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BackgroundWe previously reported associations of prenatal exposure to organophosphate (OP) pesticides with poorer neurodevelopment in early childhood and at school age, including poorer cognitive function and more behavioral problems, in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort study in an agriculture community.ObjectiveWe investigated the extent to which early-life exposure to OP pesticides is associated with behavioral problems, including mental health, in youth during adolescence and early adulthood.MethodsWe measured urinary dialkylphosphates (DAPs), nonspecific OP metabolites, in urine samples collected from mothers twice during pregnancy (13 and 26 wk) and at five different times in their children (ages 6 months to 5 y). We assessed maternal report and youth report of externalizing and internalizing behavior problems using the Behavior Assessment System for Children, 2nd edition (BASC-2), when the youth were ages 14, 16, and 18 y. Because there was evidence of nonlinearity, we estimated associations across quartiles of DAPs and modeled repeated outcome measures using generalized estimating equations.ResultsThere were 335 youths with prenatal maternal DAP measures and 14-. 16-, or 18-y BASC-2 scores. Prenatal maternal DAP concentrations (specific gravity-adjusted median, Q1-Q3=159.4, 78.7-350.4 nmol/L) were associated with higher T-scores (more behavior problems) from maternal report, including more hyperactivity [fourth vs. first quartile of exposure β=2.32; 95% confidence interval (CI): 0.18, 4.45], aggression (β=1.90; 95% CI: 0.15, 3.66), attention problems (β=2.78; 95% CI: 0.26, 5.30), and depression (β=2.66; 95% CI: 0.08, 5.24). Associations with youth report of externalizing problems were null, and associations with depression were suggestive (fourth vs. first quartile of exposure β=2.15; 95% CI: -0.36, 4.67). Childhood DAP metabolites were not associated with behavioral problems.DiscussionWe found associations of prenatal, but not childhood, urinary DAP concentrations with adolescent/young adult externalizing and internalizing behavior problems. These findings are consistent with prior associations we have reported with neurodevelopmental outcomes measured earlier in childhood in CHAMACOS participants and suggests that prenatal exposure to OP pesticides may have lasting effects on the behavioral health of youth as they mature into adulthood, including their mental health. https://doi.org/10.1289/EHP11380.

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.

BackgroundThe effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed.ObjectiveTo evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission.Study designIn this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices.ResultsA total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity.ConclusionIn this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

BackgroundStudies have documented independent adverse associations between prenatal and early-life exposure to environmental chemicals and social adversity with child neurodevelopment; however, few have considered these exposures jointly. The objective of this analysis is to examine whether associations of pesticide mixtures and adolescent neurobehavioral development are modified by early-life adversity in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort.MethodsWe used linear mixed effects Bayesian Hierarchical Models (BHM) to examine the joint effect of applications of 11 agricultural pesticides within 1 km of maternal homes during pregnancy and youth-reported Adverse Childhood Experiences (ACEs) with maternal and youth-reported internalizing behaviors, hyperactivity, and attention problems assessed via the Behavior Assessment for Children (BASC) (mean = 50, standard deviation = 10) at ages 16 and 18 years (n = 458).ResultsThe median (25th-75th percentiles) of ACEs was 1 (0-3); 72.3% of participants had low ACEs (0-2 events) and 27.7% had ACEs (3+ events). Overall, there was little evidence of modification of exposure-outcome associations by ACEs. A two-fold increase in malathion use was associated with increased internalizing behaviors among those with high ACEs from both maternal- (β = 1.9; 95% Credible Interval (CrI): 0.2, 3.7 for high ACEs vs. β = -0.1; 95% CrI: 1.2, 0.9 for low ACEs) and youth-report (β = 2.1; 95% CrI: 0.4, 3.8 for high ACEs vs. β = 0.2; 95% CrI: 0.8, 1.2 for low ACEs). Applications of malathion and dimethoate were also associated with higher youth-reported hyperactivity and/or inattention among those with high ACEs.ConclusionWe observed little evidence of effect modification of agricultural pesticide use near the home during pregnancy and adolescent behavioral problems by child ACEs. Future studies should examine critical windows of susceptibility of exposure to chemical and non-chemical stressors and should consider biomarker-based exposure assessment methods.

IntroductionYoung children may be exposed to pesticides used in child care centers and their family homes. We examined pesticide use and environmental and behavioral factors potentially associated with child exposures in these settings.MethodPreschool-age children (n = 125) wore silicone wristbands to assess pesticide exposures in their child care centers and home environments. Information about environmental and behavioral exposure determinants was collected using parent surveys, child care director interviews, and observations.ResultsCommonly detected pesticides were bifenthrin, chlorpyrifos, cypermethrin, fipronil, and cis- and trans-permethrin. Pesticide chemical storage onsite, cracks in the walls, using doormats, observed pests, or evidence of pests were associated with child exposures. Exposures were higher in counties with higher agricultural or commercial pesticide use or when children lived in homes near agricultural fields.DiscussionYoung children are being exposed to harmful pesticides, and interventions are needed to lower their risk of health problems later in life.

IntroductionPrevious studies show evidence for associations of prenatal exposure to organophosphate (OP) pesticides with poorer childhood neurodevelopment. As children grow older, poorer cognition, executive function, and school performance can give rise to risk-taking behaviors, including substance abuse, delinquency, and violent acts. We investigated whether prenatal OP exposure was associated with these risk-taking behaviors in adolescence and young adulthood in a Mexican American cohort.MethodsWe measured urinary dialkyl phosphates (DAPs), non-specific metabolites of OPs, twice (13 and 26 weeks gestation) in pregnant women recruited in 1999-2000 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort set in a primarily Latino agricultural community in the Salinas Valley, California. We followed up children throughout their childhood and adolescence; at the 18-year visit, adolescent youth (n = 315) completed a computer-based questionnaire which included questions about substance use, risky sexual activity, risky driving, and delinquency and police encounters. We used multivariable models to estimate associations of prenatal total DAPs with these risk-taking behaviors.ResultsThe prevalence of risk-taking behaviors in CHAMACOS youth ranged from 8.9% for smoking or vaping nicotine to 70.2% for committing a delinquent act. Associations of total prenatal DAPs (geometric mean = 132.4 nmol/L) with risk-taking behavior were generally null and imprecise. Isolated findings included a higher risk for smoking or vaping nicotine within the past 30 days (relative risk [RR] per 10-fold increase in prenatal DAPs = 1.89, 95% CI: 1.00, 3.56) and driving without a license (RR = 1.74, 95% CI: 1.25, 2.42). There were no consistent differences by sex or childhood adversity.DiscussionWe did not find clear or consistent evidence for associations of prenatal OP exposure with risk-taking behaviors in adolescence/early adulthood in the CHAMACOS population. Our small sample size may have prevented us from detecting potentially subtle associations of early life OP exposure with these risk-taking behaviors.

BackgroundSpot urine samples are often used to assess exposure to organophosphate (OP) pesticides in place of "gold standard" 24-hr samples, which are cumbersome to collect. Assessment of non-persistent chemicals using spot urine samples may result in exposure misclassification that could bias epidemiological analyses towards the null. Few studies have examined the validity of measurements of urinary metabolites in spot samples to estimate daily OP dose or the potential implications of reliance on spot samples for risk assessments.ObjectiveExamine the validity of using first morning void (FMV) and random non-FMV urine samples to estimate cumulative 24-hr OP pesticide dose among children living in an agricultural region.MethodsWe collected urine samples over 7 consecutive days, including two 24-hr samples, from 25 children living in an agricultural community. We used measurements of urinary dialkylphosphate (DAP) metabolites, data on nearby agricultural pesticide applications, and daily dietary intake data to estimate internal dose from exposure to a mixture of OP pesticides according to the U.S. Environmental Protection Agency Cumulative Risk Assessment guidelines. Dose estimates from volume- and creatinine-adjusted same-day FMV and non-FMV spot urine samples were compared to the "gold standard" estimates from 24-hr samples.ResultsNon-FMV samples had relatively weak ability to predict 24-hr dose (R2 = 0.09-0.38 for total DAPs) and tended to underestimate the percentage of samples exceeding regulatory guidelines. Models with FMV samples or the average of an FMV and non-FMV sample were similarly predictive of 24-hr estimates (R2 for DAPs = 0.40-0.68 and 0.40-0.80, respectively, depending on volume adjustment method).ConclusionReliance on non-FMV samples for risk assessments may underestimate daily OP dose and the percentage of children with dose estimates exceeding regulatory guidelines. If 24-hr urine sample collection is infeasible, we recommend future studies prioritize the collection of FMV samples to most accurately characterize OP dose in children.

ObjectiveLittle is known about the impact of the home environment on biomarkers of obesity, such as adipokines, in children. In this study, we examined the relationship of maternal depressive symptoms and potentially protective social factors, including maternal support and the home learning environment, with body mass index and adipokines.MethodsData were obtained from 326 Mexican American participants from the Center for the Health Assessment of Mothers and Children of Salinas cohort. Plasma adipokine levels were assessed in 326 children by enzyme-linked immunoassay at birth or ages 5, 9, or 14 years. Maternal depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale when children were 1, 3.5, 7, and 9 years old; social support was assessed by the Duke-University of North Carolina Questionnaire at ages 1 and 5 years; and home learning environment by the Home Observation for the Measurement of the Environment (HOME) at ages of 6 months and 1, 2, 3.5, 7, 9, and 10.5 years.ResultsAge was significantly associated with adiponectin (B = -5.0, SE = 0.2) and leptin (B = 0.01, SE = 0.003) levels. Individual time point analyses identified significant positive associations of HOME scores in childhood with adiponectin at ages 9 years (HOME score; age 3.5 years: B = 0.9, p = .04) and 14 years (HOME score; age 7 years: B = 0.6, p = .02, age 9 years: B = 0.6, p = .05, age 10.5 years: B = 0.5, p = .04). We observed significant relationships of maternal depressive symptoms at age 9 years with adiponectin and body mass index z-score at age 14 years (B = -0.2, p = .003 and B = 0.02, p = .002, resp.), which were confirmed in longitudinal models.ConclusionsThis study adds new evidence that adverse and protective aspects of the home environment could lead to altered obesity status in children.

Evidence suggests that early-life exposure to pesticides inside the home may be associated with childhood leukemia, however data from Latin American countries are limited. We examined whether self-reported maternal residential pesticide use and nearby pesticide applications-before and after child's birth-were associated with acute lymphoblastic leukemia (ALL) in the Costa Rican Childhood Leukemia Study (CRCLS), a population-based case-control study (2001-2003). Cases (n = 251 ALL) were diagnosed between 1995 and 2000 (age

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.

We report longitudinal serum concentrations of select persistent organic pollutants (POPs) in children at ages 7 and 9 years and in their mothers prenatally and again when the children were 9 years old. The participating families were enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort study of low-income Hispanic families residing in the Salinas Valley, California. We observed decreasing concentrations in the mothers with year of serum collection (2009 vs 2011) for six out of seven polybrominated diphenyl ether (PBDE) congeners and for 2,2',4,4',5-pentachlorobiphenyl (CB-99; p < 0.05). The 9-year-old children had similarly decreasing serum concentrations of all seven PBDE congeners, CB-99, and 2,2',3,4,4',5'- and 2,3,3',4,4',6-hexachlorobiphenyl (CB-138/158) with year of serum collection (2009 vs 2011; p < 0.05). In mixed effect models accounting for weight gain as the children aged from 7 to 9 years, we observed an annual decrease (-8.3% to -13.4%) in tri- to hexaBDE concentrations (p < 0.001), except for 2,2',3,4,4'-tetrabromodiphenyl ether (BDE-85) and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). The concentrations of these congeners were not associated with time of serum collection and instead showed an -0.9% to -2.6% decrease per kilogram of weight gain during the study period (p < 0.05). In the case of tetra- to heptachlorobiphenyls, we observed -0.5% to -0.7% decrease in serum concentration per kilogram of weight gain (p < 0.05) and -3.0% to -3.7% decrease in serum concentration per year of aging (p < 0.05), except for 2,3',4,4',5-pentachlorobiphenyl (CB-118) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), which were not associated with time of serum draw. 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) decreased -2.4%/kg of weight gain between the two sampling points (p < 0.001). These findings suggest that as children grow, dilution in a larger body size plays an important role in explaining reductions in body burden in the case of traditional POPs such as PCBs and p,p'-DDE. By contrast, in the case of PBDEs, reductions are likely explained by reduction in exposure, as illustrated by decreased concentrations in more recent years, possibly amplified by presumed shorter biological half-life than other POPs.

California has proposed limiting agricultural pesticide use within 0.4 km of schools and childcare facilities. However, the 0.4-km buffer may not be appropriate for all pesticides because of differing toxicities, fate, and application methods. Living near pesticide use has been associated with poorer birth outcomes, neurodevelopment, and respiratory function in children. More research about exposures in schools, childcare facilities, and homes is needed. Despite incomplete science, this regulation is an important step to reduce potential exposures to children. The most vulnerable exposure period may be in utero, and future regulations should also aim to reduce exposures to pregnant women.

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.

ObjectivesAssociations between parental occupational pesticide exposure and childhood acute lymphoblastic leukemia (ALL) vary across studies, likely due to different exposure assessment methodologies.MethodsWe assessed parental occupational pesticide exposure from the year before pregnancy to the child's third year of life for 669 children diagnosed with ALL and 1021 controls. We conducted expert rating using task-based job modules (JM) to estimate exposure to pesticides among farmer workers, gardeners, agricultural packers, and pesticide applicators. We compared this method to (1) partial JM using job titles and a brief description, but without completing the task-based questionnaire, and (2) job exposure matrix (JEM) linking job titles to the International Standard Classifications of Occupation Codes. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for ALL cancer risk and pesticide exposure adjusting for child's sex, age, race/ethnicity and household income.ResultsCompared to complete JMs, partial JMs and JEM led to 3.1% and 9.4% of parents with pesticide exposure misclassified, respectively. Misclassification was similar in cases and controls. Using complete JMs, we observed an increased risk of ALL for paternal occupational exposure to any pesticides (OR=1.7; 95% CI=1.2, 2.5), with higher risks reported for pesticides to treat nut crops (OR=4.5; 95% CI=0.9, 23.0), and for children diagnosed before five years of age (OR=2.3; 95% CI: 1.3, 4.1). Exposure misclassification from JEM attenuated these associations by about 57%. Maternal occupational pesticide exposure before and after birth was not associated with ALL.ConclusionsThe risk of ALL was elevated in young children with paternal occupational pesticide exposure during the perinatal period, using more detailed occupational information for exposure classification.

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.

PurposeData on parental occupational exposures and risk of childhood leukemia lack specificity. Using 19 task-based job modules, we examined the relationship between occupational exposure to organic solvents and other compounds and the risk of leukemia in children.MethodsLatino (48%) and non-Latino (52%) children with acute lymphoblastic leukemia (ALL; n=670), acute myeloid leukemia (AML; n=104), and controls (n=1021) were enrolled in a study in California (2000-2008). Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for socio-demographic factors.ResultsAmong children with non-Latino fathers, none of the exposures evaluated were associated with risks of ALL and AML. In contrast, exposure to any organic solvents in Latino fathers was associated with an increased risk of childhood ALL (OR=1.48; 95% CI: 1.01-2.16); in multivariable analyses, the OR for chlorinated hydrocarbons was 2.28 (95% CI: 0.97-5.37) while the ORs were close to one for aromatic hydrocarbons, glycol ethers, and other hydrocarbon mixtures. We also observed an increased risk of ALL with exposure to combustion exhaust/polycyclic aromatic hydrocarbons (PAHs) (ORs=1.70; 95% CI: 1.16-2.57, and 1.46; 95% CI: 0.94-2.26 with and without adjustment for chlorinated hydrocarbons, respectively). Moderately elevated risks of ALL were seen with exposure to metals, paints, and wood dust, although not statistically significant. An increased risk was reported for asbestos based on small numbers of exposed Latino fathers. No associations were reported between maternal exposures to any exposures and childhood ALL and AML.ConclusionsOur data support associations between paternal occupational exposures to chlorinated hydrocarbons, combustion exhaust, metals, and possibly asbestos and the risk of ALL in the children of Latino fathers only.

BackgroundPrevious studies have observed an adverse association between prenatal exposure to organophosphate pesticide (OPs) and child cognition, but few studies consider the potential role of social stressors in modifying this relationship.ObjectiveWe seek to explore the potential role of early social adversities in modifying the relationship between OPs and child IQ in an agricultural Mexican American population.MethodsParticipants from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a prospective longitudinal pre-birth cohort study, include 329 singleton infants and their mothers followed from pregnancy through age 7. Dialkyl phosphate metabolite concentrations (DAPs), a biomarker of organophosphate pesticide exposure, were measured in maternal urine collected twice during pregnancy and averaged. Child cognitive ability was assessed at 7 years using the Wechsler Intelligence Scale for Children - Fourth Edition. Demographic characteristics and adversity information were collected during interviews and home visits at numerous time points from pregnancy until age 7.ResultsAmong low-income Latina mothers and their children in the Salinas Valley, total adversity and specific domains of adversity including poor learning environment and adverse parent-child relationships were negatively associated with child cognition. Adverse associations between DAP concentrations and IQ were stronger in children experiencing greater adversity; these associations varied by child sex. For example, the association between prenatal OP exposure and Full-Scale IQ is potentiated among boys who experienced high adversity in the learning environment (β=-13.3; p-value

BackgroundOrganophosphate pesticides are heavily used in agriculture, and adverse associations with respiratory health in occupational settings have been reported. However, most of the evidence comes from studies where there were no biomarkers of exposure and no objective outcome measurement. Non-occupational chronic effects among residents living in agricultural communities are less well described.ObjectiveTo evaluate associations between early-life organophosphate exposure and lung function of children living in an agricultural community.MethodsParticipants were 279 children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal birth cohort. The area under the curve for organophosphate exposure was determined by urinary diethyl and dimethyl dialkylphosphate metabolites of organophosphate pesticides, which were measured five times during childhood (6-60 months). Spirometry was performed at age 7 years. Regression models controlled for maternal smoking during pregnancy, season of birth, particulate matter concentrations with aerodynamic diameter ≤2.5 μm (PM2.5), breast feeding duration, mould and pets at home, distance of home from a highway, food insecurity, maternal education, season of spirometry, sex, height and technician.ResultsChildhood diethyl, dimethyl and total dialkylphosphate concentrations were associated with significant decreases in lung function at age 7. Specifically, we found lower FEV1, (L/s) (ß=-0.16, 95% CI -0.30 to -0.02, p=0.03) and FVC (L) (ß=-0.17, 95% CI -0.34 to 0.01, p=0.06) per 10-fold increase of total dialkylphosphate levels.ConclusionsEarly-life organophosphate exposure as assessed by dialkylphosphate concentrations was adversely associated with 7-year-old children's lung function.

BackgroundRecent meta-analyses demonstrate an association between self-reported residential pesticide use and childhood leukemia risk. Self-reports may suffer from recall bias and provide information only on broad pesticide categories. We compared parental self-reported home and garden pest treatments to pesticides measured in carpet dust.MethodsParents of 277 children with leukemia and 306 controls in Northern and Central California (2001-2007) were asked about insect and weed treatments during the previous year. Carpet dust samples were analyzed for 47 pesticides. We present results for the 7 insecticides (carbaryl, propoxur, chlorpyrifos, diazinon, cyfluthrin, cypermethrin, permethrin), 5 herbicides (2,4-dichlorophenoxyacetic acid [2,4-D], chlorthal, dicamba, mecoprop, simazine), and 1 synergist (piperonyl butoxide) that were present in home and garden products during the study period and were detected in ≥25% of carpet dust samples. We constructed linear regression models for the relative change in pesticide concentrations associated with self-reported treatment of pest types in cases and controls separately and combined, adjusting for demographics, housing characteristics, and nearby agricultural pesticide applications.ResultsSeveral self-reported treatments were associated with pesticide concentrations in dust. For example, households with flea/tick treatments had 2.3 (95% Confidence Interval [CI]: 1.4, 3.7) times higher permethrin concentrations than households not reporting this treatment. Households reporting treatment for ants/cockroaches had 2.5 (95% CI: 1.5, 4.2) times higher cypermethrin levels than households not reporting this treatment. Weed treatment by a household member was associated with 1.9 (1.4, 2.6), 2.2 (1.6, 3.1), and 2.8 (2.1, 3.7) times higher dust concentrations of dicamba, mecoprop, and 2,4-D, respectively. Weed treatments by professional applicators were null/inversely associated with herbicide concentrations in dust. Associations were generally similar between cases and controls and were consistent with pesticide active ingredients in these products during the study time period.ConclusionsConsistency between self-reported pest treatments, concentrations in dust, and pesticides in products lends credibility to the exposure assessment methods and suggests that differential recall by case-control status is minimal.

We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in

ObjectiveCalifornia children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest measured worldwide. We previously reported associations for prenatal and childhood PBDE exposures with decrements in attention, processing speed, fine motor coordination, and cognition in children at ages 5 and 7 years. Here, we investigate associations of PBDEs with attention and executive function at ages 9 to 12 years in the expanded CHAMACOS cohort.MethodsWe measured PBDEs in prenatal and child age 9 year serum samples for families enrolled in the study since pregnancy ("CHAM1", N=321). In a subsequent cohort for which families were enrolled at child age 9 ("CHAM2", N=301), we measured PBDEs in maternal and child samples collected at child age 9, and used predictive modeling to estimate prenatal exposure levels. We examined associations of measured and estimated PBDE concentrations on children's attention and executive functioning at ages 9, 10½, and 12 years.ResultsGeometric means for prenatal and childhood ΣPBDE levels (sum of PBDE-47, -99, -100, -153) for the expanded CHAMACOS cohort were 26.3 and 63.2 ng/g lipid, respectively, and did not differ significantly between CHAM1 and CHAM2 families. We found consistent associations of prenatal exposure to PBDEs with poorer attention and executive function, measured with parent report and direct neuropsychological testing of the child. For example, using GEE models of repeated outcome measures at ages 9 and 12, a 10-fold increase in prenatal ΣPBDE was associated with poorer response consistency on the Conners' Continuous Performance Test II (β=2.9; 95% CI: 0.9, 4.8) and poorer working memory on the Behavioral Rating Inventory of Executive Function (β=2.5; 95% CI: 0.5, 4.4). Child age 9 ΣPBDE levels were associated with poorer parent-reported attention and executive function for girls but not boys.ConclusionsOur results suggest that the prefrontal cortex may be a potential target for PBDE exposure and add to a growing literature showing that these ubiquitous toxicants may adversely affect neurodevelopment.

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.

ObjectiveCalifornia children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest measured worldwide. We previously reported associations for prenatal and childhood PBDE exposures with decrements in attention, processing speed, fine motor coordination, and cognition in children at ages 5 and 7 years. Here, we investigate associations of PBDEs with attention and executive function at ages 9 to 12 years in the expanded CHAMACOS cohort.MethodsWe measured PBDEs in prenatal and child age 9 year serum samples for families enrolled in the study since pregnancy ("CHAM1", N=321). In a subsequent cohort for which families were enrolled at child age 9 ("CHAM2", N=301), we measured PBDEs in maternal and child samples collected at child age 9, and used predictive modeling to estimate prenatal exposure levels. We examined associations of measured and estimated PBDE concentrations on children's attention and executive functioning at ages 9, 10½, and 12 years.ResultsGeometric means for prenatal and childhood ΣPBDE levels (sum of PBDE-47, -99, -100, -153) for the expanded CHAMACOS cohort were 26.3 and 63.2 ng/g lipid, respectively, and did not differ significantly between CHAM1 and CHAM2 families. We found consistent associations of prenatal exposure to PBDEs with poorer attention and executive function, measured with parent report and direct neuropsychological testing of the child. For example, using GEE models of repeated outcome measures at ages 9 and 12, a 10-fold increase in prenatal ΣPBDE was associated with poorer response consistency on the Conners' Continuous Performance Test II (β=2.9; 95% CI: 0.9, 4.8) and poorer working memory on the Behavioral Rating Inventory of Executive Function (β=2.5; 95% CI: 0.5, 4.4). Child age 9 ΣPBDE levels were associated with poorer parent-reported attention and executive function for girls but not boys.ConclusionsOur results suggest that the prefrontal cortex may be a potential target for PBDE exposure and add to a growing literature showing that these ubiquitous toxicants may adversely affect neurodevelopment.

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.

Study sample size in prospective birth cohorts of prenatal exposure to persistent organic pollutants (POPs) is limited by costs and logistics of follow-up. Increasing sample size at the time of health assessment would be beneficial if predictive tools could reliably back-extrapolate prenatal levels in newly enrolled children. We evaluated the performance of three approaches to back-extrapolate prenatal levels of p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (DDE) and four polybrominated diphenyl ether (PBDE) congeners from maternal and/or child levels 9 years after delivery: a pharmacokinetic model and predictive models using deletion/substitution/addition or Super Learner algorithms. Model performance was assessed using the root mean squared error (RMSE), R2, and slope and intercept of the back-extrapolated versus measured levels. Super Learner outperformed the other approaches with RMSEs of 0.10 to 0.31, R2s of 0.58 to 0.97, slopes of 0.42 to 0.93 and intercepts of 0.08 to 0.60. Typically, models performed better for p,p'-DDT/E than PBDE congeners. The pharmacokinetic model performed well when back-extrapolating prenatal levels from maternal levels for compounds with longer half-lives like p,p'-DDE and BDE-153. Results demonstrate the ability to reliably back-extrapolate prenatal POP levels from levels 9 years after delivery, with Super Learner performing best based on our fit criteria.

Manganese (Mn) is an essential nutrient but at high exposure levels is a neurotoxicant. There is no well-validated biomarker to assess perinatal Mn exposure. A total of 75 mother-child pairs provided blood, urine, and/or deciduous tooth samples. We analyzed Mn in dentin and enamel of shed teeth; maternal, cord, and child blood; and maternal and child urine and examined the interrelationships of Mn levels in all matrices. We observed higher Mn levels in prenatal than postnatal dentin (geometric mean (GM) = 0.51 vs 0.16 Mn:Ca, p < 0.001), maternal blood at delivery than 26 weeks gestation (GM = 20.7 vs. 14.6 μg/L, p = 0.001), and cord blood than child blood at 24 months of age (39.9 vs 25.0 μg/L, p = 0.005). There were no significant correlations between Mn in dentin and Mn concentrations in maternal blood or maternal or child urine. Levels of Mn in prenatal dentin, prenatal maternal blood, and 24 month urine were higher (p < 0.05) among mothers and children living with a farm worker. Prenatal Mn levels in dentin were correlated with Mn loadings and concentrations in prenatal house dust. Levels of Mn measured in tooth dentin constitute a promising biomarker of perinatal exposure.

BackgroundHouse dust is a major source of exposure to polybrominated diphenyl ethers (PBDEs), which are found at high levels in U.S. homes.MethodsWe studied 167 acute lymphoblastic leukemia (ALL) cases 0-7 years of age and 214 birth certificate controls matched on date of birth, sex, and race/ethnicity from the Northern California Childhood Leukemia Study. In 2001-2007, we sampled carpets in the room where the child spent the most time while awake; we used a high-volume small-surface sampler or we took dust from the home vacuum. We measured concentrations of 14 PBDE congeners including penta (28, 47, 99, 100, 153, 154), octa (183, 196, 197, 203), and decaBDEs (206-209). Odds ratios (ORs) were calculated using logistic regression, adjusting for demographics, income, year of dust collection, and sampling method.ResultsBDE-47, BDE-99, and BDE-209 were found at the highest concentrations (medians, 1,173, 1,579, and 938 ng/g, respectively). Comparing the highest to lowest quartile, we found no association with ALL for summed pentaBDEs (OR = 0.7; 95% CI: 0.4, 1.3), octaBDEs (OR = 1.3; 95% CI: 0.7, 2.3), or decaBDEs (OR = 1.0; 95% CI: 0.6, 1.8). Comparing homes in the highest concentration (nanograms per gram) tertile to those with no detections, we observed significantly increased ALL risk for BDE-196 (OR = 2.1; 95% CI: 1.1, 3.8), BDE-203 (OR = 2.0; 95% CI: 1.1, 3.6), BDE-206 (OR = 2.1; 95% CI: 1.1, 3.9), and BDE-207 (OR = 2.0; 95% CI: 1.03, 3.8).ConclusionWe found no association with ALL for common PBDEs, but we observed positive associations for specific octa and nonaBDEs. Additional studies with repeated sampling and biological measures would be informative.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant. Although experimental evidence suggests that TCDD alters thyroid hormone levels in rodents, human data are inconsistent. In 1976, a trichlorophenol plant exploded in Seveso, Italy. Women living in highly exposed areas were followed through the Seveso Women's Health Study. TCDD concentrations were measured in 1976 (n = 981) and 1996 (n = 260), and levels of total thyroxine, free thyroxine, free triiodothyronine, and thyroid-stimulating hormone were measured in 1996 (n = 909) and 2008 (n = 724). We used conditional multiple linear regression and marginal structural models with inverse-probability-of-treatment weights to evaluate associations and causal effects. TCDD concentration in 1976 was inversely associated with total thyroxine level in 1996 but not in 2008. Associations were stronger among women who had been exposed before menarche. Among these women, associations between total thyroxine and concurrent 1996 TCDD were slightly weaker than those with 1976 TCDD. A model including both 1976 and 1996 measurements strengthened the relationship between 1976 TCDD and total thyroxine but drove the association with 1996 TCDD to the null. TCDD exposure was not associated with levels of other thyroid hormones. TCDD exposure, particularly exposure before menarche, may have enduring impacts on women's total thyroxine levels. Initial exposure appears to be more influential than remaining body burden.

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.

Objectives To examine the relationship between residential proximity to agricultural fumigant use and respiratory symptoms and lung function in 7-year old children. Methods Participants 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 (FEV 1 ), forced vital capacity (FVC), and forced expiratory flow 25–75% (FEF 25–75 ) 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. Results There 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 FEV 1 and FEF 25–75 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 FEV 1 (β = 0.06 L/s; 95% CI: 0.00, 0.12) and higher FEF 25–75 (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 FEV 1 and prenatal proximity to methyl bromide use (p = .07) and we only observed higher FEV 1 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). Conclusions Residential 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. [ABSTRACT FROM AUTHOR]