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Phthalates are ubiquitous environmental contaminants. Because of potential adverse effects on human health, butylbenzyl phthalate [BBzP; metabolite, monobenzyl phthalate (MBzP)], di-n-butyl phthalate [DnBP; metabolite, mono-n-butyl phthalate (MnBP)], and di(2-ethylhexyl) phthalate (DEHP) are being replaced by substitutes including other phthalates; however, little is known about consequent trends in population-level exposures. We examined temporal trends in urinary concentrations of phthalate metabolites in the general U.S. population and whether trends vary by sociodemographic characteristics. We combined data on 11 phthalate metabolites for 11,071 participants from five cycles of the National Health and Nutrition Examination Survey (2001-2010). Percent changes and least square geometric means (LSGMs) were calculated from multivariate regression models. LSGM concentrations of monoethyl phthalate, MnBP, MBzP, and ΣDEHP metabolites decreased between 2001-2002 and 2009-2010 [percent change (95% CI): -42% (-49, -34); -17% (-23, -9); -32% (-39, -23) and -37% (-46, -26), respectively]. In contrast, LSGM concentrations of monoisobutyl phthalate, mono(3-carboxypropyl) phthalate (MCPP), monocarboxyoctyl phthalate, and monocarboxynonyl phthalate (MCNP) increased over the study period [percent change (95% CI): 206% (178, 236); 25% (8, 45); 149% (102, 207); and 15% (1, 30), respectively]. Trends varied by subpopulations for certain phthalates. For example, LSGM concentrations of ΣDEHP metabolites, MCPP, and MCNP were higher in children than adults, but the gap between groups narrowed over time (pinteraction < 0.01). Exposure of the U.S. population to phthalates has changed in the last decade. Data gaps make it difficult to explain trends, but legislative activity and advocacy campaigns by nongovernmental organizations may play a role in changing trends. Zota AZ, Calafat AM, Woodruff TJ. 2014. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001-2010. Environ Health Perspect 122:235-241; http://dx.doi.org/10.1289/ehp.1306681.

In the last decades, the availability of sophisticated analytical chemistry techniques has facilitated measuring trace levels of multiple environmental chemicals in human biological matrices (i.e. biomonitoring) with a high degree of accuracy and precision. As biomonitoring data have become readily available, interest in their interpretation has increased. We present an overview on the use of biomonitoring in exposure and risk assessment using phthalates and bisphenol A as examples of chemicals used in the manufacture of plastic goods. We present and review the most relevant research on biomarkers of exposure for phthalates and bisphenol A, including novel and most comprehensive biomonitoring data from Germany and the United States. We discuss several factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information.

Despite considerable evidence on a negative association between pregnancy pesticide exposure and child development in high-income countries, evidence from low- and middle-income countries (LMICs) is limited. Therefore, we assessed associations between pregnancy pesticide exposure and child development in rural Bangladesh and summarised existing literature in a systematic review and meta-analysis. We used data from 284 mother-child pairs participating in a birth cohort established in 2008. Eight urinary pesticide biomarkers were quantified in early pregnancy (mean gestational age 11.6±2.9 weeks) as an index of pesticide exposure. The Bayley Scales of Infant and Toddler Development, Third Edition were administered at 20-40 months of age. Associations between creatinine-adjusted urinary pesticide biomarker concentrations and child development scores were estimated using multivariable generalised linear models. We searched ten databases up to November 2021 to identify prospective studies on pregnancy pesticide exposure and child development conducted in LMICs. We used a random-effects model to pool similar studies, including our original analysis. The systematic review was pre-registered with PROSPERO: CRD42021292919. In the Bangladesh cohort, pregnancy 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPY) concentrations were inversely associated with motor development (-0.66 points [95% CI -1.23, -0.09]). Pregnancy 3,5,6-trichloro-2-pyridinol (TCPY) concentrations were inversely associated with cognitive development, but the association was small: -0.02 points (-0.04, 0.01). We observed no associations between 4-nitrophenol and 3-phenoxybenzoic acid (3-PBA) concentrations and child development. The systematic review included 13 studies from four LMICs. After pooling our results with one other study, we found consistent evidence that pregnancy 3-PBA concentrations were not associated with cognitive, language, or motor development. Evidence suggests that pregnancy exposure to some organophosphate pesticides is negatively associated with child development. Interventions to reduce in-utero pesticide exposure in LMICs may help protect child development.

Few studies have examined whether prenatal exposure to perfluoroalkyl substances (PFASs) is associated with childhood adiposity. We examined associations of prenatal exposure to PFASs with adiposity in early and mid-childhood. We measured plasma PFAS concentrations in 1,645 pregnant women (median, 9.6 weeks gestation) enrolled in Project Viva, a prospective pre-birth cohort study in Massachusetts (USA), between 1999 and 2002. We assessed overall and central adiposity in 1,006 children in early childhood (median, 3.2 years) and 876 in mid-childhood (median, 7.7 years) using anthropometric and dual X-ray absorptiometry (DXA) measurements. We fitted multivariable linear regression models to estimate exposure-outcome associations and evaluated effect modification by child sex. Median (25-75th percentiles) prenatal plasma perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) concentrations in children assessed in early childhood were 5.6 (4.1-7.7), 24.8 (18.4-33.9), 2.4 (1.6-3.8), and 0.6 (0.5-0.9) ng/mL, respectively. Among girls, each interquartile range increment of prenatal PFOA concentrations was associated with 0.21 kg/m (95% CI: -0.05, 0.48) higher body mass index, 0.76 mm (95% CI: -0.17, 1.70) higher sum of subscapular and triceps skinfold thickness, and 0.17 kg/m (95% CI: -0.02, 0.36) higher DXA total fat mass index in mid-childhood. Similar associations were observed for PFOS, PFHxS, and PFNA. We observed null associations for boys and early-childhood adiposity measures. In this cohort, prenatal exposure to PFASs was associated with small increases in adiposity measurements in mid-childhood, but only among girls. Citation: Mora AM, Oken E, Rifas-Shiman SL, Webster TF, Gillman MW, Calafat AM, Ye X, Sagiv SK. 2017. Prenatal exposure to perfluoroalkyl substances and adiposity in early and mid-childhood. Environ Health Perspect 125:467-473; http://dx.doi.org/10.1289/EHP246.

Certain perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widespread, persistent environmental contaminants. Prenatal PFAS exposure has been associated with lower birth weight; however, impacts on body composition and factors responsible for this association are unknown. We aimed to estimate associations between maternal PFAS concentrations and offspring weight and adiposity at birth, and secondarily to estimate associations between PFAS concentrations and maternal glucose and lipids, and to evaluate the potential for these nutrients to mediate associations between PFAS and neonatal outcomes. Within the Healthy Start prospective cohort, concentrations of 11 PFAS, fasting glucose, and lipids were measured in maternal mid-pregnancy serum (n=628). Infant body composition was measured using air displacement plethysmography. Associations between PFAS and birth weight and adiposity, and between PFAS and maternal glucose and lipids, were estimated via linear regression. Associations were decomposed into direct and indirect effects. Five PFAS were detectable in >50% of participants. Maternal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) concentrations were inversely associated with birth weight. Adiposity at birth was approximately 10% lower in the highest categories of PFOA, PFNA, and perfluorohexane sulfonate (PFHxS) compared to the lowest categories. PFOA, PFNA, perfluorodecanoate (PFDeA), and PFHxS were inversely associated with maternal glucose. Up to 11.6% of the effect of PFAS on neonatal adiposity was mediated by maternal glucose concentrations. Perfluorooctane sulfonate (PFOS) was not significantly associated with any outcomes studied. Follow-up of offspring will determine the potential long-term consequences of lower weight and adiposity at birth associated with prenatal PFAS exposure. https://doi.org/10.1289/EHP641.

Background: Parabens are widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Objectives: We assessed exposure to methyl, ethyl, propyl, and butyl parabens in a representative sample of persons ≥ 6 years of age in the U.S. general population from the 2005–2006 National Health and Nutrition Examination Survey. Methods: We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution—high-performance liquid chromatography/tandem mass spectrometry. Results: We detected methyl paraben (MP) and propyl paraben (PP) in 99.1% and 92.7% of the samples, respectively. We detected ethyl (42.4%) and butyl (47%) parabens less frequently and at median concentrations at least one order of magnitude lower than MP (63.5 μg/L) and PP (8.7 μg/L). Least-square geometric mean (LSGM) concentrations of MP were significantly higher (p ≤ 0.01) among non-Hispanic blacks than among non-Hispanic whites except at older ages (≥ 60 years). Adolescent and adult females had significantly higher (p < 0.01) LSGM concentrations of MP and PP than did adolescent and adult males. Females were more likely than males [adjusted odds ratios (ORs) and 95% confidence intervals (CIs): MP, 3.2 (2.99–5.27); PP, 4.19 (2.34–7.49)] and non-Hispanic blacks were more likely than non-Hispanic whites [MP, 4.99 (2.62–9.50); PP, 3.6 (1.86–7.05)] to have concentrations above the 95th percentile. Conclusions: The general U.S. population was exposed to several parabens during 2005–2006. Differences in the urinary concentration of MP and PP by sex and race/ethnicity likely reflect the use of personal care products containing these compounds.

Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age. In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-isobutyl phthalate (DiBP), di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ). Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b = -2.69 (95% confidence interval [CI] = -4.33, -1.05) and b = -2.69 (95% CI = -4.22, -1.16) per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI = 1.9, 11.4) and 7.6 (95% CI = 3.2, 12.1) points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning. Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children's intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.

Endocrine-disrupting chemicals (EDCs) may be involved in the etiology of autism spectrum disorders, but identifying relevant chemicals within mixtures of EDCs is difficult. Our goal was to identify gestational EDC exposures associated with autistic behaviors. We measured the concentrations of 8 phthalate metabolites, bisphenol A, 25 polychlorinated biphenyls (PCBs), 6 organochlorine pesticides, 8 brominated flame retardants, and 4 perfluoroalkyl substances in blood or urine samples from 175 pregnant women in the HOME (Health Outcomes and Measures of the Environment) Study (Cincinnati, OH). When children were 4 and 5 years old, mothers completed the Social Responsiveness Scale (SRS), a measure of autistic behaviors. We examined confounder-adjusted associations between 52 EDCs and SRS scores using a two-stage hierarchical analysis to account for repeated measures and confounding by correlated EDCs. Most of the EDCs were associated with negligible absolute differences in SRS scores (≤ 1.5). Each 2-SD increase in serum concentrations of polybrominated diphenyl ether-28 (PBDE-28) (β = 2.5; 95% CI: -0.6, 5.6) or trans-nonachlor (β = 4.1; 95% CI: 0.8-7.3) was associated with more autistic behaviors. In contrast, fewer autistic behaviors were observed among children born to women with detectable versus nondetectable concentrations of PCB-178 (β = -3.0; 95% CI: -6.3, 0.2), β-hexachlorocyclohexane (β = -3.3; 95% CI: -6.1, -0.5), or PBDE-85 (β = -3.2; 95% CI: -5.9, -0.5). Increasing perfluorooctanoate (PFOA) concentrations were also associated with fewer autistic behaviors (β = -2.0; 95% CI: -4.4, 0.4). Some EDCs were associated with autistic behaviors in this cohort, but our modest sample size precludes us from dismissing chemicals with null associations. PFOA, β-hexachlorocyclohexane, PCB-178, PBDE-28, PBDE-85, and trans-nonachlor deserve additional scrutiny as factors that may be associated with childhood autistic behaviors.

Per- and polyfluoroalkyl substances (PFAS) are associated with less favorable blood lipid profiles in epidemiological studies. However, little is known about the potential role of PFAS in longitudinal changes in lipids among midlife women even though women become more susceptible to metabolic alterations during the menopausal transition. To examine associations of serum PFAS concentrations with longitudinal trajectories of blood total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in midlife women undergoing menopausal transition. The sample included 1,130 women from the Study of Women's Health Across the Nation 45-56 y of age at baseline (1999-2000). We measured serum PFAS concentrations including linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), linear and branched perfluorooctanesulfonic acid (n-PFOS and Sm-PFOS, respectively), and perfluorohexanesulfonic acid (PFHxS) at baseline. We used -means clustering to identify subgroups with different patterns of PFAS mixture. Blood lipids were measured annually or biannually through 2016 with an average follow-up of 14.8 y. We identified longitudinal trajectories of each lipid using latent class growth models. We used multinomial log-linear models adjusted for covariates to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of lipid trajectory classes by PFAS and their mixtures. Three distinct trajectories (low, middle, high) of total, LDL, and HDL cholesterol and two distinct trajectories (low and high) of triglycerides were identified. n-PFOS, Sm-PFOS, and PFHxS were positively associated with total and LDL cholesterol trajectories. n-PFOS was inversely associated with triglycerides trajectories. PFAS mixtures (high vs. low) showed positive associations with total and LDL cholesterol trajectories (high vs. low), showing ORs (95% CIs) of 1.69 (95% CI: 1.36, 2.12) and 1.79 (95% CI: 1.44, 2.22), respectively. Concentrations of serum PFAS were positively associated with trajectories of total and LDL cholesterol, providing a line of evidence supporting adverse effects of PFAS on lipid homeostasis. https://doi.org/10.1289/EHP12351.

Background: Human exposure to bisphenol A (BPA) is widespread. After exposure, BPA is rapidly metabolized and eliminated in urine. Therefore, there is considerable within-person and betweenperson variability of BPA concentrations in spot urine samples. However, no information exists on the within-day variability of urinary BPA concentrations. Objectives: We examined the between-person and within-person and between-day and withinday variability in the urinary BPA concentrations of eight adults who collected all voids for 1 week to investigate the impact of sampling strategy in the exposure assessment of BPA using spot, first morning, or 24-hr urine collections. Methods: We determined the urinary concentrations of BPA using on-line solid-phase extraction coupled to isotope dilution high-performance liquid chromatography/tandem mass spectrometry. Results: The between-day and within-person variability was the primary contributor to the total variance both for first morning voids (77%) and 24-hr urine collections (88%). For the spot collections, we observed considerable within-day variance (70%), which outweighed the between-person (9%) and between-day and within-person (21%) variances. Conclusions: Regardless of the type of void (spot, first morning, 24-hr collection), urinary BPA concentrations for a given adult changed considerably—both within a day and for the 7 days of the study period. Single 24-hr urine collections accurately reflect daily exposure but can misrepresent variability in daily exposures over time. Of interest, when the population investigated is sufficiently large and samples are randomly collected relative to meal ingestion times and bladder emptying times, the single spot—sampling approach may adequately reflect the average exposure of the population to BPA.