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 Dr J. Sekizawa,
    National Institute of Health Science, Japan

    Published under the joint sponsorship of the United Nations
    Environment Programme, the International Labour Organisation, and the
    World Health Organization

    World Health Organization
    Geneva, 1996

         The International Programme on Chemical Safety (IPCS) is a joint
    venture of the United Nations Environment Programme, the International
    Labour Organisation, and the World Health Organization. The main
    objective of the IPCS is to carry out and disseminate evaluations of
    the effects of chemicals on human health and the quality of the
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    carried out by the IPCS include the development of know-how for coping
    with chemical accidents, coordination of laboratory testing and
    epidemiological studies, and promotion of research on the mechanisms
    of the biological action of chemicals.

    WHO Library Cataloguing in Publication Data


    (Environmental health criteria ; 177)

    1.Ethylene dibromide - adverse effects  2.Solvents
    3.Environmental exposure  I.Series

    ISBN 92 4 157177 2                 (NLM Classification: QV 633)
    ISSN 0250-863X

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    1. SUMMARY

         1.1. Identity, physical and chemical properties, and analytical
         1.2. Sources of human and environmental exposure
         1.3. Environmental levels and degradation
         1.4. Kinetics and metabolism in laboratory animals
         1.5. Effects on laboratory mammals and  in vitro test systems
         1.6. Effects on humans
         1.7. Effects on organisms in the environment


         2.1. Identity
         2.2. Physical and chemical properties
         2.3. Conversion factors
         2.4. Analytical methods
               2.4.1. Air
               2.4.2. Water
               2.4.3. Soils and sediment
               2.4.4. Food


         3.1. Natural occurrence
         3.2. Anthropogenic sources
               3.2.1. Production levels and processes
                 World production figures
                 Manufacturing processes
               3.2.2. Uses
                 Petrol additive


         4.1. Transport and distribution between media
               4.1.1. Air
               4.1.2. Soil


         5.1. Environmental levels
               5.1.1. Air

               5.1.2. Water
               5.1.3. Food
         5.2. Occupational exposure


         6.1. Absorption
         6.2. Distribution
         6.3. Metabolic transformation
         6.4. Elimination and excretion in expired air, faeces and urine
         6.5. Retention and turnover
         6.6. Reaction with body components


         7.1. Single exposure
               7.1.1. Oral
               7.1.2. Inhalation
               7.1.3. Intraperitoneal injection
         7.2. Short-term exposure
               7.2.1. Oral
               7.2.2. Inhalation
         7.3. Eye and skin irritation
               7.3.1. Rabbit
         7.4. Long-term exposure
               7.4.1. Oral
               7.4.2. Inhalation
         7.5. Developmental toxicity
               7.5.1. Reproduction
                 Effects on sperm
                 Effects on ova
               7.5.2. Teratogenicity
                 Effects on neonatal behaviour

         7.6. Mutagenicity and related end-points
               7.6.1.  In vitro assays
               7.6.2.  In vivo assays
               7.6.3. Other studies
         7.7. Carcinogenicity
               7.7.1. Administration by gavage
               7.7.2. Administration in drinking-water
               7.7.3. Inhalation
               7.7.4. Dermal application
               7.7.5. Cell transformation
         7.8. Biochemical studies and species specificity


         8.1. Acute toxicity
         8.2. Occupational exposure
               8.2.1. Cancer incidence
               8.2.2. Reproductive effects


         9.1. Aquatic organisms
               9.1.1. Invertebrates
               9.1.2. Fish
         9.2. Terrestrial biota
         9.3. Microorganisms
         9.4. Plants


         10.1. Evaluation of human health risks
         10.2. Evaluation of effects on the environment








         Every effort has been made to present information in the criteria
    monographs as accurately as possible without unduly delaying their
    publication.  In the interest of all users of the Environmental Health
    Criteria monographs, readers are requested to communicate any errors
    that may have occurred to the Director of the International Programme
    on Chemical Safety, World Health Organization, Geneva, Switzerland, in
    order that they may be included in corrigenda.

                           *     *     *

         A detailed data profile and a legal file can be obtained from the
    International Register of Potentially Toxic Chemicals, Case postale
    356, 1219 Châtelaine, Geneva, Switzerland (Telephone No. 9799111).

                           *     *     *

         This publication was made possible by grant number 5 U01
    ES02617-15 from the National Institute of Environmental Health
    Sciences, National Institutes of Health, USA, and by financial support
    from the European Commission.

    Environmental Health Criteria



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    FIGURE 1

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    these rules are followed.



    Dr T. Bailey, US Environmental Protection Agency, Washington DC, USA

    Dr A.L. Black, Department of Human Services and Health, Canberra,

    Mr D.J. Clegg, Carp, Ontario, Canada

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

    Dr P.E.T. Douben, Her Majesty's Inspectorate of Pollution, London,
         United Kingdom  (EHC Joint Rapporteur)

    Dr P. Fenner-Crisp, US Environmental Protection Agency, Washington DC,

    Dr R. Hailey, National Institute of Environmental Health Sciences,
         National Institutes of Health, Research Triangle Park, USA

    Ms K. Hughes, Environmental Health Directorate, Health Canada, Ottawa,
         Ontario, Canada  (EHC Joint Rapporteur)

    Dr D. Kanungo, 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, Denmans Lane, Fontwell,
         Arundel, West Sussex, United Kingdom  (CAG Joint Rapporteur)

    Professor M. Lotti, Institute of Occupational Medicine, University of
         Padua, Padua, Italy  (Chairman)

    Professor D.R. Mattison, University of Pittsburgh, Graduate School of
         Public Health, Pittsburgh, Pennsylvania, USA

    Dr J. Sekizawa, National Institute of Health Sciences, Tokyo, Japan

    Dr P. Sinhaseni, Chulalongkorn University, Bangkok, Thailand

    Dr S.A. Soliman, King Saud University, Bureidah, Saudi Arabia

    Dr M. Tasheva, National Centre of Hygiene, Medical Ecology and
         Nutrition, Sofia, Bulgaria  (CAG Joint Rapporteur)

    Mr J.R. Taylor, Pesticides Safety Directorate, Ministry of
         Agriculture, Fisheries and Food, York, United Kingdom

    Dr H.M. Temmink, Wageningen Agricultural University, Wageningen, The

    Dr M.I. Willems, TNO Nutrition and Food Research Institute, Zeist, The


    Ms A. Sundén Byléhn, International Register of Potentially Toxic
         Chemicals, United Nations Environment Programme, Châtelaine,

    Dr P. Chamberlain, International Programme on Chemical Safety, World
         Health Organization, Geneva, Switzerland

    Dr J. Herrman, International Programme on Chemical Safety, World
         Health Organization, Geneva, Switzerland

    Dr K. Jager, International Programme on Chemical Safety, World Health
         Organization, Geneva, Switzerland

    Dr P. Jenkins, International Programme on Chemical Safety, World
         Health Organization, Geneva, Switzerland

    Dr W. Kreisel, World Health Organization, Geneva, Switzerland

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

    Dr M.I. Mikheev, Occupational Health, World Health Organization,
         Geneva, Switzerland

    Dr G. Moy, Food Safety, World Health Organization, Geneva, Switzerland

    Mr I. Obadia, International Labour Organisation, Geneva,    

    Dr R. Plestina, International Programme on Chemical Safety, World
         Health Organization, Geneva, Switzerland

    Dr E. Smith, International Programme on Chemical Safety, World Health
         Organization, Geneva, Switzerland  (EHC Secretary)

    Mr J. Wilbourn, International Agency for Research on Cancer, Lyon,


         The Core Assessment Group (CAG) of the Joint Meeting on
    Pesticides (JMP) met at the World Health Organization, Geneva from
    25 October to 3 November 1994.  Dr W. Kreisel, Executive Director,
    welcomed the participants on behalf of WHO, and Dr M. Mercier,
    Director, IPCS, on behalf of the IPCS and its cooperating
    organizations (UNEP/ILO/WHO).  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-dibromoethane
    (ethylene dibromide).

         The preparation of the first draft of the monograph was
    coordinated by Dr J. Sekizawa, National Institute of Health Sciences,
    Japan.  The second draft, revised in the light of international
    comment, was prepared under the coordination of Dr Sekizawa.
    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 efforts of all who helped in the preparation and finalization
    of the monograph are gratefully acknowledged.

         The authors who contributed to the first draft were:

         Dr C. Hashida     The Jikei University School of Medicine, Japan
         Dr Y. Hayashi     National Institute of Health Sciences, Japan
         Dr E. Kamata      National Institute of Health Sciences, Japan
         Dr Y. Kurokawa    National Institute of Health Sciences, Japan
         Dr A. Matsuoka    National Institute of Health Sciences, Japan
         Dr T. Matsushima  The Japan Industrial Safety and Health
         Dr K. Morimoto    National Institute of Health Sciences, Japan
         Dr M. Nakadate    National Institute of Health Sciences, Japan
         Dr G. Ohmori      The Jikei University School of Medicine, Japan
         Dr Y. Saito       National Institute of Health Sciences, Japan
         Dr J. Sekizawa    National Institute of Health Sciences, Japan
         Dr T. Sohuni      National Institute of Health Sciences, Japan
         Dr M. Takeda      National Institute of Health Sciences, Japan
         Dr M. Takemura    Ashiya University, Japan
         Dr Y. Takenaka    National Institute of Health Sciences, Japan
         Dr S. Tanaka      National Institute of Health Sciences, Japan


    BCF           bioconcentration factor

    BUN           blood urea nitrogen

    ECD           electron capture detector

    EDB           1,2-dibromoethane (ethylene dibromide)

    FID           flame ionization detector

    GC            gas chromatography

    GSH           glutathione

    gamma-GT      gamma-glutamyltranspeptidase

    HECD          Hall electron capture detector

    LOEL          lowest-observed-effect level

    MS            mass spectrometry

    NADPH         reduced nicotinamide adenine dinucleotide phosphate

    NOEL          no-observed-effect level

    PIB           piperonyl butoxide

    SGOT          serum glutamic-oxalic transaminase

    SGPT          serum glutamic-pyruvic transaminase

    TEAM          total exposure assessment methodology

    TWA           time-weighted average

    UDS           unscheduled DNA synthesis

    VHH           volatile halogenated hydrocarbon

    VOC           volatile organic carbon compound

    1.  Summary

    1.1  Identity, physical and chemical properties, and analytical

         1,2-Dibromoethane (ethylene dibromide) is a colourless liquid
    (melting point 9.9°C, boiling point 131.4°C) with a chloroform-like
    odour.  It is quite volatile, with a vapour pressure of 1.47 kPa
    (11 mmHg) at 25°C and a vapour density compared to air of 6.1. 
    1,2-Dibromoethane is miscible with most organic solvents.  Its
    solubility in water is 4.3 g/litre at 30°C.

         1,2-Dibromoethane in ambient air is analysed by GC after
    absorption to porous polymers followed by rapid thermal desorption.  A
    purge-trap method is used for water samples.  1,2-Dibromoethane
    residues in foods and other media can either be extracted by solvents
    or be subjected to automated headspace analysis under cryogenic
    conditions followed by analysis by GC and HPLC after derivatization.

    1.2  Sources of human and environmental exposure

         1,2-Dibromoethane is used as a scavenger of lead antiknock agents
    in gasoline.  It is also used as a soil fumigant and for fumigation of
    grains and fruits.  Reduced use of leaded gasoline in some countries
    and cancellations of registrations for the use of 1,2-dibromoethane
    for agricultural applications has reduced human exposure to
    1,2-dibromoethane.  However, it is still used as a lead scavenger in
    gasoline in some countries, as a fumigant, for quarantine purposes, as
    a solvent and as an intermediate for industrial chemicals.

    1.3  Environmental levels and degradation

         Concentrations of 1,2-dibromoethane measured in air range from
    undetectable to the order of ng/m3 in urban areas.  1,2-Dibromoethane
    has been found in ground water at up to 0.2 µg/litre and in surface
    water at up to 50 µg/litre in areas of extensive agricultural use. 
    Although 1,2-dibromoethane leaches through soil, some is retained in
    the soil matrix and may later contaminate irrigation wells.  There is
    a lack of information on microbial breakdown in soils.

         The high volatility of 1,2-dibromoethane means that the major
    environmental sink is the atmosphere.  Stratospheric photolysis may
    lead to the formation of breakdown products with ozone-depleting

    1.4  Kinetics and metabolism in laboratory animals

         1,2-Dibromoethane is rapidly absorbed orally, dermally and by
    inhalation.  Metabolites are thought to play an important role in
    1,2-dibromoethane toxicity for humans.  It can be metabolized by an
    oxidative pathway (cytochrome P-450 system) and a conjugation pathway

    (glutathione  S-transferase system).  Two reactive metabolites,
    bromacetaldehyde formed via the oxidation pathway and thiiranium ion
    formed via the conjugation pathway, are thought to interact with
    cellular macromolecules (proteins, DNA) to form covalently bound

    1.5  Effects on laboratory mammals and  in vitro test systems

         1,2-Dibromoethane is acutely toxic to animals (oral LD50 for
    rats of 146-417 mg/kg body weight, inhalation LC50 for rats of
    3080 mg/m3 after a 2-h exposure, mortality observed following dermal
    application of 210 mg/kg to rabbits).  Toxic effects of
    1,2-dibromoethane were mainly observed in the liver and kidneys. 
    Inhaled 1,2-dibromoethane vapour produced nasal irritation and
    depression of the central nervous system.  In rats exposed to
    concentrations between 1540 and 77 000 mg/m3 (200-10 000 ppm) for
    exposure durations between 0.1 and 16.0 h, deaths occurred in all
    groups and were related to concentration and time.  1,2-Dibromoethane
    (1.0% solution) caused irritation of shaved abdominal skin and eye
    irritation in rabbits.

         After oral subchronic exposure, mortality and decreases in weight
    gain were observed in rats and mice at 100 mg/kg body weight per day. 
    Decreases in weight gain and nasal pathological effects were noted in
    rats exposed to 1,2-dibromoethane at 115 mg/m3 (578 ppm) for
    6 h/day, 5 days/week, for 13 weeks.  The NOEL for histopathological
    alterations of the nasal cavity was 23 mg/m3 (3 ppm) in this study. 
    In a similar study in mice, the same pathological changes were
    observed, also with a NOEL of 23 mg/m3 (3 ppm).

         After mice or rats were administered 1,2-dibromoethane by gavage
    at 37-107 mg/kg body weight per day (TWA) for 49-90 weeks or mice were
    administered 103-117 mg/kg body weight per day in drinking-water for
    15-17 months, non-carcinogenic changes such as liver degeneration,
    testicular atrophy, and forestomach acanthosis and hyperkeratosis in
    addition to mortality were observed.  After inhalation exposure (mice
    or rats exposed to 77-388 mg/m3 for 6-18 months), inflammation of
    the trachea and nasal cavity, testicular degeneration and hepatic
    necrosis were observed.

         1,2-Dibromoethane was not teratogenic in rats or mice following
    inhalational exposure.  Developmental toxicity (impairment of
    development of motor coordination) was observed in the offspring of
    male rats treated intraperitoneally with 1.25 mg/kg body weight per
    day and in the offspring of female rats treated by inhalation
    509 mg/m3, 4 h/day, 3 days/week from day 3 to day 20 of gestation. 
    1,2-Dibromoethane affected the reproductive performance of rats (in
    males at the exposure level of 684 mg/m3, 7 h/day, 5 days/week, for
    10 weeks, and in females at the exposure level of 614 mg/m3,
    7 h/day, 7 days/week, for 3 weeks). The NOEL for this parameter was
    300 mg/m3 in both sexes.  The NOEL for reproductive performance of

    male rats in a feeding study was 50 mg/kg per day after a 90-day
    exposure.  Spermatogenesis was affected in bulls following oral dosing
    with 2 mg/kg per day for less than 21 days and in rabbits following
    subcutaneous injection of 15 mg/kg for 5 days.  Feeding of
    1,2-dibromoethane caused diminution of egg size in hens after exposure
    to 12.5 mg/kg per day for 12 weeks.

         1,2-Dibromoethane did not induce dominant lethal mutations in
    mice or rats, and did not produce chromosomal aberrations or
    micronuclei in the bone-marrow cells of mice treated  in vivo.
    However, it was mutagenic in bacterial assays and caused single-strand
    DNA breaks. Metabolites of 1,2-dibromoethane were covalently bound to
    DNA,  in vivo and  in vitro.  Sister chromatid exchange, mutations
    and unscheduled DNA synthesis were observed in human cells  in vitro.

         Carcinogenicity studies involving oral administration (mice and
    rats exposed by gavage to 37-107 mg/kg body weight per day (TWA) for
    49-90 weeks; mice given 1,2-dibromoethane in drinking-water at
    103-117 mg/kg body weight per day for 15-17 months), inhalational
    exposure (mice and rats exposed at 10-40 ppm for 6-18 months) or skin
    administration (25-50 mg/mice, 3 times/week for 400-594 days) showed
    that 1,2-dibromoethane is carcinogenic to rats and mice, causing
    tumours in a variety of organs (both at the application site and
    distant sites, including the nasal cavity, lung, stomach, liver, skin,
    circulatory system and mammary glands).  In many cases it reduced the
    latency period in developing tumours.

    1.6  Effects on humans

         1,2-Dibromoethane may produce adverse effects on the respiratory,
    nervous and renal systems.

         Acute (single) inhalation exposure to 1,2-dibromoethane at
    215 mg/m3 (28 ppm) for 30 min or more has been shown to be fatal for
    humans.  Ingestion of 140 mg/kg body weight was fatal.  Long-term
    exposure to 1,2-dibromoethane (5 y) at a concentration of 0.68 mg/m3
    in the breathing zone significantly decreased sperm counts and
    fertility in occupationally exposed workers.

    1.7  Effects on organisms in the environment

         Few aquatic ecotoxicity studies have been performed with
    1,2-dibromoethane.  The LC50s for aquatic organisms are greater than
    5 mg/litre.  No information is available on terrestrial organisms.


    2.1  Identity

    Chemical name             1,2-dibromoethane

    Chemical structure:       Br - CH2 - CH2 - Br

    Molecular formula:        C2H4Br2

    Relative molecular        187.9

    CAS chemical name:        ethylene dibromide

    CAS registry number:      106-93-4

    Synonyms:                  sym-dibromothane, DBE, dibromo, bromure
                              d'ethylene, 1,2-ethylene dibromide, ethylene

    Major trade names:        Nematron, Nemafume, Bromofume, Dowfume W-85,
                              Aadibrom, Iscobrome D

    Formulations:             kerosene (30 and 97%),
                              emulsifiable concentrate (40 and 48%)
                              in combination with other pesticides

    2.2  Physical and chemical properties

    Appearance:               colourless liquid with chloroform-like odour

    Melting point:            9.9°C (Stenger, 1983)

    Boiling point:            131.4°C (Stenger, 1983)

    Vapour pressure:          1.47 kPa (11.0 mmHg)
      (at 25°C)               (Verschueren, 1983)

    Vapour density:           6.1

    Specific gravity:         2.172 (Stenger, 1983)
      (at 25°C)

    Refractive index (n20):   1.5379

    Solubility in water:      4.3 g/litre at 30°C (Verschueren, 1983)
                              soluble in ether, etanol, benzene, acetone
                              (Weast et al., 1988)

    Saturating concentration  113 g/m3 (at 20°C), 168 g/m3 (at 30°C)
      in air:

    Log Pow                   1.76 or 1.93

    Stability:                decomposes gradually when exposed to light

         1,2-Dibromoethane is flammable.  Chemically, 1,2-dibromoethane is
    a bifunctional alkylating agent.

    2.3  Conversion factors

         1 ppm     = 7.68 mg/m3 (at 25°C);
         1 mg/m3   = 0.13 ppm

    2.4  Analytical methods

         Analytical methods for volatile halogenated hydrocarbons (VHH)
    are applicable to 1,2-dibromoethane.  Determination of
    1,2-dibromoethane is usually carried out by gas chromatography with
    electron capture detection (GC-ECD).  High resolution GC capillary
    columns can be used for multiple analysis in high-resolution gas
    chromatography (HR-GC) or high-resolution gas chromatography - mass
    spectrometry (HR-GC-MS).  A sensitive photoionization detector (Dumas
    & Bond, 1982; Collins & Barker, 1983), a Hall electroconductivity
    detector (Cairns et al., 1984) or mass spectrometry can also be used
    for determination and confirmation of 1,2-dibromoethane.  GC-ECD is
    the most sensitive method.

         The preconcentration of trace 1,2-dibromoethane in samples is
    usually carried out through collection by cryogenic trapping or by
    absorption on solid absorbents.  The former is the preferred 
    preconcentration technique.  Ice formation in the trap-tube during
    sampling can be a problem, especially with ambient water and
    homogenized food samples.  Co-collected water can alter sample or
    column flow rates in separation techniques that require subfreezing at
    initial GC oven temperature (Pleil et al., 1987).

    2.4.1  Air

         A convenient analytical method for trace levels of
    1,2-dibromoethane in ambient air is a combination of preconcentration
    by absorption on porous polymers, such as Tenax, Porapack, Florisil,
    silica-gel or charcoal, followed by rapid thermal desorption and
    direct application for GC.  Tenax GC resin is widely used for
    1,2-dibromoethane sampling in ambient air (Barkley et al., 1980; Clark
    et al., 1982, 1984a,b; Krost et al., 1982; Harkov et al., 1984),
    although Porapack, Chromosorb, silica gel and charcoal have also been
    used extensively (Kojima & Seo, 1976; Jagielski et al., 1978; Mann et
    al., 1980).  1,2-Dibromoethane is absorbed by passing air samples
    through the columns followed by thermal desorption and direct

    application to GC.  Alternatively, 1,2-dibromoethane in air is
    collected by cryogenic cooling in capillary trap-tubes and then
    thermally desorbed for GC analysis using trap-ovens with carrier gases
    (Barkley et al., 1980; Harkov et al., 1984; McClenny et al., 1984;
    Ballschmiter et al., 1986).

         The relatively high concentrations of 1,2-dibromoethane in or
    near fumigation chambers for foods and in automobile exhaust gases can
    be directly determined by sampling with a gas-tight syringe followed
    by GC analysis (Hasanen et al., 1979; Dumas & Bond, 1982; Morris et
    al., 1982; Collins & Barker, 1983).

         Analytical methods for measuring 1,2-dibromoethane in ambient air
    are summarized in Table 1.

    2.4.2  Water

         A purge-trap method using absorbents such as Tenax GC and
    Amberlite XAD-4 resin is the most effective concentration technique
    for recovering 1,2-dibromoethane from water samples before GC
    analysis.  The GC test solution is prepared by eluting the absorbent
    columns with a small volume of hexane (Spingarn et al., 1982;
    Stottmeister et al., 1986).  Another method for 1,2-dibromoethane
    concentration is direct absorption on organic resins like Amberlite
    XAD-1, 2, 4, 7 and 8, and XE-340 (Libbey, 1986).  Direct absorption of
    water samples on, for example, Amberlite XAD resins can be used for
    the concentration of 1,2-dibromoethane in aquatic media (Libbey, 1986;
    Woodrow et al., 1986). 

         Solvent extraction and headspace collection are simple methods
    for recovering 1,2-dibromoethane from water samples (Saito et al.,
    1978; Keough et al., 1984; Koida et al., 1986).

         Analytical methods for measuring 1,2-dibromoethane in water are
    summarized in Table 2.

    2.4.3  Soils and sediment

         1,2-Dibromoethane in sediments can be concentrated by a purge-
    trap procedure, either after dilution of sediment samples with water
    or after vacuum extraction from sediment samples into a cryogenically
    cooled trap (Amin & Narang, 1985).

         Analytical methods for measuring 1,2-dibromoethane in soils are
    summarized in Table 3.

        Table 1.  Analytical methods for 1,2-dibromoethane in air
    Collection from air          Preparation for GC        GC conditions                         Minimum detection  Detectora  Reference
                                                                                                 limit (amount)
    Collected on Chromosorb      extracted with hexane     1.5% OV-17+1.95% OV-210;              100 pg             ECD        Mann et al.
    101 cartridge                (20 ml); extracted with   column temp: 75°C;                    in 70%             FSRD       (1980)
    (10 mm i.d. × 10 cm)         1% MeOH in benzene,       gas flow: N2
    (ambient air)                extract kept in a         70 ml/min
                                 screw-capped test tube
                                 and injected into GC

    Collected directly with a    applied directly with     5.5% DC-200+11% GF-1/Ga               0.1 ng             ECD        Morris et al.
    gas-tight syringe            gas-tight syringe         Chrim Q (0.3 mm o.d. × 150 cm,                                      (1982); Morris
                                                           stainless steel); column temp:                                      & Rippon (1985)
                                                           90°C; gas flow: 40 ml/min

    Collected directly with a    applied directly with     5% Carbowax 20M/Chromosorb            2 µg               PID        Dumas &
    gas-tight syringe            gas-tight syringe         W (3 mm i.d. × 200 cm, stainless                         FSRD       Bond (1982)
                                                           steel); column temp: 120°C;
                                                           gas flow: N2 30 ml/min (portable
                                                           gas chromatograph)

    Collected with a gas-tight   applied by direct         CPS-20 M (1/8- × 4 tefron tube);      1 ppb              PID        Cairns et al.
    syringe (ambient air)        injection                 column temp: ambient temp;                                          (1984)

    Collected on Tenax GC        applied by rapidly        Fused silica SP-2000 FSOT             not given          ECD        Harkov et al.
    cartridge at a flow rate of  raising trap oven                                                                  GC/MS      (1984)
    approx.300-1000 ml/min for   temperature to 140°C
    24 h; desorbed from the      with purge of high
    cartridge by heating         purity N2 (50 ml/min)
    rapidly at 250°C and
    collected in an evacuated
    stainless steel cylinder 
    under cryogenic conditions
    using vacuum distillation
    for 30 min (ambient air)

    Table 1 (cont'd)
    Collection from air          Preparation for GC        GC conditions                         Minimum detection  Detectora  Reference
                                                                                                 limit (amount)
    Collected on a double        applied by rapidly        OV-1 fused silica capillary           1 ppb              ECD        McClenny et
    loop of 0.32 mm (o.d.)       heating the tube (-150    column (0.32 mm i.d. × 50 m);                                       al. (1984)
    nickel tubing packed with    to 100°C in 55 sec) and   column temp: -50°C (3 min)
    60-80 mesh Pyrex beads       cooling quickly (120      8°C/min 150°C (7 min)
    under cryogenic conditions   to -150°C in 225 sec)     -50°C (10 min); gas flow:
    (-150°C) (ambient air)                                 H2 4 ml/min

    a  ECD = electron caputure detector; PID = photoionization detector; GC = gas chromatography; MS = mass spectrometry;
       FSRD = full-scale recorder deflection

    Table 2.  Analytical methods for 1,2-dibromoethane in water
    Collection                   Preparation for GC        GC conditions                         Minimum detection  Detectora  Reference
                                                                                                 limit (amount)

    Headspace method             applied on a fused        1.J & W FSOT (0.326 mm i.d. × 30 m);  1.8 pg             GC/MS      Keough et al.
                                 silica line               Temp: column 70°C, ion source 299°C;                                (1984)
                                 (0.25 mm i.d. × 100 cm)   split ratio: 1:10; gas flow:
                                 at 250-275°C with a       1.5 ml/min; ion dwell time:
                                 gas-tight syringe         100 msec;
                                                           2.OV-1 FSOT (0.32 mm i.d. × 50 m);    not given          ECD
                                                           column temp: 60-90°C; split ratio:
                                                           1:1; gas flow: He 10 ml/min
                                                           N2 100 ml/min

    Extracted with               applied directly with a   1.5% OV-17 on Chromosorb W            0.05 mg/litre      GC/MS      Koida et al.
    hexane                       micro-syringe             (3 mm i.d. × 150 cm); temp: column                       (CI-NID)   (1986)
                                                           200°C; separator 120°C; ion source
                                                           200°C; reaction gas: isotutane;
                                                           gas flow: H2 20 ml/min

    Collected by purging         applied by rapidly        0.2% Carbowax 1500 on Carbopack C     0.3 mg/litre       FID        Stottmeister et
    into purge-trap              thermal desorption        (3 mm i.d. × 200 cm); column temp:                                  al. (1986)
    tubing (Tenax GC             (200°C)                   35°C (4 min), (8°C/min) 170°C
    155 mg) at flow                                        (20 min); gas flow: N2 4 ml/min
    rate of 50 ml/min
    for 30 min

    Table 2 (cont'd)
    Collection                   Preparation for GC        GC conditions                         Minimum detection  Detectora  Reference
                                                                                                 limit (amount)

    Collected by absorption      extracted with ether      1.DB-1701 FSOT(0.25 mm i.d. × 30 m);  1 ppt              ECD        Woodrow et
    on Amberlite                 and concentrated in       column temp: 230°C; split ratio:                         al. (1986)
    XAD-4 cartridge              Kudernadanish             1:10; gas flow: H2 19 ml/sec at
    column ball                  concentrator with 3       230°C; make-up gas Ar/CH4 20 ml/sec;
    (4.7 mm o.d. × 12 cm) at     Snyder column; applied    2.SE-54 FSOT (0.25 mm i.d. × 30 m);
    flow rate of 10 ml/min       with a microsyringe       column temp: 100°C (5°C/min)
    for 18-24 h                                            250°C (other conditions described

    a  ECD = electron capture detector; GC = gas chromatography; MS = mass spectrometry; FID = flame ionization detector;
       CI = chemical ionization; NID = negative ion detector

    Table 3.  Analytical methods for 1,2-dibromoethane in soil
    Collection                   Preparation for GC        GC conditions                         Minimum detection  Detectora  Reference
                                                                                                 limit (amount)

    Collected by steam           fortify 50 ml of the                                            not given          ECD        Abdel-Kader
    distillation of an           extract to folder paper                                                                       et al. (1979)
    aqueous slurry of soil       and then measure with
    into dry-ice-cooled          molecular emission cavity
    solvent (acetone:            analyser; 4 mm × 4 mm
    isooctane = 1:1)             deep stainless steel 
    under N2 stream at           cavity; gas flow:
    60°C and drying              H2 2.5 litre/min;
    over Na2SO4                  N2 4.0 litre/min;
                                 wave length: 376 nm;
                                 split: 1.4 nm

    Collected on Prapack         apply by thermal          4% OV-11 & 6% SP 2100 Supelcopor      7 ppb              PID        Amin &
    N by purge of                desorption of the         (2.0 mm × 2.7 m); column temp: 40°C                                 Narang (1985)
    an aqueous slurry            absorbent spiked with     (5 min), (3°C/min) 70°C; gas flow:
    of soil for 30 min           fluorobenzene as an       N2 30 ml/min, 15% SF-95 & 6% OV-225   1 ppb              ECD
                                 internal standard         on Chromosorb W (2 mm i.d. × 3.6 m);
                                                           column temp: 60°C (10 min),
                                                           (3°C/min) 80°C (10 min) 65°C-75°C

                                                           DB-5 FSOT(0.25 mm i.d. × 60 m)        PID
                                                           column temp: 50°C (15 min) (4°C/min)  ECD
                                                           170°C (14 min); gas flow:
                                                           He 60 cm/sec make-up gas He 8 ml/min

    a  ECD = electron caputure detector; PID = photoionization detector; GC = gas chromatography; FID = flame ionization detector

    2.4.4  Food

         Continuous extraction with hexane in a Dean-Stark apparatus for
    one hour or soaking in a solvent solution of ethanol or acetone and
    water (1 : 5) for 2 or 3 days is used for the analysis of
    1,2-dibromoethane in agricultural crops and their products. A highly
    sensitive method for the analysis of 1,2-dibromoethane in flour and
    biscuits was developed by Rains & Holder (1981).  Continuous
    extraction with hexane is used for fruit, vegetables and grains
    (Sekita et al., 1981, 1983; Kato et al., 1982; Iwata et al., 1983;
    Konishi et al., 1985; De Vries et al., 1985; Alleman et al., 1986;
    Nakamura, 1986).

         Soaking in aqueous ethanol or acetone and water solution is used
    for grains and their products (Clower, 1980; Daft, 1983, 1985, 1987;
    Cairns et al., 1984; Barry & Petzinger, 1985; Sawyer & Walters, 1986;
    Clower et al., 1986).  For fruit (papaya and lemon), hexane, hexane-
    water and acetonitrile are used.  In the case of grain, intermediate
    products, ready-to-eat products, corn bread mix, baby cereal and
    bread, 1,2-dibromoethane can be extracted with an acetone-water (5+1)
    solution, 0.1N HCl or light petroleum.  Where necessary, Florisil
    cleanup is useful for the removal of materials interfering with GC

         The purge-trap method on layers of Tenax TA (Heikes, 1985a,b),
    Tenax resins (GC and TA) or Amberlite XAD-4 (Heikes & Hopper, 1986;
    Daft, 1988) under a nitrogen gas stream is also used for the
    collection of 1,2-dibromoethane from grains and their products.  The
    resins are eluted with hexane.

         Automated headspace analysis is employed for measurement of
    1,2-dibromoethane in fumigated crops in combination with GC-ECD and
    GC-MS (Mestres et al., 1980; Entz & Hollifield, 1982; Gilbert et al.,
    1985; Pranoto-Soetardhi et al., 1986).  Equilibrium partitioning
    between the samples and the gaseous headspace can be accelerated by
    warming the vials.  For detection, the gas chromatographic method with
    an electron capture detector is used in all the above-mentioned
    methods. Gas chromatography-mass spectrometry is also used.  The
    detection limit ranges from 0.1 µg/kg to a few µg/kg according to the
    method used and the food being tested.

         1,2-Dibromoethane can be analysed in animal feed by continuous
    extraction with hexane in a Dean-Stark apparatus, followed by cleanup
    on a Florisil column (Ishikuro, 1986).


    3.1  Natural occurrence

         1,2-Dibromoethane is not a naturally occurring substance.

    3.2  Anthropogenic sources

    3.2.1  Production levels and processes  World production figures

         In 1975, 1400 tonnes was produced in Japan. Production in
    Belgium, France, Italy, the Netherlands, Spain, Switzerland and the
    United Kingdom, was estimated to be between 3000 and 30 000 tonnes
    (IARC, 1977).  Manufacturing processes

         1,2-Dibromoethane is made by direct bromination of ethylene or
    reacting hydrobromic acid with acetylene (Roskill, 1992).

    3.2.2  Uses

         Major uses of 1,2-dibromoethane are as a lead scavenger in
    tetraalkyllead petrol and antiknock preparations, as a soil and grain
    fumigant, as an intermediate in the synthesis of dyes and
    pharmaceuticals, and as a solvent for resins, gums and waxes (IARC,

         Reduction in the use of leaded gasoline from the late-1970s in
    developed countries and of 1,2-dibromoethane for agricultural
    applications in the 1980s, owing to its carcinogenicity in animals, 
    reduced human exposure to 1,2-dibromoethane. However, it is still used
    in large amounts for many industrial purposes in developed countries,
    and as a petrol additive in developing countries.  Petrol additive

         1,2-Dibromoethane has been added to scavenge the inorganic lead
    compounds (e.g., lead oxide and sulfate) remaining after fuel
    combustion.  Lead accumulation is prevented by the reaction of
    1,2-dibromoethane with lead oxide to form volatile lead bromide, which
    can pass from the combustion chamber to the atmosphere (IARC, 1977).
    In 1981, use as a lead scavenger represented 83% of the
    1,2-dibromoethane consumed (SRI International, 1982).

         In 1972, 122 000 tonnes 1,2-dibromoethane was added to petrol
    formulations in the USA; this figure declined to 73 000 tonnes in 1980
    and to 24 000 tonnes in 1992 (Roskill, 1992). In 1992, sales of
    unleaded petrol accounted for more than 90% of petrol in the USA. In

    the European Community, all new vehicles must be fitted  with
    three-way convertors that can only use unleaded petrol by the
    mid-1990s.  This is also true of Japan, where almost all cars run on
    unleaded petrol (Roskill, 1992).

         In 1992, demand for 1,2-dibromoethane as a gasoline additive in
    the USA was 24 000 tonnes and consumption outside the USA, principally
    in Europe, was 25 000 to 30 000 tonnes, giving an estimated world
    demand of 49 000 to 54 000 tonnes. The amount of 1,2-dibromoethane
    used in Germany in 1989 was 980 tonnes, calculated on the basis of the
    petrol consumed in the Federal Republic of Germany in 1989 (BUA,
    1991). Legislation banning the use of lead in gasoline and controlling
    the agricultural use of 1,2-dibromoethane has reduced world demand for
    1,2-dibromoethane by at least 75% (Roskill, 1992).  Fumigant

         The volatility of 1,2-dibromoethane allows it to be distributed
    as a gas through substances such as soil in sufficiently high
    concentrations to kill target pests.  Its chemical and biocidal
    properties allowed it to be effectively utilized in a wide range of
    applications.  Its primary pesticidal use has been as a soil
    nematocide (Pignatello & Cohen, 1989).

         1,2-Dibromoethane has been used in the spot fumigation of grain
    milling machinery, post-harvest fumigation of grain, and in the
    control and prevention of infestations in produce.  Additional minor
    uses have been the control of bark beetles in felled logs, moths in
    stored furniture and clothing, termites under concrete slab
    foundations and porches, Japanese beetles in balled ornamental trees
    and grass sod, and wax moths in stored honeycombs and beehive

         In post-harvest grain fumigation of barley, maize, oats,  rice,
    rye, sorghum and wheat, 1,2-dibromoethane has often been used in
    conjunction with 1,2-dichloroethane (ethylene dichloride) or carbon

         Residues of 1,2-dibromoethane in tropical fruits, imported wheat
    and beans have been prohibited in Japan (MHW, 1985, 1987, 1988).  Use
    of 1,2-dibromoethane for agricultural purposes has been prohibited in
    Egypt, Kenya, the Netherlands, Sweden, the United Kingdom and the USA
    (BUA, 1991; IRPTC, 1993).  However, it is still used for quarantine
    purpose in some countries.


    4.1  Transport and distribution between media

         The use of 1,2-dibromoethane on a field contaminated both the
    field and crops for 2 years (Yuita, 1984).  About 10% of bromine-
    containing pesticides was retained, in the form of bromine, in the
    soil and crops.  The remaining 90% seemed to have moved to underground
    water and rivers.

    4.1.1  Air

         The atmospheric chemistry of bromine compounds has received
    attention because of the role that they play in the depletion of the
    stratospheric ozone layer.  Wofsy et al. (1975) suggested that bromine
    atoms can be more effective than chlorine atoms in the catalytic
    destruction of ozone.  A major uncertainty is the absolute
    concentration of bromine compounds in both the troposphere and the

    4.1.2  Soil

         Injection of 1,2-dibromoethane as a soil fumigant at 70 kg/ha
    into fine sandy loam resulted in a concentration of 130 µg/kg nearly
    one year later (Steinberg et al., 1987).

         The disappearance with time of 1,2-dibromoethane was measured in
    a sediment-water mixture (ratio 0.075) and a half-life of 55 h was
    calculated (Jafvert & Wolfe, 1987).

         Important factors influencing the movement of soil fumigants 
    include their physical and chemical characteristics, temperature,
    moisture, presence of organic matter, soil texture and soil profile
    variability (Munnecke & Van Gundy, 1979).

         1,2-Dibromoethane is moderately hydrophillic, having a calculated
    octanol-water partition coefficient of 58 (Lyman, 1982).  At
    environmental levels (10-1000 ppb), 1,2-dibromoethane has a soil
    organic carbon partition coefficient of 66 ml/g (Rogers & McFarlane,

         1,2-Dibromoethane has a low vapour pressure and moves slowly in
    the vapour phase.  Little, if any, mass flow occurs except in
    extremely warm soil or when water is applied.  Soil temperature is
    important and may affect 1,2-dibromoethane movement in several ways. 
    A rise in temperature increases the vapour pressure and decreases the
    solubility.  This alters the phase distribution and results in an
    increase in the rate of diffusion of 1,2-dibromoethane through soils.
    Fumigation of warm soils (25°C) results in a faster rate and greater
    distance of nematicide diffusion.  In colder soils (5°C), the rate of
    diffusion is slower and the persistence of the chemical is longer, but

    the total distance of diffusion of an effective dosage is decreased. 
    The approximate movement and fate of 1,2-dibromoethane in two soils
    were predicted using extrapolations from laboratory experiments and
    soil-vapour phase concentrations obtained from simulated field
    experiments.  The most far-reaching diffusion patterns in mineral
    soils are those obtained in soils whose moisture content is nearest
    the wilting point of plants (15 bars moisture tension).  As the
    moisture content of the soil is increased, the diffusion pattern
    gradually becomes more limited.  The soil texture and type determine
    to a large extent the amount of soil moisture present and the size of
    the connecting air spaces.  Soil air space and the size of pores are
    important because these chemicals move primarily in the vapour phase
    and smaller pores are most easily blocked when water is present.  A
    material balance for 1,2-dibromoethane was surveyed when
    1,2-dibromoethane (equivalent to 47 litres/ha) was applied under
    various conditions to several soils using a soil fumigation technique
    in both field and laboratory experiments.  Most of the
    1,2-dibromoethane was accounted for; the remainder was mostly
    irreversibly adsorbed or lost during sampling.  The 1,2-dibromoethane
    not accounted for represented between 10 and 40%.  After 3 days at
    15°C, about 40% of the 1,2-dibromoethane was absorbed in the
    soil-particle phase, 25% was in the soil-water phase, and 20% remained
    in the liquid state (McKenry & Thomason, 1974).

         1,2-Dibromoethane soil fumigation is used for the control of
    plant parasitic nematodes on high value crops.  In Ontario, Canada,
    soil types fumigated varied from loamy sand to muck.  Three soils
    differing in texture (Fox loam sand, Vineland silt loam and Lincoln
    clay) were studied for penetration of 1,2-dibromoethane (Townshend et
    al., 1980).  Fox loam sand (highest content of sand and lowest of
    organic matter) showed the most rapid penetration; moisture level,
    temperature and their interactions had the greatest effects on
    movement of 1,2-dibromoethane.  On Vineland silt loam (medium-textured
    soil) the degree of penetration was dependent on moisture, temperature
    and bulk density, and there were relatively small interaction effects. 
    On Lincoln clay (high content of organic matter and fine-textured
    soil) 1,2-dibromoethane did not move in the soil, regardless of
    edaphic factors, thus explaining the difficulty of using
    1,2-dibromoethane fumigation to control nematodes in clay.

         1,2-Dibromoethane persists in top soil at µg/kg levels for at
    least 20 years, despite its predicted lability in the environment
    (high water solubility and low soil-water partition coefficient).
    Misleading results were obtained when studies of microbial
    degradation, sorption, desorption and analytical recovery were
    conducted with freshly spiked soils or sediments (Pignatello, 1986). 
    1,2-Dibromoethane can serve as a C1 unit and energy source for some
    soil aerobic or anaerobic microorganisms.  However, residual
    1,2-dibromoethane is strongly bound to soils and can only be extracted
    from them by warming with polar solvents.  Surfactants showed no
    enhanced extraction ability.  Thermal desorption at temperatures as

    high as 200°C in an N2 stream resulted in more decomposition than
    desorption, while a fresh spike of 14C-labelled 1,2-dibromoethane
    was recovered quantitatively.

         Diffusion of residual 1,2-dibromoethane from soil to water is
    very slow and highly temperature-dependent (diffusion coefficient:
    10-16 cm2/sec) (Pignatello et al., 1987).  1,2-Dibromoethane, when
    present as a groundwater contaminant in areas where it had been used
    as a soil fumigant, was degraded anaerobically by microorganisms in
    two types of soils from 1,2-dibromoethane-contaminated groundwater
    discharge areas.  At initial concentrations of 6 to 8 µg/litre,
    1,2-dibromoethane was degraded in a few days to near or below the
    detection limit (0.02 µg/litre).  At 15 to 18 µg/litre degradation was
    slow.  Bromide ion released at the higher concentration was 1.4 ± 0.3
    and 23.1 ± 0.2 molar equivalents for the two soil types.  A study
    using 14C-1,2-dibromoethane showed that 1,2-dibromoethane was
    converted to approximately equal amounts of CO2 and cellular carbon;
    only small amounts of 14C were not attributable to these products. 
    However, 1,2-dibromoethane was not degraded in autoclaved soil water
    samples.  The results suggested that, initially, microbial degradation
    of 1,2-dibromoethane in the topsoil was too slow to prevent leaching
    of large quantities to groundwater.  With continued application the
    microbial community may have adapted to the higher levels and
    degradation rates increased; this has been observed with other
    agricultural chemicals.  The results of acetate incorporation studies
    suggested that the highest application rates of 1,2-dibromoethane are
    definitely toxic to topsoil microbial communities.


    5.1  Environmental levels

    5.1.1  Air

         1,2-Dibromoethane enters the atmosphere from its use as a petrol
    additive to scavenge the lead oxide resulting from the combustion of
    alkyllead antiknock additive, and from its use in agriculture as an
    insecticidal and fungicidal fumigant.

         Nilsson et al. (1987) reported that the exhaust gas of chain saws
    fuelled with petrol contained a mean 1,2-dibromoethane level of
    0.0008 (0.0001-0.001) mg/m3 under snow-free conditions and
    0.002 (0.0001-0.005) mg/m3 with snow on the ground during the
    winter.  1,2-Dibromoethane levels are around 45% higher in cold start
    than in hot start conditions and have a tendency to decrease with
    increasing vehicle speed (see Tables 4 and 5).  Concentrations of
    1,2-dibromoethane in raw, undiluted exhaust from vehicles using leaded
    petrol are in the range of 55-146 µg/m3 (7.2-19 ppb), 46-122 µg/m3
    (6.0-16 ppb) and 38-115 mg/m3 (5.0-15 ppb) under the conditions of
    USA Federal test driving, idle, and a steady speed of 30 mph,
    respectively (Jacobs, 1980).  Based on these levels, 1,2-dibromoethane
    concentrations in air alongside roads due to vehicle exhaust emissions
    may range from 0.04 to 122 µg/m3 (0.005-0.19 ppb).  These results
    are similar to the observations of Leinster et al. (1978).

    Table 4.  1,2-Dibromoethane produced by motor vehicles (petrol engine)
              under constant speed test conditions

    Vehicle speed km/h                Concentration (µg/m3)

                       Engine not    Vehicle with        Vehicle with
                        defineda    3 litre engineb   0.85 litre engineb

    Cold start (idle)       70            878                332
               10           78
               30        62-70            618                165
               40           61
               50            2            669                155
               64                         180                139
               80                          98                135

    a  Leinster et al. (1978)
    b  Tsani-Bazaca et al. (1981)

    Table 5.  1,2-Dibromoethane in the exhaust emission of motor vehicles
              (petrol engine) (µg/m3)a

    Conditions             3 litre engine      0.85 letre engine

         cold start          292-560               733-538
         hot start           200-234               533-538

    ECD/CVSc                   14-25                 26-34

    USA Federald
         cold start               48                    29
         hot start                                      22

    a  From: Tsani-Bazaca et al. (1981)
    b  standard European driving cycle
    c  ECE driving cycle under constant volume sampling condition
    d  1973 driving cycle

         1,2-Dibromoethane levels in air have been measured at several
    sites around the world (Table 6). Leinster et al. (1978) concluded
    that the lower levels during the autumn were the result of a reduction
    in evaporative loss particularly from parked vehicles (the calculated
    evaporation rate for 1,2-dibromoethane at 5°C is less than one third
    of that at 30°C).  An indication of the  magnitude of evaporative loss
    from parked vehicles was provided by levels of 0.02-0.05 µg/m3
    measured in a car park.  It was also probable that an opposite trend
    would be produced by a change in driving conditions.  For example,
    cold starts and driving speeds of vehicles have a marked influence on
    the 1,2-dibromoethane content of exhaust emissions.

         The 1,2-dibromoethane added to leaded petrol contributes to a
    large amount of methyl bromide in urban atmospheres.  IPCS (1995)
    estimated that per annum between 7000 and 18 000 tonnes of methyl
    bromide could be emitted from car exhausts.  Reactions in the lower
    troposphere with hydroxyl radicals and other chemical species are the
    most important of the possible removal mechanisms within the
    atmosphere (UNEP, 1992).  The end-products of both photodissociation
    of methyl bromide and reactions with hydroxyl radicals in the
    atmosphere include bromide species (BUA, 1987).  Active bromine
    species react with ozone mainly in the lower stratosphere and are
    thought to be partly responsible for the destruction of the ozone
    layer.  However, 1,2-dibromoethane was not included as a controlled
    substance in the "Montreal Protocol on Substances that Deplete the
    Ozone Layer".

        Table 6.  Environmental concentrations of 1,2-dibromoethane
    Location                           Measuring period         Concentration (µg/m3)                   Reference

    London                             August 1976a             0.08-0.09 µg/m3                         Leinster et al. (1978)
                                       December 1976b           0.001-0.01 µg/m3

    12 Canadian cities                 1989-1992                mean 0.05 ± 0.05 µg/m3                  Environment Canada
                                                                range n.d.-1.73 µg/m3                   (1994)

    Busy streets at 2 m height                                  0.07-1.26 µg/m3                         Tsani-Bazaca et al.
    and 5 m from kerbside                                                                               (1981)

    Los Angeles, California, USA       9-21 April 1979          0.25 ± 0.20 ng/m3 (33.2 ± 26.2 ppt)     Singh et al. (1981)
                                                                range 0.041-1.4 ng/m3 (5.4-187.2 ppt)

    Oakland, California, USA           28 June-10 July 1979     0.12 ± 0.10 ng/m3 (15.8 ± 12.5 ppt)     Singh et al. (1981)
                                                                range 0.018-0.65 ng/m3 (2.4-84.5 ppt)

    Phoenix, Arizona, USA              23 April-6 May 1979      0.31 ± 0.29 ng/m3 (40.3 ± 38.3 ppt)     Singh et al. (1981)
                                                                range 0.018-1.6 ng/m3 (2.4-204.4 ppt)

    Background                                                  38 ng/m3

    Various cities (7)                 1-2 weeks in 1980        0.122-0.453 ng/m3 (0.016-0.059 ppt)c    Singh et al. (1982)
                                                                2.826 ng/m3 (0.368 ppt)d

    Denver, Colorado, USA              1-2 weeks                n.d.-2.304 µg/m3 (0.3 ppb)              Going & Spigarelli (1976);
                                                                                                        Leinster et al. (1978)

    Sites in New Jersey, USA           late 1983-Spring 1984    0.077-5.4 µg/m3                         Harkov et al. (1985)

                                       Summer 1981              < 0.038 µg/m3                           Harkov et al. (1983)

                                       Winter 1982              < 0.038 µg/m3                           Harkov et al. (1983)

    Table 6 (cont'd)
    Location                           Measuring period         Concentration (µg/m3)                   Reference

    Central London                     Summer 1982              0.23 µg/m3 (0.03 ppb)e,f                Clark et al. (1984a,b)
    Exhibition Road                    May-August 1983          0.23 µg/m3 (0.03 ppb)e

    Rural site                         Summer 1982              0.12 µg/m3 (0.015 ppb)e,g               Clark et al. (1984a,b)
    Silwood Park, United Kingdom       May-August 1983          0.15 µg/m3 (0.019 ppb)e

    Motorway outside London,           Summer 1982              0.39 µg/m3 (0.05 ppb)e,h                Clark et al. (1984a,b)
    Toddington                         May-August 1983          0.31 µg/m3 (0.04 ppb)e

    Central London                     Summer 1982              1.0 µg/m3 (0.13 ppb)i                   Clark et al. (1984a,b)
                                       May-August 1983          0.62 µg/m3 (0.08 ppb)i

    Motorway site                      Summer 1982              2.0 µg/m3 (0.26 ppb)i                   Clark et al. (1984a,b)
                                       May-August 1983          1.2 µg/m3 (0.15 ppb)i

    Anchorage (Alaska)                 March 1983               31-177 ng/m3 (4-23 ppt)                 Berg et al. (1984)

    Barrow (Alaska)                    March 1983               n.d.-177 ng/m3 (n.d.-28 ppt)            Berg et al. (1984)

    Mould Bay Coast (Alaska)           March 1983               38-284 ng/m3 (5-37 ppt)                 Berg et al. (1984)

    Thule (Greenland)                  March 1983               15-246 ng/m3 (2-32 ppt)                 Berg et al. (1984)

    North Pole                         March 1983               92.2 ng/m3 (12 ppt)                     Berg et al. (1984)

    Ny-Alesund (Norway)                March-April 1983         31-150 ng/m3 (4-20 ppt)                 Berg et al. (1984)

    Table 6 (cont'd)
    Location                           Measuring period         Concentration (µg/m3)                   Reference

    Bear Island (Norway)               March-April 1983         23-100 ng/m3 (3-13 ppt)                 Berg et al. (1984)

    Bodo (Norway)                      March-April 1983         38-110 ng/m3 (5-14 ppt)                 Berg et al. (1984)

    a  temperature range 28-30°C
    b  temperature range 4-8°C
    c  average level for each city
    d  maximum concentration found in Houston, Texas, USA
    e  mean hourly concentrations
    f  range 0.078-1 µg/m3 (0.01-0.13 ppb)
    g  range ND-0.78 µg/m3 (ND-0.01 ppb)
    h  range 0.07-2.0 µg/m3 (0.009-0.26 ppb)
    i  maximum hourly concentrations

         1,2-Dibromoethane levels of 0.07-1.26 µg/m3 have been found in
    busy streets.  Higher levels were found in a road tunnel and were
    associated with poor ventilation (Tsani-Bazaca et al., 1981).  Three
    field studies on the measurement of selected potentially hazardous
    organic compounds in urban environments were conducted in  the USA in
    1979 (Los Angeles, California, 9-21 April; Oakland, California,
    28 June-10 July; and Phoenix, Arizona, 23 April-6 May).  These studies
    were performed to characterize the atmospheric abundance, fate and
    human exposure to these compounds (Table 6).  The background
    concentration of 1,2-dibromoethane was 38 ng/m3 (5 ppt).  Assuming
    an average respiratory volume of 23 m3 at 25°C and 1 atm for a 70-kg
    male, the average daily dose (µg/day) of 1,2-dibromoethane at these
    locations can be calculated as 6.0 ± 2.7 for Los Angeles, 2.9 ± 0.8
    for Oakland and 7.0 ± 2.7 for Phoenix.  The ratios of
    1,2-dibromoethane to total haloethane and VHH (volatile halogenated
    hydrocarbons) in the average daily doses were 2.7% and 0.57%, 5.6% and
    1.14%, and 2.8% and 1.03%, respectively.  The chemical loss rate of
    1,2-dibromoethane was 2.8% per day (sunlight = 12 h).  There was
    diurnal variation in 1,2-dibromoethane levels at the three locations.
    The afternoon minimum at Phoenix was attributed to deep vertical
    mixing associated with hot and dry weather.  The afternoon maximum at
    Oakland was most likely a result of transport from upwind sources
    (Singh et al., 1981).

         Other studies measuring 1,2-dibromoethane in the ambient
    atmosphere of urban and rural areas have been performed (Going & Long,
    1975; Going & Spigarelli, 1976).  Sources of 1,2-dibromoethane in air
    were considered to be emissions from stations dispensing leaded petrol
    and evaporative emissions from motor vehicles using leaded petrol. 
    Atmospheric levels of 1,2-dibromoethane were low (0.046 to
    3.5 µg/m3) (0.006 to 0.45 ppb) in worst case conditions near petrol
    stations and with heavy traffic in cities.  These levels are 10 to
    10 000 times less than the occupational exposure level of 1 mg/m3
    (0.13 ppm) for 15 min recommended by the US National Institute of
    Occupational Safety and Health (Jacobs, 1980).

         Tsani-Bazaca et al. (1981) monitored the concentrations of VHH
    collected in 1979 at several locations and utilizing vehicles
    operating under various conditions on a busy road in central London
    (2000 vehicles/h), a poorly ventilated tunnel (1600 vehicles/h at peak
    traffic flow), and a semi-rural industrialized area.  The
    concentration of 1,2-dibromoethane varied between 0.07 and
    1.26 µg/m3.  There was a good correlation between 1,2-dibromoethane
    and benzene concentrations (correlation coefficient : 0.93) at the
    three locations and a higher correlation between 1,2-dibromoethane and
    1,2-dichloroethane (correlation coefficient : 0.94).

         In 1983, 54 air samples at 6 urban sites and 54 air samples at
    6 mountainous sites were collected in Japan and were analysed for the
    presence of 1,2-dibromoethane.  A total of 35 samples from 5 urban
    sites contained 1,2-dibromoethane at concentrations of

    0.008-0.322 µg/m3 (0.001-0.042 ppb).  The detection limit was
    0.005-0.008 µg/m3 (0.0007-0.001 ppb).  A total of 36 samples from
    5 mountainous sites contained 1,2-dibromoethane at concentrations of
    0.008-0.515 µg/m3 (0.001-0.067 ppb).  The detection limit was
    0.002-0.008 µg/m3 (0.0003-0.001 ppb) (Environment Agency Japan,

         Urban 1,2-dibromoethane levels at seven sites in selected cities
    in the USA in 1980, using on-site and real-time measurement instrument
    following a 24-h measurement schedule for a period of 1-2 weeks, were
    0.12-0.45 µg/m3 (16-59 ppt) (Singh et al., 1982).  The average
    concentration of 1,2-dibromoethane did not exceed 0.015-0.46 µg/m3
    (0.06 ppb) (average range 0.002-0.06 ppb) at any study site and
    average levels ranged from 0.122 µg/m3 (0.016 ppb) at St. Louis,
    Missouri, to 0.46 µg/m3 (0.059 ppb) at Houston, Texas.  The maximum
    concentration of 2.83 µg/m3 (0.368 ppb) was found at Houston.  In
    general, the highest average levels were found during the night and
    early morning.  In the case of Denver, Colorado, typical ambient
    concentration data suggested a range of not detectable to 2.3 µg/m3
    (0.300 ppb) (Going & Spigarelli, 1976; Leinster et al., 1978).

         The Office of Science and Research (USA) monitored VHH in ambient
    air at listed abandoned hazardous waste sites and sanitary landfills
    in New Jersey (Harkov et al., 1985).  1,2-Dibromoethane was found at
    mean levels of 2.1 µg/m3 (0.27 ppb), 2.2 µg/m3 (0.288 ppb),
    3.6 µg/m3 (0.47 ppb), 5.4 µg/m3 (0.7 ppb), 0.38 µg/m3
    (0.05 ppb), 0.077 µg/m3 (0.01 ppb) and 0.15 µg/m3 (0.02 ppb) at
    different sites during late 1983 and early 1984.  It was below the
    detection limit 0.038 µg/m3 (0.005 ppb) at three sites during the
    summer of 1981 (Harkov et al., 1983) and the winter of 1982 (Harkov et
    al., 1984).

         Ambient air monitoring survey of VHH at a busy road in central
    London, a rural site and a motorway location near London showed mean
    hourly 1,2-dibromoethane concentrations of 0.23, 1.2 and 0.39 µg/m3
    (0.03, 0.15 and 0.05 ppb), respectively, in summer 1982 and 0.23, 0.15
    and 0.31 µg/m3 (0.03, 0.019 and 0.04 ppb) between May and August
    1983 (Clark et al., 1984a,b).  The maximum hourly concentrations of
    1,2-dibromoethane at the urban and motorway sites were 1.0 and
    2.0 µg/m3 (0.13 and 0.26 ppb) in 1982, and 0.61 and 1.2 µg/m3
    (0.08 and 0.15 ppb) in 1983, respectively.  1,2-Dibromoethane
    concentrations at the urban site were in the same ranges
    0.07-0.31 ng/m3 (0.01-0.04 ppt) as those measured by other workers
    (Leinster et al., 1978; Tsani-Bazaca et al., 1981; Singh et al.,
    1982). The low concentrations found at the rural site were primarily
    related to the low incidence of vehicular pollutant sources in the
    area.  However, the site was near the urban fringe of London and near
    several small towns and this may explain occasional elevated

         1,2-Dibromoethane concentrations were measured at Point Arena,
    California between 1979 and 1981; the background level of
    1,2-dibromoethane in the troposphere was found to be less than
    0.023 µg/m3 (3 ppt) (Singh et al., 1983).

         Berg et al. (1984) measured atmospheric 1,2-dibromoethane
    concentrations at eight arctic sites in 1983.  Concentrations at three
    sites in Alaska (Anchorage, Barrow, Mould Bay Coast) in March were
    0.031-0.177 µg/m3 (4-23 ppt), not detectable to 0.22 µg/m3
    (29 ppt) and 0.038-0.284 µg/m3 (5-37 ppt), respectively. 
    1,2-Dibromoethane levels in Greenland (Thule) and at the North Pole in
    March were 0.015-0.246 µg/m3 (2-32 ppt) and 0.096 µg/m3 (12 ppt),
    respectively.  Those at Norwegian sites (Ny-Alesund, Bear Island,
    Bodo) during March-April were 0.031-0.15 µg/m3 (4-20 ppt),
    0.023-0.10 µg/m3 (3-13 ppt) and 0.038-0.11 µg/m3 (5-14 ppt),
    respectively.  The mean concentration ± standard deviation was
    0.084-0.77 µg/m3 (11 ± 10 ppt).  Other organobromine compounds, such
    as methyl bromide, methylene dibromide and bromoform, were detected at
    similar concentrations.

         Monthly monitoring of the atmosphere of Barrow, Alaska (72 °N),
    showed that the 1,2-dibromoethane concentration was higher in winter
    than in other seasons, although the monthly average concentrations did
    not differ greatly (7.68-10.7 ng/m3) (1.0-1.4 ppt) except in
    January.  From the results of atmospheric VHH monitoring, Rasmussen &
    Khalil (1984) suggested that VHH in arctic air might be an indicator
    of polluted air transported from industrial mid-latitude sources.

    5.1.2  Water

         Widespread use of 1,2-dibromoethane as a soil fumigant in the USA
    resulted in its detection in both groundwater and surface water in
    California, Florida, Georgia, and Hawaii (Sun, 1984), Connecticut
    (Isaacson et al., 1984) and New Jersey (Page, 1981), and in wells used
    for  irrigation in Georgia (Martl et al., 1984).  1,2-Dibromoethane
    was reported in groundwater in Georgia, California, Florida, and
    Hawaii by US EPA (1986).

         Laboratory studies have shown that 1,2-dibromoethane
    photohydrolyses rapidly in aqueous solutions when irradiated.  The
    degradation is a two-stage process in which 1,2-dibromoethane is
    converted to bromoethanol (half-life, 7.6 min) and then to ethylene
    oxide (half-life, 64 min).  Further degradation to ethylene glycol was
    less influenced by light, as shown by a half-life of 10 days (Castro &
    Belser, 1978).  While the above study provides some understanding of
    aqueous degradation, Logan (1988) cautions that the efficiency of the
    photo-reactions were not reported in terms of quantum yield.

         1,2-Dibromoethane was found in ground- and surface water in New
    Jersey (over 1000 different wells and 600 different sites) during
    1977-1979; the highest levels were 0.2 µg/litre in surface water and
    48.8 µg/litre in groundwater (Page, 1981).

         Analyses of 350 well water samples from Connecticut in 1984 
    revealed concentrations of up to 2 µg/litre.  1,2-Dibromoethane was
    rapidly lost from water samples exposed to the atmosphere or boiled
    for few minutes.  It could not be detected in water samples purged
    with nitrogen for 10 min (Isaacson et al., 1984).

         In southwest Georgia, USA, agricultural practices involve
    intensive use of groundwater for irrigation and pesticides for control
    of plant and insect pests.  1,2-Dibromoethane was found at levels of
    between 1 and 90 µg/litre in water samples from three irrigation wells
    collected between 1981 and 1983.  Application at ratios of
    14-19 litres/ha) near wells showed that 1,2-dibromoethane
    concentrations in the aquifer did not appear to be directly related to
    the application rate of the compound to the surface.  The
    concentrations in the wells may reflect application of the compound at
    sites some distance from the wells (Martl et al., 1984).

         In 1982, 27 water samples and 27 bottom sediment samples were
    collected at nine sites in Japan and were analysed for the presence of
    1,2-dibromoethane.  None of the water or bottom sediment samples
    contained 1,2-dibromoethane.  The detection limit was 0.3-2 µg/litre
    for water and 0.0016-0.01 µg/kg for bottom sediment (Environment
    Agency Japan, 1985).

         In 1983, 1,2-dibromoethane surveillance of the water of six rural
    wells in Ibaraki prefecture, Japan, where 1,2-dibromoethane was used
    for soil fumigation or as a pesticide on pine tree, showed no
    1,2-dibromoethane contamination (detection limit, 5 µg/litre) (Nemoto
    et al., 1984).

         Groundwater samples from nine sites in and around vegetable-
    growing areas in Gifu Prefecture, Japan, were collected twelve times
    between July 1983 and December 1984.  1,2-Dibromoethane levels ranged
    from 0.06 to 0.55 µg/litre at seven sites and the mean values of
    1,2-dibromoethane at each site varied between 0.15 and 0.28 µg/litre. 
    1,2-Dibromoethane levels in groundwater around the vegetable-growing
    areas did not differ from those within the areas, where
    1,2-dibromoethane application was limited to once a year in the first
    two weeks of July. Sites where 1,2-dibromoethane were detected around
    these areas overlapped completely the stream of groundwater coming
    from these areas (Terao et al., 1985).  The annual variation of
    concentrations in the groundwater was small.  1,2-Dibromoethane
    concentration showed good correlation with bromine ion concentration
    and bromine ion/chlorine ion ratio at each site (Terao et al., 1984).

         Mayer et al. (1991) studied 1,2-dibromoethane concentrations in
    detail in water from a domestic well, approximately 10 m deep, in a
    fruit growing area of Whatcom County, Washington, USA where
    1,2-dibromoethane had been used extensively prior to its 1983 ban. 
    Additional wells (n = 107) were also sampled over a 4-year period; no
    details of well depths were given.  Correlation analysis showed no
    relationship between 1,2-dibromoethane concentration in water and
    temperature but significant negative correlation between precipitation
    and 1,2-dibromoethane.  The analysis allowed lag times of between
    0 and 12 months; a 3-month lag was found to give the best relationship
    between precipitation and 1,2-dibromoethane in the water.  The
    dilution effect of precipitation was followed by slow
    1,2-dibromoethane infiltration from overlying soils which tended to
    re-establish prior concentrations over about 3 months.  The authors
    stated that water contamination can result from such continuing
    infiltration of soil-matrix-derived 1,2-dibromoethane long after
    agricultural use has ceased.

    5.1.3  Food

         Beckman et al. (1967) reported that part of the inorganic bromine
    in foods and raw agricultural commodities comes from the soil. 
    1,2-Dibromoethane was applied annually at 54 kg/ha and samples from
    40 crops grown in soil treated with 1,2-dibromoethane were analysed
    over a 3-year period.  In general, leafy portions of plants contained
    the highest levels of bromide on the basis of weight.  Residue levels
    were calculated as inorganic bromide ion present in the crop after
    harvest.  Levels in crop samples from untreated soil were less than
    1.6 mg/m3 (0.2 ppm), and the highest level in crops from treated
    soil was 137 mg/kg (17.8 ppm) in sugar beet tops.  Most of the crops
    were harvested about 100 days after soil treatment but time from
    treatment to harvest ranged from 55 days for strawberries to 10 years
    for walnuts.

         1,2-Dibromoethane was absorbed strongly by cereal, grains, cereal
    products and other produce during the fumigation period.  Even when
    normal ventilation procedures were followed, residues of
    1,2-dibromoethane disappeared very slowly.  Nearly all the
    1,2-dibromoethane was physically sorbed and at normal temperatures
    there was little formation of inorganic bromide.  However,
    occasionally in produce at higher temperatures and moisture content
    there was rapid breakdown to inorganic bromide (Heuser & Scudamore,

         Levels of 1,2-dibromoethane in wheat were between 10 and
    20 mg/kg, and, for its products, between 2 and 4 mg/kg in flour,
    0.002-0.04 in white bread and 0.006-0.16 in wholemeal bread.  When
    flour was treated directly with 1,2-dibromoethane, ventilated
    thoroughly, and then baked into loaves, there were residues of
    20-24 mg/kg in the flour and 0.33-0.47 mg/kg in the bread (FAO/WHO,

    1972).  Desorption of 1,2-dibromoethane occurred at low (14-17°C)
    rather than high (30-37°C) temperatures, and was abolished by grinding
    the grain (Bielorai & Alumot, 1975).

         Rappaport et al. (1984) reported that the decay of the outgassing
    rate over time from fumigated oranges was approximately first order. 
    Outgassing was significantly slowed by reducing either the temperature
    or the ventilation rate.  In laboratory trials, ventilation at
    0.6 air changes/h removed 1,2-dibromoethane vapours from the surface
    of oranges, and prevented reabsorption onto the fruits.

         A pesticide formulation, consisting of carbon tetrachloride (CT),
    1,2-dichloroethane (EDC), 1,2-dibromoethane in 63 : 30 : 7 w/w
    proportions, was applied to 27.3 tonnes of wheat stored in a paper
    laminate bin (Berck, 1974). The CT-EDC-1,2-dibromoethane distribution-
    persistence patterns were monitored at 16 bin locations over a 14-day
    period by GC.  Fumigant residues in the wheat, in flour, bran, and
    middlings derived from the wheat, and in bread baked from the flour
    were determined over a 7-week period.  1,2-Dibromoethane residues in
    the wheat varied, depending on the bin location and contact time, and
    ranged from 0 to 3.3 mg/kg. Residues in bran and middlings were
    greater than those in flour, and ranged from 0 to 0.4 mg/kg.  No
    1,2-dibromoethane residues were found in any of the bread tested
    (detection limit, 10 ng/kg).

         1,2-Dibromoethane levels were studied in biscuits (22 samples)
    and flour (22 samples), the biscuits being baked from each of the
    flour samples for 12 min at 268°C.  After baking, the samples were
    sealed in plastic bags and frozen to prevent any further loss of
    1,2-dibromoethane.  Flour samples were also sealed in plastic bags and
    frozen. Levels of 1,2-dibromoethane in flour and biscuits ranged from
    non-detectable to 4.2 mg/kg and to 0.26 mg/kg, respectively.  There
    was poor correlation between the levels of 1,2-dibromoethane in flour
    and biscuits.

    5.2  Occupational exposure

         Air concentrations of 1,2-dibromoethane in ventilated containers
    dropped from several ppm immediately after fumigation to a few ppb
    after 5-10 days; levels remained between 15 and 23 mg/kg (2 and 3 ppm)
    for 15-20 days during unventilated, refrigerated storage.  Results of
    experiments on a laboratory scale (0.25 carton) and a large scale
    (400 cartons) suggested that workers transporting and distributing
    fumigated citrus fruit could routinely be exposed to airborne
    1,2-dibromoethane at concen  trations greater than 998 µg/kg (130 ppb)
    (OSHA, 1983).

         The US National Institute for Occupational Safety and Health
    (NIOSH) estimated that approximately 108 000 workers in the USA were
    potentially exposed to 1,2-dibromoethane in their workplaces (Table 7)

    and that another 875 000 workers handling leaded petrol were exposed
    to very low levels (NIOSH, 1981).  There is no estimate of the number
    of motorists exposed to 1,2-dibromoethane during self-service
    operations at filling stations.

    Table 7.  Occupations with potenial exposure to 1,2-dibromoethanea
    Antiknock compound makers       Motor fuel workers

    Cabbage growers                 Oil processors

    Corn growers                    Organic chemical synthesizers

    1,2-Dibromoethane workers       Petrol blenders

    Drug makers                     Resin makers

    Fat processors                  Seed corn maggot controllers

    Fire-extinguisher makers        Soil fumigators

    Fruit fumigators                Termite controllers

    Fumigant workers                Tetraethyllead makers

    Grain elevator workers          Waterproofing makers

    Grain fumigators                Waxmakers

    Gum processors                  Wood insect controllers

    Lead scavenger makers           Wool reclaimers

    a  From: NIOSH (1977)

         In the 1970s, US EPA examined the exposure of professional
    pesticide applicators involved with 1,2-dibromoethane soil fumigation. 
    It was estimated that applicators applying 1,2-dibromoethane for
    30-40 days/year would receive a total annual inhalation dose of
    3-40 mg/kg and farmer-applicators applying 1,2-dibromoethane for
    7-10 days/year would receive a total annual inhalation dose of
    0.7-10 mg/kg (US EPA, 1977).

         1,2-Dibromoethane exposures were measured in a plant where lead
    antiknock blends for petrol were prepared (Jacobs, 1980).  The
    antiknock blend constituents were mixed in tanks under enclosed-system
    conditions and the only manual operations were connecting and

    disconnecting hoses while loading and unloading tank cars, taking
    quality control samples, and processing and loading drums.  The levels
    of worker exposure to 1,2-dibromoethane in antiknock blending and
    storage areas were 0.77 µg/m3 (0.1 ppb) (laboratory technician) to
    6.3 µg/m3 (0.82 ppb) (raw maternal blender).  In addition to
    long-term personal sampling, some short-term monitoring of specific
    tasks was conducted.  The results are shown in Table 8.

    Table 8.  Short-term air levels of 1,2-dibromoethane in antiknock
              blending plant tank cars (Jacobs, 1980)

    Taska                      Sampling time       Concentration

                                                  mg/m3      ppm

    Quality control sample     13 min, 10 sec     5.38       0.7

    Loading tank car           7 min              1.07      0.14

    a  Respirator worn during these tasks

         Personal air monitoring during vehicle refuelling at a petroleum
    laboratory 10 m downwind of the fuel pump and fuel-handling facilities
    was performed at a USA plant in July, 1975 (Table 9).  The average
    exposure of filling station attendants to 1,2-dibromoethane during
    refuelling was 1.8 µg/m3 (0.24 ppb).  Measurements at the car fuel
    tank filler pipe showed maximum instantaneous 1,2-dibromoethane
    concentrations of 105 µg/m3 (13.7 ppb), with an average for four
    samples of 10.0 µg/m3 (1.3 ppb).  This represented the maximum for a
    short-term exposure.  The concentration of 1,2-dibromoethane in air at
    the fuel pump island was similar to values measured at upwind and
    downwind sites.  Overall, the very low 1,2-dibromoethane air levels
    measured in this study indicated that the potential for filling
    station attendant exposure to 1,2-dibromoethane while refuelling cars
    was low and less than the current or proposed USA occupational air
    standard for 1,2-dibromoethane exposure (Jacobs, 1980).

         Exhaust emissions from various types of internal combustion
    engines, including four-stroke Otto engines and diesel engines, are a
    major source of environmental and occupational exposure to
    1,2-dibromoethane (Hasanen et al., 1981).  There are few data on the
    composition of and exposure to exhaust emissions from two-stroke

    Table 9.  Petrol station attendant exposure to 1,2-dibromoethane
              during vehicle refuelling (Jacobs, 1980)

    Sample                                Concentration

                                   mg/m3            ppb

    Upwind background              < 0.77         < 0.1
    Downwind background            < 0.77         < 0.1
    Fuel pump island                 0.99           0.13
    Near vehicle fuel pipe           9.98           1.3a
      during refueling             105.2           13.7b
    Personal air sampler             2.15           0.28

    a  Average
    b  Maximum

         Seven chain saws fuelled with 93-octane standard petrol-
    containing tetramethyllead (lead content 0.15 g/litre) and
    1,2-dibromoethane as a scavenger were tested on a test-bench
    permitting a variable load to be applied by an electric power brake
    (Nilsson et al., 1987).  1,2-Dibromoethane emissions were low
    (2.5 mg/m3).  Exposure to chain saw exhaust during logging was
    studied under snowy and snow-free conditions.  The time-weighted
    average exposure to 1,2-dibromoethane was lower in the snow-free
    conditions (0.0008 (0.0004-0.001) mg/m3) than in the snowy
    conditions (0.002 (0.0001-0.005) mg/m3).

         1,2-Dibromoethane is mainly used as a scavenger in tetraalkyllead
    petrol and antiknock preparations, as a soil and  grain fumigant, as
    an intermediate in the synthesis of dyes and pharmaceuticals and as a
    solvent for resins, gums and waxes (Alexeeff et al., 1990).

         Rumsey & Tanita (1978) performed an industrial hygiene survey of
    two manufacturing and two user facilities involving 1,2-dibromoethane.
    Samples were taken from more than 69 potentially-exposed workers in
    17 job classifications.  Median 1,2-dibromoethane exposure (by similar
    job types) in the manufacturing process ranged from 0.076 to
    3.8 mg/m3 (0.010 to 0.5 ppm) (35 TWA personal samples).  General
    area samples collected at breathing zone heights had median TWA levels
    of 1.5 mg/m3 (0.2 ppm) for 10 samples at process sites, and
    3.8 mg/m3 (0.5 ppm) for 3 samples at laboratory sites.

         Papaya workers in Hawaii were exposed to a geometric mean of
    676 mg/m3 (88 ppb), and peaks up to 2.01 mg/m3 (262 ppb) were
    measured (Steenland et al., 1986).


    6.1  Absorption

         1,2-Dibromoethane was found in the blood of rodents almost
    immediately after dermal and oral exposure.  Jakobson et al. (1982)
    reported that during a 6-h dermal exposure of guinea-pigs of both
    sexes (weighing between 600 and 1000 g) with undiluted
    1,2-dibromoethane applied to 3.1 cm2 of shaved skin on the back
    (1.0 ml/animal), the blood concentration of 1,2-dibromoethane
    increased rapidly during 1 h to a level of 2 mg/litre and then slowly
    decreased.  The influx of 1,2-dibromoethane into the blood after 1 h
    was largely in equilibrium with its disappearance.

         In male Sprague-Dawley rats given 15 mg/kg body weight of
    [14C-1,2] 1,2-dibromoethane in corn oil by gavage, the blood levels
    at 24 h and 48 h were 0.90 and 0.64 mg/litre, respectively (Plotnick
    et al., 1979).  The excretion of radioactivity in faeces within 24 h
    was 1.7% of the dose.  The remainder was recovered either in the urine
    (72%) or in the tissues (2.8%) (Table 10).  The results indicated
    rapid 1,2-dibromoethane absorption from the gastrointestinal tract.

         No absorption information regarding inhalation exposure exists.

    Table 10.  The distribution of 14C in selected tissues and body
               fluids of male rats 24 h after a single oral dose of
               14C-1,2-dibromoethane (15 mg/kg)a

    Tissue         Tissue concentrationsb          Percentage of dose
                (mg equivalent/kg or mg/litre)             (%)

    Liver              4.78 ± 0.24                     1.7 ± 0.07
    Kidneys            3.32 ± 0.42                     0.21 ± 0.02
    Spleen             1.00 ± 0.03                     0.22 ± < 0.01
    Testes             0.49 ± 0.05                     0.04 ± < 0.01
    Brain              0.41 ± 0.04                     0.02 ± < 0.01
    Fat                0.35 ± 0.04                     0.15 ± 0.02
    Blood              0.90 ± 0.05                     0.59 ± 0.03
    Plasma             0.46 ± 0.04
    Urinec                                            72.38 ± 0.98
    Faecesc                                            1.65 ± 0.28

    a  From: Plotnick et al. (1979)
    b  Values represent mean concentrations (expressed as parent
       compound) ± S.E.M. of duplicate determinations for six animals.
    c  n = 12

    6.2  Distribution

         Plotnick et al. (1979) compared levels of 14C in selected
    tissues of male Sprague-Dawley rats following oral administration of
    14C-1,2-dibromoethane.  One day after the administration, the
    highest levels of radioactivity were found in the liver and kidneys
    (Table 10).

         Distribution of 14C-1,2-dibromoethane (30 mg/kg body weight)
    after intraperitoneal administration to male guinea-pigs was studied
    by Plotnick & Conner (1976).  The liver and kidneys contained the
    highest levels of radioactivity followed by the adrenal glands
    (Table 11).

    Table 11.  Distribution of 14C-1,2-dibromoethane in selected tissues
               of male guinea-pigs at various time intervals following
               intraperitoneal administrationa

    Tissues/organs    4 h            8 h          24 h         72 h

    Liver            129.0          104.9         38.0         15.6
    Kidneys          286.6b         236.5          3.5         10.5
    Adrenals          60.7           60.8         28.6         10.4
    Pancreas          35.0           36.8         18.7          6.0
    Spleen            15.8           14.0         14.9          7.0
    Heart             14.0           15.6          9.5          3.3
    Lungs             20.9           19.0         15.4          5.8
    Testes            10.7           10.7          8.3          4.0
    Brain              6.2            7.6          6.5          2.5
    Fatc              21.4            7.9          3.2          2.1
    Muscle             5.5            5.0          4.2          2.2
    Blood             10.0            3.4          5.0          2.8

    a  From: Plotnick & Conner (1976)
    b  Values represent mean levels in mg equivalent/kg of tissue or
       litre of fluid for three animals at each time interval
    c  Suprarenal fat

         Kowalski et al. (1985) reported epithelial binding of
    1,2-dibromoethane in the respiratory and upper alimentary tracts of
    C57BL mice, Sprague-Dawley rats and Fischer-344 rats after intravenous
    and intraperitoneal injection of 14C-1,2-dibromoethane.  In C57BL
    mice, there was a high level of radioactivity in the nasal and
    bronchial mucosa and liver 5 min after intravenous injection of
    14C-1,2-dibromoethane.  In the nose, the highest labelling was
    present in a spotty band beneath the epithelium of the
    ethmoturbinates.  The radioactive labelling of the mucosa of the

    respiratory tract was persistent, and 10 days after injection a
    selectively bound radioactivity remained.  High labelling was also
    present in the mucosa of the forestomach, whereas there was no
    selective uptake of radioactivity in the glandular stomach or
    intestine.  Similar distribution patterns were observed in the
    intraperitoneally injected mice killed after 30 min or subsequently.

    6.3  Metabolic transformation

         The metabolism of 1,2-dibromoethane has been extensively studied
    and metabolites have been identified in  in vivo and  in vitro
    studies (Table 12, Fig. 1).

    Table 12.  Metabolites of 1,2-dibromoethane

    (a)  In vivo

    Metabolite               Animal; route; substrate      Reference

    Bromide                  Swiss-Webster mice;           White et al.
                             intraperitoneal; plasma       (1983)

    N-acetyl-S-(2-hydroxy    male Wistar rat; oral;        Van Bladeren et
      ethyl)-L-cysteine      urine                         al. (1981b)

    GS-CH2-CH2SG             female white rat; oral;       Nachtomi (1970)

    GSCH2CH2OH sulfoxide     liver                         Nachtomi (1970)

    GSCH2CH2OH               liver and kidney              Nachtomi (1970)

    S-(2-hydroxyethyl)       kidney                        Nachtomi (1970)
      mercapturic acid

    (b) In vitro

    Metabolite               Tissue                        Reference

    GSCH2CH2SG               rat liver and kidney extract  Nachtomi (1970)

    GSCH2CH2OH               rat liver and kidney extract  Nachtomi (1970)

    Bromide (1984)           rat liver cytosols            White et al.

    Bromide (1983)           mouse liver cytosols          White et al.

    FIGURE 1

         Inorganic bromide may be formed as a consequence of attack by GSH
    or oxidative catabolism.  In the first case, the expected intermediate
    would be  S-(2-bromoethyl)-GSH, which can be converted to bis-GSH or
     S-(2-hydroxyethyl)-GSH.  Sulfoxidation of  S-(2-hydroxyethyl)-GSH
    would yield  S-(2-hydroxyethyl)-GSH- S-oxide or further metabolism
    would produce  S-(2-hydroxyethyl)-cysteine, which in turn may undergo
    sulfoxidation to yield  N-acetyl- S-(2-hydroxyethyl)-cysteine-
     S-oxide.  The oxidative metabolism of 1,2-dibromoethane by
    cytochrome P-450-dependent mixed function oxidases would be expected
    to yield 2-bromoacetaldehyde as the initial product. This may be
    converted by dehydrogenase to 2-bromoacetic acid or undergo attack by
    GSH and subsequent dehydrogenase activity to give rise to
     S-carboxymethyl-GSH.   S-carboxymethyl-cysteine may be further
    metabolized to thioglycolic acid.  A reactive intermediate binds
    mainly to DNA guanyl remnants and may be responsible for the

         White et al. (1983) reported a deuterium isotope effect on the
    metabolism of 1,2-dibromoethane.  The metabolism of 1,2-dibromoethane
    and tetradeutero-1,2-dibromoethane (d4-1,2-dibromoethane) was compared
    in male Swiss-Webster mice.  Three hours after intraperitoneal
    administration of 1,2-dibromoethane or d4-1,2-dibromoethane
    (50 mg/kg), there was 42% less bromide in the plasma of
    d4-1,2-dibromoethane-treated mice than in the plasma of
    1,2-dibromoethane-treated mice.  This difference demonstrated a
    significant deuterium isotope effect on the metabolism of
    1,2-dibromoethane  in vivo.  In  in vitro studies, which measured
    bromide ion released from the substrate to monitor the rate of
    metabolism, hepatic glutathione- S-transferase was unaffected.  Since
    the decreased metabolism of d4-1,2-dibromoethane was apparently due to
    a reduced rate of microsomal oxidation, these data supported the
    hypothesis that conjugation with GSH is responsible for the genotoxic
    effect of 1,2-dibromoethane.

         White et al. (1984) studied metabolism in isolated rat
    hepatocytes.  Cytosolic metabolism of 1,2-dibromoethane was not
    affected by deuterium substitution.  Both compounds caused DNA
    single-strand breaks, as measured by the alkaline elution technique,
    when incubated at a concentration of 0.1 mM with hepatocytes.  No
    difference in the degree of DNA damage was demonstrated between
    hepatocytes incubated with 1,2-dibromoethane and those incubated with

         1,2-Dibromoethane can be metabolized by freshly isolated rat
    hepatocytes to  S-(2-hydroxyethyl)glutathione,  S-(carboxymethyl)
    glutathione and  S,S'-(1,2-ethanediyl)bis(glutathione). These three
    metabolites account for 84% of the total intracellular glutathione
    depletion (Jean & Reed, 1992).  These reactions were negligible in the
    presence of rat glutathione- S-transferase, but conjugation was
    catalysed by the rat alpha class enzyme 2-2 and, to a lesser extent,

    the rat µ class enzyme 3-3.  Of the three classes of human cytosolic
    glutathione- S-transferases, 1,2-dibromoethane conjugation was
    catalysed by the alpha class enzymes (Cmarik et al., 1990).

         Human fetal liver appears to be especially active (several times
    higher specific activity of glutathione- S-transferase, compared to
    adult liver, as reported by Wiesma et al., 1986) in metabolizing
    1,2-dibromoethane  in vitro (Kulkarni et al., 1992).

         1,2-Dibromoethane-induced lipid peroxidation and cytotoxicity
    were increased upon concomitant exposure to carbon tetrachloride. 
    Similarly, the amount of 1,2-dibromoethane metabolites bound
    covalently to proteins was enhanced.  The effect of carbon
    tetrachloride has been related to a shift in the 1,2-dibromoethane
    metabolism from GSH-dependent to P-450-dependent (Chiarpotto et al.,

         Oral administration of large doses of 1,2-dibromoethane
    (37.6 mg/animal) to male Wistar rats (weighing around 200 g),
    following a single dose of disulfiram (12 mg/kg), led to decreased
    excretion of the mercapturic acid metabolite, a phenomenon associated
    with a decrease in cytochrome P-450 levels (van Bladeren et al.,
    1981a).  In an additional reaction, 1,2-dibromoethane is debrominated
    by an oxidative process catalysed by an enzyme in hepatic microsomes. 
    This system requires NADPH and oxygen and is inducible by
    phenobarbital but not by methyl-cholanthrene (Hill et al., 1978).

         Simula et al. (1993) reported an increased mutagenicity of
    1,2-dibromoethane in the  Salmonella typhimurium strain TA100
    expressing human glutathione- S-transferase A1-1, indicating that
    human glutathione- S-transferases are able to metabolize
    1,2-dibromoethane to reactive intermediates.

         In a study with isolated human hepatocytes (Cmarik et al., 1990),
    it was found that concurrent treatment with diethylmaleate reduced the
    intracellular glutathione level and inhibited 1,2-dibromoethane
    concentration-dependent unscheduled DNA synthesis.

    6.4  Elimination and excretion in expired air, faeces and urine

         When 14C-1,2-dibromoethane (30 mg/kg body weight) was given
    intraperitoneally to male guinea-pigs of the Hartley strain, 66% of
    the radioactivity was excreted in the urine within 72 h of
    administration (Plotnick & Conner, 1976).  Faecal excretion was
    relatively insignificant, representing less than 3% of the dose.  The
    excretion of unchanged 1,2-dibromoethane in the expired air was
    significant (10-12% of dose).

         Plotnick et al. (1979) reported that urinary extraction of
    radioactivity from male rats of the Sprague-Dawley strain, 24 h after
    a single oral dose of 14C-1,2-dibromoethane (15 mg/kg), was 72.4%. 
    Faecal radioactivity was 1.7%.  Concomitant exposure to dietary
    disulfiram significantly depressed urinary excretion of

    6.5  Retention and turnover

         Following intraperitoneal administration of [1,2-14C]-
    1,2-dibromoethane (40 mg/kg) to RF/Hiraki mice, the circulating
    radiolabel was mainly accounted for by S-(2-hydroxyethyl)
    cysteine- N-acetate.  Less than 1% of the dose was present in the
    blood as a volatile component (Edwards et al., 1970).

         Jakobson et al. (1982) reported that the elimination curve for
    1,2-dibromoethane from blood after a 4-h dermal exposure of
    guinea-pigs was non-linear and corresponded to a kinetic model
    involving at least two compartments.

    6.6  Reaction with body components

         Radioactivity from [1,2-14C]-1,2-dibromoethane is bound
    irreversibly to macromolecules in rat tissues after intraperitoneal
    injection.  For protein, DNA, and RNA, the largest amounts of bound
    radioactivity were found to be present in the liver and kidney.  Lung,
    testis, stomach and the large and small intestines showed less
    radioactivity (Hill et al., 1978).

         Ozawa & Guengerich (1983) reported the formation of an
     S-[2-(N7-guanyl)ethyl]glutathione adduct.  1,2-Dibromoethane and
    GSH were irreversibly bound to calf thymus DNA in equimolar amounts
    when  in vitro incubation was carried out in the presence of
    glutathione- S-transferase.  The labelled DNA was enzymatically
    digested to deoxyribonucleosides and separated by HPLC.  The level of
    adducts in DNA isolated from human hepatocytes incubated with 0.5 mM
    1,2-dibromoethane was about 40% of the value obtained for rat
    hepatocytes (Cmarik et al., 1990).

         S-[2-(N7-guanyl)ethyl]glutathione was the only major DNA adduct
    formed  in vivo in rat (male Sprague-Dawley) liver (1.3 nmol/mg DNA)
    or kidney (0.95 nmol/mg DNA) 8 h after intraperitoneal administration
    of 37 mg 1,2-dibromoethane/kg body weight. The  in vivo half-life of
     S-[2-(N7-guanyl)ethyl] glutathione in rat liver, kidney, stomach
    and lung was estimated to be between 70 and 100 h (Inskeep et al.,

         Following intraperitoneal injection of 1,2-dibromoethane
    (37 mg/kg) in rats and mice of several strains, it was found that more
    of the  S-[2-(N7-guanyl)ethyl]glutathione adduct of DNA was formed
    in the livers of rats than in those of mice (Kim & Guengerich, 1990).

    Incubation of 1,2-dibromoethane with calf thymus DNA and cytosol from
    rats or mice did not result in different adduct levels, whereas the
    level of adduct formation by human liver cytosol was about half of
    those values for rats or mice.  Induction of glutathione-
     S-transferase in rat liver by phenobarbital or ß-naphthoflavone did
    not increase DNA adduct levels, whereas cytochrome P-450 inhibition by
    disulfiram did increase DNA adducts without altering the transferase
    activity.  Depletion of reduced glutathione  in vivo by
    diethylmaleate correlated with a reduction in DNA adduct levels.

         Bromine atoms generated upon reductive degradation of
    1,2-dibromoethane have been shown to react with polyunsaturated fatty
    acids via both abstraction of bisallylic hydrogen and addition to the
    double bond.  Bromine atoms may be a potential initiator for lipid
    peroxidation and provide a chemical basis for the toxic action of
    1,2-dibromoethane (Guha et al., 1993).

         The cytotoxic action of 1,2-dibromoethane has been studied by
    Khan et al. (1993).  They found that both cytochrome P-450- and
    GSH-dependent metabolism of 1,2-dibromoethane contributed to its
    cytotoxic effect in hepatocytes.  Antioxidants or removal of oxygen
    delayed the cytotoxicity.  Furthermore, cytotoxicity could be
    increased markedly if aldehyde dehydrogenase was inhibited with
    disulfiram.  In addition, cytotoxicity could be reduced if the
    hepatocytes were depleted of GSH before the addition of

         1,2-Dibromoethane has also been shown to cause cytotoxicity in
    rabbit pulmonary cells (Nichols et al., 1992), being cytotoxic to
    Clara cells, type II cells and alveolar macrophages.

         The irreversible binding of radioactivity from [1,2-14C]-
    1,2-dibromoethane to protein, DNA and RNA in rats was measured 24 h
    after an intraperitoneal injection of 14C-1,2-dibromoethane
    (2.6-3.2 mg/kg) (Hill et al., 1978).  For each of these classes of
    macromolecules, the largest amounts of bound radioactivity were found
    in the liver and kidneys.

         Botti et al. (1982) evaluated the effect of 1,2-dibromoethane on
    GSH levels and cytosolic glutathione- S-transferase activity
    following administration by gavage to male rats.  Doses of either 75
    or 150 mg/kg were found to decrease GSH and glutathione- S-
    transferase activities. Maximal effects were observed 2 h following
    exposure, although a significant decrease in GSH levels was observed
    within 15 min.  Mann & Darby (1985) also noted GSH depletion in both
    male and female rats, the maximum effect occurring 2 h after an
    intraperitoneal 1,2-dibromoethane dose of 80 mg/kg.  A greater effect
    was observed in males.

         Brandt et al. (1987) used autoradiography and 14C-labelled
    1,2-dibromoethane to study the tissue distribution of
    1,2-dibromoethane following an intraperitoneal injection to a
    cynomolgus monkey.  1,2-Dibromoethane was found to bind preferentially
    to the liver and renal tubules, particularly the adrenal zona

         Kaphalia & Ansari (1992) measured the rate of incorporation of
    label into albumin and other large plasma proteins following exposure
    to [14C]-1,2-dibromoethane either  in vivo or  in vitro.  About
    37% of the total label, administered by gavage (25 mg/kg body weight
    in mineral oil over a 12-day period), was estimated to be bound to
    plasma proteins, the majority (72%) being bound to albumin.  In the
    case of  in vitro exposure, the incorporation of label to human
    albumin or plasma after incubation with radioactive 1,2-dibromoethane
    could be increased by the addition of either microsomal enzymes or an
    NADPH-generating system.


    7.1  Single exposure

         Toxic effects of 1,2-dibromoethane have been mainly observed in
    the liver and kidneys.  Inhaled 1,2-dibromoethane vapour produces
    nasal irritation and depression of the central nervous system.  In
    solution, 1,2-dibromoethane causes skin irritation on the shaved
    abdomen, and eye irritation.

    7.1.1  Oral  Rat

         1,2-Dibromoethane (99% pure) in olive or corn oil was given by
    gavage to albino rats, guinea-pigs, rabbits, mice and chickens.  The
    difference in LD50 of 1,2-dibromoethane in male and female rats was
    statistically significant; rabbits appeared to be the most sensitive
    and mice the least sensitive (Rowe et al., 1952) (Table 13).

         Adult male albino rats (weight 140-160 g) were given 110 mg
    1,2-dibromoethane/kg in olive oil by gavage and were killed 2, 4, 8,
    12, 17 or 22 h later.  During the first 4 h, no changes in the liver
    were detectable by light microscopy.  From 8 h after administration,
    1,2-dibromoethane induced sinusoidal dilatation and centrilobular
    necrosis in the liver (Broda et al., 1976).  Chicken

         Leghorn chickens of both sexes were given 1,2-dibromoethane
    (110 mg/kg body weight) in soybean oil by gavage.  There was an
    increase in liver weight and NAD concentration, and a decrease in
    liver and blood alkaline phosphatase activity (Nachtomi et al., 1968).

         Five-week-old male Leghorn chicks (weight 580-620 g) were given
    1,2-dibromoethane (110 mg/kg body weight) in olive oil by gavage and
    were killed 8, 12 or 22 h later.  The central areas of the liver were
    not changed, but portal areas were affected by 1,2-dibromoethane.  The
    concentration of eosinophilic granulocytes was much greater in
    1,2-dibromoethane-treated livers than in controls (Broda et al.,

    7.1.2  Inhalation  Rat

         When rats were exposed to concentrations of 770, 1540, 3080,
    6610, 12 300, 23 100, 38 500 or 77 000 mg/m3 (20 males and females
    per group in most concentrations, and no control group) for durations

        Table 13.  Acute toxicity of 1,2-dibromoethane
    Species         Route              Vehicle      Parameter    Value         Reference

    Rat (M)         oral               olive oil    LD50         146 mg/kg     Rowe et al. (1952)

    Rat (F)         oral               olive oil    LD50         117 mg/kg     Rowe et al. (1952)

    Rat (M,F)       oral               corn oil     LD50         140 mg/kg     McCollister
                                                                               et al. (1956)

    Mouse (F)       oral               olive oil    LD50         420 mg/kg     Rowe et al. (1952)

    Rabbit (F)      oral               olive oil    LD50         55 mg/kg      Rowe et al. (1952)

    Guinea-pig      oral               olive oil    LD50         110 mg/kg     Rowe et al. (1952)

    Chicken (M,F)   oral               olive oil    LD50         79 mg/kg      Rowe et al. (1952)

    Rabbit          skin                            LD50         450 mg/kg     Rowe et al. (1952)

    Rat             inhalation         vapour by    LC50         4620 mg/m3    Rowe et al. (1952)
                                       aeration     1 h

    Rat (M,F)       inhalation         vapour by    LC50         2304 mg/m3    McCollister
                                       aeration     4 h                        et al. (1956)

    Mouse (ICR)     intraperitoneal    corn oil     LD50         205 mg/kg     Kluwe et al.
    ranging from 0.01 to 16.0 h (exposure time varied at different
    concentrations), slight anaesthetic actions and depression of the
    central nervous system were observed in rats exposed to 1540 mg/m3
    or more.  Deaths occurred within 24 h at concentrations between 1540
    and 3080 mg/m3, related to exposure duration, due to respiratory or
    cardiac failure. The LC50 concentration for a 2-h exposure was
    3080 mg/m3.  Deaths occurring from exposures at lower concentrations
    were almost always delayed, sometimes as long as 12 days after
    exposure. The majority of these deaths were due to pneumonia.  The
    animals usually lost weight, appeared rough and unkempt, became
    irritable, had a bloodstained nasal discharge, and died.  Animals
    surviving the exposure at the lower concentrations exhibited a typical
    progression of symptoms for several days before recovery took place. 
    Rats exposed to concentrations producing mortality, which were
    sacrificed and autopsied 16-24 h after exposure, showed an increased

    weight of lungs, liver and kidneys.  The lungs showed congestion,
    oedema, haemorrhages and inflammation; the liver cells had cloudy
    swelling, centrilobular fatty degeneration and necrosis; the kidneys
    showed slight interstitial congestion and oedema, with slight cloudy
    swelling of the tubular epithelium in some cases (Rowe et al., 1952).  Guinea-pig

         All guinea-pigs (20 males and females per group) exposed to 1540
    or 3080 mg/m3 (no control group) for 2 to 7 h died, whereas all
    those exposed to 770 mg/m3 for 7 h or 1540 mg/m3 for 2 h survived
    (Rowe et al., 1952).

    7.1.3  Intraperitoneal injection  Mouse

         Intraperitoneal injection (46.8 and 93.7 mg/kg; 0.25 and
    0.5 mmol/kg) of 1,2-dibromoethane (> 99.9%) in corn oil in male
    B6C3F1 mice (weight 20-26 g) produced hepatic damage. The mice were
    killed 4 h later and  in vivo genotoxicity was determined by a
    sensitive  in vivo/in vitro alkaline DNA unwinding assay for the
    presence of single-strand breaks and/or alkali-labile sites in hepatic
    DNA. Significant hepatic DNA damage was found with a dose of
    0.5 mmol/kg.  In an assessment of the acute hepatotoxicity and
    nephrotoxicity of 1,2-dibromoethane, male B6C3F1 mice were given
    intraperitoneal injections (93.7, 140, 187.7 or 281.6 mg/kg; 0.5,
    0.75, 1.0 or 1.5 mmol/kg) of 1,2-dibromoethane in corn oil and
    sacrificed 24 h later. Serum L-iditol dehydrogenase (IDH), alanine
    aminotransferase (ATT), and blood urea nitrogen were determined. At a
    dose of 187.7 mg/kg 1,2-dibromoethane produced statistically
    significant increases in relative liver and kidney weights, serum IDH
    and ATT levels, and blood urea nitrogen levels.  Four out of five
    animals given a dose of 281.6 mg/kg died (Storer & Conolly, 1983).  Rat

         Adult male Fischer-344 rats were given a single intraperitoneal
    injection of 99% 1,2-dibromoethane (50 mg/kg; 0.27 mmol/kg) in corn
    oil; they were sacrificed 2, 12, 24, 48 or 96 h later and the kidneys
    were removed.  Histopathological alterations in the kidney were most
    prominent 48 h after 1,2-dibromoethane injection, and consisted of
    acute proximal tubular degeneration (proximal tubular swelling and
    vacuolation) (Kluwe et al., 1982).

    7.2  Short-term exposure

    7.2.1  Oral  Chicken

         In a study by Schlinke (1970), 1,2-dibromoethane (formulation
    which contains 83% of active ingredient) was administered orally at
    doses of 50, 100 or 200 mg/kg per day to groups of five unsexed SPF
    White Leghorn chickens (6-7 weeks old) for 10 days.  There was an
    untreated control group.  All five chickens given 200 mg/kg per day
    showed lack of appetite and depression, and died after the third dose.
    Chickens which died had inflamed crops, excess pericardial fluid, and
    congestion of the liver.  Chickens given 50 or 100 mg/kg per day
    showed no toxic effects.

    7.2.2  Inhalation  Mouse

         B6C3F1 mice (10 males and 10 females per group) were exposed by
    inhalation to 23.1, 115.5 and 577.5 mg/m3 (3, 15 and 75 ppm) of
    1,2-dibromoethane (6 h/day, 5 days per week) for 13 weeks.  Four male
    mice in the low dose group died before the end of the exposure period. 
    At 13 weeks, mice showed severe necrosis and atrophy of the olfactory
    epithelium in the nasal cavity after inhaling the highest
    concentration.  Lower concentrations induced squamous cell metaplasia,
    hyperplasia and cytomegaly of the epithelium of the respiratory nasal
    turbinals.  Squamous metaplasia, hyperplasia and cytomegaly of the
    epithelium were also seen in larynx, trachea, bronchi and bronchioles. 
    The NOEL, based on histopathological alterations in the nasal cavity,
    was 23.1 mg/m3 (3 ppm) (Reznik et al., 1980).  Rat

         A group of 10 female rats (strain unknown) exposed to a
    concentration of 768 mg/m3 (100 ppm) of 1,2-dibromoethane vapour for
    7 h/day, lost weight steadily and three died after 1, 5 and
    7 exposures, respectively.  Surviving rats were thin and unkempt after
    7 exposures in 9 days.  At autopsy the stomachs were full of food, and
    the contents were bloodstained.  Lung, liver and kidney weights were
    significantly elevated.  Microscopic examination revealed some
    thickening of the  alveolar walls, with slight leukocytic infiltration
    of the lungs, widespread cloudy swelling of the liver (but no fatty
    degeneration), and slight congestion and haemosiderosis of the spleen
    (Rowe et al., 1952).

         F-344 rats (five males and five females per group) were exposed
    by inhalation to 23.1, 115.5 and 577.5 mg/m3 (3, 15 and 75 ppm) of
    1,2-dibromoethane (6 h/day, 5 days per week) for 13 weeks.  At 13
    weeks, they showed severe necrosis and atrophy of the olfactory

    epithelium in the nasal cavity after inhalation of 577.5 mg/m3. 
    Lower concentrations induced squamous cell metaplasia, hyperplasia and
    cytomegaly of the epithelium of the respiratory nasal turbinals. 
    Squamous metaplasia, hyperplasia and cytomegaly of the epithelium were
    also seen in the larynx, trachea, bronchi and bronchioles.  Other
    compound-related toxic lesions in rats were seen in the liver, kidney
    and testes.  At 115.5 mg/m3, 1,2-dibromoethane induced only minor
    changes in the nasal cavity.  No lesions were seen in other tissues. 
    The NOEL based on histopathological alterations in the nasal cavity
    was 23.1 mg/m3 (3 ppm) (Reznik et al., 1980).

         Nitschke et al. (1981) conducted a 13-week inhalation study on
    1,2-dibromoethane in rats.  Male and female F-344 rats were exposed to
    0, 23, 77 or 307 mg/m3 (0, 3, 10 or 40 ppm) (6 h/day, 5 days per
    week) for 13 weeks.  Those exposed to 307 mg/m3 (40 ppm) of
    1,2-dibromoethane exhibited a decrease in body weight gain, an
    increase in liver and kidney weight, and hyperplasia and metaplasia of
    the respiratory epithelium of the nasal turbinates.  A slight
    epithelial hyperplasia of the nasal tubinates was also noted at
    77 mg/m3 (10 ppm).  A recovery period of 88 days resulted in
    regression of the lesions in all but one animal.  Guinea-pig

         Guinea-pigs (8 of each sex per group) that were administered
    385 mg/m3 (50 ppm) of 1,2-dibromoethane for up to 7 h, 57 times in
    80 days, had decreased final body weight and increased lung, liver and
    kidney weights.  Microscopic examination of the tissues showed slight
    central fatty degeneration in the liver, and slight interstitial
    congestion and oedema, with some parenchymatous degeneration of the
    tubular epithelium in the kidney.  Blood urea nitrogen values were
    normal.  In females, the total lipid content in the liver revealed no
    significant variation.  Guinea-pigs (4-8 of each sex per group)
    tolerated without toxic effects 145 exposures (7 h each) in 205 days
    at a 1,2-dibromoethane concentration of 193 mg/m3 (25 ppm). 
    However, four out of eight males and two out of eight females died of
    pulmonary infection during the experiment (Rowe et al., 1952).  Rabbit

         When four female rabbits were exposed by inhalation to
    770 mg/m3 (7 h/day) for 4 days, two of the rabbits died after the
    second exposure.  Microscopic examination of tissues revealed
    widespread central fatty degeneration of the liver with areas of
    necrosis.  Rabbits given 59 exposures each lasting 7 h (385 mg/m3)
    in 84 days showed no evidence of adverse effects except for a slight
    increase in liver and kidney weights; those given 152 exposures
    (each 7 h) (192.5 mg/m3) in 214 days showed no adverse effects
    (Rowe et al., 1952).  Monkey

         When one male and one female monkey were given 7-h exposures
    (385 mg/m3) 49 times in 70 days, they appeared ill, nervous and
    unkempt throughout the experiment.  Liver weights were increased with
    slight central fatty degeneration and increased total lipid values. 
    No significant changes were observed in other organs except for a
    slight increase in kidney weight.  Another pair (one male and one
    female) of monkeys received 7-h exposures (193 mg/m3) 156 times in
    214 days.  This group showed no evidence of adverse effects and the
    NOEL was established as 193 mg/m3 (25 ppm) (Rowe et al., 1952).

    7.3  Eye and skin irritation

    7.3.1  Rabbit

         1,2-Dibromoethane (undiluted, 1% and 10% in propylene glycol,
    quantity not stated) was introduced into both eyes of a rabbit and
    after 30 seconds one eye was flushed for 3 min with copious amounts of
    running water.  Conjunctival irritation occurred in both eyes, and
    there was slight superficial necrosis of the cornea.  However, healing
    was prompt and complete 12 days after exposure; there was no corneal
    scarring and no apparent injury to the iris or the lens.  A 1%
    1,2-dibromoethane solution in propylene glycol elicited a response
    very similar to undiluted 1,2-dibromoethane (Rowe et al., 1952).

         A 1.0% solution of 1,2-dibromoethane in butyl carbitol acetate
    was applied 10 times in 14 days to the rabbit ear and also to the
    shaved abdomen where it was then protected by a bandage. On the ear,
    it caused slight irritation (erythema and exfoliation), whereas on the
    shaved abdomen there was marked irritation with erythema and oedema
    progressing to necrosis and sloughing of the superficial layers of the
    skin.  Healing was complete without scarring within 7 days after
    termination of exposure (Rowe et al., 1952).

    7.4  Long-term exposure

         Designs of long-term/carcinogenicity studies are given in Table
    14 and tumorigenic effects seen in these studies are summarized in
    Table 15.

    7.4.1  Oral  Mouse

         Groups of 50 male and 50 female B6C3F1 mice (5 weeks old) were
    given technical-grade 1,2-dibromoethane (99.6% pure) in corn oil by
    gavage on 5 consecutive days per week.  The time-weighted average high
    and low doses of 1,2-dibromoethane were 107 and 62 mg/kg per day for

        Table 14.  Carcinogenicity studies on 1,2-dibromoethane
    Route          Species        Number of animals     Sexa      Dose and dosing scheduleb        Durationc           Reference
                   (strain)       per group

                   Mouse          50                    M         62 mg/kg body weight TWAd        78 weeks(53)        NCI (1978)
                   (B6C3F1)       (treated)                       107 mg/kg body weight TWAd       77 weeks(53)
                                                        F         62 mg/kg body weight TWAd        90 weeks(53)
                                                                  107 mg/kg body weight TWAd       78 weeks(53)
                                  20                    M,F

                   Rat            50                    M         38 mg/kg body weight TWAd        49 weeks(47)        NCI (1978)
                   (Osborn-       (treated)                       41 mg/kg body weight TWAd        49 weeks(34)
                   Mendel)                              F         37 mg/kg body weight TWAd        61 weeks(57)
                                                                  39 mg/kg body weight TWAd        61 weeks(44)
                                  20                    M,F

                   Mouse          30                    M         117 mg/kg body weight per day    15 months           Van Duuren et
                   (B6C3F1)       (treated)             F         103 mg/kg body weight per day    17 months           al. (1985)
                                  50                    M,F

                   Mouse          60                    F         154 mg/m3 6 h/day, 5 days/week   6 months            Adkins et al.
                   (A/J)          (treated)                       384 mg/m3 6 h/day, 5 days/week   6 months            (1986)
                                  60                    F         154 mg/m3 6 h/day, 5 days/week   6 months
                                  (control)e                      384 mg/m3 6 h/day, 5 days/week   6 months
                                  90                    F

    Table 14 (cont'd)
    Route          Species        Number of animals     Sexa      Dose and dosing scheduleb        Durationc           Reference
                   (strain)       per group

                   Mouse          50                    M         77 mg/m3 6 h/day, 5 days/week    78 weeks            NTP (1982)
                   (B6C3F1)       (treated)                       307 mg/m3 6 h/day, 5 days/week   78 weeks
                                  50                    F         77 mg/m3 6 h/day, 5 days/week    103 weeks
                                  (treated)                       307 mg/m3 6 h/day, 5 days/week   90 weeks
                                  50                    M,F

                   Mouse          50                    M         77 mg/m3 6 h/day, 5 days/week    103 weeks           Stinson et
                   (B6C3F1)       (treated)                       307 mg/m3 6 h/day, 5 days/week   90 weeks            al. (1981)
                                  50                    F         77 mg/m3 6 h/day, 5 days/week    103 weeks
                                  (treated)                       307 mg/m3 6 h/day, 5 days/week   90 weeks
                                  50                    M,F                                        104 weeks

                   Rat            50                    M         77 mg/m3 6 h/day, 5 days/week    103 weeks           NTP (1982)
                   (Fisher-344)   (treated)                       307 mg/m3 6 h/day, 5 days/week   88 weeks
                                  50                    F         77 mg/m3 6 h/day, 5 days/week    103 weeks
                                  (treated)                       307 mg/m3 6 h/day, 5 days/week   90 weeks
                                  50                    M,F

                   Rat            48                    M,F       disulfiramf (0.05% in diet)      18 months           Wong et
                   (Sprague-      (treated)                       ± EDB (119-167 mg/m3 TWAb)                           al. (1982)
                   Dawley)                                        7 h/day, 5 days/week
                                  48                    M,F

    Table 14 (cont'd)
    Route          Species        Number of animals     Sexa      Dose and dosing scheduleb        Durationc           Reference
                   (strain)       per group

                   Mouse          30                    F         25 mg/mouse, 3 times/week        400-594 days        Van Duuren et
                   (Ha:ICR        (treated)                       50 mg/mouse, 3 times/week                            al. (1979)
                   Swiss)         100                   F

    a  M = male, F = female
    b  TWA = time-weighted average
    c  observation period: treated and untreated weeks (exposed weeks)
    d  doses changed in the course of the experiment with intermitting untreated weeks
    e  the controls consisted of vehicle (corn oil) & untreated controls
    f  This combination was chosen to examine effects of disulfiram used for alcoholism control programmes on workers
       who were exposed to 1,2-dibromoethane occupationally.
    g  controls consisted of vehicle (acetone) & untreated controls

    Table 15.  Summaries of results of carcinogenicity studies on 1,2-dibromoethane
    Study                       Route          Animal         Statistically significant effects dose (numbers of animals with
                                                              effects/total numbers of animals)

    NCI (1978)                  gavage         mouse          squamous cell carcinoma of the forestomach
                                                              control (M: 0/20, F: 0/20), 62 mg/kg (M: 45/50, F: 46/49)
                                                              107 mg/kg (M: 29/49, F: 28/50)
                                                              alveolar/bronchiolar adenoma
                                                              control (M: 0/20, F: 0/20), 62 mg/kg (M: 4/45, F: 11/43)
                                                              107 mg/kg (M: 10/47, F: 6/46)

                                               rat            squamous cell carcinoma of the forestomach
                                                              control (M: 0/20, F: 0/20), 38 mg/kg (M: 45/50), 37 mg/kg (F: 40/50)
                                                              41 mg/kg (M: 33/50), 39 mg/kg (F: 29/50)
                                                              hepatocellular carcinoma
                                                              control (M: 0/20, F: 0/20), 39 mg/kg (F: 6/48)
                                                              control (M: 0/20, F: 0/20), 38 mg/kg (M: 11/50), 41 mg/kg (M: 4/50)

    Van Duuren et al. (1985)    drinking-      mouse          squamous cell carcinoma
                                water                         117 mg/kg (M: 26/30), 103 mg/kg (F: 22/30)
                                                              oesophageal papilloma
                                                              103 mg/kg (F: 3/30)
                                                              squamous cell papillomaa
                                                              115 mg/kg (M: 9/30, F: 10/30)

    Adkins et al. (1986)        inhalation     mouse (A/J)    i) pulmonary adenoma
                                               (all females)  control (F: 0/60), 154 mg/m3 (F: 60/60), 384 mg/m3 (F: 60/60)
                                                              ii) pulmonary adenoma
                                                              control (F: 0/60), 154 mg/m3 (F: 75/90), 384 mg/m3 (F: 90/90)

    Table 15 (cont'd)
    Study                       Route          Animal         Statistically significant effects dose (numbers of animals with
                                                              effects/total numbers of animals)

    NTP (1982)                  inhalation     mouse          alveolar/bronchiolar carcinoma
                                                              control (M: 0/41, F: 1/49), 77 mg/m3 (M: 3/48, F: 5/49),
                                                              307 mg/m3 (M: 19/46, F: 37/50)
                                                              alveolar/bronchiolar adenoma
                                                              control (M: 0/41, F: 3/49), 77 mg/m3 (F: 7/49),
                                                              307 mg/m3 (M: 11/46, F:13/50)
                                                              haemangiosarcoma of the circulatory system
                                                              control (F: 0/50), 77 mg/m3 (F: 11/50), 307 mg/m3 (F: 23/50)
                                                              subcutaneous fibrosarcoma
                                                              control (F: 0/50), 77 mg/m3 (F: 5/50), 307 mg/m3 (F: 11/50)
                                                              nasal cavity carcinoma, or adenoma
                                                              control (F: 0/50), 307 mg/m3 (F: 6/50, 8/50)
                                                              mammary gland adenocarcinoma
                                                              control (F: 2/50), 77 mg/m3 (F: 14/50), 307 mg/m3 (F: 8/50)

                                inhalation     rat            nasal cavity carcinoma, adenocarcinoma, adenoma
                                                              control (M: 0/50, F: 0/50), 77 mg/m3 (M: 1/50, 20/50, 11/50, F: 0/50,
                                                              20/50, 11/50), 307 mg/m3 (M: 21/50, 0/50, 28/50, F: 25/50, 29/50, 3/50)
                                                              haemangiosarcoma of the circulatory system
                                                              control (M: 0/50, F: 0/50), 307 mg/m3 (M: 15/50, F: 5/50)
                                                              tunica vaginalis mesothelioma
                                                              control (M: 0/50), 77 mg/m3 (M: 7/50), 307 mg/m3 (M: 25/50)
                                                              alveolar/bronchiolar adenoma, carcinoma (combined)
                                                              control (F: 0/50), 307 mg/m3 (F: 5/47)
                                                              nasal cavity adenomatous polyps
                                                              control (M: 0/50), 77 mg/m3 (M: 18/50), 307 mg/m3 (M: 5/50)
                                                              mammary gland fibroadenoma
                                                              control (F: 4/50), 77 mg/m3 (F: 29/50), 307 mg/m3 (F: 24/50)

    Table 15 (cont'd)
    Study                       Route          Animal         Statistically significant effects dose (numbers of animals with
                                                              effects/total numbers of animals)

    Stinson et al. (1981)       inhalation     mouse          nasal cavity carcinoma (squamous carcinoma, adenocarcinoma)
                                                              control (M: 0/45, F: 0/50), 77 mg/m3 (M: 0/44, F: 0/49)
                                                              307 mg/m3 (M: 0/46, F: 7/49)
                                                              control (M: 0/45, F: 0/50), 77 mg/m3 (M: 0/44, F: 1/49)
                                                              307 mg/m3 (M: 0/46, F: 2/49)
                                                              benign neoplasms (squamous papilloma, adenoma)
                                                              control (M: 0/45, F: 0/50), 77 mg/m3 (M: 0/44, F: 0/49)
                                                              307 mg/m3 (M: 3/46, F: 7/49)

    Wong et al. (1982)          inhalation     rat            hepatocellular tumour
                                                              control (M: 0/48, F: 0/48), EDB (M: 3/46, F: 1/48)
                                                              EDB+DSb (M: 36/48, F: 32/48)

                                                              kidney (adenoma and adenocarcinoma)
                                                              control (M: 0/48, F: 0/48), EDB (M: 3/46, F: 1/48)
                                                              EDB+DSb (M: 17/48, F: 7/48)

    Van Duuren et al. (1979)    skin           mouse          lung tumours
                                                              control untreated (F: 30/100)
                                                              control acetone (F: 11/100)
                                                              25 mg/mouse (F: 24/30), 50 mg/mouse (F: 26/30)
                                                              skin carcinoma
                                                              control untreated (F: 0/100)
                                                              control acetone (F: 0/100)
                                                              25 mg/mouse (F: 2/30), 50 mg/mouse (F: 8/30)

    a  carcinogenicity study on bromoethanol
    b  DS: disulfirum given in diet

    both sexes.  All surviving male mice and high-dose female mice were
    killed on week 78, and low-dose females were killed on week 90.  In
    low-dose females, body weight depression was apparent after the first
    10 weeks.  Soft faeces, alopecia and body sores were observed in all
    surviving animals at week 14.  In mice receiving the high dose,
    acanthosis of the forestomach was observed in 5/49 males and 9/50
    females, compared with 1/50 in low-dose females. Hyperkeratosis
    occurred in the stomachs of 13/49 high-dose males, 12/50 high-dose
    females, and 1/48 low-dose females.  There was testicular atrophy
    (10/47) related to compound administration in males receiving the high
    dose (NCI, 1978).  Rat

         Groups (50 of each sex per group) of Osborne-Mendel rats (8 weeks
    old) were administered technical-grade 1,2-dibromoethane in corn oil
    by gavage on five consecutive days per week.  The time-weighted
    average high and low doses of 1,2-dibromoethane in treated groups were
    41 and 38 mg/kg per day for male rats, and 39 and 37 mg/kg per day for
    females.  Body weight depression was apparent in the treated rats
    after the first 10 weeks.  Reddened ears, a hunched appearance, firm
    distended abdomens and abdominal urine stains were observed in treated
    groups.  There was high mortality in both the high- and low-dose
    groups.  All surviving treated male (24 out of 100) and female (3 out
    of 100) rats were sacrificed on weeks 49 and 61, respectively.  In
    rats given the high dose, hyperkeratosis and acanthosis of the
    forestomach were observed in 12/50 males and 18/50 females, and in
    low-dose females the value was 4/50.  In the treated rats,
    degenerative changes in the liver and adrenal gland and early
    development of testicular atrophy were reported (NCI, 1978).  However,
    total development of testicular atrophy in controls, low-dose group
    and high-dose group were 11/20, 14/49 and 18/5, respectively.

    7.4.2  Inhalation  Mouse

         In an NTP carcinogenicity study (NTP, 1982), groups of 50 male
    and 50 female B6C3F1 mice were exposed to 1,2-dibromoethane
    (> 99% pure) concentrations of 0, 77 or 308 mg/m3 (0, 10, or
    40 ppm) for 6 h/day, 5 days per week, for 78 to 103 weeks, throughout
    the study.  Mean body weights of high-dose male and female mice were
    lower than those of the untreated controls.  Survival of high-dose
    female mice was significantly reduced compared with controls. 
    Survival was also reduced in both control and treated male mice, the
    principal cause of death being an ascending suppurative urinary tract
    infection unrelated to compound administration.  Surviving male mice
    were killed at 79 weeks, while female mice were killed at 104-106
    weeks, except for the high-dose group (killed at 91 weeks).  The NTP
    also reported inflammation of the nasal cavity and epithelial
    hyperplasia of the respiratory system in both sexes (NTP, 1982).

         Stinson et al. (1981) reported similar findings in mice using
    data from a 2-year study.  Epithelial hyperplasia of the urinary
    bladder and inflammation of the prostate gland were also observed in
    dosed male mice.  Rat

         Groups of 50 male and 50 female inbred Fischer-344 rats were
    exposed to 1,2-dibromoethane (> 99% pure) concentrations of 0, 77 or
    308 mg/m3 (0, 10 or 40 ppm) for 6 h/day, 5 days per week, for 78 to
    103 weeks, throughout the study.  Mean body weights of high-dose rats
    were lower than those of untreated controls.  Survival of high-dose
    male and female rats was significantly reduced compared with the
    controls.  Surviving female and male rats were killed at 104-106
    weeks, except for the male high-dose group (5 out of 50 alive, killed
    at 89 weeks) and female high-dose group (8 out of 50 alive, killed at
    91 weeks).  Among the observed compound-related non-neoplastic lesions
    were hepatic necrosis and toxic nephropathy in both sexes, testicular
    degeneration and atrophy in males, and retinal degeneration in females
    (NTP, 1982).

         Four groups of 48 male and 48 female Sprague-Dawley rats were
    exposed to either control air, 154 mg 1,2-dibromoethane/m3, 0.05%
    disulfiram in the diet, or 20 mg 1,2-dibromoethane/kg and 0.05%
    disulfiram in the diet for 18 months.  Disulfiram which is used in
    alcohol control programmes is known to inhibit acetaldehyde
    dehydrogenase.  It may therefore alter the biotransformation of
    1,2-dibromoethane and cause the accumulation of 2-bromoacetaldehyde,
    one of the possible toxic metabolites of 1,2-dibromoethane.  The
    average starting weights ranged from 131 to 134 g for male rats and
    118 and 124 g for females.  Between inhalation exposures (7 h/day,
    5 days/week), rats were permitted free access to water and food.  Rats
    receiving 0.05% disulfiram showed reduced body weight gain compared
    with control rats or those given 20 mg 1,2-dibromoethane/kg or the
    control diet.  Rats exposed to 154 mg/m3 of 1,2-dibromoethane alone
    and those receiving a combination of 20 mg 1,2-dibromoethane/kg and
    0.05% disulfiram had high mortality compared with control and
    disulfiram-treated rats.  In rats exposed by inhalation to 154 mg
    1,2-dibromoethane/m3 alone, mortality was 90% in males and 77% in
    females at 18 months.  Haematological parameters were within the
    normal range for moribund rats in this group.  Male rats receiving
    20 mg 1,2-dibromoethane/kg with 0.05% disulfiram had a high incidence
    of testicular atrophy and there was atrophy of the spleen in 30/48
    males and 19/48 females (Wong et al., 1982).

    7.5  Developmental toxicity

         1,2-Dibromoethane causes testicular effects and mating failure in
    rats at high inhalation levels that result in mortality.  It also
    causes temporary malformation of sperm cells in bulls and rams, but
    not in chickens.  In laying hens, it causes decreased egg size.  In

    rats and mice there is no evidence of embryotoxicity and
    teratogenicity.  In rats, paternal exposure causes behavioural changes
    in F1 progeny.

    7.5.1  Reproduction

         Male Sprague-Dawley rats (3-4 per group) were exposed by
    inhalation to average daily concentrations of 146, 300 or 684 mg/m3
    (19, 39 or 89 ppm) of 1,2-dibromoethane for 7 h/day, 5 days/week, for
    10 weeks.  There was reduced weight gain in the 300 and 684 mg/m3
    groups with mortality (21%) and morbidity in the 684 mg/m3 group.
    Animals in this group had reduced testicular weights, reduced serum
    testosterone levels, and atrophy of the testes (10/10), epididymis
    (10/10), prostate (10/10), and seminal vesicles (9/9).  When mated
    with untreated females none of the males exposed to 684 mg/m3
    impregnated any females, while 90% of those exposed to the low and
    intermediate concentrations impregnated females who produced litters
    that were normal in terms of total implants, viable implants and
    resorptions.  In female Sprague-Dawley rats, inhaling average daily
    concentrations of 154, 300 or 614 mg/m3 (20, 39 or 80 ppm) of
    1,2-dibromoethane for 7 h/day, 7 days/week, for 3 weeks, there was
    reduced weight gain, morbidity and mortality (20%) in the 614 mg/m3
    group.  At the end of the 3-week exposure, females were mated with
    untreated males.  Females in the 614 mg/m3 group were in diestrus
    and did not cycle normally until 3-4 days later; consequently fewer
    females mated during a 10-day mating period than in the case of the
    other two groups.  The vaginal smears from females exposed to 154 or
    300 mg/m3 were normal.  In all three groups the reproductive
    performance (total implants/dam, viable implants/dam and resorptions/
    dam) was unimpaired.  Histopathological examination of the ovaries and
    uterus did not reveal any significant lesions (Short et al., 1979). 
    It was considered that the NOEL for reproductive performance was
    300 mg/m3 for male and female rats.

         Weanling male albino rats (10 rats per group) were fed
    1,2-dibromoethane in the diet at levels of 100 or 500 mg/kg
    (equivalent to 10 or 50 mg/kg body weight per day) for 90 days.  There
    was no evidence of toxicity; serum enzyme activities were unchanged. 
    Five rats from each group were mated with untreated virgin females. 
    There was no impairment of reproductive performance in the male rats. 
    At the end of the 2-week mating period the males were sacrificed. 
    Histology of the testis was normal.  The pregnant females were allowed
    to go to term, and the mean number of litters per group, mean pup
    weight at birth, and sex ratio were found to be similar to the values
    for a control group mated with untreated males (Shivanandappa et al.,
    1987).  The NOEL for male rat reproductive performance was considered
    to be 50 mg/kg body weight per day.

         In a study of sperm quality and fertility, mature (12 months old)
    male New Zealand White rabbits (8-10 group) were injected
    subcutaneously with 1,2-dibromoethane in corn oil at dose levels of

    15, 30 or 45 mg/kg body weight per day for 5 days. There were also
    untreated and vehicle control groups.  Male fertility was assessed
    before exposure, and at 4 and 12 weeks after injection, by artificial
    insemination of three females/male per time point with one million
    motile sperm.  The percentage of pregnant females, litter size, fetal
    body weights and structural development were assessed.  In the highest
    dose group there was 30% mortality and liver damage in 43% of the
    survivors, indicated by increased levels of serum enzymes.  There were
    also changes in some sperm parameters (see  The percentage
    of pregnant females and mean litter sizes were similar to those
    produced by sperm from vehicle control animals, demonstrating that
    fertilizing capacity and gestational outcome were unaffected (Williams
    et al., 1991).  Effects on sperm

         Four bull calves of the Israel-Friesian breed were administered
    1,2-dibromoethane orally at a dose of 2 mg/kg body weight from the age
    of 4 days by adding 1,2-dibromoethane to milk or feed concentrates. 
    When the calves reached an age of about 12 months, 1,2-dibromoethane
    was administered in gelatin capsules.  The treatment did not affect
    the growth or health of the treated animals, and their libido was
    similar to that of untreated animals.  However, sperm density in
    treated bulls was low, and sperm motility was poor.  Semen showed
    abnormally shaped spermatozoa (tailless, coiled tail, pyriform head). 
    Recovery after discontinuation of treatment varied from 10 days to
    about 3 months in different animals. In a further study,
    1,2-dibromoethane (4 mg/kg body weight) was administered orally to a
    previously untreated bull.  Two weeks after the start of the treatment
    the semen exhibited abnormalities (Amir & Volcani, 1965). Other
    studies also showed that 1,2-dibromoethane caused reversible
    abnormalities of sperm cells in bulls (Amir, 1973, 1975; Amir et al.,
    1979; Courtens et al., 1980) and in rams (ElJack & Hrudka, 1979), but
    not in chickens (Alumot et al., 1968).

         In a study by Williams et al. (1991), male New Zealand White
    rabbits (8-10/group) were injected subcutaneously with
    1,2-dibromoethane in corn oil (0, 15, 30 or 45 mg/kg body weight for
    5 days).  Weekly semen samples (for 6 weeks before exposure, during
    treatment and 12 weeks after dosing) were analysed for sperm
    concentration, number, morphology, viability and motion parameters
    (velocity, linearity, beat cross-frequency, amplitude of lateral head
    displacement (ALH) and circularity), and for semen pH, osmolality,
    volume, and levels of fructose, citric acid, carnitine, protein and
    acid phosphatase (AP).  In the 45-mg/kg dose group, 1,2-dibromoethane
    produced significant decreases in sperm velocity, percentage motility
    and ALH (up to 25% at various times after dosing). There were also
    dose-related decreases in semen pH (up to 2%) and total ejaculate
    volume (up to 23%, 15 and 30 mg/kg groups only).  Acid phosphatase
    activities were significantly elevated (up to 116%) 2 weeks after
    dosing in the 45 mg/kg dose group.  All other semen parameters

    evaluated were unaffected.  Rabbits appear less sensitive than humans
    to the reproductive effects of 1,2-dibromoethane, since semen
    parameters were affected only at doses close to the LD50 and some
    parameters (sperm numbers, viability and morphology) were unaffected. 
    A NOEL was not obtained in this study.  Effects on ova

         Feeding studies with laying hens showed that 1,2-dibromoethane
    absorbed by grain adversely affected egg production.  When hens were
    fed grain containing 200 mg/kg (corresponding to 25 mg/kg per day) for
    56 days or grain containing 300 mg/kg (corresponding to 38 mg/kg per
    day) for 46 days, the hens ceased laying completely.  Feeding of grain
    containing 10 mg/kg (corresponding to 12.5 mg/kg per day) caused a
    diminution of egg size after 12 weeks (Bondi et al., 1955).

    7.5.2  Teratogenicity

         Pregnant Sprague-Dawley rats and CD-1 mice inhaled
    1,2-dibromoethane concentrations of 146, 292 or 614 mg/m3 (20, 38 or
    80 ppm) (23 h/day for 10 days) from day 6 to day 15 of gestation. 
    Adverse effects on maternal animals, measured by body weight gain and
    food consumption, were observed in both species at all doses tested. 
    A marked increase in maternal mortality occurred in rats exposed to
    614 mg/m3 and in mice exposed to 292 or 614 mg/m3.  Some
    morphological changes, such as haematomas, exencephaly and skeletal
    variations, were observed in the fetuses of rats and mice.  However,
    these changes occurred only at high concentrations that caused
    maternal toxicity (Short et al., 1978).

         The embryotoxic effects of 1,2-dibromoethane bioactivation,
    mediated by purified rat liver glutathione- S-transferases (GST),
    were investigated using rat embryos in culture (Mitra et al., 1992). 
    Significant 1,2-dibromoethane metabolism was observed with rat liver
    GST purified by affinity chromatography.  1,2-Dibromoethane activation
    caused a significant reduction in general development as measured by
    crown-rump length, yolk sac diameter, somite number, and the composite
    score for different morphological parameters.  Structures most
    significantly affected were the central nervous and olfactory systems
    as well as the yolk sac circulation and allantois.  The results of
    this study clearly indicate that under  in vitro conditions,
    bioactivation of 1,2-dibromoethane by GST can lead to embryotoxicity. 
    GST isozymes from human fetal liver were purified and used to
    investigate the toxicity of 1,2-dibromoethane in an  in vitro model
    of rat embryos in culture as passive targets (Mitra et al., 1992). 
    1,2-Dibromoethane bioactivation by the GST isozyme P-3 resulted in
    toxicity to cultured rat embryos.  Significant reductions in crown
    rump length, yolk sac diameter, and the composite score of
    morphological parameters were observed.  The central nervous, optic
    and olfactory systems, and the hind limb were most significantly

         When pregnant Sprague-Dawley rats were injected intraperitoneally
    with 1,2-dibromoethane at a dose of 50 mg/kg body weight from day 1 to
    day 15 of gestation, there was no evidence of embryotoxicity or
    teratogenicity, although there were maternal toxic effects (change in
    organ weights) (Hardin et al., 1981).  Effects on neonatal behaviour

         Pregnant Long-Evans rats (16 animals/group, litter size 8-10)
    were exposed to 3.3, 51.2 or 512 mg/m3 by inhalation (4 h/day,
    3 days/week) from day 3 to day 20 of gestation.  The highest
    concentration produced enhanced rotorod performance and T-maze
    brightness discrimination acquisition in the offspring.  Similar
    behavioural changes were noted in the offspring of mothers exposed to
    51.2 mg/m3, but the magnitude of the effect was reduced.  Exposure
    to 3.3 mg/m3 produced no effects.  DRL-20 acquisition (differential
    reinforcement of low rates), straight alley running speed, and passive
    avoidance were not affected at any dose level (Smith & Goldman, 1983).

         In a study by Fanini et al. (1984), adult male Fischer-344 rats
    were injected intraperitoneally with 1,2-dibromoethane at daily doses
    of 0, 1.25, 2.5, 5 or 10 mg/kg body weight for 5 days.  The treated
    males were then mated with untreated female rats 4 or 9 weeks after
    treatment.  A total of 19 litters composed of 172 animals, 84 males
    and 88 females were obtained from breeding the exposed males with
    untreated females.  Behavioural assessments of all F1 progeny were
    carried out up to 21 days of age.  Assessment of behavioural
    development was made by means of an extensive testing battery. 
    Pre-weaning behavioural assessment included simple reflexes (surface
    righting, cliff avoidance and negative geotaxis), motor coordination
    (e.g., swimming and open field activity) and locomotor activity. 
    Significant impairment in the development of motor coordination and
    motor activity was observed in the F1 progeny of males of all
    treated groups.  A NOEL was not found in this study.

         The effects of 1,2-dibromoethane exposure on several
    neurotransmitter enzymes in male rats were examined in various brain
    regions of the F1 progeny (from 7 to 90 days of age) (Hsu et al.,
    1985).  Significant increase of choline acetyltransferase in the
    cerebellum, corpus striatum, hippocampus and hypothalamus, alterations
    of acetylcholinesterase in various brain regions, and an increase of
    glutamic acid decarboxylase activity in the corpus striatum may be
    related to early-development behavioural abnormalities.

    7.6  Mutagenicity and related end-points

         Mutagenicity assays are summarized in Table 16.

        Table 16.  Mutagenicity studies on 1,2-dibromoethane
    Test method       Species (route        Strain/cell type     Resultsb  Reference
                      of administration)a

    In vitro

    Gene mutation     Salmonella            E503                     -     Alper & Ames (1975)
                      typhimurium           G46(-S9)                 +     Ames & Yanofsky (1971); Von Buselmaier et al. (1972)
                                            TA1530(-S9)              +     Ames & Yanofsky (1971); Brem et al. (1974); Rosenkranz
                                                                           (1977); Buijs et al. (1984)
                                            TA1535(+/-S9)            +l    Brem et al. (1974); McCann et al. (1975); Rannug & Beije (1979);
                                                                           Shiau et al. (1980); Barber et al. (1981); Principe et al. (1981);
                                                                           Moriya et al. (1983); Buijs et al. (1984); Dunkel et al. (1985);
                                                                           Tennant et al. (1986, 1987); Zoetemelk et al. (1987); Barber &
                                                                           Donish (1982)
                                            TA98(+/-S9)              +l    Barber et al. (1981); Moriya et al. (1983);Dunkel et al. (1985);
                                                                           Tennant et al. (1986)
                                            TA100(+/-S9)             +l    McCann et al. (1975); Barber et al. (1981); Stolzenberg & Hine
                                                                           (1980); van Bladeren et al. (1980, 1981b); Principe et al. (1981);
                                                                           Moriya et al. (1983); Buijs et al. (1984); Dunkel et al. (1985);
                                                                           Kerklaan et al. (1985); Guobaitis et al. (1986);
                                                                           Tennant et al. (1986);
                                                                           Hughes et al. (1987); Zoetemelk et al. (1987); Barber & Donish (1982)
                                            TA1535(GSH-)             +     Kerklann et al. (1983)
                                            (-S9,+ GSH)                    Zoetemelk et al. (1987)
                                            TA100(GSH-)              +     Kerklaan et al. (1985)
                                            (-S9,+GSH)                     Zoetemelk et al. (1987)
                                            TA100W(Str',8AGr')(-S9)  +g    Ong et al. (1989)
                                            TA1535 (bile of rats)    +     Rannug & Beije (1979)
                                            TA1537(+/-S9)            -     Principe et al. (1981); Moriya et al. (1983); Dunkel et al. (1985);
                                                                           Tennant et al. (1986)
                                            TA1538(+/-S9)            -     Brem et al. (1974); Principe et al. (1981); Moriya et al. (1983);
                                                                           Dunkel et al. (1985)
                                            TA98 (+/-S9)             -     Principe et al. (1981); Wildeman & Nazar (1982)
                                            TA100(+/-S9)             -     Shiau et al. (1980); Wildeman & Nazar (1982)

    Table 16 (cont'd)
    Test method       Species (route        Strain/cell type     Resultsb  Reference
                      of administration)a

                      Serratia              a21 (-S9)                -     Von Buselmaier et al. (1972)

                      Escherichia coli      WP2 (+/-S9)              +     Scott et al. (1978); Hemminki et al. (1980); Moriya et al. (1983);
                                                                           Dunkel et al. (1985)
                                            CHY832 (-S9)             +     Hayes et al. (1984)
                                            343/286 (+/-S9)          +     Mohn et al. (1984)
                                            KI201, KI211 (-S9)       +     Izutani et al. (1980)
                                            uvrB5                    +     Foster et al. (1988)
                                            343/113 (-S9)            -     Mohn et al. (1984)

                      Bacillus subtilis     TKJ5211, TKJ6321 (+S9)   +     Shiau et al. (1980)

                      Streptomyces          (-S9, spot test)         +     Principe et al. (1981)
                      coelicolor            (-S9, plate method)      -     Principe et al. (1981)

                      Aspergillus           methG1BiA1               +     Scott et al. (1978)
                      nidulans              (+/-plant extract)
                                            haploid strain 35 (-S9)  +     Principe et al. (1981)

                      Neurospora crassa     ad-3 (forward mutation)  +     de Serres & Malling (1983)

                      Tradescantia          clone 02, 0106, 4430     +g    Sparrow et al. (1974); Nauman et al. (1976);
                                                                           Vant'Hof & Schairer (1982)

                      Mouse                 L5178Y (+/-S9)           +     Clive et al. (1979); Tennant et al. (1986, 1987)

                      Chinese hamster       CHO-K1 (+/-S9)           +     Tan & Hsie (1981); Brimer et al. (1982)
                      Human                 cell line AHH-1, TK6     +     Crespi et al. (1985)
                      Human                 cell line EUE (-S9)      +     Ferreri et al. (1983)

    Table 16 (cont'd)
    Test method       Species (route        Strain/cell type     Resultsb  Reference
                      of administration)a

    Unscheduled       Rat                   hepatocytes              +     Williams et al. (1982); Tennant et al. (1986)
    DNA synthesis
                      Opossum               lymphocytes              +     Meneghini (1974)
                      Human                 lymphocytes (+/-S9)      +     Perocco & Prodi (1981)
                      Mouse                 (C3Hfx101)F1,            +     Sega & Rene (1980)
                                            germ cells

    Sister-chromatid  Fish                  lymphocytes (- S9)       +     Ellingham et al. (1986)
    exchange          Chinese hamster       V79 cl-15 (-S9)          +     Tezuka et al. (1980)
                      Chinese hamster       CHO (+/-S9)              +     Tennant et al. (1987)
                      Human                 lymphocytes (-S9)        +g    Ong et al. (1989); Tucker et al. (1984)

    Chromosome        Fish                  lymphocytes (- S9)       +     Ellingham et al. (1986)
    aberrations       Chinese hamster       V79 cl-15 (-S9)          +     Tezuka et al. (1980)
                                            CHO (+/-S9)              +     Tennant et al. (1987)

    Micronuclei       Tradescantia          clone 03, 4430           +l    Ma et al. (1978, 1984)

    DNA damage        E. coli               polA1-/polA+ (-S9)       +w    Brem et al. (1974)
                      B. subtilis           TKJ5211, TKJ6321         -     Shiau et al. (1980)

    SOS induction     S. typhimurium        TA1535/pSK1002           +g    Ong et al. (1987)
                      E. coli               PQ37 (-S9)               +     Ohta et al. (1984); Quillardet et al. (1985)

    Mitotic gene      Saccharomyces         ade2, trp5               +     Fahrig (1974)
    conversion        cerevisiae

    Somatic           A. nidulans           diploid 35 x 17 (-S9)    +g    Crebelli et al. (1984)

    Table 16 (cont'd)
    Test method       Species (route        Strain/cell type     Resultsb  Reference
                      of administration)a

    DNA binding       E. coli               Q13 (+/-S9)              -     Kubinski et al. (1981)
                      Mouse                 Ehrlich ascites (+/-S9)  -     Kubinski et al. (1981)

    Cell              Human                 lymphocyte               +     Channarayappa et al. (1992)

    DNA strand        Rat                   hepatocytes              +     Sina et al. (1983)

    Cell              Mouse                 Balb/c 3T3 (-S9)         -     Tennant et al. (1986); Perocco et al. (1991)

    In vivo

    Gene mutation     S. typhimurium        G46 (host-mediated)      +     Von Buselmaier et al. (1972)

                      Serratia              a21 (host-mediated)      -     Von Buselmaier et al. (1972)

                      Barley                                         +     Ehrenberg et al. (1974)
                      Silkworm              (egg color mutation)     -     Sugiyama (1980)

                      Drosophila            (wing spot)              +g    Graf et al. (1984)

    Recombination     D. melanogaster       (wing spot)              +g    Graf et al. (1984)

    Sex-linked        D. melanogaster                                +l    Kale & Baum (1979a,b, 1981, 1982, 1983); Yoshida & Inagaki
    recessive lethal                                                       (1986); Vogel & Chandler (1974)
    mutations         D.melanogaster        spermatozoa              +     Ballering et al. (1993)

    Table 16 (cont'd)
    Test method       Species (route        Strain/cell type     Resultsb  Reference
                      of administration)a

    Specific          Mouse                                          -     Russell (1986)
    locus test        Mouse                 DBA/2J                   -     Barnett et al. (1992)

    Chromosome        Barley                root tips                +     Ehrenberg et al. (1974)
    aberration        Mouse (ip)            CD1, (bone marrow)       -     Krishna et al. (1985)

    Sister-chromatid  Mouse (ip)            CD1, bone marrow         -     Krishna et al. (1985)

    Dominant lethal   Rat (ih, po)          CD, SD                   -     Short et al. (1979); Teramoto et al. (1980)
                      Mouse (po)            BDF1                     -     Teramoto et al. (1980)
                      Mouse (ip, po)        ICR/Ha                   -     Epstein et al. (1972)
                      Mouse                 DBA/2J                   -     Barnett et al. (1992)

    DNA strand        Rat (po)              hepatocytes              +     Nachtomi & Sarma (1977)
    breaks            Mouse (ip)            hepatocytes              +     Storer & Conolly (1983)
    breaks            Mouse (ip)            hepatocytes              +     White (1982)

    Micronuclei       Amphibians:           erythrocytes                   Fernandez et al. (1993)
                      Pleurodeles waltl                              +
                      Ambystoma                                      +
                      mexicanum (axolotl)
                      Anuran: Xenopus                                +
                      laevis (toad)

                      Mouse                 ddY(peripheral blood     -     Asita et al. (1992)
                      Mouse(ip)             CD1, bone marrow         -     Krishna et al. (1985)

                      Tradescantia          tetrads of               +     Ma et al. (1978)

    Table 16 (cont'd)
    Test method       Species (route        Strain/cell type     Resultsb  Reference
                      of administration)a

    Sperm             Bull                  Friesian                 +     Amir et al. (1977)

    a  ip = intraperitoneal administration; ih = inhalation exposure; iv = intravenous administration; po = oral administration
    b  g = test in gaseous phase; l = test in liquid or gaseous phase; w = weak positive results
    7.6.1  In vitro assays

         1,2-Dibromoethane was mutagenic in reverse mutation assays
    (Ames test) using  Salmonella typhimurium strains G46, TA1530,
    TA1535, TA98, TA100 and TA100W, and in the host-mediated assay using
    strain G46.  Bile from mice and rats injected intraperitoneally with
    1,2-dibromoethane or following liver perfusion was mutagenic in a test
    using strain TA1535.  Gene mutation assays using  Escherichia coli,
    strain WP2 and several other strains, were positive.  A positive
    response was reported in assays using  Bacillus subtilis, Streptomyces
     coelicolor, Aspergillus nidulans and  Neurospora crassa.

         A requirement for intracellular activation of 1,2-dibromoethane
    was observed for a mutagenic response in  S. typhimurium TA1535. 
    Glutathione- S-transferase 5-5 transfected into the bacteria allowed
    the induction of base-pair mutations on exposure to 1,2-dibromoethane,
    whereas a 20-fold extracellular excess of the enzyme did not permit
    1,2-dibromoethane-induced mutations in non-transfected bacteria in the
    presence of reduced glutathione (Thier et al., 1993).

         1,2-dibromoethane failed to induce reverse mutations in a number
    of assays using  S. typhimurium E503, TA1537 and TA1538, with or
    without S9 mix.  A negative response was reported in several assays
    using  E. coli, Serratia marcescens and silkworms, and in the mouse
    specific locus test.

         Chromosomal aberrations were induced by 1,2-dibromoethane in
    cultured fish lymphocytes (Ellingham et al., 1986), Chinese hamster
    V79 and CHO cell lines (Tezuka et al., 1980; Tennant et al., 1987). 
    1,2-Dibromoethane was negative in a test for dominant lethal and
    specific locus mutations in germ cells from DBA/2J male mice (Barnett
    et al., 1992).

         1,2-Dibromoethane increased significantly the frequency of sister
    chromatid exchanges in cultured fish lymphocytes (Ellingham et al.,
    l986), Chinese hamster cell line (V79) and cultured human lymphocytes
    (Tucker et al., 1984; Ong et al., 1989), but not in bone marrow cells
    of mice injected intraperitoneally (Krishna et al., 1985).

         In isolated human mononucleated and binucleated peripheral
    lymphocytes, 1,2-dibromoethane caused an increased frequency of
    micronuclei  in vitro (Channarayappa et al., 1992).

         A positive response was obtained in the unscheduled DNA synthesis
    assay using cultured rat hepatocytes (Williams et al., 1982; Tennant
    et al., 1986), cultured opossum lymphocytes (Meneghini, 1974),
    cultured human lymphocytes (Perocco & Prodi, 1981) and mouse germ
    cells (Sega & Rene, 1980), and in the DNA strand break assay using rat
    or mouse hepatocytes (Nachtomi & Sarma, 1977; White, 1982; Sina et
    al., l983).  Tests for DNA damage using  E. coli (Brem et al., 1974),
    SOS induction using  S. typhimurium and  E. coli (Ohta et al., 1984;

    Quillardet et al., 1985; Ong et al., 1987), mitotic gene conversion
    using  Saccharomyces cerevisiae (Fahrig, 1974), somatic segregation
    using  A. nidulans (Crebelli et al., 1984), recombinant DNA synthesis
    using  D. melanogaster (Graf et al., 1984), and sperm abnormality in
    bulls (Amir et al., 1977) were positive.  However, there was a
    negative response in a test for DNA damage using  B. subtilis (Shiau
    et al., 1980), in DNA-binding tests using  E. coli and Ehrlich
    ascites tumour cells (Kubinski et al., 1981), and in the cell
    transformation assay using mouse Balb/c 3T3 cells (Tennant et al.,

    7.6.2  In vivo assays

         1,2-Dibromoethane did not induce chromosomal aberrations or
    sister chromatid exchanges in occupationally exposed papaya fruit
    packers (Steenland et al., 1986).

         1,2-Dibromoethane was negative in tests for specific locus
    mutations in germ cells in male mice (Russell, 1986; Barnett et al.,
    1992).  It did not induce dominant lethal mutations in mice (Epstein
    et al., 1972; Teramoto et al., 1980; Barnett et al., 1992) or rats
    (Short et al., 1979; Teramoto et al., 1980), chromosomal aberrations
    in mice (Krishna et al., 1985) or micronuclei in bone-marrow cells of
    mice (Krishna et al., 1985); there was a weak sister chromatid
    exchange response that was not dose-related (Krishna et al., 1985).

         Tests for recombinant DNA synthesis using  D. melanogaster (Graf
    et al., 1984) and sperm abnormality using bulls (Amir et al., 1977),
    and a sex-linked recessive lethal test using  D. melanogaster with
    exposure to 1,2-dibromoethane in the gaseous phase (Kale & Baum, 1982)
    were all positive.

         The frequency of micronuclei in pollen mother cells of
    Tradescantia was significantly increased by exposure to
    1,2-dibromoethane in the liquid or gaseous phase (Ma et al., 1978,
    1984).  Gene mutation was demonstrated in barley (Ehrenberg et al.,
    1974) and  Drosophila melanogaster (wing spot) (Graf et al., 1984). 
    It induced DNA strand breaks in rat (Nachtomi & Sarma, 1977) and mouse
    (White, 1982) hepatic cells.  1,2-Dibromoethane was negative in a gene
    mutation assay (egg colour mutation) in silkworms (Sugiyama, 1980).

    7.6.3  Other studies

         Two doses of 1,2-dibromoethane with dose levels ranging between
    10 and 300 µmol/kg body weight (1.8-56 mg/kg body weight) were given
    by gavage to 90-day-old female Sprague-Dawley rats, 21 and 4 h before
    sacrifice.  1,2-Dibromoethane caused marked DNA damage.  The fraction
    of DNA eluted from samples of blood, bone marrow, liver, kidney,
    spleen or thymus of the rats given 1,2-dibromoethane doses of 100 µmol

    body weight (18 mg/kg body weight) 21 and 4 h before sacrifice was
    higher than in controls.  However, the difference was statistically
    significant only for kidney and liver (Kitchin & Brown, 1986).

         Intraperitoneal injection (0.25 and 0.5 mmol/kg) of
    1,2-dibromoethane (> 99 9%) in corn oil in B6C3F1 mice (weight
    20-26 g) produced hepatic damage.  The mice were sacrificed 4 h later
    and  in vivo genotoxicity was determined by a sensitive  in vivo/
     in vitro alkaline DNA-unwinding assay for the presence of
    single-strand breaks and/or alkali-labile sites in hepatic DNA. 
    Significant hepatic DNA damage was found with a dose of 0.5 mmol/kg.

         Although 1,2-dibromoethane is a direct-acting mutagen, its
    mutagenicity is generally enhanced by metabolic activation.  Two
    different pathways have been postulated for its activation to the
    ultimate mutagenic form.  One is mediated by the mixed-function
    oxygenases of liver microsomes, in which 1,2-dibromoethane is
    converted to bromoacetaldehyde and 2-bromoethanol, both of which are
    potential DNA-damaging agents (Hill et al., 1978; Banerjee et al.,
    1979).  The other pathway is mediated by enzymes present in liver
    cytosol, in which glutathione conjugation can yield a half-sulfur-
    mustard or an episulfonium ion as reaction products (Rannug, 1980; Van
    Bladeren et al., 1980).

         Glutathione conjugation also contributes to the binding of
    1,2-dibromoethane to DNA, and an  S-[2-(N7-guanyl)ethyl]
    glutathione adduct has been identified (Ozawa & Guengerich, 1983;
    Inskeep & Guengerich, 1984).  Foster et al. (1988) reported that the
    majority of mutations induced by 1,2-dibromoethane consist of GC to AT
    and AT to GC base changes, suggesting that it acts like an alkylating

         This glutathione conjugate accounts for > 95% of the total DNA
    adducts formed by 1,2-dibromoethane.   S. typhimurium TA100 and
    sequence analysis were used to determine the type, site and frequency
    of mutations in a portion of the  lacZ gene resulting from  in vitro
    modification of bacteriophage M13mp18 DNA with  S-(2-chloroethyl)
    glutathione, an analogue of the 1,2-dibromoethane-glutathione
    conjugate.  An adduct level of approx.8 nmol per mg DNA resulted in a
    10-fold increase in mutation frequency.  The mutations were mainly
    base substitutions in which GC to AT transitions accounted for 75%
    (70% of the total mutations) (Cmarik et al., 1992).

         The steady-state levels of  c-fos, c-jum, and  c-myc mRNA were
    investigated in male Wistar rat liver following oral dosing with
    100 mg 1,2-dibromoethane/kg body weight.  This dose induced
    hyperplasia.  Increases in the expression of  c-myc and  c-jum genes
    were observed in the absence of  c-fos expression (Coni et al.,

         Sundheimer et al. (1982) examined the relationship between
    glutathione metabolism and the rate of DNA alkylation by
    1,2-dibromoethane in cultured hepatocytes.  The rate of alkylation was
    decreased by the addition of diethyl maleate and increased by the
    addition of cytosolic microsomal enzymes.  While high concentrations
    of 1,2-dibromoethane were capable of depleting glutathione in the
    hepatocytes, depletion did not appear to be necessary for binding to
    occur.  On the basis of these results, the authors concluded that
    glutathione- S-transferases are involved in the bioactivation of
    1,2-dibromoethane to an alkylating species.

         Working et al. (1986) assessed the ability of 1,2-dibromoethane
    to cause DNA damage by quantifying the rate of unscheduled DNA
    synthesis (UDS) in F-344 rat hepatocytes and spermatocytes exposed to
    1,2-dibromoethane  in vivo and  in vitro.  Pretreatment of cells
    with inhibitors of cytochrome-P450-mediated oxidation had no effect on
    the induction of UDS by 1,2-dibromoethane (10-100 µmol/litre)
     in vitro, whereas depletion of cellular glutathione strongly
    inhibited UDS induction in both cell types.  Pretreatment of rats with
    metyrapone (an inhibitor of hepatic mixed-function oxidases)  in vivo
    had no effect on 1,2-dibromoethane-induced UDS in hepatocytes, but
    produced a positive UDS response in spermatocytes.  This suggests that
    the mixed-function oxidase pathway in metabolism is the primary route
    of clearance of 1,2-dibromoethane and the inhibition of this enzyme
    system leads to more extensive tissue distribution of the parent
    compound.  The data also suggest that the pathway which produces
    genotoxic metabolites from 1,2-dibromoethane in hepatocytes and
    spermatocytes,  in vivo and  in vitro, involves the conjugation of
    1,2-dibromoethane to glutathione and its subsequent metabolism.

         In studies of DNA adducts, Kim & Guengerich (1989) measured
    urinary excretion of  S-[2-( N7-guanyl)ethyl]- N-acetyl-cysteine,
    derived from the nucleic acid adduct,  S-[2-( N7-guanyl)
    ethyl]glutathione, in rats treated with 1,2-dibromoethane.  A good
    correlation was found between the excretion of this mercapturic acid
    and the  in vivo formation of the DNA adduct in liver and kidney DNA. 
    Inskeep et al. (1986) determined that the major DNA adduct formed upon
    exposure to 1,2-dibromoethane,  S-[2-( N7-guanyl)ethyl]glutathione,
    had a half-life in rat liver, kidney, stomach and lung between 70 and
    100 h.

         Inskeep & Guengerich (1984) measured the rate of formation of
    1,2-dibromoethane adducts to calf thymus DNA  in vitro.  Adduct
    formation was dependent on the presence of both glutathione and
    glutathione- S-transferase.

    7.7  Carcinogenicity

         1,2-Dibromoethane has been tested for carcinogenicity by oral
    administration and inhalation in mice and rats, and by skin
    application in mice (IARC, 1987) (see Table 14).

         It has been shown to cause tumours in various organs, by several
    dosage routes and, in some cases, with a latency of less than
    12 months (Table 15).

         The following tumours have been observed:

    a)  By oral administration

         hepatocellular carcinomas and neoplastic nodules in female rats

         haemangiosarcomas in various circulatory system organs in male

         alveolar/bronchiolar adenomas in male and female mice

    b)  By inhalation exposure

         nasal cavity carcinomas and adenocarcinomas in male and female

         alveolar/bronchiolar carcinomas in female rats

         alveolar/bronchiolar carcinomas in male and female mice

         haemangiosarcomas in the circulatory system of male and female

         mesotheliomas in male rats

         mammary fibroadenomas in female mice

         subcutaneous fibrosarcomas in female mice

    c)  By skin administration

         skin papillomas and lung papillomas in female mice

    7.7.1  Administration by gavage  Mouse

         When technical grade 1,2-dibromoethane (99.1% pure) in corn oil
    was administered on 5 consecutive days per week by gavage to B6C3F1
    mice (groups of 50 males and 50 females in the treated groups, and 20
    of each sex in the untreated and vehicle control groups) at time-
    weighted average dose levels of 62 and 107 mg/kg per day, early
    development of squamous cell carcinomas of the forestomach was
    observed in both sexes.  The incidence of alveolar/bronchiolar
    adenomas was significantly higher in treated mice of both sexes than
    in controls (NCI, 1978).  Rat

         Osborne-Mendel rats (50 animals of each sex in the treated groups
    and 120 animals of each sex in the untreated and vehicle control
    groups) were given on 5 consecutive days per week, by gavage,
    technical grade 1,2-dibromoethane (99.1% pure) in corn oil at time-
    weighted average dose levels of 38 or 41 mg/kg per day for males, and
    37 or 39 mg/kg per day for females.  Squamous cell carcinomas of the
    forestomach were observed in more than half the male and female rats
    at both dose levels, while none were observed in controls.  The
    lesions, seen as early as week 12, were locally invasive and
    eventually metastasized.  Significantly higher incidences of
    hepatocellular carcinomas and haemangiosarcomas were observed in
    treated males and females, respectively (NCI, 1978).

         Ledda-Columbano et al. (1987b) examined the interaction of an
    intragastric dose of either 1,2-dibromoethane or carbon tetrachloride
    (CCl4) with diethylnitrosomine (DENA).  The administration of either
    1,2-dibromoethane or CCl4 resulted in similar increases in cell
    proliferation. However, while pretreatment with CCl4 caused an
    increase in the incidence of hepatic foci resulting from subsequent
    DENA administration, pretreatment with 1,2-dibromoethane did not. 
    This difference in the ability of the two compounds to act as a
    promoter was attributed to the nature of cell proliferation response. 
    The authors concluded that the cell proliferation induced by
    1,2-dibromoethane, unlike the compensatory cell proliferation induced
    by CCl4, is not an effective process for increasing the rate of
    tumour initiation.

    7.7.2  Administration in drinking-water  Mouse

         1,2-Dibromoethane (> 99% purity) and its metabolites,
    bromoethanol or bromoacetaldehyde, were administered to B6C3F1 mice
    (groups of 30 males and 30 females) at a concentration of 4 mmol/litre
    in distilled drinking-water (equivalent to 116 mg/kg body weight for
    males and 103 mg/kg body weight for females), for 450 days in the case
    of 1,2-dibromoethane and for 560 days in the case of the metabolites. 
    A control group (60 males and 60 females) was given distilled
    drinking-water.  1,2-Dibromoethane induced squamous cell carcinomas of
    the forestomach in 26/30 males and 27/30 females, and squamous cell
    papillomas of the oesophagus in 3/30 females.  Bromoethanol in
    drinking-water at a concentration of 4 mmol/litre (equivalent to
    76 mg/kg body weight for males and 71 mg/kg body weight for females)
    induced squamous cell papillomas of the forestomach in 9/29 males and
    10/29 females, but bromoacetaldehyde at the same concentration
    (equivalent to 62 mg/kg body weight for females and 62 mg/kg body
    weight for males) did not induce a significant incidence of
    forestomach tumours.  The incidence of tumours in the control group

    was not significant.  Bromoethanol and bromoacetaldehyde were not
    considered likely to be active intermediates of 1,2-dibromoethane
    carcinogenicity (Van Duuren et al., 1985).

    7.7.3  Inhalation  Mouse

         Groups of 50 male and 50 female B6C3F1 mice were exposed in
    inhalation chambers to air containing 77 or 308 mg/m3 (10 or 40 ppm)
    of 1,2-dibromoethane (99.3-99.4% pure) for 78-106 weeks.  The
    incidences of alveolar/bronchiolar carcinomas and alveolar/bronchiolar
    adenomas were significantly higher in exposed male and female mice
    than in controls.  Haemangiosarcomas of the circulatory system,
    fibrosarcomas in subcutaneous tissue, carcinomas of the nasal cavity,
    and adenocarcinomas of the mammary gland were significantly increased
    in females.  Exposure to 1,2-dibromoethane was also associated with
    epithelial hyperplasia of the respiratory system (NTP, 1982).  Rat

         Groups of 50 male and 50 female F-344 rats were exposed in
    inhalation chambers to air containing 77 or 308 mg/m3 (10 or 40 ppm)
    of 1,2-dibromoethane (99.3-99.4%) for 88-106 weeks.  Carcinomas,
    adenocarcinomas and adenomas of the nasal cavity, and
    haemangiosarcomas of the circulatory system were significantly
    increased in exposed male and female rats.  The incidences of
    mesotheliomas of the tunica vaginalis and adenomatous polyps of the
    nasal cavity in males, and of fibroadenomas of the mammary gland and
    alveolar/bronchiolar adenomas and carcinomas (combined) in females
    were significantly increased (NTP, 1982).

         Wong et al. (1982) reported that the coadministration of dietary
    disulfiram increases the rate of tumour incidence in rats exposed to
    1,2-dibromoethane (153.6 mg/m3, 20 ppm) by inhalation. There is
    evidence to suggest that the synergistic effect of disulfiram may be
    the result of increased liver glutathione- S-transferase activity in
    animals treated with this drug (Elliot & Ashby, 1980).

    7.7.4  Dermal application  Mouse

         Doses (25 mg or 50 mg) of 1,2-dibromoethane (> 99% pure)
    dissolved in 0.2 ml acetone were applied 3 times/week to the shaved
    dorsal skin of female Ha:ICR Swiss mice (groups of 30 animals).  There
    were an acetone only and untreated control groups.  The times to first
    appearance of skin tumour (papilloma) were 434 days for the 25-mg
    group and 395 days for 50-mg group.  By comparison with controls, both
    groups showed a statistically significant increase in skin papillomas,
    and in the 50-mg group there was also a significant increase in lung

    papillomas.  Both groups also had dermal squamous carcinomas and
    stomach, tumours but these were not statistically significant (Van
    Duuren et al., 1979).

    7.7.5  Cell transformation

         1,2-Dibromoethane caused transformation of BALB/C 3T3 cells both
    in the presence and absence of an exogenous metabolism system (Perocco
    et al., 1991).

    7.8  Biochemical studies and species specificity

         1,2-Dibromoethane (75-100 mg/kg body weight) given by gavage to
    non-fasted Wistar rats induced DNA synthesis and cell  division in the
    liver.  The peak of DNA synthesis, as measured by 3H-methyl
    thymidine incorporation, was attained at or shortly after 24 h.  The
    mitotic waves measured with the aid of colchicine occurred at 24-30 h
    and 48 to 54 h after 1,2-dibromoethane treatment.  Increase in DNA
    synthesis was confirmed by autoradiography.  The stimulation of liver
    cell mitosis occurred in non-fasted animals without any apparent cell
    necrosis.  1,2-Dibromoethane was an effective mitogen for liver under
    these experimental conditions (Nachtomi & Farber, 1978).

         In a study by Ledda-Columbano et al. (1987a) 1,2-dibromoethane in
    corn oil was administered by gavage at a dose of 100 mg/kg body weight
    to male Wistar rats (weight 250-280 g).  The rats were given an
    intraperitoneal injection of 3H-thymidine 1 h prior to sacrifice,
    10, 20, 30, 36 and 48 h after the treatment.  No mortality
    attributable to 1,2-dibromoethane was observed in the treated rats. 
    The body weights of 1,2-dibromoethane-treated rats were similar to
    those of controls.  No changes in the specific activity of DNA were
    observed in kidney 10 h after treatment.  There was an increase in
    labelled thymidine incorporation into DNA and this was maximal after
    20-30 h.  At 48 h the extent of incorporation of labelled thymidine
    decreased rapidly even though it was still higher than in controls. 
    When effects on the kidneys were investigated, mitotic activity was
    noted predominantly in the proximal tubular epithelium of the renal
    cortex.  Histological examination of the kidney did not reveal any
    signs of necrosis.

         Of possible significance for the prediction of species
    differences in response to 1,2-dibromoethane are the observations
    (Dibiasio et al., 1991) that hepatic cytosolic glutathione-
     S-transferase activities are similar in rats and mice, but about 40%
    of these values in rhesus monkeys.  In addition, cytosolic
    glutathione- S-transferase activities in rhesus monkey and human
    testis are only about 5% of the activities in rat and mouse testes.


    8.1  Acute toxicity

         1,2-Dibromoethane is strongly irritant to the eyes, skin, and
    respiratory tract (Peoples et al., 1978; Letz et al., 1984).  Deaths
    from acute exposure to high concentrations of 1,2-dibromoethane are
    usually due to pneumonia following damage to the lungs.  In addition,
    acute inhalation exposure may lead to liver and kidney damage.

         Six people who attempted suicide by ingesting 1,2-dibromoethane
    suffered from vomiting, nausea and burning throat; death followed in
    two cases.  The characteristic pathological lesions were present in
    liver, lungs and kidneys.  Intense jaundice was observed and was due
    to massive necrosis of the liver (Sarawat et al., 1986).

         It is estimated that 200 mg/kg is lethal to humans, based on the
    observation that 12 g caused the death of a woman weighing about 60 kg
    (Alexeef et al., 1990).

    8.2  Occupational exposure

         In cases of poisoning following occupational exposure, headache,
    severe vomiting, diarrhoea, respiratory tract irritation and death
    have been reported.  Exposure to 1,2-dibromoethane in air at
    concentrations above 384 mg/m3 (50 ppm) caused nasal and throat
    irritation.  Two deaths were reported after exposure by inhalation to
    a mean concentration of 215 mg/m3 (28 ppm) for 30 and 45 min,
    respectively, during the cleaning of a storage tank containing
    residues of 1,2-dibromoethane (Letz et al., 1984, Jacobs, 1985). 
    There was also absorption from dermal exposure to the 0.1-0.3%
    solution in the tank (Letz et al., 1984).  The first worker collapsed
    while working inside the tank and died 12 h later with metabolic
    acidosis, depression of the CNS, and laboratory evidence of liver
    damage.  A supervisor attempting to rescue the worker also collapsed
    inside the tank and died 64 h later with intractable metabolic
    acidosis, hepatic and renal failure, and necrosis of skeletal muscle
    and other organs.  Coughing, vomiting, diarrhoea, eye, skin and
    respiratory irritation, coma, metabolic acidosis, delirium, confusion,
    nausea,  low urine output, renal failure, tachycardia and asystole
    were noted.  Autopsy revealed pulmonary oedema, liver damage and
    extensive autolysis in the kidney.

         Inhalation exposure to concentrations over 154 mg/m3 (20 ppm)
    for more than 30 min is considered fatal to humans.

    8.2.1  Cancer incidence

         Mortality in employees exposed to 1,2-dibromoethane in two
    production units operated from 1942 to 1969 and from the mid-1920s to
    1976 was investigated (Ott et al., 1980).  The study population was

    161 employees.  In the first production unit two deaths from malignant
    neoplasms were observed against 3.6 expected, and in the second unit,
    where there was potential exposure to various organic bromide
    products, there were five deaths from malignant neoplasms against
    2.2 expected (p < 0.072).  However, no statistically significant
    increase in total deaths or malignant neoplasms relatives to duration
    of exposure was observed.

         Epidemiological studies of four worker populations did not show
    any increase in cancer that could be attributed to 1,2-dibromoethane
    (Ter Haar, 1980)

    8.2.2  Reproductive effects

         In an investigation of possible sterility from exposure to
    1,2-dibromoethane, sperm levels in workers exposed to
    1,2-dibromoethane were not affected, and there was no evidence of
    effects on offspring (Ter Haar, 1980).

         Ratcliffe et al. (1987) and Schrader et al. (1987) conducted a
    cross-sectional study of semen quality in 46 men employed in the
    papaya fumigation industry in Hawaii, with an average duration of
    exposure of 5 years and a geometric mean breathing zone exposure to
    airborne 1,2-dibromoethane of 0.68 mg/m3 (88 ppb) (8-h time-weighted
    average).  The control group consisted of 43 unexposed men from a
    nearby sugar refinery.  Statistically significant decreases in sperm
    count per ejaculate and percentage of viable and motile sperm,
    together with increases in the proportion of sperm with specific
    morphological abnormalities, were observed among exposed men, compared
    to controls, after consideration of smoking, caffeine and alcohol
    consumption, subject's age, abstinence, history of urogenital
    disorders, and other potentially confounding variables.  The data
    indicated that 1,2-dibromoethane could cause reproductive inpairment
    in males exposed to this concentration.  Schrader et al. (1988)
    conducted a short-term longitudinal study on the effect of
    1,2-dibromoethane exposure on male reproductive potential in ten
    forestry workers and six unexposed men in Colorado.  The time-weighted
    average inhalation exposure over 6 weeks was 0.46 mg/m3 (peak
    exposure of 16 mg/m3) and there was extensive skin exposure.  Sperm
    velocity and semen volume were decreased significantly in the exposed
    workers.  Both studies suggested that 1,2-dibromoethane has multiple
    sites of action on male accessory sex glands and testes.

         In five studies on the reproductive effects of occupational
    exposure to 1,2-dibromoethane, four showed potential reproductive
    impairment but this was not large enough to be statistically
    significant.  The power of all of the studies was low and they were
    considered inconclusive for assessing reproductive risk (Dobbins,

         A retrospective study of four plants in the United Kingdom where
    male workers were exposed to 1,2-dibromoethane revealed statistically
    marginally reduced fertility rates (i.e., live births to their wives). 
    The average exposure was probably below 38.5 mg/m3 (5 ppm), although
    actual concentrations were not measured (Wong et al., 1985).


    9.1  Aquatic organisms

    9.1.1  Invertebrates

         Nishiuchi (1980, 1981) studied the acute toxicity of
    1,2-dibromoethane in aquatic larvae of insects and aquatic
    invertebrates, such as a mayfly  (Cloeon dipterum), two dragonflies
     (Sympetrum frequens and  Orthetrum albistylum speciosum), a
    Japanese diving beetle  (Eretes sticticus) and a water boatman
     (Micronecta sedula) (Table 17).  The toxicity threshold (48-h LC50
    values) of 1,2-dibromoethane machine oil formulation for the above
    aquatic invertebrates and that of 1,2-dibromoethane for mayfly were
    greater than 40 mg/m3.  In mayfly the reported 48-h toxicity
    thresholds for two mixed formulations, which consisted of
    1,2-dibromoethane, malathion, diazinon and machine oil (3:1:1:80), and
    1,2-dibromoethane, diazinon and  O-sec-butylphenyl methylcarbamate
    (25:5:3) were 28 and 65 mg/m3, respectively (Nishiuchi & Asano,
    1979).  There was no apparent difference in toxicity of technical
    1,2-dibromoethane and an oil-based formulation at least up to
    40 mg/litre.

        Table 17.  Acute toxicity of 1,2-dibromoethane to aquatic
               invertebrates (From: Nishiuchi, 1980)
    Species                  Test material              Temperature   48-h LC50

    Mayfly                   Technical material             25          > 40
     (Cloeon dipterum)       (in acetone)

    Dragonfly                1,2-dibromoethane (oil)        25          > 40
     (Sympetrum frequens)

    Dragonfly                1,2-dibromoethane (oil)        25          > 40
     (Orthetrum albistylum

    Japanese diving beetle   1,2-dibromoethane (oil)        25          > 40
     (Eretes sticticus)

    Water boatman            1,2-dibromoethane (oil)        25          > 40
     (Micronecta sedula)
         Herring et al. (1988) evaluated the toxicity of 1,2-dibromoethane
    to  Hydra oligactis in a series of three experiments.  Study 1
    evaluated lethality, feeding behaviour and mobility in a series of
    concentrations ranging from 7.5 to 75 mg/litre.  In Study 2, adult
     Hydra were pre-treated for 14 days with a sublethal dose of
    1,2-dibromoethane (5 mg/litre) prior to exposure to a range of
    1,2-dibromoethane concentrations (25-300 mg/litre) for a total of
    72 h.  In the third study, the F1 offspring of pre-treated adult
     Hydra were also exposed to a series of 1,2-dibromoethane
    concentrations.  The 48-h LC50 for  Hydra was determined to be
    70 mg/litre.  When adult  Hydra were pre-treated with sublethal
    concentrations of 1,2-dibromoethane, the 48-h LC50 was increased to
    200 mg/litre.  Furthermore, the F1 offspring of pre-treated adult
    exhibited mortalities of only 10% and 20%, respectively, after 24-h
    and 48-h exposures to 200 mg 1,2-dibromoethane/litre.  These results
    suggest that  Hydra and first-generation offspring are capable of
    developing tolerance to 1,2-dibromoethane.

         Adams & Kennedy (1992) exposed first-stage budding  Hydra
     oligactis to 1,2-dibromoethane at 5 mg/litre.  The 1,2-dibromoethane
    was dissolved using acetone at 15 mg/litre, and an acetone control was
    used.  Exposure was for 24, 48 or 72 h.  Following exposure, the
    animals were washed several times with the medium, sectioned through
    the gastric region, and the base/apical sections were grafted. 
    Regeneration was significantly affected by all exposures to
    1,2-dibromoethane but not by acetone.  The severity of the effect
    increased with increasing exposure.

         Adams et al. (1989) reported dose-sensitive relationships for the
    loss and recovery of locomotor response, chromatophore expansion and
    lethality in three species of laboratory-reared octopus.  Three
    species of octopus  (Octopus bimaculoides, O. joubini, and  O. maya)
    were exposed to 25, 50, 75 and 100 mg 1,2-dibromoethane/litre for
    either one hour, followed by transfer to chemical-free water, or
    continuously for a period of 72 h.  Generally, responses by the
    octopuses were evident after only 1 min of exposure.  Chromatophore
    expansion and loss of locomotor response occurred at 25 mg/litre after
    30 min, but recovery was noted 6 h after transfer to chemical-free
    water.  Lethality occurred in all three species at 25 mg/litre after
    48 h of exposure.   O. maya was the most sensitive species,
    exhibiting 100% mortality after 3 h of exposure.  The acute LC50
    values for  O. bimaculoides, O. joubini and  O. maya were 42.7, 35.3
    and 30.6 mg/litre respectively (Table 18).  Although the authors
    reported a chronic LC50 of 100 mg/litre occurring within 12 h, the
    Task Group considered this to be an acute exposure.

    Table 18.  Acute LC50 values approximated for lethality data
               (Adams et al., 1989) using either the moving average,
               binomial or probit methods

    Test species             Estimated 48-h LC50      95% confidence
                                  (mg/litre)              limits

    Octopus bimaculoides          42.7                   28.1-58.8a

    Octopus joubini               35.3                       -b

    Octopus maya                  30.6                   0-52.02c

    a  moving average method
    b  confidence limits exceeded 95%, therefore the limits would
       range from 0 to infinity
    c  probit method used

    9.1.2  Fish

         There are few data for the acute toxicity of 1,2-dibromoethane in
    fish.  A study of the effect of pH on the acute toxicity of
    1,2-dibromoethane in killifish  (Oryzias latipes) was carried out in
    open static systems.  Altering the pH of the breeding water between pH
    5.0 and pH 10.0 had no effect on 48-h LC50 values (Nishiuchi, 1982). 
    Goldfish quickly absorbed 1,2-dibromoethane from water (at 1 mg/litre)
    and quickly eliminated it.  The concentration in the goldfish
    (1.75 ± 0.041 mg/kg) was in equilibrium with the concentration in the
    water 1.5 h after the initiation of exposure.  From the results of the
    elimination study, the biological half-life was calculated to be less
    than 30 min (Ogino, 1978).

         Landau & Tucker (1984) found the 48-h LC50 values for
    sheepshead minnow  Cyprinodon variegautus and snook  Centropomus
     undecimatis, both estuarine fish, to be 4.8 and 6.2 mg/litre,

         Nishiuchi & Asano (1979) measured toxicity thresholds for carp
     (Cyprinus carpio) exposed to pesticide mixtures containing various
    concentrations of 1,2-dibromoethane (Table 19).  After 24 h of
    exposure at 24°C, no difference in the toxicity threshold (> 40)
    could be detected at unit pH increases between 5 and 9.

    Table 19.  Toxicity threshold after 48 h exposure of Cyprinus carpio
               to mixtures containing 1,2-dibromoethane at 25°C
               (Nishiuchi & Asano, 1979)

    Mixture constituents          Concentrations       Toxicity threshold

    1,2-Dibromoethane             2.5% oil                 > 100
    Fenitrothion                  0.5% oil

    1,2-Dibromoethane             2.5% oil                    86
    Fenitrothion                  0.5% oil

    1,2-Dibromoethane             1.5% emulsion
    Fenitrothion                  10% emulsion                45
    Carbaryl                      5% emulsion

    Diazinon                      20% emulsion                28
    1,2-Dibromoethane             10% emulsion

    Cyanophos                     10% emulsion                32
    1,2-Dibromoethane             10% emulsion

    1,2-Dibromoethane             25% oil
    Diazinon                      5% oil                      65

    O-sec-butylphenyl             3% oil

    9.2  Terrestrial biota

         Data on the effects of 1,2-dibromoethane on terrestrial biota
    (other than mammals) are limited.  In a study on the effects of
    different foods on the susceptibility of the adzuki bean weevil
     (Callosobruchus chinensis Linn.) to 1,2-dibromoethane, the 24-h
    LC50 at 29°C was 4.40, 7.232, 6.130, 5.249 and 4.951 mg/litre for
    chickpea, pea, green gram, black gram, and pigeon pea, respectively
    (Mundhe & Pandey, 1980).

         Exposure of the nematode  Aphelenchus avenae to low
    concentrations of 1,2-dibromoethane resulted in a very small
    conversion of the halide just before death.  A study with
    14C-labelled 1,2-dibromoethane showed that two primary products were
    ethylene (5%) and  O-acetylserine (> 95%).  These transformations
    were indicative of two primary modes of intoxication of the nematodes,
    postulated to be a direct reaction of 1,2-dibromoethane with an iron
    centre in the respiratory sequence and the substitution of a serine at
    the active site of an esterase or protease (Castro & Belser, 1978).

    9.3  Microorganisms

         The toxicity of 1,2-dibromoethane to microsclerotia of
     Verticillium dahliae in air and in soil was determined in a sealed
    container.  At concentrations of 470 mg/litre in air or 12.5 mg/kg in
    soil, 1,2-dibromoethane killed 97% of the microsclerotia, after
    incubation for 16 days in both cases. The toxicity of
    1,2-dibromoethane increased with increasing temperature and with
    increase in soil moisture (0-80%) (Ben-Yephet et al., 1981).

         Pignatello (1986) investigated 1,2-dibromoethane effects on
    microorganisms from two soils/sediments taken from a
    1,2-dibromoethane-contaminated groundwater discharge area.  Labelled
    potassium acetate was added to slurries of soil, which had been shaken
    with added 1,2-dibromoethane (up to 1000 mg/litre), for 3 or 12 h. 
    Incorporation of acetate into microbial lipids was used as the
    end-point.  The EC50 for inhibition of acetate incorporation
    following 12-h incubation with 1,2-dibromoethane was 50 and
    100 mg/litre for the two soils; soil 1 showed an EC50 of 100
    following 3 h of incubation.  Both soils showed "slight" inhibition at
    10 mg 1,2-dibromoethane/litre and > 94% at 1000 mg/litre.  Soil 1 was
    a muddy soil with a total organic carbon (TOC) content of 14%, whereas
    soil 2 was a stream-bed soil with a TOC of 0.24%.

    9.4  Plants

         1,2-Dibromoethane was phytotoxic to fruit after they had been
    fumigated against several species of fruit flies.  Fumigation with
    1,2-dibromoethane at a concentration of 4 g/m3 stimulated fruit
    respiration and ethylene evolution.  A higher concentration
    (32 g/m3) increased respiration rate and ethylene evolution in the
    fruits and increased tissue leakage.  Fruits stored at 1°C after
    fumigation with 32 g/m3 suffered more severe damage than those
    stored at 20°C.  Storage at 1°C abolished the increases in gas
    exchange observed in fumigated fruits at 20°C.  The injurious effect
    of cooling might be ascribed to a higher residue of unchanged fumigant
    persisting in the cooled fruits or to a decreased capacity of the
    fruits to repair cellular damage at low temperatures (Wade & Rigney,


    10.1  Evaluation of human health risks

         1,2-Dibromoethane is carcinogenic for rats and mice causing
    tumours (adenomas and carcinomas) in a variety of organs including the
    nasal cavity, lung, stomach, liver, skin, and mammary gland, as well
    as haemangiosarcomas.  In many cases, a reduced latency period for
    developing tumours was observed.  1,2-Dibromoethane has been shown to
    be mutagenic in various  in vivo and  in vitro assays and to cause
    single-strand DNA breaks  in vitro.  Some metabolites have been shown
    to covalently bind to DNA.  Based on these data, 1,2-dibromoethane is
    thought to be a genotoxic carcinogen to rodents.  Although adequate
    studies in humans are not available, the extensive evidence for
    carcino  genicity in animal studies indicates that 1,2-dibromoethane
    is a potential human carcinogen.

    10.2  Evaluation of effects on the environment

         The high volatility of 1,2-dibromoethane makes the atmosphere the
    predominant environmental sink.  Consequently, measured concentrations
    in surface waters are low (< 0.2 µg/litre).  Air concentrations of
    < 0.2 µg/litre have been measured in cities, while concentrations of
    up to 90 µg/litre in irrigation wells reflect the mobility of the
    compound in soil.  Persistent contamination of irrigation wells may
    result from the slow release of 1,2-dibromoethane from the soil matrix
    many years after its use as a soil fumigant.

         There is a lack of information on the degradation of
    1,2-dibromoethane in the aquatic and soil environments.

         Stratospheric photodegradation occurs and potentially leads to
    breakdown products with ozone-depleting capacity.  However,
    1,2-dibromoethane is not listed in the Montreal Convention.

         Few aquatic ecotoxicity tests have been conducted with
    1,2-dibromoethane.  Those reported show LC50s greater than
    5 mg/litre.  There is a difference of at least 4 orders of magnitude
    between measured water concentrations and these toxic concentrations,
    indicating that 1,2-dibromoethane poses no risk to aquatic organisms.


         Considering the toxicological characteristics of
    1,2-dibromoethane, both qualitatively and quantitatively, it was
    concluded that an exposure that would not cause adverse effects in
    humans after any route of exposure could not be estimated. 
    Consequently, all appropriate measures should be taken to eliminate or
    minimize human exposure to 1,2-dibromoethane.


         Further information from epidemiology studies on
    1,2-dibromoethane would be useful.


         IARC (1977, 1982, 1987) concluded, from biological data relevant
    to the  evaluation of carcinogenic risk, that 1,2-dibromoethane is
    carcinogenic in mice and rats after oral administration, and by
    inhalation, producing squamous cell carcinomas of the forestomach.
    1,2-Dibromoethane given orally or by intraperitoneal injection did not
    produce dominant lethal mutations in mice.  Prolonged contact with
    1,2-dibromoethane causes skin irritation.  However, no case reports or
    epidemiological studies were available to the Working Group.  IARC has
    classified 1,2-dibromoethane as a Group 2A carcinogen (probably
    carcinogenic to humans).

         WHO has not established a drinking-water quality guideline for
    1,2-dibromoethane.  This is because 1,2-dibromoethane appears to be a
    genotoxic carcinogen and the studies are inadequate for mathematical
    extrapolation (WHO, 1993).

         1,2-Dibromoethane was evaluated by the Joint FAO/WHO Expert
    Committee on Pesticide Residues in 1965 (FAO/WHO, 1965) and 1966
    (FAO/WHO, 1967).  The 1965 evaluation concluded that 1,2-dibromoethane
    should be used for fumigation of food only on the condition that no
    residue of the unchanged compound reached the consumer.  In the 1966
    evaluation an Acceptable Daily Intake (ADI) of 1 mg/kg body weight as
    bromide was established.  In 1991 the Codex Alimentarius Commission
    deleted the Guideline Levels for 1,2-dibromoethane in food commodities
    (FAO/WHO, 1992).


    Abdel-Kader MHK, Peach ME, & Stiles DA (1979) Determination of
    ethylene dibromide in fortified soils by molecular emission cavity
    analysis using a modified extraction process. J Assoc Off Anal Chem,
    62(1): 114-118.

    Adams JA & Kennedy AA (1992) Sublethal effects of ethylene dibromide
    on wound healing and morphogenesis in  Hydra oligactis. Arch Environ
    Contam Toxicol, 22: 272-277.

    Adams PM, Hanlon RT, & Forsythe JW (1989) Toxic exposure to ethylene
    dibromide and mercuric chloride: Effects on laboratory-reared
    octopuses. Neurotoxicol Teratol, 10: 519-523.

    Adkins B, Van Stee EW, Simmons JE, & Eustis SL (1986) Oncogenic
    response of strain A/J mice to inhaled chemicals. J Toxicol Environ
    Health, 17: 311-322.

    Alexeeff GV, Kilgore WW, & Li MY (1990) Ethylene dibromide: Toxicology
    and risk assessment. Berlin, Heidelberg, New York, Spinger Verlag
    Inc., pp 49-122.

    Alleman TG, Sanders RA, & Madison BL (1986) Simultaneous analysis of
    grain and grain-based products for ethylene dibromide, carbon
    tetrachloride, and ethylene dichloride. J Assoc Off Anal Chem,
    69(4): 575-580.

    Alper MD & Ames BN (1975) Positive selection of mutants with deletions
    of the gal-ch1 region of the salmonella chromosome as a screening
    procedure for mutagens that cause deletions. J Bacteriol,
    121(1): 259-266.

    Alumot E, Nachtomi E, Kempenich-Pinto O, Mandel E, & Schindler H
    (1968) The effect of ethylene dibromide in feed on the growth, sexual
    development and fertility of chickens. Poult Sci, 47: 1979-1985.

    Ames BN & Yanofsky C (1971) The detection of chemical mutagens with
    enteric bacteria. In: Hollaender A ed. Chemical mutagens: Principles
    and methods for their detection. New York, London, Plenum Press,
    vol 1, pp 267-282.

    Amin TA & Narang RS (1985) Determination of volatile organics in
    sediment at nanogram-per-gram concentrations by gas chromatography.
    Anal Chem, 57: 648-651.

    Amir D (1973) The sites of the spermicidal action of ethylene
    dibromide in bulls. J Reprod Fertil, 35: 519-525.

    Amir D (1975) Individual and age differences in the spermicidal effect
    of ethylene dibromide in bulls. J Reprod Fertil, 44: 561-565.

    Amir D & Volcani R (1965) Effect of dietary ethylene dibromide on bull
    semen. Nature (Lond), 206(4979): 99-100.

    Amir D, Esnault C, Nicolle JC, & Courot M (1977) DNA and protein
    changes in the spermatozoa of bulls treated orally with ethylene
    dibromide. J Reprod Fertil, 51: 453-456.

    Amir D, Nicolle JC, & Courot M (1979) Changes induced to bull
    spermatids and testicular spermatozoa by a single peritesticular
    injection of ethylene dibromide. Int J Androl, 2: 162-170.

    Asita AO, Hayashi M, Kodama Y, Matsuoka A, Suzuki T, & Sofuni T (1992)
    Micronucleated reticulocyte induction by ethylating agents in mice.
    Mutat Res, 271: 29-37.

    Ballering LAP, Nivard MJM, & Vogel EW (1993) Characterization of the
    genotoxic action of three structurally related 1,2-dihaloalkanes in
     Drosophila melanogaster. Mutat Res, 285: 209-217.

    Ballschmiter K, Mayer P, & Class Th (1986) Chemistry of organic traces
    in air. IV. Analysis of C1- and C2-halocarbons in ambient air by
    cold trap injection and wide bore glass capillary gas chromatography.
    Fresenius Z Anal Chem, 323: 334-339.

    Banerjee S, Van Duuren BL, & Kline SA (1979) Interaction of potential
    metabolites of the carcinogen ethylene dibromide with protein and DNA
     in vitro. Biochem Biophys Res Commun, 90(4): 1214-1220.

    Barber ED & Donish WH (1982) An exposure system for quantitative
    measurements of the microbial mutagenicity of volatile liquids.
    Measurements of microbial mutagenicity. In: Tice RR, Costa DL, &
    Schaich KM ed. Genotoxic effects of airborne agents. New York, London,
    Plenum Press, pp 3-18.

    Barber ED, Donish WH, & Mueller KR (1981) A procedure for the
    quantitative measurement of the mutagenicity of volatile liquids in
    the Ames Salmonella/microsome assay. Mutat Res, 90: 31-48.

    Barkley J, Bunch J, Bursey JT, Castillo N, Cooper SD, Davis JM,
    Erickson MD, Harris BSH III, Kirkpatrick M, Michael LC, Parks SP,
    Pellizzari ED, Ray M, Smith D, Tomer KB, Wagner R, & Zweidinger RA
    (1980) Gas chromatography mass spectrometry computer analysis of
    volatile halogenated hydrocarbons in man and his environment - a
    multimedia environmental study. Biomed Mass Spectrom, 7(4): 139-147.

    Barnett LB, Lovell DP, Felton CF, Gibson BJ, Cobb RR, Sharpe DS,
    Shelby MD, & Lewis SE (1992) Ethylene dibromide: Negative results with
    the mouse dominant lethal assay and the electrophoretic specific-locus
    test. Mutat Res, 282: 127-133. 

    Barry TL & Petzinger G (1985) GC/MS confirmation of ethylene dibromide
    residue in foods. J Food Saf, 7: 171-176.

    Beckman H, Crosby DG, Allen PT, & Mourer C (1967) The inorganic
    bromide content of foodstuffs due to soil treatment with fumigants.
    J Food Sci, 32: 138-140.

    Ben-Yephet Y, Letham D, & Evans G (1981) Toxicity of 1,2-dibromoethane
    and 1,3-dichloropropene to microsclerotia of  Verticillium dahliae.
    Pestic Sci, 12: 170-174.

    Berck B (1974) Fumigant residues of carbon tetrachloride, ethylene
    dichloride, and ethylene dibromide in wheat, flour, bran, middlings,
    and bread. J Agric Food Chem, 22(6): 977-984.

    Berg WW, Heidt LE, Pollock W, Sperry PD, & Cicerone RJ (1984)
    Brominated organic species in the arctic atmosphere. Geophys Res Lett,
    11(5): 429-432.

    Bielorai R & Alumot E (1975) The temperature effect on fumigant
    desorption from cereal grain. J Agric Food Chem, 23(3): 426-429.

    Bondi A, Olomucki E, & Calderon M (1955) Problems connected with
    ethylene dibromide fumigation of cereals. II. Feeding experiments with
    laying hens. J Sci Food Agric, 6: 600-602.

    Botti B, Moslen MT, Trieff NM, & Reynolds ES (1982) Transient decrease
    of liver cytosolic glutathione s-transferase activities in rats given
    1,2-dibromoethane or CCL. Chem-Biol Interact, 42: 259-270.

    Brandt I, Brittebo EB, Kowalski B, & Lund B-O (1987) Tissue binding
    of 1,2-dibromoethane in the cynomolgus monkey  (Macaca fascicularis).
    Carcinogenesis, 8(9): 1359-1361.

    Brem H, Stein AB, & Rosenkranz HS (1974) The mutagenicity and
    DNA-modifying effect of haloalkanes. Cancer Res, 34: 2576-2579.

    Brimer PA, Tan E-L, & Hsie AW (1982) Effect of metabolic activation on
    the cytotoxicity and mutagenicity of 1,2-dibromoethane in the
    CHO/HGPRT system. Mutat Res, 95: 377-388.

    Broda C, Nachtomi E, & Alumot E (1976) Differences in liver morphology
    between rats and chicks treated with ethylene dibromide. Gen
    Pharmacol, 7: 345-348.

    BUA (Society of German Chemists-Advisory Committee on Existing
    Chemicals of Environmental Relevance) (1987) [Methyl bromide.]
    Weinheim, VCH Publishers, 64 pp (BUA Report 14) (in German).

    BUA (Society of German Chemists-Advisory Committee on Existing
    Chemicals of Environmental Relevance) (1991) [1,2-Dibromoethane.]
    Weinheim, VCH Publishers, 290 pp (BUA Report 66) (in German).

    Buijs W, Van Der Gen A, Mohn GR, & Breimer DD (1984) The direct
    mutagenic activity of alpha,omega-dihalogenoalkanes in  Salmonella
     typhimurium. Mutat Res, 141: 11-14.

    Cairns T, Siegmund EG, Doose GM, Hundley HK, Barry T, & Petzinger G
    (1984) Confirmation of ethylene dibromide in fruits and grains by mass
    spectrometry. Anal Chem, 56: 2138-2141.

    Castro CE & Belser NO (1978) Intoxication of  Aphelenchus avenae by
    ethylene dibromide. Nematologica, 24: 37-44.

    Channarayappa, Ong T, & Nath J (1992) Cytogenetic effects of
    vincristine sulfate and ethylene dibromide in human peripheral
    lymphocytes: Micronucleus analysis. Environ Mol Mutagen, 20: 117-126.

    Chiarpotto E, Biasi F, Aragno M, Scavazza A, Danni O, Albano E, &
    Poli G (1993) Change of liver metabolism of 1,2-dibromoethane during
    simultaneous treatment with carbon tetrachloride. Cell Biochem Funct,
    11: 71-75.

    Clark AI, McIntyre AE, Lester JN, & Perry R (1982) Evaluation of a
    tenax GC sampling procedure for collection and analysis of vehicle-
    related aromatic and halogenated hydrocarbons in ambient air.
    J Chromatogr, 252: 147-157.

    Clark AI, McIntyre AE, Lester JN, & Perry R (1984a) Ambient air
    measurements of aromatic and halogenated hydrocarbons at urban, rural
    and motorway locations. Sci Total Environ, 39: 265-279.

    Clark AI, McIntyre AE, Perry R, & Lester JN (1984b) Monitoring and
    assessment of ambient atmospheric concentrations of aromatic and
    halogenated hydrocarbons at urban, rural and motorway locations.
    Environ Pollut, B7: 141-158.

    Clive D, Johnson KO, Spector JFS, Batson AG, & Brown MMM (1979)
    Validation and characterization of the L5178Y/TK+/-mouse lymphoma
    mutagen assay system. Mutat Res, 59: 61-108.

    Clower M (1980) Modification of the AOAC method for determination of
    fumigants in wheat. J Assoc Off Anal Chem, 63(3): 539-545.

    Clower M, McCarthy JP, & Carson LJ (1986) Comparison of methodology
    for determination of ethylene dibromide in grains and grain-based
    foods. J Assoc Off Anal Chem, 69(1): 87-90.

    Cmarik JL, Inskeep PB, Meredith MJ, Meyer DJ, Ketterer B, & Guengerich
    FP (1990) Selectivity of rat and human glutathione S-transferases in
    activation of ethylene dibromide by glutathione conjugation and DNA
    binding and induction of unscheduled DNA synthesis in human
    hepatocytes. Cancer Res, 50(9): 2747-2752.

    Cmarik JL, Humphreys WG, Bruner KL, Lloyd RS, Tibbetts C, & Guengerich
    FP (1992) Mutation spectrum and sequence alkylation selectivity
    resulting from modification of bacteriophage M13mp18 DNA with
    s-(2-chloroethyl)glutathione. Evidence for a role of s-[2-(N-guanyl)
    ethyl]glutathione as a mutagenic lesion formed from ethylene
    dibromide. J Biol Chem, 267(10): 6672-6679.

    Collins M & Barker NJ (1983) Direct monitoring of ambient air for
    ethylene oxide and ethylene dibromide. Am Lab (Fairfield, Conn),
    15: 72, 74-76, 78-81.

    Coni P, Simbula G, De Prati AC, Menegazzi M, Suzuki H, Sarma DSR,
    Ledda-Columbano GM, & Columbano A (1993) Differences in the
    steady-state levels of c-fos, c-jun and c-myc messenger RNA during
    mitogen-induced liver growth and compensatory regeneration.
    Hepatology, 17: 1109-1116.

    Courtens JL, Amir D, & Durand J (1980) Abnormal spermiogenesis in
    bulls treated with ethylene dibromide: An ultrastructural and
    ultracytochemical study. J Ultrastruct Res, 71: 103-115.

    Crebelli R, Conti G, Conti L, & Carere A (1984) Induction of somatic
    segregation by halogenated aliphatic hydrocarbons in  Aspergillus
     nidulans. Mutat Res, 138: 33-38.

    Crespi CL, Seixas GM, Turner TR, Ryan CG, & Penman BW (1985)
    Mutagenicity of 1,2-dichloroethane and 1,2-dibromoethane in two human
    lymphoblastoid cell lines. Mutat Res, 142: 133-140.

    Daft JL (1983) Gas chromatographic determination of fumigant residues
    in stored grains, using isooctane partitioning and dual column
    packings. J Assoc Off Anal Chem, 66(2): 228-233.

    Daft JL (1985) Preparation and use of mixed fumigant standards for
    multiresidue level determination by gas chromatography. J Agric Food
    Chem, 33: 563-566.

    Daft JL (1987) Determining multifumigants in whole grains and legumes,
    milled and low-fat grain products, spices, citrus fruit, and
    beverages. J Assoc Off Anal Chem, 70(4): 734-760.

    Daft JL (1988) Rapid determination of fumigant and industrial chemical
    residues in food. J Assoc Off Anal Chem, 71(4): 748-760.

    De Serres FJ & Malling HV (1983) The role of  Neurospora in
    evaluating environmental chemicals for mutagenic activity. Ann NY Acad
    Sci, 407: 177-185.

    De Vries JW, Larson PA, Bowers RH, Keating AM, Broge JM, Wehling PS,
    Patel HH, & Zurawski JW (1985) Improved codistillation method for
    determination of carbon tetrachloride, ethylene dichloride and
    ethylene dibromide in grain and grain-based products. J Assoc Off Anal
    Chem, 68(4): 759-762.

    Dibiasio KW, Silva MH, Shull LR, Overstreet JW, Hammock BD, & Miller
    MG (1991) Xenobiotic metabolizing enzyme activities in rat, mouse,
    monkey, and human testes. Drug Metab Dispos, 19(1): 227-232.

    Dobbins JG (1987) Regulation and the use of "Negative" results from
    human reproductive studies: The case of ethylene dibromide. Am J Ind
    Med, 12: 33-45.

    Dumas T & Bond EJ (1982) Microdetermination of ethylene dibromide in
    air by gas chromatography. J Assoc Off Anal Chem, 65(6): 1379-1381.

    Dunkel VC, Zeiger E, Brusick D, McCoy E, McGregor D, Mortelmans K,
    Rosenkranz HS, & Simmon VF (1985) Reproducibility of microbial
    mutagenicity assays: Testing of carcinogens and noncarcinogens in
     Salmonella typhimurium and  Escherichia coli. Environ Mutagen,
    7(5): 1-248.

    Edwards K, Jackson H, & Jones AR (1970) Studies with alkylating
    esters-II: A chemical interpretation through metabolic studies of the
    antifertility effects of ethylene dimethanesulphonate and ethylene
    dibromide. Biochem Pharmacol, 19: 1783-1789.

    Ehrenberg L, Osterman-Golkar S, Singh D, & Lundqvist U (1974) On the
    reaction kinetics and mutagenic activity of methylating and
    beta-halogenoethylating gasoline additives. Radiat Bot, 15: 185-194.

    ElJack AH & Hrudka F (1979) Pattern and dynamics of teratospermia
    induced in rams by parenteral treatment with ethylene dibromide.
    J Ultrastruct Res, 67: 124-134.

    Ellingham TJ, Christensen EA, & Maddock MB (1986)  In vitro induction
    of sister chromatid exchanges and chromosomal aberrations in
    peripheral lymphocytes of the oyster toadfish and American eel.
    Environ Mutagen, 8: 555-569.

    Elliott BM & Ashby J (1980) Ethylene dibromide and disulfiram: Studies
     in vivo and  in vitro on the mechanism of the observed synergistic
    carcinogenic response. Carcinogenesis, 1(12): 1049-1057.

    Entz RC & Hollifield HC (1982) Headspace gas chromatographic analysis
    of foods for volatile halocarbons. J Agric Food Chem, 30: 84-88.

    Environment Agency Japan (1985) Chemicals in the environment: Annual
    report - Annex. Tokyo, Environment Agency, pp 16-28.

    Environment Canada (1994) Summary of EDB concentration at Canadian
    sites. Ottawa, Environment Canada, Environment Protection Service,
    Pollution Measurement Division (Unpublished report).

    Epstein SS, Arnold E, Andrea J, Bass W, & Bishop Y (1972) Detection of
    chemical mutagens by the dominant lethal assay in the mouse. Toxicol
    Appl Pharmacol, 23: 288-325.

    Fahrig R (1974) Comparative mutagenicity studies with pesticides.
    In: Chemical carcinogenesis essays. Lyon, International Agency for
    Research on Cancer, pp 161-181 (IARC Scientific Publications No. 10).

    Fanini D, Legator MS, & Adams PM (1984) Effects of paternal ethylene
    dibromide exposure on F1 generation behavior in the rat. Mutat Res,
    139: 133-138.

    FAO/WHO (1965) Evaluation of the hazards to consumers resulting from
    the use of fumigants in the protection of food. Report of the 2nd
    Meeting of the FAO/WHO Joint Expert Committee on Pesticide Residues.
    Rome, Food and Agriculture Organization of the United Nations,
    pp 36-42 (FAO Meeting Report No. PL/1965/10/2).

    FAO/WHO (1967) Pesticide residues in food. Joint report of the FAO
    Working Party on Pesticide Residues and the WHO Expert Committee on
    Pesticide Residues. Geneva, World Health Organization, 19 pp (WHO
    Technical Report Series 370).

    FAO/WHO (1972) 1971 Evaluations of some pesticide residues in food.
    Geneva, World Health Organization, p 267 (WHO Pesticide Residues
    Series, No. 1).

    FAO/WHO (1992) Report of the Twenty-Fourth Session of the Codex
    Committee on Pesticide Residues. Rome, Food and Agriculture
    Organization of the United Nations, Codex Alimentarius Commission,
    82 pp (Alinorm 93/24).

    Fernandez M, L'Haridon J, Gauthier L, & Zoll-Moreux C (1993) Amphibian
    micronucleus test(s): A simple and reliable method for evaluating
     in vivo genotoxic effects of freshwater pollutants and radiations.
    Initial assessment. Mutat Res, 292: 83-99.

    Ferreri AM, Rocchi P, Capucci A, & Prodi G (1983) Induction of
    diphtheria toxin-resistant mutants in human cells by halogenated
    compounds. J Cancer Res Clin Oncol, 105: 111-112.

    Foster PL, Wilkinson WG, Miller JK, Sullivan AD, & Barnes WM (1988) An
    analysis of the mutagenicity of 1,2-dibromoethane to  Escherichia
     coli: influence of DNA repair activities and metabolic pathways.
    Mutat Res, 194: 171-181.

    Gilbert J, Startin JR, & Grew C (1985) Automated headspace GC-MS
    analysis of ethylene dibromide fumigant residues in fresh fruits. Food
    Addit Contam, 2(1): 55-61.

    Going JE & Long S (1975) Sampling and analysis of selected toxic
    substances: Task II - Ethylene dibromide. Washington, DC, US
    Environmental Protection Agency, Office of Toxic Substances

    Going JE & Spigarelli JE (1976) Sampling and analysis of selected
    toxic substances: Task IV - Ethylene dibromide. Washington, DC, US
    Environmental Protection Agency, Office of Toxic Substances

    Graf U, Wurgler FE, Katz AJ, Frei H, Juon H, Hall CB, & Kale PG (1984)
    Somatic mutation and recombination test in  Drosophila melanogaster.
    Environ Mutagen, 6: 153-188.

    Guha SN, Schoneich C, & Asmus KD (1993) Free radical reductive
    degradation of  vic-dibromoalkanes and reaction of bromine atoms with
    polyunsaturated fatty acids: possible involvement of Br* in the
    1,2-dibromoethane-induced lipid peroxidation. Arch Biochem Biophys,
    305(1): 132-140.

    Guobaitis RJ, Ellingham TJ, & Maddock MB (1986) The effects of
    pretreatment with cytochrome P-450 inducers and preincubation with a
    cytochrome P-450 effector on the mutagenicity of genotoxic carcinogens
    mediated by hepatic and renal S9 from two species of marine fish.
    Mutat Res, 164: 59-70.

    Hardin BD, Bond GP, Sikov MR, Andrew FD, Beliles RP, & Niemeier RW
    (1981) Testing of selected workplace chemicals for teratogenic
    potential. Scand J Work Environ Health, 7(4): 66-75.

    Harkov R, Kebbekus B, Bozzelli J, & Lioy PJ (1983) Measurement of
    selected volatile organic compounds at three locations in New
    Jersey during the summer season. J Air Pollut Control Assoc,
    33(12): 1177-1183.

    Harkov R, Kebbekus B, Bozzelli JW, Lioy P, & Daisy J (1984) Comparison
    of selected volatile organic compounds during the summer and winter at
    urban sites in New Jersey. Sci Total Environ, 38: 259-274.

    Harkov R, Gianti SJ, Bozzelli JW, & LaRegina JE (1985) Monitoring
    volatile organic compounds at hazardous and sanitary landfills in New
    Jersey. J Environ Sci Health, A20(5): 491-501.

    Hasanen E, Soininen V, Pyysalo H, & Leppamaki E (1979) On the
    occurrence of aliphatic chlorine and bromine compounds in automobile
    exhaust. Atmos Environ, 13: 1217-1219.

    Hasanen E, Karlsson V, Leppamaki E, & Juhala M (1981) Benzene, toluene
    and xylene concentrations in car exhausts and in city air. Atmos
    Environ, 15(9): 1755-1757.

    Hayes S, Gordon A, Sadowski I,& Hayes C (1984) RK bacterial test for
    independently measuring chemical toxicity and mutagenicity: Short-term
    forward selection assay. Mutat Res, 130: 97-106.

    Heikes DL (1985a) Purge and trap method for determination of ethylene
    dibromide in table ready foods. J Assoc Off Anal Chem, 68(3): 431-436.

    Heikes DL (1985b) Purge and trap method for determination of ethylene
    dibromide in whole grains, milled grain products, intermediate
    grain-based foods and animal feeds. J Assoc Off Anal Chem,
    68(6): 1108-1111.

    Heikes DL & Hopper ML (1986) Purge and trap method for determination
    of fumigants in whole grains, milled grain products and intermediate
    grain-based foods. J Assoc Off Anal Chem, 69(6): 990-998.

    Hemminki K, Falck K, & Vainio H (1980) Comparison of alkylation rates
    and mutagenicity of directly acting industrial and laboratory
    chemicals. Arch Toxicol, 46: 277-285.

    Herring CO, Adams JA, Wilson BA, & Pollard S (1988) Dose-response
    studies using ethylene dibromide(EDB) in  Hydra oligactis. Bull
    Environ Contam Toxicol, 40: 35-40.

    Heuser SG & Scudamore KA (1967) Determination of ethylene
    chlorohydrin, ethylene dibromide and other volatile fumigant residues
    in flour and whole wheat. Chem Ind, 37: 1557-1560.

    Hill DL, Shih TW, Johnston TP, & Struck RF (1978) Macromolecular
    binding and metabolism of the carcinogen 1,2-dibromoethane. Cancer
    Res, 38: 2438-2442.

    Hsu LL, Adams PM, Fanini D, & Legator MS (1985) Ethylene dibromide:
    Effects of paternal exposure on the neurotransmitter enzymes in the
    developing brain of progeny. Mutat Res, 147: 197-203.

    Hughes TJ, Simmons DM, Monteith LG, & Claxton LD (1987) Vaporization
    technique to measure mutagenic activity of volatile organic chemicals
    in the Ames/Salmonella assay. Environ Mutagen, 9: 421-441.

    IARC (1977) Ethylene dibromide. In: Some fumigants, the herbicides
    2,4-D and 2,4,5-T, chlorinated dibenzodioxins and miscellaneous
    industrial chemicals. Lyon, International Agency for Research on
    Cancer, pp 195-209 (IARC Monographs on the Evaluation of Carcinogenic
    Risks to Humans, Volume 15).

    IARC (1982) Ethylene dibromide. In: Chemicals, industrial processes
    and industries associated with cancer in humans - IARC monographs,
    volumes 1 to 29. Lyon, International Agency for Research on Cancer,
    pp 124-126 (IARC Monographs on the Evaluation of Carcinogenic Risks to
    Humans, Supplement 4).

    IARC (1987) Ethylene dibromide. In: Overall evaluations of
    carcinogenicity: An updating of IARC monographs, volumes 1 to 42.
    Lyon, International Agency for Research on Cancer, pp 204-205 (IARC
    Monographs on the Evaluation of Carcinogenic Risks to Humans,
    Supplement 7).

    Inskeep PB & Guengerich FP (1984) Glutathione-mediated binding of
    dibromoalkanes to DNA: Specificity of rat glutathione-S-transferases
    and dibromoalkane structure. Carcinogenesis, 5(6): 805-808.

    Inskeep PB, Koga N, Cmarik JL, & Guengerich FP (1986) Covalent binding
    of 1,2-dihaloalkanes to DNA and stability of the major DNA adduct,
    S-[2-(N7-guanyl)ethyl]glutathione1. Cancer Res, 46: 2839-2844.

    IPCS (International Programme on Chemical Safety) (1995) Environmental
    health criteria 166: Methyl bromide. Geneva, World Health
    Organization, 324 pp.

    IRPTC (1993) Legal file. Geneva, International Register of Potentially
    Toxic Chemicals, United Nations Environment Programme.

    Isaacson PJ, Hankin L, & Frink CR (1984) Boiling drinking water
    removes ethylene dibromide. Science, 225: 672.

    Ishikuro E (1986) [Quantitative analysis of ethylene dibromide (EDB)
    in feed ingredients and mixed feed.] Shiryo Kenkyo Hokoku, 11: 1-7
    (in Japanese).

    Iwata Y, Dusch ME, & Gunther FA (1983) Use of sulfuric acid cleanup
    step in the determination of 1,2-dibromoethane residues in lemons,
    oranges, and grapefruits. J Agric Food Chem, 31: 171-174.

    Izutani K, Nakata A, Shinagawa H, & Kawamata J (1980) Forward mutation
    assay for screening carcinogens by alkaline phosphatase constitutive
    mutations in  Escherichia coli K-12. J Res Inst Microb Dis (Biken J),
    23: 69-75.

    Jacobs ES (1980) Use and air quality impact of EDC and EDB scavengers
    in leaded gasoline. In: Ames B, Infante P, & Peirtz R ed. Ethylene
    dichloride: A potential health risk? Cold Spring Harbor, New York,
    Cold Spring Harbor Laboratory, pp 239-255 (Banbury Report No. 5).

    Jacobs RS (1985) Ethylene dibromide poisoning. J Am Med Assoc,
    253: 2961.

    Jafvert CT & Wolfe NL (1987) Degradation of selected halogenated
    ethanes in anoxic sediment-water systems. Environ Toxicol Chem,
    6: 827-837.

    Jagielski J, Scudamore KA, & Heuser SG (1978) Residues of carbon
    tetrachloride and 1,2-dibromoethane in cereals and processed foods
    after liquid fumigant grain treatment for pest control. Pestic Sci,
    9: 117-126.

    Jakobson I, Wahlberg JE, Holmberg B, & Johansson G (1982) Uptake via
    the blood and elimination of 10 organic solvents following
    epicutaneous exposure of anesthetized guinea pigs. Toxicol Appl
    Pharmacol, 63: 181-187.

    Jean PA & Reed DJ (1992) Utilization of glutathione during
    1,2-dihaloethane metabolism in rat hepatocytes. Chem Res Toxicol,
    5: 386-391.

    Kale PG & Baum JW (1979a) Sensitivity of  Drosophila melanogaster to
    low concentrations of the gaseous 1,2-dibromoethane: I. Acute
    exposures. Environ Mutagen, 1: 15-18.

    Kale PG & Baum JW (1979b) Sensitivity of  Drosophila melanogaster to
    low concentrations of gaseous mutagens: II. Chronic exposures. Mutat
    Res, 68: 59-68. 

    Kale PG & Baum JW (1981) Sensitivity of  Drosophila melanogaster to
    low concentrations of gaseous mutagens: III. Dose-rate effects.
    Environ Mutagen, 3: 65-70.

    Kale PG & Baum JW (1982) Genetic effects of ethylene dibromide in
     Drosophila melanogaster. In: Tice RR, Costa DL, & Schaich KM ed.
    Genotoxic effects of airborne agents. New York, London, Plenum Press,
    pp 291-300.

    Kale PG & Baum JW (1983) Sensitivity of  Drosophila melanogaster to
    low concentrations of gaseous mutagens: IV. Mutations in embryonic
    spermatogonia. Mutat Res, 113: 135-143.

    Kaphalia BS & Ansari GAS (1992) Covalent binding of ethylene dibromide
    and its metabolites to albumin. Toxicol Lett, 62: 221-230.

    Kato K, Nakamura M, Nakaoka T, & Ito K (1982) [Determination of
    ethylene bromide residues in fruits.] Kanagawa-ken Eisei Kenkyosho
    Hokoku, 12: 33-34 (in Japanese).

    Keough T, Strife RJ, Rodriguez PA, & Sanders RA (1984) Separation and
    use of the perdeuterated analogue as an internal standard for the
    analysis of ethylene dibromide. J Chromatogr, 312: 450-455.

    Kerklaan P, Bouter S, & Mohn G (1983) Isolation of a mutant of
     Salmonella typhimurium strain TA1535 with decreased levels of
    glutathione (GSH-): Primary characterization and chemical mutagenesis
    studies. Mutat Res, 122: 257-266.

    Kerklaan P, Zoetemelk CEM, & Mohn GR (1985) Mutagenic activity of
    various chemicals in Salmonella strain TA100 and glutathione-deficient
    derivatives: On the role of glutathione in the detoxification or
    activation of mutagens inside bacterial cells. Biochem Pharmacol,
    34(12): 2151-2156.

    Khan S, Sood C, & O'Brien PJ (1993) Molecular mechanisms of
    dibromoalkane cytotoxicity in isolated rat hepatocytes. Biochem
    Pharmacol, 45(2): 439-447.

    Kim DH & Guengerich FP (1989) Excretion of the mercapturic acid
    S-[2-(N7-guanyl) ethyl]-N-acetylcysteine in urine following
    administration of ethylene dibromide to rats. Cancer Res,
    49: 5843-5847.

    Kim DH & Guengerich FP (1990) Formation of the DNA adduct
    S-[2-(N7-guanyl)ethyl] glutathione as an adduct formed in RNA and DNA
    from 1,2-dibromoethane. Chem Res Toxicol, 3(6): 587-594.

    Kitchin KT & Brown JL (1986) 1,2-dibromoethane causes rat hepatic DNA
    damage at low doses. Biochem Biophys Res Commun, 141(2): 723-727.

    Kluwe WM, McNish R, Smithson K, & Hook JB (1981) Depletion by
    1,2-dibromoethane, 1,2-dibromo-3-chloropropane, tris(2,3-
    dibromopropyl)phosphate, and hexachloro-1,3-butadiene of reduced
    non-protein sulfhydryl groups in target and non-target organs. Biochem
    Pharmacol, 30(16): 2265-2271.

    Kluwe WM, Harrington FW, & Cooper SE (1982) Toxic effects of
    organohalide compounds on renal tubular cells  in vivo and  in vitro.
    J Pharmacol Exp Ther, 220: 597-603.

    Koida K, Tokumori Y, Saimatsu J, Sekigawa K, Kohno U, & Oka A (1986)
    [Determination of ethylene dibromide and dibromochloropropane in
    groundwater by gas chromatography-negative ion chemical ionization
    mass spectrometry.] Hiroshima-shi Eisei Kenkyusho Nenpo, 5: 34-36
    (in Japanese).

    Kojima T & Seo Y (1976) [Selective detection of alkyl nitrites, alkyl
    nitrates, nitroparaffins and halogen compounds by gas chromatography.]
    Bunseki Kagaku, 25: 855-858 (in Japanese).

    Konishi Y, Yoshida S, & Nakamura A (1985) [Determination of EDB on
    capillary ECD-GC.] Osaka-furitsu Koshu Eisei Kenkyusho Kenkyu Hokoku,
    Shokuhin Eisei Hen, 16: 63-67 (in Japanese).

    Kowalski B, Brittebo EB, & Brandt I (1985) Epithelial binding of
    1,2-dibromoethane in the respiratory and upper alimentary tracts of
    mice and rats. Cancer Res, 45: 2616-2625.

    Krishna G, Xu J, Nath J, Petersen M, & Ong T (1985)  In vivo
    cytogenetic studies on mice exposed to ethylene dibromide. Mutat Res,
    158: 81-87.

    Krost KJ, Pellizzari ED, Walburn SG, & Hubbard SA (1982) Collection
    and analysis of hazardous organic emissions. Anal Chem, 54: 810-817.

    Kubinski H, Gutzke GE, & Kubinski ZO (1981) DNA-cell-binding (DCB)
    assay for suspected carcinogens and mutagens. Mutat Res, 89: 95-136.

    Kulkarni AP, Edwards J, & Richards IS (1992) Metabolism of
    1,2-dibromoethane in the human fetal liver. Gen Pharmacol, 23(1): 1-5.

    Landau M & Tucker JW (1984) Acute toxicity of EDB and aldicarb to
    young of two estuarine fish species. Bull Environ Contam Toxicol,
    33: 127-132.

    Ledda-Columbano GM, Columbano A, Coni P, Curto M, Faa G, & Pani P
    (1987a) Cell proliferation in rat kidney induced by 1,2-dibromoethane.
    Toxicol Lett, 37: 85-90.

    Ledda-Columbano GM, Columbano A, Coni P, Liguori C, & Pani P (1987b)
    Liver cell proliferation induced by the mitogen ethylene dibromide
    unlike compensatory cell proliferation, does not achieve initiation of
    rat liver carcinogenesis by diethylnitrosamine. Cancer Lett,
    36: 247-252.

    Leinster P, Perry R, & Young RJ (1978) Ethylene dibromide in urban
    air. Atmos Environ, 12: 2383-2387.

    Letz GA, Pond SM, Osterloh JD, Wade RL, & Becker CE (1984) Two
    fatalities after acute occupational exposure to ethylene dibromide.
    J Am Med Assoc, 252(17): 2428-2431.

    Libbey AJ (1986) Determination of ethylene dibromide in aquatic
    environments. Analyst, 111: 1221-1222.

    Logan SR (1988) Comments on photohydrolysis of ethylene dibromide.
    J Agric Food Chem, 36: 872-873.

    Lyman WJ (1982) Octanol/water partition coefficient. In: Lyman WJ &
    Peehl WF ed. Handbook of chemical property estimation methods -
    Environmental behaviour of organic compounds. New York, McGraw-Hill
    Publishers, pp 1/1-1/54.

    Ma T-H, Sparrow AH, Schairer LA, & Nauman AF (1978) Effect of 1,2
    dibromoethane (EDB) on meiotic chromosomes of Tradescantia. Mutat Res,
    58: 251-258.

    Ma T-H, Harris MM, Anderson VA, Ahmed I, Mohammad K, Bare JL, & Lin G
    (1984) Tradescantia-micronucleus (Trad-MCN) tests on 140 health-
    related agents. Mutat Res, 138: 157-167.

    McCann J, Choi E, Yamasaki E, & Ames BN (1975) Detection of
    carcinogens as mutagens in the Salmonella/microsome test: Assay of 300
    chemicals. Proc Natl Acad Sci (USA), 72(12): 5135-5139.

    McClenny WA, Pleil JD, Holdren MW, & Smith RN (1984) Automated
    cryogenic preconcentration and gas chromatographic determination of
    volatile organic compounds in air. Anal Chem, 56: 2947-2951.

    McCollister DD, Hollingsworth RL, Oyen F, & Rowe VK (1956) Comparative
    inhalation toxicity of fumigant mixtures. Am Med Assoc Arch Ind
    Health, 13: 1-7.

    McKenry MV & Thomason IJ (1974) 1,3-Dichloropropene and
    1,2-dibromoethane compounds: I. Movement and fate as affected by
    various conditions in several soils: II. Organism-dosage-response
    studies in the laboratory with several nematode species. Hilgardia,
    42(11): 393-438. 

    Mann AM & Darby FJ (1985) Effects of 1,2-dibromoethane on glutathione
    metabolism in rat liver and kidney. Biochem Pharmacol,
    34(16): 2827-2830.

    Mann JB, Freal JJ, Enos HF, & Danauskas JX (1980) Evaluation of
    methodology for determining 1,2-dibromoethane (EDB) in ambient air. J
    Environ Sci Health, B15(5): 507-518.

    Martl LR, de Kanel J, & Dougherty RC (1984) Screening for organic
    contamination of groundwater: ethylene dibromide in Georgia irrigation
    wells. Environ Sci Technol, 18: 973-974. 

    Mayer JR, Lacher TE, Elkins NR, & Thorn CJ (1991) Temporal variation
    of ethylene dibromide (EDB) in an unconfined aquifer, Whatcom County,
    Washington, USA: a twenty-seven month study. Bull Environ Contam
    Toxicol, 47: 368-373.

    Meneghini R (1974) Repair replication of opossum lymphocyte DNA:
    effect of compounds that bind to DNA. Chem-Biol Interact, 8: 113-126.

    Mestres R, Atmawijaya S, & Francois CL (1980) XXXV. Méthode de
    recherche et de dosage des résidus de pesticides dans les produits
    céréaliers. Ann Fals Exp Chim, 73(788): 407-420.

    MHW (1985) Prohibition of EDB residues in imported wheat, tropical
    fruit etc. Official notice of the Ministry of Health and Welfare.
    Tokyo, Ministry of Health and Welfare.

    MHW (1987) Prohibition of EDB residues in imported wheat, tropical
    fruit etc. Official notice of the Ministry of Health and Welfare.
    Tokyo, Ministry of Health and Welfare.

    MHW (1988) Prohibition of EDB residues in imported wheat, tropical
    fruit etc. Official notice of the Ministry of Health and Welfare.
    Tokyo, Ministry of Health and Welfare.

    Mitra A, Hilbelink DR, Dwornik JJ, & Kulkarni A (1992) A novel model
    to assess developmental toxicity of dihaloalkanes in humans:
    Bioactivation of 1,2-dibromoethane by the isozymes of human fetal
    liver glutathione S-transferase. Teratog Carcinog Mutagen,
    12(3): 113-127.

    Mohn GR, Kerklaan PRM, Van Zeeland AA, Ellenberger J, Baan RA, Lohman
    PHM, & Pons F-W (1984) Methodologies for the determination of various
    genetic effects in permeable strains of  E. coli K-12 differing in
    DNA repair capacity: Quantification of DNA adduct formation,
    experiments with organ homogenates and hepatocytes, and animal-
    mediated assays. Mutat Res, 125: 153-184.

    Moriya M, Ohta T, Watanabe K, Miyazawa T, Kato K, & Shirasu Y (1983)
    Further mutagenicity studies on pesticides in bacterial reversion
    assay systems. Mutat Res, 116: 185-216.

    Morris SC & Rippon LE (1985) Distribution of ethylene dibromide within
    a fumigation chamber during fumigation of citrus fruit. J Agric Food
    Chem, 33: 801-803.

    Morris SC, Rippon LE, & Halamek R (1982) Rapid analysis and gas
    sampling of ethylene dibromide in the gaseous phase and as residues in
    citrus fruit. J Chromatogr, 246: 136-140.

    Mundhe DR & Pandey ND (1980) Effect of different foods on the
    susceptibility of  Callosobruchus chinensis Linn, to some fumigants.
    Indian J Entomol, 42: 787-790.

    Munnecke DE & Van Gundy SD (1979) Movement of fumigants in soil,
    dosage responses, and differential effects. Annu Rev Phytopathol,
    17: 405-429.

    Nachtomi E (1970) The metabolism of ethylene dibromide in the rat: the
    enzymic reaction with glutathione  in vitro and  in vivo. Biochem
    Pharmacol, 19: 2853-2860.

    Nachtomi E & Farber E (1978) Ethylene dibromide as a mitogen for
    liver. Lab Invest, 38(3): 279-283.

    Nachtomi E & Sarma DSR (1977) Repair of rat liver DNA  in vivo
    damaged by ethylene dibromide. Biochem Pharmacol, 26: 1941-1945.

    Nachtomi E, Alumot E, & Bondi A (1968) Biochemical changes in organs
    of chicks and rats poisoned with ethylene dibromide and carbon
    tetrachloride. Israel J Chem, 6: 803-811.

    Nakamura M (1986) [Analytical method for ethylene dibromide in wheat
    products using capillary column GC-mass spectrometry.] Fukuoka-shi
    Eisei Shikenshiho, 11: 47-53 (in Japanese).

    Nauman CH, Sparrow AH, & Schairer LA (1976) Comparative effects of
    ionizing radiation and two gaseous chemical mutagens on somatic
    mutation induction in one mutable and two non-mutable clones of
    Tradescantia. Mutat Res, 38: 53-70.

    NCI (1978) Bioassay of 1,2-dibromoethane for possible carcinogenicity.
    Bethesda, Maryland, National Cancer Institute, Division of Cancer
    Cause and Prevention, Carcinogenesis Testing Program, 64 pp (Technical
    Report Series No 86; DHEW Publication No. (NIH) 78-1336).

    Nemoto Y, Sasamoto T, Nakata M, Suzuki Y, Kubota K, & Kurokawa K
    (1984) [Survey of EDB groundwaters in Ibaraki Prefecture.] Ibaraki-ken
    Eisei Kenkyujo Nenpo, 22: 80-81 (in Japanese).

    Nichols WK, Covington MO, Seiders CD, Safiullah S, & Yost GS (1992)
    Bioactivation of halogenated hydrocarbons by rabbit pulmonary cells.
    Pharmacol Toxicol, 71(5): 335-339.

    Nilsson CA, Lindahl R, & Norstrom A (1987) Occupational exposure to
    chain saw exhausts in logging operations. Am Ind Hyg Assoc J,
    48(2): 99-105.

    NIOSH (1977) Criteria for a recommended standard: occupational
    exposure to ethylene dibromide. Cincinnati, Ohio, National Institute
    for Occupational Safety and Health, 208 pp (DHEW (NIOSH) Publication
    No. 77-221).

    NIOSH (1981) Current intelligence bulletin No. 37: Ethylene bromide
    (revised). Cincinnati, Ohio, National Institute for Occupational
    Safety and Health, 13 pp (Publication No. 82-105).

    Nishiuchi Y (1980) [Toxicity of pesticide formulas to some fresh water
    organisms - LXX.] Suisan Zoushoku, 27(4): 225-237 (in Japanese).

    Nishiuchi Y (1981) [Toxicity of pesticides to some aquatic organisms:
    I. Toxicity of pesticides to some aquatic insects.] Seitai Kagaku,
    4(2): 31-46 (in Japanese).

    Nishiuchi Y (1982) [Toxicity of pesticide formulas to some fresh water
    organisms: effects of pH on toxicity revelation.] Suisan Zoushoku,
    30(3): 172-177 (in Japanese).

    Nishiuchi Y & Asano K (1979) [Toxicity of pesticide formulas to some
    fresh water organisms - LXVI.] Suisan Zoushoku, 27(3): 172-177 (in

    Nitschke KD, Kociba RJ, Keyes DG, & Mckenna MJ (1981) A thirteen week
    repeated inhalation study of ethylene dibromide in rats. Fundam Appl
    Toxicol, 1: 437-442.

    NTP (1982) Carcinogenesis bioassay of 1,2-dibromoethane in F344 rats
    and B6C3F1 mice (inhalation study). Research Triangle Park, North
    Carolina, US Department of Health and Human Services, National
    Toxicology Program, 163 pp (NTP Technical Report Series No. 210).

    Ogino Y (1978) [Study of the effect of the environment - polluting
    substances on ecological systems: I. Translocation of
    bromohydrocarbons to the fish body.] Okayamo Igakkai Zasshi,
    90: 1451 -1455 (in Japanese).

    Ohta T, Nakamura N, Moriya M, Shirasu Y, & Kada T (1984) The
    SOS-function-inducing activity of chemical mutagens in  Escherichia
     coli. Mutat Res, 131: 101-109.

    Ong T-M, Stewart JD, Wen Y-F, & Whong W-Z (1987) Application of SOS
    umu-test for the detection of genotoxic volatile chemicals and air
    pollutants. Environ Mutagen, 9: 171-176.

    Ong T-M, Stewart JD, Tucker JD, & Whong W-Z (1989) Development of an
    in situ test system for detection of mutagens in the workplace. In:
    Waters MD, Sandhu SS, Lewtas J, Claxton L, Strauss G, & Nesnow S, ed.
    Short-term bioassays in the analysis of complex environmental
    mixtures, IV. New York, Plenum Publishing Corporation, pp 25-36.

    OSHA (Occupational Safety and Health Agency) (1983) Occupational
    exposure to ethylene dibromide. Fed Reg, 48(196): 45956-46003.

    Ott MG, Scharnweber HC, & Langner RR (1980) Mortality experience of
    161 employees exposed to ethylene dibromide in two production units.
    Br J Ind Med, 37: 163-168.

    Ozawa N & Guengerich FP (1983) Evidence for formation of an
    S-[2-(N7-guanyl)ethyl] glutathione adduct in glutathione-mediated
    binding of the carcinogen 1,2-dibromoethane to DNA. Proc Natl Acad Sci
    (USA), 80: 5266-5270.

    Page GW (1981) Comparison of groundwater and surface water for
    patterns and levels of contamination by toxic substances. Environ Sci
    Technol, 15(12): 1475-1481.

    Peoples SA, Maddy KT, & Riddle LC (1978) Human occupational health
    problems resulting from exposure to ethylene dibromide in California
    in 1975 and 1976. Vet Hum Toxicol, 20: 241-244.

    Perocco P & Prodi G (1981) DNA damage by haloalkanes in human
    lymphocytes cultured  in vitro. Cancer Lett, 13: 213-218.

    Perocco P, Colacci A, Santucci MA, Vaccari M, & Grilli S (1991)
    Transforming activity of ethylene dibromide in BALB/c 3T3 cells. Res
    Commun Chem Pathol Pharmacol, 73(2): 159-172. 

    Pignatello JJ (1986) Ethylene dibromide mineralization in soils under
    aerobic conditions. Appl Environ Microbiol, 51(3): 588-592.

    Pignatello JJ & Cohen SZ (1989) Environmental chemistry of ethylene
    dibromide in soil and ground water. Rev Environ Contam Toxicol,
    112: 1-47.

    Pignatello JJ, Sawhney BL, & Frink CR (1987) EDB: Persistence in soil.
    Science, 236: 898.

    Pleil JD, Oliver KD, & McClenny WA (1987) Enhanced performance of
    nation dryers in removing water from air samples prior to gas
    chromatographic analysis. JAPCA, 37(30): 244-248.

    Plotnick HB & Conner WL (1976) Tissue distribution of 14C-labeled
    ethylene dibromide in the guinea pig. Res Commun Chem Pathol
    Pharmacol, 13(2): 251-259.

    Plotnick HB, Weigel WW, Richards DE, & Cheever KL (1979) The effect of
    dietary disulfiram upon the tissue distribution and excretion of
    14C-1,2-dibromoethane in the rat. Res Commun Chem Pathol Pharmacol,
    26(3): 535-545.

    Pranoto-Soetardhi LA, Rijk MAH, De Kruijf N, & De Vos RH (1986)
    Automatic headspace sampling for determination of ethylene dibromide
    residues in cereals. Int J Environ Anal Chem, 25: 151-159.

    Principe P, Dogliotti E, Bignami M, Crebelli R, Falcone E, Fabrizi M,
    Conti G, & Comba P (1981) Mutagenicity of chemicals of industrial and
    agricultural relevance in Salmonella, Streptomyces and Aspergillus. J
    Sci Food Agric, 32: 826-832.

    Quillardet P, De Bellecombe C, & Hofnung M (1985) The SOS chromotest,
    a colorimetric bacterial assay for genotoxins: validation study with
    83 compounds. Mutat Res, 147: 79-95.

    Rains DM & Holder JW (1981) Technical Communications: Ethylene
    dibromide residues in biscuits and commercial flour. J Assoc Off Anal
    Chem, 64(5): 1252.

    Rannug U (1980) Genotoxic effects of 1,2-dibromoethane and
    1,2-dichloroethane. Mutat Res, 76: 269-295.

    Rannug U & Beije B (1979) The mutagenic effect of 1,2-dichloroethane
    on  Salmonella typhimurium. II. Activation by the isolated perfused
    rat liver. Chem-Biol Interact, 24: 265-285.

    Rappaport SM, Cameron W, & McAllister J (1984) Outgassing of ethylene
    dibromide from fumigated oranges. J Agric Food Chem, 32(5): 1112-1116.

    Rasmussen RA & Khalil MAK (1984) Gaseous bromine in the arctic and
    arctic haze. Geophys Res Lett, 11(5): 433-436.

    Ratcliffe JM, Schrader SM, Steenland K, Clapp DE, Turner T, & Hornung
    RW (1987) Semen quality in papaya workers with long term exposure to
    ethylene dibromide. Br J Ind Med, 44: 317-326.

    Reznik G, Stinson SF, & Ward JM (1980) Respiratory pathology in rats
    and mice after inhalation of 1,2-dibromo-3-chloropropane or 1,2
    dibromoethane for 13 weeks. Arch Toxicol, 46: 233-240.

    Rogers RD & McFarlane JC (1981) Sorption of carbon tetrachloride,
    ethylene dibromide, and trichloroethylene in soil and clay. Environ
    Monit Assess, 1: 155-162.

    Rosenkranz HS (1977) Mutagenicity of halogenated alkanes and their
    derivatives. Environ Health Perspect, 21: 79-84.

    Roskill (1992) The economics of bromine, 1992. London, Roskill
    Information Services, pp 57-58.

    Rowe VK, Spencer HC, McCollister DD, Hollingsworth RL, & Adams EM
    (1952) Toxicity of ethylene dibromide determined on experimental
    animals. Am Med Assoc Arch Ind Hyg Occupat Med, 6: 158-173.

    Rumsey DW & Tanita RK (1978) NIOSH industrial hygiene survey.
    Cincinnati, Ohio, National Institute for Occupational Safety and
    Health, 20 pp (Publication No. 79-112).

    Russell WL(1986) Positive genetic hazard predictions from short-term
    tests have proved false for results in mammalian spermatogonia with
    all environmental chemicals so far tested. In: Genetic toxicology of
    environmental chemicals - Part B: Genetic effects and applied
    mutagenesis. New York, Alan R. Liss Inc., pp 67-74.

    Saito N, Ogino Y, Katayama Y, Matsunaga K, Nagao M, & Ishida T (1978)
    [Determination of aliphatic brominated hydrocarbons in environmental
    samples.] Kogaito Taisaku, 14(3): 316-320 (in Japanese).

    Sarawat PK, Kandara M, Dhurva AK, Malhotra VK, & Jhanwar RS (1986)
    Poisoning by ethylene dibromide - six cases: A clinicopathological and
    toxicological study. Indian J Med Sci, 40(5): 121-123.

    Sawyer LD & Walters SM (1986) Gas chromatographic method for ethylene
    dibromide in grains and grain-based products: Collaborative study. J
    Assoc Off Anal Chem, 69(5): 847-851.

    Schlinke JC (1970) Toxicologic effects of five soil nematocides in
    chickens. Am J Vet Res, 31(6): 1119-1121.

    Schrader SM, Ratcliffe JM, Turner T, & Hornung RW (1987) The use of
    new field methods of semen analysis in the study of occupational
    hazards to reproduction the example of ethylene dibromide. J Occup
    Med, 29: 963-966.

    Schrader SM, Turner TW, & Ratclife JM (1988) The effects of ethylene
    dibromide on semen quality: A comparison of short-term and chronic
    exposure. Reprod Toxicol, 2: 191-198.

    Schultz K, Ghosh L, & Banerjee S (1992) Neoplastic expression in
    murine cells induced by halogenated hydrocarbons.  In vitro Cell Dev
    Biol, 28A: 267-272.

    Scott BR, Sparrow AH, Schwemmer SS, & Schairer LA (1978) Plant
    metabolic activation of 1,2-dibromoethane (EDB) to a mutagen of
    greater potency. Mutat Res, 49: 203-212.

    Sega GA & Rene E (1980) Chemical dosimetry and unscheduled DNA
    synthesis studies of ethylene dibromide in the germ cells of male
    mice. Environ Mutagen, 5: 274.

    Sekita H, Takeda M, & Uchiyama M (1981) [Studies on analysis of
    pesticide residues in foods. XXXIII. Determination of ethylene
    dibromide residues in litchi (lychee) fruits imported from Formosa.]
    Bull Natl Inst Hyg Sci (Tokyo), 99: 130-132 (in Japanese).

    Sekita H, Takeda M, & Uchiyama M (1983) [Ethylene dibromide (EDB)
    residues in fresh fruits imported after fumigation with EDB and
    decrease of the residues with time.] Shokuhin Eisei Gaku Zasshi,
    24(1): 57-63 (in Japanese).

    Shiau SY, Huff RA, Wells BC, & Felkner IC (1980) Mutagenicity and
    DNA-damaging activity for several pesticides tested with  Bacillus
     subtilis mutants. Mutat Res, 71: 169-179.

    Shivanandappa T, Krishnakumari MK, & Majumder SK (1987) Reproductive
    potential of male rats fed dietary ethylene dibromide. J Food Saf,
    8: 147-155.

    Short RD, Minor JL, Winston JM, Seifter J, & Lee CC (1978) Inhalation
    of ethylene dibromide during gestation by rats and mice. Toxicol Appl
    Pharmacol, 46: 173-182.

    Short RD, Winston JM, Hong CB, Minor JL, Lee CC, & Seifter J (1979)
    Effects of ethylene dibromide on reproduction in male and female rats.
    Toxicol Appl Pharmacol, 49: 97-105.

    Simula TP, Glancey MJ, & Wolf CR (1993) Human glutathione
    S-transferase-expressing  Salmonella typhimurium tester strains to
    study the activation/detoxification of mutagenic compounds: studies
    with halogenated compounds, aromatic amines and aflatoxin B1.
    Carcinogenesis, 14: 1371-1376.

    Sina JF, Bean CL, Dysart GR, Taylor VI, & Bradley MO (1983) Evaluation
    of the alkaline elution/rat hepatocyte assay as a predictor of
    carcinogenic/mutagenic potential. Mutat Res, 113: 357-391.

    Singh HB, Salas LJ, Smith AJ, & Shigeishi H (1981) Measurements of
    some potentially hazardous organic chemicals in urban environments.
    Atmos Environ, 15: 601-612.

    Singh HB, Salas LJ, & Stiles RE (1982) Distribution of selected
    gaseous organic mutagens and suspect carcinogens in ambient air.
    Environ Sci Technol, 16(12): 872-880.

    Singh HB, Salas LJ, & Stiles RE (1983) Selected man-made halogenated
    chemicals in the air and oceanic environment. J Geophys Res,
    88(C6): 3675-3683.

    Sipes IG, Wiersma DA, & Armstrong DJ (1986) The role of glutathion in
    the toxicity of xenobiotic compounds: Metabolic activation of
    1,2-dibromoethane by glutathione. Adv Exp Med Biol, 197: 457-467.

    Smith RF & Goldman L (1983) Behavioral effects of prenatal exposure to
    ethylene dibromide. Neurobehav Toxicol Teratol, 5: 579-585.

    Sparrow AH, Schairer LA, & Villalobos-Pietrini R (1974) Comparison of
    somatic mutation rates induced in Tradescantia by chemical and
    physical mutagens. Mutat Res, 26: 265-276.

    Springarn NE, Northington DJ, & Pressely T (1982) Analysis of volatile
    hazardous substances by GC/MS. J Chromatogr Sci, 20: 286-288.

    SRI International (1982) Ethylene dibromide: US salient statistics -
    Chemical economics handbook. Menlo Park, California, Stanford Research

    Steenland K, Carrano A, Ratcliffe J, Clapp D, Ashworth L, & Meinhardt
    T (1986) A cytogenetic study of papaya workers exposed to ethylene
    dibromide. Mutat Res, 170: 151-160. 

    Steinberg SM, Pignatello JJ, & Sawhney BL (1987) Persistence of
    1,2-dibromomethane in soils: entrapment in intraparticle micropores.
    Environ Sci Technol, 21: 1202-1208.

    Stenger VA (1978) Bromine compounds. In: Kirk-Othmer encyclopedia of
    chemical technology, 3rd ed. New York, John Wiley, vol 4, pp 243-263.

    Stinson SF, Reznik G, & Ward JM (1981) Characteristics of
    proliferative lesions in the nasal cavities of mice following chronic
    inhalation of 1,2-dibromoethane. Cancer Lett, 12: 121-129.

    Stolzenberg SJ & Hine CH (1980) Mutagenicity of 2-and 3-carbon
    halogenated compounds in the Salmonella/mammalian-microsome test.
    Environ Mutagen, 2: 59-66.

    Storer RD & Conolly RB (1983) Comparative  in vivo genotoxicity and
    acute hepatotoxicity of three 1,2-dihaloethanes. Carcinogenesis,
    4(11): 1491-1494.

    Stottmeister E, Hendel P, & Engewald W (1986) [Gas-chromatographic
    trace analysis of highly volatile halogenated hydrocarbons in water
    with FID detection.] Acta Hydrochim Hydrobiol, 14(6): 573-580 (in

    Sugiyama H (1980) Effects of EDB (1,2-dibromoethane) on the silkworm
     (Bombyx mori L.). J Pestic Sci, 5: 599-602.

    Sun M (1984) EDB contamination kindles federal action. Science,
    233: 464-466.

    Sundheimer DW, White RD, & Sipes IG (1982) The bioactivation of
    1,2-dibromoethane in rat hepatocytes: Covalent binding to nucleic
    acids. Carcinogenesis, 3(10): 1129-1133.

    Tan E-L & Hsie AW (1981) Mutagenicity and cytotoxicity of haloethanes
    as studied in the CHO/HGPRT system. Mutat Res, 90: 183-191.

    Tennant RW, Stasiewicz S, & Spalding JW (1986) Comparison of multiple
    parameters of rodent carcinogenicity and  in vitro genetic toxicity.
    Environ Mutagen, 8: 205-227.

    Tennant RW, Margolin BH, Shelby MD, Zeiger E, Haseman JK, Spalding J,
    Caspary W, Resnick M, Stasiewicz S, Anderson B, & Minor R (1987)
    Prediction of chemical carcinogenicity in rodents from  in vitro
    genetic toxicity assays. Science, 236: 933-941.

    Teramoto S, Saito R, Aoyama H, & Shirasu Y (1980) Dominant lethal
    mutation induced in male rats by 1,2-dibromo-3-chloropropane (DBCP).
    Mutat Res, 77: 71-78.

    Terao H, Kajikawa M, Morishita Y, & Kato K (1984) [Bromide ion
    concentration and Br/Cl ratio of ground water in the southwest region
    of Gifu Prefecture.] Chikyu Kagaku, 18: 21-28 (in Japanese).

    Terao H, Kajikawa M, Morishita K, & Kato K (1985) [Influence of
    pesticide and fertilizer on the ground water in vegetable field zone.]
    Chikyu Kagaku, 19: 31-38 (in Japanese).

    Ter Haar G (1980) An investigation of possible sterility and health
    effects from exposure to ethylene dibromide. In: Ames B, Infante O, &
    Peirtz R ed. Ethylene dichloride: A potential health risk? Cold Spring
    Harbor, New York, Cold Spring Harbor Laboratory, pp 167-188 (Banbury
    Report No. 5).

    Tezuka H, Ando N, Suzuki R, Terahata M, Moriya M, & Shirasu Y (1980)
    Sister-chromatid exchanges and chromosomal aberrations in cultured
    Chinese hamster cells treated with pesticides positive in microbial
    reversion assays. Mutat Res, 78: 177-191.

    Thier R, Taylor JB, Pemble SE, Humphreys WG, Persmark M, Ketterer B, &
    Guengerich FP (1993) Expression of mammalian glutathione S-transferase
    5-5 in  Salmonella typhimurium TA1535 leads to base-pair mutations
    upon exposure to dihalomethanes. Proc Natl Acad Sci (USA),
    90: 8576-8580.

    Townshend JL, Dirks VA, & Marks CF (1980) Temperature, moisture and
    compaction and their effects on the diffusion of ethylene dibromide in
    three Ontario soils. Can J Soil Sci, 60: 177-184.

    Tsani-Bazaca E, McIntyre AE, Lester JN, & Perry R (1981)
    Concentrations and correlations of 1,2-dibromoethane,
    1,2-dichloroethane, benzene and toluene in vehicle exhaust and ambient
    air. Environ Technol Lett, 2: 303-316.

    Tucker JD, Xu J, Stewart J, & Ong T-M (1984) Detection of sister-
    chromatid exchanges in human peripheral lymphocytes induced by
    ethylene dibromide vapor. Mutat Res, 138: 93-98.

    UNEP (1992) Methyl bromide and the ozone layer: a summary of current
    understanding. Montreal Protocol assessment supplement: Synthesis
    report of the methyl bromide interim scientific assessment and methyl
    bromide interim technology and economic assessment requested by the
    United Nations Environment Programme on behalf of the Contracting
    Parties to the Montreal Protocol. Nairobi, United Nations Environment

    US EPA (1977) EPA notice of rebuttable presumption against
    registration and continued registration of pesticide products
    containing ethylene dibromide. Fed Reg, 42: 63134. 

    US EPA (1986) US EPA reports results of study of pesticides in
    groundwater. J Am Water Works Assoc, 1986: 128-129.

    Van Bladeren PJ, Breimer DD, Rotteveel-Smijs GMT, De Jong RAW, Buus W,
    Van Der Gen A, & Mohn GR (1980) The role of glutathione conjugation in
    the mutagenicity of 1,2-dibromoethane. Biochem Pharmacol,
    29: 2975-2982.

    Van Bladeren PJ, Hoogeterp JJ, Breimer DD, & Van Der Gen A (1981a) The
    influence of disulfiram and other inhibitors of oxidative metabolism
    on the formation of 2-hydroxyethyl-mercapturic acid from
    1,2-dibromoethane by the rat. Biochem Pharmacol, 30(21): 2983-2987.

    Van Bladeren PJ, Breimer DD, Rotteveel-Smijs GMT, De Knijff P, Mohn
    GT, Van Meeteren-Walchli B, Buijs W, & Van der Gen A (1981b) The
    relation between the structure of vicinal dihalogen compounds and
    their mutagenic activation via conjugation to glutathione.
    Carcinogenesis, 2(6): 499-505.

    Van Duuren BL, Goldschmidt BM, Loewengart G, Smith AC, Melchlonne S,
    Seldman I, & Roth D (1979) Carcinogenicity of halogenated olefinic and
    aliphatic hydrocarbons in mice. J Natl Cancer Inst, 63(6): 1433-1439.

    Van Duuren BL, Seidman I, Melchionne S, & Kline SA (1985)
    Carcinogenicity bioassays of bromoacetaldehyde and bromoethanol-
    potential metabolites of dibromoethane. Teratogen Carcinogen Mutagen,
    5: 393-403.

    Vant'Hof J & Schairer LA (1982) Tradescantia assay system for gaseous
    mutagens: A report of the US Environmental Protection Agency Gene-Tox
    Program. Mutat Res, 99: 303-315.

    Verschueren K (1983) Handbook of environmental data on organic
    chemicals, 2nd ed. New York, Van Nostrand Reinhold, pp 635-636.

    Vogel E & Chandler JLR (1974) Mutagenicity testing of cyclamate and
    some pesticides in Drosophila melanogaster. Experientia (Basel),
    30: 621-623.

    Von Buselmaier W, Rohrborn G, & Propping P (1972) [Mutagenicity
    investigations with pesticides in the host mediated assay and the
    dominant lethal test in mice.] Biol Zent.bl, 91: 311-325 (in German).

    Wade NL & Rigney CJ (1979) Phytotoxicity of ethylene dibromide to
    cherry and banana fruit. J Am Soc Hortic Sci, 104(6): 900-903.

    Weast RC, Astle MJ, & Beyer WH (1988) CRC Handbook of chemistry and
    physics, 68th ed. Boca Raton, Florida, CRC Press, p C-264.

    White RD (1982) Chemical induction of genetic injury: The
    bioactivation of 1,2-dibromoethane. Diss Abstr Int, 43(03): 696B-697B.

    White RD, Gandolfi AJ, Bowden GT, & Sipes IG (1983) Deuterium isotope
    effect on the metabolism and toxicity of 1,2-dibromoethane. Toxicol
    Appl Pharmacol, 69: 170-178.

    White RD, Petry TW, & Sipes IG (1984) The bioactivation of
    1,2-dibromoethane in rat hepatocytes: deuterium isotope effect.
    Chem-Biol Interact, 49: 225-233.

    WHO (1993) Guidelines for drinking-water quality: Volume 1 - WHO
    Recommendations, 2nd ed. Geneva, World Health Organization, 130 pp.

    Wildeman AG & Nazar RN (1982) Significance of plant metabolism in the
    mutagenicity and toxicity of pesticides. Can J Genet Cytol,
    24: 437-449.

    Williams GM, Laspia MF, & Dunkel VC (1982) Reliability of the
    hepatocyte primary culture/DNA repair test in testing of coded
    carcinogens and noncarcinogens. Mutat Res, 97: 359-370.

    Williams J, Gladen BC, Turner TW, Schrader SM, & Chapin RE (1991) The
    effects of ethylene dibromide on semen quality and fertility in the
    rabbit: Evaluation of a model for human seminal characteristics.
    Fundam Appl Toxicol, 16: 687-700. 

    Wofsy SC, McElroy MB, & Yung YL (1975) The chemistry of atmospheric
    bromine. Geophys Res Lett, 2(6): 215-218.

    Wong LCK, Winston JM, Hong CB, & Plotnick H (1982) Carcinogenicity and
    toxicity of 1,2-dibromoethane in the rat. Toxicol Appl Pharmacol,
    63: 155-165.

    Wong O, Morgan RW, & Whorton MD (1985) An epidemiologic surveillance
    program for evaluating occupational reproductive hazards. Am J Ind
    Med, 7: 295-306.

    Woodrow JE, Majewski MS, & Seiber JN (1986) Accumulative sampling of
    trace pesticides and other organics in surface water using XAD-4
    resin. J Environ Sci Health, B21(2): 143-164.

    Working PK, Smith-Oliver T, White RD, & Butterworth BE (1986)
    Induction of DNA repair in rat spermatocytes and hepatocytes by
    1,2-dibromoethane: the role of glutathione conjugation.
    Carcinogenesis, 7(3): 467-472.

    Yoshida YH & Inagaki E (1986) [Mutagenicity of ethylene dibromide in
     Drosophila melanogaster]. Tachikawa Tandai Kiyo, 19: 49-50
    (in Japanese).

    Yuita K (1984) [Residues and pollutions of bromine derived from soil
    fumigants and disinfectants crops, soils and ground water.] Seitai
    Kogaku, 7(2): 3-12 (in Japanese).

    Zoetemelk CEM, Mohn GR, Van Der Gen A, & Breimer DD (1987)
    Mutagenicity in Salmonella strains differing in glutathione content
    and their alkylating potential. Biochem Pharmacol, 36(11): 1829-1835.


    1.  Identité, propriétés physiques et chimiques, et méthodes d'analyse

         Le 1,2-dibromoéthane (dibromure d'éthylène) est un liquide
    incolore d'odeur chloroformique dont le point de fusion est de 9,9°C
    et le point d'ébullition de 131,4°C.  Il est assez volatil, avec une
    tension de vapeur de 1,47 kPa (11 mmHg) à 25°C et une densité de
    vapeur par rapport à l'air de 6,1.  Le 1,2-dibromoéthane est miscible
    à la plupart des solvants organiques.  Sa solubilité dans l'eau est de
    4,3 g/litre à 30°C.

         Dans l'air ambiant, l'analyse s'effectue par chromatographie en
    phase gazeuse après absorption sur polymères poreux puis désorption
    thermique rapide.  Pour les échantillons d'eau, on utilise un système
    avec piège et purgeur.  Les résidus de 1,2-dibromoéthane présents dans
    les denrées alimentaires et d'autres milieux peuvent être soit
    extraits par solvent, soit soumis à une analyse par la technique de
    l'espace de tête dans des conditions cryogéniques, après quoi on
    prépare un dérivé et on poursuit par chromatographie en phase gazeuse
    ou chromatographie liquide à haute performance.

    2.  Sources d'exposition humaine et environnementale

         Le 1,2-dibromoéthane est utilisé comme agent d'épuration des
    agents antidétonnants à base de plomb ajoutés à l'essence.  On
    l'emploie aussi pour la fumigation du sol ou de certains fruits ou
    céréales.  L'essence additionnée de plomb étant moins utilisée dans
    certains pays et les homologations pour les usages agricoles ayant été
    annulées, l'exposition humaine à ce produit a diminué.  Il reste
    cependant encore en usage dans certains pays comme épurateur de
    l'essence au plomb, comme fumigant, au fins de quarantaine, comme
    solvent et comme intermédiaire dans l'industrie chimique.

    3.  Concentrations et dégradation dans l'environnement

         Dans l'air, on mesure des concentrations qui vont de zéro à des
    teneurs de l'ordre du ng/m3 en zone urbaine.  On a trouvé du
    1,2-dibromoéthane dans des eaux souterraines à des concentrations
    allant jusqu'à 0,2 µg/litre, la teneur pouvant atteindre 50 µg/litre
    dans les eaux superficielles des zones d'exploitation agricole
    intensive.  Bien qu'il y ait lessivage du 1,2-dibromoéthane à travers
    le sol, il en reste une certaine quantité dans la matrice
    édaphique,d'où risque de contamination ultérieure de la nappe
    phréatique.  On connaît mal les conditions de dégradation microbienne
    du 1,2-dibromoéthane dans le sol.

         Le composé étant très volatil, c'est l'atmosphère qui en est le
    principal réceptacle.  Par photolyse dans la stratosphère, il peut se
    former des produits de décomposition susceptibles d'attaquer la couche

    4.  Cinétique et métabolisme chez les animaux de laboratoire

         Le 1,2-dibromoéthane est rapidement absorbé par la voie orale,
    percutanée et respiratoire.  On pense que la toxicité du composé est
    largement due à ses métabolites.  La métabolisation s'effectue soit
    par une voie oxydative (cytochrome P-450), soit par conjugaison
    (glutathion- S-transférase).  Deux métabolites réactifs, le
    bromoacétaldéhyde formé par la voie oxydative, et l'ion thiiranium,
    formé par conjugaison, interagissent avec les macromolécules
    cellulaires (protéines, ADN), pour donner naissance à divers produits
    par l'établissement de liaisons covalentes.

    5.  Effets sur les mammifères de laboratoire et les systèmes d'épreuve
        in vitro

         Le 1,2-dibromoéthane est fortement toxique pour les animaux
    (DL50 par voie orale pour le rat égale à 146-417 mg/kg de poids
    corporel; CL50 inhalatoire pour le rat égale à 3080 mg/m3 après
    2 h d'exposition; mortalité observée chez des lapins à la suite d'une
    application cutanée à raison de 210 mg/kg).  Les effets toxiques
    observés se sont produits principalement au niveau des reins et du
    foie.  L'inhalation de vapeurs provoque une irritation de la muqueuse
    nasale et une dépression du système nerveux central.  Chez des groupes
    de rats exposés à des concentrations comprises entre 1540 et
    77 000 mg/m3 (200-10 000 ppm) pendant 0,1 à 16,0 h, on a observé
    dans tous les groupes une mortalité qui était fonction de la durée
    d'exposition et de la concentration.  En solution à 1,0%, le
    1,2-dibromoéthane a provoqué une irritation sur la peau abdominale de
    lapins après rasage ainsi qu'une irritation oculaire.

         Chez des rats et des souris qui avaient reçu du 1,2-dibromoéthane
    par voie orale de manière subchronique, on a observé une certaine
    mortalité et une baisse du gain de poids à la dose quotidienne de
    100 mg/kg de poids corporel.  Chez des rats exposés au composé à la
    dose de 115 mg/m3 (578 ppm), 6 h par jour, 5 jours par semaine et
    ce, pendant 13 semaines, on a noté un moindre gain de poids et des
    effets pathologiques au niveau du nez.  Cette étude a permis d'établir
    que la dose sans effets histopathologiques observables au niveau de la
    cavité nasale était égale à 23 mg/m3 (3 ppm).  Lors d'une étude
    analogue sur des souris, on a observé le même genre d'effets
    histopathologiques avec la même dose sans effets observables
    (23 mg/m3, 3 ppm).

         On a administré du 1,2-dibromoéthane par gavage à des rats selon
    les modalités suivantes: 37-107 mg/kg de poids corporel (moyenne
    pondérée par rapport au temps) tous les jours pendant 49-90 semaines;
    de même des souris en ont reçu pendant 15-17 mois dans leur eau de
    boisson à raison de 103-117 mg/kg de poids corporel.  A la suite de
    cela, on a observé des anomalies non malignes telles qu'une
    dégénérescence hépatique, une atrophie testiculaire, ainsi qu'une
    acanthose et une hyperkératose au niveau de la portion cardiaque de
    l'estomac.  Après exposition par la voie respiratoire de rats et de

    souris à des doses de 77-388 mg/m3 pendant 6 à 18 mois, on a observé
    une inflammation de la trachée et de la cavité nasale, une
    dégénérescence testiculaire et une nécrose hépatique.

         Après exposition par la voie respiratoire, le 1,2-dibromoéthane
    ne se révèle pas tératogène pour le rat ou la souris.  Chez des rats
    qui en avaient reçu par la voie intrapéritonéale une dose  quotidienne
    de 1,25 mg/kg de poids corporel (mâles) ou de 509 mg/m3 (voie
    respiratoire, femelles, 4 h/jour, 3 jours par semaine, du jour 3 au
    jour 20 de la gestation), on a constaté une action toxique sur le
    développement (anomalies de la coordination motrice).  Le
    1,2-dibromoéthane a également eu une action délétère sur la fonction
    de reproduction de rats (chez les mâles, dans les conditions
    d'exposition suivantes: 684 mg/m3, 7 h/jour, 5 jours par semaine,
    pendant 10 semaines; chez les femelles, aux doses et pendant les
    durées suivantes: 614 mg/m3, 7 h/jour, 7 jours par semaine, pendant
    3 semaines).  La dose sans effet observable pour ce paramètre était
    égale à 300 mg/m3 chez les deux sexes.  Lors d'une étude où des rats
    mâles ont reçu pendant 90 jours une alimentation  contenant le
    composé, on a constaté que la dose sans effet observable sur la
    capacité de reproduction était égale à 50 mg/kg et par jour.  On a
    observé une atteinte de la spermatogénèse chez des taureaux après
    administration du composé par voie orale à la dose quotidienne de
    2 mg/kg pendant moins de 21 jours et chez des lapins après injection
    sous-cutanée du produit à raison de 15 mg/kg pendant 5 jours.  Chez
    des poules qui avaient reçu pendant 12 semaines une nourriture
    contenant du 1,2-dibromoéthane à la dose de 12,5 mg/kg, on a constaté
    une diminution du calibre des oeufs.

         Le composé n'a pas entraîné de mutations léthales dominantes chez
    des souris ou des rats, ni produit d'aberrations chromosomiques ou de
    micronoyaux dans les cellules de la moëlle osseuse de souris traitées
     in vivo.  Toutefois, il s'est révélé mutagène dans les épreuves sur
    bactéries et a provoqué des ruptures de l'ADN monocaténaire.  On a
    constaté  in vivo comme  in vitro, que les métabolites du
    1,2-dibromoéthane étaient fixés à l'ADN par des liaisons covalentes. 
    Des échanges entre chromatides soeurs, des mutations et une synthèse
    non programmée de l'ADN, ont été observées dans des cellules humaines
     in vitro.

         Des études de cancérogénicité ont été effectuées selon le schéma
    suivant: souris et rats ayant reçu par gavage une dose quotidienne de
    1,2-dibromoéthane égale à 37-107 mg/kg de poids corporel (en moyenne
    pondérée par rapport au temps), pendant 49-90 semaines; souris ayant
    reçu dans leur eau de boisson une dose de 1,2-dibromoéthane de
    103-117 mg/kg de poids corporel, quotidiennement pendant 15-17 mois;
    souris et rats exposés à une dose de 10-40 ppm pendant 6-18 mois par
    voie respiratoire ou encore, souris badigeonnées au 1,2-dibromoéthane
    pendant 400-594 jours, 3 fois par semaine à raison de 25-50 mg/souris. 
    Ces études ont montré que le 1,2-dibromoéthane était cancérogène pour
    les rats et les souris et provoquait l'apparition de tumeurs au niveau

    de divers organes, soit au point d'application, soit à distance de ce
    point: cavité nasale, poumons, estomac, foie, peau, système
    circulatoire et glandes mammaires.  Dans de nombreux cas, il y avait
    réduction du temps de latence des tumeurs.

    6.  Effets sur l'homme

         Le 1,2-dibromoéthane peut avoir des effets nocifs sur le système
    respiratoire, le système nerveux et les reins.

         Ainsi, une seule exposition, par la voie respiratoire, à ce
    composé (215 mg/m3, soit 28 ppm) pendant 30 min ou davantage, s'est
    révélée mortelle pour l'homme.  L'ingestion d'une dose de 140 mg/kg de
    poids corporel s'est également révélée mortelle.  Chez des
    travailleurs exposés de par leur profession, une exposition de longue
    durée au 1,2-dibromoéthane (5 ans), à la concentration de 0,68 mg/m3
    dans la zone de respiration, a provoqué une diminution sensible du
    nombre de spermatozoïdes et une baisse de la fécondité.

    7.  Effets sur les êtres vivants dans leur milieu naturel

         Peu d'études d'ecotoxicité aquatique ont été consacrées au
    1,2-dibromoéthane.  Les valeurs de la CL50 pour les organismes
    aquatiques sont supérieures à 5 mg/litre.  On ne possède aucune donnée
    au sujet des organismes terrestres.


    1.  Identidad, propiedades físicas y químicas y métodos analíticos

         El 1,2-dibromoetano (dibromuro de etileno) es un líquido incoloro
    (punto de fusión: 9,9°C; punto de ebullición: 131,4°C) con olor
    similar al del cloroformo.  Es muy volátil, con una presión de vapor
    de 1,47 kPa (11 mmHg) a 25°C y una densidad de vapor, en comparación
    con el aire, de 6,1.  El 1,2-dibromoetano es invisible en la mayor
    parte de los disolventes orgánicos.  Su solubilidad en el agua es de
    4,3 g/litro a 30°C.

         El 1,2-dibromoetano existente en el aire ambiental se analiza por
    cromatografía de gases tras su absorción por polímeros porosos,
    seguida por una rápida desasorpción térmica.  Para las muestras de
    agua se utiliza un método de «purge-and-trap».  Los residuos de
    1,2-dibromoetano presentes en los alimentos y en otros medios pueden
    extraerse mediante disolventes o ser sometidos a un análisis
    automatizado  de la fase gaseosa superior en condiciones criogénicas,
    seguido de análisis por cromatografía de gases y cromatografía líquida
    de alta resolución, previa derivación.

    2.  Fuentes de exposición humana y ambiental

         El 1,2-dibromoetano se utiliza para eliminar las sustancias
    antidetonantes derivadas del plomo presentes en la gasolina. 
    Asimismo, se utiliza como fumigante de suelos y para la fumigación de
    granos y frutas.  El consumo reducido de gasolina con plomo en algunos
    países y la anulación de inscripciones para la utilización de
    1,2-dibromoetano con fines agrícolas ha reducido la exposición humana
    a esa sustancia.  Sin embargo, aún se utiliza para eliminar el plomo
    de la gasolina en algunos países, como fumigante, para fines de
    cuarentena, como disolvente y como producto intermedio en las
    sustancias químicas industriales.

    3.  Niveles ambientales y degradación

         Las concentraciones de 1,2-dibromoetano medidas en el aire
    abarcan desde niveles indetectables hasta otros expresados en ng/m3
    en las zonas urbanas.  En zonas de explotación agrícola extensiva se
    han detectado concentraciones de 1,2-dibromoetano superiores a
    0,2 µg/litro en aguas subterráneas y a 50 µg/litro en aguas
    superficiales.  Aunque el 1,2-dibromoetano se filtra a través de la
    tierra, parte de él queda retenido en la matriz del suelo y puede
    contaminar posteriormente los pozos de riego.  Se carece de
    información suficiente sobre la descomposición microbiana en los

         La alta volatilidad del 1,2-dibromoetano determina que el
    principal receptor ambiental sea la atmósfera.  La fotólisis
    estratosférica puede dar lugar a la formación de productos de
    descomposición potencialmente destructores del ozono.

    4.  Cinética y metabolismo en animales de laboratorio

         El 1,2-dibromoetano se absorbe rápidamente por vía oral y cutánea
    y por inhalación.  Se cree que los metabolitos desempeñan una función
    importante en la toxicidad de esa sustancia para los seres humanos. 
    El 1,2-dibromoetano se puede metabolizar por vía oxidativa (sistema
    del citocromo P-450) y por vía conjugada (sistema de la glutatión
     S-transferasa).  Según parece, dos metabolitos reactivos, el
    bromacetaldehído formado por oxidación y el ion de tiranio formado por
    conjugación interactúan con las macromoléculas celulares (proteínas,
    ADN) para formar productos de enlace covalente.

    5.  Efectos en mamíferos de laboratorio y en sistemas de pruebas
        in vitro

         El 1,2-dibromoetano tiene una toxicidad aguda para los animales
    (DL50 por vía oral en ratas de 146-417 mg/kg de peso corporal,
    CL50 por inhalación en ratas de 3080 mg/m3 tras una exposición de
    2 h, y una mortalidad observada tras la aplicación cutánea de
    210 mg/kg a conejos).  Los efectos tóxicos del 1,2-dibromoetano se
    observaron principalmente en el hígado y en los riñones.  La
    inhalación de vapor de 1,2-dibromoetano produjo irritación nasal y
    depresión del sistema nervioso central.  En ratas expuestas a
    concentraciones de 1540 mg/m3 a 77 000 mg/m3 (200 a 10 000 partes
    por millón), con una duración de la exposición de 0,1 a 16,0 h, se
    produjeron muertes en todos los grupos, en función de la concentración
    y del tiempo.  El 1,2-dibromoetano (solución al 1,0%) causó irritación
    de la piel abdominal afeitada e irritación ocular en conejos.

         Tras la exposición oral subcrónica, se observaron efectos
    mortales y menor adquisición de peso en ratas y ratones con dosis de
    100 mg/kg de peso corporal al día. Asimismo, se observaron reducciones
    en la adquisición de peso y efectos patológicos nasales en ratas
    expuestas al 1,2-dibromoetano en una proporción de 115 mg/m3
    (578 partes por millón) durante 6 h al día y 5 días por semana a lo
    largo de 13 semanas.  El NOEL relativo a las alteraciones
    histopatológicas de la cavidad nasal fue de 23 mg/m3 (3 ppm) en ese
    estudio.  En otro similar realizado en ratones se observaron los
    mismos cambios patológicos, también con un NOEL de 23 mg/m3 (3 ppm).

         Tras la administración por sonda a ratones o ratas de
    1,2-dibromoetano en dosis de 37 a 107 mg/kg de peso corporal al día
    (promedio ponderado por el tiempo) durante un periodo de 49 a
    90 semanas, o la administración a ratones en dosis de 103 a 117 mg/kg
    de peso corporal al día en el agua de beber durante un periodo de 15 a
    17 meses, se observaron cambios no carcinogénicos tales como

    degeneración hepática, atrofia testicular, y acantosis e
    hiperqueratosis del preestómago, además de mortalidad.  Tras la
    exposición por inhalación (ratones o ratas expuestos a dosis de 77 a
    388 mg/m3 durante un periodo de 6 a 18 meses), se observaron
    inflamación de la tráquea y de la cavidad nasal, degeneración
    testicular y necrosis hepática.

         El 1,2-dibromoetano no resultó teratogénico en ratas o ratones
    tras la exposición por inhalación.  Se observó toxicidad para el
    desarrollo (daños en el desarrollo de la coordinación motora) en la
    descendencia de ratas macho tratadas por vía intraperitoneal con
    1,25 mg/kg de peso corporal al día y en la descendencia de ratas
    hembra tratadas mediante la inhalación de 509 mg/m3 durante 4 h al
    día y 3 días por semana desde el día 3 al día 20 de la gestación.  El
    1,2-dibromoetano influyó en el comportamiento reproductivo de las
    ratas (en los machos, con un nivel de exposición de 684 mg/m3
    durante 7 h al día y 5 días/semana a los largo de 10 semanas, y en las
    hembras con un nivel de exposición de 614 mg/m3 durante 7 h al día y
    7 días por semana a lo largo de 3 semanas).  El NOEL para ese
    parámetro fue de 300 mg/m3 en ambos sexos.  El NOEL para el
    comportamiento reproductivo de las ratas macho en un estudio de
    alimentación fue de 50 mg/kg al día tras una exposición de 90 días. 
    La espermatogénesis resultó afectada en toros tras la administración
    de dosis orales de 2 mg/kg al día durante menos de 21 días, y en
    conejos tras la inyección subcutánea de 15 mg/kg durante 5 días.  La
    administración de 1,2-dibromoetano a gallinas a través de la
    alimentación causó una disminución del tamaño de los huevos tras la
    exposición a 12,5 mg/kg al día durante 12 semanas.

         El 1,2-dibromoetano no indujo mutaciones dominantes letales en
    los ratones o las ratas, ni produjo aberraciones cromosómicas o
    micronúcleos en las células de médula ósea de ratones tratados
     in vivo.  Sin embargo, resultó mutagénico en análisis bacterianos y
    causó roturas del ADN de una sola hebra.  Los metabolitos del
    1,2-dibromoetano se fijaron al ADN mediante enlaces covalentes,
     in vivo e  in vitro.  En células humanas  in vitro se observó
    intercambio de cromátides hermanas, mutaciones y síntesis de ADN no

         Los estudios de carcinogenicidad en los que se administró la
    sustancia por vía oral (ratones y ratas sometidas mediante sonda a
    dosis de 37 a 107 mg/kg de peso corporal al día (promedio ponderado
    por el tiempo) durante un periodo de 49 a 90 semanas; y ratones a los
    que se administró 1,2-dibromoetano en el agua de beber en dosis de
    103 a 117 mg/kg de peso corporal al día durante un periodo de 15 a
    17 meses), mediante exposición inhalacional (ratones y ratas expuestos
    a dosis de 10 a 40 partes por millón durante un periodo de 6 a
    18 meses) o por vía cutánea de 25 a 50 mg/ratón, 3 veces por semana
    durante un periodo 400 a 594 días) mostraron que el 1,2-dibromoetano
    es carcinogénico para las ratas y los ratones y causa tumores en
    diversos órganos (tanto en la zona de aplicación como en zonas

    distantes, entre ellas, la cavidad nasal, los pulmones, el estómago,
    el hígado, la piel, el sistema circulatorio y las glándulas mamarias). 
    En muchos casos reduce el periodo de latencia de tumores en

    6.  Efectos en el ser humano

         El 1,2-dibromoetano puede producir efectos adversos en los
    sistemas respiratorio, nervioso y renal.

         La exposición aguda (única) a la inhalación de 1,2-dibromoetano
    en dosis de 215 mg/m3 (28 ppm) durante 30 minutos o más ha resultado
    mortal para el ser humano. La ingestión de 140 mg/kg de peso corporal
    resultó asimismo mortal.  La exposición duradera (5 años) de la zona
    respiratoria al 1,2-dibromoetano a una concentración de 0,68 mg/m3
    redujo notablemente la densidad de espermatozoides y la fecundidad en
    los trabajadores expuestos en su entorno laboral.

    7.  Efectos en otros organismos en el medio ambiente

         Se han realizado pocos estudios sobre la ecotoxicidad acuática
    del 1,2-dibromoetano.  La CL50 para los organismos acuáticos es
    superior a 5 mg/litro.  No se dispone de información acerca de los
    organismos terrestres.

    See Also:
       Toxicological Abbreviations
       Dibromoethane, 1,2- (WHO Pesticide Residues Series 1)