Developmental toxicity study with triethylene glycol given by gavage to CD rats and CD-1 mice

Abstract

Triethylene glycol (TEG) is a liquid industrial chemical with a potential for human exposure. The likelihood for developmental toxicity was investigated in two species. Timed-pregnant CD rats and CD-1 mice were dosed daily by gavage with undiluted TEG over gestational days (gd) 5-15 at 0.0 (water control), 1126, 5630 or 11,260 mg kg(-1) day(-1) with rats and 0.0, 563, 5630 or 11,260 mg kg(-1) day(-1) with mice. They were examined daily, and gestational body weights and food and water consumption measured throughout gestation. At necropsy on gd 21 (rats) or gd 18 (mice) dams were examined for body, gravid uterine, liver and kidney weights, and implantation sites. Maternal kidneys were examined histologically. Fetuses were weighed, sex determined, and examined for external, soft tissue and skeletal variations and malformations. Rat dams had reduced body weights, body weight gains, and food consumption, and increased water consumption and relative kidney weights at 11,260 mg kg(-1) day(-1). They also had reduced body weight and increased water consumption at 5630 mg kg(-1) day(-1). Mice had clinical signs and increased relative kidney weight at 11,260 mg kg(-1) day(-1). Renal histology was normal in both species. Neither species had treatment-related effects on corpora lutea or implantations. Fetal body weights were reduced at 11,260 mg kg(-1) day(-1) (both species) and 5630 mg kg(-1) day(-1) (mice). In rat fetuses there was a pattern of delayed ossification in the thoracic region at 11,260 mg kg(-1) day(-1). Mouse fetuses had delayed ossification in the frontal and supraoccipital bones, cervical region, hindlimb proximal phalanges and reduced caudal segments at 11,260 mg kg(-1) day(-1), and in the skull bones at 5630 mg kg(-1) day(-1). These patterns of delayed ossification are consistent with reduced fetal body weights. No biologically significant embryotoxicity or teratogenicity was observed at any dosage in either species. The NOEL for TEG given by gavage over the period of organogenesis was 1126 mg kg(-1) day(-1) in the rat and 5630 mg kg(-1) day(-1) in the mouse for maternal toxicity, and 5630 mg kg(-1) day(-1) (rat) and 563 mg kg(-1) day(-1) (mouse) for developmental toxicology.