ASSESSMENT OF THE DEVELOPMENTAL TOXICITY OF ETHYLENE-GLYCOL APPLIED CUTANEOUSLY TO CD-1 MICE

Ethylene glycol (EG; CAS No. 107-21-1) is teratogenic to mice by whole -body exposure to an aerosol at high concentrations, but results were confounded by possible exposure from ingestion after grooming and/or f rom percutaneous absorption. Therefore, CD-1 mice were exposed to EG o n Gestational Days (GD) 6 through 15, 6 hr/day by occluded cutaneous a pplication at 0, 12.5, 50, or 100% (undiluted) EG (0.1 ml/animal, equi valent to similar to 0, 404, 1677, or 3549 mg/kg/day, respectively) or by gavage on GD 6 through 15 at 3000 mg/kg/day [10 ml/kg, positive co ntrol gavage group (PCGG)], 30 females/group. Dams were weighed and ev aluated daily (including application site) for clinical signs and wate r consumption throughout gestation. On GD 18, maternal uterus, liver, and paired kidneys were weighed; kidneys of 0 and 100% and the PCGG we re examined microscopically. Corpora lutea and implantation sites were recorded. Live fetuses were weighed, sexed, and examined for structur al alterations. For cutaneously exposed dams, there was no treatment-r elated maternal toxicity, no differences in pre- or postimplantation l oss or in fetal body weights/ litter, and no increased incidences of a ny fetal malformations. Two skeletal variations, increased at 100%, ma y represent effects of restraint stress and/or findings due to chance. In the PCGG, 8 females (26.7%) died, water consumption was increased, fetal body weights/litter were reduced, and fetal malformations and v ariations were increased. PCGG kidneys exhibited tubular nephrosis and tubular cell degeneration, with no oxalate crystals, documenting rena l toxicity at this oral dose in mice. Minimal-grade renal tubular lesi ons observed in 3 mice (of 30) at 100% EG may represent treatment-rela ted or incidental findings. Therefore, exposure of pregnant CD-1 mice to 0, 12.5, 50, or 100% EG during organogenesis by occluded cutaneous application resulted in minimal or no observable maternal or developme ntal toxicity at 100% (similar to 3549 mg/kg/day), the NOEL. (C) 1995 Society of Toxicology