Contribution of toxicology towards risk assessment of carcinogens

Abstract

In the last decade many tests have been designed to detect possible carcinogenicity of compounds. Presently, many more or less simple and convenient systems are available to detect mutations, effects on chromosomes, DNA binding and damage and malignant transformation. These systems, which have been extensively refined during the last years, often show reasonably good relevance to carcinogenicity. Although inconsistencies in the patterns of response do indicate that their role as predictive indicators of carcinogenicity remains still uncertain, the use of such short-term tests in carcinogen risk assessment does seem feasible.

Factors other than these tests should also be taken into consideration, since other characteristics like chemical structure, biotransformation, toxicokinetics, qualitative and quantitative physiological and/or morphological effects, species, strains, organ specificity, dose-response relation and information on studies in man, if available, are of importance too.

In conjunction with the results of adequately performed carcinogenicity tests in mammals, one may attempt to classify carcinogens. Current knowledge does not permit a rigid classification, but may warrant a subclassification into carcinogens acting via a genetic or a non-genetic mechanism. It is emphasized that on theoretical and practical grounds a different extrapolation system should be used for the different types of carcinogens in risk assessment procedures. Evaluations on individual compounds should be made to decide whether such genotoxic or non-genotoxic compounds should be permitted in the human environment.