Determination of a No-Observed-Effect Level for Developmental Toxicity of Ethylene Glycol Administered by Gavage to CD Rats and CD-1 Mice

Previous studies have indicated that ethylene glycol (EG) isa developmental toxicant in rats and mice primarily when ingested.This study was designed to establish no-observed-effect levels(NOELs) for developmental toxicity of EG administered by gavagein both rodent species. Dams were administered EG on GestationDays 6–15; rats were given 0, 150, 500, 1000, or 2500mg EG/kg/ day; mice were dosed with 0, 50, 150, 500, or 1500mg EG/kg/day. In rat dams given 2500 mg EG/kg/day, water consumptionwas increased during treatment and body weights were reducedthroughout gestation; liver and kidney weights were increasedat euthanization (Gestation Day 21). Relative liver weightswere also increased at 1000 mg/kg/day. Effects observed in ratfetuses at 2500 mg/kg/day included the following hydrocephaly;gastroschisis; umbilical hernia; fused, duplicated, or missingarches, centra, and ribs; poor ossification in thoracic andlumbar regions; and reduced body weights. Reduced body weights,duplicated or missing ribs, centra, and arches, and poor ossificationwere also ob served in rat fetuses at 1000 mg/kg/day. In mice,there was no apparent treatment-related maternal toxicity. Inmouse fetuses (Gestation Day 18), effects were observed at 1500mg/kg/day and included reduced body weights, fused ribs andarches, poor ossification in thoracic and lumbar centra, andincreased occurrence of an extra 14th rib. At 500 mg/kg/day,slight reductions in fetal body weight and increased incidencesof extra ribs were observed. Under conditions of these studies,NOELs for developmental toxicity were 500 mg/kg/day for ratsand 150 mg/kg/day for mice, indicating that mice were more susceptiblethan rats to the teratogenic effects of EG.     

Evaluation of the Developmental Toxicity of Dermally Applied Monoethanolamine in Rats and Rabbits

Pregnant Sprague-Dawley rats and New Zealand White rabbits wereexposed dermally to 0, 10,25, and 75 mg/kg/day of monoethanolamine(MEA) for approximately 6 hr/day on Days 6 through 15 (rats)or 6 through 18 (rabbits) of gestation. A fifth dose group of225 mg MEA/kg/day was evaluated in rats only. Dermal exposureof pregnant rats to 225 mg/kg/day and rabbits to 75 mg/kg/dayresulted in significant increases in the incidence of skin irritation/lesionsand maternal body weight effects. In general, the dermal irritationobserved at the high dose was progressive, beginning with erythemaand leading to necrosis, scabs, and scar formation. Doses of25 mg/kg/day to rabbits produced only minor irritation. Despitematernal effects observed in rats and rabbits, no evidence ofdevelopmental or fetal toxicity was observed at any dose leveltested. Thus, it was concluded that MEA was not developmentallytoxic following dermal application at exposure levels up toand including 225 mg/kg/day for rats and 75 mg/kg/day for rabbits.     

Teratologic Evaluations of N,N-Diethyl-m-toluamide (DEET) in Rats and Rabbits

The potential for DEET to produce developmental toxicity wasevaluated in Charles River CD rats and New Zealand White rabbits.Rats were administered undiluted DEET by gavage on GestationalDays (gd) 6–15 at dosage levels of 0, 125, 250, and 750mg/kg/day. Rabbits were administered undiluted DEET by gavageon gd 6–18 at dosage levels of 0, 30, 100, and 325 mg/kg/day.Group sizes were 25 females per group for rats and 16 femalesper group for rabbits. Control rats and rabbits were ad ministeredcorn oil at the same dosage volumes administered in the high-doseDEET groups. In rats, maternal toxicity in the form of clinicalsigns including two deaths and depressed body weight and foodconsumption was observed at the high-dose level of 750 mg/kg/day.Rat fetal body weights per litter also were reduced at 750 mg/kg/day.In rabbits, maternal toxicity in the form of depressed bodyweight and food consumption was observed at the high-dose levelof 325 mg/kg/day. No maternal toxicity was observed at the low-or mid-dose groups for rats or rabbits. With the exception ofthe reduced fetal weights in rats at 750 mg/kg, there was noevidence of fetal toxicity, no effects on any of the gestationalparameters, nor were there any treat ment-related increasesin external, visceral, or skeletal variations or malformationsin the offspring from the rats and rabbits from these studies.1994 Society of Toxicology.