Urinary Phthalate Metabolite Concentrations Research Articles

The sex-specific association of phthalate exposure with DNA methylation and characteristics of body fat in children

The present study assessed the association between phthalate exposure and mitochondrial DNA (mtDNA) polymerase γ (POLG) methylation along with the potential effect on the characteristics of body fat in children. A total of 152 children were enrolled. The urinary concentrations of phthalate metabolites were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Genomic DNA was extracted from the buffy coat, and bisulfite-treated DNA was subjected to a pyrosequencing assay. In total, 17 CpG sites in the exon 2 region of POLG were included in the analysis. A multivariable regression model was applied to determine whether characteristics of body fat were associated with phthalate exposure and methylation of POLG. After adjustment for covariates, male children with a ten-fold increase in mono-methyl phthalate (MMP) or mono-benzyl phthalate (MBzP) concentrations had significantly higher measurements for total body fat (MMP: β = 6.47%; MBzP: β = 3.54%), and trunk fat (MMP: β = 6.67%; MBzP: β = 3.90%). Male children who had hypermethylation at the 2nd CpG site in exon 2 of POLG also had high measurements for BMI (β = 1.66 kg/m2), waist (β = 4.49 cm) and hip (β = 4.81 cm) circumference, total body fat (β = 5.48%), and trunk fat (β = 6.21%). A dose-response relationship existed between methylation at the 2nd CpG site in exon 2 of POLG and characteristics of body fat (p for trend<0.01). This study suggested that male children who are exposed to phthalic acid esters have high body weight, BMI, and body and trunk fat percentages. Methylation of the exon 2 region of POLG is a possible mechanism behind the causal effect of endocrine-disrupting substances.

Thyroxine-binding globulin, peripheral deiodinase activity, and thyroid autoantibody status in association of phthalates and phenolic compounds with thyroid hormones in adult population

Exposure to consumer chemicals such as phthalates and phenolic compounds has been associated with thyroid hormone disruption in humans. However, information related to factors that may influence such associations, e.g., transport and activation of the hormones, and autoimmunity status, is limited. In the present study, we employed a subpopulation of adults (n = 1,254) who participated in the Korean National Environmental Health Survey (KoNEHS) 2015–2017, and associated urinary concentrations of major phthalate metabolites, bisphenol A (BPA), and parabens, with thyroid hormone-related measures, including free and total T3 and T4, TSH, thyroxine-binding globulin (TBG), calculated peripheral deiodinase (DIO) activity, and thyroid autoantibodies of thyroperoxidase (TPO) and thyroglobulin (Tg). Phthalate metabolites were negatively associated with total T4 and free T3, and positively associated with total T3. These observations could be explained by TBG levels and calculated peripheral DIO activity that were positively associated with phthalates exposure. In contrast, BPA was positively associated with total T4 and negatively associated with total T3, without any changes in TBG concentration. Serum TPO and Tg antibodies were not associated with urinary phthalate metabolites and BPA. However, thyroid autoantibody status appeared to modulate the association of some phthalates with thyroid hormones. For parabens, little to negligible association was observed. The results of our observation show potential underlying mechanisms of phthalates-induced thyroid hormone disruption, and suggests the importance of consideration of thyroid autoimmunity status in association studies for thyroid disrupting chemicals.

Associations of prenatal urinary phthalate exposure with preterm birth: the Maternal-Infant Research on Environmental Chemicals (MIREC) Study.

To examine the relation between prenatal urinary phthalate metabolite concentrations and preterm birth (PTB). The data were drawn 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 urinary concentrations of 7 phthalate metabolites that were detected in > 70% of urine samples collected during the first trimester. Gestational age was obtained from either the last menstrual period or early ultrasound. We used Cox proportional hazard models to examine the associations of urinary phthalate metabolite concentrations, plus the molar sum of di-2-ethylhexyl phthalate metabolites (∑DEHP), with time to delivery before 37weeks of gestation. We also examined PTB by clinical presentation. PTBs presented with either spontaneous labour or premature rupture of the membrane were considered spontaneous PTB (sPTB). Additionally, we used multiple linear regression to model changes in mean gestational age in relation to phthalate exposure. We found no evidence of an association between first trimester phthalate metabolite concentrations and PTB among the MIREC study participants. For example, each 2-fold increase in any of the 7 phthalate concentrations or ∑DEHP was associated with hazard ratios (HRs) for PTB ranging from 0.95 to 1.07 with 95% confidence intervals including the null. An assessment of non-linear trends showed some evidence of non-monotonic dose-response relationships between phthalates and PTB. Furthermore, male infants exposed to MCPP showed higher sPTB risk compared with female infants. Phthalate exposure during early pregnancy is not clearly associated with the risk of PTB among this Canadian population.

Correlations of phthalate metabolites in urine samples from fertile and infertile men: Free-form concentration vs. conjugated-form concentration

In previous studies, the total content of urinary phthalate metabolites was commonly used to evaluate human exposure to phthalates. However, phthalate metabolites are mainly present in urine in two forms, conjugated and free. These metabolite forms in urine are more relevant to the biotransformation pathways of the phthalates in humans. Therefore, the concentration of these forms is more relevant to exposure related health outcomes than total content. In this study, instead of measuring total content, the free- and conjugated-form concentrations of phthalate metabolites in the urine of fertile and infertile men were measured. The main metabolites in urine of both groups are monoethyl phthalate (MEP) and the di-(2-ethylhexyl) phthalate (DEHP) metabolites. The geometric means of their both conjugated- and free-forms in the infertile group were higher than in the fertile group, specifically, 24.3 and 43.4 μg/g creatinine vs 8.5 and 28.9 μg/g creatinine, respectively, for MEP, and 50.0 and 9.1 μg/g creatinine vs 39.1 and 8.4 μg/g creatinine, respectively for total DEHP metabolites. We investigated the correlations of free- and conjugated-form phthalate metabolite concentrations between the infertile and fertile group as well as among different phthalate metabolites. The results showed that there was a statistically significant difference between the infertile and fertile group for monobenzyl phthalate (MBzP) in both free-form and conjugated-form. However, there was only a statistically significant difference between the two groups for conjugated-form MEP and MEHP, and no statistically significant difference between the two groups for free-form MEP and MEHP. The results of the Pearson correlation test revealed that the correlations between DEHP metabolites and the correlations between mid-sized phthalate metabolites (mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP) and mono-benzyl phthalate (MBzP)) were stronger than between these two clusters of metabolites. This study is the first attempt to examine possible effects of conjugated-form concentrations of phthalate metabolites on human fertility. The results of this study suggest that conjugated-form and free-form concentrations of urinary phthalate metabolites may be appropriate biomarkers for assessing human exposure to phthalates and association with health outcomes.

Association of urinary concentrations of phthalate metabolites with quinolinic acid among women: A potential link to neurological disorders

BackgroundQuinolinic acid (QA), a neuroactive metabolite produced during tryptophan degradation, is implicated in the pathogenesis of several neurological disorders. Phthalates are structurally similar to QA, and exposure to phthalates has demonstrated increased QA production and excretion in rodent studies. We recently showed that very high exposure to dibutyl phthalate was associated with higher concentrations of urinary QA in men. However, no human studies examined the associations between background (low) phthalate exposures and QA. ObjectivesTo examine the associations of urinary concentrations of phthalate metabolites with QA. MethodsFemale participants (N = 126) who participated in a prospective cohort study at the Massachusetts General Hospital Fertility Center provided 758 urine samples (273 during pregnancy and 485 during non-pregnancy). Concentrations of 11 phthalate metabolites and QA in urine were measured. We used multivariable linear mixed effect models to estimate the percent change in urinary QA concentrations associated with a doubling (100%) of urinary phthalate metabolite concentration, and evaluated whether there was effect modification by pregnancy status. ResultsWomen’s mean (standard deviation) age was 34.2 (4.0) years with a body mass index of 23.5 (3.7) kg/m2. The women were primarily Caucasian (92%), had at least a college degree (98%), and none were current smokers. Pairwise Spearman correlations between concentrations for phthalate metabolites and QA measured in the same urine samples ranged from 0.36 for MEHP to 0.68 for dibutyl phthalate (DBP) metabolites. In multivariable-adjusted models, the percent change in urinary QA concentrations was significantly higher for each doubling of several urinary phthalate metabolite concentrations. For example, each doubling of DBP metabolites was associated with a 13.7% (95%CI: 10.6, 16.9)% higher QA. Associations between the low molecular weight phthalate metabolites and QA were stronger among samples collected during pregnancy as compared to non-pregnancy samples from the same women. ConclusionsUrinary concentrations of several phthalate metabolites were positively associated with QA among women. These findings, along with the known neurotoxicity of QA, warrant the need to examine whether QA concentrations may serve as a pathway for the adverse neurodevelopment outcomes found in children’s health studies.

Maternal phthalate exposure and asthma, rhinitis and eczema in 552 children aged 5\u2009years; a prospective cohort study

BackgroundPrenatal phthalate exposure has been suggested to alter immune responses and increase the risk of asthma, eczema and rhinitis. However, few studies have examined the effects in prospective cohorts and only one examined rhinitis. We therefore studied associations between maternal urinary concentrations of phthalate metabolites and asthma, eczema and rhinitis in offspring aged 5 years.MethodsFrom 552 pregnant women in the Odense Child Cohort, we quantified urinary concentrations of 12 phthalate metabolites in third trimester. We assessed asthma, rhinitis and eczema in their offspring at age 5 years with a questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC), and conducted logistic regression adjusting for relevant confounders.Results7.4% of the children had asthma, 11.7% eczema and 9.2% rhinitis. Phthalate exposure was low compared to previous cohorts. No significant associations between prenatal phthalate exposure and asthma were found. Odds ratios (ORs) of child rhinitis with a doubling in ΣDiNPm and di-2-ethylhexyl phthalate metabolite (ΣDEHPm) concentrations were, respectively, 1.15 (95% confidence interval (CI) 0.97,1.36) and 1.21 (CI 0.93,1.58). The OR of eczema when doubling ΣDiNPm was 1.24 (CI 1.00,1.55), whereas the OR of using medicine against eczema when doubling a di-ethyl phthalate (DEP) metabolite was 0.81 (CI 0.68,0.96).ConclusionThe lack of association between maternal phthalate exposure and asthma in the offspring may be due to low exposure and difficulties in determining asthma in 5-year-olds. The higher odds of rhinitis may raise public concern but further research in larger cohorts of older children is warranted.

Lowering Urinary Phthalate Metabolite Concentrations among Children by Reducing Contaminated Dust in Housing Units: A Randomized Controlled Trial and Observational Study.

Dust in homes can contain phthalates that may adversely affect child development, but whether residential interventions and dust removal can prevent children's exposure to phthalates is unknown. We quantified the influence of a residential lead hazard intervention and dust control on children's urinary phthalate metabolite concentrations. Between 2003 and 2006, The Health Outcomes and Measures of the Environment (HOME) Study randomized 355 pregnant women to receive an intervention to reduce either residential lead or injury hazards before delivery. We quantified eight urinary phthalate metabolites from 288 children at ages 1, 2, or 3 years (680 observations). During yearly home visits, we assessed dust accumulation in housing units. Children in the lead intervention group had 11-12% lower concentrations of the sum of di(2-ethylhexyl) phthalate metabolites, monocarboxyoctyl phthalate, and monocarboxynonyl phthalate compared to the injury intervention group. Monoethyl phthalate concentrations did not differ by group. In observational analyses, children living in housing units that appeared clean had 12-17% lower concentrations of these phthalate metabolites and monobenzyl phthalate, compared to children living in housing units with more dust accumulation. Features of this lead hazard intervention and measures to control dust may reduce children's exposure to phthalates found in building materials and household furnishings.

Urinary concentrations of phthalate metabolites during gestation and intrahepatic cholestasis of pregnancy: a population-based birth cohort study.

Phthalates, a class of widely used endocrine-disrupting chemicals (EDCs), are toxic to various organ systems in animals and humans. Intrahepatic cholestasis of pregnancy (ICP) is a reversible liver dysfunction causing cholestasis in late pregnancy. Evidence on the associations between exposure to phthalates and ICP is still lacking. In the present study, we investigated the relationships between urinary concentrations of phthalate metabolites and the risk of ICP in a Chinese population-based birth cohort. Pregnant women participated in the Ma'anshan Birth Cohort (MABC) study in China. Seven phthalate metabolites were detected in a urine sample in early pregnancy. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for urine creatinine, race, education, poverty status, smoking status, alcohol consumption, maternal age, prepregnancy body mass index (BMI), parity, twin pregnancy, and pregnancy-related liver complications. Of 3474 women recruited into the Ma'anshan Birth Cohort, 2760 met the inclusion criteria and contributed to further analysis and biomonitoring data. Elevated odds ratios (ORs) of ICP were observed in the highest quartiles of monomethyl phthalate (MMP) exposure (OR = 1.59, 95% confidence intervals (CI) = 1.01-2.51) and monobutyl phthalate (MBP) exposure (OR = 1.82, 95% CI = 1.16-2.85) in the adjusted analyses. Our findings add to the evidence that supports the role of maternal phthalate exposure in the first trimester of gestation as a risk factor for ICP.

Relationship between urinary phthalate metabolites and diabetes: Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017).

BackgroundWe aimed to determine relationship diabetes according to urinary phthalate metabolites using adult data from Korean National Environmental Health Survey cycle 3 (2015–2017).MethodThis study was conducted on 3,781 adults aged 19 years and older (1,648 men and 2,133 women) based on KoNEHS cycle 3. Participants' data were analyzed by gender; Relationship between phthalate metabolites in the urine and diabetes was analyzed by dividing the sociodemographic variables, health behavior-related variables, and urinary phthalate metabolite concentrations into quartiles. To determine the relationship between urinary phthalate metabolites and the prevalence of diabetes, the odds ratio (OR) was calculated using logistic regression analysis.ResultsBased on the 1st quartile of each metabolite, the ORs for di-2-ethylhexyl phthalate (DEHP) (4th quartile), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (2nd quartile, 3rd quartile and 4th quartile), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (4th quartile), mono-(2-ethyl-5-carboxypentyl) phthalate (MECCP) (4th quartile), mono-n-butyl phthalate (MnBP) (3rd quartile and 4th quartile), mono-benzyl phthalate (MBzP) (2nd quartile) and 4th quartile), and mono (3-carboxypropyl) phthalate (MCPP) (3rd quartile and 4th quartile) were significantly higher after the adjustment in men. The ORs for DEHP (2nd quartile, 3rd quartile and 4th quartile), MEHHP (2nd quartile, 3rd quartile and 4th quartile), MEOHP (4th quartile), MECCP (4th quartile), MBzP (4th quartile), and MCPP (4th quartile) were significantly higher after the adjustment in women.ConclusionThis study investigated relationship between urinary phthalate metabolites and diabetes. The higher urinary phthalate metabolites, the higher the prevalence of diabetes. Further regulation of phthalate may be needed, and further studies are warranted to confirm the association between phthalate concentration and other chronic diseases (such as hypertension, hyperlipidemia, and cardiovascular disease).

Joint impact of phthalate exposure and stressful life events in pregnancy on preterm birth

BackgroundUrinary phthalate metabolites and psychosocial stress in pregnancy have each been associated with preterm birth (PTB), but no study has examined the joint impact of these two environmental exposures. We hypothesized that there would be stronger associations between phthalate exposure and PTB in mothers with higher stress in pregnancy compared to mothers with lower stress. MethodsWe addressed this question using data from The Infant Development and the Environment Study (TIDES), a prospective birth cohort conducted at four US sites (N = 783). We examined urinary phthalate metabolite concentrations measured in samples collected from up to three trimesters of pregnancy. Mothers reported their exposure to stressful life events (SLE) in each trimester in a questionnaire administered in the third trimester. PTB was defined as delivery before 37 weeks completed gestation (n = 71, 9.1%). We examined associations between urinary phthalate metabolite concentrations (individual time points and on average) and PTB using logistic regression models adjusted for maternal race, age, pre-pregnancy body mass index, education, specific gravity, and gestational age at sample collection. In addition, we created models stratified by whether or not mothers were exposed to any or no SLE in pregnancy. ResultsSummed di-2-ethylhexyl phthalate (ΣDEHP) metabolites measured in urine samples from the third trimester, but not the first trimester, were associated with an increased odds ratio (OR) of PTB (OR = 1.44, 95% confidence interval [CI] = 1.06, 1.95). In models stratified by SLE, associations between third trimester ΣDEHP concentrations and PTB were significant only for women experiencing one or more SLE during pregnancy (OR for ΣDEHP: 2.09, 95% CI: 1.29, 3.37) but not for women with no SLE during pregnancy (OR for ΣDEHP: 1.04, 95% CI: 0.66, 1.63) (p for interaction = 0.07). ConclusionsWe observed an association between urinary ΣDEHP levels and PTB that was modified by whether a mother was exposed to one or more psychosocial stressors during pregnancy. Additional research to understand the joint impacts of chemical and non-chemical exposures, with an emphasis on timing of exposure, is needed in order to advance the state of the science on how the environment influences pregnancy.

Human exposure levels of PAEs in an e-waste recycling area: Get insight into impacts of spatial variation and manipulation mode

Phthalic acid esters (PAEs) are one important category of additives in plastics, which are ubiquitous products of e-waste recycling areas, where PAEs are released to the environment intensively and higher exposure level is expected for the employees. This study investigated human exposure levels of PAEs in an e-waste recycling area (Ziya Circular Economy Park (ZCEP) in Tianjin, China) with intending to explore the impacts of residence spatial variation and dismantling manipulation mode. We collected 157 urine samples from three sites around ZCEP with different distances from the core dismantling site and urinary phthalate metabolites (mPAEs) concentrations were measured and were compared among these three sites. The exposure levels of PAEs exhibited spatial variation according to the distance from the core dismantling site, and urinary median ∑mPAEs concentrations (389 ng/mL) of the employees in ZCEP were significantly higher than those of residents in Ziya town (285 ng/mL) and the downtown of Jinghai district (207 ng/mL) (p < 0.05). Moreover, PAEs exposure levels were significantly affected by the manipulation modes in the e-waste recycling area and the urinary median ∑mPAEs concentrations in the employees of family workshops (401 ng/mL) were significantly higher than those in plants with centralized management (298 ng/mL). There were obvious differences on the urinary median mPAEs concentrations between subgroups based on age, BMI, and sex; however, no significant statistical associations were found between PAEs exposure levels and these socio-demographic indices (p > 0.05). Besides, there was no correlation between exposure levels of different PAEs and their physicochemical parameters like the logKow (p > 0.05).

Associations of urinary phthalate metabolites with risk of papillary thyroid cancer.

Some studies have revealed thyrotoxicity of phthalates; however, associations of phthalate exposure with papillary thyroid cancer (PTC) remain unclear. We conducted a pair-matching case-control study of 111 PTC cases and 111 age- and sex-matched non-PTC controls to examine associations between urinary concentrations of phthalate metabolites and PTC. Phthalate metabolites were determined in fasting urine specimens by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS). After adjusting for potential confounders and other phthalate metabolites, the concentrations of the sum of di (2-ethylhexly) phthalate (DEHP) metabolites in urine were positively associated with PTC [odds ratio (OR) = 5.35; 95% confidence interval (CI): 1.61-17.83], suggesting the effect of phthalates exposure on PTC development. The findings require confirmation.

Phthalate exposure and stressful life events in pregnancy have a joint effect on preterm birth

TPS 632: Health effects of flame retardants and plasticizers, Johan Friso Foyer, Floor 1, August 27, 2019, 3:00 PM - 4:30 PM Background: Urinary phthalate metabolites and psychological stress in pregnancy have been individually associated with preterm birth (PTB), but no study has examined the joint effect of these two environmental exposures. We hypothesized that there would be stronger associations between phthalate exposure and PTB in mothers with higher stress in pregnancy compared to mothers with lower stress. Methods: We addressed this question using data from The Infant Development and the Environment Study (TIDES), a prospective birth cohort conducted at four US sites (N=785). Urinary phthalate metabolite concentrations were measured in samples collected in the first and third trimesters of pregnancy. Stressful life events (SLE) during gestation were assessed by a questionnaire administered in the third trimester. PTB was defined as delivery before 37 weeks completed gestation (n=71). We examined associations between urinary phthalate metabolite concentrations at each visit in association with PTB using logistic regression models adjusted for maternal race, age, pre-pregnancy body mass index, specific gravity, and gestational age at sample collection. Results: Summed di-2-ethylhexyl phthalate (ΣDEHP) metabolites measured in urine samples from the third trimester, but not the first trimester, were associated with an increased odds ratio (OR) of PTB (OR=1.38, 95% confidence interval [CI] =1.01, 1.89). In models stratified by SLE, associations between third trimester ΣDEHP concentrations and PTB were significant only for women experiencing 1 or more SLE during pregnancy (OR: 2.05, 95% CI: 1.28, 3.29) but not for women with no SLE during pregnancy (OR: 0.99, 95% CI: 0.63, 1.55); the interaction was marginally significant (p=0.05). Conclusions: We observed an association between urinary ΣDEHP levels and PTB that was modified by psychological stress in pregnancy. Additional research to understand the joint effects of chemical as well as non-chemical exposures is necessary in order to advance the state of the science on how the environment impacts pregnancy.

Urinary concentrations of phthalate metabolites in relation to circulating fatty acid profile

Urinary concentrations of phthalate metabolites in relation to circulating fatty acid profile

Associations between in utero phthalate exposure and non-nutritive suck

TPS 731: Neurological effects in children, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background/Aim: Infant non-nutritive suck (NNS), or sucking on a pacifier with no nutrient being delivered, has been linked to childhood language, motor, IQ and overall neurodevelopment and is considered an index of early brain development. However, it remains unknown if an infant’s NNS pattern is a sensitive indicator of neurotoxicity induced by exposure to environmental contaminants. Our aim was to examine associations between in utero exposure to phthalates, chemicals widely used in plastics and personal care products, and infant NNS. Methods: The Center for Research on Early Childhood Exposure and Development (CRECE) examines how environmental exposures impact the health and development of infants and children living on the heavily-contaminated island of Puerto Rico. In this ongoing birth cohort, we measure maternal urinary concentrations of phthalate metabolites throughout pregnancy as measures of intrauterine exposure to their child. NNS is then measured in infants at 4-6 weeks of age using a custom research pacifier, yielding NNS amplitude (CmH20), frequency, bursts/min, cycles/min, and cycles/burst. Results: Thus far, we have NNS and in utero phthalate measures on 88 full-term infants (47 males) in this ongoing study. Linear models, controlling for sex, birthweight, and specific gravity reveal that the phthalate metabolites MCNP, MEHHP, and MEOHP were significantly associated with slower NNS frequencies, while MECPP, MEHHP, MEOHP, MONP, and MEHHTP were associated with higher NNS amplitudes (all p<0.05). In addition, MEHHP and MEOHP were also associated with fewer NNS cycles/min (p<0.05). Conclusions: These preliminary data suggest that certain features of infant suck, particularly NNS frequency and amplitude, are associated with in utero exposure to several phthalates, particularly di(2-ethylhexyl) phthalate. Results from this study will be the first to prospectively determine the sensitivity of NNS as an early indicator of exposure-related changes in neurodevelopment.

Trimester-specific urinary phenol, paraben, and phthalate metabolite concentrations in relation to singleton preterm birth

Trimester-specific urinary phenol, paraben, and phthalate metabolite concentrations in relation to singleton preterm birth

Is Breastfeeding a Source of Non-Persistent Chemical Exposure in Infants?

PDS 62: Chemicals and metals: exposure and biomarkers, Johan Friso Foyer, Floor 1, August 28, 2019, 10:30 AM - 12:00 PM Background: Exclusive breastfeeding is the recommended practice for the first 6 months following birth. Previous studies have detected phthalates and phenols in breast milk, but the contribution of breastfeeding to an infant’s exposure to these chemicals is unknown. We hypothesized that breastfed children would have higher urinary phthalate metabolite and phenol concentrations compared with non-breastfed children. Methods: We used data from 295 mother-child pairs in the HOME Study (Cincinnati, Ohio, enrolled: 2003-2006). Research assistants assessed breastfeeding duration via maternal report when infants were approximately 12 months old. We also quantified concentrations of eight phthalate metabolites and three phenols (bisphenol A, triclosan, and benzophenone-3) in infants’ urine collected at the same time. We estimated geometric mean (GM) phthalate metabolite and phenol concentrations by breastfeeding status, after adjusting for sociodemographic and perinatal factors, as well as urinary creatinine. Results: Eighty-two (28%) infants were breastfeeding at age 12 months. After adjusting for covariates, GM phthalate metabolite and phenol concentrations were 4-25% higher in children who were breastfed at 12 months than those who were not being breastfed. However, the 95% CIs of these estimates included the null and were imprecise. For example, urinary concentrations of bisphenol A and di-2-ethylhexyl phthalate metabolites were 13% (95% CI: -12, 46) and 4% (95% CI: -18, 31) higher, respectively, in breastfed children compared to non-breastfed children. Conclusion: In this cohort, we found little evidence to suggest that breastfeeding is a major source of exposure to phthalates and phenols in nursing infants. Future studies could consider examining whether plastic feeding bottles or pumped milk are potential sources of phthalate and phenol exposures among infants.

Prenatal Exposure to Phthalates and Neurodevelopment in the CHAMACOS Cohort

Background:Previous studies suggest that prenatal exposure to phthalates, ubiquitous synthetic chemicals, may adversely affect neurodevelopment. However, data are limited on how phthalates affect cognition, executive function, and behavioral function into adolescence.Objective:We aimed to investigate associations of prenatal phthalate exposure with neurodevelopment in childhood and adolescence in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.Methods:We examined associations between maternal urinary phthalate metabolite concentrations measured twice during pregnancy and a range of neurodevelopmental outcomes from ages 7 through 16 y in the CHAMACOS birth cohort (). We used age-specific linear regression models and generalized estimating equation models to assess longitudinal effects and examined differences by sex.Results:Phthalate metabolites were detected in 88%–100% of samples, depending on the metabolite. Associations of phthalates with neurodevelopmental outcomes were largely null with some noteworthy patterns. Higher prenatal concentrations of metabolites of low-molecular weight phthalates () were associated with more self-reported hyperactivity [, 95% confidence interval (CI): 0.1, 1.4 per 2-fold increase in phthalates], attention problems (, 95% CI: 0.7, 2.2), and anxiety (, 95% CI: 0.0, 1.8) at age 16. We observed sex-specific differences for the sums of high-molecular-weight and di(2-ethylhexyl) metabolites and cognitive outcomes (e.g., for Full-Scale IQ for , 95% CI: , 0.3 and , 95% CI: , 0.3, respectively; for , 95% CI: 0.1, 3.4 and 1.6, 95% CI: 0.0, 3.2, respectively; for both).Conclusion:We found predominantly null associations of prenatal phthalates with neurodevelopment in CHAMACOS, and weak associations of phthalates with internalizing and externalizing behaviors in adolescence. No previous studies have examined associations of prenatal phthalate exposure with neurodevelopment into adolescence, an important time for manifestations of effects. https://doi.org/10.1289/EHP5165

Determinants of exposure levels, metabolism, and health risks of phthalates among pregnant women in Wuhan, China

Concerns on minimizing health risks of phthalates have been raised due to their widespread exposure and well-documented endocrine disrupting properties, but the determinants of levels, metabolism, and health risks of phthalate exposures have not been thoroughly characterized among the Chinese population, particularly pregnant women. The metabolites of five phthalates were analyzed: diethyl (DEP), diisobutyl (DiBP), di-n-butyl (DnBP), di-(2-ethylhexyl) (DEHP), and benzyl butyl phthalate (BBzP) were analyzed in urine samples collected from 946 mothers in Wuhan during 2014–2015. We applied linear mixed models to investigate the relationships between biomarkers (e.g., urinary concentrations of phthalate metabolites, phthalates, and ratios of metabolites) and factors including sampling seasons and epidemiological characteristics. We calculated estimated daily intake (EDI) using average phthalate concentrations over three trimesters and hazard index (HI) by dividing EDI by tolerance daily intake. About 24.9% of participants were at health risks with HI > 1. The largest health risks were driven by one specific phthalate (DnBP or DEHP). We observed lower urinary levels of phthalate metabolites in winter. Elevated levels were found in mothers with higher education levels or those employed. Mothers who got pregnant on purpose had lower phthalate concentrations than those got pregnant by accident. More recent exposure to phthalates was observed among groups of mothers giving birth to girls, or those who got excessive gestational weight gain. Younger mothers were more susceptible to phthalate exposure. This repeated measurement study suggests that the intervention should be taken to limit application and production of DnBP and DEHP, and highlights that typical demographic factors should be taken into account in demographic studies.

Serum beta-carotene modifies the association between phthalate mixtures and insulin resistance: The National Health and Nutrition Examination Survey 2003–2006

Animal models suggest a protective role of antioxidants against the adverse effect of di-2-ethylhexyl phthalate (DEHP) on insulin resistance. However, no epidemiologic study has examined the effects observed in the animal model. We conduct a study to examine associations of urinary concentrations of phthalate metabolites (individually and as a mixture) with insulin resistance, along with potential effect modification by serum antioxidant concentrations. This cross-sectional study included 1605 participants (51% males) aged 12–85 from the National Health and Nutrition Examination Surveys (2003–2006). Urinary concentrations of 9 phthalate metabolites were measured from spot urine samples. Antioxidant (vitamin A, C, E, and carotenoids) concentrations were measured from a fasting serum sample. We used Bayesian Kernel Machine Regression (BKMR) to evaluate associations between phthalate metabolite mixtures and insulin resistance, and examined whether serum antioxidant levels modified these associations, while accounting for the correlations of multiple concurrent exposures. A change in urinary ΣDEHP concentrations from the 25th to the 75th percentile was associated with a higher log HOMA-IR of 0.07 (95% CI = 0.01, 0.14) (4.85% increase in HOMA-IR). In contrast, the same change in urinary monoethyl phthalate (MEP) was associated with a lower HOMA-IR of −0.07 (95% CI = −0.14, −0.02) (6.68% decrease in HOMA-IR). The positive association between ΣDEHP and HOMA-IR became weaker at higher concentrations of serum β-carotene. The relationship between MEP and HOMA-IR, however, was not modified by the serum antioxidants examined. The remaining phthalate metabolites were unrelated to HOMA-IR. In this cross-sectional study, the positive association between DEHP exposure and insulin resistance weakened among participants with higher concentrations of serum β-carotene. As this is the first human report on the protective role of serum β-carotene on DEHP induced insulin resistance, future studies are needed.