? OCT 1981
Advisory Opinion for 1,1-Dichloroethylene
(Vinylidene Chloride)
5013 Office of Drinking Water
U.S. Environmental Protection Agency
Washington, D.C. 20460
AN OFFICE OF DRINKING WATER HEALTH EFFECTS ADVISORY
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-
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 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
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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-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,
1977)s
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).
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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
instability.
No data were found to indicate contamination of foodstuffs
with 1,1-dichloroethylene residues.
m
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).
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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
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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
metabolites.
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>. -- - - - -
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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.,
1977).
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).
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Health"Effects
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
treatment-related.
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8
Teratogenicity
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.
Mutagehicity
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,
1977).
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
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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.,
1977c).
Carcinogenicifcy
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.
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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
adenocarcinoma.
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
inhalation.
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.
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11
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.
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12
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
Where:
100 mg/kg
10 kg
100%
1000
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
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13
Where:
7 mg/kg = daily consumption by rat at 60 ppm dose
level
10 kg = weight of child
1.0 = measure of absorption from GI tract
1000 = safety factor employed with minimal effect
dose
1 liter = volume of drinking water consumed daily by 10
kg child
Analysis
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
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14
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.
Treatment
(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.
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15
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18
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DISCLAIMER
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.
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