Freedman, D.A., Gold, L.S., and Slone, T.H. How tautological are inter-species correlations of carcinogenic potency? Risk Anal. 13: 265-272 (1993).
Crouch and Wilson demonstrated a strong correlation between carcinogenic potencies for rats and mice in NCI/NTP bioassays, supporting the extrapolation from rodents to humans. Bernstein et al., however, show that the observed correlation is mainly a statistical artifact of bioassay design-- and the selection by Crouch and Wilson of statistically significant potencies. Indeed, if the potency is statistically significant and not all animals get tumors, then the potency is restricted to a narrow range around 1/MTD. The MTDs for rats and mice are highly correlated and span a wide range. The potency correlation follows. Crouch, Wilson & Zeise respond with permutation tests to show that the potency correlation is not artifactual.
This paper reviews the arguments and presents some new data which confirm results in Bernstein et al. We develop statistical models in which the potency is purely tautological. We compare the models and the data, and suggest that at least 80% of the correlation is tautological. There may be some basis for extrapolation from rodents to humans, but the interspecies correlation of potencies in bioassays does not say much about the validity of that extrapolation.
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Last updated: November 10, 1995