Safety evaluation concepts.

Abstract

The approach to safety evaluation is strongly influenced by the standard of safety to which one aspires. Practical considerations demand that realistic limits be set to the attainable assurances of freedom from anticipated hazard under actual conditions of use of a product. The fact is that, in the interests of consumer health, more can be expected from a flexible, intelligent, and experienced approach to safety evaluation than from efforts at conformity with a set of rigidly standardized requirements that are theoretically all-encompassing. Establishment of safety demands a wide background of information about the properties and likely uses of the product; above all, knowledge of the chemical composition of the product and its impurities, degradation products, and metabolites is essential. Lack of such information is a frequent source of errors in safety evaluation. Based on a secure foundation of this sort, a program of investigations may be designed, aimed at establishing the basic biological properties of the material. Determination of the metabolic dynamics of the principal chemical agent or agents makes possible the emergence of a clear picture of the behavior of the compound(s) in the body and paves the way for more specialized studies of long term toxicity, carcinogenicity, effects on reproduction and teratogenesis, and investigations of multitest mutagenic potential. Emphasis is laid on the problems of interpretation of results in terms of hazard to man and on the crucial contribution that experience of human exposure can make toward assuring safety-in-use. Decisions on acceptable risk are the joint responsibility of many individuals but an essential element in reaching such decisions is contributed by the depth of understanding and broad experiences of the toxicologist.