Maldonado George, Delzell Elizabeth, Tyl Rochelle W, Sever Lowell E
School of Public Health, University of Minnesota, 420 Delaware St. SE, Mayo Mail Code 807, Minneapolis, MN 55455-0392, USA.
Int Arch Occup Environ Health. 2003 Jul;76(6):405-23. doi: 10.1007/s00420-003-0441-x. Epub 2003 Jun 19.
This commentary reviews toxicological information and critically evaluates epidemiological information on the relationship between glycol ethers and congenital malformations.
The authors identified and assessed toxicological and epidemiological research on glycol ethers used in occupational settings and congenital malformations. Sensitivity analyses evaluated the possible role of methodological problems in explaining the findings of the epidemiological studies.
Exposure to certain glycol ethers, including ethylene glycol monomethyl ether and ethylene glycol mono-ethyl ether, throughout the period of major organogenesis, has induced malformations of many organ systems in some of the animal models studied. Other glycol ethers, including ethylene glycol butyl and propyl ethers and most propylene glycol ethers, have not induced fetal malformations in the animal models studied. Four epidemiological studies have assessed the relationship between occupational exposure to glycol ethers and congenital malformations in humans. One study was uninformative because of small numbers, two found a positive association between glycol ethers and malformations of a number of different organs, and one found no association with neural-tube defects. Sensitivity analyses indicated that the results of the latter three investigations could be due to methodological problems. The positive studies, further, lack biological plausibility, in that the glycol ethers to which the subjects were exposed have not been, for the most part, teratogenic in the animal models that have been studied.
The current evidence is insufficient for one to determine whether occupational exposure to glycol ethers causes human congenital malformations. We suggest that future studies quantify the effect of methodological problems on study results, using methods such as validation studies and sensitivity analysis.
本述评回顾了毒理学信息，并对乙二醇醚与先天性畸形之间关系的流行病学信息进行了批判性评估。
作者识别并评估了关于职业环境中使用的乙二醇醚与先天性畸形的毒理学和流行病学研究。敏感性分析评估了方法学问题在解释流行病学研究结果方面的可能作用。
在一些研究的动物模型中，在主要器官形成期全程接触某些乙二醇醚，包括乙二醇单甲醚和乙二醇单乙醚，已诱发多个器官系统的畸形。其他乙二醇醚，包括乙二醇丁醚和丙醚以及大多数丙二醇醚，在所研究的动物模型中未诱发胎儿畸形。四项流行病学研究评估了职业接触乙二醇醚与人类先天性畸形之间的关系。一项研究因样本量小而无信息价值，两项研究发现乙二醇醚与多种不同器官的畸形之间存在正相关，一项研究发现与神经管缺陷无关联。敏感性分析表明，后三项调查的结果可能是由于方法学问题。此外，阳性研究缺乏生物学合理性，因为受试者接触的乙二醇醚在大多数已研究的动物模型中并非致畸剂。
目前的证据不足以确定职业接触乙二醇醚是否会导致人类先天性畸形。我们建议未来的研究使用验证研究和敏感性分析等方法，量化方法学问题对研究结果的影响。
