Occupational exposure to glycol ethers and human congenital malformations

Objectives: This commentary reviews toxicological information and critically evaluates epidemiological information on the relationship between glycol ethers and congenital malformations. Methods: 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. Results: 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. Conclusions: 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.