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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    CONCISE INTERNATIONAL CHEMICAL ASSESSMENT DOCUMENT NO. 1


    1,2-Dichloroethane

    INTER-ORGANIZATION PROGRAMME FOR THE SOUND MANAGEMENT OF CHEMICALS
    A cooperative agreement among UNEP, ILO, FAO, WHO, UNIDO, UNITAR and
    OECD

    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.

    First draft prepared by Ms K. Hughes and Ms M.E. Meek,
    Environmental Health Directorate,
    Health Canada


    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and
    the World Health Organization, and produced within the framework
    of the Inter-Organization Programme for the Sound Management of
    Chemicals.


    World Health Organization
    Geneva, 1998

         The International Programme on Chemical Safety (IPCS),
    established in 1980, is a joint venture of the United Nations
    Environment Programme (UNEP), the International Labour
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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
    4.Environmental exposure  I.International Programme for
    Chemical Safety  II.Series

         ISBN 92 4 153001 4       (NLM Classification: QV 633)
         ISSN 1020-6167

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    TABLE OF CONTENTS

    FOREWORD

    1. EXECUTIVE SUMMARY

    2. IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES

    3. ANALYTICAL METHODS

    4. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    5. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

    6. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

        6.1. Environmental levels
        6.2. Human exposure

    7. COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS

    8. EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

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

    9. EFFECTS ON HUMANS

        9.1. Case reports
        9.2. Epidemiological studies

    10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD

        10.1. Aquatic environment
        10.2. Terrestrial environment

    11. EFFECTS EVALUATION

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

    12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    13. HUMAN HEALTH PROTECTION AND EMERGENCY ACTION

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

    14. CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

        INTERNATIONAL CHEMICAL SAFETY CARD

        REFERENCES

        APPENDIX 1 - SOURCE DOCUMENTS

        APPENDIX 2 - CICAD FINAL REVIEW BOARD

        RÉSUMÉ D'ORIENTATION

        RESUMEN DE ORIENTACION
    

    FOREWORD

         Concise International Chemical Assessment Documents (CICADs)
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    chemicals.

         CICADs are concise documents that provide summaries of the
    relevant scientific information concerning the potential effects
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    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).

         While every effort is made to ensure that CICADs represent
    the current status of knowledge, new information is being
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         The first draft is based on an existing national, regional,
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    FIGURE 1

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    They are selected because of their expertise in human and
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    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 environmental 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 carcinogenicity 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
    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 haemangiosarcomas 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-Dichloro-ethane has been consistently genotoxic 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 northwestern
    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 µg/m3 or 0.36-2.0 µg/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 µg/kg
    body weight per day or 0.12-0.68 µg/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
    20°C), and soluble in water, with a solubility of 8690 mg/litre
    (at 20°C). 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 detection, or mass
    spectrometry.  Detection limits range from 0.016 to >4 µg/m3
    for air, from 0.001 to 4.7 µg/litre for water, and from 6 to 10
    µg/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.  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
    environment, 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
    µg/m3 in Canada, <0.004-3.8 µg/m3 in Japan, and 1.2 µg/m3 in
    the United Kingdom and the Netherlands.  Earlier surveys in the
    USA reported mean levels of 0.33-6.05 µg/m3; however, peak
    levels near chemical manufacturing plants have ranged as high as
    736 µg/m3 (US EPA, 1985).  Mean levels in residential indoor air
    are reported to be <0.1 µg/m3 in Canada, 0.1-0.5 µg/m3 in the
    USA, and 3.4 µg/m3 in the Netherlands.

         In drinking-water, mean 1,2-dichloroethane concentrations
    are generally less than 0.5 µg/litre, based on the results of
    surveys in Canada, the USA, Japan, and Spain.  Although there are
    few recent data, 1,2-dichloroethane has only very rarely been
    detected in surface water at concentrations greater than 10
    µg/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.

    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 environmental 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.



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

                                                                                                                          

    Medium                     Location      Year            Concentrations               Reference
                                                                                                                          

    Ambient air                Canada        1988-1990       0.07-0.28 µg/m3 (means)      T. Dann, unpublished data, 1992

    Ambient air                Japan         1992            <0.004-3.8 µg/m3 (means)     Environment Agency Japan, 1993

    Ambient air                UK            1982, 1983      1.2 µg/m3 (mean)             Clark et al., 1984a,b

    Ambient air                Netherlands   1980            1.2 µg/m3 (mean)             Guicherit & Schulting, 1985

    Ambient air                USA           1980-1982       0.33-6.05 µg/m3 (means)      Singh et al., 1980, 1981, 1982

    Indoor air (residential)   Canada        1991            <0.1 µg/m3 (mean)            Fellin et al., 1992

    Indoor air (residential)   USA                           0.1-0.5 µg/m3 (means)        US EPA, 1992

    Indoor air (residential)   Netherlands   1984-1985       3.4 µg/m3 (mean)             Kliest et al., 1989

    Drinking-water             Canada        1988-1991       <0.05-0.139 µg/litre         P. Lachmaniuk, personal
                                                             (mean)                       communication, 1991
                                             1990            <0.2 µg/litre (mean)         Ecobichon & Allen, 1990
                                             1982-1983       <0.1 µg/litre (mean)         Otson, 1987

    Drinking-water             USA           Early 1980s     NDa - 19 µg/litre            Letkiewicz et al., 1982
                                                             ND - 0.05 µg/litre           Barkley et al., 1980

    Drinking-water             Japan         1976            <0.5-0.9 µg/litre            Fujii, 1977

    Drinking-water             Spain         1987            2-22 µg/litre                Freiria-Gandara et al., 1992
                                                                                                                          

    Table 1 (continued)

                                                                                                                          
    Medium                     Location      Year            Concentrations               Reference
                                                                                                                          

    Surface water              Canada        1981-1985       <0.08 µg/litre               Kaiser et al., 1983; Comba &
                                                                                          Kaiser, 1985; Kaiser & Comba,
                                                                                          1986; Lum & Kaiser, 1986

    Surface water              Japan         1992            0.01-3.4 µg/litre            Environment Agency Japan, 1993

    Food (34 groups)           Canada        1991            <50 µg/kg (solids);          Enviro-Test Laboratories, 1991
                                                             <1 µg/litre (liquids)

                                             1992            <5 µg/kg (solids);           Enviro-Test Laboratories, 1992
                                                             <1 µg/litre (liquids)

    Food (19 items)            USA           Not specified   ND - 0.31 µg/kg              Heikes, 1987, 1990
                                             Not specified   ND - 8.2 µg/kg               Heikes, 1987

    Food (231 items)           USA           Not specified   <9-30 µg/kg                  Daft, 1988
                                                                                                                          

    a  Detection limit not reported.
    

         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
    µg/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 µg/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 µg/m3, is estimated to range from
    <0.03 to 0.1 µg/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 µg/litre, the
    mean intake from drinking-water is estimated to range from
    <0.001 to 0.003 µg/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.

    7.  COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS

         1,2-Dichloroethane is readily absorbed following inhalation,
    ingestion, and dermal exposure and is rapidly and widely
    distributed throughout the body.  Relative distribution of
    radioactivity (presumably as metabolites) was similar in rats
    administered a single oral dose of 150 mg/kg body weight and
    those exposed by inhalation to 150 ppm (600 mg/m3) for 6 hours
    (Reitz et al., 1982).  1,2-Dichloroethane is rapidly and
    extensively metabolized in rats and mice, with principally
    sulfur-containing metabolites being eliminated in the urine in a
    dose-dependent manner.  Metabolism appears to be saturated or
    limited in rats at levels of exposure resulting in concentrations
    in blood of 5-10 µg/ml (Reitz et al., 1982).  Levels of DNA
    alkylation were higher following exposure to a bolus dose of 150
    mg/kg body weight by gavage compared with inhalation of 150 ppm
    (600 mg/m3) over a 6-hour period (Reitz et al., 1982).

         Available data suggest that 1,2-dichloroethane is
    metabolized via two principal pathways.  The first involves a
    saturable microsomal oxidation mediated by cytochrome P-450 to 
    2-chloroacetaldehyde and 2-chloroethanol, followed by conjugation
    with glutathione.  The second pathway entails direct conjugation
    with glutathione to form  S-(2-chloroethyl)-glutathione, which
    may be non-enzymatically converted to a glutathione episulfonium
    ion; this ion can form adducts with proteins, DNA, or RNA. 
    Although DNA damage has been induced by the P-450 pathway  in 
     vitro (Banerjee et al., 1980; Guengerich et al., 1980; Lin et
    al., 1985), several lines of evidence indicate that the
    glutathione conjugation pathway 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).

    8.  EFFECTS ON LABORATORY MAMMALS AND  IN VITRO TEST SYSTEMS

    8.1  Single exposure

         1,2-Dichloroethane is moderately acutely toxic in
    experimental animals.  For example, LC50s for rats 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
    LD50s for rats, mice, dogs, and rabbits ranged from 413 to 2500
    mg/kg body weight (Barsoum & Saad, 1934; McCollister et al.,
    1956; Smyth, 1969; Larionov and Kokarovtseva, 1976; Munson et
    al., 1982; NIOSH, 1994a).

    8.2  Irritation and sensitization

         Application of 1,2-dichloroethane to the skin of
    experimental animals has resulted in microscopic changes and
    moderate oedema (Duprat et al., 1976; Kronevi et al., 1981;
    Jakobson et al., 1982).  Similarly, histological changes and mild
    irritation in the eye have been observed in animals following
    direct application (Kuwabara et al., 1968; Duprat et al., 1976). 
    No information on the sensitization potential of this substance
    was identified.

    8.3  Short-term exposure

         Few data were identified on the toxicity of
    1,2-dichloroethane following short-term exposure.  Degeneration
    and necrosis of the liver and kidneys, accompanied by congestion
    and haemorrhage of the lungs and adrenal glands, were observed in
    small groups of rats, rabbits, guinea-pigs, dogs, and pigs
    exposed to 1,2-dichloroethane by inhalation at 6000 mg/m3, 7
    hours/day, for 6 days (Heppel et al., 1945).  No effects on body
    or organ weights, histology, or clinical chemistry were noted in
    rats administered oral doses of up to 150 mg/kg body weight per
    day for 2 weeks (van Esch et al., 1977; Reitz et al., 1982).

    8.4  Long-term exposure

    8.4.1  Subchronic exposure

         The results of subchronic studies in several species of
    experimental animals indicate that the liver and kidneys are the
    target organs of 1,2-dichloroethane exposure; however, most of
    these studies were inadequate to serve as a basis for
    establishing reliable no-observed-effect levels or lowest-
    observed-effect levels, 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 several
    species following subchronic exposure (7 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 observed in rats following subchronic oral
    administration of doses of 49-82 mg/kg body weight per day and
    above for 13 weeks (van Esch et al., 1977; NTP, 1991).

    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 experimental 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-dichloroethane 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, 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 papillomas) was
    significantly increased in female non-inbred Ha:ICR mice ( n =
    30) following repeated dermal application 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 episulfonium 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).  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-dichloroethane 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).



        Table 2:  Genotoxicity of 1,2-dichloroethane  in vitro 
    (modified from ATSDR, 1992).

                                                                                                                                     
                                                                                      Result
                                                                                                        
    Species (test system)                     End-point                       With           Without
                                                                              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
                                                                                                                                     

    Table 2 (continued)

                                                                                                                                     
                                                                                      Result
                                                                                                        
    Species (test system)                     End-point                       With           Without
                                                                              activation     activation     Reference
                                                                                                                                     

    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 C3H1OT´                             Cell transformation             NT             +b             Schultz et al., 1992
    Syrian hamster embryo cells               Cell transformation             NT             +              Hatch et al., 1983

                                                                                                                                     

    Table 2 (continued)

                                                                                                                                     
                                                                                      Result
                                                                                                        
    Species (test system)                     End-point                       With           Without
                                                                              activation     activation     Reference
                                                                                                                                     
    - 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 cells                               Gene mutation                   NT             +              Ferreri et al., 1983
    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.
    

        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, and stomach                   DNA binding                      +              Reitz et al., 1982
    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
                                                                                                                         

    Table 3 (continued)

                                                                                                                         

    Species (test system)                         End-point                        Results        Reference
                                                                                                                         

    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-mediated assay                         Gene mutation                    -              King et al., 1979
                                                                                                                         

    - = 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).

         Based on available data, the most sensitive freshwater
    vertebrate species appears to be the northwestern 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-dichloroethane 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
    limited bioassays, the production of a reactive intermediate 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, haemangiosarcomas, 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
    µg/m3 or 0.36-2.0 µg/m3.  (Corresponding values for ingestion
    are 1.2-6.8 µg/kg body weight per day or 0.12-0.68 µg/kg body
    weight per day.)

         It should be noted, however, that the risk of exposure in
    air is most likely overestimated, as the TD0.05s were based on a
    study in which the experimental animals were administered bolus
    doses of 1,2-dichloroethane 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 genotoxic
    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
    carcinogenicity (i.e. 3.6-20 µg/m3 or 0.36-2.0 µg/m3, the 
    TD0.05s 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 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 characterization 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 sufficient 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 compound 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-dichloroethane in
    drinking-water estimated to be associated with excess risks of
    10-4, 10-5, and 10-6 are 300, 30, and 3 µg/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.

    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.

    13.1  Human health hazards

         1,2-Dichloroethane is highly flammable.  On long-term or
    repeated exposure, it is considered to be a probable human
    carcinogen.

    13.2  Advice to physicians

         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.

    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 vicinity. 
    Because the substance is absorbed through the skin, do not touch
    or walk through the spilled material without proper equipment. 
    To avoid the flammability hazard, remove wet or contaminated
    clothing immediately, 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).

    14.  CURRENT REGULATIONS, GUIDELINES, AND STANDARDS

         Information on national regulations, guidelines, 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.



        INTERNATIONAL CHEMICAL SAFETY CARD
    1,2-DICHLOROETHANE                                                                    ICSC:0250

                                                              1,2-DICHLOROETHANE
                                                              Ethylene dichloride
                                                            1,2-Ethylene dichloride
                                                               Ethanedichloride
                                                              ClCH2CH2Cl/C2H4Cl2
                                                             Molecular mass: 98.96
    CAS #       107-06-2
    RTECS #     KI0525000
    ICSC #      0250
    UN #        1184
    EC #        602-012-00-7

    FIGURE 2

                                                                                                                                        

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

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

    EXPLOSION                  Vapour/air mixtures are         Closed system, ventilation,     In case of fire: keep drums,
                               explosive.                      explosion-proof electrical      etc., cool by spraying with
                                                               equipment and lighting.         water.
                                                               Prevent build-up of
                                                               electrostatic charges (e.g.,
                                                               by grounding) (see Notes).
                                                                                                                                        

    INTERNATIONAL CHEMICAL SAFETY CARD (continued)

                                                                                                                                        

    TYPES OF                   ACUTE HAZARDS/                  PREVENTION                      FIRST AID/
    HAZARD/                    SYMPTONS                                                        FIRE FIGHTING
    EXPOSURE
                                                                                                                                        
    EXPOSURE                                                   AVOID ALL CONTACT!              IN ALL CASES CONSULT A
                                                                                               DOCTOR!

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

    * SKIN                     Redness.                        Protective gloves.              Remove contaminated clothes.
                                                                                               Rinse and then wash skin with
                                                                                               water and soap. Refer for
                                                                                               medical attention.

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

    * INGESTION                Abdominal cramps. Diarrhoea     Do no eat, drink, or smoke      Give nothing to drink. Refer
                               (further see Inhalation).       during work. Wash hands         for medical attention.
                                                               before eating.
                                                                                                                                        

    INTERNATIONAL CHEMICAL SAFETY CARD (continued)

                                                                                                                                        

    SPILLAGE DISPOSAL                             STORAGE                                   PACKAGING & LABELLING
                                                                                                                                        

    Evacuate danger area! Collect leaking         Fireproof. Separated from strong          Unbreakable packaging; put breakable
    and spilled liquid in sealable                oxidants, food and feedstuffs and         packaging into closed unbreakable
    containers as far as possible. Absorb         other incompatible substances (see        container. Do not transport with food
    remaining liquid in sand or inert             Chemical Dangers). Cool. Dry.             and feedstuffs.
    absorbent and remove to safe place. Do                                                  F symbol
    NOT wash away into sewer (extra                                                         Y symbol
    personal protection: self-contained                                                     R: 45-11-22-36/37/38
    breathing apparatus).                                                                   S: 53-45
                                                                                            Note: E
                                                                                            UN Hazard Class:      3
                                                                                            UN Subsidiary Risks:  6.1
                                                                                            UN Packing Group:     11
                                                                                            Marine Pollutant.
                                                                                                                                        

    INTERNATIONAL CHEMICAL SAFETY CARD (continued)

                                                                                                                                        

    IMPORTANT DATA      PHYSICAL STATE; APPEARANCE:                          INHALATION RISK:

                        COLOURLESS, VISCOUS LIQUID, WITH                     A harmful contamination of the air can be
                        CHARACTERISTIC ODOUR, TURNS DARK ON EXPOSURE         reached very quickly on evaporation of this
                        TO AIR, MOISTURE AND LIGHT                           substance at 20°C.

                        PHYSICAL DANGERS:                                    EFFECTS OF SHORT-TERM EXPOSURE:

                        The vapour is heavier than air and may travel        The vapour irritates the eyes, the skin and
                        along the ground; distant ignition possible.         the respiratory tract. Inhalation of the
                        As a result of flow, agitation, etc.,                vapour may cause lung oedema (see Notes). The
                        electrostatic charges can be generated.              substance may cause effects on the central
                                                                             nervous system, kidneys, liver, resulting in
                        CHEMICAL DANGERS:                                    impaired functions.

                        The substance decomposes on heating and on           EFFECTS OF LONG-TERM OR REPEATED EXPOSURE:
                        burning producing toxic and corrosive fumes
                        including hydrogen chloride (ICSC #0163) and         Repeated or prolonged contact with skin may
                        phosgene (ICSC #0007). Reacts violently with         cause dermatitis. This substance is probably
                        aluminium, alkali metals, alkali amides,             carcinogenic to humans.
                        ammonia bases, strong oxidants. Attacks many
                        metals in presence of water. Attacks plastic.

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

                        ROUTES OF EXPOSURE:

                        The substance can be absorbed into the body by
                        inhalation of its vapour, through the skin and
                        by ingestion.
                                                                                                                                        

    INTERNATIONAL CHEMICAL SAFETY CARD (continued)

                                                                                                                                        

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

    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 tehrefore essential.
    Immediate administration of an appropriate spray, by a doctor or a person authorized by him/her, should be considered.

    EXPLOSION/PREVENTION: Do NOT use compressed air for filling, discharging, or handling.

    ICSC: 0250 1.1                                                                                   Transport Emergency Card: TEC (R)-605
                                                                                                                  NFPA Code: H 2; F 3; R 0
                                                                                                                                        
    

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    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

         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.

    FIGURE 3

    APPENDIX 2 - CICAD FINAL REVIEW BOARD

    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

    Mr R. Cary, Toxicology and Existing Substances Regulation Unit,
    Health and Safety Executive, Merseyside, United Kingdom

    Dr J. de Fouw, National Institute of Public Health and
    Environmental Protection, Bilthoven, The Netherlands

    Dr C. DeRosa, Director, Division of Toxicology, Agency for Toxic
    Substances and Disease Registry, Atlanta, GA, USA

    Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood,
    Abbots Ripton, Huntingdon, Cambridgeshire, United Kingdom

    Dr W. Farland, Director, National Center for Environmental
    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

    Professor S. Tarkowski, Department of Environmental Health
    Hazards, The Nofer Institute of Occupational Medicine, Lodz,
    Poland

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

    Secretariat

    Dr M. Baril, International Programme on Chemical Safety, World
    Health Organization, Geneva, Switzerland

    Dr L. Harrison, International Programme on Chemical Safety, World
    Health Organization, Geneva, Switzerland

    Dr M. Mercier, Director, International Programme on Chemical
    Safety, World Health Organization, Geneva, Switzerland

    Dr P. Toft, Associate Director, International Programme on
    Chemical Safety, World Health Organization, Geneva, Switzerland

    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'environnement).  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, subchronique 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-dichloréthane 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 augmentation 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 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 µg/m3 ou 0,36-2,0 µg/m3; il faut cependant noter que
    cette méthode surestime les risques, car les données disponibles
    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 µg/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.

    RESUMEN DE ORIENTACION

         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 ambientales 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 
    información 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 internacional, 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.  
    Comunicándose 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
    Internacional 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 principalmente 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 fumigante, 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 moderadamente 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 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 sistemáticamente genotóxica en numerosas pruebas
    realizadas  in vitro en células de procariotas, hongos y
    mamíferos (incluidas células humanas).  Análogamente, se han
    obtenido resultados invariablemente positivos indicadores 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 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.




    See Also:
       Toxicological Abbreviations
       Dichloroethane, 1,2- (EHC 176, 1995, 2nd edition)
       Dichloroethane, 1,2- (EHC 62, 1987, 1st edition)
       Dichloroethane, 1,2- (FAO Nutrition Meetings Report Series 48a)
       Dichloroethane, 1,2- (WHO Food Additives Series 30)
       Dichloroethane, 1,2-  (WHO Pesticide Residues Series 1)
       Dichloroethane, 1,2- (Pesticide residues in food: 1979 evaluations)
       Dichloroethane, 1,2- (IARC Summary & Evaluation, Volume 71, 1999)