Specificity and dosimetry of toxicologic responses

Toxicology has two goals. The first is to identify and characterize the adverse effects that can be produced in biological systems by exposure to chemicals and the second is to use this information to predict the type and severity of responses in other species and exposure situations. The tools that the toxicologist uses to detect and describe the adverse effects of chemical exposure include the traditional acute, subchronic, and chronic studies in animals plus a variety of special studies designed to demonstrate specific organ damage, reproductive and teratogenic effects, neurotoxicity, immunotoxicity, genotoxicity, and other responses. These are often supplemented with studies of the kinetics and the mechanism of action and more recently with studies designed to elucidate the molecular basis for cancer and other effects. Theses studies together with the information on exposure provide the basis for subsequent toxicologic predictions. Although general effects such as weight loss and mortality are included in toxicity protocols, most of the toxicology tests are related to specific end-organ toxicity or to mechanism or behavioral studies. We do not have animal protocols to study individually the subjective symptoms described for multiple chemical sensitivity, such as depression, fatigue, headache, and memory loss, and our tests lack sufficient specificity to evaluate a syndrome which is composed primarily of such symptoms. Since all chemicals can produce adverse effects under some conditions of exposure, toxicologic predictions are most useful when they specify both the type of adverse effect anticipated and the dose required to produce the effect. Multiple chemical sensitivity does not appear to consistently involve specific chemicals or specific adverse effects and the effects observed are reported to lack evidence of a threshold and to occur at extremely low levels. It is difficult to include these parameters in any reasonable toxicologic prediction relating cause and response in multiple chemical sensitivity or similar conditions.