A MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING .3. NEUROBEHAVIORAL TOXICITY

The neurobehavioral effects of 10 known toxicants were examined as par t of a multidisciplinary screening battery. The toxicants included car baryl (CAR), triadimefon (TDM), heptachlor (HEP), chlordane (CDN) diet hylhexyl phthalate (DEHP), carbon tetrachloride (CCl4) phenol, trichlo roethylene (TCE), tetrachloroethylene (PER or perchlorethylene), and d ichloromethane (DCM or methylene chloride). A functional observational battery and motor activity measurements were conducted before exposur e, at specified times after an acute exposure, and during and after 14 -d exposure. Severity scoring analysis was used to generate profiles o f effect. The pesticides, CAR, TDM, HEP, and CDN, displayed the most a cute neurotoxicity and were active at lower proportions of their respe ctive acute LD50 values than were the solvents or the industrial chemi cals. Although CAR and TDM showed little or no neurobehavioral effects with repealed dosing, cumulative neurotoxicity and lethality were evi dent with HEP and; CDN. Phenol produced acute convulsive effects, and the most prominent finding with repeated exposure was lethality. DEHP displayed no neurobehavioral toxicity. The organic solvents, TCE, PER, CCl4, and DCM, produced various degrees of general nervous system dep ression following acute administration of high dose levels. Repeated d osing produced little or no effect with TCE or PER, marked physiologic al changes with CCl4, and cumulative toxicity and lethality with DCM. Some results of these studies were unexpected and should provide impet us for further research. Overall, these findings illustrate the utilit y of these screening methods.