Pesticide exposure, birth size, and gestational age in the ISA birth cohort, Costa Rica.

Purpose: To examine associations of prenatal biomarkers of pesticide exposure with birth size measures and length of gestation among newborns from the Infants' Environmental Health (ISA) birth cohort, Costa Rica. Methods: We included 386 singleton liveborn newborns with data on birth size measures, length of gestation, and maternal urinary biomarkers of chlorpyrifos, synthetic pyrethroids, mancozeb, pyrimethanil, and 2, 4-D during pregnancy. We associated biomarkers of exposure with birth outcomes using multivariate linear regression and generalized additive models. Results: Concentrations were highest for ethylene thiourea (ETU, metabolite of mancozeb), median = 3.40; p10-90 = 1.90-6.79 µg/L, followed by 3,5,6-trichloro-2-pyridinol (TCP, metabolite of chlorpyrifos) p50 = 1.76 p10-90 = 0.97-4.36 µg/L, and lowest for 2,4-D (p50 = 0.33 p10-90 = 0.18-1.07 µg/L). Among term newborns (≥37 weeks), higher prenatal TCP was associated with lower birth weight and smaller head circumference (e.g., ß per 10-fold-increase) during the second half of pregnancy = -129.6 (95% confidence interval [CI] = -255.8, -3.5) grams, and -0.61 (95% CI = -1.05, -0.17) centimeters, respectively. Also, among term newborns, prenatal 2,4-D was associated with lower birth weight (ß per 10-fold-increase = -125.1; 95% CI = -228.8, -21.5), smaller head circumference (ß = -0.41; 95% CI = -0.78, -0.03), and, during the second half of pregnancy, with shorter body length (ß = -0.58; 95% CI = -1.09, -0.07). Furthermore, ETU was nonlinearly associated with head circumference during the second half of pregnancy. Biomarkers of pyrethroids and pyrimethanil were not associated with birth size, and none of the biomarkers explained the length of gestation. Conclusions: Prenatal exposure to chlorpyrifos and 2,4-D, and, possibly, mancozeb/ETU, may impair fetal growth.

Per- and polyfluoroalkyl ether acids in well water and blood serum from private well users residing by a fluorochemical facility near Fayetteville, North Carolina.

BACKGROUND: A fluorochemical facility near Fayetteville, North Carolina, emitted per- and polyfluoroalkyl ether acids (PFEAs), a subgroup of per- and polyfluoroalkyl substances (PFAS), to air. OBJECTIVE: Analyze PFAS in private wells near the facility and in blood from well users to assess relationships between PFEA levels in water and serum. METHODS: In 2019, we recruited private well users into the GenX Exposure Study and collected well water and blood samples. We targeted 26 PFAS (11 PFEAs) in water and 27 PFAS (9 PFEAs) in serum using liquid chromatography-mass spectrometry. We used regression modeling to explore relationships between water and serum PFAS. For the only PFEA detected frequently in water and serum, Nafion byproduct 2, we used generalized estimating equation (GEE) models to assess well water exposure metrics and then adjusted for covariates that may influence Nafion byproduct 2 serum concentrations. RESULTS: We enrolled 153 participants ages 6 and older (median = 56 years) using 84 private wells. Most wells (74%) had ≥6 detectable PFEAs; median ∑PFEAs was 842 ng/L (interquartile range = 197-1760 ng/L). Low molecular weight PFEAs (PMPA, HFPO-DA [GenX], PEPA, PFO2HxA) were frequently detected in well water, had the highest median concentrations, but were not detectable in serum. Nafion byproduct 2 was detected in 73% of wells (median = 14 ng/L) and 56% of serum samples (median = 0.2 ng/mL). Cumulative dose (well concentration × duration at address) was positively associated with Nafion byproduct 2 serum levels and explained the most variability (10%). In the adjusted model, cumulative dose was associated with higher Nafion byproduct 2 serum levels while time outside the home was associated with lower levels. IMPACT: PFAS are a large class of synthetic, fluorinated chemicals. Fluorochemical facilities are important sources of environmental PFAS contamination globally. The fluorochemical industry is producing derivatives of perfluoroalkyl acids, including per- and polyfluoroalkyl ether acids (PFEAs). PFEAs have been detected in various environmental samples but information on PFEA-exposed populations is limited. While serum biomonitoring is often used for PFAS exposure assessment, serum biomarkers were not good measures of long-term exposure to low molecular weight PFEAs in a private well community. Environmental measurements and other approaches besides serum monitoring will be needed to better characterize PFEA exposure.

Estimation of the Half-Lives of Recently Detected Per- and Polyfluorinated Alkyl Ethers in an Exposed Community.

To estimate half-lives for novel fluoroethers, the GenX Exposure Study obtained two serum measurements for per- and polyfluoroalkyl substances (PFAS) for 44 participants of age 12-86 years from North Carolina, collected 5 and 11 months after fluoroether discharges into the drinking water source were controlled. The estimated half-lives for these compounds were 127 days (95% confidence interval (95% CI) = 86, 243 days) for perfluorotetraoxadecanoic acid (PFO4DA), 296 days for Nafion byproduct 2 (95% CI = 176, 924 days), and 379 days (95% CI = 199, 3870 days) for perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA). Using these estimates and the literature values, a model was built that predicted PFAS half-lives using structural properties. Three chemical properties predicted 55% of the variance of PFAS half-lives based on 15 PFAS. A model with only molecular weight predicted 69% of the variance. Some properties can predict the half-lives of PFAS, but a deeper understanding is needed. These fluoroethers had biological half-lives longer than published half-lives for PFHxA and PFHpA (30-60 days) but shorter than those for PFOA and PFOS (800-1200 days). These are the first and possibly only estimates of human elimination half-lives of these fluoroethers.

Factors associated with per- and polyfluoroalkyl substances (PFAS) serum concentrations in residents of New Hanover County, North Carolina: The GenX exposure study.

In 2017, people living in New Hanover County, North Carolina, learned that for ∼40 years they were unknowingly exposed to per- and polyfluoroalkyl substances (PFAS) through drinking water sourced by the Cape Fear River. Using data from the GenX Exposure Study, which measured serum PFAS levels in county residents, we aimed to understand questionnaire-measured factors associated with serum PFAS levels. Because most residents were served by the same municipal water source, we focused on surrogate factors of drinking water exposure that may contribute to variability in PFAS levels. Our analysis included 335 participants aged 6 and older. We included seven chemicals detected in ≥75% of the study population: four well-studied perfluoroalkyl acids (PFOA, PFOS, PFNA, PFHxS) and three understudied fluoroethers (Nafion byproduct 2, PFO4DA, PFO5DoA). For each PFAS, we evaluated associations of variables with serum PFAS levels adjusting for key demographic characteristics. Additionally, we developed predictive models for each PFAS. We used years of residence in the lower Cape Fear Region as a surrogate for water consumption. Duration of drinking water exposure was associated with higher serum levels of all seven PFAS. Drinking municipal water treated by home filters or other sources of water (non-city) were associated with lower PFAS concentrations for all seven PFAS compared to drinking municipal water without additional filtration. Males had higher levels of well-studied PFAS, but there was no difference for fluoroethers. For six PFAS, the predictive models explained ≥30% of the variance in serum PFAS levels. While some factors were significantly associated with levels of individual PFAS, their relative importance to overall prediction was low, such as microwave popcorn consumption. Consistently, water consumption-related variables were important for both the association and predictive investigations. These analyses provide additional evidence that drinking water is a primary source for serum PFAS concentrations among New Hanover County residents.

Detection of the fungicide transformation product 4-hydroxychlorothalonil in serum of pregnant women from Sweden and Costa Rica.

BACKGROUND: 4-hydroxychlorothalonil (HCT, R182281), a transformation product of the fungicide chlorothalonil, was recently identified in human serum and breast milk. There are indications that HCT may be more toxic and environmentally persistent than chlorothalonil. OBJECTIVE: Our aim was to investigate serum concentrations of HCT in pregnant women in Sweden and Costa Rica. METHODS: We developed a quantitative analytical method for HCT using liquid chromatography tandem mass spectrometry. We measured HCT in 1808 serum samples from pregnant women from the general population in Sweden (1997-2015) and in 632 samples from 393 pregnant women from an agricultural population in Costa Rica (2010-2011). In Swedish samples, we assessed time trends and investigated seasonality. In the Costa Rican samples, we evaluated variability between and within women and explanatory variables of HCT concentrations. RESULTS: HCT was detected in all serum samples, and the limit of detection was 0.1 µg/L. The median HCT concentration in the Swedish samples was 4.1 µg/L (interquartile range [IQR] of 2.9 - 5.8 µg/L), and 3.9 times higher in the Costa Rican samples (median: 16.1 µg/L; IQR: 10.6 - 25.0 µg/L). We found clear seasonal variation with higher concentrations in the first half of each year among Swedish women. In the Costa Rican study, women working in agriculture and living near banana plantations had higher HCT concentrations, whilst higher parity and having a partner working in agriculture were associated with decreased HCT, and no clear seasonal pattern was observed. IMPACT STATEMENT: For the first time, this study quantifies human exposure to the fungicide chlorothalonil and/or its transformation product 4-hydroxychlorothalonil (HCT, R182281) and finds higher serum concentrations in women from a tropical agricultural setting as compared with women from the general population in Sweden.

A cross-sectional analysis of medical conditions and environmental factors associated with fractional exhaled nitric oxide (FeNO) in women and children from the ISA birth cohort, Costa Rica.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation. Elevated FeNO has been associated with environmental exposures, however, studies from tropical countries are limited. Using data from the Infants' Environmental Health Study (ISA) birth cohort, we evaluated medical conditions and environmental exposures' association with elevated FeNO. METHODS: We performed a cross-sectional analysis of 277 women and 293 8-year old children who participated in the 8-year post-partum visit in 2019. We measured FeNO and collected information on medical conditions and environmental exposures including smoke from waste burning, work in banana plantations, and home pesticide use. We defined elevated FeNO as >25 ppb for women and >20 ppb for children. To evaluate factors associated with elevated FeNO, we used logistic regression models adjusted for obesity in women and unadjusted in children. RESULTS: Overall elevated FeNO was common (20% of women, 13% of children). Rhinitis diagnosis was significantly associated with elevated FeNO in both women (odds ratio (OR): 3.67 95% Confidence Interval (CI): 1.81,7.35) and children (OR: 8.18 95%CI: 3.15, 21.22); wheeze was associated with elevated FeNO in women (OR: 4.50 95% CI: 2.25, 8.99). Environmental exposures were associated with elevated FeNO, but not significantly. Waste burning was associated with elevated FeNO in both women (OR: 1.58 95%CI 0.68, 4.15) and children (OR: 2.49 95%CI:0.82, 10.79). Para-occupational pesticide exposures were associated with elevated FeNO in women and children. For women, having a partner working in agriculture was associated with elevated FeNO (OR: 1.61 95%CI:0.77, 3.58) and for children, maternal work in agriculture was associated with elevated FeNO. (OR 2.08 95%CI 0.86, 4.67) CONCLUSION: Rhinitis and wheeze were associated with elevated FeNO in this rural, agricultural population. Smoke from waste burning as well as para-occupational pesticide exposure may contribute to elevated FeNO in rural communities.

PFAS levels in paired drinking water and serum samples collected from an exposed community in Central North Carolina.

The community of Pittsboro, North Carolina has been documented to have extensive per- and polyfluoroalkyl substances (PFAS) contamination in its drinking water source, the Haw River, over the last 20 years. However, a detailed exposure assessment has never been conducted. In this study, we sought to characterize the PFAS in paired drinking water and blood samples collected from a small cohort of Pittsboro residents (n = 49). Drinking water and serum from blood were collected from adults in late 2019 and early 2020 and were analyzed to quantify 13 PFAS analytes. In order to explore potential health effects of PFAS exposure, serum was further analyzed for clinical chemistry endpoints that could be potentially associated with PFAS (e.g., cholesterol, liver function biomarkers). PFAS were detected in all serum samples, and some serum PFAS concentrations were 2 to 4 times higher than the median U.S. serum concentrations reported in the general U.S. population. Of the 13 PFAS in drinking water, perfluorohexanoic acid (PFHxA) was measured at the highest concentrations. PFAS levels in the current drinking water were not associated with current serum PFAS, suggesting that the serum PFAS in this cohort likely reflects historical exposure to PFAS with long half-lives (e.g., PFOS and PFOA). However, one PFAS with a shorter half-life (PFHxA) was observed to increase in serum, reflecting the temporal variability of PFHxA in river and drinking water. Statistical analyses indicated that serum PFOA and PFHxS were positively associated with total cholesterol and non-HDL cholesterol. No serum PFAS was associated with HDL cholesterol. In the clinical chemistry analyses, serum PFHxA was found to be negatively associated with electrolytes and liver enzymes (e.g., AST and ALT), and serum PFOS was found to be positively associated with the ratio of blood urea nitrogen to creatinine (BUN:Cre). While small in size, this study revealed extensive exposure to PFAS in Pittsboro and associations with clinical blood markers, suggesting potential health impacts in community residents.

Timing and Trends for Municipal Wastewater, Lab-Confirmed Case, and Syndromic Case Surveillance of COVID-19 in Raleigh, North Carolina.

Objectives. To compare 4 COVID-19 surveillance metrics in a major metropolitan area. Methods. We analyzed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater influent and primary solids in Raleigh, North Carolina, from April 10 through December 13, 2020. We compared wastewater results with lab-confirmed COVID-19 cases and syndromic COVID-like illness (CLI) cases to answer 3 questions: (1) Did they correlate? (2) What was the temporal alignment of the different surveillance systems? (3) Did periods of significant change (i.e., trends) align? Results. In the Raleigh sewershed, wastewater influent, wastewater primary solids, lab-confirmed cases, and CLI were strongly or moderately correlated. Trends in lab-confirmed cases and wastewater influent were observed earlier, followed by CLI and, lastly, wastewater primary solids. All 4 metrics showed sustained increases in COVID-19 in June, July, and November 2020 and sustained decreases in August and September 2020. Conclusions. In a major metropolitan area in 2020, the timing of and trends in municipal wastewater, lab-confirmed case, and syndromic case surveillance of COVID-19 were in general agreement. Public Health Implications. Our results provide evidence for investment in SARS-CoV-2 wastewater and CLI surveillance to complement information provided through lab-confirmed cases. (Am J Public Health. 2023;113(1):79-88. https://doi.org/10.2105/AJPH.2022.307108).

Source apportionment of serum PFASs in two highly exposed communities.

Per- and polyfluoroalkyl substances (PFASs) are synthetic chemicals that are ubiquitous in environmental and biological systems, including human serum. PFASs are used in many products and industrial processes and are tied to numerous health effects. Due to multiple sources and exposure pathways, methods are needed to identify PFAS sources in communities to develop targeted interventions. We assessed effectiveness of three source apportionment methods (UNMIX, positive matrix factorization [PMF], and principal component analysis - multiple linear regression [PCA-MLR]) for identifying contributors to human serum PFAS concentrations in two highly exposed populations in Colorado and North Carolina where drinking water was contaminated via upstream sources, including a Space Force base and a fluorochemical manufacturing plant. UNMIX and PMF models extracted three to four potential PFAS exposure sources in the Colorado and North Carolina cohorts while PCA-MLR classified two in each cohort. No sources were characterized in NHANES (National Health and Nutrition Examination Study). Results suggest that these three methods can successfully identify sources in highly exposed populations. Future PFAS exposure research should focus on analyzing serum for an expanded PFAS panel, identifying cohorts with other distinct point source exposures, and combining biological and environmental data to better understand source apportionment results in the context of PFAS toxicokinetic behavior.

Drinking Water-Associated PFAS and Fluoroethers and Lipid Outcomes in the GenX Exposure Study.

BACKGROUND: Residents of Wilmington, North, Carolina, were exposed to drinking water contaminated by fluoroethers and legacy per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), with fluoroether exposure occurring from 1980 to 2017. PFOA and PFOS have previously been associated with metabolic dysfunction; however, few prior studies have examined associations between other PFAS and lipid levels. OBJECTIVES: We measured the association between serum fluoroether and legacy PFAS levels and various cholesterol outcomes. METHODS: Participants in the GenX Exposure Study contributed nonfasting blood samples in November 2017 and May 2018 that were analyzed for 20 PFAS (10 legacy, 10 fluoroethers) and serum lipids [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] and calculated non-HDL cholesterol. We estimated covariate-adjusted associations between quartiles of exposure to each of the PFAS measures (as well as the summed concentrations of legacy PFAS, fluoroethers, and all 10 targeted PFAS) and lipid outcomes by fitting inverse probability of treatment weighted linear regressions. RESULTS: In this cross-sectional study of 326 participants (age range 6-86 y), eight PFAS were detected in >50% of the population. For PFOS and perfluorononanoic acid (PFNA), non-HDL cholesterol was approximately 5mg/dL higher per exposure quartile increase: [PFOS: 4.89; 95% confidence interval (CI): 0.10, 9.68 and PFNA: 5.25 (95% CI: 0.39, 10.1)], whereas total cholesterol was approximately 6mg/dL higher per quartile [PFOS: 5.71 (95% CI: 0.38, 11.0), PFNA: 5.92 (95% CI: 0.19, 11.7)]. In age-stratified analyses, associations were strongest among the oldest participants. Two fluoroethers were associated with higher HDL, whereas other fluoroether compounds were not associated with serum lipid levels. DISCUSSION: PFNA and PFOS were associated with higher levels of total and non-HDL cholesterol, with associations larger in magnitude among older adults. In the presence of these legacy PFAS, fluoroethers appeared to be associated with HDL but not non-HDL lipid measures. https://doi.org/10.1289/EHP11033.

Allergic and non-allergic wheeze among farm women in the Agricultural Health Study (2005-2010).

BACKGROUND: Farms represent complex environments for respiratory exposures including hays, grains and pesticides. Little is known about the impact of these exposures on women's respiratory health. We evaluated the association of farm exposures with allergic and non-allergic wheeze among women in the Agricultural Health Study, a study of farmers and their spouses based in Iowa and North Carolina. METHODS: We used self-reported data (2005-2010) on current use (≤12 months) of 15 pesticides (selected based on frequency of use) and occupational farm activities from 20 164 women. We defined allergic wheeze as reporting wheeze and doctor-diagnosed hay fever (7%) and non-allergic wheeze as wheeze but not hay fever (8%) in the past 12 months. Using polytomous logistic regression, we evaluated associations of wheeze subtypes with pesticides and other farm exposures (eg, raising farm animals) using no wheeze/hay fever as the referent, adjusting for age, body mass index, state, current asthma, glyphosate use and smoking. RESULTS: Current use of any pesticide, reported by 7% of women, was associated with both allergic (OR: 1.36, 95% CI: 1.10 to 1.67) and non-allergic (OR: 1.25, 95% CI: 1.04 to 1.51) wheeze. Four pesticides were associated with at least one wheeze subtype: glyphosate, with both wheeze subtypes; diazinon and fly spray with only allergic wheeze; carbaryl with only non-allergic wheeze. Working weekly with mouldy hay was associated with allergic (OR: 1.88, 95% CI: 1.26 to 2.80) and non-allergic wheeze (OR: 1.69, 95% CI: 1.18 to 2.42). CONCLUSION: Use of specific pesticides and certain farm activities may contribute to wheeze among farm women.

Pyrimethanil and chlorpyrifos air concentrations and pregnant women's urinary metabolites in the Infants' Environmental Health Study (ISA), Costa Rica.

BACKGROUND: Only few studies have compared environmental pesticide air concentrations with specific urinary metabolites to evaluate pathways of exposure. Therefore, we compared pyrimethanil and chlorpyrifos concentrations in air with urinary 4-hydroxypyrimethanil (OHP, metabolite of pyrimethanil) and 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) among pregnant women from the Infant's Environmental Health Study (ISA) in Matina County, Costa Rica. METHODS: During pregnancy, we obtained repeat urinary samples from 448 women enrolled in the ISA study. We extrapolated pyrimethanil and chlorpyrifos concentrations measured with passive air samplers (PAS) (n = 48, from 12 schools), across space and time using a Bayesian spatiotemporal model. We subsequently compared these concentrationswith urinary OHP and TCPy in 915 samples from 448 women, usingseparatemixed models andconsidering several covariables. RESULTS: A 10% increase in air pyrimethanil (ng/m3) was associated with a 5.7% (95% confidence interval (CI 4.6, 6.8) increase in OHP (µg/L). Women living further from banana plantations had lower OHP: -0.7% (95% CI -1.2, -0.3) for each 10% increase in distance (meters) as well as women who ate rice and beans ≥15 times a week -23% (95% CI -38, -4). In addition, each 1 ng/m3 increase in chlorpyrifos in air was associated with a 1.5% (95% CI 0.2, 2.8) increase in TCPy (µg/L), and women working in agriculture tended to have increased TCPy (21%, 95% CI -2, 49). CONCLUSION: The Bayesian spatiotemporal models were useful to estimate pyrimethanil and chlorpyrifos air concentrations across space and time. Our results suggest inhalation of pyrimethanil and chlorpyrifos is a pathway of environmental exposure. PAS seems a useful technique to monitor environmental current-use pesticide exposures. For future studies, we recommend increasing the number of locations of environmental air measurements, obtaining all air and urine measurements during the same month, and, ideally, including dermal exposure estimates as well.

Environmental exposures contribute to respiratory and allergic symptoms among women living in the banana growing regions of Costa Rica.

OBJECTIVES: This research evaluates whether environmental exposures (pesticides and smoke) influence respiratory and allergic outcomes in women living in a tropical, agricultural environment. METHODS: We used data from 266 mothers from the Infants' Environmental Health cohort study in Costa Rica. We evaluated environmental exposures in women by measuring seven pesticide and two polycyclic aromatic hydrocarbons metabolites in urine samples. We defined 'high exposure' as having a metabolite value in the top 75th percentile. We collected survey data on respiratory and allergic outcomes in mothers as well as on pesticides and other environmental exposures. Using logistic regression models adjusted for obesity, we assessed the associations of pesticide exposure with multiple outcomes (wheeze, doctor-diagnosed asthma, high (≥2) asthma score based on symptoms, rhinitis, eczema and itchy rash). RESULTS: Current pesticide use in the home was positively associated with diagnosed asthma (OR=1.99 (95% CI=1.05 to 3.87)). High urinary levels of 5-hydroxythiabendazole (thiabendazole metabolite) and living in a neighbourhood with frequent smoke from waste burning were associated with a high asthma score (OR=1.84 (95%CI=1.05 to 3.25) and OR=2.31 (95%CI=1.11 to 5.16), respectively). Women who worked in agriculture had a significantly lower prevalence of rhinitis (0.19 (0.01 to 0.93)), but were more likely to report eczema (OR=2.54 (95%CI=1.33 to 4.89)) and an itchy rash (OR=3.17 (95%CI=1.24 to 7.73)). CONCLUSIONS: While limited by sample size, these findings suggest that environmental exposure to both pesticides and smoke may impact respiratory and skin-related allergic outcomes in women.

Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica.

BACKGROUND: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. OBJECTIVES: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). METHODS: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (µg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (µg/g) and blood (MnB) (µg/L), and blood lead (PbB) (µg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. RESULTS: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: ß = -0.79 (95%CI = -1.51, -0.08) and ß = -0.29 (95%CI = -0.62, -0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (ß = 0.04 (95%CI = 0.00, 0.07 per 1 µg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. DISCUSSION: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.

Gestational Phthalate Exposure and Preschool Attention Deficit Hyperactivity Disorder in Norway.

Prenatal phthalate exposure has been linked to altered neurobehavioral development in both animal models and epidemiologic studies, but whether or not these associations translate to increased risk of neurodevelopmental disorders is unclear. We used a nested case-cohort study design to assess whether maternal urinary concentrations of 12 phthalate metabolites at 17 weeks gestation were associated with criteria for Attention Deficit Hyperactivity Disorder (ADHD) classified among 3-year-old children in the Norwegian Mother, Father and Child Cohort Study (MoBa). Between 2007 and 2011, 260 children in this substudy were classified with ADHD using a standardized, on-site clinical assessment; they were compared with 549 population-based controls. We modeled phthalate levels both linearly and by quintiles in logistic regression models adjusted for relevant covariates and tested for interaction by child sex. Children of mothers in the highest quintile of di-iso-nonyl phthalate (∑DiNP) metabolite levels had 1.70 times the odds of being classified with ADHD compared with those in the lowest quintile (95% confidence interval [CI] = 1.03 to 2.82). In linear models, there was a trend with the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP); each natural log-unit increase in concentration was associated with 1.22 times the odds of ADHD (95% CI = 0.99 to 1.52). In boys, but not girls, mono-n-butyl phthalate exposure was associated with increased odds of ADHD (odds ratio [OR] 1.42; 95% CI = 1.07 to 1.88). Additional adjustment for correlated phthalate metabolites attenuated estimates. These results suggest gestational phthalate exposure may impact the behavior of children as young as 3 years.