Fetal and Infancy Exposure to Phenols, Parabens, and Phthalates and Anthropometric Measurements up to 36 Months, in the Longitudinal SEPAGES Cohort.

BACKGROUND: Endocrine-disrupting chemicals may play a role in adiposity development during childhood. Until now literature in this scope suffers from methodologic limitations in exposure assessment using one or few urine samples and missing assessment during the infancy period. OBJECTIVES: We investigated the associations between early-life exposure to quickly metabolized chemicals and post-natal growth, relying on repeated within-subject urine collections over pregnancy and infancy. METHODS: We studied the associations of four phenols, four parabens, seven phthalates, and one nonphthalate plasticizer from weekly pooled urine samples collected from the mother during second and third trimesters (median 18 and 34 gestational weeks, respectively) and infant at 2 and 12 months of age, and child growth until 36 months. We relied on repeated measures of height, weight and head circumference from study visits and the child health booklet to predict growth outcomes at 3 and 36 months using the Jenss-Bayley nonlinear mixed model. We assessed associations with individual chemicals using adjusted linear regression and mixtures of chemicals using a Bayesian kernel machine regression model. RESULTS: The unipollutant analysis revealed few associations. Bisphenol S (BPS) at second trimester was positively associated with all infant growth parameters at 3 and 36 months, with similar patterns between exposure at third trimester and all infant growth parameters at 3 months. Mono-n-butyl phthalate (MnBP) at 12 months was positively associated with body mass index (BMI), weight, and head circumference at 36 months. Mixture analysis revealed positive associations between exposure at 12 months and BMI and weight at 36 months, with MnBP showing the highest effect size within the mixture. CONCLUSIONS: This study suggests that exposure in early infancy may be associated with increased weight and BMI in early childhood, which are risk factors of obesity in later life. Furthermore, this study highlighted the impact of BPS, a compound replacing bisphenol A, which has never been studied in this context. https://doi.org/10.1289/EHP13644.

Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) - a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health.

PURPOSE: Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health. PARTICIPANTS: Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at <15 weeks of gestation from Boston, Massachusetts area hospitals. Participants completed ≤4 prenatal study visits (median: 12, 19, 26, 36 weeks of gestation) and 1 postpartum visit (median: 9 weeks), during which we collected biospecimens, health histories, demographic and behavioural data, and vitals and anthropometric measurements. Participants completed a postpartum fasting 2-hour 75 g oral glucose tolerance test. Clinical data were abstracted from electronic medical records. Ongoing (as of 2024) extended post-pregnancy follow-up visits occur annually following similar data collection protocols. FINDINGS TO DATE: We enrolled 653 unique pregnancies and retained 633 through delivery. Participants had a mean age of 33 years, 10% (n=61) developed gestational diabetes and 8% (n=50) developed pre-eclampsia. Participant pregnancy and postpartum urinary phthalate metabolite concentrations and postpartum glycaemic biomarkers were quantified. To date, studies within ERGO found higher exposure to phthalates and phthalate mixtures, and separately, higher exposure to radioactive ambient particulate matter, were associated with adverse gestational glycaemic outcomes. Additionally, certain personal care products used in pregnancy, notably hair oils, were associated with higher urinary phthalate metabolite concentrations, earlier gestational age at delivery and lower birth weight. FUTURE PLANS: Future work will leverage the longitudinal data collected on pregnancy and cardiometabolic outcomes, environmental exposures, questionnaires, banked biospecimens and paediatric data within the ERGO Study.

The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies.

BACKGROUND: Exposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated. OBJECTIVE: To investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies. METHODS: In 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry. Serum kisspeptin (kiss54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were measured by immunosorbent assays. Free Androgen Index (FAI) was calculated as a proxy of free testosterone. Adjusted sex-stratified linear regression models for individual studies, mixed effect models (LME) accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the phthalate/DINCH mixture were performed. RESULTS: The LME suggested that each IQR increase in ln-transformed levels of several phthalates was associated with lower kisspeptin [MnBP: %change (95%CI): -2.8 (-4.2;-0.4); MEHP: -1.4 (-3.4,0.2)] and higher FSH [∑DINP: 11.8 (-0.6;25.1)] levels in females from pooled studies. G-computation showed that the phthalates/DINCH mixture was associated with lower kisspeptin [-4.28 (-8.07;-0.34)] and higher FSH [22.13 (0.5;48.4)] also in females; BKMR showed similar although non-significant pattern. In males, higher phthalates metabolites [MEHP: -12.22 (-21.09;-1.18); oxo-MEHP: -12.73 (-22.34;-1.93)] were associated with lower TT and FAI, although higher DINCH [OH-MINCH: 16.31 (6.23;27.35), cx-MINCH: 16.80 (7.03;27.46), ∑DINCH: 17.37 (7.26;29.74)] were associated with higher TT levels. No mixture associations were found in males. CONCLUSION: We observed sex-specific associations between urinary concentrations of phthalate/DINCH metabolites and the panel of selected effect biomarkers (kisspeptin and reproductive hormones). This suggests that exposure to phthalates would be associated with changes in kisspeptin levels, which would affect the HPG axis and thus influence reproductive health. However, further research is needed, particularly for phthalate replacements such as DINCH.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients.

Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4-10 samples per patient) born at <31 weeks gestational age and/or <1500 g birth weight in the Antwerp University Hospital, Belgium. Term control neonates (n = 21, 1 sample per patient) were included from the maternity ward. Phthalate and alternative plasticizers' metabolites were analyzed using liquid-chromatography coupled to tandem mass spectrometry. Phthalate metabolites were detected in almost all urine samples. Metabolites of alternative plasticizers, di-(2-ethylhexyl)-adipate (DEHA), di-(2-ethylhexyl)-terephthalate (DEHT) and cyclohexane-1,2-dicarboxylic-di-isononyl-ester (DINCH), had detection frequencies ranging 30-95 %. Urinary phthalate metabolite concentrations were significantly higher in premature compared to control neonates (p = 0.023). NICU exposure to respiratory support devices and blood products showed increased phthalate metabolite concentrations (p < 0.001). Phthalate exposure increased from birth until four weeks postnatally. The estimated phthalate intake exceeded animal-derived no-effect-levels (DNEL) in 10 % of samples, with maximum values reaching 24 times the DNEL. 29 % of premature neonates had at least once an estimated phthalate intake above the DNEL. Preterm neonates are still exposed to phthalates during NICU stay, despite the EU Medical Devices Regulation. NICU exposure to alternative plasticizers is increasing, though currently not regulated, with insufficient knowledge on their hazard profile.

Endocrine disrupting chemical Bisphenol A and its association with cancer mortality: a prospective cohort study of NHANES.

Introduction: There is evidence suggesting that Bisphenol A (BPA) is associated with increased all-cause mortality in adults. However, the specific nature of the relationship between BPA exposure and cancer mortality remains relatively unexplored. Methods: The National Health and Nutrition Examination Survey (NHANES) dataset was used to recruit participants. Urinary BPA was assessed using liquid chromatography-mass spectrum (LC-MS). Through the use of multivariable Cox proportional hazard regressions and constrained cubic splines, the relationships between urine BPA and death from all causes and cancer were investigated. Results: This study has a total of 8,035 participants, and 137 died from cancers after a 7.5-year follow-up. The median level of BPA was 2.0 g/mL. Urinary BPA levels were not independently associated with all-cause mortality. For cancer mortality, the second quartile's multivariable-adjusted hazard ratio was 0.51 (95% confidence interval: 0.30 to 0.86; p = 0.011) compared to the lowest quartile. The restricted cubic splines showed that the association was nonlinear (p for nonlinearity = 0.028) and the inflection point was 1.99 ng/mL. Conclusion: Urinary BPA exposure was U-shaped associated with the risk of cancer mortality, and a lower level of BPA less than 1.99 ng/mL was associated with a higher risk of cancer mortality.

Cholesterol mediates the effects of single and multiple environmental phenols in urine on obesity.

BACKGROUND: Overweight and obesity are among the leading chronic diseases worldwide. Environmental phenols have been renowned as endocrine disruptors that contribute to weight changes; however, the effects of exposure to mixed phenols on obesity are not well established. METHODS: Using data from adults in National Health and Nutrition Examination Survey, this study examined the individual and combined effects of four phenols on obesity. A combination of traditional logistic regression and two mixed models (weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR)) were used together to assess the role of phenols in the development of obesity. The potential mediation of cholesterol on these effects was analyzed through a parallel mediation model. RESULTS: The results demonstrated that solitary phenols except triclosan were inversely associated with obesity (P-value < 0.05). The WQS index was also negatively correlated with general obesity (ß: 0.770, 95% CI: 0.644-0.919, P-value = 0.004) and abdominal obesity (ß: 0.781, 95% CI: 0.658-0.928, P-value = 0.004). Consistently, the BKMR model demonstrated the significant joint negative effects of phenols on obesity. The parallel mediation analysis revealed that high-density lipoprotein mediated the effects of all four single phenols on obesity, whereas low-density lipoprotein only mediated the association between benzophenol-3 and obesity. Moreover, Cholesterol acts as a mediator of the association between mixed phenols and obesity. Exposure to single and mixed phenols significantly and negatively correlated with obesity. Cholesterol mediated the association of single and mixed environmental phenols with obesity. CONCLUSIONS: Assessing the potential public health risks of mixed phenols helps to incorporate this information into practical health advice and guidance.

Identifying critical windows of prenatal phenol, paraben, and pesticide exposure and child neurodevelopment: Findings from a prospective cohort study.

BACKGROUND: This study aimed to investigate how exposure to a mixture of endocrine disrupting chemicals (EDCs) during two points in pregnancy affects early childhood neurodevelopment. METHODS: We analyzed publicly-available data from a high-risk cohort of mothers and their children (2007-2014) that measured six EDCs including methyl-, ethyl- and propyl parabens (MEPB, ETPB, PRPB), Bisphenol-A (BPA), 3,5,6-trichloro-2-pyridinol (TCPy), 3-phenoxybenzoic acid (3-PBA) in prenatal urine samples during the second and third trimesters. Neurodevelopmental scores were assessed using Mullen Scales of Early Learning (MSEL) at age 3. We used mean field variational Bayes for lagged kernel machine regression (MFVB-LKMR) to investigate the association between trimester-specific co-exposure to the six EDCs and MSEL scores at age 3, stratified by sex. RESULTS: The analysis included 130 children. For females, the relationship between BPA and 3PBA with MSEL score varied between the two trimesters. In the second trimester, effect estimates for BPA were null but inversely correlated with MSEL score in the third trimester. 3PBA had a negative relationship with MSEL in the second trimester and positive correlation in the third trimester. For males, effect estimates for all EDCs were in opposing directions across trimesters. MFVB-LKMR analysis identified significant two-way interaction between EDCs for MSEL scores in both trimesters. For example, in females, the MSEL scores associated with increased exposure to TCPy were 1.75 units (95%credible interval -0.04, -3.47) lower in the 2nd trimester and 4.61 (95%CI -3.39, -5.84) lower in the third trimester when PRPB was fixed at the 75th percentile compared to when PRPB was fixed at the 25th percentile. CONCLUSION: Our study provides evidence that timing of EDC exposure within the prenatal period may impact neurodevelopmental outcomes in children. More of these varying effects were identified among females. Future research is needed to explore EDC mixtures and the timing of exposure during pregnancy to enhance our understanding of how these chemicals impact child health.

Bisphenol A and cardiometabolic risk in adolescents: Data from the Generation XXI cohort.

BACKGROUND AND AIMS: Bisphenol A (BPA), an endocrine disruptor widely used in food contact materials, has been linked to a worse health profile. This study intends to estimate the association between BPA exposure and cardiometabolic patterns at adolescence. METHODS AND RESULTS: Data from the Portuguese population-based birth cohort Generation XXI at the age of 13 were used (n = 2386 providing 3-day food diaries and fasting blood samples). BPA exposure was measured in 24-h urine from a subsample (n = 206) and then predicted in all participants using a random forest method and considering dietary intake from diaries. Three cardiometabolic patterns were identified (normal, modified lipid profile and higher cardiometabolic risk) using a probabilistic Gaussian mixture model. Multinomial regression models were applied to associate BPA exposure (lower, medium, higher) and cardiometabolic patterns, adjusting for confounders. The median BPA exposure was 1532 ng/d, corresponding to 29.4 ng/kg/d. Adolescents higher exposed to BPA (compared to medium and lower levels) had higher BMI z-score (kg/m2) (0.68 vs. 0.39 and 0.52, respectively; p = 0.008), higher levels of body fat (kg) (16.3 vs. 13.8 and 14.6, respectively; p = 0.002), waist circumference (76.2 vs. 73.7 and 74.9, respectively; p = 0.026), insulinemia (ug/mL) (14.1 vs. 12.7 and 13.1, respectively; p = 0.039) and triglyceridemia (mg/dL) (72.7 vs. 66.1 and 66.5, respectively; p = 0.030). After adjustment, a significant association between higher BPA and a higher cardiometabolic risk pattern was observed (OR: 2.55; 95%CI: 1.41, 4.63). CONCLUSION: Higher BPA exposure was associated with a higher cardiometabolic risk pattern in adolescents, evidencing the role of food contaminants in health.

EDC mixtures during pregnancy and body fat at 7 years of age in a Swedish cohort, the SELMA study.

BACKGROUND: Some endocrine disrupting chemicals (EDC), are "obesogens" and have been associated with overweight and obesity in children. Daily exposure to different classes of EDCs demands for research with mixtures approach. OBJECTIVES: This study evaluates the association, considering sex-specific effects, between prenatal exposure to EDC mixture and children's body fat at seven years of age. METHODS: A total of 26 EDCs were assessed in prenatal urine and serum samples from first trimester in pregnancy from 737 mother-child pairs participating in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. An indicator for children's "overall body fat" was calculated, using principal component analysis (PCA), based on BMI, percent body fat, waist, and skinfolds measured at seven years of age. Weighted quantile sum (WQS) regression was used to assess associations between EDC mixture and children's body fat. RESULTS: Principal component (PC1) represented 83.6 % of the variance, suitable as indicator for children's "overall body fat", with positive loadings of 0.40-0.42 for each body fat measure. A significant interaction term, WQS*sex, confirmed associations in the opposite direction for boys and girls. Higher prenatal exposure to EDC mixture was borderline significant with more "overall body fat" for boys (Mean ß = 0.20; 95 % CI: -0.13, 0.53) and less for girls (Mean ß = -0.23; 95 % CI: -0.58, 0.13). Also, higher prenatal exposure to EDC mixture was borderline significant with more percent body fat (standardized score) for boys (Mean ß = 0.09; 95 % CI: -0.04, 0.21) and less for girls (Mean ß = -0.10 (-0.26, 0.05). The chemicals of concern included bisphenols, phthalates, PFAS, PAH, and pesticides with different patterns for boys and girls. DISCUSSION: Borderline significant associations were found between prenatal exposure to a mixture of EDCs and children's body fat. The associations in opposite directions suggests that prenatal exposure to EDCs may present sex-specific effects on children's body fat.

Associations of urinary non-persistent endocrine disrupting chemical biomarkers with early-to-mid pregnancy plasma sex-steroid and thyroid hormones.

BACKGROUND/OBJECTIVES: Pregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. METHODS: Illinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8-40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. RESULTS: In women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with -5.65% (95% CI: -9.79, -1.28) lower testosterone and -0.09 µIU/mL (95% CI: -0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: -0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with -1.77% (95% CI: -4.08, 0.58) lower TT4 and -0.18 µIU/mL (95% CI: -0.33, -0.03) lower TSH. We also identified select chemical interactions. CONCLUSION: Some biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes.

A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals.

Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1.

[Associations of a mixture of eleven endocrine disruptors in human urine with the risk of papillary thyroid cancer].

OBJECTIVE: To examine the associations of human exposure to a mixture of 11 endocrine disruptors(EDCs) with the risk of papillary thyroid cancer(PTC), and to identify the priority of these EDCs. METHODS: EDCs were determined in fasting urine specimens to represent human exposure. Logistics regressions were performed to examine the associations between individual EDC and PTC risk. Bayes kernel machine regression was applied to examine the associations between the mixture of EDCs and PTC risk. Weighted quantile sum(WQS) regression and LASSO regression were performed to identify the main contributor. RESULTS: In the multivariate logistic regression model, after adjusting for a series of variables, 11 endocrine disruptors were statistically significantly correlated with the risk of PTC(P<0.05). In BKMR models, the mixture of EDCs was positively correlated with the risk of PTC(P<0.05). The weight and coefficient of mono(2-ethyl-5-hydroxyhexyl) phthalate(MEHHP) was 0.62 and 1.58 in WQS and LASSO models, respectively, which were much higher than those of the other EDCs. CONCLUSION: Combined exposure to o a variety of EDCs might promote the risk of PTC, and MEHHP was identified as the main contributor.

Cross-sectional associations between phthalates, phenols, and parabens with metabolic syndrome risk during early-to-mid adolescence among a cohort of Mexican youth.

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 [ß = 0.21 (95% CI: 0.04, 0.37; p < 0.01)], phthalates from plastic sources (Σ Plastic) [ß = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], anti-androgenic phthalates (Σ AA) [ß = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], and individual phthalate metabolites (MEHHP, MEOHP, and MECPP) among males. Among females, BPA [ß = 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) [ß = 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.

Adolescent endocrine disrupting chemical exposure and academic achievement.

BACKGROUND: Epidemiologic studies support associations of exposure to endocrine disrupting chemicals (EDCs), such as some phthalates, phenols, and parabens with a wide range of cognitive and behavioral traits. While many of these traits are associated with academic achievement, the relationship of EDC exposure specifically with academic achievement in adolescence has not yet been studied. OBJECTIVE: We assessed the association of urinary biomarker concentrations of EDCs with academic achievement in adolescents as well as the potential for psychosocial factors to modify associations. METHODS: We quantified urinary concentrations of select EDCs in 205 adolescent participants from the New Bedford Cohort (NBC), a prospective birth cohort of children born to mothers residing near the New Bedford Harbor Superfund site in Massachusetts, and estimated associations between EDCs and adolescent academic achievement assessed with the Wide Range Achievement Test (WRAT). Measures of socioeconomic status and the home environment were used to estimate psychosocial stress. RESULTS: Urinary concentrations of antiandrogenic phthalates were inversely associated with Math Computation scores. For example, each doubling of the concentration of antiandrogenic phthalate metabolites in urine was associated with a 1.94 point decrease (95% CI: 3.84, -0.05) in Math Computation scores, indicating poorer performance. For the most part, associations were stronger in adolescents with more, as compared to less, social disadvantage, but most of these differences did not achieve statistical significance. CONCLUSION: Our findings support the potential for adolescents' exposure to antiandrogenic phthalates to correlate with poorer academic achievement in math, particularly among participants with greater psychosocial stress.

Associations between endocrine disruptor contamination and thyroid hormone homeostasis in Belgian type 1 diabetic children.

PURPOSE: Humans are daily exposed to many environmental pollutants, some of which being suspected to be thyroid disruptors. Some populations could be particularly susceptible to thyroid disruption, such like diabetics due to the well-known relation between the thyroid function and the control of carbohydrate homeostasis by pancreas. Therefore, the aim of this study was to investigate the associations between the exposure to several persistent and non-persistent chemicals and thyroid hormones levels in children with type 1 diabetes. METHODS: Blood and urine sample were collected from 54 children diagnosed for type 1 diabetes mellitus. The concentrations of 7 phthalate metabolites, 4 parabens, 7 bisphenols, benzophenone 3 and triclosan were measured in urine, while 15 organochlorine pesticides, 4 polychlorinated biphenyls (PCBs) and 7 perfluoroalkyl substances were analyzed in serum samples. In the same time, the blood levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and glycated hemoglobin (Hb1Ac) were determined. RESULTS: We highlighted positive associations between serum perfluorohexane sulfonate and urinary monoethylphthalate levels, and TSH level in blood. We also found that PCB 138 was positively associated to fT4 while urinary levels of bisphenol F were negatively correlated to this hormone. Finally, we observed positive associations between Hb1Ac levels and the contamination by PCB 153 and two urinary phthalate metabolites: mono-2-ethyl-5-hydroxyhexyl phthalate and mono-2-ethyl-5-oxoxyhexyl phthalate. CONCLUSION: Our results showed that our small cohort of children with type 1 diabetes mellitus is potentially susceptible to thyroid disruptions by some pollutants. Moreover, for these children, both di-(2-ethylhexyl) phthalate metabolites would potentially hamper the glucose homeostasis. Nevertheless, additional studies are mandatory to further explore these findings.

Comprehensive monitoring of a special mixture of prominent endocrine disrupting chemicals in human urine using a carefully adjusted hydrolysis of conjugates.

Many xenobiotics were identified as possible endocrine disruptors during the last decades. Structural analogy of these substances to natural hormones may lead to agonists or antagonists of hormone receptors. For a comprehensive human biomonitoring of such substances, we developed a simple, reliable, and highly sensitive method for the simultaneous monitoring of the parameters bisphenol A, triclosan, methylparaben, ethylparaben, propylparaben, butylparaben, benzophenone-1, benzophenone-3, 3,5,6-trichloropyridin-2-ol, p-nitrophenol, genistein, and daidzein in urine. Thereby, optimization of the enzymatic hydrolysis and the use of ß-glucuronidase from E. coli K12 as well as sulfatase from Aerobacter aerogenes ensures the acquisition of intact analytes without cleavage of ester bonds among parabens. Validation of the method revealed limits of detection between 0.02 and 0.25 µg/L as well as limits of quantification between 0.08 and 0.83 µg/L. Thereby, the use of analyte-free surrogate matrix for calibration and control material influenced the sensitivity of the procedure positively. Furthermore, excellent precision in and between series was observed. Good absolute and relative recoveries additionally proved the robustness of the multimethod. Thus, the procedure can be applied for exploring the exposome to these prominent endocrine disruptors in the general population.

Predictors of urinary biomarker concentrations of phthalates and some of their replacements in children in the Project Viva cohort.

BACKGROUND: Some phthalates are still widely used in food packaging, toys, and personal care products, and links to adverse health have motivated substitution with replacement chemicals. Few studies have examined patterns and predictors of phthalate replacement biomarkers in children. OBJECTIVE: To examine associations of sociodemographic, dietary, and urine collection characteristics with urinary concentrations of biomarkers of select phthalates and their replacements in mid-childhood. METHODS: We studied 830 children ages 6-10 years in 2007-2010 in a Boston-area cohort. We quantified urinary metabolites and summed their concentrations to calculate biomarkers of the concentrations of ten parent phthalates/replacements. We used linear regression to examine mutually adjusted associations of each predictor with each phthalate biomarker. We used logistic regression to examine predictors of 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH) biomarker detectability. RESULTS: Predictor characteristics explained 25-48% of urinary biomarker variability. Di-2-ethylhexyl terephthalate (DEHTP) biomarker was higher in females (18.7% [95% CI: 0.7, 39.9]), children who consumed more meat and dairy, and samples collected from later years. DINCH biomarker was more detectable in females (odds ratio [OR] 2.1 [95% CI: 1.5, 3.0]) and samples from later years. SIGNIFICANCE: Populations of children with increased urinary concentrations of phthalate and replacement biomarkers can be targeted for future study of sources of exposure, and identifying dietary predictors of biomarkers will directly guide future interventions. IMPACT: Our study uses data from a large cohort that is one of the first to measure DINCH, DEHTP, and metabolites of di-isononyl phthalate and di-isodecyl phthalate. Additionally, we evaluate predictors during mid-childhood when biomarkers might be highest. As the use of replacement phthalates increases, our study is one of the first to examine biomarker patterns and predictors among children.

Urinary phthalates, phenols, and parabens in relation to sleep health markers among a cohort of Mexican adolescents.

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.