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    Published under the joint sponsorship of
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    and the World Health Organization

    World Health Orgnization
    Geneva, 1987

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     2.1. Identity
     2.2. Physical and chemical properties
     2.3. Analytical methods


     3.1. Natural occurrence
     3.2. Man-made sources
          3.2.1. Production, disposal of waste, and uses
        Production levels
        Production processes
        Disposal of wastes
     3.3. Transport and fate in the environment


     4.1. Environmental levels
          4.1.1. Water
          4.1.2. Air
          4.1.3. Food
          4.1.4. Industrial wastes
     4.2. General population exposure
     4.3. Occupational exposure


     5.1. Absorption
     5.2. Distribution
     5.3. Metabolism
     5.4. Excretion and elimination


     6.1. Aquatic organisms
          6.1.1. Acute toxicity
          6.1.2. Short-term exposures
          6.1.3. Long-term exposure
          6.1.4. Bioconcentration
     6.2. Microorganisms
     6.3. Terrestrial toxicity
          6.3.1. Birds
          6.3.2. Plants


     7.1. Single exposures
          7.1.1. Inhalation and oral exposure
          7.1.2. Skin and eye irritation
     7.2. Short-term exposures
          7.2.1. Inhalation exposure
          7.2.2. Oral exposure
     7.3. Long-term exposure
          7.3.1. Inhalation exposure
          7.3.2. Oral exposure
     7.4. Carcinogenicity
          7.4.1. Inhalation exposure
          7.4.2. Oral exposure
          7.4.3. Dermal exposure
     7.5. Mutagenicity and related end-points
          7.5.1. Mutations
          7.5.2. Chromosome damage/DNA damage
          7.5.3. Cell transformation
     7.6. Reproduction and teratogenicity
          7.6.1. Inhalation exposure
          7.6.2. Oral exposure
     7.7. Immunotoxicity


     8.1. Accidental exposures
          8.1.1. Inhalation exposure
          8.1.2. Oral exposure
          8.1.3. Acute effects on eyes and skin
     8.2. Occupational exposure


     9.1. Evaluation of human health risks
     9.2. Evaluation of effects on the environment
          9.2.1. Air
          9.2.2. Water
          9.2.3. Soil






Dr B. Gilbert, CODETEC, University City, Campinas, Brazil
Professor P. Grasso, Robens Institute, University of Surrey,
    Guildford, Surrey, United Kingdom
Mr M. Greenberg, Environmental and Criteria Assessment Office,
    US  Environmental Protection Agency MD-52, Research Triangle
    Park, North Carolina, USA (Rapporteur)
Professor M. Ikeda, Department of Environmental Health, Tohoku
    University School of Medicine, Sendai, Japan (Chairman)
Dr N.N. Litvinov, A.N. Sysin Institute of General and Community
    Hygiene,  USSR  Academy  of Medical  Science,  Moscow,  USSR
Dr G.B. Maru, Carcinogenesis Division, Cancer Research Insti-
    tute, Tata Memorial Center, Parel, Bombay, India
Professor M. Noweir, Occupational Health Research Centre, High
    Institute   of  Public  Health,  University  of  Alexandria,
    Alexandria, Egypt
Dr E. Rauckman, Carcinogenesis and Toxicologica Evaluation
    Branch, National Institute of Environmental Health Sciences,
    National  Toxicology Program, Research Triangle  Park, North
    Carolina, USA
Professor D.J. Reed, Environmental Health Sciences Center,
    Oregon State University, Corvallis, Oregon, USA
Dr E. Rosskamp, Institute for Water, Soil and Air Hygiene of
    the Federal Ministry of Health, Berlin (West)
Dr S. Susten, Document Development Branch, Division of Standards
    Development  and Technology Transfer, National Institute for
    Occupational Safety and Health, Cincinnati, Ohio, USA


Professor F. Valic, Andrija Stampar School of Public Health,
    University of Zagreb, Zagreb, Yugoslavia (Secretary)a
Dr T. Ng, Office of Occupational Health, World Health Organ-
    ization, Geneva, Switzerland
Ms F. Ouane, International Register of Potentially Toxic
    Chemicals,  United  Nations  Environment Programme,  Geneva,
Dr T. Vermeire, National Institute of Public Health and
    Environmental  Hygiene,  Bilthoven,  Netherlands  (Temporary
Mr J. Wilbourn, Unit of Carcinogen Identification and
    Evaluation,  International  Agency  for Research  on Cancer,
    Lyons, France


a   IPCS Consultant.


    Every  effort has been  made to present  information in  the
criteria  documents  as  accurately as  possible  without unduly
delaying their publication.  In the interest of all users of the
environmental  health  criteria  documents, readers  are  kindly
requested  to communicate any errors  that may have occurred  to
the Manager of the International Programme on  Chemical  Safety,
World  Health Organization, Geneva,  Switzerland, in order  that
they  may  be  included in  corrigenda,  which  will  appear  in
subsequent volumes.

                             *    *    *

    A  detailed data profile  and a legal  file can be  obtained
from  the International Register of Potentially Toxic Chemicals,
Palais des Nations, 1211 Geneva 10, Switzerland  (Telephone  no.
988400 - 985850).


    A  WHO  Task  Group  on  Environmental  Health  Criteria for
1,2-Dichloroethane  met in Geneva  from 25 to  30 August,  1986.
Professor F. Valic opened the meeting on behalf of the Director-
General.  The Task Group reviewed and revised the draft criteria
document  and made an evaluation of the health risks of exposure
to 1,2-dichloroethane.

    The  drafts of this document were prepared by DR T. VERMEIRE
of  the National Institute  of Public Health  and  Environmental
Hygiene, Bilthoven, the Netherlands.

    The  efforts  of  all who  helped  in  the  preparation  and
finalization of the document are gratefully acknowledged.

                                * * *

    Partial  financial  support  for  the  publication  of  this
criteria  document  was kindly  provided  by the  United  States
Department of Health and Human Services, through a contract from
the   National  Institute  of  Environmental   Health  Sciences,
Research   Triangle   Park,  North   Carolina,   USA  -   a  WHO
Collaborating  Centre  for  Environmental Health  Effects.   The
United   Kingdom  Department  of  Health   and  Social  Security
generously supported the costs of printing.


    1,2-Dichloroethane  (DCE)  is  a colourless,  flammable, and
volatile liquid that decomposes slowly in the presence  of  air,
moisture, and light; its vapour decomposes in flame and  on  hot
surfaces   yielding  hydrogen  chloride,  phosgene,   and  other
chlorine-containing compounds.

    Sensitive  analytical  methods  have been  developed for the
determination  of  1,2-dichloroethane using  gas chromatography.
Detection  limits are  in the  range of  0.02 - 1.2 µg/m3   air,
0.001  - 10 µg/litre   water, 25 µg/litre   blood, and  44 - 100
µg/kg   food  or  tissue.   Methods   used   for   air  analysis
include  direct ultraviolet or infrared  spectroscopy and direct
reading colorimetry tubes.

    World production of 1,2-dichloroethane in 1981 was estimated
to be about 23 000 kilotonnes.  In 1983, the chemical was ranked
as  the 15th highest volume chemical produced in the USA.  It is
principally  used  in the  synthesis  of vinyl  chloride.  Human
exposure  mainly occurs at, and  in the vicinity of,  production
facilities,  through skin contact and inhalation.  Almost 60% of
the total emission (about 0.2% of production) is estimated to be
lost to the air, water, and soil from these  industries;  nearly
one-third  of this loss  is estimated to  occur via disposal  of
heavy  ends  in vinyl  chloride  production (EDC  tars).   Human
exposure  to the vapour as  a result of dispersive  uses of 1,2-
dichloroethane  can occur when  it is used  in gasoline or  as a
solvent  or seed fumigant.   Losses via dispersive  uses account
for  about 40% of the total emission.  Emissions also occur from
contaminated water and from waste-disposal sites.

    Average  concentrations found in the  vicinity of production
facilities  have been below 40 µg/m3.    In the air  of  cities,
average  concentrations  of  between 0.3  and 6.5 µg/m3,  with a
reported maximum of 30 µg/m3,  have been measured.  Only two old
reports  on  small  groups  of  occupationally-exposed  men  are
available, indicating exposure levels of 40 - 800 mg/m3.

    In  air, 1,2-dichloroethane is  degraded by sunlight  fairly
rapidly  yielding  mainly  carbon oxides  and hydrogen chloride.
This prevents accumulation in the atmosphere.

    Emissions of 1,2-dichloroethane entering water may amount to
about  0.1%  of  production volume;  in  addition,  some of  the
emissions from EDC tars will also contaminate  water.   However,
average   levels   in   drinking-water  are   generally  below 1
µg/litre.     The   main    removal  process   from   water   is
evaporation,  since  chemical  degradation, biodegradation,  and
bioconcentration are unlikely to occur.

    LC50 values for fish exposed for 1 - 4 days  ranged  between
85 and 550 mg/litre water, with bioaccumulation unlikely.  A no-
observed-adverse-effect  level  of  11 mg/litre  was  found  for

 Daphnia  magna, following  long-term  exposure.   1,2-Dichloro-
ethane  does  not  pose a  signficant  hazard  for  the  aquatic
environment,  except  in  cases  of  accident  or  inappropriate

    1,2-Dichloroethane is readily absorbed via the dermal, oral,
or inhalation routes.

    After  oral administration, blood  levels peak earlier  with
low  than with  high doses,  and are  5 times  higher with  oral
exposure  to doses of  the order of  150 mg/kg body  weight than
with   similar   inhalation   exposure.   After   inhalation,  a
disproportionate  increase in blood level occurs with increasing
dose.   At an exposure level of 3200 mg/m3, a steady blood level
is  achieved after 2  - 3 h.  After  oral dosing,  1,2-dichloro-
ethane  showed  a  preference  for  adipose  tissue  and  liver.
Following   inhalation,  accumulation  was  mainly  observed  in
adipose  tissue, but  not in  the liver.   At higher  levels  of
exposure, relatively more 1,2-dichloroethane accumulated.

    1,2-Dichloroethane  was found in  fetal tissues and  in  the
placenta, when pregnant rats were exposed by inhalation  to  the
compound at 1000 mg/m3 for 3 days.

    When  administered orally, parenterally, or by inhalation to
rats  and  mice, it  is  extensively biotransformed  to  urinary
metabolites (55 - 90%).  Relatively more is metabolized at lower
doses.   Metabolism may occur via  two known pathways:  one  via
cytochrome   P-450-mediated   oxidation   and  the   other   via
glutathione   conjugation.   The  former  pathway  involves  the
formation of 2-chloroacetaldehyde and 2-chloroethanol.  Although
this  pathway  appears  to be  important  in  vitro in  producing
intermediates  capable  of interacting  with  DNA, it  does  not
appear  to  be  important  in vivo.   Reactive  intermediates are
formed  when  1,2-dichloroethane is  metabolized via glutathione
conj ugation.  The identity of these intermediates has  not  been
confirmed,  though some evidence suggests the formation of S-(2-
chloroethyl)  glutathione  and its  alkylating episulfonium ion,
which,  by reaction with DNA,  yield an indicated adduct,  S-[2-
(N7-guanyl)-ethyl]  glutathione.

    Excretion  of  1,2-dichloroethane  or its  metabolites  from
rodents  is rapid.  At least 89% of the body burden was excreted
via the lungs or urine within 24 h in intraperitoneally-injected
mice and within 48 h in orally-dosed mice.

    The oral LD50 was found to be 413 - 489 mg/kg body weight in
the  mouse,  680 - 850  mg/kg body weight  in the rat,  and 2500
mg/kg  body weight in the dog.  The 6-h LC50 was estimated to be
1060  mg/m3  in  the mouse  and 5100  - 6660  mg/m3 in  the rat.
Deaths occurred within a narrow range of concentrations.

    In an exposure-response inhalation study on rats, no adverse
effects were observed in a 7-h exposure to 1200 mg/m3.   At  the
next  higher  exposure level  (2400  mg/m3), depression  of  the

central  nervous system (CNS) was observed, and some of the rats
died after 7 h.  As the exposure levels increased, depression of
the   CNS  became  more   severe,  and  deaths   occurred  after
progressively   shorter   exposure  periods.    At  the  highest
concentration (81 000 mg/m3), rats became comatose and some died
within  0.3 h.  Liver and kidney damage was found in most of the
animals that died.

    After  single  oral doses  of 615 -  770 mg/kg body  weight,
liver  damage was observed  histologically in rats.   Myocardial
oedema and damage to coronary vessels were observed.

    In  3  short-term  inhalation studies,  various species were
exposed  to  concentrations  of between  405  and  3900 mg  1,2-
dichloroethane/m3  air, 6 or 7 h per day, for 5 days/week.  Mice
and  rats  appeared  to  be  more  sensitive  than  guinea-pigs,
rabbits,  monkeys,  dogs,  and cats.   The  overall no-observed-
adverse-effect  level for exposure periods  ranging from 4 to  9
monhts in the rat was about 400 mg/m3.  Signs  of  intoxication,
including  central  nervous  system depression  and  death, were
observed  in all species exposed to the higher concentrations of
between  1620 and 3900  mg/m3.  For rats,  liver damage,  mainly
consisting of fatty changes, was observed after exposure to 1540
mg/m3 for up to 12 weeks, 1620 mg/m3 for up to 8 weeks, and 1900
mg/m3  for  up to  1 week.  In  rats, guinea-pigs, and  mice, an
increased mortality rate was observed at concentrations  of  730
mg/m3  or  more.   In rabbits,  there  was  an increase  in  the
mortality rate from 1540 mg/m3 and, in monkeys, from 1620 mg/m3.
Dogs and cats only showed increased mortality at 3900 mg/m3.

    Repeated oral administration of 1,2-dichloroethane at a dose
of 300 mg/kg body weight was lethal for rats after 5  doses  and
produced  necrosis and fatty changes  in the liver.  No  effects
were observed when the chemical was given orally to rats  at  10
mg/kg body weight daily for 90 days or at 150 mg/kg, 5 times per
week, for 2 weeks.

    1,2-Dichloroethane   is   weakly   mutagenic   in Salmonella
typhimurium TA 1535, both in the absence of, and in the presence
of, a microsomal activation system.  However, in the presence of
cytosolic   glutathione-S-transferase,   a   stronger   positive
response  was  obtained.   Negative results  were  obtained with
strains  TA 1537,  TA 1538,  and TA 98.   Mutagenicity occurs in
fungi,  Drosophila, and  mammalian cells  in vitro.  In  two human
cell  lines exposed to 1,2-dichloroethane, the incidence of gene
mutations  was  found  to  increase  with  increasing  levels of
glutathione-S-transferase.  Micronuclei or dominant lethals were
not  induced, and a weak mutagenic effect was reported in a spot
test  on  mice.   DNA damage  has  been  observed  in  bacteria,
mammalian   cells  in   vitro, and  in   mammals  in  vivo.   1,2-
Dichloroethane  did not induce cell transformation in one of two
assays,  and enhanced virus-induced  cell transformation in  the

    1,2-Dichloroethane   is  carcinogenic  in  B6C3F1  mice  and
Osborne-Mendel  rats following administration  of doses of  50 -
300 mg/kg body weight, given by gavage, in oil.  In  male  rats,
squamous   cell  carcinomas  of  the  forestomach,  subcutaneous
fibromas,  and haemangiosarcomas in  several organs (mainly  the
spleen)  were produced following gavage; in female rats, mammary
gland  fibromas and mammary adenocarcinomas  were increased.  In
mice, increased incidences of hepatocellular carcinomas in males
and  mammary gland adenocarcinomas in females, and lung adenomas
in  both sexes were observed.   No increase in tumour  incidence
was  reported in inhalation  studies on Swiss  mice and  Sprague
Dawley rats exposed to concentrations of up to 607 mg/m3.

    A prolongation of the estrus cycle, an increase in embryonal
mortality,  pre-implantation  losses, and  haematomas were found
when  female  rats  were exposed  to  15 mg/m3,  4 h  per day, 6
days/week,  for 4 months prior  to mating and during  pregnancy.
While the fetal toxicity of 1,2-dichloroethane was not confirmed
at  higher exposure levels,  severe toxic effects  on rats  were
observed   and  all  implantation  sites   resorbed.   No  fetal
abnormalities  were observed in the  rabbit.  Oral adminstration
to  male and female  rats of up  to 35 mg  1,2-dichloroethane/kg
body  weight  per  day, via the food, for up to 2 years, did not
affect  reproduction.   No  effects on  fertility  or  gestation
index,  and  no  teratological effects  were  observed  in a  2-
generation  study  on  mice  treated  with  5  -  50   mg   1,2-
dichloroethane/kg  body weight per day,  via drinking-water, for
up to 25 weeks.

    1,2-Dichloroethane   may  cause  severe  corneal  damage  in
animals, but no gross skin reactions occurred in a 12-h occluded
patch  test  on guinea-pigs.   Corneal  opacity was  observed in
dogs, following subcutaneous injection.

    In  man, immersion  of the  hands for  4 h  at  intermittent
intervals  caused  severe  dermatitis.  Conjunctivitis  has been
reported  from  exposure to  vapour,  and corneal  opacity  from
accidental ingestion.

    Two  early reports describe human  effects from occupational
exposure,  and  a  number  of  fatal  case   histories   through
accidental  oral ingestion.  Complaints  referrable to the  CNS,
liver,  and  gastrointestinal  tract were  reported  in  workers
occupationally  exposed to concentrations  of 1,2-dichloroethane
of  250 -  800 mg/m3.   Similar complaints  were  reported  less
frequently  by workers  exposed to  concentrations of  40 -  150
mg/m3.   Liver  and  bile-duct disorders,  neurotic  conditions,
autonomous dystonia, neuromyalgia, and hyperthyroidism have been
reported in workers exposed to 5 - 150 mg 1,2-dichlorethane/m3.

    Accidental  ingestion  of  10  -  250  g  1,2-dichloroethane
resulted  in  death in  all  instances.  Haemorrhage  at various
sites,  depression of  the CNS,  liver and  kidney  damage,  and
pulmonary oedema occurred.

    Making  an overall evaluation, in the absence of human data,
and  taking into account that: (a) 1,2-dichloroethane produces a
reactive  intermediate that alkylates DNA, (b) it is positive in
a number of mutagenicity tests  in vitro, though weakly  so,  and
(c)  both rare and common tumours are produced in rats and mice,
it would be prudent to consider 1,2-dichloroethane as a possible
human  carcinogen.  Thus, it  should be regarded,  for practical
purposes,  as if it presented  a carcinogenic risk for  man.  In
evaluating   reproduction  hazards  and  teratogenicity,  it  is
necessary  to rely on the limited data available from laboratory
investigations  since there are  no human data.   The weight  of
evidence   does   not   suggest  that   exposure  to  prevailing
environmental   levels  poses  a  reproductive   or  teratogenic

    Degradation  processes are rapid  enough to prevent  accumu-
lation of 1,2-dichloroethane in the atmosphere.  Except  in  the
case  of accidents or inappropriate disposal, 1,2-dichloroethane
does   not  present  a   significant  hazard  for   the  aquatic
environment.   Available data are not sufficient to evaluate its
effects on soil.

    Further  studies are needed  on: (a) DNA  alkylation (adduct
identification);  (b) sub-chronic toxicity by  various routes of
exposure;  (c)   assessment  of the  extent  to  which EDC  tars
contribute  to  contamination  of groundwater  by  1,2-dichloro-
ethane;   and  (d)   dose-response  on  sensitive,  commercially
important fish species (particularly studies relevant to EDC tar


2.1  Identity

Structural formula:                  H   H
                                     |   |
                                     |   |
                                     H   H

Molecular formula:                   C2H4Cl2

Abbreviation:                        EDC

Synonyms:                            alpha,beta-dichloroethane, 1,2-bi-
                                     chloroethane, ethane dichloride,
                                     ethylene chloride, ethylene dichlor-
                                     ide, 1,2-ethylene dichloride, sym-

Common trade names:                  Borer-Sol, Brocide, Destruxol
                                     Dichlor-emulsion, Dichlor-mulsion,
                                     Dutch Liquid, Dutch Oil, ENT 1656,
                                     Gaze Olefiant

CAS registry number:                 107-06-2

Conversion factor:                   1 ppm = 4.05 mg/m3 air at 25 °C and
                                     101.3 kPa (760 mmHg)

2.2  Physical and Chemical Properties

    1,2-Dichloroethane is a flammable compound that burns with a
smoky flame.  When dry, 1,2-dichloroethane is stable at ordinary
temperatures.   In the presence of air, moisture, and light, the
liquid  decomposes slowly, yielding hydrogen  chloride and other
corrosive  products.   Vapour-air mixtures  are readily ignited.
In  a flame, or at a hot surface, 1,2-dichloroethane decomposes,
yielding   hydrogen  chloride,  phosgene,  and  other  chlorine-
containing  compounds.   Some  physical characteristics  of 1,2-
dichloroethane are given in Table 1.

2.3  Analytical Methods

    A  summary of relevant methods  of sampling and analysis  is
presented in Table 2.

Table 1.  Some physical characteristics of 1,2-dichloroethane

Physical state             liquid

Colour                     colourless

Taste                      sweet

Odour                      chloroform-like

Odour threshold            25 - 450 mg/m3, for perception;
                           162 - 750 mg/m3 for recognitiona

Relative molecular mass    98.96

Melting point              -35 °C

Boiling point              83 °C

Water solubility           8.69 g/litre, 20 °C

log n-Octanol/water        1.48
partition coefficient

Relative density           1.23, 20 °C

Relative vapour density    3.42

Vapour pressure            8.53 kPa (64 mmHg), 20 °C

Flash point                13 °C (closed cup)

Flammable limits           0.25 - 0.64 g/litre, 6 to 16 vol %

a    From: May (1966), Hellmann & Small (1974), 
     and Kleinschmidt (1983).

Table 2.  Sampling, preparation, analysis
Medium  Sampling method       Analytical method   Detection      Sample   Comments              Reference
                                                   limit          size

air     manual sampling       colorimetry,                                not specific          Saltzman 
        pump                  direct reading                                                    (1972)
                              indicating tube

air     continuous monit-     UV-photodetection   approximately           not specific, contin- Nelson & 
        oring with or                             4 mg/m3                 uous monitoring por-  Shapiro
        without built-in                                                  table halide meter    (1971)

air     continuous monitoring infra-red spectro-                          subject to interfer-  Baretta 
        and breath analysis   scopy                                       ence by similar com-  et al.
                                                                          pounds                (1969)

air     sampling on charcoal  desorption by car-  0.013 ug       3 - 40                         NIOSH 
                              bon disulfide, gas  per sample     litre                          (1977)
                              chromatography with
                              flame ionization

air     sampling on charcoal  thermal desorption; 1.2 ug/m3      10 litre                       Parkes 
        or Chromosorb         gas chromatography                                                et al.
                              with flame ioniza-                                                (1976)
                              tion detection

air                           gas chromatography  0.02 ug/m3     20 ml    direct injection      Grimsrud &
                              with mass spectro-                                                Rasmussen 
                              metric detection                                                  (1975)

air     sampling on Tenax     thermal desorption; 0.032 ug/m3                                   Krost et 
        polymeric beads       gas chromatography                                                al. (1982)
                              with mass spectro-
                              metric detection

Table 2 (contd).

water   stripping by helium   thermal desorption; 0.001 ug/litre                                Sauer 
        adsorption on Tenax   gas chromatography                                                (1981)
                              with flame ioniza-
                              tion detection or
                              mass spectrometric

water   stripping by helium   thermal desorption; 0.1 - 0.4      5 ml                           Symons 
        or nitrogen, sorption gas chromatography  ug/litre                                      et al.
        on Tenax or Chromo-   with microcoulo-                                                  (1975)
        sorb                  metric detection

water                         gas chromatography  0.5 ug/litre   0.1 ml   direct injection, di- Fujii 
                              with mass spectro-                          glycerol precolumn    (1977)
                              metric detection

water                         gas chromatography  10 ug/litre    1 litre  headspace analysis    Piet 
                              with electron cap-                                                et al.
                              ture detection                                                    (1978)

blood,                        gas chromatography  25 ug/litre    1 ml     headspace analysis of Zuccato 
tissue                        with flame ioniza-  blood,         blood,   acidified blood and   et al.
                              tion detection      50 ug/kg       0.5 g    tissue homogenate     (1980)
                                                  tissue (wet    tissue

food    extraction by         gas chromatography  100 ug/kg      5 -      analysis of fumigant  Heuser &
        acetone-water (5:1    with ß-ionization                  10 g     residues              Scudamore 
        by volume)            detection                                                         (1969)

food,   stripping by nitrogen elution by pentane, 44 ug/kg       10 g     also suitable for air Bauer 
tissue, sorption on XAD-2     gas chromatography  solid          solid,   analysis (elution by  (1981)
water                         with electron cap-  (wet weight),  2 litre  pentane-ether, detec-
                              ture detection      0.2 ug/litre            tion limit 2.9 ug/m3
                                                  water                   for a 0.3 m3 sample)


3.1  Natural Occurrence

    There  are no reports  of 1,2-dichloroethane occurring  as a
natural product.

3.2  Man-Made Sources

3.2.1   Production, disposal of waste, and uses Production levels 

    In 1983, 1,2-dichloroethane was ranked as the  15th  highest
volume  chemical  produced in  the  USA (Webber,  1984).   World
production  in 1981 was estimated to be 23 130 kilotonnes (Gold,
1980).    In  the  countries  of  the  European  Community,  the
production  capacity was estimated to be 9446 kilotonnes in 1982
(DeQuinze  et al., 1984),  an increase over  the estimated  5290
kilotonnes capacity reported for 1977 (Atri, 1984).  In the USA,
production  increased  from 4750  kilotonnes  in 1977  (Drury  &
Hammons,  1979) to 5740 kilotonnes  in 1983 (Webber, 1984).   In
Japan,  a total production  of 1800 kilotonnes  was reported  in
1976 (IARC, 1979). Production processes 

    Two processes are used, which are very often  combined  into
one  so-called "balanced process".  The  first is the vapour  or
liquid phase reaction of chlorine with ethene in the presence of
a  catalyst, usually 1,2-dibromoethane or  metal chlorides.  The
second  is  the  reaction of  ethene  with  oxygen and  hydrogen
chloride in the presence of the catalyst, copper  (II)  chloride
(Drury & Hammons, 1979).

    Most  commercial  1,2-dichloroethane is  97  - 99%  pure and
contains  approximately 0.1% by weight of alkylamines to inhibit
decomposition.   Impure  1,2-dichloroethane  may  contain  poly-
chlorinated  ethanes,  and  the  uninhibited  product  may  also
contain  chlorine  and/or  hydrogen chloride  (Drury  & Hammons,
1979; IARC, 1979).

    The  above production processes  and the production  of end-
products,  mainly  vinyl  chloride,  are  important  sources  of
emission  of 1,2-dichloroethane into the  environment.  In 1979,
in  the USA, almost 60%  of the total emission  of 12 kilotonnes
was  lost by these  industries to the  air, water, and  soil and
about  40%  via dispersive  uses as a  solvent (Seufert et  al.,
1980).   In the USA, in 1977, approximately 35% of the emissions
of  1,2-dichloroethane  associated  with the  production  of the
compound  itself and end-products  were estimated to  occur  via
disposal  of heavy ends,  the so-called EDC  tars, a mixture  of
low- and high-boiling chlorinated hydrocarbons (Gold, 1980). Disposal of wastes   

    Large  amounts of western European tars used to be dumped in
the North Sea, but incineration at sea seems to be  the  present
practice  (Jensen et al.,  1975).  In the  USA, disposal of  EDC
tars is usually by burial in a landfill or incineration (Drury &
Hammons, 1979; Gold, 1980). Uses 

    The major industrial use of the compound is in the synthesis
of  vinyl chloride (approximately 90% of the total production in
Japan  and approximately  85% of  total production  in the  USA)
(IARC,  1979).  Other chemicals produced from 1,2-dichloroethane
are  1,1,1-trichloroethane, ethyleneamines, vinylidene chloride,
trichloroethylene,  and tetrachloroethylene.  In 1977, 2 - 4% of
the total production of 1,2-dichloroethane in the USA  was  used
for  the synthesis of each  of these chemicals.  Another  2% was
used  in  the  USA  as  a  lead  scavenger  in  gasoline.   This
application  will  decline  in importance  with  the  world-wide
conversion  to unleaded  fuel.  A  small fraction  of the  total
production,  approximately 0.1% in the USA in 1977, was used for
solvent  and fumigant applications (Gold, 1980).  When used as a
fumigant,   1,2-dichloroethane  is  usually  mixed  with  carbon
tetrachloride to reduce the fire hazard, and small  portions  of
other fumigants may be added (WHO, 1972).

3.3  Transport and Fate in the Environment

    Out of the total production of 1,2-dichloroethane in the USA
in  1979,  approximately 0.2%  was estimated to  be lost to  the
atmosphere,  40% of this during  dispersive use as a  solvent or
fumigant  (Seufert  et  al., 1980).   Evaporation  from disposal
sites  also occurs.   In 1977,  losses to  the  atmosphere  were
estimated  to  be  higher  (1%  of  total  production).  Minimal
estimates  for emissions entering  water and for  emissions  via
EDC  tars  in  1977  were  0.1  and  0.5% of  total  production,
respectively (Gold, 1980).

    Evaporation  appears to be the  major pathway by which  1,2-
dichloroethane  is  lost from  water.   In a  controlled outdoor
experiment,  the  half-life  for the  disappearance from running
river water was found to be 1.4 h (Scherb, 1978).   This  agrees
well with laboratory findings (Dilling et al., 1975).   Loss  by
chemical reaction with water is insignificant (Radding  et  al.,

    In  the troposphere, rain-out and  adsorption on atmospheric
aerosols  are unlikely because of  the high vapour pressure  and
the  low solubility of the  compound (Cupitt, 1980).  The  major
part  of the 1,2-dichloroethane  is removed from  the atmosphere
via  oxidation by hydroxyl  radicals.  On the  basis of  experi-
mentally-derived  rate  constants, and  hydroxyl radical concen-
trations of 4.8 x 106 and 1.0 x 106  radicals/ml,  respectively,
half-lives  for this reaction  have been calculated  of 10  days

(Radding  et al., 1977) and 36 days (Howard & Evenson, 1976).  A
lifetime   of  53  days  was  predicted,  which  would  preclude
accumulation  in the troposphere  and transport to  the  strato-
sphere  (Howard  &  Evenson, 1976).   The  reported  degradation
products are formyl chloride, hydrogen chloride, carbon dioxide,
carbon   monoxide,  and  monochloroacetyl  chloride  (Pearson  &
McConnell,  1975;  Spence  & Hanst,  1978).  Since 1,2-dichloro-
ethane  absorbs light within  the solar spectral  region, photo-
lytic  transformation is possible (Cupitt,  1980).  However, the
extent of this reaction has not been verified experimentally.

    Slow  biodegradation  of 1,2-dichloroethane  was observed in
fresh  water,  seeded by  settled  domestic waste  water.   Non-
acclimated  cultures caused a  biological demand of  16% of  the
theoretical  oxygen demand for the compound in 10 days (Price et
al., 1974).  1,2-Dichloroethane was biodegraded in aqueous media
by acclimated aerobic mixed cultures from soil or sewage samples
(Stucki et al., 1981; Tabak et al., 1981).  An aerobic bacterium
G10,  a  Pseudomonas strain, that was  able to use  1,2-dichloro-
ethane  as a sole  source of carbon  and energy for  growth, was
isolated from samples containing a mixture of  activated  sludge
and  soil samples  (Janssen et  al., 1984).   In addition,  slow
anaerobic biodegradation, mainly to carbon dioxide, was observed
in an aqueous medium with a mixed methanogenic culture, grown on
waste   activated  sludge  with  sodium  acetate  as  a  primary
substrate (Bouwer & McCarty, 1983).

    In   soil,   1,2-dichloroethane   adsorbs  aselectively   to
bentonite clay and peat moss, but not to dolomitic limestone and
silica (Dilling et al., 1975).


4.1  Environmental Levels

4.1.1   Water 

    Concentrations  of 1,2-dichloroethane measured  at different
locations  are  summarized in  Table 3.  It  will be noted  that
Symons  et al. (1975) observed more positive samples in finished
water  than in untreated water.  This suggests treatment-related
contamination during water chlorination.

4.1.2   Air

    Concentrations  of  1,2-dichloroethane  measured in  air  at
various locations are summarized in Table 4.

4.1.3   Food

    Reports  on  1,2-dichloroethane  in food  are scarce.  Bauer
(1981)  found that  levels were  generally low  in  the  Federal
Republic  of Germany.  Milk products with added fruits contained
an  average of 0.8 µg/kg.   In Canada,  15 out of 34  samples of
spice  oleoresins  contained  between  2  and  34 mg   of   1,2-
dichloroethane, used as an extractant, per kg (Page  &  Kennedy,

    In  residue  studies, various  amounts of 1,2-dichloroethane
were found to remain in fumigated grain, depending on  the  type
of  grain and fumigation  mixture, exposure conditions,  and the
extent of subsequent ventilation (Berck, 1965, 1974).  Wheat was
found  to contain the highest residue levels, varying from 16 to
213 mg/kg,  following  common fumigation  practices.  Processing
reduces residue levels; for example, 1 - 10 mg/kg were recovered
in  ground wheat flour; less  than 2 mg/kg was present  in bread
(Lynn & Vorhes, 1957; Wit et al., 1969).  In the United Kingdom,
1  out of 281 samples of wheat contained 1,2-dichloroethane at a
level  of 290 mg/kg; in the remaining samples, the concentration
was  below the  detection limit  of 4.0 mg/kg  (Bailey  et  al.,
1982).  1,2-Dichloroethane at a level of 51 mg/kg  in  fumigated
soybeans   was  completely  extracted  by   hexane,  during  the
production of oil by solvent extraction (Storey et al., 1972).

4.1.4   Industrial wastes 

    EDC tar originating from vinyl chloride production  in  1974
(400 000  tonnes  on a  global basis) contained  up to 35%  1,2-
dichloroethane  together with other  components, seven of  which
have been identified.

Table 3.  Environmental levels in water
Type of water   Location                  Detection   Levels observeda   Reference
                                          limit       (ug/litre)

Sea water       Gulf of Mexico, open      0.001       nd                 Sauer (1981)
                near Mississippi mouth                0.05 - 0.21

                Osaka Bay                             0.69 (average)     Okamoto & 
                                                                         Tatsukawa (1981)

River water     Germany, Federal Rep-     1.0         1.0 (average)      Bauer (1978)
                ublic of; 3 rivers                    nd - 4.0

                USA; 14 industrial        1.0         5.6 (average in    Ewing et al. 
                river basins                          25% of samples)    (1977)
                                                      nd - 90

Untreated       USA; 80 drinking-water    0.2 - 0.4   nd (86%)           Symons et al. 
water           stations                              3.0 (maximum)      (1975)

                Netherlands; 232 ground-  0.5         nd (229 stations)  Zoeteman 
                water stations                        0.8 - 1.7          et al. (1979)
                                                      (3 stations)

Drinking-water  USA; 80 stations          0.2 - 0.4   nd (68%)           Symons et 
                                                      6.0 (maximum)      al. (1975)

                Japan; 5 locations        0.5         nd (4 locations)   Fujii (1977)
                                                      0.9 (1 location)

                Germany, Federal Rep-     1.0         nd                 Bauer (1981)
                ublic of; 100 cities
a  nd = not detected.

4.2  General Population Exposure

    Daily intake from urban air in the USA has been estimated to
be between 8 and 140 µg  per day (Singh et al., 1983).   In  the
Netherlands,  the  figure  is 26.5  µg   per  day  (Guicherit  &
Schulting, 1985).

    More  specifically, people  can be  exposed via  air at,  or
near, sites of production and dispersive use, notably  in  anti-
knock  agents  in gasoline.   At  12 locations  near  production
facilities   in  each  of  3  areas  in  the  USA,  average  air
concentrations gradually decreased from 61 µg/m3  to 2 µg/m3  at
distances  of  1 km  and  3 -  4 km,  respectively.   Thus, near
production  facilities, approximately 12.5 million people in the
USA  were estimated to be  exposed to average annual  concentra-
tions  of  up to 40 µg/m3   (Elfers,  1979; Kellam  & Dusetzina,

    The annual average population exposure to 1,2-dichloroethane
from  gasoline, in the USA,  has been estimated to  remain below
0.12 µg/m3 (Kellam & Dusetzina, 1980).

4.3  Occupational Exposure

    No data were available to the Task Group concerning exposure
levels   in   the   1,2-dichloroethane-  and   vinyl   chloride-
synthesizing    industries.    Poisoning   incidents   following
inhalation  or skin exposure  have been reported  frequently for
places  of work where 1,2-dichloroethane is used as a solvent or
fumigant,  but  data  concerning  exposure  levels  are   scarce
(Hadengue  & Martin,  1953; Paparopoli  & Cali,  1956; Suveev  &
Babichenko, 1969).

    1,2-Dichloroethane levels of up to 150 mg/m3  (Kozik,  1957)
and  ranging  from  40 to  800  mg/m3  (Cetnarowicz, 1959)  were
detected in industrial plants using the chemical as a solvent.

    Time-weighted  averages  of  0.1 and  1 mg/m3, respectively,
have been reported for 2 different jobs in an  anti-knock  agent
blending  plant in the USA.  The maximum exposure level measured
was 8.9 mg/m3 (Jacobs, 1980).

Table 4.  Environmental levels in air
Type of site        Location         Detection  Average       Reference
                                     limit      levels  
                                     (ug/m3)    observed

Marine              Osaka Bay                   8.4           Okamoto & 
                                                              Tatsukawa (1981)

                    Pacific                     0.168         Singh et al. 

Rural               USA              0.02       nd            Grimsrud & 
                                                              Rasmussen (1975)

                    Japan            0.05       0.3 - 0.4a    Environment Agency,  
                                                              Japan (1983)

                    United Kingdom              0.08          Clark et al. 

                    Netherlands                 0.2           Guicherit & 
                                                              Schulting (1985)

Urban               United Kingdom              0.48 - 2.14a  Tsani-Bazaca 
                                                              et al. (1981)

                    USA; 10 cities              0.335 - 6.11  Singh et al.
                                                30 (maximum)  (1983)

                    United Kingdom              1.2           Clark et al. 

                    Netherlands                 1.2           Guicherit & 
                                                              Schulting (1985)

Industrial area     USA              0.02       nd            Harkov et al. 

Heavily             USA                         5.3b          Bozzelli & 
industrialized                                  65 (maximum)  Kebbekus (1982)
                    Japan            0.05       0.09 - 3.5a   Environment Agency, 
                                                              Japan (1983)

Near gasoline       USA                         0.2b          Tsani-Bazaca 
station                                                       et al. (1982)

Gasoline station    Sweden           0.01       4.0           Jonsson & Berg 

Table 4 (contd.)
Type of site        Location         Detection  Average       Reference
                                     limit      levels  
                                     (ug/m3)    observed

Parking garage and  Sweden           0.01       2.0 - 6.5     Jonsson & Berg 
repair shop                                                   (1980)

Inside cars         Sweden           0.01       0.4 - 1.2     Jonsson & Berg 

Exhaust gases       United Kingdom              38 - 3250a    Tsani-Bazaca 
(cars)                                                        et al. (1981)

Airport vicinity    USA                         nd            Tsani-Bazaca 
                                                              et al. (1982)

Motorway            United Kingdom              0.08          Clark et al. 
a   Range of values (not average).
b   Many sites with undetectable levels of 1,2-dichloroethane were not 
    considered in the average.
nd = not detected.


5.1  Absorption

    1,2-Dichloroethane  can be found  in the blood  of  rodents,
almost immediately after dermal, oral, or inhalation exposure.

    During  a 12-h dermal  exposure of guinea-pigs  to undiluted
1,2-dichloroethane,  blood concentrations of  1,2-dichloroethane
increased  rapidly during  the first  half hour  and  then  more
slowly, up to the end of exposure (Jakobson et al.,  1982).   In
mice,  a  dermal  absorption  rate  of 47 µg/cm2   per  min  was
measured   over  the  first  15  min  following  application  of
undiluted 1,2-dichloroethane (Tsuruta, 1975).

    Oral  exposure of rats to 25 or 250 mg EDC/kg body weight in
corn  oil  produced  peak blood  levels  within  9  and  90 min,
respectively.   Blood levels appeared to  increase linearly with
exposure from 13 mg/litre at 25 mg/kg up to levels of between 30
and  70 mg/litre  at 150  and  250 mg/kg.  Small  quantities  of
metabolites,  but  no detectable  amounts of 1,2-dichloroethane,
were recovered in faeces (Sopikov & Gorshunova, 1979;  Reitz  et
al., 1982).

    During  inhalation  at  concentrations of  up to 3200 mg/m3,
steady-state blood levels of the chemical in rats  were  reached
within  2 - 3 h.  The  blood levels increased  disproportionally
with  exposure from 1.4 mg/litre at 202 mg/m3 to 8.3 mg/litre at
607 mg/m3  and  56 mg/litre  at 3200 mg/m3.   These data suggest
saturation  of  the  metabolic capacity  at  a  blood  level  of
approximately  5 mg/litre.   Peak blood  levels of 1,2-dichloro-
ethane  were almost 5  times higher following  oral exposure  to
150 mg/kg   body  weight  than  after   inhalation  exposure  to
607 mg/m3,  which appeared equivalent  to 113 mg/kg  body weight
(Sopikov  & Gorshunova, 1979; Spreafico  et al., 1980; Reitz  et
al.,  1982).  These exposure  concentrations were the  high dose
levels  for  the NCI  (1978) oral study  and the Maltoni  et al.
(1980) inhalation study.

5.2  Distribution

    The  distribution of 1,2-dichloroethane in tissue has mainly
been  investigated during exposure of  laboratory animals.  How-
ever, one report, has been identified that gives  an  indication
of  the  relative  distribution of  1,2-dichloroethane  in human
tissues  (Luznikov  et al.,  1985).  As shown  in Table 5,  1,2-
dichloroethane  concentrations  were measured  in ten biological
compartments  following  acute  oral  poisoning.   2-Chloroacet-
aldehyde,  a  metabolite  of 1,2-dichloroacetaldehyde,  was  not
detected.    In   addition  to   1,2-dichloroethane,  detectable
quantities  of  2-chloroethanol  and monochloroacetic  acid were
reported.   In this report,  the omentum and  stomach  contained
similar  high  levels  of 1,2-dichloroethane;  liver  and kidney
contents  were comparable, but approximately 10 times less.  The
detectable  amounts  of  metabolites  were  too  low   to   make

Table 5.  Levels of 1,2-dichloroethane and its metabolites determined by
gas chromatography in cadaveric organs and tissues of 15 human beings
who died after acute oral poisoninga

Tissues/       1,2-dichloro-  2-chloro-      2-chloro-      Monochloro-
organs         ethane         acetalde-      ethanol        acetic acid
               (mg/kg)        (mg/kg)        (mg/kg)        (mg/kg)

Liver            5 - 100         nd              nd             nd

Kidney           5 - 80          nd             0.1            1.0

Myocardium      10 - 150         nd         0.12 - 1.1      2.3 - 3.8

Spleen           1 - 50          nd             0.1            1.0

Omentum        100 - 950         nd             0.1            1.0

Brain           10 - 100         nd         0.12 - 0.28     1.0 - 2.0

Stomach        100 - 1000        nd         0.14 - 0.56     1.0 - 2.0

Small           10 - 90          nd         0.13 - 0.21         0

Large            5 - 60          nd              nd             nd

Blood           10 - 150         nd              nd             nd
a From: Luznikov et al. (1985).
nd = not detected.

Note:   The  analytical detection limit  for 1,2-dichloroethane and  all meta-
        bolites  except monochloroacetic  acid was  100 g/litre  or  100  g/kg
        tissue;  for monochloroacetic acid, the  limit was 100 g/litre  or 100
        g/kg tissue.
    After  oral  exposure  of rats  to  25,  50, or  150 mg 1,2-
dichloroethane/kg,  in  corn  oil,  peak  levels  of  the parent
compound  in adipose  tissue at  45 - 60 min  exceeded those  in
blood  by  3.9 - 8.3  times.  Peak levels  in the liver,  10 min
after  exposure, exceeded  those in  blood by  1.3 - 2.2  times.
This  accumulation  was  lower than  expected  at  the 2  higher
exposure  levels, indicating saturation of the tissues at higher
doses.   During inhalation, steady-state  levels in rat  tissues
were  reached within 2 - 3 h  and increased 20- to  30-fold when
the  exposure  increased from  202  to 1012 mg/m3,  suggesting a
saturable  metabolic capacity (section 5.3).   Levels in adipose
tissue, at steady-state, were 7 - 8 times higher than  those  in

blood,  while levels in the liver were 20% below those in blood.
At  comparable blood levels,  the maximum concentration  of 1,2-
dichloroethane  after  inhalation was  lower  in the  liver  and
higher  in lung  and adipose  tissue than  after oral  exposure.
Levels in the spleen, brain, and kidney were similar to those in
the   blood,  irrespective  of   the  route  of   administration
(Spreafico et al., 1980).

    Forty-eight h  after ingestion of  150 mg/kg body weight  or
inhalation exposure to a concentration of 607 mg/m3, 3 -  4%  of
the  body burden of labelled 1,2-dichloroethane was recovered in
the  carcass of rats.  Most radioactivity was found in the liver
and kidneys.  Residual radioactivity in selected tissues was 1 -
2  times  higher  after  oral  exposure  than  after inhalation.
Another  difference between oral and inhalation exposure was the
higher residual activity in the forestomach, well after the oral
exposure.   A  similar  distribution pattern  emerged for macro-
molecular  binding, as determined  4 h after  oral ingestion  or
directly after inhalation.  At these times, oral  exposure  pro-
duced lower levels of total macromolecular binding,  but  higher
levels of DNA alkylation than inhalation exposure.  The absolute
levels  of DNA  alkylation (2  - 14 µmol   equivalents  of  1,2-
dichloroethane  per  mol  DNA  at  1 mmol/kg  body  weight) were
considered low (Reitz et al., 1982).

    In another study, rats and mice were compared  with  respect
to DNA binding in liver, kidney, stomach, and lung, 22 h after a
single  intraperitoneal  injection  of  0.86  mg  labelled  1,2-
dichloroethane/kg body weight in ethanol.  Binding to  lung  DNA
was low compared with that in the other tissues.  Binding to DNA
of  mouse organs  was always  greater than  that to  DNA of  rat
organs (Arfellini et al., 1984).

    When  pregnant rats inhaled 1,2-dichloroethane at a level of
1000 mg/m3, for 4 h per day, the compound was found  to  accumu-
late  in the placental and fetal tissues over a period of 7 days
(Vosovaya,  1977).   Withey  & Karpinski  (1985)  also  obtained
evidence  that  exposure  of  rats  to  1,2-dichloroethane   via
inhalation  results in detectable levels  in fetuses in a  dose-
related manner.

    Binding of 1,2-dichloroethane to protein, lipid, and DNA was
also observed  in vitro (Guengerich et al., 1980).

5.3  Metabolism

    Metabolism  of 1,2-dichloroethane appears  to have a  signi-
ficant role in the manifestation of the toxic, carcinogenic, and
mutagenic effects of this chemical.

    Biotransformation  of 1,2-dichloroethane is extensive in the
mouse;  ip doses of 50 and 170 mg/kg body weight were associated
with 88 and 55% conversion to metabolites, respectively (Yllner,
1971).  The metabolites identified by Yllner (1971) are shown in
Table 6.  Reitz et al. (1982) observed extensive  metabolism  of

1,2-dichloroethane  in the rat, i.e., 70 and 91% transformation,
with oral (150 mg/kg) and inhalation (607 mg/m3; 6 h) exposures,
respectively,  85% of the  metabolites appearing in  the  urine.
Biotransformation of 1,2-dichloroethane approaches saturation at
high blood levels.

Table 6.  Non-volatile urinary metabolites of 1,2-dichloroethane in rodents
Species  Route    Metabolite                Fraction of   Reference
                                            total (%)

mouse    oral     (conjugated) S-carboxy-      48         Yllner (1971)
         (in      methylcysteine

                  thiodiacetic acid            33

                  chloroacetic acid            16

                  S,S'-ethene-bis-cysteine     0.9

                  2-chloroethanol              0.3

rat      inhal-   thiodiacetic acid          67 - 68       Reitz et al.
         ation                                             (1982)
         (in      thiodiacetic acid          26 - 29
         oil)     sulfoxide

         oral     S-(2-hydroxyethyl)mercap-                Nachtomi et al.
         (in      turic acid                               (1966)


                  2-chloroethanol                          Kokarovtseva &
                                                           Kiselyova (1978)

    1,2-Dichloroethane  metabolism  involves  the  formation  of
sulfur-containing  metabolites, which appear in  the urine.  Two
proposed   pathways  of  metabolism  of  1,2-dichloroethane  are
depicted  in Fig. 1; one  pathway begins with cytochrome  P-450-
mediated  oxidation,  and  the  other  begins  with  glutathione
conjugation.   There is a  lack of evidence  that doses of  1,2-
dichloroethane, either by gavage or inhalation, have any effects
on the distribution of its metabolites between  these  pathways.
Cytochrome P-450 enzymes catalyse an oxidative transformation of
1,2-dichloroethane  to form reactive intermediates, which result
in  the  formation  of 2-chloroacetaldehyde  and 2-chloroethanol
(Guengerich et al., 1980)  (Fig. 1).  Johnson (1965, 1966, 1967)
has  shown  that 2-chloroacetaldehyde  reacts both enzymatically
and non-enzymatically with glutathione (GSH).


    Rannug et al. (1978) first reported that mutagenic compounds
could be formed by the reaction of GSH with 1,2-dihaloalkanes in
the  presence  of  cytosolic  glutathione-S-transferases.   This
observation  led workers to  investigate in greater  detail  the
role  of glutathione-S-transferases in  the metabolism and  bio-
activation  of  both dibromoethane  (DBE) and 1,2-dichloroethane
(Rannug,  1980;  Sundheimer et  al.,  1982; Ozawa  & Guengerich,
1983;  Inskeep  &  Guengerich,  1984).   This  pathway  (Fig. 1)
involves the direct reaction of GSH with  1,2-dichloroethane  to
form S-(2-chloroethyl) glutathione, which is a half mustard with
a half-life of 69 min at 20 °C (Schasteen & Reed, 1983) and less
than  15 min  at 37 °C  (Foureman &  Reed,  1985).   Non-enzymic
conversion of the half mustard to the corresponding episulfonium
ion  gives a putative  alkylating agent (episulfonium  ion) that
has  several fates (Fig. 1).   Reaction can occur with  water to
form S-(2-hydroxyethyl) glutathione or reaction with thiols such
as  GSH  to  form ethene  bis-glutathione  or  with DNA  to form
adducts.  With the exception of DNA adducts, the  reaction  pro-
ducts  are considered non-toxic and  undergo further metabolism.
These  reactions and subsequent  metabolism of the  products can
account for all of the known sulfur-containing metabolites found
in the urine of 1,2-dichloroethane-treated animals.

    Although much evidence has been reported that  supports  the
P-450  mediated metabolism of 1,2-dihaloethanes,  this branch of
the  pathway  (Fig. 1)  does not appear  relevant to DNA  adduct
formation by 1,2-dichloroethane (Koga et al., 1986).  Guengerich
et  al. (1980) proposed  the possibility of  chloroso  oxidation
products of 1,2-dichloroethane in DNA adduct formation (Fig. 1).

However, they observed that the apparent stimulation  of  P-450-
directed  DNA adduct formation by GSH was a result of incomplete
removal of GSH conjugates during analysis (Koga et  al.,  1986).
In  addition, they  concluded that  2H and  18O studies  on  the
formation  of  2-haloethanols and  2-haloacetaldehydes from 1,2-
dihaloethanes  are inconsistent  with a  major role  of  such  a
mechanism  for DNA damage (Guengerich et al., 1986; Koga et al.,

    It should be pointed out that the P-450 directed pathway can
presumably  form considerable quantities of 2-haloacetaldehydes,
which readily bind to protein and non-protein thiols,  as  shown
for vinyl bromide and vinyl chloride (Guengerich et  al.,  1981)
and dibromoethane (DBE) (van Bladeren et al., 1981).

    Although some DNA damage can be produced via the P-450 path-
way  under  in vitro conditions (Hill  et al., 1978;  Banerjee et
al., 1980; Guengerich et al., 1980; Lin et al.,  1985),  several
lines  of evidence suggest that  the GSH conjugation pathway  is
probably of greater significance than the P-450 pathway  as  the
major  in  vivo route for DNA  damage (Guengerich et  al.,  1980;
Rannug, 1980; Sundheimer et al., 1982; Inskeep et al., 1986).

    It  has been possible  to correlate the  1,2-dichloroethane-
induced  mutation frequency  of two  human cell  lines with  the
difference  in  levels of  glutathione-S-transferase activities.
AHH-1  cell line mutation frequency was 25 times that in the TK6
cell line in the presence of 1,2-dichloroethane.  The difference
was  attributed to the fact that the AHH-1 cell line possesses 5
times  more glutathione-S-transferase activity than the TK6 cell
line (Crespi et al., 1985).

    Male  B6C3F1 mice, pretreated with piperonyl butoxide (PIB),
were  examined for the extent of hepatic DNA damage produced 4 h
after  1,2-dichloroethane  administration  (Storer  &   Conolly,
1985).   PIB  is  a P-450  inhibitor.   Hepatic  DNA damage,  as
measured by the alkaline DNA unwinding assay  for  single-strand
breaks  and  alkali-labile  lesions,  was  potentiated  by  PIB.
Treatment of mice with high doses of 2-chloroethanol  failed  to
produce  DNA damage, as measured by this assay.  Diethylmaleate,
a  GSH  depletor,  potentiated the  hepatotoxicity  of 2-chloro-
ethanol but not DNA damage.  Although the significance  of  this
observation  is  uncertain,  it  is  not  inconsistent  with the
hypothesis  that reduction of  GSH levels is  associated with  a
reduction in DNA damage.

    Recent evidence suggests that the putative episulfonium ion,
resulting  from a non-enzymatic conversion  of S-(2-chloroethyl)
glutathione,  is a major  intermediate in the  formation of  DNA
adducts  in  vivo from  1,2-dichloroethane  exposures  (Fig.   2)
(Inskeep  et al., 1986).  When  rats were administered a  single
dose  of 14C-1,2-dichloroethane  in vivo and the liver analysed 8
h  later, 78% of  the DNA adducts  (0.25 nmol/mg DNA)   could be
released  by  neutral thermal  hydrolysis.   A major  adduct and
several  minor  adducts  were  present;  the  major  adduct  co-

chromatographed  with  S-[2-(N7-guanyl)ethyl] glutathione.   DNA
adducts  released  from  kidney preparations  by neutral thermal
hydrolysis  were represented by 5 different fractions containing
radioactivity  after  chromatography.  The  postulated adduct of
liver  DNA  after  14C-1,2-dichloroethane  exposure,   S-[2-(N7-
guanyl)ethyl]  glutathione,  appears  to be  chromatographically
identical  to  the major  adduct in rats  after exposure to  DBE
(Koga et al., 1986).  This DBE adduct, which has  been  isolated
and  characterized by NMR  and mass spectrometry,  gives  strong
support  to an identical adduct  being the principal DNA  adduct
from  exposure to 1,2-dihaloethanes.  The  formation of apurinic
sites, as this adduct cleaves from DNA, may be a key  factor  in
the mutagenic and carcinogenic effects of these compounds.


5.4  Excretion and Elimination

    Excretion  of  1,2-dichloroethane  from  rodents  is  rapid.
Approximately 89% or more of the body burden of the compound was
excreted  within 24 h in ip-injected mice (Yllner, 1971), within
48 h  in orally exposed mice  (Mitoma et al., 1985),  and within
48 h  in rats exposed  orally or via  inhalation (Reitz et  al.,
1982;  Mitoma et  al., 1985).   In the  3 studies  cited  above,

excretion   of  1,2-dichloroethane  or  its  metabolites  mainly
occurred  in exhaled  air via  the lungs  and in  urine via  the
kidneys.  In both species, and at various exposure levels,  7  -
18% of the metabolized 1,2-dichloroethane was excreted as carbon
dioxide  (CO2)  and  approximately  80  -  85%  as  non-volatile
metabolites  (Table 6).  The metabolism of 1,2-dichloroethane in
mice and rats is dose-dependent.  For example, in mice,  11  and
45% of the body burdens of 1,2-dichloroethane, resulting from ip
exposure  to 50 and  170 mg/kg body  weight, respectively,  were
excreted unchanged via the lungs within 72 h (Yllner, 1971).  In
rats,  1.8, 11.5,  and 29%  of the  body burdens  were  excreted
unchanged  via the lungs  within 48 h following:  an  inhalation
exposure at 607 mg/m3 for 6 h (equivalent to a dose of 113 mg/kg
body  weight) (Reitz et  al., 1982), an  oral dose of  100 mg/kg
body weight (Mitoma et al., 1985), and an oral dose of 150 mg/kg
body weight (Reitz et al., 1982), respectively.

    The  rate of elimination from  blood and tissues appears  to
depend on the exposure level; the higher the exposure level, the
slower  the elimination rate  of 1,2-dichloroethane, after  both
oral  and inhalation exposure.  Half-lives in the blood of rats,
exposed orally, increased from 25 min at 25 mg/kg body weight to
57 min  at  150 mg/kg  body  weight.  With  inhalation exposure,
half-lives  increased from 13 min at 202 mg/m3 to 22 min at 1012
mg/m3, after a 6-h inhalation exposure (Spreafico et al., 1980).
In  addition, after  oral exposure  of rats  to 150  mg/kg  body
weight,  an initial half-life  of 90 min in  blood decreased  to
20 -  30 min, when blood levels fell below 5 - 10 mg/litre after
3  h (Reitz et  al., 1982).  Elimination  of  1,2-dichloroethane
from  blood, adipose tissue,  lung, liver, brain,  kidneys,  and
spleen  was comparable after oral  exposures of up to  150 mg/kg
body  weight.  Elimination  from the  liver was  reported to  be
biphasic with a higher elimination rate just after reaching peak
levels of 1,2-dichloroethane.  Elimination from other organs was
monophasic.   Following inhalation, elimination was  the slowest
in  adipose tissue and  the most rapid  in the lung,  up  to  an
exposure level of 1012 mg/m3 (Spreafico et al., 1980).  Withey &
Collins  (1980)  also  reported  that  the  elimination  of 1,2-
dichloroethane  was dose-dependent.  After iv  administration of
from  3 to 15 mg/kg body weight to male Wistar rats, the authors
found that the elimination fitted a two-compartment model  at  a
low-dose  level  and  a  three-compartment  model  at  high-dose


6.1  Aquatic Organisms

6.1.1   Acute toxicity

    The   acute  toxicity  of  1,2-dichloroethane   for  aquatic
organisms is summarized in Table 7.  The concentration  of  1,2-
dichloroethane  was measured in four  of the studies cited  (see
footnotea    in  Table 7);  the  concentrations reported  in the
other  studies were nominal.  It  should be noted that,  in open
systems,  the  toxic  effects  observed  must  have  occurred at
concentrations  lower than the  nominal ones reported  in latter
studies,  due  to  the anticipated  evaporation of 1,2-dichloro-
ethane in the aquatic media.

    The   species  most  sensitive  to  1,2-dichloroethane  were
members  of  the class  Crustacea.  A no-observed-adverse-effect
level  below 68 mg/litre was found  for  Daphnia magna (Le Blanc,
1980).    The  shrimp Crangon crangon showed  a  96-h   LC50  of
85 mg/litre  in sea water,  measured by the  flow-through method
(Adema, 1976).  When the brine shrimp  Artemia salina was exposed
to   1,2-dichloroethane   at   levels  ranging   from   0.25  to
25 mg/litre, growth inhibition was noted 24 h after cyst wetting
(Kerster & Schaeffer, 1983).

    EDC  tar  is much  more toxic for  marine species than  1,2-
dichloroethane, the heavy fractions of the tar being responsible
for  the high toxicity observed  (Jernelöv et al., 1972;  Rosen-
berg, 1972; Jensen et al., 1975; Rosenberg et al., 1975).

6.1.2   Short-term exposures

     When   blue  algae  Mycrocystis aerigunosa and  green  algae
 Scenedesmus  quadricauda were  exposed  in closed  containers to
1,2-dichloroethane  at 105 and 710 mg/litre, respectively, for 8
days, cell multiplication started to be inhibited  (Bringmann  &
Kühn,  1978).  Guppies  (Poecilia reticulata) were exposed  for 7
days  in a static test,  and an LC50 of  106 mg/litre was found.
Solutions  were renewed daily, but  no water analysis data  were
reported (Könemann, 1981).  Finally, an early life  stage  flow-
through  test was done.   Fathead minnows  (Pimephales promelas) 
were  exposed to  concentrations of  between 4  and 56  mg/litre
beginning  from  2  to 5  days  after  spawning  and  continuing
throughout the subsequent embryonal, larval, and juvenile stages
up  to 28  days after  hatching.  Water  was analysed  for  1,2-
dichloroethane.   Body weight was  reduced at 59 mg/litre.   The
survival of juveniles, the percentage of normal larvae at hatch,
and  the hatchability of  embryos were not  affected (Benoit  et
al., 1982).

Table 7.  Acute aquatic toxicity
Organism  Description      t (°C)   pH     Dissolved  Hardness   Flow/b  Parameter   Concen-   Reference
                                           oxygen     (mg CaCO3/ stat                tration
                                           (mg/litre) litre)     open/               (mg/litre)
Fresh water

Bacteria  Pseudomonas       25       7                           stat    16-h MICc     135     Bringmann 
          putida                                                 closed                        & Kühn
Protozoa  Entosipon sulc-   25       7                           stat    72-h MIC    943-1127  Bringmann 
          atum, Uronema                                          closed                        & Kühn
          parduczi, Chilo-                                                                     (1981)
          monas paramecium

Crustacea water flea        22    6.7-8.1  6.5-9.1    72         stat    24-h LC50     250     Le Blanc 
          (Daphnia magna)                                        open    no-observed-  < 68   (1980)
                                                                         effect level

Crustacea water flea        20      8.0    > 2       -          stat    24-h EC50     540a,d  Bringmann 
          (Daphnia magna)                                        open                          & Kühn

Crustacea water flea        20    7.1-7.7  7.9-9.9    44.7       stat    48-h LC50     270a,d  Richter 
          (Daphnia magna)                                        closed  48-h EC50     160a,d  et al.
                            20    7.0-7.5  4.1-8.4    44.7       stat    48-h LC50     320a,e  (1983)
                                                                 closed  48-h EC50     180a,e

Fish      bluegill sunfish 21-23  6.5-7.9             32-48      stat    96-h LC50     430     Buccafusco 
          (Lepomis macro-                                        closed                        et al.
           chirus)                                                                             (1981)

Fish      bluegill sunfish  23    7.6-7.9             55         stat    96-h LC50     550     Dawson 
          (Lepomis macro-                                        open                          et al.
           chirus)                                                                             (1977)

Fish      fathead minnow    25    6.7-7.6  8.0        45.1       flow    96-h LC50     116a    Walbridge 
          (Pimephales prom-                                      open                          et al.
           elas)                                                                               (1983)

Table 7 (contd.)
Sea water
Alga      Phaeodactylum                                          stat    EC50          340a    Pearson &
          tricornutum                                                                          McConnell 

Worm      chaetopod         23                                   stat    96-h LC50     400     Rosenberg 
          (Ophryotrocha                                          closed                        et al.
           labronica)                                                                          (1975)g

Crustacea shrimp            15      8.0    > 8.0                flow    96-h LC50     85a     Adema 
          (Crangon crangon)                                      open                          (1976)

Crustacea shrimp            16                                   stat    24-h LC50     170     Rosenberg 
          (Crangon crangon)                                      open                          et al.
Mollusca  barnacle nauplii                                       stat    48-h LC50     186a    Pearson &
          (Elminius modestus)                                    closed                        McConnell 

Fish      dab                                                    flow    96-h LC50     115a    Pearson &
          (Limanda limanda)                                      open                          McConnell 

Fish      tidewater silver- 20    7.6-7.9             55         stat    96-h LC50     480     Dawson 
          sides (Menidia                                         open                          et al.
          beryllina)                                                                           (1977)

Fish      sheepshead minnow 25-31                                stat    96-h LC50   130-230   Heitmüller 
          (Cyprinodon                                            open    no-observed-  130     et al.
           variegatus)                                                   adverse-              (1981)
                                                                         effect level

Fish      goby              15      8.0    > 8.0                flow    96-h LC50     185a    Adema 
          (Gobius minutus)                                       open                          (1976)

a  Water analysis for 1,2-dichloroethane was reported.
b  Flow-through or static method; open or closed system.
c  MIC  =  minimum  inhibitory concentration for cell multipication. EC50 and LC50 = concentration, 
   causing an effect and death, respectively, in 50% of the population.
d  Fleas unfed. Effect was complete immobilization.
e  Fleas fed. Effect was complete immobilization.
f  Effect was growth inhibition, measured by 4C uptake during photosynthesis.
g  When  the concentration was gradually built up during the first hour, the 96-h LC50 was 
   900 mg/litre, and the percentage of hatched eggs, laid within 15 days, was decreased by 90% at 
   400 mg/litre.  The latter was not noted at 200 mg/litre.
h  Concentration was gradually built up during the first hour.

6.1.3   Long-term exposure

    No-observed-adverse-effect  and  effect concentrations  were
determined  on the basis  of reproduction or  length for  Daphnia
magna in  a 28-day test, in stoppered flasks.  The test solution
was analysed by gas chromatography.  The lowest observed adverse
effect concentrations were 21 mg/litre, on the basis  of  repro-
duction,  and 72 mg/litre,  on the  basis of  length.   The  no-
observed-adverse-effect  concentrations were 11 mg/litre, on the
basis  of reproduction and 42 mg/litre,  on the basis of  length
(Richter et al., 1983).

6.1.4   Bioconcentration

    Bioconcentration of 1,2-dichloroethane in aquatic species is
unlikely  in view of its physical and chemical properties.  In a
tracer  study, a  bioconcentration factor  of 2  was  found  for
bluegill  sunfish  (Lepomis  macrochirus) in flowing  water.  The
half-life for the elimination of 1,2-dichloroethane from tissues
was 1 - 2 days (Barrows et al., 1980).

    When tissues of several aquatic species, collected from near
the  discharge zone of a  wastewater treatment plant, were  ana-
lysed  for 1,2-dichloroethane, the concentration of the compound
was  less than 0.5 µg/kg   wet weight  in all  cases, while  the
average  effluent concentration was 41 µg/litre  and the average
sediment  concentration  was  less  than 0.5 µg/kg   dry  weight
(Gossett et al., 1983).

6.2  Microorganisms

    1,2-Dichloroethane   at   an   influent   concentration   of
258 mg/litre did not affect the treatment efficiency of a bench-
scale   activated  sludge  system.   The   compound  itself  was
virtually completely removed by stripping but not  by  biodegra-
dation  (Stover  &  Kincannon,  1983).   In  a  batch  anaerobic
toxicity  assay,  1,2-dichloroethane  was slightly  toxic to the
anaerobic    digestion   process   from   a   concentration   of
2.5 mg/litre,  though  acclimation  was observed  after  several
days.   A  concentration  of  20 mg/litre  caused  more   severe
retardation,  while  acclimation  was slow.   In semi-continuous
assays,  stress became evident at  1,2-dichloroethane concentra-
tions of between 5 and 7.5 mg/litre (Stuckey et al., 1980).

6.3  Terrestrial Organisms

6.3.1   Birds

    The effects on reproduction were investigated in  groups  of
10  male and 20 female  white leghorn chickens after  2 years of
oral  exposure to 0,  250, or 500 mg  1,2-dichloroethane/kg feed
mash.   From the fourth month  of laying onwards, decreased  egg
weight  was observed at  both dose levels,  while at the  higher
dose  level, the number  of eggs and  the feed intake  were also

reduced.   1,2-Dichloroethane  did not  affect serum composition
and  growth,  semen  characteristics, or  fertility  of chickens
(Alumot et al., 1976b).

6.3.2   Plants

    1,2-Dichloroethane  is used as  a seed fumigant,  usually in
combination  with compounds such  as carbon tetrachloride,  1,2-
dibromomethane,  or  2-chloroethanol.  Such  fumigants inhibited
the  germination  of seeds  (Caswell  & Clifford,  1958;  Kamel,
1959),  broke the  dormancy period  of potato  tubers  (Varga  &
Ferenczy,  1956; Jolivet, 1968)  and beech (Thorup,  1957),  and
adversely affected the nodulation status and yield of groundnuts
treated  with  Rhizobium (Kulkarni et al.,  1975).  1,2-Dichloro-
ethane  vapour was both lethal and mutagenic for barley seeds at
3 mg/m3 during 24 h (Ehrenberg et al., 1974).


7.1  Single Exposures

7.1.1   Inhalation and oral exposure

    The  available acute mortality data following inhalation and
oral exposure are summarized in Table 8.

Table 8.  Acute mortality after inhalation or oral exposure to
Species/ Route       Vehicle   Parameter    Result         Reference
strain                         studied

dog      oral        acacia     LD50        2500 mg/kg     Barsoum & Saad
                     gum                                   (1934)

rat      oral        corn oil   LD50         680 mg/kg     McCollister et
                                                           al. (1956)

CD-1     oral        water      LD50         489 mg/kg     Munson et al.
mouse                                                      (1982)

CD-1     oral        water      LD50         413 mg/kg     Munson et al.
mouse                                                      (1982)

Wistar   inhalation            6-h LC50     5100 mg/m3     Spencer et al.
rat                                                        (1951)

Sprague  inhalation    -       6-h LC50     6660 mg/m3     Bonnet et al.
Dawley                                                     (1980)

OF1      inhalation            6-h LC50     1060 mg/m3     Gradiski et al.
mouse                                                      (1978)

rat      oral                   LD50         850 mg/kg     Larionov &

albino   inhalation             LC50(expo-   30 000 mg/m3  Nevrotsky et al.
rat                             sure period                (1971)

    Deaths  occur within a  narrow range of  concentrations.  In
rats,  the difference  between the  6-h LC10  and 6-h  LC90  was
approximately  2800 mg/m3 (Bonnet et al., 1980).  No deaths were
observed in rats after 6 h of exposure to 2000 mg/m3 (Spencer et
al.,  1951).   In  mice, an  extremely  narrow  range  of  about
500 mg/m3  was observed between  the 6-h LC10  and the 6-h  LC90
(Gradiski et al., 1978).

    Exposure  of rats to single high doses of 1,2-dichloroethane
resulted   in  adverse  effects  on  the  CNS,  liver,  kidneys,
adrenals, and lungs (Spencer et al., 1951).  Groups of 10  -  52
Wistar  rats were exposed to 81 000, 48 600, 12 100, 6100, 4000,
3200, 2400, or 1200 mg 1,2-dichloroethane/m3 for various lengths
of  time.  At the  highest concentration (81 000  mg/m3), deaths
were  observed in animals exposed  for 0.3 h or  longer.  Deaths
were observed at all except the lowest of the  other  concentra-
tions  with  exposure periods  of 0.4, 0.7,  3.0, 4.0, 7.0,  and
7.0 h, respectively.  No deaths were observed in rats exposed to
the lowest concentration for 7 h.

    Severe depression of the central nervous system resulting in
coma  was observed in rats exposed to the highest concentration.
At lower concentrations, this depressant action expressed itself
as  various  levels  of "drunkeness".   In  this  investigation,
Spencer et al. (1951) did not specify the sex of the rats.

    In  the same publication, the authors reported another study
in  which groups of 4  - 6 female rats  were exposed to  48 600,
12 100,  4000,  1200,  or  800  mg/m3.   "Adverse  effects" (not
described  by the authors) were observed at the 4 highest levels
in  rats exposed for 0.2, 0.5, 3.0, and 5.5 h, respectively.  No
adverse  effects were  observed in  female rats  exposed to  the
lowest concentration, for 7 h.

    Examination  of internal organs  in groups of  rats  killed,
either  when moribund or  24 h after the  last exposure,  showed
that,  after exposure to 1,2-dichloroethane levels of 2400 mg/m3
or  more, the  most severe  damage occurred  in the  kidney  and
consisted of haemorrhage and tubular necrosis.  The liver showed
fatty  changes and hepatocellular necrosis with haemorrhage, and
adrenal glands were haemorrhagic.  Lung oedema was  observed  at
concentrations above 12 100 mg/m3.  The injury to organs in this
study was accompanied by high blood-urea levels, a  decrease  in
serum-phosphatase activity, and increased lipid concentration in
the liver (Spencer et al., 1951).

    Depression  of the central  nervous system was  noted during
exposure  of rats to 1,2-dichloroethane concentrations exceeding
1200 mg/m3  (Bonnet et al.,  1980).  From an  exposure level  of
4000 mg/m3,  for 4 h, rats showed altered behaviour.  A narcotic
effect was observed at 9100 mg/m3 (Wolff et al., 1979).

    Albino  rats,  given a  single oral dose  of 615 mg/kg  body
weight, showed congested livers with cloudy swelling  and  fatty
degeneration.  The myocardium showed oedema and haemorrhaging in

the  walls of the coronary  vessels, stasis, and thrombi  in the
vessels.   These  changes  were  associated  with  an  increased
activity of alanine- and aspartate aminotransferase in the serum
and decreased tissue levels of nicotinamide coenzymes (Natsyuk &
Chekman,  1975).   A  single  administration  of  861  mg/kg, by
gavage,  was reported to partially uncouple oxidative phosphory-
lation measured  in vitro in albino rat livers, 1, 3, or  6  days
after exposure (Natsyuk et al., 1974).  In rat liver microsomes,
cytochrome  P-450 levels were  slightly decreased after  an oral
dose  of 625 mg/kg  (Moody et al.,  1981).  After a  single oral
dose  of 1,2-dichloroethane in corn oil at 770 mg/kg body weight
in  rats, dystrophy in the cytoplasm and hyperchromatosis in the
nuclei  of  hepatocytes were  observed.   A decrease  in protein
synthesis  and lysosomal enzyme activity was also reported.  The
same  changes took place in renal nephrons (Boikova & Kravtsova,
1982).   A single dose of 850 mg/kg in albino rats resulted in a
decrease  in  RBC  count, haematocrit,  and other haematological
changes (Larionov & Kokarovtseva, 1976).  Oral administration of
1,2-dichloroethane  (615  mg/kg)  to rabbits  induced pronounced
morphological  changes in  the liver  in about  24 h (Nazikhi  &
Skrizhinsky,  1973).   Effects  on fibrinolytic  activity in the
blood  of rabbits administered 1,2-dichloroethane  at 1476 mg/kg
have  been reported by  Kagramanov & Kazieva  (1972).   Electro-
cardiographic changes in albino rats associated with doses of 1,
1.5,  and  2 mg/kg have  been  reported (Saitanov  &  Arsenieva,

7.1.2   Skin and eye irritation

    When  undiluted  1,2-dichloroethane was  applied directly on
the clipped skin of guinea-pigs for up to 12 h in occluded patch
tests,  no gross skin reactions  were visible (Jakobson et  al.,
1982).   Microscopic  changes  appeared 4 h  after  application,
comprising  karyopyknosis,  perinuclear oedema,  spongiosis, and
junctional  separation (Kronevi et al., 1981).  In similar tests
on  rabbits, moderate erythema  and oedema were  observed,  24 h
after  application.   Microscopy  on  the  third  day   revealed
necrosis and other lesions such as ulcerations  and  acanthosis.
The  severity of the changes  was not indicated (Duprat  et al.,

    Instillation  of 0.1 ml of undiluted 1,2-dichloroethane into
the conjunctival sac of the eye of rabbits generated reversible,
mild  irritation characterized by conjunctivitis  and epithelial
abrasion.   Epithelial keratitis, described as being "in a state
of   repair",  was  observed   microscopically,  7  days   after
application (Duprat et al., 1976).  Reversible clouding  of  the
cornea   was  observed  in  dogs  within  10 h  of  subcutaneous
administration  of  undiluted 1,2-dichloroethane  at 0.9/kg body
weight.   The clouding  continued up  to 48 h,  but the  corneas
appeared   clear  after  5  days.    The  histological  changes,
including necrosis of the corneal endothelium, partially denuded
Descemet's  membrane, formation of excess basement membrane, and
swelling  of the  corneal stroma,  were also  observed in  dogs,
cats,  and  rabbits  after  ocular  injection  of  1.8  mg  1,2-
dichloroethane  (0.15 ml  of a  1% solution)  into the  anterior
chamber (Kuwabara et al., 1968).

7.2  Short-Term Exposures

7.2.1   Inhalation exposure

    The  effects of repeated exposure to 1,2-dichloroethane have
been  studied in mice,  rats, guinea-pigs, rabbits,  cats, dogs,
and  monkeys (Heppel et al., 1946; Spencer et al., 1951; Hofmann
et al., 1971).

    Heppel et al. (1946) exposed rats of the Wistar and Osborne-
Mendel strains to 1,2-dichloroethane concentrations of 420, 730,
1540,  or 3900 mg/m3 in air, 7 h daily, 5 days/week, for several
weeks.  The duration varied with each exposure level.   No  loss
of  weight  and  no deaths  occurred  in  rats of  either strain
exposed to 420 mg/m3 for up to 4 months (74  exposures).   Seven
out  of 12 Wistar rats exposed to 730 mg/m3 died within 15 weeks
(after 1 - 73 exposures)  and 8/12 similarly treated rats of the
Osborne-Mendel strain died after 1 - 6 exposures.  Nine  out  of
16  rats (strain unspecified)  died within 12 weeks after 2 - 60
exposures  to 1540 mg/m3; 20/26 (strain unspecified) died within
3  weeks after 3 - 15 exposures to 3900 mg/m3.  Guinea-pigs were
exposed  to the same concentrations of 1,2-dichloroethane as the
rats.   Several deaths, which  occurred in the  lowest  exposure
group  (420  mg/m3)  and in  controls,  were  attributed  to  an
intercurrent  disease.   At  higher dose  levels,  mortality was
related  to 1,2-dichloroethane exposure.  Five out of 14 guinea-
pigs  died after 5 - 115 exposures to 730 mg/m3 within 23 weeks.
Fourteen  out of 20 guinea-pigs  died after 8 -  65 exposures to
1,2-dichloroethane at 1540 mg/m3 within 13 weeks.   All  guinea-
pigs  exposed  to  3900 mg/m3  had died  by the  4th day  of the

    Rabbits were exposed to the three higher  concentrations  of
1,2-dichloroethane  only.  No deaths were  observed when rabbits
were exposed to 730 mg/m3 for 25 weeks.  All 5  rabbits  exposed
to  1540 mg/m3 died, one  after one exposure and  the rest after
89 -  97  exposures  within 19  weeks.   Five  out of  6 rabbits
exposed  to 3900  mg/m3 died  after 2  - 43  exposures within  9

    A  group of 19 mice survived for 4 weeks when exposed to 420
mg/m3,  but  18/20  mice died  within 10  days by  the end  of 7
exposures to 730 mg/m3.  In other species, a group of  6  female
dogs survived up to 35 weeks of exposure to 1540 mg/m3.  Two out
of  6 dogs exposed to 3900 mg/m3 died after 30 and 43 exposures,
respectively.   Two out of six  cats exposed to 3900  mg/m3 died
after   43   exposures.   Cats   were   not  exposed   to  lower
concentrations.   Two  monkeys died  after  2 and  32 exposures,
respectively, to 3900 mg/m3, but 2 others exposed to  730  mg/m3
survived for 25 weeks.

    Kidney  and liver damage,  consisting of fatty  changes  and
necrosis  in both organs,  was found in  animals that died  from
exposure to the highest dose level (3900 mg/m3).   In  addition,
the rats showed pulmonary congestion and haemorrhage; one monkey

that  died  after  32  exposures  and  one  dog showed  a  focal
myocarditis.   Approximately half of the animals that died after
exposure  to 1540 mg/m3  showed similar histological  changes in
the liver and kidneys, but no such changes were observed in rats
that  died from exposure to lower levels.  Hepatic fatty changes
were observed in guinea-pigs exposed to 730 mg/m3.  Histological
examinations were not carried out on mice.

    Spencer  et al. (1951)  exposed rats, guinea-pigs,  monkeys,
and  rabbits  to  1,2-dichloroethane at  concentrations of 1620,
810, or 405 mg/m3, 7 h per day, 5 days/week, for various lengths
of time.  In a group of 15 male and 15 female rats,  exposed  to
the  highest level, no animals  survived for more than  8 weeks,
and 60% mortality occurred in a second group exposed to the same
regime  after 2 or  3 exposures.  Mortality  was also high  in a
group  of 8 male and 8 female guinea-pigs exposed to 1620 mg/m3.
All  males  had  died by  the  second  week and  all  females by
approximately  the 5th week.  Two male monkeys experienced rapid
and severe intoxication.  Both were killed when  moribund  after
10  - 12 exposures.   On the other  hand, 2 male  and  1  female
rabbits  tolerated 33 weeks exposure with no evidence of adverse
effects.  No mortality was observed when groups of 15  male  and
15  female rats and 8 male and 8 female guinea-pigs were exposed
to  810 mg/m3 for  about 30 weeks  (151 exposures)  or  36 weeks
(180  exposures), respectively.  Similarly, no  clinical effects
were  observed  in  groups of 15 male and female rats, 8 male or
female  guinea-pigs, 2 male and 1 female rabbits, and 1 male and
1 female monkey exposed for approximately 30 - 36 weeks  to  405

    Histological  examination was carried out on animals exposed
to  the three dose levels.  In both guinea-pigs and rats exposed
to  the highest dose level,  liver changes consisting of  cloudy
swelling  and fatty changes  were observed.  None  of the  other
organs  were  affected.  Similar  but  less marked  changes were
observed  in the monkeys, while no adverse changes were found in
the  rabbits.   In  rats exposed  to  810  mg/m3, there  were no
adverse changes in the liver or other organs, but reduced growth
and some fatty changes were found in the liver  of  guinea-pigs.
No adverse changes were found in animals exposed to  the  lowest
dose level (405 mg/m3).

    Hofmann  et al. (1971)  exposed cats, rabbits,  guinea-pigs,
and  rats to 1,2-dichloroethane at  1980 mg/m3 or 405  mg/m3 for
6 h/day,  5  days/week,  for up  to  17  weeks.  At  the  higher
concentration,  rats became dyspnoeic and guinea-pigs apathetic.
Three  out  of  4 rabbits died after 10 - 17 exposures, and 9/10
guinea-pigs  died  after  4 -  14  exposures.   Rats  were  more
sensitive,  dying after only 1 - 5 exposures.  All cats survived
30  exposures.  Histologically, rats showed pulmonary hyperaemia
and  oedema, fatty liver,  and adrenal and  myocardial necrosis.
Cats and rabbits exhibited a heart lesion and guinea-pigs, fatty
changes in the myocardium, liver, and adrenals and  necrosis  in
the  myocardium  and liver.   At  the lower  concentration  (405
mg/m3),  rats,  guinea-pigs, rabbits,  and  cats exposed  for 17
weeks did not show any clinical or histological changes.

    Of  the  species studied,  mice and rats  appear to be  more
sensitive  than other  species to  the adverse  effects of  1,2-
dichloroethane.  The no-observed-adverse-effect level for short-
term  exposures  (4  - 9  months)  in  rats  studied  in  the  3
investigations is about 400 mg/m3.

    Signs of central nervous system depression observed  in  the
above  studies were apathy in guinea-pigs at 1980 mg/m3 (Hofmann
et  al., 1971) and 3900 mg/m3 (Heppel et al., 1946), and coma in
dogs and monkeys at 3900 mg/m3 (Heppel et al., 1946).  When rats
were  exposed continuously for 3.5 months to 5 mg/m3, changes in
EEG were observed (Dmitrieva & Kuleshova, 1971).   However,  the
significance of these findings is not known.

7.2.2   Oral exposure

    The   liver  appeared  to  be  the  principal  target  organ
following  oral  exposure.  Rats,  treated  by gavage  with 1,2-
dichloroethane  in corn oil  for 2 weeks,  5 times per  week, at
doses  of  150 mg/kg  body  weight  or  less  did not  show  any
treatment-related   abnormalities  in  organ  or  body  weights,
histology,  clinical chemistry, or haematology (Van Esch et al.,
1977; Reitz et al., 1982).

    Rats  were also exposed for 90 days, 5 times per week, to 0,
10, 30, or 90 mg/kg body weight (Van Esch et al., 1977).  At the
2 highest exposure levels, a tendency to decreased  weight  gain
was  observed.   At  90 mg/kg, rats  of  both  sexes  showed  an
increase in the relative weight of kidneys, but only the females
on  this dose  showed increased  relative weights  of liver  and
brain  compared with controls.  Histology and clinical chemistry
were  normal.  Some haematological parameters  were altered, but
not in a dose-related manner.  In another study, after  5  doses
of  300 mg 1,2-dichloroethane/kg body  weight in 5  days, all  6
rats  died, and their livers  showed fatty degeneration with  an
increase in the triglycerides level (Van Esch et al., 1977).

    Total fat and triglycerides were elevated in the  livers  of
rats  exposed to approximately 100 mg/kg body weight per day via
the  feed,  which  was administered  twice  daily,  for 7  weeks
(Alumot et al., 1976a).

    No adverse effects related to liver and kidney function were
observed at the lowest dose (10 mg/kg).

7.3  Long-Term Exposure

7.3.1   Inhalation exposure

    Clinical  chemical investigations were performed  on Sprague
Dawley rats exposed by inhalation to 1,2-dichloroethane at 0, 5,
40, 202, or 1012 mg/m3 for 7 h per day, 5  days/week  (Spreafico
et  al., 1980).  The highest  exposure level was reduced  to 607
mg/m3 after a few weeks because of high mortality.   Animals  of
each sex were exposed, starting at 3 months of age, for 3, 6, or

18  months.  In addition, animals  starting at 14 months  of age
were  exposed  for  12 months.  Groups of 8 - 10 animals of each
sex were sacrificed at the specified time intervals and clinical
chemistry   tests   performed.   Changes  in   SGOT,  SGPT,  and
c-glutamyl    transpeptidase activities in the  12-month animals
were  not observed in the 18-month animals.  Likewise, increases
in  serum-uric acid and  blood urea-nitrogen levels  in the  12-
month  animals were not  observed in the  18-month animals.   In
addition,  the 12-month animals,  but not the  18-month animals,
displayed decreases in serum-cholesterol.  On the basis  of  the
negative  results obtained in the animals starting exposure at 3
months  of age  and sacrificed  after 3,  6, or  18 months,  the
authors  suggested a lack of  significant toxicity, in spite  of
the biochemical changes found in the older 12-month animals.

    Neurotoxic  changes  (conditioned  reflexes) in  albino rats
have  been associated with  a 1,2-dichloroethane exposure  of 50
mg/m3, 4 h/day, for 6 months (Borissova, 1957, 1960).

7.3.2   Oral exposure

    In a controlled feeding schedule for 2 years,  three  groups
of  18  locally-bred rats  of each sex  were provided with  feed
fumigated   with   1,2-dichloroethane.    The  doses   of   1,2-
dichloroethane  administered were estimated to be 0, 11 - 17, or
23 -  35 mg  1,2-dichloroethane/kg  body  weight  per  day.   No
adverse  effects were observed  on growth, mortality  rates,  or
serum  composition.  The mean survival  period was 18 months  or
more (Alumot et al., 1976a).

7.4  Carcinogenicity

7.4.1   Inhalation exposure

    Groups  of  11-week-old  Swiss mice  and 12-week-old Sprague
Dawley  rats, comprising 90 animals of each sex, were exposed to
20, 40, 202, and 1012 mg 1,2-dichloroethane/m3 air (5,  10,  50,
and  250 ppm) for 78  weeks, 7 h per day,  5 days per week,  and
observed for a lifetime.  Purity was reported to be greater than
99%.  The highest exposure was reduced to 607 mg/m3   (150  ppm)
after  a few weeks  because of high  mortality.  Control  groups
contained  115 male mice, 134  female mice, or 180  rats of each
sex.   Percentage survival  in male  and female  mice, 52  weeks
after  the beginning of treatment, was, respectively, 63 and 84%
in the controls; 47 and 93% at 20 mg/m3; 66 and 80% at 40 mg/m3;
51  and 81% at 202 mg/m3; and 43 and 64% at 607 mg/m3.  The last
mouse  died about 100 weeks  after initiation of treatment.   In
male and female rats, survival at 52 weeks was, respectively, 67
and 73% in the controls; 75 and 85% at 20 mg/m3; 70 and  81%  at
40  mg/m3; 70 and 84% at 202 mg/m3; and 67 and 79% at 607 mg/m3.
Most  rats  had  died by  about  140  weeks after  the  start of
treatment.   No specific  types of  tumours or  changes  in  the
incidence  of tumours  were found  in either  species, with  the
exception  of  an  increased incidence  (not  dose-related)   of
fibromas  and fibroadenomas of the mammary glands of female rats

at 20, 202, and 607 mg/m3.  The average latency time  for  these
tumours  was  83 weeks  in control rats  and in rats  exposed at
20 mg/m3,  and 79 weeks at the 2 highest exposures.  The authors
ascribe  the  differences in  the  incidence of  mammary tumours
between the groups to the different survival rates in the groups
(Maltoni et al., 1980).

7.4.2   Oral exposure

    Groups of 50 Osborne-Mendel rats of each sex were exposed to
average   doses  of  1,2-dichloroethane  (technical  grade  with
reported  purity > 90%)a  in  corn oil of 47  or 95 mg/kg  body
weight  for 78 weeks (NCI, 1978).  Treatment was usually given 5
times per week, and the animals were observed for  another  15 -
32 weeks after the end of treatment.  Control  groups  consisted
of  20 matched controls of each sex treated with corn oil and 60
pooled   control-treated  rats  of   each  sex.   Eleven   minor
contaminants  were detected in the test compound.  The rats were
housed in the same room as rats intubated with other halogenated
hydrocarbons  or  carbon  disulfide.   Body  weights  were   not
affected by the exposures.  A dose-related increase was found in
mortality  rate, which  was 100%,  27 weeks  after cessation  of
exposure  to 95 mg/kg body  weight.  As shown  in Table 9,  male
rats  had  a  dose-related increased  incidence  of subcutaneous
fibromas,   and   forestomach  squamous   cell  carcinomas  were
observed.   In treated females, the  stomach showed hyperplastic
lesions.  The incidence of haemangiosarcomas (in various organs,
mainly  the spleen) was  increased in a  dose-related manner  in
both  sexes, but the  increase was statistically  significant in
males  only.  In females, an increase was found in the incidence
of adenocarcinomas of the mammary gland (NCI, 1978).


a       Subsequent  analysis indicated a  purity of about  98 -  99%
        (Hooper et al., 1980; Ward, 1980).

Table 9.  Summary of main tumour types after oral administration of 1,2-dichoroethane to mice and ratsa
Group                     Maximum                      Number of animals with:                    
                          number of  Forestomach    Subcutaneous   Mammary     Haemangiosarcomas
                          animals    squamous cell  fibromas       adeno-      (several organs)
                          examined   carcinomas                    carcinomas
Rat (male)
  Pooled vehicle controls     59         0              0              0             0
  Matched vehicle controls    19         0              0              1             0
  Low dose                    46         3              5              2             9
                                                    (P < 0.002)b               (P = 0.003)b
  High dose                   47         9              6              0             7
                                     (P < 0.04)c    (P < 0.01)b                (P < 0.02)b

Rat (female)                                        Mammary gland
  Pooled vehicle controls     59         0              5              1             0
  Matched vehicle controls    20         0              0              0             0
  Low dose                    50         0              14             1             4
                                                    (P < 0.01)b
  High dose                   50         0              8              18            4
                                                                   (P < 0.001)b

Group                     Maximum                      Number of animals with:                    
                          number of  Hepatocellular Alveolar/      Forestomach      Mammary gland
                          animals    carcinomas     bronchiolar    squamous         adenocarcinomas
                          examined                  adenomas       cell carcinomas
Mice (male)
  Pooled vehicle controls     59         4              0              1                  -      
  Matched vehicle controls    19         1              0              1                  -      
  Low dose                    46         6              1              1                  -      
  High dose                   47         12             15             2                  -      
                                     (P < 0.01)b   (P < 0.001)b     (NS)                       
Mice (female)                                                                                    
  Pooled vehicle controls     60         0              2              1                  0      
  Matched vehicle controls    20         1              1              1                  0      
  Low dose                    50         0              7              2                  9      
                                                                                    (P = 0.001)b 
  High dose                   48         1              15             5                  7      
                                                    (P < 0.001)b     (NS)          (P = 0.003)b 
a       Adapted from: NCI (1978).
b       Statistical analyses shown are in comparison with the pooled matched controls.
c       Statistical analyses shown are in comparison with the matched vehicle controls.
    In  the same set of  studies, B6C3F1 mice were  exposed in a
similar fashion to average doses of 0, 97, or  195 mg  technical
grade compound/kg body weight for males and 0, 149, or 299 mg/kg
body  weight  for females.   They were housed  in the same  room
where  several  other  hydrocarbons  or  other  substances  were
tested.   After exposure, they were observed for another 12 - 13
weeks.  In females, body weights were depressed at  the  highest
doses from week 15 onwards, while the survival rate decreased in
a dose-related manner.  Mean survival exceeded 65 weeks  in  all
groups.   Many treated mice suffered  from bronchopneumonia.  As
shown  in Table 9, dose-related increased incidences of alveolar
or bronchiolar adenomas were found in both sexes.  In  males,  a
dose-related  increased  incidence of  hepatocellular carcinomas
was observed.  Female mice showed slight, dose-related increases
in the incidence of squamous cell carcinomas of the forestomach,
but  this  was not  statistically  significant.  In  male  mice,
hyperplastic  changes were found at this site.  The incidence of
adenocarcinomas of the mammary gland was significantly increased
in females at both doses (NCI, 1978).

7.4.3   Dermal exposure

    Groups of 30 female Ha:ICR Swiss mice were treated  with  42
or  126 mg 1,2-dichloroethane in  acetone on the  shaven  dorsal
skin,  3  times  per week for 440 - 594 days.  In a third group,
each  female received  one application  of 126 mg  of  the  test
compound  followed 2 weeks later by phorbol myristate acetate, a
promotor, in acetone 3 times per week for 428 - 576 days.  There
were 3 control groups, a positive control, one for the promotor,
and one for no treatment.  1,2-Dichloroethane did  not  initiate
skin  tumours.   There  was  an  elevated  incidence   of   lung
papillomas  at  the highest  dose  compared with  controls  (Van
Duuren et al., 1979).

7.5  Mutagenicity and Related End-Points

7.5.1   Mutations

        Information in this section is summarized in Table 10. Bacteria

    Several investigators have observed a weak or no  effect  of
1,2-dichloroethane in  Salmonella typhimurium TA1535 or TA 100 in
spot  tests  or  standard  plate  incorporation  assays  with or
without rat liver S9 fraction or pure microsomes (Brem  et  al.,
1974; McCann et al., 1975; King et al., 1979; Guengerich et al.,
1980;  Principe et  al., 1981).   A weak  mutagenic  effect  was
observed  in 1,2-dichoroethane vapour-exposed  S.  typhimurium TA
1535  and TA 100, which did not increase further by the addition
of a metabolic activation system (Barber et al., 1981). However,
a stronger positive response was observed by others  (Rannug  et
al.,  1978; Rannug & Beije,  1979; Principe et al.,  1981) in TA
1535 in the presence of rat liver metabolic  activation  system.

It  has  been established  that this effect  has been caused  by
cytosolic glutathione-S-transferases (Rannug et al., 1978; Guen-
gerich  et al., 1980; Reitz  et al., 1982), and  similar results
have  also been obtained in TA 100 (van Bladeren et al., 1981b).
 In  vitro  Salmonella tests  using the  bile  of  mice or  rats
exposed  to 1,2-dichloroethane, probably containing  active con-
jugates, have confirmed these results (Rannug & Beije, 1979).

    No mutagenic effects were observed in forward mutation tests
with   Escherichia coli (King et al., 1979).

Table 10.  Tests for gene mutations/chromosome/DNA damage and cell transformation induced 
by 1,2-dichloroethane
Test description              System description             Activation  Result     Reference
                      Organism      Strain/cell type         system (S9)
Gene mutations

reverse mutation      bacteria      S. typhimurium TA 1530      A        + (weak)   Brem et al. (1974)
                                                   TA 1535      A        + (weak)
                                                   TA 1538      A        + (weak)

reverse mutation      bacteria      S. typhimurium TA 100       A        + (weak)   McCann et al. (1975)

reverse mutation      bacteria      S. typhimurium TA 1535      P        -          King et al. (1979)
                                                   TA 100       P        -
                                                   TA 1537      P        -
                                                   TA 1538      P        -
                                                   TA 98        P        -

reverse mutation      bacteria      S. typhimurium TA 1535      P        +          Principe et al. 
                                                   TA 1537    A or P     -          (1981)
                                                   TA 1538    A or P     -
                                                   TA 98      A or P     -
                                                   TA 100     A or P     -

reverse mutation      bacteria      S. typhimurium TA 1535      Pa        -          Guengerich et al.
                                                                Pb        +          (1980)

reverse mutation      bacteria      S. typhimurium TA 1535    A or P     +          Barber et al.  
                                                   TA 100     A or P     ±          (1981)
                                                   TA 1538    A or P     -
                                                   TA 98      A or P     -

Table 10 (contd).
Gene mutations (contd)

reverse mutation      bacteria      S. typhimurium TA 1535      A        ±          Rannug et al. (1978)
                                                   TA 1535      P        +
                                                   TA 1535      Pb       +

reverse mutation      bacteria      S. typhimurium TA 1535      P        +          Rannug & Beije (1979)

reverse mutation      bacteria      S. typhimurium TA 1535      P        +          Reitz et al. (1982)

reverse mutation      bacteria      S. typhimurium TA 100       Pb       +          van Bladeren et al.

forward mutation      fungi         S. coelicolor               A        -          Principe et al. 
                                    A. nidulans                 A        -          (1981)

sex-linked lethals    insect        D. melanogaster                      +          Rapoport (1960); Shak-
                                                                                    arnis (1969, 1970);
                                                                                    King et al. (1979)

somatic cell mutation insect        D. melanogaster                      +          Nylander et al. 
forward mutation      Chinese       ovary cells in vitro        P        ++         Tan & Hsie (1981)
                      hamster                                   A        +
                                                                P        +          Zamora et al. (1983)

forward mutation      human         lymphoblastoid cell line    A        +          Crespi et al. (1985)
                                    AHH-1 and TK6 in vitro

somatic cell mutation mouse         C57BL/6J Han (female)       NA       +?         Gocke et al. (1983)
(spot test)                         x T stock (male)/embryos

Table 10 (contd).
Test description               System description            Activation  Result     Reference
                      Organism      Strain/cell type         system (S9)
Chromosome/DNA damage

micronucleus test     mice          NMRI/polychromatic          NA       -          King et al. (1979)
(ip or gavage exposure)             erythrocytes

micronucleus test     mice          CBA/polychromatic           NA       -          Jenssen & Ramel 
(ip exposure)                       erythrocytes                                    (1980)

dominant lethal       mice          ICR Swiss/germ cells        NA       -          Lane et al. (1982)
(ip exposure)

alkaline DNA          mice          B6C3F1/liver in vivo/       NA       +          Storer & Conolly
unwinding                           in vitro                                        (1983)

alkaline DNA          mice          B6C3F1/liver in vivo/       NA       +          Storer et al. (1984)
unwinding                           in vitro

unscheduled DNA       human         lymphocytes in vitro        NA       +          Perocco & Prodi 
synthesis (exposure by                                                              (1981)
addition in the medium)

Cell transformation

cell transformation   Syrian        embryo cells in vitro       A        +c         Hatch et al. (1983)
(gas/vapour exposure) golden hamster

cell transformation   mice          BALB/c-3T3 in vitro         A        -          Tu et al. (1985)
(exposure by addition
in the medium)
a       Pure microsomes.
b       Cytosol.
c       Enhanced viral induced transformation.
NA = not applicable. Fungi

    Forward  mutation  tests conducted  with  Streptomyces coeli-
color and  Aspergillus  nidulans were  negative  in plate  incor-
poration  assays and  spot tests  (Principe et  al., 1981).   In
 A. nidulans, 1,2-dichoroethane   induced   non-disjunction  and
haploidization  (Crebelli et al., 1984).  1,2-Dichloroethane was
found   to   be  a   weak  inducer  of   mitotic  crossing  over
in  Saccharomyces cerevisiae (Simmon, 1980). Insects

    Sex-linked   recessive   lethal   mutations   were   induced
in  Drosophila   melanogaster by   1,2-dichloroethane  (Rapoport,
1960;  Shakarnis, 1970; King et al., 1979).  Non-dysjunction was
observed  inconsistently  (Shakarnis,  1969,  1970),  while  the
frequency  of somatic mutations  for eye pigmentation  increased
(Nylander et al., 1978). Mammals/mammalian cells

    A  spot test  using mice  provided weak  evidence that  1,2-
dichloroethane  can  induce  somatic mutations  (Gocke  et  al.,

    In  Chinese hamster ovary cells,  1,2-dichloroethane induced
mutations at the HGPRT-locus (Tan & Hsie, 1981; Zamora  et  al.,
1983).  Metabolic activation increased the mutation frequency in
the  presence of NADPH  (Tan & Hsie,  1981).  1,2-Dichloroethane
also  induced  a  dose-related  increase  in  the  frequency  of
mutations  at the HGPRT-locus  in two human  lymphoblastoid cell
lines,  AHH-1 and TK6.  The mutation frequency in the AHH-1 cell
line  was 25 times that in the TK6 cell line.  The difference in
sensitivity  was attributed to the  difference in the levels  of
glutathione-S-transferase  (EC activity.  The activity
of  this  enzyme  in the AHH-1 cell line was 5 times that in the
TK6 cell line (Crespi et al., 1985).

7.5.2   Chromosome damage/DNA damage

    In  in  vivo studies,  no  effects were  observed in dominant
lethal assays in 2 generations of ICR Swiss mice (Lane  et  al.,
1982)  and in the micronucleus test with CBA and NMRI mice (King
et al., 1979; Jenssen & Ramel, 1980).

    1,2-Dichloroethane  was  a  weak inducer  of unscheduled DNA
synthesis  in  cultured  human  lymphocytes  (Perocco  &  Prodi,

    DNA alkylation in  Salmonella by activated 1,2-dichloroethane
was  directly related to  the mutation frequency,  but  absolute
levels  of  DNA  alkylation  in  Salmonella were  considered  low
(Reitz et al., 1982).

    1,2-Dichloroethane weakly inhibited growth of DNA polymerase
deficient  E. coli (Brem et al., 1974; Rosenkranz, 1977).

    Administration   of  1,2-dichloroethane  to  mice  and  rats
resulted  in covalent binding  to macromolecules (Reitz  et al.,
1982; Arfellini et al., 1984; Inskeep et al.,  1986).   Absolute
levels   of   DNA  alkylation  in  rats,  either  by  gavage  or
inhalation, were considered low (Reitz et al., 1982).

    Hepatic DNA damage was demonstrated using the  alkaline  DNA
unwinding  assay in male B6C3F1  mice after a single  intraperi-
toneal  or oral dose of 1,2-dichloroethane that failed to induce
toxic effects in the liver.  It was also shown that,  after  one
inhalation  exposure,  hepatic  DNA  damage  only  occurred   at
exposure  levels that caused  high mortality (Storer  & Conolly,
1983; Storer et al., 1984).

7.5.3   Cell transformation

    1,2-Dichloroethane  did not transform BALB/c-3T3 mouse cells
in a test conducted without any exogenous  metabolic  activating
system  (Tu et al., 1985).  It enhanced transformation of Syrian
hamster embryo cells by simian adenovirus (Hatch et al., 1983).

7.6  Reproduction and Teratogenicity

7.6.1   Inhalation exposure

    It  has been reported  that 1,2-dichloroethane was  found in
the  fetuses of rats after exposure to 600 mg/m3 for 5 h (Withey
& Karpinski, 1985).

    Female  rats (strain unspecified) were exposed to 15 mg 1,2-
dichloroethane/m3,  for 4  h daily,  6 days/week,  for 4  months
prior  to mating.  During this  period, the estrus cycle  became
longer  than normal.   The rats  were then  mated  and  exposure
continued.   No  information on  the  effects on  fertility  was
given,   but  the  total  embryonal   mortality  increased  from
approximately 11% in controls to 27% in treated dams, while pre-
implantation  losses were found to be 5 times greater in treated
animals  than  in the  controls.   No fetal  abnormalities  were
reported,  with the exception of haematomas in the region of the
head, neck, and anterior extremities (Vozovaya, 1977).

    In  a second study,  1,2-dichloroethane was administered  to
female albino rats at a concentration of 57 ± 10 mg/m3  in  air,
for 4 h daily, 6 days/week, for 6 and 9 months.  When  the  rats
were mated, a reduction in fertility was observed  (6.5  fetuses
per  treated female  versus 9.7  in controls).   The  weight  of
newborn  rats  was  reduced (5.06  g  versus  6.44 in  unexposed
females).  Perinatal mortality was increased (Vozovaya, 1974).

    1,2-Dichloroethane  was  detected  in  placental  and  fetal
tissues  after inhalation  exposure to  1000 mg/m3  for  3  days
(daily duration not stated).  It was also found in  the  stomach
of 12- to 14-day-old mice, when lactating females  were  exposed
to   an  unspecified  concentration  of   1,2-dichloroethane  by
inhalation (Vozovaya, 1977).

    While the above results indicate a possible  adverse  effect
of  1,2-dichloroethane  on  reproduction, the  following  repro-
ductive  studies yielded negative results.  Groups of 20 Sprague
Dawley  rats  of  each sex  were  exposed  for 60  days prior to
mating,  for 6 h per day,  and 5 days per  week to 101, 304,  or
607 mg  1,2-dichloroethane/m3 in air.   After mating, they  were
exposed  similarly,  for another  116 days, but  for 7 days  per
week.  Females were not exposed between gestation day 21 and day
4  post partum.  Control  groups contained 30  rats each.   Pups
were  removed and examined  at 21 days  of age, and  the females
were  remated following the  removal of the  last litter.   Each
female produced 2 litters.  The parents did not show  any  toxic
effects  and  the  fertility  index  and  gestation  period were
normal.   In  the  pups, no  effects  were  found on  sex ratio,
survival indices, organ weights, or histology.  A small decrease
was  noted  in  the number  of  pups  in the  first  litters  at
304 mg/m3 (Rao et al., 1980).

    A  teratogenicity study was further performed with groups of
16 -  30  female rats  and 19 - 21  female rabbits (Rao  et al.,
1980).   These groups were exposed through inhalation to 0, 405,
or  1215 mg 1,2-dichloroethane/m3 air, for 7 h per day, from the
6th  day  of  pregnancy onwards  (rats  up  to the  15th day and
rabbits  up to the  18th day of  gestation).  Exposures at  both
levels  were toxic for rabbit  dams.  The higher exposure  level
was severely toxic for the rat dams; only 1 of the few surviving
females  was  pregnant,  and  all  the  implantation  sites were
resorbed.   No  adverse  effects on  reproduction  were observed
among  rats exposed at 405 mg/m3  and rabbits exposed at  405 or
1215 mg/m3.  The only gross change observed in rat fetuses was a
decreased incidence of bilobed thoracic centra.  There  were  no
significant alterations in rabbit fetuses.

7.6.2   Oral exposure

    Groups  of 18 female rats  that had received 0,  11 - 17, or
23 -  35 mg 1,2-dichloroethane/kg body  weight per day  via  the
feed, for up to 2 years, were mated with untreated  males.   The
purity  of  the  substance was  not  reported.   No  effects  on
reproduction were observed (Alumot et al., 1976a).

    Lane  et  al.  (1982) reported  a  2-generation reproduction
study  on  groups  of 10  male  and  30 female  ICR  Swiss  mice
receiving  nominally 5, 15, or  50 mg 1,2-dichloroethane/kg body
weight  per day  via the  drinking-water, for  up to  25  weeks.
Control  groups contained 20 male  and 60 female mice.   After 5
weeks of treatment, the mice were mated to produce F1A, F1B, and
F1C litters.  After weaning and 11 weeks of treatment,  the  F1B
mice were mated to produce F2A and F2B litters.  Remating always
occurred  2 weeks after  weaning.  In the  F1C and F2B  matings,
females  were  co-housed  with untreated  males  for  teratology
screening.   The parents  did not  show any  toxic  effects  and
fertility  and  gestation indexes  were  normal.  There  were no
effects  on survival, litter  size, postnatal body  weight,  and
gross  pathology  of  pups.  No  congenital  malformations  were

detected.   In  the F1C  and  F2B litters,  no  exposure-related
reproductive  effects were found.  In the F2B litters, there was
no  increase in  the incidence  of fetal  visceral  or  skeletal
anomalies.    F1C  litters  were   not  examined  for   skeletal

7.7  Immunotoxicity

    When  rabbits  were  exposed for  7.5 -  8  months  to  1,2-
dichloroethane  vapour  of  unspecified  purity  at  a  level of
100 mg/m3,  for 3 h per day,  6 h per week, an  80% reduction in
the  production  of  antibodies  against  typhoid  vaccine   was
observed.  Concomitantly, there was a 2-fold increase in Forsman
sheep erythrocyte antibodies (Shmuter, 1977).

    Immunosuppression was also noted in a later oral  study,  in
which  groups  of 32  male CD-1 mice  were exposed to  3, 24, or
189 mg  1,2-dichloroethane/kg  body weight  (purity unknown) via
the  drinking-water for 90 days.  In addition, groups of 10 male
CD-1  mice  were exposed,  once a day,  to 4.9 or  49 mg/kg body
weight by water gavage for 14 days.  Control groups comprised 48
mice in the 90-day study and 12 mice in the 14-day study.  Apart
from  a 30% reduction  in the leukocyte  count after 14  days of
exposure to 49 mg/kg body weight, no effects were found on other
haematological parameters and relative organ weights.  After the
90-day  exposure, decreases in body weight and fluid consumption
were  noted.   There  was a  tendency  towards  a  reduction  in
immunoglobulin  spleen antibody-forming cells and  in the serum-
antibody  level after sheep  erythrocyte immunization, while  no
effects  were observed  in the  response to  the B-cell  mitogen
lipopolysaccharide  S.  After the  14-day exposure, 25%  and 40%
suppression of antibody-forming cells were measured at  4.9  and
49 mg/kg  body weight, respectively.  After the 90-day exposure,
no  effects were seen on the cell-mediated immunity, assessed by
measuring   the  delayed  hypersensitivity  response   to  sheep
erythrocytes  and the spleen cell response to the T-cell mitogen
Concanavalin A.  After the 14-day exposure, a slight suppression
of  the delayed hypersensitivity  response was found,  which was
not dose-dependent (Munson et al., 1982).


    Limited  data are available  on the effects  on man of  1,2-
dichloroethane.   There are no  adequate controlled studies,  no
recent occupational studies, and no mortality studies.  However,
case studies of accidental exposures have been reported.

8.1  Accidental Exposures

8.1.1   Inhalation exposure

    Many  reports are concerned with  mixed exposures.  However,
in this publication, only case studies are considered  in  which
the  exposure was reported  to be to  1,2-dichloroethane  alone.
According  to a  review by  NIOSH (1976),  no data  on  exposure
levels and duration of exposure were reported.

    Inhalation  of 1,2-dichloroethane vapour first  afflicts the
central  nervous system.  Symptoms include  headache, dizziness,
weakness,  cyanosis,  muscular spasms,  hypotonia, vomiting, and
unconsciousness.   Death  often follows.   The respiratory tract
can  be irritated and inflamed  with such symptoms as  cough and
rales over the chest.  Cyanosis may occur either as  the  result
of  respiratory insufficiency due  to depression of  the central
nervous  system or by bronchial obstruction due to inflammation.
Epigastric or visceral pains and diarrhoea have  been  observed.
Autopsy reports frequently mention damage to the  lungs,  liver,
and kidneys (Wirtschafter & Schwartz, 1939; Hadengue  &  Martin,
1953;  Menschick,  1957; Troisi  &  Cavallazzi, 1961;  Suveev  &
Babichenko,  1969).  Changes in heart rhythm have been reported,
which are probably secondary effects (section 8.1.2)  (Suveev  &
Babichenko,  1969).   Clinical findings  include elevated serum-
bilirubin  levels  and  leukocytosis (Wirtschafter  &  Schwartz,
1939; Menschick, 1957) and elevations of blood-lactate, ammonia,
ornithine carbamyl transferase, serum aspartate transaminase (EC,  lactate  dehydrogenase,  and  creatine  phosphokinase
(Nouchi et al., 1984).

8.1.2   Oral exposure

    The effects of acute oral exposure are very similar to those
found after inhalation, but they are more pronounced.  A summary
of  acute oral intoxications was  prepared by US NIOSH  in 1976.
The  lethal effects of  1,2-dichloroethane associated with  oral
exposure  are presented in Table  11.  Oral doses of  20 - 50 ml
1,2-dichloroethane  have been identified as being lethal (IRPTC,
1984).   Several  major  syndromes can  be  identified including
central   nervous   system   depression,  gastroenteritis,   and
disorders   of  the  liver  and   kidneys.   Frequently-observed
cardiovascular  insufficiency and haemorrhagic diathesis  may be
related  to changes  in oxygenation  and effects  on  the  liver
(Weiss, 1957; Morozov, 1958; Hinkel, 1965; Bogoyavlenski et al.,
1968;  Martin et al., 1968;  Schönborn et al., 1970;  Yodaiken &
Babcock, 1973; Dorndorf et al., 1975; Andriukin, 1979).

Table 11.  Effects associated with acute lethal oral doses of 1,2-dichloroethane in human beingsa
Amount ingested (g)   Findingsb                                              Reference

    188 - 250         death of 4 males up to 35 h; internal                  Bryzhin (1945)c
                      haemorrhage at various sites; liver damage;
                      symptoms at 3 - 4 h

     87 - 125         death of 3 males after 5 - 8 h; internal               Kaira (1966)c
                      haemorrhage; symptoms immediate (uncon-
                      sciousness, vomiting, dizziness)

       103            death after 6 h; haemorrhagic lesions                  Noetzel (1944)c

        75            death after 22 h; symptoms at 2 h (cyanosis,           Hueper & Smith (1935)
                      (cyanosis, vomiting, dilated pupils); brain
                      haemorrhage, liver damage, nephrosis

        63            death at 91 h; lack of eye reflex to light             Roubal (1947)c
                      on 4th day; vomiting; rapid pulse

        63            death in 3 - 4 h; liver damage                         Secchi et al. (1968)c

        63            death at 17 h; cyanosis, diarrhoea; impaired           Schonborn et al. (1970)
                      blood coagulation

        50            death at 24 h; haemorrhage at various sites;           Martin et al. (1968)
                      signs of cardiac damage

Table 11 (contd).
Amount ingested (g)   Findingsb                                              Reference

        50            death at 28 h; internal haemorrhage                    Garrison & Leadingham (1954)c

        37            death at 10 h; internal haemorrhage at                 Lochhead & Close (1951)
                      various sites; adverse lung effects

        25            death at 24 h; epigastric pain; slow                   Roubal (1947)c

        25            death at 13 h; symptoms at 1 h (cyanosis,              Flowtow (1952)c

        25            death within 12 h; symptoms not reported               Flowtow (1952)c

        19            death after 6 days; liver, kidney, renal               Yodaiken & Babcock (1973)
                      damage; pulmonary oedema; hypoglycaemia;
                      clotting time decreased; some haemorrhaging

        10            death after 56 h; delirium; pulse deterior-            Bogoyavlenski et al. (1968)

a   Studies  in which doses could  not be estimated have  not been cited.  The  reader is referred to  
    NIOSH (1976) for  a description of these case reports.
b   Unless otherwise stated, death refers to single male individuals.
c   The reader is referred to NIOSH (1976) for a more complete description of symptomology.
    Symptoms  of  central  nervous  system  depression  commonly
appear  within 1 h, frequently with  cyanosis, nausea, vomiting,
diarrhoea, epigastric and abdominal pains, and irritation of the
mucous  membranes.  Irreversible brain damage  has been reported
in  one case, and brain  damage has been found  in several fatal
cases (Rohmann et al., 1969; Dorndorf et al., 1975).  In some of
the  cases,  an interval  relatively  free of  symptoms followed
ingestion  (Hinkel, 1965; Martin et  al., 1968; Komarov et  al.,
1973;  Dorndorf et al.,  1975).  In the  next phase,  decreasing
consciousness and circulatory and respiratory failure may occur,
often leading to death some hours to some days  after  exposure.
During the intoxication, heart rhythm disturbances can  lead  to
cardiac arrest (Morozov, 1958; Martin et al., 1968;  Yodaiken  &
Babcock,  1973; Andriukin, 1979).  Autopsy reports have revealed
damage  to  the mucosae  of  the gastrointestinal  tract, liver,
kidney,  lung, heart, and brain.  Livers can be enlarged.  Liver
and  kidney epithelium can show fatty degeneration and necrosis.
Renal insufficiency has been reported to follow  development  of
hepatic  insufficiency and has been known to progress to uraemic
coma  (Natsyuk & Mudritsky,  1974).  Lung oedema  is  frequently
found.   Hyperaemia and haemorrhagic  lesions are found  in some
organs.   According  to  some  authors  (Martin  et  al.,  1968;
Schönborn et al., 1970; Yodaiken & Babcock, 1973),  it  appeared
that  the blood  coagulation time  was increased  because  of  a
decrease  in  blood  clotting factors  and  thrombocytes.  These
effects  appear  secondary  to liver  cell  necrosis complicated
further  by  intravascular  coagulation.   Biochemically,  liver
damage  is illustrated by  increased serum levels  of bilirubin,
transaminases,  and lactate dehydrogenase (Martin  et al., 1968;
Yodaiken  &  Babcock, 1973;  Dorndorf  et al.,  1975; Andriukin,
1979).   Kidney  damage  is  expressed  by  anuria  or  oliguria
(Morozov,  1958; Bogoyavlenski et al., 1968; Yodaiken & Babcock,
1973)   and  albumin, leukocytes,  and  epithelium cells  in the
urine.  Together with the histopathology, this points  to  acute
necrosis of the kidney tubule, possibly as a result of the liver
cell  necrosis and the  changes in circulation  (Morozov,  1958;
Hinkel, 1965; Yodaiken & Babcock, 1973).  Haematological changes
include  decreases  in  the erythrocyte  count  and  haemoglobin
content (Morozov, 1958; Dorndorf et al., 1975).

8.1.3   Acute effects on eyes and skin

    Dysfunction  of the central  nervous system, which  could be
caused  by brain oedema, can lead to effects on the eyes such as
dilation  or constriction of  the pupils and  impairment of  eye
reflexes (Weiss, 1957; Troisi & Cavallazzi, 1961).  Weiss (1957)
reported a cloudy cornea in 2 cases of oral exposure;  this  has
also  been reported in dogs (section 7.1.2).  Conjunctivitis was
found  in 2 out  of 4 patients,  who had been  exposed  to  1,2-
dichloroethane  vapour  (Menschick,  1957).  After  intermittent
immersion of the hands of 3 men in 1,2-dichloroethane  for  4 h,
severe dermatitis developed (Wirtschafter & Schwartz, 1939).

8.2  Occupational Exposure

    Only  2 reports are  available, and these  date from  before
1960.  In the first study (Cetnarowicz, 1959), 16  male  workers
from  an oil refinery, exposed  for 2 - 8 months,  were selected
for  close  examination.  A  group of 6  workers was exposed  to
concentrations  of  between 40  and 150 mg 1,2-dichloroethane/m3
air,  and a group  of 10 workers  was exposed to  concentrations
between  250 and 800 mg/m3.   The workers were  also exposed  to
benzene  at levels between 10 and 25 mg/m3, which was considered
not  significant by the  authors.  A general  reduction in  body
weight was observed.  Complaints came mainly from the group with
the  higher exposure  and included  a burning  sensation of  the
eyes,  lachrymation,  dizziness, lassitude,  sleepiness, nausea,
vomiting,  constipation,  poor  appetite, epigastric  pain,  and
weight  loss.  There was no  control group, but symptoms  repor-
tedly  disappeared  when  workers were  removed  from  exposure;
symptoms  returned upon re-exposure.  Most, but not all, abnorm-
alities  were  found  in the  group  with  higher  exposure  and
involved  the  liver  (8  workers),  central  nervous  system (3
workers), gastrointestinal tract (7 workers), and haematological
parameters (1 - 7 workers).  No lesions were found in  the  eye,
respiratory tract, lung, or heart.

    The  second study (Kozik,  1957), was conducted  on  workers
employed  in an aircraft factory  using a gum dissolved  in 1,2-
dichloroethane.   No data were given  on the composition of  the
glue or on the employment status of the workers.  Air concentra-
tions of 1,2-dichloroethane varied considerably, the level being
5  mg/m3  or  less during 70 - 75% of the working time, and 80 -
150 mg/m3 during 25 - 30% of the working time.  The morbidity of
the  workers in this  department during the  whole period  under
study  (1951-55)  was increased  for  all disease  categories in
comparison  with that in workers in the entire factory.  A group
of  83 workers was examined further, in the absence of controls.
There  were 19 workers with diseases of the liver and bile duct,
13  workers with neurotic conditions, 11 workers with autonomous
dystonia, and 10 workers with hyperthyroidism and goitre.

    These   reports  are  difficult  to   evaluate,  because  no
indication  is given of the  prevalence in unexposed workers  of
the symptoms and signs described in the case studies.


9.1  Evaluation of Human Health Risks

    In spite of the high volume of production  of  1,2-dichloro-
ethane,  there are no quantitative exposure-effect data on human
beings.  Frequently, 1,2-dichloroethane is not the only chemical
involved in an exposure and thus, cause-effect relationships are
difficult  to derive.  No  epidemiological or mortality  studies
are available.  There are only two old reports on  small  groups
of  occupationally-exposed men (section 8.2).   These data indi-
cate  that repeated inhalation exposures in the range of approx-
imately  40  -  800 mg/m3  may  lead  to central  nervous system
depression  and  gastrointestinal  and liver  abnormalities.  As
might  be expected, such symptoms were more prevalent in indivi-
duals exposed to high levels.  The only available data regarding
oral exposure are those involving fatal intoxications (Table 11,
section 8.1).

    Because  of the limitations  of the human  data base, it  is
necessary to rely on the available experimental animal  data  to
derive  a  no-observed-adverse-effect  level for  human  beings.
This  is possible because of  the similarity in the  spectrum of
adverse  effects in man  and laboratory animals,  which  include
central  nervous  system  depression, liver  and possibly kidney
abnormalties,  lung  oedema, and  cardiovascular disorders.  The
dose-response  data from animal  studies include a  no-observed-
adverse-effect level for the rat of about 400  mg  1,2-dichloro-
ethane/m3  air (section 7.2.1), equivalent to an intake of about
35 mg/kg body weight per day (assuming inhalation of  42  litres
over  7  h for  a 500-g rat  and 100% absorption).   The highest
registered  air  exposure level  of  the general  population  is
65 µg/m3    (Table 4,  section 4.1.2).   This level  leads to  a
calculated  intake  of 1.3  mg per person  per day (20  m3/day x
65 µg/m3).    A comparable intake from drinking-water containing
the  highest  level  recorded (6 µg/litre)   (Table  3,  section
4.1.1)  would  amount  to a  daily intake of  12 µg  (6 µg/litre
litre/day).   Thus, a combined  air and water  exposure, in  the
context  of a worst-case  scenario for the  general  population,
when  compared  with  the no-observed-adverse-effect  level  for
animals,  is lower by a factor of well over 1000.  Consequently,
for  the biological  end-points considered  so far,  it  can  be
concluded that 1,2-dichloroethane is unlikely to present a toxic
hazard  for  the  general population,  under prevailing exposure

    In an oral administration study, 1,2-dichloroethane produced
a  statistically-significant increase in squamous cell carcinoma
of the forestomach, haemangiosarcoma, and mammary adenocarcinoma
in rats, and mammary adenocarcinoma and hepatocellular carcinoma
in  mice (section 7.4.2).  In one carcinogenicity study, inhala-
tion  exposure did not result in an increase in tumour incidence
(section 7.4.1).  The natural occurrence of forestomach squamous
cell  carcinomas  in  rats and  haemangiosarcomas  in laboratory
rodents is unusual.  Taking into consideration that  cancer  has

been  produced in  two species  of experimental  animals and  in
several  target organs, it  can be concluded  that 1,2-dichloro-
ethane is carcinogenic for rats and mice, when  administered  by

    In  the absence of human  data, and taking into  account the
fact  that  1,2-dichloroethane produces  a reactive intermediate
that alkylates DNA, that it is positive in a number of  in vitro 
mutagenicity  tests, though weakly so (section 7.5), and that it
results  in the production  of both rare  and common tumours  in
rats  and mice, it  would be prudent  to consider  1,2-dichloro-
ethane as a possible human carcinogen.  Therefore, 1,2-dichloro-
ethane  should be  regarded, for  practical purposes,  as if  it
presented  a carcinogenic  risk for  man.  Thus,  levels in  the
environment should be kept as low as feasible.

    Since  there are no human  data, it is necessary  to rely on
the limited data available from experimental animal  studies  in
evaluating  reproduction hazards and teratogenicity.  The weight
of  evidence (section  7.6) does  not suggest  that exposure  to
prevailing  environmental levels would pose a human reproductive
or teratogenic hazard.

9.2  Evaluation of Effects on the Environment

9.2.1   Air

    Emissions of 1,2-dichloroethane into the air mainly occur in
process industries.  Other emissions occur during its use  as  a
fumigant,  solvent, and lead scavenger, and via evaporation from
contaminated water and from waste disposal sites.   Total  emis-
sions  are estimated to amount to 0.2% of the production volume.
Photochemical  degradation via oxidation by hydroxyl radicals is
the most important route of elimination from air.   Rainout  and
adsorption on atmospheric particles are unlikely to be important
processes of elimination.  Photolysis is theoretically a possib-
ility,  but no evidence of  this is available.  The  products of
the   photochemical  degradation  are  carbon  monoxide,  carbon
dioxide,  hydrogen chloride, formyl chloride,  and chloroacetyl-
chloride.   The two last  compounds will degrade  further.   The
process  is rapid enough to prevent accumulation of the compound
in the atmosphere (section 3.3).

9.2.2   Water 

    Emissions  of  1,2-dichloroethane  into water  may amount to
0.1% of the production volume.  Some of the emissions  from  EDC
tars,  which total  about 0.5%  of the  production volume,  will
contaminate water.  The main process of removal of 1,2-dichloro-
ethane from water is evaporation.  Chemical degradation  is  not
expected,  nor is biodegradation fast enough to be of any signi-
ficance  (section 3.1).  Bioconcentration in  aquatic species is
unlikely  in  view of  the  rather low  octanol/water  partition
coefficient.  This conclusion is supported by a  low  bioconcen-
tration factor found experimentally (section 6.1.4).

    The  compound was only  slightly toxic for  aquatic  species
tested.   A no-observed-adverse-effect concentration for  Daphnia
magna in  a long-term test was 11 mg/litre (section 6.1.3).  The
lowest LC50 value (85 mg/litre) was found for the shrimp  Crangon
crangon (section  6.1.1).   Average environmental  levels of the
compound  in surface water are generally below 1 µg/litre,  but,
in  heavily  polluted  surface  water,  average  levels   of 5.6
µg/litre   have  been  measured with  a  maximum of 90 µ g/litre
(Table 3, section 4.1.1).

    On  the basis of the  above data, it can  be concluded that,
except  in case of  accidents and inappropriate  disposal,  1,2-
dichloroethane  does  not  pose  a  significant  hazard  for the
aquatic  environment.  However, it should be noted that EDC tars
are much more toxic than 1,2-dichloroethane (section 6.1.1).

9.2.3   Soil

    Data  are not  sufficient to  evaluate the  effects of  1,2-
dichloroethane in soil.


1.      DNA alkylation (adduct identification).

2.      Studies  on  sub-chronic  toxicity using  various  routes of

3.      Assessment  of the extent  to which EDC  tars contribute  to
        contamination of groundwater by 1,2-dichloroethane.

4.      Dose-response  studies on sensitive,  commercially important
        fish  species  (particularly  studies relevant  to  EDC  tar


    1,2-Dichloroethane  was evaluated by IARC in 1979 (Volume 20
of the IARC Monographs).  It was concluded that:

    "There  is  sufficient  evidence that  1,2-dichloroethane is
carcinogenic  in mice and rats.  In the absence of adequate data
in humans, it is reasonable, for practical purposes,  to  regard
1,2-dichloroethane  as if it  presented a carcinogenic  risk  to


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    See Also:
       Toxicological Abbreviations
       Dichloroethane, 1,2- (EHC 176, 1995, 2nd edition)
       Dichloroethane, 1,2- (FAO Nutrition Meetings Report Series 48a)
       Dichloroethane, 1,2- (WHO Food Additives Series 30)
       Dichloroethane, 1,2-  (WHO Pesticide Residues Series 1)
       Dichloroethane, 1,2- (Pesticide residues in food: 1979 evaluations)
       Dichloroethane, 1,2- (CICADS 1, 1998)
       Dichloroethane, 1,2- (IARC Summary & Evaluation, Volume 71, 1999)