Needs for biological risk assessment in interspecies extrapolation.

Abstract

This paper suggests that not all chemicals shown to be carcinogenic in animals may exert this effect in humans exposed to much lower amounts of the chemical. It is possible that agents which differ in their effects in humans and animals may be identified through the application of Biological Risk Assessment to the experimental results. Chemicals tested in systems in which untreated animals develop high background yields of tumors or in which high-dose toxicity may be a critical factor in the induction of carcinogenesis are suggested as candidates requiring very careful consideration before their carcinogenicity in humans is assumed.

Predicting the Carcinogenicity of Chemicals in Humans from Rodent Bioassay Data

“…However, we believe that it is already clear that a study of the interspecies correlation factor K cannot be separated from a study of the relationship between toxicity and carcinogenic potency, or ofthe relationship between carcinogenic potency and activities at the cellular level (including cytotoxicity and genotoxicity). We agree with Clayson (152,153) and others who declare the necessity to improve the carcinogen risk assessment process by increasing and utilizing our understanding of the biological mechanisms of carcinogenesis.…”

Large Animal Toxicology: Introduction and General Principles

“…The disadvantages are that group sizes are smaller (the implications of which are addressed in the separate paper on statistics in this set), that the groups of animals are much more heterogeneous (less inbred, which may also be an advantage in some cases), and that more test material is needed (due to the greater individual animal sizes and weights-see Tables 2 and 3). There are a number of ways to extrapolate or scale doses of biologically active agents between species (Anderson and Weber 1975;Angervall and Carlstrom 1963;Benedict 1938;Borzelleca 1984;Boxenbaum 1982;Calabese 1983;Clayson 1988;Davidson, Parker, and Beliles 1986;Gad and Chengelis, 1992). More space is also needed for housing these animals (Animal Welfare Act 1987), causing them to demand increased prices at contract facilities (National Institutes of Health 1985).…”