Multiple end point procedure to evaluate risk from pesticides.

Because of the potential environmental impact of pesticides and the large population potentially exposed, the effects of chronic exposure to pesticides need to be determined. Mutagenicity studies have been used to identify specific agents as potential carcinogens or other human health hazards. However, short-term tests are only theoretically correlated to carcinogenesis because their end points can measure only the genotoxic potential of chemicals, i.e., their activities as initiating agents in multistep carcinogenesis. The objective of our research presented here is to provide a comprehensive examination of the mechanism of toxicity of a series of pesticides. These are substances for which toxicity, at both the genetic and metabolic level, has not been adequately described. Preliminary results on a broad series of compounds belonging to different biological classes (herbicide, insecticide, fungicide) seem to indicate that pesticides are toxic but are poor initiating agents, as shown by negative or weak positive results on different genetic end points (gene mutations, DNA effects, and chromosome aberrations in vitro and in vivo). Immunochemical and biochemical studies, however, seem to indicate the cocarcinogenic and promoting potential of these chemicals. As an example, the genotoxic and biochemical effects induced by Fenarimol (a fungicide) are discussed. The results reported stress the importance of identifying chemicals that act at different levels of the multistep carcinogenesis process to ascertain the risk associated with exposure.