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for carcinogenicity in human epidemiology studies, vinyl chloride isconsidered to best fit the weight-of-evidence characterization Category A,according to current EPA Risk Assessment Guidelines (USEPA, 1986). Agentsclassified into this category are considered known human carcinogens. Thisclassification is supported by positive evidence for carcinogenicity inanimal bioassays including several species and strains, and strongevidence for genotoxicity. Under the Proposed Guidelines for CarcinogenRisk Assessment (USEPA, 1996), it is concluded that vinyl chloride is aknown human carcinogen by the inhalation route of exposure, based on humanepidemiological data, and by analogy the oral route because of positiveanimal bioassay data as well as pharmacokinetic data allowing doseextrapolation across routes. Vinyl chloride is also considered highlylikely to be carcinogenic by the dermal route because it is well absorbedand acts systemically. The weight of evidence for human carcinogenicity isbased on 1) consistent epidemiologic evidence of a causal associationbetween occupational exposure to vinyl chloride via inhalation and thedevelopment of angiosarcoma, an extremely rare tumor; 2) consistentevidence of carcinogenicity in rats, mice, and hamsters by both the oraland inhalation routes; 3) mutagenicity and DNA adduct formation by vinylchloride and its metabolites in numerous in vivo and in vitro testsystems; and 4) efficient vinyl chloride absorption via all routes ofexposure tested, followed by rapid distribution throughout the body. Inlight of the very high percentage of angiosarcoma worldwide that areassociated with vinyl chloride exposure, the evidence for /its/carcinogenicity is considered strong. The International Agency forResearch on Cancer (IARC) has also concluded that sufficient evidence forcarcinogenicity in humans exists and has placed vinyl chloride incarcinogenicity category 1, that is, carcinogenic to humans. Vinylchloride carcinogenicity occurs via a genotoxic pathway and is understoodin some detail. Vinyl chloride is metabolized to a reactive metabolite,probably chloroethylene oxide, which is believed to be the ultimatecarcinogenic metabolite of vinyl chloride. The reactive metabolite thenbinds to DNA, forming DNA adducts that, if not repaired, ultimately leadto mutations and tumor formation. Therefore, a linear extrapolation wasused in the dose-response assessment. Because of uncertainty regardingexposure levels in the occupationally exposed cohorts, recommended potencyestimates are based on animal bioassay data. HUMAN CARCINOGENICITY DATA:Sufficient. ANIMAL CARCINOGENICITY DATA: Sufficient. [U.S. EnvironmentalProtection Agency's Integrated Risk Information System (IRIS) on VinylChloride (75-01-4) Available from: http://www.epa.gov/ngispgm3/iris on theSubstance File List as of August 8, 2000]**PEER REVIEWED**NON-HUMAN TOXICITY EXCERPTS:... 26 MALE AR/IRE WISTAR RATS ... EXPOSED TO ... 3% VOL/VOL ...COMMERCIAL-GRADE VINYL CHLORIDE MONOMER ... (99% PURE) 4 HR/DAY ON 5DAY/WK FOR 12 MO. ... SKIN TUMORS DEVELOPED IN SUBMAXILLARY PAROTID REGION... (14 EPIDERMOID CARCINOMAS, 2 MUCOEPIDERMOID CARCINOMAS, 1 PAPILLOMA)... LUNG TUMORS DEVELOPED IN 7 RATS AND OSTEOCHONDROMAS IN 5. NO TUMORS... IN 25 UNTREATED CONTROLS ... /SKIN TUMORS WERE ZYMBAL GLAND TUMORS ANDLUNG TUMORS WERE METASTASIS FROM THESE/. [IARC. Monographs on theEvaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: WorldHealth Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).V19 386 (1979)]**PEER REVIEWED**GROUPS OF MALE AND FEMALE 11 WEEK OLD SWISS MICE WERE EXPOSED TOCONCENTRATIONS OF 50 TO 10,000 PPM VINYL CHLORIDE IN AIR FOR 4 HOURS/DAYON 5 DAYS/WEEK FOR 30 WEEKS. AT 81 WEEKS, 70% (OF THE 10,000 PPM GROUP)