Van Miller J P, Ballantyne B
Applied Toxicology Group, Union Carbide Corporation, Danbury, CT 06817, USA.
Vet Hum Toxicol. 2001 Oct;43(5):269-76.
Ethylene and diethylene glycols produce systemic toxicity, including nephrotoxicity, by acute and repeated po dosing. To determine the potential for triethylene glycol (TEG; CAS Number 112-27-61) to produce nephrotoxicity, or other organ/tissue injury, a subchronic (90-d) study was conducted by continuous inclusion of TEG in the diet of Fischer 344 rats. This was preceded by a probe 14-d study. For both studies the dietary concentrations were 0 ppm (control), 10,000, 20,000 or 50,000 ppm TEG, resulting in daily TEG consumptions in the 14-d study of 1132, 2311 or 5916 mg/kg with males, and 1177, 2411 or 6209 mg/kg with females. The corresponding values for the 90-d study were 748, 1522 or 3849 mg/kg (males), and 848, 1699 or 4360 mg/kg (females). In the 14-d study there were no mortalities or clinical signs, and no effects on body weight, hematology, serum chemistry, organ weights, and gross or microscopic pathology. Food consumption was increased at the high dosage. Urinalysis showed increased urine volume and decreased pH with high dose males and females, and increased volume with mid-dose males. In the subchronic study there was neither mortality nor signs of toxicity, and no dosage-related effects with serum chemistry, gross and microscopic pathology. Body weights were reduced during the dosing period with both males and females of the high dosage. Body weight gains were reduced at all dosages with males and females. No hematological effects were seen with females, but males of the mid- and high-dosage groups had slightly reduced erythrocyte count and hematocrit, and high-dose males had decreased hemoglobin concentration with increased mean corpuscular volume. These were considered to reflect a mild hemodilution related to the absorption of large TEG doses. Urinalysis showed dosage-related decreased pH, and increased urine volume mainly at the high dose. These were probably related to the renal excretion of absorbed TEG and/or metabolites. Kidney weight was increased for high-dose females, and increased relative (to body) weight of kidneys for males and females from the mid- and high-dose groups were observed, probably related to the renal excretion of the absorbed TEG and/or its metabolites. These findings indicate that the subchronic continuous po dosing of TEG to rats does not result in local or systemic specific organ or tissue toxicity. These findings contrast with the known repeated po toxicity, notably nephrotoxicity, produced by ethylene and diethylene glycols. Thus, TEG has significantly lesser potential for systemic toxicity by the po route than its lower molecular weight homologues.
通过急性和重复经口给药，乙二醇和二甘醇会产生全身毒性，包括肾毒性。为了确定三甘醇（TEG；化学物质登记号112 - 27 - 61）产生肾毒性或其他器官/组织损伤的可能性，在Fischer 344大鼠的饮食中持续添加TEG进行了一项亚慢性（90天）研究。在此之前进行了一项为期14天的探索性研究。在这两项研究中，饮食中的TEG浓度分别为0 ppm（对照组）、10000、20000或50000 ppm，在14天研究中，雄性大鼠每日TEG摄入量分别为1132、2311或5916 mg/kg，雌性大鼠分别为1177、2411或6209 mg/kg。90天研究的相应数值为748、1522或3849 mg/kg（雄性），以及848、1699或4360 mg/kg（雌性）。在14天研究中，没有死亡或临床症状，对体重、血液学、血清化学、器官重量以及大体或显微镜下病理学均无影响。高剂量组食物消耗量增加。尿液分析显示，高剂量雄性和雌性大鼠尿量增加，pH值降低，中剂量雄性大鼠尿量增加。在亚慢性研究中，既没有死亡也没有毒性迹象，血清化学、大体和显微镜下病理学方面也没有剂量相关影响。高剂量组雄性和雌性大鼠在给药期间体重减轻。所有剂量组雄性和雌性大鼠的体重增加均减少。雌性大鼠未见血液学影响，但中剂量和高剂量组雄性大鼠红细胞计数和血细胞比容略有降低，高剂量雄性大鼠血红蛋白浓度降低，平均红细胞体积增加。这些被认为反映了与大量TEG吸收相关的轻度血液稀释。尿液分析显示剂量相关的pH值降低，主要在高剂量时尿量增加。这些可能与吸收的TEG和/或其代谢产物的肾脏排泄有关。高剂量雌性大鼠肾脏重量增加，中剂量和高剂量组雄性和雌性大鼠肾脏相对（相对于体重）重量增加，这可能与吸收的TEG和/或其代谢产物的肾脏排泄有关。这些发现表明，对大鼠进行亚慢性连续经口给予TEG不会导致局部或全身特定器官或组织毒性。这些发现与乙二醇和二甘醇已知的重复经口毒性（尤其是肾毒性）形成对比。因此，与较低分子量的同系物相比，TEG经口途径产生全身毒性的可能性要小得多。
