Munley S M, Kennedy G L, Hurtt M E
Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours, Inc., Newark, Delaware, USA.
Drug Chem Toxicol. 1999 Nov;22(4):569-82. doi: 10.3109/01480549908993168.
The developmental toxicity of glycolic acid was assessed in rats by orally administering solutions of the test material in water over days 7-21 of gestation (the day of copulation plug detection was defined as day 1 of gestation). Groups of 25 mated female Crl: CD BR rats were gavaged at daily dose levels of 0, 75, 150, 300 or 600 mg/kg. The dams were euthanized on day 22 and the offspring were weighed, sexed, and examined for external, visceral, and skeletal alterations. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg; adverse clinical observations were statistically significantly increased (wheezing/lung noise, abnormal gait/staggering, lethargy). In addition, maternal body weights, weight changes, and food consumption were statistically significantly reduced at this dose level. Marginal evidence of maternal toxicity was demonstrated at 300 mg/kg; wheezing/lung noise similar to that seen at 600 mg/kg was observed in 2 of 25 dams. This increase approached statistical significance (p = 0.0553). There was marked evidence of developmental toxicity at 600 mg/kg. Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. At 300 mg/kg/day, there was a slight (2 affected fetuses from 2 litters) increase in the incidence of two skeletal malformations: fused ribs and fused vertebra. Although these increases were not statistically significant (p = 0.0555), they were consistent with findings seen at 600 mg/kg/day and thus were considered relevant. There was no other evidence of developmental toxicity at 300 mg/kg/day nor was any developmental toxicity seen at 150 or 75 mg/kg/day. Thus, the maternal and developmental no-observed-effect level (NOEL) was considered 150 mg/kg.
通过在妊娠第7至21天经口给予试验物质的水溶液来评估乙醇酸对大鼠的发育毒性（检测到交配栓的当天定义为妊娠第1天）。将25只交配的雌性Crl:CD BR大鼠分为几组，分别给予0、75、150、300或600 mg/kg的日剂量。在第22天对母鼠实施安乐死，并对其后代进行称重、性别鉴定，并检查外部、内脏和骨骼的改变。在600 mg/kg剂量下显示出明显的母体毒性证据；不良临床观察结果在统计学上显著增加（喘息/肺部杂音、异常步态/蹒跚、嗜睡）。此外，在该剂量水平下，母体体重、体重变化和食物摄入量在统计学上显著降低。在300 mg/kg剂量下显示出边缘性母体毒性证据；在25只母鼠中有2只观察到与600 mg/kg剂量下相似的喘息/肺部杂音。这种增加接近统计学显著性（p = 0.0553）。在600 mg/kg剂量下有明显的发育毒性证据。平均胎儿体重在统计学上显著降低，而骨骼（肋骨、椎骨和胸骨）畸形和变异的发生率在统计学上显著增加。在300 mg/kg/天的剂量下，两种骨骼畸形（融合肋骨和融合椎骨）的发生率略有增加（来自2窝的2只受影响胎儿）。尽管这些增加在统计学上不显著（p = 0.0555），但与600 mg/kg/天的观察结果一致，因此被认为具有相关性。在300 mg/kg/天的剂量下没有其他发育毒性证据，在150或75 mg/kg/天的剂量下也未观察到任何发育毒性。因此，母体和发育无观察到有害作用水平（NOEL）被认为是150 mg/kg。
