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三甘醇HO(CH₂CH₂O)₃H。

Triethylene glycol HO(CH2CH2O)3H.

作者信息

Ballantyne Bryan, Snellings William M

机构信息

Consultant in Clinical and Occupational Toxicology, 871 Chappell Road, Charleston, WV 25304, USA.

出版信息

J Appl Toxicol. 2007 May-Jun;27(3):291-9. doi: 10.1002/jat.1220.

Abstract

TEG is a liquid higher glycol of very low vapor pressure with uses that are primarily industrial. It has a very low order of acute toxicity by i.v., i.p., peroral, percutaneous and inhalation (vapor and aerosol) routes of exposure. It does not produce primary skin irritation. Acute eye contact with the liquid causes mild local transient irritation (conjunctival hyperemia and slight chemosis) but does not induce corneal injury. Animal maximization and human volunteer repeated insult patch tests studies have shown that TEG does not cause skin sensitization. A study with Swiss-Webster mice demonstrated that TEG aerosol has properties of a peripheral chemosensory irritant material and caused a depression of breathing rate with an RD(50) of 5140 mg m(-3). Continuous subchronic peroral dosing of TEG in the diet of rats did not produce any systemic cumulative or long-term toxicity. The effects seen were dose-related increased relative kidney weight, increased urine volume and decreased urine pH, probably a result of the renal excretion of TEG and metabolites following the absorption of large doses of TEG. There was also decreased hemoglobin concentration, decreased hematocrit and increased mean corpuscular volume, probably due to hemodilution following absorption of TEG. The NOAEL was 20 000 ppm TEG in diet. Short-term repeated aerosol exposure studies in the rat demonstrated that, by nose-only exposure, the threshold for effects by respiratory tract exposure was 1036 mg m(-3). Neither high dosage acute nor repeated exposures to TEG produce hepatorenal injury characteristic of that caused by the lower glycol homologues. Elimination studies with acute peroral doses of TEG given to rats and rabbits showed high recoveries (91-98% over 5 days), with the major fraction appearing in urine (84-94%) and only 1% as CO(2). TEG in urine is present in unchanged and oxidized forms, but only negligible amounts as oxalic acid. Developmental toxicity studies with undiluted TEG given by gavage produced maternal toxicity in rats (body weight, food consumption, water consumption, and relative kidney weight) with a NOEL of 1126 mg kg(-1) day(-1), and mice (relative kidney weight) with a NOEL of 5630 mg kg(-1) day(-1). Developmental toxicity, expressed as fetotoxicity, had a NOEL of 5630 mg kg(-1) day(-1) with the rat and 563 mg kg(-1) day(-1) with mice. Neither species showed any evidence of embryotoxicity or teratogenicity. There was no evidence for reproductive toxicity with mice given up to 3% TEG in drinking water in a continuous breeding study. TEG did not produce mutagenic or clastogenic effects in the following in vitro genetic toxicology studies: Salmonella typhimurium reverse mutation test, SOS-chromotest in E. coli, CHO forward gene mutation test (HGPRT locus), CHO sister chromatid exchange test, and a chromosome aberration test with CHO cells. The use patterns suggest that exposure to TEG is mainly occupational, with limited exposures by consumers. Exposure is normally by skin and eye contact. Local and systemic adverse health effects by cutaneous exposure are likely not to occur, and eye contact will produce transient irritation without corneal injury. The very low vapor pressure of TEG makes it unlikely that significant vapor exposure will occur. Aerosol exposure is not a usual exposure mode, and acute aerosol exposures are unlikely to be harmful, although a peripheral sensory irritant effect may develop. However, repeated exposures to a TEG aerosol may result in respiratory tract irritation, with cough, shortness of breath and tightness of the chest. Recommended protective and precautionary measures include protective gloves, goggles or safety glasses and mechanical room ventilation. LC(50) data to various fish, aquatic invertebrates and algae, indicate that TEG is essentially nontoxic to aquatic organisms. Also, sustained exposure studies have demonstrated that TEG is of a low order of chronic aquatic toxicity. The bioconcentration potential, environmental hydrolysis, and photolysis rates are low, and soil mobility high. In the atmosphere TEG is degraded by reacting with photochemically produced hydroxyl radicals. These considerations indicate that the potential for ecotoxicological effects with TEG is low.

摘要

三甘醇是一种蒸气压极低的液态高级二醇,主要用于工业。经静脉注射、腹腔注射、口服、经皮和吸入(蒸气和气溶胶)暴露途径,其急性毒性等级非常低。它不会引起原发性皮肤刺激。液体与眼睛急性接触会引起轻度局部短暂刺激(结膜充血和轻微水肿),但不会导致角膜损伤。动物最大化试验和人体志愿者重复刺激斑贴试验研究表明,三甘醇不会引起皮肤过敏。一项对瑞士韦伯斯特小鼠的研究表明,三甘醇气雾剂具有外周化学感应刺激物质的特性,可导致呼吸频率降低,半数反应浓度(RD(50))为5140毫克/立方米。在大鼠饮食中持续亚慢性口服给药三甘醇未产生任何全身性累积或长期毒性。观察到的影响包括与剂量相关的相对肾重量增加、尿量增加和尿液pH值降低,这可能是大量吸收三甘醇后其经肾脏排泄及其代谢产物的结果。还观察到血红蛋白浓度降低、血细胞比容降低和平均红细胞体积增加,这可能是吸收三甘醇后血液稀释所致。无观察到有害作用水平(NOAEL)为饮食中三甘醇20000 ppm。对大鼠进行的短期重复气雾剂暴露研究表明,仅通过经鼻暴露,呼吸道暴露的效应阈值为1036毫克/立方米。无论是高剂量急性暴露还是重复暴露于三甘醇,均未产生低级二醇同系物所引起的肝肾损伤特征。对大鼠和兔子急性口服给予三甘醇的消除研究表明,回收率很高(5天内为91 - 98%),大部分出现在尿液中(84 - 94%),仅1%以二氧化碳形式排出。尿液中的三甘醇以未改变和氧化形式存在,但以草酸形式存在的量可忽略不计。对未稀释的三甘醇经口灌胃进行的发育毒性研究在大鼠中产生了母体毒性(体重、食物消耗、水消耗和相对肾重量),无观察到有害作用水平(NOEL)为1126毫克/千克·天,在小鼠中(相对肾重量)NOEL为5630毫克/千克·天。发育毒性表现为胚胎毒性,大鼠的无观察到有害作用水平(NOEL)为5630毫克/千克·天,小鼠为563毫克/千克·天。两种动物均未显示任何胚胎毒性或致畸性证据。在一项连续繁殖研究中,给小鼠饮用含高达3%三甘醇的水,未发现生殖毒性证据。在以下体外遗传毒理学研究中,三甘醇未产生致突变或染色体断裂效应:鼠伤寒沙门氏菌回复突变试验、大肠杆菌SOS - 显色试验、中国仓鼠卵巢细胞(CHO)正向基因突变试验(次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶位点)、CHO姐妹染色单体交换试验以及CHO细胞染色体畸变试验。使用模式表明,接触三甘醇主要是职业性的,消费者接触有限。接触通常通过皮肤和眼睛接触。经皮肤接触不太可能产生局部和全身性不良健康影响,眼睛接触会产生短暂刺激而无角膜损伤。三甘醇极低的蒸气压使得不太可能发生显著的蒸气接触。气雾剂接触不是常见的接触方式,急性气雾剂接触不太可能有害,尽管可能会产生外周感觉刺激效应。然而,重复接触三甘醇气雾剂可能导致呼吸道刺激,出现咳嗽、呼吸急促和胸部发紧。推荐的防护和预防措施包括防护手套、护目镜或安全眼镜以及机械通风。对各种鱼类、水生无脊椎动物和藻类的半数致死浓度(LC(50))数据表明,三甘醇对水生生物基本无毒。此外,持续暴露研究表明,三甘醇的慢性水生毒性等级较低。生物浓缩潜力、环境水解和光解速率较低,土壤迁移性较高。在大气中,三甘醇通过与光化学产生的羟基自由基反应而降解。这些因素表明,三甘醇产生生态毒理学效应的可能性较低。

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