Fetal detriment used as an index of effects of diethylene glycol on Syrian hamster fetuses.
The effect of diethylene glycol (digol, diEG; specific gravity = 1.12) on the embryo was studied in the pregnant Syrian hamster at dosages from 2 1/4 to 4 ml/kg (2.52-4.48 g/kg). The hamsters were dosed by (single) intraperitoneal injection because previous experiments had indicated that oral dosing in the drinking water (and therefore possibly gavage dosing also) causes the hamsters to drink less. The digol was diluted with distilled water and injected on d 8 of pregnancy. Distilled water was used for the controls. At all dosages, fetuses from treated animals examined at autopsy on d 15 were found to be lighter than those from control animals. Abnormalities were seen at all dosages, mainly neural-tube defects (exencephaly, cranial bleb, and myelomeningocele). No neural-tube defects were observed in control animals. A dosage-related deficit in the number of live, externally nonmalformed fetuses was observed and was matched by a dosage-related increase in the number of live externally abnormal fetuses. Few dead full-term fetuses were found, but there was a dosage-related increase in the "late" resorption rate. A new summarizing measure, the fetal detriment (FD), the deficit from control expectations of live, nonmalformed litter mass per live litter, was found to be proportional to the square of the dose-rate D, the regression through the origin in this study being FD = (0.934 +/- 0.329)D2. The 50% attrition dosage, the AD50, was 2.90 ml/kg (3.25 g/kg) in the hamster, with 95% confidence interval 2.21-5.41 ml/kg (2.48-6.06 g/kg). Diethylene glycol in high dosage produces damage to the fetuses of pregnant Syrian hamsters. It is not known whether this is an indirect result of the maternal toxicity, which was observed even at the lowest dosage used, or is the effect of digol or of its metabolites on the conceptus.
Renwick
J H
JH
Department of Epidemiology and Population Sciences, London School of Hygiene, United Kingdom.
Cameron
K M
KM
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005026:Ethylene Glycols / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005317:Fetal Growth Retardation / Q000139:chemically induced; D005327:Fetal Resorption / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D008432:Mathematical Computing; D008647:Mesocricetus; D011247:Pregnancy
D005026:Ethylene Glycols; C013484:diethylene glycol