Toxicity and Carcinogenic Potency

In our recent paper,'') we called attention to some of the points raised by Wlupple and by Zeise, Crouch, and Wilson. Our interest in this subject developed as we began analyzing our database of animal carcinogenesis bioas~ays.(*~~)In our analyses, we used as a measure of carcinogenic potency, the TD,,, defined as the dose rate (in mg/kg/body wt/day) which, if administered chronically for a standard period, would halve the probability of an animal remaining tumorless. By analogy with LD,,, the TD,, is that daily dose which would induce tumors in half of the animals that would have re- mained tumor-free at zero dose. We demonstrated that the potency of a carcinogen is restncted to an approximately thirty-fold range, about the maximum dose tested in the experiment in the absence of 100% tumor incidence in treated animals. The maximally tolerated doses (MTDs) of chem- icals tested in chronic animal bioassays span a range of seven orders of magnitude, and these doses are highly correlated between rats and mice. These fact, together with the restricted range of potency about the MTD, (1) account for hgh correlations in carcinogenic potency between rats and mice, and (2) provide a statistical basis for the relationship between potency values and MTDs. One would expect to observe a similar relationship between carcinogenic potency (TD,,) and LD,,, qssuming that the acute and the chronic toxic doses are related.