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IntroductionEpigenetic marks are key biomarkers linking the prenatal environment to health and development. However, DNA methylation associations and persistence of marks for prenatal exposure to multiple Endocrine Disrupting Chemicals (EDCs) in human populations have not been examined in great detail.MethodsWe measured Bisphenol-A (BPA), triclosan, benzophenone-3 (BP3), methyl-paraben, propyl-paraben, and butyl-paraben, as well as 11 phthalate metabolites, in two pregnancy urine samples, at approximately 13 and 26 weeks of gestation in participants of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (N = 309). DNA methylation of cord blood at birth and child peripheral blood at ages 9 and 14 years was measured with 450K and EPIC arrays. Robust linear regression was used to identify differentially methylated probes (DMPs), and comb-p was used to identify differentially methylated regions (DMRs) in association with pregnancy-averaged EDC concentrations. Quantile g-computation was used to assess associations of the whole phenol/phthalate mixture with DMPs and DMRs.ResultsPrenatal BPA exposure was associated with 1 CpG among males and Parabens were associated with 10 CpGs among females at Bonferroni-level significance in cord blood. Other suggestive DMPs (unadjusted p-value

Several studies have reported immune modulation by organophosphate (OP) pesticides, but the relationship between OP exposure and SARS-CoV-2 infection is yet to be studied. We used two different measures of OP pesticide exposure (urinary biomarkers (N = 154) and residential proximity to OP applications (N = 292)) to examine the association of early-childhood and lifetime exposure to OPs and risk of infection of SARS-CoV-2 using antibody data. Our study population consisted of young adults (ages 18-21 years) from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal cohort of families from a California agricultural region. Urinary biomarkers reflected exposure from in utero to age 5 years. Residential proximity reflected exposures between in utero and age 16 years. SARS-CoV-2 antibodies in blood samples collected between June 2022 and January 2023 were detected via two enzyme linked immunosorbent assays, each designed to bind to different SARS-CoV-2 antigens. We performed logistic regression for each measure of pesticide exposure, adjusting for covariates from demographic data and self-reported questionnaire data. We found increased odds of SARS-CoV-2 infection among participants with higher urinary biomarkers of OPs in utero (OR = 1.94, 95% CI: 0.71, 5,58) and from age 0-5 (OR = 1.90, 95% CI: 0.54, 6.95).

BackgroundPhthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.ObjectivesWe investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity.MethodsWe pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth.ResultsIn comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants.ConclusionsPhthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

BackgroundThe prevalence of liver disorders and metabolic syndrome has increased among youth. Glyphosate, the most widely used herbicide worldwide, could contribute to the development of these conditions.ObjectiveWe aimed to assess whether lifetime exposure to glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), is associated with elevated liver transaminases and metabolic syndrome among young adults.MethodsWe conducted a prospective cohort study (n=480 mother-child dyads) and a nested case-control study (n=60 cases with elevated liver transaminases and 91 controls) using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We measured glyphosate and AMPA concentrations in urine samples collected during pregnancy and at child ages 5, 14, and 18 y from cases and controls. We calculated glyphosate residue concentrations: [glyphosate + (1.5×AMPA)]. We estimated the amount of agricultural-use glyphosate applied within a 1-km radius of every residence from pregnancy to age 5 y for the full cohort using California Pesticide Use Reporting data. We assessed liver transaminases and metabolic syndrome at 18 y of age.ResultsUrinary AMPA at age 5 y was associated with elevated transaminases [relative risk (RR) per 2-fold increase=1.27, 95% confidence interval (CI): 1.06, 1.53] and metabolic syndrome (RR=2.07, 95% CI: 1.38, 3.11). Urinary AMPA and glyphosate residues at age 14 y were associated with metabolic syndrome [RR=1.80 (95% CI: 1.10, 2.93) and RR=1.88 (95% CI: 1.03, 3.42), respectively]. Overall, a 2-fold increase in urinary AMPA during childhood was associated with a 14% and a 55% increased risk of elevated liver transaminases and metabolic syndrome, respectively. Living near agricultural glyphosate applications during early childhood (birth to 5 y of age) was also associated with metabolic syndrome at age 18 y in the case-control group (RR=1.53, 95% CI: 1.16, 2.02).DiscussionChildhood exposure to glyphosate and AMPA may increase risk of liver and cardiometabolic disorders in early adulthood, which could lead to more serious diseases later in life. https://doi.org/10.1289/EHP11721.

BackgroundBecause fine particulate matter [PM, with aerodynamic diameter ≤2.5μm (PM2.5)] is a ubiquitous environmental exposure, small changes in cognition associated with PM2.5 exposure could have great societal costs. Prior studies have demonstrated a relationship between in utero PM2.5 exposure and cognitive development in urban populations, but it is not known whether these effects are similar in rural populations and whether they persist into late childhood.ObjectivesIn this study, we tested for associations between prenatal PM2.5 exposure and both full-scale and subscale measures of IQ among a longitudinal cohort at age 10.5 y.MethodsThis analysis used data from 568 children enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort study in California's agricultural Salinas Valley. Exposures were estimated at residential addresses during pregnancy using state of the art, modeled PM2.5 surfaces. IQ testing was performed by bilingual psychometricians in the dominant language of the child.ResultsA 3-μg/m3 higher average PM2.5 over pregnancy was associated with -1.79 full-scale IQ points [95% confidence interval (CI): -2.98, -0.58], with decrements specifically in Working Memory IQ (WMIQ) and Processing Speed IQ (PSIQ) subscales [WMIQ -1.72 (95% CI: -2.98, -0.45) and PSIQ -1.19 (95% CI: -2.54, 0.16)]. Flexible modeling over the course of pregnancy illustrated mid-to-late pregnancy (months 5-7) as particularly susceptible times, with sex differences in the timing of susceptible windows and in which subscales were most affected [Verbal Comprehension IQ (VCIQ) and WMIQ in males; and PSIQ in females].DiscussionWe found that small increases in outdoor PM2.5 exposure in utero were associated with slightly lower IQ in late childhood, robust to many sensitivity analyses. In this cohort there was a larger effect of PM2.5 on childhood IQ than has previously been observed, perhaps due to differences in PM composition or because developmental disruption could alter the cognitive trajectory and thus appear more pronounced as children get older. https://doi.org/10.1289/EHP10812.

BackgroundPersonal care products may contain many chemicals, some of which are suspected endocrine disrupters. This is an important source of chemical exposure for women, but little is known about how chemical exposure differs among different races/ethnicities.ObjectiveThis study examines differences in personal care product use among Black, Latina, Vietnamese, Mixed Race, and White women in California.MethodsWe used a community-based participatory process to create and administer a personal care product usage survey to 321 Black, Latina, Vietnamese, Mixed Race, and White women. We used multivariate regression models with pairwise comparisons to examine the frequency of product use by race/ethnicity.ResultsWe found distinct trends of personal care product use by race/ethnicity: Latina women typically used makeup most frequently; Black women used certain hair products or styles most frequently; and Vietnamese women were most likely to use facial cleansing products compared to other races/ethnicities. Latina and Vietnamese women were less likely to try to avoid certain ingredients in their products.SignificanceThese findings can help estimate disparities in chemical exposure from personal care product use and complement future research on health inequities due to chemical exposures in the larger environmental and social context.

BackgroundPhthalates and bisphenol A (BPA) are endocrine disrupting chemicals used in consumer products, building materials, and food processing and packaging materials. They are associated with adverse health outcomes, especially when exposure occurs during heightened windows of susceptibility.ObjectiveWe evaluated the relationship between housing and dietary characteristics and the concentration of several high-molecular-weight (HMW) phthalate metabolites and BPA in a cohort of Latina adolescents.MethodsWe collected information on recent food consumption and housing characteristics and quantified the concentration of HMW phthalate and BPA metabolites in urine collected at two different time points. We used generalized estimating equations (GEE) to assess predictors of each metabolite.ResultsNo significant associations were observed between housing and dietary characteristics and metabolites of di(2-ethylhexyl) phthalate (DEHP) or BPA. In contrast, higher urinary monobenzyl phthalate (MBzP) concentration was associated with living in a home with vinyl or linoleum flooring (66.7% change, p-value

BackgroundHousehold cleaning products may be a significant source of chemical exposures, including carcinogens and suspected endocrine disruptors.ObjectivesWe characterized exposures during routine household cleaning and tested an intervention to reduce exposures to cleaning product chemicals.MethodsThe Lifting Up Communities with Interventions and Research (LUCIR) Study is a youth-led, community-based intervention project. Youth researchers conducted personal air monitoring with 50 Latina women while they cleaned their homes with their regular cleaning products (preintervention visit) and then 1 week later while they used "green" cleaning products provided by the study (postintervention visit). Air samples were analyzed for volatile and semivolatile organic compounds using gas chromatography-mass spectrometry and high-performance liquid chromatography. We compared pre- and postintervention air concentrations of 47 chemicals of concern, selected because they were on California's Proposition 65 list of carcinogens or reproductive/developmental toxicants or were suspected endocrine disruptors. Youth researchers were integrally involved in the study design, data collection, interpretation, and dissemination of findings.ResultsWe observed statistically significant decreases in air concentrations of 17 chemicals of concern when participants switched to green cleaning products, including decreases in geometric mean concentrations of 1,4-dioxane (-46.4%), chloroform (-86.7%), benzene (-24.8%), naphthalene (-40.3%), toluene (-24.2%), and hexane (-35.5%). We observed significant increases in air concentrations of three fragrance compounds: the plant-derived terpene, beta-myrcene (221.5%), and the synthetic musks celestolide (31.0%) and galaxolide (79.6%). Almost all participants (98%) said the replacement products worked as well as their original products, and 90% said that they would consider buying the replacement products in the future.DiscussionThis study demonstrates that choosing cleaning products that are marketed as green may reduce exposure to several carcinogens and endocrine disruptors. Future studies should determine whether use of unscented green products would further reduce exposure to terpenes and musks. https://doi.org/10.1289/EHP8831.

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

Phthalates, compounds commonly used in plastics and personal care products, have been associated with childhood obesity in cross-sectional and some longitudinal studies. Using advanced statistical methods, we characterized the heterogeneity in body mass development patterns over childhood (ages 2-14 years) and explored associations with maternal prenatal urinary concentrations of phthalates among 335 children in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study. Height and weight were measured every one to two years in this cohort, which had a high prevalence of obesity and overweight. Building upon a previous analysis that showed a positive association between prenatal phthalate exposure and body mass index (BMI) in CHAMACOS children, we used three advanced statistical methods: generalized additive models, growth mixture models, and functional principal component analysis with tree-based methods to identify patterns of childhood BMI development and allow for non-linear relationships with the environmental exposures. Our results highlight the heterogeneity in childhood BMI development patterns and suggest a sex-specific non-linear association between prenatal monoethyl phthalate urinary concentrations and BMI level in children, confirmed across a variety of statistical methods. There is also evidence to suggest positive associations between DEHP metabolites and BMI stabilization during puberty for girls.

Personal exposure to pesticides has not been well characterized, especially among adolescents. We used silicone wristbands to assess pesticide exposure in 14 to 16 year old Latina girls (N = 97) living in the agricultural Salinas Valley, California, USA and enrolled in the COSECHA (CHAMACOS of Salinas Examining Chemicals in Homes and Agriculture) Study, a youth participatory action study in an agricultural region of California. We determined pesticide concentrations (ng/g/day) in silicone wristbands worn for one week using gas chromatography electron capture detection and employed gas chromatography mass spectrometry to determine the presence or absence of over 1500 chemicals. Predictors of pesticide detections and concentrations were identified using logistic regression, Wilcoxon rank sum tests, and Tobit regression models. The most frequently detected pesticides in wristbands were fipronil sulfide (87%), cypermethrin (56%), dichlorodiphenyldichloroethylene (DDE) (56%), dacthal (53%), and trans-permethrin (52%). Living within 100 m of active agricultural fields, having carpeting in the home, and having an exterminator treat the home in the past six months were associated with higher odds of detecting certain pesticides. Permethrin concentrations were lower for participants who cleaned their homes daily (GM: 1.9 vs. 6.8 ng/g/day, p = 0.01). In multivariable regression models, participants with doormats in the entryway of their home had lower concentrations (p

Use of personal care products, such as makeup, soaps, and sunscreen, may expose adolescent girls to potential endocrine disruptors, including phthalates, parabens, and other phenols. We evaluated the relationship between recent self-reported personal care product use and concentrations for urinary metabolites of phthalates, parabens, triclosan, and benzophenone-3 (BP-3) in 100 Latina adolescents. Girls who reported using makeup every day vs. rarely/never had higher urinary concentrations of monoethyl phthalate (MEP) (102.2 ng/mL vs. 52.4 ng/mL, P-value: 0.04), methyl paraben (MP) (120.5 ng/mL vs. 13.4 ng/mL, P-value

BackgroundPersonal care product chemicals may be contributing to risk for asthma and other atopic illnesses. The existing literature is conflicting, and many studies do not control for multiple chemical exposures.MethodsWe quantified concentrations of three phthalate metabolites, three parabens, and four other phenols in urine collected twice during pregnancy from 392 women. We measured T helper 1 (Th1) and T helper 2 (Th2) cells in their children's blood at ages two, five, and seven, and assessed probable asthma, aeroallergies, eczema, and lung function at age seven. We conducted linear and logistic regressions, controlling for additional biomarkers measured in this population as selected by Bayesian Model Averaging.ResultsThe majority of comparisons showed null associations. Mono-n-butyl phthalate (MnBP) was associated with higher Th2% (RR: 10.40, 95% CI: 3.37, 17.92), and methyl paraben was associated with lower Th1% (RR: -3.35, 95% CI: -6.58, -0.02) and Th2% at borderline significance (RR: -4.45, 95% CI: -8.77, 0.08). Monoethyl phthalate was associated with lower forced expiratory flow from 25 to 75% of forced vital capacity (FEF25-75%) (RR: -3.22 L/s, 95% CI: -6.02, -0.34). Propyl paraben (OR: 0.86, 95% CI: 0.74, 0.99) was associated with decreased odds of probable asthma.ConclusionsWhile some biomarkers, particularly those from low molecular weight phthalates, were associated with an atopic cytokine profile and poorer lung function, no biomarkers were associated with a corresponding increase in atopic disease.

BackgroundAnimal studies suggest that phthalates and bisphenol A (BPA), endocrine-disrupting chemicals found in many consumer products, may impact the timing of puberty.ObjectivesWe aimed to determine the association of prenatal exposure to high-molecular-weight phthalates and BPA with pubertal timing in boys and girls participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study.MethodsWe quantified urinary concentrations of eight phthalate metabolites and BPA at two time points during pregnancy among participating mothers ([Formula: see text]) and conducted clinical Tanner staging of puberty on their children every 9 months between 9 and 13 y of age. We conducted accelerated failure time models and examined the role of child overweight/obese status in this association.ResultsThe sum of urinary metabolites of di(2-ethylhexyl) phthalate [Formula: see text], monobenzyl phthalate (MBzP), and BPA were associated with later onset of at least one of the three outcomes assessed in girls (thelarche, pubarche, or menarche) and with earlier onset of at least one of the two outcomes assessed in boys (gondarche and pubarche). We found that monocarboxynonyl phthalate, monocarboxyoctyl phthalate, mono(3-carboxypropyl) phthalate, and BPA were associated with later pubarche and menarche mostly among normal-weight girls but not overweight/obese girls. MBzP was associated with later thelarche in all girls, and [Formula: see text] was associated with later thelarche and menarche in all girls. BPA and all phthalate biomarkers were associated with earlier gonadarche and pubarche in all boys as well as in overweight/obese boys when stratified by weight. Among normal-weight boys, associations with BPA were also inverse, whereas associations with phthalate metabolites were close to the null or positive.ConclusionsSeveral high-molecular-weight phthalates and BPA were associated with later puberty in girls and earlier puberty in boys included in the CHAMACOS cohort study. Childhood overweight/obesity may modify these associations. https://doi.org/10.1289/EHP3424.

Environmental phenols and parabens are commonly used in personal care products and other consumer products and human exposure to these chemicals is widespread. Although human and animal studies suggest an association between exposure to phenols and parabens and thyroid hormone levels, few studies have investigated the association of in utero exposure to these chemicals and thyroid hormones in pregnant women and their neonates. We measured four environmental phenols (triclosan, benzophenone-3, and 2,4- and 2,5-dichlorophenol), and three parabens (methyl-, propyl-, and butyl paraben) in urine collected from mothers at two time points during pregnancy as part of the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in serum of the pregnant women (N = 454) and TSH in their neonates (N = 365). We examined potential confounding by a large number of additional chemical exposures and used Bayesian Model Averaging (BMA) to select the most influential chemicals to include in regression models. We observed negative associations of prenatal urinary concentrations of propyl paraben and maternal TSH (β for two-fold increase = -3.26%, 95% CI: -5.55, -0.90) and negative associations of 2,4-dichlorophenol and maternal free T4 (β for two-fold increase = -0.05, 95% CI: -0.08, -0.02), after controlling for other chemical exposures. We observed negative associations of triclosan with maternal total T4 after controlling for demographic variables, but this association became non-significant after controlling for other chemicals (β for two-fold increase = -0.05, 95% CI: -0.11, 0.00). We found evidence that environmental phenols and parabens are associated with lower TSH and free T4 in pregnant women after controlling for related chemical exposures.

[This corrects the article DOI: 10.1289/EHP2580.].

ObjectivesTo examine the relationship between residential proximity to agricultural fumigant use and respiratory symptoms and lung function in 7-year old children.MethodsParticipants were 294 children living in the agricultural Salinas Valley, California and enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study. We obtained information on respiratory symptoms and asthma medication use from maternal questionnaires and children performed spirometry to determine the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25-75% (FEF25-75) at 7-years of age. We estimated agricultural fumigant use within 3, 5 and 8 km of residences during pregnancy and from birth to age 7 using California's Pesticide Use Report data. We evaluated the association between prenatal and postnatal residential proximity to agricultural use of methyl bromide, chloropicrin, metam sodium and 1,3-dichloropropene with respiratory symptoms and use of asthma medication with logistic regression models and continuous lung function measurements with linear regression models adjusted for confounders.ResultsThere were no significant associations between residential proximity to use of fumigants and respiratory symptoms or use of asthma medication. We did not observe any adverse relationships between residential proximity to fumigant use and lung function measurements. Unexpectedly, we observed suggestive evidence of improved FEV1 and FEF25-75 with higher use of methyl bromide and chloropicrin during the prenatal period. For example, for each 10-fold increase in methyl bromide use during the prenatal development period we observed higher FEV1 (β = 0.06 L/s; 95% CI: 0.00, 0.12) and higher FEF25-75 (β = 0.15 L/s; 95% CI: 0.03, 0.27). Maternal report of child allergies (runny nose without a cold during the previous year) modified the relationship between FEV1 and prenatal proximity to methyl bromide use (p = .07) and we only observed higher FEV1 among children without allergies (β = 0.08 L/s; 95% CI: 0.02, 0.14 for a 10-fold increase in methyl bromide use during the prenatal period).ConclusionsResidential proximity to agricultural fumigant use during pregnancy and childhood did not adversely affect respiratory health in the children through 7 years of age. These findings should be explored in larger studies.

BackgroundPrenatal exposure to organophosphate (OP) pesticides has been linked with poorer neurodevelopment and behaviors related to autism spectrum disorders (ASD) in previous studies, including in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort living in the agricultural Salinas Valley in California.ObjectivesTo investigate the association of prenatal exposure to OP pesticides with traits related to ASD, in childhood and adolescents in CHAMACOS.MethodsWe assessed OP exposure during pregnancy with measurements of dialkyl phosphates (DAP) metabolites in urine, and residential proximity to OP use during pregnancy using California's Pesticide Use Reporting (PUR) data and estimated associations with ASD-related traits using linear regression models. We measured traits reported by parents and teachers as well as the child's performance on tests that evaluate the ability to use facial expressions to recognize the mental state of others at 7, 101/2, and 14 years of age.ResultsPrenatal DAPs were associated with poorer parent and teacher reported social behavior [e.g., a 10-fold DAP increase was associated with a 2.7-point increase (95% confidence interval (CI): 0.9, 4.5) in parent-reported Social Responsiveness Scale, Version 2, T-scores at age 14]. We did not find clear evidence of associations between residential proximity to OP use during pregnancy and ASD-related traits.ConclusionsThese findings contribute mixed evidence linking OP pesticide exposures with traits related to developmental disorders like ASD. Subtle pesticide-related effects on ASD-related traits among a population with ubiquitous exposure could result in a rise in cases of clinically diagnosed disorders like ASD. https://doi.org/10.1289/EHP2580.

Flame retardants are commonly used in consumer products found in U.S. households. Restrictions on the use of polybrominated diphenyl ether flame retardants have resulted in increased use of replacement chemicals, including Firemaster 550® (FM 550®) and organophosphate flame retardants (PFRs): tris(1,3- dichloro-2-propyl) phosphate (TDCIPP); tris(chloropropyl) phosphate (TCIPP); tris(2-chloroethyl) phosphate (TCEP); and triphenyl phosphate (TPHP). Animal research suggests that PFRs may affect neurodevelopment through noncholinergic mechanisms similar to some organophosphate (OP) pesticides. Despite the widespread presence of these compounds in home environments, and their structural similarity to neurotoxic OP pesticides, understanding of human exposure and health effects of PFRs is limited. We measured four urinary PFR metabolites from pregnant women in the CHAMACOS birth cohort study (n = 310) and assessed neurodevelopment of their children at age 7. Metabolites of TDCIPP (BDCIPP: bis(1,3-dichloro-2-propyl) phosphate) and TPHP (DPHP: diphenyl phosphate) were detected in >75% of urine samples, and isopropylphenyl phenyl phosphate (ip-PPP), a metabolite of one component of FM 550®, was detected in 72% of urine samples. We observed decreases of 2.9 points (95% Confidence Interval (CI): -6.3, 0.5) and 3.9 points (95% CI: -7.3,-0.5) in Full-Scale intelligence quotient and Working Memory, respectively, for each ten-fold increase in DPHP in adjusted regression models (n = 248). Decreases in Full-Scale IQ and Working Memory were greater in models of the molar sum of the PFR metabolites compared to the DPHP models. This is the first study to examine PFR and FM 550® exposures and potential neurodevelopmental outcomes in pregnant women and children. Additional research is warranted.

ObjectivesOur objective was to examine the relationship between residential proximity to agricultural fumigant use and neurodevelopment in 7-year old children.MethodsParticipants were living in the agricultural Salinas Valley, California and enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study. We administered the Wechsler Intelligence Scale for Children (4th Edition) to assess cognition and the Behavioral Assessment System for Children (2nd Edition) to assess behavior. We estimated agricultural fumigant use within 3, 5 and 8km of residences during pregnancy and from birth to age 7 using California's Pesticide Use Report data. We evaluated the association between prenatal (n = 285) and postnatal (n = 255) residential proximity to agricultural use of methyl bromide, chloropicrin, metam sodium and 1,3-dichloropropene with neurodevelopment.ResultsWe observed decreases of 2.6 points (95% Confidence Interval (CI): -5.2, 0.0) and 2.4 points (95% CI: -4.7, -0.2) in Full-Scale intelligence quotient for each ten-fold increase in methyl bromide and chloropicrin use within 8km of the child's residences from birth to 7-years of age, respectively. There were no associations between residential proximity to use of other fumigants and cognition or proximity to use of any fumigant and hyperactivity or attention problems. These findings should be explored in larger studies.

BackgroundElemental sulfur, "the oldest of all pesticides," is the most heavily used agricultural pesticide in California and Europe. Sulfur is considered relatively safe and is used in both conventional and organic farming systems. Adverse respiratory effects have been reported in applicators and animals, but the effect on residential populations, and especially on children living in proximity to fields treated with elemental sulfur, is not known.ObjectivesWe evaluated associations between residential proximity to elemental sulfur applications and respiratory symptoms and spirometry of children living in an agricultural community.MethodsParticipants were enrolled in the CHAMACOS longitudinal birth cohort. We collected respiratory symptomatology for 347 children at 7 y of age and measured spirometry on a subset of 279. Of these, estimations of proximity to sulfur application and relevant covariate data were available for 237 and 205 children for whom we had symptomatology information and FEV1 measurements, respectively. Data from the California Pesticide Use Reporting System were used to estimate the amount of elemental sulfur applied within 0.5, 1, and 3km of a child's residence during the week, month, and 12 mo prior to pulmonary evaluation. Regression models controlled for maternal smoking during pregnancy; season of birth; PM2.5 (particulate matter ≤2.5mm in aerodynamic diameter); breast feeding duration; child's sex, age, and height; technician; and other covariates.ResultsAdverse associations with respiratory outcomes were found for sulfur applications within 0.5- and 1-km radii. Specifically, asthma medication usage and respiratory symptoms increased [OR=3.51; 95% confidence interval (CI): 1.50, 8.23, p=0.004; OR=2.09; 95% CI: 1.27, 3.46, p=0.004, respectively] and FEV1 decreased (β=−0.143; 95% CI: −0.248, −0.039, p=0.008) per 10-fold increase in the estimated amount of sulfur used within 1 km of child residence during the year prior to pulmonary evaluation.ConclusionsThis study suggests that elemental sulfur use, allowed in both organic and conventional farming, in close proximity to residential areas, may adversely affect children's respiratory health. https://doi.org/10.1289/EHP528.

Organophosphate flame retardants (PFRs), used in consumer products since the 1970s, persist in the environment. Restrictions on penta-polybrominated diphenyl ether (PBDE) flame retardants resulted in increased use of Firemaster® 550 (FM® 550), and the organophosphate triesters: tris(1,3- dichloro-2-propyl) phosphate (TDCIPP); tris(chloropropyl) phosphate (TCIPP); tris(2-chloroethyl) phosphate (TCEP); and triphenyl phosphate (TPHP). The objectives of this study were to (1) identify determinants of flame retardants (4 PFRs, PentaBDEs and FM® 550) in house dust, (2) measure urinary PFR metabolites in pregnant women, and (3) estimate health risks from PFR exposure. We measured flame retardants in house dust (n = 125) and metabolites in urine (n = 310) collected in 2000-2001 from Mexican American women participating in the CHAMACOS birth cohort study in California. We detected FM® 550 and PFRs, including two (TCEP and TDCIPP) known to the state of California to cause cancer, in most dust samples. The maximum TCEP and TDCIPP dust levels were among the highest ever reported although the median levels were generally lower compared to other U.S. cohorts. Metabolites of TDCIPP (BDCIPP: bis(1,3-dichloro-2-propyl) phosphate) and TPHP (DPHP: diphenyl phosphate) were detected in 78% and 79% of prenatal urine samples, respectively. We found a weak but positive correlation between TPHP in dust and DPHP in 124 paired prenatal urine samples (Spearman rho = 0.17; p = 0.06). These results provide information on PFR exposure and risk in pregnant women from the early 2000's and are also valuable to assess trends in exposure and risk given changing fire safety regulations and concomitant changes in chemical flame retardant use.

BackgroundResidential proximity to agricultural pesticide use has been associated with neural tube defects and autism, but more subtle outcomes such as cognition have not been studied.ObjectivesWe evaluated the relationship between prenatal residential proximity to agricultural use of potentially neurotoxic pesticides and neurodevelopment in 7-year-old children.MethodsParticipants included mothers and children (n=283) living in the agricultural Salinas Valley of California enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. We estimated agricultural pesticide use within 1 km of maternal residences during pregnancy using a geographic information system, residential location, and California’s comprehensive agricultural Pesticide Use Report data. We used regression models to evaluate prenatal residential proximity to agricultural use of five potentially neurotoxic pesticide groups (organophosphates, carbamates, pyrethroids, neonicotinoids, and manganese fungicides) and five individual organophosphates (acephate, chlorpyrifos, diazinon, malathion, and oxydemeton-methyl) and cognition in 7-year-old children. All models included prenatal urinary dialkyl phosphate metabolite concentrations.ResultsWe observed a decrease of 2.2 points [95% confidence interval (CI): −3.9, −0.5] in Full-Scale IQ and 2.9 points (95% CI: −4.4, −1.3) in Verbal Comprehension for each standard deviation increase in toxicity-weighted use of organophosphate pesticides. In separate models, we observed similar decrements in Full-Scale IQ with each standard deviation increase of use for two organophosphates (acephate and oxydemeton-methyl) and three neurotoxic pesticide groups (pyrethroids, neonicotinoids, and manganese fungicides).ConclusionsThis study identified potential relationships between maternal residential proximity to agricultural use of neurotoxic pesticides and poorer neurodevelopment in children. https://doi.org/10.1289/EHP504.

BackgroundPolybrominated diphenyl ether (PBDE) flame retardants are endocrine-disrupting chemicals that exhibit estrogenic and androgenic properties and may affect pubertal timing.MethodsStudy subjects were participants between 1999 and 2013 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal cohort study of predominantly Mexican origin families in Northern California. We measured serum concentrations of four PBDEs (BDE-47, -99, -100, -153) in blood collected from mothers during pregnancy (N=263) and their children at age 9years (N=522). We determined timing of pubertal onset in 309 boys and 314 girls using clinical Tanner staging every 9months between 9 and 13years of age, and timing of menarche by self-report. We used Poisson regression for relative risk (RR) of earlier puberty and parametric survival analysis for time ratios (TR) of pubertal milestones.ResultsPrenatal concentrations of all 4 congeners and ƩPBDEs were associated with later menarche in girls (RRearlier menarche=0.5, 95% confidence interval (CI): 0.3, 0.9 for ƩPBDEs) but earlier pubic hair development in boys (RRearlier pubarche=2.0, 95% CI: 1.3, 3.3 for ƩPBDEs). No associations were seen between prenatal exposure and girls' breast or pubic hair development or boys' genital development. Childhood PBDE exposure was not associated with any measure of pubertal timing, except for an association of BDE-153 with later menarche.ConclusionsWe found that prenatal PBDE exposure was associated with later menarche in girls but earlier pubarche in boys, suggesting opposite pubertal effects in girls and boys.

BackgroundPersonal care products are a source of exposure to potentially endocrine-disrupting chemicals such as phthalates, parabens, triclosan, and benzophenone-3 (BP-3) for adolescent girls.MethodsWe enrolled 100 Latina girls in a youth-led, community-based participatory research intervention study to determine whether using personal care products whose labels stated they did not contain these chemicals for 3 days could lower urinary concentrations. Pre- and postintervention urine samples were analyzed for phthalate metabolites, parabens, triclosan, and BP-3 using high-performance liquid chromatography/tandem mass spectrometry.ResultsUrinary concentrations of mono-ethyl phthalate (MEP) decreased by 27.4% (95% CI: -39.3, -13.2) on average over the 3-day intervention; no significant changes were seen in urinary concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP). Methyl and propyl paraben concentrations decreased by 43.9% (95% CI: -61.3, -18.8) and 45.4% (95% CI: -63.7, -17.9), respectively. Unexpectedly, concentrations of ethyl and butyl paraben concentrations increased, although concentrations were low overall and not detected in almost half the samples. Triclosan concentrations decreased by 35.7% (95% CI: -53.3, -11.6), and BP-3 concentrations decreased by 36.0% (95% CI: -51.0, -16.4).DiscussionThis study demonstrates that techniques available to consumers, such as choosing personal care products that are labeled to be free of phthalates, parabens, triclosan, and BP-3, can reduce personal exposure to possible endocrine-disrupting chemicals. Involving youth in the design and implementation of the study was key to recruitment, retention, compliance, and acceptability of the intervention.CitationHarley KG, Kogut K, Madrigal DS, Cardenas M, Vera IA, Meza-Alfaro G, She J, Gavin Q, Zahedi R, Bradman A, Eskenazi B, Parra KL. 2016. Reducing phthalate, paraben, and phenol exposure from personal care products in adolescent girls: findings from the HERMOSA Intervention Study. Environ Health Perspect 124:1600-1607; http://dx.doi.org/10.1289/ehp.1510514.

BackgroundLow-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity.ObjectivesTo examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children.MethodsWe evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression.ResultsChildren of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [β = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [β = -4.0; (-7.6, -0.4)], and Working Memory [β = -2.8; (-5.6, -0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory.ConclusionsResidential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age.

BackgroundOrganophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent.ObjectivesWe pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143).MethodsData were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes.ResultsWe found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, ΣDAP and ΣDMP were negatively associated with length (β = -0.4 cm; 95% CI: -0.9, 0.0 and β = -0.5 cm; 95% CI: -0.9, -0.1).ConclusionsThis study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations.CitationHarley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. 2016. Prenatal exposure to organophosphorous pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environ Health Perspect 124:1084-1092; http://dx.doi.org/10.1289/ehp.1409362.

BackgroundOrganophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001.ObjectivesWe conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months.MethodsUsing general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (ΣDMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype.ResultsThere was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (β = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (β = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of ΣDAP and ΣDEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics.ConclusionsData pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure.CitationEngel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K, Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM, Lanphear BP, Eskenazi B. 2016. Prenatal organophosphorus pesticide exposure and child neurodevelopment at 24 months: an analysis of four birth cohorts. Environ Health Perspect 124:822-830; http://dx.doi.org/10.1289/ehp.1409474.

Although banned in most countries, dichlorodiphenyl-trichloroethane (DDT) continues to be used for vector control in some malaria endemic areas. Previous findings from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study found increased prenatal levels of DDT and its breakdown product dichlorodiphenyl-dichloroethylene (DDE) to be associated with altered neurodevelopment in children at 1 and 2years of age. In this study, we combined the measured maternal DDT/E concentrations during pregnancy obtained for the prospective birth cohort with predicted prenatal DDT and DDE levels estimated for a retrospective birth cohort. Using generalized estimating equation (GEE) and linear regression models, we evaluated the relationship of prenatal maternal DDT and DDE serum concentrations with children's cognition at ages 7 and 10.5years as assessed using the Full Scale Intelligence Quotient (IQ) and 4 subtest scores (Working Memory, Perceptual Reasoning, Verbal Comprehension, and Processing Speed) of the Wechsler Intelligence Scale for Children (WISC). In GEE analyses incorporating both age 7 and 10.5 scores (n=619), we found prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales (p-value>0.05). In linear regression analyses assessing each time point separately, prenatal DDT levels were inversely associated with Processing Speed at age 7years (n=316), but prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales at age 10.5years (n=595). We found evidence for effect modification by sex. In girls, but not boys, prenatal DDE levels were inversely associated with Full Scale IQ and Processing Speed at age 7years. We conclude that prenatal DDT levels may be associated with delayed Processing Speed in children at age 7years and the relationship between prenatal DDE levels and children's cognitive development may be modified by sex, with girls being more adversely affected.

BackgroundNumerous cross-sectional studies of school-age children have observed that exposure to manganese (Mn) adversely affects neurodevelopment. However, few prospective studies have looked at the effects of both prenatal and postnatal Mn exposure on child neurodevelopment.MethodsWe measured Mn levels in prenatal and early postnatal dentine of shed teeth and examined their association with behavior, cognition, memory, and motor functioning in 248 children aged 7, 9, and/or 10.5 years living near agricultural fields treated with Mn-containing fungicides in California. We used generalized linear models and generalized additive models to test for linear and nonlinear associations, and generalized estimating equation models to assess longitudinal effects.ResultsWe observed that higher prenatal and early postnatal Mn levels in dentine of deciduous teeth were adversely associated with behavioral outcomes, namely internalizing, externalizing, and hyperactivity problems, in boys and girls at 7 and 10.5 years. In contrast, higher Mn levels in prenatal and postnatal dentine were associated with better memory abilities at ages 9 and 10.5, and better cognitive and motor outcomes at ages 7 and 10.5 years, among boys only. Higher prenatal dentine Mn levels were also associated with poorer visuospatial memory outcomes at 9 years and worse cognitive scores at 7 and 10.5 years in children with higher prenatal lead levels (≥0.8 μg/dL). All these associations were linear and were consistent with findings from longitudinal analyses.ConclusionsWe observed that higher prenatal and early postnatal Mn levels measured in dentine of deciduous teeth, a novel biomarker that provides reliable information on the developmental timing of exposures to Mn, were associated with poorer behavioral outcomes in school-age boys and girls and better motor function, memory, and/or cognitive abilities in school-age boys. Additional research is needed to understand the inconsistencies in the neurodevelopmental findings across studies and the degree to which differences may be associated with different Mn exposure pathways and biomarkers.

BackgroundNumerous cross-sectional studies of school-age children have observed that exposure to manganese (Mn) adversely affects neurodevelopment. However, few prospective studies have looked at the effects of both prenatal and postnatal Mn exposure on child neurodevelopment.MethodsWe measured Mn levels in prenatal and early postnatal dentine of shed teeth and examined their association with behavior, cognition, memory, and motor functioning in 248 children aged 7, 9, and/or 10.5 years living near agricultural fields treated with Mn-containing fungicides in California. We used generalized linear models and generalized additive models to test for linear and nonlinear associations, and generalized estimating equation models to assess longitudinal effects.ResultsWe observed that higher prenatal and early postnatal Mn levels in dentine of deciduous teeth were adversely associated with behavioral outcomes, namely internalizing, externalizing, and hyperactivity problems, in boys and girls at 7 and 10.5 years. In contrast, higher Mn levels in prenatal and postnatal dentine were associated with better memory abilities at ages 9 and 10.5, and better cognitive and motor outcomes at ages 7 and 10.5 years, among boys only. Higher prenatal dentine Mn levels were also associated with poorer visuospatial memory outcomes at 9 years and worse cognitive scores at 7 and 10.5 years in children with higher prenatal lead levels (≥0.8 μg/dL). All these associations were linear and were consistent with findings from longitudinal analyses.ConclusionsWe observed that higher prenatal and early postnatal Mn levels measured in dentine of deciduous teeth, a novel biomarker that provides reliable information on the developmental timing of exposures to Mn, were associated with poorer behavioral outcomes in school-age boys and girls and better motor function, memory, and/or cognitive abilities in school-age boys. Additional research is needed to understand the inconsistencies in the neurodevelopmental findings across studies and the degree to which differences may be associated with different Mn exposure pathways and biomarkers.

IntroductionManganese (Mn) is an essential nutrient but higher exposure has been associated with poorer neurodevelopment in children.MethodsWe measured Mn levels in prenatal (Mnpre) (n=197) and postnatal (Mnpost) dentin (n=193) from children's shed teeth using laser ablation inductively coupled plasma mass spectroscopy and examined the relationship with children's scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) on the Bayley Scales of Infant Development at 6, 12, and 24-months. We explored non-linear associations and interactions by sex, blood lead concentrations and maternal iron status during pregnancy.ResultsA two-fold increase of Mnpost levels in dentin was associated with small decreases in MDI at 6-months and 12-months of age. We also observed a non-linear relationship between Mnpost levels and PDI at 6-months. We found effect modification by sex for Mnpost levels and neurodevelopment at 6-months with stronger effects among girls for both MDI (-1.5 points; 95% Confidence Interval (CI): -2.4, -0.6) and PDI (-1.8 points; 95% CI: -3.3, -0.3). Girls whose mothers had lower hemoglobin levels experienced larger decreases in MDI and PDI associated with Mnpre levels than girls whose mothers had higher hemoglobin levels (pinteraction=0.007 and 0.09, respectively). We did not observe interactions with blood lead concentrations or any relationships with neurodevelopment at 24-months.ConclusionsUsing Mn measurements in tooth dentin, a novel biomarker that provides prenatal and early postnatal levels, we observed negative transient associations between postnatal Mn levels and early neurodevelopment with effect modification by sex and interactions with prenatal hemoglobin.

BackgroundPolybrominated diphenyl ethers (PBDEs) are lipophilic flame retardants that bioaccumulate in humans. Child serum PBDE concentrations in California are among the highest worldwide. PBDEs may be associated with obesity by disrupting endocrine systems.ObjectiveIn this study, we examined whether pre- and postnatal exposure to the components of pentaBDE mixture was associated with childhood obesity in a population of Latino children participating in a longitudinal birth cohort study in the Salinas Valley, California.MethodsWe measured PBDEs in serum collected from 224 mothers during pregnancy and their children at 7 years of age, and examined associations with body mass index (BMI) at age 7 years.ResultsMaternal PBDE serum levels during pregnancy were associated with higher BMI z-scores in boys (BMI z-score βadjusted = 0.26; 95% CI: -0.19, 0.72) but lower scores in girls (BMI z-score βadjusted = -0.41; 95% CI: -0.87, -0.05) at 7 years of age (pinteraction = 0.04). In addition, child's serum BDE-153 concentration (log10), but not other pentaBDE congeners, demonstrated inverse associations with BMI at age 7 years (BMI z-score βadjusted = -1.15; 95% CI: -1.53, -0.77), but there was no interaction by sex.ConclusionsWe estimated sex-specific associations with maternal PBDE levels during pregnancy and BMI at 7 years of age, finding positive associations in boys and negative associations in girls. Children's serum BDE-153 concentrations were inversely associated with BMI at 7 years with no difference by sex. Future studies should examine the longitudinal trends in obesity with PBDE exposure and changes in hormonal environment as children transition through puberty, as well as evaluate the potential for reverse causality.

IntroductionOrganophosphate (OP) pesticides remain widely used in agriculture. Previously, we reported that PON1 genotype was directly associated with neurodevelopment at age two, and that PON1 genotype may increase susceptibility to OP exposure.ObjectivesWe examined the relationships of maternal and child PON1 genotype and enzyme activity levels and neurodevelopment at school age and examined their interaction with maternal dialkyl phosphate (DAP) metabolite levels to investigate differential susceptibility to OP-related neurotoxicity.MethodsParticipants were from the CHAMACOS longitudinal birth cohort of Latino families in an agricultural region of California. We measured DAP metabolites of OP pesticides in maternal and child urine samples, and analyzed PON1192 and PON1-108 genotypes and enzyme activity [arylesterase (ARYase), paraoxonase (POase)] in maternal and child blood. We examined their association with children׳s performance on the Conners׳ Kiddie Continuous Performance Test (K-CPT) at 5 years (n=296) and the Wechsler Intelligence Scale for Children (WISC-IV) at 7 years (n=327).ResultsMaternal and child PON1 genotype was not related to performance on K-CPT or WISC, although WISC scores tended to be lowest in children and children of mothers who carried the PON-108TT genotype. Pregnancy ARYase levels were positively associated with all WISC subscales (e.g., 4.0 point increase in Full Scale IQ per standard deviation increase in ARYase, 95% CI=1.6, 6.4), while pregnancy POase levels were positively associated with WISC Processing Speed only. Maternal PON1-108 weakly modified the relationship of maternal DAPS and K-CPT scores (pinteraction=0.21) and WISC verbal IQ (pinteraction=0.71). The association between DAPs and Full-Scale IQ was strongest for children of mothers with lowest-tertile ARYase levels (pinteraction=0.27). This relationship held for both diethyl and dimethyl DAPs and for all subscales of the WISC.ConclusionsWe extend our previous findings that PON1 genotype and enzyme levels may be directly related to performance on certain domains of neurodevelopment in school-age children. Lower maternal PON1 enzyme levels during pregnancy may also increase susceptibility of children to neurotoxicity from OP pesticide exposure.

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Methylation of Alu and long interspersed nucleotide elements (LINE-1) is a well-established measure of DNA methylation often used in epidemiologic studies. Yet, few studies have examined the effects of host factors on LINE-1 and Alu methylation in children. We characterized the relationship of age, sex, and prenatal exposure to persistent organic pollutants (POPs), dichlorodiphenyl trichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs), with DNA methylation in a birth cohort of Mexican-American children participating in the CHAMACOS study. We measured Alu and LINE-1 methylation by pyrosequencing bisulfite-treated DNA isolated from whole blood samples collected from newborns and nine-year old children (n = 358). POPs were measured in maternal serum during late pregnancy. Levels of DNA methylation were lower in nine-year olds compared to newborns and were higher in boys compared to girls. Higher prenatal DDT/E exposure was associated with lower Alu methylation at birth, particularly after adjusting for cell type composition (P = 0.02 for o,p' -DDT). Associations of POPs with LINE-1 methylation were only identified after examining the co-exposure of DDT/E with PBDEs simultaneously. Our data suggest that repeat element methylation can be an informative marker of epigenetic differences by age and sex and that prenatal exposure to POPs may be linked to hypomethylation in fetal blood. Accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies.

Manganese (Mn) is an essential nutrient, but overexposure can be neurotoxic. Over 800 000 kg of Mn-containing fungicides are applied each year in California. Manganese levels in teeth are a promising biomarker of perinatal exposure. Participants in our analysis included 207 children enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort study in an agricultural area of California. Mn was measured in teeth using laser-ablation-inductively coupled plasma-mass spectrometry. Our purpose was to determine environmental and lifestyle factors related to prenatal Mn levels in shed teeth. We found that storage of farmworkers' shoes in the home, maternal farm work, agricultural use of Mn-containing fungicides within 3 km of the residence, residence built on Antioch Loam soil and Mn dust loading (μg/m(2) of floor area) during pregnancy were associated with higher Mn levels in prenatal dentin (p < 0.05). Maternal smoking during pregnancy was inversely related to Mn levels in prenatal dentin (p < 0.01). Multivariable regression models explained 22-29% of the variability of Mn in prenatal dentin. Our results suggest that Mn measured in prenatal dentin provides retrospective and time specific levels of fetal exposure resulting from environmental and occupational sources.

BackgroundMethyl bromide, a fungicide often used in strawberry cultivation, is of concern for residents who live near agricultural applications because of its toxicity and potential for drift. Little is known about the effects of methyl bromide exposure during pregnancy.ObjectiveWe investigated the relationship between residential proximity to methyl bromide use and birth outcomes.MethodsParticipants were from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study (n = 442), a longitudinal cohort study examining the health effects of environmental exposures on pregnant women and their children in an agricultural community in northern California. Using data from the California Pesticide Use Reporting system, we employed a geographic information system to estimate the amount of methyl bromide applied within 5 km of a woman's residence during pregnancy. Multiple linear regression models were used to estimate associations between trimester-specific proximity to use and birth weight, length, head circumference, and gestational age.ResultsHigh methyl bromide use (vs. no use) within 5 km of the home during the second trimester was negatively associated with birth weight (β = -113.1 g; CI: -218.1, -8.1), birth length (β = -0.85 cm; CI: -1.44, -0.27), and head circumference (β = -0.33 cm; CI: -0.67, 0.01). These outcomes were also associated with moderate methyl bromide use during the second trimester. Negative associations with fetal growth parameters were stronger when larger (5 km and 8 km) versus smaller (1 km and 3 km) buffer zones were used to estimate exposure.ConclusionsResidential proximity to methyl bromide use during the second trimester was associated with markers of restricted fetal growth in our study.

BackgroundIn utero exposure to endocrine disrupting compounds including dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) has been hypothesized to increase risk of obesity later in life.ObjectivesThe Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study is a longitudinal birth cohort of low-income Latinas living in a California agricultural community. We examined the relation of in utero DDT and DDE exposure to child obesity at 7 years of age. We also examined the trend with age (2, 3.5, 5, and 7 years) in the exposure-obesity relation.MethodsWe included 270 children with o,p´-DDT, p,p´-DDT, and p,p´-DDE concentrations measured in maternal serum during pregnancy (nanograms per gram lipid) and complete 7-year follow-up data including weight (kilograms) and height (centimeters). Body mass index (BMI; kilograms per meter squared) was calculated and obesity was defined as ≥ 95th percentile on the sex-specific BMI-for-age Centers for Disease Control and Prevention 2000 growth charts.ResultsAt 7 years, 96 (35.6%) children were obese. A 10-fold increase in o,p´-DDT, p,p´-DDT, or p,p´-DDE, was nonsignificantly associated with increased odds (OR) of obesity [o,p´-DDT adjusted (adj-) OR = 1.17, 95% CI: 0.75, 1.82; p,p´-DDT adj-OR = 1.19, 95% CI: 0.81, 1.74; p,p´-DDE adj-OR = 1.22, 95% CI: 0.72, 2.06]. With increasing age at follow-up, we observed a significant trend toward a positive association between DDT and DDE exposure and odds of obesity.ConclusionWe did not find a significant positive relation between in utero DDT and DDE exposure and obesity status of 7-year-old children. However, given the observed trend with age, continued follow-up will be informative.

BackgroundCalifornia children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals.ObjectiveHere we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort.MethodsWe measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children's attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323).ResultsMaternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination-particularly in the nondominant-at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels.ConclusionsBoth prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.

BackgroundBisphenol A (BPA) is widely used in the manufacture of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt thyroid function. Although thyroid hormones play a determinant role in human growth and brain development, no studies have investigated relations between BPA exposure and thyroid function in pregnant women or neonates.ObjectiveOur goal was to evaluate whether exposure to BPA during pregnancy is related to thyroid hormone levels in pregnant women and neonates.MethodsWe measured BPA concentration in urine samples collected during the first and second half of pregnancy in 476 women participating in the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We also measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in women during pregnancy, and TSH in neonates.ResultsAssociations between the average of the two BPA measurements and maternal thyroid hormone levels were not statistically significant. Of the two BPA measurements, only the one taken closest in time to the TH measurement was significantly associated with a reduction in total T4 (β = -0.13 µg/dL per log2 unit; 95% CI: -0.25, 0.00). The average of the maternal BPA concentrations was associated with reduced TSH in boys (-9.9% per log2 unit; 95% CI: -15.9%, -3.5%) but not in girls. Among boys, the relation was stronger when BPA was measured in the third trimester of pregnancy and decreased with time between BPA and TH measurements.ConclusionResults suggest that exposure to BPA during pregnancy is related to reduced total T4 in pregnant women and decreased TSH in male neonates. Findings may have implications for fetal and neonatal development.

ContextOrganophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children's cognitive development.ObjectiveWe examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children.MethodsWe conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment.ResultsUrinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children's urinary DAP concentrations were not consistently associated with cognitive scores.ConclusionsPrenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population.

BackgroundParaoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.ObjectiveWe determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior.MethodsWe measured DAP concentrations in maternal urine during pregnancy, PON1₁₉₂ and PON1₋₁₀₈ genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds' blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD.ResultsChildren with the PON1(-108T) allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1(-108T) allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant.ConclusionPON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure.

BackgroundHuman exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy.ObjectivesOur goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women.MethodsWe measured the concentration of 10 PBDE congeners, free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation.ResultsSerum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (ΣPBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), -20.6 to 0.0] and 18.7% (95% CI, -29.2 to -4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T4) were also significantly elevated in participants in the highest quartile of ΣPBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T4 were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ΣPBDEs.ConclusionsResults suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development.

BackgroundExposure to polybrominated diphenyl ether (PBDE) flame retardants is widespread, with 97% of Americans having detectable levels. Although PBDEs have been associated with reproductive and hormonal effects in animals, no human studies have examined their association with fertility.ObjectivesThis study was designed to determine whether maternal concentrations of PBDEs in serum collected during pregnancy are associated with time to pregnancy and menstrual cycle characteristics.MethodsPregnant women (n = 223) living in a low-income, predominantly Mexican-immigrant community in California were interviewed to determine how many months they took to become pregnant. Blood samples were collected and analyzed for PBDEs. PBDE concentrations were lipid adjusted and log10 transformed. Analyses were limited to PBDE congeners detected in > 75% of the population (BDEs 47, 99, 100, 153). Cox proportional hazards models modified for discrete time were used to obtain fecundability odds ratios (fORs) for the association of PBDEs and time to pregnancy.ResultsWe detected all four congeners in > 97% of women. Increasing levels of BDEs 47, 99, 100, 153 and the sum of these four congeners were all associated with longer time to pregnancy. We observed significantly reduced fORs for BDE-100 [adjusted fOR = 0.6; 95% confidence interval (CI), 0.4-0.9], BDE-153 (adjusted fOR = 0.5; 95% CI, 0.3-0.8), and the sum of the four congeners (adjusted fOR = 0.7; 95% CI, 0.5-1.0). PBDEs were not associated with menstrual cycle characteristics.ConclusionsWe found significant decreases in fecundability associated with PBDE exposure in women. Future studies are needed to replicate and confirm this finding.