This report contains the collective views of an international group of experts and does not

necessarily represent the decisions or the stated policy of the United Nations Environment
Programme, the International Labour Organisation, or the World Health Organization.

Concise International Chemical Assessment Document 1

1,2-DICHLOROETHANE

First draft prepared by Ms K. Hughes and Ms M.E. Meek,

Environmental Health Directorate,
Health Canada

Please note that thelayout and pagination of this pdf file are not identical to the printed
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Published under the joint sponsorship of the United Nations Environment Programme, the
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World Health Organization

Geneva, 1998
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WHO Library Cataloguing in Publication Data

1,2-Dichloroethane.

(Concise international chemical assessment document ; 1)

1.Ethylene dichlorides – toxicity 2.Ethylene dichlorides –

administration and dosage 3.Dose-response relationship, Drug
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 TABLE OF CONTENTS

FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1. EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

3. ANALYTICAL METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

4. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

5. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION . . . . . . . . . . . . . . . . . . . 5

6. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

6.1 Environmental levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

6.2 Human exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

7. COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND

HUMANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

8. EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS . . . . . . . . . . . . . . . . . . . . . . . 7

8.1 Single exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

8.2 Irritation and sensitization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
8.3 Short-term exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
8.4 Long-term exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
8.4.1 Subchronic exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
8.4.2 Chronic exposure and carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
8.5 Genotoxicity and related end-points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
8.6 Reproductive and developmental toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
8.7 Immunological and neurological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

9. EFFECTS ON HUMANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

9.1 Case reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

9.2 Epidemiological studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD . . . . . . . . . . . . . . . . . . . . . . . . . 9

10.1 Aquatic environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

10.2 Terrestrial environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

11. EFFECTS EVALUATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

11.1 Evaluation of health effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

11.1.1 Hazard identification and dose–response assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
11.1.2 Criteria for setting guidance values for 1,2-dichloroethane . . . . . . . . . . . . . . . . . . . . . . . . . . 12
11.1.3 Sample risk characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
11.2 Evaluation of environmental effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

iii
Concise International Chemical Assessment Document 1

13. HUMAN HEALTH PROTECTION AND EMERGENCY ACTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

13.1 Human health hazards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

13.2 Advice to physicians . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
13.3 Health surveillance advice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
13.4 Explosion and fire hazards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
13.4.1 Explosion hazards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
13.4.2 Fire hazards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
13.4.3 Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
13.5 Spillage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

14. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

INTERNATIONAL CHEMICAL SAFETY CARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

APPENDIX 1 — SOURCE DOCUMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

APPENDIX 2 — CICAD FINAL REVIEW BOARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

RÉSUMÉ D’ORIENTATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

RESUMEN DE ORIENTACIÓN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

iv

FOREWORD
Concise International Chemical Assessment
Documents (CICADs) are the latest in a family of
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Chemical Safety (IPCS) — a cooperative programme of
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Labour Organisation (ILO), and the United Nations
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authoritative documents on the risk assessment of
chemicals.
CICADs are concise documents that provide
summaries of the relevant scientific information
concerning the potential effects of chemicals upon
human health and/or the environment. They are based
on selected national or regional evaluation documents or
on existing EHCs. Before acceptance for publication as
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to ensure their completeness, accuracy in the way in
which the original data are represented, and the validity
of the conclusions drawn.
The primary objective of CICADs is character-
ization of hazard and dose–response from exposure to a
chemical. CICADs are not a summary of all available data
on a particular chemical; rather, they include only that
information considered critical for characterization of the
risk posed by the chemical. The critical studies are,
however, presented in sufficient detail to support the
conclusions drawn. For additional information, the
reader should consult the identified source documents
upon which the CICAD has been based.
Risks to human health and the environment will
vary considerably depending upon the type and extent
of exposure. Responsible authorities are strongly
encouraged to characterize risk on the basis of locally
measured or predicted exposure scenarios. To assist the
reader, examples of exposure estimation and risk
characterization are provided in CICADs, whenever
possible. These examples cannot be considered as
representing all possible exposure situations, but are
provided as guidance only. The reader is referred to
EHC 1701 for advice on the derivation of health-based
guidance values.
1
International Programme on Chemical Safety (1994)
Assessing human health risks of chemicals: derivation
of guidance values for health-based exposure limits.
Geneva, World Health Organization (Environmental
Health Criteria 170).
1
1,2-Dichloroethane
While every effort is made to ensure that CICADs
represent the current status of knowledge, new informa-
tion is being developed constantly. Unless otherwise
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 Concise International Chemical Assessment Document 1

CICAD PREPARATION FLOW CHART

SELECTION OF PRIORITY CHEMICAL

SELECTION OF HIGH QUALITY

NATIONAL/REGIONAL
ASSESSMENT DOCUMENT(S)

FIRST DRAFT
PREPARED

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REVIEW BY IPCS CONTACT POINTS

R E V I E W O F C O M M E N T S (PRODUCER/RO ),
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EDITING

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PUBLICATION

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2 Taking into account the comments from reviewers.
3 The second draft of documents is submitted to the Final Review Board together with the reviewers’ comments (6-10 CICADs are usually reviewed at
the Final Review Board). In the case of pesticides the role of the Final Review Board is fulfilled by a joint meeting on pesticides.
4 Includes any revisions requested by the Final Review Board.

2
 1,2-Dichloroethane

Board members serve in their personal capacity, not as

representatives of any organization, government, or
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3
Concise International Chemical Assessment Document 1
1. EXECUTIVE SUMMARY
This CICAD on 1,2-dichloroethane was prepared
by the Environmental Health Directorate of Health
Canada based on an International Programme on
Chemical Safety (IPCS) Environmental Health Criteria
(EHC) document (IPCS, 1995), which assesses the
potential effects on human health of indirect exposure to
1,2-dichloroethane in the general environment as well as
the chemical’s environmental effects. Data identified as
of May 1993 (human health effects) and October 1994
(environmental effects) were considered in these
reviews. Information on the nature of the peer review
process and the availability of the EHC document is
presented in Appendix 1. For this CICAD, the peer
review process prior to consideration by the Final
Review Board was covered by the peer review carried
out for the EHC. This CICAD on 1,2-dichloroethane was
finalized and approved for publication, through
correspondence, by members of the Final Review Board,
who also considered the peer review comments provided
during the development of the EHC. The composition of
the Final Review Board is outlined in Appendix 2. The
International Chemical Safety Card (ICSC 0250) produced
by the IPCS (1993) has also been reproduced in this
document.
1,2-Dichloroethane (CAS no. 107-06-2) is a volatile,
synthetic hydrocarbon that is used principally in the
synthesis of vinyl chloride monomer and other
chlorinated solvents. It has also been used as a leaded
gasoline additive and a fumigant, although its use as a
gasoline additive is declining. The majority of environ-
mental releases are to ambient air, where it is moderately
persistent. However, it is not expected to contribute to
ozone depletion. 1,2-Dichloroethane has a low potential
for bioaccumulation; inhalation in air is likely the primary
source of human exposure.
Little information is available on the effects of
1,2-dichloroethane in humans. The few identified
epidemiological investigations on its potential carcino-
genicity are inconclusive.
1,2-Dichloroethane is moderately acutely toxic in
experimental animals. Limited information on non-
neoplastic effects presented in short-term, subchronic,
and chronic studies indicates that the liver and kidneys
are the principal target organs; lowest reported effect
levels for ingestion and inhalation were 49–82 mg/kg
body weight per day (increases in liver weight in rats
exposed for 13 weeks) and 202 mg/m3 (effects on liver
and kidney function in rats exposed for 12 months),
respectively. Based on the results of a limited number of
studies, there is no evidence that 1,2-dichloroethane is
4
teratogenic in experimental animals or that it induces
reproductive or developmental effects at levels of
exposure lower than those that cause other systemic
effects.
Exposure to 1,2-dichloroethane by gavage for
78 weeks induced a significant increase in the incidence
of tumours at several sites (including haemangiosar-
comas and tumours of the stomach, mammary gland,
liver, lung, and endometrium) in both rats and mice.
Although there were no significant increases in tumour
incidence in rats or mice exposed via inhalation, repeated
dermal or intraperitoneal application of 1,2-
dichloroethane resulted in an increase in lung tumours in
mice. 1,2-Dichloroethane has been consistently geno-
toxic in numerous in vitro assays in prokaryotes, fungi,
and mammalian (including human) cells. Similarly,
results were consistently positive for genotoxic activity
(as well as binding to DNA) in in vivo studies in rats,
mice, and insects.
The lowest reported IC50s and EC50s for various
end-points in aquatic organisms were 25 and 105
mg/litre, respectively. The lowest reported LC50 value for
Daphnia was 220 mg/litre, whereas effects on
reproduction occurred at 20.7 mg/litre. The most
sensitive freshwater vertebrate tested was the north-
western salamander (Ambystoma gracile), in which
reduced larval survival was observed at 2.5 mg/litre.
Only limited data are available on the effects of 1,2-
dichloroethane on terrestrial species.
Based on available data, 1,2-dichloroethane is
considered to be a probable human carcinogen, and
therefore exposure should be reduced to the extent
possible. The carcinogenic potency (expressed as the
dose associated with a 5% increase in tumour incidence),
derived on the basis of studies in which animals were
exposed by gavage, was calculated to be 6.2–34 mg/kg
body weight per day. Guidance values for air (the
principal source of human exposure) of 3.6–20 :g/m3 or
0.36–2.0 :g/m3, calculated on the basis of a margin 5000-
or 50 000-fold less than the estimated carcinogenic
potency, have been derived; however, it should be
noted that risks are overestimated on this basis, as
available data indicate that 1,2-dichloroethane is less
potent when inhaled. (Corresponding values for
ingestion are 1.2–6.8 :g/kg body weight per day or
0.12–0.68 :g/kg body weight per day.) These values
correspond to those considered by some agencies to
represent “essentially negligible” risk (i.e. 10–5 to 10–6 for
a genotoxic carcinogen). Based on a sample estimate,
indirect exposure in the general environment is up to
approximately 300 times less than these values.

2. IDENTITY AND PHYSICAL/CHEMICAL
PROPERTIES
1,2-Dichloroethane (CAS no. 107-06-2; ethylene
dichloride, dichloro-1,2-ethane; see structural diagram
below) is a synthetic chemical that is a colourless liquid
at room temperature. It is also highly volatile, with a
vapour pressure of 8.5 kPa (at 20ºC), and soluble in
water, with a solubility of 8690 mg/litre (at 20ºC). The log
octanol/water partition coefficient of 1,2-dichloroethane
is 1.76. Additional physical/chemical properties are
presented in the International Chemical Safety Card,
reproduced in this document.
H H
* *
Cl ) C ) C ) Cl
* *
H H
3. ANALYTICAL METHODS
Analysis for 1,2-dichloroethane in environmental
media is usually by gas chromatography, in combination
with electron capture detection, flame ionization detec-
tion, or mass spectrometry. Detection limits range from
0.016 to >4 :g/m3 for air, from 0.001 to 4.7 :g/litre for
water, and from 6 to 10 :g/kg for various foodstuffs
(ATSDR, 1992).
4. SOURCES OF HUMAN AND
ENVIRONMENTAL EXPOSURE
There are no known natural sources of 1,2-
dichloroethane. The principal use for 1,2-dichloroethane
is in the synthesis of vinyl chloride monomer and, to a
lesser extent, in the manufacture of various chlorinated
solvents. It is also incorporated into antiknock gasoline
additives (although this use is declining with the phase-
out of leaded gasoline in some countries) and has been
used as a fumigant. Total annual production of 1,2-
dichloroethane in Canada (1990) and the USA (1991) is
about 922 and 6318 kt, respectively (CPI, 1991; Chemical
Marketing Reporter, 1992).
5
1,2-Dichloroethane
5. ENVIRONMENTAL TRANSPORT,
DISTRIBUTION, AND TRANSFORMATION
The majority of 1,2-dichloroethane released to the
environment is in emissions to air. 1,2-Dichloroethane is
moderately persistent in air; its estimated atmospheric
lifetime is between 43 and 111 days. Small amounts of
1,2-dichloroethane are transported to the stratosphere,
where photolysis may produce chlorine radicals, which
may in turn react with ozone (Spence & Hanst, 1978;
Callaghan et al., 1979). Some 1,2-dichloroethane may be
released in industrial effluents to the aquatic environ-
ment, from where it is removed rapidly by volatilization
(Dilling et al., 1975). 1,2-Dichloroethane may also leach
to groundwater near industrial waste sites. It is not
expected to bioconcentrate in aquatic or terrestrial
species.
6. ENVIRONMENTAL LEVELS AND
HUMAN EXPOSURE
6.1 Environmental levels
Data considered to be most representative of
current levels of 1,2-dichloroethane in environmental
media are summarized in Table 1. Mean concentrations
of 1,2-dichloroethane in surveys of ambient air in non-
source-dominated areas in cities are 0.07–0.28 :g/m3 in
Canada, <0.004–3.8 :g/m3 in Japan, and 1.2 :g/m3 in the
United Kingdom and the Netherlands. Earlier surveys in
the USA reported mean levels of 0.33–6.05 :g/m3;
however, peak levels near chemical manufacturing plants
have ranged as high as 736 :g/m3 (US EPA, 1985).
Mean levels in residential indoor air are reported to be
<0.1 :g/m3 in Canada, 0.1–0.5 :g/m3 in the USA, and 3.4
:g/m3 in the Netherlands.
In drinking-water, mean 1,2-dichloroethane con-
centrations are generally less than 0.5 :g/litre, based on
the results of surveys in Canada, the USA, Japan, and
Spain. Although there are few recent data, 1,2-dichloro-
ethane has only very rarely been detected in surface
water at concentrations greater than 10 :g/litre.
1,2-Dichloroethane has only rarely been detected
in foodstuffs in extensive surveys in Canada and the
USA. Also, as 1,2-dichloroethane has low potential for
bioaccumulation, food is unlikely to be a major source of
exposure.
Concise International Chemical Assessment Document 1

Table 1: Levels of 1,2-dichloroethane in environmental media.

Medium Location Year Concentrations Reference

Ambient air Canada 1988–1990 0.07–0.28 :g/m 3 (means) T. Dann, unpublished data,
1992
Ambient air Japan 1992 <0.004–3.8 :g/m 3 (means) Environment Agency Japan,
1993
Ambient air UK 1982, 1983 1.2 :g/m 3 (mean) Clark et al., 1984a,b
Ambient air Netherlands 1980 1.2 :g/m 3 (mean) Guicherit & Schulting, 1985
Ambient air USA 1980–1982 0.33–6.05 :g/m 3 (means) Singh et al., 1980, 1981, 1982
Indoor air (residential) Canada 1991 <0.1 :g/m 3 (mean) Fellin et al., 1992
Indoor air (residential) USA 0.1–0.5 :g/m 3 (means) US EPA, 1992
Indoor air (residential) Netherlands 1984–1985 3.4 :g/m 3 (mean) Kliest et al., 1989
Drinking-water Canada 1988–1991 <0.05–0.139 :g/litre (mean) P. Lachmaniuk, personal
communication, 1991
1990 <0.2 :g/litre (mean) Ecobichon & Allen, 1990
1982–1983 <0.1 :g/litre (mean) Otson, 1987
Drinking-water USA Early 1980s NDa – 19 :g/litre Letkiewicz et al., 1982
ND – 0.05 :g/litre Barkley et al., 1980
Drinking-water Japan 1976 <0.5–0.9 :g/litre Fujii, 1977
Drinking-water Spain 1987 2–22 :g/litre Freiria-Gandara et al., 1992
Surface water Canada 1981–1985 <0.08 :g/litre Kaiser et al., 1983; Comba &
Kaiser, 1985; Kaiser & Comba,
1986; Lum & Kaiser, 1986
Surface water Japan 1992 0.01–3.4 :g/litre Environment Agency Japan,
1993
Food (34 groups) Canada 1991 <50 :g/kg (solids); <1 :g/litre Enviro-Test Laboratories, 1991
(liquids)
1992 <5 :g/kg (solids); <1 :g/litre Enviro-Test Laboratories, 1992
(liquids)
Food (19 items) USA Not specified ND – 0.31 :g/kg Heikes, 1987, 1990
Not specified ND – 8.2 :g/kg Heikes, 1987
Food (231 items) USA Not specified <9–30 :g/kg Daft, 1988
a Detection limit not reported.

6.2 Human exposure
An example of estimated indirect exposure in the
general environment is presented here. Exposure of the
general population to 1,2-dichloroethane in environ-
mental media may be estimated based on concentrations
determined in various media and reference values for
body weight and consumption patterns. Owing to the
availability of relevant data, exposure has been estimated
based primarily on data from North America. However,
countries are encouraged to estimate total exposure on
the basis of national data, possibly in a manner similar to
that outlined here.
Based on a daily inhalation volume for adults of 22
m3, a mean body weight for males and females of 64 kg,
the assumption that 4 of 24 hours are spent outdoors
(IPCS, 1994), and the range of mean levels of 1,2-
dichloroethane in ambient air of 0.07–0.28 :g/m3 in a
survey of cities across Canada, the mean intake of 1,2-
dichloroethane from ambient air for the general
population is estimated to range from 0.004 to 0.02 :g/kg
body weight per day. The mean intake of 1,2-
dichloroethane in indoor air, based on the assumption
that 20 of 24 hours are spent indoors (IPCS, 1994) and
the range of concentrations in indoor or “personal” air in
Canada and the USA of <0.1–0.5 :g/m3, is estimated to
range from <0.03 to 0.1 :g/kg body weight per day.
Based on a daily volume of water consumption for adults
of 1.4 litres, a mean body weight of 64 kg (IPCS, 1994),
and the mean levels of 1,2-dichloroethane in provincial
surveys in Canada of <0.05–0.139 :g/litre, the mean
intake from drinking-water is estimated to range from
<0.001 to 0.003 :g/kg body weight per day. Intake of
1,2-dichloroethane in food is likely to be negligible, as it
has not been detected in extensive surveys and as it has
low potential for bioaccumulation. Therefore, the
principal source of exposure of the general population to
1,2-dichloroethane is indoor and outdoor air, with only
minor amounts being contributed by drinking-water.
Few data on occupational exposure to 1,2-
dichloroethane were identified. In North America,
workers are exposed to 1,2-dichloroethane principally in
the manufacture of other chemical substances; in such
situations, the principal route of exposure is most likely
inhalation and, possibly, dermal contact.

6
 1,2-Dichloroethane

7. COMPARATIVE KINETICS AND (Barsoum & Saad, 1934; McCollister et al., 1956; Smyth,
METABOLISM IN LABORATORY ANIMALS 1969; Larionov and Kokarovtseva, 1976; Munson et al.,
AND HUMANS 1982; NIOSH, 1994a).

8.2 Irritation and sensitization

1,2-Dichloroethane is readily absorbed following
Application of 1,2-dichloroethane to the skin of
inhalation, ingestion, and dermal exposure and is rapidly
experimental animals has resulted in microscopic
and widely distributed throughout the body. Relative
changes and moderate oedema (Duprat et al., 1976;
distribution of radioactivity (presumably as metabolites)
Kronevi et al., 1981; Jakobson et al., 1982). Similarly,
was similar in rats administered a single oral dose of
histological changes and mild irritation in the eye have
150 mg/kg body weight and those exposed by inhalation
to 150 ppm (600 mg/m3) for 6 hours (Reitz et al., been observed in animals following direct application
1982). 1,2-Dichloroethane is rapidly and extensively (Kuwabara et al., 1968; Duprat et al., 1976). No
metabolized in rats and mice, with principally sulfur- information on the sensitization potential of this
substance was identified.
containing metabolites being eliminated in the urine in a
dose-dependent manner. Metabolism appears to be
8.3 Short-term exposure
saturated or limited in rats at levels of exposure resulting
in concentrations in blood of 5–10 :g/ml (Reitz et al.,
Few data were identified on the toxicity of 1,2-
1982). Levels of DNA alkylation were higher following
dichloroethane following short-term exposure. Degener-
exposure to a bolus dose of 150 mg/kg body weight by
ation and necrosis of the liver and kidneys, accompanied
gavage compared with inhalation of 150 ppm (600 mg/m3)
by congestion and haemorrhage of the lungs and
over a 6-hour period (Reitz et al., 1982).
adrenal glands, were observed in small groups of rats,
rabbits, guinea-pigs, dogs, and pigs exposed to 1,2-
Available data suggest that 1,2-dichloroethane is
metabolized via two principal pathways. The first dichloroethane by inhalation at 6000 mg/m3, 7 hours/day,
involves a saturable microsomal oxidation mediated by for 6 days (Heppel et al., 1945). No effects on body or
cytochrome P-450 to 2-chloroacetaldehyde and 2-chloro- organ weights, histology, or clinical chemistry were
noted in rats administered oral doses of up to 150 mg/kg
ethanol, followed by conjugation with glutathione. The
body weight per day for 2 weeks (van Esch et al., 1977;
second pathway entails direct conjugation with
Reitz et al., 1982).
glutathione to form S-(2-chloroethyl)-glutathione, which
may be non-enzymatically converted to a glutathione
8.4 Long-term exposure
episulfonium ion; this ion can form adducts with
proteins, DNA, or RNA. Although DNA damage has
8.4.1 Subchronic exposure
been induced by the P-450 pathway in vitro (Banerjee et
al., 1980; Guengerich et al., 1980; Lin et al., 1985), several
The results of subchronic studies in several
lines of evidence indicate that the glutathione
species of experimental animals indicate that the liver
conjugation pathway is probably of greater significance
and kidneys are the target organs of 1,2-dichloroethane
than the P-450 pathway as the major route for DNA
exposure; however, most of these studies were inade-
damage (Guengerich et al., 1980; Rannug, 1980;
quate to serve as a basis for establishing reliable no-
Sundheimer et al., 1982; Inskeep et al., 1986; Koga et al.,
observed-effect levels or lowest-observed-effect levels,
1986; Simula et al., 1993).
generally because of the inadequate documentation and
the limited range of end-points examined in small groups
of animals. In a series of early limited studies,
morphological changes in the liver were observed in
8. EFFECTS ON LABORATORY MAMMALS
several species following subchronic exposure (7
AND IN VITRO TEST SYSTEMS hours/day) to airborne concentrations as low as 800
mg/m3 (Heppel et al., 1946; Spencer et al., 1951; Hofmann
et al., 1971). Increases in relative liver weight have been
8.1 Single exposure observed in rats following subchronic oral
administration of doses of 49–82 mg/kg body weight per
1,2-Dichloroethane is moderately acutely toxic in day and above for 13 weeks (van Esch et al., 1977; NTP,
experimental animals. For example, LC50s for rats 1991).
exposed by inhalation for 6 or 7.25 hours ranged from
4000 mg/m3 (Spencer et al., 1951) to 6600 mg/m3 (Bonnet
et al., 1980), whereas oral LD 50s for rats, mice, dogs, and
rabbits ranged from 413 to 2500 mg/kg body weight

7
Concise International Chemical Assessment Document 1
8.4.2 Chronic exposure and carcinogenicity
Little information was presented on non-neoplastic
effects in available chronic studies. Changes in serum
parameters indicative of liver and kidney toxicity were
observed in groups of 8–10 male or female Sprague-
Dawley rats exposed to airborne concentrations as low
as 202 mg/m3 for 12 months, although histopathological
examinations were not conducted in this study
(Spreafico et al., 1980).
The carcinogenicity of 1,2-dichloroethane has
been investigated in a few limited bioassays in experi-
mental animals (limitations include short duration of
exposure and high mortality). In an inhalation study, no
significant increase in the incidence of any type of
tumour was reported in groups of 90 male or female
Sprague-Dawley rats exposed to concentrations of
1,2-dichloroethane up to 150 ppm (607 mg/m3), 7 hours/
day, 5 days/week, for 78 weeks and observed until
spontaneous death (Maltoni et al., 1980). However,
mortality was high in this study, although it was not
related to concentration, and incidence rates were not
adjusted for differential mortality among groups. There
was a non-significant increase in the incidence of
mammary gland adenomas and fibroadenomas in female
Sprague-Dawley rats (n = 50) exposed to 1,2-dichloro-
ethane at 50 ppm (200 mg/m3), 7 hours/day, 5 days/ week,
for 2 years in an assay in which no other compound-
related toxicity was observed (Cheever et al., 1990). No
increase in the incidence of any type of tumour was
observed in groups of 90 male or female Swiss mice
exposed to concentrations of 1,2-dichloroethane up to
150 ppm (607 mg/m3), 7 hours/day, 5 days/ week, for 78
weeks and observed until spontaneous death (Maltoni
et al., 1980).
In contrast, there has been convincing evidence of
increases in tumour incidence in two species following
ingestion. There were significant increases in the
incidence of tumours at several sites in Osborne-Mendel
rats (n = 50 of each sex in exposed groups; n = 20
matched controls; n = 60 pooled controls) administered
time-weighted-average doses of 47 or 95 mg/kg body
weight per day in corn oil by gavage, 5 days/week, for 78
weeks, followed by 32 weeks of observation. The
incidence of squamous cell carcinomas of the stomach
was significantly increased in both groups of exposed
males (0/60, 0/20, 3/50, and 9/50 in pooled [from
concurrent studies] vehicle controls, matched vehicle
controls, low-dose group, and high-dose group,
respectively). There were also significant increases in
the incidence of haemangiosarcomas in exposed males
(1/60, 0/20, 9/50, and 7/50) and females (0/59, 0/20, 4/50,
and 4/50). The incidence of fibromas of the
subcutaneous tissue was significantly increased in
exposed males (0/60, 0/20, 5/50, and 6/50). In females,
8
there were significant increases in the incidences of
adenocarcinomas and fibroadenomas (combined) of the
mammary gland (6/59, 0/20, 15/50, and 24/50). Mortality
was significantly higher in both males and females in the
high-dose group, and there was a greater frequency of
clinical signs of toxicity in exposed rats compared with
controls. Chronic murine pneumonia was present in
60–94% of rats in each group, although the incidence
was not related to dose (NCI, 1978).
In a similar bioassay, B6C3F1 mice (n = 50 of each
sex in exposed groups; n = 20 matched controls;
n = 60 pooled controls) were administered time-
weighted-average doses of 97 or 195 mg/kg body weight
per day (males) and 149 or 299 mg/kg body weight per
day (females) in corn oil by gavage, 5 days/week, for 78
weeks, followed by 13 weeks of observation. The
incidence of hepatocellular carcinomas was significantly
increased in exposed males (4/59, 1/19, 6/47, and 12/48 in
pooled vehicle controls, matched vehicle controls, low-
dose group, and high-dose group, respectively),
although the authors noted that the increase in the
incidence of this tumour could not be convincingly
attributed to the test chemical, owing to the high
variability of hepatocellular neoplasms among historical
controls. The incidence of alveolar/bronchiolar
adenomas was significantly increased in males in the
high-dose group (0/59, 0/19, 1/47, and 15/48) and in both
groups of exposed females (2/60, 1/20, 7/50, and 15/48);
one female in the high-dose group had an
alveolar/bronchiolar carcinoma. The incidence of
mammary gland adenocarcinomas was significantly
increased in females at both doses (0/60, 0/20, 9/50, and
7/48). The incidence of endometrial stromal polyp or
endometrial stromal sarcoma (combined) in females was
significantly elevated at both doses (0/60, 0/20, 5/49, and
5/47). There was a dose-related increase in mortality in
females, but not in males; in addition, body weight was
decreased in females receiving the higher dose (NCI,
1978).
The incidence of lung tumours (benign lung papil-
lomas) was significantly increased in female non-inbred
Ha:ICR mice (n = 30) following repeated dermal applica-
tion of 1,2-dichloroethane, 3 times/week, for 440–594
days (van Duuren et al., 1979). Repeated intraperitoneal
injections of 1,2-dichloroethane resulted in a dose-
related increase in the number of pulmonary adenomas
per mouse in a screening bioassay in a susceptible strain
(A/St), although none of these increases was significant
(Theiss et al., 1977). Concomitant exposure to inhaled
1,2-dichloroethane and disulfiram in the diet resulted in
an increased incidence of intrahepatic bile duct
cholangiomas and cysts, subcutaneous fibromas,
hepatic neoplastic nodules, interstitial cell tumours in the
testes, and mammary adenocarcinomas in rats, compared
with rats administered either compound alone or

untreated controls (Cheever et al., 1990). No potential to
initiate or promote tumour development was evident in
three bioassays (van Duuren et al., 1979; Klaunig et al.,
1986; Story et al., 1986; Milman et al., 1988), although the
extent of histopathological examination was limited in
these studies.
8.5 Genotoxicity and related end-points
1,2-Dichloroethane has been consistently
demonstrated to be genotoxic in numerous in vitro
(Table 2) and in vivo (Table 3) assays for a wide range of
end-points. It has been mutagenic in Salmonella
typhimurium, especially in the presence of an exogenous
activation system, and induces unscheduled DNA
synthesis, induces gene mutation, and forms adducts
with DNA in mammalian cells in vitro. It binds to DNA
in all reported in vivo studies in rats and mice. 1,2-
Dichloroethane has also induced somatic cell and sex-
linked recessive lethal mutations in Drosophila
melanogaster.
Available data on genotoxicity are consistent
with the hypothesis that the glutathione pathway of
conjugation (i.e. production of the glutathione epi-
sulfonium ion) is probably of greater significance than
the P-450 pathway as the major route for DNA damage
(Guengerich et al., 1980; Rannug, 1980; Sundheimer et al.,
1982; Inskeep et al., 1986; Koga et al., 1986; Simula et al.,
1993); mutation frequency in human cell lines has been
correlated with variations in levels of glutathione-S-
transferase activities (Crespi et al., 1985).
8.6 Reproductive and developmental
toxicity
Based on the results of a limited number of
studies, there is no evidence that 1,2-dichloroethane is
teratogenic in experimental animals and little convincing
evidence that it induces reproductive or developmental
effects at doses below those that cause other systemic
effects (Alumot et al., 1976; Vozovaya, 1977; Kavlock et
al., 1979; Rao et al., 1980; Lane et al., 1982).
8.7 Immunological and neurological
effects
Immunological effects, including reduced
resistance to streptococcal challenge, decreased
pulmonary bactericidal activity in mice, and altered levels
of antibody production in rabbits, have been observed
following acute or subchronic exposure to
1,2-dichloroethane at 20 and 10 mg/m3 and above,
respectively (Shmuter, 1977; Sherwood et al., 1987),
whereas there were no effects in rats exposed to up to
800 mg/m3 for several days (Sherwood et al., 1987).
9
1,2-Dichloroethane
Effects on antibody levels and reversible effects on cell-
mediated responses were also noted in mice exposed to
1,2-dichloroethane in drinking-water at concentrations
equivalent to doses of 3 mg/kg body weight per day and
above for 14 or 90 days (Munson et al., 1982).
Data on the neurological effects of 1,2-dichloro-
ethane have not been identified.
9. EFFECTS ON HUMANS
9.1 Case reports
Acute incidental exposure to 1,2-dichloroethane by
inhalation or ingestion has resulted in a variety of effects
in humans, including effects on the central nervous
system, liver, kidney, lung, and cardiovascular system
(e.g. Hinkel, 1965; Suveev & Babichenko, 1969; Dorndorf
et al., 1975; Andriukin, 1979; Nouchi et al., 1984). Based
on limited available data in humans, the lethal oral dose
of 1,2-dichloroethane has been estimated to be between
20 and 50 ml.
9.2 Epidemiological studies
The potential carcinogenicity of 1,2-dichloroethane
in exposed human populations has not been extensively
investigated. Mortality due to pancreatic cancer was
significantly increased (standardized mortality ratio
[SMR] = 492, based on eight cases) in a group of 278
workers at a chemical production plant who had been
principally exposed to 1,2-dichloroethane in combination
with other chemicals. Mortality due to this cause
increased with duration of exposure. In addition,
although the number of cases was small (i.e. four) and
the association with duration of exposure was less
consistent, mortality due to leukaemia was also
increased in these workers (Benson & Teta, 1993).
No association between occupational exposure to
1,2-dichloroethane and brain cancer was noted in a small
case–control study (Austin & Schnatter, 1983).
Although the incidence of colon and rectal cancer
increased with concentration of 1,2-dichloroethane in
drinking-water in an inherently limited ecological study,
concomitant exposure to other substances may have
contributed to the observed effects (Isacson et al., 1985).
Concise International Chemical Assessment Document 1

Table 2: Genotoxicity of 1,2-dichloroethane in vitro

(modified from ATSDR, 1992).

Result
With Without
Species (test system) End-point activation activation Reference
PROKARYOTIC SYSTEMS
Salmonella typhimurium Gene mutation + + Milman et al., 1988

+ + Barber et al., 1981

+ + Kanada & Uyeta, 1978

+ + Nestmann et al., 1980

+ + Rannug et al., 1978

+ + van Bladeren et al., 1981

+ NT Rannug & Beije, 1979

+ – Cheh et al., 1980

+ – Moriya et al., 1983

– – King et al., 1979

+ + Strobel & Grummt, 1987

NT +a Simula et al., 1993

S. typhimurium/spot test Gene mutation NT (+) Brem et al., 1974

(+) – Principe et al., 1981

NT – Buijs et al., 1984

S. typhimurium/Ara test (standard) Gene mutation + – Roldan-Arjona et al., 1991

S. typhimurium/Ara test (liquid) Gene mutation (+) (+) Roldan-Arjona et al., 1991

Streptomyces coelicolor Gene mutation NT – Principe et al., 1981

Escherichia coli K12/343/113 Gene mutation – – King et al., 1979

E. coli wp2 Gene mutation NT (+) Hemminki et al., 1980

– – Moriya et al., 1983

E. coli Pol A DNA damage NT (+) Brem et al., 1974

Bacillus subtilis/rec– assay DNA damage NT – Kanada & Uyeta, 1978

EUKARYOTIC ORGANISMS
— FUNGI
Aspergillus nidulans Gene mutation NT – Crebelli & Carere, 1988

NT – Principe et al., 1981

A. nidulans Mitotic segregation aberrations NT + Crebelli et al., 1984

A. nidulans Aneuploidy induction NT + Crebelli et al., 1988

Saccharomyces cerevisiae Mitotic recombination NT (+) Simmon, 1980

— ANIMAL SYSTEMS
Hamster CHO/HGPRT Gene mutation + (+) Tan & Hsie, 1981

+ (+) Zamora et al., 1983

Rat hepatocytes Unscheduled DNA synthesis NT + Williams et al., 1989

Mouse hepatocytes Unscheduled DNA synthesis NT + Milman et al., 1988

Mouse liver DNA DNA binding + NT Banerjee, 1988

Calf thymus DNA DNA binding + NT Prodi et al., 1986

Salmon sperm DNA DND binding + – Banerjee & van Duuren,

1979; Banerjee et al., 1980

Mouse BALB/c-3T3 Cell transformation NT – Milman et al., 1988

NT – Tu et al., 1985

Mouse C3H1OT½ Cell transformation NT +b Schultz et al., 1992

Syrian hamster embryo cells Cell transformation NT + Hatch et al., 1983

— HUMAN CELLS
Human lymphoblasts AHH-1 Gene mutation NT + Crespi et al., 1985

Human lymphoblasts TK6 Gene mutation NT + Crespi et al., 1985

Human embryo epithelial-like EUE Gene mutation NT + Ferreri et al., 1983

cells

Human peripheral lymphocytes Unscheduled DNA synthesis + – Perocco & Prodi, 1981

NT = not tested – = negative result + = positive result (+) = weakly positive or marginal result
a Increase in cells expressing GSTA1-1.

b Transformed cells induced tumours in nude mice.

10
 1,2-Dichloroethane

Table 3: Genotoxicity of 1,2-dichloroethane in vivo

(modified from ATSDR, 1992).

Species (test system) End-point Results Reference

MAMMALIAN ASSAYS
Mouse Dominant lethal mutations – Lane et al., 1982

Mouse/spot test Gene mutation (+) Gocke et al., 1983

Mouse bone marrow Sister chromatid exchange + Giri & Que Hee, 1988

Mouse bone marrow Micronuclei – King et al., 1979; Jenssen & Ramal, 1980

Mouse peripheral erythrocytes Micronuclei – Armstrong & Galloway, 1993

Mouse liver, kidney, lung, and stomach DNA binding + Prodi et al., 1986

Mouse liver, kidney, lung, and stomach DNA binding + Arfellini et al., 1984
Mouse forestomach and kidney DNA binding + Hellman & Brandt, 1986

Mouse liver DNA binding + Banerjee, 1988

Rat liver, kidney, spleen, lung, forestomach, DNA binding + Reitz et al., 1982
and stomach

Rat liver, kidney, lung, and stomach DNA binding + Arfellini et al., 1984

Rat liver, kidney, lung, and stomach DNA binding + Prodi et al., 1986

Rat liver and kidney DNA binding + Inskeep et al., 1986

Rat liver and lung DNA binding + Baertsch et al., 1991

Rat liver DNA binding + Banerjee, 1988

Rat liver DNA binding + Cheever et al., 1990

Mouse liver DNA damage + Storer & Conolly 1983, 1985; Storer et al., 1984

Mouse liver DNA damage + Taningher et al., 1991

INSECT ASSAYS
Drosophila melanogaster/somatic mutation Gene mutation + Nylander et al., 1978
D. melanogaster/somatic mutation Gene mutation + Romert et al., 1990

D. melanogaster/somatic mutation Gene mutation + Kramers et al., 1991

D. melanogaster/somatic mutation Gene mutation (+) Ballering et al., 1993

D. melanogaster/recessive lethal Gene mutation + Ballering et al., 1993

D. melanogaster/vermilion locus Gene mutation + Ballering et al., 1993

D. melanogaster/sex-linked recessive Gene mutation + King et al., 1979

D. melanogaster/sex-linked recessive Gene mutation + Kramers et al., 1991

D. melanogaster Chromosomal loss/gain +/+ Valencia et al., 1984

HOST-MEDIATED ASSAYS
Escherichia coli K12/343/113 mouse host- Gene mutation – King et al., 1979
mediated assay

– = negative result + = positive result (+) = weakly positive or marginal result

10. EFFECTS ON OTHER ORGANISMS IN
THE LABORATORY AND FIELD
10.1 Aquatic environment
The effects of exposure to 1,2-dichloroethane on a
number of aquatic organisms in the laboratory and field
have also been investigated. In bacteria, the lowest
reported IC50s for inhibition of gas production and
ammonia consumption were 25 and 29 mg/litre in
methanogens and Nitrosomonas, respectively (Blum &
Speece, 1991). The most sensitive freshwater alga
studied was Microcystis aeruginosa, in which an EC50
for inhibition of cell multiplication of 105 mg/litre was
observed (Bringmann & Kühn, 1978); in the only
identified study in marine algae, an EC50 for carbon
uptake of 340 mg/litre was reported in Phaeodactylum
tricornutum (Pearson & McConnell, 1975). Toxicity
thresholds (cell multiplication inhibition) were above 800
mg/litre for three species of aquatic protozoa (Bringmann
& Kühn, 1980).
The lowest reported LC50 value for Daphnia was
220 mg/litre (Leblanc, 1980), whereas the lowest EC50 (for
10% immobilization) was 150 mg/litre (Freitag et al., 1994).
Effects on reproductive success and growth were
observed in Daphnia at 20.7 and 71.7 mg/litre,
respectively. There were no effects on these end-points
at 10.6 and 41.6 mg/litre, respectively (Richter et al.,
1983).

11
Concise International Chemical Assessment Document 1
Based on available data, the most sensitive
freshwater vertebrate species appears to be the north-
western salamander, in which 9-day larval survival (4
days post-hatch) was reduced at 2.5 mg/litre (Black et al.,
1982).
10.2 Terrestrial environment
Identified data on the toxicity of 1,2-dichloro-
ethane to terrestrial organisms are inadequate to permit
assessment.
11. EFFECTS EVALUATION
11.1 Evaluation of health effects
11.1.1 Hazard identification and dose–response
assessment
Based on limited available data in humans, the
lethal oral dose of 1,2-dichloroethane has been estimated
to be between 20 and 50 ml. 1,2-Dichloroethane is
moderately acutely toxic by inhalation, based on the
results of studies in experimental animals. Skin and eye
irritation may also be induced by 1,2-dichloroethane.
Owing to the limitations of the available studies in
humans, it is necessary to rely on available experimental
data in animal species as a basis for derivation of no-
effect levels or quantitative estimates of carcinogenic
potency. However, in most of the identified short-
term and subchronic studies, only a limited range of end-
points was examined and documentation was
incomplete. Similarly, little information on non-
neoplastic effects was presented in the long-term
carcinogenicity bioassays. Lowest reported effect levels
were 49–82 mg/kg body weight per day for 13 weeks
(increases in liver weight in rats) for ingestion (NTP,
1991) and 202 mg/m3 (effects on liver and kidney
function in rats exposed for 12 months) for inhalation
(Spreafico et al., 1980). Based on limited data, there is no
evidence that 1,2-dichloroethane is teratogenic in
experimental animals or that it induces reproductive or
developmental effects at doses below those that cause
other systemic effects.
Based on the limited evidence of carcinogenicity in
workers exposed principally to 1,2-dichloroethane in the
most reliable epidemiological study conducted to date
(Benson & Teta, 1993), the induction of both rare and
common tumours in rats and mice exposed by ingestion
(NCI, 1978) and supporting evidence in other
12
limited bioassays, the production of a reactive inter-
mediate that alkylates DNA in vivo, and positive results
in a range of in vitro assays for genotoxicity, 1,2-
dichloroethane is considered to be a probable human
carcinogen.
The carcinogenic potency of 1,2-dichloroethane
has been calculated based on the increased incidence of
squamous cell carcinomas of the stomach, haemangio-
sarcomas, fibromas of the subcutaneous tissue, and
adenocarcinomas or fibroadenomas (combined) of
the mammary gland in Osborne-Mendel rats exposed
orally by gavage, as well as the increased incidence of
alveolar/bronchiolar adenomas, hepatocellular
carcinomas, mammary gland adenocarcinomas, and
endometrial stromal polyps or sarcomas (combined) in
similarly exposed B6C3F1 mice; data from both the
matched (same study) and pooled (concurrent studies)
vehicle controls were incorporated. It should be noted,
however, that mortality was higher at the high dose in
female mice and rats of both sexes than in other dose
groups in this study. Therefore, these high-dose groups
were not included in the derivation of quantitative
estimates of carcinogenic potency.
Based on multistage modelling of these data,
amortized for continuous exposure for a standard
duration of 104 weeks and corrected for the expected rate
of increase in tumour formation in rodents in a standard
bioassay of 104 weeks, the doses associated with a 5%
increase in tumour incidence (TD0.05s) range from 6.2 to
34 mg/kg body weight per day. Incorporation of a
scaling factor for the differences in body surface area
between rodents and humans was not considered
appropriate, as it is likely that the carcinogenicity of 1,2-
dichloroethane is due to a metabolite, rather than to the
parent compound.
11.1.2 Criteria for setting guidance values for 1,2-
dichloroethane
As available data indicate that 1,2-dichloroethane
is a genotoxic carcinogen, exposure should be reduced
to the extent possible. The following guidance is
provided as a possible basis for derivation of limits of
exposure and judgement of the quality of environmental
media by relevant authorities, based on the potential
carcinogenicity of 1,2-dichloroethane in humans. Based
on available data, air is believed to be the principal
source of exposure in the general environment (see
section 6.2) and, therefore, is the principal medium
addressed here. Available data are considered
inadequate to serve as a basis for development of
tolerable intakes for non-neoplastic effects.

Although it is desirable to reduce exposure to
genotoxic carcinogens to the extent possible, a value, for
example, 5000 or 50 000 times less than the TD0.05s might
be considered appropriate as a guidance value. This
margin (5000–50 000) affords protection similar to that
associated with the range for low-dose risk estimates
generally considered by various agencies to be
“essentially negligible” (i.e. 10–5 to 10–6). This
corresponds to a range of airborne concentrations of
3.6–20 :g/m3 or 0.36–2.0 :g/m3. (Corresponding values
for ingestion are 1.2–6.8 :g/kg body weight per day or
0.12–0.68 :g/kg body weight per day.)
It should be noted, however, that the risk of
exposure in air is most likely overestimated, as the
TD 0.05s were based on a study in which the experimental
animals were administered bolus doses of 1,2-dichloro-
ethane by gavage, whereas exposure in the general
population is likely to be mostly via inhalation. Based
on available data, the carcinogenic potency of 1,2-
dichloroethane appears to be less following inhalation
than following ingestion of bolus doses, most likely
because of inter-route variations in toxicokinetics.
11.1.3 Sample risk characterization
Non-neoplastic effects in animals have been
observed only at concentrations more than 700 000 times
greater than those in the principal medium of exposure
(air) in the general environment, based on the sample
estimation of exposure presented in section 6.2 for
indirect exposure in the general environment. Identified
data are inadequate to allow an estimation of exposure to
1,2-dichloroethane in the occupational environment.
Although, wherever possible, exposure to geno-
toxic carcinogens should be reduced to the extent
possible, indirect population exposure in the general
environment, based on the sample estimate presented in
section 6.2, is up to approximately 300 times less than a
guidance value that might be considered appropriate on
the basis of available dose–response data for carcino-
genicity (i.e. 3.6–20 :g/m3 or 0.36–2.0 :g/m3, the
TD 0.05s divided by 5000 or 50 000). Identified data are
inadequate to estimate exposure to 1,2-dichloroethane in
the occupational environment.
11.2 Evaluation of environmental effects
Because 1,2-dichloroethane is released principally
in emissions from industrial sources and because of its
high volatility, the atmosphere is the predominant
environmental sink for 1,2-dichloroethane. It is
moderately persistent in air. Stratospheric photolysis
may produce chlorine radicals, which may in turn react
13
1,2-Dichloroethane
with ozone. However, the ozone depleting potential is
low (0.001 relative to CFC-11), and the compound is not
listed in the Montreal Protocol on Substances that
Deplete the Ozone Layer.
Terrestrial organisms will have the greatest
potential for exposure to 1,2-dichloroethane in ambient
air. However, available data on the effects of 1,2-
dichloroethane are inadequate to allow the character-
ization of risks in terrestrial species.
Although 1,2-dichloroethane may be released to
surface waters or soil through industrial processes and
disposal, and although hydrolysis and microbial
degradation are slow, the substance is not likely to
persist in these media because of its volatility. A range
of toxicity tests in aquatic species have indicated that
effect levels are generally above 10 mg/litre. As
concentrations in surface waters are generally several
orders of magnitude less than those demonstrated to
cause effects, it is likely that 1,2-dichloroethane poses
negligible risk to aquatic organisms.
12. PREVIOUS EVALUATIONS BY
INTERNATIONAL BODIES
The International Agency for Research on Cancer
(IARC, 1979) has classified 1,2-dichloroethane in group
2B (possibly carcinogenic to humans) based on suffi-
cient evidence of carcinogenicity in experimental
animals.
The Joint FAO/WHO Expert Committee on Food
Additives (JECFA) has evaluated 1,2-dichloroethane on
three occasions (WHO, 1971, 1980, 1992). In its last
evaluation, the Committee concluded that this com-
pound is genotoxic in both in vitro and in vivo test
systems and carcinogenic in mice and rats when
administered by the oral route. No acceptable daily
intake (ADI) was therefore allocated. The Committee
expressed the opinion that 1,2-dichloroethane should
not be used in food.
In the current WHO Guidelines for drinking-water
quality (WHO, 1993), the concentrations of 1,2-dichloro-
ethane in drinking-water estimated to be associated with
excess risks of 10–4, 10–5, and 10–6 are 300, 30, and 3
:g/litre, respectively, based on linear multistage
modelling of the incidence of haemangiosarcomas in
male rats in the NCI (1978) study.
Information on international hazard classification
and labelling is included in the International Chemical
Safety Card reproduced in this document.
Concise International Chemical Assessment Document 1

vicinity. Because the substance is absorbed through the

13. HUMAN HEALTH PROTECTION AND
EMERGENCY ACTION
Human health hazards, together with preventative
and protective measures and first aid recommendations,
are presented on the International Chemical Safety Card
(ICSC 0250) reproduced in this document.
skin, do not touch or walk through the spilled material
without proper equipment. To avoid the flammability
hazard, remove wet or contaminated clothing immediate-
ly, and use non-sparking tools for clean-up. Do not let
the substance enter the drains or watercourses.
The IDLH (Immediately Dangerous to Life or
Health) value for this substance is very low, at 50 ppm
(200 mg/m3) (NIOSH, 1994b).

13.1 Human health hazards

1,2-Dichloroethane is highly flammable. On long- 14. CURRENT REGULATIONS,

term or repeated exposure, it is considered to be a GUIDELINES, AND STANDARDS
probable human carcinogen.

13.2 Advice to physicians Information on national regulations, guidelines,

In case of emergency, it is important to wash skin
with soap and water after removing contaminated
clothing. In the event of poisoning, the treatment is
symptomatic and supportive. Survival for 48 hours
usually implies complete recovery, although deaths have
occurred up to 5 days after exposure.
13.3 Health surveillance advice
Monitoring of both liver and kidney functions
should be included in the health surveillance programme
of humans exposed to 1,2-dichloroethane.
and standards is available from the International Register
of Potentially Toxic Chemicals (IRPTC) legal file.
The reader should be aware that regulatory
decisions about chemicals taken in a certain country can
be fully understood only in the framework of the
legislation of that country. The regulations and
guidelines of all countries are subject to change and
should always be verified with appropriate regulatory
authorities before application.

13.4 Explosion and fire hazards

13.4.1 Explosion hazards

1,2-Dichloroethane vapours of between 6 and 12%

in air form an explosive mixture.

13.4.2 Fire hazards

1,2-Dichloroethane is highly flammable.

13.4.3 Prevention

Because of its low electroconductivity, 1,2-

dichloroethane can generate electrostatic charges as a
result of flow or agitation. Use only closed systems,
ventilation, and explosion-proof electrical equipment.
All equipment must be grounded.

13.5 Spillage

1,2-Dichloroethane is highly flammable. In the

event of spillage, eliminate all sources of ignition in the

14
1,2-DICHLOROETHANE 0250
March 1995
CAS No: 107-06-2 Ethylene dichloride
RTECS No: KI0525000 1,2-Ethylene dichloride
UN No: 1184 Ethane dichloride
EC No: 602-012-00-7 ClCH2CH2Cl / C2H4Cl2
Molecular mass: 98.96

TYPES OF
HAZARD/ ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING
EXPOSURE

FIRE Highly flammable. Gives off NO open flames, NO sparks, and Powder, water spray, foam, carbon
irritating or toxic fumes (or gases) NO smoking. dioxide.
in a fire.

EXPLOSION Vapour/air mixtures are explosive. Closed system, ventilation, In case of fire: keep drums, etc.,
explosion-proof electrical equipment cool by spraying with water.
and lighting. Prevent build-up of
electrostatic charges (e.g., by
grounding). Do NOT use
compressed air for filling,
discharging, or handling.

EXPOSURE AVOID ALL CONTACT! IN ALL CASES CONSULT A

DOCTOR!

Inhalation Abdominal pain. Cough.
Dizziness. Drowsiness. Headache.
Nausea. Sore throat.
Unconsciousness. Vomiting.
Symptoms may be delayed (see
Notes).
Ventilation, local exhaust, or Fresh air, rest. Half-upright
breathing protection. position. Artificial respiration if
indicated. Refer for medical
attention.

Skin Redness. Protective gloves. Remove contaminated clothes.

Rinse and then wash skin with
water and soap. Refer for medical
attention.

Eyes Redness. Pain. Blurred vision. Safety goggles, face shield, or eye First rinse with plenty of water for
protection in combination with several minutes (remove contact
breathing protection. lenses if easily possible), then take
to a doctor.

Ingestion Abdominal cramps. Diarrhoea Do not eat, drink, or smoke during Give nothing to drink. Refer for
(further see Inhalation). work. Wash hands before eating. medical attention.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Evacuate danger area! Collect leaking and spilled F Symbol Unbreakable packaging; put
liquid in sealable containers as far as possible. T Symbol breakable packaging into closed
Absorb remaining liquid in sand or inert absorbent R: 45-11-22-36/37/38 unbreakable container. Do not
and remove to safe place. Do NOT wash away into S: 53-45 transport with food and feedstuffs.
sewer (extra personal protection: self-contained Note: E Marine pollutant.
breathing apparatus). UN Hazard Class: 3
UN Subsidiary Risks: 6.1
UN Pack Group: II

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-605 Fireproof. Separated from strong oxidants, food and feedstuffs and other
NFPA Code: H 2; F 3; R 0; incompatible substances (see Chemical Dangers). Cool. Dry.

Prepared in the context of cooperation between the International

IPCS Programme on Chemical Safety and the European Commission
International © IPCS 1999
Programme on
Chemical Safety SEE IMPORTANT INFORMATION ON THE BACK.
0250 1,2-DICHLOROETHANE

IMPORTANT DATA
Physical State; Appearance
COLOURLESS, VISCOUS LIQUID, WITH CHARACTERISTIC
ODOUR. TURNS DARK ON EXPOSURE TO AIR, MOISTURE
AND LIGHT.
Physical Dangers
The vapour is heavier than air and may travel along the ground;
distant ignition possible. As a result of flow, agitation, etc.,
electrostatic charges can be generated.
Chemical Dangers
The substance decomposes on heating and on burning
producing toxic and corrosive fumes including hydrogen
chloride (ICSC # 0163) and phosgene (ICSC # 0007). Reacts
violently with aluminium, alkali metals, alkali amides,
ammonia, bases, strong oxidants. Attacks many metals in
presence of water. Attacks plastic.
Routes of Exposure
The substance can be absorbed into the body by inhalation of
its vapour, through the skin and by ingestion.
Inhalation Risk
A harmful contamination of the air can be reached very quickly
on evaporation of this substance at 20
C.
Effects of Short-term Exposure
The vapour irritates the eyes, the skin and the respiratory tract.
Inhalation of the vapour may cause lung oedema (see Notes).
The substance may cause effects on the central nervous
system, kidneys, liver, resulting in impaired functions.
Effects of Long-term or Repeated Exposure
Repeated or prolonged contact with skin may cause dermatitis.
This substance is probably carcinogenic to humans.

Occupational Exposure Limits

TLV: 10 ppm; 40 mg/m3 (as TWA) (ACGIH 1994-1995).

PHYSICAL PROPERTIES
Boiling point: 83.5
C Relative density of the vapour/air-mixture at 20
C (air = 1): 1.2
Melting point: -35.7
C Flash point: 13
C c.c.
Relative density (water = 1): 1.235 Auto-ignition temperature: 413
C
Solubility in water, g/100 ml: 0.87 Explosive limits, vol% in air: 6.2-16
Vapour pressure, kPa at 20
C: 8.7 Octanol/water partition coefficient as log Pow: 1.48
Relative vapour density (air = 1): 3.42

ENVIRONMENTAL DATA

NOTES
Depending on the degree of exposure, periodic medical examination is indicated. The symptoms of lung oedema often do not
become manifest until a few hours have passed and they are aggravated by physical effort. Rest and medical observation are
therefore essential. Immediate administration of an appropriate spray, by a doctor or a person authorized by him/her, should be
considered.

ADDITIONAL INFORMATION

Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible
LEGAL NOTICE
for the use which might be made of this information

© IPCS 1999

REFERENCES
Alumot E, Nachtomi E, Mandel E, Holstein P (1976) Tolerance
and acceptable daily intake of chlorinated fumigants in the rat
diet. Food and cosmetics toxicology, 14:105–110.
Andriukin AA (1979) [Toxic effect of dichloroethane on the
cardiovascular system.] Klinicheskaya Meditsina (Moscow),
57:43–47 (in Russian).
Arfellini G, Bartoli S, Colacci A, Mazzullo M, Galli MC, Prodi G,
Grilli S (1984) In vivo and in vitro binding of 1,2-dibromoethane
and 1,2-dichloroethane to macromolecules in rat and mouse
organs. Journal of cancer research and clinical oncology,
108:204–213.
Armstrong MJ, Galloway SM (1993) Micronuclei induced in
peripheral blood of E :-PIM-1 transgenic mice by chronic oral
treatment with 2-acetylaminofluorene or benzene but not with
diethylnitrosamine or 1,2-dichloroethane. Mutation research,
302:61–70.
ATSDR (1992) Toxicological profile for 1,2-dichloroethane
(draft). Atlanta, GA, US Department of Health and Human
Services, Public Health Service, Agency for Toxic Substances
and Disease Registry.
Austin SG, Schnatter AR (1983) A case–control study of
chemistry exposures and brain tumors in petrochemical workers.
Journal of occupational medicine, 25(4):313–320.
Baertsch A, Lutz WK, Schlatter C (1991) Effect of inhalation
exposure regimen on DNA binding potency of 1,2-
dichloroethane in the rat. Archives of toxicology, 65:169–176.
Ballering LAP, Nivard MJM, Vogel EW (1993) Characterization
of the genotoxic action of three structurally related 1,2-
dihaloalkanes in Drosophila melanogaster. Mutation research,
285:209–217.
Banerjee S (1988) DNA damage in rodent liver by 1,2-dichloro-
ethane, a hepatocarcinogen. Cancer biochemistry and
biophysics, 10:165–173.
Banerjee S, van Duuren BL (1979) Binding of carcinogenic
halogenated hydrocarbons to cell macromolecules. Journal of
the National Cancer Institute, 63:707–711.
Banerjee S, van Duuren BL, Oruambo FI (1980) Microsome-
mediated covalent binding of 1,2-dichloroethane to lung
microsomal protein and salmon sperm DNA. Cancer research,
40:2170–2173.
Barber RD, Donish WH, Mueller KR (1981) A procedure for the
quantitative measurement of the mutagenicity of volatile liquids
in the Ames Salmonella microsome assay. Mutation research,
90:31–48.
Barkley J, Bunch J, Bursey JT, Castillo N, Cooper SD, Davis JM,
Erickson MD, Harris BSH III, Kirkpatrick M, Michael LC, Parks SP,
Pellizzari ED, Ray M, Smith D, Tomer KB, Wagner R,
Zweidinger RA (1980) Gas chromatography mass spectrometry
computer analysis of volatile halogenated hydrocarbons in man
and his environment — A multimedia environmental study.
Biomedical and environmental mass spectrometry, 7:139–147.
17
1,2-Dichloroethane
Barsoum GS, Saad K (1934) Relative toxicity of certain chlorine
derivatives of the aliphatic series. Quarterly journal of pharmacy
and pharmacology, 7: 205–214.
Benson LO, Teta MJ (1993) Mortality due to pancreatic and
lymphopoietic cancers in chlorohydrin production workers. British
journal of industrial medicine, 50:710–716.
Black JA, Birge WJ, McDonnell WE, Westerman AG, Ramey BA,
Bruser DM (1982) The aquatic toxicity of organic compounds to
embryo–larval stages of fish and amphibians. Lexington, KY,
University of Kentucky (Research Report No. 133).
Blum DJW, Speece RE (1991) A database of chemical toxicity to
environmental bacteria and its use in interspecies comparisons
and correlations. Research journal of the Water Pollution Control
Federation, 63(3):198–207.
Bonnet P, Francin J-M, Grakiski D, Raoult G, Zissu D (1980)
Détermination de la concentration léthale 50 des principaux
hydrocarbures aliphatiques chlorés chez le rat. Archives des
maladies professionnelles de medecine du travail et de securité
sociale (Paris), 41(6–7):317–321.
Brem H, Stein AB, Rosenkranz HS (1974) The mutagenicity and
DNA-modifying effect of haloalkanes. Cancer research,
34:2576–2579.
Bringmann G, Kühn R (1978) Testing of substances for their
toxicity threshold: model organisms Microcystis (Diplocystis)
aeruginosa and Scenedesmus quadricauda. Mitteilungen
Internationale Vereinigung für Theoretische und Angewandte
Limnologie, 21:275–284.
Bringmann G, Kühn R (1980) Comparison of the toxicity
thresholds of water pollutants to bacteria, algae, and protozoa in
the cell multiplication inhibition test. Water research,
14:231–241.
Buijs W, van der Gen A, Mohn GR, Breimer DD (1984) The
direct mutagenic activity of alpha, omega-dihalogenoalkanes in
Salmonella typhimurium. Mutation research, 141:11–14.
Callaghan MA, Slimak MW, Gabel NW, May IP, Fowler CF,
Freed JR, Jennings P, Durfee RL, Whitmore FC, Maestri B,
Mabey WR, Holt BR, Gould C (1979) Water-related fate of 129
priority pollutants. Vol. II. Washington, DC, US Environmental
Protection Agency (EPA 40/4-79-029b).
Cheever KL, Cholakis JM, El-Hawari AM, Kovatch RM,
Weisburger EK (1990) Ethylene dichloride: the influence of
disulfiram or ethanol on oncogenicity, metabolism and DNA
covalent binding in rats. Fundamental and applied toxicology,
14:243–261.
Cheh AM, Hooper AB, Skochdopole J, Henke CA, McKinnell RG
(1980) A comparison of the ability of frog and rat S-9 to activate
promutagens in the Ames test. Environmental and molecular
mutagenesis, 2:487–508.
Chemical Marketing Reporter (1992) Chemical profile: ethylene
dichloride. Chemical Marketing Reporter magazine, 241(19):42.
Clark AI, McIntyre AE, Lester JN, Perry R (1984a) Ambient air
measurement of aromatic and halogenated hydrocarbons at
urban, rural, and motorway locations. The science of the total
environment, 39:265–279.
Concise International Chemical Assessment Document 1
Clark AI, McIntyre AE, Perry R, Lester JN (1984b) Monitoring and
assessment of ambient atmospheric concentrations of aromatic
and halogenated hydrocarbons at urban, rural, and motorway
locations. Environmental pollution series B, 7:141–158.
Comba ME, Kaiser KLE (1985) Volatile halocarbons in the
Detroit River and their relationship with contaminant sources.
Journal of Great Lakes research, 11(3):404–418.
CPI (1991) CPI product profiles: ethylene dichloride. Don Mills,
Ontario, Canadian Process Industries, Corpus Information
Services.
Crebelli R, Carere A (1988) Genotoxic activity of halogenated
aliphatic hydrocarbons in Aspergillus nidulans. Journal of
occupational toxicology, 8:437–442.
Crebelli R, Conti G, Conti L, Carere A (1984) Induction of
somatic segregation by halogenated aliphatic hydrocarbons in
Aspergillus nidulans. Mutation research, 138:33–38.
Crebelli R, Benigni R, Franekic J, Conti G, Conti L, Carere A
(1988) Induction of chromosome malsegregation by
halogenated organic solvents in Aspergillus nidulans: unspecific
or specific mechanism? Mutation research, 201:401–411.
Crespi CL, Seixas GM, Turner TR, Ryan CG, Penman BW (1985)
Mutagenicity of 1,2-dichloroethane and 1,2-dibromoethane in
two human lymphoblastoid cell lines. Mutation research,
142:133–140.
Daft JL (1988) Rapid determination of fumigant and industrial
chemical residues in food. Journal of the Association of Official
Analytical Chemists, 71(4):748–760.
Dilling WL, Tefertiller NB, Kalos GJ (1975) Evaporation rates
and reactivities of methylene chloride, chloroform, 1,1,1-
trichloroethane, trichloroethylene, tetrachloroethylene, and
other chlorinated compounds in dilute aqueous solutions.
Environmental science and technology, 9(9):833–838.
Dorndorf W, Kresse M, Christian W, Katritzki KG (1975)
[Dichloroethane poisoning with myoclonic syndrome, epileptic
attacks, and irreversible cerebral effects.] Archiv für Psychiatrie
und Nervenkrankheiten, 220:373–379 (in German).
Duprat P, Delsaut L, Gradiski D (1976) Pouvoir irritant des
principaux solvants chlorés aliphatiques sur la peau et les
muqueuses oculaires du lapin. European journal of toxicology,
9:171–177.
Ecobichon DJ, Allen MC (1990) New Brunswick — Water Quality
Surveillance Program, New Brunswick public water supplies,
data summary report 1990. New Brunswick Department of Health
and Community Services.
Environment Agency Japan (1993) Chemicals in the
environment — 1993. Tokyo.
Enviro-Test Laboratories (1991) Cayley background study:
analysis of food products for target organic and inorganic
parameters. Edmonton (Report No. 91-E1208).
Enviro-Test Laboratories (1992) Windsor area background study:
analysis of food products for target organic and inorganic
parameters. Edmonton (Report No. E1052).
18
Fellin P, Barnett SE, Tran QA (1992) Results of a national pilot
survey of airborne volatile organic compounds in Canadian
residences. Vol. 1. Prepared by Concord Environmental
Corporation for Health and Welfare Canada, Ottawa, Ontario.
Ferreri AM, Rocchi P, Capucci A, Prodi G (1983) Induction of
diphtheria toxin-resistant mutants in human cells by
halogenated compounds. Journal of cancer research and
clinical oncology, 105:111–112.
Freiria-Gandara MJ, Lorenzo-Ferreira RA, Alvarez-Devesa A,
Bermejo F (1992) Occurrence of halogenated hydrocarbons in
the water supply of different cities of Galicia (Spain).
Environmental technology, 13:437–447.
Freitag D, Ballhorn L, Behechti A, Fischer K, Thumm W (1994)
Structural configuration and toxicity of chlorinated alkanes.
Chemosphere , 28(2):253–259.
Fujii T (1977) Direct aqueous injection gas
chromatography–mass spectrometry for analysis of organohalides
in water at concentrations below the parts per billion level.
Journal of chromatography, 139:297–302.
Giri AK, Que Hee SS (1988) In vitro sister chromatid exchange
induced by 1,2-dichloroethane on bone marrow cells of mice.
Environmental and molecular mutagenesis, 12:331–334.
Gocke E, Wild D, Eckhardt K, King MT (1983) Mutagenicity
studies with the mouse spot test. Mutation research,
117:201–212.
Guengerich FP, Crawford WM, Domoradzki JY, MacDonald TL,
Watanabe PG (1980) In vitro activation of 1,2-dichloroethane by
microsomal and cytosolic enzyme. Toxicology and applied
pharmacology, 55:303–317.
Guicherit R, Schulting FL (1985) The occurrence of organic
chemicals in the atmosphere of the Netherlands. The science of
the total environment, 43:193–219.
Hatch GG, Mamay PD, Ayer ML, Casto BC, Nesnow W (1983)
Chemical enhancement of viral transformation in Syrian hamster
embryo cells by gaseous and volatile chlorinated methanes and
ethanes. Cancer research, 43:1945–1950.
Heikes DL (1987) Pesticide and industrial chemical residues —
purge and trap method for determination of volatile halocarbons
and carbon disulfide in table-ready foods. Journal of the
Association of Official Analytical Chemists, 70(2):215–226.
Heikes DL (1990) Environmental contaminants in table-ready
foods from the Total Diet Program of the Food and Drug
Administration. In: Food contamination from environmental
sources. New York, NY, John Wiley and Sons, pp. 31–57
(Advances in Environmental Science and Technology Series
No. 23).
Hellman B, Brandt I (1986) Effects of carcinogenic halogenated
aliphatic hydrocarbons on [3H]thymidine incorporation into
various organs of the mouse. A comparison between 1,2-
dibromoethane and 1,2-dichloroethane. Mutation research,
163:193–199.
Hemminki K, Falck K, Vaino H (1980) Comparison of alkylation
rates and mutagenicity of directly acting industrial and
laboratory chemicals: epoxides, glycidyl ethers, methylating and
ethylating agents, halogenated hydrocarbons, hydrazine

derivatives, aldehydes, thiouram and dithiocarbamate
derivatives. Archives of toxicology, 46:277–285.
Heppel LA, Neal PA, Perrin TL, Endicott KM, Porterfield VT
(1945) The toxicology of 1,2-dichloroethane (ethylene
dichloride). III. Its acute toxicity and the effect of protective
agents. Journal of pharmacology and experimental therapeutics,
84:53–63.
Heppel LA, Neal PA, Perrin TL, Endicott KM, Porterfield VT
(1946) The toxicology of 1,2-dichloroethane (ethylene
dichloride). V. The effects of daily inhalations. Journal of
industrial hygiene and toxicology, 28(4):113–120.
Hinkel GK (1965) [Oral dichloroethane intoxication of children.]
Deutsche Gesundheitswesen, 20:1327–1331 (in German).
Hofmann HT, Birnsteil H, Jobst P (1971) Zur inhalations toxicitat
von 1,1- und 1,2-dichloroathan. [The inhalation toxicity of 1,1-
and 1,2-dichloroethane.] Archiv für Toxikologie, 27:248–265.
IARC (1979) Some halogenated hydrocarbons. Lyon,
International Agency for Research on Cancer (IARC Monographs
on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans, Vol. 20).
Inskeep PB, Koga N, Cmarik JL, Guengerich FP (1986) Covalent
binding of 1,2-dihaloalkanes to DNA and stability of the major
DNA adduct, S-[2[(N7-guanyl)ethyl]glutathione. Cancer research,
46:2839–2844.
IPCS (1993) International Chemical Safety Card — 1,2-Dichloro-
ethane. Geneva, World Health Organization, International
Programme on Chemical Safety (No. 0250).
IPCS (1994) Environmental health criteria for assessing health
risks of chemicals: derivation of guidance values for health-
based exposure limits. Geneva, World Health Organization,
International Programme on Chemical Safety.
IPCS (1995) 1,2-Dichloroethane. Geneva, World Health
Organization, International Programme on Chemical Safety
(Environmental Health Criteria No. 176).
Isacson P, Bean JA, Splinter R, Olson DB, Kohler J (1985)
Drinking water and cancer incidence in Iowa: III. Association of
cancer with indices of contamination. American journal of
epidemiology, 121(6):856–869.
Jakobson I, Wahlberg JE, Holmberg B, Johansson G (1982)
Uptake via the blood and elimination of 10 organic solvents
following epicutaneous exposure of anesthetized guinea pigs.
Toxicology and applied pharmacology, 63:181–187.
Jenssen D, Ramel C (1980) The micronucleus test as part of a
short-term mutagenicity test programme for the prediction of
carcinogenicity evaluated by 43 agents tested. Mutation
research, 75:191–202.
Kaiser KLE, Comba ME (1986) Volatile hydrocarbon
contaminant survey of the St. Clair River. Water pollution
research journal of Canada, 21(3):323–331.
Kaiser KLE, Comba ME, Huneault H (1983) Volatile
hydrocarbon contaminants in the Niagara River and in Lake
Ontario. Journal of Great Lakes research, 9(2):212–223.
19
1,2-Dichloroethane
Kanada T, Uyeta M (1978) Mutagenicity screening of organic
solvents in microbial systems. Mutation research, 54:215.
Kavlock R, Chernoff N, Carver B, Kopfler F (1979) Teratology
studies in mice exposed to municipal drinking water
concentrates during organogenesis. Food and cosmetics
toxicology, 17:343–347.
King M-T, Beikirch H, Eckhardt K, Gocke E, Wild D (1979)
Mutagenicity studies with X-ray-contrast media, analgesics,
antipyretics, antirheumatics and some other pharmaceutical
drugs in bacterial, Drosophila and mammalian test systems.
Mutation research, 66:33–43.
Klaunig JE, Ruch RJ, Pereira MA (1986) Carcinogenicity of
chlorinated methane and ethane compounds administered in
drinking water to mice. Environmental health perspectives,
69:89–95.
Kliest J, Fast T, Boley JSM, van de Wiel H, Bloemen H (1989)
The relationship between soil contaminated with volatile
organic compounds and indoor air pollution. Environment
international, 15:419–525.
Koga N, Inskeep PB, Harris TM, Guengerich FP (1986) S-[2-(N7-
guanyl)ethyl] glutathione, the major DNA adduct formed from
1,2-dibromoethane. Biochemistry, 25:2192–2198.
Kramers PG, Mout HC, Bissumbhar B, Mulder CR (1991)
Inhalation exposure in Drosophila mutagenesis assays:
experiments with aliphatic halogenated hydrocarbons, with
emphasis on the genetic activity profile of 1,2-dichloroethane.
Mutation research, 252:17–33.
Kronevi T, Wahlberg JE, Holmberg B (1981) Skin pathology
following epicutaneous exposure to seven organic solvents.
International journal of tissue reactions, 3:21–30.
Kuwabara T, Quevedo AR, Cogan DG (1968) An experimental
study of dichloroethane poisoning. Archives of ophthalmology,
79:321–330.
Lane RW, Riddle BL, Borzelleca JF (1982) Effects of 1,2-
dichloroethane and 1,1,1-trichloroethane in drinking water on
reproduction and development in mice. Toxicology and applied
pharmacology, 63:409–421.
Larionov VG, Kokarovtseva MG (1976) Morphological
constitution of peripheral blood in intoxication with
dichloroethane and its metabolites. In: Actual problems of
pesticide application in different climatographic zones. Yerevan,
Aiastan Publishers, pp. 131–133.
Leblanc GA (1980) Acute toxicity of priority pollutants to water
flea (Daphnia magna). Bulletin of environmental contamination
and toxicology, 24:684–691.
Letkiewicz F, Johnston P, Coleman J (1982) Occurrence of 1,2-
dichloroethane in drinking water, food and air. Prepared by JRB
Associates, Washington DC, under Contract No. 68-01-6185 for
the US Environmental Protection Agency.
Lin ELC, Mattox JK, Pereira MA (1985) Glutathione plus cytosol-
and microsome-mediated binding of 1,2-dichloroethane to poly-
nucleotides. Toxicology and applied pharmacology,
78:428–435.
Concise International Chemical Assessment Document 1
Lum KR, Kaiser KLE (1986) Organic and inorganic contaminants in the
St. Lawrence River: some preliminary results on their distribution. Water
pollution research journal of Canada, 21(4):592–603.
Maltoni C, Valgimigli L, Scarnato C (1980) Long-term carcinogenic
bioassays on ethylene dichloride administered by inhalation to rats and
mice. In: Ames BN, Infante P, Reitz R, eds. Ethylene dichloride: a
potential health risk? Cold Spring Harbor, NY, Cold Spring Harbor
Laboratory, pp. 3–33 (Banbury Report No. 5).
McCollister DD, Hollingsworth RL, Oyen F, Rowe VK (1956)
Comparative inhalation toxicity of fumigant mixtures. Individual and
joint effect of ethylene dichloride, carbon tetrachloride, and ethylene
dibromide. Archives of industrial health, 13:1–7.
Milman HA, Storey DL, Riccio ES, Sivak A, Tu AS, Williams GM, Tong
C, Tyson CA (1988) Rat liver foci and in vitro assays to detect initiating
and promoting effects of chlorinated ethanes and ethylenes. Annals of
the New York Academy of Sciences, 534:521–530.
Moriya M, Ohta T, Watanabe K, Miyazawa T, Kato K, Shirasu Y (1983)
Further mutagenicity studies on pesticides in bacterial reversion assay
systems. Mutation research, 116:185–216.
Munson AE, Sanders VM, Douglas KA, Sain LE, Kauffmann BM, White
KL Jr (1982) In vivo assessment of immunotoxicity. Environmental
health perspectives, 43:41–52.
NCI (1978) Bioassay of 1,2-dichloroethane for possible carcinogenicity.
Bethesda, MD, US Department of Health, Education and Welfare,
Public Health Services, National Institutes of Health, National Cancer
Institute (HEW (NIH) Publication No. 78-1305).
Nestmann ER, Lee EGH, Matula TI, Douglas GR, Mueller JC (1980)
Mutagenicity of constituents identified in pulp mill effluents using
Salmonella/mammalian-microsome assay. Mutation research,
79:203–212.
NIOSH (1994a) Registry of toxic effects of chemical substances.
Cincinnati, OH, National Institute for Occupational Safety and Health
(last revision May 1994).
NIOSH (1994b) NIOSH pocket guide to chemical hazards. US
Department of Health and Human Services, Public Health Service,
Center for Disease Control and Prevention, National Institute for
Occupational Safety and Health, June.
Nouchi T, Miura H, Kanayama M, Mizuguchi O, Takano T (1984) Fatal
intoxication by 1,2-dichloroethane — A case report. International
archives of occupational and environmental health, 54:111–113.
NTP (1991) Toxicity studies of 1,2-dichloroethane (ethylene dichloride) in
F344/N rats, Sprague Dawley rats, Osborne-Mendel rats, and B6C3F 1
mice (drinking water and gavage studies). Research Triangle Park, NC,
National Institutes of Health, National Toxicology Program (NIH
Publication No. 91-3123).
Nylander P-O, Olofsson H, Rasmuson B, Svahlin H (1978) Mutagenic
effects of petrol in Drosophila melanogaster. I. Effects of benzene and
1,2-dichloroethane. Mutation research, 57:163–167.
Otson R (1987) Purgeable organics in Great Lakes raw and treated
water. International journal of environmental analytical chemistry,
31(1):41–53.
Pearson CR, McConnell G (1975) Chlorinated C1 and C2 hydrocarbons
in the marine environment. Proceedings of the Royal Society of London
B, 189:305–332.
Perocco P, Prodi G (1981) DNA damage by haloalkanes in human
lymphocytes cultured in vitro. Cancer letters, 13:213–218.
20
Principe P, Dogliotti E, Bignami M, Crebelli R, Falcone E, Fabrizi M,
Conti G, Comba P (1981) Mutagenicity of chemicals of industrial and
agricultural relevance in Salmonella, Streptomyces, and Aspergillus.
Journal of the science of food and agriculture, 32:826–832.
Prodi G, Arfelini G, Colacci A, Grilli S, Mazzulo M (1986) Interaction of
halocompounds with nucleic acids. Toxicologic pathology, 14:438–444.
Rannug U (1980) Genotoxic effects of 1,2-dibromoethane and 1,2-
dichloroethane. Mutation research, 76:269–295.
Rannug U, Beije B (1979) The mutagenic effect of 1,2-dichloroethane
on Salmonella typhimurium. II. Activation by the isolated perfused rat
liver. Chemico-biological interactions, 24:265–285.
Rannug U, Sundvall A, Ramel C (1978) The mutagenic effect
of 1,2-dichloroethane on Salmonella typhimurium. I. Activation through
conjugation with glutathione in vitro. Chemico-biological interactions,
20:1–16.
Rao KS, Murray JS, Deacon MM, John JA, Calhoun LL, Young JT
(1980) Teratogenicity and reproduction studies in animals inhaling
ethylene dichloride. In: Ames BN, Infante P, Reitz R, eds. Ethylene
dichloride: a potential health risk? Cold Spring Harbor, NY, Cold Spring
Harbor Laboratory, pp. 149–166 (Banbury Report No. 5).
Reitz RH, Fox TR, Ramsey JC, Quast JF, Langvardt PW, Watanabe
PG (1982) Pharmacokinetics and macro-molecular interactions of
ethylene dichloride in rats after inhalation or gavage. Toxicology and
applied pharmacology, 62:190–204.
Richter JE, Peterson SF, Kleiner CF (1983) Acute and chronic toxicity
of some chlorinated benzenes, chlorinated ethanes, and
tetrachloroethylene to Daphnia magna. Archives of environmental
contamination and toxicology, 12:679–684.
Roldan-Arjona T, Garcia-Pedrajas MD, Luque-Romero RL, Hera C,
Pueyo C (1991) An association between mutagenicity of the Ara test of
Salmonella typhimurium and carcinogenicity in rodents for 16 halogenated
aliphatic hydrocarbons. Mutagenesis, 6:199–205.
Romert L, Magnusson J, Ramel C (1990) The importance of glutathione
and glutathione transferase for somatic mutations in Drosophila
melanogaster induced in vivo by 1,2-dichloroethane. Carcinogenesis,
11:1399–1402.
Schultz K, Ghosh L, Banerjee S (1992) Neoplastic expression in murine
cells induced by halogenated hydrocarbons. In vitro cellular and
developmental biology, 28A:267–272.
Sherwood RL, O’Shea PT, Thomas W, Ratajczak HV, Aranyi C, Graham
JA (1987) Effects of inhalation of ethylene dichloride on pulmonary
defences of mice and rats. Toxicology and applied pharmacology,
91:491–496.
Shmuter LM (1977) [Effects of chronic exposure to low concentrations
of chlorinated hydrocarbons of the ethane series on specific and non-
specific reactivity of animals in vivo.] Gigiena Truda i Professional'nye
Zabolevaniya, 8:38–42 (in Russian).
Simmon VF (1980) Review of non-bacterial tests of the genotoxic
activity of ethylene dichloride. In: Ames BN, Infante P, Reitz R, eds.
Ethylene dichloride: a potential health risk? Cold Spring Harbor, NY,
Cold Spring Harbor Laboratory, pp. 97–103 (Banbury Report No. 5).
Simula TP, Glancey MG, Wolf CR (1993) Human glutathione
S-transferase-expressing Salmonella typhimurium tester strains to study
the activation/detoxification of mutagenic compounds: studies with
halogenated compounds, aromatic amines and aflatoxin B1.
Carcinogenesis, 14:1371–1376.
Singh HB, Salas LJ, Smith AJ, Shigeishi H (1980) Atmospheric
measurements of selected toxic organic chemicals. Research Triangle

Park, NC, US Environmental Protection Agency, Environmental
Sciences Research Laboratory (EPA-600/3-80-072; PB80-198989).
Singh HB, Salas LJ, Smith AJ, Shigeishi H (1981) Measurements of
some potentially hazardous organic chemicals in urban environments.
Atmospheric environment, 15:601–612.
Singh HB, Salas LF, Stiles RE (1982) Distribution of selected gaseous
organic mutagens and suspect carcinogens in ambient air.
Environmental science and technology, 16:872–880.
Smyth HF Jr (1969) Acute toxicity of ethyl compounds. In: Spector
WC, ed. Handbook of toxicology. Vol. 1. Philadelphia, PA, W.B.
Saunders Company.
Spence JW, Hanst PL (1978) Oxidation of chlorinated ethanes. Journal
of the Air Pollution Control Association, 28(3):250–253.
Spencer HC, Rowe VK, Adams EM, McCollister DD, Irish DD (1951)
Vapor toxicity of ethylene dichloride determined by experiments on
laboratory animals. American Medical Association archives of industrial
hygiene and occupational medicine, 4:482–493.
Spreafico F, Zuccato E, Marcucci F, Sironi M, Paglialunga S, Madonna
M, Mussini E (1980) Pharmacokinetics of ethylene dichloride in rats
treated by different routes and its long-term inhalatory toxicity. In:
Ames BN, Infante P, Reitz R, eds. Ethylene dichloride: a potential
health risk? Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, pp.
107–133 (Banbury Report No. 5).
Storer RD, Conolly RB (1983) Comparative in vivo genotoxicity and
acute hepatotoxicity of three 1,2-dihaloethanes. Carcinogenesis,
4:1491–1494.
Storer RD, Conolly RB (1985) An investigation of the role of
microsomal oxidative metabolism in the in vivo genotoxicity of 1,2-
dichloroethane. Toxicology and applied pharmacology, 77:36–46.
Storer RD, Jackson NM, Conolly RB (1984) In vivo genotoxicity and
acute hepatotoxicity of 1,2-dichloroethane in mice: comparison of oral,
intraperitoneal, and inhalation routes of exposure. Cancer research,
44:4267–4271.
Story DL, Meierhenry EF, Tyson CA, Milman HA (1986) Differences in
rat liver enzyme-positive foci produced by chlorinated aliphatics and
phenobarbital. Toxicology and industrial health, 2:351–362.
Strobel K, Grummt T (1987) Aliphatic and aromatic halocarbons as
potential mutagens in drinking water. III. Halogenated ethanes and
ethenes. Toxicology and environmental chemistry, 15:101–128.
Sundheimer DW, White RD, Brendel K, Sipes IC (1982) The
bioactivation of 1,2-dibromoethane in rat hepatocytes: covalent binding
to nucleic acids. Carcinogenesis, 3:1129–1133.
Suveev IM, Babichenko ME (1969) [On the clinic and cure of acute
intoxication with dichloroethane vapours.] Gigiena Truda i
Professional'nye Zabolevaniya, 13:50–51 (in Russian).
Tan E-L, Hsie AW (1981) Mutagenicity and cytotoxicity of haloethanes
as studied in the CHO/HGPRT system. Mutation research, 90:183–191.
Taningher M, Parodi S, Grilli S, Colacci A, Mazzullo M, Bordone R, Santi
L (1991) Lack of correlation between alkaline DNA fragmentation and
DNA covalent binding induced by polychloroethanes after in vivo
administration. Problems related to the assessment of a carcinogenic
hazard. Cancer detection and prevention, 15:35–39.
Theiss JC, Stoner GD, Shimkin MB, Weisberger EK (1977) Test for
carcinogenicity of organic contaminants of United States drinking
waters by pulmonary tumor response in strain A mice. Cancer research,
37:2717–2720.
21
1,2-Dichloroethane
Tu AS, Murray TA, Hatch KM, Sivak A, Milman HA (1985) In vitro
transformation of BALB/c-3T3 cells by chlorinated ethanes and
ethylenes. Cancer letters, 28:85–92.
US EPA (1985) Health assessment document for 1,2-dichloroethane
(ethylene dichloride). Final report. Washington, DC, US Environmental
Protection Agency (EPA/600/8-84/006F; NTIS PB86-122702).
US EPA (1992) Indoor air quality data base for organic compounds.
Research Triangle Park, NC, US Environmental Protection Agency
(EPA-600-R-92-025; NTIS PB92-158468).
Valencia R, Abrahamson S, Lee WR, von Halle ES, Woodruff RC,
Wurgler FE, Zimmering S (1984) Chromosome mutations for
mutagenesis in Drosophila melanogaster: a report of the US
Environmental Protection Agency Gene-Tox Program. Mutation
research, 134:61–88.
van Bladeren PJ, Breimer DD, Rotteveel-Smijs RMT, de Knijff P, Mohn
GV, van Meeteren-Walchli B, Buijs W, van der Gen A (1981) The
relation between the structure of vicinal dihalogen compounds and their
mutagenic activation via conjugation to glutathione. Carcinogenesis,
2:499–505.
van Duuren BL, Goldschmidt BM, Loewengart G, Smith A, Mechionne S,
Seldman I, Roth D (1979) Carcinogenicity of halogenated olefinic and
aliphatic hydrocarbons in mice. Journal of the National Cancer Institute,
63:1433–1439.
van Esch GJ, Kroes R, van Logten MJ, den Tonkelaar EM (1977)
Ninety-day toxicity study with 1,2-dichloroethane (DCE) in rats.
Bilthoven, National Institute of Public Health and Environmental
Hygiene (Report 195/77 Al. Tox.).
Vozovaya M (1977) [The effect of dichloroethane on the sexual cycle
and embryogenesis of experimental animals.] Akusherstvo i
Ginekologiya (Moscow), 2:57–59 (in Russian).
WHO (1971) Evaluation of food additives: specifications for the identity
and purity of food additives and their toxicological evaluation: some
extraction solvents and certain other substances; a review of the
technological efficacy of some antimicrobial agents. Fourteenth report of
the Expert Committee. Geneva, World Health Organization (WHO
Technical Report Series No. 462).
WHO (1980) Evaluation of certain food additives. Twenty-third report of
the Joint FAO/WHO Expert Committee on Food Additives. Geneva, World
Health Organization (WHO Technical Report Series No. 648 and
corrigenda).
WHO (1992) Evaluation of certain food additives and naturally occurring
toxicants. Thirty-ninth report of the Joint FAO/WHO Expert Committee on
Food Additives. Geneva, World Health Organization (WHO Technical
Report Series No. 828).
WHO (1993) Guidelines for drinking-water quality, 2nd ed. Vol. 1.
Recommendations. Geneva, World Health Organization.
Williams GM, Mori H, McQueen CA (1989) Structure–activity
relationships in the rat hepatocyte DNA-repair test for 300 chemicals.
Mutation research, 221:263–286.
Zamora PO, Benson JM, Li AP, Brooks AL (1983) Evaluation of an
exposure system using cells grown on collagen gels for detecting highly
volatile mutagens in the CHO/HGPRT mutation assay. Environmental
mutagenesis, 5:795–801.
Concise International Chemical Assessment Document 1
APPENDIX 1 — SOURCE DOCUMENTS
International Programme on Chemical Safety
— Environmental Health Criteria Monograph
No. 176 (1995)
Copies of the Environmental Health Criteria document on 1,2-
dichloroethane, prepared by the International Programme on Chemical
Safety, as well as the Health and Safety Guide (1991) and the
International Chemical Safety Card (1993), may be obtained from:
International Programme on Chemical Safety
World Health Organization
Geneva, Switzerland
The first draft of the monograph, prepared by Ms K. Hughes of
the Environmental Health Directorate, Health Canada, was circulated to
IPCS Contact Points (approximately 150 government, industrial,
academic, and independent organizations and individuals) for comment
in June 1994. The second draft, revised on the basis of the comments
received, was also prepared by Ms K. Hughes. Dr E. Smith and Dr
P.G. Jenkins, both members of the IPCS Central Unit, were responsible
for the scientific content and technical editing, respectively.
The monograph on 1,2-dichloroethane was finalized by the Core
Assessment Group (CAG) of the Joint Meeting on Pesticides (JMP),
which met in Geneva from 25 October to 3 November 1994. The Core
Assessment Group reviewed and revised the draft monograph and
made an evaluation of the risks for human health and the environment
from exposure to 1,2-dichloroethane. Participants at the Core
Assessment Group meeting were:
Dr T. Bailey, Ecological Effects Branch, Environmental Fate and
Effects Division, US Environmental Protection Agency,
Washington, DC, USA
Dr A.L. Black, Department of Human Services and Health,
Canberra, ACT, Australia
Mr D.J. Clegg, Carp, Ontario, Canada
Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood,
Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom
(Vice-Chairperson)
Dr P.E.T. Douben, Her Majesty’s Inspectorate of Pollution,
London, United Kingdom (EHC Joint Rapporteur)
Dr P. Fenner-Crisp, Office of Pesticide Programs, US
Environmental Protection Agency, Washington, DC, USA
Dr R. Hailey, National Institute of Environmental Health Sciences,
National Institutes of Health, Public Health Service, Department
of Health and Human Services, Research Triangle Park, NC, USA
Ms K. Hughes, Priority Substances Section, Environmental Health
Directorate, Health Canada, Ottawa, Ontario, Canada (EHC Joint
Rapporteur)
Dr D. Kanungo, Division of Medical Toxicology, Central
Insecticides Laboratory, Government of India, Ministry of
Agriculture & Cooperation, Directorate of Plant Protection,
Quarantine & Storage, Faridabad, Haryana, India
Dr L. Landner, MFG, European Environmental Research Group
Ltd, Stockholm, Sweden
Dr M.H. Litchfield, Melrose Consultancy, Fontwell, Arundel, West
Sussex, United Kingdom
22
Professor M. Lotti, Institute of Occupational Medicine, University
of Padua, Padua, Italy (Chairperson)
Dr D.R. Mattison, University of Pittsburgh, Graduate School of
Public Health, Pittsburgh, PA, USA
Dr J. Sekizawa, Division of Information on Chemical Safety,
National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan
Dr P. Sinhaseni, Department of Pharmacology, Chulalongkorn
University, Bangkok, Thailand
Dr S.A. Soliman, Pesticide Chemicals & Toxicology, King Saud
University, Bureidah, Saudi Arabia
Dr M. Tasheva, Department of Toxicology, National Center of
Hygiene, Medical Ecology and Nutrition, Sofia, Bulgaria
Mr J.R. Taylor, Pesticides Safety Directorate, Ministry of
Agriculture, Fisheries and Food, York, United Kingdom
Dr H.M. Temmink, Department of Toxicology, Wageningen
Agricultural Unviersity, Wageningen, The Netherlands
Dr M.I. Willems, Department of Occupational Toxicology, TNO
Nutrition and Food Research Institute, AJ Zeist, The Netherlands
Procedures for the preparation of an
Environmental Health Criteria document
The order of procedures that result in the publication of an EHC
monograph is shown in the flow chart. A designated staff member of
IPCS, responsible for the scientific quality of the document, serves as
Responsible Officer (RO). The IPCS Editor is responsible for layout
and language. The first draft, prepared by consultants or, more
usually, staff from an IPCS Participating Institution, is based initially on
data provided from the International Register of Potentially Toxic
Chemicals and reference databases such as Medline and Toxline.
The draft document, when received by the RO, may require an
initial review by a small panel of experts to determine its scientific
quality and objectivity. Once the RO finds the document acceptable as
a first draft, it is distributed, in its unedited form, to well over 150 EHC
Contact Points throughout the world who are asked to comment on its
completeness and accuracy and, where necessary, provide additional
material. The Contact Points, usually designated by governments,
may be Participating Institutions, IPCS Focal Points, or individual
scientists known for their particular expertise. Generally, some four
months are allowed before the comments are considered by the RO and
author(s). A second draft incorporating comments received and
approved by the Director, IPCS, is then distributed to Task Group
members, who carry out the peer review, at least six weeks before their
meeting.
The Task Group members serve as individual scientists, not as
representatives of any organization, government, or industry. Their
function is to evaluate the accuracy, significance, and relevance of the
information in the document and to assess the health and
environmental risks from exposure to the chemical. A summary and
recommendations for further research and improved safety aspects are
also required. The composition of the Task Group is dictated by the
range of expertise required for the subject of the meeting and by the
need for a balanced geographical distribution.
The three cooperating organizations of the IPCS recognize
the important role played by nongovernmental organizations.
Representatives from relevant national and international
associations may be invited to join the Task Group as observers.
While observers may provide a valuable contribution to the
process, they can speak only at the invitation of the Chairperson.
Observers do not participate in the final evaluation of the
chemical; this is the sole responsibility of the Task Group
members. When the Task Group considers it to be appropriate,
it may meet in camera.
All individuals who as authors, consultants, or advisers
participate in the preparation of the EHC monograph must, in
addition to serving in their personal capacity as scientists, inform
the RO if at any time a conflict of interest, whether actual or
potential, could be perceived in their work. They are required to
sign a conflict of interest statement. Such a procedure ensures
the transparency and probity of the process.
When the Task Group has completed its review and the RO
is satisfied as to the scientific correctness and completeness of
the document, it then goes for language editing, reference
checking, and preparation of camera-ready copy. After approval
by the Director, IPCS, the monograph is submitted to the WHO
Office of Publications for printing. At this time, a copy of the
final draft is sent to the Chairperson and Rapporteur of the Task
Group to check for any errors.

EHC PREPARATION FLOW CHART

CCoom
mmmiittm
meenntt ttoo ddrraafftt EEHHCC

Document preparation initiated

Possible meeting
Revision as of a few experts
Draft sent to IPCS Responsible Officer (RO) to resolve
necessary
controversial issues

Responsible Officer, Editor check for coherence of text and

Responsible Officer, Editor check for coherence of text and
readability (not language editing)
readability (not language editing)

FFiirrsstt DDrraafftt

International circulation to Contact Points (150+)

Comments to IPCS (RO)

Review of comments, reference cross-check;

preparation of Task Group (TG) draft

Working group,
Editor if required
Task Group meeting

Insertion of TG changes

Post-TG draft; detailed reference cross-check

Editing
Editing French/Spanish
translations of Summary
Graphics
Word-processing

Camera-ready copy Library for

CIP Data

Final editing

Approval by Director, IPCS

WHO Publication Office

routine procedure
optional procedure
Printer Proofs Publication
Publication

23
Concise International Chemical Assessment Document 1

APPENDIX 2 — CICAD FINAL REVIEW Professor S. Tarkowski, Department of Environmental Health

Hazards, The Nofer Institute of Occupational Medicine, Lodz,
BOARD Poland

Dr M. Wallen, National Chemicals Inspectorate (KEMI), Solna,

Sweden
Members

Dr A. Aitio, Institute of Occupational Health, Helsinki, Finland

Dr K. Bentley, Director, Environment Policy Section,

Commonwealth Department of Human Services and Health,
Canberra, Australia
Secretariat
Mr R. Cary, Toxicology and Existing Substances Regulation
Unit, Health and Safety Executive, Merseyside, United Kingdom Dr M. Baril, International Programme on Chemical Safety, World
Health Organization, Geneva, Switzerland
Dr J. de Fouw, National Institute of Public Health and
Environmental Protection, Bilthoven, The Netherlands Dr L. Harrison, International Programme on Chemical Safety,
World Health Organization, Geneva, Switzerland
Dr C. DeRosa, Director, Division of Toxicology, Agency for Toxic
Substances and Disease Registry, Atlanta, GA, USA Dr M. Mercier, Director, International Programme on Chemical
Safety, World Health Organization, Geneva, Switzerland
Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood,
Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom Dr P. Toft, Associate Director, International Programme on
Chemical Safety, World Health Organization, Geneva,
Dr W. Farland, Director, National Center for Environmental Switzerland
Assessment, Office of Research and Development, US
Environmental Protection Agency, Washington, DC, USA
(Chairperson)

Dr T.I. Fortoul, Depto. Biologia Celular y Tisular, National

University of Mexico and Environmental Health Directorate of
the Health Ministry, Mexico D.F., Mexico

Dr H. Gibb, National Center for Environmental Assessment, US

Environmental Protection Agency, Washington, DC, USA

Dr R.F. Hertel, Federal Institute for Health Protection of

Consumers & Veterinary Medicine, Berlin, Germany

Mr J.R. Hickman, Environmental Health Directorate, Health

Canada, Ottawa, Ontario, Canada

Dr T. Lakhanisky, Head, Division of Toxicology, Institute of

Hygiene and Epidemiology, Brussels, Belgium (Vice-
Chairperson)

Dr I. Mangelsdorf, Documentation and Assessment of Chemicals,

Fraunhofer Institute for Toxicology and Aerosol Sciences,
Hanover, Germany

Ms E. Meek, Head, Priority Substances Section, Environmental

Health Directorate, Health Canada, Ottawa, Ontario, Canada

Dr K. Paksy, National Institute of Occupational Health, Budapest,

Hungary

Mr D. Renshaw, Department of Health, London, United Kingdom

Dr J. Sekizawa, Division of Chemo-Bio Informatics, National

Institute of Hygienic Sciences, Tokyo, Japan

Dr H. Sterzl-Eckert, GSF-Forschungszentrum für Umwelt und

Gesundheit GmbH, Institut für Toxikologie, Oberschleissheim,
Germany

24

RÉSUMÉ D’ORIENTATION
La Direction de l’Hygiène du Milieu de Santé
Canada a rédigé ce CICAD (Document international
succinct sur l’évaluation des risques chimiques) sur le
1,2-dichloréthane en s’inspirant d’un document de la
série Critères d’hygiène de l’environnement (CHE) du
Programme international sur la Sécurité chimique (PISC)
(IPCS, 1995), qui évalue les conséquences potentielles
pour la santé humaine d’une exposition indirecte au 1,2-
dichloréthane dans l’environnement général ainsi que les
effets de cette substance sur l’environnement. Les
données prises en compte dans cette analyse sont celles
qui étaient disponibles en mai 1993 (effets sur la santé
humaine) ou en octobre 1994 (effets sur l’environne-
ment). L’appendice 1 donne des informations sur la
nature du processus d’évaluation par les pairs et sur la
disponibilité du document CHE. Pour ce CICAD, c’est
l’évaluation pratiquée lors de l’élaboration du document
CHE qui a fait office d’évaluation par les pairs préalable à
l’examen du Comité d’évaluation finale. Les membres du
Comité d’évaluation finale ont apporté les dernières
corrections à ce CICAD et en ont approuvé la
publication par correspondance, après avoir examiné les
observations présentées lors de l’élaboration du CHE
dans le cadre de l’évaluation par les pairs. La
composition du Comité d’évaluation finale est indiquée à
l’appendice 2. La fiche internationale sur la sécurité
chimique (ICSC 0250) produite par le PISC (IPCS, 1993)
est également reproduite dans ce document.
Le 1,2-dichloréthane (CAS N/ 107-06-2) est un
hydrocarbure synthétique volatil utilisé principalement
dans la synthèse du chlorure de vinyle monomère et
d’autres solvants chlorés. Il a également été utilisé
comme additif de l’essence au plomb et comme fumigant,
mais son utilisation comme additif de l’essence est en
déclin. La plus grande partie du 1,2-dichloréthane libéré
dans l’environnement se retrouve dans l’air ambiant où
sa persistance est modérée. Toutefois, il ne devrait pas
contribuer à la destruction de l’ozone. Le potentiel de
bioaccumulation du 1,2-dichloréthane est faible; son
inhalation avec l’air est probablement la principale
source d’exposition humaine.
On dispose de peu d’information sur les effets
du 1,2-dichloréthane chez l’homme. Les quelques études
épidémiologiques qui ont été faites sur sa
cancérogénicité potentielle ne sont guère concluantes.
Le 1,2-dichloréthane présente une toxicité aiguë
modérée chez les animaux d’expérience. Les quelques
données que l’on trouve sur ses effets non néoplasiques
dans des études de chronicité à court terme, sub-
25
1,2-Dichloroethane
chronique ou chronique indiquent que les principaux
organes cibles sont le foie et le rein; les doses les plus
faibles pour lesquelles on ait signalé un effet après
ingestion et inhalation sont respectivement de 49–82
mg/kg de poids corporel par jour (augmentation du poids
du foie chez des rats exposés pendant 13 semaines) et
202 mg/m3 (effets sur les fonctions hépatique et rénale
chez des rats exposés pendant 12 mois). D’après les
résultats d’un petit nombre d’études, il n’y a pas de
preuve que le 1,2-dichloréthane soit tératogène chez les
animaux de laboratoire, ni qu’il induise des effets sur la
reproduction ou le développement lorsque les niveaux
d’exposition sont inférieurs aux niveaux qui entraînent
d’autres effets systémiques.
L’exposition au 1,2-dichloréthane par gavage
pendant 78 semaines a été suivie d’une augmentation
significative de l’incidence des tumeurs de différents
organes (notamment des hémangiosarcomes et des
tumeurs de l’estomac, des glandes mammaires, du foie,
des poumons et de l’endomètre), tant chez le rat que
chez la souris. Il n’y a eu aucune augmentation
significative de l’incidence des tumeurs chez des rats ou
des souris exposés par inhalation, mais l’administration
répétée par voie dermique ou intrapéritonéale a
provoqué une augmentation du nombre des tumeurs des
poumons chez la souris. Le 1,2-dichloréthane s’est
constamment révélé génotoxique dans de nombreuses
épreuves in vitro sur des cellules de procaryotes, de
champignons et de mammifères (y compris des cellules
humaines). De même, les résultats ont été constamment
positifs en ce qui concerne l’activité génotoxique (ainsi
que la fixation sur l’ADN) dans des études in vivo chez
le rat, la souris et les insectes.
Les valeurs les plus faibles de la CI50s et de la
CE50s qui aient été signalées pour différents effets sur
des organismes aquatiques sont respectivement de 25 et
105 mg/litre. La CL50 la plus faible pour les daphnies était
de 220 mg/litre, des effets ayant toutefois été observés
sur la reproduction à 20,7 mg/litre. Le vertébré d’eau
douce le plus sensible a été une salamandre (Ambystoma
gracile) chez laquelle on a constaté une réduction de la
survie des larves à 2,5 mg/litre. On ne dispose que de
données limitées sur la toxicité du 1,2-dichloréthane pour
les espèces terrestres.
D’après les données disponibles, le 1,2-dichlor-
éthane peut être considéré comme un cancérogène
probable pour l’homme, de sorte que l’exposition doit
être réduite dans toute la mesure possible. Le potentiel
cancérogène (exprimé par la dose associée à une aug-
mentation de 5 % de l’incidence des tumeurs), calculé à
partir d’études de gavage, a été évalué à 6,2–34 mg/kg de
poids corporel par jour. En appliquant un facteur de
Concise International Chemical Assessment Document 1

sécurité de 5000 ou de 50 000 au potentiel cancérogène

estimé, on arrive à une valeur guide pour l’air (principale
source d’exposition humaine) de 3,6–20 :g/m3 ou
0,36–2,0 :g/m3; il faut cependant noter que cette
méthode surestime les risques, car les données dispon-
ibles montrent que le 1,2-dichloréthane est moins actif
lorsqu’il est inhalé. (Les valeurs correspondantes pour
l’ingestion sont respectivement de 1,2–6,8 ou
0,12–0,68 :g/kg de poids corporel par jour.) Ces valeurs
correspondent à ce que certains organismes considèrent
comme un risque “pratiquement négligeable” (c’est-à-
dire 10!5–10!6 pour un cancérogène génotoxique).
D’après une des estimations qui ont été faites,
l’exposition indirecte dans un environnement normal est
approximativement 300 fois inférieure à ces valeurs.

26

RESUMEN DE ORIENTACIÓN
Esta reseña de la evaluación química internacional
del 1,2-dicloroetano ha sido preparada por la Dirección
de Higiene del Medio de Health Canada sobre la base
de un documento de la serie “Criterios de Salud
Ambiental” (EHC) del Programa Internacional de
Seguridad de las Sustancias Químicas (IPCS, 1995) en el
que se evalúan los efectos potenciales sobre la salud
humana de la exposición indirecta al 1,2-dicloroetano en
el medio ambiente general, así como los efectos ambien-
tales de dicha sustancia química. En este análisis se
examinan datos obtenidos en mayo de 1993 (efectos
sobre la salud humana) y octubre de 1994 (efectos
ambientales). En el apéndice 1 se proporciona infor-
mación sobre el proceso de revisión científica y los
documentos disponibles de la serie EHC. Por lo que
respecta a esta reseña de la evaluación química inter-
nacional, el proceso de revisión científica previo al
examen realizado por el Comité de Revisión Final se ha
cumplido mediante la revisión científica efectuada para la
elaboración del documento de la serie EHC. Comuni-
cándose por correspondencia, los miembros del Comité
de Revisión Final ultimaron esta reseña de la evaluación
química internacional del 1,2-dicloroetano, aprobaron su
publicación y examinaron las observaciones dimanantes
de la revisión científica efectuada durante la preparación
del documento de la serie EHC. La composición del
Comité de Revisión Final figura en el apéndice 2. En el
presente documento también se reproduce la Ficha Inter-
nacional de Seguridad Química (ICSC 0250) emitida por el
IPCS (1993).
El 1,2-dicloroetano (CAS n/ 107-06-2) es un
hidrocarburo sintético volátil que se utiliza principal-
mente en la síntesis del monómero cloruro de vinilo y de
otros disolventes clorados. También se ha utilizado
como aditivo de la gasolina con plomo y como fumi-
gante, aunque su uso como aditivo de la gasolina se está
reduciendo. La mayor parte de la liberación en el
entorno se produce en el aire ambiente, donde es moder-
adamente persistente. Sin embargo, no parece que
contribuya al agotamiento de la capa de ozono. El 1,2-
dicloroetano tiene un potencial de bioacumulación bajo;
la inhalación con el aire probablemente sea la principal
fuente de exposición humana.
Se dispone de poca información sobre los efectos
del 1,2-dicloroetano en el ser humano. Las pocas
investigaciones epidemiológicas conocidas sobre su
carcinogenicidad potencial no son concluyentes.
El 1,2-dicloroetano tiene una toxicidad aguda
moderada en animales de experimentación. La escasa
27
1,2-Dichloroethane
información sobre efectos no neoplásicos presentada en
estudios de corta duración, subcrónicos y crónicos
indica que los principales órganos afectados son el
hígado y los riñones; los niveles mínimos de ingestión e
inhalación con efectos comunicados fueron de 49–82
mg/kg de peso corporal por día (aumento de peso del
hígado en las ratas expuestas durante 13 semanas) y 202
mg/m3 (efectos sobre la función hepática y renal en las
ratas expuestas durante 12 meses), respectivamente.
Los resultados de un número limitado de estudios, no
aportaron indicios de que el 1,2-dicloroetano sea
teratogénico en animales de experimentación o que tenga
efectos sobre la reproducción o el desarrollo a niveles de
exposición inferiores a los que causan otros efectos
sistémicos.
La exposición al 1,2-dicloroetano administrado
por sonda durante 78 semanas produjo un aumento
significativo de la incidencia de tumores en distintos
lugares (hemangiosarcomas y tumores en el estómago,
las glándulas mamarias, el hígado, los pulmones y el
endometrio) tanto en ratas como en ratones. Aunque no
hubo un aumento significativo de la incidencia de
tumores en las ratas y los ratones expuestos por
inhalación, la aplicación cutánea o intraperitoneal
repetida de 1,2-dicloroetano se ha revelado sistemática-
mente genotóxica en numerosas pruebas realizadas in
vitro en células de procariotas, hongos y mamíferos
(incluidas células humanas). Análogamente, se han
obtenido resultados invariablemente positivos indica-
dores de actividad genotóxica (así como enlaces con el
ADN) en estudios realizados in vivo con ratas, ratones e
insectos.
Las CI50 y CE50 más bajas notificadas en relación
con diversos puntos finales en organismos acuáticos
fueron de 25 y 105 mg/litro respectivamente. La CL50 más
baja notificada para Daphnia fue de 220 mg/litro,
mientras que los efectos sobre la reproducción se
produjeron con concentraciones de 20,7 mg/litro. El
vertebrado de agua dulce más sensible estudiado fue la
salamandra noroccidental (Ambystoma gracile), en la
que se observó una reducción de la supervivencia de las
larvas con niveles de 2,5 mg/litro. Se dispone sólo de
datos limitados sobre los efectos del 1,2-dicloroetano en
especies terrestres.
Teniendo en cuenta los datos disponibles, es
probable que el 1,2-dicloroetano sea carcinógeno para el
ser humano y, por lo tanto, la exposición a éste debería
reducirse en la medida de lo posible. Sobre la base de
estudios realizados en animales expuestos a una
administración por sonda, se ha calculado que la
potencia carcinogénica (expresada como la dosis
asociada a un aumento del 5% en la incidencia de
Concise International Chemical Assessment Document 1

tumores) oscila entre 6,2 y 34 mg/kg de peso corporal por

día. Con respecto al aire (fuente principal de exposición
humana), se han obtenido valores orientativos 3,6–20
g/m3 o 0,36–2,0 g/m3, calculados para un margen 5.000 a
50.000 veces inferior a la potencia carcinogénica
estimada; sin embargo, hay que tener en cuenta que se
han sobreestimado los riesgos, ya que los datos
disponibles indican que el 1,2-dicloroetano inhalado
resulta menos potente. (En cuanto a la ingestión, los
valores correspondientes son de 1,2–6,8 g/m3 de peso
corporal por día o 0,12–0,68 g/m3 de peso corporal por
día.) Estos valores comportan lo que algunas entidades
consideran como un riesgo “prácticamente
insignificante” (es decir, 10–5 – 10–6 para un carcinógeno
genotóxico). Según las estimaciones estadísticas, la
exposición indirecta a través del medio ambiente general
es aproximadamente 300 veces inferior a esos valores.

28