Toxicity Profiles
Condensed Toxicity Summary for VINYL CHLORIDE
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.
March 1993Prepared by Rosmarie A. Faust, Ph.D, Chemical Hazard Evaluation Grou, Biomedical 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 Vinyl chloride (CAS Reg. No. 75-01-4), a colorless gas, is a halogenated aliphatic hydrocarbon with the empirical formula of C2H3Cl. It is used primarily as an intermediate in the manufacture of polyvinyl chloride (PVC); limited quantities are used as a refrigerant and as an intermediate in the production of chlorinated compounds (ATSDR, 1989).
Vinyl chloride is rapidly absorbed from the gastrointestinal tract and lungs. Metabolism of vinyl chloride occurs primarily in the liver via oxidation by hepatic microsomal enzymes to polar compounds which can be conjugated with glutathione and/or cysteine. These covalently bound metabolites are then excreted in the urine (U.S. EPA, 1980, 1985).
In humans and animals, vinyl chloride is a CNS depressant, inducing narcosis and anesthesia at high concentrations (Torkelson and Rowe, 1981; Patty et al., 1930). Nonneoplastic toxic effects observed in workers exposed by inhalation to vinyl chloride include hepatotoxicity, acroosteolysis and scleroderma, and Raynaud's syndrome, a vascular disorder of the extremities. Also reported were abnormalities of CNS function, high blood pressure, and occasional pulmonary effects (ATSDR, 1989; U.S. EPA, 1985; Lloyd et al., 1984; Langauer-Lewowicka et al., 1983; Waxweiler et al., 1977). The evidence for potential developmental effects in humans (increased fetal loss and birth defects) is equivocal (ATSDR, 1989; Waxweiler et al., 1977; Infante et al., 1976). Occupational exposure to vinyl chloride has been associated with reduced sexual function in both sexes and gynecological effects in women (Makarov, 1984; Makarov et al., 1984).
For the oral route of exposure, the primary target organ of vinyl chloride toxicity in animals is the liver. Chronic oral administration of 1.7-14.1 mg/kg/day of vinyl chloride induced dose-related increases in nonneoplastic lesions of the liver of rats (Feron et al., 1981). In addition to the CNS, target organs for inhalation exposure include the liver, kidneys, lungs, spleen, and testes. Subchronic inhalation studies with rodents documented hepatic effects at concentrations as low as 50 ppm (Sokal et al., 1980) and degenerative changes of the liver and kidneys at >= 500 ppm (Torkelson et al., 1961). Exposure to higher concentrations caused proliferative changes in the lungs of mice (Suzuki, 1980), extensive liver and kidney damage in rats and guinea pigs, cerebral and cerebellar nephrosis in rats, and degeneration of the spleen in guinea pigs (Prodan et al., 1975; Viola, 1971). Subchronic exposure of rats to 100 ppm vinyl chloride produced significantly decreased testes weights and testicular regeneration (Bi et al., 1985). Evidence of developmental toxicity was seen in rats exposed to vinyl chloride during the first trimester of gestation (Ungvary et al., 1978).
Neither an oral reference dose (RfD) nor an inhalation reference concentration (RfC) have been derived for vinyl chloride (U.S. EPA, 1992).
The carcinogenicity of vinyl chloride in humans has been demonstrated in a number of epidemiological studies and case reports, many of which associated occupational exposure to vinyl chloride to the development of angiosarcomas of the liver. In addition to liver cancer, exposure to vinyl chloride also has been linked to an increased risk of lung, brain, hematopoietic, and digestive tract cancers (U.S. EPA, 1985; Heldaas et al., 1984; IARC, 1979; Byren et al., 1976; Waxweiler et al., 1976; Monson et al., 1974). Vinyl chloride has been shown to be carcinogenic in numerous animal studies. Inhalation exposure to vinyl chloride induced an increased incidence of liver angiosarcomas; kidney nephroblastomas; and lung, brain, and forestomach tumors in rodents (Maltoni et al., 1980, 1981; Feron et al., 1981; Hong et al., 1981; Suzuki, 1978; Lee et al., 1977, 1978). Oral administration of vinyl chloride induced liver, lung, and kidney tumors in rodents (Feron et al., 1981; Maltoni, 1977). Angiosarcomas observed in offspring of rats exposed by inhalation during gestation indicates that vinyl chloride has the potential to initiate cancer in utero (Radike et al., 1988).
EPA has classified vinyl chloride as a Group A chemical, human
carcinogen (U.S. EPA, 1985). A slope factor of 1.9E+0 (mg/kg/day)-1
and a drinking water unit risk of 5.4E-5 (µg/L)-1 was calculated
for oral exposure to vinyl chloride (U.S. EPA, 1992). For inhalation
exposure, the slope factor and inhalation unit risk are 3.0E-1
(mg/kg/day)-1 and 8.4E-5 (µg/m3)-1, respectively. The oral slope
factor and inhalation unit risk are currently under review and
may be subject to change (U.S. EPA, 1992).
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Last Updated 8/29/97