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...

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Bibliographic Details
Published in:Pharmacology & therapeutics (Oxford) 1996, Vol.71 (1), p.7-28
Main Authors: Whysner, John, Conaway, C.Clifford, Verna, Lynne, Williams, Gary M.
Format: Article
Language:English
Subjects:
Angiosarcoma
Animals
Carcinogenicity Tests
Carcinogens - toxicity
Cricetinae
DNA - drug effects
DNA - metabolism
DNA adducts
genotoxicity
Humans
Mice
Neoplasms - chemically induced
Rats
Risk Assessment
Rodentia
Species Specificity
vinyl chloride
Vinyl Chloride - toxicity
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Summary: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.
ISSN:0163-7258
1879-016X
DOI:10.1016/0163-7258(96)00060-5