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Interspecies extrapolation in carcinogenesis: prediction between rats and mice
L S Gold1, L Bernstein, R Magaw
1Biology and Medicine Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
Environmental Health Perspectives
|May 1, 1989
Summary
Predicting rodent carcinogenicity between rats and mice shows moderate agreement, with 76% overall concordance. Factors like chemical class and mutagenicity influence prediction accuracy for cancer testing.
Area of Science:
- Toxicology
- Carcinogenesis Research
- Comparative Oncology
Background:
- Interspecies extrapolation of carcinogenesis data is crucial for risk assessment.
- The Carcinogenic Potency Database (CPDB) contains extensive data on chemical carcinogenicity in rodents.
Purpose of the Study:
- To evaluate the accuracy of predicting carcinogenicity from rats to mice and vice versa.
- To identify factors influencing interspecies concordance in rodent cancer bioassays.
Main Methods:
- Analysis of 3500 cancer tests from the CPDB involving 955 compounds tested in rats and/or mice.
- Calculation of concordance rates for carcinogenicity between species.
- Investigation of chemical class, mutagenicity, and toxicity dose as predictive factors.
Main Results:
- Overall concordance between rat and mouse carcinogenicity predictions is 76%.
- 76% of rat carcinogens were positive in mice, and 70% of mouse carcinogens were positive in rats for chemicals tested in both species.
- Prediction accuracy improved for mutagens and chemicals toxic at lower doses.
Conclusions:
- Rodent carcinogenicity data show significant, though not perfect, concordance between rats and mice.
- Chemical properties and toxicological profiles, rather than bioassay limitations, influence interspecies prediction accuracy.
- Most common target organs are generally predictive of carcinogenicity in the other species, with exceptions like the rat urinary bladder and mouse liver.