Advisory Opinion for Cis-I,2-Dichloroethylene
                       Off ice of Drinking Water
                 O.S. Environmental Protection: Agency
                       Washington, D.C  20460

/AN OFFICE OF DRINKING WATER: HEALTH EFFECTS ADVISOR*

 The Office of Drinking Water provides advice on health
 effects upon requestr concerning unregulated contaminants
 found in drinking water supplies.  This information suggests
 the level of a contaminant in drinking water at which ad-
 verse health effects would not be anticipated.  A margin of
 safety is factored.in so as to protect the most sensitive
 members of the general population.  The advisories are
 called Suggested No Adverse Response Levels (SNARLs).
 SNARLs have been calculated by EPA and by the National
 Academy of Sciences. (NAS) for selected contaminants in
 drinking water*  An SPA-SNARL and a NAS-SNARL may well
 differ due to the possible selection of different experimen-
 tal studies for use as the basis for the calculations.  Fur-
 thermore, NAS-SNARLs are calculated for adults while the
 EPA-SNARLs are established for a 10 kg body weight child.
 Normally EPA-SNARLs are provided for one-day, ten-day and
 longer-term exposure periods where available data exist.  A
 SNARL does not condone the  presence of a contaminant in
 drinking water, but rather provides useful information to
 assist in the setting of control priorities in cases where
 contamination occurs.  EPA-SNARLs are provided on a case-by-
 case basis in. emergency situations such as spills, and acci-
 dents.

 In the absence of a formal drinking water standard for an
.identified drinking water contaminant, the Office of Drink-
 ing Water develops EPA-SNARLs following the state-of-the-art
 concepts in toxicology for non-carcinogenic risk for short
 and longer term exposures.  In cases where a substance has
 been identified as having carcinogenic potential, a range of
 estimates for carcinogenic risk based upon lifetime exposure
 as developed by the HAS (1977 or 1980) and/or EPA Carcinogen
 Assessment Group (EPA, 1980a) is presented.  However, the
 EPA-SNARL calculations for all exposures ignore the possible
 carcinogenic risk that may result from these exposures*  In
 addition, EPA-SNARLs usually do not consider the health risk
 resulting from possible synergistic effects of other
 chemicals; in drinking water,  food, and air.

 EPA-SNARLs are not legally enforceable standards; they are
 not issued as an official regulation, and they may or may
 not lead ultimately to the issuance of national standards or
 Maximum Contaminant Levels (MCLs).  The latter must take
 into account occurrence,  relative source contribution
 factors, treatment technology,  monitoring capability, and

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costs, in addition to health effects*  It is quite conceiv-
able that the concentration set for EPA-SNARL purposes might.
differ from an eventual MCL.  The EPA-SNAALs may also change
as additional information becomes available.  In short, EPA-
SNARLs. are offered as advice to assist those such as Region-
al and State environmental and health officials, local pub-
lic officials, and water treatment facility personnel who
are responsible for the protection of public health when
dealing with specific contamination situations.

General'Information and Properties

Cis-l,2-dichloroethylene is one of three isomers of
dichloroethylene, all clear, colorless liquids with the
molecular formula of C2H2C12 and a molecular weight bf
96.95 (Irish, 1963).  It is moderately soluble in water (3.5
g/1 at 25C) , but soluble in most organic solvents.  The
cis-isomer has a vapor pressure of 208 Torr ( mm Hg) at 25C
and a boiling point of 60*C.  Its vapor density is 3.34,
over three times that of air, so that it will settle in low
places in a still atmosphere-  Its specific gravity is 1.27
at 25C.   Thus, it also would tend to sink in a still body
of water.

Horsely (1947) lists a binary azeotrope with water (3.35%
water by weight, boiling at 55.3C)  and a ternary azeotrope
with water and ethanol (2.85% water, 90.5% cis-l,2-dichloro-
ethylene  and 6.65% ethanol by weight, boiling at 53.8 C).
This* isomer also forms an azeotrope with ethanol or methanol
alone.

In air, one (1) ppm is equivalent to 3.97 mg/m3 and one
(1) mg/1 is equivalent to 252 ppm (Irish, 1963).

The existing threshold limit value (TLV) for the dichloro-
ethylenes in the United States is 200 ppm (794 mg/m3)
(ACGIH, 1977).

1,2-Dichloroethylene, as a mixture of the cis- and trans-
isomers,  is used as a solvent for such substances as fats,
rubber, phenol and camphor and for retarding fermentation
(Windholz et al., 1976).  It also is used as a low tempera-
ture extraction solvent for heat sensitive substances and
has been  employed as a coolant in refrigeration plants
(Bardie,  1964).

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Sources'of Exposure

Cis-l,2-dichloroethylene has beea detected in a number of
raw and finished drinking waters, principally from ground
water sources.  During the National Organics Reconnaissance
Survey (NORS), this isoraer was detected in Miami drinking
water at 16*0 ug/1 (U.S. EPA, 1975)  Concentrations of 0.1
ug/1 were observed in samples from Cincinnati and
Philadelphia; none was detected in drinking waters from the
other cities.  '..,.-.....

Cis-l,2-dichloroethylene was detected at an average concen-
tration of 0.17 ug/1 in three of 105 raw surface waters
examined (2.9%) in a number of surveys (Coniglio, et al,
1980).  An average of 0.66 ug/1 was detected in five of 103
samples (4.9%) of finished water from these surface water
supplies.  Of 13 ground water samples collected in 13 cities
during- one or: more of several surveys (NORS, MOMS, or the
recent. SRI survey conducted for EPA), four (30.8%) of the
samples were positive for cis-l,2-dichloroethylene.  Three
samples contained less than 1 ug/1; one sample contained 37
ug/1.,

Pellizzari (1978) found slightly higher levels of 1,2-
dichloroethylene (cis- and trans isomers not distinguished)
than 1,1-dichloroethylene during his air sampling survey.
The maximum amount of 1,1-dichloroethylene measured was 2500
ng/m^ at Front Royal, Virginia.  Maximum concentrations of
1,2-dichloroethylenes detected in various areas of the
United States varied from a trace (detection limit  260
ng/nH or higher) near Magna, Utah, South Charleston, West
Virginia, and Grand Canyon, Arizona, to 5263 ng/ra3 at the
Kin-Buc Disposal Site in Edison, New Jersey (an industrial
site near an urban area).

No data are available on the presence of either isomer of
1,2-dichloroethylene in foodstuffs.

Pnarmacbkihetics  -

Cis-l,2-dichloroethylene, as a neutral, low molecular
weight, lipid soluble material, should be systemically
absorbed following any route of administration.

No pharmacokinetic data appear to exist which define the
absorption rate of cis-l,2-dichloroethylene after oral
exposure.  However, pharmacokinetic studies based on urinary
and biliary excretion data show that administration of a
single oral dose of 1,1-dichloroethylene (1 or 50 mgAg)
results in rapid and complete absorption in rats and mice
(McKenna, et air 1978b).  Rapid absorption and distribution

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 of 1,1-dichloroethylene after intraperitoneal administration
 to rats also occurs (Jones  and Hathway,  1978).  For purposes
 of SNARL development,  then, we will  assume  that cis-1,2-
 dichloroethylene  is absorbed rapidly and completely after
 oral exposure.

 Hie absorption  of gases from the lung is highly dependent
 upon the blood:gas partition coefficient.   Sato and NaJcajima
 (1979)  showed that cis-l,2-dichioroethylene has a  blood:gas
 partition coefficient  of 9.2 in the  rat. While it has a
 high blood solubility, this chemical in  air reaches a
 steady-state within the whole rat in about  2 hours (Filser
 and Bolt, 1979).

 Distribution data on cis-l,2-dichloroethylene are  not avail-
 able.   However, if this isomer follows the  same distribution
 pattern as that observed for 1,1-dichloroethylene,  the
 highest concentration  would  be found in  the  liver  and kidney
 (McKenna, et al,  1978a).  These studies  were performed in
 rats, exposed by  inhalation  to concentrations varying from
 10-2000 ppm C-v^40-8000 mg/m3)  for 2  or 6 hours.

 Bonse,  et al. (1975) observed  that metabolism of cis-1,2-
 dichloroethylene  in  perfused  rat  liver produced detectable
 amounts of dichloroethanol and dichloroacetic acid,  possibly
 indicating  the  initial  formation  of  dichloroacetaldehyde.
 Liebman and Ortiz (1977)  have  postulated the  metabolic
 pathways  for cis-l,2-dichloroethylene.   One proposed pathway
 would be conversion  to a  reactive epoxide intermediate,  then
 to monochloroacetyl  chloride and  monochloroacetic acid.   The
 authors also suggested  that  the production of dichloroace-
 taldehyde may occur  by rearrangement of  the glycol or the
 epoxide with migration  of a chloride ion.  Their attempts to
 identify a  chromatographic peak as dichloroacetaldehyde  were
 inconclusive.

An essential feature of the metabolic pathway is that the
compound appears  to be metabolized to an epoxide intermedi-
ate which is reactive and which may  form covalent bonds  with
tissue macromolecules  (Henschler, 1977; Henschler and Bonse,
1977).  These authors have synthesized chemically the epox-
ides for both isomers of  1,2-dichloroethylene;  they believe
that these epoxides are formed in vivo during  the metabolic
process.  Each was inactive when  tested for mutagenic
potential in a modified Ames system  (Greim et al, 1975).
However, these results only added support to  the hypothesis
of Henschler and co-workers that  the epoxides with symmetri-
cal chlorines are more stable and less likely to be mutagen-
ic.  This does not exclude the possibility that these

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symmetrical, epoxides may still interact with tissue macro-
molecules other than DNA, a process which may result in some
form of damage other than autagenesis or carcinogenesis.

There apparently are no published studies which test the
interaction of the isomers of 1, 2-dichloroethylene with DNA;
nor are there any which evaluate the interaction of these
two isomers with other tissue macromolecules .

No data concerning the excretion of cis-1, 2-dichloroethylene
are available.  The rate of elimination of 1,1-dichloroethy-
lene is relatively rapid, with most of a dose being excreted
in the first, 24-72 hours after cessation of exposure*  One
might assume that cis-1, 2-dichloroethylene would be elimina-
ted at a similar rate.

Health" fiffects

There are no published studies available to us at this time
which describe accidental, occupational or controlled expo-
sures to cis-1 r 2-dichloroethylene in humans by any route or
for any duration of exposure.  At high concentrations (4000
ppm) central nervous system effects have been described from
unpublished data (Irish, 1963).  This concentration was
estimated to be sufficient to rapidly produce a state
resembling drunkenness and was judged likely to result in
unconsciousness if exposure were continued.

Data on the toxicity of cis-1, 2-dichloroethylene in animals
are severely limited..  No LDso values for the cis- isomer
alone have been published.  The lowest lethal oral dose for
the mixture in the human (70 kg) is estimated to be 500
      (McBirney, 1954).
Jenkins, et al. (1972) tested the effects of single 400 or
1500 mg/kg oral doses of each isomer of dichloroethylene in
corn oil given to adult female Holtzman rats weighing
200-470 g.  Liver and plasma enzyme activities were deter-
mined 20 hours after dosing.  The cis- isomer appeared to
exert a more potent effect than did the trans- isomer at the
higher dose.  No significant difference between the two iso-
mers was seen at the lower dose.  Each was less potent than
1,1-dichloroethylene. At 400 mg/kg, cis-1, 2-dichloroethylene
significantly increased liver alkaline phosphatase to a*
level 10% above control (P < 0.05).  At 1500 mgAg/ this
isomer significantly decreased the level of liver glucose-6-
phosphatase to about 88% of control (P < 0.05).  Liver
tyros ine transaminase was decreased to 80% of control, and
plasma alanine transaminase to 14% of control (P < 0.05).
Plasma alkaline phosphatase was not altered.       x

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 In an animal study reporting on the central nervous system
effect of the cis- isomer,  the  chemical, did not anesthetize
 rats in 4 hours at 8000 pom (^-32,000 mg/m3),  but at
 16,000 ppm (/^64,000 mg/m3), they were anesthetized in 8
 minutes and killed within 4 hours (Irish,  1963).

 Preundt, and Macholz (1978)  showed that single  8-hour inhala-
 tion exposures to cis-1,2-dichloroethylene at  20Qf 600 or
 1000 ppm. (/"-'BOO,  2400  or 4000 mg/m3,  respectively) concen-
 trations resulted in a dose-dependent and  significant in-
 crease in hexobarbital sleeping time, zoxazolamine paralysis
 time and the metabolic formation of 4-aminoantipyrine (AAP)
 from aminopyrine  in adult female Wistar rats.   The effects
 induced by the cis- isomer  were more  severe than those
 induced by the trans-  isomer*  The authors attributed this
 difference to the higher uptake of the cis- isomer by liver
 tissue.  The investigators  concluded  that  the  inhibition of
 hepatic drug metabolism,  as reflected in the change in AAP
 levels, was caused by  a competitive,  reversible interaction
 of, the chemical with the mixed  function: oxidase system.

 Teratbgehlcity

 No reports on the teratogenic potential of cis-1,2-dichloro-
 ethylene are available at the present time.

 ftutagenicity

 Both*cis and trans-1,2-dichloroethylene were  non-mutagenic
 when assayed with E. coli K12 at similar concentrations used
 for 1,1-dichloroetEylene at which the latter was found to be
 mutagenic (Greim, et al,  1975).   The  medium concentration of
 the cis-isomer was 2.9 mM,  that of t-l,2-DCE was 2.3 mM, and
 that of 1,1-DCE was 2.5 mM.

 Both 1,1-dichloroethylene and cis-1, 2-dichloroethylene were
 mutagenic in the  host-mediated  assay  using Salmonella tester
 strains in- mice (Gerna and  Kypenova,  1977). Of the three
 isomeric dichloroethylenes, only cis-1,2-dichloroethylene
 produced chromosomal aberrations in bone marrow cells of
 mice following repeated intraperitoneal injections (daily
 injections at 1/2 LD$Q for  five or ten days).

 Carcinogenic!ty

 No studies have been completed  which  test  the  carcinogenic
 potential of cis-1,2-dichloroethylene.  It is  currently
 under consideration by the  National Toxicology Program.

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SNARL Development

     One-day SNARL

There are few animal studies available which provide dose-
response data on the toxicity of cis-l,2-dichloroethylene
(Irish, 1963; Jenkins et al, 1972; Freundt and Macholz,
1973).  Only the study by Jenkins and co-workers provides
information on what might be identified as a minimal effect
level.  In measuring levels of three liver enzymes and two
plasma enzymes, indicators of liver function, these authors
showed that a single 400 mg/kg oral dose to the rat produced
a significant change only in liver alkaline phosphatase,
while the other enzyme levels were not significantly affec-
ted.  This slight degree of liver involvement is felt not to
be life-threatening; evidence developed for 1,1-dichloro-
ethylene points to the fact that this degree of liver effect
appears to be quite rapidly and completely reversible once
exposure has ceased.

The Jenkins et al. results may be used to develop a one-day
SNARL.  It would be derived thusly:

     400 mg/kg x 10 kg x 100%  4 mg/1
       .1000 x 1

Where: 400 mg/kg * minimal effect dose
     
       10 kg - weight of protected individual (child)

       100%  percentage of dose absorbed

       1000 * safety factor

       1 * volume in liters of drinking water imbibed per
       day by 10 kg child                ,

     Ten-day SNARL

A ten-day SNARL can be derived from the one-day SNARL which
will adequately protect the sensitive individual from
adverse health effects over that duration of exposure.  As
stated above, any slight alteration in liver function is
felt to be quickly and readily reversible after cessation of
exposure.

A ten-day SNARL would be derived simply by dividing the one-
day SNARL by 10 to get 0.4 mg/1.

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                              8

Analysis
^^MM^H^HM^^B^^B^" ,                        

Cis-l,2-dichloroethylene and trans-l,2-dichloroethylene can
be analyzed by the purge-and-trap gas chromatographic proce-
dure used  for the determination of volatile organohalides in
drinking waters  (U.S. EPA, 198Ob; Bellar and Lichtenberg,
1979).  In this  procedure, volatile components are extracted
by an inert gas  which is bubbled through the aqueous sample.
The  compounds are swept from the purging device into a short
sorbent trap.  After a predetermined period of time, the
trapped components are thermally desorbed and backflushed
onto the head of a gas chromatographic column where separa-
tion takes place.

The  recommended  primary columns for organohalide analysis do
not adequately resolve the cis- and trans-l,2-dichloroethy-
lene isomersv  Therefore, it is suggested that the column
recommended for  confirmatory analysis be used when these two
chemicals  are being determined.  The recommended chromato-
graphic conditions for the analysis are given belowr

Column: Six feet long x 0.1 inch ID stainless steel or
        glass.

Packing; n  octane on Porisil - C (100/120 mesh).

Temperature; 50C isothermal for 3 minutes, then program at
             6'/minute to 170C.

Carrier"gas? Helium at 40 ml/minute*

Detection; Hall  model electrolytic conductivity or other
           halogen specific detector.

Sample"volume; 5 ml.

The retention time for- the cis- isomer is 726 seconds and
for the trans- isomer is 563 seconds under the conditions
specified  above.  Confirmatory analysis of each isomer by a
second column or by GC-MS techniques is recommended.  Al-
though the MS itself will not distinguish between cis- and
trans-l,2-dichloroethylene, the difference in GC retention
times will allow for proper identification.

The purge-and-trap procedure is applicable to the measure-
ment of most, organohalides over a concentration range of 0.1
to 1500 ug/1 when the Hall model electrolytic conductivity
detector is used.  Other halogen specific detectors are
generally  limited to measurements of 1.0 ug/1 or above.

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treatment

The best options for community systems to remove cis-1,2-
dichloroethylene appear to be granular activated carbon
(GAC), diffused or packed tower aeration/ and synthetic
resins.  The preferred treatment needs to be evaluated on a
case-by-case basis*  Pilot scale testing is essential to
estimate cost effectiveness since the quality of water may
greatly affect performance for each of the treatments*
Pilot scale data indicate that this compound is not as
easily removed by aeration (GAC or synthetic resins) as is
trichloroethylene or tetrachloroethylene.

Counter current diffused aeration, in a 30* diameter 10*
deep column, operating with a 10 minute contact time and an
air to water ratio of 30:1, removed 85% of cis-1,2-dichloro-
ethylene (present in groundwater at concentrations of 18-118
ug/1).  At an air to water ratio of 5:1, and the same oper-
ating conditions, 58% cis-1,2-dichloroethylene was removed
from the same water.  Counter current diffused aeration with
1.5 in. diameter columns, a 10 minute contact time and an
air to water ratio~of 4:1 removed 80% of the chemical in a
different groundwater sample containing 0.5 ug/1 of the
chemical.  The performance of diffused aeration will be
affected by the design of the diffusers and matrix effects
(e.g., TOC and dissolved solids content).  The extent to
which each of these effects performance has not yet been
evaluated.

Packed column aeration may be a more economical treatment
alternative than diffused aeration.  However, no empirical
data are yet available to compare costs.
                   t

GAC with a bed depth of 2.5 ft and an Empty Bed Contact Time
(EBCT) of 6 minutes was used to treat a groundwater contain-
ing 25 ug/1 cis-1,2-dichloroethylene and 10 mg/1 TOC. Break-
through of the chemical (when concentrations in the effluent
exceeded .1 ug/1) occurred after 18 days of service or 4,300
bed volumes of throughput.  The loading of cis-1,2-dichloro-
ethylene on the carbon at breakthrough was 0.3 mg/gm. Amber-
sorb XE-340, a synthetic resin, with the same bed depth and
EBCT, did not have  breakthrough until after 60 days of
service or 14,400 bed volumes of throughput; the loading of
the chemical on the resin at breakthrough was 0.7 mg/gm.
The extent that service life of the adsorbent will be
affected by other organic substances competing for
adsorption sites is not yet known.

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                             10

In emergency situations,, or where funding is not available
for community treatment, boiling can be effectively used to
reduce cis-l,2-dichloroethylene concentrations to acceptable
levels.  Ten minutes of boiling at a water depth of 8 cm.
should reduce concentrations of 150 ug/1 to 5 ug/1 or less.

Conclusions'and Recommendations        ,         -

One-day and ten-day SNARLs of 4 mg/1 and 0.4 mg/1, respec-
tively, have been developed for cis-l,2-dichloroethylene.
At this time, no satisfactory dose-response, no-effect level
data exist from which a longer-term SNARL can be derived.
In addition, it would be preferable to have dose-response,
no-effect data for the one-day and ten-day SNARLs as well.
A grant has been awarded under the EPA Competitive Grants
program to study the toxicity of all three dichloroethylenes
and compare the percentage absorption via ingestion and
inhalation.  Data from this study, which will include no-
effect, dose-response data, should be available in 1982.  At
that time, the data will be reviewed and, if found suitable,
will form the basis for the revision of the existent SNARLs.
If the data are fpund lacking, further research will be
requested.

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                            11

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                             12

Henschlerv D and G Bonse.  1977  Metabolic activation of
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                             13

Pellizzarl, E.D.  1978.  Quantification of chlorinated
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