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Uncertainty in cancer risk estimates
D W Gaylor1, J J Chen, D M Sheehan
1National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079.
Summary
Cancer potency (TD50) estimates show significant variability across experiments, strains, and species. This variability suggests current methods for human cancer risk assessment may overestimate risks from experimental animal data.
Area of Science:
- Toxicology
- Carcinogenesis
- Risk Assessment
Background:
- Existing databases on carcinogenesis bioassays provide data for evaluating cancer rate reproducibility.
- Carcinogenic potency is quantified using the TD50, the daily dose causing tumors in 50% of animals.
Purpose of the Study:
- To estimate the reproducibility of cancer rates across different experimental conditions.
- To assess the variability in carcinogenic potency (TD50) estimates.
Main Methods:
- Analysis of existing carcinogenesis bioassay databases (Gold et al.).
- Modeling uncertainty in TD50 estimates and interspecies ratios using lognormal distribution.
- Calculation of factors representing variability between near-replicate bioassays, strains, and species.
Main Results:
- Near-replicate bioassays show TD50 variability within a factor of 4 (95%).
- Inter-strain variability in TD50 is within a factor of 11 (95%), with a genetic component of 6.8.
- Inter-species variability: factor of 32 between rats and mice, and 110 between humans and experimental animals for 20 chemicals.
Conclusions:
- Significant variability exists in cancer potency estimates across experimental settings and species.
- Current practices of using sensitive rodent data and body surface area scaling may overestimate human cancer risk by approximately one order of magnitude.