Association of prenatal chlorpyrifos exposure with sexually dimorphic differences in anogenital distance among Thai farmworker children.

Organophosphate (OP) insecticides are some of the most abundantly used insecticides, and prenatal exposures have been linked to adverse maternal and child health outcomes. Anogenital distance (AGD) has emerged as an early marker of androgen activity, and later reproductive outcomes, that is sensitive to alteration by environmental chemicals. Here, we examined associations between prenatal exposure to chlorpyrifos, an OP insecticide, with AGD. Pregnant farmworkers were enrolled in the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE; N = 104) between 2017 and 2019 in Northern Thailand. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos, were measured in composited urine samples obtained from each trimester of pregnancy. AGD was measured at 12 months of age. Sex-specific adjusted linear regression models were used to examine associations between average and trimester-specific TCPy levels and AGD. In adjusted models for females and males, increasing TCPy was consistently associated with a modest, non-significant reduction in AGD. Across both strata of sex, associations were greatest in magnitude for trimester 3 (females: ß = -2.17, 95 % confidence interval (CI) = -4.99, 0.66; males: ß = -3.02, 95 % CI = -6.39, 0.35). In the SAWASDEE study, prenatal chlorpyrifos exposure was not strongly associated with AGD at 12 months of age.

Association between a Mixture of Per- and Polyfluoroalkyl Substances (PFAS) and Inflammatory Biomarkers in the Atlanta African American Maternal-Child Cohort.

Per- and polyfluoroalkyl substances (PFAS) have been identified as environmental contributors to adverse birth outcomes. One potential mechanistic pathway could be through PFAS-related inflammation and cytokine production. Here, we examined associations between a PFAS mixture and inflammatory biomarkers during early and late pregnancy from participants enrolled in the Atlanta African American Maternal-Child Cohort (N = 425). Serum concentrations of multiple PFAS were detected in >90% samples at 8-14 weeks gestation. Serum concentrations of interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at up to two time points (8-14 weeks and 24-30 weeks gestation). The effect of the PFAS mixture on each inflammatory biomarker was examined using quantile g-computation, Bayesian kernel machine regression (BKMR), Bayesian Weighted Sums (BWS), and weighted quantile sum (WQS) regression. Across all models, the PFAS mixture was associated with increased IFN-γ, IL-10, and TNF-α at both time points, with the strongest effects being observed at 24-30 weeks. Using quantile g-computation, increasing concentrations of a PFAS mixture were associated with a 29% (95% confidence interval = 18.0%, 40.7%) increase in TNF-α at 24-30 weeks. Similarly, using BWS, the PFAS mixture was associated with increased TNF-α at 24-30 weeks (summed effect = 0.29, 95% highest posterior density = 0.17, 0.41). The PFAS mixture was also positively associated with TNF-α at 24-30 weeks using BKMR [75th vs 50th percentile: 17.1% (95% credible interval = 7.7%, 27.4%)]. Meanwhile, PFOS was consistently the main drivers of overall mixture effect across four methods. Our findings indicated an increase in prenatal PFAS exposure is associated with an increase in multiple pro-inflammatory cytokines, potentially contributing to adverse pregnancy outcomes.

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort.

Prenatal exposure to single chemicals belonging to the per- and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in the mother, fetus, and placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed to multiple PFAS, the potential joint effects of PFAS on the metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics to identify metabolites and metabolic pathways perturbed by exposure to a PFAS mixture during pregnancy. Targeted assessment of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS), along with untargeted metabolomics profiling, were conducted on nonfasting serum samples collected from pregnant African Americans at 6-17 weeks gestation. We estimated the overall mixture effect and partial effects using quantile g-computation and single-chemical effects using linear regression. All models were adjusted for maternal age, education, parity, early pregnancy body mass index, substance use, and gestational weeks at sample collection. Our analytic sample included 268 participants and was socioeconomically diverse, with the majority receiving public health insurance (78%). We observed 13.3% of the detected metabolic features were associated with the PFAS mixture (n = 1705, p < 0.05), which was more than any of the single PFAS chemicals. There was a consistent association with metabolic pathways indicative of systemic inflammation and oxidative stress (e.g., glutathione, histidine, leukotriene, linoleic acid, prostaglandins, and vitamins A, C, D, and E metabolism) across all metabolome-wide association studies. Twenty-six metabolites were validated against authenticated compounds and associated with the PFAS mixture (p < 0.05). Based on quantile g-computation weights, PFNA contributed the most to the overall mixture effect for γ-aminobutyric acid (GABA), tyrosine, and uracil. In one of the first studies of its kind, we demonstrate the feasibility and utility of using methods designed for exposure mixtures in conjunction with metabolomics to assess the potential joint effects of multiple PFAS chemicals on the human metabolome. We identified more pronounced metabolic perturbations associated with the PFAS mixture than for single PFAS chemicals. Taken together, our findings illustrate the potential for integrating environmental mixture analyses and high-throughput metabolomics to elucidate the molecular mechanisms underlying human health.

Exposure to phthalate metabolites, bisphenol A, and psychosocial stress mixtures and pregnancy outcomes in the Atlanta African American maternal-child cohort.

BACKGROUND: Consumer products are common sources of exposure for phthalates and bisphenol A (BPA), which disrupt the endocrine system. Psychosocial stressors have been shown to amplify the toxic effects of endocrine disruptors but, information is limited among African Americans (AAs), who experience the highest rates of adverse pregnancy outcomes and are often exposed to the highest levels of chemical and non-chemical stressors. We examined the association between an exposure mixture of phthalate metabolites, BPA, and psychosocial stressors with gestational age at delivery and birthweight for gestational age z-scores in pregnant AA women. STUDY DESIGN: Participants were enrolled in the Atlanta African American Maternal-Child Cohort (N = 247). Concentrations of eight phthalate metabolites and BPA were measured in urine samples collected at up to two timepoints during pregnancy (8-14 weeks gestation and 20-32 weeks gestation) and were averaged. Psychosocial stressors were measured using self-reported, validated questionnaires that assessed experiences of discrimination, gendered racial stress, depression, and anxiety. Linear regression was used to estimate individual associations between stress exposures (chemical and psychosocial) and birth outcomes. We leveraged quantile g-computation was used to examine joint effects of chemical and stress exposures on gestational age at delivery (in weeks) and birthweight for gestational age z-scores. RESULTS: A simultaneous increase in all phthalate metabolites and BPA was associated with a moderate reduction in birthweight z-scores (mean change per quartile increase = -0.22, 95% CI = -0.45, 0.0). The association between our exposure mixture and birthweight z-scores became stronger when including psychosocial stressors as additional exposures (mean change per quantile increase = -0.35, 95% CI = -0.61, -0.08). Overall, we found null associations between exposure to chemical and non-chemical stressors with gestational age at delivery. CONCLUSIONS: In a prospective cohort of AA mother-newborn dyads, we observed that increased prenatal exposure to phthalates, BPA, and psychosocial stressors were associated with adverse pregnancy outcomes.

Associations between prenatal organophosphate pesticide exposure and placental gene networks.

BACKGROUND: Exposure to organophosphate (OP) pesticides during pregnancy has been linked to deficiencies of neurobehavioral development in childhood; however, the molecular mechanisms underlying this association remain elusive. The placenta plays a crucial role in protecting the fetus from environmental insults and safeguarding proper fetal development including neurodevelopment. The aim of our study is to evaluate changes in the placental transcriptome associated with prenatal OP exposure. METHODS: Pregnant farm workers from two agricultural districts in northern Thailand were recruited for the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. For 254 participants, we measured maternal urinary concentrations of six nonspecific dialkyl phosphates (DAP) metabolites in early, middle, and late pregnancy. In parallel, we profiled the term placental transcriptome from the same participants using RNA-Sequencing and performed Weighted Gene co-expression Network Analysis (WGCNA). Generalized linear regression modeling was used to examine associations of urinary OP metabolites and placental co-expression module eigenvalues. RESULTS: We identified 21 gene co-expression modules in the placenta. From the six DAP metabolites assayed, diethylphosphate (DEP) and diethylthiophosphate (DETP) were detected in more than 70% of the urine samples. Significant associations between DEP at multiple time points and two specific placental gene modules were observed. The 'black' module, enriched in genes involved in epithelial-to-mesenchymal transition (EMT) and hypoxia, was negatively associated with DEP in early (p = 0.034), and late pregnancies (p = 0.016). The 'lightgreen' module, enriched in genes involved in myogenesis and EMT, was negatively associated with DEP in late pregnancy (p = 0.010). We observed 2 hub genes (CELSR1 and PYCR1) of the 'black' module to be negatively associated with DEP in early and late pregnancies. CONCLUSIONS: Our results suggest that prenatal OP exposure may disrupt placental gene networks in a time-dependent manner. Such transcriptomic effects may lead to down-stream changes in placental function that ultimately affect the developing fetus.

Metabolome-wide association study of the relationship between chlorpyrifos exposure and first trimester serum metabolite levels in pregnant Thai farmworkers.

INTRODUCTION: Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides. METHODS: This study included 50 participants from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels. RESULTS: In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 µg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide. DISCUSSION: The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.

Temporal Trends of Phenol, Paraben, and Triclocarban Exposure in California Pregnant Women during 2007-2014.

Little is known about temporal trends of pregnant women's exposures to environmental phenols and parabens. We quantified four phenols [bisphenol A (BPA), bisphenol F, bisphenol S, and triclosan), four parabens [butyl paraben, ethyl paraben (ETPB), methyl paraben (MEPB), and propyl paraben (PRPB)], and triclocarban in 760 urine samples collected during 2007-2014 from 218 California pregnant women participating in a high-familial risk autism spectrum disorder cohort. We applied multiple regression to compute least square geometric means of urinary concentrations and computed average annual percent changes. We compared our urinary concentrations with those of other study populations to examine geographic variations in pregnant women's exposure to these target compounds. Urinary concentrations of BPA, MEPB, ETPB, and PRPB in this study population decreased over the study period [percent change per year (95% confidence interval): -5.7% (-8.2%, -3.2%); -13.0% (-18.1%, -7.7%); -5.5% (-11.0%, 0.3%); and -13.3% (-18.3%, -8.1%), respectively] and were consistently lower than those in pregnant women in other U.S. regions during the same study period. In recent years, certain phenols and parabens with known adverse health effects are being regulated or replaced with alternatives, which explains decreased body burdens observed in this study population. Either the national regulations or the advocacy campaigns in California may have influenced exposures or consumer product choices.

Variability of Urinary Concentrations of Phenols, Parabens, and Triclocarban during Pregnancy in First Morning Voids and Pooled Samples.

Urinary concentrations of phenols, parabens, and triclocarban have been extensively used as biomarkers of exposure. However, because these compounds are quickly metabolized and excreted in urine, characterizing participants' long-term average exposure from a few spot samples is challenging. To examine the variability of urinary concentrations of these compounds during pregnancy, we quantified four phenols, four parabens, and triclocarban in 357 first morning voids (FMVs) and 203 pooled samples collected during the second and third trimesters of 173 pregnancies. We computed intraclass correlation coefficients (ICCs) by the sample type (FMV and pool) across two trimesters and by the number of composite samples in pools, ranging from 2 to 4, within the same trimester. Among the three compounds detected in more than 50% of the samples, the ICCs across two trimesters were higher in pools (0.29-0.68) than in FMVs (0.17-0.52) and the highest ICC within the same trimester was observed when pooling either two or three composites. Methyl paraben and propyl paraben primarily exposed via cosmetic use had approximately 2-3 times higher ICCs than bisphenol A primarily exposed via diet. Our findings support that within-subject pooling of biospecimens can increase the reproducibility of pregnant women's exposure to these compounds and thus could potentially minimize exposure misclassification.

Serum per- and polyfluoroalkyl substance (PFAS) concentrations and predictors of exposure among pregnant African American women in the Atlanta area, Georgia.

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with adverse health outcomes, especially when exposure occurs within sensitive time windows such as the pre- and post-natal periods and early childhood. However, few studies have focused on PFAS exposure distribution and predictors in pregnant women, especially among African American women. We quantified serum concentrations of the four most common PFAS collected in all 453 participants and an additional 10 PFAS in 356 participants who were pregnant African American women enrolled from 2014 to 2018 in Atlanta, Georgia, and investigated the sociodemographic predictors of exposure. Additional home environment and behavior predictors were also examined in 130 participants. Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in >95% of the samples with PFOS having the highest concentrations (geometric mean (GM) 2.03 ng/mL). N-Methyl perfluorooctane sulfonamido acetic acid (NMeFOSAA), perfluoropentanoic acid (PFPeA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were found in 40-50% of the samples, whereas the detection frequencies for the other six PFAS were below 15%. When compared to National Health and Nutrition Examination Survey (NHANES) participants matching sex, race, and age with this study, our results showed similar concentrations of most PFAS, but higher concentrations of PFHxS (GM 0.99 ng/mL in this study; 0.63 and 0.4 ng/mL in NHANES, 2014-2015 and 2016-2017 cycles). A decline in concentrations over the study period was found for most PFAS but not PFPeA. In adjusted models, education, sampling year, parity, BMI, tobacco and marijuana use, age of house, drinking water source, and cosmetic use were significantly associated with serum PFAS concentrations. Our study reports the first PFAS exposure data among pregnant African American women in the Atlanta area, Georgia. The identified predictors will facilitate the setting of research priorities and enable development of exposure mitigation strategies.

Associations of single and multiple per- and polyfluoroalkyl substance (PFAS) exposure with vitamin D biomarkers in African American women during pregnancy.

Vitamin D has been linked to various physiological functions in pregnant women and their fetuses. Previous studies have suggested that some per- and polyfluoroalkyl substances (PFAS) may alter serum vitamin D concentrations. However, no study has investigated the relationship between PFAS and vitamin D in pregnant women. This study aims to evaluate the associations of serum PFAS with serum total and free 25-hydroxyvitamin D (25(OH)D) during pregnancy in a cohort of African American women in Atlanta, GA. Blood samples from 442 participants were collected in early pregnancy (8-14 weeks of gestation) for PFAS and 25(OH)D measurements, and additional samples were collected in late pregnancy (24-30 weeks) for the second 25(OH)D measurements. We fit multivariable linear regressions and weighted quantile sum (WQS) regressions to estimate the associations of individual PFAS and their mixtures with 25(OH)D concentrations. We found mostly positive associations of total 25(OH)D with PFHxS (perfluorohexane sulfonic acid), PFOS (perfluorooctane sulfonic acid), PFDA (perfluorodecanoic acid), and NMeFOSAA (N-methyl perfluorooctane sulfonamido acetic acid), and negative associations with PFPeA (perfluoropentanoic acid). For free 25(OH)D, positive associations were observed with PFHxS, PFOS, PFOA (perfluorooctanoic acid), and PFDA, and a negative association with PFPeA among the women with male fetuses in the models using 25(OH)D measured in late pregnancy. In mixture models, a quartile increase in WQS index was associated with 2.88 ng/mL (95%CI 1.14-4.59) and 5.68 ng/mL (95%CI 3.31-8.04) increases in total 25(OH)D measured in the early and late pregnancy, respectively. NMeFOSAA, PFDA, and PFOS contributed the most to the overall effects among the eight PFAS. No association was found between free 25(OH)D and the PFAS mixture. These results suggest that PFAS may affect vitamin D biomarker concentrations in pregnant African American women, and some of the associations were modified by fetal sex.

Biofumigation activities of volatile compounds from two Trichoderma afroharzianum strains against Fusarium infections in fresh chilies.

BACKGROUND: Two Fusarium fungi, F. oxysporum and F. proliferatum, have been recognized as major pathogenic fungi that cause postharvest decay of chili fruits. Ozone and some toxic chemicals are used to control pathogenic infections, leading to longer storage lives of agricultural commodities. However, these chemicals may pose some risks to the applicators and the environment. Therefore, alternative, easy-to-use fumigants for effective control of Fusarium infections in harvested fresh chilies are needed. RESULTS: Two endophytic fungi, Trichoderma afroharzianum strain MFLUCC19-0090 and T. afroharzianum strain MFLUCC19-0091, were isolated from Schefflera leucantha leaves. Their volatile compounds were investigated for antifungal activities against F. oxysporum and F. proliferatum. In vitro results showed that the volatile compounds produced by each strain inhibited pathogen growth. Additionally, the Trichoderma-derived volatile compounds significantly reduced Fusarium-related disease severity and incidence percentages in the inoculated fresh chilies. Antifungal properties of the volatile compounds were found to be specific to the species of the tested pathogens (MFLUCC19-0090 greatly suppressed F. oxysporum and MFLUCC19-0091 greatly suppressed F. proliferatum). Seventy-three volatile compounds were detected from both strains. Among the major volatile compounds detected, phenyl ethyl alcohol was found to possess the strongest antifungal activity against both pathogens. CONCLUSION: These Trichoderma-derived volatile compounds may be used as alternative fumigants for controlling Fusarium rot in harvested fresh chilies. The successful use of volatile compounds as biofumigants can prevent significant market losses and, more importantly, may reduce the health hazards caused by Fusarium-associated mycotoxin exposures among consumers. © 2021 Society of Chemical Industry.

Prenatal phenol and paraben exposures in relation to child neurodevelopment including autism spectrum disorders in the MARBLES study.

BACKGROUND: Environmental phenols and parabens are endocrine disrupting chemicals (EDCs) with the potential to affect child neurodevelopment including autism spectrum disorders (ASD). Our aim was to assess whether exposure to environmental phenols and parabens during pregnancy was associated with an increased risk of clinical ASD or other nontypical development (non-TD). METHODS: This study included mother-child pairs (N = 207) from the Markers of Autism Risks in Babies - Learning Early Signs (MARBLES) Cohort Study with urinary phenol and paraben metabolites analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from repeated pregnancy urine samples. Because family recurrence risks in siblings are about 20%, MARBLES enrolls pregnant women who already had a child with ASD. Children were clinically assessed at 3 years of age and classified into 3 outcome categories: ASD, non-TD, or typically developing (TD). Single analyte analyses were conducted with trinomial logistic regression and weighted quantile sum (WQS) regression was used to test for mixture effects. RESULTS: Regression models were adjusted for pre-pregnancy body mass index, prenatal vitamin use (yes/no), homeowner status (yes/no), birth year, and child's sex. In single chemical analyses phenol exposures were not significantly associated with child's diagnosis. Mixture analyses using trinomial WQS regression showed a significantly increased risk of non-TD compared to TD (OR = 1.58, 95% CI: 1.04, 2.04) with overall greater prenatal phenol and paraben metabolites mixture. Results for ASD also showed an increased risk, but it was not significant. DISCUSSION: This is the first study to provide evidence that pregnancy environmental phenol exposures may increase the risk for non-TD in a high-risk population.

Essential Oil Compositions and Antibacterial and Antioxidant Activities of Five Lavandula stoechas Cultivars Grown in Thailand.

The essential oils of five Lavandula stoechas cultivars grown in Thailand were characterized for their volatile compounds using GC-FID and GC/MS methods as well as screened for antibacterial and antioxidant activities. Dried aerial parts, including flowers and stems from each cultivar, were subjected to hydrodistillation for 4 h. The essential oil yields were 0.18 %-0.82 % w/w. Of the 95 compounds detected and identified, 1,8-cineole, fenchone, and camphor were considered the major compounds. Essential oil from each cultivar demonstrated different patterns of antibacterial activity and a variety of antioxidant properties. The highest antibacterial activity, MIC=0.39 mg mL-1 , was observed from the essential oil of L. stoechas 'major' (against Klebsiella pneumoniae and Salmonella typhimurium) and the essential oil of L. stoechas 'white lavender' (against S. typhimurium). The essential oil of L. stoechas×viridis 'St. Brelade' possessed the highest antioxidant capacity, as determined by the DPPH and ABTS assays (IC50 of 67.65 and 89.26 mg mL-1 , respectively). The results indicated that some of these essential oils could be used as key ingredients in lavender oil products in Thailand to increase their therapeutic efficacy, depending on their intended application.

Predictors of Serum Polybrominated Diphenyl Ether (PBDE) Concentrations among Children Aged 1-5 Years.

Serum concentrations of PBDEs were measured using gas chromatography-tandem mass spectrometry in 80 children aged 15-71 months. Demographic and behavioral data were collected on parental questionnaires; a research nurse recorded anthropometric measures and insurance status. For a subset of children (n = 17), PBDEs were measured in house dust and child handwipes sampled during a home visit. In linear and Tobit regression, log-transformed PBDE congeners were modeled as a function of child characteristics, including neighborhood-level socioeconomic indicators. BDE congeners 47, 99, and 100 were highly correlated and summed for analysis; BDE-153 was examined individually. PBDE serum concentrations were associated with socioeconomic factors; for example, a $20,000 increase in median household income in a child's ZIP code was associated with a 34% decrease (95%CI = 14-49%) in BDE-153 and a 26% decrease (95%CI = 6-42%) in ∑BDE-47,-99,-100. Lower body-mass index (BMI) z-score and household smoking were strong predictors of higher BDE-153 levels. Among children who participated in a home visit, serum PBDE was positively correlated with handwipe PBDE (Spearman r ∑BDE-47, -99, -100 = 0.48, p = 0.09), but not dust PBDE. Results indicate socioeconomic factors and BMI are strong predictors of serum PBDE levels among young children. PBDEs measured on handwipes are more predictive of serum PBDE levels than vacuum-collected dust.

Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: Distribution and relationships with child neurodevelopment.

BACKGROUND: In recent years, pyrethroid pesticide use has increased in Mexico, the United States, and elsewhere, resulting in extensive human exposure. There is growing concern that pregnant women may be a particularly vulnerable population, as in utero fetal exposure during critical periods of development could adversely affect long-term neurobehavioral function. METHODS: We measured maternal urinary 3-phenoxybenzoic acid (3-PBA) concentrations during the third trimester of pregnancy as a measure of in utero pyrethroid exposure to the fetus among participants in an established Mexico City birth cohort (n=187). In a subset of mothers, we measured 3-PBA during the first, second, and third trimester (n=21) to assess variability across pregnancy. We examined associations between third trimester 3-PBA concentrations and children's scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from the Bayley Scales for Infant Development (BSID-IIS) at 24 and 36 months of age. RESULTS: 3-PBA was detected in 46% of all urine samples, with similar detection rates and geometric mean concentrations across pregnancy among the 21 participants who provided repeat samples. Participants in the medium and high 3-PBA categories (≥LOD) had lower MDI scores at 24 months compared to those in the low 3-PBA category (

Associations of maternal organophosphate pesticide exposure and PON1 activity with birth outcomes in SAWASDEE birth cohort, Thailand.

Prenatal organophosphate (OP) pesticide exposure has been reported to be associated with adverse birth outcomes and neurodevelopment. However, the mechanisms of toxicity of OP pesticides on human fetal development have not yet been elucidated. Our pilot study birth cohort, the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE cohort) aimed to evaluate environmental chemical exposures and their relation to birth outcomes and infant neurodevelopment in 52 pregnant farmworkers in Fang district, Chiang Mai province, Thailand. A large array of data was collected multiple times during pregnancy including approximately monthly urine samples for evaluation of pesticide exposure, three blood samples for pesticide-related enzyme measurements and questionnaire data. This study investigated the changes in maternal acetylcholinesterase (AChE) and paraoxonase 1 (PON1) activities and their relation to urinary diakylphosphates (DAPs), class-related metabolites of OP pesticides, during pregnancy. Maternal AChE, butyrylcholinesterase (BChE) and PON1 activities were measured three times during pregnancy and urinary DAP concentrations were measured, on average, 8 times from enrollment during pregnancy until delivery. Among the individuals in the group with low maternal PON1 activity (n=23), newborn head circumference was negatively correlated with log10 maternal ∑DEAP and ∑DAP at enrollment (gestational age=12±3 weeks; ß=-1.0 cm, p=0.03 and ß=-1.8 cm, p<0.01, respectively) and at 32 weeks pregnancy (ß=-1.1cm, p=0.04 and ß=-2.6 cm, p=0.01, respectively). Furthermore, among these mothers, newborn birthweight was also negatively associated with log10 maternal ∑DEAP and ∑DAP at enrollment (ß=-219.7 g, p=0.05 and ß=-371.3g, p=0.02, respectively). Associations between maternal DAP levels and newborn outcomes were not observed in the group of participants with high maternal PON1 activity. Our results support previous findings from US birth cohort studies. This is the first study to report the associations between prenatal OP pesticide exposure and birth outcomes in Thailand.

The effect of farming techniques on degradation of DDT in historical cotton farms.

DDT was used in the mid 20th century for crop and livestock production. After use, DDT and its degradates DDE and DDD (collectively DDX) remain in the environment for decades. A few studies have reported that the rate of degradation of DDT into its metabolites is affected by various farming techniques like tillage, irrigation, and use of fertilizers. However, most of these studies did not evaluate active farms, and none of them focused on the Southeast US or historical cotton farms. Therefore, in this study, we aimed to determine if different farming techniques affect the decomposition of DDT in Walton County, Georgia, where farms historically grew cotton. Five Walton County farms were sampled for soil, and churches were sampled as control sites. The extensive land history of the farms was recorded, and the soil levels of p,p'-DDT, p,p'-DDE, p,p'-DDD, o,p'-DDT, and o,p'-DDE were measured using gas chromatography-tandem mass spectrometry. All farm sites had detectable levels of p,p'-DDT, p,p'-DDE, and p,p'-DDD, while few sites had detectable levels of o,p'-DDT and o,p'-DDE. Tillage was found to speed up p,p'-DDE degradation, but there was no effect on p,p'-DDT degradation. Plowing was associated with an increase in decomposition of p,p'-DDT, but p,p'-DDE and p,p'-DDD were not significantly increased. The largest difference in the degradation of DDT was based on the fertilizer type. Natural fertilizer sped up degradation of p,p'-DDT and p,p'-DDE; synthetic fertilizer increased p,p'-DDE degradation, but not p,p'-DDT degradation.

Per- and polyfluoroalkyl substances (PFAS) in senior care facilities and older adult residents.

Per- and polyfluoroalkyl substances (PFAS) are fluorinated organic compounds used in a variety of consumer products and industrial applications that persist in the environment, bioaccumulate in biological tissues, and can have adverse effects on human health, especially in vulnerable populations. In this study, we focused on PFAS exposures in residents of senior care facilities. To investigate relationships between indoor, personal, and internal PFAS exposures, we analyzed 19 PFAS in matched samples of dust collected from the residents' bedrooms, and wristbands and serum collected from the residents. The median ∑PFAS concentrations (the sum of all PFAS detected in the samples) measured in dust, wristbands, and serum were 120 ng/g, 0.05 ng/g, and 4.0 ng/mL, respectively. The most abundant compounds in serum were linear- and branched-perfluorooctane sulfonic acid (L-PFOS and B-PFOS, respectively) at medians of 1.7 ng/mL and 0.83 ng/mL, respectively, followed by the linear perfluorooctanoic acid (L-PFOA) found at a median concentration of 0.59 ng/mL. Overall, these three PFAS comprised 80 % of the serum ∑PFAS concentrations. A similar pattern was observed in dust with L-PFOS and L-PFOA found as the most abundant PFAS (median concentrations of 13 and 7.8 ng/g, respectively), with the overall contribution of 50 % to the ∑PFAS concentration. Only L-PFOA was found in wristbands at a median concentration of 0.02 ng/g. Significant correlations were found between the concentrations of several PFAS in dust and serum, and in dust and wristbands, suggesting that the indoor environment could be a significant contributor to the personal and internal PFAS exposures in seniors. Our findings demonstrate that residents of assisted living facilities are widely exposed to PFAS, with several PFAS found in blood of each study participant and in the assisted living environment.

Predictors of executive function among 2 year olds from a Thai birth cohort.

Executive function (EF) is a critical skill for academic achievement. Research on the psychosocial and environmental predictors of EF, particularly among Southeast Asian, agricultural, and low income/rural populations, is limited. Our longitudinal study explored the influence of agricultural environmental, psychosocial, and temperamental factors on children's emerging EF. Three-hundred and nine farm worker women were recruited during the first trimester of pregnancy. We evaluated the effects of prenatal insecticide exposure and psychosocial factors on "cool" (i.e., cognitive: A-not-B task, looking version) and "hot" EF (i.e., affective, response inhibition) measures of emerging EF. Maternal urine samples were collected monthly during pregnancy, composited, and analyzed for dialkylphosphate (DAP) metabolites of organophosphate insecticides. Psychosocial factors included socioeconomic status, maternal psychological factors, and quality of mother-child behavioral interactions. Backward stepwise regressions evaluated predictors of children's EF at 12 (N = 288), 18 (N = 277) and 24 (N = 280) months of age. We observed different predictive models for cool EF, as measured by A-not-B task, vs. hot EF, as measured by response inhibition tasks. Report of housing quality as a surrogate for income was a significant predictor of emerging EF. However, these variables had opposite effects for cool vs. hot EF. More financial resources predicted better cool EF performance but poorer hot EF performance. Qualitative findings indicate that homes with fewer resources were in tribal areas where children must remain close to an adult for safety reasons. This finding suggests that challenging physical environments (e.g., an elevated bamboo home with no electricity or running water), may contribute to development of higher levels of response inhibition through parental socialization methods that emphasize compliance. Children who tended to show more arousal and excitability, and joy reactivity as young infants in the laboratory setting had better cognitive performance. In contrast, maternal emotional availability was a significant predictor of hot EF. As expected, increased maternal exposure to pesticides during pregnancy was associated with worse cognitive performance but was not associated with inhibitory control. Identifying risk factors contributing to the differential developmental pathways of cool and hot EF will inform prevention strategies to promote healthy development in this and other unstudied rural, low income Southeast Asian farming communities.