Developmental toxicity screen: Results of rat studies with diethylhexyl phthalate and ethylene glycol monomethyl ether

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Abstract
The purpose of these investigations was to develop a protocol for an in vivo developmental toxicity screen (DETS) that would provide sufficient data to determine whether to 1) do a full developmental toxicity evaluation without additional range‐finding studies, or, depending on the results, to 2) do no further testing of a chemical. In order to evaluate this screen, we compared results obtained by using the DETS protocol with results of previously conducted developmental toxicity evaluations of diethylhexyl phthalate (DEHP) and ethylene glycol monomethylether (EGME). Five groups (n ± 17) of F344 rats were treated on days 6–15 of gestation by dosed feed (DEHP levels = 0, 0.5, 1.0, 1.5, 2.0%) or gavage (EGME doses = 0, 12.5, 25, 50, 100 mg/kg/day). One half of the rats in these studies were killed on day 16 of gestation, and the remaining animals were allowed to deliver litters which were killed on day 4. EGME caused only a small decrease in maternal weight gain during treatment (100 mg/kg group) that was accompanied by a decrease in gravid uterine weight. The percentage of resorptions was increased in the 50 and 100 mg/kg groups. The number of live pups was decreased in the 25, 50, and 100 mg/kg groups, and litter weight and postnatal survival were decreased in the 100 mg/kg group. These results are consistent with those reported in developmental toxicity studies on EGME conducted by the inhalation and dermal routes. With DEHP, there were treatment‐related reductions in maternal body weight and weight gain. There was also a nonstatistical increase in percentage of resorptions per litter that was also observed, but at relatively high levels, in a definitive study in which F344 dams were treated on days 0–20 of gestation. The results of studies on these two chemicals compare well with published results and would have led to the selection of proper dose levels for subsequent FDA segment 2 studies.