Uncertainty in cancer risk estimates.
Several existing databases compiled by Gold et al. for carcinogenesis bioassays are examined to obtain estimates of the reproducibility of cancer rates across experiments, strains, and rodent species. A measure of carcinogenic potency is given by the TD50 (daily dose that causes a tumor type in 50% of the exposed animals that otherwise would not develop the tumor in a standard lifetime). The lognormal distribution can be used to model the uncertainty of the estimates of potency (TD50) and the ratio of TD50's between two species. For near-replicate bioassays, approximately 95% of the TD50's are estimated to be within a factor of 4 of the mean. Between strains, about 95% of the TD50's are estimated to be within a factor of 11 of their mean, and the pure genetic component of variability is accounted for by a factor of 6.8. Between rats and mice, about 95% of the TD50's are estimated to be within a factor of 32 of the mean, while between humans and experimental animals the factor is 110 for 20 chemicals reported by Allen et al. The common practice of basing cancer risk estimates on the most sensitive rodent species-strain-sex and using interspecies dose scaling based on body surface area appears to overestimate cancer rates for these 20 human carcinogens by about one order of magnitude on the average.(ABSTRACT TRUNCATED AT 250 WORDS)
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
D W
DW
Gaylor
J J
JJ
Chen
D M
DM
Sheehan
D000818:Animals; D015197:Carcinogenicity Tests / Q000706:statistics & numerical data*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D051381:Rats; D012307:Risk Factors; D013045:Species Specificity
D002273:Carcinogens