采用灌胃方式给予CD大鼠和CD-1小鼠三甘醇的发育毒性研究。

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

作者信息

Ballantyne Bryan, Snellings William M

机构信息

Toxicology Research, The Dow Chemical Company, Danbury, Connecticut 06817, USA.

出版信息

J Appl Toxicol. 2005 Sep-Oct;25(5):418-26. doi: 10.1002/jat.1089.

DOI:10.1002/jat.1089

PMID:16092104

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.

摘要

三甘醇（TEG）是一种液态工业化学品，有可能使人接触到。在两个物种中研究了其发育毒性的可能性。对妊娠时机明确的CD大鼠和CD-1小鼠在妊娠第5至15天每天经口灌胃给予未稀释的TEG，大鼠的剂量为0.0（水对照）、1126、5630或11260 mg kg⁻¹天⁻¹，小鼠的剂量为0.0、563、5630或11260 mg kg⁻¹天⁻¹。每天对它们进行检查，并在整个妊娠期测量妊娠体重以及食物和水的消耗量。在妊娠第21天（大鼠）或第18天（小鼠）进行尸检时，检查母鼠的身体、妊娠子宫、肝脏和肾脏重量以及着床部位。对母鼠的肾脏进行组织学检查。对胎儿称重、确定性别，并检查其外部、软组织和骨骼的变异及畸形情况。在剂量为11260 mg kg⁻¹天⁻¹时，大鼠母鼠的体重、体重增加量和食物消耗量减少，而水消耗量和相对肾脏重量增加。在剂量为5630 mg kg⁻¹天⁻¹时，它们的体重也减少且水消耗量增加。在剂量为11260 mg kg⁻¹天⁻¹时，小鼠出现临床症状且相对肾脏重量增加。两个物种的肾脏组织学均正常。两个物种均未出现与处理相关的黄体或着床方面的影响。在剂量为11260 mg kg⁻¹天⁻¹（两个物种）和5630 mg kg⁻¹天⁻¹（小鼠）时，胎儿体重降低。在剂量为11260 mg kg⁻¹天⁻¹时，大鼠胎儿的胸部区域出现骨化延迟模式。在剂量为11260 mg kg⁻¹天⁻¹时，小鼠胎儿的额骨和枕骨、颈部区域、后肢近端指骨出现骨化延迟且尾节减少，在剂量为5630 mg kg⁻¹天⁻¹时，颅骨出现骨化延迟。这些骨化延迟模式与胎儿体重降低一致。在任何剂量下，两个物种均未观察到具有生物学意义的胚胎毒性或致畸性。在器官形成期经口给予TEG时，大鼠母体毒性的无观察到有害作用水平（NOEL）为1126 mg kg⁻¹天⁻¹，小鼠为5630 mg kg⁻¹天⁻¹；发育毒理学方面，大鼠为5630 mg kg⁻¹天⁻¹，小鼠为563 mg kg⁻¹天⁻¹。