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Studies characterizing associations between phenols, phthalates and thyroid hormones during pregnancy produce inconsistent results. This divergence may be partly attributable to false positives due to multiple comparison testing of large numbers of chemicals, and measurement error as studies rely on small numbers of biospecimens despite high intra-individual variability in urinary chemical metabolite concentrations.This study employsA two-tiered approach was implemented:The ToxCast/Tox21 screening reduced the chemical set from 16 to 13 and the associated number of statistical comparisons by 19%. Parabens were negatively associated with free triiodothyronine (T3) and the T3/T4 (total thyroxine) ratio. Monobenzyl phthalate was positively associated with total T4 and negatively with the T3/T4 ratio. Effect modification by iodine status was detected for several compounds (among themFor these chemicals, screening for compounds with an increased likelihood for thyroid-related effects and relying on repeated urine samples to assess exposures improved the overall performance of multichemical analyses of thyroid disruption. This approach may improve future evaluations of human data for the thyroid pathway with implication for fetal health and may serve as a model for evaluating other toxicity outcomes. https://doi.org/10.1289/EHP10239.

Review human literature on the relationship between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and epigenetic modifications in infants, children, and adolescents 18 years of age.Eleven studies were identified, with study populations located in the U.S., Taiwan, Japan, and the Kingdom of Denmark. Many studies (n = 5) were cross-sectional, with PFAS exposure and epigenetic outcomes measured in the same tissue collected at delivery via cord blood or dried newborn blood spots. The other six studies were prospective, with prenatal PFAS measured on maternal blood during pregnancy and DNA methylation (DNAm) assessed in cord blood and childhood peripheral leukocytes (n = 1 study). Epigenetic marks of interest included global DNAm measures (LINE-1, Alu, and an ELISA-based method), candidate genes (IFG2, H19, and MEST), and epigenome-wide DNA methylation via array-based methods (Infinium 450 K and EPIC). Two studies using array-based methods employed discovery and validation paradigms, in which a small subset of loci (n = 6 and n = 4) were replicated in the discovery population. One site (TNXB) was a hit in two independent studies. Collectively, loci associated with PFAS were in regions involved in growth and development, lipid metabolism, and nutrient metabolism. There is moderate human evidence supporting associations of prenatal PFAS exposure on DNAm at birth, with one study suggesting sustained effects into childhood. Future studies are warranted to link PFAS-associated DNAm to health outcomes, as well as to investigate the role of other epigenetic marks such as hydroxymethylation, miRNA expression, and histone modifications.

BACKGROUND: Exposure to certain synthetic phenols is of growing concern, in particular among pregnant women, because of their endocrine disrupting nature. Many phenols are still authorized in personal care products (PCP). We aimed to assess if use of PCPs, by pregnant women could influence their urinary concentrations of synthetic phenols. METHODS: We used a panel design with intense urine sample collection. Eight women completed a diary with exact time and use of PCP in three weeks. We measured the concentrations of phenols (four parabens, bisphenol A and S, two dichlorophenols, triclosan, and benzophenone-3) in 178 urine samples, collected during 7 consecutive days at 3 time points during pregnancy. We characterized PCP use as the total number of PCP applications or as a single PCP use (yes / no) in three time windows (0 to 6, 6 to 12 and 12 to 24 before each urine sample collection). We used adjusted linear and Tobit regressions to assess associations between PCP use and phenol urinary concentrations. RESULTS: The total number of PCP applications was positively associated with ethylparaben, propylparaben and butylparaben concentrations. We observed a peak in urinary concentration of ethylparaben, butylparaben and propylparaben at 2.86, 2.55 and 2.67 hours since last PCP use, respectively and twelve different types of PCPs were positively associated with at least one of these parabens. The bisphenol S concentration increased by 12.4% (95%CI: confidence interval: 5.9; 19.3) for each additional PCP application in the 12 to 24 time window and use of specific PCPs such as anti-stretchmarks cream, facial cleanser and shower gel. Associations varied by time window. CONCLUSION: Our study showed that PCP use was associated with a short-term increase in the urinary concentration of ethylparaben, butylparaben and propylparaben, but not methylparaben. This study also reported a positive association between the use of PCPs and the bisphenol S concentration, a finding that warrants further investigation in cohorts with repeated collection of urine samples and detailed information on PCP use.

Background/Aim: Some phenols are endocrine disruptors commonly used in production of personal care products (PCP). These compounds have a short half-life and past studies have reported detection of...

Background/aim There are concerns neuro-developmental due to exposure to endocrine disrupting chemicals. Previous epidemiological studies have mainly focused on phthalate metabolites and bisphenol A. Our study aimed to assess associations between in-utero exposure to the afore mentioned compounds and other ubiquitous phenolic compounds and the Intelligence Quotient (IQ) of boys at 5–6 years. Methods In 452 mother-son dyads from the French EDEN cohort, we measured 11 phthalate metabolites and 9 phenolic compounds (4 parabens, benzophenone-3, bisphenol A, 2 dichlorophenols and triclosan) in spot urine samples collected between 22 and 29 gestational weeks. Verbal and performance IQ of children was assessed at 5–6 years by a psychologist using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). We used adjusted Structural Equation Models (SEM) and the Benjamini and Hochberg false discovery rate (FDR) correction to assess the associations between maternal urine phenol and phthalate metabolite concentrations considered simultaneously and the boys’ IQ. Results No phenol or phthalate metabolite concentration was negatively associated with child verbal or performance IQ (p-values≥0.09). Mono (3-carboxypropyl) phthalate tended to be associated with increased verbal IQ (β=0.136, 95% confidence interval, 0.01; 0.27) but this association disappeared after correction for multiple comparison (corrected p- 64 value, 0.71). Conclusion To our knowledge, our study is the first to consider developmental exposure to parabens, dichlorophenols, triclosan and benzophenone-3 in relation to child cognitive development. Our findings did not suggest an inverse association between in-utero phenols and phthalates exposure and child verbal and performance IQ.

Background: Sex-specific associations have been reported between phthalates, bisphenol A (BPA), and child behavior. No data on large study populations are available for other phenols with possible endocrine-disrupting properties. Objectives: We aimed to study associations between prenatal exposure to phthalates and several phenols on behavior among male infants. Methods: We quantified 11 phthalate metabolites and nine phenols (four parabens, benzophenone-3, BPA, two dichlorophenols, triclosan) in spot urine samples collected during pregnancy among EDEN cohort mothers who delivered a boy. Mothers completed the Strength and Difficulties Questionnaire (SDQ) when their children were 3.1 (n=529) and 5.6 (n=464) y old. Results: BPA was positively associated with the relationship problems subscale at 3 y [incidence rate ratio (IRR): 1.11; 95% confidence interval (CI): 1.03, 1.20] and the hyperactivity–inattention subscale scores at 5 y (IRR: 1.08; 95% CI: 1.01, 1.14). Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problem, and emotional symptom scores at 3 y. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 y. After dichotomizing SDQ scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 y. Conclusions: The observed associations between BPA, MnBP, and behavior in boys are consistent with previous findings. Further health impact assessment studies based on dose–response functions corrected for exposure misclassification are required to quantify the public health burden possibly entailed by such associations. https://doi.org/10.1289/EHP1314

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