Phthalate Metabolite Concentrations Research Articles

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.

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.

Phthalate exposure in pregnant women with systemic lupus erythematous (SLE)

TPS 632: Health effects of flame retardants and plasticizers, Johan Friso Foyer, Floor 1, August 27, 2019, 3:00 PM - 4:30 PM Background: Environmental chemicals might contribute to the pathogenesis of autoimmune diseases in combination with established genetic factors. Phthalate exposure in pregnant women may influence fetal growth and birth outcomes. Hence, we assessed phthalate exposure in pregnant women with systemic lupus erythematous (SLE) and compared levels with nationally-representative and pregnant populations. Methods: Participants were 50 pregnant women from the New York City (NYC) sample of PROMISSE (2003-2010), a multi-ethnic/racial cohort designed to prospectively assess adverse pregnancy outcomes in SLE women with inactive or mild/moderate disease activity. We measured urinary concentrations of 21 phthalate metabolites during each trimester and compared median concentrations with 1) 15-to-50 year-old women in the National Health and Nutrition Examination Survey (NHANES) 2003-2010; and 2) a contemporary population-based cohort of pregnant women in NYC (n=240). Results: Intraclass correlations for three measurements across pregnancy varied between r=0 [mono-carboxy isooctyl phthalate (mCIOP)] and r=0.57 [mono-n-butyl-phthalate (mBP)]. Mono-(3-carboxypropyl) phthalate (mCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (mECPP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), mCIOP, and mono-carboxy isononyl phthalate (mCINP) were detected in all pregnant women, comparable to NHANES. Metabolites of di-(2-propylheptyl) phthalate (DPHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were detected in 4-55% of participant. Compared to NHANES, pregnant women with SLE had higher first trimester concentration of mono-(2-ethylhexyl) phthalate (MEHP) [median=3.9 ng/mL interquartile range (IQR)=6.0 vs 2.5 ng/mL, IQR=5.45], mono-isobutyl phthalate (mIBP) (median=12.8 vs 7.6 ng/mL), mono-isononyl phthalate (mINP) (median=2.7 vs. 0.87 ng/mL), and mCIOP (median=14.9 vs 6.9 ng/mL). Concentrations of other phthalate metabolites were comparable between groups. Pregnant women with SLE had higher phthalate levels than the NYC cohort. Conclusions: Pregnant women with SLE had higher concentrations of certain phthalate metabolites than controls. This cross-sectional analysis cannot rule out that SLE might influence phthalate metabolism. Sociodemographic and lifestyles factors might also explain the results; therefore, further investigation is needed.

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

Phthalate and bisphenol metabolite concentrations in urine during pregnancy and offspring non-verbal IQ

Phthalate and bisphenol metabolite concentrations in urine during pregnancy and offspring non-verbal IQ

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.

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.

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

Household cleanliness and urinary phthalate concentrations among toddlers in the HOME Study

PDS 62: Chemicals and metals: exposure and biomarkers, Johan Friso Foyer, Floor 1, August 28, 2019, 10:30 AM - 12:00 PM Background/Aim: Household dust can contain butylbenzyl phthalate (BBzP) and di-2-ethylhexyl phthalate (DEHP), which may adversely impact childhood health. Cleaning may lower dust phthalate concentrations, but the relationship between household cleanliness and urinary phthalates among toddlers is unknown. We evaluated the association between household cleanliness and concentrations of monobenzyl phthalate (MBzP), a metabolite of butylbenzyl phthalate, and the sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) among toddlers in the HOME Study. Methods: We measured phthalate metabolites in serial urine samples collected from 312 Cincinnati, Ohio area toddlers at ages 1, 2, and 3 years (n=714 samples collected from 2004 to 2009). During home visits, we assessed household cleanliness and classified homes into three groups based on dust buildup, presence of debris, and evidence of cleaning. We used linear mixed models to evaluate associations between repeated measures of household cleanliness and log-transformed phthalate metabolite concentrations adjusting for creatinine and covariates. Results: Overall, toddlers living in homes with less evidence of cleaning and heavier dust and debris buildup had higher urinary concentrations of MBzP and ∑DEHP. Compared to urine samples collected from toddlers living in clean homes (n=412), those collected from toddlers living in homes with only some (n=285) or no evidence of housecleaning (n=37) had 14% (95% CI= -3%, 35%) and 58% (95%CI= 9%, 130%) higher MBzP concentrations, respectively, as well as 10% (95% CI= -4%, 26%) and 39% (95%CI= 2%, 90%) higher ∑DEHP concentrations. We found statistically significant trends in the relationship of household cleanliness with urinary MBzP (p= 0.016) and ∑DEHP (p= 0.042) concentrations. Conclusions: Household cleaning may lower toddlers’ phthalate body burden. Future intervention studies will be useful to test the efficacy of cleaning methods.

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.

Dietary Predictors of Phthalate and Bisphenol Exposures in Pregnant Women

ABSTRACTEndocrine disrupting chemicals (EDCs) can disrupt fetal developmental processes during pregnancy, leading to long-term adverse outcomes in humans. A major source of exposure to EDCs, such as phthalates and bisphenols, is the food supply, primarily due to contamination from processing and packaging. Therefore, this review aimed to 1) review food-monitoring sources of phthalates and bisphenols, and 2) evaluate methodologies and provide future directions needed to establish EDC-limiting dietary recommendations in pregnancy. Using PubMed, 10 peer-reviewed studies were found on dietary predictors of EDC exposure in pregnancy, and all were selected for review. Use of plastic containers in pregnancy was associated with higher urinary phthalate metabolites, whereas canned food consumption was associated with higher urinary bisphenol A (BPA) concentrations. Foods and dietary patterns associated with healthier food choices (e.g., organic/grown/raised/caught foods, folic acid supplements, vegetarianism) were generally associated with lower urinary phthalate metabolite and BPA concentrations. Despite the many food-monitoring studies reporting high BPA and phthalate concentrations in various foods, the designs of most studies described here were not sufficiently robust to consistently detect associations of specific foods/food groups with phthalates and BPA. Given the limitations of currently available research, future studies should incorporate more valid questionnaires to accurately assess dietary EDC exposure, strive for concurrent diet and exposure assessment, and assess whether geographical and cultural differences modify associations of diet with gestational EDC exposures. Such progress will be critical for developing dietary recommendations that ensure the safety and health of pregnant women.

Association of urinary concentrations of early pregnancy phthalate metabolites and bisphenol A with length of gestation

BackgroundEnvironmental exposure to phthalates and bisphenol A (BPA) may have endocrine disrupting effects that alter length of gestation. We assessed the association between the urinary concentrations of 11 phthalate metabolites and BPA with length of gestation in a cohort of women followed from before conception with daily 1st-morning urinary hormone measures that identified day of implantation.MethodsPre-implantation and post-implantation urinary phthalate metabolites and BPA concentrations were measured in pooled urine samples designed to limit single-measure variability due to the likely episodic nature of these exposures and the short half-life of these compounds. We estimated associations between these exposure biomarkers early in pregnancy with length of gestation from implantation to spontaneous birth. Cox proportional hazards models were used to estimate the hazard of birth among 125 naturally-conceived, singleton live births with censoring for medical interventions that artificially shortened pregnancy.ResultsHigher concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (a metabolite of di (2-ethylhexyl) phthalate (DEHP)) during the pre-implantation window were associated with reduced probability of birth, i.e., longer gestations (hazard ratio (HR): 0.55, 95% CI: 0.35, 0.86; p = 0.01). The HR for the molar sum of the four DEHP metabolites measured showed a similar association (HR: 0.67, 95% CI: 0.43, 1.05). Higher concentrations of mono (3-carboxypropyl) phthalate (MCPP), a non-specific metabolite of several high molecular-weight phthalates, measured post-implantation were associated with increased risk of earlier birth, i.e. shorter length of gestation, HR: 1.59, CI: 1.02, 2.49.ConclusionsEarly gestational exposure to DEHP and possibly other high-molecular weight phthalates, (as reflected by urinary MCPP concentrations) may influence the length of pregnancy. Such effects could have consequences for neonatal and maternal health.

Prenatal and childhood phthalate exposure and attention deficit hyperactivity disorder traits in child temperament: A 12-year follow-up birth cohort study

Temperamental tendencies may form the basis of personality development, and specific personality constellations are associated with increased incidences of behavioural problems. Phthalic acid ester (PAE) has been associated with symptoms of attention deficit hyperactivity disorder (ADHD) in cross-sectional studies. We hypothesised that early-life exposure to PAE affects the temperaments of children, particularly ADHD traits. In this study, we analysed the temperament evaluations completed at least once by maternal–infant pairs (n = 208) when the child was aged 2, 5, and/or 11 years between 2000 and 2012. We measured seven PAE metabolites in the urine of the mothers during pregnancy and their children using liquid chromatography-electrospray ionisation-tandem mass spectrometry. These metabolites included mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and three metabolites of di (2-ethylhexyl) phthalate. The phthalate metabolite levels in pregnant women were significantly associated with a decreased threshold of responsiveness (coefficients from −0.21 to −0.46) and increased distractibility (coefficients from 0.23 to 0.46) in pre-school children. After adjustment for maternal exposure, the phthalate metabolite concentrations of the children exhibited significantly increased odds ratios (ORs) with respect to the ADHD symptom traits. Specifically, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), the sum of the DEHP metabolites, and MBzP yielded ORs and 95% confidence intervals of 2.98 (1.05–8.48), 3.28 (1.15–9.35), and 9.12 (1.07–78.06), respectively, for every log10 creatinine unit (g/g creatinine) increase. Thus, early-life phthalate exposure was found to be associated with the behavioural characteristics of children, particularly temperamental traits associated with ADHD.

Phthalate and BPA Exposure in Women and Newborns through Personal Care Product Use and Food Packaging.

Phthalates and bisphenol A (BPA) are used in some personal care products (PCPs) and containers for food processing and packaging. The Plastics and Personal-Care Product use in Pregnancy (P4) Study (2009-10) explored the association between PCP use during pregnancy and the postpartum period among 80 pregnant women and 55 infants and BPA and phthalate concentrations in multiple maternal and infant urine specimens collected throughout the study (n = 1260 samples). The type, frequency, and timing of PCP and food packaging use 24 h before and during the urine collection period was collected at 5 time points for the mother using prospective diaries. Infant urine was collected up to 2 times before 3 months of age, and mothers answered questions about infant feeding and PCP use on their baby. In mothers, monoethyl phthalate (MEP) metabolite concentrations were significantly higher when women reported using makeup or body lotion in the last 24 h. MEP concentrations were consistently higher when the usage occurred within 0-6 h before the urine sample collection for almost all of the PCP categories. Infant lotion or baby powder application in the previous 24 h was associated with higher phthalate metabolite concentrations in infants. Total BPA metabolite concentrations were lower in exclusively breastfed infants compared to those who were exclusively formula fed or breastfed with supplementation. Given that PCPs tend to undergo frequent formulation changes, which could impact the relative importance of a certain product type as a source of exposure, continued research of this type is warranted.

Environmental phthalate exposure and preterm birth in the PROTECT birth cohort

BackgroundPreterm birth is a global public health issue and rates in Puerto Rico are consistently among the highest in the USA. Exposures to environmental contaminants might be a contributing factor. MethodsIn a preliminary analysis from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort (n = 1090), we investigated the association between urinary phthalate metabolite concentrations measured at three study visits (targeted at 20, 24, and 28 weeks of gestation) individually and averaged over pregnancy with gestational age at delivery and preterm birth. We additionally assessed differences in associations by study visit and among preterm births with a spontaneous delivery. ResultsCompared to women in the general USA population, urinary concentrations of metabolites of di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP) were higher among pregnant women in Puerto Rico. Interquartile range (IQR) increases in pregnancy-averages of urinary metabolites of DBP and DiBP were associated with shorter duration of gestation and increased odds of preterm birth. An IQR increase in mono-n-butyl phthalate (MBP), a metabolite of DBP, was associated with 1.55 days shorter gestation (95% confidence interval [CI] = −2.68, −0.42) and an odds ratio (OR) of 1.42 (95% confidence interval [CI]: 1.07, 1.88) for preterm birth. An IQR increase in mono-isobutyl phthalate (MiBP), a metabolite of DiBP, was associated with 1.16 days shorter gestation (95% CI = −2.25, −0.08) and an OR of 1.32 (95% CI: 1.02, 1.71) for preterm birth. Associations were greatest in magnitude for urinary concentrations measured at the second study visit (median 23 weeks gestation). DiBP metabolite associations were greatest in magnitude in models of spontaneous preterm birth. No associations were detected with other phthalate metabolites, including those of di-2-ethylhexyl phthalate. ConclusionAmong pregnant women in the PROTECT cohort, DBP and DiBP metabolites were associated with increased odds of preterm birth. These exposures may be contributing to elevated rates of preterm birth observed in Puerto Rico.

Phthalates and asthma in children and adults: US NHANES 2007\u20132012

Environmental exposure to phthalates may contribute to an increased risk of asthma in children and adults. We aimed to assess the direction and strength of the association between urinary phthalates metabolites and current asthma in children and adults that participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2012. Data on ten urinary phthalate metabolites, self-reported questionnaires, spirometry measures, and covariates were obtained from 7765 participants (28.1% were children aged 6–17 years) taking part in the NHANES 2007–2012. Asthma was assessed using self-reported questionnaires for children and adults, and via spirometry measures for adults alone. We used crude and adjusted logistic regression models to estimate the odds ratios (ORs) and 95% confidence interval (CI) per one log10 unit change in the concentration of phthalate metabolites. We further modeled the effect modification by sex. Out of 10 metabolites, only mono-benzyl phthalate (MBzP) was positively associated with the prevalence of self-reported asthma in children, after adjusting for a range of potential confounders (odds ratio 1.54; 95% confidence interval 1.05–2.27). No significant relationship was observed for adults. The association of mono-ethyl phthalate (MEP) was modified by sex, with significantly increased odds of asthma among males [boys (2.00; 1.14–3.51); adult males (1.32; 1.04–1.69)]. While no other phthalates showed a positive relationship with current asthma in males, mono-(carboxynonyl) phthalate (MCNP) and mono-(3-carboxylpropyl) phthalate (MCPP) were inversely associated with spirometrically defined asthma in adult females. A sex-specific relationship in adults was evident when spirometry, but not self-reported measures were used to define asthma. We found no clear association between exposure to phthalates and current asthma, except for a significant relationship between MBzP metabolites and self-reported asthma in children. As a result, exposure to phthalates and asthma development and/or exacerbations remains controversial, suggesting a need for a well-designed longitudinal study.

Phthalate Exposures, DNA Methylation and Adiposity in Mexican Children Through Adolescence.

Phthalates are a class of endocrine disrupting chemicals with near ubiquitous exposure to populations around the world. Phthalates have been associated with children's adiposity in previous studies, though discrepancies exist across studies that may be due to timing of exposure or outcome assessment and population differences (i.e., genetics, other confounders). DNA methylation, an epigenetic modification involved in gene regulation, may mediate the effects of early life phthalate exposures on health outcomes. This study aims to evaluate the mediating effect of DNA methylation at growth-related genes on the association between phthalate exposure and repeat measures of adiposity (BMI-for-age z-score, waist circumference, and skinfolds thickness) in Mexican children. Urinary phthalate metabolite concentrations were quantified in mothers at each of the three trimesters of pregnancy and in children at the first peri-adolescent study visit. Blood leukocyte DNA methylation at H19 and HSD11B2 was quantified during the first peri-adolescent visit, and adiposity was measured at the first visit and again ~3 years later among participants (n = 109 boys, 114 girls) from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) project. Associations between phthalates or DNA methylation and repeat outcome measures were assessed separately in boys and girls using generalized estimating equation models including covariates (urinary specific gravity, maternal education, and child's age). Sobel tests were used to assess DNA methylation as a mediator in models adjusting for the same covariates. Associations between phthalates and adiposity varied by phthalate and timing of exposure. Early gestation MBP, MIBP, and MBzP were associated with adiposity among girls. For example, among girls first trimester maternal urine concentrations of MIBP were associated with increases in skinfold thickness, BMI-for-age, and waist circumference (p < 0.01). Second trimester and adolescent MBzP were associated with adiposity among boys in opposite directions. In girls, H19 methylation was positively associated with skinfold thickness. No significant mediation of phthalate exposure on adiposity by DNA methylation of H19 or HSD11B2 was observed (Sobel p > 0.05). However, the mediation analysis was underpowered to detect small to medium effect sizes, and the role of DNA methylation as a mediator between phthalates and outcomes merits further study.