Fowles Jeff, Banton Marcy, Klapacz Joanna, Shen Hua
Tox-Logic Consulting, Santa Rosa, CA, USA.
Lyondell Chemical Company, Houston, TX, USA.
Toxicol Lett. 2017 Aug 15;278:66-83. doi: 10.1016/j.toxlet.2017.06.009. Epub 2017 Jul 6.
This review summarizes the hazards, exposure and risk that are associated with ethylene glycols (EGs) in their intended applications. Ethylene glycol (EG; CAS RN 107-21-1) and its related oligomers include mono-, di-, tri-, tetra-, and penta-EG. All of the EGs are quickly and extensively absorbed following ingestion and inhalation, but not by the dermal route. Metabolism involves oxidation to the mono- and dicarboxylic acids. Elimination is primarily through the urine as the parent compound or the monoacid, and, in the case of EG, also as exhaled carbon dioxide. All EGs exert acute toxicity in a similar manner, characterized by CNS depression and metabolic acidosis in humans and rodents; the larger molecules being proportionally less acutely toxic on a strict mg/kg basis. Species differences exist in the metabolism and distribution of toxic metabolites, particularly with the formation of glycolic acids and oxalates (OX) from EG and diethylene glycol (DEG); OX are not formed to a significant degree in higher ethylene glycols. Among rodents, rats are more sensitive than mice, and males more sensitive than females to the acute and repeated-dose toxicity of EG. The metabolic formation of glycolic acid (GA), diglycolic acid (DGA), and OX are associated with nephrotoxicity in humans and rodents following single and repeated exposures. However, physiological and metabolic differences in the rate of formation of GA, DGA and OX and their distribution result in EG and DEG causing embryotoxicity in rats, but not rabbits. This rodent-specific sensitivity indicates that EG and its higher oligomers are not anticipated to be embryotoxic in humans at environmentally relevant doses. None of the compounds present developmental toxicity concerns at doses that do not also cause significant maternal toxicity, nor do any of the EGs cause adverse effects on fertility. The EGs are neither genotoxic nor carcinogenic. A read-across matrix is presented, which considers the common and distinct toxicological properties of each compound. It is concluded that EGs pose no risk to human health as a result of their intended use patterns.
本综述总结了乙二醇（EGs）在其预期应用中所涉及的危害、暴露情况及风险。乙二醇（EG；化学物质登记号107 - 21 - 1）及其相关低聚物包括单乙二醇、二乙二醇、三乙二醇、四乙二醇和五乙二醇。所有的乙二醇经口摄入和吸入后均可快速且大量被吸收，但经皮肤途径则不然。代谢过程包括氧化为单羧酸和二羧酸。排泄主要通过尿液以母体化合物或单酸形式排出，就乙二醇而言，还会以呼出二氧化碳的形式排出。所有乙二醇均以类似方式产生急性毒性，其特征为人类和啮齿动物出现中枢神经系统抑制和代谢性酸中毒；严格按照毫克/千克计算，分子量较大的分子急性毒性相对较小。在有毒代谢物的代谢和分布方面存在物种差异，尤其是乙二醇和二甘醇（DEG）形成乙醇酸和草酸盐（OX）的情况；在高级乙二醇中不会大量形成OX。在啮齿动物中，大鼠比小鼠对乙二醇的急性和重复剂量毒性更敏感，雄性比雌性更敏感。单次和重复暴露后，乙醇酸（GA）、二乙醇酸（DGA）和OX的代谢形成与人类和啮齿动物的肾毒性有关。然而，GA、DGA和OX形成速率及其分布的生理和代谢差异导致乙二醇和二甘醇在大鼠中引起胚胎毒性，但在兔子中则不会。这种啮齿动物特有的敏感性表明，在环境相关剂量下，乙二醇及其高级低聚物预计不会对人类产生胚胎毒性。在不引起明显母体毒性的剂量下，这些化合物均不存在发育毒性问题，任何一种乙二醇也不会对生育能力产生不利影响。乙二醇既无遗传毒性也无致癌性。本文给出了一个类推矩阵，该矩阵考虑了每种化合物常见和独特的毒理学特性。得出的结论是，由于其预期使用模式，乙二醇对人类健康不构成风险。
