Developmental toxicity of nine selected compounds following prenatal exposure in the mouse: naphthalene, p-nitrophenol, sodium selenite, dimethyl phthalate, ethylenethiourea.
The reproductive toxicity potential of chemicals selected by NIOSH were screened in mice. Female Cd-1-mice had maximum tolerated doses (MTD) determined for ethylene-glycol-dimethyl-ether (110714), (EGdiME), diethylene-glycol-dimethyl-ether (111966) (diEGdiME), triethylene-glycol-dimethyl-ether (112492) (triEGdiME), diethylene- glycol-diethyl-ether (112367) (diEGdiEE), ethylenethiourea (96457) (ETU), sodium-selenite (10102188), dimethyl-phthalate (131113) (DMP), naphthalene (91203) (NAP), and p-nitrophenol (100027) (PNP) by administering several dose concentrations for 8 consecutive days and recording weights, deaths, and necropsies. The dose lethal to 10 percent of the mice was the MTD. The median lethal dose (LD50) was determined. Pregnant mice received eight doses, once daily, of the chemicals based on their MTD. Maternal body weights were recorded. Pups were weighed as a litter and examined individually for gross structural abnormalities. Sodium-selenite, NAP, and PNP had LD50s of 8.4 milligrams per kilogram (mg/kg), 353.6mg/kg, and 625.7mg/kg, respectively, MTD of 7.0mg/kg, 300mg/kg, and 400mg/kg, respectively, and showed no significant effects in reproductive indices. ETU, EGdiME, diEGdiME, and triEGdiME had LD50s of 5985, 2525.8, 2978.7, and 4136.7mg/kg, respectively, and MTD of 600.0, 2000.0, 2000.0, and 3500mg/kg, respectively. These were the only compounds significantly affecting reproductive indices. No EGdiME, diEGdiME, or triEGdiME groups delivered any viable pups. DMP with an LD50 and an MTD of 6281.9mg/kg and 3500.0mg/kg, respectively, had no effect on fetal survival. Sodium-selenite and diEGdiEE moderately, but not significantly, reduced reproductive indices. Maternal lethality was significant in EGdiME, diEGdiME, PNP, and NAP groups. The authors conclude that these chemicals fall into four categories with ETU, diEGdiEE, and triEGdiME in a high priority category for further testing.