Toxicology of environmental agents: a blend of applied and basic research.

The purpose of this paper is to present some of the more carefully studied aspects of the preclinical toxicology of antineo-plastic agents, and apply these findings (with certain obvious cautions) to the area of environmental toxicology. Most of the studies to be described here are the result of applied toxicologic studies performed in support of the clinical introduction of new chemicals in the treatment of cancer. These considerations are somewhat superficial and restricted due to the fact that many questions regarding the chemical mechanisms of action, and the absorption, distribution, excretion, and metabolism of these drugs are unanswered. However, as valuable as this basic pharma-cologic information will someday be to the complete understanding of therapeutic and toxic actions and effects, waiting is not a realistic option. The cancer problem is now. Thus, we are faced with the necessity of defining problems and taking reasonable actions based on the currently available data base; while, at the same time supporting, appreciating, and being careful to nurture more basic studies. The ideal situation is obviously a blend of applied and basic research. A similar situation most likely exists in the area of Environmental Toxicology. Preclinical toxicology has been defined (1) as an area of Economic Toxicology primarily concerned with the development of drugs. Anticancer agents, almost by design, are extremely toxic and potent, nonspecific, and have a very low therapeutic index. The major toxic effects of immediate concern are usually acute or subacute effects, and because of the seriousness of the disease being treated, probable long-term toxic hazards are reluctantly accepted. The physicians using these drugs are well aware of their toxic potential, and clinical support facilities are excellent. Considering these aspects it appears that the experimental (preclinical) definition of the toxicity of anticancer drugs is probably the most straightforward of any clinically useful drug. The toxicologist concerned with environmental agents has almost the opposite situation. Environmental toxicology is concerned primarily with the biological effects of chemicals that are encountered by man either incidentally because they are in the atmosphere, or by contact during occupational or recreational activities, or by inges-tion of food additives. When air is the source of chemicals, it is obvious that exposure is unavoidable, whereas exposure to chemicals used in industry is determined by industrial practices. With the increasing rate of synthesis and the growing commercial use of chemicals, it seems that no one is entirely free of exposure …