Neeper-Bradley T L, Tyl R W, Fisher L C, Kubena M F, Vrbanic M A, Losco P E
Bushy Run Research Center, Union Carbide Corporation, Export, Pennsylvania 15632-8902, USA.
Fundam Appl Toxicol. 1995 Aug;27(1):121-30. doi: 10.1006/faat.1995.1115.
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.
以往研究表明，乙二醇（EG）主要在大鼠和小鼠经口摄入时是一种发育毒性物质。本研究旨在确定经灌胃给予EG对两种啮齿类动物发育毒性的未观察到有害作用水平（NOELs）。在妊娠第6至15天给母鼠灌胃EG；大鼠给予0、150、500、1000或2500 mg EG/kg/天；小鼠给予0、50、150、500或1500 mg EG/kg/天。在给予2500 mg EG/kg/天的大鼠母鼠中，治疗期间水消耗量增加，整个妊娠期体重减轻；处死时（妊娠第21天）肝脏和肾脏重量增加。在1000 mg/kg/天剂量下，相对肝脏重量也增加。在2500 mg/kg/天剂量下，观察到的大鼠胎儿效应包括：脑积水；腹裂；脐疝；椎弓、椎体和肋骨融合、重复或缺失；胸腰椎区域骨化不良；体重减轻。在1000 mg/kg/天剂量下的大鼠胎儿中也观察到体重减轻、肋骨、椎体和椎弓重复或缺失以及骨化不良。在小鼠中，未观察到明显的与治疗相关的母体毒性。在小鼠胎儿（妊娠第18天）中，在1500 mg/kg/天剂量下观察到效应，包括体重减轻、肋骨和椎弓融合、胸腰椎椎体骨化不良以及第14肋额外出现的发生率增加。在500 mg/kg/天剂量下，观察到胎儿体重略有减轻以及额外肋骨发生率增加。在这些研究条件下，大鼠发育毒性的NOELs为500 mg/kg/天，小鼠为150 mg/kg/天，表明小鼠比大鼠对EG的致畸作用更敏感。
