A MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING .4. COMPARISON OF RESULTS

Toxicity data collected under standardized test conditions may be of t he utmost importance in health risk assessment, in which human exposur e limits are often derived from laboratory experiments. A standardized approach to data collection is also important for evaluating the sens itivity and specificity of test methods used to determine toxic potent ial. Several experiments were undertaken to determine the effects of c hemical exposures using a multidisciplinary screening battery, which i ncluded rests for systemic, neurological and developmental toxicity. T he effects of 1- and 14-d exposures to 10 chemicals on systemic and ne urological indices of toxicity were determined in female F344 rats usi ng standardized test batteries. Parallel experiments determined chemic al effects on prenatal and postnatal development following exposure of the darns for 14 d. The chemicals included four pesticides (carbaryl, triadimefon, chlordane, and heptachlor), four solvents (trichloroethy lene, tetrachloroethylene, carbon tetrachloride, and dichloromethane), and two industrial compounds (phenol and diethylhexyl phthalate). The results showed that the chemicals produced markedly different qualita tive patterns of effect on systemic, neurological, and developmental i ndices of toxicity. Differences in the pattern of systemic and neurolo gical effects were also obtained that depended on dosing duration. Qua ntitative analyses indicated that the highest ineffective dose as well as the lowest effective dose could vary by as much as two orders of m agnitude across the different indices of toxicity. These results clear ly show that a test battery focused on a single endpoint of toxicity c annot be used to accurately predict either qualitatively or quantitati vely a chemical's systemic, neurological, and developmental toxicity p rofile.