March 31, 1987
820K87115
1,1-DICHLOROETHYLENE
Health Advisory
Office of Drinking Water
U.S. Environmental Protection Agency
I. INTRODUCTION
The Health Advisory (HA) Program, sponsored by the Office of Drinking
Water (ODW), provides information on the health effects, analytical method-
ology and treatment technology that would be useful in dealing with the
contamination of drinking water. Health Advisories describe nonregulatory
concentrations of drinking water contaminants at which adverse health effects
would not be anticipated to occur over specific exposure durations. Health
Advisories contain a margin of safety to protect sensitive members of the
population.
Health Advisories serve as informal technical guidance to assist Federal,
State and local officials responsible for protecting public health when
emergency spills or contamination situations occur. They are not to be
construed as legally enforceable Federal standards. The HAs are subject to
change as new information becomes available.
Health Advisories are developed for One-day, Ten-day, Longer-term
.(approximately 7 years, or 10% of an individual's lifetime) and Lifetime
exposures based on data describing noncarcinogenic end.points of toxicity.
Health Advisories do not quantitatively incorporate any potential carcinogenic
risk from such exposure. For those substances that are known or probable
human carcinogens, according to the Agency classification scheme (Group A or
B), Lifetime HAs are not recommended. The chemical concentration values for
Group A or B carcinogens are correlated with carcinogenic risk estimates by
employing a cancer potency (unit risk) value together with assumptions for
lifetime exposure and the consumption of drinking water. The cancer unit
risk is usually derived from the linear multistage model with 95% upper
confidence limits. This provides a low-bose estimate of cancer risk to
humans that is considered unlikely to pose a carcinogenic risk in excess
of the stated values. Excess cancer risk estimates may also be calculated
using the One-hit, Weibull, Logit or Probit models. There is no current
understanding of the biological mechanisms involved in cancer to suggest that
any one of these models is able to predict risk more accurately than another.
Because each model is based on differing assumptions, the estimates that are
derived can differ by several orders of magnitude.
U.S. Environmental Protection Agency
Region V, Library
230 South Dearborn Street
Chicago, Illinois 60604
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1,1-Dichloroethylene March 31, 1987
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This Health Advisory is based on information presented in the Office
of Drinking Water's Health Effects Criteria Document (CD) for the dichloro-
ethylenes (U.S. EPA, 1984a). The HA and CD formats are similar for easy
reference. Individuals desiring further information on the toxicological
data base or rationale for risk characterization should consult the CD. The
CD is available for review at each EPA Regional Office of Drinking Water
counterpart (e.g., Water Supply Branch or Drinking Water Branch), or for a
fee from the National Technical Information Service, U.S. Department ol
Commerce, 5285 Port Royal Rd., Springfield, VA 22161, PB #86-117785/AS.
The toll-free number is (800) 336-4700; in the Washington, D.C. area: (703)
487-4650.
II. GENERAL INFORMATION AND PROPERTIES
CAS No. 75-35-4
Chemical structure
Cl
i
C1-C=C-H
I
H
Synonyms
0 Vinylidene chloride, 1,1 -DCE, dichloroethene
Uses
0 1,1-Dichloroethylene has been used as a chemical intermediate and in
the manufacture of polyvinylidene copolymers.
Properties (Irish, 1963; Windholz et al., 1976)
Chemical Formula '
Molecular Weight ' 96.95
Physical State (room temp.) clear, colorless liquid
Boiling Point 31.5 °C
Melting Point -122.2 °C
Density
Vapor Pressure 591 torr (208C)
Specific Gravity 1.3
Water Solubility 250 mg/L (20°C)
Log Octanol/Water Partition 5.37
Coefficient
Taste Threshold (water)
Odor Threshold (water)
Odor Threshold (air) 2000-5500 mg/m3
Conversion Factor
Occurrence
0 1,1-Dichloroethylene (1,1 -DCE) is a synthetic chemical with no known
natural sources (U.S. EPA, 1983).
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0 Approximately 200 million pounds of 1,1-DCE were produced in 1980.
The major use of 1,1-DCE is as a co-monomer in the production of a
number of polymers. Polymers of 1,1-DCE and vinyl chloride are used
as food wrap (CEH, 1983).
0 The major releases of 1,1-DCE to the environment are during its
production and its use in the manufacture of polymers. Due to its
volatile nature, the majority of releases are expected to be to air.
Small amounts of 1,1-DCE may be released to water and land in
industrial effluents and from the disposal of solid wastes (U.S. EPA,
1983). 1,1-Dichloroethylene may be a degradation product of trichloro-
ethylene and perchloroethylene. While laboratory studies are currently
inconclusive, 1/1-DCE has been found to co-occur in ground water with
trichloroethylene and tetrachloroethylene and their other degradation
products, cis- and trans-1,2-dichloroethylene and vinyl chloride.
0 There is relatively little information on the behavior of 1,1-DCE in
the environment. However, the behavior of this chemical has been
estimated based upon the information on similar chlorinated compounds
(U.S. EPA, 1979). 1,1-Dichloroethylene released to the atmosphere is
expected to chemically degrade in hours; when released to surface
waters, it is expected to volatilize rapidly. 1,1-DCE is chemically
stable in water and mobile in soils and is expected to migrate with
ground water. 1,1-Dichloroethylene is not believed to bioaccumulate
in plants or animals.
0 Available data suggest that 1,1-DCE is not a common contaminant of
drinking water. It has not been reported to occur at levels higher
than 0.1 ug/L in surface water. However, 1,1-DCE has been reported
to occur at levels up to 40 ug/L in wells contaminated with other
chlorinated solvents.
0 No information is available on the occurrence of 1,1-DCE in food.
While 1,1-DCE is used in the manufacture of food wrap, residual levels
are expected to be very low because of its high volatility. Due to
limited release and rapid degradation, little or no contamination of
food by 1,1-DCE is expected.
0 1,1-Dichloroethylene contamination of air has been reported to occur
in urban and suburban areas in the low ppt range. Levels in th& ppb
range have been reported in the areas where 1,1-DCE and its
polymers are manufactured (U.S. EPA, 1983).
III. PHARMACOKINETICS
Absorption
8 1,1-Dichloroethylene is completely absorbed after gavage, since 96 to
100% of a single dose is excreted within 72 hours (Jones and Hathway,
1978a; McKenna et al., 1978b).
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Distribution
0 Distribution in rats following a single oral dose of 25 mg of 1,1-DCE/kg
resulted in high concentrations in the liver and kidneys after 30
minutes with more general distribution throughout other soft tissues
after 1 hour (Jones and Hathway, 1978a).
0 Single oral doses of 14c-1,1-DCE, at i or 50 mg/kg, were administered
to rats (McKenna et al., 1978a,b). At 72 hours after dosing, the
greatest percentage of radioactivity was found in the liver.
Metabolism
0 The metabolic end products of chlorinated ethylenes are predominately
alcohols and carboxylic acids. The known metabolites of 1,1-DCE are
chloroacetic acid, chloroacetyl chloride and dichloroacetaldehyde
(Liebler and Guengerich, 1983; Liebler et al., 1984). Toxic inter-
• mediates that are formed may interact with tissue macromolecules.
Excretion
The rate of excretion is relatively rapid, since most of a dose is
eliminated within the first 24-72 hours after administration (Jaeger
et al., 1977). At low doses, a greater percentage of the metabolites
are eliminated via renal and biliary excretion. Carbon dioxide
formed during metabolism is expired through the lungs.
As maximal metabolic capacity is approached at the higher dose levels,
proportionally less of the compound is removed from the blood as it
passes through the liver. As a result, increasing amounts of unchanged
1,1-DCE are eliminated via the lungs (McKenna et al; 1977).
IV. HEALTH EFFECTS
Humans
At high concentrations (>_ 4000 ppm; 15,880 mg/m3), inhalation of
1,1-DCE results in rapid onset of CMS depression, with unconsciousness
following if exposure is continued (Irish, 1963).
Reports of effects on workers exposed to this chemical in combination
with other vinyl compounds include liver function abnormalities,
headaches, vision problems, weakness, fatigue and neurological sensory
disturbances (NIOSH, 1979).
Animals
Short-term Exposure
Reported oral LDSQS in adult rats range from 200 to 1800 mg/kg (NIOSH,
1978? Ponomarkov and Tomatis, 1980). Young or fasted rats are more
sensitive to the acute effects of 1,1-DCE, with LD50s of approximately
50 mg/kg (Andersen and Jenkins, 1977).
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0 The oral LD5QS in the mouse and the dog were reported to be 200 mg/kg
(Jones and Hathway, 1978b) and 5750 mg/kg (NIOSH, 1978), respectively.
0 The most sensitive end-point of 1,1-DCE toxicity is liver damage,
ranging from fatty infiltration to necrosis (Reynolds et al., 1975;
Chieco et al., 1982). In rats, after doses of 50 to 700 mg of
1,1-DCE/k9» tne liver toxicity of 1,1-DCE followed a complex dose-
response pattern, with a threshold level, a rapid increase in effect
and an extended plateau where increasing doses caused slight increases
in effect (Andersen and Jenkins, 1977).
0 After a 90 day continuous exposure to 1,1-DCE (189 mg/m3) liver and
kidney lesions have been demonstrated (Prendergast et al., 1967).
0 Since glutathione depletion increases toxicity (Jaeger et al., 1974;
Andersen et al., 1980), the acute toxicity of the chemical is probably
the result of a toxic metabolite.
Long-term Exposure
0 As with acute exposure, the liver appears to be the principal target
of 1,1-DCE toxicity following extended periods of exposure. Chronic
exposure of rats to 0 to 200 ppm (0 to 26 mg/kg) in drinking water
resulted in fatty changes and hypertrophy of liver cells in females
and males at the highest dose (Rampy et al., 1977; Quast et al.,
1983).
Reproductive Effects
0 In a three-generation rat reproductive study, Nitschke et al. (1983)
reported that, at concentrations of 0, 50, 100 or 200 "ppm (0 to 26
mg/kg) in the drinking water, 1,1-DCE did not affect rat reproductive
capacity.
Developmental Effects
t
0 At levels producing no maternal toxicity (inhalation; 20 ppm in rats
and 80 ppm in rabbits and ingestion; 200 ppm in rats) 1,1-DCE did not
produce teratogenic effects in rats or rabbits following exposure of
dams during organogenesis (Murray et al., 1979).
Mutagenicity
0 With S-9 activation, 1,1-DCE was mutagenic in the Ames Salmonella
test at concentrations of 3.3 x 10~4 to 3.3 x 10-2 M (Bartsch et al.,
1975) or when exposed to an atmosphere containing 5% 1,1-DCE for 3
hours (Simmon et al., 1977). The chemical had no mutagenic activity
in the absence of the S-9 fraction.
0 1,1-Dichloroethylene was mutagenic to E. coli Ki2 at a concentration
of 2.5 mM with, but not without, microsomal activation (Greim et al.,
1975).
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1,1-Dichloroethylene March 31, 1987
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0 In mammalian assay systems, a mutagenic effect was not observed.
Using the dominant lethal assay, it was reported that exposure to
1,1-DCE at 55 ppm for 6 hr/day for 11 weeks (Short et al., 1977) or
to 10 to 50 ppm for 6 hr/day for 5 days (Anderson et al., 1977) did
not produce germinal mutation. In addition, using V79 Chinese hamster
ovary cells, exposed to 1,1-DCE at concentrations of 2 or 10%, Drevon
and Kuroki (1979) did not observe any adverse effects.
0 1,1-Dichloroethylene binds with DNA to a slight degree in the liver
and kidneys of both rats and mice after inhalation exposure to 10 or
50 ppm for 6 hours. However, massive tissue damage also occurred.
In mice, the kidneys seem to be a more sensitive indicator of tissue
damage than the liver (Reitz et al., 1980).
0 The International Agency for Research on Cancer (IARC) concluded that
there is sufficient evidence to state that 1,1-DCE is mutagenic
(IARC, 1982).
0 For a recent review of this area, the reader is referred to the
article by Jacobson-Kram (1986).
Carcinogenic!ty
0 The results of most studies of the carcinogenic potential of this
substance fail to support a significant, treatment-related increase
in tumor incidence (U.S.-EPA, 1984a). No oral study .has resulted
in a significant tumor response (NTP, 1982; Quast et al., 1983).
Some, but not all, of the inhalation studies have reported significant
tumor increases (e.g., mammary tumors in female rats and mice and
kidney adenocarcinomas in mice) (Maltoni et al., 1985).
0 1,1-Dichloroethylene was inactive as a whole mouse skin carcinogen
when administered subcutaneously (Van Duuren et al., 1979). It was
active as a skin tumor initiator following several topical applications
of phorbol ester as a promoter.
V
V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS
Health Advisories (HAs) are generally determined for One-day, Ten-day,
Longer-term (approximately 7 years) and Lifetime exposures if adequate data
are available that identify a sensitive noncarcinogenic end point of toxicity.
The HAs for noncarcinogenic toxicants are derived using the following formulas
HA - (NOAEL or LOAEL) X (BW) = mg/L ( ug/L)
(UF) x ( L/day)
where:
NOAEL or LOAEL • No- or Lowest-Observed-Adverse-Effect-Level
in mg/kg bw/day.
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BW » assumed body weight of a child (10 kg) or
an adult (70 kg).
UF = uncertainty factor (10, 100 or 1,000), in
accordance with NAS/ODW guidelines.
L/day = assumed daily water consumption of a child
(1 L/day) or an adult (2 L/day).
One-day Health Advisory
The study by Chieco and coworkers (1981) has been selected to derive the
One-day HA. The authors reported that when 200 mg/kg of 1,1-DCE was given in
water containing 0.5% Tween 80, the chemical caused only a slight increase in
the plasma levels of alanine, but not aspartate, transaminase. In addition,
the pathological changes observed in the liver were limited to a few scattered
microfoci of necrosis. Accordingly, the 200 mg/kg is taken to be the LOAEL.
The One-day HA for the 10 kg child is calculated as follows:
One-day HA = (200 mg/kg/day) (10 kg) = 2.
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in the livers of both sexes exposed to the highest dose. A NOAEL of 100 ppm
(10 to 12.6 mgAg) was identified.
A Longer-term HA for the 10-kg child is calculated as follows:
Longer-term HA = (10 mg/kg/day) (10 kg) = ^ .0 /L (1/000 ug/L)
(100) (1 L/day)
where:
10 mg/kg/day = NOAEL based on the absence of liver effects.
10 kg * assumed body weight of a child.
100 = uncertainty factor, chosen in accordance with NAS/ODW
guidelines foruse with a NOAEL from an animal study.
1 L/day = assumed daily water consumption of a child.
A Longer-term HA for the 70-kg adult is calculated as follows:
Longer-term HA = (10 mg/kg/day) (70 kg) = 3.5 /L (3 500 ug/L)
(100) (2 L/day)
where:
10 mg/kg/day = NOAEL based on the absence of liver effects.
70 kg - assumed body weight of an adult.
100 » uncertainty factor, chosen in accordance with NAS/ODW
guidelines foruse with a NOAEL from an animal study.
2 L/day - assumed daily water consumption of an adult.
%
Lifetime Health Advisory
The Lifetime HA represents that portion of an individual's total exposure
that is attributed to drinking water and is considered protective of noncar-
cinogenic adverse health effects over a lifetime exposure. The Lifetime HA
is derived in a three step process. Step 1 determines the Reference Dose
(RfD), formerly called the Acceptable Daily Intake (ADI). The RfD is an esti-
mate of a daily exposure to the human population that is likely to be without
appreciable risk of deleterious effects over a lifetime, and is derived from
the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided
by an uncertainty factor(s)* From the RfD, a Drinking Water Equivalent Level
(DWEL) can be determined (Step 2). A DWEL is a medium-specific (i.e., drinking
water) lifetime exposure level, assuming 100% exposure from that medium, at
which adverse, noncarcinogenic health effects would not be expected to occur.
The DWEL is derived from the multiplication of the RfD by the assumed body
weight of an adult and divided by the assumed daily water consumption of an
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1,1-Dichloroethylene March 31, 1987
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adult. The Lifetime HA is determined in Step 3 by factoring in other sources
of exposure, the relative source contribution (RSC). The RSC from drinking
water is based on actual exposure data or, if data are not available, a
value of 20% is assumed for synthetic organic chemicals and a value of 10%
is assumed for inorganic chemicals* If the contaminant is classified as a
Group A or B carcinogen, according to the Agency's classification scheme of
carcinogenic potential (U.S. EPA, 1986), then caution should be exercised in
assessing the risks associated with lifetime exposure to this chemical.
The Lifetime HA can be calculated from the 2-year chronic study in rats
(Quast et al., 1983). 1,1-Dichloroethylene, at nominal concentrations of 0,
50, 100 or 200 ppm (0 to 20 mg/kg/day) in drinking water, was administered to
animals of both sexes. No consistent treatment-related biochemical changes
were observed in any parameter measured. The only abnormal histopathology
observed was mid-zonal fatty accumulation in the livers of both sexes
receiving the highest dose. No liver degeneration was noted. A LOAEL of
100 ppm (10 mg/kg) was identified, based upon a trend towards increased fatty
deposition in the liver.
A Drinking Water Equivalent Level (DWEL) and Lifetime HA for the 70-kg
adult are calculated as follows:
Step 1: Determination of the Reference Dose (RfD)
RfD = (10 mg/kg/day) = 0.01 mg/kg/day
(1,000)
where:
10 mg/kg/day « LOAEL for hepatic effects.
1,000 * uncertainty factor, chosen in accordance with NAS/ODW
guidelines for use with a LOAEL from an animal study.
Step 2: Determination of the Drinking Water Equivalent Level (DWEL)
t
DWEL - (0.01 ing/kg/day) (70 kg) m 0.35 mg/L (350 ug/L)
(2 L/day)
where:
0.01 mgAg/day - RfD.
70 kg » assumed body weight of an adult.
2 L/day = assumed daily water consumption of an adult.
Step 3: Determination of the Lifetime Health Advisory
Lifetime HA - (0.35 mg/L) (20%) _ Q.007 mg/L (7 ug/L)
(10)
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where:
0.35 mg/L = DWEL.
20% = assumed relative source contribution from water.
10 « additional uncertainty factor for class C carcinogens.
Evaluation of Carcinogenic Potential
0 Qualitative and quantitative assessment of the carcinogenic potential
of 1,1-DCE is complicated by the fact that there is only one positive
bioassay (Maltoni et al., 1985) among the 18 oncogenic studies (U.S.
EPA, 1985c).
0 IARC (1982) reported that the data were inadequate to assess the
carcinogenic potential in humans, but that it would reevaluate the
assessment after reviewing the rat drinking water study (Rampy et al.,
1977; Quast et al., 1983) and the NTP gavage bioassays (NTP, 1982).
At the present time, this has not been done.
0 Applying the criteria described- in EPA's guidelines for assessment
of carcinogenic risk (U.S. EPA, 1986), 1,1-dichloroethylene may be
classified in Group C: Possible human carcinogen. Group C includes
agents with limited evidence of carcinogenicity in animals in the
absence of human data.
VI. OTHER CRITERIA, GUIDANCE AND STANDARDS
0 In June, 1984, EPA proposed a Recommended Maximum Contaminant Level
(RMCL) of zero for 1,1-dichloroethylene in drinking water (U.S. EPA,
1984b). In 1985, a RMCL of 7 was promulgated for 1,1-dichloroethylene.
This value also was proposed for the MCL (U.S. EPA, 1985a).
0 In 1980, EPA estimated a range of excess cancer risks for lifetime
exposure to 1,1-dichloroethylene when developing ambient water quality
criteria (U.S. EPA, 1980a). This range was 23 ug/L, 2.3 ug/L and
0.23 ug/L, respectively, for risks of 10~4, 10~5 and 10~6, assuming
consumption of 2 liters of water and 6.5 grams of contaminated fish
per day by 70-kg adult.
9 The National Academy of Sciences calculated a chronic SNARL (Suggested-
No-Adverse-Response-Level) of 100 ug/L, based upon non-carcinogenic
effects only (NAS, 1983). The Academy identified a NOAEL of 2 mg/kg
from the 1982 NTP bioassay in mice. An uncertainty factor of 100
was applied. It was assumed that a 70 kg adult consumes 2 liters of
water daily and 20% of the exposure of most individuals would be
from drinking water. In addition, a factor of 5/7 to correct from
5- to 7-day/week exposure was used.
0 The World Health Organization has established a guideline for 1,1-DCE
in drinking water of 0.3 ug/L, set on evidence of carcinogenicity
(WHO, 1984).
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1,1-Dichloroethylene March 31, 1987
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0 The threshold limit value (TLV) for 1,1-DCE in occupational settings
is 5 ppm (20 mg/m3) (ACGIH, 1982).
VII. ANALYTICAL METHODS
0 Analysis of 1,1-DCE is by a purge-and-trap gas chromatographic procedure
used for the determination of volatile organohalides in drinking water
(U.S. EPA, 1985). This method calls for the bubbling of an inert gas
through the sample and trapping 1,1-DCE on an adsorbant material.
The adsorbant material is heated to drive off the 1,1-DCE onto a gas
chromatographic column. This method is applicable to the measurement
of 1,1-DCE over a concentration range of 0.03 to 1500 ug/L. Confirma-
tory analysis for 1,1-DCE is by mass spectrometry (U.S. EPA, 1985b).
The detection limit for confirmation by mass spectometry is 0.2 ug/L.
VIII. TREATMENT TECHNOLOGIES
0 Granular activated carbon (GAC) adsorption and aeration treatment
technologies are available for the removal of 1,1-DCE from water
and have been reported to be effective. Selection of individual or
combinations of technologies to achieve chemical reduction must be
based on a case-by-case technical evaluation and an assessment of the
economics involved.
0 Aeration has been shown to be effective in removing 1,1-DCE from
water, based upon its carbon adsorption isotherm (Henry's Law
Constant * 498 atm) and pilot and full-scale testing. The chemical
was removed successfully from contaminated ground water at 12-14°C in
an EPA pilot packed tower aerator containing 18 feet of 1-inch plastic
saddle packing (ESE, 1984). The average percent removal varied with
air-to-water volume ratio, from 90.6% to 99.99% at ratios of 5 to 80,
respectively. Similarly, the concentration of 1,1-DCE in contaminated
well water decreased from 122 ug/L to 4 ug/L (97%) using diffused
aeration (ESE, 1984). Aeration was conducted in a pilot (1.5 inch
diameter, 4-foot long) countercurrent glass column, using a 10-minute
contact time and an air-to-water ratio of 4.
0 Air stripping is an effective, simple and relatively inexpensive
process for removing 1,1-DCE from water. However, the use of this
process transfers the contaminant directly to the air stream. When
considering use of air stripping as a traetment process, it is
suggested that careful consideration be given to the overall
environmental occurrence, fate, route of exposure and various hazards
associated with the chemical.
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1,1-Dichloroethylene March 31, 1987
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IX. REFERENCES
ACGIH. 1982. American Conference of Government Industrial Hygienists.
TLVs. Threshold limit values for chemical substances in work air.
Andersen, M.E., and L.R. Jenkins, Jr. 1977. Oral toxicity of 1,1-dichloro-
ethylene in the rat: Effects of sex, age and fasting. Environ. Health
Perspect. 21:157-163.
Andersen, M.E., O.E. Thomas, M.L. Gargas, R.A. Jones and L.J. Jenkins, Jr.
1980. The significance of multiple detoxification pathways for reactive
metabolites in the toxicity of 1,1-dichloroethylene. Toxicol. Appl.
Pharmacol. 52:422-432.
Anderson, D. 1977. Dominant lethal studies with the halogenated olefins
vinyl chloride and vinylidene chloride in male CD-1 mice. Environ.
Health Perspect. 21:71-78.
Bartsch, H., C. Malaveille, R. Montesano and L. Tomatis. 1975. Tissue-
mediated mutagenicity of vinylidene chloride and 2-chlorobutadiene in
Salmonella typhimurium. Nature. 255:641-643.
CEH. 1983. Chemical Economics Handbook, Stanford Research Institute,
Menlo Park, California.
Chieco, P., M.T. Moslen and E.S. Reynolds. 1981. Effect of administrative
vehicle on oral 1,1-dichloroethylene toxicity. Toxicol. Appl. Pharmacol.
57:146-155.
Chieco, P., M.T. Moslen and E.S. Reynolds* 1982. Histochemical evidence that
plasma ana^~mrtochondrial membranes are primary foci of hepatocellular
injury caused by 1j1-dichloroethylene. Lab. Invest. 46:413-421.
Dobbs, R.A., and J.M. Cohen. 1980. Carbon adsorption isotherms for toxic
organics. EPA 600/80-023. MERL, Cincinnati, OH.
h
Drevon, C., and T. Kuroki. 1979. Mutagenicity of vinyl chloride, vinyli-
dene chloride and chloroprene in V79 Chinese hamster cells. Mutat. Res.
67:173-182.
ESE. 1984. Environmental Science and Engineering. Draft technologies
and costs for the removal of volatile organic chemicals from potable
water supplies. ESE No. 84-912-0300. Prepared for the U.S. EPA,
Science and Technology Branch, CSD, ODW, Washington, DC.
Greim, H., G. Bonse, Z. Radwan, D. Reichert and D. Henschler. 1975.
Mutagenicity iri vitro and potential carcinogenicity of chlorinated
ethylenes as a function of metabolic oxirane formation. Biochem.
Pharmacol. 24:2013-2017.
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1,1-Dichloroethylene March 31, 1987
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McKenna, M.J., P.G. Watanabe and P.J. Gehring. 1977. Pharmacokinetics of
vinylidene chloride in the rat. Environ. Health Perspect. 21:99-105.
McKenna, M.J., J.A. Zempel, E.O. Madrid and P.J. Gehring. 1978a. The
Pharmacokinetics of (14C) 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 administration. Toxicol. Appl. Pharmacol. 45:821-835.
Murray, F.J., K.D. Nitschke, L.W. Rampy and B.A. Schwetz. 1979. Embryo-
toxicity and fetotoxicity of inhaled or ingested vinylidene chloride
in rats and rabbits. Toxicol. Appl, Pharmacol. 49:189-202.
NAS. 1983. National Academy of Sciences. Drinking Water and Health.
Volume 5. National Academy Press, Washington, DC.
NIOSH. 1978. National Institute for Occupational Safety and Health.
1,1-Dichloroethylene. Registry of toxic effects of chemical substances.
p. 563.
NIOSH. 1979. [ C.D. for Occupational Standard]
Nitschke, K.D., F.A. Smith, J.F. Quast, J.M. Norris and B.A. Schwetz. 1983.
A three-generation rat reproductive toxicity study of vinylidene chloride
in the drinking water. Fund. Appl. Toxicol. 3:75-79.
NTP. 1982. National Toxicology Program. Carcinogenesis bioassay of vinylidene
chloride (CAS No. 75-35-4) in F344 rats and B6C3F1 mice (gavage study).
U.S. HHS. PHS. NIH NTP-80-2 NIH Publication No. 82-1784.
Ponomarkov, V., and L. Tomatis. 1980. Long-term testing of vinylidene
chloride and chloroprene for carcinogenicity in rats. Oncology
37:136-141.
Prendergast, J.A., R.A. Jones, L.J. Jenkins, Jr. and J. Siegel. 1967.
Effects on experimental animals of long-term inhalation of trichloro-
ethylene, carbon tetrachloride, 1,1,1-trichloroethane, dichlorodifluoro-
methane, and 1,1-dichloroethylene. Toxicol. Appl. Pharmacol. 10:270-289.
Quast, J.F., C.G. Humiston, C.E. Wade, J. Ballard, J.E. Beyer, R.W. Schwetz
and J.M. Norris. 1983.. A chronic toxicity and oncogenicity study in
rats and subchronic toxicity study in dogs on ingested vinylidene
chloride. Fund. Appl. Toxicol. 3:55-62.
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 Perspect. 21:33-43.
-------
1,1-Dichloroethylene March 31, 1987
-15-
Reitz, R.H., P.G. Watanabe, M.J. McKenna, J.F. Quast and P.J. Gehring. 1980.
Effects of vinylidene chloride on DNA synthesis and DNA repair in the
rat and mouse: A comparative study with dimethyInitrosamine. Toxicol.
Appl. Pharmacol. 52:357-370,
Reynolds, E.S., M.T. Moslen, S. Szabo, R.J. Jaeger and S.D. Murphy. 1975.
HepaLoi-oxicity of vinyl chloride and 1,1-dichloroethylene. Amer. J.
Pathol. 81:219.
Short, R.D., J.L. Minor, J.M. Winston and C.C. Lee. 1977. A dominant lethal
study in male rats after repeated exposure to vinyl chloride or vinylidene
chloride. J. Toxicol. Environ. Health. 3:965-968.
Simmon, V.F., K. Kauhanen and R.G. Tardiff. 1977. Mutagenic activity of
chemicals identified in drinking water. Dev. Toxicol. Environ. Sci.
2:249-258.
U.S. EPA. 1979, U.S. Environmental Protection Agency. Water Related Environ-
mental Fate of 129 Priority Pollutants. Office of Water Planning and
Standards, EPA-440/4-79-029, December.
U.S. EPA. 1980. U.S. Environmental Protection Agency. Ambient water quality
criteria for dichloroethylenes. Office of Water Regulations and Standards.
Criteria and Standards Division. Washington, D.C. EPA 440/5-80-041.
U.S. EPA. 1983. U.S. Environmental Protection Agency. Vinylidine chloride
occurrence in drinking water, food, and air. Office of Drinking Water.
U.S. EPA. 1984a. U.S. Environmental Protection Agency. Draft criteria
document for the dichloroethylenes. Criteria and Standards Division,
Office of Drinking Water, Washington, DC.
U.S. EPA. 1984b. U.S. Environmental Protection Agency. National primary
drinking water regulations; Volatile synthetic organic chemicals;
Proposed rulemaking. Federal Register 49(114):24330-24355. June 12.
U.S. EPA. 1984c. U.S. Environmental Protection Agency. Method 501.1.
Volatile halogenated organic compounds in water by purge and trap gas
chromatography. Environmental Monitoring and Support Laboratory,
Cincinnati, Ohio 45268. June.
U.S. EPA. 1985a. U.S. Environmental Protection Agency. Final RMCL,
proposed MCLs for VOCs. November 13, 1985.
U.S. EPA. 1985b. U.S. Environmental Protection Agency. Method 524.1.
Volatile organic compounds in water by purge and trap gas chromatography/
mass spectrometry. Environmental Monitoring and Support Laboratory,
Cincinnati, Ohio. June.
U.S. EPA. 1985c. U.S. Environmental Protection Agency. Health assessment
document for vinylidene chloride. August.
-------
1,1-Dichloroethylene March 31, 1987
-16-
U.S. EPA. 1986. U.S. Environmental Protection Agency. Guidelines for
carcinogen risk assessment. Federal Register. 51(185):33992-34003.
September 24.
U.S. ITC. 1982. United States International Trade Commission. Synthetic
organic chemicals United States production. 1983 USITC Publication
1422, Washington, D.C. 20436.
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. 63:1433-1439,
WHO. 1984. World Health Organization. Guidelines for drinking water
quality. Volume 1. Recommendations. Geneva, Switzerland.
Windholz, M., ed. 1976. The Merck Index. 10th edition. Merck and Co., Inc.
Rahway, NJ.
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