PESTICIDES - AN IMPORTANT BUT UNDERUSED MODEL FOR THE ENVIRONMENTAL-HEALTH SCIENCES

Pesticides are high-volume, widely used, environmental chemicals and t here is continuous debate concerning their possible role in many chron ic human health effects. Because of their known structures, known rate s of application, and the presence of a large occupationally exposed p opulation, they are not only important in their own right but are idea l models for the effects of environmental chemicals on the population in general. For reasons that are not always clear, this potential has not been realized. These exposed populations represent an underused as set in the study of the human health effects of environmental contamin ants. Chronic effects thought to involve pesticides include carcinogen esis, neurotoxicity, and reproductive and development effects. In this paper we attempt to summarize this concern and, relying to a large ex tent on studies in our own laboratory, to indicate the importance and present status of studies of the mammalian metabolism of pesticides an d indicate the need for further use of this model. Aspects considered include the role of pesticides as substrates for xenobiotic-metabolizi ng enzymes such as cytochrome P450 and the flavin-containing monooxyge nase and their role as inducers or inhibitors of metabolic enzymes. Th e interaction of pesticides with complex multienzyme pathways, the rol e of biological characteristics, particularly gender, in pesticide met abolism, and the special role of pesticides at portals of entry and in target tissues are also considered.