-butoxyethanol will be
readily degraded by micro-organisms present at sewage treatment plants.
Any 2-butoxyethanol that passes through sewage treatment plants and enter receiving
waters is likely to remain in the water column until biodegraded by micro-organisms
present in the water. 2-Butoxyethanol half-lives in surface water range from 7 days to four
weeks (Howard et al 1991).
Alcohols and ethers are generally resistant to hydrolysis and they do not absorb UV light
in the environmentally significant range (>290 nm). Therefore, 2-butoxyethanol is not
expected to undergo hydrolysis or direct photolysis in the environment (Howard et al
1993). The complete miscibility of 2-butoxyethanol in water suggests that volatilisation,
adsorption and bioconcentration are not important fate processes (Howard et al 1993).
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Due to its short atmospheric residence time and lack of direct photochemical activity, 2-
butoxyethanol does not fall within the definition of a volatile organic compound (VOC)
f o r the purposes of VOC emission estimates and the contribution of VOCs to
photochemical smog.
Calculations using the MacKay level 1 environmental partitioning model indicate that 2-
butoxyethanol will partition predominantly into water (84%) and to a lesser extent air
(16%), and with less than 0.1% associated with sediment/soil. These results were obtained
from the US EPA's ASTER database (US EPA Mid-continent Ecology Division (b)). It
should be noted that the Mackay level 1 model is an equilibrium, steady state system,
assuming no movement of the chemical between the various environmental compartments,
for example, air, water, soil, sediment (Mackay and Paterson 1982).
Incineration of waste 2-butoxyethanol will produce oxides of carbon.
D i s p o s a l of waste 2-butoxyethanol to landfills may result in contamination of
groundwater. A Koc of 67 for 2-butoxyethanol indicates it will be highly mobile in soil,
and it is unlikely to partition from the water column to organic matter contained in
sediments and suspended solids (Howard et al 1993). 2-Butoxyethanol has been detected
in aquifers underlying a municipal landfill and a hazardous waste site in the US (Howard
et al 1993).
Biodegradation test results
The biodegradability of 2-butoxyethanol was evaluated (Microtech Labs, pers. comm.
1993) using a test method (ISO 7827) based on the OECD ready biodegradability tests
(TG301A and 301E). The test was performed over a 7 day period and the level of organic
carbon was measured as an indicator for biodegradation. The inoculum used was mixed
activated sludge and secondary effluent, incubated at 20-25oC. 2-Butoxyethanol achieved
a biodegradation rate of 77.7% after 3 days and 100% biodegradation by the end of the
study. The result indicates that 2-butoxyethanol is readily biodegradable.
An additional study (CEFIC to ICI(UK) pers. comm. 1993) was provided for the
biodegradation potential of 2-butoxyethanol. The test methods used were the 20-day
Biochemical Oxygen Demand (BOD20) and the 28-day Closed Bottle Test (OECD TG
301D). The inoculums used in the BOD2 0 test and 28-day Closed Bottle Test were
domestic sewage micro-organisms and a mixture of soil and Hach Polyseed sewage micro-
organisms, respectively. The biodegradation rate at the end of the BOD20 and 28-day
Closed Bottle tests were 75% and 88%, respectively. The results indicate that 2-
butoxyethanol is likely to be biodegraded by micro-organisms in sewage treatment plants.
The ASTER ecotoxicity profile of 2-butoxyethanol calculated a BOD half-life from two to
16 days, confirming the ready biodegradability of 2-butoxyethanol. Test results provided
by notifiers from additional biodegradation studies (reports not provided but literature
references given) confirm the ready biodegradation of 2-butoxyethanol. The studies
included ready biodegradability (OECD TG 301E), inherent biodegradability (OECD TG
302B), and 5-day BOD studies.
Bioaccumulation
No bioaccumulation studies were provided. Because 2-butoxyethanol is miscible in water,
bioconcentration in aquatic systems is not expected to be an important fate process. Based
upon the log Ko w, a bioconcentration factor of 0.40 was calculated, which indicates 2-
butoxyethanol is unlikely to bioaccumulate in aquatic organisms (Howard et al 1993).
The ASTER ecotoxicity profile for 2-butoxyethanol has provided a calculated value for
bioaccumulation in fish. The calculated bioconcentration factor of two indicates that 2-
butoxyethanol is unlikely to accumulate in aquatic organisms.
2-butoxyethanol 103
16.1.3 Summary
2-Butoxyethanol will predominantly enter the environment from the disposal of wash
water from the cleaning process and also via effluent at sites where it is formulated into
cleaning products. 2-Butoxyethanol will be readily degraded by micro-organisms present
at sewage treatment plants and in the receiving waters and is unlikely to bioaccumulate.
2-Butoxyethanol disposed to landfill may leach to groundwater due to its expected high
mobility in soil and low adsorption potential.
16.2 Environmental effects
The following ecotoxicological study reports have been provided for 2-butoxyethanol.
Table 21 - Results of Ecotoxicological Studies Provided by Notifiers
Test Species Result Reference
Acute toxicity Fathead minnow 4d LC50 = 2137 mg/L (Bartlett 1979)
Acute toxicity Daphnia magna 2d LC50 = 835 mg/L (Bartlett 1979)
4d LC50 = 89.4 mg/L (US EPA 1984)
Acute toxicity Oyster (Crassotera
virginicas)
4d LC50 = 116 mg/L (US EPA 1984)
Acute toxicity Sheepshead minnow
4d LC50 = 130 mg/L (US EPA 1984)
Acute toxicity White shrimp
(Panaeus setiferus)
7d EC50 > 1000 mg/L (Dill and Minazzo 1988)
Growth inhibition Green algae
(Selenastrum
capricornutum)
16h IC50 > 1000 mg/L (Waggy 1989)
Growth inhibition Bacteria from
sewage
The above results indicate that 2-butoxyethanol is slightly toxic to oysters and practically
non-toxic to fish, aquatic invertebrates, algae and sewage micro-organisms. The above
studies were conducted according to US EPA toxicity test methods for aquatic organisms.
Test results from other aquatic toxicity studies (reports not provided but literature
references given) indicated that 2-butoxyethanol has low toxicity to aquatic organisms.
These included a 24h LC50 of 1650 mg/L for the goldfish and a 7d LC50 of 983 mg/L for
the guppy (Verscheuren 1983).
Additional information was obtained from the US EPA's AQUIRE database, which is an
aquatic toxicological database containing peer reviewed aquatic toxicity test results (US
EPA Mid-continent Ecology Division (a)). A selection of the results is tabled below.
Table 22 - Aquatic Toxicity Results in AQUIRE Database
Test Species Result
Growth inhibition Blue-green algae EC50 > 35 mg/L
Acute toxicity Daphnia magna 24h EC50 = 1815 mg/L
4d LC50 = 1250 mg/L
Acute toxicity Inland silverside
24h LC50 = 1000 mg/L
Acute toxicity Brine shrimp
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The results indicate that 2-butoxyethanol is practically non-toxic to fish and aquatic
invertebrates, and is slightly toxic to algae.
The ASTER ecotoxicity profile for 2-butoxyethanol has provided calculated QSAR values
for the acute and chronic toxicity to fish and aquatic invertebrates, with the results tabled
below.
Table 23 - QSAR Results Provided in ASTER Database
Test Species Result
Acute toxicity Daphnia magna 2d LC50 = 478 mg/L
Acute toxicity Bluegill sunfish 4d LC50 = 782 mg/L
4dLC50 = 1078 mg/L
Acute toxicity Fathead minnow
4d LC50 = 463 mg/L
Acute toxicity Channel catfish
4d LC50 = 532 mg/L
Acute toxicity Rainbow trout
Chronic toxicity Fathead minnow 32d MATC = 135 mg/L
The above results indicate that 2-butoxyethanol is practically non-toxic to fish and aquatic
invertebrates.
16.2.1 Summary
From the studies and test results provided by notifiers and the information gained from the
AQUIRE and ASTER databases, 2-butoxyethanol can be classified as being practically
non-toxic to fish, aquatic invertebrates and sewage micro-organisms, slightly to practically
non-toxic to algae and slightly toxic to oysters.
16.3 Environmental risk
2-Butoxyethanol is unlikely to present a hazard when it enters the environment via effluent
at sites where it is formulated into cleaning products and via the disposal of wash water
from cleaning operations. 2-Butoxyethanol will be biodegraded by micro-organisms
present at sewage treatment plants. Any 2-butoxyethanol that passes through the sewage
treatment plant and enters the receiving waters will be further degraded by micro-
organisms. 2-Butoxyethanol is of low toxicity to aquatic organisms and is likely to exist at
concentrations below that which would be hazardous to the environment.
Approximately 1000 tonnes of 2-butoxyethanol are formulated into cleaning products per
annum. Assuming 300 tonnes per year may be used in a metropolitan area, for example,
Melbourne, a worst-case situation may occur where 1000 kg enters the sewer per day as a
result of the formulation process and from the use of cleaning products. The resultant
concentration of 2-butoxyethanol at a sewage treatment plant (500 ML flow per day)
would be approximately 2 ppm. Further dilution in the order of 1:5 to 1:25 is likely to
occur in the receiving waters. Therefore the expected environmental concentration of 2-
butoxyethanol is likely to be in the order of sub-ppm.
These calculations are based on a worst-case scenario and assume no degradation of 2-
butoxyethanol by micro-organisms at the sewage treatment plant or in the receiving
waters. The calculations give an expected environmental concentration several orders of
m a g n i t u d e below toxic levels for aquatic organisms. Therefore, the risk of 2-
butoxyethanol to the environment is expected to be low.
2-butoxyethanol 105
17. Recommendations
The assessment focussed on the use of 2-butoxyethanol in cleaning products. However,
many of the recommendations are applicable to the other uses of 2-butoxyethanol.
17.1 Classification
17.1.1 NOHSC hazard classification
In accordance with the NOHSC Approved Criteria for Classifying Hazardous Substances
(NOHSC 1994(a)) and based on an assessment of health hazards, the recommended
classification for 2-butoxyethanol is:
?R20/21/22 Harmful by inhalation, in contact with skin, and if swallowed
?R36 Irritating to eyes
?R37 Irritating to respiratory system.
It is therefore recommended to NOHSC that the risk phrase `R36 Irritating to eyes' be
added to the classification of 2-butoxyethanol on the List of Designated Hazardous
Substances (NOHSC 1994(b)).
In determining whether a mixture containing 2-butoxyethanol is hazardous, the following
concentration cut-offs apply: 12.5% for R20/21/22 and 20% for R36 and R37.
It is recommended that the differences in concentration cut-offs for 2-butoxyethanol be
brought to the attention of the National Drugs and Poisons Scheduling Committee
(NDPSC) and NOHSC and, notwithstanding policy issues, that consideration be given to
harmonising on a cut-off of 10%.
17.1.2 SUSDP listing
At present, 2-butoxyethanol is listed on the SUSDP under `ethylene glycol monoalkyl
ethers', and is often listed on labels as such. However, the health effects of the members
of this class of chemicals vary significantly, so it is recommended that the NDPSC
consider a separate listing for 2-butoxyethanol.
It is recommended to NDPSC that, during consideration of a separate listing, they
reconsider the first aid instructions for 2-butoxyethanol, in particular the standard
statement to be used in case of swallowing (see 17.3.2).
17.1.3 Dangerous goods classification
This report confirms that 2-butoxyethanol should be classified as `harmful' by all three
routes of exposure under the EC Directive (on which the Australian Approved Criteria are
based). The criteria for acute inhalational toxicity are the same under the EC Directive
and the UN Recommendations on the Transport of Dangerous Goods (and the ADG
Code). Therefore, the recent decision by the UN Committee of Experts on the Transport
of Dangerous Goods to delist 2-butoxyethanol raises concerns regarding possible
differences in the application of the criteria and resulting inconsistencies between EU and
UN classifications of 2-butoxyethanol.
17.2 Control measures
2-Butoxyethanol is a hazardous substance which is acutely toxic, readily absorbed through
the skin and is an irritant to the eyes and respiratory system. In accordance with the
National Code of Practice for the Control of Workplace Hazardous Substances (NOHSC
1994(c)) exposure to hazardous substances should be prevented, or where that is not
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practicable, controlled so as to minimise risks to health. Control measures should be
implemented in accordance with the following hierarchy of controls.
In devising effective control measures for cleaning products containing 2-butoxyethanol,
suppliers and end-users should also consider the hazards of other ingredients in each
product, for example, phosphoric acid in rust removers and sodium or potassium
hydroxide in oven cleaners.
In relation to 2-butoxyethanol, particular care needs to be given to control measures to
minimise inhalational and dermal exposure. It should be noted that 2-butoxyethanol can
be readily absorbed through the skin and absorption can occur in the absence of irritation.
17.2.1 Elimination
To minimise risks to health, elimination should be the first control option considered.
Elimination is the removal of all chemicals from the cleaning process, such as by
employing a physical cleaning process or process redesign.
17.2.2 Substitution
Where elimination of 2-butoxyethanol from cleaning processes is not practicable,
substitution with another chemical or method of application should be considered. Any
substitution of 2-butoxyethanol should be with safer alternatives which have been
thoroughly tested and have demonstrated a lower toxicity, irritancy and potential for skin
absorption in humans.
With a view towards minimising exposure, formulators should consider reducing the 2-
butoxyethanol content in cleaning products. Similarly, it is recommended that methods of
application be reviewed by suppliers and end-users, for example, substituting spray use
with use as a liquid stream and application and dilution of cleaning products without heat.
17.2.3 Engineering controls
Formulation
It is appropriate that formulators take into account the health and safety hazards of all
ingredients in the formulation to arrive at a safe process that will minimise exposure to 2-
butoxyethanol.
Accordingly, it is recommended that the mixing and transfer process be enclosed and that
2-butoxyethanol be added to the mixing vessel in a safe manner, for example, as one of the
last ingredients. The mixing and storage tanks should be covered and exhaust fans
installed above them if they are not completely sealed. The mixing area should be bunded
so that any spills can be confined.
The packing line at the point of filling should be enclosed as much as possible, with local
exhaust ventilation recommended if complete enclosure is not achievable.
Good dilution ventilation in accordance with Australian standards is essential in all
production areas, with the ventilation rate capable of being substantially increased in case
of emergencies such as spillage. Total loss ventilation is recommended.
Cleaning
In some workplaces, for example, mechanical workshops, local exhaust ventilation can be
used, but in most work situations, for example, in the cleaning of schools and offices, this
is not practical. In these cases, dilution ventilation should be used as much as possible, for
example, air conditioning, portable fans, open windows and doors. Good ventilation is
essential during the dilution and mixing of solutions.
2-butoxyethanol 107
17.2.4 Safe work practices
Cleaning products should be formulated and applied in a manner which minimises
exposure. Recommended safe working practices include:
?avoidance of splashing and aerosol generation;
?avoidance of heat where possible;
?keeping of lids on tanks and containers;
?prompt clean up of spills;
?storage of products and cleaning solutions in cool, well-ventilated areas;
?use of appropriate personal protective equipment;
?minimisation of spray use during cleaning operations;
?if spray is used, spray away from the breathing zone;
?proper labelling of containers, including those used for diluted product during
application;
?prompt rinsing (with cold water) and cleanup of cloths and other equipment used in
cleaning, for example, mops, buckets and brushes, followed by safe disposal; and
?use of as little cleaning solution as possible during end-use.
17.2.5 Personal protective equipment
The following personal protective equipment is recommended where occupational
exposure to 2- butoxyethanol may occur:
?butyl or nitrile rubber gloves;
?protective clothing which includes protection of the arms, legs and feet; and
?eye protection when aerosols or vapours may be generated, for example, during
handling of large quantities, during dilution, when heat is used, or when splashing may
occur; eye protection may also be required when the product is applied as a spray.
All personal protective equipment should be in accordance with the relevant Australian
standards.
17.3 Hazard communication
17.3.1 MSDS
It is recommended that suppliers amend their MSDS where necessary in order to rectify
the deficiencies identified in this assessment.
Deficiencies in MSDS noted in the assessment indicate that attention needs to be paid to
the following:
?inclusion of a statement of hazardous nature where appropriate;
?under `Health Effects', state that 2-butoxyethanol is readily absorbed through the skin;
?under `Exposure Standard', state the complete Australian exposure standard;
?under `Engineering Controls', sufficient and appropriate guidance should be provided
for the use of cleaning products in spray form, for example, `Avoid inhalation of
vapours or spray', `Use local exhaust ventilation', or `Ensure good ventilation,
especially during spray use';
?under `Personal Protection', specify the use of butyl or nitrile rubber gloves; and
?under `Spills/Disposal', specify the use of the proper gloves, safety eyewear, and
protective clothing.
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17.3.2 Labels
It is recommended that suppliers amend their labels where necessary in order to rectify the
deficiencies identified in this assessment.
The assessment of labels showed that a number of products available to consumers were
not labelled with the safety directions required by the SUSDP. Products available to the
public which contain more than 10% 2-butoxyethanol must include the following first aid
instructions and safety directions on the product label, in accordance with the following
labelling standards recommended by the SUSDP for the ethylene glycol monoalkyl ethers
(and their acetates).
Safety directions:
?Avoid contact with eyes (SD1).
?Avoid contact with skin (SD4).
?Avoid breathing vapour (SD8).
First aid instructions:
?If poisoning occurs, contact a doctor or Poisons Information Centre.
?If skin contact occurs, remove contaminated clothing and wash skin thoroughly.
?If in eyes, hold eyes open, flood with water for at least 15 minutes and see a doctor.
In accordance with SUSDP, the current first aid instruction for ingestion of preparations
containing more than 10% 2-butoxyethanol (listed under ethylene glycol monoalkyl
ethers) is `If swallowed, and if more than 15 minutes from a hospital, induce vomiting,
preferably using Ipecac Syrup APF.' As 2- butoxyethanol is a respiratory irritant and a
large number of cleaning products which contain 2- butoxyethanol also contain
substances which may be corrosive, it is recommended that consideration of the specific
formulation be made when developing first aid advice. For example, when products are
formulated with a corrosive substance, the induction of vomiting would be contra-
indicated and the following instruction would be warranted: `If swallowed, do NOT
induce vomiting. Give water to drink.'
The assessment of labels also showed that the labels of cleaning products which are likely
to be used in the workplace, and contain 12.5% or more of 2-butoxyethanol, had
inadequate labelling, lacking the designated risk phrases or equivalent statements required
by the NOHSC National Code of Practice for the Labelling of Workplace Substances
(NOHSC 1994(e)). It is therefore recommended that, where necessary, suppliers of
products for industrial use amend their labels to conform to the Code. It is also
recommended that the following safety phrases be included (if not already covered by
equivalent SUSDP safety directions):
?S24/25 Avoid contact with skin and eyes
?S36/37/39 Wear suitable protective clothing, gloves and eye protection.
For all products which may be used in spray form in the workplace, it is recommended that
the following safety phrase be included on the label:
?S23 Do not breathe vapour or spray.
17.3.3 Training and education
In accordance with the National Model Regulations for the Control of Workplace
Hazardous Substances (NOHSC 1994(c)), it is recommended that workers potentially
exposed to 2-butoxyethanol be educated about its hazards and be trained in the safe
handling of 2-butoxyethanol and cleaning products containing the chemical. Accordingly,
2-butoxyethanol 109
it is recommended that suppliers, formulators and employers adequately educate and train
their customers and employees. Specifically, matters which need to be addressed include:
?the health effects of 2-butoxyethanol;
?the skin absorption potential of 2-butoxyethanol, including the fact that it can be
absorbed without skin irritation, and that absorption will be greater when the skin is
cracked or damaged;
?explanation of MSDS and labels of cleaning products used;
?instruction in the proper handling and use of cleaning solutions containing 2-
butoxyethanol, including information about the additional risks posed by spray use and
the use of heat; and
?the specific protective equipment to be worn.
The training and education of workers who use cleaning products containing 2-
butoxyethanol should be in accordance with the elements listed in the National Code of
Practice for the Control of Workplace Substances (NOHSC 1994(c)), and should include
specific information about the hazards of 2-butoxyethanol and the specific precautions
required for safe handling.
A s many cleaners employed are from a non-English speaking background, it is
recommended that practical and audiovisual methods be used as much as possible, and that
some written material about the hazards of 2-butoxyethanol and precautions for the safe
use of cleaning products containing the chemical be available in languages other than
English, for example, a single page facts sheet.
17.4 Exposure standard
I t is recommended that NOHSC use this assessment report to prepare updated
documentation for the occupational exposure standard. It is also recommended that
NOHSC consider whether the basis of the exposure standard should be haemolytic effects
or other effects such as irritation, nausea and headache, as overseas regulatory agencies
have adopted a lower standard based on these effects.
17.5 Biological monitoring and biological exposure index
It is recommended that NOHSC develop guidelines for biological monitoring (including
analytical method, time of sampling, type of specimen, etc.). These guidelines would
assist in the further work recommended to investigate skin absorption (see 17.7.2) and
provide assistance to medical practitioners investigating possible exposures to 2-
butoxyethanol.
In developing guidelines for biological monitoring and following the further study to
investigate the extent of skin absorption, NOHSC should consider whether it is appropriate
to establish a Biological Exposure Index (BEI).
17.6 Disposal
It is recommended that waste 2-butoxyethanol not be disposed of to landfill because of its
high mobility, low abiotic degradation and its demonstrated ability to leach into
groundwater from landfills in the USA. Preferred disposal options are incineration,
recycling or removal by a licensed reclaimer.
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17.7 Health hazards
17.7.1 Case reports
I t is recommended that instances of adverse health effects after exposure to 2-
butoxyethanol be fully documented and investigated by the employer and that the cases be
reported to the Director, Chemicals Notification and Assessment at Worksafe Australia.
17.7.2 Further testing
A number of gaps were identified in the knowledge base regarding the health effects of 2-
butoxyethanol, including:
?the mechanism of action of BAA on the red blood cell in various species, in particular,
comparative data on the rat (sensitive species), guinea pig (insensitive species), and
human (species of concern) to enable better extrapolation from animals to humans;
?clarification of the skin absorption rate of 2-butoxyethanol from various strengths of
aqueous solution and comparison with the rate for undiluted 2-butoxyethanol; and
?the extent of dermal exposure for the various work scenarios.
Skin absorption is a significant route of exposure and there is a degree of uncertainty in the
estimates of dermal exposure in this assessment. It is therefore recommended that a study
be conducted, including biological and atmospheric monitoring, to more thoroughly
understand the extent of skin absorption of 2-butoxyethanol for workers in the cleaning
industry.
It is noted that a 2-year inhalational study in rats and mice is currently being conducted
under the NTP, and an epidemiological study in workers exposed to glycol ethers,
including 2-butoxyethanol, is under way in France. These studies will be reviewed when
available as a secondary notification.
2-butoxyethanol 111
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 2-butoxyethanol, a secondary notification may be required if significant new
information about its health and/or environmental effects becomes available, for example,
the results of a 2-year inhalational study in rats and mice currently being conducted under
the NTP, and the results of an epidemiological study in workers exposed to glycol ethers,
including 2-butoxyethanol, in France.
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APPENDIX 1
CLEANING PRODUCTS CONTAINING 2-BUTOXYETHANOL
The list of cleaning products includes the main use of the product and the concentration of
2-butoxyethanol in the formulation. The list also denotes whether an MSDS and label was
provided for the assessment of 2-butoxyethanol in cleaning products.
The list was compiled from responses to a questionnaire sent to formulators in late 1994. It
is not intended to be a comprehensive listing. Formulations may have changed since the
preparation of this list.
2-butoxyethanol 113
Appendix 1 - Cleaning products containing 2-butoxyethanol
Product MSDS Label % 2-BE Formulator Use
2-534 Acidic Train Wash Detergent Y Y <10% Applied Chemicals Pty Ltd Removal of brake dust on railway rolling stock and equipment
3-123 Multi Purpose Detergent Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
3-273 General Purpose Pine Detergent Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
3-275 General Purpose Cleaner/Deodorant Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
3M Brand 001 Glass Cleaner Y Y 5-10% 3M Australia Pty Ltd Glass/window cleaner ; Laminate cleaner
3M Brand Glass and Laminate Cleaner Y Y 10-15% 3M Australia Pty Ltd Glass/window cleaner ; Laminate cleaner
3M Brand Glass and Laminate Cleaner Y Y 5-10% 3M Australia Pty Ltd Glass/window cleaner ; Laminate cleaner
3M Topline Brand Floor Conditioner Y Y 10-15% 3M Australia Pty Ltd Floor stripper
4-415 Hot Tank Emulsion Degreaser Y Y <10% Applied Chemicals Pty Ltd Degreaser
4-492 General Purpose Detergent Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
4-500 General Purpose Solvent Degreaser Y Y <10% Applied Chemicals Pty Ltd Automotive degreaser
4-852 Alkaline Detergent Degreaser Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
4-855 Multi Purpose Spray Cleaner Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
8-240 Dewatering/Corrosion Preventive Y Y <10% Applied Chemicals Pty Ltd Surface cleaner/rust preventative
8-370 Concentrated Degreasing Solvent Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
8-480 Specialty Solvent Cleaner Y Y 93% Applied Chemicals Pty Ltd Ink removal
A.S.L. Cleaner Y Y 5% Demack Enterprises Surface cleaner - general purpose
Acidiquat-NF cleaner/sanitiser Y Y <10% Applied Chemicals Pty Ltd Surface cleaner/sanitiser in food industry
Action Plus Y Y <10% Newland Products Pty Ltd Laundry detergent
Activ D.O.T Y Y <10% Peerless Emulsion Products Pty Ltd Surface cleaner - heavy duty
AD 25-D Y N <10% Ardelve P/L Surface cleaner - heavy duty
AD 25-E Y N <10% Ardelve P/L Surface cleaner - heavy duty
Agri Chem Sooty Mould Cleaner Y Y <10% Castle Chemicals Pty Ltd Removal of sooty mould from citrus fruit
Aim U.V. Wash Y Y <50% Recochem Inc U.V ink removal from rollers and presses
Al-U-Clean Y Y <10% Chemsolve Aluminium and stainless steel cleaner
Alkaclean Y Y 12% Micelle Chemical Products Pty Ltd Surface cleaner - general purpose
Priority Existing Chemical Number 6
114
Alkafoam Y Y <10% Elite Chemicals Pty Ltd Surface cleaner - recommended for food processing areas
All Clear Y Y <10% Chemsolve Glass/window cleaner
All Purpose Cleaner Y Y 10% Jamac-Safe and Clean Pty Ltd Surface cleaner - heavy duty
All Purpose Cleaner Y Y <5% IDL Chemicals Pty Ltd Surface cleaner - general purpose
All Purpose Stripping Emulsion Y Y 20.6% Peerless Emulsion Products Pty Ltd Floor stripper
All Surface Cleaner Y Y 12% Micelle Chemical Products Pty Ltd Surface cleaner - general purpose
Aluwash Y Y <10% Acid etch cleaner for aluminium surfaces
Novamax Technologies (A'Asia) Pty
Ltd
Amdet Y N 11.2% Floor stripper
Bunzl Ltd (reseller - products
manufactured by JC Allen)
Ammonia Free Stripper Y N 30.5% Bunzl Ltd (reseller - products Floor stripper
manufactured by JC Allen)
Amsolve Y Y <10% Agar Chemicals Carpet stain remover
Anglomoil Degreaser N Y 0.5% Anglo Design Pty Ltd Surface cleaner - heavy duty
Apple Clean Y Y <10% Castle Chemicals Pty Ltd Detergent for removal of fats and greasy soils from apples
Aquafoam Y Y <10% Ecolab Pty Ltd Surface cleaner - general purpose
Aquasolve Y Y 1-10% Challenge Chemicals Aust. Cleaning of metal parts (esp. automotive components) in soak
tanks
Assault Y Y 0-10% True Blue Chemicals Pty Ltd Floor stripper
Automatic Carpet Shampoo Y Y Not stated Peerless Emulsion Products Pty Ltd Carpet cleaner
Autowash Y Y <5% Cleveland Chemical Co. Pty Ltd Vehicle surface cleaner
Away Y Y <10% Alliance Technology Pty Ltd Surface cleaner - general purpose, for use in food processing
areas
Betz 407C Y N <10% Betz Laboratories Pty Ltd Cooling water cleaner
Blast Off Y Y <10% Shamrock Chemicals Pty Ltd Surface cleaner - heavy duty
Blast Off Y Y 1-10% Lustral Removal of wax from new vehicles
Blue Lazer Y Y 0-10% True Blue Chemicals Pty Ltd Surface cleaner/disinfectant - washrooms
Break Up Y Y <10% S.C.Johnson Surface cleaner - heavy duty
Breakthru Y Y <10% Castle Chemicals Pty Ltd Surface cleaner - heavy duty
Brill Y Y <7% BettaChem Chemical Manufacturers Glass/window cleaner
2-butoxyethanol 115
Brilliant Y Y <10% Chemsolve Laundry detergent
Bushland Industrial Multipurpose Cleaner Y N <10% Campbell Brothers Limited Surface cleaner
Butron Y Y 10-<30% Ecolab Pty Ltd Laundry detergent
Carpet Care Y Y Not stated Alliance Technology Pty Ltd Carpet cleaner ; Upholstery cleaner
Carpet Prespray N Y Not stated Demack Enterprises Carpet cleaner
CC Extractor Y Y 1-11% Challenge Chemicals Aust. Carpet cleaner
CC Prespray Y Y 1-10% Challenge Chemicals Aust. Carpet cleaner
CC Solspray Y Y 1-10% Challenge Chemicals Aust. Carpet cleaner
Cerfa Kleen CST Y N <10% Houghton Australia Pty Ltd Surface cleaner
Champ Y Y <10% Newland Products Pty Ltd Oven cleaner
Charger Y Y 1-10% Challenge Chemicals Aust. Laundry detergent
Chemkleen Plus Y Y 1.5% Demack Enterprises Surface cleaner - general purpose
Clean Easy Y Y "low" Dari Cleaning Products Surface cleaner - heavy duty (for floors)
Cleans All Y Y 1-10% Cyndan Chemicals Surface cleaner - general purpose
Cleanscene Y Y <1% Cleveland Chemical Co. Pty Ltd Glass/window cleaner
Clear Vision Y Y Not stated Young's Motor Products Pty Ltd Glass/window cleaner ; Windscreen cleaner additive
Clearclean Plus Y Y <10% S.C.Johnson Surface cleaner - general purpose
Clearstrip MK II Y Y <10% S.C.Johnson Floor stripper
Clearview Y Y <10% Cleveland Chemical Co. Pty Ltd Glass/window cleaner
Clockwork Y Y 1-10% Lustral Surface cleaner - heavy duty ; Oven cleaner
Colorfast Y N 10-30% Cleancare of Australia Carpet cleaner ; Upholstery cleaner
Commando Y Y <10% Castle Chemicals Pty Ltd Carpet cleaner
Complete Y Y <2% Cleveland Chemical Co. Pty Ltd Surface cleaner and disinfectant for bathrooms
Continuum Y Y <10% IDL Chemicals Pty Ltd Laundry detergent
Corexit 6792ES Y Y <10% Corrosion inhibitor
Nalco/Exxon Energy Chemicals
Australia Pty Ltd
Corexit CL 8561 Y Y <10% Surface cleaner - general purpose
Nalco/Exxon Energy Chemicals
Australia Pty Ltd
Priority Existing Chemical Number 6
116
Countdown Y Y <10% Elite Chemicals Pty Ltd Surface cleaner - general purpose
Countdown Blue Y Y <10% Elite Chemicals Pty Ltd Surface cleaner - general purpose
Cross Link Strip Y Y 1-10% Dominant (Australia) Pty Ltd Floor stripper
Crystal Clear Y Y <10% Amway of Australia Pty Ltd Window/glass cleaner
Crystal Clear Chemkleen Y Y Not stated Crystal Clear (reseller) Surface cleaner - general purpose ; Fabric cleaner
Crystal Clear Degreaser Y Y Not stated Crystal Clear (reseller) Surface cleaner - general purpose
Crystal Clear Stripper Y Y Not stated Crystal Clear (reseller) Floor stripper
Crystal Clear Window Cleaner Y Y Not stated Crystal Clear (reseller) Glass/window cleaner
CT 13 Y Y 7% Castle Chemicals Pty Ltd Removal of travel wax from new vehicles
D-Rust Y Y <10% Chemsolve Rust remover ; Masonry cleaner
Deckhand Y Y <10% Elite Chemicals Pty Ltd Surface cleaner - recommended for boats
Degreaser Y Y Not stated Demack Enterprises Surface cleaner - general purpose
Degreaser N N Not stated Anglo Design Pty Ltd Surface cleaner - general purpose
Degreaser Detail Y Y <5% Cleveland Chemical Co. Pty Ltd Surface cleaner - general purpose ; Engine cleaner
Degreaser STG Y Y <5% Cleveland Chemical Co. Pty Ltd Surface cleaner - general purpose ; Engine cleaner
Degreaser, (Hot Plate and Oven Cleaner) Y Y 5% Maxpro Detergents Pty Ltd Oven cleaner
Degreaser-O3 Y Y <5% Cleveland Chemical Co. Pty Ltd Surface cleaner - general purpose ; Engine cleaner
Delo Y Y low Dari Cleaning Products Oven cleaner
Delvolin LLC Y Y <1.5% Tulloch & Kapeco Pty Ltd Laundry detergent
Dewaxer/solvent cleaner Y Y <2% Micelle Chemical Products Pty Ltd Surface cleaner / Removal of travel wax from new vehicles
Diverfos F69 Y Y <1% Combined cleaner/phosphate powder
Novamax Technologies (A'Asia) Pty
Ltd
Diverfos F69S Y Y <1% Novamax Technologies (A'Asia) Pty Combined cleaner/phosphate powder
Ltd
Dry Foam Y Y <10% Castle Chemicals Pty Ltd Carpet cleaner
Dry Foam Y Y 1-10% Lustral Carpet cleaner
Dry'N'Wet Spotter Y N <10% Cleancare of Australia Carpet cleaner ; Upholstery cleaner
Duroclean 16B N Y Not stated Immersion cleaner for aluminium
Novamax Technologies (A'Asia) Pty
Ltd
2-butoxyethanol 117
Duroclean 19A Y Y <5% Spray or immersion cleaner for aluminium
Novamax Technologies (A'Asia) Pty
Ltd
Duroclean 40 Y Y <5% Spray or immersion cleaner for aluminium
Novamax Technologies (A'Asia) Pty
Ltd
Easy Solve Y Y 20% Elite Chemicals Pty Ltd Laundry detergent
Easy-Up Y Y 12% Castle Chemicals Pty Ltd Floor stripper
Easyclean Y Y <10% Challenge Chemicals Aust. Surface cleaner - heavy duty
Eazykleen Y Y Not stated Dynamic Laboratories Surface cleaner - heavy duty
ECTA Y Y <10% Chemsolve Cleaning of exhaust scrubber tanks of locomotives and
personnel carriers used in underground mining operations.
Energen Y Y <10% Gibson Chemicals Limited Floor stripper
Energizer Y N 10-30% Cleancare of Australia Carpet cleaner
Extra Carpet Pre-Spray Y Y "minor %" Agar Chemicals Carpet cleaner
Extract Y Y <10% Castle Chemicals Pty Ltd Carpet cleaner ; Upholstery cleaner
Extractomax Y Y 5% Carpet cleaner
North Queensland Chemicals and
Paints
Farmland Window Cleaner Y Y <10% Pax Australia Pty Ltd Glass/window cleaner
Fibretone Carpet Shampoo Y Y 3.8% Peerless Emulsion Products Pty Ltd Carpet cleaner
First Step Y Y Not stated The Major Chemical Co. Pty Ltd Carpet cleaner
Fleet Y Y <10% Gibson Chemicals Limited Surface cleaner - general purpose
Flexiclean Y Y <10% Surface cleaner - heavy duty
Kempo Manufacturing Company Pty
Ltd
Floorstar TFR II Y Y 18-21% Peerless Emulsion Products Pty Ltd Floor stripper
Floorstrip Y Y 10-30% Challenge Chemicals Aust. Floor stripper
Florstrip Y Y 10-60% Agar Chemicals Floor stripper
Formula 208B Y Y <5% Gibson Chemicals Limited Surface cleaner - general purpose
Formula 217B Y Y 1-10% Gibson Chemicals Limited Surface cleaner - general purpose
Formula 245 Y Y <10% Newland Products Pty Ltd Surface cleaner - general purpose
Formula 650S Y Y Not stated Gibson Chemicals Limited Electrical equipment and metal solvent cleaner
Formula 951B Y Y <10% Gibson Chemicals Limited Surface cleaner for use on aluminium and stainless steel
Priority Existing Chemical Number 6
118
Formula 955B Y Y Not stated Gibson Chemicals Limited Aircraft exterior cleaner
Freshline Floor Cleaner and Deodorant N Y Not stated Nature's Land Products Floor cleaner
Freshline Window and Mirror Cleaner N Y Not stated Nature's Land Products Glass/window cleaner
Fulgeo 213 Heavy Duty Y Y <10% Industrial Cleansers Pty Ltd Surface cleaner - heavy duty
Fulgeo Decarboniser Y Y <10% Industrial Cleansers Pty Ltd Decarboniser
Fulgeo Graffiti Remover Y Y 10-60% Industrial Cleansers Pty Ltd Surface cleaner - graffiti remover
Fulgeo K.B.4 Y Y <10% Industrial Cleansers Pty Ltd Vehicle surface cleaner
Fulgeo Meatworks Multi-Cleanse Y Y <10% Industrial Cleansers Pty Ltd Surface cleaner - abbatoir meat hooks, floors, walls, plant,
vehicles
Fulgeo Sanitiser Y Y <10% Industrial Cleansers Pty Ltd Surface cleaner - general purpose
Fulgeo Unique Y Y <10% Industrial Cleansers Pty Ltd Surface cleaner - heavy duty ; Floor stripper
Fulgeo Window Cleaner Y Y <10% Industrial Cleansers Pty Ltd Glass/window cleaner
Gemini Y Y <10% Elite Chemicals Pty Ltd Surface cleaner - recommended for meat and food processing
establishments
General Purpose Cleaner Y Y 16% Micelle Chemical Products Pty Ltd Surface cleaner - general purpose
Glance Glass Cleaner Y Y 30% S.C.Johnson Glass/window cleaner
Glass & Chrome Cleaner Y N 5-10% Castrol Australia Pty Ltd Glass/window cleaner
Glass Act (3-180) Y Y <10% Applied Chemicals Pty Ltd Glass/window cleaner
Glass and Laminate Cleaner (Trigger Pack) Y Y 5-10% 3M Australia Pty Ltd Glass/window cleaner ; Laminate cleaner
Glass Cleaner Y Y Not stated Young's Motor Products Pty Ltd Glass/window cleaner
Glaze Y Y 1-10% Challenge Chemicals Aust. Glass/window cleaner
Greasaway Y Y Not stated Cleveland Chemical Co. Pty Ltd Surface cleaner ; Machine parts degreaser
Grease Lightning Y Y 1-10% Lustral Surface cleaner - general purpose
Greasoff Y Y 5-10% Surface cleaner - heavy duty
North Queensland Chemicals and
Paints
Greasol Y Y Not stated Alliance Technology Pty Ltd Surface cleaner - heavy duty, for removal of animal or
vegetable fats.
Green Lazer Y Y 0-10% True Blue Chemicals Pty Ltd Surface cleaner/disinfectant - general purpose
Greencare Multipurpose Spray and Window Y Y <10% w/w Harcros Chemicals Limited Window cleaner / Surface cleaner - general purpose
Cleaner
2-butoxyethanol 119
Greencare Prewash Stain Remover Y Y 10-30% Harcros Chemicals Limited Prewash stain remover
Grenade Y Y 10-30% True Blue Chemicals Pty Ltd Floor stripper
Grill, BBQ & Hot Plate Cleaner Y Y <10% Chemwell Products Pty Ltd Oven cleaner
GSB Fast U V Wash Y N 10-60% GSB Chemicals Ink and resin removal from silk screens
H.D.C Y Y <10% Newland Products Pty Ltd Surface cleaner - heavy duty
Hammer Y Y 15.4% The Major Chemical Co. Pty Ltd Floor stripper
Hand Clean Y Y Not stated Young's Motor Products Pty Ltd Hand cleaner
HD Cleaner Y Y <10% Challenge Chemicals Aust. Surface cleaner - heavy duty
Heavy Duty Cleaner No.4 Y Y 1-10% Dominant (Australia) Pty Ltd Surface cleaner - heavy duty
Heavy Duty Soil Lifter Y N 10-30% Cleancare of Australia Carpet cleaner ; Upholstery cleaner
Hi Shine (3-182) Y Y <10% Applied Chemicals Pty Ltd Glass/window cleaner
Hook Guard Y Y <10% Ecolab Pty Ltd Temporary rust preventative and lubricant for meat hooks
Hot Shot Y Y <10% Castle Chemicals Pty Ltd Oven cleaner
Hulk Y Y 1-10% Lustral Surface cleaner - general purpose
Hydrakleen Y Y 10% Castle Chemicals Pty Ltd Surface cleaner - general purpose
Impact Y Y Gibson Chemicals Limited Hand cleaner
"minor
quantity"
Industroclean Y Y <10% Albright & Wilson (Australia) Limited Surface cleaner - heavy duty
Industroclean N Y Not stated Amway of Australia Pty Ltd Surface cleaner - heavy duty
J Shop 300 Y Y <10% S.C.Johnson Surface cleaner - general purpose
J Shop 600 Y Y <10% S.C.Johnson Solvent degreaser
Jack N Y 15.3% w/v Lustral Floor stripper
Jackpot Y Y <10% Chemsolve Surface cleaner - general purpose
JP50 Y Y <1.5% Tulloch & Kapeco Pty Ltd Laundry detergent
Jupiter Y Y <10% Elite Chemicals Pty Ltd Surface cleaner - general purpose
Just Mop It Y Y <10% Gibson Chemicals Limited Floor stripper
Karpet Life Y Y 1-10% Dominant (Australia) Pty Ltd Carpet shampoo
Kenco Degreaser N Y Not stated Kenco Car Care Pty Ltd Surface cleaner - heavy duty
Priority Existing Chemical Number 6
120
Kitchen Degreaser Y Y 2% Chemwell Products Pty Ltd Surface cleaner - heavy duty, for food preparation areas and
processing equipment
Kleebond 24/55 Y Y <10% Rust remover
Novamax Technologies (A'Asia) Pty
Ltd
Kleen Etch Plus Y Y <10% Novamax Technologies (A'Asia) Pty Acid etch cleaner for aluminium
Ltd
Kleen Rite Y N <10% Cleancare of Australia Upholstery cleaner
Kleen Rite - Superbase Y N 10-30% Cleancare of Australia Upholstry cleaner
Kleen Strip Y Y 15% Newland Products Pty Ltd Floor stripper
Knab Water Soluble Dampener Wash Y Y 1-10% Knab Industries Ink removal from cotton covers on dampening rollers of offset
printing machines
Lab 230 Y Y 10-30% Castle Chemicals Pty Ltd Surface cleaner - heavy duty ; Engine cleaner ; Vehicle
exterior cleaner
Lab 563 Y Y 12% Castle Chemicals Pty Ltd Cleaning of exhaust scrubber tanks of locomotives and
personnel carriers used in underground mining operations.
Laser Q Y Y 1-10% Dominant (Australia) Pty Ltd Surface cleaner - heavy duty
Lazer Y Y <10% Peerless Emulsion Products Pty Ltd Floor stripper
Lazer Super Y Y 20% Peerless Emulsion Products Pty Ltd Floor stripper
Lenz Y Y <10% Castle Chemicals Pty Ltd Glass/window cleaner
Lift Off Plus Y Y 7.5% Demack Enterprises Surface cleaner - general purpose
Lift-off Y Y 10-30% S.C.Johnson Floor stripper
Liqua Steam - Superbase Y N <10% Cleancare of Australia Carpet cleaner
Liqua-steam Y N <1% Cleancare of Australia Carpet Cleaner
Liquipol L61-FE Y Y <10% Surface cleaner
Novamax Technologies (A'Asia) Pty
Ltd
LL-300 Y Y Not stated Ecolab Pty Ltd Jeans de-sizing detergent
M1000 Y Y <5% Town & Country Chemicals Pty Ltd Surface cleaner - general purpose
Machine Tool Cleaner Y N 17.6% Houghton Australia Pty Ltd Cleaner for metal working machines
Magic Cleaner Y Y 2% Chemwell Products Pty Ltd Surface cleaner - heavy duty, for kitchen areas.
Major Plus Y Y 10-29% Advanced Chemicals Pty Ltd Surface cleaner - heavy duty; oven cleaner
2-butoxyethanol 121
Marine Clene Y Y <10% Septone Products Pty Ltd Surface cleaner for boats
Max Multipurpose Cleaner Y Y 5% Atherton Chemicals Pty Ltd Surface cleaner - general purpose
Maxi-Strip Y Y 1-5% Floor stripper
North Queensland Chemicals and
Paints
Maxiclean Y Y 1-5% North Queensland Chemicals and Surface cleaner - heavy duty
Paints
Meat Hook Derust Y Y Not stated Peerless Emulsion Products Pty Ltd Rust remover
Metal Prep Y Y 30-60% Septone Products Pty Ltd Rust remover
Mirrors & Glass Y Y 10-30% Cyndan Chemicals Glass/window cleaner ; Floor stripper
Mop N Strip Y Y <10% Alliance Technology Pty Ltd Floor stripper
MP1000 Y Y <10% Chemsolve Surface cleaner - heavy duty
MP2000 Y Y <10% Chemsolve Surface cleaner - general purpose
Mrs Beeton's Range Cleaner Y Y <10% Gibson Chemicals Limited Oven cleaner
Multi Clean Y Y 13.7% Elite Chemicals Pty Ltd Surface cleaner- general purpose
Multi Purpose Cleaner Y Y 2% Chemwell Products Pty Ltd Surface cleaner - general purpose
Multi UV Washup Y N <40% GSB Chemicals Ink and resin remover
Multikleen Y N 6% Bunzl Ltd (reseller - products Surface cleaner - general purpose
manufactured by JC Allen)
Multikleen Y Y 5% Dynamic Laboratories Surface cleaner - general purpose
Multisolve Y Y <10% Town & Country Chemicals Pty Ltd Surface cleaner - heavy duty
Multistrip Y Y 13% Ecolab Pty Ltd Floor stripper
N.A.Stripper Y N 10-60% Tasman Chemicals Pty Ltd Floor stripper
Naturally Clean Chrome and Glass Cleaner Y Y <10% Benckiser Australia Glass/window cleaner
NC 160 N Y Not stated Ecolab Pty Ltd Surface cleaner - general purpose
New Liquid Degreaser Y Y 1-10% Lustral Surface cleaner - general purpose
New Look Y Y 3% The Major Chemical Co. Pty Ltd Glass/window cleaner
New Multi Purpose Cleaner Y Y 7% Protect-A-Clean Surface cleaner - general purpose
No Frills Grime Fighter Y Y <2% Surface cleaner - general purpose
The Phase Corporation of Australia Pty
Ltd
Priority Existing Chemical Number 6
122
No Frills Prewash Y Y <5% Pre-wash stain remover
The Phase Corporation of Australia Pty
Ltd
No Frills Window Cleaner Y Y <1% Glas/window cleaner
The Phase Corporation of Australia Pty
Ltd
No Scrub - No Rinse Stripper Y Y 10-30% S.C.Johnson Floor stripper
No.1 Marine Metal Cleaner Y Y 22.5% Protect-A-Clean Rust remover
Nth Power N N Not stated Cosmic Products Surface cleaner - general purpose
Nth Power Plus N N Not stated Cosmic Products Surface cleaner - general purpose
Nutral Floor Cleaner Y N <1% Cleancare of Australia Surface cleaner - general purpose
Oakite Rust Preventative 2 Y Y 5% Tak Pty Ltd Rust preventative
Oasis 111 (Imported) Y Y 4% Ecolab Pty Ltd Surface cleaner - floors
Oasis 122 (Imported) Y Y <1% Ecolab Pty Ltd Floor stripper
Oasis 255 (Imported) Y Y 23% Ecolab Pty Ltd Glass/window cleaner
Outrite Y Y 0-10% True Blue Chemicals Pty Ltd Carpet cleaner
Overhaul P.F Y Y Not stated Cleveland Chemical Co. Pty Ltd Vehicle surface cleaner
PHA Shift It N Y Not stated Kenco Car Care Pty Ltd Surface cleaner - heavy duty; laundry pre-spray
Pile High Y Y <10% Gibson Chemicals Limited Carpet cleaner
Plush Y Y <10% Chemsolve Carpet cleaner
Polish & Wax Stripper Y Y 7% Chemwell Products Pty Ltd Floor stripper
Poly-Cot Y Y 10-<30% Ecolab Pty Ltd Laundry detergent
Polyglaze Auto Glass Cleaner Y Y 1-9% Selleys Chemical Company Pty Ltd Glass/window cleaner
Polyglaze Foaming Mag Wheel Cleaner Y Y <10% Selleys Chemical Company Pty Ltd Cleaner for automotive mag wheels
Polyglaze Mag Wheel Cleaner Y Y 1-9% Selleys Chemical Company Pty Ltd Cleaner of automotive mag wheels
Polywash Sugar Soap Y Y <10% Selleys Chemical Company Pty Ltd Surface cleaner - heavy duty - for use prior to painting and
wallpapering
Power Y Y Not stated Alliance Technology Pty Ltd Surface cleaner - heavy duty ; Engine cleaner ; Vehicle
exterior cleaner
Power Kleen Y Y 1-10% Cyndan Chemicals Surface cleaner - heavy duty
Power Wash Y Y 5% Cyndan Chemicals Surface cleaner - general purpose
2-butoxyethanol 123
Prepare Y Y <10% Elite Chemicals Pty Ltd Floor stripper
Presto Detergent Y Y <10% Agar Chemicals Surface cleaner - general purpose
Print Wash Y Y <10% Chemsolve Dampener roller wash
Pro-Kleen Floor Stripper Y Y <10% Peerless Emulsion Products Pty Ltd Floor stripper
Pro-Kleen Glass Cleaner Y Y <10% Peerless Emulsion Products Pty Ltd Glass/window cleaner
Pro-Kleen Spray and Wipe Y Y <10% Peerless Emulsion Products Pty Ltd Surface cleaner - general purpose
Pro-Spot Y Y Not stated Gibson Chemicals Limited Pre-wash stain remover
Professional Spot Lifter Y N Not stated Cleancare of Australia Carpet cleaner
Proof (3-261) Y Y <10% Applied Chemicals Pty Ltd Machine glasswashing detergent
Pure Acrylic Stripper Y Y 29% Castle Chemicals Pty Ltd Floor stripper
Q Fire Y N >60% Quality Auto Treatment Pty Ltd Solvent for cleaning petrol and diesel fuel systems
Quik Fill 320 (Imported) Y Y 25% Ecolab Pty Ltd Floor stripper
Quik Fill 510 (Imported) Y Y 13% Ecolab Pty Ltd Surface cleaner - general purpose
Quik Fill 520 (Imported) Y Y 40% Ecolab Pty Ltd Glass/window cleaner
R.39 Y Y <10% B & J Chemicals Surface cleaner - general purpose
Range Cleaner Y Y 10-30% Shamrock Chemicals Pty Ltd Oven cleaner
Range Cleaner Y Y <1% Dominant (Australia) Pty Ltd Oven cleaner
Rapi-Klenz Y Y 5-10% Surface cleaner - general purpose
North Queensland Chemicals and
Paints
Rapid U V Washup Y N 10-30% GSB Chemicals Ink and resin remover
RC 40 Y Y <10% Demack Enterprises Carpet cleaner
Red Baron Y Y 1-10% Lustral Surface cleaner - general purpose
Red Multi Purpose Cleaner Y Y 7% Protect-A-Clean Surface cleaner - general purpose
Release Y N <1% Cleancare of Australia Carpet cleaner
Remove Y Y >10% Elite Chemicals Pty Ltd Floor stripper
Render Y Y <10% Elite Chemicals Pty Ltd Oven cleaner
Reveal HD Cleaner Y Y <10% S.C.Johnson Surface clenaer - heavy duty
Rik LT Y Y Ecolab Pty Ltd Floor and wall cleaner for use in cold storage areas
"Glycol
ethers <10%"
Priority Existing Chemical Number 6
124
Ripper Y Y 25% Alliance Technology Pty Ltd Floor stripper
RM 44 Acid Cleaner Y Y Not stated Peerless Emulsion Products Pty Ltd Aluminium brightener and stainless steel cleaner
Roto-Brite Y N 10-30% Cleancare of Australia Carpet cleaner
Rugbee Foam Shampoo Y Y <10% S.C.Johnson Carpet cleaner
Rugbee Jetstream Plus Liquid Extraction Y Y <10% S.C.Johnson Carpet Cleaner
Cleaner
Rugbee Soil Release Concentrate Y Y <10% S.C.Johnson Carpet cleaner
Rugbee Spotto Heavy Duty Spot and Stain Y Y <10% S.C.Johnson Carpet cleaner
Remover
Sanclean 400 Y Y 1-10% Dominant (Australia) Pty Ltd Surface cleaner - general purpose
Scene (Aerosol) Y Y <10% Gibson Chemicals Limited Glass/window cleaner
Scotchbrite Brand Dri-Strip 303 Y Y 8-11% 3M Australia Pty Ltd Floor stripper
Scrub N Shine Y Y Not stated Alliance Technology Pty Ltd Floor cleaner and polisher
SD-37 Detergent Y Y 20% Agar Chemicals Surface cleaner - general purpose ; Floor stripper
SF 100 Y Y 4% Demack Enterprises Surface cleaner - heavy duty ; Engine cleaner
Shift It Y Y 15.1% Lustral Surface cleaner - general purpose ; Engine cleaner
Shor Kleen Y Y 1-10% Dominant (Australia) Pty Ltd Surface cleaner - heavy duty
Simplicity Y Y 3% The Major Chemical Co. Pty Ltd Surface cleaner - for washroom and hard floor
Sirio HD Cleaner Y Y 4.75% Demack Enterprises Surface cleaner - heavy duty
Slik No.5 Y N <10% Nalco/Exxon Energy Chemicals Surface cleaner - general purpose (oil rig equipment)
Australia Pty Ltd
Slipstream Y Y <10% Elite Chemicals Pty Ltd Specialised detergent for use in breweries and bottling plants
Soil Breaker Y Y Not stated Alliance Technology Pty Ltd Carpet cleaner ; Upholstery cleaner
Sol Fome Y Y Not stated Alliance Technology Pty Ltd Surface cleaner - for use in abattoirs and food processing
plants
Solid Regain (Imported) N N Not stated Ecolab Pty Ltd Surface cleaner - floors
Solocleaner Y Y <10% Cleveland Chemical Co. Pty Ltd Surface cleaner - general purpose
Solspray Y Y "low" Agar Chemicals Carpet cleaner ; Hard surface cleaner
2-butoxyethanol 125
Solv Kleen Y Y Not stated Alliance Technology Pty Ltd Printers dampener wash
Solv-It Y Y <10% Elite Chemicals Pty Ltd Laundry detergent
Solveclean Y Y 1-10% Challenge Chemicals Aust. Surface cleaner - heavy duty
Solveen Y Y 12% Ecolab Pty Ltd Laundry detergent
Solvex 09WS Y Y <10% Novamax Technologies (A'Asia) Pty Detergent additive for spray phosphating
Ltd
Solvex 50A Y Y 10-30% Detergent additive for phosphating
Novamax Technologies (A'Asia) Pty
Ltd
Solvobreak Y Y 12.9% Castle Chemicals Pty Ltd Laundry detergent
Sparkle Glass Cleaner Y Y <10% S.C.Johnson Glass/window cleaner
Special Linen Solvent Y Y <10% Kempo Manufacturing Company Pty Laundry detergent for tablecloths soiled with spillages of food
Ltd products containing vegetable oils
Speed Y Y "low" Agar Chemicals Surface cleaner - heavy duty ; Floor stripper
Speedkleen Y Y 1-5% North Queensland Chemicals and Surface cleaner - heavy duty
Paints
Spindle Cleaner N Y Not stated Castrol Australia Pty Ltd Spindle cleaner - added to water tank on cotton harvesters
Spot Go Y Y 30% Castle Chemicals Pty Ltd Carpet cleaner ; Upholstery cleaner
Spray and Wipe Y Y <10% Challenge Chemicals Aust. Surface cleaner - general purpose
Spray Clean Y Y 10-60% Lustral Surface cleaner - heavy duty
Spray Kleen Y Y Not stated Alliance Technology Pty Ltd Spray burnishing of floors
Spray Kleen Concentrate Y Y Not stated Alliance Technology Pty Ltd Spray burnishing of floors
Spray Shine Y Y Not stated Alliance Technology Pty Ltd Spray burnishing compound for floors
Spray Wipe Y Y <10% Shamrock Chemicals Pty Ltd Surface cleaner - general purpose
Sprayclean Y Y 5% Castle Chemicals Pty Ltd Surface cleaner - general purpose
Spraycleen Y Y <10% Town & Country Chemicals Pty Ltd Surface cleaner - general purpose
Sprayoff Oven Cleaner Y Y Not stated Cleveland Chemical Co. Pty Ltd Oven cleaner
Sprint Y Y <10% Castle Chemicals Pty Ltd Carpet cleaner ; Upholstery cleaner
Sprite Y Y Not stated B & J Chemicals Surface cleaner - general purpose
Squirt Y Y 1-10% Lustral Surface cleaner - general purpose
Priority Existing Chemical Number 6
126
Stainless Y Y <2% Cleveland Chemical Co. Pty Ltd Surface cleaner and disinfectant for bathrooms and toilets
Stainof Y N Not stated Cleancare of Australia Not stated
Status Non Smear Glass Cleaner Y Y 4.8% Peerless Emulsion Products Pty Ltd Glass/window cleaner
Steamate Y Y <10% Cyndan Chemicals Cleanser solvent used in steam or cold presssure washers
Step-off Heavy Duty Stripper Y Y 10-30% S.C.Johnson Floor stripper
Strike Y Y 0-10% True Blue Chemicals Pty Ltd Surface cleaner - general purpose ; Engine cleaner
Strip Y Y <10% Chemsolve Floor stripper
Strip Clean Y Y "medium" Dari Cleaning Products Floor stripper
Stripper Y Y 7.5% Demack Enterprises Floor stripper
Supar Y Y 24% Lustral Surface cleaner - general purpose ; Print screen/ink cleaner
Super Clear Y Y <10% Tak Pty Ltd Glass/window cleaner
Super Kleen Y Y <7% BettaChem Chemical Manufacturers Surface cleaner - general purpose
Superb Y Y 1-10% Dominant (Australia) Pty Ltd Surface cleaner - general purpose
Superclean Y Y <10% Chemsolve Surface cleaner - general purpose
Supreme Y Y Not stated Newland Products Pty Ltd Surface cleaner - heavy duty, for kitchen and food preparation
areas
Supreme (4-490) Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
Surmax CS-555 Y N <2% Swift and Co General purpose cleaner
SW Supercleaner Y Y 10-20% Surface cleaner - general purpose
North Queensland Chemicals and
Paints
Tak Det 12LS Y Y 6% Tak Pty Ltd Surface cleaner - general purpose
Tak Det 32LS Y Y <10% Tak Pty Ltd Surface cleaner - general purpose
Tak Det 5LS Y Y 18% Tak Pty Ltd Surface cleaner - general purpose
Tak Det 6LS Y Y 12% Tak Pty Ltd Surface cleaner - general purpose
Tak Det 7L Y Y <10% Tak Pty Ltd Ammoniated detergent
Tak Spec 996L Y Y <10% Tak Pty Ltd Glass/window cleaner
Take Off Y N 0-10% True Blue Chemicals Pty Ltd Surface cleaner - general purpose
Take Off Y Y <10% Shamrock Chemicals Pty Ltd Surface cleaner - heavy duty
2-butoxyethanol 127
Take Off (4-480) Y Y <10% Applied Chemicals Pty Ltd Surface cleaner - general purpose
Techniclean PR Y N 10-30% Castrol Australia Pty Ltd Paint stripper
Terminator Y N Not stated Whiteley Chemicals Australia Pty Ltd Floor stripper
Threes Y Y 5.3% The Major Chemical Co. Pty Ltd Carpet cleaner
TKO Build Up Remover Y Y <10% Agar Chemicals Floor stripper
Toilet Bowl and Urinal Cleaner Y Y 22.5% Protect-A-Clean Toilet bowl and urinal cleaner
Tonizone Glass and Mirror Cleaner Y N <10% Multi-Fill Pty Ltd Glass/window cleaner
Top Marks Y Y 3.4% The Major Chemical Co. Pty Ltd Surface cleaner - general purpose
Top Quartile Y Y 10-<30% Ecolab Pty Ltd Floor stripper
Touch Up Y Y 0-10% True Blue Chemicals Pty Ltd Surface cleaner - general purpose
Traffic Zone Y Y <5% Gibson Chemicals Limited Heavy duty floor cleaner
Trap Solve Y Y 1-10% Dominant (Australia) Pty Ltd Grease trap cleaner
Triples Y Y 4% The Major Chemical Co. Pty Ltd Surface cleaner - general purpose
Trouble Spot Y Y Not stated Peerless Emulsion Products Pty Ltd Carpet cleaner
Truck Wash Plus Y Y <10% w/w Harcros Chemicals Limited Truck wash
Truckwash Y Y Not stated Gladstone Chemicals Vehicle surface cleaner
Truk Wash Y Y 1-10% Dominant (Australia) Pty Ltd Heavy duty cleaner for trucks and other vehicles
Turco 4258NP Y Y 0-10% Ajax Chemicals Surface cleaner - aircraft parts
Turco 5884 Y Y <10% Ajax Chemicals Surface cleaner - heavy duty ; Jet engine compressor washer
Turco 5948 A Y Y <10% Ajax Chemicals Aircraft exterior surface cleaner
Turco 5974 BNF Y Y 5% Ajax Chemicals Surface cleaner
Turco 5975 A Y Y <10% Ajax Chemicals Surface cleaner - heavy duty
Turco 6336 Y Y <5% Ajax Chemicals Not stated
Turco 9128 Y N <10% Ajax Chemicals Surface cleaner - general purpose
Turco Airtec 19 Y Y <10% Ajax Chemicals Aircraft exterior surface cleaner
Turco Airtec 22 Y Y <10% Ajax Chemicals Aircraft exterior surface cleaner
Turco Aquasorb Y Y <10% Ajax Chemicals Rust preventative/removal of fingerprints
Priority Existing Chemical Number 6
128
Turco Cleansolv Y Y <10% Ajax Chemicals Electrical and general equipment cleaning solvent
Turco Deodar Y Y <10% Ajax Chemicals Toilet deodorant and cleaner
Turco Flash Y Y <10% Ajax Chemicals Rust remover
Turco HT 301 Y N >60% Ajax Chemicals Alkaline stripper
Turco Jetclean No. 2 Y Y <10% Ajax Chemicals Surface cleaner - general purpose, for use in food, transport
and metal industries
Turco Metal Glo 6 Y Y <10% Ajax Chemicals Surface cleaner - aircraft and aluminium surfaces
Turco Meteor Y Y <10% Ajax Chemicals Surface cleaner - general purpose
Turco Mulsirex Y Y <10% Ajax Chemicals Surface cleaner - general purpose
Turco Odorshield Y Y <10% Ajax Chemicals Sanitary deodorant, cleaner and bacteriostat
Turco Rust Converter Y Y 1-10% Ajax Chemicals Rust remover
Turco Spray & Wipe Y Y <10% Ajax Chemicals Surface cleaner - general purpose
Turco Turcosolv Q Y Y Not stated Ajax Chemicals Electrical cleaning solvent
Turco WO1 Y Y 10-30% Ajax Chemicals Rust remover
Turcosolv Y Y <10% Ajax Chemicals Electrical cleaning solvent
Turcosolv Trsk 54 Y Y 1-10% Ajax Chemicals Electrical cleaning solvent
Twinkle Y Y "medium" Dari Cleaning Products Surface cleaner - general purpose
Ultrasolv Y Y <10% Town & Country Chemicals Pty Ltd Surface cleaner - heavy duty
Ultrastrip Y Y 16.5% Cleveland Chemical Co. Pty Ltd Floor stripper
Ultrastrip Y Y "low" Agar Chemicals Floor stripper
Use All Y Y 0-10% True Blue Chemicals Pty Ltd Surface cleaner - general purpose
UV Blanket Roller Wash Y N 35% GSB Chemicals UV blanket roller wash
Versaclean Y Y <5% Cleveland Chemical Co. Pty Ltd Surface cleaner - heavy duty ; Engine cleaner
Vetro Y N "low" Tasman Chemicals Pty Ltd Glass/window cleaner
Vision Y Y <1% Newland Products Pty Ltd Glass/window cleaner
WDI Degreaser Y N Not stated KCB Pty Ltd Engine cleaner
Windex Y Y <10% S.C.Johnson Glass/window cleaner
Window and Mirror Cleaner Y Y 3% Chemwell Products Pty Ltd Glass/window cleaner
2-butoxyethanol 129
Window Cleaner Y Y 0-10% True Blue Chemicals Pty Ltd Glass/window cleaner
Window Cleaner Y Y 5% Jamac-Safe and Clean Pty Ltd Glass/window cleaner
Window Cleaner Y Y <10% Ecolab Pty Ltd Window cleaner
Window Cleaner Y Y 10% Town & Country Chemicals Pty Ltd Glass/window cleaner
Window Cleaner Y Y <10% Alliance Technology Pty Ltd Glass/window cleaner
Window Clear Y Y <10% B & J Chemicals Glass/window cleaner
Window Shine Y Y 10-30% Shamrock Chemicals Pty Ltd Glass/window cleaner
Window Wash Y Y <10% Agar Chemicals Glass/window cleaner
Wipe Away Detergent Y Y <10% Agar Chemicals Surface cleaner - general purpose
Wipe Clean Y N 1% Sadies Cleaning Products Surface cleaner - general purpose
Wipe Clean Y Y <10% Alliance Technology Pty Ltd Surface cleaner - general purpose
Wipe Clean Concentrate Y Y 71% Alliance Technology Pty Ltd Surface cleaner - general purpose
Wipe Out N Y <7% BettaChem Chemical Manufacturers Surface cleaner - general purpose
ZC2 Y Y <10% Elite Chemicals Pty Ltd Surface cleaner - heavy duty
Zip 282 Y Y <10% S.C.Johnson Oven cleaner
Zip Strip Y N Not stated Whiteley Chemicals Australia Pty Ltd Floor stripper
Zoom Y Y <10% Amway of Australia Pty Ltd Surface cleaner - general purpose
[Not stated] N N Not stated Plaza Chemical Surface cleaner
[Not stated] N N Not stated Symbio Products Surface cleaner
[Not stated] N N Not stated Blacktown Custom Packers Pty Ltd Surface cleaner - general purpose ; Engine cleaner
[Not stated] N N Not stated JAL Chemicals Pty Ltd Floor stripper ; Surface cleaner - general purpose
[Not stated] N N Not stated R & E Chemicals Pty Ltd Surface cleaner
[Not stated] N N Not stated Home Carpet Shampoo Australia Carpet cleaner
[Not stated] N N "minor" Colbar Aust Rust converter
[Not stated] N N Not stated Calman Manufacturing Pty Ltd Surface cleaner - general purpose ; Floor stripper
[Not stated] N N 94% Fasson Pty Ltd Cleaning of coating cylinders used in a silicone coating
process
Priority Existing Chemical Number 6
130
APPENDIX 2
QUESTIONNAIRE
Company name:......................................................................................................
Contact person:.....................................................tel.............................................
[Please tick appropriate box(es)]
Are you:
a reseller of 2-butoxyethanol
a formulator of cleaning products containing 2-butoxyethanol
a past formulator of cleaning products containing 2-butoxyethanol (before 5
April 1994)
an end-user of cleaning products containing 2-butoxyethanol
other (please specify)..........................................
What is the product used for? (if not specified on MSDS) e.g. surface cleaner, floor stripper
..........................................................................................................................................
Who uses the product? e.g. household, office cleaners, mechanics
..........................................................................................................................................
How many workers are involved in the formulation process?
..........................................................................................................................................
How many hours/week (approx) are they potentially exposed to 2-butoxyethanol?
..........................................................................................................................................
What precautions are taken/recommended when using the product? (if not on MSDS)
..........................................................................................................................................
..........................................................................................................................................
Are you aware of any adverse health effects experienced by workers/customers after
exposure to 2-butoxyethanol or products containing 2-butoxyethanol? If so, please
describe. ..................................................................................................................
..........................................................................................................................................
Are you aware of any atmospheric monitoring that has been conducted during formulation
and/or use of cleaning products containing 2-butoxyethanol?
................................................................................................................................
If so, please forward results.
2-butoxyethanol 131
APPENDIX 3
OCCUPATIONAL EXPOSURE CALCULATIONS
1. FORMULAE FOR EXPOSURE CALCULATIONS
For 2-butoxyethanol, the total body dose (D) is the sum of doses resulting from absorption
of vapours (Dv) and dermal absorption of liquid (Ddl).
That is, D = Dv + Ddl (equation 1)
As vapour absorption (Dv) comprises absorption across the lungs (Div) and dermal
absorption of vapours (Ddv), that is, Dv = Div + Ddv ,
D = (Div + Ddv) + Ddl (equation 1a)
Exposure to vapours
The daily dose arising from the inhalation of vapours (Div) is as follows:
Div = C x R x E x B mg/kg/day (equation 2)
BW
C = concentration of substance in air (mg/m3),
where
R = inhalation rate (m3/h),
E = exposure duration (h/day),
B = bioavailability of vapours across the lungs (1 = 100%),
BW = average body weight of worker (kg).
In addition, 2-butoxyethanol vapours are also absorbed across the skin. From the results
of recent studies in volunteers (Corley et al 1995) and PBPK modelling (Corley et al
1994), the dermal absorption of 2-butoxyethanol vapours (Ddv) comprises up to 20% of the
total absorption of vapours (Dv). That is, for 2-butoxyethanol, Div is approximately 80%
of Dv (see sections 9.2 and 9.6).
That is, Div = 0.8 Dv , or Dv = Div . (equation 3)
0.8
Therefore, combining equations 2 and 3, the daily dose arising from vapour exposure (Dv),
inhalational plus dermal, is as follows:
Dv = C x R x E x B mg/kg/day (equation 4)
0.8 x BW
Priority Existing Chemical Number 6
132
For vapour exposure, the bioavailability (B) is the proportion of inhaled substance which
is absorbed through the lungs, for example, some of the substance is exhaled. In
inhalational (breathing zone) tests in volunteers, 57-78% of the inspired amount of 2-
butoxyethanol was absorbed (see subsection 9.2.3). As these values are similar to the
default value of 0.75 (75%) often used in international assessments, a value of 0.75 was
used in this report.
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). Similarly, a value of 70 kg was used for body weight (BW).
The exposure duration (E) that workers may be potentially exposed to 2-butoxyethanol
during a work shift, either during formulation or cleaning, was obtained from
questionnaires sent to formulators (see section 8.4) or from assumptions regarding
working times during end use (see section 8.5).
Exposure to liquid
The daily total dose arising from liquid exposure (Ddl) is as follows:
Ddl = W x S x A x E x F mg/kg/day (equation 5)
BW
where: W = weight fraction of substance in product, for example, 0.1 for a 10% solution,
S = skin absorption rate (mg/cm2/h),
A = skin surface area exposed (cm2),
E = exposure duration (h/day)
F = skin contact time (as fraction of exposure duration, for example, 0.2 for
20% of time),
BW = average body weight of worker (kg).
For skin absorption rate (S), two sets of human tissue data were available (see subsection
9.2.2). In one of the experiments, the results were reasonably consistent, with a mean of
0.20 mg/cm2/h (range 0.14-0.35) obtained. Extremely variable results were obtained in the
other tissue experiment, with the mean considerably higher at 1.19 mg/cm2/h (range 0.57-
1.91). The results of the former test agreed reasonably well with controlled studies in
volunteers, where the mean rate was 0.14 mg/cm2/h (range 0.05-0.68) (see section 9.2.3),
so the value of 0.2 mg/cm2/h was used for skin absorption rate (S) in this assessment.
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
2-butoxyethanol 133
In this assessment, it was considered that dermal exposure would reasonably consist of no
more than exposure to both hands (840 cm2) or a hand and a forearm (1000 cm2). For
consistency, a value of 1000 cm2 for was considered appropriate for feasible worst-case
estimates.
For the case of dermal exposure to aerosols, for example, during spray use, exposed parts
of the body may include the face, neck, hands and forearms. However, as exposure to
aerosols would not be expected to occur simultaneously with exposure to liquid 2-
butoxyethanol (as a solution), the skin surface area of 1000 cm2 was considered
appropriate for feasible worst-case estimates.
Liquid 2-butoxyethanol can be in contact with the skin for various fractions (F) of the
exposure duration (E), so skin contact with liquid can be extensive, intermittent or
incidental. For the purposes of this assessment, 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=0.2), 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 system in development by
the UK Health and Safety Executive (HSE), and was formerly called EES (Exposure
Expert System). For a further description of EES, see: Marquart et al, Evaluation of
Methods of Exposure Assessment for Premarket Notifications, TNO report V 94.229 TNO
Nutrition and Food Research (Zeist), 1994.
2. CALCULATIONS FOR VARIOUS SCENARIOS
The following estimates for exposure to vapours and liquid incorporate exposure to
aerosols.
2.1 Manufacture (see section 8.3)
Exposure to vapours
For a maximum atmospheric concentration of 1.8 ppm (8.8 mg/m3),
Dv = 8.8 mg/m3 x 1.3 m3/h x 8h x 0.75 = 1.2 mg/kg/day.
0.8 x 70 kg
Liquid (Dermal) exposure
For incidental skin contact (F=0.01) with a hand and a forearm (1000 cm2) to 100% 2-
butoxyethanol,
Ddl = 1 x 0.2 mg/cm2/h x 1000 cm2 x 8h x 0.01 = 0.2 mg/kg/day.
70 kg
Combined inhalational and dermal exposure
The combined inhalational and dermal uptakes would not be expected to exceed 1.4
mg/kg/day.
Priority Existing Chemical Number 6
134
2.2 Formulation (see section 8.4)
Exposure to vapours
Substituting the constants in equation 4 above
Dv = C mg/m3 x 1.3 m3/h x E h x 0.75 mg/kg/day.
0.8 x 70 kg
Liquid (Dermal) exposure
For intermittent skin contact (F = 0.2) with a hand and a forearm (1000 cm2), and by
substituting the constants in equation 5 above
Ddl = W x 0.2 mg/cm2/h x 1000 cm2 x E h x 0.2 mg/kg/day.
70 kg
Combined inhalational and dermal exposure
For each of the various scenarios, the combined inhalational and dermal uptakes would not
be expected to exceed the values in the following table.
Table 1. Combined inhalational and dermal exposure during formulation
% 2-BE W C E Daily dose (mg/kg/day)
Dd Dv + Ddl
Dv
10 0.1 9.8 3 0.5 0.2 0.7
10 0.1 9.8 8 1.4 0.5 1.9
30 0.3 49 3 2.6 0.5 3.1
30 0.3 49 8 6.8 1.4 8.2
60 0.6 49 3 2.6 1.0 3.6
60 0.6 49 8 6.8 2.7 9.5
Key: W = weight fraction of 2-BE in product
C = concentration of 2-BE in air (mg/m3)
E = duration of exposure (h/day)
Dv = dose resulting from absorption of vapours
Ddl = dose resulting from dermal absorption of liquid
2.3 Cleaning (see section 8.5)
The combined inhalational and dermal uptakes for exposure during cleaning were
calculated as for formulation, except that liquid (dermal) contact was assumed to be
extensive, that is, continuous skin contact (F=1). The equations used for vapour
absorption and dermal exposure to liquid respectively were therefore
Dv = C mg/m3 x 1.3 m3/h x E h x 0.75 mg/kg/day, and
0.8 x 70 kg
Ddl = W x 0.2 mg/cm2/h x 1000 cm2 x E h x 1 mg/kg/day.
70 kg
2-butoxyethanol 135
For each of the various scenarios, the daily dose would not be expected to exceed the
values in the following table.
Table 2. Combined inhalational and dermal exposure during cleaning
% 2-BE W C E Daily dose (mg/kg/day)
Ddl Dv + Ddl
Dv
0.1 0.001 9.8 5 0.9 0.01 0.9
0.1 0.001 9.8 8 1.4 0.02 1.4
1 0.01 9.8 5 0.9 0.1 1.0
1 0.01 9.8 8 1.4 0.2 1.6
10 0.1 19.6 5 1.7 1.4 3.1
10 0.1 19.6 8 2.7 2.3 5.0
30 0.3 49 5 4.3 4.3 8.6
30 0.3 49 8 6.8 6.9 13.7
Key: W = weight fraction of 2-BE in product
C = concentration of 2-BE in air (mg/m3)
E = duration of exposure (h/day)
Dv = dose resulting from absorption of vapours
Ddl = dose resulting from dermal absorption of liquid
Priority Existing Chemical Number 6
136
APPENDIX 4
OTHER INFORMATION SUBMITTED TO NICNAS DURING ASSESSMENT
During the assessment period, cleaners in NSW were invited to provide information to
NICNAS regarding the use of cleaning products containing 2-butoxyethanol. The
invitation was placed in the Winter 1994 edition of Focus, the newsletter of the Liquor,
Hospitality and Miscellaneous Workers Union - Miscellaneous Workers Division. Also, a
number of unsubstantiated case reports from persons previously exposed to cleaning
products containing 2-butoxyethanol were submitted to Worksafe.
Survey of Cleaners in NSW
Information was provided by cleaners in the following locations. In all cases a surface
cleaning solution of <10% 2-butoxyethanol or a dilution of the product was used.
Town/suburb Workplace Comments
Berkeley school Solution diluted 1:10 and used as spray; workers (6)
have cough, nausea.
Blayney school Solution used to be used as spray; worker
still has cough; no gloves worn.
Bonville school Cleaner experienced respiratory irritation.
Campbelltown school Spray use; worker had cough.
Cartwright school Solution used as spray; worker had persistent cough;
rubber gloves worn.
Dunedoo Solution diluted 1:10 and used as spray; worker has
wheezing; gloves not worn.
Inverell school Spray use; worker had cough, eye, skin problems;
rubber gloves worn.
Macksville Solution applied by cloth; workers get eye irritation and
nausea.
Moruya school Solution diluted 1:3 and used as spray; worker
experienced headache, nausea, coughing; worked
28h/wk; mask and rubber gloves worn.
Narwee school Spray use; worker experienced skin irritation; rubber
gloves worn.
Nowra club Spray use; workers have cough, sore eyes, headache.
Thornleigh office Spray use; worker experienced headache, fatigue,
nausea; gloves worn.
Other Reports
Written submissions were received from a number of workers who had used cleaning
solutions containing 2-butoxyethanol during their employment. These are summarised
below.
2-butoxyethanol 137
Town/State Workplace Comments
Coffs Harbour NSW contract Floor stripping, solution diluted 1:1, worker
cleaner reported symptoms including eye and respiratory
irritation
Cranbourne Vic school General cleaning, including spray use, with
cleaner diluted solution, and floor stripping with 10-
12% 2-BE solution; worker reported symptoms
including eye irritation, dry cough, sleepiness,
dizziness, confusion
Hampton Vic office Heavy duty cleaning, including use of 18.5%
cleaner solution; poor ventilation; worker reported
symptoms including headache, nausea, eye
irritation, anaemia, sleepiness, dizziness,
confusion
Priority Existing Chemical Number 6
138
APPENDIX 5
ABSA STRUCTURED TRAINING PROGRAM FOR CLEANERS
This course has been designed by the Australian Building Services Association (ABSA) to
cover the requirements of cleaning operatives (cleaners) and is available on an `in-house'
basis, for use by company trainers. It is a practical course covering basic cleaning skills
and tasks, use of cleaning chemicals and equipment, and safety. The course can be
modified to meet particular circumstances. The syllabus is as follows:
I INDUCTION
II SAFETY
III BASIC SKILLS
Dusting
Dust Mopping
Damp Mopping
Wet Mopping
Cleaning Status
Toilet Cleaning
Shower Cleaning
Other Cleaning Tasks and Methods
Safety
CLEANING HARD FLOORS
Buffing
Spray Buffing
Floor Scrubbing
Stripping and Sealing
Use of Chemicals and Equipment
CARPET CLEANING AND MISCELLANEOUS
Carpet Spotting and Stain Removal
Spot Vacuuming (Back-Pack)
Vacuum Cleaning
Carpet Shampooing
Internal Glass Cleaning
Venetian Blind Cleaning
Wall Washing
Refrigeration Cleaning
Cupboards
Other Cleaning Tasks as Required
2-butoxyethanol 139
Sample Material Safety Data Sheet
for 2-butoxyethanol
1 6
Date of issue Page of Total
2-Butoxyethanol is classified as hazardous according to the National
Occupational Health and Safety Commission's Approved Criteria for
Classifying Hazardous Substances.
Company details
Company name
Address
State Postcode
Telephone number Emergency telephone number
Facsimile number Telex number
Identification
Product name
2-Butoxyethanol
Other names
Ethylene Glycol Monobutyl Ether, Butyl Ethoxol, EGBE
Manufacturer's product code
UN Number
Dangerous goods class and subsidiary risk
Combustible liquid
Hazchem code
2R
Poisons Schedule number
Schedule 6 (under Ethylene Glycol Monoalkyl Ethers)
Use
140 2-butoxyethanol
2 6
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Physical description and properties
Appearance
Colourless liquid with unpleasant odour
Boiling point Freezing point
171癈
Vapour pressure
1.17 hPa
Specific Gravity
0.90 g/mL
Flashpoint
62癈 (closed cup)
Flammability limits
1.10 - 12.7%
Solubility in water
Miscible
Other properties
Vapour density: 4.91 g/L (20癈)
Density: 0.9 g/mL (20癈)
Autoignition Temperature: 230-245癈
Reactivity: Reacts with strong oxidising agents and strong
caustics
Ingredients
Chemical entity CAS Number Proportion
2-Butoxyethanol 111-76-2
Impurities
2-butoxyethanol 141
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Health hazard information
HEALTH EFFECTS
Acute:
Swallowed: May cause nausea, vomiting, irritation of the gastro-
intestinal tract and loss of consciousness. Ingestion of very
high doses may cause haemolysis of the red blood cells.
Eye: Severe irritant. Vapour also irritating.
Skin: Mild to moderate irritant in test animals. Slight irritant
in humans but repeated or prolonged contact may cause contact
dermatitis. Has degreasing action on skin. Readily absorbed
through skin. Vapour also absorbed through skin.
Inhalation: Vapour irritating to respiratory system. May cause
headache and nausea. Inhalation of high concentrations caused
loss of co-ordination and breathing difficulties in animals.
Chronic:
No studies are available on the effects of long term exposure to
2-butoxyethanol in humans. Studies indicate that repeated
exposure causes blood, liver and kidney disorders in animals.
FIRST AID
Swallowed: Rinse mouth with water. Give plenty of water to drink.
Seek immediate medical attention.
Eye: Hold the eyes open and irrigate with lots of water for at
least 15 minutes. Keep the eyelids open. Seek immediate medical
attention.
Skin: Wash contaminated skin thoroughly with lots of water.
Remove contaminated clothing and wash before re-use. Seek medical
attention if irritation persists.
Inhalation: Remove person from exposure - avoid becoming a
casualty. Remove contaminated clothing and loosen remaining
clothing. Keep patient comfortable and warm. Make sure airways
are clear and monitor breathing. Seek medical attention.
First aid facilities:
For further information, contact the Poisons Information Centre.
ADVICE TO DOCTOR
Treat symptomatically.
Priority Existing Chemical Number 6
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Precautions for use
2-Butoxyethanol is readily absorbed through the skin and
absorption can occur in the absence of irritation. Precautions
should be taken to minimise skin exposure to the chemical.
EXPOSURE STANDARDS
Australian Exposure Standard: 25 ppm (12/mg/m3) TWA with `skin'
notation.
The `skin' notation indicates that absorption through the skin may
be a significant source of exposure.
ENGINEERING CONTROLS
Ensure that the process is enclosed or that ventilation is
provided to maintain atmospheric concentrations below the exposure
standard. Use local exhaust ventilation.
Engineering controls should be designed so that splashing and
vapour and aerosol generation are avoided.
PERSONAL PROTECTION
Wear overalls, chemical goggles or safety spectacles with
sideshields, and butyl or nitrile gloves. Where atmospheric
concentrations may exceed the exposure standard, for example,
during the cleanup of spills, wear an organic vapour respirator.
Ensure that all personal protective equipment complies with the
relevant Australian Standards. Wash contaminated clothing or
equipment before re-use or storage. Ensure good personal hygiene.
FLAMMABILITY
Combustible liquid.
2-butoxyethanol 143
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Safe handling information
STORAGE AND TRANSPORT
Correct Shipping Name: Combustible liquid
Identification Number: NA 1993
Packaging Group: III
Classified as a C1 (Combustible Liquid) for the purpose of storage
and handling, in accordance with AS1940.
Store in a cool, well-ventilated area. Keep away from strong
oxidising agents and strong caustics. Keep containers closed at
all times and check regularly for leaks.
SPILLS
Increase ventilation. Shut off all possible ignition sources.
Wear the appropriate personal protective equipment to prevent
exposure. Contain the spill, clean up using an absorbent (soil,
sand, vermiculite) and collect in labelled drums for disposal.
Flush the contaminated area with water to drain.
DISPOSAL
Dispose of by incineration, recycling or removal by a licensed
reclaimer. The relevant State Land Waste Management Authority
should be consulted. Should not be disposed of to landfill.
FIRE/EXPLOSION HAZARD
Combustible liquid. On burning, will liberate toxic fumes of
carbon monoxide and carbon dioxide. Cool containers with water-
spray. To fight fires, use water-fog, dry chemical or carbon
dioxide extinguishers. Firefighters should wear self-contained
breathing apparatus if risk of exposure to vapours or combustion
products.
Other information
References
Gingell et al `Glycol Ethers and Other Selected Glycol
Derivatives', ch 31 in Patty's Industrial Hygiene and Toxicology,
4th edition, vol 2, part D, 1994.
ECETOC, Special Report No 7 - Butoxyethanol Criteria Document,
Brussels, Belgium, April 1994.
NICNAS 2-Butoxyethanol Full Public Report, AGPS, 1996.
Environmental Impact
Readily biodegradable. Unlikely to accumulate in aquatic
organisms.
Aquatic Toxicity
24h LC50 (goldfish): 1650 mg/L; 24h LC50 (brine shrimp): 1000 mg/L
4d LC50 (white shrimp): 130 mg/L; 4d LC50 (oyster): 90 mg/L
7d LC50 (guppy): 983 mg/L.
Priority Existing Chemical Number 6
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Other information
TOXICITY
Oral LD50: male rat 560-3000 mg/kg, female rat 530-2800 mg/kg.
Dermal LD50: rabbit 100-610 mg/kg, guinea-pig 210->2000 mg/kg.
Inhalational LC50: rat 450-490 ppm/4h
Death in acute studies was generally caused by narcosis or
respiratory failure, with kidney failure seen as a secondary
cause.
The main toxic effect observed in acute and repeated-dose animal
studies is haemolysis. The effect varies considerably between
species, with rats and mice the most susceptible, rabbits less
susceptible, and humans and guinea pigs least susceptible. In
animals, the haemolytic effects are transient at low levels in
repeated exposure studies.
In reproductive toxicity studies in animals, adverse effects are
only observed at or above doses which are severely toxic to the
adults. No evidence of teratogenicity has been observed.
In vitro genotoxicity studies indicate that 2-butoxyethanol is
probably not genotoxic. No information is available on
carcinogenicity.
Contact point
Contact name Telephone number
Position title
Address
State Postcode Country
2-butoxyethanol 145
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G r o w t h and Survival Using Ethylene Glycol Monoethyl Ether, Ethylene Glycol
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Priority Existing Chemical Number 6
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Glossary
abraded skin Skin that has been scraped or roughened.
acidosis A disturbance in the acid-base balance of the body in
which there is an accumulation of acids or an excessive
loss of bicarbonate in the blood and body tissues.
anaemia A condition in which there is reduction in the number
of circulating red blood cells, or in haemoglobin, or both.
antigen A substance which induces the formation of antibodies.
atrophy A wasting away, or reduction in size of a cell, tissue, organ
or part.
BEI Biological exposure index, a reference value related to the
evaluation of worker exposure to a substance or agent
through measurement of the substance or agent or its
metabolite(s) in tissue, fluids or exhaled air.
bunded Embanked, for example, to prevent the spread of spills.
cytotoxic Cell destroying.
depot effect Temporary storage of absorbed material, for example, in
the skin.
dermatitis Inflammation of the skin.
The concentration of a substance in water that has an effect
EC50
on 50% of exposed organisms, relative to unexposed
controls.
embryotoxic Toxic to the developing embryo (2 to 8 weeks).
epididymis A small oblong body along the posterior border of the
testis, consisting of a convoluted tube which provides
for the storage, transit and maturation of spermatozoa.
erythema Redness of the skin which may result from a variety of
causes.
erythrocyte A mature red blood cell or corpuscle.
eschar A hard crust or scab on the skin.
foetotoxic Toxic to the foetus.
gavage Forced feeding through a tube passed into the stomach.
genotoxic Toxic to cellular genetic material such as DNA.
haematocrit The volume percentage of red blood cells in whole blood.
haematological Pertaining to the blood.
haematotoxic Poisonous to the blood and haematopoietic system
haemoglobin The iron-containing pigment of the red blood cells.
haemoglobinuria The presence of free haemoglobin in the urine.
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haemolysis The separation of haemoglobin from red blood cells and its
diffusion into the plasma.
hepatic Pertaining to the liver.
hydrolysis Chemical decomposition in which a substance is split into
simpler compounds by the addition of water.
hydrophilic Having a strong tendency to bind or absorb water.
hydrophobic Incapable of dissolving in water.
hypokalaemia Abnormally low potassium concentration in the blood.
hypotension Abnormally low blood pressure.
in vitro study A test conducted outside the body of the organism, for
example, with cell cultures.
in vivo study A test carried out within the living body of an experimental
animal.
intraperitoneal Within the peritoneal cavity of the body.
The concentration of a substance that will produce death in
LC50
50% of a population of test animals or organisms. It is
used for estimating the acute lethality of chemicals to
aquatic organisms or of airborne chemicals to terrestrial
animals.
The single dose of a substance that can produce death in
LD50
50% of test animals.
leucocyte White blood cell.
lymphocyte A type of leucocyte.
manifold system A system of pipes with a number of inlets and outlets.
metabolic acidosis A disturbance in the acid-base balance of the body in
which there is an accumulation of acids due to loss of base
or retention of noncarbonic or fixed (non-volatile) acids.
mitogen A substance that induces mitosis and cell transformation,
especially lymphocyte transformation.
morphology The science of the forms and structures of organisms.
narcosis Depression of function of the central nervous system
marked by stupor or unconsciousness.
necropsy The examination of the organs of and body tissues of a
dead animal to determine the cause of death or
pathological condition.
necrosis Death of areas of tissue or bone surrounded by healthy
parts.
nephrosis Kidney condition characterised by degenerative changes in
the renal tubules without the occurrence of inflammation.
nystagmus A constant, involuntary, rapid movement of the eyeball.
occlusive Covered with a closely fitting dressing to maximise the
retention and absorption of the test substance (in relation to
dermal studies).
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oedema Swelling.
osmotic fragility The susceptibility of erythrocytes to haemolysis when
exposed to increasing hypotonic saline solutions.
ossification The formation of bone or of a bony substance.
oxaluria An excess in excretion of oxalates in the urine (also known
as hyperoxaluria).
perineal Pertaining to the area of the body between the anus and the
scrotum or vulva.
photolysis Chemical decomposition by the action of light.
Poisons Schedule The Standard for the Uniform Scheduling of Drugs and
Poisons, or SUSDP.
QSAR Quantitative Structure Activity Relationship relates to a
method used to predict the physical properties of a
chemical and specific biological effects, using known
information on structurally related chemicals.
renal Pertaining to the kidney.
reticulocyte A young red blood cell.
S9 fraction An enzyme preparation used in in vitro genotoxicity
testing for the purpose of determining whether the test
substance requires metabolic activation to exert its effect.
sister chromatid The reciprocal exchange of DNA between two sister
exchange (SCE) chromatids of a duplicating chromosome.
sickle cell disease Refers to sickle cell anaemia, a hereditary disease in which
abnormal crescent shaped red blood cells, and an abnormal
type of haemoglobin, haemoglobin S, are present.
spherocytosis The presence of spherical red blood cells in the blood.
surfactants Surface-active chemicals used in a wide variety of
chemical products, especially cleaning agents.
teratogenic Causing permanent structural or functional abnormalities
in offspring during the period of embryonic development.
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