SPECIFICITY AND DOSIMETRY OF TOXICOLOGIC RESPONSES

Toxicology has two goals. The first is to identify and characterize th e adverse effects that can be produced in biological systems by exposu re to chemicals and the second is to use this information to predict t he type and severity of responses in other species and exposure situat ions. The tools that the toxicologist uses to detect and describe the adverse effects of chemical exposure include the traditional acute, su bchronic, and chronic studies in animals plus a variety of special stu dies designed to demonstrate specific organ damage, reproductive and t eratogenic effects, neurotoxicity, immunotoxicity, genotoxicity, and o ther responses. These are often supplemented with studies of the kinet ics and the mechanism of action and more recently with studies designe d to elucidate the molecular basis for cancer and other effects. These studies together with the information on exposure provide the basis f or subsequent toxicologic predictions. Although general effects such a s weight loss and mortality are included in toxicity protocols, most o f the toxicology tests are related to specific end-organ toxicity or t o mechanism or behavioral studies. We do not have animal protocols to study individually the subjective symptoms described for multiple chem ical sensitivity, such as depression, fatigue, headache, and memory lo ss, and our tests lack sufficient specificity to evaluate a syndrome w hich is composed primarily of such symptoms. Since all chemicals can p roduce 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. Multi ple chemical sensitivity does not appear to consistently involve speci fic chemicals or specific adverse effects and the effects observed are reported to lack evidence of a threshold and to occur at extremely lo w levels. It is difficult to include these parameters in any reasonabl e toxicologic prediction relating cause and response in multiple chemi cal sensitivity or similar conditions. (C) 1996 Academic Press, Inc.