Screening procedures for evaluating the potential carcinogenicity of food-packaging chemicals

Abstract

The testing of chemicals for possible carcinogenic effects has as its aim the detection of agents with the potential to cause cancer in humans. In the early days of cancer research, the only way to test for potential carcinogens was by long-term studies, mostly in rodents. It still remains that the reliable induction of cancer in animals, according to generally accepted criteria (International Agency for Research on Cancer, 1986), defines a chemical as a carcinogen. Nevertheless, rapid and more efficient approaches to carcinogenic hazard identification (Weisburger and Williams, 1981) have begun to supplant chronic bioassay (International Agency for Research on Cancer, 1986). Moreover, the current knowledge that chemical carcinogens exert their effects through varied modes of action (Williams and Weisburger, 1986), necessitates mechanistic studies for eventual assessment of potential human hazard. Of prime importance, evidence must be developed relative to DNA reactivity or epigenetic effects in order to enable distinction between carcinogens of these two types (Table 1). A mechanism-based to chemical evaluation is the point approach (Weisburger and Williams, 1978), which provides a framework within which the data base required for risk extrapolation can be obtained in a systematic manner. The decision point is appropriate for the evaluation of any chemical (Weisburger and Williams, 1984), but can be customized for specific types of chemicals, e.g., pharmaceuticals (Williams and Weisburger, 1985). This paper presents strategies for safety assessment of candidate food-packaging chemicals. The decision point is especially appropriate for these agents whose large numbers make chronic bioassay impractical. In the decision point approach, a series of data acquisition steps is followed (Table 2) and at the end of each phase a critical evaluation of the information obtained and its significance in relation to the testing objective is performed. A decision is made as to whether the data generated are sufficient to reach a definitive conclusion on the potential hazard of the chemical. The information developed in the decision point includes all types of experimental data that are currently secured in testing for potential carcinogens (see Milman and Weisburger, 1985). Therefore, the provides a mechanism-oriented framework for a comprehensive analysis of