Developmental toxicity of nine selected compounds following prenatal exposure in the mouse: naphthalene, p-nitrophenol, sodium selenite, dimethyl phthalate, ethylenethiourea, and four glycol ether derivatives.
Ethylene glycol dimethyl ether (EGdiME), diethylene glycol dimethyl ether (diEGdiME), triethylene glycol dimethyl ether (triEGdiME), diethylene glycol diethyl ether (diEGdiEE), ethylenethiourea (ETU), sodium selenite (SS), dimethyl phthalate (DMP), naphthalene (NAP), or p-nitrophenol (PNP) were administered by gavage for eight consecutive days to female CD-1 mice. Weight loss was insensitive as an index of sublethal adult toxicity and was inadequate for determining a maximum tolerated dose. LD50 values indicate that SS, NAP, and PNP were more toxic (8.4, 353.6, and 625.7 mg/kg, respectively) than the polyglycol ethers, ETU, and DMP (LD50 values ranged from 2525.8 to 6281.9 mg/kg). Each of the compounds was administered on d 7 through 14 to pregnant animals at a single dose estimated to be at or just below the threshold of adult lethality. In such a reproductive study, each of the compounds could be categorized on the basis of the pattern of maternal lethality and fetotoxicity which it produced. The number of dams with complete resorptions was significantly increased after administration of ETU, and no mice in the EGdiME-, diEGdiME-, or triEGdiME-treated groups delivered any viable offspring. Maternal lethality was significant in the EGdiME, triEGdiME, PNP, and NAP groups. There was a slight reduction in the average number of live pups per litter in the diEGdiEE- and PNP-treated groups and a significant reduction in the NAP group. The number dead per litter was increased with diEGdiEE. SS and DMP had no effect on maternal or fetal survival at the doses administered. Individual pup weight at d 1 postpartum was only significantly reduced by diEGdiEE, and no gross congenital abnormalities were detected in neonates from any treatment group. These results provide guidelines for the subsequent toxicity testing of these chemicals.
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001724:Birth Weight; D001835:Body Weight; D004353:Drug Evaluation, Preclinical; D005026:Ethylene Glycols / Q000633:toxicity*; D005031:Ethylenethiourea / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects*; D007093:Imidazoles / Q000633:toxicity*; D007928:Lethal Dose 50; D008431:Maternal-Fetal Exchange; D051379:Mice; D009281:Naphthalenes / Q000633:toxicity*; D009596:Nitrophenols / Q000633:toxicity*; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D012098:Reproduction / Q000187:drug effects*; D020887:Selenious Acid; D012643:Selenium / Q000633:toxicity*
D005026:Ethylene Glycols; D007093:Imidazoles; D009281:Naphthalenes; D009596:Nitrophenols; D010795:Phthalic Acids; C024629:dimethyl phthalate; C031721:naphthalene; D005031:Ethylenethiourea; D020887:Selenious Acid; D012643:Selenium; C024836:4-nitrophenol