Prenatal Exposure to Glycol Ethers and Male Genital Anomalies

Abstract

Introduction: Glycol ethers (GE) are solvents present in a wide range of occupational and domestic products. Numerous animal studies reported reprotoxic effects of GE and showed that some of them alter testicular functions and fetal development. The aim of our study is to evaluate the relation between prenatal exposure to GE and male genital anomalies. Methods: We carried out a case-control study nested in two mother–child cohorts (5,300 pregnant women). Concentrations of 5 GE metabolites were measured in spot maternal urine samples, collected before 28 weeks of gestation. Cases of male genital anomalies (n=14 hypospadias and n=14 cryptorchidism) were identified at birth by pediatricians and later validated by surgery reports. Three controls per case were randomly selected and matched on district of inclusion and gestational age at urine sampling. Odds ratios (OR) were estimated using multiple conditional logistic regressions with a Firth’s penalization to prevent small-sample bias. Results: Detection rates of GE metabolites ranged from 7% (ethoxyacetic acid [EAA]) to 93% (phenoxyacetic acid [PhAA]). Significant increased risks of male genital anomalies were observed among offspring of women with detected levels of EAA (OR [95%CI]=4.0 [1.2; 14.9]) and 2-methoxypropionic acid (OR=5.3 [1.1; 35.8]). In the subgroup of cases of hypospadias, we observed an increased risk in the highest tercile of methoxyacetic acid (OR=6.3 [1.1; 55.0]) and in association with detected levels of EAA (OR=8.9 [1.2; 122.1]). No significant association was found for the two others GE metabolites or in association with cryptorchidism specifically. Conclusion: To our knowledge, this is the first human study about GE exposures and subtypes of male genital anomalies using a biomarker-based and prospective assessment of exposure. Although limited by the small sample size, these results add some evidence for the potential developmental effect of GE on male reproductive organs.