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 Group, 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).
Vinyl chloride (CAS Reg. No. 75-01-4), also known as chloroethene, is a halogenated aliphatic hydrocarbon with the empirical formula of C2H3Cl and a molecular weight of 62.5. It is a colorless gas with a mild sweetish odor, a melting point of -153.71 oC, a boiling point of -13.8 oC, a specific gravity of 0.9121 (20/4 oC), and a vapor pressure of 2580 torr (20 oC). Vinyl chloride is slightly soluble in water and soluble in hydrocarbons, oil, alcohol, chlorinated solvents, and most common organic liquids. It polymerizes in light or in the presence of a catalyst (Budavari et al., 1989; U.S. EPA, 1985; Torkelson and Rowe, 1981). Vinyl chloride is produced by thermal cracking of ethylene chloride and does not occur naturally. 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, an anthropogenic environmental contaminant, has been detected in the ambient air in the vicinity of vinyl chloride and PVC manufacturing plants and hazardous waste sites. It is a biodegradation product of trichloroethylene, tetrachloroethylene, and 1,1,1-trichloroethane. Vinyl chloride may leach into groundwater from spills, landfills, and industrial sources. Released to the atmosphere, reaction with photochemically generated hydroxyl radicals is the primary removal process. Due to its relatively high vapor pressure, volatilization is expected to be the primary removal process following vinyl chloride releases to water or soils (ATSDR, 1989; U.S. EPA, 1985).
Vinyl chloride is rapidly absorbed from the gastrointestinal tract and lungs. Based on fecal recovery, the absorption of vinyl chloride (in PVC powder) from the gastrointestinal tract of rats was 83-92% (Feron et al., 1981). Maximum blood levels in rats were reached within 10-20 minutes of oral administration of vinyl chloride in an aqueous or oily vehicle (Withey, 1976). In humans exposed to 7.5-60 mg/m3 of vinyl chloride by gas mask for 6 hours, 42% of the inhaled compound was retained by the lungs (Krajewski et al., 1980). Although the retention varied among individuals tested, the percentage retained was independent of the exposure concentration. A study with animals indicates that the dermal absorption of vinyl chloride gas is not significant. Hefner et al. (1975a) estimated that rhesus monkeys dermally absorbed 0.031 or 0.023% of the available compound following exposure to 800 ppm for 2.5 hours or to 7000 ppm for 2 hours, respectively.
No data were available concerning the tissue distribution of vinyl chloride in humans. In rats administered single oral doses of radiolabeled vinyl chloride, the highest level of radioactivity occurred in the liver, up to three times that found in other tissues examined (skin, lungs, plasma, fat, carcass, and muscle) (Watanabe et al., 1976a). Radioactivity was detected in the liver, kidney, skin, lungs, muscle, carcass, plasma, and fat 72 hours following inhalation exposure to 10 or 100 ppm of radiolabeled vinyl chloride (Watanabe et al., 1976b). Immediately after a 5-hour inhalation exposure to 50 ppm vinyl chloride, the highest levels occurred in the kidneys and liver of rats, with lower levels in the spleen and brain (Bolt et al., 1976). Ungvary et al. (1978) demonstrated that vinyl chloride crosses the placenta and is found in the amniotic fluid and fetal blood as well as in the maternal blood of rats.
Metabolism of vinyl chloride occurs primarily in the liver via oxidation by hepatic microsomal enzymes to polar compounds that can be conjugated to glutathione and/or cysteine. These covalently bound metabolites are then excreted in the urine (U.S. EPA, 1980, 1985). Based on inhalation studies with rats, postulated metabolic pathways involve an alcohol dehydrogenase and a mixed-function oxidase system. At low concentrations, vinyl chloride is sequentially oxidized to 2-chloroethanol, 2-chloroacetaldehyde, and 2-chloroacetic acid in the presence of alcohol dehydrogenase. When this pathway becomes saturated, 2-chloroethanol may be oxidized by catalase in the presence of hydrogen peroxide to a peroxide, which then may undergo dehydration to form 2-chloroacetaldehyde. At higher concentrations, an alternate pathway involves the oxidation by mixed-function oxidases to form a highly reactive epoxide intermediate, 2-chloroethylene oxide, which can rearrange spontaneously to form 2-chloroacetaldehyde (ATSDR, 1989; Hefner et al., 1975b; U.S. EPA, 1980). Chloroacetaldehyde can be oxidized to chloroacetic acid, which may be excreted as such or bound to glutathione to form S-carboxy-methyl glutathione and excreted as thiodiglycolic acid upon further enzymatic degradation (IARC, 1979). In rats, vinyl chloride appears to be metabolized extensively with saturation of metabolic pathways occurring at concentrations exceeding 220-250 ppm (U.S. EPA, 1985).
In human volunteers, exhalation of unchanged vinyl chloride following inhalation exposure represented 4-5% of the inhaled concentration and decreased to undetectable levels within 30 min after exposure was terminated (Krajewski et al., 1980).
Following inhalation exposure of rats to 10 ppm of radiolabeled vinyl chloride for 6 hours, urinary and expired radioactivity comprised 68 and 2% of the recovered radioactivity, respectively; after exposure to 1000 ppm, the proportion of radioactivity was lower in the urine but higher in expired air, representing 56 and 12% of the radioactivity, respectively. Approximately 4% of radioactivity was excreted in the feces at either exposure concentration. Urinary metabolites were identified as N-acetyl(S-2-hydroxyethyl)cysteine, thiodiglycolic acid, and possibly S-(2-hydroxyethyl)cysteine (Watanabe and Gehring, 1976). The elimination of vinyl chloride and its metabolites in rats following oral exposure appears to follow a similar pattern (Watanabe et al., 1976a).
Information on the acute oral toxicity of vinyl chloride in humans was not available.
Sax (1984) reported an oral LD50 of 500 mg/kg for rats.
Information on the subchronic oral toxicity of vinyl chloride in humans was not available.
Vinyl chloride dissolved in soybean oil was administered to Wistar rats by gavage at doses of 0, 30, 100, or 300 mg/kg, 6 days/week for 13 weeks (Feron et al., 1975). Behavior, food intake, or body weights were not affected at any dose level. A dose-related increase in liver weights was seen in both sexes; only high-dose rats exhibited ultrastructural changes of the liver. A dose-related decrease in adrenal weights occurred in males.
Information on the chronic oral toxicity of vinyl chloride in humans was not available.
Feron et al. (1981) administered PVC powder with a high vinyl chloride content to Wistar rats in the diet or by gavage for life. The estimated dietary doses of vinyl chloride were 0, 1.7, 5.0, or 14.1 mg/kg/day; 300 mg/kg/day by gavage was given 5 days/week. Treatment with 14.1 or 300 mg/kg/day resulted in shortened blood-clotting times, slightly increased -fetoprotein levels, liver enlargement and increased hematopoietic activity in the spleen. There was a dose-related increase of nonneoplastic liver lesions, characterized as swollen and irregularly shaped mitochondria in hepatocytes. Mortality of rats treated by gavage approached 40% by 18 months; most rats that died had severe lesions of the liver and lungs. In another chronic study, Wistar rats were administered vinyl chloride as dietary powdered PVC fortified with the monomer at doses of 0.0, 0.014, 0.13, or 1.3 mg vinyl chloride/kg/day for 149 weeks (Dow Chemical Company, 1984). General health, behavior, body weight, food intake, and clinical chemistry parameters were not affected at any dose tested. In the high-dose group, mortality was slightly increased among males and hepatotoxic effects, characterized as hepatocellular polymorphism, hepatic cysts, cellular alterations including clear cell foci and basophilic foci, occurred in both sexes.
Information on the developmental and reproductive toxicity of vinyl chloride in humans or animals following oral exposure was not available.
An oral reference dose (RfD) for vinyl chloride has not been derived.
The primary acute effect of vinyl chloride inhalation is central nervous system (CNS) depression, which occurs at concentrations approaching 1% (10,000 ppm); anesthesia requires concentrations greater than 10% (Torkelson and Rowe, 1981). Acute exposure to vinyl chloride gas has resulted in deaths of two workers. Autopsy findings revealed congestion of the liver, spleen, and kidneys (Danziger, 1960).
Reported 2-hour LC50 values for vinyl chloride range from 117,000 ppm for mice to 230,800 ppm for rabbits (U.S. EPA, 1985). Exposure to 25,000-50,000 ppm vinyl chloride for 2-5 minutes produced ataxia and narcosis in guinea pigs; exposure to 100,000 ppm caused death within 30 minutes (Patty et al., 1930).
Information regarding the subchronic inhalation toxicity of vinyl chloride in humans was not available.
Torkelson et al. (1961) conducted an inhalation study by exposing rats, guinea pigs, rabbits, and dogs to vinyl chloride at concentrations ranging from 50-500 ppm for 7 hours/day, 5 days/week. Rats exposed to 500 ppm for 4.5 months showed significantly (p=0.001, males) increased liver weights and degenerative changes in the liver and kidneys. Exposure to 200 and 100 ppm for 6 months induced significantly (p<0.05) increased liver weights in male and female rats and degenerative liver changes in rabbits, but no such effects were detected in guinea pigs or dogs. All species tolerated 50 ppm for 6 months without adverse effects.
Male rats exposed by inhalation to 50, 500, or 20,000 ppm vinyl chloride, 5 hours/day, 5 days/week for 10 months exhibited morphological lesions of the liver and testes, decreased body weight gain, increased organ weights (not specified), and slight hematological and biochemical changes in the blood (Sokal et al., 1980).
Mice exposed to 2500 or 6000 ppm vinyl chloride 5 hours/day, 5 days/week for 5 or 6 months, respectively, exhibited bronchiolar epithelial proliferation and hyperplasia of the alveolar epithelium (Suzuki, 1980).
Inhalation exposure of rats to 30,000 ppm vinyl chloride for 4 hours/day, 5 days/week for 12 months resulted in hepatic effects, including interstitial inflammation, Kupffer cell hypertrophy, and partial necrosis, and renal effects characterized as tubulonephrosis and interstitial nephritis. Also noted were cerebral and cerebellar nephrosis and an increase of perifollicular cells in the thyroid. Examination of the paws revealed metaplasia of the metatarsal bones, chondroid metaplasia, epidermal keratosis, basal layer vacuolization and degeneration, and general epidermal edema (Viola, 1971).
Slowed growth, decreased spontaneous mobility, increased kidney weights, and extensive hepatocellular lesions (necrosis and proliferation of fibroblasts and Kupffer cells) and glomerular and tubular lesions of the kidneys were observed in guinea pigs exposed by inhalation to 10% (100,000 ppm) vinyl chloride for 2 hours/day for 90 days. Also noted were cellular changes of the spleen (almost complete disappearance of red pulp) and pulmonary fibrosis (Prodan et al., 1975).
A number of chronic toxic effects have been reported in humans occupationally exposed to vinyl chloride (Lilis et al., 1975). In workers exposed to vinyl chloride during the production of PVC, the effects included acroosteolysis (dissolution of bone involving the distal phalanges of fingers and toes) and scleroderma, hepatotoxicity, and some pulmonary effects. Raynaud's syndrome (a vascular disorder characterized by intermittent severe pallor of fingers and toes) occurred in about 10% of workers with >20 years of exposure. Abnormal peripheral circulation was associated with length of exposure to vinyl chloride. Symptoms and signs of liver disease associated with occupational exposure to vinyl chloride include tenderness, hepatomegaly, thrombocytopenia, esophageal varices, fibrosis and cirrhosis, and abnormal liver function tests (ATSDR, 1989; U.S. EPA, 1985). A survey by the National Institute of Occupational Safety and Health (Waxweiler et al., 1977) of vinyl chloride-exposed workers in a PVC and rubber tire production plant found an association between vinyl chloride exposure and the prevalence of hepatomegaly, CNS abnormalities, and high blood pressure. Langauer-Lewowicka et al. (1983) reported a number of neurological symptoms, scleroderma, and Raynaud's syndrome in vinyl chloride production workers. The neurological effects may have been due to the direct toxic effects of vinyl chloride or to vascular deficiency. In a case-control study, Lloyd et al. (1984) found an association between vinyl chloride exposure and impaired lung function. Recent data from the foreign literature reported in ATSDR (1989) suggest that occupational exposure to vinyl chloride may induce mild neurotoxic effects, EEG changes, and psychiatric disorders.
Information regarding the chronic inhalation toxicity of vinyl chloride in animals was not available.
Epidemiological studies conducted in the 1970's suggested an association between paternal occupational exposure to vinyl chloride and fetal loss and between parental residence in the vicinity of a vinyl chloride plant and an increased incidence of birth defects (Infante et al., 1976; Waxweiler et al., 1977). However, evaluations of these studies and additional studies found no solid association between vinyl chloride exposure and the incidence of fetal loss and/or birth defects (ATSDR, 1989). Two Russian studies, that provided few details, reported a decrease in sexual function in occupationally exposed men and women at vinyl chloride concentrations ranging from 12 to 60 ppm. This decline in sexual function was related to concentration and duration of exposure. Ovarian dysfunction, benign uterine growths, and prolapsed genital organs were reported in 77% of exposed women (Makarov, 1984; Makarov et al., 1984).
In a teratogenicity study using three species of animals, pregnant CF1 mice, Sprague-Dawley rats, and New Zealand white rabbits were exposed 7 hours daily to 500 ppm vinyl chloride during organogenesis (John et al., 1977). Another group of mice were also exposed to 50 ppm and additional groups of rats and rabbits were exposed to 2500 ppm. Vinyl chloride treatment did not induce gross teratogenic abnormalities in offspring of exposed mothers. However, an excess of minor skeletal abnormalities, increased fetal deaths, and maternal toxicity occurred at concentrations of >= 500 ppm. Maternal toxicity was most pronounced in mice.
Ungvary et al. (1978) exposed pregnant rats to 4000 mg/m3 (1543 ppm) vinyl chloride for 24 hours/day during days 1-9, 8-14, or 14-21 of gestation. Significantly increased mortality and fetotoxic effects were seen in offspring of dams exposed to vinyl chloride during the first trimester of gestation. Similar effects were not seen in offspring of dams exposed in the second or last trimester of gestation.
Pregnant Sprague-Dawley rats were exposed to 600 ppm vinyl chloride, 5 hours/day on gestation days 9-21 (Radike et al., 1988). Angiosarcomas of the liver were found in offspring of dams exposed during gestation. Another treatment group additionally exposed during lactation exhibited a greatly increased incidence of liver tumors.
Exposure of male Wistar rats to 100 or 3000 ppm vinyl chloride, 6 hours/day, 6 days/week for 6 months produced testicular degeneration and a significant reduction of testicular weight (Bi et al., 1985).
An inhalation reference concentration (RfC) for vinyl chloride has not been derived.
Information regarding the acute toxicity of vinyl chloride by other routes of exposure in humans or animals was not available.
Information regarding the subchronic toxicity of vinyl chloride by other routes of exposure in humans or animals was not available.
Information on the chronic toxicity of vinyl chloride by other routes of exposure in humans or animals was not available.
Information on the developmental or reproductive toxicity of vinyl chloride in humans by other routes of exposure in humans or animals was not available.
Liver: Subchronic and chronic oral exposure of rats produced increased liver weights and histopathological changes of the liver.
Blood: Chronic exposure of rats produced mild hematological changes.
Target organs following exposure to vinyl chloride by other routes were not identified.
Information on the carcinogenicity of vinyl chloride in humans following oral exposure was not available.
Feron et al. (1981) conducted an oral carcinogenicity study with male and female Wistar rats by exposing them for life to a diet containing PVC powder with a high vinyl chloride content. The estimated doses were 1.8, 5.6, or 17 mg vinyl chloride/kg/day. Compared with controls, treatment with vinyl chloride induced a dose-related increase of neoplastic nodules of the liver, hepatocellular carcinomas, and liver and lung angiosarcomas in rats of both sexes. An increased incidence of liver angiosarcomas and renal nephroblastomas was reported in rats given vinyl chloride by gavage at doses of 16.65 or 50 mg/kg for 136 weeks (Maltoni, 1977).
Epidemiological studies and case reports have demonstrated an association between angiosarcomas of the liver and occupational exposure to vinyl chloride. In addition to liver cancer, exposure to vinyl chloride also has been associated with an increased risk of lung, brain, hematopoietic system, and digestive tract cancers (U.S. EPA, 1985; IARC, 1979). Vinyl chloride is classified as a Group 1 Chemical by the International Agency for Research on Cancer (IARC, 1979), designating that there is sufficient evidence that the compound is carcinogenic to humans.
A retrospective study of 161 deaths among vinyl chloride workers conducted by Monson et al. (1974) identified eight cases of hepatic and biliary cancer (all angiosarcomas), five cases of brain cancer, thirteen cases of lung cancer, thirteen cases of digestive tract cancer, and five cases of hematopoietic system cancer. All cancers presented risk ratios greater than expected and resulted in a 50% excess of death due to all types of cancer. Waxweiler et al. (1976) studied the cancer mortality of 1287 workers exposed to vinyl chloride for >= 5 years in four vinyl chloride production plants. When compared with the U.S. white male population, an excess of malignant neoplasms was found in four organ systems: the CNS, respiratory system, hepatic system, and lymphatic and hematopoietic systems. Three of the 136 deaths were due to brain and CNS cancer (0.9 expected); twelve to respiratory tract cancer (7.7 expected); seven to biliary and liver cancer (0.6 expected); and four to lymphatic and hematopoietic system cancer (2.5 expected). The tumors occurred after a 15-year latency period following onset of exposure. Most of the liver cancers were classified as angiosarcomas. Byren et al. (1976) reported a 4- to 5-fold excess of cancer of the liver and pancreas among 750 Swedish workers exposed to vinyl chloride for >10 years. The incidence of cancers of the brain and lung were also increased, but they were not statistically significant. A more recent mortality study of 454 male workers engaged in the production and polymerization of PVC for at least one year during 1950-1969 was conducted by Heldaas et al. (1984). The cohort was followed up from 1953 through 1979. A total of 23 cancer deaths were recorded (20.2 expected), with one case of liver angiosarcoma, five lung cancers (2.8 expected), three colon cancers (1.4 expected), two thyroid cancers (0.26 expected), and four malignant melanomas of the skin (0.8 expected). Two additional cases of malignant melanoma were reported after termination of the study.
Genotoxicity studies showing that vinyl chloride may induce chromosomal aberrations in the peripheral lymphocytes of occupationally exposed workers provide supportive evidence for the carcinogenicity of vinyl chloride in humans (ATSDR, 1989).
Numerous inhalation experiments with laboratory animals support the carcinogenicity of vinyl chloride. Maltoni and coworkers (Maltoni et al., 1980, 1981) conducted a series of inhalation experiments by exposing Sprague-Dawley rats, Swiss mice, and golden hamsters to vinyl chloride at concentrations of 1-30,000, 50-10,000, or 50-10,000 ppm, respectively, 4 hours/day, 5 days/week for 1 year (rats) or 30 weeks (mice and hamsters). Liver angiosarcomas were seen in rats exposed to >= 10 ppm; kidney nephroblastomas occurred >= 25 ppm. In mice, liver angiosarcomas occurred in all treated groups and lung tumors were more prevalent in animals treated with >= 250 ppm. A dose-related increase of papillomas and acanthomas of the forestomach was seen in hamsters treated with vinyl chloride. Keplinger et al. (1975) exposed rats, mice, and hamsters to 50 or 2500 ppm vinyl chloride for 9 or 12 months. All three species developed liver angiosarcomas at >= 50 ppm, with frequent metastases to the lungs and lymph nodes. Also reported were Zymbal's gland tumors and brain tumors in rats and lung tumors in mice. Lung tumors were the primary carcinogenic response in mice exposed to 2500 or 6000 ppm vinyl chloride for 5-6 months (Suzuki, 1978).
An increased incidence of liver and lung hemangiosarcomas was reported by Lee et al. (1977, 1978) in male and female CD rats exposed to 250 or 1000 ppm vinyl chloride, 6 hours/day, 5 days/week for 12 months. No liver or lung tumors were observed at 50 ppm. Male and female CD-1 mice treated with 50, 250, or 1000 ppm vinyl chloride for the same time period exhibited a dose-related increased incidence of liver hemangiosarcomas and bronchioalveolar adenomas. Rats treated with 250 or 1000 ppm, 6 hours/day, 5 days/week for 6 or 10 months developed hepatocellular carcinomas, bronchioalveolar tumors, and hemangiosarcomas of the liver and lung (Hong et al., 1981). Treatment of mice with 250 or 1000 ppm vinyl chloride for only 1 month induced bronchioalveolar tumors within 12 months.
In a perinatal carcinogenesis study, Radike et al. (1988) exposed pregnant rats by inhalation to 600 ppm vinyl chloride, 4 hours/day on days 9-21 of gestation. Additional animals were also exposed through the lactation period. The development of angiosarcomas of the liver, lung, and muscle in offspring demonstrated the transplacental potential of vinyl chloride to initiate cancer in utero. Continued exposure during lactation greatly increased the occurrence of liver tumors.
Information on the carcinogenicity of vinyl chloride in humans or animals by other routes of exposure was not available.
Classification -- Group A - Human carcinogen (U.S. EPA, 1985)
Basis -- High incidence of liver, kidney, lung, and brain tumors in rodents and epidemiological evidence of an increased risk of similar tumors among vinyl chloride-exposed workers (U.S. EPA, 1985).
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