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Introduction: Environmental phenols are endocrine disrupting chemicals hypothesized to affect early life development. Previous research examining the effects of phenols on fetal growth has focused primarily on associations with measures of size at delivery. Few have included ultrasound measures to examine growth across pregnancy., Objective: Investigate associations between prenatal exposure to phenols and ultrasound and delivery measures of fetal growth., Methods: Using the LIFECODES Fetal Growth Study (n = 900), a case-cohort including 248 small-for-gestational-age, 240 large-for-gestational age, and 412 appropriate-for-gestational-age births, we estimated prenatal exposure to 12 phenols using three urine samples collected during pregnancy (median 10, 24, and 35 weeks gestation). We abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-average phenol biomarker concentrations and repeated ultrasound measures of fetal growth using linear mixed effects models and associations with birthweight using linear regression models. We also used logistic regression models to estimate associations with having a small- or large-for-gestational birth., Results: We observed positive associations between 2,4-dichlorophenol, benzophenone-3, and triclosan (TCS) and multiple ultrasound measures of fetal growth. For example, TCS was associated with a 0.09 (95 % CI: 0.01, 0.18) higher estimated fetal weight z-score longitudinally across pregnancy. This effect size corresponds to a 21 g increase in estimated fetal weight at 30 weeks gestation. Associations with delivery measures of growth were attenuated, but TCS remained positively associated with birthweight z-scores (mean difference: 0.13, 95 % CI: 0.02, 0.25). Conversely, methylparaben was associated with higher odds of a small-for-gestational age birth (odds ratio: 1.45, 95 % CI: 1.06, 1.98)., Discussion: We observed associations between some biomarkers of phenol exposure and ultrasound measures of fetal growth, though associations at the time of delivery were attenuated. These findings are consistent with hypotheses that phenols have the potential to affect growth during the prenatal period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Modifiable factors, such as environmental exposures, can impact human fertility. The objective of this review is to summarize the potential effects of exposure to important endocrine-disrupting chemicals on male reproductive health. Most experimental and animal data demonstrate strong evidence for the negative effects of exposure to phenols, phthalates, pesticides, and perfluoroalkyl and polyfluoroalkyl substances on male reproductive health. Although evidence of negative associations in humans was overall strong for phthalates and pesticides, limited and inconclusive relationships were found for the other examined chemical biomarkers. Reasons for the discrepancies in results include but are not limited to, differences in study populations, exposure concentrations, number of samples collected, sample sizes, study design, and residual confounding. Additional studies are needed, particularly for newer phenols and perfluoroalkyl and polyfluoroalkyl substances, given the scarce literature on the topic and increasing exposures over time., Competing Interests: Declaration of interests L.M.A. has nothing to disclose. A.J.G. has nothing to disclose. J.D.M. has nothing to disclose. J.M.B. was financially compensated for serving as an expert witness for plaintiffs in litigation related to tobacco smoke exposures and received an honorarium for serving on an advisory board for Quest Diagnostics. J.M.B.’s institution was financially compensated for his services as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water; these funds were not paid to JMB directly. J.E.C. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological studies on children and adults have linked toxicants from plastics and personal care products to metabolic disruption. Yet, the impact of endocrine-disrupting chemicals (EDCs) on adolescent metabolic syndrome (MetS) risk during early and mid-adolescence is unclear., Methods: To examine the links between exposure to EDCs and MetS risk and its components, cross-sectional data from 344 Mexican youth in early-to-mid adolescence (10-17 years) were analyzed. Urinary biomarker concentrations of phthalates, phenol, and paraben analytes were measured from a single spot urine sample collected in 2015; study personnel obtained anthropometric and metabolic measures. We examined associations between summary phthalates and metabolites, phenol, and paraben analytes with MetS risk z-scores using linear regression, adjusted for specific gravity, sex, age, pubertal status, smoking, alcohol intake, physical activity level, and screen time. As a secondary aim, mediation analysis was conducted to evaluate the role of hormones in the association between summary phthalates with lipids and MetS risk z-scores., Results: The mean (SD) age was 13.2 (1.9) years, and 50.9% were female. Sex-stratified analyses revealed associations between summary phthalates and lipids ratio z-scores, including Σ DEHP [β = 0.21 (95% CI: 0.04, 0.37; p < 0.01)], phthalates from plastic sources (Σ Plastic) [β = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], anti-androgenic phthalates (Σ AA) [β = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], and individual phthalate metabolites (MEHHP, MEOHP, and MECPP) among males. Among females, BPA [β = 0.24 (95% CI: 0.03, 0.44; p < 0.05)] was positively associated with lipids ratio z-score and one phenol (2,5 DCP) [β = 0.09 (95% CI: 0.01, 0.18); p < 0.05)] was associated with increased waist circumference z-score. Results showed no evidence of mediation by hormone concentrations in the association between summary phthalates with lipids ratio or MetS risk z-scores., Conclusion: Higher EDC exposure was positively associated with serum lipids during adolescence, particularly among males., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endocrine-disrupting chemicals (EDCs) may impact sleep during the menopausal transition by altering sex hormones. However, these studies are scarce among Latin American women. This investigation utilized cross-sectional and retrospective data from midlife women enrolled in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study to examine associations between exposure to EDCs (phthalates, phenols, and parabens) and sleep health measures. For cross-sectional analyses, single spot urine samples were collected between 2017-2019 from a pilot sample of women (N = 91) of midlife age to estimate the urinary concentration of individual phthalates, phenols, and parabens and to calculate the summary concentration of phthalate mixtures. Seven-day nightly sleep duration, midpoint, and fragmentation were obtained from wrist-actigraphy devices and estimated from the actigraphy data using a pruned dynamic programming algorithm. Self-reported poor sleep quality was assessed by one item from the Pittsburgh Sleep Quality Index (PSQI). We examined associations between urinary summary phthalate mixtures, phthalate metabolites, phenol, and paraben analytes with each sleep measure using linear or logistic (to compute odds of poor sleep quality only) regression models adjusted for specific gravity, age, and socioeconomic status. We ran similar regression models for retrospective analyses (N = 74), except that urine exposure biomarker data were collected in 2008 when women were 24-50 years old. At the 2017-2019 midlife visit, 38% reported poor sleep quality. Cross-sectionally, EDCs were associated with longer sleep duration, earlier sleep timing, and more fragmented sleep. For example, every 1-unit IQR increase in the phenol triclosan was associated with a 26.3 min per night (95% CI: 10.5, 42.2; P < 0.05) longer sleep duration and marginally associated with 0.2 decimal hours (95% CI: -0.4, 0.0; P < 0.10) earlier sleep midpoint; while every 1-unit IQR increase in the phthalate metabolite MEHP was associated with 1.1% higher sleep fragmentation (95% CI: 0.1, 2.1; P < 0.05). Retrospective study results generally mirrored cross-sectional results such that EDCs were linked to longer sleep duration, earlier sleep timing, and more fragmented sleep. EDCs were not significantly associated with odds of self-reported poor sleep quality. Results from cross-sectional and retrospective analyses revealed that higher exposure to EDCs was predictive of longer sleep duration, earlier sleep timing, and more fragmented sleep among midlife women., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Emerging research has shed light on the potential impact of environmental toxicants on sleep health, however, it remains unclear if these associations exist during adolescence and whether associations differ by sex. This study aimed to examine associations between phthalates, parabens, and phenols on adolescent sleep health using cross-sectional data from 470 participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study., Material and Methods: In 2015, spot urine samples were analyzed for exposure biomarkers of 14 phthalate metabolites, seven phenol, and four paraben analytes. Over seven consecutive days, sleep duration, midpoint, and fragmentation were assessed with wrist-actigraphy. We examined associations between summary phthalates, individual phthalate metabolites, and phenol and paraben analytes with mean weekday sleep duration, midpoint, and fragmentation using linear regression models adjusted for specific-gravity and sex, age, pubertal status, smoking and alcohol behavior, physical activity, and screen time., Results: Mean (SD) age was 13.8 (2.1) years; 53.5 % were female. Σ Plastic - summary measure for toxicants from plastic sources - and Σ DEHP and its metabolites, were associated with longer sleep duration in the unstratified sample. To illustrate, every 1-unit log increase in Σ DEHP was associated with 7.7 min (95 % CI: 0.32, 15.1; p < 0.05) longer duration. Summary measures of toxicants from plastic sources, personal care products, anti-androgenic toxicants, and multiple individual phthalates, phenols, and parabens were associated with later midpoint. The midpoint associations were largely female-specific. There were no associations with sleep fragmentation., Conclusions: Higher EDC exposure may be related to longer sleep duration and later sleep timing during adolescence, and associations may vary by toxicant and according to sex., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations., (© 2021 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

The prevalence of Attention Deficit/Hyperactivity Disorder (ADHD) has been increasing. Research suggests that exposure to endocrine disrupting chemicals such as phthalates may play a role, but studies of in utero phthalate exposure and ADHD-related symptoms beyond early childhood are limited. We investigated associations between measures of in utero phthalate exposure and ADHD symptoms, such as inattention and impulsivity, in childhood (age 6-11 years, n = 221) and in adolescence (age 9-18 years, n = 200), as well as cross-sectional relationships between phthalate exposure and ADHD symptoms in adolescence (n = 491) among participants in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort. Women provided urine samples up to three times during pregnancy and adolescents provided a urine sample at 9-18 years of age for phthalate metabolite measurement. We administered the Conners' Continuous Performance Test (CPT) when children were age 6-11 years and again at 9-18 years of age. We used multivariable linear regression to examine associations between the geometric mean of phthalate metabolite levels across pregnancy and CPT scores in childhood or adolescence separately, adjusting for age, years schooling (at 9-18 only), maternal education, and specific gravity. Although average in utero phthalate concentrations were not associated with CPT scores in childhood, interquartile range (IQR) increases of in utero MBzP, MCPP, and MBP were associated with 4.2%, 4.7%, and 4.5% (p < 0.05) higher Omissions scores in adolescence, respectively, indicating higher inattention. In utero MiBP levels were also associated with higher Inter-Stimulus Interval (ISI) and Variability scores (5.4% and 5.5% per IQR, p < 0.05) in adolescence. In addition, urinary DEHP metabolite levels during adolescence were cross-sectionally associated with poorer scores on several CPT indices indicating greater inattention. These findings suggest that in utero phthalate exposure may have adverse effects on attention, but these effects may not appear until adolescence, a period of extensive neurodevelopment. Future research investigating the long-term effects of in utero phthalate exposure on attention and ADHD in adolescence, as well as identification of potential mechanisms involved, is needed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Polybrominated diphenyl ethers (PBDEs) have been phased out of production for nearly a decade yet are still frequently detected in serum of U.S. adults. PBDE concentrations have been associated with adverse reproductive outcomes and laboratory studies suggest hydroxylated-BDEs (OH-BDEs) may act as endocrine disruptors. We set out to assess the joint effects of paternal and maternal serum PBDE concentrations on in vitro fertilization (IVF) outcomes and the association between paternal serum OH-BDE concentrations and IVF outcomes., Methods: This analysis included 189 couples (contributing 285 IVF cycles) recruited between 2006 and 2016 from a longitudinal cohort based at Massachusetts General Hospital Fertility Center who completed at least one IVF cycle and had an available blood sample at study entry. Congeners (47, 99, 100, 153, and 154) and OH-BDEs (3-OH-BDE47, 5-OH-BDE47, 6-OH-BDE47 and 4-OH-BDE49) were quantified in serum. Log-transformed PBDEs and OH-BDEs were modeled in quartiles for associations with IVF outcomes using multivariable generalized mixed models and cluster weighted generalized estimating equations., Results: Lipid-adjusted concentrations of PBDEs and OH-BDEs were higher in females than in male partners. There were no clear patterns of increases in risk of adverse IVF outcomes associated with PBDEs and OH-BDEs. However, some decreases in associations with IVF outcomes were observed in isolated quartiles., Conclusions: Our assessment of couple level exposure is unique and highlights the importance of including male and female exposures in the assessment of the influence of environmental toxicants on pregnancy outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are byproducts of incomplete combustion reactions and are ubiquitous in the environment, leading to widespread human exposure via inhalation and ingestion pathways. PAHs have been implicated as endocrine disrupting compounds in previous animal and in vitro studies, but human studies are currently lacking. Pregnant women and their developing fetuses are particularly susceptible populations to environmental contaminants, in part because alterations in hormone physiology during gestation can have adverse consequences on the health of the pregnancy. We utilized data on 659 pregnant women from the PROTECT longitudinal birth cohort in Puerto Rico to assess associations between repeated measures of 8 urinary hydroxylated PAH (OH-PAH) metabolites and 9 serum hormones during gestation. Urine samples were collected at 3 study visits (median gestational ages of 18, 22, and 26 weeks at each visit, respectively) and serum samples were collected at the first and third study visits. Linear mixed effects models were used to ascertain longitudinal associations between OH-PAHs and hormones, and sensitivity analyses were employed to assess potential nonlinearity and differences in associations on the basis of fetal sex and timing of biomarker measurement. Among the multiple positive associations we observed between OH-PAHs and CRH, estriol, progesterone, T3, and the ratio of T3 to T4, and inverse associations with testosterone, the most notable are a 24.3% increase (95% CI: 13.0, 36.7) in CRH with an interquartile range (IQR) increase in 1-hydroxyphenanthrene and a 17.2% decrease (95% CI: 8.13, 25.4) in testosterone with an IQR increase in 1-hydroxynapthalene. Many associations observed were dependent on fetal sex, and some relationships showed evidence of nonlinearity. These findings demonstrate the importance of studying PAH exposures during pregnancy and highlight the potential complexity of their impacts on the physiology of human pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The postpartum period may be a vulnerable life stage for a woman's cardiometabolic health. We examined associations of exposure to common endocrine-disrupting chemicals (EDCs) during pregnancy with weight from delivery through 1 year postpartum among 199 women in Mexico City. Materials and Methods: During each trimester of pregnancy, we collected a urine sample to assay bisphenol A (BPA), mono- n -butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and monoethyl phthalate (MEP). We calculated summary scores for di-2-ethylhexyl phthalate metabolites (ΣDEHP) and dibutyl phthalate metabolites (ΣDBP). We calculated the geometric mean of each EDC across pregnancy for use in the analysis. At delivery and three additional times during the first year postpartum, we measured the women's weight. We used mixed-effects linear regression models to estimate associations of each EDC with weight at delivery (kg) and weight change (kg/year) from delivery through 1 year postpartum. Covariates included urinary specific gravity, maternal age, parity, height, first trimester body mass index, and gestational age at enrollment. Results: Mean ± standard deviation weight change during the first postpartum year was -0.49 ± 4.04 kg. The EDCs were inversely associated with weight at delivery, but positively associated with weight change through 1 year postpartum. For example, each interquartile range of urinary ΣDEHP corresponded with 1.38 (95% confidence interval: 0.44-2.33) kg lower weight at delivery and 1.01 (0.41--1.61) kg/year slower rate of weight loss. We observed similar associations for other EDCs. Conclusions: Prenatal exposure to EDCs is associated with lower weight at delivery, but slower rate of weight loss through the first postpartum year.

Context: Early pregnancy exposure to endocrine disrupting chemicals (EDCs) may contribute to poor birth outcomes through oxidative stress (OS)-mediated disruption of the maternal and fetal milieu. Most studies have investigated the effect of single EDC exposures on OS., Objective: Assess the association of uniquely weighted mixtures of early pregnancy exposures with the maternal and neonatal OS markers., Design: Prospective analysis of mother-infant dyads., Setting: University hospital., Participants: 56 mother-infant dyads., Main Outcome Measures: The association of OS markers (nitrotyrosine, dityrosine, chlorotyrosine) in maternal first trimester and term, and cord blood plasma with maternal first trimester exposure levels of each of 41 toxicants (trace elements, metals, phenols, and phthalates) from 56 subjects was analyzed using Spearman correlations and linear regression. The association of OS markers with inflammatory cytokines and birth outcomes were analyzed by Spearman correlation and linear regression analysis, respectively. Weighted mixtures of early pregnancy exposures were created by principal component analysis and offspring sex-dependent and independent associations with oxidative stress markers were assessed., Results: (1) An inverse relationship between levels of maternal/cord OS markers and individual EDCs was evident. In contrast, when assessed as EDC mixtures, both direct and inverse associations were evident in a sex-specific manner; (2) the maternal term OS marker, nitrotyrosine, was inversely associated with gestational age, and (3) both direct and inverse associations were evident between the 3 OS markers and individual cytokines., Conclusions: Provides proof of concept that effects of exposures on OS varies when assessed as EDC mixtures versus individually., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is increasing evidence that several metals are endocrine disrupting chemicals (EDCs). In utero development and adolescence are critical windows of susceptibility to EDC exposure. With the exception of a few heavy metals, few human studies have evaluated the impact of metal exposure on pubertal development. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among girls from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. We measured urinary concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), and zinc (Zn) in samples collected from women during their third trimester of pregnancy and from their female children at 8-13 years (n = 132). We measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) at age 8-13, and assessed Tanner stages for sexual maturation (breast, pubic hair development, and menarche status), at two time points (8-13, 14-18 years). We used linear regression to independently examine in utero and peripubertal metal concentrations as predictors of peripubertal hormones. In a longitudinal analysis using generalized estimation equations, we evaluated Tanner stage and menarche progression in relation to individual in utero and peripubertal metal concentrations. We found that higher in utero Zn was associated with increased inhibin B. Several metals at 8-13 years were associated with higher DHEA-S and estradiol, while Ni was positively but Cu was negatively associated with testosterone. In utero Ni, Al, and Cd were associated with slower progression of breast development after adjustment for child age and BMI z-score. For example, an IQR increase in in utero Al exposure was associated with 0.82 times lower odds of progressing to a higher Tanner stage for breast development per year (95% CI: 0.68, 0.99). Peripubertal concentrations of Ba and Al were also associated with being at a higher pubic hair Tanner stage and menarche at 8-13, but lower odds of progressing to the next stage at 14-18 years. We used Bayesian kernel machine regression (BKMR) to model the joint effect of multiple metals while accounting for correlated exposures, as well as potential non-linear relationships between metals and outcomes of interest, which yielded results similar to individual analyses. These findings suggest that female reproductive development may be vulnerable to the effects of metal exposure, and using both Tanner stages and hormone levels may provide clues about underlying mechanisms in two sensitive periods of development., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exposures to endocrine disrupting chemicals and metals are near ubiquitous worldwide, and their potential impact on children is a major public health concern. This pilot study was designed to characterize exposures to phthalates, phenols and metals among pregnant women in the first trimester, and to examine associations with fetal biometrics and birth weight. A total of 41 chemicals and elements were analyzed in urine from 56 mothers with full-term newborns from the Michigan Mother-Infant Pairs study. Bivariate analyses identified predictors of exposure biomarkers. Associations between birth weight, Fenton z-scores and second trimester fetal biometrics with toxicants were examined via multivariable linear regression. An average of 30 toxicants were detected in maternal urine. Fast food consumption was associated with several phthalate metabolites, phenols and metals, and canned food consumption with bisphenol F (P &lt;0.05). Mono (3-carboxypropyl) phthalate was significantly associated with higher birth weight and Fenton z-score while the opposite was observed for bisphenol S. Estimated femur length from ultrasonography was significantly inversely associated with arsenic, barium and lead. While limited by sample size, this study is one of the first to evaluate birth outcomes with respect to emerging endocrine disrupting chemicals and to examine associations between toxicants and fetal biometrics. Exposure assessment was provided by the National Institute of Environmental Health Sciences' Children's Health Exposure Analysis Resource (NIEHS CHEAR), a resource available to children's studies with the goal of combining data across cohorts in an effort to characterize the impact of toxicants on child health from birth and beyond.

Background: A number of phenols and parabens are added to consumer products for a variety of functions, and have been found at detectable levels in the majority of the U.S., Population: Among other functions, thyroid hormones are essential in fetal neurodevelopment, and could be impacted by the endocrine disrupting effects of phenols and parabens. The present study investigated the association between ten maternal urinary phenol and paraben biomarkers (bisphenol S, triclosan, triclocarban, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and ethyl, butyl, methyl and propyl paraben) and four plasma thyroid hormones in 439 pregnant women in a case-control sample nested within a cohort study based in Boston, MA., Methods: Urine and blood samples were collected from up to four visits during pregnancy (median weeks of gestation at each visit: Visit 1: 9.64, Visit 2: 17.9, Visit 3: 26.0, Visit 4: 35.1). Linear mixed models were constructed to take into account the repeated measures jointly, followed by multivariate linear regression models stratified by gestational age to explore potential windows of susceptibility., Results: We observed decreased total triiodothyronine (T3) in relation to an IQR increase in benzophenone-3 (percent change [%Δ] = -2.07; 95% confidence interval [CI] = -4.16, 0.01), butyl paraben (%Δ = -2.76; 95% CI = -5.25, -0.26) and triclosan (%Δ = -2.53; 95% CI = -4.75, -0.30), and triclocarban at levels above the LOD (%Δ = -5.71; 95% CI = -10.45, -0.97). A 2.41% increase in T3 was associated with an IQR increase in methyl paraben (95% CI = 0.58, 4.24). We also detected a negative association between free thyroxine (FT4) and propyl paraben (%Δ = -3.14; 95% CI = -6.12, -0.06), and a suggestive positive association between total thyroxine (T4) and methyl paraben (%Δ = 1.19; 95% CI = -0.10, 2.47). Gestational age-specific multivariate regression analyses showed that the magnitude and direction of some of the observed associations were dependent on the timing of exposure., Conclusion: Certain phenols and parabens were associated with altered thyroid hormone levels during pregnancy, and the timing of exposure influenced the association between phenol and paraben, and hormone concentrations. These changes may contribute to downstream maternal and fetal health outcomes. Additional research is required to replicate the associations, and determine the potential biological mechanisms underlying the observed associations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Endocrine disrupting chemicals (EDCs) pose a public health risk through disruption of normal biological processes. Identifying toxicoepigenetic mechanisms of developmental exposure-induced effects for EDCs, such as phthalates or bisphenol A (BPA), is essential. Here, we investigate whether maternal exposure to EDCs is predictive of infant DNA methylation at candidate gene regions. In the Michigan Mother-Infant Pairs (MMIP) cohort, DNA was extracted from cord blood leukocytes for methylation analysis by pyrosequencing (n = 116) and methylation changes related to first trimester levels of 9 phthalate metabolites and BPA. Growth and metabolism-related genes selected for methylation analysis included imprinted (IGF2, H19) and non-imprinted (PPARA, ESR1) genes along with LINE-1 repetitive elements. Findings revealed decreases in methylation of LINE-1, IGF2, and PPARA with increasing phthalate concentrations. For example, a log unit increase in ΣDEHP corresponded to a 1.03 [95% confidence interval (CI): -1.83, -0.22] percentage point decrease in PPARA methylation. Changes in DNA methylation were also inversely correlated with PPARA gene expression determined by RT-qPCR (r = -0.34, P = 0.02), thereby providing evidence in support of functional relevance. A sex-stratified analysis of EDCs and DNA methylation showed that some relationships were female-specific. For example, urinary BPA exposure was associated with a 1.35 (95%CI: -2.69, -0.01) percentage point decrease in IGF2 methylation and a 1.22 (95%CI: -2.27, -0.16) percentage point decrease in PPARA methylation in females only. These findings add to a body of evidence suggesting epigenetically labile regions may provide a conduit linking early exposures with disease risk later in life and that toxicoepigenetic susceptibility may be sex specific.

Background: Over the past several decades, the age of pubertal onset in girls has shifted downward worldwide. As early pubertal onset is associated with increased risky behavior and psychological issues during adolescence and cardiometabolic disease and cancer in adulthood, this is an important public health concern. Exposure to endocrine disrupting chemicals during critical windows of in utero development may play a role in this trend. Our objective was to investigate trimester-specific phthalate and BPA exposure in relation to pubertal development among girls in the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort., Methods: We measured maternal urinary phthalate metabolites and BPA in samples collected during the first, second, and third trimesters of pregnancy. To assess reproductive development among their female children, we measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation, including Tanner staging for breast and pubic hair development and menarche status, at age 8-13 years (n = 120). We used linear and logistic regression to examine measures of trimester-specific in utero exposure as predictors of peripubertal hormone levels and pubertal onset, respectively. In secondary analyses, we evaluated estimated exposure at the midpoint of the first trimester and rates of change in exposure across pregnancy in relation to outcomes., Results: Several phthalate metabolites measured throughout in utero development were associated with higher serum testosterone concentrations, while a number of metabolites measured in the third trimester were associated with higher DHEA-S. For example, an interquartile range (IQR) increase in mean monoethyl phthalate (MEP) levels across pregnancy was associated with 44% higher peripubertal testosterone (95% CI: 13-83%), while an IQR increase in di-2-ethylhexyl phthalate metabolites (ΣDEHP) specifically in the third trimester was associated with 25% higher DHEA-S (95%CI: 4.7-47%). In IQR increase in mean mono-2-ethylhexyl phthalate (MEHP) levels across pregnancy was associated with lower odds of having a Tanner Stage >1 for breast development (OR = 0.32, 95%CI: 0.11-0.95), while MEHP in the third trimester was associated with higher odds of having a Tanner Stage >1 for pubic hair development (OR = 3.76, 95%CI: 1.1-12.8). Results from secondary analyses were consistent with findings from our main analysis., Conclusion: These findings suggest that female reproductive development may be more vulnerable to the effects of phthalate or BPA exposure during specific critical periods of in utero development. This highlights the need for comprehensive characterizations of in utero exposure and consideration of windows of susceptibility in developmental epidemiological studies. Future research should consider repeated measures of in utero phthalate and BPA exposure within each trimester and across pregnancy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: In addition to its well-established role in maintaining skeletal health, vitamin D has essential regulatory functions in female reproductive and pregnancy outcomes. Phthalates and bisphenol A (BPA) are endocrine disruptors, and previous research has suggested that these chemical agents may disrupt circulating levels of total 25(OH)D in adults., Objectives: We investigated the relationships between repeated measures of urinary phthalate metabolites and BPA and circulating total 25(OH)D in a prospective cohort of pregnant women., Methods: The present study population includes participants (n=477) in a nested case-control study of preterm birth drawn from a prospective birth cohort of pregnant women at Brigham and Women's Hospital in Boston, Massachusetts. Urine and blood samples were collected for biomarker measurements at median 10 wk and 26 wk of gestation., Results: In repeated measures analysis, we observed that an interquartile range (IQR) increase in urinary mono-3-carboxypropyl phthalate (MCPP) was associated with a 4.48% decrease [95% confidence interval (CI): -7.37, -1.58] in total 25(OH)D. We also detected inverse associations for metabolites of di(2-ethylhexyl) phthalate (DEHP) [percent difference (%Δ)=-2.83 to -2.16]. For BPA, we observed a nonsignificant inverse association with total 25(OH)D in the overall population. Our sensitivity analysis revealed that the associations for some metabolites (e.g., MEHP) varied by race/ethnicity, which may reflect potential differences in susceptibility. In agreement with findings from repeated measures analysis, we reported that DEHP metabolites and BPA were significantly associated with an approximate 20% increase in the odds of vitamin D deficiency (≤20 ng/mL) [odds ratio (95% CI): 1.19 (1.06, 1.35) for molar sum of DEHP metabolites and 1.22 (1.01, 1.47) for BPA] at median 10 wk and 26 wk, respectively., Conclusions: Our results provide suggestive evidence of the potential for environmental exposure to phthalates and/or BPA to disrupt circulating vitamin D levels in pregnancy. https://doi.org/10.1289/EHP1178.

Animal models indicate that endocrine disrupting chemicals (EDCs) affect circulating lipid concentrations by interfering with hepatic fatty acid oxidation. Little is known of the relationship between EDC exposure and lipid profile in humans. We measured bisphenol A (BPA) and 9 phthalate metabolites in maternal urine collected at up to three time points during pregnancy as a measure of in utero exposure, and in the child's urine at 8-14 years as a measure of concurrent, peripubertal exposure among 248 participants of a Mexico City pre-birth cohort. We used linear regression to examine relations of BPA and phthalate exposure with peripubertal serum lipids, while also adjusting for child age, sex, and specific gravity. While in utero EDC exposure was not associated with lipid profile, higher concurrent levels of mono-3-carboxypropyl phthalate (MCPP), monoethyl phthalate (MEP), and dibutyl phthalate metabolites (DBP) corresponded with lower total cholesterol and low-density lipoprotein (LDL-C) in boys; e.g., an interquartile range increment in MCPP corresponded with 7.4% (2.0%, 12.8%) lower total cholesterol and 12.7% (3.8%, 21.6%) lower LDL-C. In girls, higher urinary di-2-ethylhexyl phthalate metabolites (ΣDEHP) correlated with lower LDL-C (-7.9% [-15.4%, -0.4%]). Additional longitudinal research is needed to determine whether these associations persist beyond adolescence., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Bisphenol-A (BPA) exposure occurs commonly and may adversely impact pregnancy. Endocrine disruption is posited as the primary mechanism of action, but oxidative stress and inflammation pathways may also be important. We investigated associations between BPA exposure and oxidative stress and inflammation in 482 pregnant women. Participants were recruited early in pregnancy and provided urine and plasma at up to four visits. We measured total BPA and two biomarkers of oxidative stress (8-hydroxydeoxyguanosine and 8-isoprostane) in urine from each visit. Inflammation markers, including C-reactive protein and four cytokines were measured in plasma from the same time points. In adjusted models, an interquartile range increase in BPA was associated with significant increases in both oxidative stress biomarkers (5-9% increase). Additionally, we observed significantly higher IL-6 concentrations in association with an interquartile range increase in BPA (8.95% increase). These systemic changes consequent to BPA exposure may mediate adverse birth outcomes and/or fetal development., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Context: Exposure to endocrine-disrupting chemicals during development may play a role in the increasing prevalence of metabolic syndrome and type 2 diabetes among children and adolescents by interfering with metabolic homeostasis., Objective: To explore associations between in utero and peripubertal urinary phthalate metabolite and bisphenol A (BPA) concentrations and markers of peripubertal metabolic homeostasis., Design: Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT): a longitudinal cohort study of pregnant women in Mexico City and their offspring., Setting: Public maternity hospitals in Mexico City., Patients or Other Participants: Women recruited during pregnancy; offspring recruited for follow-up at age 8-14 years (n = 250)., Interventions: None., Main Outcome Measures: Fasting serum c-peptide, IGF-1, leptin, and glucose concentrations among children at follow-up; calculated measures of insulin secretion and insulin resistance., Results: Phthalate metabolites and BPA were associated with metabolism biomarkers at age 8-14 years in patterns that varied by sex, pubertal status, and exposure timing. For example, in utero monoethyl phthalate was associated with lower insulin secretion among pubertal boys (P = .02) and higher leptin among girls (P = .04). In utero di-2-ethylhexyl phthlate was associated with higher IGF-1 among pubertal girls; peripubertal di-2-ethylhexyl phthlate was associated with higher IGF-1, insulin secretion, and resistance among prepubertal girls. In contrast, peripubertal dibutyl phthalate, monobenzyl phthalate, and mono-3-carboxypropyl phthalate were associated with lower IGF-1 among pubertal boys. Peripubertal BPA was associated with higher leptin in boys (P = .01)., Conclusions: Considering the long-term health effects related to metabolic syndrome, additional research on exposure and metabolic outcomes across developmental periods and early adulthood is needed.

Background: The past decade has seen numerous human health studies seeking to characterize the impacts of environmental exposures, such as organophosphate (OP) insecticides, on male reproduction. Despite an extensive literature on OP toxicology, many hormone-mediated effects on the testes are not well understood., Objectives: This study investigated environmental exposures to OPs and their association with the frequency of sperm chromosomal abnormalities (i.e., disomy) among adult men., Methods: Men (n=159) from a study assessing the impact of environmental exposures on male reproductive health were included in this investigation. Multi-probe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine XX18, YY18, XY18 and total disomy in sperm nuclei. Urine was analyzed using gas chromatography coupled with mass spectrometry for concentrations of dialkyl phosphate (DAP) metabolites of OPs [dimethylphosphate (DMP); dimethylthiophosphate (DMTP); dimethyldithiophosphate (DMDTP); diethylphosphate (DEP); diethylthiophosphate (DETP); and diethyldithiophosphate (DEDTP)]. Poisson regression was used to model the association between OP exposures and disomy measures. Incidence rate ratios (IRRs) were calculated for each disomy type by exposure quartiles for most metabolites, controlling for age, race, BMI, smoking, specific gravity, total sperm concentration, motility, and morphology., Results: A significant positive trend was seen for increasing IRRs by exposure quartiles of DMTP, DMDTP, DEP and DETP in XX18, YY18, XY18 and total disomy. A significant inverse association was observed between DMP and total disomy. Findings for total sum of DAP metabolites concealed individual associations as those results differed from the patterns observed for each individual metabolite. Dose-response relationships appeared nonmonotonic, with most of the increase in disomy rates occurring between the second and third exposure quartiles and without additional increases between the third and fourth exposure quartiles., Conclusions: This is the first epidemiologic study of this size to examine the relationship between environmental OP exposures and human sperm disomy outcomes. Our findings suggest that increased disomy rates were associated with specific DAP metabolites, suggesting that the impacts of OPs on testis function need further characterization in epidemiologic studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Octylphenol (OP) and Trichlorophenol (TCP) act as endocrine disruptors and have effects on male reproductive function. We studied the interactions between 4-tert-Octylphenol (4-t-OP), 4-n- Octylphenol (4-n-OP), 2,3,4-Trichlorophenol (2,3,4-TCP), 2,4,5-Trichlorophenol (2,4,5-TCP) urinary exposure levels and polymorphisms in selected xenobiotic metabolism enzyme genes among 589 idiopathic male infertile patients and 396 controls in a Han-Chinese population. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to measure alkylphenols and chlorophenols in urine. Polymorphisms were genotyped using the SNPstream platform and the Taqman method. Among four phenols that were detected, we found that only exposure to 4-t-OP increased the risk of male infertility (P(trend) = 1.70×10(-7)). The strongest interaction was between 4-t-OP and rs4918758 in CYP2C9 (P(inter) = 6.05×10(-7)). It presented a significant monotonic increase in risk estimates for male infertility with increasing 4-t-OP exposure levels among men with TC/CC genotype (low level compared with non-exposed, odds ratio (OR) = 2.26, 95% confidence intervals (CI) = 1.06, 4.83; high level compared with non-exposed, OR = 9.22, 95% CI = 2.78, 30.59), but no associations observed among men with TT genotype. We also found interactions between 4-t-OP and rs4986894 in CYP2C19, and between rs1048943 in CYP1A1, on male infertile risk (P(inter) = 8.09×10(-7), P(inter) = 3.73×10(-4), respectively).We observed notable interactions between 4-t-OP exposure and metabolism enzyme gene polymorphisms on idiopathic infertility in Han-Chinese men.

Exposure to exogenous chemicals can affect endocrine function at multiple sites and through numerous specific modes of action, which may have far-reaching effects on human health and development. Widespread human exposure to known or suspected endocrine disrupting chemicals (EDCs) has been documented in the United States and worldwide, as have trends for increased rates of endocrine-related diseases and disorders among children. While human epidemiology studies of exposure to EDCs and children's health remain extremely limited, a growing body of evidence shows that exposure to a number of chemicals commonly found in consumer goods, personal care products, food, drinking water, and other sources may adversely affect child development through altered endocrine function. This narrative review provides a brief introduction to several common EDCs (with a specific focus on persistent organic pollutants, phthalates, bisphenol A, and contemporary-use pesticides, which represent only a small number of all known or suspected EDCs), an overview of the state of the human evidence for adverse effects of EDCs on child development (fetal growth, early reproductive tract development, pubertal development, neurodevelopment, and obesity), guidance for health care providers based on current knowledge, and recommendations for future research.

Bisphenol A (BPA) impairs spermatogenesis in animals, but human studies are lacking. We measured urinary BPA concentrations, semen quality, and sperm DNA damage (comet assay) in 190 men recruited through an infertility clinic. BPA was detected in 89% of samples, with a median (interquartile range [IQR]) concentration of 1.3 (0.8-2.5) ng/mL. Urinary BPA concentration was associated with slightly elevated, though not statistically significant, odds for below reference sperm concentration, motility, and morphology. When modeled as continuous dependent variables, an IQR increase in urinary BPA concentration was associated with declines in sperm concentration, motility, and morphology of 23% (95%CI -40%, -0.3%), 7.5% (-17%, +1.5%), and 13% (-26%, -0.1%), respectively, along with a 10% (0.03%, 19%) increase in sperm DNA damage measured as the percentage of DNA in comet tail. In conclusion, urinary BPA may be associated with declined semen quality and increased sperm DNA damage, but confirmatory studies are needed., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Human exposure to environmental endocrine disrupting compounds (EDCs) have received increased attention in recent years due to the documentation of widespread exposure to a number of EDCs among the general population, experimental data demonstrating endocrine-related effects on reproduction, development, metabolism, and cancer, and observations for increasing trends (as well as geographic trends) in endocrine-related disorders among populations. However, human studies of exposure to most environmental EDCs in relation to adverse health outcomes remain limited. This review focuses on the human data generated to date on the relationship between exposures to environmental EDCs and men's health. The agents discussed here, which include polychlorinated biphenyls (PCBs), pesticides, phthalates, bisphenol A (BPA), and polybrominated diphenyl ethers (PBDEs), were chosen based on their exposure prevalence and the presence of existing human data in studies of male reproductive health, altered reproductive and thyroid hormone levels, diabetes and/or metabolic syndrome, and endocrine-related cancers. Taken together, the epidemiologic data on the environmental EDCs suggest that there may be associations between exposure and adverse health outcomes in men. However, the limited human data, and in many instances inconsistent data across studies, highlight the need for further research on these chemicals. Future longitudinal molecular epidemiology studies with appropriately designed exposure assessments are needed to determine potential causal relationships, to identify the most important time windows/life stages of exposure, and to define individual susceptibility factors for adverse effects on men's health in response to exposure., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

BackgroundPhthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs.MethodsIn this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery.FindingsWe identified 5006 mother-child dyads from 13 cohorts in the ECHO Program. Phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) were most strongly associated with gestational age, birth length, and birthweight, especially compared with DEHP or other metabolite groupings. Although DEHP was associated with preterm birth (odds ratio 1·45 [95% CI 1·05-2·01]), the risks per log10 increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion).InterpretationIn a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class.FundingNational Institutes of Health.

BackgroundWidespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results.ObjectivesWe conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex.MethodsWe included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex.ResultsThree OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z-scores (β for detect vs. nondetect=0.04-0.07); other chemicals showed null associations.DiscussionIn the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently included in the U.S. biomonitoring were detected in ≥90% of samples: benzophenone-1, thiamethoxam, mono-2-(propyl-6-carboxy-hexyl) phthalate, monocarboxy isooctyl phthalate, and monohydroxy-iso-decyl phthalate. Many analyte concentrations were higher among women of Hispanic ethnicity compared to those of non-Hispanic White women. Concentrations of certain chemicals decreased with the calendar year, whereas concentrations of their replacements increased. Our largest study to date identified widespread exposures to prevalent and understudied chemicals in a diverse sample of pregnant women in the U.S.

Background: The postpartum period may be a vulnerable life stage for a woman's cardiometabolic health. We examined associations of exposure to common endocrine-disrupting chemicals (EDCs) during pregnancy with weight from delivery through 1 year postpartum among 199 women in Mexico City. Materials and Methods: During each trimester of pregnancy, we collected a urine sample to assay bisphenol A (BPA), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and monoethyl phthalate (MEP). We calculated summary scores for di-2-ethylhexyl phthalate metabolites (ΣDEHP) and dibutyl phthalate metabolites (ΣDBP). We calculated the geometric mean of each EDC across pregnancy for use in the analysis. At delivery and three additional times during the first year postpartum, we measured the women's weight. We used mixed-effects linear regression models to estimate associations of each EDC with weight at delivery (kg) and weight change (kg/year) from delivery through 1 year postpartum. Covariates included urinary specific gravity, maternal age, parity, height, first trimester body mass index, and gestational age at enrollment. Results: Mean ± standard deviation weight change during the first postpartum year was -0.49 ± 4.04 kg. The EDCs were inversely associated with weight at delivery, but positively associated with weight change through 1 year postpartum. For example, each interquartile range of urinary ΣDEHP corresponded with 1.38 (95% confidence interval: 0.44-2.33) kg lower weight at delivery and 1.01 (0.41--1.61) kg/year slower rate of weight loss. We observed similar associations for other EDCs. Conclusions: Prenatal exposure to EDCs is associated with lower weight at delivery, but slower rate of weight loss through the first postpartum year. [ABSTRACT FROM AUTHOR]

Environmental phenols are used commonly in personal care products and exposure is widespread in pregnant women. In this study, we sought to assess the association between maternal urinary phenol concentrations in pregnancy and fetal growth. The study population included 476 mothers who participated in the prospective LIFECODES birth cohort between 2006 and 2008 at Brigham and Women's Hospital in Boston, Massachusetts, USA. Dichlorophenols (DCPs), benzophenone-3, parabens, triclosan, triclocarban, and bisphenol-S were measured in urine from three time points during pregnancy and averaged. Outcome measures were all standardized to create gestational-age specific z-scores and included: 1) birth weight; 2) ultrasound parameters measured at up to two time points in pregnancy (head and abdominal circumference and femur length); and 3) ultrasound estimates of fetal weight from two time points in combination with birth weight. Models were stratified to investigate sex differences. Inverse associations were observed between average 2,4- and 2,5-DCP concentrations and birth weight z-scores in males. For example, an interquartile range difference in 2,4-DCP was associated with a 0.18 standard deviation decrease in birth weight z-score (95% confidence interval [CI] = − 0.33, − 0.02). These associations were observed in models that included repeated ultrasound estimates of fetal weight during gestation as well. Also in males, we noted inverse associations between average triclosan exposure over pregnancy and estimated fetal weight combined with birth weight in repeated measures models. For females, associations were generally null. However, mothers with a detectable concentration of bisphenol-S at any of the study visits had lower weight females. In conclusion, we observed inverse associations between indicators of maternal phenol exposure during pregnancy and fetal growth, with several differences observed by sex. [ABSTRACT FROM AUTHOR]

Background: Phthalates and BPA are endocrine disrupting chemicals (EDCs) widely used in consumer products. Evidence suggests that phthalate and BPA exposure alters steroid hormone levels in adults, while in utero exposure has been associated with altered fetal reproductive development in boys. However, the impact of exposure during distinct critical windows of in utero development on hormone concentrations and sexual maturation during the pubertal transition has not been examined. The objective of this study was to assess trimester-specific in utero phthalate and BPA exposure in relation to measures of reproductive development among peripubertal boys in a Mexico City birth cohort.Methods: We measured maternal urinary phthalate metabolites and BPA during the first, second, and third trimesters of pregnancy. We measured serum levels of testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation (Tanner staging and testicular volume) among male children at age 8-14 years (n = 109). Linear and logistic regression were used to investigate trimester-specific in utero exposure as predictors of peripubertal hormone levels and sexual maturation, respectively. In sensitivity analyses we evaluated estimated exposure at 7 weeks gestation and rates of change in exposure across pregnancy in relation to outcomes.Results: Exposure to phthalates during the third trimester was associated with reduced odds of having a Tanner stage >1 for pubic hair development (e.g. MBzP OR = 0.18 per interquartile range (IQR) increase; 95% CI:0.03-0.97) and higher peripubertal SHBG levels (e.g. MBzP 15.2%/IQR; 95% CI:3.2-28%), while first and second trimester phthalates were not. In contrast, exposure to DEHP during the first trimester was associated with higher estradiol (11%/IQR; 95% CI:1.5-22%), while second or third trimester DEHP exposure was not. Sensitivity analyses yielded similar findings.Conclusions: Associations between in utero phthalate and BPA exposure and peripubertal measures of male reproductive development are dependent on the timing of that exposure during gestation. These findings suggest that future epidemiological studies relating in utero EDC exposure to pubertal outcomes should consider windows of susceptibility. [ABSTRACT FROM AUTHOR]

Growth of the fetus is highly sensitive to environmental perturbations, and disruption can lead to problems in pregnancy as well as later in life. This study investigates the relationship between maternal exposure to common plasticizers in pregnancy and fetal growth. Participants from a longitudinal birth cohort in Boston were recruited early in gestation and followed until delivery. Urine samples were collected at up to four time points and analyzed for concentrations of phthalate metabolites and bisphenol A (BPA). Ultrasound scans were performed at four time points during pregnancy for estimation of growth parameters, and birthweight was recorded at delivery. Growth measures were standardized to a larger population. For the present analysis we examined cross-sectional and repeated measures associations between exposure biomarkers and growth estimates in 482 non-anomalous singleton pregnancies. Cross-sectional associations between urinary phthalate metabolites or BPA and growth indices were imprecise. However, in repeated measures models, we observed significant inverse associations between di-2-ethylhexyl phthalate (DEHP) metabolites and estimated or actual fetal weight. An interquartile range increase in summed DEHP metabolites was associated with a 0.13 standard deviation decrease in estimated or actual fetal weight (95% confidence interval = − 0.23, − 0.03). Associations were consistent across different growth parameters (e.g., head circumference, femur length), and by fetal sex. No consistent associations were observed for other phthalate metabolites or BPA. Maternal exposure to DEHP during pregnancy was associated with decreased fetal growth, which could have repercussive effects. [ABSTRACT FROM AUTHOR]

Puerto Rico has higher rates of a range of endocrine-related diseases and disorders compared to the United States. However, little is known to date about human exposures to known or potential endocrine disrupting chemicals (EDCs) in Puerto Rico. We recruited 105 pregnant women in Northern Puerto Rico who provided urine samples and questionnaire data at three times (18 ± 2, 22 ± 2, and 26 ± 2 weeks) during gestation. We measured the urinary concentrations of five phenols and three parabens: 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP), benzophenone-3 (BP-3), bisphenol A (BPA), triclosan (TCS), butyl paraben (B-PB), methyl paraben (M-PB), and propyl paraben (P-PB). The frequent detection of these chemicals suggests that exposure is highly prevalent among these Puerto Rican pregnant women. Urinary concentrations of TCS, BP-3, and 25-DCP were higher than among women of reproductive age in the US general population, while concentrations of BPA, 24-DCP, and parabens were similar. Intraclass correlation coefficients (ICC) varied widely between biomarkers; BPA had the lowest ICC (0.24) and BP-3 had the highest (0.62), followed by 25-DCP (0.49) and TCS (0.47). We found positive associations between biomarker concentrations with self-reported use of liquid soap (TCS), sunscreen (BP-3), lotion (BP-3 and parabens), and cosmetics (parabens). Our results can inform future epidemiology studies and strategies to reduce exposure to these chemicals or their precursors. [ABSTRACT FROM AUTHOR]

Background: The role of environmental pesticide exposures, such as pyrethroids, and their relationship to sperm abnormalities are not well understood. This study investigated whether environmental exposure to pyrethroids was associated with altered frequency of sperm sex chromosome disomy in adult men.Methods: A sample of 75 subjects recruited through a Massachusetts infertility clinic provided urine and semen samples. Individual exposures were measured as urinary concentrations of three pyrethroid metabolites ((3-phenoxybenzoic acid (3PBA), cis- and trans- 3-(2,2-Dichlorovinyl)-1-methylcyclopropane-1,2-dicarboxylic acid (CDCCA and TDCCA)). Multiprobe fluorescence in situ hybridization for chromosomes X, Y, and 18 was used to determine XX, YY, XY, 1818, and total sex chromosome disomy in sperm nuclei. Poisson regression analysis was used to examine the association between aneuploidy rates and pyrethroid metabolites while adjusting for covariates.Results: Between 25-56% of the sample were above the limit of detection (LOD) for the pyrethroid metabolites. All sex chromosome disomies were increased by 7-30% when comparing men with CDCCA and TDCCA levels above the LOD to those below the LOD. For 3PBA, compared to those below the LOD, those above the LOD had YY18 disomy rates 1.28 times higher (95% CI: 1.15, 1.42) whereas a reduced rate was seen for XY18 and total disomy (IRR = 0.82; 95% CI: 0.77, 0.87; IRR = 0.93; 95% CI: 0.87-0.97), and no association was seen for XX18 and 1818.Conclusions: Our findings suggest that urinary concentrations of CDCCA and TDCCA above the LOD were associated with increased rates of aneuploidy. However the findings for 3BPA were not consistent. This is the first study to examine these relationships, and replication of our findings is needed before the association between pyrethroid metabolites and aneuploidy can be fully defined. [ABSTRACT FROM AUTHOR]

Human exposure to bisphenol A (BPA) is widespread. Animal studies have demonstrated that BPA can alter endocrine function, but human studies are limited. For the present study, we measured urinary BPA concentrations and serum thyroid and reproductive hormone levels in 167 men recruited through an infertility clinic. BPA was detected in 89% of urine samples with a median (range) of 1.3 (<0.4 - 36.4) ng/mL. In multivariable regression models adjusted for potential confounders, BPA concentrations in urine collected on the same day as a blood sample were inversely associated with serum levels of inhibin B and estradiol:testosterone ratio (E2:T) and positively associated with follicle-stimulating hormone (FSH) and FSH:inhibin B ratio. Because BPA is metabolized quickly and multiple urine measures may better reflect exposure than a single measure, we also considered among a subset of the men the BPA concentrations in repeated urine samples collected weeks or months following serum sample collection. In these analyses, the effect estimates remained consistent for FSH and E2:T but were somewhat weakened for inhibin B. In addition, we observed inverse relationships between urinary BPA concentrations and free androgen index (ratio of testosterone to sex hormone binding globulin), estradiol, and thyroid stimulating hormone. Our results suggest that urinary BPA concentrations may be associated with altered hormone levels in men, but these findings need to be substantiated through further research. [ABSTRACT FROM AUTHOR]

Abstract: Experimental studies have reported that pyrethroid insecticides affect male endocrine and reproductive function, but human data are limited. We recruited 161 men from an infertility clinic between years 2000–2003 and measured serum reproductive and thyroid hormone levels, as well as the pyrethroid metabolites 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA and trans-DCCA) in spot urine samples. When adjusting for potential confounders, categories for all three metabolites, as well as their summed values, were positively associated with FSH (all p-values for trend <0.05). Statistically significant or suggestive positive relationships with LH were also found. In addition, cis-DCCA and trans-DCCA were inversely associated with inhibin B (p for trend=0.03 and 0.02, respectively). Finally, there was evidence that trans-DCCA was inversely associated with testosterone and free androgen index (the ratio of testosterone to sex hormone binding globulin; p for trend=0.09 and 0.05, respectively). The observed relationships were consistent with previous findings, but further research is needed for a better understanding of the potential association between pyrethroid insecticides and male reproduction. [Copyright &y& Elsevier]

Background: Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone concentrations and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.Methods: Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone concentrations [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8-14, 10-18 years). We used linear regression to independently examine urinary metal concentrations in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.Results: In utero and prepubertal concentrations of some urinary metals were associated with increased concentrations of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.Conclusion: These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows. [ABSTRACT FROM AUTHOR]

Disentangling the separate and synergistic effects of chemicals poses methodological challenges for accurate exposure assessment and for investigating epidemiologically how chemicals affect reproduction. We investigated combined exposures to ubiquitous contemporary use pesticides, specifically organophosphates (OP) and pyrethroids (PYR), and their association with germ cell abnormalities among adult men. Fluorescence in situ hybridization was used to determine disomy in sperm nuclei and urine was analyzed for concentrations of PYR metabolites (3-phenoxybenzoic acid; 3PBA) and OP dialkyl phosphate (DAP) metabolites. Incidence rate ratios using Poisson models were estimated for each disomy type by exposure quartile of DAP metabolites and 3PBA, controlling for confounders. The shape of the associations between PYRs, OPs and disomy were frequently nonmonotonic. There were consistent interactions between OP and PYR metabolite concentrations and the risk for sperm abnormalities. Taking both chemicals into account simultaneously resulted in quantitatively different associations than what was reported previously for OPs and PYRs separately, demonstrating the importance of modeling multiple concentrations simultaneously. Methods investigating interactions using Poisson models are needed to better quantify chemical interactions and their effects on count-based health outcomes, the importance of which was shown here for germ cell abnormalities. [ABSTRACT FROM AUTHOR]

Abstract Background Understanding important sources and pathways of exposure to common chemicals known or suspected to impact human health is critical to eliminate or reduce the exposure. This is particularly important in areas such as Puerto Rico, where residents have higher exposures to numerous chemicals, as well as higher rates of many adverse health outcomes, compared to the mainland US. Objective The aim of this study was to assess distributions, time trends, and predictors of urinary triclocarban, phenol, and paraben biomarkers measured at multiple times during pregnancy among women living in Northern Puerto Rico. Methods We recruited 1003 pregnant women between years 2010 and 2016 from prenatal clinics and collected urine samples and questionnaire data on personal care product use at up to three separate visits, between 16 and 28 weeks gestation. Urine samples were analyzed for triclocarban, seven phenols and four parabens: 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, bisphenol A (BPA), bisphenol S (BPS), bisphenol F, triclosan, butylparaben, ethylparaben, methylparaben, and propylparaben. Results Detectable triclocarban, phenol and paraben concentrations among pregnant women were prevalent and tended to be higher than levels measured in women of reproductive age from the general US population, especially triclocarban, which had a median concentration 37 times higher in Puerto Rico participants (2.6 vs 0.07 ng/mL). A decreasing temporal trend was statistically significant for urine concentrations of BPA during the study period, while the BPA substitute BPS showed an increasing temporal trend. Significant and positive associations were found between biomarker concentrations with the products use in the past 48-h (soap, sunscreen, lotion, cosmetics). There was an increasing trend of triclocarban/triclosan urinary concentrations with increased concentrations of triclocarban/triclosan listed as the active ingredient in the bar soap/liquid soap products reported being used. Conclusion Our results suggest several potential exposure sources to triclocarban, phenols, and parabens in this population and may help inform targeted approaches to reduce exposure. Highlights • Urinary triclocarban levels of pregnant women were 37-fold higher than women of same age in NHANES. • First study to quantify the reliability of BPF and triclocarban in pregnant women urine samples • Decreased exposure to BPA but increased exposure to BPS was observed during study period. • Elevated triclocarban/triclosan levels were associated with the use of products containing them. [ABSTRACT FROM AUTHOR]

Abstract Diet is a major route of phthalate exposure in humans due to use in food packaging materials. School lunches may be an important contributor to phthalate exposure in children and adolescents in the US because of the large amount of packaging necessary for mass-produced foods. We used 2003–2014 National Health and Nutrition Examination Survey data to study the association between school lunch consumption and urinary phthalate metabolite concentrations in children (ages 6–11 years, N = 2196) and adolescents (ages 12–19 years, N = 2314). After adjustment for other covariates, children who Always consumed school lunch had significantly elevated urinary concentrations of the following phthalate metabolites compared to levels in children who Never ate school lunch: sum of di(2‑ethylhexyl) phthalate metabolites, (28% higher, 95% confidence interval, CI: 10, 49%); mono‑(carboxy‑octyl) phthalate (MCOP; 43% higher, 95% CI: 17, 76%) and mono‑ n ‑butyl phthalate (18% higher, 95% CI: 3.5, 34%). We did not find statistically significant associations in adolescents, but the trend for MCOP concentrations was similar to that of children. In sensitivity analyses, associations between 24-hour recall of cafeteria food and urinary phthalate metabolites were not statistically significant, which could indicate that associations observed with Always consuming school lunch are due to residual confounding. Our findings show that children who Always eat school lunch had higher levels of exposure to some phthalates, but the source of differences in exposure need to be evaluated in additional studies. Highlights • We examined urinary phthalate metabolites by school lunch consumption categories. • Children reporting Always eating school lunch had higher levels of some metabolites. • Calories consumed from school cafeteria food were not associated with metabolites. • No associations were observed between school lunch and phthalates in US adolescents. • Further investigation of elevated phthalate exposure in children who Always eat school lunch is required. [ABSTRACT FROM AUTHOR]

Phthalates have endocrine activity that may interfere with bone health, particularly during pregnancy and the early postpartum period, when bone resorption increases. We evaluated associations between prenatal phthalate exposure and perinatal bone health among 289 mothers in the ELEMENT birth cohort in Mexico City who were randomized upon recruitment to receive 1,200 mg daily calcium supplementation or placebo throughout pregnancy. Spot urine samples at up to three timepoints during pregnancy were assayed for 9 phthalate metabolites. Bone integrity was assessed by quantitative ultrasound speed of sound (SOS) measurements of the phalange and distal radius at 3, 6, and 8 months of pregnancy and 1, 3, 7, and 12 months postpartum. Geometric means of specific gravity-corrected phthalate concentrations were used as overall measures of prenatal exposure. Linear mixed effect models estimated associations between phthalate exposure and repeated perinatal bone SOS measures, adjusting for age, pre-pregnancy body mass index (BMI), education, parity, calcium supplementation, and month of pregnancy/postpartum. Effect modification by calcium supplementation and BMI were assessed in sensitivity analyses. An interquartile range increase in MEP and MiBP increased pregnancy phalange z-scores (β: 0.11; 95%CI: 0.003, 0.31 and β: 0.15; 95%CI: 0.00,0.42, respectively). Higher concentrations of several phthalate metabolites resulted in lower SOS measures among women who received calcium supplements (compared to placebo group) but higher SOS measures among women with a BMI≥25 (compared to BMI<25). These results suggest that phthalate exposure may interfere with bone remodeling during pregnancy, and that consideration of effect modifiers is paramount to fully understand the effects of environmental exposures on bone health. • Gestational MEP and MiBP were associated with increased pregnancy phalange SOS. • The Ca supplementation group saw lower SOS values with greater phthalate exposure. • Women with a BMI≥25 saw higher SOS values with greater phthalate exposure. • Numerous significant findings differed between cortical and trabecular bone sites. [ABSTRACT FROM AUTHOR]

Introduction Phenols and parabens are ubiquitous environmental contaminants. Evidence from animal studies and limited human data suggest they may be endocrine disruptors. In the current study, we examined associations of phenols and parabens with reproductive and thyroid hormones in 106 pregnant women recruited for the prospective cohort, “Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)”. Methods Urinary exposure biomarkers (bisphenol A, triclosan, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, butyl, methyl and propyl paraben) and serum hormone levels (estradiol, progesterone, sex hormone-binding globulin (SHBG), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone) were measured at up to two time points during pregnancy (16–20 weeks and 24–28 weeks). We used linear mixed models to assess relationships between exposure biomarkers and hormone levels across pregnancy, controlling for urinary specific gravity, maternal age, BMI and education. In sensitivity analyses, we evaluated cross-sectional relationships between exposure and hormone levels stratified by study visit using linear regression. Results An IQR increase in methyl paraben was associated with a 7.70% increase (95% CI 1.50, 13.90) in SHBG. Furthermore, an IQR increase in butyl paraben as associated with an 8.46% decrease (95% CI 16.92, 0.00) in estradiol, as well as a 9.34% decrease (95% CI −18.31,−0.38) in estradiol/progesterone. Conversely, an IQR increase in butyl paraben was associated with a 5.64% increase (95% CI 1.26, 10.02) in FT4. Progesterone was consistently negatively associated with phenols, but none reached statistical significance. After stratification, methyl and propyl paraben were suggestively negatively associated with estradiol at the first time point (16–20 weeks), and suggestively positively associated with estradiol at the second time point (24–28 weeks). Conclusions Within this ongoing birth cohort, certain phenols and parabens were associated with altered reproductive and thyroid hormone levels during pregnancy. These changes may contribute to adverse health effects in mothers or their offspring, but additional research is required. [ABSTRACT FROM AUTHOR]

The age of pubertal onset for girls has declined over past decades. Research suggests that endocrine disrupting chemicals (EDCs) may play a role but exposure at multiple stages of development has not been considered. We examined in utero and peripubertal exposure to bisphenol-A (BPA) and phthalates in relation to serum hormones and sexual maturation among females in a Mexico City birth cohort. We measured phthalate metabolite and BPA concentrations in urine collected from mothers during their third trimester ( n =116) and from their female children at ages 8–13 years ( n =129). Among girls, we measured concurrent serum hormone concentrations, Tanner stages for breast and pubic hair development, and collected information on menarche onset. We used linear and logistic regression to model associations between in utero and peripubertal measures of exposure with hormones and sexual maturation, respectively, controlling for covariates. An interquartile range (IQR) increase in in utero urinary mono-2-ethylhexyl phthalate (MEHP) was positively associated with 29% (95% CI: 9.2–52.6%) higher dehydroepiandrosterone sulfate (DHEA-S), an early indicator of adrenarche, and 5.3 (95% CI: 1.13–24.9) times higher odds of a Tanner stage >1 for pubic hair development. Similar relationships were observed with other in utero but not peripubertal di-2-ethylhexyl phthalate (DEHP) metabolites. IQR increases in in utero monobenzyl phthalate (MBzP) and monoethyl phthalate (MEP) were associated with 29% and 25% higher serum testosterone concentrations (95% CI: 4.3–59.3; 2.1–54.1), respectively. In addition, we observed suggestive associations between in utero and peripubertal MEP concentrations and increased odds of having undergone menarche, and between peripubertal MnBP concentrations and increased odds of having a Tanner stage >1 for both breast and pubic hair development. BPA was not associated with in utero or peripubertal serum hormones or sexual maturation. Our findings suggest in utero phthalate exposure may impact hormone concentrations during peripubescence and timing of sexual maturation. Efforts to control phthalate exposure during pregnancy should be of high priority. [ABSTRACT FROM AUTHOR]

Abstract: Triclosan and parabens are broad spectrum antimicrobials used in a range of consumer products. In vitro and animal studies have suggested the potential for these compounds to disrupt thyroid function, though studies in humans have been limited. The objective of the study was to assess the relationship of urinary concentrations of triclosan and parabens with serum thyroid measures in a large, representative sample of the US population. We conducted an exploratory, cross-sectional analysis of data on urinary biomarkers of triclosan and paraben exposure and serum thyroid measures obtained from 1831 subjects (ages≥12years) as part of the 2007–2008 National Health and Nutrition Examination Survey (NHANES). We found evidence of some inverse associations between parabens and circulating thyroid hormone levels in adults, with the strongest and most consistent associations among females. We also observed a positive association between triclosan and total triiodothyonine (T3) concentrations in adolescents. These results, in accordance with the in vitro and animal literature, suggest that paraben, and potentially triclosan, exposures may be associated with altered thyroid hormone levels in humans. Further research is needed for confirmation and to determine the potential clinical and public health significance of these findings. [Copyright &y& Elsevier]