Effects of diethylene glycol monomethyl ether on pregnancy and postnatal development in rats.
The effects of oral treatment of Wistar rats with diethylene glycol monomethyl ether (diEGME) were examined. In a preliminary dose-finding study with non-pregnant rats, diEGME treatment at doses up to 4,000 mg/kg/day on 11 consecutive days decreased relative weights of thymus and pituitary gland, white and red blood cell counts, hemoglobin concentrations and hematocrit levels. In pregnant rats, treatment at doses of > 3,000 mg/kg/day (over gestation days 7-17) caused total resorption of all litters. In teratology and postnatal studies, pregnant rats were treated with diEGME at doses of 0, 200, 600, and 1,800 mg/kg/day from day 7 through 17 of gestation. At 200 mg/kg, there were no adverse effects on either dams, fetuses, or neonates. At 600 mg/kg, dams were not affected, but fetal body weights were decreased, and fetal thymus and ossification were adversely affected. At 1,800 mg/kg, maternal thymus weights and food consumption were decreased, and visceral malformations of the cardiovascular system were seen in 28.0% of the fetuses. Only 6.3% of the pups delivered by dams treated with 1,800 mg/kg of diEGME survived for 4 days after birth. Thus, diEGME was teratogenic in Wistar rats, but the spectrum differed from that in Sprague-Dawley rats. In addition to teratogenicity, diEGME had significant adverse effects on postnatal development. The most sensitive organ to diEGME was the thymus in both dams and fetuses.
Yamano
T
T
Osaka City Institute of Public Health and Environmental Sciences, Japan.
Noda
T
T
Shimizu
M
M
Morita
S
S
Nagahama
M
M
D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000401:mortality; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000002:abnormalities* / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D005026:Ethylene Glycols; C048214:diethylene glycol monomethyl ether