?  OCT 1981
             Advisory Opinion for 1,1-Dichloroethylene
                       (Vinylidene Chloride)
5013                  Office of Drinking Water
               U.S.  Environmental Protection  Agency
                      Washington, D.C.   20460


   The Office of Drinking Water provides advice on health
   effects  upon request,  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 EPA-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-

   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 NAS (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

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-SNARLs 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

1,1-Dichloroethylene (1,1-DCE, vinylidene chloride) is used
industrially as a chemical intermediate and in the manufac-
ture of polyvinylidene copolymers (PVDCs).  PVDCs are widely
used in food wrappings in the manufacture of non-flammable
synthetic fibers and as interior coatings for storage tanks
and piping.

1,1-Dichloroethylene is a clear, colorless liquid with the
molecular formula C2H2C12 and a molecular weight of
96.95.  It is slightly soluble in water (400 mg/1 at 20°C),
but readily soluble in organic solvents.  In air, one (1)
ppm is equivalent to 3.97 mg/ra3 and one (1) mg/1 is
equivalent to 252 ppm, when measured at 25°C and 760 mm^ Hg
(Irish, 1963).  It is extremely, volatile, having a vapor-
pressure of 591 Torr (mm Hg) at 20°C and a boiling point of
31.5°C.  It has a melting point of -122.1°C and a mild,
sweet odor similar to that of chloroform.  The liquid is
heavier than water with a specific gravity of 1.3. Its vapor
is over three times heavier than air and will, therefore,
settle in low places in a still atmosphere.  The monomer
polymerizes to a plastic at temperatures above 0°C, espe-
cially in the presence of oxygen or other catalysts.  The
octanol/water partition coefficient for 1,1-dichloroethylene
is 5.37 (Radding et all, 1977).

The present threshold limit value (TLV) for 1,1-dichloro-
ethylene in the United States is 10 ppm (40 mg/m3).. (ACGIH,

Sources'of Exposure

Pearson and McConnell (1975) indicated that degradation of a
chlorinated hydrocarbon such as 1,1-dichloroethylene when
dissolved in water is much slower than in the atmosphere.
They estimated a tropospheric half-life of eight weeks»  A.---
rapid degradation in aqueous systems does occur in the
presence of metallic iron (McConnell, et al., 1975).

1,1-Dichloroethylene has been detected in 2% of the finished
drinking water samples from 103 cites tested (Coniglio et
al., 1980).  The mean concentration was 0.36 ug/1, with a
range of 0.2-0.51 ug/1.  None was detected in 105 raw water
samples.  Thirteen cities were sampled whose water came from
ground water sources.  Of the raw waters tested, 15.4% (2
cities) were positive, (mean =0.5 ug/1).  Of the finished
waters tested, 7.7% (1 city) were positive (0.2 ug/1).

One might expect that the population most exposed to 1,1-
dichloroethylene would be workers in industries manufactur-
ing or using the chemical.  For example, time weighted
average (TWA) concentrations as high as 70 ppm were
estimated during air sampling studies at a polyvinylidene
chloride copolymer fiber production facility (Ott et al.,
1976).  1,1-Dichloroethylene was also identified as a
co-contaminant with vinyl chloride monomer in the working
environment of polyvinyl chloride production plants, present
at concentrations below 5 ppm, but typically at trace levels
(Kramer and Mutchler, 1972).

Ambient levels of 1,1-dichloroethylene have been measured by
Tenax sampling/gas chromatography-mass spectrometry analysis
(Pellizzari, 1978).  Maximum concentrations detected in var-
ious areas of the United States varied from a trace (260
ng/m3) near Grand Canyon, Arizona-,- up to 2500 ng/m3~at   -  ~~
Front Royal, Virginia.  The data may be low due to sample

No data were found to indicate contamination of foodstuffs
with 1,1-dichloroethylene residues.

1,1-Dichloroethylene, as a neutral> low molecular weight,
lipid soluble material, should be readily absorbed following
any route of administration.  Pharraacokinetic studies in
rats and mice based on urinary and biliary excretion data
have shown that administration-'of a-single oral dose of
1,1-dichloroethylene in the dose range 0.5-50 mg/kg results
in rapid and complete absorption (McKenna et al., 1978b;
Reichert et al., 1979;  Jones and Hathway, 1978a).  Rapid
absorption and distribution of 1,1-DCE after intraperitoneal
administration has also been demonstrated (Jones and
Hathway, 1978a).

 It  is  well  established  that  the  absorption of gases from the
 lung is  highly dependent  on  the  blood:gas partition coeffi-
 cient.  1,1-Dichloroethylene has a high blood:gas partition
 coefficient (4.0),  albeit less than trans-1,2-dichloroethy-
 lene  (10.9) (Andersen et  al.,  1980).   During  inhalation
 exposure, steady-state  conditions are reached in the whole
 animal within one  hour  (Filser and Bolt, 1979; Andersen et
 al., 1980).

 Distribution of  1,1-DCE to the organs of rats following
 intragastric administration  of an unspecified dose of
 [14C]1,1-DCE in  sequential autoradiograms of  longitudi-
 nal sagittal sections through whole animals showed large
 14C concentrations  in the kidneys and liver after 30
 minutes  and a more  general distribution of ^4C throughout
 the soft organs  of  the  body  at 1 hour (Jones  and Hathway,
 1978a).  The kidneys and  liver retained 14C for the
 longest  time after  dosing.

 Subcellular distribution  of  [14C]  30  minutes  following
 inhalation  of 2,000 ppm (8000 mg/ro3)  of [14C]1,1-DCE for
 2 hours  was determined  in the microsomal, mitochondrial, and
 cytosolic compartments  of the liver (Jaeger et al., 1977).
 More 14C was found  in liver  fractions from fasted rats
 than from fed rats. There was no marked subcellular
 localization of  14C since its concentration was about the
 same in  mitochondria, cytoplasm  and microsomes.  The ^4C
 found  in microsomes and mitochondria  was largely covalently
 bound  (TCA-insoluble).  In contrast,  the cytosol contained
 substantial amounts of  TCA-soluble^4C, suggesting the
 presence of metabolites.   Significant amounts of the 14C
 in microsoraes and mitochondria was CHCl3-soluble, sug-
 gesting  that there  is considerable binding of 14C to
 lipids.  The turnover rate of TCA-insoluble radioactivity
 derived  from 1,1-DCE has  a half-life.of_2-3.hours.	.

 Metabolic end products  of chlorinated ethylenes are predomi-
 nantly alcohols  and carboxylic acids.   Liebman and Ortiz
 (1977) have postulated  the various metabolic  pathways for
 1,1-DCE.  Chloroacetic  acid  has  been  identified as a product
 in perfused rat  liver.  Inhibition of epoxide hydrase
 resulted in a stimulation of Chloroacetic acid formation
 from 1,1-DCE, leading to  the conclusion that  the glycol
 intermediate is  relatively unimportant in the conversion of
.1,1-DCE  to  Chloroacetic acid (Leibman and Ortiz, 1977).
 Additionally, studies using  competitive epoxide substrates
 have shown  that  epoxide hydrating pathways are of minimal
 significance in .the jne.tabol lsm_of. .re a c.tl ve_ .jjLt e rmed iat e s .of..
 1,1-DCE  (Andersen  et al., 1980).  The essential feature of

 the  metabolic pathway for dichloroethylenes is that  all  of
 these  compounds appear to be metabolized through epoxide
 intermediates which are reactive and may form covalent bonds
 with tissue  macromolecules (Henschler, 1977; Henschler and
 Bonse, 1977).

 In whole animals,  it has been established that 1,1-DCE meta-
 bolites are  conjugated with glutathione, presumably  a detox-
 ification process  (McKenna et al., 1977, 1978a, 1978b; Jones
 and  Hathway, 1978a; Reichert et al., 1978, 1979).

 Reichert et  al. (1979) identified three metabolites  in rat
 urine, among these methylthioacetylaminoethanol.   In addi-
 tion,  three  unidentified materials were present in lesser
 concentrations. The identification of methylthioacetyl-
 aminoethanol suggests that, in addition to glutathione
 conjugation, a totally different reaction mechanism  must
 exist  which  leads  to the formation of ethanolamine deriva-
 tives.  The  ethanolamine is postulated to originate  from
 membrane lipids which react with 1,1-DCE epoxide and/or  its

 Data show that the metabolism of 1,1-DCE is readily  satur-
 able (Reichert et  al., 1979; Jones and Hathway, 1978a;
 Jaeger et al., 1977; Mcifenna-et-al., 1977, 1978a,  1978b) .
 Thus,  as the dosage is increased a larger absolute amount  of
 metabolite-- is ' formed r^bot--a lesser percgnl:au;trjo£ -the-^adnritr-"^"^
 istered -dose-dls - metaboH-zedv-"Tfris has* been—obs-erveTt-^rf-ter 	
 various routes of  administration.  As the dose is  increased
 and  metabolism reaches saturation, more parent compound  is
 excreted into the  air.

 Studies comparing  the relative ability of mice and rats  to
 metabolize 1,1-DCE have been conducted.  Data on disposition
 of 14C from inhaled [14C]1,1-DCE in mice and rats
 (McKenna- et--al% p-'19i77> -show1 that^he-Tnouse- ^ev^I'ops-^s higher -•>•
 body burden of 1,1-DCE than the rat-at-10 ppm (.5.3 meq 1,1-^  .
 DCE/kg vs. 2.89 meq/kg )-;— -The- dispositroir-o-f- -t;-l-"DCE- -appears—
 quite  similar in the two species.  However, as a result  of
 the  overall  greater rate of metabolism, covalently bound _
 1,1-DCE metabolites are more than four times higher  in the
 mouse  liver  than in the rat liver, and more than 6 times
 higher in mouse kidney -thrair in trhe ratrr  The- substantial"	
 difference in distribution may be responsible for  the
"different sensitivity of the two species to the carcinogenic
 effects, -of -1,1-DCE^tHathway^-ldT7>. --    -  - - -

Considerable work on the excretion of  1,1-DCE  and  its meta-
bolites has been done using  [14C]1,1-DCE  (Jaeger et  al.,
1977; McKenna et al., 1977,  1978a, 1978b;  Jones and  Hathway,
1978a; Reichert and Werner,  1978; Reichert et  al., 1979).
The data show that both unmetabolized  1,1-DCE  and  CC^
formed by metabolism of 1,1-DCE are excreted via the lung,
whereas the other metabolites are eliminated via renal and
biliary excretion.  However, the pattern of excretion de-
pends upon the concentration of 1,1-DCE in the blood, which
is affected by the amount of chemical  administered and to a
certain extent, by the route of administration.  At  low dose
levels, where metabolism is  effective  and  the  concentration
of 1,1-DCE in the blood is low, most of the 14C is elimi-
nated as metabolites via renal and biliary excretion. It has
been shown that a portion of the material  excreted in the
urine was actually of biliary origin and entered the urine
by means of enterohepatic circulation  (Jones and Hathway,
1978a).  At higher. dose levels, (/v, 200 ppm.)- where  the.   	
concentration of 1,1-DCE in  blood is much  higher, metabolism
approaches saturation and becomes less effective irr  removing
the xenobiotic from the blood as it passes through the liver
(Andersen et al., 1979).  As a result> increasing amounts-of--
unmetabolized 1,1-DCE are eliminated through the lung.

For 1,1-DCE the rate of elimination is relatively  rapid,
since most of the total absorbed dose  is eliminated  in the
first 24-72 hours after administration.  Disappearance of
covalently bound metabolites of 1,1-DCE, measured as
TCA-insoluble fractions, also appears _.to be fairly rapid.
with a reported half-life of 2-3 hours (Jaeger et  al.,

It is interesting to note that, based  on the analysis of
pharmacokinetic data from gas uptake studies,  it has been
suggested that the rate limiting step  in metabolism  of. DCEs .-
at low concentration is blood flow to  the  liver (Andersen et
al., 1980).  The rate at which an inhaled  chemical is
presented to the liver-is related to pulmonary absorption..
Since the weight-adjusted breathing volume decreases as body
weight increases?—the~coTicentra-tron—of- DCEs~in~ the- blood and—
presented to the liver would be expected to be reduced to a
similar-degree*— -For-.a rat,_the_re.st-ing~breathing-volume.JLs	
estimated to be 32 liters/kg-hr.— For  a modera-tely active-7^)	
kg man, the 8-hr, work shift breathing volume  is usually—
taken to be 10m3, i.e., 18 liters/kg hr.   Therefore, it is
expected that at lower exposure concentrations, a lesser
amount of DCEs would be presented to the liver in man
relative to the rat.  It has therefore been suggested that
at low atmosphericr^coTicentrations,--DCE" metabolism- would be   T
slower -in man . than; .rafca,^; - Shis.; would .-s-h-if±L. th^_Km^i^pmir-io=--^ - -
atmosphere) to even higher concentrations  for  man  (Andersen
et al., 1980).


1,1-Dichloroethylene, like other  chlorinated  hydrocarbons,
causes depression of the central  nervous  system after acute
exposures to high levels of the substance.   Exposure to high
concentrations can cause narcosis and  presumably could lead
to death due to depression of  the respiratory system.  In
addition, 1,1-dichloroethylene causes  liver  and kidney
damage in animals; similar damage could be expected to occur
in humans following prolonged  exposures to high concentra-
tions.  Inhalation exposure to this  compound  also has been
shown to sensitize the myocardium of rats to  catecholamines
(Siletchnik and Carlson, 1974).

Jenkins, et al. (1972) tested  the effects of  single 100, 300
or 500 mg/kg oral" doses of 1,1-dichloroethylene in corn oil
administered to adult male Holtzman  rats. Activities of
five liver or plasma enzymes were determined.   Twenty-two to
46 hours after dosing with 100 mg/kg,  liver  glucose-6-phos-
phatase (G-6-P) was reduced to 80% of  control  and liver
alkaline phosphatase (AP) was  doubled  (P  < 0.05).  At 300
mg/kg, after 22-46 hours, liver G-6-P  was further reduced to
53% of control, liver AP nearly quintupled,  liver tyrosine
transaminase quadrupled, and plasma  alkaline  transaminase
was elevated 150% (P <-0.05).  At--500  mg/kg,--all four en-- -
zymes were further affected; in addition, plasma alkaline
phosphatasejjwa3*"ejlevLa-fced"fovjer^4;0^!%-a^ovg-;eonbro-l--(-P~-< 0vG5).
A single long-term study has been  conducted  with 1,1-DCE
administered in the drinking water of-rats  (Humiston et al.,
1978).  Groups of 96 Sprague-Dawley  rats  (48 males anci~48
females) were exposed for 2 years  at nominal concentrations
of 60 ppm, 100 ppm, and 200 ppm;-  These dose levels oorres--
ponded to approximate daily intakes  in the range of 7 mg/kg,
11 mg/kg, and 22 mg/kg. at the  60,  100, and 200  ppm concen-
trations r - respectively? """'Sir-comparr JrsorF^to-^control" an ima-ls 7-- ---=•
treated rats displayed.no.significant or  consistent differr-
ences in general- -appearance/ -body-  we-ig-ht /—food  corcs-umption?—
water consumption, hematologic values, urinalysis, clinical
chemistry ~va2ruesyor ~orgair verghts-;—Gross- and  histopatho-	
logic examination of tissues from  treated rats, however,
revealed a number of statistically significant  lesions.   The
authors considered - the-raost-iraportant-iresrons -to -be the-—	
hepatocellular fatty change and periportal hepatocellular
hypertrophy which occurred  in male rats at the  200 ppm dose
level and - in-f emales ^at..all«dose-le«els*=—The ..authors .did .-^ ~ ,.
not observe any hepatocellular necrosis that was considered



The teratogenic potential of inhaled or ingested 1,1-DCE has
been evaluated in rats and rabbits (Murray et al., 1979).
Inhalation exposure for both species was 7 hours/day at 20
(rats only), 80, and 160 ppm.  In the ingestion study, rats
were given drinking water with 200 ppm 1,1-DCE or approxi-
mately 40 mg/kg/day.  Administration to rats was on days 6
to 15 of gestation and on days 6 to 18 for rabbits.  In
rats, inhalation of 80 to 160 ppm of DCE produced signifi-
cant maternal effects including decreased weight gain, de-
creased food consumption, increased water consumption and
increased liver weight (160 ppm only).  In the offspring,
there was a significantly increased incidence of skeletal
alterations at 80 and 160 ppm; these alterations included
delayed ossification of various bones and wavy-ribs.  -In- ~
rabbits, 160 ppra caused a significant increase in resorp-
tions in the dams and a significant change in several minor
skeletal variations in the offspring.  In both rats and
rabbits exposed to 1,1-DCE by inhalation, the authors noted
that concentrations which caused little evidence of maternal
toxicity (20 ppm in rats and 80 ppm in rabbits) caused no
adverse effect on embryonal or fetal development.  In rats
receiving 1,1-DCE by ingestion, the only significant effect
noted was an increase in mean fetal crown rump length.  The.
authors concluded that 1,1-DCE was not teratogenic at this
exposure level.


1,1-DCE was mutagenic in Salmonella typhimurium strains TA
1530, TA 100 (Bartsch et al., 1975; Simmon et al., 1977;
Simmon and Tardiff, 1978) and TA 1535 (Jones and Hathway,
1978b) and in 12. coll K12 (Greira et al., 1975).  In both
bacterial systems, mutagenic activity required microsomal
activation.  It also was rautagenic in the host-mediated
assay using Salmonella tester strains in mice (Cerna and
Kypenova, 1977).  1,1-Dichloroethylene did not produce any
chromosomal aberrations in bone marrow cells following
repeated intraperitoneal injections (Cerna and Kypenova,

The finding of increased mutation rates in bacterial systems
has not been confirmed in mammalian systems.  1,1-DCE was
non-mutagenic in V79 Chinese hamster cells in the presence
of 15,000 g liver supernatant from phenobarbital-pretreated
rats and mice (Drevon and Kuroki, 1979).  CD-I male mice

exposed to 10, 30, or 50 ppm of 1,1-DCE for 6 hours/day for
5 days failed to produce dominant lethal mutations (Andersen
and Jenkins, 1977).  Similarly, adult CD male rats exposed
to 55 ppm 1,1-DCE for 6 hours/day, 5 days/week for 11 weeks
failed to produce dominant lethal mutations (Short et al.,

The carcinogenicity of 1,1-DCE is currently being evaluated
in studies with mice and rats sponsored by the National
Toxicology Program. . These studies have been completed but
the reports were not yet available at the time this SNARL
package was drafted.

Studies of the potential carcinogenicity of 1,1-DCE have
been conducted with mice, rats and hamsters using either
oral administration or inhalation exposure.  Preliminary
results, after a total of 98 weeks observation in the
inhalation study and 93 weeks in the gavage study have been
reported (Maltoni 1977, Maltoni et al., 1977).  In the
inhalation study, Swiss mice were exposed to 10 or 25 ppm of
1,1-DCE for 4 hours/day, 4 to 5 days/week for 52 weeks and
then observed for the remainder of the study.  Exposure to
10 ppm of 1,1-DCE caused no statistically significant in-
crease in incidence of any tumor rn Swiss mice,  'fttr 25 ppm,
17% of the mice  (25/300) exposed to 1,1-DCE had developed
kidney adenocarcinomas compared to none in the control group
(190 males, 190 females).  The majority of tumors were
observed in male mice (24 males, 1 female).  In contrast, no
kidney adenocarcinomas were observed in Sprague-Dawley rats
under the same exposure regimen at exposures up to 200 ppm.
Data from this study also showed a significant increase in
mammary adenocarcinomas in female Swiss mice inhaling 25 ppm
and in female Sprague-Dawley rats inharing 100 and 150 ppm
of 1,1-DCE.  At 10, 25 or 50 ppm of 1,1-DCE there was no
increase in tumor incidence in Sprague-Dawley rats of either
sex.  Oral administration of 20 mg/kg of 1,1-DCE 4 to 5
days/week for'52 weeks to female Sprague-Dawley rats
resulted in a 42% incidence of mammary tumors in 21 of 30
animals, whereas control animals had a 34% incidence
(34/100).  Hamsters exposed for 52 weeks by inhalation to 25
ppm of 1,1-DCE did not exhibit an increased tumor incidence
after 74 weeks.

                              10  ~

In another inhalation study,  (Lee  et  al.,  1978)  CD-I mice
and CD rats were exposed to 55 ppm of 1,1-DCE for 6 hours/
day, 5 days/week for 7 to 12  months.   Hepatic heraangiosar-
comas were observed in the mice exposed  to 1,1-DCE: 2/35 for
males and 1/35 for females in the  treated  group  compared to
0/26 for males and 0/36 for females in the control group.
The significance of these hepatomas was  judged to be ques-
tionable because such tumors  have  been reported  to occur
spontaneously in small numbers at  this age (Percy and Jonas,
1971; Shen, 1974).  However,  two rats developed  hemangiosar-
comas in the mesenteric lymph node or subcutaneous tissue
which were judged probably to be caused  by 1,1-DCE.  Al-
though kidney pathology was observed, there was  no report of

An inhalation study using both Wistar rats and Sprague-
Dawley rats has been reported (Viola  and Caputo, 1977).
Exposures were to 1,1-DCE concentrations from 75 to 200 ppm
for 4 hours/day, 5 days/week  for 12 months.  Data from this
study were interpreted as showing  no  grossly observable
interrelation between tumor production and 1,1-DCE

Additionally, male and female Sprague-Dawley rats were
exposed -to -1,-1-DCE either ~by~dnhaiafcion>--f-2-5 or -75 ppra for 6
hours/day, 5 days/week for 18 months) or by ingestion in
drinking -water (6XX^-100^-or-2.00-^xpm--for--two-.year-s) .-•- In the  -
interim report of this study  (Rampy et al., 1977), there was
no evidence of increased tumor incidence in animals treated
with 1,1-DCE.

The effect of weekly oral administration of 50 mg/kg of 1,1-
DCE following in utero exposure  (150  mg/kg on day 17 of ges-*
tation) was studied in BDIV rats (Ponomarkov and Tomatis,
-1980).  The oral administration was continued throughout the
lifetime -of -the animals--un-til* -the*study-was- ter-rainated -after-
120 weeks.  There was no statistically significant increase
in the -total number -of.—tumo-r-bear-ing-  animals^ -However,-an-
increased incidence of tumors at certain sites was observed:
liver tumors in females -and-Tnenangiomars-in-males.—Addition-
ally, hyperplastic nodules of the  liver  were observed in
both male and female rats; these were not  seen in control
animals.  The authors concluded that-the-results-provided
limited evidence of carcinogenicity of 1,1-DCE.


The carcinogenic effects of lrl-DCE were also investigated
in Ha:ICR Swiss mice by several routes of administration
(Van Duuren et al./ 1979).  1,1-DCE was inactive as a whole
mouse skin carcinogen and inactive by subcutaneous injec-
tion.  In the two stage carcinogenesis assay using phorbal
myristate acetate as a promoter, 1,1-DCE was shown to be
active as a skin tumor initiator.

There are no published studies with adequately good data to
permit an evaluation of the carcinogenic risk of vinylidene
chloride to humans (Bahlman et al., 1979).  One study repor-
ted no excessive cancer risk among 138 workers occupational-
ly exposed to 1,1-DCE, but methodological limitations of
this study (Ott et al., 1976)'do not permit an adequate
evaluation of the carcinogenic risk, since the number of
individuals lost to follow-up in this study was high and the
period of observation was relatively short.  In a second
study, mortality was examined among 629 workers occupation-
ally exposed in a vinylidene chloride (1,1-DCE) production
and polymerization plant where there was also exposure to
vinyl chloride and acrylonitrile.  It was reported that 7 of
the 35 deaths that occurred were from malignant tumors.
This was not greater than the expected number.  Two bron-
chial carcinomas occurred in persons aged 35-39, whereas 0.8
were expected.  However, no information was given on smoking
habits (Theiss et al., 1977).

The Office'of Water Regulations and Standards (U.S. EPA,
1980a) in setting ambient water quality criteria for 1,1-
DCE, based its development of these criteria upon the find-
ing of Maltoni (1977) that this chemical caused a signifi-
cant increase in the number of renal adenocarcinomas ob-
served in Swiss mice exposed to 25 ppm, 4 hours/day, 4-5
days/week for 52 weeks.  The Office established a range of
criteria based upon levels estimated to increase the
lifetime'risk'of cancer "1 in 100,000," 1'in 1,000,000, or I
in 10,000,000.  The criteria ranged from 3.3-0.033 ug/1,
respectively, for an "adult co'nsuming 2 liters of that
contaminated ambient water per day and ingesting. 6.5 g/day
of contaminated aquatic organisms.  If total exposure were
solely from drinking the water, the resulting criteria would
range from 3.4-0.034 ug/1, representing a 10~5-10~7
risk, respectively.

SNARL' Development

     One-day SNARL

There are very limited ingestion data upon which  to base  a
one-day SNARL.  The results of_the. Jenkins et al. study
(1972) in which the authors measured the level of activity
of five liver or plasma enzymes after single oral doses of
100/ 300 or 500 mg/kg 1,1-dichloroethylene in corn oil may
be used.  The SNARL would be derived thusly:
     100'mg/kg x10'kg'x'100%  = 1.0 mg/1
          1000 x 1 liter
     100 mg/kg

     10 kg



     1 liter
minimal effect dose

weight of protected individual  (child)

percentage of dose absorbed

safety factor

volume in liters of drinking water imbibed
per day by 10 kg child
     Longe'r-fcerm' SNARL

A longer-term SNARL can be calculated from a two-year study
in which I/1-dichloroethylene was administered to rats at
60, 100 or 200 ppm in drinking water for 18 months  (Rampy et
al., 1977; Humiston et al., 1978).  Interim results  indica-
ted that- no. adverse effects occurred as determined by clini-
cal chemistry, hematology, mortality or histology (Rampy et
al., 1977).  However, when the study was completed,  it was
shown that minimal liver cha-ages fead*-ocearred:-im-females-'at '
all dose levels  (Humiston et al., 1978).  The 60 ppm dose
level could be considered.^a_minimal.-r-e£fect-lev-el.—A— longer--
term SNARL could be calculated thusly:
     7 mg/kg/aay' x^10'kg'x'1.0
           1000 x 1 liter
                 0.07 mg/1



     7 mg/kg = daily consumption  by  rat  at 60 ppm dose

     10 kg   = weight of child

     1.0     = measure of absorption from GI  tract

     1000    = safety factor employed with minimal effect

     1 liter = volume of drinking water  consumed  daily by 10
               kg child


1,1-DCE can be analyzed by a purge-and-trap gas chromato--
graphic procedure used for the determination  of volatile
organohalides in ~dr inking water (U.S. EPA,  1980b).  Volatile
chemicals are extracted by an inert  gas  which is  bubbled
through the aqueous sample.  The compounds, now in the gas-
eous phase, are swept from the purging device and are
trapped in a short column containing an  adsorbent material.
After a predetermined .per iod_o£~tome^.-tiie~trapped.-componen4is.-
are thermally desorbed and backf lushed onto the head of a
gas chroma tographic., column where-. separation-take^- place-. — — _

The suggested chromatographic parameters are  given below:

Primary column; eight feet long x 0.1 inch ID stainless
steel or glass tubing, packed with 1% SP-1000 on  Carbopack-B
(60-80) mesh.

Carrier7 gas i helium at" 4-0 mi/min7  ---------

Temperature; 45 °C for 3 minutes, then program at  8°C/minute
to 220°C.
Detector; r-Hall .model e-ieetro-ly tic -conductivity ;or^- other- ~-— T>*
halogen specific detector.

Sample" size; 5 ml.    -

This procedure is applicable to the measurement  of  1,1-DCE
over a concentration range of 0.4 to 1500  ug/liter.   The
retention time for this compound  in the  recommended  primary
column is 476-seconds-- --Ally! -chloride .may interfere -with -
the analysis of 1,1-DCE under the chroma tographic conditions


specified above.  However,  this  chemical does not appear to
occur at detectable levels  in most  drinking waters.  Never-
theless, confirmatory analysis by a GC-MS or by a secondary
analytical column is highly recommended.


(Forthcoming from STB)
Conclusloris'ahd' Recommendations

EPA-SNARLs for  1,1-DCE have been  developed for durations of
exposures of one-day and longer-term.   The potential for
carcinogenici-ty of this substance-has- not -been -considered" in
the development of these SNARLs,  although evidence does
exist to suggest that the  chemical  does interact with tissue
macroraolecules  and appears to-be  a  carcinogen in-Swiss mice
and perhaps in  CD rats.

To summarize, the one-day  SNARL is  1.0  mg/1;
              the longer-term-~SNARL
In order to be -afcle~to--deve3^^^-^en*H^
ingestion -data ,  ifc- can be "recofnmenderh~tha±~ strbehroTrxc -------
studies in animals receiving  1,1-DCE  in  their drinking water
be conducted to  better define the  toxicity of this compound
in water.  In fact, funding under  the EPA Competitive Grants
program has been made to an investigator to carry out these
experiments in rats exposed" to this 'substance "by ingestion
and inhalation.  No-effect levels  will be identified.  When
•these data become available,  they  will be reviewed for
acceptability in -their-' application in-«the^developmen-t-"af^" -----
SNARLs.  If they can be used,  this presently proposed. series.
of SNARLs will be evaluated -and -perhaps-changed -on— the basis
of the new information.



American Council of Governmental Industrial Hygienists
  (ACGIH).  1977.  TLVs.  Threshold limit values for
  chemical substances and physical agents in the workroom
  environment,  p. 30.

Andersen/ M.E., M.L. Gargas/ R.A. Jones and L.J. Jenkins/
  Jr.  1979.  The use of inhalation techniques to assess the
  kinetic constants of 1,1-dichloroethylene metabolism.
  Toxicol. Appl. Pharmacol. 47:395-409.

Andersen/ M.E., M.L. Gargas/ R.A. Jones and L.J. Jenkins/
  Jr.  1980.  Determination of the kinetic constants for
  metabolism of inhaled toxicants in vivo using gas uptake
  measurements.  Toxicol. Appl. Pharraacol. 54:100-116.

Andersen/ M.E. and L.J. Jenkins/ Jr.  1977.  Oral toxicity
  of 1,1-dichloroethylene in the rat: Effects of sex/ age
  and fasting.  Environ. Health Perspec. 21:157-163.

Bartsch, H., C. Malaveille, R. Montesano and L. Tomatis.
  1975.  Tissue-mediated mutagenicity of vinylidene chloride
  and 2-chlorobutadiene in Salmonella typhimurium.  Nature.

Cerna, M. and H. Kypenova.  1977.  Mutagenic activity -O-f—  -.-
  chloroethylenes analyzed by screening system tests.
  Mutat. Res. 46:214.

Coniglio, W., K. Miller and D. MacKeever.  1980.  The occur-
  rence of volatile organics in drinking water.  Briefing
  prepared for DAA for Drinking Water.  U.S. EPA.  48 pp.

Drevon, C. and Kuroki. • 1979.  Mutagenicity of vinyl chlor-
  ide/ vinylidene chloride and chloroprene in V79 Chinese
  hamster cells.  Mutat. Res. 67:173-182.

Filser/ J.G. and H.M. Bolt.  1979.  Pharmacokinetics of
  halogenated ethylenes in rats.  Arch. Toxicol. 42:123-136.

Greim, H., G. Bonse, Z. Radwan, D. Reichert, D. Henschler.
  1975.  Mutagenicity in vitro and potential carcinogenicity
  of chlorinated ethylenes as a function of metabolic oxi-
  rane formation.  Biochem. Pharmacol. 24:2013-2017.

Hathway, D.E.  1977.  Comparative.mammalian metabolism of
  vinyl chloride and vinylidene chloride in relation to
  oncogenic potential.  Environ. Health Perspec. 21:55-59.


Henschler, D.  1977.  Metabolism and mutagenicity of halo-
  genated olefins - a comparison of structure and activity.
  Environ. Health Perspec. 21:61-64.

Henschler, D. and G. Bonse.  1977.  Metabolic activation of
  chlorinated ethylenes; Dependence of mutagenic effect on
  electrophilic reactivity of the metabolically formed epox-
  ides.  Arch. Toxicol. 26:62-65.

Humiston/ C.G., J.F. Quast, C.E. Wade, J. Ballard, J.E.
  Beyer and R.W. Lisowe.  1978.  Results of a two-year toxi-
  city and oncogenicity study with vinylidene chloride
  incorporated in the drinking water of rats.  Report MCA
  No.: VCD 1.3-Tox-Orl-Dow.  Toxicology Research Laboratory
  Health and Environmental Research, Dow Chemical U.S.A.,
  Midland, Michigan.

Irish, D.D.  1963.  Vinylidene chloride.  In: Industrial
  Hygiene and Toxicology, 2nd ed. P.A. Patty, ed. Vol. II.
  John Wiley and Sons, Inc., New York.  pp. 1305-1309.

Jaeger, J.J., L.G. Shoner and L. Coffraan.  1977.  1,1-
  Dichloroethylene hepatotoxicity: Proposed mechanism of
  action of distribution and binding of 14C radioactivity
  following inhalation exposure in rats.  Environ. Health
  Perspec. 21:113-119.

Jenkins, L.J., Jr., M.J. Trabulus and S.D. Murphy.  1972.
  Biochemical effects of 1,1-dichloroethylene in rats:
  Comparison with carbon tetrachloride and 1,2-dichloro-
  ethylene.  Toxicol. Appl. Pharraacol. 23:501-510.

Jones, B.K. and D.E. Hathway.  1978a.  The biological fate
  of vinylidene chloride.  Chera. Biol. Interactions. 20:27-

Jones, B.K. and D.E. Hathway.  1978b.  Tissue-mediated rauta-
  genicity of vinylidene chloride in Salmonella typhimuriura
  TA 1535.  Cancer Lett. 5:1-6.  ._

Kramer, C. and J. Mutchler.  1972.  The correlation of
  clinical and environmental measurements for workers
  exposed to vinyl chloride.  Am. Ind. Hyg. Assoc. J. 33:

Lee, C.C., J.C. Bhandari, J.M. Winston and W.B. House.

  chloride.  J. Toxicol. Environ. Health. 4:15-30.


 Liebman, K.C. and E. Ortiz.  1977.  Metabolism of halogena-
   ted ethylenes.  Environ. Health Perspec.  21:91-97.

 Maltoni, C.  1977.  Recent findings on the carcinogenicity
   of chlorinated olefins.  Environ. Health Perspec. 21:1-5.

 Maltoni, C., G. Cotti, L. Morisi and P. Chieco.  1977.  Car-
   cinogenicity bioassays of vinylidene chloride.  Research
   plan and early results,.  Med. Lav-.. 68-:241-262.

 McConnell, G., D.M. Ferguson and C.R.  Pearson.  1975.
   Chlorinated hydrocarbons and the environment.  Endeavour

 McKenna, M.J., P.G. Watanabe and P.J.  Gehring.  1977.  Phar-
   macokinetics of vinylidene chloride  in the rat.  Environ.
   Health Perspec.  21:99-105.

 McKenna, M.J., J.A. Zempel, E.O. Madrid, and P.J. Gehring.
   1978a. The pharmacokinetics of (^C) vinylidene chloride
   in rats following inhalation exposure.  Toxicol. Appl.
   Pharmacol.  45:599-610.

 McKenna, M.J., J.A. Zempel, E.O. Madrid, W.H. Braun and P.J.
   Gehring.  1978b.  Metabolism and pharmacokinetic profile
   of vinylidene chloride in rats following oral administra-
   tion.  Toxicol. Appl. Pharmacol.  45:821-835.

 Murray, F. J., K.D. NitschJce, L.W. Rampy and B.A. Schwetz.
   1979.  Embryotoxicity and fetotoxicity of inhaled or
   ingested vinylidene chloride in rats and rabbits.  Toxi-
   col. Appl. Pharmacol. 49:189-202.

 National Academy of Sciences.  1977.  Drinking Water and
   Health, Volume 1.  Safe Drinking Water Committee, Wash-
   ington, D.C.

 National Academy of Sciences.  1980.  Toxicity of selected
   drinking water contaminants.  In; Drinking Water and
   Health, Volume -3 i - ~-?^Saf e Drinking "Water-€onim±t1?ee7'WasteiTig-^^--r -
   ton, D.C.

 Ott, M.G., W.A. Fishbeck, J.C. Townsend and E.J. Schneider.
   1976.  A health study of employees exposed to vinylidene
   chloride.  J. Occup. Med. 18:735-738.

-Pearson, C.R. and G. McConnell.  1975.  Chlorinated Cl and
   C2 hydrocarbons in the marine environment.  Proc. R. Soc.
   London B. 189:305-332.

Pellizzari, E.D.  1978.  Quantification of chlorinated
  hydrocarbons in previously collected air samples.  U.S.
  EPA, Research Triangle Park, NC.  EPA-450/3-78-112.

Percy, D.H. and A.M. Jonas.  1971.  Incidence of spontaneous
  tumors in CD-I HaM/ICR mice.  J. Natl. Cancer Inst. 46:

Ponomarkov, V. and I. Tomatis.  1980.  Long-term testing of
  vinylidene chloride and chloropropene for carcinogenicity
  in rats.  Oncology 37:136-141.

Radding, S.B., D.H. Liu, H.L. Johnson and T. Mill.  1977.
  Review of environmental fate of selected chemicals.  U.S.
  EPA, Contract No. 68-01-2681.

Rampy, L.W., J.F. Quast, C.G. Humiston, M.F. Blamer and
  B.A. Schwetz.  1977.  Interim results of two-year
  toxicological studies in rats of vinylidene chloride
  incorporated in the drinking water or administered by
  repeated inhalation.  Environ. Health Perspec. 21:33-

Reichert, D., H.W. Werner and D. Henschler.  1978.  Role
  of liver glutathione in 1,1-dichloroethylene metabolism
  and hepatotoxicity in intact rats and isolated perfused
  rat liver.  Arch. Toxicol. 41:169-178.

Reichert, D., H.W. Werner, M. Metzler and D. Henschler.
  1979.  Molecular mechanism of 1,1-dichloroethylene toxi-
  city: excreted metabolites reveal different pathways of
  reactive intermediates.  Arch. Toxicol. 42:159-169.

Reichert, D. and H.W. Werner.  1978.  Disposition and
  metabolism of (^C) l, 1-dichloroethylene after single
  oral administration in rats. (Abstract)  Naunyn-Schmie-
  deberg's Arch. Pharmacol. (Suppl.) R-22.

Shen, P.  1974.  Tumors in control mice: Literature tabula-
  tion.  Toxicol. Appl. Pharmacol. 30:337-359.

Short, R.D., J.L. Minor, J.M. Winston and C.C. Lee.  1977 .
  A dominant lethal study in male rats after repeated expo-
  sures to vinyl chloride or vinylidene chloride.  J. Toxi-
  col. Environ. Health 3:965-968.


Siletchnik, L.M. and G.P. Carlson.  1974.  Cardiac sensitiz-
  ing effects of 1,1-dichloroethylene: Enhancement by pheno-
  barbital pretreatment.  Arch. Int. Pharmacodyn. 210:359-

Simmon, V.F., K. Kauhanen and R.G. \ Tardiff.  1977.  Muta-
  genic activity of chemicals identified in drinking water.
  Dev. Toxicol. Environ. Sci. 2:249-258.

Simmon, V.F. and R.G. Tardiff.  1978.  The mutagenic acti-
  vity of halogenated" compounds found in chlorinated drink-
  ing water.  Water Chlorination: Environ. Impact Health
  Effects Proc. Conf. 2:417-431.

Theiss, A.M.  1977.  Mortality study of vinylidene chloride
  exposed persons in BASF.  Proceedings of 5th Medichem.
  Congr. San Francisco, 1977.  Reported by Ponomarkov and
  Tomatis.  1980.  Oncology. 37:136-141.

U.S. EPA.  1980a.  Water Quality Criteria Documents; Avail-
  ability.  Federal Register 45(231):79318-79379.

U.S. EPA.  1980b.  The determination of halogenated chemical
  indicators of industrial contamination in water by the
  purge and trap method, Method 502.1.  Environmental Moni-
  toring and Support Laboratory, Cincinnati, Ohio 45268.

Van Duuren, B.L., B.M. Goldschmidt, G. Loewengart, A.C.
  Smith, S. Melchionne, I. Seldman and D. Roth.  1979.
  Carcinogenicity of halogenated olefinic and aliphatic
  hydrocarbons in mice.  J.-Natl. Cancer Inst. 63:1433-

Viola, P.L. and A. Caputo.- 1977.  Carcinogenicity studies
  on vinylidene chloride.  Environ. Health Perspec. 21:45-

This health advisory is a preliminary draft.  It has
not been released formally by the Office of Drinking
Water, U.S. Environmental Protection Agency, and.should
not at this stage be construed to represent the position
of the Office of Drinking Water.  It is being circulated
for comments on its technical merit.