NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.
Prepared by Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation and Communication Program, Biomedical and Environmental Information Analysis Section, Health and Safety Research Division, *, Oak Ridge, Tennessee.
Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM.
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under contract No. DE-AC05-84OR21400.
1,1-Dichloroethylene (CAS No. 75-35-4), also known as 1,1-dichloroethene and vinylidine chloride, is a colorless liquid that is used primarily in the production of polyvinylidine chloride (PVC) copolymers and as an intermediate for synthesis of organic chemicals. The major application for PVC copolymers is the production of flexible films for food packaging such as Saran® wrap (ATSDR, 1993).
1,1-Dichloroethylene does not occur naturally (IARC, 1986) but is found in the environment due to releases associated with its production and transport and with the production of its polymers. Because of its high volatility, releases to the atmosphere are the greatest source of ambient 1,1-dichloroethylene. Smaller amounts are released to surface waters and soils (ATSDR, 1993). Loss of 1,1-dichloroethylene from water and soils is primarily due to volatilization. In the atmosphere, reaction with photochemically generated hydroxyl radicals is expected to be the predominant removal mechanism (EPA, 1987). Human exposure to 1,1-dichloroethylene is potentially highest in workplace settings and in the vicinity of hazardous waste sites where the compound may contaminate environmental media (ATSDR, 1993).
The primary effect of acute exposure to high concentrations (approximately 4000 ppm) of 1,1-dichloroethylene vapor in humans is central nervous system (CNS) depression which may progress to unconsciousness (Gosselin et al., 1984). Occupational exposure has been reported to cause liver dysfunction in workers (Tierney et al., 1979). 1,1-Dichloroethylene is irritating when applied to the skin and prolonged contact can cause first degree burns (Tierney et al., 1979). Direct contact with the eyes may cause conjunctivitis and transient corneal injury (IARC, 1986).
In experimental animals, the liver and kidneys are target organs for the toxic effects of 1,1-dichloroethylene. Subchronic oral exposure for 90 days to 1,1-dichloroethylene in drinking water produced slight hepatotoxic effects at 200 ppm (Rampy et al., 1977), and chronic oral exposure to drinking water for 2 years produced hepatocellular changes in males at >=100 ppm and in females at >=50 ppm (Quast et al., 1983). Gavage administration of 10 mg/kg/day, 5 days/week for 2 years produced chronic inflammation of the kidney in male and female rats and liver necrosis in male and female mice (NTP, 1982). Exposure by inhalation to 55 ppm 1,1-dichloroethylene, 6 hours/day, 5 days/week for up to 1 year produced fatty liver changes in rats and focal degeneration and necrosis in mice (Lee et al., 1977).
In a three-generation study, no treatment-related effects on reproduction or neonatal development were seen in male and female Sprague-Dawley rats administered up to 200 ppm of 1,1-dichloroethylene in the drinking water (Nitschke et al., 1983). However, inhalation exposure during gestation produced increased resorptions and minor skeletal alterations in rodents at concentrations that caused maternal toxicity. These effects were reported in rats and mice at >=15 ppm (Short et al., 1977a) and in rats and rabbits at >=80 ppm and >=160 ppm, respectively (Murray et al., 1979).
An oral Reference Dose (RfD) of 9E-3 mg/kg/day was derived for chronic exposure (EPA, 1994a) and subchronic exposure to 1,1-dichloroethylene (EPA, 1994b), based on liver lesions seen in rats in a 2-year drinking water study (Quast et al., 1983). The oral RfD is currently under review and may be subject to change. An inhalation Reference Concentration (RfC) for 1,1-dichloroethylene is under review (EPA, 1994a).
An epidemiology study using a small cohort found no association between the occurrence of cancer or cancer mortality and exposure to 1,1-dichloroethylene (Ott et al., 1976). Oral carcinogenicity bioassays (drinking water or gavage exposures) with experimental animals gave generally negative results (NTP, 1982; Quast et al., 1983; Maltoni et al., 1984, 1985). In one inhalation study (Maltoni et al., 1985), statistically significant increases in renal adenocarcinomas were noted in male Swiss mice exposed to 25 ppm for 12 months. Also observed were statistically significant increases in mammary gland carcinomas in females and lung tumors in both sexes. Results of other inhalation studies with rats, mice, and hamsters have been negative (Hong et al., 1981; Maltoni et al., 1984; Quast et al., 1986).
Based on EPA guidelines, 1,1-dichloroethylene was assigned to weight-of-evidence group C, possible human carcinogen. For oral exposure, the slope factor is 6E-1 (mg/kg/day)-1 and the unit risk is 1.7E-5 (ug/L)-1 (EPA, 1994a). The inhalation slope factor and unit risk are 1.2E+0 (mg/kg/day)-1 and 5.0E-5 (ug/m3)-1 (EPA, 1994a), respectively.
1,1-Dichloroethylene (CAS No. 75-35-4), also known as 1,1-dichloroethene and vinylidine chloride, is a colorless liquid with a molecular weight of 96.95 and a chemical formula of C2H2Cl2. It has a boiling point of 31.7C, a melting point of -122.5C, a density of 1.2129 g/mL (Budavari et al., 1989), and a vapor pressure of 600 mm Hg at 25C (EPA, 1987). 1,1-Dichloro-ethylene is produced commercially by the dehydrochlorination of 1,1,2-trichloroethane by lime or sodium hydroxide (IARC, 1986).
1,1-Dichloroethylene is used primarily in the production of polyvinylidine chloride (PVC) copolymers and as an intermediate for synthesis of organic chemicals. The major application for PVC copolymers is the production of flexible films for food packaging such as Saran® wrap (ATSDR, 1993). 1,1-Dichloroethylene is also used as an intermediate in the production of 1,1,1-trichloroethane and in the manufacture of modacrylic fibers where it is combined with acrylonitrile. Because 1,1-dichloroethylene polymerizes readily and can form explosive peroxides, hydroquinone monomethyl ether (MEHQ) or phenol are generally added as a stabilizer to prevent these reactions (Haley, 1975).
1,1-Dichloroethylene does not occur naturally (IARC, 1986) but is found in the environment due to releases associated with its production and transport and with the production of its polymers. Because of its high volatility, releases to the atmosphere are the greatest source of ambient 1,1-dichloroethylene. Smaller amounts of 1,1-dichloroethylene are released to surface waters and soils (ATSDR, 1993). Estimated half-lives in air and water are 2 days and 1-6 days, respectively. Loss of 1,1-dichloroethylene from water and soils is primarily due to volatilization. In the atmosphere, reaction with photochemically generated hydroxyl radicals is expected to be the predominant removal mechanism (EPA, 1987).
Human exposure to 1,1-dichloroethylene is potentially highest in workplace settings and in the vicinity of hazardous waste sites where the compound may contaminate environmental media (ATSDR, 1993). It is found as a contaminant in nuclear submarines and spacecraft (Gosselin et al., 1984). The general population may be exposed to low levels of 1,1-dichloroethylene in ambient air, indoor air, contaminated drinking water, and food which has come in contact with plastic wrap containing residual monomer (HSDB, 1994).
No human data were available regarding the absorption of 1,1-dichloroethylene by any route of exposure. The rapid appearance of labeled 1,1-dichloroethylene in the urine and expired air of rats given intragastric doses of [14C] 1,1-dichloroethylene indicates that systemic absorption following oral dosing is rapid (EPA, 1987). 1,1-Dichloroethylene is also readily absorbed following inhalation exposure. In rats exposed to 25, 75, or 150 ppm 1,1-dichloroethylene, equilibrium levels were reached in the blood by 45 minutes, while at 300 ppm the blood level of 1,1-dichloroethylene tended to increase gradually for 3 hours (Dallas et al., 1983).
No data were available regarding the tissue distribution of 1,1-dichloroethylene in humans. In rats, 1,1-dichloroethylene is rapidly distributed to tissues following oral or inhalation exposure. Following administration of a single oral dose of 350 or 500 ug/kg, the highest concentrations were found in the liver and kidneys within 30 minutes of dosing; general tissue distribution followed (Jones and Hathway, 1978b). After 72 hours, 3% or less of the administered dose was present, indicating that 1,1-dichloroethylene is not extensively stored in body tissues. Following inhalation exposure to 2000 ppm for 2 hours, rats preferentially accumulated 1,1-dichloroethylene in the kidney and liver, with fasted rats having higher levels in these tissues than nonfasted rats (Jaeger et al., 1977).
Pharmacokinetic data in animals show that metabolism is dose-dependent and saturable at inhalation concentrations of 150-200 ppm or approximately 50 mg/kg orally (EPA, 1987). Metabolic conversion of 1,1-dichloroethylene to an epoxide as an intermediate reactive metabolite has been proposed (IARC, 1986). The main biotransformation pathway in the rat most likely involves conjugation with glutathione (GHS), either with the epoxide or following rearrangement of the epoxide to chloroacetylchloride, with subsequent hydrolysis to monochloroacetic acid (ATSDR, 1993). Major urinary metabolites of 1,1-dichloroethylene identified in rats are thiodihydroxyacetic acid and N-acetyl-S-cysteinylacetyl derivatives. Additional metabolites identified are chloroacetic acid, dithiohydroxyacetic acid (dithioglycolic acid), thiohydroxyacetic acid (thioglycolic acid), and methylthioacetylamino-ethanol. Comparative studies with rodents have shown that mice metabolize 1,1-dichloroethylene to a greater extent than rats (IARC, 1986).
No human data were available regarding the excretion of 1,1-dichloroethylene. After oral administration of 5 mg radiolabeled 1,1-dichloroethylene to rats, most of the radioactivity was recovered within 72 hours (Reichert et al., 1979). Twenty one percent of the dose was recovered in the expired air, 53.9% in urine, 14.5% in feces, 2.8 % in the carcass, and 7.5% was found in the cage rinse.
Information on the acute oral toxicity of 1,1-dichloroethylene in humans was not available.
Jones and Hathway (1978a) reported oral LD50 values of 1550 mg/kg for rats and 194 and 217 mg/kg, respectively, for male and female mice. A lethal dose of 5750 mg/kg was reported for dogs (Tierney et al., 1979).
Increased kidney weights, increased plasma urea nitrogen and creatinine concentrations, and histopathological changes of the kidneys (vacuolization, tubular dilatation, and necrosis) were seen in rats administered a single oral dose of 400 mg/kg of 1,1-dichloroethylene (Jenkins and Andersen, 1978). Fasting rats were more susceptible to the nephrotoxic effects of 1,1-dichloroethylene than nonfasting rats.
Forkert et al. (1985) reported histopathological changes in Clara cells, pulmonary edema, hemorrhage, and focal lung collapse in mice administered a single oral dose of 200 mg/kg of 1,1-dichloroethylene. In contrast, Chieco et al. (1981) found no histopathological lung changes in fasted or nonfasted rats administered a single oral dose of 200 mg/kg of 1,1-dichloroethylene.
After oral treatment of rats with 1000 mg/kg of 1,1-dichloroethylene, liver glutathione levels were decreased to 33% of the control values within 4 hours but returned to the control levels after 24 hours (Reichert et al., 1978).
Information on the subchronic oral toxicity of 1,1-dichloroethylene in humans was not available.
Rampy et al. (1977) administered 50, 100, or 200 ppm 1,1-dichloroethylene in drinking water to male and female Sprague-Dawley rats for 90 days. The only adverse effect noted was an increased incidence of cytoplasmic vacuolization of hepatocytes in the high dose group.
No adverse effects were observed in beagle dogs administered daily doses of 6.25, 12.5, or 25 mg/kg of 1,1-dichloroethylene in gelatin capsules for 97 days (Quast et al., 1983).
Information on the chronic oral toxicity of 1,1-dichloroethylene in humans was not available.
Male and female Sprague-Dawley rats were administered 50, 100, or 200 ppm 1,1-dichloroethylene in drinking water for 2 years (Quast et al., 1983). The authors calculated a daily intake of 7, 10, or 20 mg/kg/day for males and 9, 14, or 30 mg/kg/day for females. There were no treatment-related effects on mortality, body weight, clinical chemistry, urinalysis, hematology, or tumor incidence. Female rats at all dose levels developed hepatic lesions, characterized as minimal hepatocellular fatty change and hepatocellular hypertrophy. In male rats, hepatocellular hypertrophy was seen at 100 and 200 ppm.
In a 2-year gavage study conducted by NTP (1982), F344 rats and B6C3F1 mice were administered 1,1-dichloroethylene at doses of 1 or 5 mg/kg/day (rats) and 2 or 10 mg/kg/day (mice), 5 days/week for 2 years. Mortality and growth rates were not affected in either species at either dose level. Compared with controls, an increased incidence of chronic inflammation of the kidneys occurred in high-dose male and female rats, and an increased incidence of liver necrosis was observed in high-dose male and low-dose female mice.
Information on the developmental and reproductive oral toxicity of 1,1-dichloroethylene in humans was not available.
No adverse effects were reported in Sprague-Dawley rats given 200 mg/L of 1,1-dichloroethylene in drinking water on gestation days 6-15 (Murray et al., 1979). In a three-generation study, Nitschke et al. (1983) found no treatment-related effects on reproduction or neonatal development in male and female Sprague-Dawley rats administered 50, 100, or 200 mg/L of 1,1-dichloroethylene in the drinking water.
When rats were exposed to feed fumigated with 250 or 500 ppm 1,1-dichloroethylene, no changes in fetal mortality or fetal weight were found over several generations during a 2-year period (Alumot et al., 1976). Based on the amount eaten and the measured residue level, the investigators calculated that due to volatility only 60 to 70% of the fumigant was actually consumed.
The primary effect of acute exposure to high concentrations (approximately 4000 ppm) of 1,1-dichloroethylene vapor is central nervous system (CNS) depression which may progress to unconsciousness (Gosselin et al., 1984). Lesions of the trigeminal nerve, causing motor weakness of the jaw, eye, and tongue muscles, have been reported following acute inhalation exposure to 1,1-dichloroethylene (Henschler et al., 1970). However, subsequent evaluation suggested that the toxic agent was either mono- or dichloroacetylene (Haley, 1975).
The lethality of 1,1-dichloroethylene appears to be dependent on dietary parameters. Inhalation LC50s for 4-hour exposures were 10,000-15,000 ppm in fed rats and 500-2500 ppm in fasted rats; death was due to vascular collapse and shock (Jaeger et al., 1973).
Twenty 6-hour exposures to 500 ppm caused nasal irritation, reduced weight gain, and histopathological changes in the liver of rats (Gage, 1970). Exposure of fasted rats to 200 ppm 1,1-dichloroethylene for 4 hours produced injury to liver parenchymal cells (Reynolds et al., 1980).
Information on the subchronic inhalation toxicity of 1,1-dichloroethylene in humans was not available.
Prendergast et al. (1967) exposed rats, guinea pigs, squirrel monkeys, rabbits, and beagle dogs continuously to 20, 61, or 189 mg/m3 (5, 15, or 48 ppm) 1,1-dichloroethylene for 90 days. Early mortality occurred in guinea pigs and monkeys at all exposure concentrations without visible signs of toxicity compared with controls. All species had reduced body weight gains at 189 mg/m3. Also seen at the highest exposure level were increased liver alkaline phosphatase and serum glutamic-pyruvic transaminase activities in rats and guinea pigs; kidney lesions in rats; and liver lesions in rats, dogs, and monkeys. The liver lesions were described as fatty changes, focal necrosis, hemosiderin deposition, lymphocytic infiltration, bile duct proliferation, fibrosis, and pseudo-lobule formation.
Ott et al. (1976) studied mortality and health examination data of 138 Dow Chemical Company workers who had been exposed to 1,1-dichloroethylene at concentrations ranging from <5 ppm to >70 ppm (time-weighted averages) in various job categories. The length of exposure ranged from <1 year to >10 years. Except for hepatic effects noted in two individuals with a history of alcohol consumption, mortality, spirometry, blood chemistry (including liver and renal tests), hematological parameters, and blood pressure measurements did not differ from controls matched for age and smoking.
In a preliminary study, Tierney et al. (1979) reported that 27 of 46 workers exposed to 1,1-dichloroethylene for 6 years or less in a 1,1-dichloroethylene polymerization plant showed a 50% or greater loss of liver function. The study provided few details, and a follow-up study has not been reported.
Lee et al. (1977) exposed both sexes of CD rats and CD-1 mice to 55 ppm 1,1-dichloroethylene vapor, 6 hours/day, 5 days/week for up to 1 year. Most treated rats developed hepatocellular fatty changes, and treated mice developed various hepatocellular changes, as well as focal degeneration, and necrosis of the liver.
Male and female Sprague-Dawley rats were exposed by inhalation to 10 or 40 ppm 1,1-dichloroethylene, 6 hours/day, 5 days/week for 1 month (Quast et al., 1986). Because of lack of treatment-related effects, exposure was then increased to 25 or 75 ppm for 17 months, and surviving animals were held for an additional 6 months. The only effects attributed to 1,1-dichloroethylene inhalation were hepatocellular changes in both male and female rats at both exposure levels.
Information on the developmental and reproductive toxicity of 1,1-dichloroethylene following inhalation exposure in humans was not available.
Short et al. (1977a) exposed CD rats and CD-1 mice to 1,1-dichloroethylene for 23 hours/day on days 6-16 of gestation. Rats were exposed to 15, 57, 300, or 449 ppm and mice to 15, 30, 57, 144, or 300 ppm. Maternal toxicity was seen in both species. In rats, 25% mortality occurred in dams exposed to the two highest concentrations; food consumption and weight gain was adversely affected at >=15 ppm. No pregnant mice survived exposure to 144 or 300 ppm. Early resorptions were common in all exposed groups, with 49 and 64% resorptions in rats exposed to 57 and 449 ppm, respectively, and 100% resorptions in mice exposed to 30 and 57 ppm, respectively. Some soft tissue anomalies were observed in offspring of rats at 15 and 57 ppm, and a significantly (p value not given) increased incidence of incomplete ossification of sternebrae occurred in offspring of mice at 15 ppm and in offspring of rats at 15, 57, and 300 ppm.
Murray et al. (1979) exposed Sprague-Dawley rats and New Zealand rabbits to 20 ppm (rats only), 80 ppm, or 160 ppm 1,1-dichloroethylene vapor for 7 hours/day during organogenesis. Maternal toxicity (decreased weight gain, decreased food consumption, and increased liver weights) was observed in rats at 80 and 160 ppm and in rabbits at 160 ppm. A statistically significant (p<0.05) increase of skeletal variations such as delayed ossification and wavy ribs was seen in offspring of rats exposed to both 80 and 160 ppm and in offspring of rabbits exposed to 160 ppm. In rabbits, resorptions were significantly (p<0.05) greater at 160 ppm than in control dams.
In a dominant lethal assay by Short et al. (1977b), exposure of male rats to 55 ppm 1,1-dichloroethylene, 6 hours/day, 5 days/week for 11 weeks before gestation had no effects on their fertility. No pre- or postimplantation losses occurred in untreated females mated to treated males.
An inhalation reference concentration (RfC) for 1,1-dichloroethylene has not been derived. A risk assessment for this chemical is under review by an EPA work group (EPA, 1994a).
1,1-Dichloroethylene is irritating when applied to the skin of humans; prolonged contact can cause first degree burns (Tierney et al., 1979). It has been suggested that the irritant effect is due to the presence of the inhibitor MEHQ, a compound that produces skin depigmentation at concentrations of 0.25% or higher (ATSDR, 1993). Direct contact with the eyes may cause conjunctivitis and transient corneal injury (IARC, 1986).
Intravenous injection of 225 mg/kg of 1,1-dichloroethylene and subcutaneous injection of 3700 mg/kg was lethal to dogs and rabbits, respectively (Tierney et al., 1979).
1,1-Dichloroethylene is moderately irritating to the eyes of rabbits, causing pain, conjunctival irritation, and some transient corneal injury (Torkelson and Rowe, 1982). Permanent injury is unlikely. Skin irritation, noted in rabbits a few minutes after application of liquid 1,1-dichloroethylene, was attributed in part to the presence of the stabilizer MEHQ.
Mice exhibited a decrease of cytochrome P-450 levels and related monooxygenases in lung microsomes 24 hours after an intraperitoneal injection of 125 mg/kg of 1,1-dichloroethylene (Krijgsheld et al., 1983). Examination of the lung tissues revealed necrosis that was restricted to the Clara cells.
Information on the subchronic toxicity of 1,1-dichloroethylene in humans or animals by other routes of exposure was not available.
Information on the chronic toxicity of 1,1-dichloroethylene in humans or animals by other routes of exposure was not available.
Information on the developmental and reproductive toxicity of 1,1-dichloroethylene in humans or animals by other routes of exposure was not available.
Other target organs following oral exposure to 1,1-dichloroethylene were not identified.
Other target organs following inhalation exposure to 1,1-dichloroethylene were not identified.
Other target organs by other routes of exposure to 1,1-dichloroethylene were not identified.
Information on the carcinogenicity of 1,1-dichloroethylene in humans following oral exposure was not available.
Oral carcinogenicity studies with rats and mice gave negative results. In a 2-year gavage study conducted by NTP (1982), F344 rats and B6C3F1 mice were administered 1,1-dichloroethylene at doses of 1 or 5 mg/kg/day (rats) and 2 or 10 mg/kg/day (mice), 5 days/week for 2 years. An increased incidence (not statistically significant) of adrenal pheocytochromas was seen in high-dose male rats but not in female rats. Female mice administered the low dose exhibited an increased incidence of lymphomas and leukemia that was not considered treatment-related. In another gavage study, male and female Sprague-Dawley rats received 0.5, 5, 10, or 20 mg/kg/day, 4 to 5 days/week for 78 weeks, followed by a 147-week observation period (Maltoni et al., 1984, 1985). The pattern of neoplasms and their incidences was similar to that seen in controls.
No carcinogenic effects were observed in Sprague-Dawley rats administered 50 to 200 ppm (7 to 30 mg/kg/day) 1,1-dichloroethylene in drinking water for 2 years (Quast et al., 1983).
Ott et al. (1976) found no relationship between the occurrence of cancer or cancer mortality in 138 workers primarily exposed to 1,1-dichloroethylene during 1950 to 1959 and 55 workers exposed from 1960 to 1969. The subjects were divided into groups exposed to <5 ppm, 10-24 ppm, and >=25 ppm. Five deaths were observed (compared with 7.5 expected in the U.S. white male population) and 27 workers were lost to follow-up. The study was inadequate to assess cancer risk because the cohorts were limited, and no allowance was made for the latency period.
Male and female Sprague-Dawley rats were exposed by inhalation to 10 or 40 ppm 1,1-dichloroethylene, 6 hours/day, 5 days/week for 1 month (Quast et al., 1986). Because of the lack of treatment-related effects, exposure was then increased to 25 or 75 ppm for 17 months, and surviving animals were held for an additional 6 months. No treatment-related neoplasms were observed.
Maltoni et al. (1985) exposed male and female Swiss mice to 10 or 25 ppm 1,1-dichloroethylene, 4 to 5 days/week for 12 months. [Interim results of this study were reported in Maltoni et al., 1977.] A statistically significant (p value not given) increase in kidney adenocarcinomas was reported in male mice exposed to 25 ppm. There were also statistically significant increases in mammary adenocarcinomas in female mice and pulmonary adenomas in both sexes; however, a dose-response relationship was not apparent. In a second study, Sprague-Dawley rats were exposed to 10, 25, 50, 100, or 150 ppm, 4 to 5 days/week for 12 months and observed until death. A statistically significant (p value not given) increase in total mammary tumors (but not carcinomas) was seen only at 10 ppm and 100 ppm but not at the other concentrations tested.
In a study by Hong et al. (1981), small groups of CD rats and CD-1 mice of both sexes were exposed to 55 ppm 1,1-dichloroethylene, 6 hours/day, 5 days/week for 1, 3, 6 (rats and mice), or 10 months (rats only). Following treatment, all groups were observed for 12 months. There was a dose-related decrease in survival in male and female mice; survival in rats was similar to controls. No treatment-related tumors were reported in rats or mice.
Female Chinese hamsters were exposed to 25 ppm 1,1,-dichloroethylene for 4 hours/day, 4-5 days/week for 52 weeks and observed for life (164 weeks) (Maltoni et al., 1984). The tumor incidence was comparable to that in controls.
Information on the carcinogenicity of 1,1-dichloroethylene in humans by other routes of exposure was not available.
Van Duuren et al. (1979) applied 40 or 121 mg 1,1-dichloroethylene to the skin of Swiss mice three times weekly for 595 days. No skin tumors were observed. However, when 121 mg 1,1-dichloroethylene was applied once, followed 2 weeks later by dermal applications of the tumor promoter, phorbol myristate acetate (three times weekly for about 576 days), there was a statistically significant (p<0.05) increase in the incidence of skin papillomas in treated animals compared with controls treated with the promoter only.
In another experiment, Van Duuren et al. (1979) injected female Ha:ICR mice subcutaneously with 2 mg 1,1-dichloroethylene in trioctanoin once weekly for 78 weeks. No local sarcomas were observed.
Classification -- Group C - Possible human carcinogen (EPA, 1994a)
Basis -- Tumors have been observed in one mouse strain after inhalation exposure. Other studies were of inadequate design. 1,1,-Dichloroethylene is mutagenic, and a metabolite has been shown to alkylate and bind covalently to DNA. It is structurally related to the human carcinogen, vinyl chloride.
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