Vinyl chloride mechanistic data and risk assessment: DNA reactivity and cross-species quantitative risk extrapolation.
Vinyl chloride produced several tumor types among species. Angiosarcoma of the liver is found in all tested species, including humans with occupational exposures. Vinyl chloride is biotransformed by CYP2E1 to DNA-reactive chloroethylene oxide producing cyclic etheno adducts, which are mutagenic. The dose-response for angiosarcoma of the liver formation in rodents is supralinear, which is consistent with saturation of metabolic activation, and the tumor rate in humans at occupational exposure levels is similar to that for equivalent exposures in rodents.
Whysner
J
J
Toxicology and Risk Assessment Program, American Health Foundation, Valhalla, NY 10595-1599, USA.
Conaway
C C
CC
Verna
L
L
Williams
G M
GM
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D018570:Risk Assessment; D012377:Rodentia; D013045:Species Specificity; D014752:Vinyl Chloride / Q000633:toxicity*
D002273:Carcinogens; D004247:DNA; D014752:Vinyl Chloride