New issues in cancer risk assessment.
When a nonlinear dose-response at low doses can be justified, an acceptable daily intake for a carcinogen can be obtained by dividing a benchmark dose, associated with a low incidence of tumors in animals, by uncertainty factors to account for animal-to-human extrapolation, human variability, and risk reduction from a low observed adverse-effect level. This approach can utilize mechanistic information to justify smaller uncertainty factors than typical default values of 10. If a nonlinear dose-response cannot be justified, traditional linear extrapolation from the benchmark dose to zero sometimes gives similar results. This suggests a unified risk-assessment procedure based on uncertainty factors. The issue of cross-species extrapolation based on the risk relative to background risks, rather than excess risk, is examined. The relative risk approach reduces the estimates of cancer risk in humans based on common rodent tumors, such as the liver in some strains of mice.
Gaylor
D W
DW
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
D000818:Animals; D015197:Carcinogenicity Tests; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000453:epidemiology; D018570:Risk Assessment / Q000379:methods* / Q000639:trends; D013045:Species Specificity