Toxicity testing: some principles and some pitfalls in histopathological evaluation.

1. The aims of toxicity tests vary according to the use or proposed use of the substance to be tested. 2. More knowledge about physiological and homeostatic control mechanisms will be needed before one can reliably distinguish between adaptive responses and toxic effects. 3. More attention needs to be paid to quantifying the intrinsic sensitivity of certain methods used by toxicologists, particularly those with histopathological end-points. 4. Much more attention should be paid than at present to seemingly beneficial effects of exposure to test materials since an understanding of these may throw useful light on mechanisms underlying toxic effects. 5. Overfeeding gives rise to a wide variety of effects which impact in a major way on both general toxicity and oncogenicity end-points. 6. Extrapolation to man usually involves the use of tumour incidence data to predict cancer mortality in humans. Important new data on the effect of overfeeding on cancer incidence in rats aged two years are presented. 7. Complacency with regard to the relevance of rodent models for predicting toxicity for man is unwarranted.