Developmental toxicity study of glycolic acid in rats

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 ges tation (the day of copulation plug detection was defined as day 1 of gestat ion). Groups of 25 mated female Crl:CD(R)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 demonst rated at 600 mg/kg; adverse clinical observations were statistically signif icantly 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 evide nce 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 incre ase approached statistical significance (p=0.0553). There was marked eviden ce of developmental toxicity at 600 mg/kg. Mean fetal weight was statistica lly significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significant ly 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 si gnificant (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 devel opmental 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-ef fect level (NOEL) was considered 150 mg/kg.