Incorporation of biological information in cancer risk assessment: example--vinyl chloride.
Vinyl chloride (VC) is used as an example to demonstrate how biological information can be incorporated into quantitative risk assessment. The information included is the pharmacokinetics of VC in animals and humans and the data-generated hypothesis that VC primarily affects the initiation stage of the multistage carcinogenesis. The emphasis in this paper is on the improvement of risk assessment methodology rather than the risk assessment of VC per se. Sufficient data are available to construct physiologically-based pharmacokinetic models for both animals and humans. These models are used to calculate the metabolized dose corresponding to exposure scenarios in animals and in humans. On the basis of the data on liver angiosarcomas and carcinomas in rats, the cancer risk per unit of metabolized dose is comparable, irrespective of routes (oral or inhalation) of exposure. The tumor response from an intermittent/partial lifetime exposure is shown to be consistent with that from a lifetime exposure when VC is assumed to affect the first (initiation) stage of the multistage carcinogenic process. Furthermore, the risk estimates calculated on the basis of animal data are shown to be consistent with the human experience.
Chen
C W
CW
U.S. Environmental Protection Agency, Washington, D.C. 20460.
Blancato
J N
JN
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D015197:Carcinogenicity Tests; D003627:Data Interpretation, Statistical; D004781:Environmental Exposure; D006394:Hemangiosarcoma / Q000139:chemically induced; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced; D008253:Macaca mulatta; D008722:Methods; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012307:Risk Factors; D014752:Vinyl Chloride / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics
D014752:Vinyl Chloride