Laurence Labat

Exposure during pregnancy to glycol ethers and chlorinated solvents and the risk of congenital malformations.

Background: Exposure to solvents during pregnancy has long been suspected of increasing the risk of congenital malformations, but the lack of prospective assessment of specific solvent exposures has prevented definitive conclusions. Methods: In a cohort of 3421 pregnant women in Brittany (2002–2006), occupational solvent exposure was assessed from self-report during pregnancy and from a job-exposure matrix. Congenital malformations were diagnosed among live births, stillbirths, and medical pregnancy terminations. In a nested case–control sample, urinary concentrations of 10 metabolites of glycol ethers and chlorinated solvents were measured in maternal samples collected during early pregnancy (n = 79 cases, 580 controls). Results: Dose–response trends linked occupational solvent exposure (both self-reported and based on a job-exposure matrix) to the risk of major congenital malformations––especially oral clefts, urinary tract malformations, and male genital malformations. Detection of some glycol ether metabolites and trichloroacetic acid in urine was associated with increased risks of oral clefts and of urinary tract and limb defects. Conclusions: This prospective study, using three independent methods of exposure assessment, suggests several specific associations between solvent exposure during early pregnancy and congenital malformations. Results based on urinary biomarkers, although limited by small numbers, identify work situations that require further investigation.

Urinary biomarkers of exposure to glycol ethers and chlorinated solvents during pregnancy: determinants of exposure and comparison with indirect methods of exposure assessment

Objectives To describe urine levels of metabolites of glycol ethers and chlorinated solvents in a sample of pregnant women from the general population, to study their occupational and non-occupational determinants and to compare them with the results of indirect assessment methods of solvent exposure. Methods A sample of 451 pregnant women was randomly selected from a general population cohort. At inclusion, the women in this sample completed a self-administered questionnaire about their social and medical characteristics, occupation and exposure to different products at work and in non-occupational activities. Occupational exposure to solvents was assessed from the womans self-report and from a job-exposure matrix. Eight alkoxycarboxylic acids and trichloroacetic acid and trichloroethanol were measured with chromatography in urine samples collected at inclusion. Associations between metabolite levels and job titles, exposure to products used at work, and solvent exposure were studied. Results The different glycol ether metabolites were detected in 5.3%–96.4% of the urine samples, trichloroacetic acid in 6.4% and trichloroethanol in 5.5%. Nurses had butoxyacetic acid and phenoxyacetic acid in their urine most often, whereas methoxyethoxyacetic acid was the most frequent among nursing aides. Among cleaners, ethoxyacetic acid and ethoxyethoxyacetic acid were the most frequent. The occupation of hairdresser was associated with urinary excretion of ethoxyacetic acid, ethoxyethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid. Among the women classified as exposed to solvents, the agents identified most often were ethoxyacetic acid, ethoxy-ethoxyacetic acid, butoxyacetic acid, phenoxyacetic acid, trichloroacetic acid and trichloroethanol. Ethoxyethoxyacetic acid was the only metabolite associated with non-occupational exposure. Conclusions Metabolites of glycol ethers and chlorinated solvents were present at low levels in the urine of pregnant women. Most metabolites were associated with occupational exposure.

Urinary Glycol Ether Metabolites in Women and Time to Pregnancy: The PELAGIE Cohort.

Background: Glycol ethers are present in a wide range of occupational and domestic products. Animal studies have suggested that some of them may affect ovarian function. Objective: We examined the relation between women’s exposure to glycol ethers and time to pregnancy. Methods: We used chromatography coupled to mass spectrometry to measure eight glycol ether metabolites in urine samples from randomly selected women in the PELAGIE mother–child cohort who had samples collected before 19 weeks of gestation. Using time to pregnancy information collected at the beginning of the pregnancy (women were asked how many months it took for them to conceive), we estimated associations between metabolite levels and time to pregnancy in 519 women with complete data using discrete-time Cox proportional hazards models to adjust for potential confounders. Results: We detected glycol ether metabolites in 6% (for ethoxyacetic acid) to 93% (for phenoxyacetic and butoxyacetic acids) of urine samples. Phenoxyacetic acid was the only metabolite with a statistically significant association with longer time to pregnancy [fecundability OR = 0.82; 95% CI: 0.63, 1.06 for the second and third quartile combined; fecundability OR = 0.70; 95% CI: 0.52, 0.95 for a fourth-quartile (≥ 1.38 mg/L) vs. first-quartile concentration (< 0.14 mg/L)]. This association remained stable after multiple sensitivity analyses. Conclusion: Phenoxyacetic acid, which was present in most of the urine samples tested in our study, was associated with increased time to pregnancy. This metabolite and its main parent compound, 2-phenoxyethanol, are plausible causes of decreased fecundability, but they may also be surrogates for potential coexposures to compounds frequently present in cosmetics. Citation: Garlantézec R, Warembourg C, Monfort C, Labat L, Pulkkinen J, Bonvallot N, Multigner L, Chevrier C, Cordier S. 2013. Urinary glycol ether metabolites in women and time to pregnancy: the PELAGIE cohort. Environ Health Perspect 121:1167–1173; http://dx.doi.org/10.1289/ehp.1206103