CAS RN:75-35-4

Toxicity Summary

IDENTIFICATION AND USE: 1,1-Dichloroethene (1,1-DCE) is a colorless liquid. It is used as a captive intermediate in the production of hydrochlorofluorocarbons (HCFC-141b and HCFC-142b), in the production of chloroacetyl chloride, and in the production of homo-, co-, and terpolymers (latex and resin). The polymers are used in a variety of consumer products, including food packaging, textiles, and outdoor furniture. HUMAN STUDIES: Potential symptoms of overexposure are irritation of eyes, skin, throat, dizziness, headache, nausea, dyspnea, liver and kidney dysfunction, pneumonitis. Acute exposure to high concentrations of 1,1-DCE in air results in CNS depression. Repeated exposures to low concentrations are associated with liver and renal dysfunction. Contact with the eye causes conjunctivitis and transient corneal injury. Skin contact with 1,1-DCE causes irritation, which may be due partly to the presence of an inhibitor, hydroquinone monomethyl ether. In one epidemiological study of 138 workers exposed to 1,1-DCE in the United States, no excess of cancer was found, but follow-up was incomplete, and nearly 40% of the workers had less than 15 years' latency since first exposure. In a study in the Federal Republic of Germany of 629 workers exposed to 1,1-DCE, seven deaths from cancer (five bronchial carcinomas) were reported. This number was not in excess of the expected value. Two cases of bronchial carcinoma were found in workers, both of whom were 37 years old, whereas 0.07 were expected for persons aged 35 to 39 years. Three reports suggest an association between exposure to dichloroethylenes and birth defects. However, all of these situations involved exposure to multiple contaminants, so a cause-and-effect relationship between the reported birth defects and exposure to 1,1-DCE cannot be established. Hepatotoxicity has been observed in humans after repeated exposure to 1,1-DCE, presumably by the inhalation route. ANIMAL STUDIES: One study shows no evidence that 1,1-DCE causes skin sensitization. Following high-dose exposure by the oral or inhalation route, the target organs in experimental animals are the liver, the kidney, and the Clara cells of the lung. Following low-dose, long-term exposure, the liver is the major target organ in rats following oral or inhalation exposure, but the kidney is the major target organ in mice following inhalation exposure. Bioassays for cancer by the oral route of exposure have been conducted in rats, mice, and trout. Although these bioassays have protocol limitations, none provides any significant evidence that 1,1-DCE is a carcinogen by the oral route of exposure. Bioassays for cancer by the inhalation route of exposure have been conducted in rats, mice, and hamsters. One bioassay in male mice showed an increase in the incidence of kidney adenocarcinomas at one exposure level. There is evidence that the induction of kidney adenocarcinomas is a sex- and species-specific response related to the expression of CYP2E1 in the kidney of male mice. 1,1-DCE causes gene mutations in microorganisms in the presence of metabolic activation. Most tests with mammalian cells in vitro or in vivo show no evidence of genotoxicity. No reproductive or developmental toxicity was observed at an oral exposure that caused minimal toxicity in the liver of the dams. An increased incidence of total cardiac malformations of 12-13% was recorded in pups from rats imbibing water containing either 0.15 ppm or 110 ppm 1,1-DCE over a period of 2 months prior to and subsequently the whole pregnancy period (controls had a 3% incidence of similar cardiac anomalie). An increased incidence of cardiac terata was also reported when utilizing method of continuous infusion of the chemical directly into the gravid rat uterus via implanted osmotic pumps. 1,1-DCE was a cardiac teratogen in the chick embryo, cardiac anomalies included atrial and ventricular septal defects, malformations of all valves, and great vessel abnormalities. There is evidence of fetal toxicity (delayed ossification) following inhalation exposure in the absence of maternal toxicity. The toxicity of 1,1-DCE is associated with cytochrome P450-catalyzed metabolism of 1,1-DCE to reactive intermediates that bind covalently to cellular macromolecules. The extent of binding is inversely related to loss of GSH, so that severity of tissue damage parallel the decline in GSH. Thus, the responses to 1,1-DCE at low doses with little depletion of GSH are expected to be very different from the responses at high doses causing substantial GSH depletion. ECOTOXICITY STUDIES: An 18-month carcinogenicity study of 1,1-DCE in rainbow trout (Oncorhynchus mykiss) (8 weeks old) at 4 mg/kg body weight per day was conducted. 1,1-DCE was incorporated in the feed. Tissues examined for neoplasms included liver, kidney, spleen, gill, gonads, thymus, thyroid, heart, stomach, pyloric caeca, duodenum, rectum, pancreas, and swimbladder. 1,1-DCE produced no neoplasms at the exposure levels used and no increase in liver weight. There was no evidence of any other chronic toxic effects.
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