Monoethyl Phthalate Concentrations Research Articles

Screening for contamination levels of select organic environmental chemicals in medical supplies used for human specimen collection

Trace-level analysis of environmental chemicals in human specimens can be compromised by contamination introduced during sample collection and storage. Sampling devices and tools can be a source of contamination by plasticizers, additives and antimicrobials, which warrants the need for pre-screening of these products prior to use. In this study, we determined leaching of 121 environmental chemicals in 10% and 100% methanol from 24 types of human specimen collection and storage devices. Cryovials, serum tubes, cups, syringes, transfer pipettes, and gloves -commonly used for the collection of blood, urine, breast milk and stools - were screened for the presence of plasticizers, environmental phenols, and pesticides. Measurable levels of mono-ethyl phthalate (mEP) and triethyl phosphate (TEP) were leached from vials, plastic storage bags, gloves, and diapers, and parabens were leached from collection bottles, at amounts exceeding 100 ng/device. The amount leached from the devices varied depending on the lot numbers of the same product type. Storage time and temperature were found to influence the leaching rate of chemicals, with increased levels observed following prolonged storage and at high temperatures. The study underscores the importance of pre-screening for contamination in devices used for collection and storage of human specimens for biomonitoring studies.

Establishment and validation of a prediction model for gestational diabetes.

To develop a visual prediction model for gestational diabetes (GD) in pregnant women and to establish an effective and practical tool for clinical application. To establish a prediction model, the modelling set included 1756 women enrolled in the Zunyi birth cohort, the internal validation set included 1234 enrolled women, and pregnant women in the Wuhan cohort were included in the external validation set. We established a demographic-lifestyle factor model (DLFM) and a demographic-lifestyle-environmental pollution factor model (DLEFM) based on whether the women were exposed to environmental pollutants. The least absolute shrinkage and selection lasso-logistic regression analyses were used to identify the independent predictors of GD and construct a nomogram for predicting its occurrence. The DLEFM regression analysis showed that a family history of diabetes (odd ratio [OR] 2.28; 95% confidence interval [CI] 1.05-4.71), a history of GDin pregnant women (OR 4.22; 95% CI 1.89-9.41), being overweight or obese before pregnancy (OR 1.71; 95% CI 1.27-2.29), a history of hypertension (OR 2.61; 95% CI 1.41-4.72), sedentary time (h/day) (OR 1.16; 95% CI 1.08-1.24), monobenzyl phthalate (OR 1.95; 95% CI 1.45-2.67) and Q4 mono-ethyl phthalate concentration (OR 1.85; 95% CI 1.26-2.73) were independent predictors. The area under the receiver operating curves for the internal validation of the DLEFM and the DLFM constructed using these seven factors was 0.827 and 0.783, respectively. The calibration curve of the DLEFM was close to the diagonal line. The DLEFM was thus the more optimal model, and the one which we chose. A nomogram based on preconception factors was constructed to predict the occurrence of GD in the second and third trimesters. It provided an effective tool for the early prediction and timely management of GD.

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

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

Associations of early life phthalate exposures with adolescent lipid levels and insulin resistance: The HOME Study.

Early-life phthalate exposures may disrupt metabolic processes; however few prospective studies have assessed whether these associations extend to cardiometabolic outcomes during adolescence. Among 183 mother-adolescent pairs in a prospective cohort study that enrolled pregnant women in Cincinnati, OH (2003-2006), we quantified nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children. At age 12 years, we assessed triglycerides, high-density (HDL) and low-density (LDL) lipoprotein cholesterol, insulin, and glucose from fasting serum samples and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Using multiple informant models, we estimated covariate-adjusted associations between urinary phthalate concentrations at each time period and cardiometabolic biomarkers at age 12 years, including modification by child sex. Although most associations were weak or null, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and monobenzyl phthalate (MBzP) concentrations were generally associated with lower LDL at age 12 years. A 10-fold increase in 4- and 12-year MEP was associated with -15.3mg/dL (95% CI: 27.5, -3.13mg/dL) and -11.8mg/dL (-22.0, -1.51mg/dL) lower LDL, respectively. Discrepant associations were observed in females versus males: a 10-fold increase in 3-year MEP concentrations was associated with 12.0mg/dL (95% CI: 7.11, 31.1mg/dL) higher LDL levels in males and -30.4mg/dL (95% CI: 50.9, -9.8mg/dL) lower LDL levels in females. Some urinary phthalate concentrations were cross-sectionally associated with HOMA-IR. Early-life phthalate biomarker concentrations may be inversely associated with LDL during early adolescence in an exposure-period and sex-dependent manner.

Prenatal exposure to endocrine disrupting chemicals and brain development in adolescents

Background and Aim Despite growing concerns regarding the neurotoxicity of phthalates and bisphenols, brain differences associated with gestational exposure to these chemicals are understudied. We investigated the extent to which prenatal exposures to these endocrine disrupting chemicals are associated with global brain volumetric measures in adolescents and whether brain measures mediate the association of prenatal exposures with child IQ. Methods We included 908 mother-child pairs from Generation R, a population-based birth cohort, with data on maternal gestational phthalate and/or bisphenol concentrations and T1-weighted magnetic resonance imaging in children at age 10 years. Child IQ was assessed at age 14 years. Maternal urinary concentrations of phthalate metabolites and bisphenols were measured at early, mid-, and late pregnancy. We examined the associations of pregnancy-averaged, creatinine-adjusted concentrations of individual phthalate metabolites as well as ∑di-2-ethylhexyl phthalate, phthalic acid, and bisphenol A with and brain volumetric measures using linear regression. We used mediation modelling to identify the proportion mediated by brain measures in the association of prenatal exposures and child IQ. Results Higher maternal concentrations of monoethyl phthalate (mEP) were associated with smaller total gray matter volumes in offspring at age 10 years (β per log10 increase in creatinine adjusted mEP=-10.27, 95%CI:-17.85, -2.69). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (natural indirect effect=-0.27, 95%CI: -0.55,0.00, proportion mediated=20%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. We found no association between maternal prenatal bisphenols and global brain volumetric measures or child IQ. Conclusions Our findings suggest the global impact of prenatal phthalate exposure on the brain that extends into adolescence and underlies impaired general cognition. Keywords: MRI; Pregnancy, phthalates

Does early life phthalate exposure mediate racial disparities in children's cognitive abilities?

Background:Early life exposure to phthalates may be associated with reduced cognition. However, it is unknown if disproportionate exposure to phthalates contributes to racial disparities in children’s intellectual abilities.Methods:We used data from 253 mother-child pairs in Cincinnati, OH (the Health Outcomes and Measures of the Environment study, 2003–2006). We measured urinary concentrations of 11 phthalate metabolites twice during pregnancy and up to six times in childhood. We evaluated children’s cognitive abilities at ages 5 and 8 years. Using mediation models, we quantified covariate-adjusted direct and indirect effects of race on children’s Full-Scale Intelligence Quotient (IQ) scores for individual phthalate metabolite concentrations during gestation and childhood.Results:Average IQ scores among Black children (n = 90) were 7.0 points lower (95% confidence interval [CI] = −12, −1.8) than among White children (n = 145) after adjustment for socioeconomic factors. Urinary monobenzyl phthalate and monoethyl phthalate (MEP) concentrations during gestation and childhood were higher among Black than White children. We did not observe evidence that phthalate concentrations mediated the race-IQ association, with the exception of MEP. Childhood MEP concentrations partially mediated the race-IQ association. For instance, each 10-fold increase in MEP concentrations at age 2 years contributed to a 1.9-point disparity in IQ scores between Black and White children (95% CI = −4.7, 0.7). Other phthalate metabolite concentrations during pregnancy or childhood did not mediate the race-IQ association.Conclusions:Despite observing racial disparities in exposure to some phthalates and IQ, we found little evidence that phthalates contribute to IQ disparities.

Effect of childhood phthalates exposure on the risk of overweight and obesity: A nested case-control study in China.

There was growing interest in endocrine disrupting chemicals that might have effect on the obesity epidemic, but few studies on the association of phthalates (PAEs) with childhood overweight and obesity in China based on longitudinal cohort study were available, which was the purpose of the present study. A nested case-control study was conducted in a prospective cohort of 2298 children aged 7-13years from October 2017 to October 2020 with five waves visits in Xiamen city, China. A total of 829 children remained in the first wave of follow up with collection of urine for measuring seven PAEs metabolites, including mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate (MiBP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) and mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), utilizing ultra high performance liquid chromatography-triple quadrupole mass spectrometry. Overweight and obesity, defined by WHO classifications, were allocated to the cases group, and those of all normal weight and matched cases with normal weight in each wave of follow-up as two control groups. Logistic regression models after adjusting for confounders were utilized to analyze the effect of PAEs on overweight and obesity in children with divided four groups based on the quartile distribution of each and total PAEs concentration. The detection rates of children for each PAEs metabolite were 99.4% for MMP, 99.4% for MEP, 99.8% for MBP, 54.5% for MEHP, 84.4% for MEOHP, 99.9% for MEHHP, and 97.2% for MiBP. The geometric mean of concentrations of PAEs, MMP, MEP, MBP, MEHP, MEHHP, and MiBP were 310.085, 34.658, 9.127, 166.347, 7.043, 3.400, 18.571, and 24.093 (ng/ml), respectively. The total PAEs and seven metabolites concentrations were positively associated with childhood BMI Z-Scores with statistically significant slope rates and correlation coefficients, and were higher in the cases group than those in two controls groups in each wave of follow-up. The PAEs concentrations in the cases group was 5.90 (95%CI: 5.79, 6.01) ng/ml in the first wave of survey, which was higher than those normal controls group (5.68 (95%CI: 5.61, 5.75) ng/ml, P<0.001) and matched controls group (5.72 (95%CI: 5.61, 5.84) ng/ml, P=0.018). The prevalence and ORs of overweight and obesity increased with quartile group of each and total PAEs concentrations accompanying a dose-response relationship. Compared with the quartile1 reference group with lowest total PAEs concentrations, the ORs of overweight and obesity in quartile2, quartile3 and quartile4 group increased gradually and reached at 1.20 (0.74-1.95), 1.49 (0.93-2.38) and 2.22 (1.41-3.48), respectively (Ptrend<0.001). The strength of the associations between PAEs and overweight and obesity was sex-specific in children. Children in China were extensively exposed to PAEs, and the exposure to PAEs during childhood could significantly increase the risk of overweight and obesity with a dose-response relationship, particularly in girls. While limiting the exposure of PAEs products, the determination of exposure limit of plasticizer should be further strengthened.

Food Processing and Phthalate Exposure: The Nutrition and Health Survey in Taiwan (1993-1996 and 2005-2008).

Background: Phthalates esters are widely used commercially and can leach from a food container or food packaging. Few studies have been conducted in Asia regarding food processed to varying levels and human phthalate exposure. This study aimed to evaluate the association between unprocessed and ultra-processed food intake and urinary phthalate metabolite levels in the Taiwanese adult population.Methods: A total of 516 participant data were extracted from the cross-sectional 1993–1996 and 2005–2008 Nutrition and Health Survey in Taiwan of those aged over 18 years, where urinary measures and one 24-h dietary recall were collected. Urinary concentrations of dimethyl phthalate, diethyl phthalate, dibutyl phthalate, butyl benzyl phthalate, and di-(2-ethylhexyl) phthalate metabolites including monomethyl phthalate, monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate, mono-(2-ethylhexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were measured in spot urine samples. The NOVA food processing classification system was applied to divide all consumed foods into four mutually exclusive groups including unprocessed or minimally processed, processed culinary ingredients, processed and ultra-processed food. Generalized linear models were employed to examine the associations between the percentage quartiles (Qs) of unprocessed and ultra-processed foods in the total weight of food and the urinary phthalate metabolites.Results: Compared with participants in the lowest quartiles (Q1) of ultra-processed food intake, highest ultra-processed food intake (Q4) had 65.7% (95% confidence interval [CI]: 4.83, 162) higher urinary concentrations of MEP after adjusted for covariates. In contrast, the higher unprocessed food consumption was inversely associated with urinary concentrations of MEP and MBP (P for trend = 0.03). When compared to the lowest unprocessed food consumers (Q1), higher consumers (Q4) presented 38.6% (95% CI: −61.3, −2.59) lower MEP concentrations and 23.1% (95% CI: −38.5, −3.71) lower MBP concentrations.Conclusion: Ultra-processed food consumption was associated with increased concentrations of urinary MEP. Conversely, consuming unprocessed food was associated with lower concentrations of MEP and MBP in the Asian Taiwanese adult population.

Does Early Life Phthalate Exposure Mediate Racial Disparities in Children’s Cognitive Abilities?

BACKGROUND AND AIM: Early life exposure to phthalates is associated with diminished childhood cognitive abilities. However, it is unclear if disproportionate exposure to some phthalates among non-Hispanic Black individuals contributes to racial disparities in children’s intellectual abilities (e.g., IQ). Here, we assess the extent that phthalates mediate racial disparities in child IQ. METHODS: We used data from 253 mother-child pairs in Cincinnati, OH (HOME Study). We quantified urinary concentrations of eleven phthalate metabolites twice during pregnancy and up to six times in childhood (ages 1,2,3,4,5 and 8 years). We evaluated children’s cognitive abilities using the Wechsler Preschool and Primary Scale of Intelligence and Wechsler Intelligence Scale for Children at ages 5 and 8 years, respectively. Using causal mediation models, we quantified covariate-adjusted direct and indirect effects of race/ethnicity on child IQ through individual measurement-error corrected phthalate metabolite concentrations during gestation and childhood. RESULTS:Average IQ scores among non-Hispanic Black children (n=90) were 7.0-points lower (95% CI: -12.1, -1.8) than non-Hispanic White children (n=145) after adjustment for socioeconomic factors. Urinary monobenzyl phthalate (MBzP) and monoethyl phthalate (MEP) concentrations during childhood were 33-100% higher in non-Hispanic Black children than non-Hispanic White children. We found evidence that childhood MEP concentrations mediated the race-IQ association. For instance, the disparities in IQ scores between non-Hispanic Black and non-Hispanic White children would have been reduced by 1.9 points (95% CI: -4.7, 0.7), in the absence of childhood diethyl phthalate exposure, the parent metabolite of MEP, at age 2. Other phthalate metabolite concentrations during pregnancy or childhood did not mediate the race-IQ association. CONCLUSIONS:Children’s urinary concentrations of MEP partly mediated racial disparities in IQ scores among these children. While phthalate exposures do not fully explain racial disparities in IQ, reducing exposure to some phthalates might reduce IQ differences among non-Hispanic Black and non-Hispanic White children. KEYWORDS: Phthalates, children’s environmental health, Neurodevelopmental outcomes

Occupational Exposures to Phthalates among Black and Latina U.S. Hairdressers Serving an Ethnically Diverse Clientele: A Pilot Study.

Hairdressers may be differentially exposed to phthalates through hair salon services provided and products used, yet no U.S. studies have investigated these exposures in this population. We characterized concentrations and exposure determinants to nine phthalate metabolites in postshift urine samples among 23 hairdressers from three Black and three Dominican salons, as well as a comparison group of 17 female office workers from the Maryland/Washington D.C. metropolitan area. Overall, hairdressers had higher metabolite concentrations than office workers. The geometric mean (GM) for monoethyl phthalate (MEP) was 10 times higher in hairdressers (161.4 ng/mL) than office workers (15.3 ng/mL). Hairdressers providing select services and using certain products had higher GM MEP concentrations than those who did not: permanent waves/texturizing (200.2 vs 115.4 ng/mL), chemical straightening/relaxing (181.6 vs 92.1 ng/mL), bleaching (182.3 vs 71.6 ng/mL), permanent hair color (171.9 vs 83.2 ng/mL), and Brazilian blowout/keratin treatments (181.4 vs 134.6 ng/mL). Interestingly, hairdressers providing natural services had lower GM MEP concentrations than those who did not: twists (129.1 vs 215.8 ng/mL), sister locs/locs (86.0 vs 241.9 ng/mL), and afros (94.7 vs 203.9 ng/mL). Larger studies are warranted to confirm our findings and identify disparities in occupational phthalate exposures.

Demographic Assessment of Mono(2-ethylhexyl) Phthalate (MEHP) and Monoethyl Phthalate (MEP) Concentrations in Common Bottlenose Dolphins (Tursiops truncatus) From Sarasota Bay, FL, USA.

Common bottlenose dolphins (Tursiops truncatus) have previously demonstrated exposure to phthalate esters. Phthalates and phthalate esters are commonly added to consumer goods to enhance desirable properties. As the amount of plastic marine debris increases, these chemicals can easily leach from these products into the surrounding environment. To evaluate demographic variability in exposure, eight phthalate metabolites were quantified in urine samples collected from free‐ranging bottlenose dolphins sampled in Sarasota Bay, FL, USA (2010–2019; n = 51). Approximately 75% of individual dolphins had detectable concentrations of at least one phthalate metabolite. The most frequently detected metabolites were mono(2‐ethylhexyl) phthalate (MEHP; n = 28; GM = 4.57 ng/mL; 95% CI = 2.37–8.80; KM mean = 7.95; s.d. = 15.88) and monoethyl phthalate (MEP; GM = 4.51 ng/mL; 95% CI = 2.77–7.34; ROS mean = 2.24; s.d. = 5.58). Urinary concentrations of MEHP and MEP were not significantly different between sex (MEHP p = 0.09; MEP p = 0.22) or age class (i.e., calf/juvenile vs. adult; MEHP p = 0.67; MEP p = 0.13). Additionally, there were no significant group differences in the likelihood of MEHP or MEP detection for any demographic as determined by a Peto‐Peto test. Frequency of detection was similar for both metabolites between males and females (MEHP p = 0.10; MEP p = 0.40) as well as between juveniles and adults (MEHP p = 0.50; MEP: p = 0.60). These findings suggest ubiquitous exposure risk for both sexes and age classes, warranting further investigation into potential sources and health implications.

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.

Phthalate levels in urine of pregnant women and their associated missed abortion risk

Phthalates are one of the most common environmental endocrine disrupting chemicals (EDCs) in human contact. Prenatal phthalates exposure may adversely affect intrauterine growth, however, little is known about their association. This study aimed to explore the impact of phthalates on the risk of missed abortion. A total of 123 women with missed abortion (cases) and 148 normal pregnant women (controls) were simultaneously collected from Taiyuan, China. Four urinary phthalate metabolites were determined by high-performance liquid chromatography (HPLC). Logistic regression model was used to estimate odds ratios (ORs) and 95 % confidence intervals (95 % CI) of missed abortion associated with phthalate metabolite levels. Four phthalate metabolites, including monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), were detected in at least 78.97 % of all participants, with the highest geometric mean concentration of 147.19 ng/mL for MEP of the urine samples. Both MMP (Z = −3.898, P < 0.001) and MBP (Z = −2.198, P = 0.028) concentrations were higher in cases than in controls. There were no significant differences for MEP (Z = −0.285, P = 0.076) and MBzP (Z = −0.878, P = 0.380) concentrations between cases and controls. Furthermore, Logistic analysis revealed that each one-unit increase in log-transformed MMP (OR = 1.49, 95 % CI = 1.14−1.95) was positively associated with missed abortion. Increasing risks of missed abortion were observed the third quartile (Q3) and the highest quartile (Q4) of MMP(OR = 2.21, 95 % CI = 1.06−4.60; OR = 2.85, 95 % CI = 1.34−6.05) compared to the lowest quartile (Q1) of MMP concentrations. We concluded that prenatal phthalates exposure may contribute to an increased risk of missed abortion.

Gestational phthalate exposures and bone mineral density in early adolescence: the HOME Study

Background/Aim: Phthalate exposures have been associated with lower areal bone mineral density (aBMD) and osteoporosis in adults. Although early life may be a period of heightened susceptibility to environmental osteotoxicants, we are unaware of any studies of phthalate exposures in utero and aBMD in children. Thus, we examined gestational phthalate exposures and early adolescent aBMD in a prospective birth cohort study. Methods: We used data from 225 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003-2006. We measured monobutyl phthalate (MnBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), and four metabolites of di-2-ethylhexyl phthalate (DEHP) in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We measured children’s femoral neck, distal forearm (1/3 radius), spine, total hip, and total body (excluding head) aBMD with dual x-ray absorptiometry at 12 years of age and calculated height-, age-, sex-, and race-specific aBMD z-scores. We estimated covariate-adjusted associations per 2-fold increase in maternal urinary phthalate concentrations and assessed effect measure modification (EMM) by child’s sex using sex-stratified models. Results: In adjusted analyses, higher MCPP and MEP concentrations were associated with greater aBMD at all sites with estimates generally stronger for MCPP. For example, associations of MCPP and MEP concentrations with total hip aBMD z-score were 0.16 (95% CI: 0.01, 0.32) and 0.09 (95% CI: 0.01, 0.17), respectively. Sex modified urinary MEP and MiBP concentration’s associations with spine aBMD. Higher MEP concentrations were associated with greater spine aBMD z-score in males (β = 0.19, 95% CI: 0.09, 0.30; EMM p-value 0.06) while higher MiBP concentrations were associated with greater spine aBMD z-score in females (β = 0.24, 95% CI: 0.07, 0.41; EMM p-value 0.07). Conclusions: Gestational phthalate exposures may increase bone mineral density in early adolescence.

Concentration and Variability of Urinary Phthalate Metabolites, Bisphenol A, Triclosan, and Parabens in Korean Mother–Infant Pairs

Concentrations of toxic chemicals in mothers highly correlate with those in their children; moreover, the levels are higher in children than in mothers. Non-persistent chemicals with a short half-life including phthalate metabolites, bisphenol A (BPA), triclosan (TCS), and parabens are metabolized and excreted through urine. Therefore, we assessed the urine concentrations of phthalate metabolites, BPA, TCS, and parabens; correlated the concentrations with exposure levels; and assessed the within-individual variability of these chemicals in mothers and their infants. We collected 225 and 71 samples from 45 mothers and 36 infants, respectively. For the variability analysis, 189 and 42 samples were collected from nine mothers and their infants, respectively. The median concentrations of phthalate metabolites in the mothers and infants were 0.53–26.2 and 0.81–61.8 μg/L, respectively, and those of BPA, TCS, and parabens were 0.24–76.3 and 2.06–12.5 μg/L, respectively. The concentrations of monoethyl phthalate (MEP), mono-N-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and BPA in the mothers were positively correlated with those in infants (0.45, 0.62, and 0.89, respectively; p &lt; 0.05), whereas toxic chemical concentrations in infants were higher than those in the mothers. With respect to the within-individual intraclass correlation coefficient (ICC), the first morning void (FMV) of the mothers had high ICCs for all chemicals (range: 0.72–0.99), except for BPA, monobenzyl phthalate (MBzP), and monocarboxyoctyl phthalate (MCOP). The ICC values of most chemicals were moderate to high (range: 0.34–0.99) in the first morning void. However, there were different patterns of ICCs in the infants. These findings indicate the importance of mother–infant pair studies and the necessity of research in infants, as they have different exposure sources and pathways from adults.

Urinary Concentrations of Phthalate Metabolite Mixtures in Relation to Serum Biomarkers of Thyroid Function and Autoimmunity among Women from a Fertility Center.

Background:Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women.Objective:We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity.Methods:This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005–2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (, ) and triiodothyronine (, ), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores.Results:We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of , , , and [absolute difference: ; 95% confidence interval (CI): , ; ; absolute difference: ; 95% CI: , ; ; absolute difference: ; 95% CI: 0.54, ; ; and absolute difference: ; 95% CI: , ; , respectively]. Using BKMR, we observed that mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb.Conclusions:Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740

Risk assessment for humans using physiologically based pharmacokinetic model of diethyl phthalate and its major metabolite, monoethyl phthalate.

Diethyl phthalate (DEP) belongs to phthalates with short alkyl chains. It is a substance frequently used to make various products. Thus, humans are widely exposed to DEP from the surrounding environment such as food, soil, air, and water. As previously reported in many studies, DEP is an endocrine disruptor with reproductive toxicity. Monoethyl phthalate (MEP), a major metabolite of DEP in vivo, is a biomarker for DEP exposure assessment. It is also an endocrine disruptor with reproductive toxicity, similar to DEP. However, toxicokinetic studies on both MEP and DEP have not been reported in detail yet. Therefore, the objective of this study was to evaluate and develop physiologically based pharmacokinetic (PBPK) model for both DEP and MEP in rats and extend this to human risk assessment based on human exposure. This study was conducted in vivo after intravenous or oral administration of DEP into female (2mg/kg dose) and male (0.1-10mg/kg dose) rats. Biological samples consisted of urine, plasma, and 11 different tissues. These samples were analyzed using UPLC-ESI-MS/MS method. For DEP, the tissue to plasma partition coefficient was the highest in the kidney, followed by that in the liver. For MEP, the tissue to plasma partition coefficient was the highest in the liver. It was less than unity in all other tissues. Plasma, urine, and fecal samples were also obtained after IV administration of MEP (10mg/kg dose) to male rats. All results were reflected in a model developed in this study, including in vivo conversion from DEP to MEP. Predicted concentrations of DEP and MEP in rat urine, plasma, and tissue samples using the developed PBPK model fitted well with observed values. We then extrapolated the PBPK model in rats to a human PBPK model of DEP and MEP based on human physiological parameters. Reference dose of 0.63mg/kg/day (or 0.18mg/kg/day) for DEP and external doses of 0.246μg/kg/day (pregnant), 0.193μg/kg/day (fetus), 1.005-1.253μg/kg/day (adults), 0.356-0.376μg/kg/day (adolescents), and 0.595-0.603μg/kg/day (children) for DEP for human risk assessment were estimated using Korean biomonitoring values. Our study provides valuable insight into human health risk assessment regarding DEP exposure.

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.

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.

Contribution of phthalates and phthalate monoesters from drinking water to daily intakes for the general population

Although phthalates (PAEs) are ubiquitous in drinking water, and phthalate monoesters (MPAEs) have been recognized as the bioactive metabolites of PAEs, little information is available regarding the occurrence of MPAEs in drinking water and the contributions of PAEs and MPAEs to human exposure. In this study, the concentrations of PAEs and MPAEs in 146 samples of drinking water collected from 24 cities throughout China were determined. The mean concentrations of dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and di-2-ethylhexyl phthalate (DEHP) were 14.31 ± 26.28, 5.905 ± 11.57, 103.8 ± 310.5, 595.9 ± 1794, and 178.2 ± 422.0 ng/L, respectively. Monomethyl phthalate (MMP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-2-ethylhexyl phthalate (MEHP) were detected in drinking water for the first time, at mean concentrations of 12.1 ± 18.0, 2.4 ± 5.8, 11.3 ± 37.2, 36.3 ± 103, and 9.9 ± 18.0 ng/L, respectively. The geometric mean concentrations of MMP, MEP, MiBP, MnBP, and MEHP in urine samples collected from 1040 participants from 16 cities were 10.1, 19.3, 29.6, 47.3, and 3.63 μg/g creatinine, respectively. The concentrations of PAEs and MPAEs in drinking water and daily intakes (DIs) of PAEs from nine cities where drinking water and urine samples were simultaneously collected were used to estimate the contributions from drinking water. The percentages of DMP, DEP, DiBP, DnBP, and DEHP from drinking water accounted for DIs of 0.60%, 0.049%, 1.26%, 2.76%, and 0.56%, respectively. The percentages of MMP, MEP, MiBP, MnBP and MEHP via intake of drinking water accounted for urinary concentrations of 0.86%, 0.032%, 0.14%, 0.089%, and 0.045%, respectively.