A MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING .2. DEVELOPMENTAL TOXICITY

As part of the validation of an integrated bioassay for systemic toxic ity, neurotoxicity, and developmental toxicity, we evaluated the effec ts of four pesticides, four chlorinated solvents, and two other indust rial chemicals in Fischer 344 rats. The pesticides included carbaryl, triadimefon, chlordane, and heptachlor; the solvents included dichloro methane (DCM), carbon tetrachloride, trichloroethylene (TCE) and tetra chloroethylene (perchloroethylene, PER); and the industrial chemicals were di(2-ethylhexyl)phthalate (DEHP) and phenol. In the developmental toxicity studies, timed-pregnant rats were treated by gavage with veh icle or 1 of 2 dose levels of each compound on gestation d 6-19. The d arns were allowed to deliver and their litters were examined on postna tal d 1, 3, and 6. Litter weights were determined on postnatal d 1 and 6. Implants were also counted to .determine prenatal loss. Maternal t oxicity was evidenced by dose-related alterations in weight gain for a ll 10 compounds. Clinical signs of maternal toxicity were present for all chemicals except chlordane and heptachlor. DEHP exposure resulted in the most pronounced developmental toxicity (high levels of pre- and postnatal mortality), whereas chlordane induced extensive postnatal l oss. Of the solvents, only DCM did not cause a high incidence of full- litter resorption. Phenol, heptachlor, triadimefon, and carbaryl showe d only slight potential for developmental toxicity. Malformations sugg estive of teratogenicity included kinked tail (phenol), microphthalmia (TCE, PER, DEHP), and cleft palate with renal agenesis (DEHP). Althou gh several findings (eye defects caused by TCE and PER, full-litter re sorption and delayed parturition caused by PER, and delayed parturitio n/dystocia associated with triadimefon) have not been previously repor ted, the results are generally consistent with previous reports and hi ghlight the importance and relative ease of incorporation of develop m ental evaluations into a multidisciplinary screening battery.