SHORT‐TERM TESTS IN THE FRAMEWORK OF CARCINOGEN RISK ASSESSMENT TO MAN

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Abstract
Short-term tests designed to detect possible carcinogenicity have been extensively refined during the last years. Presently, many more or less simple and convenient systems are available to detect mutations, chromosome effects, DNA damage, and malignant transformation. Although their relevance to carcinogenicity is often reasonably good, inconsistencies in the pattern of response indicate that their role as predictive indicators of carcinogenicity is still uncertain. The use of short-term tests in carcinogen risk assessment does seem feasible. These tests, however, should not be the only characteristic taken into consideration in such a risk assessment. Other characteristics such as chemical structure, biotransformation, and pharmacokinetics, qualitative and quantitative physiological and/or morphological effects, species, strain, and organ specificity, dose-response relation, and information on human studies, if available, are of importance too. Current knowledge does not permit a rigid classification of carcinogens, but does warrant a subclassification into genotoxic and nongenotoxic compounds. Whereas for genotoxic compounds a real threshold cannot be expected on a theoretical basis, the existence of a threshold may well be expected for nongenotoxic compounds. In conjunction with other characteristics it may then be decided whether a genotoxic or nongenotoxic compound may be or may not be permitted in the human environment. In this evaluation process it is anticipated that for genotoxic compounds other extrapolation systems should be used, as compared to nongenotoxic compounds, where in fact a conventional food toxicology safety factor may be applied. Short-term tests are very important in the subclassification with respect to genotoxicity and seem to be of value for the detection of promoter activity as well.