Urinary Phthalate Metabolite Concentrations Research Articles

Comparison of urinary exposure profiles to phthalates and bisphenol analogues in kindergartens in Korea: Impact of environmental choices on children’s health

Phthalates and bisphenols (BPs) are well-known endocrine disrupting chemicals (EDCs) that are widely used in diverse consumer and personal care products. Despite their vulnerability, children are frequently exposed to phthalates and BPs in their surrounding environments. Although pre-school children spend most of their time in kindergarten, no comprehensive assessment of children’ exposure to EDCs has been conducted according to the type of kindergarten. In this study, the urinary concentrations of phthalate metabolites and BPs were determined in Korean children attending conventional and eco-friendly kindergartens. The exposure levels and contaminant profiles were investigated according to kindergarten type and their association with oxidative stress was assessed. Di-(2-ethylhexyl) phthalate (DEHP) metabolites, such as mono-(2-ethyl-5-carboxypentyl) phthalate (median: 47.1 ng/mL) and mono-[(2-carboxymethyl)hexyl] phthalate (8.45 ng/mL) had the highest levels, indicating that they were the primary contaminants to which the children were exposed. Urinary concentrations of phthalate metabolites and bisphenol A (BPA) were higher in children from conventional kindergarten than an eco-friendly kindergarten. Conversely, bisphenol S (BPS) concentrations were significantly higher in children from the eco-friendly kindergarten than in those from conventional kindergartens, implying that eco-friendly plastic products might contain BPS as a replacement for BPA. The estimated daily intakes of BPA for all children exceeded the new tolerable daily intake proposed by the European Food Safety Authority. Malondialdehyde levels were significantly associated with the urinary concentrations of certain phthalate metabolites, indicating potential adverse health outcomes from phthalate exposure in children. The study highlights the need for targeted interventions to reduce EDC exposure in children, especially in settings where alternative chemicals may still pose health risks.

Adolescent urinary concentrations of phthalate metabolites and indices of overweight and cardiovascular risk in Dutch adolescents

Phthalates have been linked to cardiovascular risk factors. Exposure to chemicals with endocrine disrupting properties during the pubertal period can interfere with normal endocrine processes. This study aims to determine whether adolescent urinary concentrations of phthalate metabolites are associated with indices of overweight and cardiovascular risk in 13–15-year-old children. In this Dutch observational cross-sectional cohort study, 101 adolescents were included (mean age 14.4 ± 0.8 years), 55 were boys. The concentrations of 13 phthalate metabolites were measured in morning urine samples. Levels of cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, fasting insulin, fasting glucose, leptin, and adiponectin were measured. The children’s height, weight, waist circumference, hip circumference, and blood pressure were measured. Higher urinary mono-ethyl phthalate concentrations were associated with higher BMI and a larger hip circumference. In girls, higher urinary mono-hydroxy-iso-nonyl phthalate concentrations were associated with higher levels of lipids and obesogenic traits. In boys, higher concentrations of urinary phthalate metabolites were associated with lower LDL-C. The results of this explorative study suggest that higher levels of phthalate metabolites are associated with higher levels of lipids and obesogenic traits in 13–15-year-old girls.

Urinary concentrations of phthalate and phthalate alternative metabolites and sperm DNA methylation: A multi-cohort and meta-analysis of men in preconception studies

Phthalates are ubiquitous pollutants in the environment; however, the mechanisms of phthalate-associated reproductive disorders in men are not fully understood. The aim of this study is to investigate associations between urinary phthalate metabolite concentrations and sperm DNA methylation. The study was conducted on 697 men from three prospective pregnancy cohorts: Longitudinal Investigation of Fertility and the Environment (LIFE) Study, Sperm Environmental Epigenetics and Development Study (SEEDS), and Environment and Reproductive Health (EARTH) Study. Eighteen phthalate and two phthalate alternative metabolites were quantified by mass spectrometry in preconception urinary samples and sperm DNA methylation was measured via Illumina EPIC Array (v1). Regional methylation analyses were conducted to identify cohort-specific loci associated with urinary phthalate metabolites. Models were adjusted for age, body mass index (BMI), race, smoking status, urinary creatinine/specific gravity, and analytical batch for phthalate measurements. The cohort-specific results were meta-analyzed using METAL. Participants had an average age of 30 years, most (79.6 %) of whom had BMI>25 kg/m2 and were non-smokers (90.1 %). A total of 7,979 differentially methylated regions (DMRs; 7,979 LIFE-specific DMRs, 72 SEEDS-specific DMRs, and 23 EARTH-specific DMRs) were associated with urinary MBzP, MiBP, MMP, MCNP, MCPP, MBP, and MCOCH. Meta-analysis identified fewer DMRs than cohort-specific models: 946 DMRs were associated with MBzP, 27 DMRs associated with MiBP, and 1 DMR associated with MEHP. The majority of cohort-specific and meta-analysis-derived DMRs displayed a positive association with phthalate metabolite concentrations and were enriched in genes associated with spermatogenesis, response to hormones and their metabolism, embryonic organ development and developmental growth. In conclusion, several preconception urinary phthalate metabolites were associated with increased DNA methylation patterns in sperm. These findings provide an epigenetic pathway by which environmental phthalate exposures can impact couples’ reproductive outcomes.

Mixtures of Urinary Phenol and Phthalate Metabolite Concentrations in Relation to Serum Lipid Levels among Pregnant Women: Results from the EARTH Study.

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (-0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (-0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (-0.26, 0.75) and 0.35 (-0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (-0.06, 0.07) and 0.00 (-0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings.

Possible associations between prenatal exposure to environmental pollutants and neurodevelopmental outcome in children

This study aimed to evaluate associations between prenatal and childhood exposure to phthalates and prenatal exposure to polychlorinated biphenyls (PCBs) and the development of 4-year-old children. Urinary metabolites of five phthalates were measured in women upon delivery, as well as serum concentrations of four PCB congeners. Postnatal phthalate metabolites were measured from children's urine obtained at the time of developmental assessment. The primary outcome was cognitive function as evaluated by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) administered at 4 years. Secondary outcomes were motor function and response to sensory stimuli as evaluated by the Developmental Coordination Disorder Questionnaire (DCDQ) and Short Sensory Profile (SSP) that the mothers filled out, respectively. The study included 57 mother-child pairs. Higher maternal phthalate metabolite concentrations were inversely associated with WPPSI-III scores among boys and not among girls. After using linear regression models and controlling for confounding variables, we found that higher levels of monobenzyl phthalate (MBzP) were the ones associated with lower WPPSI-III scores (p=0.004, 95 %CI [-14.18; −3.16]), lower DCDQ scores (p=0.007, 95 %CI [-6.08; −1.17] and lower SSP scores (p=0.004, 95 %CI [-7.47; −1.79]). No association was found between child urinary phthalate metabolite concentrations or maternal PCB blood concentrations and developmental function. These findings indicate that higher prenatal phthalate metabolite levels may be associated with deficits in neurologic development of young boys.

The associations between pre-conception urinary phthalate concentrations, the serum metabolome, and live birth among women undergoing assisted reproduction

BackgroundPhthalates are ubiquitous endocrine disruptors. Past studies have shown an association between higher preconception urinary concentrations of phthalate metabolites and lower fertility in women; however, the biological mechanisms remain unclear. Our exploratory study aimed to understand the metabolites and pathways associated with maternal preconception phthalate exposure and examine if any may underline the association between phthalate exposure and live birth using untargeted metabolomics. MethodsParticipants (n = 183) were part of the Environment and Reproductive Health (EARTH) study, a prospective cohort that followed women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital Fertility Center (2005–2016). On the same day, women provided a serum sample during controlled ovarian stimulation, which was analyzed for metabolomics using liquid chromatography coupled with high-resolution mass spectrometry and two chromatography columns, and a urine sample, which was analyzed for 11 phthalate metabolites using targeted approaches. We used multivariable generalized linear models to identified metabolic features associated with urinary phthalate metabolite concentrations and live birth, followed by enriched pathway analysis. We then used a meet-in-the-middle approach to identify overlapping pathways and features. ResultsMetabolic pathway enrichment analysis revealed 43 pathways in the C18 negative and 32 pathways in the HILIC positive columns that were significantly associated (p < 0.05) with at least one of the 11 urinary phthalate metabolites or molar sum of di-2-ethylhexyl phthalate metabolites. Lipid, amino acid, and carbohydrate metabolism were the most common pathways associated with phthalate exposure. Five pathways, tryptophan metabolism, tyrosine metabolism, biopterin metabolism, carnitine shuttle, and vitamin B6 metabolism, were also identified as being associated with at least one phthalate metabolite and live birth following IVF. ConclusionOur study provides further insight into the metabolites and metabolomics pathways, including amino acid, lipid, and vitamin metabolism that may underlie the observed associations between phthalate exposures and lower fertility in women.

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

PurposePregnancy 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...

Extracellular Vesicles in Environmental Toxicological Studies: Association between Urinary Concentrations of Phthalate Metabolites and Exosomal miRNA Expression Profiles.

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers.

Urinary concentrations of phthalate metabolites in relation to preeclampsia and other hypertensive disorders of pregnancy in the environmental influences on child health outcomes (ECHO) program

BackgroundPhthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. ObjectivesTo evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. MethodsUsing data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). ResultsIn adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DiscussionIn this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

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.

Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016

BackgroundAlthough adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. ObjectivesWe aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. MethodsWe conducted cross-sectional analyses of 2100 individuals aged 6–18 y enrolled in the National Health and Nutrition Examination Survey, 2011–2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. ResultsIn multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [β: −1.566; 95% confidence interval: −2.935, −0.196], 1.423 (−1.423; −2.689, −0.157), 1.309 (−1.309; −2.573, −0.044), 1.530 (−1.530; −2.918, −0.142), and 1.381 (−1.381; −2.641, −0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity (P for interaction ≥0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 (−0.888; −1.677, −0.099) ng/mL decrease in the serum folate. ConclusionsHigher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our findings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.

Associations between urinary phthalate concentrations and antral follicle count among women undergoing in vitro fertilization.

Phthalates are ubiquitously used in a variety of products and have an adverse effect on folliculogenesis. However, previous epidemiological studies on the associations between phthalate exposure and antral follicle count (AFC) produced conflicting results. The present study aimed to evaluate the associations between urinary phthalate metabolite concentrations and AFC among women undergoing in vitro fertilization (IVF). We collected 525 urine samples and measured 8 phthalate metabolites from IVF patients. Poisson regression models were conducted to evaluate the associations between phthalate metabolite concentrations and AFC. In addition, participants were stratified into a younger group (< 35 years) and an older group (≥ 35 years) to explore the potential effect modification by age. We also performed sensitivity analyses by restricting our analyses to only infertile women diagnosed with tubal factor infertility to test the robustness of the results. Significant positive associations were observed among urinary MBP, MEOHP and ∑PAEs concentrations and AFC after adjusting for age, BMI, year of study and infertility diagnosis. Compared with women in the first tertile, women in the third tertile of MBP and MEOHP had 7.02% (95% CI: 1.18%, 12.9%) and 8.84% (95% CI: 2.83%, 14.9%) higher AFC, respectively, and women in the second and third tertiles of ∑PAEs had 6.19% (95% CI: 0.37%, 12.0%) and 9.09% (95% CI: 3.22%, 15.0%) higher AFC, respectively. In addition, MBP, MEOHP and ∑PAEs also had significant positive associations with AFC in trend tests for dose-response. In the age-stratified analysis, we found a stronger relationship between phthalate metabolite concentrations and AFC among older women and an inverse association among younger women. We observed similar results in the sensitivity analyses. We found positive associations between phthalate exposure and AFC, which support the idea that phthalate exposure may accelerate primordial follicle recruitment and lead to higher AFC in women undergoing IVF. More studies are needed to better understand their relationships.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): , 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: , 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

Paternal and maternal preconception and maternal pregnancy urinary phthalate metabolite and BPA concentrations in relation to child behavior

BackgroundEpidemiologic studies on health effects of parental preconception exposures are limited despite emerging evidence from toxicological studies suggesting that such exposures, including to environmental chemicals, may affect offspring health. ObjectiveWe investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate metabolite and bisphenol A (BPA) concentrations were associated with child behavior. MethodsWe analyzed data from the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6–11 years whose parent(s) previously enrolled in the prospective preconception Environment and Reproductive Health (EARTH) study. Using linear mixed models, we estimated covariate-adjusted associations of 11 urinary phthalate metabolite and BPA concentrations collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 (BASC-3) T-scores (higher scores indicate more problem behaviors). ResultsThis analysis included 134 mothers, 87 fathers and 157 children (24 sets of twins); parents were predominantly non-Hispanic white (mothers and fathers86%). Higher maternal preconception or pregnancy monobenzyl phthalate (MBzP) concentrations were related to higher mean externalizing problems T-scores in their children (β = 1.3 per 1-loge unit increase; 95 % CI: −0.2, 2.4 and β = 2.1, 95 % CI: 0.7, 3.6, respectively). Higher maternal preconception monocarboxyoctyl phthalate (MCOP) was suggested to be related to lower mean externalizing problems T-scores (β = -0.9; 95 % CI: −1.8, 0.0). Higher paternal preconception MCOP was suggestively associated with lower internalizing problems (β = -0.9; 95 %CI:-1.9, 0.1) and lower Behavioral Symptoms Index (BSI) T-scores (β = -1.3; 95 % CI: −2.1, −0.4). ConclusionIn this cohort, higher maternal preconception and pregnancy MBzP were associated with worse parent-reported child behavior, while higher maternal and paternal preconception MCOP concentrations were related to lower BASC-3 scores.

BMI-specific inflammatory response to phthalate exposure in early pregnancy: findings from the TMCHESC study.

Studies that have evaluated associations between phthalate metabolites and inflammation have reported inconsistent results among pregnant women, and it is unclear how body mass index (BMI) affects such relationships. Therefore, the present study aimed to examine the association between urinary phthalate metabolite concentrations and the levels of inflammatory biomarkers in the general circulation among 394 pregnant women selected from the Tianjin Maternal and Child Health Education and Service Cohort (TMCHESC) and to determine the role that BMI plays in the relationship. The concentrations of eight inflammatory biomarkers and three phthalate metabolites were measured in serum and urine samples, respectively. Multivariable linear modeling was conducted to examine the association between each phthalate and inflammatory biomarker while controlling for potential confounding factors in BMI-stratified subgroups. Restricted cubic splines were also utilised to explore potential non-linear relationships. In the high-BMI group, positive associations were observed between the levels of mono-n-butyl phthalate (MBP) and interleukin 1 beta (IL-1β) (β = 0.192; 95% CI: 0.033, 0.351), monoethyl phthalate (MEP), and C-reaction protein (CRP) (β = 0.129; 95% CI 0.024, 0.233), and mono-ethylhexyl phthalate (MEHP) and interleukin 6 (IL-6) (β = 0.146; 95% CI 0.016, 0.277). Restricted cubic spline models also revealed non-linear associations between the levels of MBP and interleukins 10 and 17A (IL-10 and IL-17A) and between MEP and interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) in pregnant women. These results suggest that phthalate exposure plays a potential role in promoting inflammation in the high-BMI group. While the precise mechanisms underlying the proinflammatory effects of phthalates are not fully understood, these findings suggest that BMI may play a role.

A Mixture of Urinary Phthalate Metabolite Concentrations During Pregnancy and Offspring Social Responsiveness Scale Scores.

Phthalates are a group of chemicals with ubiquitous exposure worldwide. Exposures to phthalates during pregnancy may play a role in autism spectrum disorder (ASD) etiology by disrupting hormone levels or directly impacting fetal neurodevelopment. However, there is little research quantifying the aggregate effect of phthalates on child ASD-related behaviors. We used data from two prospective pregnancy and birth cohorts-the Health Outcomes and Measures of the Environment (HOME) and the Early Autism Risk Longitudinal Investigation (EARLI). HOME is a general population cohort while participants in EARLI were at higher familial risk for ASD. Using quantile g-computation and linear regression models, we assessed the joint and individual associations of a mixture of six phthalate metabolites during pregnancy with child ASD-related traits measured by Social Responsiveness Scale (SRS) scores at ages 3-8 years. Our analyses included 271 participants from HOME and 166 participants from EARLI. There were imprecise associations between the phthalate mixture and SRS total raw scores in HOME (difference in SRS scores per decile increase in every phthalate = 1.3; 95% confidence interval [CI] = -0.2, 2.8) and EARLI (difference in SRS scores per decile increase in every phthalate = -0.9; 95% CI = -3.5, 1.7). The cohort-specific effect sizes of the pthalates-SRS associations were small and CIs were imprecise. These results suggest that if there are associations between phthalate metabolites during pregnancy and child SRS scores, they may differ across populations with different familial liabilities. Further studies with larger sample sizes are warranted.

Maternal concentrations of phthalates and Attention-Deficit Hyperactivity Disorder (ADHD-) related symptoms in children aged 2 to 4 years from Odense child cohort

BackgroundPhthalates are endocrine disrupting chemicals used in everyday consumer products. Several epidemiological studies have examined the association between prenatal phthalate concentration and Attention-Deficit Hyperactivity Disorder (ADHD) in offspring, but the findings have been inconclusive. ObjectivesTo investigate the association between maternal urinary concentrations of phthalate metabolites during pregnancy and ADHD related symptoms in children at 2 to 4 years in a large prospective cohort. MethodsIn the Odense Child Cohort from Denmark were women recruited in early pregnancy from 2010 to 2012. Phthalate concentrations were measured in urine samples collected in 3rd trimester and separated into low and high weight phthalates. Parents filled in the Child Behavior Checklist for ages 1.5 to 5 years (CBCL/1½-5), including a 6-item ADHD symptom scale at children aged 2 to 4 years. Data were analysed by use of adjusted negative binomial regression. ResultsA total of 658 mother–child pairs were included. Urinary phthalate metabolite concentrations were generally low compared to previous cohorts. A doubling in maternal concentration of the low-weighted phthalate metabolite MCPP was significantly associated with lower ADHD symptoms score in children (IRR: 0.95 (95 % CI 0.91–0.98)), strongest in girls (IRR: 0.92 (0.87–0.98)). Sex differences were observed. High maternal phthalate metabolite concentrations were associated with lower ADHD symptom score in girls, significant trends across tertile of MCPP and MnBP (p = 0.018, p = 0.038, respectively). In boys, maternal concentrations of high-molecular-weight phthalates (MBzP, ∑DiNP and ∑DEHP) were associated with an almost significantly higher ADHD symptom score (IRR for a doubling in concentration: 1.04 (95 % CI: 0.99–1.10), IRR: 1.05 (95 % CI: 0.97–1.13), IRR: 1.04 (95 % CI: 0.99–1.10), respectively). ConclusionMaternal concentration of the low-weighted phthalate metabolite MCPP was significantly associated with a lower ADHD symptom score in children, strongest in girls. Maternal concentrations of high-molecular-weight phthalates were associated with non-significant increase in ADHD symptom score in boys.

The associations of preconception urinary phthalate metabolite concentrations with the serum metabolome and outcomes of infertility treatment

The associations of preconception urinary phthalate metabolite concentrations with the serum metabolome and outcomes of infertility treatment

Prenatal exposure to common plasticizers: a longitudinal study on phthalates, brain volumetric measures, and IQ in youth.

Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T1-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (β per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (β for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.

Assessment of phthalate exposure at a fire site in Korean firefighters

ABSTRACT To determine phthalate exposure in 32 firefighters, the concentrations of urinary phthalate metabolites, immediately (exposure day) and three weeks (control day) after fire suppression, were compared. Mono-(2-ethyl-5-carboxypentyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-n-butyl phthalate (MBP), mono-n-benzyl phthalate (MBzP), and total phthalates (∑phthalates) levels, and creatinine-adjusted levels of MBP, MBzP, and ∑phthalates were significantly higher on exposure day than on control day. Phthalate concentration was significantly higher in firefighters who performed the fire extinguishing tasks (geometric mean [GM], 149.9 μg/L) than in those who performed other tasks (GM 70.8 μg/L) (p = .012). The GM concentration of firefighters who were active ≤ 50 m from the fire was 119.0 μg/L, and 37.6 μg/L for those who were > 50 m away (p = .012). The GM concentration was significantly different (p = .039) in firefighters with subjective symptoms after fire suppression (151.9 μg/L) compared to those without symptoms (81.6 μg/L). This study showed that firefighters were exposed to phthalate.