Mathematical models in quantitative assessment of carcinogenic risk.
Regulatory guidelines have specified default assumptions for the calculation of upper bounds on potential carcinogenic risk. These default "science policy" assumptions are used in the absence of more appropriate biological information, but can, in theory, be overridden by compound-specific data. As a screening tool, the standard LMS procedure provides a useful yardstick for regulators to compare hazard potential across compounds and across exposure scenarios. This standard methodology does not estimate actual risk, however. When specific compounds are being considered for detailed evaluation, methodology for more accurately estimating the true risk is often available. Pharmacokinetic models can be used to more accurately define the high-dose to low-dose extrapolation as well as to provide insight into across route and across species extrapolations. "More central" estimates of the upper bound on risk can be derived, or decision analysis techniques can be used to define the probability distribution of risk estimates, as the assumptions are changed. These data give the risk manager more information as to the relevance of the upper bound, and should be presented in any risk estimate to provide a richer demonstration as to the true risk.
Park
C N
CN
Health & Environmental Sciences, Dow Chemical Company, Midland, Michigan 48674.
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics; D006801:Humans; D008452:Maximum Allowable Concentration; D008954:Models, Biological; D015233:Models, Statistical; D012306:Risk; D013997:Time Factors; D014481:United States; D014484:United States Environmental Protection Agency
D002274:Carcinogens, Environmental