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MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING: II. DEVELOPMENTAL TOXICITY
Citation:
Narotksy, M. AND R. Kavlock. MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING: II. DEVELOPMENTAL TOXICITY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/383.
Description:
As part of the validation of an integrated bioassay for systemic, neuro-, and developmental toxicity, we evaluated the responses of Fischer-344 rats to four pesticides, four chlorinated solvents, and two other industrial chemicals. he pesticides included carbaryl, triadimefon, chlordane, and heptachlor; the solvents were dichloromethane (DCM), carbon tetrachloride, trichloroethylene (TCE), and tetrachloroethylene (TetCE); and the remaining agents were di(2-ethylhexyl) phthalate (DEHP) and phenol. n the developmental toxicity assays, timed-pregnant rats were gavaged at control and two dose levels on gestation days 6 through 19. he dams were! allowed to deliver and their litters were examined on postnatal days 1, 3, and 6. Litter weights were determined on days 1 and 6. Implants were counted to@determine prenatal loss. aternal toxicity was evidenced by dose-related alterations in weight gain for all ten compounds. linical signs of maternal toxicity were present for all chemicals except chlordane and heptachlor. EHP exposure resulted in the most pronounced developmental toxicity (high levels of pre- and postnatal mortality), whereas chlordane induced extensive postnatal loss. f the solvents, only DCM did not cause a high incidence of full-litter resorption. henol, heptachlor, triadimefon, and carbaryl showed only slight potential for developmental toxicity. alformations suggestive of teratogenicity included kinked tail (phenol), microphthalmia (TCE, TetCE, DEHP), and cleft palate with renal agenesis (DEHP). hese results are generally consistent with published data and highlight the importance of relative ease of incorporation of developmental evaluations in an integrated battery of toxicity assays.