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National Industrial Chemicals Notification and Assessment Scheme




Priority Existing Chemical No. 3



Glutaraldehyde


Full Public Report




July 1994
Australian Government Publishing Service
Canberra
?Commonwealth of Australia 1994

ISBN 0 644 34875 1

First published 1994
Reprinted 1995

This work is copyright. Apart from any use as permitted under the Copyright Act 1968 (Cwlth),
no part may be reproduced by any process without written permission from the Director,
Publishing and Marketing, Australian Government Publishing Service. Inquiries should be
directed to the Manager, AGPS Press, Australian Government Publishing Service, GPO Box 84,
Canberra ACT 2601.




Glutaraldehyde
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 one 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 Commonwealth Environment Protection Agency and and the Department
of Human Services and Health.
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.



On publication of the Summary Report in the Chemical Gazette of 7 June 1994, the chemical
will no longer be a Priority Existing Chemical in accord with Section 62 of the Act.
Copies of the full public report can be obtained by contacting the Chemical Safety Group .
For the purposes of subsection 78(1) of the Act, copies of full public reports may be inspected
by the public at the Library, Plaza level, Alan Woods Building, 25 Constitution Avenue, Canberra,
ACT 2600, between 9am and 5pm weekday except on public holidays.




iii
Priority Existing Chemical Number 3
A pamphlet giving further details of the PEC program is available from NOHSC.
Contact the Chemicals Assessment Branch at:
GPO Box 58
SYDNEY NSW 2001
AUSTRALIA.
OR
334-336 Illawarra Road
MARRICKVILLE NSW 2204
AUSTRALIA.
Telephone: (61) (02) 8577 8800.
Facsimile: (61) (02) 8577 8888.




Glutaraldehyde
iv
Contents


Preface iii



1. Introduction 1


2. Background 2
2
2.1 Early use of glutaraldehyde
2
2.2 Health issues
2
2.3 The Australian perspective
2
2.4 The international perspective


3. Applicants 4


4. Chemical identity 5
5
4.1 Chemical name
5
4.2 Other names
5
4.3 Molecular and structural formula
5
4.4 Trade names
6
4.5 Chemical composition


5. Physical and chemical properties 7
7
5.1 Physical state
7
5.2 Physical properties
8
5.3 Chemical properties




v
Priority Existing Chemical Number 3
6. Methods of detection and analysis 10


10
6.1 Sampling
10
6.2 Glutaraldehyde in air
10
6.2.1 Thermal desorption/gas chromatographic analysis
6.2.2 OSHA method 64 -- High performance liquid
10
chromatographic analysis
10
6.2.3 NIOSH method 2531
11
6.2.4 Silica gel adsorption/gas chromatographic analysis
11
6.2.5 Alumina adsorption/gas chromatographic analysis
11
6.2.6 Colorimetric determination using MBTH
11
6.2.7 Direct-reading instruments
11
6.3 Glutaraldehyde in aqueous solution
12
6.3.1 Colorimetric determination using MBTH
12
6.3.2 Titration after reaction with sodium bisulfite
12
6.3.3 Gas chromatographic analysis


7. Uses 13


13
7.1 Introduction
14
7.2 Cold disinfectant
14
7.3 X-ray film processing
14
7.4 Tanning
15
7.5 Water treatment
15
7.6 Animal housing
15
7.7 Preservative/biocide
16
7.8 Dentistry
16
7.9 Electron and light microscopy
16
7.10 Aquaculture
16
7.11 Therapeutic agent
16
7.12 Other uses




Glutaraldehyde
vi
8. Import and production 17
17
8.1 Importation
17
8.2 Production


9. Kinetics and metabolism 18


18
9.1 Absorption and disposition
18
9.1.1 Material balance study
19
9.1.2 Pharmacokinetic studies
9.1.3 Other studies 19
19
9.2 Metabolism
19
9.3 Reactivity
19
9.3.1 Reaction with proteins
19
9.3.2 Reaction with DNA
20
9.4 Summary


10. Effects on experimental animals and in vitro test systems 21


21
10.1 Acute toxicity
21
10.1.1 Oral
24
10.1.2 Dermal
25
10.1.3 Inhalation
28
10.1.4 Evaluation
29
10.2 Irritation
29
10.2.1 Skin irritation
31
10.2.2 Eye irritation
32
10.2.3 Respiratory irritation
33
10.2.4 Synovial inflammation
33
10.2.5 Evaluation
34
10.3 Sensitisation
34
10.3.1 Skin sensitisation
35
10.3.2 Respiratory hypersensitivity in guineapigs
36
10.3.3 Evaluation




vii
Priority Existing Chemical Number 3
36
10.4 Repeated-dose toxicity
36
10.4.1 Oral
39
10.4.2 Inhalation
41
10.4.3 Dermal
10.4.4 Evaluation 42
42
10.5 Reproductive toxicity/teratogenicity
42
10.5.1 Prenatal toxicity study in drinking water of rats
43
10.5.2 Prenatal toxicity study in rabbits by gavage
44
10.5.3 Reproductive effects in rats and mice by inhalation
44
10.5.4 Teratogenic study with 25% glutaraldehyde in albino rats
45
10.5.5 Other studies
45
10.5.6 Evaluation
45
10.6 Genotoxicity
45
10.6.1 In vitro bacterial assays
46
10.6.2 In vitro mammalian cell assays
49
10.6.3 In vivo assays
50
10.6.4 Evaluation
10.7 Summary 51


11. Human health effects 53


53
11.1 Irritation
53
11.1.1 Skin irritation
53
11.1.2 Eye irritation
54
11.1.3 Respiratory irritation
54
11.2 Sensitisation
54
11.2.1 Skin sensitisation
56
11.2.2 Respiratory sensitisation
59
11.2.3 Photosensitisation




Glutaraldehyde
viii
60
11.3 Other effects
60
11.4 Mortality studies
11.4.1 Mortality study of glutaraldehyde production
60
workers
60
11.5 Medical record reviews
11.5.1 Review of workers assigned to glutaraldehyde
60
production or drumming
61
11.6 Summary


12. Hazard classification 63


63
12.1 Classification of hazardous substances
63
12.1.1 General
64
12.1.2 Health effects criteria
64
12.2 Classification of glutaraldehyde
64
12.2.1 Acute lethal effects
65
12.2.2 Corrosivity/irritancy
66
12.2.3 Sensitisation
66
12.2.4 Severe effects after repeated or prolonged exposure
67
12.2.5 Mutagenicity
67
12.2.6 Carcinogenicity
67
12.2.7 Reproductive toxicity/teratogenicity
67
12.2.8 Non-lethal irreversible effects after a single exposure
67
12.2.9 Summary
68
12.3 Dangerous goods classification
68
12.4 Poisons schedule


13. Hazard communication 70


70
13.1 Material Safety Data Sheets
13.2 Labels 71
73
13.3 Other information




ix
Priority Existing Chemical Number 3
14. Occupational exposure 74
74
14.1 Routes of exposure
74
14.2 Formulation
75
14.3 Cold disinfectant
77
14.4 X-ray film processing
80
14.5 Tanning
80
14.6 Water treatment
81
14.7 Animal housing
82
14.8 Preservative/general biocide
82
14.9 Microscopy
82
14.10 Summary


15. Examples of current practices involving glutaraldehyde ?br> photographs 83


83
15.1 Glutaraldehyde as a raw material
85
15.2 Current practice in disinfection of endoscopes
90
15.3 Current practice in x-ray photography
92
15.4 Current practices in animal housing
95
15.5 Specially-designed equipment recommended for disinfection


16. Occupational health and safety assessment 99


99
16.1 Health and safety hazards
99
16.2 Assessment of use in formulation
100
16.3 Assessment of use as cold disinfectant
101
16.4 Assessment of use in x-ray film processing
102
16.5 Assessment of use in tanning
103
16.6 Assessment of use in water treatment
103
16.7 Assessment of use in animal housing
104
16.8 Assessment of use as preservative/biocide
104
16.9 Microscopy
104
16.10 Other uses




Glutaraldehyde
x
104
16.11 Education and training
104
16.11.1 Formulation
105
16.11.2 Health care industry
105
16.11.3 Other industries
105
16.12 Control measures
105
16.12.1 Control of hazardous substances
106
16.12.2 Elimination and substitution
106
16.12.3 Isolation
106
16.12.4 Engineering controls
109
16.12.5 Administrative controls
109
16.12.6 Safe work practices
110
16.12.7 Personal protective equipment
111
16.13 Emergency procedures
111
16.14 Atmospheric monitoring


17. Regulatory controls 113


113
17.1 Exposure standard
114
17.2 Health surveillance


18. Public health assessment 116


116
18.1 Public exposure
116
18.1.1 Cold disinfectant
116
18.1.2 X-ray film processing
116
18.1.3 Tanning
116
18.1.4 Water treatment
117
18.1.5 Animal housing
117
18.1.6 Preservative/general biocide
117
18.1.7 Electron and light microscopy
117
18.2 Assessment of public health effects
117
18.2.1 Assessment of toxicological hazards
117
18.2.2 Assessment of public exposure




xi
Priority Existing Chemical Number 3
19. Environmental assessment 119


119
19.1 Environmental exposure
119
19.1.1 Formulation
119
19.1.2 Use and disposal
121
19.2 Environmental fate
122
19.2.1 Hydrolysis
122
19.2.2 Photodegradation
122
19.2.3 Biodegradation by sewage microorganisms
122
19.2.4 Metabolism in soils and aquatic systems
123
19.2.5 Bioaccumulation
123
19.2.6 Summary
123
19.3 Environmental effects
123
19.3.1 Avian toxicity
123
19.3.2 Aquatic toxicity
125
19.4 Environmental hazard
126
19.5 Conclusions
127
20. Conclusions


21. Recommendations 128


128
21.1 Hazard classification
129
21.2 Hazard communication
129
21.2.1 Labels and MSDS
130
21.2.2 Other information
130
21.2.3 Training and education
130
21.3 Control of occupational exposure
131
21.3.1 Formulation of glutaraldehyde products
131
21.3.2 Use as cold disinfectant
133
21.3.3 Use in x-ray film processing
134
21.3.4 Use in tanning
134
21.3.5 Use in water treatment
134
21.3.6 Use in animal housing




Glutaraldehyde
xii
135
21.4 Atmospheric monitoring
135
21.5 Emergency response plan
135
21.6 Disposal
136
21.7 Regulatory controls
136
21.7.1 Exposure standard
136
21.7.2 Health surveillance
136
21.7.3 Aquaculture
21.8 Further testing


22. Secondary notification 138


Appendixes


139
1. Risk phrases
140
2. MSDS submitted
143
3. Labels submitted
145
4. Survey of health care establishments using glutaraldehyde
149
5. Example of MSDS for concentrated glutaraldehyde
156
6. Example of MSDS for diluted glutaraldehyde


References 161


Additional studies provided by the applicants as part of the requests to
169
vary the report (under section 37 of the Act)
170
Further reading


Glossary 171




xiii
Priority Existing Chemical Number 3
Glutaraldehyde
xiv
1. Introduction

The chemical glutaraldehyde (CAS No. 111-30-8) 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 2 March 1993.

The declaration was made on the basis that there were reasonable grounds for believing
that the production, handling, use and disposal of glutaraldehyde could give rise to a
risk of adverse health effects.

In summary these grounds were that:

? the use of glutaraldehyde in a number of industries in Australia had led to
widespread occupational exposure; and

? exposure of workers in Australia to glutaraldehyde had resulted in significant skin,
respiratory and eye irritation and, in some cases, skin sensitisation.

In accordance with the Act, importers of glutaraldehyde applied for the assessment of
the chemical as a PEC. Information for the assessment was received from importers,
end-users, State and Territory governments, other interested persons, and from a
comprehensive literature search.




1
Priority Existing Chemical Number 3
2. Background
2.1 Early use of glutaraldehyde
The early use and synthesis of glutaraldehyde has been summarised by Russell and
Hopwood.1 The first report of the synthesis of glutaraldehyde appeared in 1908, but its
first commercial use, as a tanning agent, was not recognised until about 30 years ago.
Commercial availability led to other uses, namely as a fixative in electron microscopy,
as a cross-linking agent for proteins and enzymes, and then in the early 1960s as a
disinfectant for instruments used in the health care industry.2 Concerns about the health
risks associated with the use of formaldehyde in the early 1970s led to a further impetus
in glutaraldehyde use.

2.2 Health issues
Following the increasingly widespread use of glutaraldehyde, particularly as a
disinfectant, concerns arose about the irritant effects of the chemical. Contact dermatitis
and eye and respiratory problems were observed in nurses who were regularly exposed
to glutaraldehyde during the disinfection of instruments such as endoscopes and
bronchoscopes, and radiologists, who used glutaraldehyde as a fixative in their x-ray
developing solutions.

2.3 The Australian perspective
By 1990, glutaraldehyde was used widely in Australia in a number of industries, with an
increasing number of workers reporting adverse health effects after exposure to
glutaraldehyde, especially in the health care industry.
In response to widespread concern, Worksafe Australia issued a Hazard Alert in
October 1991, warning workers and their employers of the health hazards associated
with glutaraldehyde use. The two main results from the Hazard Alert were:
?a greater awareness of the hazards of glutaraldehyde, particularly in the health care
industry, with immediate improvements in control measures to reduce exposure to
glutaraldehyde in the workplace; and
?a decline in the use of glutaraldehyde in some other industries, particularly animal
housing.
The Hazard Alert also generated interest in potential alternatives to glutaraldehyde.
Unfortunately in some cases, glutaraldehyde was replaced with an unsuitable or more
hazardous substitute, for example, formaldehyde.
Glutaraldehyde is not manufactured in Australia, but it is currently imported by a
number of companies included in the list of 13 applicants for this assessment (see
Chapter 3, Applicants).

2.4 The international perspective
Internationally, some countries, for example, the United Kingdom and New Zealand,
have taken action to regulate and/or improve the controls required in the use of
glutaraldehyde, particularly in the health care industry.



Glutaraldehyde
2
Glutaraldehyde is listed on Phase 4 of the Organisation for Economic Cooperation and
Development (OECD) High Production Volume (HPV) Program for chemicals where
there is high risk of exposure to humans or the environment because production
volumes are in excess of 1000 te/yr. As Australia is sponsoring glutaraldehyde in the
HPV program, this report will be forwarded to the OECD as part of the screening
information data set (SIDS) requirements of the program.
No known major international reviews of glutaraldehyde have been conducted.




3
Priority Existing Chemical Number 3
3. Applicants

AGFA-Gevaert Ltd Kodak (Australasia) Pty Ltd
372 Whitehorse Road, 173 Elizabeth Street,
Nunawading Vic 3131 Coburg Vic 3058


BASF Australia Ltd Pfizer Agricare Pty Ltd
500 Princes Highway, 38-42 Wharf Road,
Noble Park Vic 3174 West Ryde, NSW 2114


Du Pont (Australia) Ltd Phoenix Medical Pty Ltd
168 Walker Street, Unit C, 6 Lyon Park Road,
North Sydney NSW 2060 North Ryde NSW 2113


Hanimex Pty Ltd T R (Chemicals Australia) Pty Ltd
108 Old Pittwater Road, 195 Briens Road,
Brookvale NSW 2100 Northmead NSW 2152


ICI Australia Operations Pty Ltd Union Carbide Chemicals (Australia)
1 Nicholson Street, Pty Ltd
Melbourne Vic 3000 Site 1, 1st floor,
1-7 Jordan Street
Ilford (Australia) Pty Ltd Gladesville NSW 2111
cnr Ferntree Gully and Foster Road,
Mount Waverley Vic 3149 Whiteley Chemicals Australia Pty Ltd
82-84 Ivy Street,
Johnson and Johnson Medical Pty Ltd Chippendale NSW 2008
1-5 Khartoum Road,
North Ryde NSW 2113




Glutaraldehyde
4
4. Chemical identity
4.1 Chemical name
Glutaraldehyde is listed on the Australian Inventory of Chemical Substances (AICS) as
pentanedial.
The IUPAC name is 1,5-pentanedial.
The Chemical Abstracts Service (CAS) number is 111-30-8.

4.2 Other names
1,3-diformylpropane
Glutaral
Glutardialdehyde
Glutaric dialdehyde
1,5-pentanedione
Potentiated Acid Glutaraldehyde

4.3 Molecular and structural formula
The molecular formula is C5H8O2.
The structure is
CH2 CH2 CH2
CHO
CHO

The molecular weight is 100.11.

4.4 Trade names
Actisan
Aidal, Aidal Plus
Aldecyde 28
Aldespray 15
Aqucar 545
Biomate 733, Biomate 5792
Cidex, Cidex Long-Life
Cronex, Cronex HSD/R
Derugan 2000, Derugan 2020
DSD (Dodge sterilant & disinfectant)
Duraflo RT Developer Replenisher
Formula 936N, Formula 9365N, Formula 9465N
G135 Developer Part C
Germ-Out



5
Priority Existing Chemical Number 3
Glutarall
GPC 8
Ilfotec RT Developer Replenisher
Industrex Developer Replenisher
Keymix Glutacide
Microcide
Nalco 7338
Neoquat LA
Parvocide
Piror Slimicide 825
Protectol GDA, Protectol GDA 25%
Protosan
Relugan GT 25, Relugan GT 50
RD III Developer/Replenisher
RP X-Omat Developer/Replenisher
Safeguard
Sepacid GA 50
Sonacide
Ucarcide 125, 225, 250
Ucarsan
Ucar Tanning Agent G50
Uconex 350


Wavicide 01

4.5 Chemical composition
Glutaraldehyde is used mainly as an aqueous solution, ranging in concentration from
50% w/w to less than 1% w/w.
Glutaraldehyde tends to polymerise in solution, with differing proposals advocated for
its chemical composition in solution. It has been reported that commercial
glutaraldehyde may contain numerous species, including oligomers, unsaturated
derivatives and cyclic aldehydes.1
Some glutaraldehyde-containing products contain other chemicals, for example,
disinfectants activated with sodium bicarbonate and x-ray film developers containing
sodium bisulfite.
Glutaraldehyde can be characterised by infra-red spectroscopy, nuclear magnetic
resonance spectroscopy and gas chromatography/mass spectroscopy.




Glutaraldehyde
6
5. Physical and chemical
properties;
5.1 Physical state
Glutaraldehyde is a colourless oily liquid. In Australia glutaraldehyde is commercially
available as a clear aqueous solution at concentrations up to approximately 50% w/w.
Commercial samples may have a slightly coloured tint and an odour of rotten apples.
In the vapour state, glutaraldehyde has a pungent odour, with an odour threshold of 0.04
ppm.

5.2 Physical properties
Where information has been available, the physical properties for glutaraldehyde as a
pure chemical have been listed below. Where data for some properties was available
only for aqueous solutions of glutaraldehyde, for example, vapour pressure, this has
been indicated.

Table 1
Physical properties of glutaraldehyde
Property 50% 100%

Freezing point -21癈 -14癈
o o
Boiling point 101 C 188 C
Density (water = 1) 1.13 0.72
Vapour density n.a. 4.1 g/L
Relative density (air = 1) n.a. 3.4
Vapour pressure (20癈) 2.03 Pa ?br> pH mildly acid n.a.
Refractive index 1.421 1.4338
(at 25癈, 589 nm)
Flash point n.a. unknown
Flammability limits n.a. unknown
n.a. Not applicable.




7
Priority Existing Chemical Number 3
5.3 Chemical properties


Table 2
Chemical properties of glutaraldehyde
Property Description

Solubility Soluble in all proportions in water and ethanol; soluble in benzene
and ether.
3
Hydrolysis Stability decreases with increasing pH.
?pH 5, half-life 508 days.
?pH 7, half-life 102 days.
?pH 9, half-life 46 days.
4
Partition log P = -0.01
Coefficient (50% solution).
(n-octanol/water)

Dissociation constant Not applicable, as glutaraldehyde is non-ionic and would not be
expected to dissociate in water.
Adsorption/
5
Desorption The soil mobility of gluaraldehyde was determined in sandy loam,
silty clay loam, loamy sand and a sandy sediment, which were
equilibrated with glutaraldehyde solutions (0-10 ppm) by
shaking for 24 hours. The respective organic content and pH values
for each soil are at Table 3.

Significant losses due to metabolism were observed during the
equilibration, with unchanged glutaraldehyde representing
between 62% and 84% of radiolabel, dropping to below 20% in
the loamy sand. However, data obtained were well correlated
with the Freundlich equation. Derived Freundlich coefficients were
normalised for organic carbon content, and indicate organic
sorption to, and moderate mobility in, the four soils, grading to
weak sorption and high mobility in the sandy sediment (Koc values
at Table 3).

Desorption coefficients could not be determined because of the
instability of glutaraldehyde under the test conditions. Little or no
desorption occurred during a 24-hour desorption phase.




Glutaraldehyde
8
Table 3
Adsorption/desorption in soils
Soil type % organic carbon pH Koc
Sandy loam 1.0 6.8 210

Silty clay loam 1.0 5.7 500

Silt loam 1.4 6.7 340

Loamy sand 0.24 5.8 460

Sandy sediment 0.5 8.1 120




Glutaraldehyde is an aliphatic dialdehyde that undergoes most of the typical aldehyde
reactions to form acetals, cyanohydrins, oximes, hydrazones and bisulfite complexes.
Glutaraldehyde in solutions is susceptible to aerial oxidation to give the corresponding
carboxylic acid.
Glutaraldehyde reacts with proteins by a cross-linking reaction which is mainly between
the NH2 groups, and which depends upon time, pH and temperature. The reaction is less
efficient under alkaline conditions.
Glutaraldehyde polymerises in water to a glassy form which regenerates the dialdehyde
on vacuum distillation. In solution, glutaraldehyde partially polymerises to oligomers to
give a mixture of variable composition. The degree of polymerisation increases with pH
and temperature. Above pH 9, polymerisation proceeds comparatively rapidly and
solutions eventually lose their sporicidal activity.
When heated to elevated temperatures (> 400癈), glutaraldehyde in aqueous solution
will decompose thermally to form carbon oxides and hydrocarbons. In standard thermal
stability tests in the laboratory, aqueous glutaraldehyde showed no exothermic
decomposition when heated to 340癈.6




9
Priority Existing Chemical Number 3
6. Methods of detection
and analysis
6.1 Sampling
All methods of detection and analysis must include reliable sampling procedures.
In the determination of glutaraldehyde in air, sampling is usually carried out by drawing
air through an adsorption tube by means of a small pump at a known flow-rate.
Sampling can be carried out at a fixed location or on the worker (personal sampling). In
personal sampling, air should be drawn through an adsorption tube attached in the
breathing zone of the worker. Sampling pumps need to be regularly calibrated to ensure
that the flow-rate is constant during the sampling period.
Further guidance on sampling by solid adsorption techniques is available in Australian
Standard AS 2986.7
In the sampling of aqueous glutaraldehyde solutions, clean dry sampling containers
should be used so that cross-contamination is avoided.

6.2 Glutaraldehyde in air
A number of analytical test methods are available for the determination of low levels of
glutaraldehyde in the atmosphere. The national exposure standard for glutaraldehyde is
0.2 ppm v/v (peak limitation),8 so the methods should have detection limits comfortably
below that level, for example, 0.05 ppm. Results may be affected by other chemicals in
the workplace, for example, alcohols and other aldehydes, so the methods should be
designed to avoid interference. Some of the methods used are listed below.

6.2.1 Thermal desorption/gas chromatographic analysis
Air is sampled by pump and drawn through an adsorption tube packed with Tenax-GC.
The tube, which also acts as the separation column, is then connected to the gas
chromatograph equipped with a flame ionisation detector, with the contents thermally
desorbed and separated using temperature programming. The method is quick
(approximately 15 minutes), accurate and very sensitive.

6.2.2 OSHA method 64 ?High performance liquid chromatographic analysis
Samples are collected (by pump) on 37 mm glass fibre filters treated with 5%
dinitrophenyl-hydrazine hydrochloride (DNPH), and then desorbed in acetonitrile. The
solution is analysed by injection into an HPLC equipped with an ultra-violet absorption
detector. The detection limit for glutaraldehyde is approximately 0.1 礸.

6.2.3 NIOSH method 2531
The United States-based National Institute of Occupational Safety and Health (NIOSH)
method 2531 is similar, except that the sample is collected on washed XAD-2 tubes
treated with DNPH. The detection limit is approximately 0.3 礸.




Glutaraldehyde
10
6.2.4 Silica gel adsorption/gas chromatographic analysis
Samples are collected by pump on adsorption tubes filled with silica gel and then
desorbed with acetone. The resulting solution is injected into a gas chromatograph
equipped with flame ionisation detection. For a 30 litre air sample, the detection limit
for glutaraldehyde is 0.02 ppm. The method is suitable for 15-minute exposures.

6.2.5 Alumina adsorption/gas chromatographic analysis
Samples are collected by pump on adsorption tubes filled with alumina and then
desorbed with a phosphate buffer solution. The resulting solution is injected into a gas
chromatograph equipped with a Tenax-GC column and a flame ionisation detector.

6.2.6 Colorimetric determination using MBTH
As glutaraldehyde is readily soluble in water, air can be drawn through impingers
containing distilled water, for example, by means of a reciprocating air pump operating
at flow rates up to 1 L/min. Glutaraldehyde absorbed in the water is then determined by
colorimetric analysis with 3-methyl-2-benzothiazolinone hydrazone (MBTH) solution
(see section 6.3). The method is sensitive and quick, but other aldehydes and ketones
may interfere.

6.2.7 Direct-reading instruments
From information received during the assessment, only one direct-reading instrument is
commercially available for the monitoring of glutaraldehyde in air. The Lion
Glutaraldemeter* has a fuel cell sensor which enables glutaraldehyde to undergo
catalytic oxidation to produce an electrical response proportional to the quantity of
glutaraldehyde in air. The detection range is 0.05 to 5 ppm v/v. The instrument is simple
and convenient to use, but readings are subject to interference from compounds such as
alcohols and other aldehydes. Regular calibration of the instrument is essential.
Monitoring with the Glutaraldemeter should therefore be carried out by trained
personnel and with regular verification by more specific analytical procedures such as
those listed above.
In a study which compared Glutaraldemeter results with those obtained using OSHA
method 64 (see above),9* it was recommended that the meter not be used in x-ray film
processing establishments, due to the presence of interfering chemicals, and that it be
used with caution in disinfection units, especially if alcohols or other aldehydes are
present.

6.3 Glutaraldehyde in aqueous solution
It has been reported that the purity of glutaraldehyde solutions can be determined by
measuring the ratio of the ultra-violet absorbances at 235 nm and 280 nm.10
The standard method for the determination of glutaraldehyde in aqueous solutions at
high concentrations, for example, 10% to 50% w/w, is titration with 0.5N
hydroxylamine hydrochloride. A potentiometric titration method is available.


*
Comments in this report on commercial equipment do not constitute an endorsement by Worksafe
Australia


11
Priority Existing Chemical Number 3
A number of analytical test methods are available for the determination of low levels of
glutaraldehyde in water, for example, below 5000 ppm w/v. Some of these are listed
below.

6.3.1 Colorimetric determination using MBTH
The water sample is added to a solution of MBTH and the absorbance measured at 605
or 610 nm. Possible interference by ketones and other aldehydes is overcome by
sampling water before the addition of glutaraldehyde to the system. The method is
suitable for 0.5 to 10 ppm w/v glutaraldehyde in water and can be used in the field.

6.3.2 Titration after reaction with sodium bisulfite
Glutaraldehyde in water is determined by reaction of the carbonyl groups with sodium
bisulfite and then titration of hydroxyl ions with standardised sulfuric acid. The range of
the method is 25 to 5000 ppm w/v, but ketones and other aldehydes interfere, and a
correction is needed for acids and bases in the sample.

6.3.3 Gas chromatographic analysis
The water sample is injected into a gas chromatograph equipped with a Tenax-GC or
Porapak PS column and a flame ionisation detector. The range of the method is 1 to
2500 ppm w/v.




Glutaraldehyde
12
7. Uses
7.1 Introduction
Glutaraldehyde has a wide variety of uses throughout the world with its use spread over
a number of different industries. It is used primarily as a biocide but it also has wide use
as a fixative, and some use as a therapeutic agent. In Australia, glutaraldehyde is
similarly used in a number of different industries. The main uses of glutaraldehyde in
Australia are:
?as a cold disinfectant in the health care industry;
?as a hardener in x-ray film processing;
?in tanning as a fixative;
?as a biocide in water treatment;
?in animal housing for disinfection;
?as a preservative in industrial oils;
?as a biocide in sanitary solutions for aircraft and portable toilets;
?in small quantities as a disinfectant for air ducts;
?as a tissue fixative in electron and light microscopy and in histochemistry;
?as a biocide in aquaculture;
?in small quantities as an embalming agent; and
?as a therapeutic agent.

Table 4
Estimated distribution of glutaraldehyde in end-use products in Australia
Use Percentage*

Cold disinfectant 55%
X-ray film processing 20%
Animal housing 5%
Water treatment 10%
Tanning 5%
Preservative/general biocide 5%
and other uses

* Approximate.




13
Priority Existing Chemical Number 3
Glutaraldehyde has been reported to be used overseas as:
?an intermediate in the production of pharmaceuticals, pesticides and crop protection
agents;
?as a water-resistant in the manufacture of wallpaper and paper towelling;
?as a cross-linking agent for microencapsulation; and
?as a preservative in cosmetics.
These uses have not been reported in Australia.

7.2 Cold disinfectant
Aqueous glutaraldehyde solutions are used throughout the health care industry in
Australia to disinfect instruments such as endoscopes, surgical instruments and dental
equipment. For proper effect, the solutions are made alkaline, for example, with sodium
bicarbonate at approximately 0.3% w/v. Normally the 1% or 2% solutions are used,
although in recent years the trend throughout the industry has been towards the 1%
solution, due to the increased occupational hazard associated with higher concentrations
of glutaraldehyde.
Disinfection is usually carried out by soaking the instruments in glutaraldehyde solution
for a fixed period, and then rinsing the equipment with clean water.
The advantages of buffered glutaraldehyde as a disinfectant are:
?its broad spectrum of activity;
?its rapid microbiocidal action; and
?its non-corrosivity (at lower concentrations) to most materials, including metals,
rubbers and lenses.
The main disadvantages are its adverse health effects and its irritating odour.

7.3 X-ray film processing
Glutaraldehyde is incorporated into developing solutions for black-and-white x-ray
photography as a hardening (or cross-linking) agent to shorten the drying cycle in film
processing. The developers containing glutaraldehyde are generally used in high
temperature, automated film processing, mainly in the medical x-ray processing field
and, to a lesser extent, in engineering applications such as the non-destructive testing of
welds.
X-ray developers are usually supplied as a concentrate containing up to 50% w/w
glutaraldehyde, and are diluted to working solutions containing glutaraldehyde at less
than 2%.

7.4 Tanning
Aqueous solutions of glutaraldehyde are used to soften leathers and to improve their
resistance to water, alkalis and mould. Depending on the type of leather or pelt to be
treated, an amount of 25% or 50% w/w glutaraldehyde solution is added to a mixing
vessel to soak the leathers, giving a final concentration of approximately 0.5 to 2% in
the mixing vessel.




Glutaraldehyde
14
Tanning with glutaraldehyde can be achieved over a wide pH range, but the amount of
glutaraldehyde bound by collagen and the rate of fixation increase with pH.
Glutaraldehyde is bound irreversibly to the collagen molecule and severe acid
hydrolysis is required to release it by the breaking of peptide bonds within the collagen
rather than the actual glutaraldehyde binding site.1

7.5 Water treatment;
Aqueous glutaraldehyde solutions at 45-50% w/w are used as microbiocides for the
treatment of water in evaporative recirculating cooling towers such as those in industry,
shopping malls and large air-conditioned commercial buildings. The glutaraldehyde
solutions are also used in air washers and brewery pasteurisers. In some cases,
glutaraldehyde is fed to the water treatment system in a more dilute form, for example,
at less than 10%.
Glutaraldehyde helps to control the slime and algae deposits which tend to cause fouling
of cooling equipment, adverse health effects, metal corrosion and poor heat transfer.
Microbiocides are usually administered in slugs as shock kill doses for maximum effect.
This can be done manually or by the use of automatic dosing equipment. The final
concentration of glutaraldehyde in cooling tower water after dosing is approximately 50
to 100 ppm w/v.

7.6 Animal housing
Aqueous glutaraldehyde solutions are used to disinfect animal and bird houses such as
pig and poultry sheds, aviaries, hatcheries, kennels, catteries, stables and veterinary
hospitals.
Dilute solutions at approximately 0.1 to 0.3% w/v glutaraldehyde are sprayed, washed
or foamed onto the walls, floors and other surfaces to clean and disinfect. In the fogging
of sheds, usually with automatic or semi-automatic equipment, a more dilute solution of
approximately 400 ppm is used.
Glutaraldehyde solutions at approximately 750 ppm are also used to sanitise egg shells
to assist in the removal of dirt and debris. Sanitising is followed by rinsing with clean
water.

7.7 Preservative/biocide
Glutaraldehyde is used as a preservative or general biocide in a number of applications.
In Australia it is used as a 5% w/v aqueous solution as a biocidal additive in conveyor
chain lubricants. The solution is fed continuously from a 25 L container to the lubricant
via an automatic feed system.
Glutaraldehyde is also used as a 2% w/v disinfectant in sanitary solutions used in
aircraft and portable toilet systems.
It is also used as a disinfectant for air ducts. A 2% w/v solution can be sprayed or
fogged directly into the air ducts; if the level of contamination in the duct is low, the
solution can be diluted to approximately 0.2%. After application, the ventilating system
is run at maximum flow rates to disperse the solution. The solution may also be mixed
with a sealing solution before spraying or fogging, but this procedure is not
recommended in heavily contaminated ductwork.



15
Priority Existing Chemical Number 3
7.8 Dentistry
Glutaraldehyde is used in dentistry as a disinfectant for dental instruments as a 1% or
2% solution. It has also been used therapeutically in dentistry as a pulpotomy
medicament and in dentin bonding.
In Australia, the use of glutaraldehyde in dentistry has been gradually reduced in recent
years, to the extent that in some regions it is not used at all, for example, the South
Australian Dental Service has reported that they discontinued use in 1992.

7.9 Electron and light microscopy
Glutaraldehyde is used in electron and light microscopy and in histology as a tissue
fixative, generally as a 3% to 6% aqueous solution. Glutaraldehyde is an effective cross-
linking agent for proteins and polyhydroxy compounds. Experiments showed that
tissues fixed in glutaraldehyde had excellent morphological preservation, superior to
that obtained with formaldehyde, since swelling and disruption were regularly absent.
Glutaraldehyde gave the best general preservation of cellular fine structure.

7.10 Aquaculture
Glutaraldehyde is used, generally in conjunction with wetting agents, to control viruses
and other micro-organisms in the aquaculture industry in some States.11 Farming of
finfish rather than crustacea consumes most of the chemicals used in aquaculture.

7.11 Therapeutic agent
Glutaraldehyde has been used as a therapeutic agent as following:
?the topical treatment of hyperhidrosis (sweating);
?the topical treatment of onychomycosis (fungal nail infection);
?in friction blister prevention in soldiers, athletes and ballet dancers; and
?in dentistry, for example, in pulpotomy and dentin bonding.

7.12 Other uses
A 2% aqueous solution of glutaraldehyde has been used in embalming, but it is believed
that usage for this purpose is low in Australia.
In overseas countries, glutaraldehyde has been used as a preservative in cosmetics, for
example, in hair conditioners, but there was no evidence during the assessment period
of any such application in Australia.




Glutaraldehyde
16
8. Import and production
8.1 Importation
Glutaraldehyde as a pure chemical is not manufactured in Australia, nor are there any
known plans for manufacture over the next five years. It is imported into the country by
a number of companies (among the applicants in this assessment), mostly as a 25%,
45% or 50% w/w aqueous solution, but also as end-use products such as x-ray
developers, tanning solutions and low concentration (1% or 2%) disinfecting solutions.
The total volume of glutaraldehyde imported into Australia per year has been in excess
of 100 tonnes in recent years (for concentrations 12-50% w/w).

8.2 Production
Glutaraldehyde end-use products in Australia are manufactured by dilution of a
glutaraldehyde concentrate, usually provided as a 25%, 45% or 50% w/w aqueous
solution in 200 litre drums.
Concentrate is pumped, generally via a closed system, into a large mixing vessel, for
example, 2000 litre capacity, for blending of the ingredients in the end-use product.
Water is added during mixing and, in some cases, at the completion of the process to
achieve the required concentration of glutaraldehyde. The blended material may be
either pumped to a holding tank for intermediate storage and/or final blending or it may
be packed directly into containers for end-use. Quality control samples are taken for
analysis from the mixing vessels or holding tanks.
In general, blending is carried out in a closed system. However, in some cases mixing is
carried out by the direct emptying of 200 litre drum contents into a mixing tank,
followed by blending with water and other ingredients to give the end-use product.
Rather than being a closed system, the mixing process may be carried out using local
exhaust ventilation.
In some cases a simple repacking of glutaraldehyde concentrate is carried out, for
example, into an end-user's labelled container or into equipment suitable for end-use, for
example, a feeding system in water treatment.




17
Priority Existing Chemical Number 3
9. Kinetics and metabolism
9.1 Absorption and disposition

Material balance study12
9.1.1
A material balance study was carried out in male and female Fischer 344 rats and New
Zealand White rabbits by the intravenous injection and dermal application of aqueous
14
C-glutaraldehyde solutions. The following doses were administered:


Table 5
Material balance study?doses used
Test volume (mL) % glutaraldehyde

Rat
intravenous 0.2 0.075, 0.75
dermal 0.2 0.075, 0.75, 7.5

Rabbit
intravenous 2.5 0.075, 0.75
dermal 2.5 0.75, 7.5



In the dermal studies, glutaraldehyde was kept in contact with the skin under an
occlusive dressing for 24 hours.
For both routes of administration, the animals were sacrificed after 24 hours and the
tissues and carcasses examined for radioactivity.
The results from intravenous injection showed that exhaled CO2 was the major
metabolite in both species (rat 65-80%, rabbit 30-70%), with approximately 80% of it
collected over the first four hours. CO2 excretion was proportionally less at the higher
dose, especially in rabbits. Recovery measurements were also made in urine (approx.
10% of administered dose for the rat, 20% for the rabbit), faeces (4%, <1%), tissues
(5%, 8%) and carcass (7%, 25%), with higher absorption at the higher concentration for
both the rat and rabbit.
The dermal studies resulted in much lower CO2 excretion (rat 1-2% of administered
dose, rabbit 5-15%). There was a much higher recovery on the skin, especially for the
rat, where only approximately 5% of the applied dose was absorbed. In the rabbit,
approximately 30-50% was absorbed, with 20-30% recovered in the carcass. For the
dermal studies in rats, the total recovery ranged from 61 to 75% of the administered
dose, whereas for the studies in rabbits, the recovery ranged from 71-100%.
There were no significant differences in the results between corresponding male and
female animals in the study.




Glutaraldehyde
18
Pharmacokinetic studies12
9.1.2
Pharmacokinetic investigations were also carried out on rats and rabbits using the same
doses and routes of administration as those used in the material balance study (see
section 9.1.1). Blood was sampled at various intervals between one minute and 24
hours, with results showing that the dermal absorption rate was low (absorption rate
constants 0.2-2hr) in both species. The terminal half-lives (t0.5) for elimination were
long for both intravenous injection (rat 10hr, rabbit 15-30 hr) and dermal application
(rat 40-110hr, rabbit 20-100hr), possibly due to the binding of glutaraldehyde to protein
and the slow excretion of metabolites.

9.1.3 Other studies
The absorption of glutaraldehyde in a number of species has been reported in the
literature. In vitro studies using human skin tissue13 showed that glutaraldehyde did not
penetrate the thick skin tissue of the sole, but 3-14% penetrated the stratum corneum of
the chest and abdomen and 3-4% penetrated the epidermis. In a more recent study, < 1%
of applied glutaraldehyde penetrated the skin of humans, rats, mice, rabbits and
guineapigs.10

9.2 Metabolism
In the material balance and pharmacokinetic studies described above, the metabolites
were not identified. However the report 12 proposed that the metabolism of
glutaraldehyde probably involved initial oxidation to the corresponding carboxylic acids
by aldehyde dehydrogenase, and then further oxidation via an acidic intermediate to
CO2.
The glutaric acid formed by oxidation is probably metabolised by synthesis of a
Coenzyme A thioester to give glutaryl CoA, which is then oxidised by glutaryl CoA
dehydrogenase to give glutaconyl CoA, leading to eventual degradation to acetate and
then to CO2.10,14

9.3 Reactivity

9.3.1 Reaction with proteins
Glutaraldehyde reacts readily with proteins as a cross-linking agent, the reaction being
rapid and pH-dependent (rate increases at pH > 9). Glutaraldehyde initially reacts with
amino acids to give Schiff bases with reactive amino groups. Further reaction occurs to
give a number of complex reaction products, with the mechanism of the cross-linking
process not yet fully understood.1,10

9.3.2 Reaction with DNA
Little information is available on the interaction between glutaraldehyde and DNA. It
has been reported15 that glutaraldehyde only reacts with DNA at >60癈. It has also been
reported10 that only some components of DNA react with glutaraldehyde.




19
Priority Existing Chemical Number 3
9.4 Summary
The results of the material balance and pharmacokinetic studies with solutions of
glutaraldehyde up to 7.5% showed that prolonged skin contact can lead to absorption
via the skin. This is supported by the results of in vitro testing with human skin tissue.
The pharmacokinetic studies indicated that the dermal absorption rates were low and
that the elimination times of absorbed glutaraldehyde were long. The material balance
studies did not identify any specific target site for distribution.
Glutaraldehyde is metabolised principally to CO2 via oxidation to glutaric acid, but the
mechanism for complete metabolism and the identification of all metabolites is yet to be
determined.
As a cross-linking agent, glutaraldehyde reacts readily with proteins, with a number of
complex reaction products formed by a mechanism not yet fully understood.




Glutaraldehyde
20
10. Effects on experimental
animals and in vitro
test systems

10.1 Acute toxicity


10.1.1 Oral
Acute oral toxicity in the rat16
The oral LD50 for UCARCIDE Antimicrobial 250 (50% w/w glutaraldehyde) in the rat
was determined using groups of five male and five female Sprague-Dawley albino rats.
The procedure was based on the United States Environmental Protection Agency's (US
EPA) guidelines 40 CFR parts 158 and 798.
In preliminary testing with groups of two male and three female rats, all five animals at
200 and 100 mg (glutaraldehyde)/kg body weight died, and all at 50, 25 and 12.5 mg/kg
survived.
In the definitive study, groups of five males were administered by gavage 50, 100, or
200 mg (glutaraldehyde)/kg body weight, with all five at 200 mg/kg dying on the first
day, and one at 100 mg/kg on the second day. Groups of five female rats were
administered 50, 70 or 100 mg/kg, with two in the high-dose group dying on the first
day, and two on the second day. At 70 mg/kg, two females died on the first day.
Necropsy findings on those that died included damage and discolouration of the lungs,
stomach and intestines, with two of the females also suffering kidney damage.
Signs of toxicity during the study included sluggishness, lacrimation, diarrhoea and
encrustation around the nose. All survivors recovered within four to five days of dosing,
and were then sacrificed after 14 days, with no significant gross lesions detected.
Under the conditions of the study, the oral LD50 results for Antimicrobial 250 (50%
glutaraldehyde) were:
? male: 246 mg/kg body weight (95% confidence limits 179-339), or 123 mg
glutaraldehyde/kg;
? female: 154 mg/kg (116-206), or 77 mg glutaraldehyde/kg; and
? combined male and female: 200 mg/kg (157-255).


LD50 at various concentrations12
In a separate study in male and female rats with various strengths of solution, the results
are listed in Table 6. The full report of this study was not available for assessment.




21
Priority Existing Chemical Number 3
Table 6
Oral LD50 at various concentrations
LD50
Conc. (% w/w ) Sex (mL soln/kg) (mg soln/kg) (mg gluta/kg)
50 male 1.3 1466 733

45 male 1.2 1344 605

25 male 1.9 1988 497
male 1.5 1636 409

15 male 1.2 1220 183
female 0.9 913 137

10 male 1.6 1680 168
female 1.1 1110 111

5 male 3.3 3300 165
female 1.3 1320 66

1 male 12.3 12300 123
female 9.9 9900 99

0.5 male >16 >32000 >160
female >16 >32000 >160
Conc. Concentration used in test.



The results in the table above show that the LD50s for glutaraldehyde in the range 5-
50% are similar, leading to relatively larger amounts of glutaraldehyde being required to
produce mortality at the higher concentrations. This is contrary to what is expected.

Findings on necropsy of the animals that died included congestion and distension of the
stomach and intestines, haemorrhage and congestion of the lungs, and congestion of the
liver, spleen, kidneys and adrenals. Signs of toxicity in the tests included piloerection,
sluggishness, rapid breathing, diarrhoea and encrustation around the eyes and nose. The
surviving animals usually recovered within five days. Some of the animals sacrificed
after the 14-day observation period showed a mild thickening of the stomach wall, but
there were no other gross pathological findings. The findings were consistent with those
of the study described in section 10.1.1, Acute oral toxicity in the rat.




Glutaraldehyde
22
Other studies

A number of other acute oral toxicity studies in various species have been carried out,
with LD50s listed in Table 7.



Table 7
Other oral LD50s
LD50
Species Sex Reference no. % Gluta. tested mg soln/kg mg gluta./kg

Rat
17 n.r. ? 134-820
male 18 n.r. ? 134
female 18 n.r. ? 165
male 18 2% 4800 96
female 18 2% 5650 113
male 19 10% 1530 153
female 19 10% 1680 168
male 20 1% 10000 100
female 20 1% 10000 100
Mouse
17 n.r. 100-352
male 18 n.r. ? 100
female 18 n.r. ? 110
male 18 2% 6100 122
female 18 2% 10450 209
Guinea pig

17 n.r. ? 50

n.r. Not reported.



The results are similar to those reported in the rat studies in the previous two sections,
with similar signs of toxicity observed.




23
Priority Existing Chemical Number 3
10.1.2 Dermal

Acute dermal toxicity at various concentrations12

In a study in rabbits summarised by Ballantyne, with various strengths of aqueous
solution, the results were as follows:


Table 8
Dermal LD50 at Various Concentrations
LD50
Conc. (% w/w ) Sex (mL soln/kg) (mg soln/kg) (mg gluta/kg)

50 male 2.5 2860 1430
male 1.6 1800 900

45 male 2.0 2200 1000
female 2.7 3020 1360

25 male 12.8 12170 3045
male 8.0 8520 2130

15 male no deaths at 16 mL/kg
female 1 death at 16 mL/kg


conc. Concentration used in test.


There were no deaths with 16 mL/kg of 10% and 5% solutions. The tests indicated that
the acute percutaneous toxicity was influenced more by the concentration of
glutaraldehyde than the amount of glutaraldehyde applied. At necropsy, the only
consistent pathological findings were congestion of the liver, lungs, kidney and spleen.

The full report of the study was not available for assessment.

Other studies

A number of other acute dermal toxicity studies in various species have been carried
out, with LD50s in Table 9 below.


Table 9
Dermal LD50 of glutaraldehyde

Species LD50 (mg/kg) Reference no.

Rabbit 640-2000 17

Rat > 2500 17

Mouse > 4500 17




Glutaraldehyde
24
In a study21 carried out with a 10% glutaraldehyde solution, 2 mL/kg body weight
(equivalent to 200 mg glutaraldehyde /kg body weight) was applied to the intact and
abraded skin of albino rabbits. There were no deaths, so the LD50 could not be
calculated.

In a similar study21 with a 1% solution, 2 mL/kg body weight (equivalent to 20 mg
glutaraldehyde /kg body weight) was applied. Again there were no deaths, so the LD50
could not be calculated.

10.1.3 Inhalation

Four-hour LC50 inhalation study on rats22

A dynamic inhalation study was conducted to determine the acute toxic effects in rats
and to derive a four-hour LC50 value. The protocol conformed with the requirements of
OECD Test Guideline 403 and the study complied with the standards of Good
Laboratory Practice.

In the study, groups of six male and six female Fischer 344 rats were exposed to
glutaraldehyde vapour concentrations of 10.6, 23.0 or 42.7 ppm v/v. A similar group of
controls was exposed to room air only. The vapour was generated by metering a 5%
glutaraldehyde solution into a rotating evaporator tube, where hot air (65癈) was
exhausted into the inhalation chamber. The vapour concentrations were regulated by
adjusting the sample liquid flow-rate or the air exhaust flow-rate.

Mortality during the study was as follows:
Male
?42.7 ppm
One during exposure, two on day 1 after exposure, two on day 2, one on day 3.
?23.0 ppm
Two on day 1.
Female
?42.7 ppm
Two on day 1, one on day 3.
?23.0 ppm
One on day 1, one on day 7.
There were no deaths in control animals or those exposed to 10.6 ppm.
Clinical observations during the four-hour exposure and immediately afterwards
included excess lacrimation and salivation, audible and mouth breathing, and wetness
and encrustation around the eyes. Wetness and encrustation around the nose and mouth
were observed in the animals exposed to the two higher doses. A slow righting reflex
was observed during exposure in one male and one female rat exposed to 42.7 ppm, and
decreased motor activity was observed during the 14-day post-exposure period in all
surviving animals in the 23.0 and 42.7 ppm groups. During exposure, body weights and
food and water consumption were reduced compared with the control group. All
symptoms decreased or disappeared during days 8-14 of the post-exposure period.
The cause of death was apparently lung damage. Breathing difficulties were observed in
most animals during exposure, and at necropsy, colour changes of the lungs were noted
in the male and female rats exposed to 42.7 and 23.0 ppm. No gross lesions of the nasal


25
Priority Existing Chemical Number 3
cavity, larynx or trachea were observed at necropsy.
Under the conditions of the study, a four-hour LC50 of 23.5 ppm v/v (96 mg/L) resulted
for the male rats (with 95% confidence limits 16.8-32.8 ppm), and 40.1 ppm (164 mg/L)
for the females (confidence limits 15.2-105.8 ppm). This high toxicity of glutaraldehyde
was attributed partly to the presence of more toxic higher molecular weight species
formed during vapour generation, but no supporting evidence has been submitted to
substantiate this claim.
Static and dynamic acute vapour inhalation toxicity study in rats23
A recent static and dynamic inhalation study was conducted with UCARCIDE
Antimicrobial 250 (an approximately 50% w/v aqueous glutaraldehyde solution) to
determine the acute toxic effects of glutaraldehyde in rats after a four-hour exposure to
the 'maximum' vapour concentrations achievable at ambient temperature. Groups of five
male and five female Sprague-Dawley albino rats were used in the study. The method
was similar to the limit test in OECD Test Guideline 403 except for the recommended
seven-hour exposure period. The study met the generally accepted standards of Good
Laboratory Practice.
In the static study, the animals were exposed to a mean vapour concentration of 3 ppm,
ranging from a peak of 6.6 ppm to less than the detection limit (2 ppm). The vapour was
generated by placing an open tray of the 50% glutaraldehyde solution above the animals
in the inhalation chamber. No deaths resulted, but eye irritation was observed. No gross
lesions were noted at necropsy after 14 days.
In the dynamic study, two tests were carried out, one at a mean glutaraldehyde vapour
concentration of 16.3 ppm (range 10-24 ppm during exposure) and the other at 14.5
ppm (range 12-17 ppm). The vapour was generated by passing compressed air at
ambient temperature through a bubbler containing the 50% glutaraldehyde solution. No
deaths resulted and the symptoms included those observed in the static test plus wetness
and encrustation around the nose and the eyes. No gross lesions were noted at necropsy
after 14 days.
Under the conditions of the study, no mortality resulted from exposure to the
glutaraldehyde vapours generated statically and dynamically. However the 'maximum'
ambient concentrations achieved in this study are inconsistent with those obtained in
other similar studies (see below), and the considerable variation in concentration during
the tests raised doubts about the reliability of the vapour generation process.
Other studies summarised by Ballantyne12,24
In addition to the above two studies, the results of a number of other acute inhalational
studies were reported (in summary form) for rats exposed to glutaraldehyde vapour
generated from various strengths of solution.
In the early studies between 1961 and 1977,24 groups of six rats were exposed for eight
hours to atmospheres saturated with vapour generated either statically or dynamically
from glutaraldehyde solutions, but no measurements of the glutaraldehyde vapour
concentration were made. No animals died during the studies and no signs of toxicity
were reported.
The results of other later acute inhalational studies are in Table 10.




Glutaraldehyde
26
Table 10
Other Acute Inhalational Studies summarised by Ballantyne
Gluta.
Study type Rats Hours Soln (%) vapour (ppm) Ref Results
Static 6f 6 50 4 or 48* 24,25 No deaths
Eye, respiratory irritation
Static 6f 6 50 5 12,24 No deaths
(2-11) Eye,respiratory irritation
Dynamic 5m,5f 4 14.5 8 24 No deaths
Eye irritation
Dynamic 5m,5f 4 43.6 22 24 No deaths
Eye, respiratory irritation
Increased motor activity
Gluta. Glutaraldehyde.
* Disagreement between two sets of analyses.

In the dynamic studies tabled above, the vapour was generated at room temperature by
the bubbler method.


Other studies
A study18 in rats and mice exposed to approximately 20 ppm v/v (82 mg/L)
glutaraldehyde resulted in the following exposure times required to produce death in
half the animals.


Table 11
50% mortality exposure times (minutes)
Animal Male Female
Rats 60 86
Mice 51 94



Marked hyperaemia was observed in the lungs of both rats and mice. During the study,
observations included sluggishness, breathing rate increase, changes in grooming
behaviour, and drooping of the eyelids, with nose bleeding in the rats only. The
glutaraldehyde vapour for the study was generated by drawing glutaraldehyde solution
into an ultrasonic nebuliser, the resultant vapour passing into the animal chamber.

Other values for the rat LC50 of glutaraldehyde are in Table 12.




27
Priority Existing Chemical Number 3
Table 12
Other LC50s for glutaraldehyde

LC50

Conc. Exposure time (h) Reference no. (mg soln/L) (mg gluta/L)

? 4 26 ? 0.48
? 4 27 ? 20.5
? 8 28 ? 12.6
1 1 20 >31.7 0.32
10 1 19 >6.67 0.67


A study29 in mice exposed to 133 mg/L glutaraldehyde vapour for 24 hours resulted in
toxic hepatitis.
In a study by St Clair30, the acute toxicity of glutaraldehyde to the nasal epithelium of
male Fischer 344 rats was determined by instilling 40 mL of 10, 20 and 40 mM
glutaraldehyde into a nostril. The minimum dose to induce nasal lesions was 20 mM,
with severe lesions at 40 mM. In the study, glutaraldehyde was shown to be
approximately 10 times more toxic to the nasal epithelium of rats than equivalent doses
of formaldehyde.
10.1.4 Evaluation
From information available from the one study submitted during the assessment period
and from values quoted in the scientific literature, the oral LD5 0 in the rat for
glutaraldehyde is in the range 77-820 mg/kg body weight. A number of measurements
have been carried out with various concentrations of glutaraldehyde from 1-50%. In the
only oral LD50 study submitted,16 the values for a 50% glutaraldehyde solution for male
and female rats respectively were 246 mg/kg body weight (95% confidence limits 179-
339) and 154 mg/kg (116-206), whereas the value reported from an earlier study12 was
much higher at 1466 mg/kg. The LD50 values in the latter study were comparatively
higher for the higher concentrations (25%, 45% and 50%); as the study was not
submitted for assessment, no evaluation of this finding is possible. At 0.5%, no signs of
toxicity were observed by the oral route.
No full studies on the acute dermal toxicity of glutaraldehyde were made available for
assessment. However, data from summaries indicated that the LD50 for glutaraldehyde
by this route is above 1000 mg/kg. Aqueous solutions of 10% showed no signs of acute
toxicity by skin contact, but the results for 45% and 50% aqueous solutions indicated
that skin absorption can occur at these higher concentrations. Material balance studies
on the rat and rabbit support this finding. Findings on the animals that died consisted of
congestion of the lungs, liver, kidneys and spleen.
Many of the acute inhalational studies were carried out at low vapour concentrations
which were too low to produce mortality, resulting in mainly irritant effects being
observed in the test animals. From the results of the studies that produced mortality,
glutaraldehyde has a high acute inhalational toxicity, with lung damage observed in rats
and mice that died after exposure to 20 ppm (82 礸/L) for 1-1.5 hours. However, the
results of the only complete study available, which allowed calculation of four-hour
LC50s of 23.5 (96 礸/L) and 40.1 ppm (164 礸/L) for male and female rats respectively,


Glutaraldehyde
28
are clouded by the method of vapour generation, which was carried out at an elevated
temperature (65癈). It was claimed that more toxic oligomers of glutaraldehyde may
have led to the high acute toxicity, but this has not been substantiated.
Other LC50s have been reported in the literature, ranging from 0.48 mg/L/4h-20.5
mg/L/4h, but no experimental details were available.
The method of vapour generation is critical in inhalational studies and, for
glutaraldehyde, a number of different techniques have been used. Glutaraldehyde has a
low volatility, and difficulty has been experienced in achieving vapour concentrations
that will result in mortality. Consequently, in early studies such as the LC50 study above,
the glutaraldehyde solution was heated to generate sufficient vapour to produce
mortality. In later studies, air was bubbled through an aqueous solution at ambient
temperature, but with a second bubbler in parallel to generate the higher vapour
concentrations (see section 10.2.3, Respiratory irritancy in mice). These later studies
have demonstrated that it is possible to generate glutaraldehyde vapours of significant
concentration at ambient temperature. In light of the uncertainty generated by the
studies at elevated temperatures, simultaneous LC50 studies at both ambient and
elevated temperatures have been planned by one manufacturer.31 Detailed vapour
generation studies at various temperatures are also required to improve the correlation
between solution and vapour concentrations.
In a limit test carried out under the 'maximum' glutaraldehyde vapour concentrations
which could be derived statically (3 ppm v/v) and dynamically (14-16 ppm) from a 50%
glutaraldehyde solution at ambient temperature, no mortality resulted. However, the
vapour concentrations achieved were low and inconsistent with those in other tests, for
example, 22 ppm was generated in a dynamic study using a 43.6% glutaraldehyde
solution.
Many of the acute inhalational toxicity studies did not produce systemic toxicity, but the
results showed that exposure of the test animals to glutaraldehyde vapours at low
concentrations leads to irritant effects such as laboured and audible breathing and
wetness and encrustation around the nose and eyes. In the studies resulting in mortality,
congestion of the lungs, kidneys and adrenals was observed.

10.2 Irritation
10.2.1 Skin irritation
A series of skin irritation tests32 was conducted on New Zealand White rabbits with
aqueous glutaraldehyde solutions ranging in concentration between 1% and 50% w/w.
The procedure was in accordance with OECD method TG 404.33
In each test, the shaven skins of three male and three female rabbits were treated with
0.5 mL glutaraldehyde solution, which was kept in contact with the skin for four hours
with an occlusive dressing. Skin reaction was measured using the Draize scoring system
at intervals from one hour to three days, with sites examined at intervals up to 21 days.
The results are at Table 13.
Other earlier studies19,20,21 in New Zealand White rabbits were carried out with 1%
and 10% Sterisol (1% and 10% aqueous glutaraldehyde) in accordance with standard
USA protocols. In each test, 0.5 mL solution was applied under a gauze patch to the
intact skin and an abraded skin area of six animals for an exposure time of 24 hours.
The results are recorded at Table 13.



29
Priority Existing Chemical Number 3
Table 13
Skin irritation at various concentrations
Conc. Ref. Result
50% 32 Moderate to severe erythema, slight to severe oedema, many
spots of necrosis.

45% 32 Moderate to severe erythema, slight to severe oedema and
spots of necrosis, with minor erythema, desquamation and
scabs persisting through the 21 days.

25% 32 Moderate erythema, slight oedema, scattered necrosis.

10% 32 Moderate erythema, slight oedema, necrosis on approximately
half the animals. In the first test, one (of six) rabbits had
erythema and three had desquamation after 21 days. In the
second test, the six rabbits were sacrificed after two days, with
microscopic examination revealing mild necrosis and
dermatitis on all animals.

10% 21 Exposure time 24 hours -- moderate to severe erythema at both
sites for all animals, with erythema still well-defined after 72
hours. Moderate oedema in all animals at 24 hours, with
oedema slight after 72 hours.

10% 19 Exposure time 24 hours -- very slight spotted necrosis at three
intact and five abraded sites.

5% 32 Slight erythema, very slight oedema, spots of necrosis on one
rabbit (of six) in each of two tests. Microscopic examination of
the animals in the second test revealed mild necrosis and
dermatitis (on two of six).
2% 32 Very slight erythema, very slight oedema on two of 12 animals,
signs of necrosis (poorly-defined) on one rabbit. Microscopic
examination in one of the two tests revealed mild necrosis and
dermatitis in two (of six) animals.

1% 32 No significant effects.

1% 20 Exposure time 24 hours -- very slight to well-defined erythema
at five intact and six abraded sites. After 72 hours, very slight
erythema at four intact and abraded sites. Very slight to slight
oedema at four intact and abraded sites after 24 hours, with no
oedema at 72 hours.

1% 21 Exposure time 24 hours -- erythema well-defined at 24 hours
and very slight after 72 hours. Oedema slight at 24 hours and
very slight after 72 hours.

Conc. Concentration used in test.
Ref. Reference number.

Yellow-brown staining was reported at the site of application in all the four-hour tests,32
being severe for all concentrations except 1% and 2%, where the staining was light.




Glutaraldehyde
30
For similar exposure times, a dose-response relationship was apparent for both the
severity and duration of irritation. Under the conditions of the four-hour studies, the
45% and 50% solutions were corrosive, the 25% solution severely irritant, the 2%
solution slightly irritant, and 1% a no-effect concentration for skin irritation. The tests
with 1% and 10% Sterisol resulted in more severe skin reactions, presumably due to the
longer exposure time of 24 hours.
10.2.2 Eye irritation
A series of tests32 was conducted on male and female New Zealand White rabbits with
5%, 2%, and 1% w/v aqueous glutaraldehyde solutions. For each concentration, 0.1 or
0.01 mL of solution was instilled into one eye of each of six rabbits, and the eyes
examined at intervals up to three weeks; for 5% and 2%, an additional dose of 0.005 mL
was also instilled. The procedure used and the scale for scoring ocular lesions were in
accordance with OECD test method TG 405. Further tests1 2 at more dilute
concentrations were later carried out by the same authors. The results are shown at
Table 14.
Other earlier studies19,20 in New Zealand White rabbits were carried out with 1% and
10% Sterisol (1% and 10% aqueous glutaraldehyde) in accordance with standard US
protocols. In both tests, 0.1 mL of solution was applied to one eye of each of six rabbits,
with the other eye serving as the control. The results are in Table 14.

Table 14
Eye Irritation at Various Concentrations
Conc. Ref. Volume Result
10% 19 0.1 mL Mild corneal opacity and moderate conjunctivitis in all
animals after 24 hours, and mild iritis in all six rabbits
within 48 hours. Corneal opacity worsened up to the end
of observation at 72 hours.

5% 32 0.1 mL Severe corneal injury, moderate iritis, severe and
persistent conjunctival irritation and necrosis


0.01 mL Slight corneal injury, moderate conjunctival irritation.


0.005 mL Very slight transient corneal injury, moderate conjunctival
irritation.

2% 32 0.1 mL Slight corneal injury, moderate iritis in all six rabbits,
moderate to severe conjunctival irritation (persistent in half
the animals for 2 weeks).

0.01 mL Minor iritis in one (of six), slight to moderate conjunctival
irritation, no corneal injury.

0.005 mL Slight conjunctival irritation, no corneal injury.

1% 20 0.1 mL Mild corneal opacity in four rabbits within 48 hours,and
moderate conjunctivitis in all rabbits within 24 hours. Mild
iritis in three rabbits within 48 hours, persisting for four
days in two animals, with iritis not being scored after day
four in the second animal due to severe corneal opacity.
Irritative effects still present in 2 of the six rabbits after
seven days.




31
Priority Existing Chemical Number 3
Conc. Ref. Volume Result

1% 32 0.1 mL Slight corneal injury and iritis in two of the six animals,
moderate to severe conjunctival irritation with necrosis in
half the animals (persistent in half the animals for two
weeks).

0.01 mL Slight conjunctival irritation which disappeared fromall
animals within three days.

0.5% 12 0.1 mL Slight conjunctival irritation.

0.01 mL Very slight conjunctival irritation.

0.2% 12 0.1 mL Very slight conjunctival irritation.

0.01 mL No effects.

0.1% 12 0.1 mL No effects.

Conc. Concentration used in test.
Ref. Reference number.


Under the conditions of the tests with concentrations 0.1-5%,12,32 a dose-response
relationship was established for conjunctival irritation and corneal injury.
Glutaraldehyde at 5% was a severe eye irritant, with 1% and 2% being moderately
irritating to the eye. The no-effects level for acute eye irritation of glutaraldehyde in
rabbits was 0.1%.
10.2.3 Respiratory irritation
Respiratory irritancy in mice34
The irritancy of glutaraldehyde vapour to the upper respiratory system of male ND4
Swiss Webster mice was determined by measuring the decrease in respiratory rate at
various concentrations. The study was conducted in accordance with ASTM method
E981-84,35 and it complied with the US EPA standards of Good Laboratory Practice.
Groups of four animals were exposed (head only) to concentrations of glutaraldehyde
vapour ranging from 1.64-36.7 ppm for 30 minutes, with a seven-day recovery period
after exposure. The respiratory rate in breaths/minute of each animal was measured
every 15 seconds and compared with the pre-exposure rate. The glutaraldehyde vapour
concentrations were generated dynamically at ambient temperature by passing
compressed air through a bubbler containing 50% aqueous glutaraldehyde solution. As
concentrations above 10-15 ppm could not be generated with the bubbler, a second
bubbler was placed in parallel to generate concentrations of 20.4 and 36.7 ppm. No
aerosol droplets were observed during the exposure periods for any concentration.
No mortality occurred during the study and no clinical signs of toxicity were observed.
The respiratory rate decreased sharply at all concentrations within three minutes of
exposure, with the depression maintained throughout the 30-minute period. The
decrease in respiratory rate was due to a lengthening of the expiratory phase of
breathing. After exposure, the respiratory rate increased, but not to the level of the pre-
exposure rate. The results are shown at Table 15.




Glutaraldehyde
32
Table 15
Decrease in respiratory rate in mice

Glutaraldehyde (ppm) Respiratory decrease (%)
1.64 26.4
3.21 30.2
4.65 41.5
5.80 39.6
7.47 41.1
20.40 57.1
36.7 59.0


The RD50, the concentration which produces a 50% decrease in respiratory rate, was
calculated to be 13.8 ppm glutaraldehyde.

Under the conditions of the study, respiratory irritation in mice, as measured by
decrease in respiratory rate, was observed at all vapour concentrations, with respiratory
rate decrease still considerable at the lowest concentration. No threshold could be
determined from the study.

Other studies

The respiratory irritant effects of glutaraldehyde at low vapour concentrations were
observed in test animals during acute inhalation studies (see sections 10.1.3 and 10.1.4).
Signs of irritation include laboured and audible breathing and wetness and encrustation
around the nose.

10.2.4 Synovial inflammation

The injection of glutaraldehyde into the synovium of rabbit knees resulted in a dose-
related response between the degree of synovial inflammation and the concentration of
glutaraldehyde.36 At 100 ppm w/v glutaraldehyde, microscopic evidence of
inflammation was observed, with necrosis, haemorrhage and gross diffuse synovitis
observed at 100 ppm or greater. The disinfection of arthroscopic instruments with
glutaraldehyde has been linked to post-operative complications.

10.2.5 Evaluation

The results of a well-conducted study were available to give a measure of the skin
irritancy of glutaraldehyde at various concentrations. At 45% and 50%, the aqueous
solution was corrosive to the skin of rabbits. Signs of skin irritation were still present
with a 2% aqueous solution, but no effects were observed with a 1% solution. The
finding is significant in terms of the general use of either 1% or 2% glutaraldehyde
solutions for disinfection in the health care industry.

Other animal tests were carried out with 1% or 10% solutions, but the duration of skin
contact was longer, for example, 24 hours, so the effects observed were more severe.



33
Priority Existing Chemical Number 3
The results of a well-conducted study were available to give a measure of the eye
irritancy of glutaraldehyde at various concentrations down to 1%, with supplementary
information 12 by the same authors available for concentrations down to 0.1%
glutaraldehyde. The tests indicated that the 5% solution was a severe irritant to the eye
of the rabbit, and that dilute solutions such as 1% and 2% were moderately irritating to
the eye. The further acute eye inflammation studies in the rabbit showed that the
minimal transient eye irritation threshold was 0.2-0.5%, and that the minor transient
corneal injury threshold was 1% glutaraldehyde. The findings emphasised the hazards
associated with glutaraldehyde solutions greater than 0.1% in strength.
The other studies with 1% and 10% aqueous glutaraldehyde solutions confirmed the
results obtained in the major study. Acute inhalation studies in test animals showed that
the vapour from glutaraldehyde solutions was a severe eye irritant at low vapour
concentrations, for example, at 3 ppm v/v.
One respiratory irritation animal study was available for assessment, with the study
showing that the breathing rate of mice was significantly reduced at all vapour
concentrations (1.64-36.7 ppm), no level of tolerance being achieved. Information
available from acute inhalation studies has shown that glutaraldehyde is a respiratory
irritant in test animals at the lowest vapour concentrations measured (2 ppm).

10.3 Sensitisation
10.3.1 Skin sensitisation
Guineapig maximisation test37
A skin sensitisation study was carried out in Dunkin Hartley albino guineapigs with
aqueous 2% glutaraldehyde and alkalinised 2% glutaraldehyde. The test was conducted
in accordance with the procedure for the guineapig maximisation test in OECD test
guideline 406. The study met the requirements of the US EPA's Good Laboratory
Practice Standards except that assays were not carried out to confirm the concentration,
stability and homogeneity of the 2% glutaraldehyde solutions and their dilutions, and
that some test samples were not archived.
Range-finding studies with the test material (2% glutaraldehyde) prior to the study
enabled the doses for the induction and challenge phases to be set at 5% v/v (0.1%
glutaraldehyde) for intradermal injection, 100% (2% glutaraldehyde) for topical
induction, and 10% (0.2% glutaraldehyde) for the challenge and rechallenge phases.
The challenge concentration was set below the skin irritation level.
On day 0, 0.1 mL of test substance was intradermally injected in the shoulders of 10
male and 10 female animals, both as a propylene glycol solution and as a 50/50 Freund's
Complete Adjuvant (FCA)/water emulsion. At a third site on each animal, 0.1 mL of
FCA/water was injected. On day 7, a patch containing approximately 0.2 mL of test
substance was applied to the skin of the same 20 animals for 48 hours.
On day 21, the challenge dose was applied under patch to the animals for 24 hours, with
dermal readings made at 24 and 48 hours after patch removal. On day 28, the challenge
dose was repeated.
To ensure that the reactions during challenge were due to sensitisation rather than
irritation, another five animals of each sex were treated with the vehicle and/or
FCA/water during induction and then subjected to the normal challenge dose. In
addition, another five animals per sex were treated with 0.1% 2,4-dinitrochlorobenzene
(DNCB) to serve as a positive control group.


Glutaraldehyde
34
During the study, one animal died of emaciation, but no internal abnormalities were
observed at necropsy. All other animals gained weight.
The results of the study are shown in Table 16.

Table 16
Skin sensitisation with 2% glutaraldehyde
Aq 2% Alk 2% DNCB Control
Incidence index (maximum 100%)
68 30 100 0
--at re-challenge 32 5
Challenge severity index (maximum 3.0)
24 h 0.8 0.4 1.7 0
48 h 0.4 0.2 1.5 0
Re-challenge severity index (maximum 3.0)
24 h 0.5 0.2 0
48 h 0 0 0
Aq Aqueous.
Alk Alkaline.
DNCB 2,4-dinitrochlorobenzene.


Under the conditions of the study, aqueous 2% glutaraldehyde was a moderate to strong
skin sensitiser in guineapigs, and alkalinised 2% glutaraldehyde was a weak to moderate
skin sensitiser. The tests with DNCB confirmed that the animals were sensitive to a
positive skin sensitisation reaction, and the results for the irritation controls indicated
that the challenge dose was below the irritation level.
Other studies
Glutaraldehyde tested positive in the mouse-ear swelling test42, an assay proposed for
the detection of skin allergens. Glutaraldehyde at 10% was used in the induction phase,
with a concentration of 1% applied at challenge.
10.3.2 Respiratory hypersensitivity in guineapigs39
The potential of glutaraldehyde vapour to induce respiratory sensitisation in male
Hartley guineapigs was investigated by comparing the respiratory response after a
challenge exposure to that of a control group. There are no standard protocols for
respiratory hypersensitivity, but a number of guineapig models under development have
been described in the literature.40 In this study, the criteria for a positive response were:
? a statistically significant increase in respiratory rate; and
? a change in the respiratory waveform, due to a lengthening of the expiratory phase.
The study complied with the US EPA standards of Good Laboratory Practice.
In the study, groups of eight animals were exposed (head only) to 14 ppm (the RD50
value (see 10.2.3, Respiratory irritancy in mice) for 1 hour/day for five days, followed
by challenge with 4-5 ppm glutaraldehyde vapour on days 19, 26 and 40. The vapour
was generated at ambient temperature by passing compressed air through a bubbler
containing 50% aqueous glutaraldehyde solution. The respiratory rate of each animal


35
Priority Existing Chemical Number 3
was measured every 15 seconds and compared with the pre-exposure rate.
No mortality occurred during the study and no clinical signs of toxicity were observed.
No change in respiratory waveform was detected and the respiratory decrease in
exposed animals was similar to that of the controls for each of the three challenge
phases. However, the glutaraldehyde vapour concentration used for challenge in the
study was at irritant level (see 10.2.3, Respiratory irritancy in mice), so any response
due to respiratory hypersensitivity may have been masked by the response to respiratory
irritation.
10.3.3 Evaluation
A well-conducted guineapig maximisation test showed that both the 2% aqueous
solution and the 2% alkalinised solution of glutaraldehyde are skin sensitisers, with the
former the stronger sensitiser. The results of a mouse-ear swelling test confirmed that
glutaraldehyde is a skin sensitiser. The skin sensitising properties of the chemical are
also demonstrated by human evidence in the scientific literature (see section 11.2.1).
In the only animal study on respiratory sensitisation, no response was observed in
guineapigs. However, the study was conducted using glutaraldehyde vapour at irritant
levels where any hypersensitivity response would be masked. Evidence for the
respiratory sensitising potential of glutaraldehyde in humans is reviewed in section
11.2.2.

10.4 Repeated-dose toxicity
10.4.1 Oral
90-day inclusion in drinking water of rats41
A subchronic oral toxicity study in rats was carried out with UCARCIDE 250
Antimicrobial (an approximately 50% w/v aqueous solution of glutaraldehyde). The
method was similar to that in OECD Test Guideline 408 and the study complied with
Good Laboratory Practice standards.
Four groups each of 20 male and 20 female Fischer 344 rats received nominal
concentrations of 0, 50, 250 or 1000 ppm w/v glutaraldehyde respectively in their
drinking water over 13 weeks. The approximate daily intakes were 5, 25, or 100 mg/kg
body weight for male rats, and 7, 35 or 120 mg/kg body weight for females. An
additional 10 animals per sex were added to the 0 and 1000 ppm dose groups for a four
week recovery phase.
A dose related reduction in water consumption was observed for males (at 250 and 1000
ppm) and females (at 1000 ppm), with the water consumption of high dose animals
returning to normal within the four week recovery period. The reduction was attributed
to an aversion to the taste and/or odour of glutaraldehyde rather than a toxicological
effect.
Food consumption was also significantly reduced for male and female rats in the high
dose group, and there were slight but inconsistent reductions in the 250 ppm groups.
Body weight changes for males and females in the high dose groups parallelled food
consumption reduction. It is likely that the decreases in food consumption and body
weight gain were related to the reduction in water consumption and were not direct
responses to glutaraldehyde toxicity.
Urine was collected for analysis from 10 rats/sex/group at six and 12 weeks, and some
changes were observed. For both males and females in the 250 and 1000 ppm groups,


Glutaraldehyde
36
urine volume decreased with an increase in specific gravity, and slight increases in
protein and ketone concentrations were noted. The effects were most likely related to
the decrease in water consumption.
Blood was sampled from 10 rats/sex/group at six and 13 weeks, and no haematological
effects were observed. The only significant effect on serum chemistry parameters was a
dose-related increase in urea nitrogen in female rats in the 250 and 1000 ppm groups at
six weeks. There was no accompanying change in serum creatinine, and urea nitrogen
and creatinine at 13 and 17 weeks were similar to the controls.
A significant dose-related increase in kidney weight relative to final body weight
occurred for males and females in the 250 and 1000 ppm groups, including an increase
in absolute kidney weight for the female rats. Changes in final body weights and the
weights of other organs were minor and/or sporadic and were unlikely to be related to
glutaraldehyde exposure.
Histologic examination of tissues from male and female rats in all dose groups and the
controls revealed no treatment-related findings. No changes to the kidney were
observed, so the changes in kidney weight may have reflected a physiological
adaptation in response to reduced water consumption.
Under the conditions of the study, 1000 ppm of glutaraldehyde was slightly toxic by
ingestion over 90 days, and 250 ppm produced physiological changes. There were no
significant effects at 50 ppm.
Two-year drinking water study in rats42
A two-year drinking water study was conducted in male and female Fischer 344 rats.
The full report of this study was not available for assessment.
The dose range for the study was based on the findings from a 14-day drinking water
study43 and the subchronic (90 day) drinking water study41 (see 10.4.1, 90-day
inclusion in drinking water of rats) conducted in Fischer 344 rats at concentrations of
glutaraldehyde up to 1000 ppm w/v. Consequently, groups of 100 male and 100 female
rats were treated with 0, 50, 250, or 1000 ppm w/v glutaraldehyde in drinking water.
Ten animals per sex per dose were sacrificed at 52 and 78 weeks, with the remainder at
104 weeks.
The mortality rate for males was 25-30%, and for females 19-23%, with no dose-related
increase. The major cause of death in all dose groups, including the controls, was large
granular cell lymphatic leukaemia (LGLL), described below in more detail. During the
study, a small increase in the incidence of urine stains was observed for the high and
low dose males and females, and signs of emaciation and laboured breathing were noted
in females at all doses, but there was no clear dose-response relationship.
Small dose-related decreases in absolute body weight and body weight gain occurred in
males at 1000 and 250 ppm, and in females at 1000 ppm. Water consumption was
reduced, with a dose-related decrease in males and females at 250 and 1000 ppm. The
mean glutaraldehyde consumption for each of the three groups was 4, 17 and 64 mg/kg
(body weight)/day for the males and 6, 25 and 86 mg/kg/day for the females. The food
consumption was reduced for males and females at 1000 ppm.
Blood was collected for analysis from 20 rats per sex per dose at 13, 26, 52, 78 and 104
weeks. The total leucocyte count was significantly increased at week 104 in males at
250 and 1000 ppm, and in females at 250 ppm only. The variation in counts was large,
possibly due to the large monocyte count at 250 and 1000 ppm. Changes in clinical


37
Priority Existing Chemical Number 3
chemistry parameters included decreases in the activities of some enzymes at 250 and
1000 ppm, and occasional decreases in total protein, globulin, and phosphorous; these
were probably due to reduced food consumption and body weight.
Urine was sampled from 10 rats per sex per group at 12, 25, 51, 77 and 103 weeks. For
both males and females at 250 and 1000 ppm, there were dose-related decreases in urine
volumes and associated increases in osmolality, both probably due to decreased water
consumption.
At necropsy at 52, 78 and 104 weeks, the only statistically significant changes in organ
weights were for the kidney. Relative kidney weights were increased for males and
females at 52 and 78 weeks. At 104 weeks the relative and absolute kidney weights
were increased in females at 250 and 1000 ppm, and decreased for males at all doses. In
the absence of any supporting biochemical signs of kidney damage, the changes were
attributed to physiological changes which compensated for the reduced water
consumption.
Gross pathology showed evidence of gastric inflammation, particularly in rats sacrificed
at the end of the study, with irritation observed as ulceration, a multifocal colour
change, and thickening of the mucosa. Histologic examination of the tissues revealed
squamous epithelial hyperplasia and keratinised cysts and oedema. Tubular
pigmentation and basophilia were observed in 104-weeks male and female rats at 250
and 1000 ppm, but this was attributed to the haemolytic changes associated with LGLL.
The main finding of the study was a statistically significant increase in the number of
LGLL observed in the liver and spleen of females only. The main cause of death during
the study was LGLL, but there were few cases of LGLL observed in the routine
sacrifice of 10 animals/sex/dose at 52 and 78 weeks (none at 52 weeks, 4 at 50 ppm
after 78 weeks but none at 250 or 1000 ppm). The cumulative incidence of LGLL is
shown in Table 17. No other significant oncogenic effects were observed during the
study.

Table 17
Incidence of LGLL in liver and spleen (%)
Dose (ppm)
Tissue Sex 0 50 250 1000
Spleen male 43 51 40 46
female 24 41 41 53

Liver male 37 48 39 45
female 23 40 40 52


Under the conditions of the study, glutaraldehyde in drinking water at 50 ppm and
above produced a statistically significant increase in the incidence of LGLL in female
rats after 104 weeks.
Factors moderating the finding were the high incidence of LGLL in the controls (43% in
males, 24% in females), the susceptibility of Fischer 344 rates to LGLL, and the higher
glutaraldehyde doses received by females. The incidence of LGLL in a previous study
conducted by the same laboratory was reported as 22% for males and 66% for females.
However, historical control data for untreated Fischer 344 rats in National Toxicology
Program (NTP) studies indicates that the ranges for this tumour are 10-72% in males


Glutaraldehyde
38
and 6-31% in females.44 Although the control data in this study fitted in with the
historical control data reported from NTP studies, the control data from the earlier study
by the same laboratory did not. Although the authors concluded that the increased
incidence may have been due to the modifying effect of glutaraldehyde on at least one
of the factors that routinely causes LGLL in Fischer 344 rats rather than a carcinogenic
effect, the variability in control data for LGLL and the wide variation reported in the
literature makes a definitive conclusion difficult. The inconsistency of control data
within the study laboratory adds to these difficulties.
10.4.2 Inhalation
A nine-day inhalational rat study25 was conducted at ambient temperature after earlier
studies carried out with heated glutaraldehyde solution had indicated a high inhalational
toxicity for glutaraldehyde, viz:
an acute study22 resulted in an LC50 of 23.5 ppm for males and 40.1 ppm for
?br> females; and
a preliminary nine-day study45 resulted in significant mortality at 2.1 ppm (see Table
?br> 18).
These studies had also confirmed the potent irritancy of glutaraldehyde to the upper
respiratory system at low concentrations.
For similar reasons, a subchronic 14-week rat study46 was also conducted by the same
research laboratory. The procedures for the nine-day and 14-week studies were similar
to OECD Test Guidelines 412 and 413 respectively, and both studies satisfied quality
assurance requirements.
Later, two-week and 13-week inhalational studies14 were carried out in F344/N rats and
B6C3F1 mice under the NTP.
The results of these studies are summarised in Table 18. In each case, exposure was for
six hours per day.

Table 18
Repeated dose inhalational studies
Species Study Ref. Exposure concentration and results

Rat 9-day 45 0, 0.2, 0.63, 2.1 ppm
(10m,f) * Mortality: 9/10 m, 7/10 f at 2.1 ppm (days 3-9), 1/10 m
at 0.63 ppm.
* Respiratory irritation at all concentrations.
* Body weight and organ weight decrease at 0.63 and
2.1 ppm.

Rat 9-day 25 0, 0.3, 1.1, 3.1 ppm
(12m,f) * Mortality: 7/12 m, 6/12 f at 3.1 ppm (days 8, 9).
* Nasal cavity lesions at 1.1 and 3.1 ppm.
* Atrophy of the liver at 3.1 ppm.
* Respiratory irritation at 1.1 and 3.1 ppm.
* Body weight and organ weight decrease at 1.1 and
3.1 ppm; small increase in lung weight for males at
0.3 ppm.
* Changes in urine and blood parameters at 1.1 and
3.1 ppm.




39
Priority Existing Chemical Number 3
Species Study Ref. Exposure concentration and results
Rat 14-wk 46 0, 21, 49, 194 ppb
(20m,f) * No mortality.
* Respiratory irritation at 49 and 194 ppb.
* Body weight decrease for males at 49 and 194 ppb,
and for females at 194 ppb.
* No lesions of nasal cavity and no significant changes
in urine and blood parameters.

Rat 2-wk 14 0, 0.16, 0.5, 1.6, 5, 16 ppm
(5m,f) * Mortality: all at 5 and 16 ppm.
* Nasal cavity and larynx lesions at 0.5 ppm and above,
with nasal cavity lesions severe in the high-dose
groups.
* Lesions of the trachea (at 5 and 16 ppm), and the
lungs and tongue (at 16 ppm).
* Respiratory irritation at 0.5 ppm, severe at 1.6 ppm.

Rat 13-wk 14 0, 62.5, 125, 250, 500, 1000 ppb
(10m,f) * No exposure-related mortality.
* Lesions of nasal cavity, dose-related and in most
animals at 1000 ppb, some at 500 ppb, and a few at
250 ppb; NOAEL 125 ppb.
* Reduced body weight gain in males at 1000 ppb and
females at 500 and 1000 ppb.
* Breathing difficulty and ruffled fur for all at 1000 ppb,
but only during the first five weeks.
* No clear evidence of systemic toxicity.

mouse 2-wk 14 0, 0.16, 0.5, 1.6, 5, 16 ppm
(5m,f) * Mortality: all at 1.6 ppm and above.
* Lesions of the nasal cavity (at 1.6 ppm and above) and
larynx (at 0.5 ppm and above), severe in the high-dose
groups.
* Lesions of the trachea at 16 ppm.
* Respiratory irritation at 0.5 ppm.

Mouse(10m,f)13-wk 14 0, 62.5, 125, 250, 500, 1000 ppb
* Mortality: all at 1000 ppb and 2f at 500 ppb.
* Lesions of the nasal cavity at all dose levels in females
and at 250 ppb and above in males; therefore no
NOAEL.
* Lesions of the larynx at 1000 ppb.
* Dose-related decrease in body weight gain at all dose
levels in males and at 250 and 500 ppb in females.
* Breathing difficulty observed in 7/10 m and 9/10 f at
1000 ppb before death, and also in 7/10 m and 5/10 fat
500 ppb in the first few weeks.

m Male.
f Female.
NOAEL No-observed adverse effect level.




Glutaraldehyde
40
Similar signs of toxicity were observed in the various studies, including encrustation
around the nose and eyes, and audible and mouth breathing. The stomach and intestines
of some animals were dilated, due to the ingestion of air through mouth breathing.
The lesions of the nasal cavity observed in the studies were similar in description in
each case, and included hyperplasia, squamous metaplasia, necrosis and acute
inflammation.
In the 13-week NTP studies, a histoaudioradiographic study was conducted to
characterise the respiratory tract responses, with the cell replication in the nasal
epithelium being assessed using the unit length labelling index (ULLI). In rats and mice,
there was a dose-related increase in cell replication for lesions in the anterior parts of the
nasal cavity. However, the glutaraldehyde-induced lesions were different from those
observed with formaldehyde, and there was no evidence of the preneoplastic changes
observed with formaldehyde.
The results of the nine-day and two-week rat studies were similar, with mortality at 2-3
ppm and above, and respiratory irritation at 0.2-0.3 ppm and above. The effects were
only slightly more severe for the study carried out with glutaraldehyde vapour generated
by heat.45
The subchronic (13-, 14-week) rat studies indicated that lesions of the nasal cavity
develop at 200-250 ppb and above, and that signs of irritation may occur at
concentrations down to 49 ppb.
Results of corresponding mice studies showed that mice were more sensitive than rats to
these effects of glutaraldehyde, with mortality and lesions of the nasal cavity occurring
at lower concentrations, probably due to the smaller nasal passages of mice.


10.4.3 Dermal
A short term repeated dose study12 in male C3H/HeJ mice was conducted by applying
50 mL of aqueous glutaraldehyde solution (from 0.5-50% w/w) to the clipped dorsal
skin of the animals for a total of 10 applications. The results were as follows:
? 25% and 50% -- all mice lost weight and died after 4-9 doses;
? 5% -- decreased body weight after four to six doses, but not thereafter; and
? 2.5% and less -- no signs of toxicity and no effect on body weight.
The results indicated that cumulative toxicity can occur through skin absorption of
glutaraldehyde solutions of 25% or greater, but there was no evidence for cumulative
toxicity for solutions of 5% or less.
A 28-day dermal study for concentrations 7% and below has recently been completed,
with the report due later in 1994.
A two-year skin painting study in Fischer 344 rats and B6C3F1 mice was begun under
the NTP but, based on an assessment of the quality of the data, it was decided that no
formal report should be prepared.




41
Priority Existing Chemical Number 3
10.4.4 Evaluation
The three short term (nine-day or two-week) repeated dose toxicity studies showed that
glutaraldehyde produced significant mortality in rats by inhalation at approximately 2
ppm v/v, and respiratory irritation at levels down to approximately 0.2 ppm. Lesions of
the nasal cavity and larynx were observed in the studies, occurring at 0.5 ppm in one
nine-day study. Atrophy of the liver was observed, at 3.1 ppm, in one of the studies. The
signs of irritation observed were similar to those seen in the acute inhalational studies,
that is, laboured breathing and discharge/encrustation around the eyes and nose. The
results observed in the nine-day study carried out at ambient temperature25 were similar
to those observed in a preliminary nine-day study45 conducted by heating
glutaraldehyde solution to generate vapour.
In two subchronic rat studies (13 or 14 weeks), lesions of the nasal cavity and signs of
irritation were observed at lower concentrations, with a no-observed adverse effect level
(NOAEL) of 125 ppb v/v in one study and signs of nasal irritation at 49 ppb in the
other.
The results of corresponding two-week and 13-week studies in mice demonstrated that
mice were more sensitive than rats, with mortality at 1.6 ppm and 500 ppb in the two-
and 13-week studies respectively. Nasal irritation was observed in the 13-week study at
62.5 ppb, the lowest dose tested.
The results highlighted the acute toxicity and irritancy of glutaraldehyde by inhalation at
low vapour concentrations, and the harmful effects of repeated or prolonged exposure to
the vapours.
The short term dermal study showed that cumulative toxicity and mortality may occur
by repeated skin contact to 25-50% glutaraldehyde, but there was no evidence of
cumulative toxicity at 5% or less.
A 90-day sub-chronic drinking water study in rats indicated some toxicity of
glutaraldehyde at 1000 ppm w/v, and a physiological response at 250 ppm. Reductions
in food and water consumption and a dose-related effect in kidney weight were
observed, but as drinking water studies at high concentrations are generally hampered
by a natural aversion of the animals to the taste/odour of glutaraldehyde, the
significance of these results is uncertain.
In a two-year drinking water study, an increased incidence of LGLL was found in the
liver and spleen of female rats only at all dose levels (50-1000 ppm w/v), but as the
strain of rats used in the study has a high natural susceptibility to LGLL, the finding is
not conclusive.
More long term studies are needed to properly define the effects of repeated or
prolonged exposure to glutaraldehyde. Under NTP, a two-year inhalation study in rats
and mice is expected to begin in 1994.


10.5 Reproductive toxicity/teratogenicity
10.5.1 Prenatal toxicity study in drinking water of rats47
Two range-finding studies were carried out in groups of pregnant Wistar rats to set the
doses for a full study of the prenatal toxicity of glutaraldehyde by the oral route. The
studies were conducted in accordance with OECD Test Guideline 414 and the USA
EPA/FIFRA Pesticide Assessment guidelines, and in accordance with the OECD
Principles of Good Laboratory Practice.



Glutaraldehyde
42
In the first range-finding study,48 groups of 10 pregnant rats were administered 10 or 50
mg/kg body weight glutaraldehyde by gavage each day from days six to 15 post coitum.
The controls were treated with distilled water.
At 50 mg/kg there were clear signs of maternal toxicity, with food consumption and
body weight gain significantly reduced. Clinical observations during the study included
a reduced nutritional state, laboured breathing and piloerection. At necropsy the relative
kidney weights were increased, and the total protein and globulin concentrations in
blood were reduced. All dams at the high dose had thickening of margo plicatus, with
lesions of the glandular stomach in three of them. At 10 mg/kg, the only sign of
maternal toxicity was thickening of the margo plicatus in one of the dams.
The only signs of embryo-/foetotoxicity was an increased postimplantation loss in one
dam at 50 mg/kg, but as the dams were sacrificed on day 16 post coitum, only limited
information could be obtained. There were no signs of teratogenicity in the study.
In the second range-finding study,49 groups of 10 pregnant rats were treated with 11 or
51 mg/kg body weight glutaraldehyde in drinking water per day from day six to 16 post
coitum. The controls drank distilled water. At 51 mg/kg (500 ppm), marginal signs of
maternal toxicity included reduced food and water consumption, and foci in the
glandular stomach of two dams. At 11 mg/kg (100 ppm), no substance-related effects on
dams or foetuses were observed. There were no adverse effects in the group exposed to
100 ppm or 11 mg/kg body weight.
Based on the findings of the two preliminary studies, the full study,47 was carried out by
treating groups of 25 pregnant rats at 50, 250 and 750 ppm w/v glutaraldehyde in
drinking water per day, measured as 5, 26 and 68 mg/kg body weight per day, from
days six to 16 post coitum, with sacrifice on day 20 post coitum The controls drank
distilled water.
A dose-related decrease in water consumption occurred for dams at 26 and 68 mg/kg,
but there were no other dose-related signs of maternal toxicity observed during the
study.
In examination of the foetuses after dissection from the uterus, no significant findings
were observed in the sex distribution, placental weight or foetal weight. External
examination revealed one foetus at 750 ppm without tongue, but this malformation is
present in the historical control data at a low frequency. Soft tissue and skeletal
examination revealed no statistically significant malformations or variations in the
foetuses.
Under the conditions of the study, the maternal no observable effect level (NOEL) for
glutaraldehyde is 5 mg/kg body weight/day (50 ppm), and 68 mg/kg body weight/day
(750 ppm) for the foetus.
10.5.2 Prenatal toxicity study in rabbits by gavage50
Two range-finding studies were carried in groups of pregnant Himalayan rabbits to set
the doses for a full study of the prenatal toxicity of glutaraldehyde by the oral route. The
studies were conducted in accordance with OECD Test Guideline 414 and USA
EPA/FIFRA Pesticide Assessment guidelines, and in accordance with the OECD
Principles of Good Laboratory Practice.
In the first range-finding study,51 groups of six pregnant rabbits were administered 5 or
25 mg/kg body weight glutaraldehyde by gavage daily from days 7-20 post
insemination. The controls were administered distilled water. At 25 mg/kg food
consumption was significantly reduced, and the concentrations of calcium, glucose,
total protein and albumin in blood from the ear vein of the animals were significantly


43
Priority Existing Chemical Number 3
lower than for the controls. Microfocal gastritis in the fundus/pylorus region was
observed in two does, but also in one control animal. At 5 mg/kg no significant
substance related effects were observed. There was no evidence of
embryotoxicity/foetotoxicity, but as the does were sacrificed on day 20 post
insemination, only limited information could be obtained.
In the second range-finding study,52 groups of six pregnant rabbits were treated with
100 or 500 ppm w/v glutaraldehyde, measured as 7 and 23 mg/kg body weight, in
drinking water daily from days 7-20 post insemination the controls drank distilled
water. Food and water consumption were reduced at both concentrations and, at 23
mg/kg, the postimplantation loss in the does was statistically higher than for the
controls. Under the conditions of the study, glutaraldehyde was maternally toxic at 23
mg/kg, with some sign of toxicity at 7 mg/kg. There was no evidence of
embryotoxicity/foetotoxicity, but as the does were sacrificed at day 20 post
insemination, only limited information was available.
Based on the findings of the two preliminary studies, the full study50 was carried out by
treating groups of 15 pregnant rabbits by gavage at 5, 15 or 45 mg/kg body weight of
glutaraldehyde daily from days 7-19 post insemination, with sacrifice on day 29 post
insemination. The controls were administered distilled water.
At 45 g/kg, five of 15 does died on days 9-11 post insemination, and food consumption
and body weight gain were significantly reduced. Clinical observations in 12 of 15 does
included soft faeces, diarrhoea and blood in the bedding. At necropsy, irritation of the
gastrointestinal tract was observed, and the uterus weight was significantly reduced.
Nine of the 10 remaining does did not produce live foetuses. Examination of the only
four foetuses indicated a reduced placental and foetal body weight. At 5 and 15 mg/kg,
no statistically significant effects were observed for the does or the foetuses.
Under the conditions of the study, glutaraldehyde was markedly maternally toxic and
embryolethal to pregnant rabbits by gavage at 45 mg/kg body weight/day. There was no
maternal toxicity or embryotoxicity/foetotoxicity at the lower doses, nor any evidence
of teratogenicity at all doses, although there were only four live foetuses at the high
dose.
The NOEL on the maternal and foetal organism was 15 mg/kg body weight/day.
10.5.3 Reproductive effects in rats and mice by inhalation14
Under the NTP, 13-week inhalation studies on rats and mice were conducted (see
section 10.4 for reports of these studies). In addition to the histopathological evaluation,
an assessment of the sperm morphology and the oestrous cycle length was performed
for rats exposed to 0, 62.5, 250 or 1000 ppb v/v glutaraldehyde vapour and mice at 0,
62.5, 250 or 500 ppb.
Sperm morphology measurements for the treated male rats and mice were similar to
those for the controls. Oestrous cycle lengths for female rats were normal, but there
were significant differences in the oestrous cycle for female mice at 250 and 500 ppb
when compared with that of the controls. The oestrus and dioestrus times were longer
and the metoestrus times were shorter than for the controls.
10.5.4 Teratogenic study with 25% glutaraldehyde in albino rats53
A teratogenic study in Charles River albino rats was carried out by dosing by gavage
with 25% glutaraldehyde solution at 0, 25 or 50 mg (glutaraldehyde)/kg body weight.
Groups of 18 or 19 pregnant rats were dosed daily during gestation days six-15 and
sacrificed on day 20. The control females were treated with distilled water.



Glutaraldehyde
44
During the study, one rat dosed at 25 mg/kg died through injury. The body weight gain
for the high dose animals was significantly less than for the controls, but similar to the
controls at 25 mg/kg. At necropsy no significant reproductive effects were revealed,
with the number of corpora lutea, implantation sites, resorption sites and foetuses
similar for dosed rats and controls.
The body weights of the foetuses were similar for all groups and there were no
significant findings related to the skeletal or internal development of the foetuses. Apart
from one runt foetus at 25 mg/kg and two at 50 mg/kg, no significant external
abnormalities resulted.
Under the conditions of the study, glutaraldehyde at 50 mg/kg body weight was not
teratogenic.
10.5.5 Other studies
In a study in pregnant albino mice,54 Sonacide (2% activated glutaraldehyde solution)
was administered by gavage at 16-100 mg glutaraldehyde/kg body weight/day, with
maternal toxicity at 40 mg/kg/day and foetal malformation at 100 mg/kg/day.
10.5.6 Evaluation
In gavage studies in rats, glutaraldehyde was maternally toxic at 40-50 mg/kg, with a
NOEL in the range 5-25 mg/kg. The same studies indicated that the embryo-
foetotoxicity of glutaraldehyde was slightly higher, in the range 50-100 mg/kg.
The drinking water studies in rats indicated that glutaraldehyde is maternally toxic at 50
mg/kg, with a NOEL of 5 mg/kg. The same studies resulted in a NOEL of 68 mg/kg for
the foetus.
Equivalent gavage and drinking water studies in rabbits resulted in maternal toxicity and
embryolethality at 25-45 mg/kg, with a NOEL of 15 mg/kg.
In all the above studies, there was no evidence of teratogenicity.
Inhalation tests conducted by the NTP showed that the oestrous cycle lengths of female
rats were unaffected at 1000 ppb v/v, but the cycles of mice were altered at
glutaraldehyde vapour concentrations of 250 ppb and above.
10.6 Genotoxicity
10.6.1 In vitro bacterial assays
Salmonella typhimurium mutagenicity -- NTP studies14
Under the NTP, a series of reverse mutation assays was carried out with various
Salmonella typhimurium strains, with and without metabolic activation provided by rat
or hamster liver S9. The tests were conducted by Haworth et al (1983) and Zeiger et al
(1992), with the results reported in the NTP report14 and presented in Table 19.




45
Priority Existing Chemical Number 3
Table 19
Mutagenicity of glutaraldehyde in Salmonella typhimurium
Result
Strain Dose (ug/plate) Ref. with S9 no S9

TA 100 0-333 H pos pos
TA 1535 0-333 H neg neg
TA 1537 0-333 H neg neg
TA 98 0-333 H neg neg

TA 100 0-3333 H neg neg
TA 1535 0-3333 H neg neg
TA 1537 0-3333 H neg neg
TA 98 0-3333 H neg neg

TA 102 0-300 Z pos pos
TA 104 0-300 Z pos pos
TA 100 0-300 Z pos pos
Ref. Reference number.
H Tests conducted by Haworth et al.
Z Tests conducted by Zeiger et al.
pos Positive.
neg Negative.



In the tests conducted by Haworth et al,14 all results were negative except for TA 100,
which indicated positive activity to glutaraldehyde in one laboratory and an equivocal
result in the presence of rat liver S9 in the second laboratory. In the series of tests
conducted by Zeiger et al,14 glutaraldehyde tested clearly positive with and without S9
in all three strains, particularly TA 102 and TA 104, which are both sensitive to
carbonyl compounds.
Other studies
The mutagenicity of glutaraldehyde in Salmonella typhimurium has been investigated in
a number of assays, with the results ranging from negative to strongly positive. Results
of the studies have been summarised by Beauchamp et al (1992)10, Ballantyne (1992)55
and BIBRA (1991)17.
Testing with Escherichia coli has also yielded both positive and negative results.10,17,55
DNA repair testing with Bacillus Subtilis gave positive results.17,55


10.6.2 In vitro mammalian cell assays
In vitro chromosomal aberrations assay in Chinese hamster ovary cells56
The genotoxic potential of glutaraldehyde was evaluated by conducting an in vitro
chromosomal aberrations assay in Chinese hamster ovary (CHO) cells. The study was
carried out in accordance with OECD Test Guidelines,33 and it complied with the US
EPA Good Laboratory Practice requirements.
The dose range was set in a preliminary toxicity test, where 0.003-10,000 mg/mL
UCARCIDE Antimicrobial 250 (50% w/w aqueous glutaraldehyde) was tested on


Glutaraldehyde
46
cultured CHO cells with and without rat liver S9 metabolic activation. The relative
survivals of treated cells without S9 activation were from 95% at 0.30 礸/mL to 25% at
10 礸/mL, whereas with S9, they were 97% at 3.0 礸/mL to 47% at 100 礸/mL.
The 50% aqueous glutaraldehyde was cytotoxic at high doses ( 30 礸/mL without S9,
and 300 礸/mL with S9).
In the definitive chromosomal aberrations assay, five doses of 50% aqueous
glutaraldehyde were used, 0.03-3.0 礸/mL without S9 metabolic activation, and 0.30-30
礸/mL with activation.
Scoring for chromosomal aberrations indicated 2-3% aberrant cells without S9
metabolic activation and 2-4% with activation. The relevant control scores were 2-3%
for the solvent, and 36% for the positive control (triethylenemelamine) without
activation, and 39% for the positive control (cyclophosphamide) with activation. No
unusual types or distributions of chromosomal aberrations were observed.
There was no dose-related increase in the frequency of chromosomal aberrations, with
and without S9 metabolic activation, so under the conditions of the study glutaraldehyde
was not clastogenic.
Chromosomal aberrations in chinese hamster ovary cells -- NTP studies14
Under the NTP, glutaraldehyde was tested in cultured CHO cells for the induction of
chromosomal aberrations, with and without rat liver S9 metabolic activation.
The tests were carried out at two laboratories, with the results shown at Table 20. The
vehicle controls in the two laboratories were distilled water and dimethyl sulfoxide
respectively, and the common positive controls were cyclophosphamide with S9, and
triethylenemelamine without S9.

Table 20
Chromosomal Aberrations in CHO Cells (NTP)
Result
Laboratory Dose (礸/mL) With S9 No S9

1 0.3-10 ? negative

1 1-30 negative ?br>
2 1.6-16 negative weak positive


Under the conditions of the tests, glutaraldehyde induced chromosomal aberrations in
CHO cells without S9 metabolic activation in one laboratory, but not the other. In the
second laboratory, the dose was higher and a different data evaluation system was used.
In both laboratories, glutaraldehyde did not induce chromosomal aberrations in CHO
cells with S9.


Induction of sister chromatid exchanges in chinese hamster ovary
cells -- NTP study14
Under the NTP, glutaraldehyde was tested in cultured CHO cells for the induction of
sister chromatid exchanges (SCE), with and without rat liver S9 metabolic activation.




47
Priority Existing Chemical Number 3
The tests were carried out at two laboratories, with the results shown at Table 21. In the
first laboratory, distilled water was the vehicle control, and in the second dimethyl
sulfoxide. With S9, cyclophosphamide was the positive control in both laboratories, and
triethylenemelamine the control for the tests without S9.



Table 21
Sister Chromatid Exchanges in CHO Cells
Result
Test Dose (mg/mL) With S9 No S9
1st laboratory
1 0.36-10.8 weak positive positive
2 10-15 positive ?br> 2nd laboratory
1 0.5-16 ? negative
2 1.6-16 weak positive ?br>

Under the conditions of the tests, glutaraldehyde induced sister chromatid exchanges in
Chinese hamster ovary cells with and without S9 metabolic activation in one laboratory,
but was negative without S9 and weakly positive with S9 in the second laboratory, the
difference being attributed to slight differences between the data evaluation systems
used in the two laboratories.
Mouse lymphoma mutagenicity -- NTP study14
Under the NTP, a forward mutation assay was conducted in mouse lymphoma L5178Y
cells to measure mutations induced by glutaraldehyde. The assay was conducted at
glutaraldehyde concentrations of 0, 0.5, 1, 2, 4, 8 and 16 礸/mL without S9 metabolic
activation. Glutaraldehyde was cytotoxic at the high dose and no significant increase in
mutations was observed up to 4 礸/mL, but at 8 礸/mL mutations were induced at the
TK locus of the mouse lymphoma cells.
Under the conditions of the test, glutaraldehyde was mutagenic at 8 mg/mL in mouse
lymphoma L5178Y cells without S9 metabolic activation.
Mouse lymphoma assay with 1% Sterisol57
A forward mutation assay was conducted in L5178Y Fischer mouse lymphoma cells
with 1% Sterisol Formula #3 (1% glutaraldehyde) according to a method similar to that
reported by Clive and Spector.58
Sterisol was completely cytotoxic at glutaraldehyde concentrations down to 29 mg/mL
with S9 mouse liver activation and down to 7.2 mg/mL without activation. At a series of
concentrations below the level of toxicity, no point mutations were induced in the cells,
with and without activation. The controls gave positive results.
Under the conditions of the test, glutaraldehyde was not mutagenic.




Glutaraldehyde
48
Other studies
In other chromosomal aberration assays, glutaraldehyde generally gave negative results,
but the doses tended to be lower than in those studies which produced positive results.
Glutaraldehyde was mutagenic in an assay using cultured human TK6 lymphoblasts.59
Glutaraldehyde-induced unscheduled DNA synthesis in rat hepatocyte cultures showed
a small dose-related response in one assay, but in a second assay, no induction was
observed.10,55
10.6.3 In vivo assays
In vivo peripheral blood micronucleus test60
UCARCIDE Antimicrobial 250 (50% w/w aqueous glutaraldehyde) was administered
by gavage to male and female Swiss-Webster mice as a single dose in a micronucleus
assay to measure the incidence of micronucleated polychromatic erythrocytes in
peripheral blood cells. The study complied with the generally accepted standards of
Good Laboratory Practice.
On the basis of an LD50 of 317 mg/kg body weight from a previous study in mice, the
doses were set at 80, 160 and 250 mg/kg (as UCARCIDE Antimicrobial 250, i.e., 40, 80
and 125 mg glutaraldehyde/kg). Five male and five female mice were dosed at 80 and
160 mg/kg, and eight per sex at 250 mg/kg. The vehicle control was water, and the
positive control triethylenemelamine.
During the study no female mice died and there were no clinical signs of toxicity.
However, four male mice died (2 at 250 mg/kg and one each at 80 and 160 mg/kg),
three of them within an hour of dosing.
Micronucleus observations were carried out for each dose on up to five mice per sex by
sampling blood from the tail vein at 30, 48 and 72 hours after treatment, and staining the
micronuclei in peripheral blood polychromatic erythrocytes (PCE). The polychromatic
erythrocyte/normoerythrocyte (NCE) ratios, that is, PCE/NCE, for 1000 cells per animal
were calculated to give an estimate of the cytotoxicity of glutaraldehyde. No significant
changes in PCE/NCE were observed between the dosed animals and those dosed with
water.
The number of micronucleated PCEs per 1000 PCEs was then calculated for each
animal per dose, and no significant increases in micronuclei were observed for the
dosed animals or the water controls. The positive control showed increased micronuclei
for both males and females.
Under the conditions of the study, glutaraldehyde did not induce micronuclei in the
PCEs in the peripheral blood of mice.


Rat bone marrow chromosomal aberration assay61
A summary only of this assay was available for assessment. UCARCIDE Antimicrobial
250 (50% w/w aqueous glutaraldehyde) was administered by gavage to Sprague-
Dawley rats at 25, 60 and 120 mg/kg body weight for the males and at 15, 40 and 80
mg/kg for the females. The dose was set from an earlier acute oral toxicity study16
which resulted in an LD50 of 246 mg Antimicrobial 250/kg body weight for male
Sprague-Dawley rats and 154 mg/kg for the females (see section 10.1.1, Acute oral
toxicity in the rat).




49
Priority Existing Chemical Number 3
Five animals per sex per dose were sacrificed at 12, 24 and 48 hours after treatment, and
bone marrow removed and examined for induced chromosomal aberrations. For each
time period, five rats per sex were treated with distilled water at 10 mg/kg by gavage as
the vehicle controls and five rats per sex were dosed with cyclophosphamide at 30
mg/kg by intraperitoneal injection as the positive controls. During the study one male
rat at 120 mg/kg died.
Scoring for the number of aberrant cells in bone marrow resulted in similar readings for
both males and females at each dose, with no evidence of any dose-response
relationship. The readings for each time period (12, 24 and 48 hours) were similar to the
counts for the vehicle control. The positive control mean counts (at 24 hours only) were
17 and 18 respectively for the males and females compared with mean counts of 0.4-3.6
for the rats treated with glutaraldehyde.
Under the conditions of the study, glutaraldehyde was not clastogenic in the rat bone
marrow chromosomal aberrations assay.


Drosophila melanogaster sex-linked recessive lethal test -- NTP studies14
Under the NTP, the ability of glutaraldehyde to induce sex-linked recessive lethal
(SLRL) mutations in the germ cells of Drosophila melanogaster was evaluated.
Two series of tests were carried out. In the first, male adult Canton-S wild-type flies
were fed for 72 hours on a glutaraldehyde-in-sucrose solution at a dose to induce 30%
mortality. No response was obtained, so insects were injected with glutaraldehyde
solution. In the tests, the number of lethal mutations from the mating of newly-emerged
flies was determined. The results were negative
In the second series of tests, the eggs of mated Canton-S flies were exposed to cornmeal
containing glutaraldehyde. The results of this larval feeding experiment were also
negative.
Under the conditions of the tests, glutaraldehyde did not induce SLRL mutations in the
germ cells of Drosophila melanogaster treated as adults by feeding or injection, or
treated as larvae by feeding.


Other studies
In a mouse dominant lethal assay10, glutaraldehyde at oral doses of 30 and 60 mg/kg
(body weight) was negative. In an assay17 for unscheduled DNA synthesis, the oral
administration of up to 600 mg (glutaraldehyde)/kg (body weight) in groups of male rats
did not induce DNA damage.


10.6.4 Evaluation
The results of in vitro bacterial assays, especially the more recent ones, have shown
glutaraldehyde to be mutagenic, with and without S9 metabolic activation.
Glutaraldehyde has also been shown to produce mutations, sister chromatid exchanges
and chromosomal aberrations in mammalian cells in vitro, with and without any
metabolic activation system.
The results of in vivo assays to date have been negative.




Glutaraldehyde
50
10.7 Summary
Animal studies indicate that the oral LD50 of glutaraldehyde in rats, mice and
guineapigs, is approximately 50-250 mg/kg, and that the acute dermal toxicity in
rabbits, rats and mice is approximately 1000-4500 mg/kg, with skin absorption at high
concentrations. Glutaraldehyde has a high acute inhalational toxicity in rats and mice
and lung damage has been reported. Four-hour LC50 values of 23.5 and 40.1 ppm have
been obtained for the male and female rat respectively, but the glutaraldehyde solution
had to be heated in order to generate glutaraldehyde vapour at high enough
concentrations. Repeat acute inhalational toxicity studies at both ambient and elevated
temperatures are being carried out.
Glutaraldehyde is corrosive to the skin and eyes of rabbits at high concentrations, with
signs of skin irritation evident at 2%, and eye irritation at 0.2%. Exposure to
glutaraldehyde vapours in acute inhalational studies resulted in nasal irritation and
respiratory difficulties. Joint irritation was seen in rabbits after intra-articular
administration. The skin sensitisation effect of glutaraldehyde was demonstrated in tests
with guineapigs.
Short term (nine day or two-week) repeated dose inhalational rat studies resulted in
significant mortality at approximately 2 ppm v/v, and nasal irritation at levels down to
approximately 0.2 ppm. Lesions of the nasal cavity and larynx were observed at 0.5
ppm and, in a nine-day study, atrophy of the liver was observed at 3.1 ppm. Signs of
irritation included laboured breathing and discharge and encrustation around the eyes
and nose.
In two subchronic (13-14 weeks) rat studies, signs of irritation were observed at lower
concentrations, with a NOAEL of 125 ppb in one study and signs of nasal irritation at
49 ppb in the other. In corresponding two-week and 13-week studies in mice, mortality
resulted at 1.6 ppm and 500 ppb respectively, with signs of nasal irritation observed at
the lowest dose (62.5 ppb) in the 13-week study. The results highlighted the toxicity and
irritancy of glutaraldehyde by inhalation at low vapour concentrations, and the harmful
effects of repeated or prolonged exposure to the vapours.
A short term dermal study in mice showed that severe cumulative toxicity and mortality
may occur by repeated skin contact to 25-50% glutaraldehyde, but there was no
evidence of cumulative toxicity at 5% or less.
A subchronic drinking water study in rats indicated some toxicity at 1000 ppm w/w, and
a physiological response at 250 ppm. Reductions in food and water consumption and a
dose-related effect in kidney weight were observed, but as drinking water studies at high
concentrations are generally hampered by a natural aversion of the animals to the
taste/odour of glutaraldehyde, the significance of these results is low.
A two-year drinking water study in rats resulted in an increased incidence of LGLL in
the liver and spleen of females only at all dose levels (50-1000 ppm), but the finding
was not conclusive as the strain of rats used in the study has a high natural susceptibility
to LGLL and variation in control data existed within the study laboratory.
Repeated oral doses given during pregnancy to rabbits, rats and mice caused
embryotoxicity and foetotoxicity, but only at maternally toxic doses. No teratogenic
effects were observed.
Early mutagenicity studies were negative, but more recent studies have indicated that
glutaraldehyde is mutagenic in vitro in bacterial assays and tests in mammalian cells. In
vivo genotoxicity tests to date have proven negative.



51
Priority Existing Chemical Number 3
In view of the information gaps in the toxicity profile for glutaraldehyde, additional
information is required in:
? two-year inhalation effects; and
? LC50 at ambient temperature.




Glutaraldehyde
52
11. Human health effects
11.1 Irritation
11.1.1 Skin irritation


Skin irritation has been experienced in workers exposed to glutaraldehyde solutions and
vapours, with numerous cases of contact dermatitis cited in the scientific literature. In
some of these cases, a local skin irritant effect has been accompanied by eye and/or
respiratory irritation. Cases in the literature include:
? Swedish hospital workers using aqueous glutaraldehyde solution experienced an
increased incidence of skin disorders compared with workers at the same hospital
not exposed to glutaraldehyde, for example, 18 of 39 workers (46%) exposed to
glutaraldehyde experienced dermatitis of the hands compared with 11 of 68 workers
(16%) for a control group;62
a cleaner and a nurse in a hospital experienced dermatitis on the hands and arms;63
?br> ? a study of 541 cleaners in a hospital indicated an increased incidence of skin disease
compared with 157 controls;64
of nine staff employed in an endoscopy unit, three experienced facial dermatitis;65
?br> fourteen of 44 hospital workers using a 2% solution experienced skin irritation;66
?br> and
? an endoscopy technician employed in making up 2% glutaraldehyde solution from a
50% stock solution experienced dermatitis on the forearms.67
In the USA, the NIOSH Hazard Evaluations and Technical Assistance (HETA) branch
has issued a number of Health Evaluation Reports on skin irritation in hospital workers
exposed to glutaraldehyde solutions.66,68,69,70
In Australia, dermatitis has been observed in a number of different types of workers
who are exposed to glutaraldehyde, including endoscopy nurses, hospital cleaners,
radiographers and dental assistants.71 In a South Australian study,72 hand dermatitis was
reported in dental assistants, and facial irritation was reported in egg collectors spraying
eggs with a glutaraldehyde sanitising solution.
In a survey carried out in 1993 by the South Australian Occupational Health and Safety
Commission, dermatitis of the hands, arms and/or face was diagnosed in a number of
health care workers (see Appendix 4).
In several cases of dermatitis, sensitisation to glutaraldehyde has been demonstrated by
patch testing (see section 11.2.1, Observed effects in workers).


11.1.2 Eye irritation
Eye irritation has resulted from exposure to glutaraldehyde in a number of cases cited in
the scientific literature, including endoscopy nurses and other hospital workers. In
NIOSH HETA reports, eye irritation occurred in hospital workers exposed to
atmospheric glutaraldehyde concentrations up to 0.5 ppm v/v,66,68,69,73 for example, in a
survey conducted at Montgomery Hospital, Pennsylvania, 28 of 44 workers (64%) who


53
Priority Existing Chemical Number 3
used a 2% glutaraldehyde solution at least once per week reported eye irritation while
using the solution.
In a case where 2% aqueous glutaraldehyde was accidentally splashed in the eye,
irritation, pain and an increased sensitivity to light resulted.74
In the survey carried out by the South Australian Occupational Health and Safety
Commission in 1993, eye irritation was reported in workers at seven different hospitals
(see Appendix 4).


? Respiratory irritation
Irritation of the nose and throat and general tightness of the chest have been experienced
by workers exposed to glutaraldehyde vapours. Cases cited in the scientific literature
include:
? Swedish hospital workers exposed to concentrations less than 0.2 ppm experienced
irritation of the nose and throat;62
? hospital staff experienced irritation of the nose and throat after working with 2%
glutaraldehyde solution;75
? four endoscopy nurses experienced asthma and rhinitis after working with 2%
aqueous glutaraldehyde;76 and
? an endoscopy technician employed in preparing 2% aqueous glutaraldehyde from a
50% stock solution experienced nose bleeding in addition to irritation of the nose
and throat.67
Symptoms reported in the NIOSH HETA reports on hospital workers exposed to
glutaraldehyde at atmospheric concentrations up to 0.5 ppm v/v included nose and
throat irritation, chest tightness and coughing.66,68,69,70,73
In the survey carried out by the South Australian Occupational Health and Safety
Commission in 1993, nine cases of nose and/or throat irritation and two cases of lower
respiratory tract irritation were reported in hospital workers (see Appendix 4).
In the documentation of threshold limit values (TLVs) by the American Conference of
Governmental Industrial Hygienists (ACGIH),77 glutaraldehyde is reported to have a
strong irritant effect on the nasal passages and the upper respiratory tract, this being the
basis of their TLV and the National Occupational Health and Safety Commission (the
National Commission) national exposure standard.8


11.2 Sensitisation
11.2.1 Skin sensitisation
Observed effects in workers
The skin sensitising effect of glutaraldehyde in workers exposed to the chemical is well-
documented, with numerous cases of allergic skin reactions reported in the scientific
literature. Some of the cases are listed below:
? a hospital cleaner without any personal or family history of atopy or dermatitis
developed dermatitis of the hands and fingers and around the mouth and eyes after
exposure to a 2% glutaraldehyde solution. Patch testing with 0.5% and 1%
glutaraldehyde gave positive results at 48 and 72 hours;78



Glutaraldehyde
54
? a surgical instruments nurse and an endoscopy nurse, each with dermatitis on the
hands, tested positive to patch testing with glutaraldehyde;79
? a hospital maintenance employee with no history of atopy or skin disease developed
allergic contact dermatitis of the hands, arms, face and neck. A positive reaction was
obtained by patch testing with 1% glutaraldehyde in accordance with standard
guidelines;80
? allergic contact dermatitis of the hands was found in 13 health care workers,
comprising five dental assistants, three endoscopy nurses, two supply nurses, a
veterinarian, a respiratory technician and an embalmer, who were exposed regularly
to glutaraldehyde. At least seven of the workers had no history of atopy. The
patients were patch tested to standard procedures on the upper back with 1%
glutaraldehyde, the patch being in place for 48 hours and readings taken soon after
removal (30-60 minutes) and at 96 hours. Nine of the workers showed a positive
response at the first reading and all 13 showed positive at 96 hours;81
? in a patch testing study of 84 funeral service workers exposed to glutaraldehyde and
38 control workers, six of the exposed workers and none of the controls tested
positive to glutaraldehyde at 48 hours after patch removal. The family history of
allergic response was similar for both groups;82
? three hospital cleaners, an endoscope cleaner and a nursing aid who developed
contact dermatitis on the hands and forearms all tested positive to patch testing with
1% glutaraldehyde solution, with three of the workers testing positive to 0.1%
glutaraldehyde (the other two were not tested at 0.1%);83
? a radiologist and an x-ray technician with dermatitis of the fingers tested strongly
positive to patch testing with 1% glutaraldehyde;84
? three dental assistants suffering dermatitis of the hands and fingers and two patients
being treated with glutaraldehyde therapeutically (one for excess sweating of the
feet, and one for fingernail infection) tested positive to patch testing with 1.0% and
0.25% glutaraldehyde solution and tanned leather containing glutaraldehyde. All
tested negative to 2.5% formaldehyde solution;85
? twenty persons were confirmed as being contact sensitive to glutaraldehyde by patch
testing with a 1% aqueous glutaraldehyde solution on the back. There was no cross-
sensitivity to formaldehyde;86 and
? a person with hair loss and dermatitis of the scalp was patch-tested with 1.0%, 0.5%,
0.1% and 0.05% aqueous glutaraldehyde. The person, an atopic, tested positive to
1.0%, 0.5% and 0.1% at 72 hours, but negative to 0.05%. The person did not work
with glutaraldehyde solutions, but she used a hair conditioner containing
glutaraldehyde at less than 1%. Her condition improved after discontinuing use of
the conditioner.87
Repeated insult patch test -- test 188 (IBL4099)
Aqueous glutaraldehyde solution was applied to the skin of two groups of volunteers in
a series of 15 primary applications, with a challenge dose applied two weeks after the
final primary dose.
In the first group of 20 persons, aged between 20 months and 55 years, the first two
applications of 5% glutaraldehyde solution each remained in contact with the skin under
an occluded patch for 24 hours. Severe erythema and oedema resulted, so the further 13
primary applications with 5% solution were left uncovered. On challenge with 5%
solution (uncovered), no reaction was detected. The application of 1% and then 2%
solution under occluded patches on the same group, followed by challenge with 2%
(occluded), produced six cases of slight erythema.


55
Priority Existing Chemical Number 3
The second group of 40 persons, aged from approximately 30-70 years, was exposed to
5% glutaraldehyde under a occluded patch for 24 hours, and then a second patch
(occluded) for five days, resulting in moderate to severe erythema and oedema. A third
patch (1% occluded) was applied for five days, a fourth (5% open) for 24 hours, and
then a fifth (2% occluded) for five days. Challenge at two sites, with 2% (occluded) and
5% (uncovered) resulted in no reaction for either dose.
Despite the positive skin reactions, the authors of the study atttributed the reactions to
the dressing adhesive rather than the chemical, concluding that 5% glutaraldehyde was
neither a primary irritant nor a sensitiser, a finding inconsistent with those of other
studies and the human experience. There were no controls of occluded dressing without
glutaraldehyde.
Repeated insult patch test -- test 289 (Testkit 80-39)
Dilute solutions of glutaraldehyde (0.1%, 0.2% and 0.5%) were applied under an
occluded patch for 48 hours to the backs of 109 male and female persons, all 12 years of
age or more. Ten patches were sequentially applied, followed by challenge at a fresh
site on the back.
With 0.5% solution, there were seven cases of erythema and nine of slight irritation. On
challenge, one case of erythema and oedema and one case of slight irritation resulted.
With both the 0.1% and 0.2% solutions, one case of erythema of two of slight irritation
resulted, but there was no reaction on challenge.
Under the conditions of the study, 0.5% glutaraldehyde was a skin irritant in humans,
and a skin sensitiser in 1-2% of the test population. The more dilute solutions (0.1% and
0.2%) indicated signs of skin irritation but no sensitisation.
11.2.2 Respiratory sensitisation
Occupational asthma is a respiratory disease characterised by variable bronchial
obstruction and variable hyperactivity caused by specific agents inhaled at work,40 and
rhinitis is a disease that invokes inflammation of the nasal mucous membrane,
characterised by periods of nasal discharge, sneezing and congestion.40 Respiratory
sensitisation is an immune status resulting from an immune response to an antigen,40
which may be a finding in the diagnosis of occupational asthma and/or rhinitis.
The definition of occupational asthma is subject to some debate in the literature,
depending on its purpose, for example, for epidemiological or medical-legal purposes.
Balmes90 proposed the broadening of the definition to include the exacerbation of
airways obstruction by workplace exposure.
When considering individual cases of occupational asthma and rhinitis, the diagnosis is
based on the following information:40
? a clinical history -- with emphasis on occupational and family history;
? a physical examination;
? lung function tests -- such as the peak expiratory flow rate (PEFR), forced
expiratory volume in one second (FEV1), forced vital capacity (FVC) and maximum
midexpiratory flow rate (MMEF);
? bronchial provocation tests -- to confirm, if necessary, the diagnosis of allergic
asthma; and
? immunological tests -- to detect the presence of specific IgE antibody.




Glutaraldehyde
56
Respiratory allergy reactions from exposure to antigens are generally but not always
effected by a specific antibody. Allergic asthma and rhinitis are usually immediate-onset
reactions, resulting from the the local release of inflammatory mediators and usually
effected by the IgE antibody. However, asthma may also be late-onset or persistent, due
to a different type of immune reaction.
Specific antibodies against occupational sensitisers have been mainly detected for high
molecular weight agents. However, for glutaraldehyde, as with other low molecular
weight chemicals, immunological tests may be limited as specific IgE antibodies have
not been demonstrated in affected workers,91 and the type of allergic mechanism is not
yet known.
A number of cases of respiratory disease such as occupational asthma and rhinitis have
been linked with exposure to glutaraldehyde in the workplace, with some cases
concerning workers with no past history of allergic response. Difficulties have arisen in
determining whether the response in each case is due to an irritant effect or to an
allergic hypersensitivity. The type of allergic mechanism that causes asthma after
exposure to glutaraldehyde is not yet known, and no specific antibody has been
identified.91
Cases of occupational asthma and rhinitis in workers exposed to glutaraldehyde that
have been reported in the scientific literature include the following:
Case 1 An endoscopy unit sister suffered asthma-like symptoms on exposure to a
2% glutaraldehyde solution. The sister was routinely exposed to
glutaraldehyde from Mondays to Fridays, and measurements with a peak-
flow meter confirmed an improvement in flow levels during the weekend
and on removal from direct exposure to glutaraldehyde.92
Case 2 Four endoscopy nurses reported respiratory symptoms after exposure to 2%
glutaraldehyde. Three of the nurses had a past history of asthma and rhinitis,
with their condition deteriorating on exposure to glutaraldehyde. The fourth
nurse experienced chest tightness on exposure. The results of lung function
testing (FEV1 and FVC) were within normal limits for the four nurses. On
provocation testing with 2% glutaraldehyde, delayed wheezing resulted in
one of the atopic cases, and an immediate and delayed increase in nasal
discharge and sneezing resulted in one other.76
Case 3 In an endoscopy unit, six of the nine workers experienced rhinitis on
exposure to 2% glutaraldehyde, with one of the workers, an endoscopy
nurse, also suffering asthma-like symptoms, watering of the eyes and facial
dermatitis. None of the workers had any history of atopy.65
Case 4 A dentist using 2% glutaraldehyde for the disinfection of instruments
reported hay fever-type symptoms which disappeared after discontinuing use
of glutaraldehyde.93
Case 5 A study of 554 cases of occupational asthma in the United Kingdom in 1989
revealed two cases attributable to glutaraldehyde exposure. The clinical
details of the cases were not available.94
Case 6 A respiratory technologist with a history of asthma in childhood suffered
severe acute exacerbation of her asthma after beginning employment in a
bronchoscopy unit where a 3.6% glutaraldehyde solution was used for
disinfection. After peak-flow measurements indicated an improvement in her
condition away from the workplace, a hypersensitivity to glutaraldehyde was
confirmed by workplace challenge testing. As her lung function parameters
(FEV1 and PEFR) did not return to normal after 24 hours, a late asthmatic
reaction was also indicated.91


57
Priority Existing Chemical Number 3
Case 7 A radiographer with a history of hay fever but not asthma experienced
breathing difficulties over a 12-month period. On provocation testing for five
minutes with the 11% glutaraldehyde solution used in the workplace, a late
asthmatic response was confirmed by FEV1 measurements. A second
radiographer with a history of hay fever also experienced wheezing at work,
but challenge testing with 1% and 2% glutaraldehyde did not affect her lung
function parameters.95
Case 8 An endoscopy nurse without any previous history of respiratory disease
experienced recurrent episodes of chest tightness, wheeziness and shortness
of breath on exposure to glutaraldehyde. The symptoms disappeared on
holidays and on weekends, and then finally after relocating to another work
area.96
Case 9 A female technician without any previous history of respiratory disease
developed occupational asthma after exposure to 2% glutaraldehyde
solution, which was used to clean and disinfect respiratory therapy
equipment. Initially she experienced eye irritation only after exposure, but
after approximately one year, she sufferred asthma, nasal congestion and
watering of the eyes approximately two hours after returning home after
work. The frequency and severity of attacks gradually increased, with the
latter apparently related to the duration of exposure. A glutaraldehyde
inhalational challenge test resulted in a delayed response only, as measured
by PEFR. However, an immunological mechanism did not appear to be
responsible, as the serum IgG and IgE levels were normal, and a skin scratch
test with 2% glutaraldehyde was negative. The worker subsequently moved
to another department and the severity and frequency of attacks decreased
markedly. However, on one day she experienced a severe asthmatic attack
after making repeated visits to the glutaraldehyde storage area.97
Case 10 In the survey carried out by the South Australian Occupational Health and
Safety Commission in 1993, occupational asthma was diagnosed in a nurse
exposed to glutaraldehyde. (see Appendix 4)
In the United Kingdom, glutaraldehyde has been added to the indicative list of
respiratory sensitisers on the recommendation of the Industrial Injuries Advisory
Committee that glutaraldehyde may cause occupational asthma.9 8 Under the
Surveillance of Work-related and Occupational Respiratory Disease (SWORD)
reporting scheme, run by the Epidemiological Research Unit of the London Chest
Hospital, in collaboration with the Society of Occupational Medicine and the British
Thoracic Society, 20 cases of occupational asthma resulting from glutaraldehyde
exposure were reported during 1989-90.99
From the case studies cited above, there is sufficient evidence to conclude that
occupational asthma and rhinitis can result from exposure to glutaraldehyde in the
workplace. Whether the responses have been due to an irritant effect or to allergic
hypersensitivity is less clear.
In most of the cases cited, no atmospheric monitoring of glutaraldehyde was conducted,
so it is not known whether the vapour concentrations were above or below the irritant
level. Similarly the vapour concentrations during provocation testing with
glutaraldehyde solutions were not measured.
Lung function measurements were carried out after provocation testing in several of the
cases, with a delayed onset of asthma in four cases (2, 6, 7, 9). Delayed nasal discharge
and sneezing occurred in one case (Case 2). As asthmatic reactions caused by irritation
generally occur immediately after exposure and are transient,91 these cases provide


Glutaraldehyde
58
some evidence for respiratory sensitisation and are therefore of concern.
In several, but not all, of the cases, the affected workers were atopic. Atopy appears to
be a significant risk factor in the onset of asthma after exposure to antigens that cause
asthma by IgE-mediated mechanisms, for example, high molecular weight antigens, but
there is no evidence that it is a risk factor in asthma caused by antigens which do not
induce an IgE-mediated response, for example, low molecular weight antigens such as
glutaraldehyde.90
The summary of cases and discussion above highlight the difficulty in determining
whether the occupational asthma seen is a result of respiratory sensitisation.
Improvements in the reporting of cases of respiratory disease caused by exposure to
glutaraldehyde, both in the literature and to occupational physicians, would help
reviews of this subject in future.
11.2.3 Photosensitisation
Phototoxicity100 (TKL 906001)
The ability of glutaraldehyde to induce a phototoxic reaction in the skin of humans was
determined by using a controlled photopatch test, where a combination of ultra-violet
(UV) light and the chemical/skin tissue complex causes a clinical sunburn-type reaction.
Glutaraldehyde at concentrations of 0.05%, 0.02%, 0.01% and 0.005% w/v was applied
to two sites on the backs of 49 female and three male healthy volunteers (aged 22-73)
for 24 hours. Atopics and individuals with skin disorders were not considered for the
tests.
One site was irradiated with 24 J/cm2 UV-A (320-400nm) and the second site remained
unexposed to UV light. A third site, without glutaraldehyde, was irradiated to serve as a
control. All sites were scored for erythema and oedema 24 and 48 hours after
irradiation.
Approximately 20 subjects experienced slight to minor erythema at all concentrations
with the irradiated product and the irradiated control, but not with glutaraldehyde only.
Eight others experienced slight to moderate erythema at the chemical/UV site only, with
six of these at 0.05% glutaraldehyde only. Faulty equipment was suspected of allowing
UV-B and excess UV-A to the sites, so the eight subjects were retested with one of the
negative subjects. Two subjects experienced very slight erythema at 24 and 48 hours
with 0.05% irradiated product, but not with glutaraldehyde or UV only.
The authors of the study concluded that there was no evidence of phototoxicity to any of
the concentrations of glutaraldehyde tested, but in view of the need for retesting, and the
very slight reaction in two subjects on retest, the study did not conclusively show that
glutaraldehyde is not phototoxic.
Photoallergy101 (TKL 907001)
The ability of glutaraldehyde to induce a photoallergic skin reaction in humans was
determined by use of a controlled photopatch test. This procedure was for the detection
of photoallergic contact dermatitis only.
Glutaraldehyde was applied to two sites on the backs of 91 female and eight male
volunteers (aged 18-77 years) at concentrations of 0.05%, 0.02%, 0.01% and 0.005%
w/v at a frequency of twice per week for a total of six inductions. Atopics and
individuals with skin disorders were not considered for the tests.
Twenty-four hours after each application, one of the sites was irradiated with UV-A
(320-400nm) at twice each subject's minimal erythemal dose. After a 10-13 day rest



59
Priority Existing Chemical Number 3
period, challenge was effected by applying glutaraldehyde to two new sites, and
irradiating one set with 6 J/cm2 of UV-A. A third site was irradiated as a control.
All sites were scored for erythema and oedema 24 hours after application of the test
material and 24, 48, and 72 hours after irradiation for both the induction and challenge
phases of the test. No significant erythema or oedema was observed.
Under the conditions of the test, glutaraldehyde did not induce photoallergic contact
dermatitis at concentrations 0.05-0.005%.
11.3 Other effects
Other symptoms reported in workers after exposure to glutaraldehyde have included
headache, nausea and light-headedness.17
In Western Australia, palpitations and tachycardia were reported in seven health care
workers after regular exposure to glutaraldehyde,102 but the reports have not been
confirmed by scientific and toxicological evidence.
A study in hospital staff engaged in the chemical disinfection of instruments found that
an increased frequency of spontaneous abortions did not correlate with exposure to
glutaraldehyde.103 A later study comparing 164 nurses who had suffered miscarriage
with 464 who had normal births indicated that glutaraldehyde exposure was similar in
both groups.104 The same study gave similar results when comparing nurses who have
borne malformed children with those producing normal children.
11.4 Mortality studies
11.4.1 Mortality study of glutaraldehyde production workers105
In a mortality study of 186 males employed during the period 1959-78 at a
glutaraldehyde production unit (GPU) in West Virginia USA, the number of cancer
deaths and the total number of deaths were compared to those of US white males and to
that of 29,000 other chemical workers during the period 1959-78.
All subjects were observed for at least 10 years, with an average time since their first
exposure to glutaraldehyde of 20.6 years, and an average duration of employment at the
GPU of 3-7 years. Standardised mortality ratio analyses were conducted, using US
mortality rates for white males up to 1988 for the calculation of the number of expected
deaths.
The number of deaths was 14 (25.4 expected) and the total number of cancer deaths four
(6.1 expected). There was no evidence of glutaraldehyde being carcinogenic, but the
study was hampered by the relatively short observation period and the number of
subjects still relatively young.
The average glutaraldehyde exposure during the period 1977-88 was 0.05 ppm (range
0.01-0.17 ppm), but unfortunately little or no monitoring was conducted prior to 1977.

11.5 Medical record reviews
11.5.1 Review of workers assigned to glutaraldehyde production or drumming106
A study of the medical records of 218 workers employed at a GPU from 1959-92 was
carried out for a chemical plant in West Virginia, USA. At the plant, workers were
exposed to an extensive range of other chemicals, some of them being skin and
respiratory sensitisers.




Glutaraldehyde
60
A mortality study105 was previously carried out on the 186 workers employed during
1959-78 (see section 11.4.1). The study population therefore comprised:
? all workers employed in the GPU during 1959-78;
? 25 shift workers at the unit during 1992; and
? seven drummers in the distribution section during 1992.
Of the 218 workers, 210 had medical records, and 193 of these were complete. The
records were screened to identify any specific or non-specific symptoms of
sensitisation, and a more detailed inspection was conducted by the plant physician to
determine whether the symptoms correlated with the possible effects of glutaraldehyde
exposure.
Glutaraldehyde monitoring at the plant began in 1977, with the mean time weighted
average (TWA) concentration for 1977 being 0.08 ppm, and the mean for the years
1977-88 being 0.05 ppm. Exposure levels prior to 1977 were probably higher.
Short term (15 minutes) exposure limit (STEL) testing began in 1989, with a STEL
mean of 0.06 ppm since that year and a range of 0.01-0.34 ppm. The mean exposure
time of all subjects was 3.8 years, although the average for drummers was 6.4 years.
Of the 210 workers with medical records, 89 were identified with symptoms, but only
11 of these were identified as being possibly related to glutaraldehyde exposure. In five
of these cases, the sensitisation symptoms were attributed to another chemical, four due
to toluene di-isocyanate and one to bis (2,3-epoxycyclopentyl) ether. The remaining six
cases were classified as 'unsure', with their diagnoses as follows:
Case 1 At GPU from 1987 -- sinusitis.
Case 2 Drummer from 1984 -- eye irritation, with earlier history of
conjunctivitis (from 1976).
Case 3 At GPU 1977-85 -- contact dermatitis.
Case 4 At GPU 1961-80s -- dermatitis, conjunctivitis, and nasal irritation,
inflammation and bleeding.
Case 5 At GPU 1965-78 -- eye irritation, contact dermatitis.
Case 6 At GPU 1966-68 -- contact dermatitis, sinusitis.
None of the above six workers was removed from possible exposure to glutaraldehyde.
On the evidence in the review, it cannot be determined whether the six cases classified
as 'unsure' were in response to a sensitisation effect by glutaraldehyde. The diagnoses
reported were consistent with the known irritant effects of glutaraldehyde, but the
workers were exposed to a number of other chemicals in the workplace.
11.6 Summary
Human evidence has shown that glutaraldehyde is an irritant to the skin, eyes and
respiratory system, with the effects consistent with those revealed in animal testing.
Many cases of dermatitis have been reported for workers exposed to glutaraldehyde
solutions, usually 2% or higher. Facial dermatitis has resulted from the use of
glutaraldehyde in spray form.
Irritation of the nose and throat and general tightness of the chest have been experienced
by workers exposed to glutaraldehyde vapours. In a study of Swedish hospital workers,
nose and throat irritation was experienced at concentrations below 0.2 ppm.



61
Priority Existing Chemical Number 3
Human evidence indicates that skin and respiratory irritant effects are exacerbated on
repeated exposure to glutaraldehyde.
Human evidence and patch testing have shown that glutaraldehyde is a skin sensitiser.
Photosensitisation testing on volunteers did not produce a positive phototoxic or
photoallergic response.
A number of reports of occupational asthma and/or rhinitis in workers exposed to
glutaraldehyde have produced concern that glutaraldehyde may be a respiratory
sensitiser. In the absence of adequate case reporting or an identified immune
mechanism, it is difficult to say definitively that glutaraldehyde is a respiratory
sensitiser, so there is debate on whether the symptoms are due to an irritant or allergic
respiratory response. However, in the United Kingdom, glutaraldehyde has been added
to the indicative list of respiratory sensitisers. Further studies are required into the
mechanism and cause of occupational asthma in workers exposed to glutaraldehyde.
Limited epidemiological data is available on the long term effects of glutaraldehyde,
and only the irritant and skin sensitising effects of glutaraldehyde have been confirmed.
There was no evidence of adverse reproductive health effects on exposure to
glutaraldehyde, consistent with the results of animal testing. A mortality study did not
reveal any increased incidence of cancer deaths.




Glutaraldehyde
62
12. Hazard classification

12.1 Classification of hazardous substances

12.1.1 General
The classification of chemical substances is the process where the toxicological,
physicochemical and ecotoxicological properties of the substances are evaluated against
defined criteria for the purposes of regulatory action.
Under the National Commission's National Model Regulations for the Control of
Workplace Hazardous Substances,107 and the imminent Commonwealth, State and
Territory government regulations to be introduced in accordance with these national
model regulations, manufacturers and importers of substances supplied for use at work
will be required to determine whether they are hazardous to health before supply.
In determining whether a substance is hazardous to health or not, manufacturers and
importers will firstly refer to the List of Designated Hazardous Substances108 (the List)
published by Worksafe Australia. If the substance is not on the List,108 then it must be
classified by the supplier in accordance with the Approved Criteria for Classifying
Hazardous Substances109 (the Approved Criteria).
The health effects criteria in the Approved Criteria109 are the same as those used by the
Commission of the European Community in its Dangerous Substances and Preparations
Directives 67/548/EEC and 88/379/EEC, except for corrosivity, which is determined in
accordance with the criteria for corrosive substances in the Australian Code for the
Transport of Dangerous Goods by Road and Rail110 (ADG Code).
In Australia, glutaraldehyde is on the List108 because it has a national exposure standard.
At present, no risk and safety phrases appear with the listing as none have been assigned
for glutaraldehyde in the Commission of European Communities' corresponding list of
dangerous substances.111 Risk and safety phrases are needed for the appropriate
labelling of glutaraldehyde.
For labelling, suppliers also need to consider the physicochemical hazards of the
substance, as defined in the ADG Code110 and addressed under the relevant dangerous
goods legislation of the Commonwealth, State and Territory governments, and any other
applicable legislation.
Glutaraldehyde is not listed separately in the ADG Code110, but it falls within the scope
of Toxic Aldehydes, NOS.
Glutaraldehyde is listed on the National Health and Medical Research Council's
Standard for the Uniform Scheduling of Drugs and Poisons112 (SUSDP).
Both the health and physicochemical hazards of glutaraldehyde must be considered
when producing labels and Material Safety Data Sheets (MSDS).




63
Priority Existing Chemical Number 3
12.1.2 Health effects criteria
The Approved Criteria109 for classifying a substance hazardous to health are in three
parts:
? fundamental criteria for the different types of health effect, for example, acute lethal
effects, irritant effects and carcinogenicity;
? concentration cut-off limits for the substance in a mixture; and
? formulae which may need to be used for a mixture where the concentrations are
below the concentration cut-off limits.
For each of the different types of health effect, a risk phrase can be assigned to the
substance, for example, R35 (causes severe burns for a Very Corrosive substance). The
risk phrases used in Australia are consistent with those used by the Commission of the
European Communities. A substance may have more than one health effect, and
therefore more than one risk phrase assigned. For the purposes of labelling, the risk
phrases used should identify the hazards present with the normal, or reasonably
foreseeable, handling or use of the substance.113

12.2 Classification of glutaraldehyde
In classifying glutaraldehyde, each of its different health effects needs to be considered.
In the classification of mixtures containing glutaraldehyde, for example, a 2% aqueous
solution of the chemical, the following information is used:
the results of testing of the mixture as a whole substance, for example, the acute oral
toxicity of a 2% glutaraldehyde solution, or
where insufficient data is available on the mixture, the appropriate concentration cut-off
limits listed in the Approved Criteria,109 together with information on a higher
concentration of glutaraldehyde.


12.2.1 Acute lethal effects
Oral
Acute oral toxicity studies in the rat have resulted in LD50 values for glutaraldehyde in
the range 77-820 mg/kg body weight. In accordance with the Approved Criteria,109
glutaraldehyde as a pure chemical is classified as Toxic in terms of its acute lethal
effects by the oral route (risk phrase R25).
From the results of acute oral toxicity studies in the rat conducted with glutaraldehyde
solutions from 0.5-50% (see section 10.1.1), glutaraldehyde solutions at concentrations
50% are classified as Toxic (risk phrase R25) on the basis of their acute oral toxicity
and at concentrations 5% and < 50%, they are classified as Harmful (risk phrase R22).
Dermal
Data for acute dermal toxicity studies in the rabbit have resulted in LD50 values in the
range 640-2000 mg/kg body weight, and in the rat > 2500 mg/kg, so glutaraldehyde as a
pure chemical is classified as Harmful in terms of its acute lethal effects by the dermal
route (risk phrase R21).
From the results of acute dermal toxicity studies in the rabbit conducted with
glutaraldehyde solutions from 5-50% (see section 10.1.2), glutaraldehyde solutions at
concentrations above 25% are classified as Harmful on the basis of their acute dermal
toxicity (R21).


Glutaraldehyde
64
Inhalation
The criterion for classification of substances on the basis of their acute inhalational
toxicity is the LC50 in the rat, with the limits for classification as Very Toxic, Toxic and
Harmful being 0.25, 1 and 5 mg/L/4hr respectively.109
For glutaraldehyde, the results of acute inhalational toxicity testing are described in
sections 10.1.3 and 10.1.4, with the LC50 values listed in section 10.1.3. In the only
complete LC50 study available for assessment, a four-hour value of 23.0 ppm (96 mg/L)
was obtained for the male rat and 40.1 ppm (164 mg/L) for the female.22 The high
toxicity in this study has been attributed to the presence of more toxic higher molecular
weight species of glutaraldehyde formed during the generation of vapours from solution
at 65癈, but no supporting evidence for this view is available. Moreover, a study18 in
rats exposed to 20 ppm glutaraldehyde (82 mg/L) resulted in 50% of the animals dying
within 90 minutes, and a four-hour rat LC50 of 480 mg/L has been reported.26 These
findings, together with the results of nine-day studies in the rat, where significant
mortality occurred at 2.1 and 3.1 ppm, tend to support the LC50 values of 23.0 and 40.1
ppm for male and female rats respectively.
The literal application of these results would indicate that glutaraldehyde as a pure
chemical should be classified as Very Toxic in terms of its actual lethal effects by
inhalation, that is, an LC50 in the rat of < 0.25 mg/L/4hr.
However, due to the limited data available, a moderated approach could be adopted in
this instance to give a provisional classification because the low vapour pressure and its
occurrence in aqueous solutions should generally limit its availability. Vapour
generation studies with various strengths of solution (see section 10.1.3) have confirmed
that glutaraldehyde, by virtue of its low vapour pressure (see Chapter 5 and Table 23 in
Chapter 14), is liberated from aqueous solutions at vapour concentrations significantly
below toxic levels. For example, a maximum of 6.6 ppm was obtained above a 50%
solution.
Consequently, on the basis of limited available data and vapour pressure data for
various concentrations of aqueous solution, solutions above 25% could be classified as
Toxic (risk phrase R23), and solutions from 1% to 25% should be classified as Harmful
(risk phrase R20).
Due to concerns regarding the method of vapour generation in the only available LC50
study, comparative LC50 tests are currently being carried out at ambient and elevated
temperatures. When data from these studies are available, together with any other
relevant data such as aerosol test results, this classification should be reviewed.

12.2.2 Corrosivity/irritancy
Testing with 45% and 50% w/w aqueous glutaraldehyde solutions on the skin of rabbits
resulted in visible necrosis at the site of application. According to the Approved
Criteria,109 45% and 50% glutaraldehyde is Corrosive (risk phrase R34).
The results of skin irritation testing at various concentrations (see section 10.2.1)
indicate that solutions above 25% are Corrosive, and that solutions at 1% and up to 25%
are Skin Irritants (risk phrase R38).
The results of eye irritation testing at various concentrations (see section 10.2.2)
indicate that solutions greater than 5% may cause Serious Eye Damage (risk phrase
R41), and that solutions greater than 0.1% and up to 5% are Eye Irritants (risk phrase
R36).



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Priority Existing Chemical Number 3
Glutaraldehyde is a Respiratory Irritant on the basis of observed effects in humans and
the results of animal inhalation studies (risk phrase R37). As respiratory irritation has
been observed in workers using dilute solutions, and as 1% and 2% solutions have
similar vapour pressures and health effects, solutions of 1% and above should be
classified as Respiratory Irritants.
12.2.3 Sensitisation
From the results of animal testing and the human evidence in the scientific literature,
glutaraldehyde is a Skin Sensitiser (risk phrase R43). By applying the concentration cut-
off limit from the Approved Criteria,109 solutions 1% should be classified as Skin
Sensitisers.
The classification of glutaraldehyde in terms of its respiratory sensitising effect is less
clear cut. From the Approved Criteria,109 a substance is classified as a sensitiser by
inhalation...
'If practical evidence is available which shows that the substance is capable of
causing a sensitisation reaction in humans by inhalation, at a greater frequency
than would be expected from the response of a general population.'
The criteria for sensitisation are currently being reviewed in the EEC to provide more
guidance in their application; the existing criteria describe sensitisation by a particular
route of exposure rather than describing the disease that may be caused by the
substance, that is, respiratory hypersensitivity and/or skin sensitisation.
There is some evidence for the possible respiratory sensitising effect of glutaraldehyde
in humans, with cases of exposure-related occupational asthma and rhinitis summarised
in section 11.2.2. In addition, glutaraldehyde has been added to the indicative list of
respiratory sensitisers in the United Kingdom after 20 cases of occupational asthma
were reported after exposure to glutaraldehyde during 1989-90.
However, in light of the history of atopy in many of the patients, the limited exposure
data for the cases listed, and the difficulty in determining whether a particular case of
occupational asthma or rhinitis is due to an irritant effect or an allergic hypersensitivity,
the classification of glutaraldehyde as a sensitiser by inhalation in terms of the
Approved Criteria109 is not conclusive. However, to reflect the evidence that is
available, the following statement is recommended for inclusion in MSDS of substances
containing 1% glutaraldehyde:
'Occupational asthma and/or rhinitis have been indicated in a number of workers
exposed to glutaraldehyde.'
Further information and better reporting from case studies, together with the study of
possible mechanisms of action, are expected to clarify this situation, as may future
changes in the classification criteria.
12.2.4 Severe effects after repeated or prolonged exposure
A two-year drinking water study42 in Fischer 344 rats revealed an increased incidence of
LGLL in females only at all dose levels (50-1000 ppm w/v), but the findings were not
conclusive, so no classification is recommended for glutaraldehyde in terms of its
repeated exposure effects by the oral route.
A number of repeated dose inhalation studies on rats and mice have shown that
glutaraldehyde at approximately 50-60 ppb v/v (0.21-0.24 mg/L) may result in an
exacerbation of the irritant effects observed in acute inhalational studies.
Therefore glutaraldehyde should not be classified in terms of any repeated exposure



Glutaraldehyde
66
effects by inhalation.
12.2.5 Mutagenicity
Glutaraldehyde has been shown to be mutagenic in some bacterial assays and evidence
of DNA damage and chromosome damage has been found in some tests in mammalian
cells. However, all in vivo tests reported to date have yielded negative results.
According to the criteria for mutagenicity, glutaraldehyde should not be classified as a
mutagen. However, in view of the number and variety of positive in vitro tests, the
following statement is recommended for inclusion in MSDS for products containing
glutaraldehyde:
'The results of more recent assays have generally shown that glutaraldehyde is
mutagenic in vitro. In vivo tests to date have been negative. Consequently
glutaraldehyde does not meet the criteria for classification as a mutagen.'
12.2.6 Carcinogenicity
The only evidence of tumour formation to date is the increased incidence of LGLL in
female Fischer 344 rats in the two-year drinking water study. However, the finding is
inconclusive so, in accordance with the Approved Criteria,109 glutaraldehyde does not
meet the criteria for classification as a carcinogen.
12.2.7 Reproductive toxicity/teratogenicity
Studies on the incidence of miscarriage in pregnant women have shown no difference
between those exposed to glutaraldehyde and those not exposed to the chemical.
Studies in female rats and mice have resulted in embryotoxicity/foetotoxicity for
glutaraldehyde, but only at doses which are maternally toxic.
A number of studies have found no evidence of teratogenicity.
12.2.8 Non-lethal irreversible effects after a single exposure
There is no evidence of any irreversible effects by glutaraldehyde after a single
exposure.
12.2.9Summary
The main concentrations of aqueous glutaraldehyde imported and produced in Australia
are 50%, 45%, 25%, 10%, 5%, 2% and 1% and, based on the above conclusions, these
can be classified as listed at Table 22.




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Priority Existing Chemical Number 3
Table 22
Risk phrase classification for concentrations of glutaraldehyde
Concentration Risk phrase(s) to be used
50% R21, R23, R25, R34, R37, R41, R43
45% R21, R22, R23, R34, R37, R41, R43
25% R20, R22, R37, R38, R41, R43
10% R20, R22, R37, R38, R41, R43
5% R20, R22, R36, R37, R38, R43
2% R20, R36, R37, R38, R43
1% R20, R36, R37, R38, R43
> 0.1-< 1% R36
0.1% no classification



For the purposes of labelling, the risk phrase for Serious Eye Damage (R41) may be
covered by R34.
In the classification of glutaraldehyde solutions which contain other hazardous
substances, for example, x-ray film processing solutions which may sodium bisulfite
and hydroquinone, consideration of all the hazardous substances in the mixture must be
taken into account.
The choice of risk phrases by suppliers in the labelling of their products is discussed in
section 13.2.


12.3 Dangerous goods classification
Glutaraldehyde is not listed in the ADG Code.110 However, it comes within the scope of
Aldehydes, Toxic, NOS. At concentrations where the aqueous glutaraldehyde solution
is Corrosive, for example, 45% and 50%, it should be classified as a Class 8 substance.
More dilute solutions should be classified as a Class 6.1(b) substance.
A Hazchem code of 2ZE is appropriate for concentrated glutaraldehyde.


12.4 Poisons schedule
Glutaraldehyde for human therapeutic use is listed on Schedule 2 of the SUSDP.112
Glutaraldehyde for preparations containing < 5%, except when on Schedule 2, is listed
on Schedule 5.
Glutaraldehyde, except when on Schedule 2 or Schedule 5, is listed on Schedule 6.




Glutaraldehyde
68
For domestic end-use products, the warning statements and safety directions listed in
Appendix F part 3 of the SUSDP112 must be assigned to the label. For glutaraldehyde,
for example, in sanitisers for aircraft toilets, these are as follows:
? warning statement 5 (Irritant) for all strengths; and
? safety directions:
? 1 (avoid contact with eyes) and 4 (avoid contact with skin) for all
strengths, or
? 1, 4 and 8 (avoid breathing vapour or spray mist) for > 25%.
For agricultural and veterinary products, the safety directions listed in Appendix H part
2 of the SUSDP112 must be assigned to the label. For glutaraldehyde, for example, in
animal health products, these are as follows:
? safety directions for all strengths:
? harmful (or poisonous for Schedule 6) if absorbed by skin contact or
inhaled,
? will irritate the eyes and skin,
? avoid contact with eyes and skin,
? do not inhale vapour when using the product,
? wear elbow-length PVC gloves and faceshield or goggles,
? after use and before eating, drinking or smoking, wash hands, arms and
face thoroughly with soap and water, and
? after each day's use, wash gloves, faceshield or goggles and
contaminated clothing.
As importers and manufacturers need to comply with requirements under the SUSDP,112
ADG Code110 and hazardous substances regulations in various circumstances, any
differences in requirements between jurisdictions may be confusing.
For glutaraldehyde, this is particularly so for corrosivity/irritancy, where under the
SUSDP112 there is a warning of irritancy rather than corrosivity for concentrations
above 25%. Also, no warning is required for skin sensitisation under the SUSDP.112
It is recommended that the warning statements in the SUSDP112 for glutaraldehyde are
reviewed to take into account this assessment.




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Priority Existing Chemical Number 3
13. Hazard communication
13.1 Material Safety Data Sheets
MSDS are the primary sources of information for workers employed in the handling,
use, storage and disposal of industrial chemicals, especially those which are classified as
hazardous substances. Glutaraldehyde is a hazardous substance and mixtures containing
> 0.1% of the chemical are hazardous substances.
Glutaraldehyde is used in approximately 40 different products in Australia. In the
information submitted for assessment, 30 MSDS of mixed quality were submitted, with
only approximately 10 of the MSDS written in accordance with the National
Commission's National Code of Practice for the Preparation of Material Safety Data
Sheets,114 or the National Commission's Guidance Note for Completion of a Material
Safety Data Sheet (1991). The MSDS submitted are listed in Appendix 2.
A good MSDS should contain:
?identifying information about the product;
?complete health hazard information;
?precautions for use; and
?safe handling instructions.
A number of the MSDS were written outside Australia, and did not contain information
specific for the use of the product in this country. These MSDS quoted ACGIH TLV's
and overseas regulations instead of the National Commission Exposure Standard8 and
other Australian regulatory requirements.
In most MSDS, the concentrations of the individual ingredients were given as a range,
as required by the National Commission's Code of Practice or Guidance Note, rather
than as an exact concentration. However, the exact concentration of glutaraldehyde is
provided on labels, so a similar approach for MSDS would assist workers and their
supervisors in determining the hazards of the product.
There was considerable variation in the health effects information on glutaraldehyde
provided on the MSDS, with many containing insufficient data on known human health
effects, and many containing little or no animal toxicity data.
In the precautions for use in the MSDS, most suppliers used standard phrases when
outlining the engineering controls to be used. Guidance could be more specific in some
cases, for example, the use of enclosed systems for formulation using concentrated
glutaraldehyde solutions, and the use of local exhaust ventilation in disinfection. Most
MSDS specified the appropriate personal protective equipment to wear during the
routine use of glutaraldehyde solutions and in case of spills.
For most MSDS, the sections on first aid and safe handling, including firefighting and
disposal procedures, were satisfactory.
To satisfy the regulatory requirement that an MSDS be included in the assessment
report, two examples submitted during the assessment have been appended to this
report:
? the Union Carbide Chemicals Australia MSDS for 50% glutaraldehyde; and
? the ICI Australia MSDS for Aldecyde 28, which contains approximately 2%
glutaraldehyde.



Glutaraldehyde
70
13.2 Labels
Preparing a label for glutaraldehyde highlights the difficulties experienced by suppliers
in satisfying the labelling requirements of the various regulatory codes and schedules.
In general, industrial chemicals are labelled in accordance with the National
Commission's National Code of Practice for the Labelling of Workplace Substances113
(the Labelling Code). There are exceptions, including:
? agricultural chemical products, as defined under the Agricultural and Veterinary
Chemicals Act and when labelled in accordance with the Code of Practice for
Labelling Agricultural Chemical Products; and
? hazardous substances imported from overseas, provided that the labels fulfil
Australian requirements.
Domestic end-use products covered by the SUSDP112 need to be labelled in accordance
with SUSDP112 requirements, but for such products used in the workplace, additional
information in accordance with National Commission requirements may be needed on
the label.
For glutaraldehyde-containing products, the following requirements should be noted:
? glutaraldehyde products used in the animal housing industry must be registered and
labelled according to the Agricultural Chemicals Labelling Code;113
glutaraldehyde is on Schedules 2, 5 and 6 of the SUSDP,112 so products in Australia
?br> designed for domestic use, for example, sanitisers for portable and aircraft toilets,
must fulfil the labelling requirements of the SUSDP;112 and
? imported products containing glutaraldehyde, for example, some x-ray film
processing solutions, are regarded as hazardous substances if they contain > 0.1% of
the chemical.
In addition, for some concentrations of glutaraldehyde the labelling requirements of the
ADG Code110 also apply. Aqueous solutions containing > 25% glutaraldehyde fall into
Class 8 (Corrosive), with more dilute solutions falling into Class 6.1(b) (Harmful
[Toxic]) substances of packaging group III.
When labelling industrial chemicals in accordance with the Labelling Code,113 risk
phrases dependent on the hazard classification of the substance in accordance with the
Approved Criteria109 are selected to describe the risks associated with the normal, or
reasonably foreseeable, handling or use of the substance. The risk phrases appropriate
for glutaraldehyde are specified in chapter 12, Hazard Classification (all the risk phrases
from the Approved Criteria109 are listed in Appendix 1). Safety phrases appropriate to
the proposed use of the product are then assigned in accordance with the Labelling
Code,113 with suitable phrases for glutaraldehyde listed at Table 23.




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Priority Existing Chemical Number 3
Table 23
Safety phrases suitable for use with glutaraldehyde
Phrase number Phrase

S23 Do not breathe vapour
S24 Avoid contact with skin
S25 Avoid contact with eyes
S26 In case of contact with eyes, rinse immediately with plenty of
water and contact a doctor or Poisons Information Centre
S29 After contact with skin, wash immediately with plenty of water
S36 Wear protective clothing
S37 Wear suitable gloves
S38 In case of insufficient ventilation, wear suitable respiratory
equipment
S39 Wear eye/face protection
S51 Use only in well-ventilated areas


Under the SUSDP112 labelling provisions, the labels of domestic end-use products
containing < 5% glutaraldehyde should contain the following signal word and phrase:
WARNING
KEEP OUT OF REACH OF CHILDREN
Other glutaraldehyde preparations for domestic end-use should contain the following
signal word and phrases on the label:
POISON
NOT TO BE TAKEN
KEEP OUT OF REACH OF CHILDREN.
The warning statement required by the SUSDP112 for glutaraldehyde is Irritant (for all
concentrations). The safety directions required on the label are listed at section 12.4.
In the information submitted for assessment, 21 labels of variable standard were
submitted. They are listed in Appendix 3 with their risk and safety phrases. As required,
all labels specified the concentration of glutaraldehyde in the product and most
contained good first aid and emergency response information. However, there was a
lack of consistency in the risk and safety phrases applied. Some products were labelled
with a fairly complete set of risk phrases in accordance with the hazard classification of
the product (see chapter 12). Some other labels had only one or no risk phrase, but most
labels contained some safety phrases. Deficiencies in hazard identification noted on
labels listed in Appendix 3 included the following:
? only 11 of the 21 labels included a risk phrase for skin sensitisation (such as R43);
? only eight of the 21 labels included a risk phrase for eye irritation or damage (such
as R36 or R41), with another five including a safety phrase for avoidance of contact
with the eyes (S25); and




Glutaraldehyde
72
? only 11 of the 21 labels included a risk phrase for respiratory irritation (such as R37)
or a safety phrase for avoidance of vapour/mist respiration (S23).
Furthermore, there was a lack of consistency in the labelling of similar products within
an industry, for example, 2% disinfectant solutions.
The labels on the four domestic end-use products fulfilled the SUSDP112 and National
Commission requirements and conveyed risk information about the hazards identified in
the classification of glutaraldehyde according to the Approved Criteria.109
Some of the labels contained excellent information about the use of the product,
whereas others contained little or no directions for use.
In the animal health industry, glutaraldehyde is sometimes used in spray form, leading
to an increased risk of exposure to workers unless control measures are implemented.
To alert workers to this hazard, it is recommended that products which may be used in
spray form carry the following warning on the label:
CAUTION: AVOID BREATHING SPRAY.


13.3 Other information
In most cases, the importers of glutaraldehyde in Australia are not end-users. Also,
many of the manufacturers of glutaraldehyde-containing products in Australia are not
end-users, so in many instances in this country, there is a potential information gap
between supplier and end-user. While glutaraldehyde solutions are repackaged and sold
"downstream" to end-users, information on glutaraldehyde often does not accompany
the product.
Some suppliers have provided specific information about the hazards of glutaraldehyde
and safe handling guidance to end-users, but in other cases the information has been
limited. Employees need to be informed of the specific hazards related to their use and
handling of the product, and of any new information about the product, for example,
results of atmospheric monitoring in their workplace, or new health effects data.
In the health care industry, guidelines have been produced in New South Wales,
Victoria and Western Australia to convey information to workers and management on
the safe use of glutaraldehyde, for example, the NSW Health Department has produced
Guidelines for the Safe Use of Glutaraldehyde in Health Care Establishments,115 which
provides guidance on the use of 1% and 2% disinfectant solutions and x-ray film
processing solutions.
Similar safe use guidelines are needed for the other industries in which glutaraldehyde

.
is used, for example:
the use of glutaraldehyde in tanning; and
. the use of glutaraldehyde in spray from, e.g., in animal housing
A number of industry members have been involved in the provision of health and
environmental use information through Responsible Care programs but, in view of
information obtained during the assessment period, some importers and suppliers of
glutaraldehyde need to be more active.




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Priority Existing Chemical Number 3
14. Occupational exposure

14.1 Routes of exposure
Workers are exposed to glutaraldehyde by inhalation and skin contact. In general,
exposure is at room temperature to simple aqueous glutaraldehyde solutions which
contain glutaraldehyde and only low concentrations of other chemicals, for example,
disinfectant solutions may be made alkaline with 0.3% of sodium bicarbonate. In some
instances aerosol exposure may occur, for example, during the use of a spray or fog in
animal housing and air duct disinfection. In other cases more complex glutaraldehyde
solutions may be used, for example, x-ray film processing solutions generally contain a
number of other chemicals, for example, sodium bisulfite, hydroquinone and acetic
acid.
The risk of adverse health effects from exposure will increase with strength of
glutaraldehyde solution handled, as the atmospheric concentration of glutaraldehyde
vapour will increase. Table 24 illustrates the increase in glutaraldehyde vapour pressure
with the concentration of glutaraldehyde in aqueous solution.

Table 24
Glutaraldehyde Vapour Pressure over Aqueous Solutions
Vapour pressure (Pa)
%w/w in solution 20癈 35癈

1 0.13 0.77
2 0.16 0.95
5 0.23 1.27
10 0.32 1.76
25 0.67 3.60
50 2.03 10.67



14.2 Formulation

Glutaraldehyde is imported into Australia mainly as a 45% or 50% concentrated
aqueous solution and diluted with water to give the end-use product, which in most
cases contains 1% or 2% glutaraldehyde. Occupational exposure during production can
therefore be to aqueous glutaraldehyde ranging from 1-50% w/w.
Dilution is carried out at approximately 15 sites, with up to 20 workers employed in the
operation at each site. Dilution is a batch process and at most sites is scheduled on an
intermittent basis, for example, the dilution of glutaraldehyde may be scheduled for two
days each month.
At some sites, the glutaraldehyde-containing product is simply repacked, with only one
or two workers employed in the repacking process.




Glutaraldehyde
74
The types of worker potentially exposed to glutaraldehyde during production are:
? mixing and blending operators;
? filling line operators;
? maintenance workers;
? storage workers;
? analysts and quality control workers; and
? supervisors.
The most concentrated glutaraldehyde solutions will be handled by those workers
involved in the mixing process, and in some cases storepersons and analysts. Most of
the blending operations in Australia are conducted in a closed system, with exposure
limited to the initial opening of the drum of raw material for transfer to the mixing
vessel.
Filling line operators may be exposed to glutaraldehyde vapours, especially if
ventilation and fume extraction is inadequate. Exposure by both inhalation and skin
contact may occur in the case of spills during the filling operation.
Atmospheric monitoring during a well-ventilated operation resulted in 15-minute
glutaraldehyde concentrations in the range 0.02-0.10 ppm v/v (the National
Commission's exposure standard is 0.2 ppm, with a peak limitation).8
14.3 Cold disinfectant
The widest exposure to glutaraldehyde is during its use as a disinfectant in the health
care industry. All large hospitals and many of the smaller ones throughout Australia use
1% or 2% aqueous glutaraldehyde solutions for the disinfection of medical and surgical
instruments, for example, endoscopes, bronchoscopes and small tools such as those used
in dentistry, ultrasound testing, and ear, nose and throat examinations.
In a questionnaire sent to 276 hospitals in Australia in 1987, 123 of the 145 hospitals
which responded used endoscopes regularly.116 Glutaraldehyde was the most common
disinfectant used.
In a questionnaire circulated to health care establishments in Tasmania in 1993 by the
Department of State Development and Resources, 19 of 47 establishments replied that
they were using glutaraldehyde (see Appendix 4).
In a survey of health care establishments conducted by the South Australian
Occupational Health and Safety Commission in 1993, 25 of 33 establishments replied
that they were using 1% and/or 2% glutaraldehyde (see Appendix 4).
Workers potentially exposed to glutaraldehyde disinfectant solution on a regular basis
include:
? endoscopy nurses;
? operating theatre nurses;
? physicians and surgeons;
? technical assistants in hospitals;
? dentists and dental nurses;
? cleaners in hospitals and clinics;
? podiatrists;


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Priority Existing Chemical Number 3
? acupuncturists;
? tattooists; and
? medical research workers.
Workers such as endoscopy nurses may be exposed to glutaraldehyde solutions daily
and, in some cases, exposure may occur throughout a working day.
Sources of exposure identified in the use of glutaraldehyde as a disinfectant include:
? preparation and dilution of solutions;
? transfer of solution into soaking baths and tanks;
? emission of vapours from open baths;
? placing of instruments in baths;
? transfer of soaking baths from one location to another;
? removal of instruments from baths for rinsing;
? emptying of baths; and
? disposal of waste glutaraldehyde.
As the use of glutaraldehyde in dentistry has been reduced in recent times, occupational
exposure is low. Most dental instruments are now autoclaved, although in some cases
the more fragile instruments are still disinfected by soaking in solutions of 0.33%, 1%
and 2% glutaraldehyde. The use of glutaraldehyde varies considerably from one State or
Territory to another.
A number of reports containing atmospheric monitoring results for glutaraldehyde
during its use in cold disinfection are available, with glutaraldehyde concentrations
generally less than 0.1 ppm in well-ventilated workplaces.
Some results of monitoring carried out in Australia are included in Table 25.




Glutaraldehyde
76
Table 25
Glutaraldehyde Concentrations in Cold Disinfection
Sample
Workplace Worker Conc (%) type Ppm Ref.
Hospital endoscopy nurse 1 P 0.005-0.105 72
Hospital endoscopy nurse 1 A 0-0.05 72
Dentist dental assistant 2 P 0.007-0.022 72
Endoscopy 1 A 0.01-0.20 9
Operating 1 A 0-0.9 9
theatre 2 A 0.01-0.16 9
Hospital 1 A 0-0.05 SA
Hospital endoscopy nurse 1,2 A 0.04-0.38 Q
Hospital endoscopy nurse 2 A 0.2 WA1
Endoscopy A 0-0.49 WA2
Dentist A 0.01-0.02 WA3
P Personal monitoring.
A Area monitoring.
S Royal Adelaide Hospital (see Appendix 4).
Q Queensland hospitals.
WA1 Fremantle Hospital.
WA2 Results of survey of 13 hospitals conducted by Health Dept of WA -- 52
measurements for a mean of 0.06 ppm.
WA3 Results of survey of 2 large dental clinics conducted by Health Dept of
WA -- 14 measurements for a mean of 0.01 ppm.


In the USA, NIOSH has issued several reports66,68,69,73 on the atmospheric monitoring of
glutaraldehyde in hospitals, with personal monitoring results of up to 0.6 ppm and area
monitoring results of up to 0.3 ppm being obtained in a number of hospitals where
workers had experienced adverse health effects on exposure to glutaraldehyde.


14.4 X-ray film processing
In the handling of glutaraldehyde-containing solutions used in x-ray film processing,
workers may be exposed to other hazardous substances, for example, sodium bisulfite,
hydroquinone and acetic acid.
? Workers potentially exposed to these solutions include:
? radiographers in hospitals, clinics and radiology practices;
? dark room technicians;
? printers; and
? engineers.




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Priority Existing Chemical Number 3
The total number of workers potentially exposed is considerable, as most large hospitals
have x-ray departments and there is a large number of radiology clinics. Some workers
such as radiographers at a large hospital may be exposed to glutaraldehyde daily
whereas others, for example, an engineer conducting a welding inspection, may be
exposed irregularly for brief periods.
X-ray developers are supplied to end-users in kit form as concentrates for subsequent
mixing and dilution. Glutaraldehyde is included in one of the solutions in the kit at a
concentration up to 50% w/w, depending on the manufacturer and supplier. It is present
as free glutaraldehyde or as a glutaraldehyde-sodium bisulfite complex. After mixing
and dilution, the concentration of glutaraldehyde is generally less than 1% in the
working solution. Automatic mixers are generally used for the preparation and
dispensation of working solutions to the processor, so the risk of exposure by both
inhalation and skin contact is reduced. Smaller radiology units still use manual
procedures.
The automatic machines generally used for the film processing stage normally operate
at high temperature, so faults with the equipment, for example, faulty seals, poor vapour
extraction, or leaking hoses, may lead to a release of glutaraldehyde vapours into the
work area and therefore increased exposure. The loading of the machines with solution
and the cleaning of the rollers within the machines may also lead to exposure by
inhalation and skin contact.
Sources of exposure identified in the use of glutaraldehyde in x-ray film processing
include:
? manual preparation of processing chemicals;
? transfer of chemicals in and out of chemical tanks and processors;
? emission of vapours from open tanks and leaking mixers, processors and piping;
? exhaust from automatic processors;
? drying of x-ray films;
? emptying of tanks; and
? cleaning of processor rollers and tanks.
Atmospheric monitoring in x-ray film processing work areas has been conducted, with
glutaraldehyde concentrations generally below the exposure standard of 0.2 ppm,
especially in areas using automatic mixing and processing equipment.
Some results of monitoring carried out in Australia are included in Table 26.




Glutaraldehyde
78
Table 26
Glutaraldehyde concentrations in x-ray film processing
Workplace Worker Conc. (%) Sample type Ppm Ref
Hospital radiographer 0.4 P,A 0.001 72
Hospital <0.5 A 0-0.1 9
Hospital 8 A 0 9
Hospital radiographer A 0.03-0.06 Q
Hospital A 0.02-0.4 WA
Conc Concentration in processing solution.
Ref Reference number.
P Personal monitoring.
A Area monitoring.
Q Queensland hospitals.
WA Results of survey of five workplaces conducted by Health Dept of WA -- 14
measurements for mean of 0.12 ppm.


In the monitoring conducted with 8% glutaraldehyde solution,9 an automatic mixer was
used to dilute the processing chemicals on some occasions, with the manual method
used on others.
A series of air monitoring studies was conducted in x-ray processing areas during the
operation of the processors and during the preparation of the working strength solutions,
with the study parameters designed to simulate poor ventilation conditions. The results
are in Table 27.

Table 27
Air monitoring results in x-ray film processing
Processor (Kodak) Acetic acid Ammonia Glutaraldehyde SO2
ML-300 0.4-0.5 0.07-0.1 <0.005 0.38-1.1

M6RA 0.2-0.6 0.09 <0.005 0.08

M6RA 0.2-1.3 0.14 <0.001 0.15-0.30

Mixing 0.9-2 0.14 <0.02 0.2

Measurements in ppm.




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Priority Existing Chemical Number 3
14.5 Tanning
Workers are exposed to glutaraldehyde in the tanning industry at about 10 different sites
in Australia. Workers are employed in the mixing of tanning solutions, the soaking of
leather and pelts in the solutions, and the discharge and cleaning of tanks after
treatment. The total number of workers exposed to glutaraldehyde in tanning in
Australia is comparatively low, as only two or three workers are employed at some
sites.
In the treatment of leather and pelts, glutaraldehyde is generally pumped from the drum
to the mixing vessel, the operation taking about 5-10 minutes. Depending on the type of
tanning, other ingredients are added at different times throughout the treatment period,
which may be up to several hours. During the tanning process, the temperature in the
mixer may be elevated up to 50癈, increasing the risk of exposure by inhalation.
Exposure to glutaraldehyde may occur during these periods of addition and also at the
completion of treatment, when unused reactants, including glutaraldehyde, are
discharged from the mixing vessel.
Depending on the type and volume of tanning at each site, glutaraldehyde may be used
in one batch per week, one batch per several months, or on a continuous basis.
Occupational exposure to glutaraldehyde is therefore variable from one site to another,
depending on tanning conditions and the ventilation and handling facilities in place at
each site.
No records of any atmospheric monitoring for glutaraldehyde at tanning worksites in
Australia were available.

14.6 Water treatment
Workers are potentially exposed to glutaraldehyde during the addition of
glutaraldehyde-containing products to the water treatment system or during the mixing
of the solutions. The types of workers potentially exposed include:
? water treatment operators;
? maintenance fitters and engineers;
? technical representatives; and
? storepersons.
Exposure may be to the concentrated biocide (up to 50% w/w aqueous glutaraldehyde
solution), diluted biocide (0.5-10%) or to the dosed water (50-200 ppm v/v
glutaraldehyde), with the risk of exposure, by inhalation or skin contact, increasing with
concentration.
Exposure by workers is intermittent, for example, during dosing or maintenance, but the
number of workers potentially exposed to glutaraldehyde is considerable, as
glutaraldehyde-containing biocides are used widely in water treatment systems
throughout Australia.
Exposure to glutaraldehyde concentrate may occur during the following circumstances:
?addition of biocide to water treatment system;
?maintenance and cleaning of the dosing system;
?during spills and leaks; and
?sampling for analysis.




Glutaraldehyde
80
Glutaraldehyde may be added manually or by the replacement of an empty feed
container with a full one. The trend towards the use of automatic feed systems has
reduced the risk of exposure, as less direct handling of the glutaraldehyde solutions is
required.
No records of any atmospheric monitoring for glutaraldehyde in water treatment were
available.

14.7 Animal housing
Workers are exposed by inhalation and skin contact to glutaraldehyde in the animal
housing industry during the preparation and application of the solutions for disinfection.
The types of workers potentially exposed include the following:
? production workers;
? cleaners;
? professional contractors;
? farmers;
? veterinarians;
? egg collectors; and
? managers and supervisors of establishments such as piggeries, poultry sheds and
catteries.
In the dilution of glutaraldehyde concentrate, workers may by exposed to solutions
containing up to 50% w/w glutaraldehyde. In the application of the dilute solution for
disinfection, generally by washing but occasionally by spraying or foaming, the
concentration of glutaraldehyde solution is usually less than 0.3% w/w. Spraying will
increase the risk of exposure.
Disinfection is carried out intermittently, for example, monthly, with groups of two to
three people generally employed in the process of dilution and application.
Some atmospheric monitoring has been carried out in Australia, with the results in
Table 28.

Table 28
Glutaraldehyde concentrations in animal housing
Workplace Worker Conc (%) Sample type Ppm Ref
Chicken Egg collector* 0.1-0.3 A 0.007 72
farm
* The glutaraldehyde solution was sprayed, and the worker experienced face and
respiratory irritation.




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Priority Existing Chemical Number 3
14.8 Preservative/general biocide
In the use of glutaraldehyde as a biocidal additive in conveyor chain lubricants, workers
are potentially exposed by inhalation and skin contact to glutaraldehyde during the
addition of biocide to the lubricant and at various points along the conveyor.
Glutaraldehyde solution is usually added to the lubricant via an automatic dosing
system, so exposure is limited to the brief connection of biocide supply to the line.
Atmospheric monitoring for glutaraldehyde along a conveyor system has been carried
out, with results up to 0.03 ppm recorded, well below the National Commission's
exposure standard of 0.2 ppm.
In the use of glutaraldehyde in sanitary fluids, workers may be exposed by inhalation
and skin contact in the preparation and addition of glutaraldehyde solution to the toilet
system.
In the disinfection of air ducts, workers may be exposed by inhalation and skin contact
to glutaraldehyde mists or vapours in the application of the solution as a spray or fog.
They may also be exposed to more concentrated glutaraldehyde in the preparation of
solutions prior to application.

14.9 Microscopy
Workers may be exposed to solutions containing up to 50% glutaraldehyde during the
preparation of fixative solutions for use in electron and light microscopy and histology,
and to the working strength solutions (3-5%) during tissue fixation.

14.10 Summary
Exposure to glutaraldehyde occurs by skin contact with the solutions or by inhalation of
the vapours liberated from solution.
The number of workers potentially exposed to glutaraldehyde is considerable, with the
chemical used in a number of different industries.
Exposure is most likely in the health care industry, where approximately 75% of
glutaraldehyde is used. Due to the frequency and method of use, health care workers
may experience frequent skin contact with solutions, and the results of atmospheric
monitoring have shown that workers may be exposed to vapour concentrations
exceeding the national exposure standard. In x-ray film processing, workers may also be
exposed to other hazardous substances.
In tanning, the number of workers and the volume of use are low, but high
glutaraldehyde concentrations and elevated temperatures are used, so the risk of
exposure may be significant.
In animal housing, the concentrations used are very low, but sometimes the solutions
are used in spray form, when the risk of exposure may be significant.
In the other industries, the number of workers potentially exposed is low and/or the use
of glutaraldehyde is well-controlled, so the risk of exposure is low compared to those
industries mentioned above. In formulation, the concentration of glutaraldehyde is high
and the quantities are often large but the number of workers is low and, in general, the
process is well-controlled, so the risk of exposure is low.




Glutaraldehyde
82
15.Examples of current practices
involving glutaraldehyde --
photographs
Section 16.12 and the recommendations in section 21.3 should be consulted when
referring to the photographs in this chapter.


15.1 Glutaraldehyde as a raw material
Photograph 1




Glutaraldehyde is not manufactured in Australia. It is usually imported in large drums as a
concentrate in drums of varying sizes or as a dilute solution for end-use purposes (right).
Photo: Union Carbide (Australia) Pty Ltd.




83
Priority Existing Chemical Number 3
Photograph 2




Transferring glutaraldehyde from an open drum to its end-use purpose, in this case, as a
biocide in coolant.
Photo: WorkCover Authority of NSW.




Glutaraldehyde
84
15.2 Current practice in disinfection of endoscopes
Photograph 3




Addition of glutaraldehyde to soaking bath in a hospital disinfection unit.
Photo: WorkCover Authority of NSW.




85
Priority Existing Chemical Number 3
Photograph 4




Disinfection of endoscopes in open bath.
Photo: WorkCover Authority of NSW.




Glutaraldehyde
86
Photograph 5




Rinsing of endoscope in open bath.
Photo: WorkCover Authority of NSW.



Photograph 6




Disposal of spent glutaraldehyde solution after disinfection.
Photo: WorkCover Authority of NSW.



87
Priority Existing Chemical Number 3
Photograph 7




A soaking disinfection bath on a mobile trolley.
Photo: WorkCover Authority of NSW.




Glutaraldehyde
88
Photograph 8




Disinfection of endoscopes using automatic equipment inside a fume cabinet.
Photo: WorkCover Authority of NSW.




89
Priority Existing Chemical Number 3
15.3 Current practice in x-ray photography

Photograph 9




Addition of solution to automatic processor.
Photo: WorkCover Authority of NSW.




Glutaraldehyde
90
Photograph 10




Mixing of chemicals for x-ray photography.
Photo: WorkCover Authority of NSW.




91
Priority Existing Chemical Number 3
15.4 Current practices in animal housing

Photograph 11




Addition of chemicals to a chemical feed system.
Photo: WorkCover Authority of NSW.




Glutaraldehyde
92
Photograph 12




The use of personal protective equipment in the application of glutaraldehyde by spraying
Photo: WorkCover Authority of NSW.




93
Priority Existing Chemical Number 3
Photograph 13




The operator is wearing and holding the personal protective equipment required for animal
housing disinfection.
Photo: WorkCover Authority of NSW.




Glutaraldehyde
94
15.5 Specially-designed equipment recommended for disinfection
Photograph 14




A washing machine with lid developed by Royal Adelaide Hospital for washing and rinsing of
scopes. Specially designed to minimise splashing and personal handling.
Photo: Royal Adelaide Hospital.




95
Priority Existing Chemical Number 3
Photograph 15




Soaking container developed by Royal Adelaide Hospital for the disinfection of scopes. The
container has a transparent cover to minimise splashing and personal exposure.
Photo: Royal Adelaide Hospital.




Glutaraldehyde
96
Photograph 16




A laminar flow (fume) cabinet designed and built by Saint Luke's Private Hospital, Launceston,
for their day surgery unit. All procedures are enclosed with well-designed local exhaust
ventilation. Note the stainless steel construction, covered edges and corners, full-width perspex
access door (opening limited to elbow height), two stainless steel lids on the sinks, and external
controls (the electrical exhaust fan control is located on the opposite wall).
Photo: Saint Luke's Private Hospital, Launceston.



97
Priority Existing Chemical Number 3
Photograph 17




Frontal view of a laminar flow cabinet. Note the full width raised perspex door. The only movable
parts are the water spout between the sinks and the waste plugs (operated by remote control).
Photo:Saint Luke's Private Hospital, Launceston.




Glutaraldehyde
98
16. Occupational health
and safety assessment
16.1 Health and safety hazards
The results of animal testing have shown that glutaraldehyde is a potent irritant to the
skin, eyes and upper respiratory system. At high liquid concentrations, it is corrosive
and studies have shown that skin absorption may be significant on repeated exposure.
Animal studies showed that glutaraldehyde has a high acute inhalational toxicity. The
results of 13- or 14-week rat studies demonstrated that the respiratory irritant effects of
glutaraldehyde are exacerbated on repeated or prolonged exposure.
The human experience has confirmed the irritant properties of glutaraldehyde, with a
number of papers and case studies reporting adverse health effects such as dermatitis,
rhinitis, sore throat and eye irritation after exposure to glutaraldehyde. Glutaraldehyde
has been shown to be a skin sensitiser, with many confirmed cases cited in the literature.
A number of cases of occupational asthma and/or rhinitis have been reported in workers
exposed to glutaraldehyde.
In industry, glutaraldehyde is used almost exclusively as an aqueous solution in
concentrations from 50% w/w to less than 1%, so glutaraldehyde solutions are not
flammable hazards. The vapour pressure of glutaraldehyde is lower than for many other
chemical disinfectants, for example, formaldehyde, so the vapour concentrations
generated from solutions are low, especially at ambient temperatures.
Like most aldehydes, glutaraldehyde is reactive and may undergo reaction with
numerous other industrial chemicals.

16.2 Assessment of use in formulation
In the occupational health and safety (OHS) assessment of the use of glutaraldehyde in
the formulation of glutaraldehyde-containing products, for example, in the manufacture
of disinfectants, x-ray developers and water treatment solutions, the most significant
factors are:
?exposure to large quantities of glutaraldehyde;
?exposure to high and low concentrations of aqueous glutaraldehyde solutions;
?small numbers of workers potentially exposed;
?periodic exposure rather than daily exposure, for example, the dilution product may
be manufactured on only one day per month; and
?enclosure of the mixing process to prevent worker exposure.

In formulation, the greatest risks to workers are:
?during the transfer of the raw material, generally 50% w/w glutaraldehyde, to the
mixing vessel;
?during mixing; and
?during handling of the diluted product.



99
Priority Existing Chemical Number 3
Glutaraldehyde concentrate is generally supplied in 200 litre drums, so the greatest risk
to workers is usually in the transference of raw material to the mixer, as concentrated
glutaraldehyde solutions are corrosive and high vapour concentrations may be generated
during transfer. However, in most manufacturing plants in Australia, production is not
continuous, so the frequency and duration of activity is significantly reduced. Regular
production of glutaraldehyde products from concentrate may significantly increase the
risk of exposure, leading to possible skin absorption and inhalation of harmful vapours.
In Australia, most mixing operations are carried out in a sealed system to minimise
worker exposure. However, if formulation is conducted in an open mixing vessel, then
the risk of adverse health effects is greater, as the vapour concentrations will be higher,
especially if the mixing temperature is elevated above ambient conditions.
During the handling of diluted product, generally more workers are potentially exposed,
although the glutaraldehyde concentration is much lower. The likelihood of spillage is
greater at this stage of production, and adverse health effects may be experienced in
workplaces without the proper procedures to handle spills.
In summary, the risk of adverse health effects in the manufacture of glutaraldehyde
products in Australia is generally low, due to:
?enclosure of the process;
?low numbers of workers potentially exposed to glutaraldehyde; and
?low frequency of production.

16.3 Assessment of use as cold disinfectant
Glutaraldehyde is generally used as a 1% or 2% w/v aqueous solution at ambient
temperature for the disinfection of medical instruments such as endoscopes,
bronchoscopes and dental instruments. The key elements in the assessment of
glutaraldehyde in this use are:
?large numbers of workers potentially exposed, for example, all large hospitals and
most other hospitals in Australia use glutaraldehyde as the chemical disinfectant of
choice;
?regular exposure to glutaraldehyde by many workers, for example, some nurses may
disinfectant endoscopes daily and a number of times each day;
?the high degree of exposure during the disinfection process;
?exposure to low concentrations of aqueous glutaraldehyde; and
?poor control measures in many workplaces.
As glutaraldehyde is often used on a regular basis as a disinfectant, the risk of adverse
health effects will be high if effective control measures are not in place. In the scientific
literature, most incidences of adverse health effects such as dermatitis and rhinitis have
occurred in health care workers, for example, endoscopy nurses, a trend confirmed in
Australia, where there have been reports of health care workers experiencing skin
irritation and, to a lesser extent, respiratory irritation.
Instruments such as endoscopes and bronchoscopes are firstly cleaned to remove
organic matter, and then disinfected in a 1% or 2% activated solution of glutaraldehyde
for a period of 5-30 minutes, depending on the concentration and the equipment to be
disinfected. After soaking, the instruments are removed from the bath and rinsed with
clean water; washing of the intricate parts of scopes with a syringe is often necessary. In
many hospitals the risk of exposure is considerable as proper control measures such as


Glutaraldehyde
100
local exhaust ventilation and good safe handling facilities have not been provided, the
emphasis being on personal protective equipment to reduce the risk of exposure.
In general, the standard of skin protection is good, although the use of unsuitable, short
or old gloves and unsuitable clothing have been reported. Short-sleeve nurses' uniforms
do not provide adequate protection against glutaraldehyde solutions. Respiratory
protection is not used in routine tasks.
Although there has been a trend towards automation of the disinfection process, much
of the disinfection of instruments and equipment is still carried out manually. Also,
glutaraldehyde solutions and soaking baths containing the solutions are often
transported from one work location to another. Splashing and spills are more likely to
occur, increasing the risk of exposure by both inhalation and skin contact.
On the evidence from hospitals and State and Territory authorities that many current
control measures in Australia are still inadequate, the risk of adverse health effects is
still high, as most hospitals use glutaraldehyde on a daily basis and the total number of
workers potentially exposed to glutaraldehyde solutions and their vapours is high. A
survey of four hospitals in Sydney carried out by the Sydney Hospital Occupational
Health and Safety Service for the NSW Health Department concluded that, in many
instances, cold disinfection was not carried out in a proper manner.117 In the survey,
only one of the disinfection units was equipped with local exhaust ventilation, with a
majority set up in rooms with poor general ventilation.
However, a number of workplaces have already demonstrated that the risk of exposure
can be significantly lowered by the implementation of effective control measures to
reduce worker exposure (see section 16.12).
Glutaraldehyde disinfectants are supplied in 5 litre plastic containers and must be stored
away from heat and sunlight. The Sydney Hospital survey117 found that glutaraldehyde
solutions were not stored properly.
Glutaraldehyde has also been used for the general surface disinfection of beds, work
benches and trays. However, the risk of exposure was unacceptably high, so this use has
been largely discontinued as safer procedures are available for general surface
disinfection.

16.4 Assessment of use in x-ray film processing
Adverse health effects experienced after the use of glutaraldehyde-containing x-ray film
products may be complicated by exposure to other hazardous substances in the
processing solutions, for example, hydroquinone, potassium hydroxide and acetic acid.
Key elements in the OHS assessment of glutaraldehyde in this application are:
?the large number of workers potentially exposed, as most hospitals have x-ray
departments, and there are many private radiology clinics;
?the high frequency of exposure by most workers;
?the high concentration of glutaraldehyde in stock solutions, for example, 30-50%
w/w;
?the handling required in preparing working strength solutions; and
?the variable level of exposure control.
Apart from the use of glutaraldehyde as a disinfectant, there have been more reports of
adverse health effects in workers handling x-ray film processing solutions than for any
other use of glutaraldehyde. Radiographers and dark room technicians have experienced
dermatitis and/or respiratory disorders after exposure.



101
Priority Existing Chemical Number 3
The risk of adverse health effects is highest in the preparation of working strength
solutions, as the strength of glutaraldehyde concentrate is 30-50% w/w, a concentration
at which significant skin absorption may occur on repeated exposure. The higher
strength solutions will also generate higher vapour concentrations, particularly in
confined workspaces such as dark rooms. The risk of exposure to glutaraldehyde in the
preparation of working strength solutions has been overcome in some workplaces by the
installation of automatic mixers, notably in the larger institutions.
In handling working strength solutions, the risk is still significant, as glutaraldehyde is
an irritant at low concentrations, and harmful vapour concentrations can still be
generated, particularly in a small enclosed work area. The risk of adverse health effects
has been reduced to some extent by the introduction of automatic film processors, but
the benefit is moderated if their exhaust gases are not completely removed from the
work area. Also, automatic processors must be maintained properly; in the survey of
four Sydney hospitals by the Sydney Hospital Occupational Health and Safety
Service,117 corrosion was observed on some of the processors. The large number of
tubes and connections on automatic processors necessitates regular inspection to prevent
leakage.
In summary, the risk of adverse health effects from the use of glutaraldehyde in x-ray
film processing is significant for those involved in the mixing of solutions, due to high
glutaraldehyde concentrations and the poor level of control in many workplaces. The
risk to workers handling the dilute working-strength solutions is significantly lower.


16.5 Assessment of use in tanning
In assessing the OHS risks associated with the use of glutaraldehyde in tanning in
Australia, the key elements are:
? small number of tanneries using the chemical;
? few workers potentially exposed at each tannery;
? usually a low frequency of use at each tannery;
? high concentrations of glutaraldehyde solution (25-50% w/w) used;
? large quantities used;
? tanning conditions, for example, soaking at elevated temperature; and
? poor control measures.
Although glutaraldehyde is often used at a low frequency in tanning, and the number of
workers potentially exposed is small, there is a significant risk of adverse health effects
in the use of glutaraldehyde in tanning. The strength of glutaraldehyde solution is high
and elevated temperatures are used in the soaking process, so potentially significant skin
absorption and inhalational exposure may occur, for example:
? during the addition of glutaraldehyde to the mixing vessel;
? during mixing if the vessel is not sealed; and
? after treatment, when the pelts are dried and the contents of the mixing vessel are
discharged.
Even though the number of workers in Australia is low, adverse health effects such as
dermatitis have been reported after exposure to glutaraldehyde.
In general, the poor level of control of glutaraldehyde use in some tanneries has resulted
in a significant risk of adverse health effects.



Glutaraldehyde
102
16.6 Assessment of use in water treatment
In the assessment of glutaraldehyde as a biocide in water treatment, the key elements
are:
? large number of sites which use glutaraldehyde;
? reasonably small number of workers potentially exposed;
? low frequency of exposure;
? small quantities usually used;
? exposure to high and low strengths of solution; and
? general use of effective controls to minimise exposure.


No reports of adverse health effects experienced after the use of glutaraldehyde in water
treatment were found in the literature, and no case reports were received during the
assessment period.
The most significant risk of adverse health effects occurs at the dilution stage, when
more concentrated solutions and large quantities are handled. However, this process is
generally carried out under good control at the formulation site rather than at the water
treatment site.
At dosing, smaller quantities of glutaraldehyde solution are handled intermittently, so
the OHS risk is less significant.
The trend towards the use of automatic feed systems has decreased the risk due to less
handling of solutions and subsequent reduced exposure.

16.7 Assessment of use in animal housing
In the assessment of glutaraldehyde use in the animal housing industry, the key
elements are:
?large number of sites;
?small number of workers potentially exposed at each site;
?low frequency of use at each site;
?low concentration of glutaraldehyde solution;
?method of application, for example, spray, foam or wash; and
?variable level of exposure control.
The use of glutaraldehyde as a disinfectant in the animal housing industry has led to
sporadic reports of adverse health effects, for example, an egg collector in South
Australia experienced facial and respiratory irritation after spraying eggs with 0.1-0.3%
glutaraldehyde solution.72 From information received during the assessment period, the
level of control during preparation and application of the solutions varies from one
worksite to another.
The risk of adverse health effects is significant during the dilution of glutaraldehyde
concentrate to working strength solution, as larger quantities may be handled and higher
vapour concentrations may be generated unless good control measures are in place. The
risk is increased if dilution is carried out in the field without sufficient control.
When applied as a liquid solution in disinfection, the risk of adverse health effects is
low as the strength of solution is low (generally less than 0.3%) and the number and
frequency of workers potentially exposed to glutaraldehyde is also low. However, the


103
Priority Existing Chemical Number 3
use of glutaraldehyde solutions in spray form increases the risk of exposure and so
increases the risk of adverse health effects.

16.8 Assessment of use as preservative/biocide
The OHS risks associated with the use of glutaraldehyde as a preservative and a general
biocide are low due to the low volume of use and the small number of workers
involved.
In the use of glutaraldehyde in conveyor chain lubricants, the glutaraldehyde solution is
added via an automatic feed system, so exposure is restricted to the periodic addition of
new 5% solution to the feed system and to low vapour concentrations along the
conveyor.
The risks associated with the application of sanitary fluids containing glutaraldehyde in
aircraft and portable toilets are low as few workers are involved, the concentration is
low and the duration of exposure is short.
In the use of glutaraldehyde as a disinfectant for air ducts, the duration of exposure is
brief and infrequent.

16.9 Microscopy
Glutaraldehyde solutions at approximately 3-5% are used in very small quantities for
fixation, but if the use is regular and the controls are poor, for example, lack of effective
ventilation, then the risk of adverse health effects may be significant. Eye, skin and
respiratory irritation have been reported for workers engaged in tissue fixing.68

16.10 Other uses
The use of glutaraldehyde in other areas, for example, embalming, is small, so the risks
to health and safety are expected to be low.

16.11 Education and training
Guidelines for the induction and training of workers who may be potentially exposed to
hazardous substances are provided in the National Model Regulations and Code of
Practice to Control Workplace Hazardous Substances,107 which lists the key elements
of a good induction and training program.
In some workplaces, there is a lack of the proper technical expertise to conduct high
quality training about the hazards of glutaraldehyde and how it should be handled. This
has led to the incorporation of glutaraldehyde-related training into special training
courses, for example, Fairfield Hospital in Melbourne conducts Disinfection: A Course
for Dental Practice as part of its HIV dental programs. This includes education in the
hazards of glutaraldehyde and training in proper handling procedures.
The Western Australia Health Department has conducted a seminar on the safe use of
glutaraldehyde and implemented extensive workplace training programs.

16.11.1 Formulation
From the information obtained for assessment, workers employed in the formulation of
glutaraldehyde-containing products are informed of the hazards of glutaraldehyde, and
trained in the proper handling procedures. The use of videos, safety manuals and
specific use information was reported by producers.



Glutaraldehyde
104
16.11.2 Health care industry
The training and education of workers is variable between hospitals and between other
health care establishments such as radiology and dental clinics. In some hospitals and
other health care workplaces, a formal program is in place to properly train workers in
the safe handling of glutaraldehyde, but in other workplaces there is little training in the
hazards of glutaraldehyde and the proper safe handling procedures. Guidelines such as
those prepared by the NSW Health Department115 are an excellent aid in training
programs; the guidelines cover the use of glutaraldehyde both as a cold disinfectant and
as an ingredient in x-ray film developers. In some health care regions, OHS
coordinators have provided training programs for workers who are potentially exposed
to glutaraldehyde.

16.11.3 Other industries
From the information submitted for the assessment of glutaraldehyde, there was little
evidence of formal training programs in industries outside formulation and the health
care industry for workers potentially exposed to glutaraldehyde. In particular, end-users
of glutaraldehyde products may be unaware of the health effects of the chemical and
therefore unaware that control measures need to be implemented to reduce exposure.
Safe use guidelines specific to the industry and similar in style to those available in the
health care industry would be an aid to effective training in the other industries.

16.12 Control measures

16.12.1 Control of hazardous substances
Glutaraldehyde is a hazardous substance and solutions of glutaraldehyde above 0.1%
concentration should be also classified as hazardous substances. Under the National
Model Regulations and Code of Practice to Control Workplace Hazardous
Substances,107 control measures to reduce exposure must be in place to minimise the
risks to health and safety. In particular, controls should be in place:
?to minimise inhalational exposure by maintaining atmospheric concentrations as low
as possible; and
?to minimise skin contact with glutaraldehyde solutions.
The control of glutaraldehyde should be achieved through the following hierarchy of
control measures to reduce exposure:
?elimination;
?substitution;
?isolation;
?engineering controls;
?administrative controls;
?safe work practices; and
?personal protective equipment.
A holistic approach to effective control is required, for example, a combination of good
workplace design and effective engineering controls and safe work practices have been
proposed to overcome the potential occupational health problems in x-ray film
processing,118 and control strategies have been proposed for disinfection units.119




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Priority Existing Chemical Number 3
16.12.2 Elimination and substitution
For most applications of glutaraldehyde, elimination is not an option. However, where
glutaraldehyde solutions have been used as simple surface disinfectants, a more
thorough cleaning process may be sufficient.
Glutaraldehyde is a very effective disinfectant and, due to its efficacy, no equivalent
substitute is available in many of its uses in the health care industry. However, in some
instances it has been successfully replaced, for example, tonometers (for measuring
eyeball pressure) have been disinfected with sodium hypochlorite solution as residual
glutaraldehyde may damage the eye. In the use of glutaraldehyde as a general surface
disinfectant, a non-hazardous substance could be substituted.
In general, any proposed alternative to glutaraldehyde should be carefully considered to
ensure that the risks to health and safety are not increased. In animal housing,
glutaraldehyde has been substituted in some cases with formaldehyde, a more hazardous
substance.

16.12.3 Isolation
In terms of the current use and application of glutaraldehyde solutions, isolation of the
chemical by the adoption of a remote control process may not be practical in many
situations. In x-ray film processing, commercially available mixers and processors are
used to enclose the mixing and processing operations, but the equipment generally
requires manual filling with glutaraldehyde solutions. Automatic washers are used in
some hospitals for instrument disinfection (see section 16.12.4).
In the formulation of glutaraldehyde-containing products by mixing and dilution, large
quantities of concentrated glutaraldehyde (up to 50% w/w) are handled, so enclosed
mixing vessels are generally used to isolate the worker from the process and reduce the
risk of spillage. Enclosure of the mixing process is essential when glutaraldehyde may
be heated, as vapour concentrations are increased at elevated temperatures.

16.12.4 Engineering controls
If elimination, substitution and isolation are not feasible options in the reduction of
exposure, then engineering controls should be considered. In the case of glutaraldehyde,
controls need to focus on reducing exposure by inhalation and skin contact so that any
reliance on personal protective equipment only is minimal. A survey by Leinster et al120
demonstrated the effectiveness of good ventilation and automatic equipment in reducing
exposure to glutaraldehyde.
Through observation and information received during the assessment period, the
standard of engineering controls in workplaces in Australia where glutaraldehyde is
used is extremely variable, with controls ranging from opening a window to a
sophisticated downflow booth. In some workplaces little or no mechanical ventilation
has been introduced. The level of control introduced should be proportional to the
quantity and concentration of glutaraldehyde solution used and the risk of exposure to
the worker. Ideally, engineering controls should be introduced at the design stage so that
the proper materials, dimensions and safety facilities are built into the work area. The
Environmental Health Branch of the Health Department of Western Australia has issued
criteria for the design of dark rooms where glutaraldehyde may be used.
In the formulation of glutaraldehyde products and in the dilution of stock solutions,
drums of glutaraldehyde concentrate can be opened in a well ventilated area and the
contents transferred to the mixing vessel or dilution matrix via a sealed pump system.


Glutaraldehyde
106
The filling of containers with diluted glutaraldehyde product should be carried out in a
well-ventilated area.
In the handling of glutaraldehyde products, both at formulation sites and at end-use,
mechanical ventilation is required to minimise exposure to glutaraldehyde by inhalation.
This may consist of one or more of the following types:
? local exhaust ventilation;
? dilution ventilation; and
? in-built exhaust ventilation, for example, in x-ray film processors.
In the handling of glutaraldehyde outdoors, engineering controls such as closed feed
tanks and automatic dosing systems have been used to reduce exposure.
Ventilation should be provided in accordance with the relevant Australian Standards, in
particular AS 1668.2-1991121. The following matters need to considered:
? type and size of fan;
? air cleaning device, for example, carbon filter to absorb glutaraldehyde;
? ductwork, including consideration of duct velocity;
? maintenance of the ventilation system; and
? final discharge to atmosphere.
Guidance in the design and maintenance of effective local exhaust ventilation is
available in the United Kingdom Health and Safety Executive literature.122,123
Engineering controls introduced to overcome the hazards associated with
glutaraldehyde use include:
?specially designed fume cupboards and soaking baths;
?soaking baths fitted with clear perspex tops and snap-down clasps to completely seal
the contents;
?gravity-feed dispensers for filling and emptying the soaking baths;
?disposable tubes for soaking scopes -- the Scope Guard disinfectant system;124
*
? the Safelab Endoscopy Work Station*, which comprises three sinks, four taps, two
pumps and two glutaraldehyde containers (under the bench-top) within a fume
cupboard;125 and
? the Labworks Portable Recirculating Fume Cabinet,* a self-contained unit which
contains disposable carbon filters to adsorb vapours.
At Royal Adelaide Hospital, a prototype mobile washing machine for scopes has been
designed and built by the engineering staff at the hospital (see photographs). An
improved version is expected to be available in early 1994.
Mobile units are available for situations where fixed locations for disinfection may be
impractical, although in general their use is discouraged, due to possible splashing and
potential problems with disposal of spent solution and monitoring of the carbon filters
for chemical breakthrough. Commercial mobile units such as the KC10 Mobile
Disinfection Station* and the Keymed 'Auto-Disinfection' system*, a later fully
automatic unit, have been used in hospitals for cleaning and disinfecting instruments
such as endoscopes. The EW10 Automatic* is a further improvement on the KC10.

*
Comments in this report on commercial equipment do not constitute an endorsement by Worksafe
Australaia


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Priority Existing Chemical Number 3
Local exhaust ventilation
A number of different types of local exhaust ventilation (LEV) have been used in
Australia to cope with the health hazards of glutaraldehyde.
The two main types of LEV are the:
? partial enclosure, for example, a booth or a fume cupboard; and
?hood, for example, a fume hood or an extraction fan.
Hoods and fans tend to give poorer control than enclosures as the air flow can be
influenced by operator movement and local air current fluctuations. A simple extraction
fan in the wall or ceiling is not appropriate for glutaraldehyde vapours.
Features of an effective fume cupboard125 for glutaraldehyde include:
?air directed from the front access of the cupboard, across the work area, and
extracted through a baffle at the rear of the cupboard;
?a fan above the work area, with air extracted via ducting to a safe location outside
the building; and
?a face velocity of 0.5-1.0 m/sec at the front of the cupboard.
The ventilation system exhaust must be sited away from air intakes so that extracted air
does not re-enter the building.
In a number of hospitals around the country, fume cupboards have been constructed to
reduce exposure to glutaraldehyde vapours, for example, at St. Luke's Private Hospital
in Launceston, an effective custom-made laminar flow unit with specially designed
soaking basins (see photographs) has been installed. In glutaraldehyde production at one
factory, the filling station has been enclosed, and the vapours exhausted into the main
extraction system.
At King Edward Memorial Hospital in Perth, a downdraught system around the rim of
the soaking trays has been utilised.
At Fremantle Hospital, fixed fume cupboards and mobile units with extractors are
provided for the handling of glutaraldehyde solutions.
In some hospitals, mobile disinfection units have been fitted with LEV to reduce
exposure to vapours, for example, at the Mater Misericordiae Children's Hospital in
South Brisbane, a modified Nederman Extractor unit* has been fitted.
LEV units in use for the reduction of glutaraldehyde exposure are often fitted with
carbon adsorption filters to prevent the escape of glutaraldehyde to either the work
environment or to the air outside the building. Activated carbon is most effective in
adsorbing glutaraldehyde, but the adsorption units (filters) need to be changed regularly
to ensure that breakthrough (of glutaraldehyde vapours) does not occur. Canisters are
available for large-scale use, for example, for the ventilati*on of storage tanks and
mixing vessels. Carbon filters in use for volatile organics often have flame arresters
attached. Some agencies have chosen not to use mobile units fitted with carbon filters
because of the risk of chemical breakthrough.
LEV units need to be maintained, examined and tested at regular intervals.

*
Comments in this report on commercial equipment do not constitute an endorsement by Worksafe
Australaia


Glutaraldehyde
108
Dilution Ventilation
Most indoor workplaces in Australia that use glutaraldehyde are equipped with some
form of mechanical dilution ventilation, with fresh air being introduced into the work
environment. The capacity and capability of the ventilation should be proportionate to
the size of the room/work area and the quantity/concentration of glutaraldehyde used. A
ventilation system based on recirculated air only is not appropriate for the control of
glutaraldehyde vapours in the workplace.
In one production area, the ventilation rate is 18 changes per hour, with a make-up of
10% outside air. In the corresponding filling area, the rate is the same, but with the
capacity to be increased to 33 changes per hour if a spillage occurs.


In-built ventilation
Much of the x-ray film processing work in Australia is carried out using automatic
processors, which have built-in fans that operate continuously. Problems often arise in
the connection of the exhaust to an existing ventilation system. The exhaust system
must be independent of indoor air supply and any air conditioning system, so additional
ductwork may be required. Exhaust air can be treated, for example, by carbon
adsorption, before discharge to the environment.

16.12.5 Administrative controls
In some work areas, individual exposure has been reduced by the introduction of
administrative controls such as job rotation, where a worker may spend only part of the
working week in the area where glutaraldehyde is handled, and the remainder of the
week in another area. Other administrative controls which may be introduced include
the rescheduling of operations involving glutaraldehyde so that potential exposure in
any work period is minimised.

16.12.6 Safe work practices
Occupational exposure to glutaraldehyde can be reduced by the adoption of safer work
methods.
Safe work practices applicable to the handling of glutaraldehyde solutions include:
? use of the minimum amount of glutaraldehyde solution for the task;
? the proper labelling of glutaraldehyde solutions in the workplace, including trays,
drums and other containers;
? prompt clean-up of spills -- a written procedure for spill clean-up is advisable;
? the handling of solutions and equipment in such a way as to prevent splashing or the
creation of a mist;
? the proper emptying, cleaning and rinsing of containers and equipment after use;
? the proper disposal of all contaminated containers and equipment;
? good housekeeping in the work area; and
? high standard of personal hygiene.




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16.12.7 Personal protective equipment
Personal protective equipment (PPE) is used to support other control measures in
preventing worker exposure to glutaraldehyde, both by inhalation and skin contact.
Guidance is provided in the Standards Australia handbook HB9.126 From the
information submitted for this assessment, there was evidence of a reliance on PPE
rather than engineering and administrative controls. PPE should always be used in
conjunction with other control strategies. If PPE is to be used, then it should be
appropriate for the concentration of glutaraldehyde to be used, and the type of task to be
carried out, for example, proper eye, respiratory and skin protection is required when
glutaraldehyde solutions are used in spray form.

Eye protection
The selection and use of eye protection should be in accordance with Australian
Standards AS 1336127 and AS 1337128.
For the handling of concentrated glutaraldehyde solutions, or in situations where
splashing may occur, chemical safety goggles should be used. For the handling of small
quantities of dilute glutaraldehyde solutions, chemical safety spectacles with side-
shields may suffice.

Gloves
The permeability of 2%, 25% and 50% w/w aqueous glutaraldehyde solution through
different types of gloves has been assessed using ASTM Permeation Test Procedure
F739-81.35 The test results129 indicated that polyethylene, butyl rubber, surgical latex
rubber and nitrile rubber would provide adequate protection from contact with aqueous
glutaraldehyde solutions. PVC and neoprene gloves were also tested but were found to
retain or absorb glutaraldehyde on extended exposure.
In hospitals in Australia, the tendency is towards the use of nitrile rubber, butyl rubber
or surgical latex gloves for the handling of 1% or 2% solutions. In some jurisdictions,
surgical latex gloves are not regarded as suitable as permeation by glutaraldehyde has
been observed. In recent years, an increasing number of severe allergic responses to
latex have been reported,130 especially in the health care industry. When latex gloves are
used, two pairs are generally worn, with the outer pair discarded after use in the
disinfection process.
In general, gloves should be discarded after use, especially latex gloves. If gloves are to
be re-used, then they must be thoroughly cleaned. Old or poor quality gloves should not
be used.
The relevant Australian Standard for the design of industrial safety gloves and mittens is
AS 2161.131

Respirators
The selection and use of respiratory protection should be in accordance with Australian
Standards AS 1715132 and AS 1716.133
In the proper handling of glutaraldehyde solutions, workers in most work situations
should not need respiratory protection. However, if it is used, then careful consideration
of the quantity and concentration of glutaraldehyde solution is required -- the more
concentrated the solution, the higher the vapour concentration. In general, respiratory
protection, for example, the half-face or full-face cartridge respirator, should be used



Glutaraldehyde
110
only for short periods, for example, during the clean-up of spills, and in the application
of glutaraldehyde solution as a spray.

Clothing
Proper protective clothing, for example, overalls and impervious aprons, should be worn
when handling glutaraldehyde solutions, particularly concentrated solutions, which are
corrosive.
The type of clothing will depend on the particular use of glutaraldehyde in the
workplace, but full skin protection, including protection of arms and legs, is
recommended as glutaraldehyde can be skin sensitising in some workers. Aprons to be
used during disinfection in hospitals should be made of proven impervious materials (as
for gloves). Special clothing may be required during maintenance or during the clean-up
of spills.
The appropriate Australian Standard for choice and use of clothing is AS 3765.134

16.13 Emergency procedures;
As for any hazardous substance an emergency response plan is essential for those
workplaces handling glutaraldehyde, especially production sites and work areas where
glutaraldehyde is handled in large quantities and/or as a concentrated solution. In the
event of a substantial leak, spill or other release of glutaraldehyde, a written procedure
is necessary for workers in the area and for emergency services who may be required to
deal with the release.
In the submission for assessment, a suitable emergency response plan for 50%
glutaraldehyde contained the following items:6
?emergency contact numbers;
?health effects and physicochemical properties of glutaraldehyde;
?first aid procedures;
?immediate action required in case of a spill or leak;
?immediate follow-up action, including decontamination;
?evacuation plan;
?protective equipment and supplies that may be required in the emergency;
?clean-up procedures and waste disposal;
?MSDS and label.

16.14 Atmospheric monitoring;
From information obtained during the assessment period, monitoring for glutaraldehyde
is carried out in some but not all worksites in Australia. As adverse health effects have
been experienced after exposure to low concentrations of glutaraldehyde, an assessment
of the workplace under the National Model Regulations and Code of Practice for the
Control of Workplace Hazardous Substances,107 may indicate that monitoring for
glutaraldehyde is required to measure occupational exposure to glutaraldehyde and/or to
ensure that the control measures are effective. Where the level of exposure is not
known, a small number of analyses is required initially to establish a baseline for
assessment of the workplace and to determine whether improved control measures
and/or regular monitoring are necessary.
Monitoring for glutaraldehyde in hospitals has been carried out in all States and
Territories by the respective Health Departments, with glutaraldehyde levels generally

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Priority Existing Chemical Number 3
below the exposure standard. The exposure standard is a peak limitation, so monitoring
is usually conducted over 15 or 30 minute periods. For most workplaces, a mix of
personal and fixed-point monitoring is generally carried out.
Except for some production sites, there is little evidence of regular monitoring for
glutaraldehyde outside the health care industry, even though exposure is potentially
significant during some operations, for example, in tanning and in dilution work.
Some results of atmospheric monitoring for glutaraldehyde are listed in Chapter 14.
A number of analytical methods are available for the determination of glutaraldehyde in
air. Some of these are listed in Chapter 6. A number of government departments and
consulting laboratories have technical experience in measuring atmospheric
glutaraldehyde in the workplace environment.




Glutaraldehyde
112
17. Regulatory controls

17.1 Exposure standard;
The National Exposure Standard for glutaraldehyde is 0.2 ppm (peak limitation), or 0.82
mg/m3, with a sensitiser notation.8
The ACGIH TLV for glutaraldehyde is also 0.2 ppm (ceiling value), set in 1979.77 The
value is for both unactivated glutaraldehyde and glutaraldehyde activated with sodium
bicarbonate, and is based on the irritation threshold of glutaraldehyde in humans.
Glutaraldehyde is currently under review by the ACGIH TLV committee. Also in the
USA, both OSHA and NIOSH have established exposure limits of 0.2 ppm (ceiling
value) for glutaraldehyde, based on irritation of the eyes, nose and throat in humans.
Exposure standards for glutaraldehyde in other parts of the world include:
?Germany
0.2 ppm, with short term level (5 min./8 times per shift) 0.4 ppm and sensitiser
notation.
? Sweden
0.2 ppm (ceiling), sensitiser.
? United Kingdom
10 min. STEL 0.2 ppm (reviewed 1987)135.
?br> The evaluation of the health effects of glutaraldehyde in this assessment supports the
need for a revision of the current exposure standard, with the following values
recommended for consideration by the National Commission's Exposure Standards
Expert Working Group:
?STEL (15 min)
0.15 ppm (0.62 mg/m3).
?TWA (8 hr)
0.1 ppm (0.41 mg/m3).
?br> Supporting evidence for the recommendations include:
?irritation of the nose and throat has been observed in workers exposed to
glutaraldehyde concentrations less than 0.2 ppm;62
a 13-week NTP inhalation study in rats14 resulted in nasal irritation at 250 ppb, with
?br> a NOAEL of 125 ppb;
in the corresponding NTP study in mice,14 no NOAEL was reached as signs of nasal
?br> irritation were observed at the lowest dose (62.5 ppb); and
? a 14-week inhalation study in rats resulted in some signs of nasal irritation at 49 and
194 ppb.
Repeated-dose animal studies have shown that the irritant effects of glutaraldehyde are
exacerbated on repeated exposure.
Experience in Australia has shown that, provided the proper control measures are in
place, atmospheric concentrations of glutaraldehyde can generally be maintained below


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Priority Existing Chemical Number 3
the proposed exposure standard. In a number of instances, the introduction of control
measures has led to lower exposure levels and a reduction in the incidence of adverse
health effects. Problems may still arise during spills or maintenance or, in some
instances, in the application of glutaraldehyde in spray form. In such instances,
respiratory protection is needed to prevent inhalation of vapours.

17.2 Health surveillance
In line with the National Model Regulations for the Control of Workplace Hazardous
Substances,107 employers have a responsibility to provide health surveillance in those
workplaces where the workplace assessment has shown that exposure to a hazardous
substance may lead to an identifiable substance-related disease or health effect.
A number of adverse health effects have been identified in workers exposed to low
concentrations of aqueous glutaraldehyde, especially skin, eye and respiratory irritation.
Skin sensitisation, occupational asthma and rhinitis have also been diagnosed in some
workers exposed to glutaraldehyde (see Chapter 11).
Some work areas such as hospitals have in place a health surveillance program which is
able to detect at an early stage any adverse health effects, for example, contact
dermatitis and occupational asthma. Where there are indications of the failure of control
mechanisms, such a program enables an immediate examination of the worksite and the
early implementation or reinforcement of control measures to reduce exposure.
However, many workplaces where exposure to glutaraldehyde may be significant do not
have formal health surveillance programs in place.
A number of workplaces have shown that the implementation of effective control
measures, for example, the introduction of automatic equipment or local exhaust
ventilation, has led to minimal exposure to glutaraldehyde and a negligible incidence of
associated adverse health effects. Atmospheric monitoring procedures are available to
ensure that the effectiveness of control measures is maintained. Consequently, the
listing of glutaraldehyde on the National Commission schedule of substances requiring
health surveillance is not considered necessary.
In those workplaces where a health surveillance program may be required, careful
planning, implementation and evaluation of the program are essential. Medical
practitioners involved in health surveillance programs for glutaraldehyde need
experience and an understanding of the relationship between pre-existing skin and
respiratory disease and glutaraldehyde-induced health effects, as well as an
understanding of the difficulty in assessing individuals for glutaraldehyde-associated
illnesses such as occupational asthma and irritant or allergic contact dermatitis.
Early diagnosis of glutaraldehyde-induced health effects is important. A baseline
medical check of workers prior to employment serves to assist in identifying future
signs of skin or respiratory disease, for example, identifying atopics and individuals
with pre-existing skin or respiratory problems who may be at greater risk. Information
available suggests that atopics are at a greater risk of sensitisation than non-atopics to
naturally-occurring agents, but for synthetic agents such as glutaraldehyde, atopy is a
much less significant risk factor.136
The incidence of skin disease in workers exposed to glutaraldehyde is detailed in
sections 11.1.1 and 11.2.1. Most occupational skin disease from exposure to
glutaraldehyde involves dermatitis of the hands and/or arms. Medical practitioners
should note that it is often impossible on appearance alone to to distinguish hand
eczema in atopics from dermatitis in non-atopics. The clinical presentation may be



Glutaraldehyde
114
affected by the duration of exposure and the concentration of chemical used. Persons
with previous hand eczema, a strong risk factor, are most at risk of aggravating their
skin disease with exposure to skin irritants such as glutaraldehyde. People with weak
risk factors, for example, those with a respiratory allergy, do not seem to develop hand
eczema more commonly than non-atopics. In cases of contact dermatitis, patch testing
using standard procedures has been utilised successfully in the diagnosis of allergic
contact dermatitis.80,81
The incidence of respiratory disease in workers exposed to glutaraldehyde is detailed in
sections 11.1.3 and 11.2.2, together with definitions of the relevant terms, for example,
respiratory sensitisation and occupational asthma. In the diagnosis of respiratory
disease, early referral of of suspected cases is important. Guidelines for the diagnosis of
occupational asthma have been proposed,40,137 based on the following criteria (see
section 11.2.2):
?clinical history;
?physical examination;
?lung function tests;
?bronchial challenge; and
?immunological tests.


However, immunological tests may not be appropriate for glutaraldehyde as the allergic
mechanism is not yet known.
Suitable tests which have been used in health surveillance programs for occupational
asthma include:
?spirometry for the measurement of FVC and FEV1;
?the PEFR, which can be measured by the workers themselves if appropriate; and
?inhalation challenge testing.


Some of the techniques used may be insensitive, for example, spirometry and peak flow
measurements, but new techniques to increase the sensitivity of early diagnosis of
occupational asthma have been recently reported.138 The standardisation of procedures
for spirometry is important,139-141 and recent work has been carried out internationally to
update them.142-144,145,146




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18. Public health assessment

18.1 Public exposure
The public is unlikely to be exposed to glutaraldehyde during importation and
transportation. Public exposure to glutaraldehyde during industrial use, disposal and use
of treated products depends on the particular use pattern and will be discussed under the
relevant heading below.

18.1.1 Cold disinfectant
Aqueous glutaraldehyde solutions (1% or 2%) are used in medical, veterinary and
dental clinics for the disinfection of heat sensitive equipment, including fibre optic and
lensed instruments, anaesthetic, respiratory and other equipment which cannot be
autoclaved. Public exposure can occur due to inadequate cleaning and rinsing, which
can leave a maximum residual volume of 3 mL, equal to the normal maximum working
volume of any individual channel in a fibre optiscope. This could result in localised
irritation or hypersensitivity.
Exposure from spillage or vapours from open containers is unlikely as the disinfection
procedure is normally conducted in non-patient areas. Disposal (to sewer diluted with
water) is unlikely to produce significant public exposure.

18.1.2 X-ray film processing
Glutaraldehyde is used in black and white, high temperature, rapid process developers
as a hardening (cross-linking) agent, mainly in automated processing. Photographic
developers containing glutaraldehyde are not used by the general public. Spent
developer is either collected for removal by a licensed agent or discharged to sewer.
Glutaraldehyde will form chemical complexes with sulfite in the fixers. No public
exposure is envisaged with this use pattern.

18.1.3 Tanning
Glutaraldehyde is used as a tanning agent in the leather industry with total quantity used
below 10 tonnes per year. Potential public exposure would be from contact with
processed hides and discharged waste. Due to its cross-linking activity, glutaraldehyde
is fixed into the leather during processing, thus minimising any public exposure. The
final concentration of glutaraldehyde in total tannery effluent is expected to be less than
1 ppm, with the majority being fixed by dissolved proteins in the effluent. Public
exposure to glutaraldehyde in tannery effluent is therefore likely to be minimal.

18.1.4 Water treatment
Glutaraldehyde is used as a water treatment microbiocide in cooling towers, air washers,
pasteurisers and other recirculating water systems. It is not for use in potable waters.
Effluents are discharged to sewerage, with a large industrial tower discharging 20,000 L
of glutaraldehyde in 1,000,000 L of combined sewerage per day.
The public is also potentially exposed to glutaraldehyde in drift escaping to the
atmosphere from cooling towers. This drift would contain 45-90 ppm glutaraldehyde.



Glutaraldehyde
116
The potential for public exposure to this drift is considered moderate but would be on an
occasional basis.

18.1.5 Animal housing
Intensive animal production industries use aqueous glutaraldehyde solutions containing
glutaraldehyde at a final concentration at approximately 0.1-0.3% w/v. The uses include
the disinfection of farrowing crates in piggeries and the sanitation of poultry sheds after
the animals have been removed from the area. The products are not recommended for
direct application to animals. No public exposure is expected with this use pattern.
Glutaraldehyde is also used in specialised disinfectants in veterinary hospitals, but
public exposure is minimal.

18.1.6 Preservative/general biocide
Fogging of air ducts is carried out using 2% glutaraldehyde products. The process is
carried out once personnel have left the area, with reoccupation only after ventilation
with maximum fresh air for 20 complete air changes. Thus public exposure is expected
to be minimal.
Glutaraldehyde (2%) is also used at 20-40 mL per 1 L water in the initial charge of
portable toilet systems. The products are used by the general public and hence potential
exposure is high.
Glutaraldehyde is also used as an oil well and metal working antimicrobial and as a
biocidal additive for conveyor chain lubricants. No public exposure is expected.

18.1.7 Electron and light microscopy
Glutaraldehyde is used in scientific establishments as a fixative in electron and light
microscopy and as a tissue preservative. No public exposure is expected.

18.2 Assessment of public health effects

18.2.1 Assessment of toxicological hazards
In humans, the main health effects reported for glutaraldehyde are described in Chapter
11.
The results of animal studies and tests in in vitro systems are discussed in Chapter 10.

18.2.2 Assessment of public exposure;
The public is unlikely to be exposed to glutaraldehyde during its routine importation,
transportation and formulation. Domestic use of glutaraldehyde is expected to be
minimal, at present there being only 2% formulations for use in portable toilets
available to the general public. This is unlikely to result in widespread public exposure.
Appropriate safety directions, as listed in Appendix F of the SUSDP,112 have been set
for products used in this manner.
The cross-linking activity and ready reactivity of glutaraldehyde would decrease the
available glutaraldehyde for public exposure. Some specific uses, for example, the cold
disinfection of fibre optic equipment and the disinfection of air ducts, can result in
direct or significant exposure if proper cleaning and ventilation procedures are not
followed.



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Priority Existing Chemical Number 3
Moderate but infrequent exposure from drift emanating from water cooling towers can
occur. However, the majority of uses of glutaraldehyde do not result in direct public
exposure.
Therefore, for the uses of glutaraldehyde described in this report, it is unlikely that
glutaraldehyde will pose a significant health and safety hazard to the public.
Improper cleaning of medical and dental equipment or inadequate ventilation of
premises following duct biocide treatment may increase public exposure and
appropriate measures to minimise glutaraldehyde residue should be employed.
Domestic products containing glutaraldehyde should be labelled with appropriate first
aid and safety directions.
The majority of effluents are discharged to sewerage in a diluted form. Discharge is not
recommended to storm water drains.
Glutaraldehyde is not recommended for use in animals or potable water.




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19. Environmental assessment
19.1 Environmental exposure

19.1.1 Formulation
Local dilution of glutaraldehyde is carried out at sites in Melbourne and Sydney, where
concentrated glutaraldehyde (45-50%) is pumped into blending vessels where it is
mixed with water before being drummed-off and transported via road or rail to the
users.
From information provided on one formulation process, it is estimated that
approximately 0.3-0.5% of the final product is lost to wastewater treatment systems.
This amounts to between 12 and 20 L per batch (approximately 3.2 and 5.3 kg of
glutaraldehyde) being discharged to effluent treatment every one to two months.
Cold chemical disinfectants containing 1-2% glutaraldehyde are formulated by pumping
glutaraldehyde concentrate via closed systems to a suitable liquids processing vessel
containing water. Other materials are pumped into the vessel and blended. The solution
is made up to volume with water and filled directly into 5 L containers for packing and
distribution. Any vapours emitted are discharged via local extraction systems to the
atmosphere.
Concentrations of glutaraldehyde discharged to sewer from one cold chemical
disinfectant formulation site have been monitored. An initial concentration of 25 mg/L
was reduced to less than 2 mg/L.
X-ray film processing chemicals are formulated by adding glutaraldehyde concentrate
via an air pump to water in a mixing tank followed by blending with other chemicals.
The release of 25% glutaraldehyde solution to the sewers from one x-ray development
formulation process has been estimated as between 10-12 L (2.5-3 kg glutaraldehyde)
per month.
Water treatment chemicals are formulated by repacking concentrated glutaraldehyde
solution into 25 L pails and 800 L returnable containers, or by pumping glutaraldehyde
solution into stainless steel blending vessels in an air conditioned isolated production
area. The turbine agitated vessel is equipped with an air extraction scrubbed emission
system.
Glutaraldehyde discharges from one formulation site are said to be negligible as tank
washings are collected and reused and the site is bunded.
The formulation of animal housing biocides involves transferring the required quantity
of glutaraldehyde to a mixing tank, adding remaining formula ingredients, mixing for
the specified time, and adjusting batch volume with purified water.
One formulator reported that minute amounts of vapour escape to the atmosphere during
manufacturing operations. Also, minute amounts of liquid are released to drain
following clean up of manufacturing equipment.

19.1.2 Use and disposal
The major releases of glutaraldehyde are expected to occur from the users rather the
formulators. Most of this will enter aqueous waste streams, with a minor proportion
discharged to the atmosphere.


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Solutions of glutaraldehyde will be disposed of to sewer when they have lost the desired
level of activity. Requirements vary from State to State, but in general they restrict
discharges of spent glutaraldehyde solutions to 10 L batches and specify that they must
be flushed with copious amounts of water (typically 100-fold dilution). Concentrated
wastes should be disposed of by incineration.
The exception appears to be South Australia where inactivation is required prior to
disposal. Inactivation can be achieved by dilution to subcidal concentrations (10 mg/L
active), treatment with dibasic ammonium phosphate, or caustic hydrolysis. Reaction
with bisulfite is another option.
Cold disinfectant
Exhausted cold chemical disinfectant solutions appear to represent the major source of
glutaraldehyde in wastewaters. A MSDS recommends that such solutions should
routinely be discarded after 28 days. Sewer discharge should involve dilution with
copious quantities of water. Where septic systems are involved, the active
glutaraldehyde should be neutralised before disposal.
Health care establishments are major users and dischargers of cold disinfectant
solutions. The glutaraldehyde solutions are discarded when the concentration of
glutaraldehyde falls by about 25% (to approximately 0.7-1.5%). Typically, this entails
discharge of 10-14 L of 1% solution from each treatment tank every four weeks.
Health care establishments range in size from major hospitals, with large wastewater
flows available for dilution, to small clinics with negligible flow at any particular time.
X-ray film processing
X-ray film developers containing glutaraldehyde are used in high temperature, rapid
process, automated developers, predominantly for medical x-ray processing but also in
radiology departments of public and private hospitals, radiology practices and clinics.
Smaller quantities are used in industrial x-ray and general purpose black and white film
processors. Concentrations of glutaraldehyde in the developers are 40-45%. When
diluted to form a working solution, the glutaraldehyde concentration should be less than
0.5%. Automated processors drain to sewer and generally vent to the atmosphere.
Spent solutions from x-ray processors are discharged via an overflow weir to a
collection system that drains the processor. Spent developer, fixer and wash water are
either collected for removal by a licensed agent or discharged to sewer after appropriate
treatment for silver removal. Free glutaraldehyde will not be present in the effluent flow
because of reaction with sulfite from the fixer.
Tanning
Glutaraldehyde is used as a tanning agent in the leather and fur industries for its
softening and filling effects, which add value to hides and skins. The tanning agents
contain 25-50% glutaraldehyde and are used at tanneries in Ballarat and South Geelong,
Victoria, Narangba, Queensland and Thebarton, South Australia. On completion of all
tanning operations the contents would be discharged for effluent treatment.
Unused glutaraldehyde from leather tanning operations amounts to between 1% and 3%
of the original charge. For example, at a usage rate of 5 kg per day, unused material
would amount to 0.05-0.15 kg of product daily. Tanneries have an effluent discharge
rate of 240-290 kL per day. Therefore, the maximum concentration of glutaraldehyde in
tannery effluent would be in the order of 0.6 mg/L. The actual concentration would be
lower as tannery effluent contains large quantities of dissolved proteins as well as amino



Glutaraldehyde
120
acids with which glutaraldehyde will largely react before reaching effluent treatment
works.
Water treatment
Glutaraldehyde is used as a water treatment microbiocide for use in cooling towers, air
washers, pasteurisers and other recirculating water systems. The products are effective
in controlling slime-forming bacteria, sulfate-reducing bacteria, and algae. One supplier
recommends that cooling towers be given an initial dosage of 68-90 mg/L
glutaraldehyde with a maintenance dosage of 45 mg/L glutaraldehyde. The product is
fed by a feed pump system.
Product strengths vary from a maximum of 40% to 0.5% depending on the application.
Chemicals are applied via metering pumps, usually on timer or auto control systems, to
maintain a regular controlled biocide level.
The half-life of glutaraldehyde in cooling tower water is approximately 24 hours.
Glutaraldehyde may enter the environment from such applications in drift from the
cooling towers. Typically, drift represents less than 0.01% of cooling tower recirculated
water volume. Such drift would contain a concentration of glutaraldehyde of 45-90
mg/L.
Cooling towers discharge glutaraldehyde to sewer at a maximum concentration of 250
mg/L. Typically a large industrial tower would discharge 20 kL per day into a flow of 1
ML per day. Therefore, approximately 5 kg glutaraldehyde would be discharged daily
from a large industrial cooling tower at a concentration of 5 mg/L.
Animal housing
Glutaraldehyde based products are used to disinfect animal and poultry housing.
Commercial products contain 12-15% glutaraldehyde. The recommended dilution factor
of 50-400 provides working concentrations between 0.30 and 0.03%. Animals are
removed prior to use and the shed cleaned of refuse and droppings before disinfection.
In the poultry industries, disinfection takes place at 6-8 week intervals.
Releases to sewer from use in animal housing are likely to be minimal as the
glutaraldehyde solution is generally applied to surfaces and allowed to dry before the
animals are rehoused. In some instances, glutaraldehyde residues may be discharged to
effluent ponding systems. Cleaning of application equipment may entail some disposal
to sewer.
Aquaculture
For the use of glutaraldehyde in aquaculture, it has proved difficult to obtain
information on the quantity used per annum, the application methods, and the release of
glutaraldehyde to the environment.
While no details are available at this time for glutaraldehyde, antiprotozoal use of
formalin in aquaria entails application at 150-250 mg/L for 30-60 minutes, while in
ponds a concentration of 25 mg/L is applied and allowed to dissipate.

19.2 Environmental fate
Glutaraldehyde will predominantly enter aqueous waste streams when waste solutions
are disposed of to sewer. Limited atmospheric exposure will also occur from vapour
emissions and from water-cooling tower drift.




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19.2.1 Hydrolysis
The hydrolysis of [1,5-14 C]-glutaraldehyde has been examined in sterile aqueous
solutions at pH 5, 7 and 9.3 The study was conducted at 25癈 in the dark at a nominal
concentration of 10 mg/L. The parent compound degraded slowly in pH 5 and 7 buffer
solutions during the 31 day study, with extrapolated half-lives of 508 and 102 days
respectively. At pH 9, degradation proceeded more rapidly (half-life 46 days) with the
formation of a cyclic dimer of glutaraldehyde.
19.2.2 Photodegradation
Photochemical processes will be important in removing glutaraldehyde from the
atmosphere. Formaldehyde vapours are reported147 to undergo direct photochemical
transformation in the troposphere, as well as photo-oxidative degradation (reaction with
hydroxyl radicals). Half-life in the sunlit troposphere is a few hours.
Hydrophilicity of glutaraldehyde will ensure removal of unreacted residues from the
atmosphere by dissolution in rain.
19.2.3 Biodegradation by sewage microorganisms
Ready biodegradability of glutaraldehyde was investigated148 at a concentration of 100
mg/L in a 15 day modified MITI-Test (OECD Guideline 301C33). The test article
proved to be 22.8% degradable after six days. After 15 days the test article was only
degraded by 35.2%. The concentration of the test article was 100 mg/L, which is known
to be biocidal.
The OECD guidelines for this test state that a result of less than 60% of biochemical
oxygen demand (BOD) does not necessarily mean that the test compound is not
biodegradable under environmental conditions, but indicates that more work will be
necessary to establish biodegradability. It should be noted that the concentration of
glutaraldehyde used may have been inhibitory to the bacteria used in the study.
Results from a five day BOD test149 are more favourable. The test involved exposure of
glutaraldehyde (0.9 and 1.7 mg/L) to unacclimated sewage sludge. At these subcidal
concentrations, the mean five day BODs were 71% and 55% of the theoretical value
respectively. Based on loss of glutaraldehyde, the degree of degradation approached
90% at both concentrations.
19.2.4 Metabolism in soils and aquatic systems
The behaviour of glutaraldehyde in soil adsorption tests5 indicates ready metabolism in
soils, with half-lives of a few days.
Aerobic studies in aquatic systems150 confirm the limited persistence. Radiolabelled
glutaraldehyde (10 ppm) was incubated in Sacramento River water/sediment (ratio 5)
for 30 days. The sediment was the same as that used in the adsorption test.
Radiocarbon was mainly found in the aqueous phase (at least 90%) in the first four
hours of the study, but declined to below 20% by 14 days, when about 20% of applied
radiocarbon was in the sediment and 48% had been liberated as carbon dioxide. At
termination, about 10% remained substantially bound to sediment and 80% could be
accounted for as carbon dioxide in headspace and water.
Analysis by HPLC indicated that glutaraldehyde was oxidised rapidly to glutaric acid,
which mineralises. The pseudo first-order half-life was 10.6 hours.
An anaerobic metabolism study is in progress. Preliminary results indicate that
anaerobic metabolism follows a completely different pathway, mainly involving
reduction to 1,5-pentanediol (half-life is appoximately one day).


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19.2.5 Bioaccumulation
Bioaccumulation of glutaraldehyde in aquatic organisms is precluded by its
hydrophilicity and limited persistence.

19.2.6 Summary
Glutaraldehyde is a hydrophilic substance that will be mainly associated with the
aquatic compartment, with minor amounts partitioning to the atmosphere, following
release to the environment. Hydrolysis is slow, but glutaraldehyde, like other aldehydes,
undergoes aerial oxidation in solution. It biodegrades rapidly in aerobic and anaerobic
aquatic environments at subcidal concentrations (below 10 mg/L) and will not
bioaccumulate. Tropospheric degradation is also rapid.

19.3 Environmental effects

19.3.1 Avian toxicity



Table 29
Avian Toxicity of Glutaraldehyde
Test Species Result Reference number


Acute oral Mallard duck LD50 = 408 mg/kg 151

Acute oral Mallard duck LD50 = 466 mg/kg 152

8 d dietary Mallard duck LC50 > 5000 ppm 153

8 d dietary Bobwhite quail LC50 > 2500 ppm 154

8 d dietary Bobwhite quail LC50 > 5000 ppm 155




The above results indicate that single doses of glutaraldehyde in corn oil are moderately
toxic to the species tested, but that the substance is practically non-toxic in the diet. This
may reflect reaction of glutaraldehyde with proteinaceous constituents of the feed.



19.3.2Aquatic toxicity
Glutaraldehyde solutions of 25 and 50% concentration were tested. Results tabulated
below refer to the nominal concentration of glutaraldehyde itself.




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Table 30

Aquatic toxicity of glutaraldehyde
Test Species Result Reference number

96 h acute Bluegill sunfish LC50 = 11.2 mg/L 156
48 h acute Oyster larvae LC550 = 2.1 mg/L 157
96 h acute Green crabs LC50 = 465 mg/L 157
96 h acute Grass shrimp LC50 = 41 mg/L 157
48 acute Daphnia magna LC50 = 0.35 mg/L 158
48 acute Daphnia magna LC50 = 16.3 mg/L 159
21 d reproduct'n Daphnia magna LOEC = 4.3 mg/L 160
96 h algal growth Selenastrum ILm = 3.9 mg/L 161
inhibition capricornutum (median inhibitory limit)
96 h algal growth Scenedesmus EC50 = 1.0 mg/L 162
inhibition subspicatus
Bacterial Sewage microbes IC50 = 25-34 mg/L --
inhibition


Static conditions and nominal concentrations were used in the bluegill sunfish test,
which followed US EPA bioassay practices with the exception that replicate
concentrations were not used. Glutaraldehyde would be expected to degrade under the
test conditions, and this is reflected in similar end-points at 48 and 96 hours. The no
effect level was 5 mg/L. A 96 hour end-point of 10 mg/L for rainbow trout is listed on a
MSDS but no data was available during the assessment period to substantiate this value.
Results indicate that glutaraldehyde is slightly to moderately toxic to fish.
The end-point in the oyster larvae test was based on nominal concentrations and
indicates moderate toxicity to these organisms. Concentrations were measured in the
crab and shrimp bioassays, and found to remain reasonably constant at concentrations
above 50 mg/L. Glutaraldehyde is practically nontoxic to the crab and slightly toxic to
the shrimp.
The more sensitive of the two acute daphnid studies was carried out under static
conditions with end-points expressed as nominal concentrations. No deaths were
observed at 0.28 mg/L, but complete mortality occurred at the next highest
concentration (0.5 mg/L). The reasons for the anomalous sensitivity are unclear but
would appear to reflect experimental error. Mortalities observed at 0.18 and 0.10 mg/L
cast further doubt on this study.
The second acute daphnid study was carried out under the same conditions but provided
results more consistent with the reproduction test. The no-effect level (based on
mortality) was 8 mg/L. Glutaraldehyde has slight acute toxicity to Daphnia magna.
The reproduction test was conducted under semi-static conditions, initially with two
duplicates containing ten daphnids at each concentration, but changing to ten duplicates


Glutaraldehyde
124
containing single organisms after four days. This falls short of requirements contained
in the OECD Test Guideline 202.33 Test solutions were renewed three times per week,
with concentrations measured for the initial and final renewal. Results should be treated
with caution as measured concentrations were extremely erratic, ranging from 99.3% of
nominal to below the limit of detection, and not correlated with nominal concentration
or exposure period.
In terms of the number of young produced, the lowest effect concentration (>50%
reduction) was 4.3 mg/L, with a no effect concentration of 2.1 mg/L (nominal
concentrations). Reductions of about 25% at concentrations of 0.2 and 1.1 mg/L were
also evident. The former was said in the report to be an artifact of two rather infertile
water fleas, while the latter was ignored. These results allow a tentative conclusion that
glutaraldehyde has a moderately toxic effect on Daphnia reproduction.
The algal end-points are nominal concentrations. Concentrations measured in the
Scenedesmus test were about an order of magnitude lower than nominal. Glutaraldehyde
is moderately to highly toxic to algae based on these results.
No test report was provided for the bacterial inhibition test as it was a preliminary study
only. The test is said to be conservative as it used low densities of unacclimated
microorganisms. Rather than the usual indicator of respiration, effects were detected by
measurement of turbidity (an indicator of population density) as described
elsewhere.163,164 No effect levels were 5-10 mg/L. This is consistent with observations
from the aerobic aquatic metabolism test,150 where a decline in bacterial colony forming
units in the water column was detected during the first 4 hours, while glutaraldehyde
concentrations in the water would have been in the order of 10 ppm. No such inhibitory
effects were detected in the sediment. Results suggest slight toxicity of glutaraldehyde
to sewage microorganisms. The full test report for the definitive study that is said to be
currently underway should be provided when available.
In summary, the test results indicate that glutaraldehyde is slightly to moderately toxic
to aquatic fauna and moderately to highly toxic to algae. In some instances,
glutaraldehyde appeared to be rapidly lost from test waters in the laboratory. Such
behaviour in aquatic toxicity tests generally means that their results will underestimate
the inherent toxicity of a substance. However, the toxicity that will prevail under
environmental conditions is likely to be lower than that recorded in the laboratory in
view of the rapid degradation that would be expected to occur in natural surface waters.

19.4 Environmental hazard
Waste glutaraldehyde from cold disinfectant solutions would appear to represent both
the largest and most concentrated source (up to 15000 mg/L leaving the sterilisation
vessel) of glutaraldehyde entering wastewater streams. Accordingly, hazard evaluations
will focus on this application as the worst case.
Based on import and production volumes provided during the assessment, a large urban
centre such as Melbourne, where about one-sixth of Australia's population resides, may
consume up to 7 tonnes of glutaraldehyde annually, or an average 20 kg per day.
Assuming that 75% is discarded as spent disinfectant solutions, and that all passes
through Werribee Sewage Treatment Works (daily flow 500 ML), glutaraldehyde at the
treatment works would be diluted to 50 mg/L simply by dilution.



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For country areas, daily sewage flows of 5 ML are typical. Assuming as a worst case
that health care establishments in such areas service a population of 100,000 -- or
roughly 0.5% -- of Australia's population, daily use of glutaraldehyde sterilants may
slightly exceed 0.5 kg, or a worst case daily discharge of about 0.4 kg. Dilution in
sewage flow would lead to a concentration in treatment works of 160 礸/L.
The above estimates indicate that safety factors for sewage microorganisms, based on a
no effect level of 5 mg/L, will be in the order of 30-100. These factors are very
conservative as they are based on a no effect level to low population densities of
unacclimated microbes, and make no allowance for the considerable losses of
glutaraldehyde that occur through reaction with proteinaceous components of sewage
effluent. Accordingly, adverse effects on sewage microbes are not anticipated. Advice
from the Sydney Water Board, which has no evidence that glutaraldehyde has ever
adversely affected sewage treatment at even its smallest treatment plant, confirms this
prediction.
As the maximum concentration expected to prevail in sewage treatment works is 160
礸/L, concentrations discharged would not be expected to impact on receiving waters
even if no degradation occurred prior to release. Given the expected degradation, the
predicted aquatic hazard is low.
Atmospheric emissions of glutaraldehyde do not represent a hazard to the environment
in view of the small amounts involved and limited atmospheric persistence.

19.5 Conclusions
Glutaraldehyde is widely used in Australia, with the main dissipative use being cold
chemical sterilisation in medical establishments. As much as 75% of the glutaraldehyde
used for this purpose is flushed to sewer with water.
Glutaraldehyde is a hydrophilic substance that will mainly partition to water upon
release to the environment. Like other aldehydes, the environmental persistence of
glutaraldehyde is extremely limited. It reacts with proteins and is rapidly biodegraded at
aqueous concentrations below about 10 mg/L.
Glutaraldehyde is moderately toxic to aquatic fauna and moderately to highly toxic to
algae. However, its lack of persistence confers adequate aquatic safety margins, and it
has not been associated with any incidents of environmental damage in the years in
which it has been used in Australia.




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126
20. Conclusions

From the assessment of information about the health and environmental effects of
glutaraldehyde, hazards during its use, exposure data and control measures currently
available, it is concluded that glutaraldehyde can be used safely in Australia if the
proper control measures are in place.
The main health hazards of glutaraldehyde are irritation of the skin, eyes and respiratory
system. The main symptoms seen in workers in Australia are contact dermatitis and eye,
nose and throat irritation, with occupational asthma and rhinitis also observed. Adverse
health effects have been observed principally in the health care industry, due to the high
number of workers in this industry and the poor controls in many workplaces.
Based on information about its human health effects and the results of animal and in
vitro testing, glutaraldehyde is a hazardous substance at concentrations > 0.1% w/w
according to the Approved Criteria.109
For the uses of glutaraldehyde described in this report, it is unlikely that glutaraldehyde
will pose a significant health and safety risk to the public or a significant risk to the
environment.




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21. Recommendations

Glutaraldehyde has a number of hazardous properties to justify its classification as a
hazardous substance according to the Approved Criteria,109 (see section 21.1). Under the
National Commission's National Model Regulationals and National Code of Practice
for the Control of Workplace Hazardous Substances,107 duties are placed on suppliers,
employers and employees regarding the provision of information, assessment of the
workplace, and the implementation and operation of proper control measures.
As all States and Territories are committed to adoption of the regulations for workplace
hazardous substances, it is recommended that suppliers and employers fulfil their
obligations under the regulations in a manner consistent with the recommendations in
this report. The recommendations have been framed to assist with the implementation of
these model regulations and therefore they cover matters such as information provision
and suitable control strategies in the various industries where glutaraldehyde is used.


21.1 Hazard classification;
The classification of glutaraldehyde at various concentrations in accordance with the
Approved Criteria109 is based on the assessment of the health effects of glutaraldehyde
at those concentrations. Glutaraldehyde is commercially available in Australia at
concentrations up to approximately 50% w/w, so the recommended classifications and
corresponding risk phrases for these mixtures are listed in Table 31 (see Appendix 1 for
a list of risk phrases).
In the classification of glutaraldehyde, products which contain other hazardous
substances, for example, x-ray film processing solutions, the health effects of all the
ingredients need to be taken into account.
It is recommended that suppliers incorporate health hazard information consistent with
the classification of glutaraldehyde in their MSDS and labels.
The evidence for the respiratory sensitising effect of glutaraldehyde is not sufficient to
recommend classification under the Approved Criteria,109 but it is recommended that the
position be further reviewed, particularly when the criteria for respiratory sensitisation
are amended by the EEC, and if evidence becomes available to confirm a respiratory
sensitisation effect.
Similarly, the acute inhalational toxicity classification should be reviewed when more
data is available.
It is recommended that the risk phrases determined from this assessment report be
added to the List108 in order to assist implementation of the Model Regulations.




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128
Table 31
Classifications for glutaraldehyde at various concentrations
Glutaraldehyde Mixture
classification Concentration classification Risk phrase
Corrosive > 25% Corrosive R34
> 1-25% Skin Irritant R38
Serious Eye Damage > 5% Serious Eye Damage R41
> 0.1-5% Eye Irritant R36
1%
Respiratory Irritant Respiratory Irritant R37
1%
Skin Sensitiser Skin Sensitiser R43
Toxic (Inhalation) > 25% Toxic R23
1-25% Harmful R20
25%
Harmful (Skin) Harmful R21
50%
Toxic (Oral) Toxic R25
5- < 50% Harmful R22


21.2 Hazard communication

21.2.1 Labels and MSDS
A survey of the labels and MSDS of glutaraldehyde-containing products indicated that
many were below the standard normally considered appropriate under the National
Commission's codes of practice. It is recommended that:
?labels be reviewed and upgraded where necessary, with the risk and safety phrases
and/or directions reflecting the health and safety risks present during the normal or
reasonably foreseeable use of the product; and
?MSDS be reviewed and upgraded where necessary in accordance with the
information in this report and the National Commission's Code of Practice for the
Preparation of Material Safety Data Sheets.114
It is also recommended that the following statements be included on MSDS for
glutaraldehyde products:
?'Occupational asthma and/or rhinitis have been indicated in a number of workers
exposed to glutaraldehyde.'
? 'The results of more recent assays have generally shown that glutaraldehyde is
mutagenic in vitro. In vivo tests to date have been negative. Consequently
glutaraldehyde does not meet the criteria for classification as a mutagen.'

In view of the differing labelling requirements for some products under the various
regulatory codes and schedules, it is recommended that the relevant regulatory
authorities use this assessment report of the hazards of glutaraldehyde as a basis for
reviewing their labelling requirements. Such a review is particularly necessary in the
case of the SUSDP112 where no warnings of sensitisation or corrosivity are currently
required.




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A small number of glutaraldehyde-containing products are sometimes used in spray
form, significantly increasing the risk of exposure unless proper precautions are taken. It
is recommended that the use of glutaraldehyde-containing products in spray form be
reduced as much as possible. However, where spray use is still necessary, it is
recommended that the product should carry an appropriate warning such as the
following on the label:
CAUTION: AVOID BREATHING SPRAY,

and that the proper control measures, detailed in section 21.3, should be implemented.

21.2.2 Other information
For the health care industry, it is recommended that safe use guidelines, similar in style
to those available in some States, be provided for health care workplaces in each of the
States and Territories. The guidelines should include information about the health
effects of glutaraldehyde and detailed guidance on the control measures available to
minimise exposure (see section 21.3).
It is also recommended that safe use guidance be provided for the use of glutaraldehyde
in dentistry.
In other industries, some end-users are not aware of the health effects of glutaraldehyde
nor the hazards present during its use. Therefore, industry specific safe use guidelines,
similar in style to those available for the health care industry, are recommended for the
tanning, animal housing and water treatment industries.
For the other minor uses of glutaraldehyde, for example, in microscopy, in toilet
sanitation and in air duct disinfection, guidance material from suppliers is recommended
for availability at each workplace.
For the sake of uniformity, it is recommended that, wherever possible, guidelines be
produced for use on a national basis.
21.2.3 Training and education
In accordance with the national model regulations, workers potentially exposed to
glutaraldehyde need to be trained in the safe work practices which are appropriate to
their particular workplace, and that a record of training be kept.
Because of the incidence of adverse health effects occurring in the past and the
widespread use of glutaraldehyde in a number of different industries, the training should
be as specific as possible. Use of information in the safe use guidelines for that industry
is recommended to facilitate those training needs.
21.3 Control of occupational exposure
As glutaraldehyde is a hazardous substance, it is recommended that worker exposure be
reduced as much as possible by the implementation of effective control measures in
accordance with the hierarchy of control measures detailed in the National Model
Regulations and Code of Practice for the Control of Workplace Hazardous
Substances.107
Where the replacement of glutaraldehyde may be considered in some application, the
health effects and hazards of any substitute need to be taken into account to ensure that
glutaraldehyde is not being replaced by a more hazardous substance.




Glutaraldehyde
130
Where possible, control measures, especially engineering controls, should be
implemented at the design stage. Engineering controls such as ventilation should be
installed by qualified professionals to ensure that specifications and Australian
standards are met and that any new installation is compatible with existing systems.
It is recommended that all workplaces handling glutaraldehyde employ safe work
practices to minimise exposure during routine operations, and to quickly reduce
exposure in the case of spillage or during maintenance. Good housekeeping and
personal hygiene is required in all workplaces. Appropriate safe work practices are
listed in section 16.12.6.
Where other control measures are inappropriate or impractical, then PPE must be used.
If PPE is to be used, then it should be selected and maintained in accordance with the
relevant Australian Standards. Detailed guidance on the appropriate PPE for
glutaraldehyde is given in section 16.12.7. The type of personal protection must be
appropriate to the concentration of glutaraldehyde in the product and to the particular
use of the product. PPE must be properly stored and maintained.
Control measures available in Australia are detailed in section 16.12. Recommended
control measures by use and industry are detailed below.
21.3.1 Formulation of glutaraldehyde products
As glutaraldehyde is usually handled in large quantities and as a concentrate in the
formulation of glutaraldehyde products, it is recommended that the process be enclosed,
with the mixing vessel and glutaraldehyde transfer system sealed.
The discharge of product, for example, to a filling line, should also be enclosed as much
as possible. If this is not achievable, then local exhaust ventilation is required.
Good dilution ventilation in accordance with Australian Standards is necessary in all
production areas, with each ventilation rate having the capacity to be increased
substantially in case of spillage.
All ventilation systems must be regularly examined, tested and maintained.
Total loss ventilation is recommended, but if the use of recirculated air cannot be
avoided, filters, for example, carbon adsorption, must be used. If carbon filters are used,
their performance must be monitored to ensure that they are replaced before chemical
breakthrough occurs.
In production areas, procedures must be in place to handle spills and leaks.
If required, PPE should consist of the items listed below for the use of glutaraldehyde as
a disinfectant. If PPE is required in handling glutaraldehyde concentrate, then goggles,
long gloves, overalls and respiratory protection are essential.
21.3.2 Use as cold disinfectant
All instruments and equipment must be thoroughly cleaned before disinfection with
glutaraldehyde.
Elimination or substitution
The use of glutaraldehyde in general surface disinfection, for example, the cleaning of
bench-tops, is not recommended, so it should be eliminated where possible by more
thorough cleaning with soap and water or replaced by a non-hazardous substance.


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The substitution of glutaraldehyde should be approached with caution, as many of the
alternatives are hazardous substances and/or less efficacious against micro-organisms.
Enclosure
Operations involving glutaraldehyde in x-ray film processing should be enclosed.
Automatic mixers and automatic processors with exhaust outlets should be used where
possible.
Engineering controls
Where the purchase of automatic equipment cannot be justified, good LEV is essential
to minimise exposure (see section 16.12.4).
LEV for fixed work stations should consist of properly constructed and maintained
fume cupboards. Mobile units must have lids or covers and be fitted with vapour
extractors and carbon adsorption filters, which must be monitored to ensure that they are
replaced before chemical breakthrough occurs.
Good dilution ventilation to a standard consistent with the relevant Australian Standards
is essential in all work areas.
Safe work practices
The following safe work practices are recommended for the use of glutaraldehyde as a
disinfectant:
? clear labelling of all containers, including those used in decanting when the solution
is not consumed immediately;
? proper storage of solutions in designated cupboards away from heat sources;
? use of the minimum amount of glutaraldehyde for the task;
? avoidance of heat or ultrasonics, as glutaraldehyde vapours may be generated;
? care taken during the soaking procedure, including use of syringes, so that any
splashing is avoided;
? lids or covers on soaking baths at all times;
? avoidance of transporting open containers of disinfectant;
? proper rinsing of instruments and soaking baths with clean running water after
disinfection;
? use of solutions only in ventilated work areas;
? no decanting of glutaraldehyde solutions from soaking containers back into bottles;
? prompt clean-up of spills; and
? the deposit of disposable items, for example, gloves and syringes, into sealed
containers prior to collection.
Personal protective equipment
Personal protective equipment recommended for the use of glutaraldehyde disinfectant
solutions are:
?chemical safety goggles or safety spectacles with sideshields;
?elbow-length nitrile or butyl rubber gloves; double layers of surgical latex rubber
gloves may be used for short contact times (<10 min.);
?aprons made from impervious material such as those used in the manufacture of
gloves, with protection of the arms and legs essential; and
?in case of spills and leaks, half-face respirator with organic vapour cartridge.



Glutaraldehyde
132
21.3.3 Use in x-ray film processing


Enclosure
Operations involving glutaraldehyde in x-ray film processing should be enclosed, with
automatic mixers and processors with exhaust outlets to be used where possible.


Engineering controls
The exhaust air from automatic processors must be completely removed from the work
area by connection to an exhaust ventilation system independent of the dilution
ventilation system. Discharge should be to atmosphere at a safe location.
If the use of an automatic mixer and/or processor is impractical or unjustifiable on
economic grounds, then all mixing and processing operations involving glutaraldehyde
must be carried out with effective local exhaust ventilation, preferably in a fume
cupboard (see section 16.12.4).
Effective dilution ventilation is essential in all work areas, with the area under slightly
negative pressure to prevent the escape of chemical vapours to adjacent work areas.
To minimise evaporation of the chemicals, including glutaraldehyde, the dark room and
processing temperatures should be kept as low as possible while attaining the desired
photographic results.
Safe work practices
Recommended safe working practices for the use of glutaraldehyde in x-ray film
processing include:
?location of mixing tanks in a well ventilated area, preferably in a fume cupboard;
?proper storage of solutions in designated cupboards away from heat;
?avoidance of splashing and generation of vapours during mixing;
?covering of tanks (with tight-fitting lids) at all times;
? avoidance of carrying open tanks or containers of chemicals, especially when they
are full;
? careful handling of processor rollers and tanks and other processing equipment so
that spillage and skin contact are avoided;
? provision of adequate wash trough for cleaning tasks, for example, washing of
processor rollers and tanks, with location of trough close to equipment;
? minimal direct handling of wet films;
? prompt clean-up of contaminated areas; and
? proper maintenance of automatic mixers and processors to prevent vapour
generation, for example, through overheating and leaking pipes and connections.


Personal protective equipment
PPE is required when filling, emptying or maintaining automatic mixers and processors
and when working with solutions during manual operations. Eye protection and gloves
should be worn at all times and respiratory protection is required during spillage and
maintenance of equipment.




133
Priority Existing Chemical Number 3
The recommended PPE for the handling of x-ray processing solutions is:
?chemical safety goggles or safety spectacles with sideshields;
?long nitrile or butyl rubber gloves;
?laboratory coat or overalls, with protection for the arms and legs; and
?in case of spills or leakage, a half-face respirator with organic vapour filter.

21.3.4 Use in tanning
Control measures similar to those used in the manufacture of glutaraldehyde products
are required for the use of glutaraldehyde in tanning (see section 21.3.1). Mixing vessels
should be covered and sealed if possible to minimise vapour generation. The transfer of
glutaraldehyde to the mixer should proceed via a sealed system, and all operations
should be carried out with good ventilation.
Procedures for handling spills must be in place, and personal protective equipment (see
section 21.3.2) should be worn during all operations involving possible exposure to
glutaraldehyde.

21.3.5 Use in water treatment
The addition of glutaraldehyde solutions to cooling water systems is generally carried
out in the field.
If automatic feed systems are used, then the proper safe handling procedures should be
followed in filling and emptying the containers and connecting them to the dosing
system.
Manual dosing should be carried out wearing the proper personal protective equipment,
that is, goggles, gloves, overalls and protective footwear. Respiratory protection is
required if glutaraldehyde vapours are generated.
The dilution of concentrated glutaraldehyde solutions should be carried out under
proper local exhaust ventilation rather than at the site of water treatment.

21.3.6 Use in animal housing
The application of glutaraldehyde solutions in animal housing is generally carried out in
the field, with the solutions used in spray form (see section 21.2.1), as a wash or as a
foam.
Recommended safe work practices for the use of glutaraldehyde as a wash or as a foam
in animal housing are:
?proper storage of solutions in designated areas away from heat sources;
?proper labelling of all containers, including those used in decanting when the
solution is not consumed immediately;
?cleaning of all equipment after use, and storage in a designated area;
? clearing area of animals or birds before disinfection and for appropriate period after
disinfection;
? availability of MSDS to workers carrying out disinfection; and
? good housekeeping in the work area.




Glutaraldehyde
134
The following personal protective equipment is to be worn during application as a wash
or foam:
?chemical goggles or faceshield;
?long-sleeved gloves of impervious material such as butyl or nitrile rubber;
?overalls; and
?rubber boots.
In the application of glutaraldehyde solutions in spray form, all the above safe work
practices need to be followed, with additional care in the clearing of the work area of
other workers and animals and birds. In addition to the PPE stipulated above, long-
sleeved overalls, hood and respiratory protection, for example, a half-face cartridge
respirator, are required, with the type of respiratory protection dependent on the
duration of application.
The use of glutaraldehyde on animals or birds is not recommended.

21.4 Atmospheric monitoring
Where an assessment of the workplace indicates that there is a significant risk of
exposure to glutaraldehyde, it is recommended that an atmospheric monitoring program
for glutaraldehyde be implemented as a means of measuring occupational exposure and
as a monitor of the effectiveness of control measures in the workplace. The program
should be in proportion to the risk of exposure, taking into account the quantity and
concentration of glutaraldehyde used, the frequency of use and the number of workers
potentially exposed.
If the level of exposure to glutaraldehyde is not known, it is recommended that a small
number of analyses be conducted initially to establish a baseline for assessment of the
workplace and to determine whether improved control measures and/or regular
monitoring are necessary. For example, no atmospheric monitoring results for exposure
to glutaraldehyde in the tanning industry were available during the PEC assessment
period.
Where atmospheric monitoring is required, both personal and fixed-point monitoring
should be carried out, and proven analytical procedures should be used (see Chapter 6).
The frequency of monitoring required will also depend on the results obtained. Once
control measures have been shown to be effective, then the frequency can be reduced.

21.5 Emergency response plan
It is recommended that a written emergency response plan be provided in all workplaces
where significant quantities of glutaraldehyde are used. The essential items in a good
emergency response plan are listed in section 16.4.

21.6 Disposal
It is recommended that no special environmental controls beyond those that currently
prevail across Australia are considered necessary. Spent solutions disposed of to sewer
should be flushed with copious amounts of water. Glutaraldehyde must not be
discharged to surface waters, storm water drains or septic systems.




135
Priority Existing Chemical Number 3
21.7 Regulatory controls

21.7.1 Exposure standard
The current Australian exposure standard for glutaraldehyde, set by the National
Commission, is 0.2 ppm v/v (0.82 mg/m3) as a peak limitation and with a sensitiser
notation. The standard, which is based on the irritant effect of glutaraldehyde on the
upper respiratory tract, has been listed for review since 1991.
In view of the results of animal testing and the human experience, where irritant effects
have been observed at or below the current exposure standard, particularly after
repeated exposure, it is recommended that the following exposure limits for
glutaraldehyde be considered by the National Commission's Exposure Standards Expert
Working Group in their review:
?STEL (15 min.) 0.15 ppm (0.62 mg/m3);
0.1 ppm (0.41 mg/m3);
?TWA (8 hr)
with a skin sensitiser notation.

21.7.2 Health surveillance
It is not recommended that glutaraldehyde be added to schedule 3 of the National Model
Regulations for the Control of Workplace Hazardous Substances,107 but under the
regulations, employers will need to provide health surveillance in workplaces where the
assessment shows that exposure to glutaraldehyde may result in a substance-related
health effect such as contact dermatitis.
As early diagnosis of glutaraldehyde-induced health effects is important, it is
recommended that workers potentially exposed to glutaraldehyde should undergo a pre-
placement medical check as a baseline to assist in identifying future signs of skin or
respiratory disease.
If the workplace assessment indicates that health surveillance is required, then it is
recommended that the following medical tests should be considered by occupational
physicians:
?patch testing in accordance with accepted standard procedures;
?PEFR measurements;
?spirometry for the measurement of FVC and FEV1; and
?bronchial challenge testing where appropriate.
So that an adequate record of occupational disease is compiled, it is recommended that
cases of skin and respiratory disease in workers exposed to glutaraldehyde be fully
evaluated and that the case studies be reported in the scientific and/or medical literature.
Available case reports should be sent to Worksafe Australia.

21.7.3 Aquaculture;
Although not reported by any of the applicants during the assessment period, there is
some evidence that glutaraldehyde may be used in aquaculture in Australia.11 It is
recommended that the National Registration Authority for Agricultural and Veterinary
Chemicals use the health and environmental effects information in this report to assist
with any review of the use of glutaraldehyde in aquaculture.




Glutaraldehyde
136
21.8 Further testing
In carrying out the assessment of glutaraldehyde, some items of toxicological,
ecotoxicological and technical information were unavailable, either because testing was
not completed or because testing had not been carried out. It is recommended that
testing be carried out, or completed, in the following areas:
?a two-year inhalation study (the NTP is expected to begin a study in 1994);
? comparative acute inhalational toxicity studies at various temperatures (repeat LC50
studies at ambient and elevated temperatures currently being carried out);
? detailed vapour generation studies at various temperatures for various strengths of
solution to improve the corrrelation between strength of solution and vapour
concentration (as ppm) above solution;
? improve the reliability of the vapour generation procedure for the purposes of
inhalational toxicity testing;
? anaerobic aquatic metabolism and bacterial inhibition tests (currently being carried
out); and
? studies into the mechanism and cause of occupational asthma in workers exposed to
glutaraldehyde.




137
Priority Existing Chemical Number 3
22. 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 glutaraldehyde, a secondary notification may be required if:
?it is manufactured in Australia;
?a new use arises, for example, in cosmetics; or
?significant new information about the health and/or environmental effects becomes
available.




Glutaraldehyde
138
Appendix 1


Risk phrases
R20 Harmful by inhalation
R21 Harmful in contact with skin
R22 Harmful if swallowed
R23 Toxic by inhalation
R24 Toxic in contact with skin
R25 Toxic if swallowed
R26 Very Toxic by inhalation
R27 Very Toxic in contact with skin
R28 Very Toxic if swallowed
R34 Causes burns (Corrosive)
R35 Causes severe burns (Very Corrosive)
R36 Irritating to eyes
R37 Irritating to respiratory system
R38 Irritating to skin
R39 Danger of very serious irreversible effects
R40 Possible risk of irreversible effects
R41 Risk of serious damage to eyes
R42 May cause sensitisation by inhalation
R43 May cause sensitisation by skin contact
R45 May cause cancer
R46 May cause heritable genetic damage
R47 May cause birth defects
R48 Danger of serious damage to health by prolonged exposure
R49 May cause cancer by inhalation




139
Priority Existing Chemical Number 3
Appendix 2


MSDS submitted
Product Name Supplier % Glutaraldehyde

Raw Materials

50% w/w glutaraldehyde Union Carbide 50%

approx 50% glutaraldehyde BASF 50%

approx 25% glutaraldehyde BASF 50%

Glutaraldehyde 25% ICI Pharmaceuticals 25%

Disinfectants


Aldecyde 28 ICI Pharmaceuticals 2.3%

Aidal Whiteley Chemicals 1%

Aidal Plus Whiteley Chemicals 2%

Wavicide 01 Whiteley Chemicals 2.1%

Cidex Johnson & Johnson Medical 2%

Cidex Long-Life Johnson & Johnson Medical 2%

General Biocides

Sepacid BASF 50%

Protectol GDA BASF 50%

Protectol GDA 25% BASF 25%

Actisan Gibson Chemicals 15%

Formula 936N Gibson Chemicals 2%

Formula 9365N Gibson Chemicals 2%

Formula 9465N Gibson Chemicals 2.5%

Uconex Antimicrobial 350 Union Carbide 50%

Ucarcide Antimicrobial 125 Union Carbide 25%

Germ-Out SterileAir 2%


Glutaraldehyde
140
Product Name Supplier % Glutaraldehyde

X-ray Photography

Industrex Developer Kodak Australasia 10-15%
Replenisher Part C 20-25% (as bisulfite)


Duraflo RT Developer Kodak Australasia 5-10% (as bisulfite)
Replenisher Part B


Rapid-X-Developer Ilford 3-7%
Replenisher


Ilfotec-RT-Developer Ilford 1-5%
Replenisher


Cronex DuPont 5-10%


Cronex High Stability DuPont 0.5-1.5% (as bisulfite)
Developer/Replenisher
Working Strength


Cronex High Stability DuPont 5-10%
Developer/Replenisher 10-30% (as bisulfite)
Part C


RP X-Omat Developer/ Kodak 40-45%
Replenisher Part C


RD III Developer/ Ilford 3-7%
Replenisher Part C


G135 Developer Agfa-Gevaert 10-20% (as bisulfite)
Part C

Tanning

Relugan GT 50 BASF 50%

Relugan GT 25% BASF 25%

Derugan 2000 T R Chemicals unknown

Derugan 2020 T R Chemicals




141
Priority Existing Chemical Number 3
Product Name Supplier % Glutaraldehyde


Water Treatment


Biomate 5792 Grace Dearborn 8.1%

Biomate 733 Grace Dearborn 30-60%

Nalco 7338 Nalco Australia 45%

Piror Slimicide 825 Union Carbide 25%

Aqucar Microbiocide 545 Union Carbide 45%

Animal Housing

Microcide/GPC8 Pfizer 12.4%

Keymix Glutacide International Animal Health 15%

Safe Guard Campbell Bros 5.3%

Embalming


DSD (Dodge Sterilant Hickey & Co P/L 2%
& Disinfectant)




Glutaraldehyde
142
Appendix 3




Labels submitted
The following table lists the labels which were submitted during the assessment period.
The suppliers of the products listed can be obtained from the list of MSDS in Appendix
2.
The approximate risk and safety phrases on the labels relating to health effects have also
been listed. In some cases, the term 'poisonous' has been used on labels in accordance
with requirements of the SUSDP,112 for example, 'poisonous if inhaled'. For the
purposes of comparison in this table, a similar EC risk phrase has been indicated, for
example, 'Toxic by inhalation' for 'poisonous if inhaled'.

Product Name % Glut. Risk Phrases Safety Phrases


Disinfectants


Aidal 1% -- S24,25,37,50

Aidal Plus 2% R43 S24,50

Wavicide 01 2.1% R43 S24,50

Aldecyde 28 2% R20,21,36,38 S23,24,25,37,39

Cidex 2% R22,38,41,43 S24,39,51

Cidex Long-Life 2% R22,38,41,43 S24,39,51

Glutarall 2.1% R36,43 S24,50,51

(Colgate-Orapharm)

General Biocides


Ucarcide 225 25% R20,21,22 S23,24,25,36,37,
34,41,43 39

*Actisan 15% R23,24,36, S23,24,25,37,39
38,43

*Formula 936N 2% R43 S23,24,25

*Formula 9365N 2% R43 S23,24,25

*Formula 9465N 2.5% R43 S23,24,25




143
Priority Existing Chemical Number 3
Product Name % Glut. Risk Phrases Safety Phrases

X-ray Photography

Kodak RP X-Omat 50% R20 S22,24,51

Part C

Cronex HSD/R Part C 14% R34 S24,25,37,39

Ilford Rapid X-D Part C 5% -- --

Hanimex RD III Part C 5% -- --

Water Treatment

Nalco 7338 45% R34,51 S23,37,39

Aqucar 545 45% R20,21,22,34, S23,24,25,36,
41,43 37,39

Biomate 5792 8.1% R34 --

Animal Housing

Keymix Glutacide 15.1% R23,24,36,37, S23,24,25,37,39
38

Microcide/GPC8 12.4% -- S23,39,50

* Domestic end-use products.


Risk phrases
See Appendix 1.
Safety phrases
S23 Do not breath vapour/spray.
S24 Avoid contact with skin.
S25 Avoid contact with eyes.
S36 Wear suitable protective clothing.
S37 Wear suitable gloves.
S39 Wear eye/face protection.
S50 Do not mix with/
S51 Use only in well-ventilated areas.




Glutaraldehyde
144
Appendix 4


Survey of health care
establishments using
glutaraldehyde

A4.1 Tasmania
The questionnaire sent to health care establishments in Tasmania by the Department of
State Development and Resources revealed that the following establishments used
glutaraldehyde:
Burnie Hospital, Burnie.
Emmerton Park, Smithton (aged care).
Eskleigh Memorial Home, Perth.
Hobart Pathology, Hobart.
Launceston General Hospital.
Launceston Presbyterian Homes for the Aged.
Melaleuca Home for the Aged, Devonport.
Nazareth House, St Leonards.
Northern Tasmanian Pathology Service, Launceston.
Queen Victoria Hospital, Launceston:
? used as disinfectant for laparoscopes in gynaecology theatre until theatre closed in
January 1993.
Rosebery District Hospital, Rosebery.
Royal Hobart Hospital:
? Anatomical Pathology Dept:
- in electron microscopy;
- used in fume cupboard;
? Microbiology Dept:
- as disinfectant.
St Helens District Hospital, St Helens:
? used as disinfectant for only six weeks.
St Helens Private Hospital, Hobart:
? as disinfectant;
? monitoring carried out, with concentrations below 0.1 ppm.



145
Priority Existing Chemical Number 3
St John's Private Hospital, Hobart.
St Luke's Private Hospital, Launceston:
?specially designed laminar flow unit installed for disinfection of endoscopes;
?written policy on use and storage.
St Vincent's Private Hospital, Launceston:
?used as disinfectant in operating suite and endoscopy unit.
Tasmanian Dental Technicians and Dental ProsthesistsAssociation, Howrah.
Webster Nursing Home and Campbell Town District Hospital, Campbell Town.

A4.2 South Australia
The survey carried out by the South Australian Occupational Health and Safety
Commission resulted in replies from the following health care establishments. Observed
adverse health effects after exposure to glutaraldehyde are also detailed.
Balaklava Soldiers' Memorial District Hospital:
? disinfection of arthroscopes.
Burra Burra Hospital:
?1% solution used for disinfection of endoscopes and laparoscopes once per month.
Flinders Medical Centre, Bedford Park
?1% and 2% solutions used in endoscopy unit;
?sore eyes and throat in 1 nurse, and facial rash on one nurse.
Glenside Hospital, Adelaide:
?used in small amounts as disinfectant in Eye and Dental Clinics;
?PPE includes goggles, chemical resistant gloves and gown.
Hillcrest Hospital, Adelaide:
?used in eye clinic for disinfection of heat sensitive tonometer prisms;
?used in well-ventilated area, but without LEV;
?PPE includes visor, nitrile gloves and long-sleeved plastic-lined gowns.
Hutchinson Hospital, Gawler:
? used in disinfection of laparoscopes;
? PPE includes elbow length gloves and safety glasses.
Lameroo District Hospital.
Loxton Hospital.
Lyell McEwin Health Service, Elizabeth Vale:
? used as 1% and 2% solutions in disinfection of fibre optic scopes, endoscope blades
and ultrasound probes;
? used in x-ray film developer;
? automixers located in fume cupboards installed to minimise exposure;
? PPE includes gowns with long sleeves, gloves, face masks or safety glasses.




Glutaraldehyde
146
Millicent and District Hospital:
? used in operating theatre for disinfection.
Modbury Hospital.
? Mount Gambier Hospital.
? 2% solution used for disinfection of colonoscopes:
? pump system, fume cupboard and exhaust fans installed for mixing and pouring
operations;
? eye irritation in 1 nurse.
Murray Bridge Soldiers' Memorial Hospital:
? five workers potentially exposed, but on an infrequent basis;
? contact dermatitis observed in two workers, but short term only;
Noarlunga Health Services.
Peterborough Soldiers' Memorial Hospital:
?used for endoscope disinfection once per month.
Port Augusta Hospital:
? soaking dishes and other containers fully covered or sealed;
? mixing and pouring avoided in inadequately ventilated areas;
? PPE includes nitrile gloves, aprons and face shields or goggles;
? spill kit, including cartridge respirators, readily accessible;
? emergency eye shower bottles readily available;
? eye irritation in one nurse.
Port Pirie Regional Health Service:
? adverse health effects observed in four of six theatre staff:
? eye irritation in one nurse;
? nose and throat irritation in two nurses;
? chest tightness in one nurse;
? headache in three nurses;
? dermatitis of hands and feet in one nurse.
Renmark and Paringa District Hospital, Renmark:
? 1% solution used for disinfection of endoscopes.
? Riverland Regional Health Services, Berri:
? used in endoscopy unit up to twice per week.
Royal Adelaide Hospital:
? developed a comprehensive Occupational Health Policy Document;
? implemented a number of engineering controls to minimise exposure;
? 18 confirmed cases in period 1986-93, including:
- dermatitis on hands or arms of six nurses and one technical officer,
- red blotches on skin of four nurses,
- whole body rash on 1 nurse,



147
Priority Existing Chemical Number 3
- coughing and/or sore throat in two nurses,
- occupational asthma in 1 nurse,
- eye burn in 1 nurse,
- nausea and lethargy in 1 nurse.
Streaky Bay Hospital:
?2% solution used to clean cytoscopy equipment twice per year;
?x-ray developers used.
The Queen Elizabeth Hospital, Adelaide:
?used in operating theatres, endoscopy room and day surgery suite;
?report of respiratory irritant effects in endoscopy room;
?exposure minimised by installation of fume extraction hoods and better drainage.
Waikerie Hospital and Health Services:
? used in disinfection of laparoscopes and laryngoscopes.
Whyalla Hospital and Health Services:
? safe work practices introduced to eliminate occupational symptoms, include:
- enclosed automatic cleaning system situated under large extractor hood,
exhausted to outside building;
- disposal into closed drums of sawdust and burnt;
- rotation of staff in endoscopy unit;
- enclosed soaking system;
? facial dermatitis in 1 physician from disinfection of eyepiece;
? rhinitis and itchy eyes in 1 anaesthetist, 1 surgeon and 2 nurses:
? wheezy bronchitis in one nurse.
? Women's and Children's Hospital:
? eye irritation in three workers.




Glutaraldehyde
148
Appendix 5


Example of MSDS for concentrated
glutaraldehyde




149
Priority Existing Chemical Number 3
150 Glutaraldehyde
151
Priority Existing Chemical Number. 3
152 Glutaraldehyde
153
Priority Existing Chemical Number 3
154 Glutaraldehyde
155
Priority Existing Chemical Number 3
156 Glutaraldehyde
157
Priority Existing Chemical Number 3
158 Glutaraldhehyde
159
Priority Existing Chemical Number 3
160 Glutaraldehyde
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Reviews in Toxicology, vol. 22 (3,4), pp. 143-174, 1992.
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Regulation and Registration of Aquacultural Chemicals and Drugs in Australia',
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13. Reifenrath et al, 'Topical glutaraldehyde -- percutaneous penetration and skin
irritation', Arch. Dermatology Res., vol. 277, pp. 242-244, 1985.
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Toxicity Report Series No.25, National Institute of Health Publication, pp. 93-3348,
U.S. Department of Health and Human Services, March 1993.
15. Hopwood, 'The Reactions of Glutaraldehyde With Nucleic Acids', Histochemistry J.,
vol. 7, p. 267, 1975.
16. Bushy Run Research Centre, 'UCARCIDE Antimicrobial 250, 'Acute Peroral
Toxicity Study in the Rat', Project Report 54-145, Pennsylvania, USA, January 1992.
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Britain, 1991.
18. Uemitsu et al, 'Studies on the Acute and Subacute Toxicity and Local Irritancy of
Glutaraldehyde', Oyo-yakuri, vol. 12, pp. 11-32, 1976.
19. International Bio-Research Inc., 'Acute Toxicity and Irritation Studies of 10% Sterisol
Formula #3', Report No. 76-166-21, Miamiville, Ohio, USA, April 1976.




161
Priority Existing Chemical Number 3
20. International Bio-Research Inc., 'Acute Toxicity and Irritation Studies of 1% Sterisol
Formula #3', Report no. 76-1085-21, Miamiville, Ohio, USA, February 1977.
21. Food and Drug Research Laboratories Inc., 'Report -- Sterisol 10%', Laboratory No.
5372, Waverly, New York, USA, February 1977.
22. Bushy Run Research Centre, 'Glutaraldehyde: Four-hour LC50 Inhalation Study on
Rats', Project Report 44-96, Pennsylvania, USA, January 1982.
23. Bushy Run Research Centre, 'UCARCIDE Antimicrobial 250: Acute Vapor
Inhalation Toxicity Test in Rats', Project Report 53-8, Pennsylvania, USA, November
1990.
24. Ballantyne, 'Glutaraldehyde: Acute Inhalation Toxicity', Personal communication,
Union Carbide Chemicals & Plastics Co., USA, April 1991.
25. Bushy Run Research Centre, 'Glutaraldehyde Vapour: Nine-day Inhalation Study on
Rats', Project Report 46-63, Pennsylvania, USA, November 1983.
26. United States Environmental Protection Agency, Office of Pesticides and Toxic
Substances, Status Report no. 8EHQ-1290-1008.
27. Sax and Lewis, Dangerous Properties of Industrial Materials, 7th ed., 1989.
28. Scientific Committee on Cosmetics, 'Opinion of the Committee Concerning:
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29. Varpela et al, 'Liberation of Alkanized Glutaraldehyde by Respirators After Cold
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30. St Clair et al, 'Pathology and Cell Proliferation Induced by Intra-nasal Instillation of
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31. Bushy Run Research Centre, 'Glutaraldehyde: Acute Vapour Inhalation Toxicity
Study in Rats', Protocol for Project no. 93U1256, Pennsylvania, USA, May 1993.
32. Bushy Run Research Centre, 'Glutaraldehyde Dilutions -- Primary Skin and Eye
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33. Organisation for Economic Co-operation and Development, Guidelines for Testing of
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34. Bushy Run Research Centre, 'Glutaraldehyde and Formaldehyde: Sensory Irritation
Study in Swiss Webster Mice', Draft Project Report 91U0123, Pennsylvania, USA,
December 1993.
35. American Society of Testing Materials, Annual Book of ASTM Standards,
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36. Harner et al, 'Cidex-induced Synovitis', Am. J. Sports Med., vol. 17, no. 1, pp. 96-102,
1989.
37. Pharmaco LSR Inc., 'Guinea Pig Maximization Test with Glutaraldehyde', study no.
93-0793, New Jersey, USA, September 1993.
38. Descotes, 'Identification of Contact Allergens: The Mouse Ear Sensitization Assay', J.
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39. Bushy Run Research Centre, 'Glutaraldehyde and Formaldehyde: Vapor Pulmonary
Hypersensitivity Study in Guineapigs', Draft Project Report 92U1193, Pennsylvania,
USA, September 1993.



Glutaraldehyde
162
40. ECETOC, 'Respiratory Allergy', Monograph No.19, Brussels, Belgium, August 1993.
41. Bushy Run Research Centre, 'Glutaraldehyde: 90-Day Inclusion in Drinking Water of
Rats', Project Report 48-107, Pennsylvania, USA, December 1985.
42. Ballantyne, 'Glutaraldehyde: Significance of Chronic Drinking Water Study in
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Summary, Union Carbide Corporation, April 1993.
43. Bushy Run Research Centre, 'Glutaraldehyde: Two-week Inclusion in Drinking
Water of Rats', Project Report 47-190, Pennsylvania, USA, March 1985.
44. Stefanski et al, 'Spleen, Lymph Nodes and Thymus', in Boorman et al (eds.),
Pathology of the Fischer Rat, Academic Press, Sydney, 1990.
45. Bushy Run Research Centre, 'Glutaraldehyde Vapour: Nine-day Inhalation Study on
Rats', Project Report 46-95, Pennsylvania, USA, November 1983.
46. Bushy Run Research Centre, 'Glutaraldehyde Vapour Subchronic Inhalation Study on
Rats', Project Report 46-101, Pennsylvania, USA, December 1983.
47. BASF Aktiengesellschaft, 'Study of the Prenatal Toxicity of Glutaraldehyde in Rats
after Oral Administration (Drinking Water)', Project No.33R0599/89025,
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48. BASF Aktiengesellschaft, 'Range-Finding Study of the Prenatal Toxicity of
Glutaraldehyde in Rats after Oral Administration (Gavage)', Project No.
10R0599/89048, Ludwigshafen, Germany, 1991.
49. BASF Aktiengesellschaft, 'Range-Finding Study of the Prenatal Toxicity of
Glutaraldehyde in Rats after Oral Administration (Drinking Water)', Project No.
13R0599/89035, Ludwigshafen, Germany, 1991.
50. BASF Aktiengesellschaft, 'Study of the Prenatal Toxicity of Glutaraldehyde in
Rabbits after Oral Administration (Gavage)', Project No. 40R0599/89026,
Ludwigshafen, Germany, 1991.
51. BASF Aktiengesellschaft, 'Range-Finding Study of the Prenatal Toxicity of
Glutaraldehyde in Rabbits after Oral Administration (Gavage)', Project No.
20R0599/89038, Ludwigshafen, Germany, 1991.
52. BASF Aktiengesellschaft, 'Range-Finding Study of the Prenatal Toxicity of
Glutaraldehyde in Rabbits after Oral Administration (Drinking Water)', Project No.
23R0599/89036, Ludwigshafen, Germany, 1991.
53. Industrial Bio-Test Laboratories Inc., 'Teratogenic Study with 25% Glutaraldehyde in
Albino Rats', IBT No. 8533-09082, Illinois, USA, November 1976.
54. Marks et al, 'Influence of Formaldehyde and sonacide (Potentiated Acid
Glutaraldehyde) on Embryo and Foetal Development in Mice', Teratol., vol. 22, pp.
21-58, 1980.
55. Ballantyne, 'Glutaraldehyde: Summary of Genotoxicity Studies', Personal
communication, Union Carbide Corporation, USA, December 1992.
56. Bushy Run Research Centre, 'UCARCIDE Antimicrobial 250: In Vitro Chromosomal
Aberrations Assay in Chinese Hamster Ovary Cells', Project Report 54-101,
Pennsylvania, USA, September 1991.
57. Litton Bionetics Inc., 'Mutagenicity Evaluation of Sterisol Formula No.3 in the
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March 1977.
58. Clive and Spector, Mut. Res., vol. 31, pp. 17-29, 1975.


163
Priority Existing Chemical Number 3
59. St Clair et al, 'Evaluation of the genotoxic Potential of Glutaraldehyde', Env. Molec.
Mut., vol. 18, pp. 113-119, 1991.
60. Bushy Run Research Centre, 'UCARCIDE Antimicrobial 250: In Vivo Peripheral
Blood Micronucleus Test with Swiss-Webster Mice', Project No. 91U0101,
Pennsylvania, USA, February 1993.
61. Ballantyne, 'Glutaraldehyde: Significance of Rat Bone Marrow Chromosomal
Aberration Assay, Bushy Run Research Centre Project Report 91U0139: Draft dated
18 Nov. 1992', CAT/SOT summary, Union Carbide Corporation, USA, December
1992.
62. Norback, 'Skin and Respiratory Symptoms from Exposure to Alkaline Glutaraldehyde
in Medical Services', Scand. J. Work Environ. Health, vol. 14, pp. 366-371, 1988.
63. Hansen, 'Glutaraldehyde Occupational Dermatitis', Contact Dermatitis, vol. 9, pp. 81-
82, 1983.
64. Hansen, 'Occupational Dermatoses in Hospital Cleaning Women', Contact
Dermatitis, vol. 9, pp. 343-351, 1983.
65. Jachuck et al, 'Occupational Hazard in Hospital Staff Exposed to 2% Glutaraldehyde
in an Endoscopy Unit', J. Soc. Occup. Med., vol. 39, pp. 69-71, 1989.
66. National Institute of Occupational Safety and Health, Health Hazard Evaluation
Report no. HETA 86-226-1769, US Dept. of Health & Human Services, Public
Health Service, Cincinnati, Ohio, USA, January 1987.
67. Wiggins et al, 'Epistaxis Due to Glutaraldehyde Exposure', J. Occup. Med., vol. 31,
no. 10, pp. 854-856, 1989.
68. National Institute of Occupational Safety and Health, Health Hazard Evaluation
Report no. HETA 84-535-1690, US Dept. of Health & Human Services, Public
Health Service, Cincinnati, Ohio, USA, May 1986.
69. National Institute of Occupational Safety and Health, Health Hazard Evaluation
Report no. HETA 83-048-1347, US Dept. of Health & Human Services, Public
Health Service, Cincinnati, Ohio, USA, 1983.
70. National Institute of Occupational Safety and Health, Health Hazard Evaluation
Report no. HETA 90-296-2149, US Dept. of Health & Human Services, Public
Health Service, Cincinnati, Ohio, USA, October 1991.
71. Tam and Freeman, 'Occupational Allergic Contact Dermatitis due to Glutaraldehyde',
J Occup. Health Safety -- Aust. NZ, vol. 5, no. 6, pp. 487-491, 1989.
72. Tkaczuk et al, 'Occupational Exposure to Glutaraldehyde in South Australia', J.
Occup. Health & Safety -- Aust. NZ, vol. 9, no. 3, pp. 237-243, 1993.
73. National Institute of Occupational Safety and Health, Health Hazard Evaluation
Report no. HETA 85-257-1791, US Dept. of Health & Human Services, Public
Health Service, Cincinnati, Ohio, USA, April 1987.
74. Murray and Ruddy, Southern Med. J., vol. 78, p. 1012, 1985.
75. D'Arcy, J.Pharmac. Belg., vol. 45, p. 47, 1989.
76. Corrado et al, 'Asthma and Rhinitis after Exposure to Glutaraldehyde in Endoscopy
Units', Human Toxicol., vol. 5, pp. 325-327, 1986.
77. American Conference of Governmental Industrial Hygienists, 'Glutaraldehyde',
Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th
ed., 1991.



Glutaraldehyde
164
78. Di Prima et al, 'Contact Dermatitis from Glutaraldehyde,' Contact Dermatitis, vol. 19,
no. 3, pp. 219-220, 1988.
79. Bardazzi et al, 'Glutaraldehyde Dermatitis in Nurses', Contact Dermatitis, vol. 14, no.
5, pp. 319-320, 1986.
80. Fowler, 'Allergic Contact Dermatitis From Glutaraldehyde Exposure', J.
Occupational Medicine, vol. 31, no. 10, pp. 852-853, 1989.
81. Nethercott et al, 'Occupational Contact Dermatitis Due to Glutaraldehyde in Health
Care Workers', Contact Dermatitis, vol. 18, pp. 193-196, 1988.
82. Nethercott and Holness, 'Contact Dermatitis in Funeral Service Workers', Contact
Dermatitis, vol. 18, pp. 263-267, 1988.
83. Goncalo et al, 'Occupational Contact Dermatitis to Glutaraldehyde', Contact
Dermatitis, vol. 10, pp. 183-184, 1984.
84. Fisher, 'Reactions to Glutaraldehyde with Particular Reference to Radiologists and X-
ray Technicians', Cutis, vol. 28, pp. 113-122, 1981.
85. Jordan et al, 'Contact Dermatitis From Glutaraldehyde.' Arch. Dermatol., vol. 105, pp.
94-94, 1972.
86. Maibach, 'Glutaraldehyde: Cross Reactions to Formaldehyde', Contact Dermatitis,
vol. 1, pp. 326-327, 1975.
87. Jaworsky et al, 'Allergic Contact Dermatitis to Glutaraldehyde in a Hair Conditioner',
Cleveland Clinic J. Med., vol. 54, no. 5, pp. 443-444, 1987.
88. Shelanski, 'Glutaraldehyde, 5% Solution -- Repeated Insult Patch Test', I.B.L. No.
4099, Industrial Biology Laboratories Inc., August 1966.
89. Testkit Laboratories Inc., 'Glutaraldehyde -- Repeated Insult Patch Test', Study no.
80-39, USA, November 1980.
90. Balmes, 'Surveillance for Occupational Asthma', Occup. Med. -- State of the Art
Reviews, vol. 6, no. 1, pp. 101-110, Jan.-Mar. 1991.
91. Chan-Yeung et al, 'Clinical Aspects of Allergic Disease -- Occupational Asthma in a
Technologist Exposed to Glutaraldehyde', J. Allergy Clin. Immunol., vol. 91, no. 5,
pp. 974-978, 1993.
92. Benson, 'Case Report -- Exposure to Glutaraldehyde', J. Soc. Occup. Med., vol. 34,
pp. 63-64, 1984.
93. Crome, 'Allergic Reactions to Cold Sterilising Solutions' (letter), Brit. Dental J., vol.
166, no. 12, p. 439, 24 June 1989.
94. Meredith et al, 'Occupational Respiratory Disease in the United Kingdom 1989: A
Report to the British Thoracic Society and the Society of Occupational Medicine by
the SWORD Project Group', Brit. J. Ind. Med., vol. 48, pp. 292-298, 1991.
95. Cullinan et al, 'Occupational Asthma in Radiographers' (letter), The Lancet, vol. 340,
p. 1477, 12 December 1992.
96. Caswell, 'Case Study: Allergic and Irritant Reactions', Australian Doctor, 10
September 1993, pp. 53-54.
97. Nicewicz et al, 'Occupational Asthma Caused by Glutaraldehyde Exposure', Immunol.
Allergy Practice, vol. 8, no. 8, pp. 272-278, August 1986.




165
Priority Existing Chemical Number 3
98. Dept. of Social Security, United Kingdom, 'Occupational Asthma'. Report by the
Industrial Injuries Advisory Committee in accordance with Section 141 of the Social
Security Act 1975 on the question of whether further sensitising agents should be
prescribed under the Act. Cm1244, HMSO, London, October 1990.
99. Health and Safety Commission, 'Draft Approved Code of Practice -- Control of
Respiratory Sensitisers -- Consultative Document', CD50, HSE, London, 1992.
100. TKL Research Inc., 'Glutaraldehyde 0.5% -- Phototoxicity Test', Study no. 906001,
New Jersey, USA, April 1990.
101. TKL Research Inc., 'Glutaraldehyde -- Photoallergy Test', Study no. 907001, New
Jersey, USA, April 1990.
102. Connaughton, 'Occupational Exposure to Glutaraldehyde Associated with
Tachycardia and Palpitations' (Letter), Medical J. Aust., vol. 159, p. 567, 18 October
1993.
103. Hemminki et al, 'Spontaneous Abortions in Hospital Staff Engaged in Sterilising
Instruments with Chemical Agents', Brit. Med. J., vol. 285, pp. 1461-1463, 1982.
104. Hemminki et al, 'Spontaneous Abortions and Malformations in the Offspring of
Nurses Exposed to Anaesthetic Gases, Cytostatic Drugs, and Other Potential Hazards
in Hospitals, Based on Registered Information of Outcome', J. Epidem. Community
Health, vol. 39, pp. 141-147, 1985.
105. Teta et al, 'Mortality Study of Glutaraldehyde Production Workers', Union Carbide
Corporation, USA, 1992.
106. Teta et al, 'A Medical Record Review of Sensitisation Among Workers Assigned to
Glutaraldehyde Production or Drumming', Union Carbide Corporation, USA, 1992.
107. National Occupational Health and Safety Commission, Control of Workplace
Hazardous Substances: National Code of Practice for the Control of Workplace
Hazardous Substances [NOHSC:0003(1993)] and National Model Regulations for
the Control of Workplace Hazardous Substances [NOHSC:0002(1993)], Australian
Government Publishing Service, Canberra, 1993.
108. National Occupational Health and Safety Commission, List of Designated Hazardous
Substances [NOHSC:0007(1993)], AGPS, Canberra, 1993.
109. National Occupational Health and Safety Commission, Approved Criteria for
Classifying Hazardous Substances [NOHSC:0006(1993)], AGPS, Canberra, 1993.
110. Australian Code for the Transport of Dangerous Goods by Road and Rail, AGPS,
Canberra, 1992.
111. Commission of the European Communities, Legislation on Dangerous Substances --
Classification and Labelling in the European Community, vol. 2, Office for the
Official Publications of the European Community, Luxembourg (regularly updated).
112. National Health and Medical Research Council, Standard for the Uniform Scheduling
of Drugs and Poisons, AGPS, Canberra, 1992.
113. National Occupational Health and Safety Commission, National Code of Practice for
the Labelling of Workplace Substances [NOHSC:0004(1993)], AGPS, Canberra, June
1993.
114. National Occupational Health and Safety Commission, National Code of Practice for
the Preparation of Material Safety Data Sheets [NOHSC:0005(1993)], AGPS,
Canberra, June 1993.




Glutaraldehyde
166
115. NSW Health Dept., Guidelines for the Safe Use of Glutaraldehyde in Health Care
Establishments, March 1993.
116. Tandon, 'Endoscopic Disinfection: Practices and Recommendations', J .
Gastroenterology and Hepatology, vol. 6, pp. 37-39, 1991.
117. Sydney Hospital Occupational Health and Safety Service, 'Report on Glutaraldehyde
Survey in Hospitals', NSW Health Department, June 1991.
118. Hewitt, 'Occupational Health Problems in Processing of X-ray Photographic Films',
Ann. Occup. Hyg., vol. 37, no. 3, pp. 287-295, 1993.
119. Aw, 'Glutaraldehyde: Action Needed Now to Control Exposure', Occup. Health,
October 1990, pp. 284-286.
120. Leinster et al, 'An Assessment of Exposure to Glutaraldehyde in Hospitals: Typical
Exposure Levels and Recommended Control Measures', Brit. J. Indust. Med., vol. 50,
pp. 107-111, 1993.
121. Australian Standard AS 1668.2-1991 -- The Use of Mechanical Ventilation and Air-
conditioning in Buildings. Standards Australia, Sydney.
122. Health and Safety Executive, An Introduction to Local Exhaust Ventilation, Booklet
HS(G)37, HMSO, London, 1987.
123. Health and Safety Executive, The Maintenance, Examination and Testing of Local
Exhaust Ventilation, HMSO, London, 1990.
124. Straughn and Barker, 'Avoiding glutaraldehyde irritation of the mucous membranes',
Gastrointest. Endosc., vol. 3, pp. 396-397, 1987.
125. Campbell and Cripps, 'Environmental control of glutaraldehyde', Health Estate J.
November 1991, 2-6.
126. HB9 -- Occupational Personal Protection, Standards Australia, Sydney, 1994.
127. Australian Standard AS1336-1982 -- Recommended Practices for Eye Protection in
the Industrial Environment. Standards Australia, Sydney.
128. Australian Standard AS1337-1984 -- Eye Protectors for Industrial Applications.
Standards Australia, Sydney.
129. Union Carbide Internal Report, 'Memo on Glove Testing', Union Carbide
Corporation, USA, May 1985.
130. Anon., 'Latex allergies', Toxic., vol. 4, no. 1, p. 9, January 1994.
131. Australian Standard AS2161-1978 -- Industrial Safety Gloves and Mittens, Standards
Australia, Sydney.
132. Australian Standard AS1715-1991 -- Selection, Use and Maintenance of Respiratory
Protective Devices, Standards Australia, Sydney.
133. Australian Standard AS1716-1991 -- Respiratory Protective Devices, Standards
Australia, Sydney.
134. Australian Standard AS3765.1-1990 -- Clothing for Protection Against Hazardous
Chemicals, Standards Australia, Sydney.
135. Health and Safety Executive, Occupational Exposure Limits: Criteria Document
Summaries, HSE Books, London, 1993.




167
Priority Existing Chemical Number 3
136. Salvaggio et al, 'Occupational Asthma and Rhinitis' in Occupational Respiratory
Diseases, National Institute of Occupational Safety and Health, Publication no. 86-
102, September 1986.
137. Sub-committee on Occupational Allergy of the European Academy of Allergology
and Clinical Immunology, 'Guidelines for the Diagnosis of Occupational Asthma',
Clin. Exper. Allergy, vol. 22, pp. 103-108, 1992.
138. Sherwood Burge, 'Use of Serial Measurements of Peak Flow in the Diagnosis of
Occupational Asthma', Occupational Medicine: State of the Art Reviews, vol. 8, no. 2,
pp. 279-294, April-June 1993.
139. American Thoracic Society, 'Standardisation of Spirometry', American Rev. Resp.
Disease, vol. 136, pp. 1285-1298, 1987.
140. Australasian Society of Respiratory Technology, Spirometry and Lung Volumes:
Review of the Methods, Indications, Normal Values, Pitfalls, Reproducibility, vol. 6,
no. 3, 1986.
141. Australasian Society of Respiratory Technology, Minimum Guidelines for
Spirometry, February 1989.
142. McKay and Lockey, 'Pulmonary Function Testing: Guidelines for Medical
Surveillance and Epidemiological Studies', Occup. Med.: State of the Art Reviews,
vol. 6, no. 1, pp. 43-57, 1991.
143. Harber and Lockey, 'Pulmonary Function Testing and Pulmonary Prevention', Occup.
Med.: State of the Art Reviews, vol. 6, no. 1, pp. 69-79, 1991.
144. Enright, 'Surveillance for Lung Disease: Quality Assurance Using Computers and a
Team Approach', Occup. Med.: State of the Art Reviews, vol. 7, no. 2, pp. 209-225,
1992.
145. Bascom and Ford, 'Don't Just Do Spirometry -- Closing the Loop in Workplace
Spirometry Programs', Occup. Med.: State of the Art Reviews, vol. 7, no. 2, pp. 347-
363, 1992.
146. Eisen (ed.), 'Spirometry', Occup. Med.: State of the Art Reviews, vol. 8, no. 2, April-
June 1993.
147. Howard (Ed), Handbook of Environmental Fate and Exposure Data for Organic
Chemicals, Volume I, Large Production and Priority Pollutants, Lewis Publishers Inc,
USA, 1989.
148. Ritter, 'Ready Biodegradability: Modified MITI-Test (I) for Piror 850', RCC Project
245327, May 1990.
149. Waggy, 'Glutaraldehyde Ecological Fate and Effects Studies', Union Carbide
Research and Development Department Project No 515G02, October 1981.
Esser, 'Aerobic Aquatic Metabolism of [14C] Gluaraldehyde in River Water and
150.
Sediment', PTRL Project No. 364W-1, PTRL West Inc, California, USA, November
1993.
151. Wildlife International Ltd, 'Acute Oral LD50 -- Mallard Duck Glutaraldehyde 25%',
Project No 142-114, January 1978.
152. Wildlife International Ltd, 'Acute Oral LD50 -- Mallard Duck Glutaraldehyde 50%',
Project No 142-111, February 1978.
153. Wildlife International Ltd, 'Eight Day Dietary LC50 -- Mallard Duck Glutaraldehyde
50%', Project No 142-110, January 1978.



Glutaraldehyde
168
154. Wildlife International Ltd, 'Eight Day Dietary LC 5 0 -- Bobwhite Quail
Glutaraldehyde 25%', Project No 142-112, January 1978.
155. Wildlife International Ltd, 'Eight Day Dietary LC 5 0 -- Bobwhite Quail
Glutaraldehyde 50%', Project No 142-112, January 1978.
156. Vilkas, 'The Acute Toxicity of 50% Glutaraldehyde to Bluegill Sunfish, Lepomis
macrochirus Rafinesque', Union Carbide Environmental Services Project No 11506-
61-06, January 1978.
157. Union Carbide Aquatic Environmental Sciences, 'Acute Toxicity of Glutaraldehyde
to Oyster Larvae (Crassostrea virginica), Green Crabs (Carcinus maenas) and Grass
Shrimp (Palaemonetes vulgaris)', December 1975.
158. Vilkas, 'The Acute Toxicity of 50% Glutaraldehyde to the Water Flea, Daphnia
magna Straus', Union Carbide Environmental Services Project No 11506-61-04,
January 1978.
159. Union Carbide Environmental Services, 'The Acute Toxicity of 25% Aqueous
Glutaraldehyde to the Water Flea, Daphnia magna Straus', Project No 11506-61-03,
December 1977.
160. Cytotest Cell Research, 'Influence of Piror 850 on the Reproduction of Daphnia
magna', Project No 164002, March 1990.
161. Vilkas, 'Toxicity of Glutaraldehyde (25%) to Selenastrum capricornutum in PAAP
Medium', Union Carbide Aquatic Environmental Sciences, December 1974.
162. Ritter, 'Acute Toxicity of Piror 850 to Scenedesmus subspicatus', RCC
Umweltchemie Project No 245340, May 1990.
163. Strotmann et al, -Development and Evaluation of a Growth Inhibition Test with
Sewage Bacteria for Assessing Bacterial Toxicity of Chemical Compounds-,
Chemosphere, vol. 28, no. 4, pp. 755-766, 1994.
164. Alsop et al, 'Bacterial Growth Inhibition Test', Journal WPCF, vol. 52, pp. 2452-
2456, 1980.

Additional studies provided by the applicants as part of the requests to vary
the report (under section 37 of the Act);**
Chemical Hygiene Fellowship, '25% Aqueous Glutaraldehyde: Range Finding Toxicity
Studies', Project Report 40-120, Pennsylvania, USA, September 1977.
Chemical Hygiene Fellowship, '50% Aqueous Glutaraldehyde Solution: Range Finding
Toxicity Studies', Project Report no. 40-50, Pennsylvania, USA, April 1977.
Bushy Run Research Centre, 'Glutaraldehyde Dilutions: Percutaneous Toxicity and Eye
Irritation Studies', Project Report no. 44-65, Pennsylvania, USA, June 1981.
Hermansky and Loughran, 'Glutaraldehyde: Combined Chronic Toxicity/Oncogenicity
in the Drinking Water of Rats', Project report no. 91U0012, Bushy Run Research
Centre, Pennsylvania, USA, 1994.




**
This list of additional toxicity studies was provided by the applicqnts during the variation of the
assessment report under section 37 of the Act. The studeis have not been included as they did not lead to
any significant amendment of the assessment report.


169
Priority Existing Chemical Number 3
Meckley and DePass, 'Evaluation of the Subacute Dermal Toxicity of Glutaraldehyde in
Mice', Project Report no. 44-107, Bushy Run Research Centre, Pennsylvania,
USA, December 1981.*
Myers, 'Glutaraldehyde Dilutions: Acute Peroral Toxicity Studies', Project Report no.
45-124 (revised), Bushy Run Research Centre, Pennsylvania, USA, May 1990.
Myers, 'Glutaraldehyde Dilutions (45%, 15%, 10%): Acute Percutaneous Toxicity
Studies', Project Report no. 48-51, Bushy Run Research Centre, Pennsylvania,
USA, June 1985.
Nachreiner and Dodd, 'UCARCIDE Antimicrobial 250: Acute Vapour Inhalation
Toxicity Test in Rats', Project Report 53-8, Bushy Run Research Centre,
Pennsylvania, USA, November 1990.
Bushy Run Research Centre, 'Protocol for Dynamic Acute Inhalational Study', Project
no. 81-15-12707, Pennsylvania, USA, March 1981.
Mellon Institute, 'Range Finding Tests on 45% Aqueous Glutaraldehyde', Report no. 27-
137, Pennsylvania, USA, October 1964.


Further reading
Ballantyne and Berman, 'Dermal sensiting potential of glutaraldehyde: a review and
recent observations', J. Toxicol. Cut. -- Ocular Toxicol., vol. 3, no. 3, pp. 251-
262, 1984.
Budavari (Ed), The Merck Index, 11th ed., Merck and Co, USA, 1989.
Gardner and Peel, Introduction to Sterilization, Disinfection and Infection Control, 2nd
ed., 1991.
Haley, 'A review of the literature of glutaraldehyde,' Dang. Prop. Indust. Mat., vol. 1,
no. 7, pp. 2-4, 1981.
Sanderson and Cronin, 'Glutaraldehyde and contact dermatitis', Brit. Med. J., vol. 3, p.
802, 1968.
Slesinski et al, 'Mutagenicity Evaluation of Glutaraldehyde in a Battery of In vitro
Bacterial and Mammalian Test Systems', Food Cosmet. Toxicol., vol. 21, pp.
621-629, 1983.
Weaver and Maibach, 'Dose Response Relationships in Allergic Contact Dermatitis:
Glutaraldehyde-containing Liquid Fabric Softener.' Contact Dermatitis, vol. 3,
pp. 65-68, 1977.
Weller, 'Cleaning and Disinfection of Equipment for Gastrointestinal Flexible
Endoscopy: Interim Recommendations of a Working Party of the British Society
of Gastroenterology', Gut., vol. 29, pp. 1134-1151, 1988.




Glutaraldehyde
170
Glossary
Acetal An organic compound formed by the combination of an
aldehyde with an alcohol.
ACGIH American Conference of Governmental Industrial Hygenists.
ADG Code The Australian Code for the Transport of Dangerous Goods
by Road and Rail.
AICS Australian Inventory of Chemical Substances.
Approved Criteria The National Commission's Approved Criteria for Classifying
Hazardous Substances.
Arthroscopy Examination of the interior of a joint, for example, the knee,
with an instrument called an arthroscope.
AST Aspartate aminotansferase.
Asthma A condition marked by recurrent episodes of wheezing and/or
breathlessness characterised by a significant increase in
resistance to air flow.
ASTM American Society of Testing Materials.
Atopy An inherited tendency to develop some form of allergy.
Basophilia A blue or gray discolouration of immature blood cells.
Blepharospasm Spasm of the eyelids causing more or less complete closure of
the eyelids.
BOD Biochemical oxygen demand.
14
C A radioactive isotope of carbon which is used in the radio
isotope labelling of a molecule.
Carbonyl group The carbon-oxygen double bond occurring in organic
compounds such as aldehydes and ketones.
Carcinogenicity The tendency to produce cancer.
CHO cells Chinese hamster ovary cells used for in vitro mutagenicity
testing to detect clastogenic agents and agents causing sister
chromatid exchange (SCE).
Chromosomal A change which results from damage expressed in both sister
aberration chromatids at the same site.
Chromosome A structure in the nucleus of animal cells containing a
substance (DNA) which transmits genetic (hereditary)
information.
Clastogenic Giving rise to, or inducing, breakages in chromosomes.
Conjunctival Refers to the delicate mucous membrane that lines the eyelids
and eyeball.
Corpora lutea Yellow glandular masses in the ovary formed by ovarian
follicles that have matured and discharged their ova.
CPK Creatinine phosphokinase.



171
Priority Existing Chemical Number 3
Cross-linker A compound, group, or element which joins 2 chains of
polymer molecules.
Cyanohydrin A compound formed by the addition of hydrocyanic acid to
an aldehyde or ketone.
Cyclophosphamide A drug used in the treatment of many types of malignancies.
Dentin The substance which surrounds the tooth pulp, covered by
enamel on the crown and by cementum on the roots of the
teeth.
Dermatitis Inflammation of the skin.
DNA Deoxyribonucleicacid, carrier of genetic information.
DNCB 2,4-dinitrochlorobenzene.
EC50 The concentration of a substance in water that has an effect
on 50% of exposed organisms, relative to unexposed controls.
Embryotoxicity The toxicity of a substance to the developing embryo (2 to 8
weeks).
Endoscopy Visual inspection of any cavity in the body using an
instrument called an endoscope.
Epidemiological Relating to the study of the relationships determining the
frequency and distribution of a disease in a human
community.
Epidermis The outermost layer of the skin.
Erythema Redness of the skin which may result from a variety of
causes.
Erythrocytes Red blood cells.
FCA Freund's complete adjuvant.
FIFRA Federal Insecticide, Fungicide and Rodenticide Act 1975
(USA).
FEV1 Forced expiratory volume in one second.
Foetotoxicity The toxicity of a substance to the foetus.
Fundus That portion of a hollow organ furthest from its mouth.
FVC Forced vital capacity.
Gastritis Inflammation of the stomach.
Gavage Forced feeding through a tube passed into the stomach.
Genotoxicity The tendency to cause damage to genetic material such as
DNA.
Glutaconyl CoA The oxidation product of glutaric acid after undergoing
enzymatic changes.
GPU Glutaraldehyde production unit.
HETA Hazard Evaluations and Technical Assistance branch of
NIOSH.
Hepatitis Inflammation of the liver.


Glutaraldehyde
172
HPLC High performance liquid chromatography (or
chromatograph), an analytical technique (or instrument) based
on the separation of compounds for measurement.
HPV High production volume. Refers to a program of the OECD
for chemicals where there is a high risk of exposure to
humans or the environment because production volumes are
in excess of 1000 te/yr.
Hydrazone An organic compound formed from the reaction of an
aldehyde or ketone with the chemical phenylhydrazine.
Hyperaemia An excess of blood in any part of the body.
Hyperplasia Abnormal multiplication or increase in the number of normal
cells.
Hypersensitivity A state of heightened reactivity to an antigen resulting from
previous sensitisation.
IC50 The concentration of a substance in water that produces a
50% inhibition of the growth of bacteria, relative to
unexposed controls.
Ileum The lowest part of the small intestine.
In vitro toxicity test A test conducted outside the body of the organism, for
example, with cell cultures.
In vivo toxicity test A test carried out within the living body of an experimental
animal.
Iritis Inflammation of the iris (membrane behind the cornea).
IUPAC International Union for Pure and Applied Chemistry.
Keratinised Coated with a protein which is not soluble in the stomach.
Lacrimation Secretion and discharge of tears.
Laryngeal Pertaining to the larynx.
LC50 The median lethal concentration, that is, the concentration of
a substance that is estimated to produce death in 50% of test
organisms; it is used for estimating the acute lethality of
chemicals to aquatic organisms or of air-borne chemicals to
terrestrial animals.
LD50 The median lethal dose, that is, the single dose of a substance
that can produce death in 50% of test animals.
Lesion A discontinuity of tissue or loss of function of a part of
the body as a result of disease or trauma.
Leukaemia A progressive, malignant disease of the blood-forming organs
characterised by excessive white blood cells and their
precursors in the blood and bone marrow.
LEV Local exhaust ventilation.
LGLL Large granular cell lymphatic leukaemia.
The List The National Commission's Designated List of Hazardous
Substances.


173
Priority Existing Chemical Number 3
Lymphatic Pertaining to the vessels which convey the clear fluid derived
from the tissues of the body to the bloodstream.
Lymphoma A cancerous disease of the lymphatic tissues.
Margo plicatus The marginal fold in a membrane.
MBTH 3-methyl-2-benzothiazolinone hydrazone.
MED Minimal erythemal dose.
Medicament A medicinal substance or agent.
Metaplasia A change from normal to abnormal cells in a tissue.
Micronucleus A type of nucleus which functions in sexual reproduction in
lower forms of living organisms.
Mitotic cells Cells which have divided.
MMEF Maximum mid-expiratory flow rate.
MSDS Material Safety Data Sheet.
Mutagenicity The property of being able to induce a change in the genetic
pattern in cells.
National Commission The National Occupational Health and Safety Commission.
Necropsy The examination of the organs and body tissues of a dead
animal to determine the cause of death or pathological
conditions.
NHMRC The National Health and Medical Research Council.
NIOSH The United States-based National Institute of Occupational
Safety and Health.
NOAEL No observed adverse effect level. The highest dose level of a
substance that, in a given toxicity test, causes no observable
adverse effect in the test animal.
NOEL No observable effect level.
Normoerythrocyte A red blood cell of normal size.
NOS Not otherwise specified.
NTP The United States-based National Toxicology Program.
Occluded dressing A dressing which is covered or closely fitting.
Occupational asthma A respiratory disease characterised by variable bronchial
obstruction and variable hyperactivity caused by specific
agents inhaled at work.
OECD The Organisation for Economic Cooperation and
Development.
Oedema Swelling.
Oncogenic Giving rise to tumours.
Ophthalmological Pertaining to the eye.
Osmolality The property of a solution which depends on the concentration
of the solute per unit of solvent.



Glutaraldehyde
174
Oxime A compound formed by the action of a hydroxylamine on an
aldehyde or ketone.
Palpitations Unduly rapid heart beat.
Patch test A skin test used to determine allergic manifestations in an
individual.
PCE Polychromatic erythrocyte.
PEFR Peak expiratory flow rate.
Percutaneous Performed through the skin.
Perinasal Around the area of the nose.
Periocular Around the area of the eyes.
Pharmacokinetic Pertaining to the action of drugs in the body over a period of
time.
Photoallergy An allergic type of sensitivity to light.
Photosensitisation The development of abnormally increased reactivity of the
skin to sunlight.
Phototoxicity Increase of sunburn response to ultraviolet light, without any
allergic effect.
Piloerection Erection of the hair.
Polychromatic Exhibiting many colours.
Post coitum After the sexual act.
PPE Personal protective equipment.
Pulpotomy Excision of a portion of the pulp (of the tooth).
Pylorus The distal opening of the stomach through which the stomach
contents are emptied into the duodenum.
RD50 The concentration of a substance which produces a 50%
decrease in respiratory rate.
Refractive index The number which gives a measure of the change in angle of
light beam passing from a medium of different density.
Respiratory allergy The clinical disease (or adverse reaction) mediated by an
immune response to an antigen.
Respiratory An immune status resulting from an immune response to an
sensitisation antigen.
Rhinitis A disease that invokes inflammation of the nasal mucous
membrane, characterised by periods of nasal discharge,
sneezing and congestion.
S9 fraction An enzyme preparation used in in vitro toxicity testing for the
purpose of determining whether the test substance requires
metabolic activation to exert its mutagenic effect.
SCE See sister chromatid exchange.
Schiff base A class of compounds derived by the chemical reaction of
aldehydes or ketones with primary amines.


175
Priority Existing Chemical Number 3
SIDS Screening information data set (for HPV chemicals).
Sinusitis Inflammation of the air-containing spaces (sinuses) in the
face.
Sister chromatids The two spiral filaments of a chromosome.
Sister chromatid The reciprocal exchange of DNA between two sister
exchange (SCE) chromatids of a duplicating chromosome.
SLRL Sex-linked recessive lethal.
SMR Standardised mortality rate.
Sporicidal Capable of destroying spores.
Squamous Scaly or plate-like.
STEL Short term exposure limit.
Stratum corneum The horny outermost layer of the skin containing dead cells.
SUSDP The National Health and Medical Research Council's
Standard for the Uniform Scheduling of Drugs and Poisons.
SWORD Surveillance of Work-related and Occupational Respiratory
Disease. A reporting scheme, run by the Epidemiological
Research Unit of the London Chest Hospital in collaboration
with the Society of Occupational Medicine and the British
Thoracic Society.
Synovial Pertaining to the secretion of a transparent viscid fluid
(synovia) from a joint cavity, for example, in the knee.
Teratogenicity The property of causing defects in the reproduction process,
resulting either in reduced productivity due to foetal or
embryonic mortality, or in birth defects.
Thioester An ester in which sulfur replaces oxygen.
TLV Threshold limit value.
Tonometer An instrument used to measure the pressure of the eyeball.
Troposphere The lowest level of the atmosphere, between the Earth's
surface and the stratosphere.
TWA Time-weighted average.
ULLI Unit length labelling index.
USEPA United States Environmental Protection Agency.
Virucidal Capable of destroying a virus.




Glutaraldehyde
176

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