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) is a 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 gavage in both rodent species. Dams were administered EG on Gestation Days 6-15; rats were given 0, 150, 500, 1000, or 2500 mg EG/kg/day; mice were dosed with 0, 50, 150, 500, or 1500 mg EG/kg/day. In rat dams given 2500 mg EG/kg/day, water consumption was increased during treatment and body weights were reduced throughout gestation; liver and kidney weights were increased at euthanization (Gestation Day 21). Relative liver weights were also increased at 1000 mg/kg/day. Effects observed in rat fetuses at 2500 mg/kg/day included the following: hydrocephaly; gastroschisis; umbilical hernia; fused, duplicated, or missing arches, centra, and ribs; poor ossification in thoracic and lumbar regions; and reduced body weights. Reduced body weights, duplicated or missing ribs, centra, and arches, and poor ossification were also observed in rat fetuses at 1000 mg/kg/day. In mice, there was no apparent treatment-related maternal toxicity. In mouse fetuses (Gestation Day 18), effects were observed at 1500 mg/kg/day and included reduced body weights, fused ribs and arches, poor ossification in thoracic and lumbar centra, and increased occurrence of an extra 14th rib. At 500 mg/kg/day, slight reductions in fetal body weight and increased incidences of extra ribs were observed. Under conditions of these studies, NOELs for developmental toxicity were 500 mg/kg/day for rats and 150 mg/kg/day for mice, indicating that mice were more susceptible than rats to the teratogenic effects of EG.
Neeper-Bradley
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Bushy Run Research Center, Union Carbide Corporation, Export, Pennsylvania 15632-8902, USA.
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Fisher
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Kubena
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Vrbanic
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MA
Losco
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PE
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019855:Ethylene Glycol; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D051381:Rats; D012098:Reproduction / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*
D005026:Ethylene Glycols; D013723:Teratogens; D019855:Ethylene Glycol