United States
Environmental Protection
Agency
Office of Health and
Environmental Assessment
Washington DC 20460
Research and Development
EPA/600/S8-83/031F Aug. 1989
&EPA Project Summary
Health Assessment
Document for
Vinylidene Chloride
The Office of Health and Environ-
mental Assessment has prepared
this health assessment to serve as a
"source documenf'for EPA use. The
health assessment document was
originally developed for use by the
Office of Air Quality Planning and
Standards to support decision-
making regarding possible regulation
of vinylidene chloride as a hazardous
air pollutant However, the scope of
this document has since been
expanded to address multimedia
aspects.
In the development of the assess-
ment document, the scientific litera-
ture has been inventoried, key
studies have been evaluated and
summary/conclusions have been pre-
pared so that the chemical's toxicity
and related characteristics are quali-
tatively identified. Observed effect
levels and other measures of dose-
response relationships are discuss-
ed, where appropriate, so that the
nature of the adverse health
responses are placed in perspective
with observed environmental levels.
Any information regarding sources,
emissions, ambient air concentra-
tions, and public exposure has been
included only to give the reader a
preliminary indication of the potential
presence of this substance in the
ambient air. While the available
information is presented as accur-
ately as possible, it is acknowledged
to be limited and dependent in many
instances on assumption rather that
specific data. This information is not
intended, nor should it be used, to
support any conclusions regarding
risks to public health.
This Project Summary was devel-
oped by EPA's Environmental Criteria
and Assessment Office, Research
triangle Park, NC, to announce key
findings of the research project that is
fully documented in a separate report
of the same title (see Project Report
ordering information at back).
Introduction
Vinylidene chloride is a highly reactive,
flammable, clear, colorless liquid that, in
the presence of air, can form complex
peroxides in the absence of chemical
inhibitors. The peroxkles are violently
explosive, and formaldehyde, phosgene,
and hydrochloric acid are produced as
decomposition products. Vinylidene chlo-
ride has a boiling point of 31.6°C at 760
mm Hg and a vapor pressure of 600 mm
Hg at 25°C. The solubility of vinylidene
chloride in water is 2250 mg/l at 25°C,
and the density of the liquid is 1.2132
g/cm3 (20°C). Vinylidene chloride vapor
is 3.34 times as dense as air.
Synonyms for vinylidene chloride are
1,1-dichloroethene, 1,1-DCE, and 1,1-di-
chloroethylene. Vinylidene chloride has a
molecular weight of 96.95 and a molec-
ular formula of C2H2CI2. The structural
formula is given below.
H
.
Cl
,
Vinylidene chloride monomer
production capacity in the United States
is approximately 178 million pounds per
year. Virtually all of the vinylidene chlo-
ride produced is used in the production
of copolymers with vinyl chloride or
acrylonitrile. A small percentage (4%) of
vinylidene chloride is used as chemical
intermediates.
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Sampling and Analytical
Methods
The two primary methods that have
been used in recent years for the samp-
ling and analysis of vinylidene chloride in
ambient air are the freeze-trap method
and the sorption onto Tenax-GC method
with subsequent analysis of the desorbed
vinylidene chloride by high resolution gas
chromatography with either flame ion-
ization, electron capture, electrical con-
ductivity, or mass spectrometric detec-
tors. Both the freeze-trap and Tenax-GC
methods of sample collection have some
disadvantages. For example, the freeze-
trap method using liquid oxygen is a
cumbersome method both for sample
collection and transportation, and the
Tenax-GC method may suffer from seri-
ous problems of artifact formation.
The two methods commonly used for
the analysis of vinylidene chloride in grab
aqueous samples are the static head-
space method and the dynamic purge-
trap method. However, for aqueous
samples containing very low levels of
vinylidene chloride (e.g., potable water),
the dynamic purge-trap method is more
suitable than the static head-space
method because of the higher sensitivity
of the former. Although gas chroma-
tography with either flame ionization,
electron capture, electrical conductivity or
mass spectrometric detectors has been
used for the final quantification of
vinylidene chloride by both methods, the
electrical conductivity detector is prefer-
able to other detectors because of its
greater sensitivity and selectivity The
mass spectrometric method is usually
used as a confirmatory technique.
Vinylidene chloride in soil samples has
been analyzed by solvent extraction in
sealed vials with subsequent quantifica-
tion by gas chromatography—flame ion-
ization detector (GC-FID), and using
mass spectrometry as the confirmatory
technique. The analysis of vinylidene
chloride in food wrapping materials,
foods, and biological tissues has been
performed either by the static head-
space method or by the dynamic purge-
trap method in a manner similar to that
employed for aqueous samples.
Sources in the Environment
Due to its high volatility, vinylidene
chloride is lost to the atmosphere during
industrial manufacture of the monomer
and polymer, and during storage and
handling. The total emission of vinylidene
chloride to all media from these facilities
has been estimated to be 1,300,400
pounds per year. Moreover, vinylidene
chloride originally in aqueous solution is
likely to contribute to air contamination as
a result of its high volatility from water.
Under atmospheric smog conditions,
the half-life of vinylidene chloride in air
has been determined to be 5 to 12 hours.
In the absence of smog conditions,
vinylidene chloride may persist in the
atmosphere with a half-life of approxi-
mately 2 days. Volatilization from aquatic
media is probably the most significant
fate-determining process for vinylidene
chloride, although the role of biode-
gradation still remains uncertain. The
half-lives of volatilization of vinylidene
chloride from pond, river, and lake water
have been estimated to be 6.1 days, 1.2
days, and 4.2 days, respectively. The fate
of vinylidene chloride in soils has not
been evaluated with certainty However, it
has been concluded from the limited data
that both volatilization and leaching may
play significant roles in determining the
fate of this chemical in soils.
The median ambient air level of
vinylidene chloride in urban/suburban
areas of the U.S. was estimated to be 5
ppt (20 ng/m3). However, the median
concentration value is substantially
higher, 2182 ppt (8.66 ug/m3) for ambient
air in the vicinity of point sources of
emission. The estimated daily vinylidene
chloride intake from ambient air in
urban/suburban areas through inhalation
is 0.4 jig. However, the daily inhalation
exposure from ambient air may be as
high as 0.17 mg in the immediate vicinity
of point sources. Vinylidene chloride has
been detected in approximately 3% of
the total drinking water supplies in the
U.S. at an estimated mean concentration
of 0.3 iig/l and a concentration range of
0.2 to 0.5 ng/l. For the majority of the
U.S. population, the daily exposure to
vinylidene chloride from ingestion of
drinking water has been estimated to be
less than 0.6 ng, although the maximum
daily exposure in certain communities
could exceed 1 ug. Because of the
paucity of data, no estimate of the dietary
intake of vinylidene chloride in the U.S.
can be made at the present time.
Biological Effects on Aquatic
Organisms
Vinylidene chloride is acutely toxic to
aquatic animals at exposure concen-
trations in the milligrams per liter range.
The lowest concentration reported to be
acutely toxic to an aquatic organism is
2.4 mg/l. Reported acute and subchronic
LC50 values ranged between 11.6 and
250 mg/l for aquatic animals. Vinylidene
chloride was not acutely toxic to aquatic
algae at concentrations of 712 to 798
mg/l. Vinylidene chloride was, however,
toxic to yeast. No information was found
concerning the toxicity of vinylidene
chloride to domestic animals and non-
aquatic wildlife.
Biological Effects in Animals
and Man
Vinylidene chloride is readily absorbed
by mammals following oral or inhalation
exposure. Vinylidene chloride is metab-
olized in the liver with a number ol
possible reactive intermediates, including
an epoxide, being formed. These reactive
intermediate metabolites can react witl"
macromolecules; this is a characteristic
of many chemical carcinogens. The
metabolites of vinylidene chloride pro
duce toxic lesions in the liver anc
kidneys, with inhibitors of metabolisrr
providing protection from vinylidenf
chloride toxicity. The heptatotoxic effec
can be extensive and histological effect;
can be noted within 2 hours after th(
onset of exposure. The acute hepato
toxicity of vinylidene chloride was showi
to be greater than that of any othe
chloroethylene. The liver and kidney
remain the target organs for toxic effect
regardless of the route of administratioi
(administration vehicle may influenci
vinylidene chloride metabolism ani
therefore affect the extent of toxicity) c
whether acute, subacute, or chroni
exposure occurs.
Vinylidene chloride has been describe)
as a possible weak teratogen in a stud
using rats and mice. In this study, th
experimental levels of vinylidene chlorid
were toxic to the dams, confounding th
interpretation of the results. It was clea
however, that exposure of pregnant rai
and mice to high levels of vinyliden
chloride could cause fetotoxicity an
adversely affect the outcome of prec
nancy. Another study reported n
teratogenic effect in rats or rabbi
inhaling up to 160 ppm vinylidene chli
ride for 7 hours per day or in rats give
drinking water containing 200 pp
vinylidene chloride. Embryo and matern
toxicity were observed among rats inh<
ing 80 or 160 ppm vinylidene chloric
and rabbits inhaling 160 ppm. ,
exposures causing little or no materr
toxicity (20 ppm in rats, 80 ppm
rabbits), there was no effect on embr
or fetal development. The effect of vin'
idene chloride on reproduction and fe
and neonatal development of rats w
tested in a three generation study with t
litter groups being produced. Hepal
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Cellular fatty changes were observed in
ats ingesting 50, 100 or 200 ppm vinyl-
idene chloride.
A large number of studies indicate that
vinylidene chloride is mutagenic to bac-
teria and that this activity is largely
dependent on microsomal activation.
Vinylidene chloride was reported to pro-
duce positive results for gene reversion
and conversion in yeast, which was also
dependent on metabolic activation, and
was positive in Tradescantia. In mam-
malian systems, vinylidene chloride failed
to induce gene mutations in V79 cells at
two separate loci, failed to induce
cromosomal aberrations in mouse bone
marrow in vivo, and failed to induce
dominant lethals in either mice or rats.
Vinylidene chloride was found to alkylate
the DNA of mice exposed through inhala-
tion and may have caused unscheduled
DNA synthesis in the kidneys of similarly
exposed mice.
Analysis of the data relating to the
potential of vinylidene chloride to behave
as a human germ-cell mutagen indicates
that based on the criteria established in
the Agency's Proposed Guidelines for
Mutagenicity Risk Assessment, the evi-
dence at the present time is classified as
limited. This designation indicates that
there are insufficient data on either muta-
jemcity or interaction with germ cells to
classify the evidence as either sufficient
or suggestive of potential germ-cell muta-
genicity. However, available data also do
not permit the classification of vinylidene
chloride as a non-germ-cell mutagen.
Based on the limited evidence from
animal studies, supporting evidence from
mutagemcity studies, and related bio-
chemical and toxicity considerations, it is
recommended that vinylidene chloride be
considered a "possible" carcinogen for
humans.
A total of 18 chronic studies in animals
were evaluated for evidence of carcino-
genicity The exposure regimes for these
studies were as follows. 11 were
inhalation, 4 were gavage, 1 was drinking
water, 1 was subcutaneous injection, and
1 was skin application. Evidence for car-
cmogenicity was found in Swiss mice
exposed to vinylidene chloride by inha-
lation, 4 hours daily for 12 months. A
statistically significant increase of kidney
adenocarcinomas, a rare tumor type, was
observed in male mice. Statistically
significant increases in mammary carcin-
omas and pulmonary adenomas were
observed in mice of both sexes, although
the importance of these findings is un-
certain because no clear dose-response
relationship was evident. Vinylidene chlo-
ride has also been shown to be a tumor
initiator in mouse skin, the remaining 16
animal studies have negative (assuming
non-treatment related increases are also
negative) findings for carcinogenicity;
however, these negative findings may be
partially explained by study charac-
teristics such as, less than lifetime
dosing, below maximum tolerated dose
levels, and single dose studies, which
individually or in combination, reduce the
sensitivity of detecting a carcinogenic
response While the number of studies
are many, the inadequacy of test con-
ditions demonstrates the need for addi-
tional testing to elucidate the potential for
human carcinogenicity. The mutagenic
activity of vinylidene chloride, its chem-
ical structure, its activity as a tumor
initiator in mouse skin, and the ability of
metabolites to react with DNA, signal that
the animal evidence should not be lightly
dismissed.
There is only one epidemiologic study
for vinylidene chloride While the study
concluded that a carcinogenic effect
could not be attributed to vinylidene
chloride, limiting characteristics made it
inadequate to evaluate the carcinogenic
potential.
The carcinogenicity evidence has been
evaluated using the EPA's Proposed
Guidelines for Carcinogen Risk Assess-
ment as well as the International Agency
for Research for Cancer (IARC) criteria
for assessing weight of evidence. Using
the EPA criteria, the weight of evidence is
such that the animal data for carcino-
genicity is limited and the epidemiologic
data is inadequate The overall ranking of
the weight of evidence is Group C mean-
ing that the substance is a "possible"
carcinogen for humans. Using the IARC
weight-of-evidence criteria, the animal
and epidemiologic data have the same
ranking as in the EPA classification,
limited and inadequate; however, the
overall ranking is considered to be Group
3. An IARC Group 3 classification means
that while the evidence may range from
limited to inadequate, the overall con-
clusion is that the data are "inadequate"
to assess the human carcinogenic poten-
tial. The Agency believes that its ranking
criteria are more instructive for public
health impact analysis. The Group C
(possible carcinogen) classification given
to vinylidene chloride is one of five that
could be assigned to a substance. The
five classifications are: human carcino-
gen, probable human carcinogen, pos-
sible human carcinogen, not classified
(inadequate evidence for assessing car-
cinogenicity), and no evidence of carcino-
genicity for humans.
Although vinylidene chloride has only
limited carcinogenicity evidence, an
upper-bound estimate of incremental
cancer risk can be estimated from the
kidney adenocarcinoma data in male
mice. The development of this risk
estimate is for the purpose of evaluating
the "what-if" question: If vinylidene
chloride is carcinogenic in humans, what
is the possible magnitude of the public
health impact? Any use of the risk
estimates should include a recognition of
the weight-of-evidence likelihood for the
carcinogenicity of vinylidene chloride in
humans The upper-bound incremental
cancer risk is calculated to be 1.16 x10-3
for 1 ng/kg body weight/day for a continu-
ous lifetime exposure to vinylidene chlo-
ride under the presumption that vinyl-
idene chloride is carcinogenic in humans.
The upper-bound nature of this estimate
is such that the true risk is not likely to
exceed this value and may be lower.
Expressed in terms of relative potency,
vinylidene chloride ranks in the third
quartile among the 54 suspect or known
human carcinogens evaluated by EPA's
Carcinogen Assessment Group.
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This Project Summary was prepared by staff of the Environmental Criteria and
Assessment Office, Research Triangle Park, NC 27711.
The complete report, entitled "Health Assessment Document for Vinylidene Chlo-
ride," (Order No. PB 86-100 641/AS; Cost: $36.95, subject to change) will be
available only from:
National Technical Information Service
5285 Port Royal Road
Springfield, VA 22161
Telephone: 703-487-4650
For information contact:
Environmental Criteria and Assessment Office
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
O.ZU 1"
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