Mg. Narotsky et Rj. Kavlock, A MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING .2. DEVELOPMENTAL TOXICITY, Journal of toxicology and environmental health, 45(2), 1995, pp. 145-171
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.