Phthalate Metabolites Research Articles

Phthalate exposure in association with the use of personal care products among general population from Shanghai.

Phthalates are used in a wide variety of personal care products (PCPs) as solubilizer, denaturant or color fixative. However, there are few studies referring the correlation between phthalate exposure and PCPs use among general population in China. In this study, ten metabolites of phthalates in spot urine samples (N = 500) were quantified using ultra-performance liquid chromatography tandem mass spectrometry. The frequency and duration of 12 types of PCPs were collected by questionnaire survey. The associations of phthalate metabolites and PCPs use were assessed by multivariable liner regression models. Median concentration of mono-benzylphthalate (MBzP) was significantly higher among frequent users of almost all PCPs. Low molecular weight phthalates (monomethyl phthalate (MMP), mono-n-butylphthalate (MnBP) and monoisobutylphthalate (MiBP)) were significantly lower among frequent user of some rinse-off PCPs (e.g., shampoo, facial cleanser, and body wash). Meanwhile, monoethylphthalate (MEP) was positive correlated with frequently use of facial moisturizer. Mono-2-ethylhexylphthalate (MEHP) and MBzP showed a significant positive association with frequently use of body lotion. Univariate linear analyses indicated a significant decreasing trend between urinary concentrations of MMP, MnBP, and the number of rinse-off PCPs being frequently used, and a significant increasing trend between urinary MBzP and the number of leave-on products being frequently used. These findings indicated that the use of some PCPs, especially leave-on PCPs, could be a potential source of exposure to some phthalates.

Associations of Prenatal Exposure to Phthalates with Measures of Cognition in 4.5-Month-Old Infants.

The association of prenatal phthalate exposure with physical reasoning was assessed in 159 (78 female; 81 male) 4.5-month-old infants from a prospective cohort. Phthalate metabolites were quantified in urine from 16–18 gestational weeks and a pool of five urines from across pregnancy. Infants’ looking times to physically impossible and possible events were recorded via infrared eye-tracking. Infants that recognize that one of the events is impossible will look at that event longer. Associations of phthalate biomarkers with looking time differences (impossible–possible) were adjusted for maternal age, infant sex, and order of event presentation, and effect modification by infant sex was assessed. Each interquartile range (IQR) increase of monoethyl phthalate in the pooled sample was associated with females’ increased looking time (β = 1.0; 95%CI = 0.3, 1.7 s) to the impossible event. However, for males, an IQR increase in monoethyl phthalate at 16–18 weeks (β = −2.5; 95%CI = −4.4,−0.6 s), the sum of di(isononyl) phthalate metabolites in the pooled sample (β = −1.0; 95%CI = −1.8, −0.1 s), and the sum of all phthalate metabolites in both samples (β = −2.3; 95%CI = −4.4, −0.2 s) were associated with increased looking to the possible event, suggesting that higher prenatal phthalate exposure is associated with poorer physical reasoning in male infants.

Maternal Food and Beverage Consumption Behaviors and Discrepant Phthalate Exposure by Race.

Background: Differential exposure to endocrine-disrupting chemicals, including phthalate diesters, may contribute to persistent racial/ethnic disparities in women’s reproductive health outcomes. We sought to characterize sources of gestational exposure to these agents that may differ according to maternal race. Methods: We enrolled pregnant Black (n = 198), including African American, and White (n = 197) women during the second trimester, and measured eight phthalate monoester metabolites in urine. We assessed confounder-adjusted associations between multiple food and beverage consumption habits, summarized using a principal component analysis, as predictors of maternal urinary phthalate metabolite levels, stratified by race. Results: Whites reported significantly greater unprocessed food consumption (42.5% vs. 32.0%; p < 0.001) and storage of food in clear unbreakable plastic containers (66.5% vs. 49.3%; p < 0.001) than Blacks, while Blacks consumed more canned fruits and vegetables (23.5% vs. 12.2%; p < 0.001) than Whites. Using plastics for food storage, microwaving in plastic containers, and using hard plastic water bottles was associated with urinary phthalate concentrations, especially DEHP metabolites (e.g., mean difference = 5.13%; 95% CI: 3.05, 7.25). These associations were driven primarily by Black pregnant women. Conclusions: Targeted interventions to reduce maternal exposure to phthalates need to be designed with specific attention to differences in food and beverage consumption behaviors among Black and White women.

Prenatal Exposure to Mixtures of Phthalates, Parabens, and Other Phenols and Obesity in Five-Year-Olds in the CHAMACOS Cohort.

Exposures to phthalates, parabens, and other phenols are often correlated due to their ubiquitous use in personal care products and plastics. Examining these compounds as a complex mixture may clarify inconsistent relationships between individual chemicals and childhood adiposity. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal cohort of children in Salinas Valley, California (n = 309), we examined biomarkers of 11 phthalate metabolites and 9 phenols, including several parabens and bisphenol A, measured in maternal urine at two time points during pregnancy. We measured child height and weight at age five to calculate the body mass index (BMI) z-scores and overweight/obesity status. The association between prenatal urinary concentrations of biomarkers with the childhood BMI z-score and overweight/obesity status was analyzed using single-pollutant models and two mixture methods: Bayesian hierarchical modeling (BMH) and Bayesian kernel machine regression (BKMR). Urinary concentrations of monoethyl phthalate, monocarboxy-isononly phthalate (metabolites of diethyl phthalate and di-isodecyl phthalate, respectively), and propylparaben were consistently associated with an increased BMI z-score and overweight/obesity status across all modeling approaches. Higher prenatal exposures to the cumulative biomarker mixture also trended with greater childhood adiposity. These results, robust across two methods that control for co-pollutant confounding, suggest that prenatal exposure to certain phthalates and parabens may increase the risk for obesity in early childhood.

Gestational Exposure to Phthalates and Social Responsiveness Scores in Children Using Quantile Regression: The EARLI and HOME Studies.

Linear regression is often used to estimate associations between chemical exposures and neurodevelopment at the mean of the outcome. However, the potential effect of chemicals may be greater among individuals at the ‘tails’ of outcome distributions. Here, we investigated distributional effects on the associations between gestational phthalate exposure and child Autism Spectrum Disorder (ASD)-related behaviors using quantile regression. We harmonized data from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 140) Study, an enriched-risk cohort of mothers who had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study (n = 276), a general population cohort. We measured concentrations of 9 phthalate metabolites in urine samples collected twice during pregnancy. Caregivers reported children’s ASD-related behaviors using the Social Responsiveness Scale (SRS) at age 3–8 years; higher scores indicate more ASD-related behaviors. In EARLI, associations between phthalate concentrations and SRS scores were predominately inverse or null across SRS score quantiles. In HOME, positive associations of mono-n-butyl phthalate, monobenzyl phthalate, mono-isobutyl phthalate, and di-2-ethylhexyl phthalate concentrations with SRS scores increased in strength from the median to 95th percentile of SRS scores. These results suggest associations between phthalate concentrations and SRS scores may be stronger in individuals with higher SRS scores.

Association between gestational phthalate exposure and newborn head circumference; impacts by race and sex

Observational and experimental studies report associations between gestational phthalate exposure and fetal development, yet few data exist to characterize phthalate effects on head circumference (HC) or to estimate the impact of race or sex. To address this data gap, we enrolled 152 African American and 158 white mothers with uncomplicated singleton pregnancies from the Charleston, South Carolina (USA) metropolitan area in a prospective birth cohort. Study participants provided up to two urine specimens during mid and late gestation, completed a study questionnaire, and allowed access to hospital birth records. We measured eight phthalate monoester metabolites using liquid chromatography with tandem mass spectrometry, and calculated molar sums of phthalate parent diesters. After specific gravity correction, we tested for associations between phthalates and neonatal HC (cm) and cephalization index (cm/g) using multiple informant linear regression with inverse probability weighting to account for selection bias between repeated urine sampling, adjusted for maternal race, age, body mass index, education, and smoking. We explored interactions by maternal race and infant sex. A doubling of urinary monoethyl phthalate (MEP) concentration was associated with a −0.49% (95%CI: -0.95%, −0.02%) smaller head circumference, although seven other phthalate metabolites were null. There were no statistically significant associations with cephalization index. HC was larger for whites than African American newborns (p < 0.0001) but similar for males and females (p = 0.16). We detected interactions for maternal race with urinary monobutyl phthalate (MBP; p = 0.03), monobenzyl phthalate (MBzP; p = 0.01), monoethylhexyl phthalate (MEHP; p = 0.05), monomethyl phthalate (MMP; p = 0.02), and the sum of dibutyl phthalate metabolites (∑DBP; p = 0.05), in which reduced HC circumference associations were stronger among whites than African Americans, and interactions for sex with MBP (p = 0.08) and MiBP (p = 0.03), in which associations were stronger for females than males. Our results suggest that gestational phthalate exposure is associated with smaller neonatal HC and that white mothers and female newborns have greater susceptibility.

Prenatal phthalate exposures and executive function in preschool children

BackgroundPrenatal phthalate exposure has been linked with altered neurodevelopment, including externalizing behaviors and attention-deficit hyperactivity disorder (ADHD). However, the implicated metabolite, neurobehavioral endpoint, and child sex have not always been consistent across studies, possibly due to heterogeneity in neurodevelopmental instruments. The complex set of findings may be synthesized using executive function (EF), a construct of complex cognitive processes that facilitate ongoing goal-directed behaviors. Impaired EF can be presented with various phenotypes of poor neurodevelopment, differently across structured conditions, home/community, or preschool/school. We evaluated the relationship between prenatal phthalate exposure and comprehensive assessment of preschool EF. MethodsOur study comprised 262 children with clinically significant/subthreshold ADHD symptoms and 78 typically developing children who were born between 2003 and 2008 and participated in the Preschool ADHD Substudy, which is nested within a population-based prospective cohort study, the Norwegian Mother, Father, and Child Cohort (MoBa). Twelve phthalate metabolites were measured from urine samples that their mothers had provided during pregnancy, at 17 weeks’ gestation. All children, at approximately 3.5-years, took part in a detailed clinical assessment that included parent-and teacher-rated inventories and administered tests. We used instruments that measured constructs related to EF, which include a parent-and teacher-reported Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and three performance-based tests: A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet intelligence test V (SB5), and the cookie delay task (CDT). The standard deviation change in test score per interquartile range (IQR) increase in phthalate metabolite was estimated with multivariable linear regression. We applied weighting in all models to account for the oversampling of children with clinically significant or subthreshold symptoms of ADHD. Additionally, we assessed modification by child sex and potential co-pollutant confounding. ResultsElevated exposure to mono-benzyl phthalate (MBzP) during pregnancy was associated with poorer EF, across all domains and instruments, in both sex. For example, an IQR increase in MBzP was associated with poorer working memory rated by parent (1.23 [95% CI: 0.20, 2.26]) and teacher (1.13 [0.14, 2.13]) using BRIEF-P, and administered tests such as SB5 (no-verbal: 0.19 [0.09, 0.28]; verbal: 0.13 [0.01, 0.25]). Adverse associations were also observed for mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP), although results varied by instruments. EF domains reported by parents using BRIEF-P were most apparently implicated, with stronger associations among boys (e.g., MnBP and inhibition: 2.74 [1.77, 3.72]; MiBP and inhibition: 1.88 [0.84, 2.92]) than among girls (e.g., MnBP and inhibition: −0.63 [−2.08, 0.83], interaction p-value: 0.04; MiBP and inhibition: −0.15 [−1.04, 0.74], interaction p-value: 0.3). Differences by sex, however, were not found for the teacher-rated BRIEF-P or administered tests including NEPSY, SB5, and CDT. Conclusion and relevanceElevated mid-pregnancy MBzP, MiBP, and MnBP were associated with more adverse profiles of EF among preschool-aged children across a range of instruments and raters, with some associations found only among boys. Given our findings and accumulating evidence of the prenatal period as a critical window for phthalate exposure, there is a timely need to expand the current phthalate regulations focused on baby products to include pregnancy exposures.

Environmentally relevant mixtures of phthalates and phthalate metabolites differentially alter the cell cycle and apoptosis in mouse neonatal ovaries†.

Phthalates are a group of chemicals used as additives in various consumer products, medical equipment, and personal care products. Phthalates and their metabolites are consistently detected in humans, indicating widespread and continuous exposure to multiple phthalates. Thus, environmentally relevant mixtures of phthalates and phthalate metabolites were investigated to determine the effects of phthalates on the function of the ovary during the neonatal period of development. Neonatal ovaries from CD-1 mice were cultured with dimethyl sulphoxide (DMSO; vehicle control), phthalate mixture (0.1-100μg/mL), or phthalate metabolite mixture (0.1-100μg/mL). The phthalate mixture was composed of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. The phthalate metabolite mixture was composed of 37% monoethyl phthalate, 19% mono(2-ethylhexyl) phthalate, 15% monobutyl phthalate, 10% monoisononyl phthalate, 10% monoisobutyl phthalate, and 8% monobenzyl phthalate. After 96h of culture, ovaries were harvested for histological analysis of folliculogenesis, gene expression analysis of cell cycle and apoptosis regulators, and immune staining for cell proliferation and apoptosis. The metabolite mixture significantly decreased the number and percentage of abnormal follicles (100μg/mL) compared to controls. The metabolite mixture also significantly increased the expression of cell cycle inhibitors (100μg/mL) and the antiapoptotic factor Bcl2l10 (10μg/mL) compared to controls. The phthalate mixture did not significantly alter gene expression or follicle counts, but ovaries exposed to the phthalate mixture (0.1μg/mL) exhibited marginally significantly increased apoptosis as revealed by DNA fragmentation staining. Overall, these data show that parent phthalates and phthalate metabolites differentially impact ovarian function.

Determination of phthalate concentrations in paper-based fast food packaging available on the U.S. market

ABSTRACT Phthalates are one of many chemical compounds that are used as plasticisers. Packaging can transfer plasticisers to the surfaces of foods or other materials. A recent study suggested a link between fast food consumption and increased urine phthalate metabolites even though phthalates are most commonly found in food contact materials made of PVC while fast food packaging is most commonly composed of paper and paper board. Phthalates in PVC are usually present in percent concentrations. In non-PVC food contact materials, such as paper or paperboard, the concentrations, if any, are expected to be significantly lower which can greatly impact the analytical method used for their determination. Due to the widespread use of plasticised PVC in many commercial applications, background concentrations of phthalates are a concern for trace concentration analyses and background contamination must be avoided when performing these analyses. A glassware cleaning method was developed and a solvent extraction with dichloromethane and hexane was used to extract phthalates from paper-based food packaging. The extracts were then analysed using a GC-MS/MS. The minimum reporting concentrations for the method were determined to be 0.10–0.40 µg/g depending on the phthalate investigated. Phthalate concentrations in several different non-PVC printed and unprinted packaging are presented. Of the 54 packaging samples tested, 10 samples contained no reportable concentrations of any of the 6 phthalates investigated. Of those that were reportable, all measured lower than 10 µg/g and in fact, most had concentrations less than 1 µg/g. These data demonstrate that phthalates from fast food packaging do not significantly contribute to overall consumer exposure.

Phthalate and Bisphenol Urinary Concentrations, Body Fat Measures, and Cardiovascular Risk Factors in Dutch School-Age Children.

ObjectiveThe purpose of this study was to investigate the associations of urinary phthalates and bisphenols at age 6 years old with body fat and cardiovascular risk factors at 6 and 10 years and with the change from 6 to 10 years.MethodsAmong 471 Dutch children, the phthalates and bisphenols urinary concentrations at 6 years and BMI, fat mass index, android fat mass, blood pressure, glucose, insulin, and lipids blood concentrations at 6 and 10 years were measured.ResultsAn interquartile range increase in di‐n‐octyl phthalate (DNOP) metabolites concentrations at 6 years was associated with an increased risk of overweight at 6 and 10 years (odds ratio: 1.44; 95% CI: 1.11‐1.87, and 1.43; 95% CI: 1.09‐1.86, respectively). Also, higher DNOP metabolites concentrations were associated with higher fat mass index at 6 years, higher systolic blood pressure at 10 years, a decrease in high‐density lipoprotein cholesterol, and an increase in triglycerides concentrations from 6 to 10 years (P < 0.05). Higher total bisphenols and bisphenol A concentrations were associated with a decrease in BMI from 6 to 10 years (P < 0.01).ConclusionsDNOP metabolites are associated with overweight and an adverse cardiovascular profile in childhood. Total bisphenols and bisphenol A are associated with a decrease in BMI from 6 to 10 years.

Prenatal exposure to endocrine disrupting chemical mixtures and infant birth weight: A Bayesian analysis using kernel machine regression

BackgroundPregnant women are regularly exposed to a multitude of endocrine disrupting chemicals (EDCs). EDC exposures, both individually and as mixtures, may affect fetal growth. The relationship of EDC mixtures with infant birth weight, however, remains poorly understood. We examined the relations between prenatal exposure to EDC mixtures and infant birth weight. MethodsWe used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1857 pregnant women enrolled between 2008 and 2011. We quantified twenty-one chemical concentrations from five EDC classes, including organochlorine compounds (OCs), metals, perfluoroalkyl substances (PFAS), phenols and phthalate metabolites that were detected in >70% of urine or blood samples collected during the first trimester. In our primary analysis, we used Bayesian kernel machine regression (BKMR) models to assess variable importance, explore EDC mixture effects, and identify any interactions among EDCs. Our secondary analysis used traditional linear regression to compare the results with those of BKMR and to quantify the changes in mean birth weight in relation to prenatal EDC exposures. ResultsWe found evidence that mixtures of OCs and metals were associated with monotonic decreases in mean birth weight across the whole range of exposure. trans-Nonachlor from the OC mixture and lead (Pb) from the metal mixture had the greatest impact on birth weight. Our linear regression analysis corroborated the BKMR results and found that a 2-fold increase in trans-nonachlor and Pb concentrations reduced mean birth weight by −38 g (95% confidence interval (CI): −67, −10) and −39 g (95% CI: −69, −9), respectively. A sex-specific association for OC mixture was observed among female infants. PFAS, phenols and phthalates were not associated with birth weight. No interactions were observed among the EDCs. ConclusionsUsing BKMR, we observed that both OC and metal mixtures were associated with decreased birth weight in the MIREC Study. trans-Nonachlor from the OC mixture and Pb from the metal mixture contributed most to the adverse effects.

Urinary phthalate metabolites and alternatives and serum sex steroid hormones among pre- and postmenopausal women from NHANES, 2013–16

BackgroundExposure to phthalates is ubiquitous across the United States. While phthalates have anti-androgenic effects in men, there is little research on their potential impacts on sex hormone concentrations in women and that also take into account menopausal status. MethodsCross-sectional data on urinary phthalate metabolites, serum sex hormones, and relevant covariates were obtained from the National Health and Nutrition Examination Survey 2013–14 and 2015–16. Women over the age of 20 who were not pregnant or breastfeeding and had not undergone oophorectomy were included (n = 698 premenopausal, n = 557 postmenopausal). Weighted multivariable linear and Tobit regression models stratified by menopausal status were fit with natural log-transformed phthalate concentrations and sex hormone outcomes adjusting for relevant covariates. ResultsPhthalate metabolites were associated with differences in sex hormone concentrations among postmenopausal women only. Di-2-ethylhexyl phthalate (DEHP) was associated with lower serum estradiol and bioavailable testosterone concentrations. Specifically, a doubling of DEHP concentrations was associated with 5.9% (95% Confidence Interval (CI): 0.2%, 11.3%) lower estradiol and 6.2% (95% CI: 0.0%, 12.1%) lower bioavailable testosterone concentrations. In contrast, 1,2-cyclohexane dicarboxylic acid di-isononyl ester (DINCH) was associated with higher free testosterone, bioavailable testosterone, and free androgen index. Finally, di-2-ethylhexyl terephthalate (DEHTP) was associated with a higher testosterone-to-estradiol ratio. None of these results retained statistical significance when adjusted for multiple comparisons. ConclusionsDEHP, DINCH, and DEHTP were associated with differences in serum sex hormone concentrations among postmenopausal women, highlighting the need for further research into the safety of these chemicals.

Prenatal exposure to phthalates and maternal metabolic outcomes in a high-risk pregnant Latina population

BackgroundPhthalates are a group of endocrine disrupting chemicals that are heavily used throughout industry in flexible plastic and personal-care products. As a result, detectable levels of their metabolites are readily found in humans. Some studies have shown associations of phthalates with diabetes, but associations with gestational diabetes mellitus (GDM) are less clear. ObjectiveTo investigate the association of 11 prenatal urinary phthalate metabolites and development of GDM, impaired glucose tolerance (IGT), continuous plasma glucose level, and excessive gestational weight gain (GWG) in a population of pregnant Latina women (N = 415) enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study. MethodsPhthalate metabolite levels were measured via mass spectrometry from two urine samples collected in the end of the first and second trimester. Maternal plasma glucose levels, prior diabetes diagnosis, GDM diagnosis, and weight gain were abstracted from medical records. Multiple regression was used to evaluate the association between the average of the two urinary phthalate metabolites levels and maternal metabolic outcomes. In our sensitivity analysis, phthalate levels were categorized by level (as quartiles of exposure) and by timing of urine sample collection (as taken in first and second half of pregnancy). ResultsConsistent with findings from a nationally representative sample, all of the individual phthalate metabolites were detected in majority of mothers. Thirty-one mothers (7.5%) were diagnosed with GDM, 49 mothers (14.7%) displayed IGT, and 223 mothers (55.1%) gained an excessive amount of weight during their pregnancy. MEP concentrations were associated with an increased odds of excessive GWG (OR: 1.1, 95% CI: 1.0 to 1.3). We did not find an association between any phthalate metabolite and any maternal glucose outcome. ConclusionContrary to previous studies, our findings do not support an association of prenatal phthalate levels and increased odds for hyperglycemia, IGT, or GDM. But, we did find an increased odds of excessive GWG, a well-known risk factor for GDM.

Exposure of the French population to bisphenols, phthalates, parabens, glycol ethers, brominated flame retardants, and perfluorinated compounds in 2014–2016: Results from the Esteban study

BackgroundAs part of the French Human Biomonitoring (HBM) programme, the Esteban study described, among other things, biomarkers levels of various chemicals in adults (18–74 years old) and children (6–17 years old). This paper describes the design of the study and provides, for the first time, data on the biological exposure of the general French population to a wide range of contaminants posing a threat to human health which are currently found in domestic environments. MethodsEsteban is a cross-sectional study conducted on a nationwide sample of the French general population. Exposure biomarkers of six families of contaminants deemed detrimental to adults’ and children’s health were measured in biological samples collected either at participants’ homes by a nurse, or brought to a National Health Insurance examination centre. All participants were randomly selected (2503 adults and 1104 children). The geometric mean and percentiles of the distribution of levels were estimated for each biomarker. Most of the descriptive statistical analyses were performed taking into account the sampling design. ResultsResults provided a nationwide description of biomarker levels. Bisphenols (A, S and F), and some metabolites of phthalates and perfluorinated compounds (PFCs) (specifically, PFOS and PFOA) were quantified in almost all the biological samples analysed. Higher levels were observed in children (except for PFCs). Levels were coherent with international studies, except for bisphenols S and F, brominated flame retardants (BFRs) and parabens (with higher levels reported in the USA than in France). Conclusion and perspectivesThis study is the first to provide a representative assessment of biological exposure to domestic contaminants at the French population level. Our results show that the French general population was exposed to a wide variety of pollutants in 2014–2016, and identify the determinants of exposure. These findings will be useful to stakeholders who wish to advocate an overall reduction in the French population’s exposure to harmful substances. Similar future studies in France will help to measure temporal trends, and enable public policies focused on the reduction of those chemicals in the environment to be evaluated.

Urinary phthalates and body mass index in preschool children: The MIREC Child Development Plus study.

Childhood exposure to phthalates, a class of chemicals with known reproductive and developmental effects, has been hypothesized to increase the risk of obesity, but this association is not well understood in preschool children. We examined the association between urinary concentrations of phthalate metabolites and concurrently measured body mass index (BMI) and skinfolds among children between the ages of two and five years. We collected anthropometric measures and biomonitoring data on approximately 200 children enrolled in the Maternal-Infant Research on Environmental Chemicals Child Development Plus study. We measured 22 phthalate metabolites in children's urine and used the 19 metabolites detected in at least 40% of samples. Our primary outcome was BMI z-scores calculated using the World Health Organization growth standards. Skinfold z-scores were secondary outcomes. We used multivariable linear regression to evaluate the association between tertiles of phthalate concentrations and each anthropometric measure. We also used weighted quantile sum regression to identify priority exposures of concern. Our analytic sample included 189 singleton-born children with complete anthropometric data. Children with concentrations of the parent compound di-n-butyl phthalate (∑DnBP) in the third tertile had 0.475 (95% CI: 0.068, 0.883) higher BMI z-scores than those in the lower tertile. ∑DnBP was identified as a priority exposure in the weighted quantile sum regression BMI model. In this population of Canadian preschool aged children, we identified DnBP as a potential chemical of concern in regard to childhood obesity. Future research with serial phthalate measurements and anthropometric measurements in young children will help confirm these findings.

Phthalate mixtures in pregnancy, autistic traits, and adverse childhood behavioral outcomes

BackgroundPrenatal exposure to multiple phthalates is ubiquitous, and yet few studies have evaluated these exposures as a mixture in relation to child autistic traits and behavioral problems. ObjectivesTo assess cumulative associations between prenatal phthalate mixtures and child behaviors, including effect modification by exposure timing and child sex. MethodsAnalyses included 501 mother/child pairs from the multicenter pregnancy cohort The Infant Development and Environment Study (TIDES). Nine maternal urinary phthalate metabolites were measured in early and late pregnancy, and behavior was assessed at ages 4–5 years using composite T scores for the Behavioral Assessment System for Children (BASC-2), which measures several dimensions of child behavior, and the Social Responsiveness Scale (SRS-2), which measures social impairment consistent with autistic traits. We utilized weighted quantile sum (WQS) regressions to examine pregnancy period-specific associations between phthalate mixtures and behavioral outcomes. Full-sample 95% WQS confidence intervals are known to be anti-conservative, so we calculated a confirmatory p-value using a permutation test. Effect modification by sex was examined with stratified analyses. ResultsA one-quintile increase in the early pregnancy phthalate mixture was associated with increased SRS-2 total score (coefficient = 1.0, confirmatory p = 0.01) and worse adaptive skills (coefficient = −1.0, confirmatory p = 0.06) in both sexes. In sex-stratified analyses, the early pregnancy phthalate mixture was associated with increased SRS-2 total score in boys (coefficient = 1.2, confirmatory p = 0.04) and girls (coefficient = 1.0, confirmatory p = 0.10) and worse BASC-2 adaptive skills score in girls (coefficient = −1.5, confirmatory p = 0.06), while the late pregnancy phthalate mixture was associated with increased BASC-2 externalizing score in boys (coefficient = 1.3, confirmatory p = 0.03). ConclusionOur results suggest cumulative adverse associations between prenatal phthalate mixtures and multiple facets of childhood behavior.

Urinary phthalate metabolite concentrations, oxidative stress and thyroid function biomarkers among patients with thyroid nodules.

Prior human studies have explored effects of phthalate exposures on thyroid function, but the underlying biological mechanisms remain poorly unclear. We aimed to explore the associations between phthalate exposures and thyroid function among a potentially susceptible population such as patients with thyroid nodules, and further to assess the mediating role of oxidative stress. We measured eight phthalate metabolites, three oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine and three thyroid function biomarkers [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)] in serum among 214 patients with thyroid nodules. Multivariate regression models were applied to assess the associations among urinary phthalate metabolites, oxidative stress and thyroid function biomarkers. The potential mediating role of oxidative stress was explored by mediation analysis. We observed that multiple urinary phthalate metabolites were associated with altered FT4 and increased oxidative stress biomarkers (all FDR-adjusted P≤0.05). Meanwhile, we found that 8-isoPGF2α was negatively associated with FT3/FT4 among patients with benign thyroid nodules (FDR-adjusted P=0.08). The mediation analysis indicated that 8-isoPGF2α mediated the associations of urinary MEHHP and %MEHP with FT3/FT4, with 55.6% and 32.6% proportion of the mediating effects, respectively. Our data suggest that lipid peroxidation may be an intermediate mechanism involved in the effects of certain phthalate exposures on altered thyroid function among patients with benign thyroid nodules.

Association of phthalates and early menarche in Korean adolescent girls from Korean National Environmental Health Survey (KoNEHS) 2015–2017

BackgroundPhthalates are one of renowned endocrine-disrupting chemicals, although inconsistent results are present around their effect on onset of menarche. Our hypothesis is that pre-pubertal exposure to phthalates is associated with acceleration of menarche.MethodsWe analyzed a total of 236 middle school (7th to 9th grade) girls from Korean National Environmental Health Survey 2015–2017. We used multiple linear regression to investigate impact of eight phthalate metabolites on age of menarche. We also conducted logistic regression to evaluate association between phthalate metabolite concentrations and early onset of menarche, adjusting for grade, maternal age of menarche and body mass index (BMI).ResultsIn linear regression analysis, no significant association was found for any phthalate metabolites. In logistic regression analysis, however, odds ratios (ORs) of early menarche were significantly increased for mono-n-butyl phthalate (MnBP) and for sum of all phthalates. When compared to group with the lowest level, high concentration group for MnBP presented significantly increased odds of early menarche (OR: 2.09; 95% confidence interval [CI]: 1.03, 4.23) after adjusting for grade, maternal age of menarche and BMI. Furthermore, high concentrations of sum of all phthalates were associated with significant increase of OR of early menarche (OR: 2.22; 95% CI: 1.10, 4.49) after adjustment, compared to the lowest concentration group.ConclusionsResults of our study suggest that exposure to phthalates around puberty may be associated with increased risk of early menarche.

Prenatal phthalate exposures and autism spectrum disorder symptoms in low-risk children

BackgroundPrenatal exposure to environmental chemicals has been associated with Autism Spectrum Disorder (ASD) symptoms in some, but not all, studies, but most research has not accounted for other childhood behavior problems. ObjectivesTo evaluate the specific associations of prenatal phthalate exposures with ASD symptoms in children (ages 3–6) accounting for other behavior problems, and to assess sex differences in these associations. MethodsWe measured phthalate metabolites in prenatal urine samples. Mothers completed the Social Responsiveness Scale-2nd edition (SRS-2) to assess child ASD symptoms and the Child Behavior Checklist (CBCL) to assess general behavior problems. We assessed associations of the sum of di-(2-ethylhexyl) phthalate metabolites, monobutyl phthalate, mono-isobutyl phthalate, and monoethyl phthalate (mEP) with ASD symptoms, adjusting for other behavior problems, using linear regression models (n=77). ResultsMost associations were null, and the sample size limited power to detect associations, particularly in the stratified analyses. After adjusting for internalizing and externalizing problems from the CBCL, ASD symptoms increased for each doubling of prenatal mEP concentration among boys only. ConclusionsFurther investigation of maternal prenatal urinary phthalate metabolite concentrations and ASD symptoms while adjusting for other behavioral problems is warranted.

Phthalate Metabolites in Paired Human Serum and Whole Blood

Phthalate Metabolites in Paired Human Serum and Whole Blood