Placental transcriptome variation associated with season, location, and urinary prenatal pyrethroid metabolites of Thai farm-working women.

Prenatal exposure to pyrethroids is linked to adverse health effects in early life and proper placental function is critical to fetal development. This study explores the impact of prenatal pyrethroid exposure, as well as factors impacting exposure and effect, on the placental transcriptome, to understand pyrethroid exposures' relationship to placental function. The study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) recruited pregnant farm-working women from two agricultural districts in the Chiang Mai province of Thailand between 2017 and 2019. This cohort was predominantly exposed to cypermethrin (type II), alongside pyrethroids such as cyfluthrin (type II) and permethrin (type I). In 253 participants, maternal urinary pyrethroid metabolites, 3-phenoxybenzoic acid (PBA), cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), and trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA) were measured in early, middle, and late pregnancy and adjusted for urinary creatinine. The placental transcriptome was analyzed using RNA-Seq. Using generalized linear regression, we identified differentially expressed genes (DEGs) associated with the sum of each metabolite across pregnancy, as well as those associated with location of residence and season of birth. Pathway and upstream transcription factor analyses were performed to examine potential mechanisms associated with DEGs. Notably, TDCCA and CDCCA levels peaked in late pregnancy, with significant regional differences, particularly higher levels in the Fang region. Placental gene expression analysis showed no DEGs associated with individual metabolites at FDR<0.05. However, 251 DEGs by location, implicating immune response and oxidative phosphorylation pathways, were identified, while season of birth was associated with 2585 DEGs, over-represented in fibrosis signaling and metabolism pathways. Finally, transcription factor analysis identified 226 and 282 transcription factors associated with location and season, respectively, related to cell proliferation, differentiation, and the immune system. These alterations may have significant implications for fetal development and other pathologic processes, highlighting the importance of monitoring environmental exposures during pregnancy.

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.

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.

An Evaluation of a Pesticide Training Program to Reduce Pesticide Exposure and Enhance Safety among Female Farmworkers in Nan, Thailand.

BACKGROUND: Although exposure to chemical pesticides is known to cause negative effects on human health, farmers in Ban Luang, Nan, Thailand, continue to use them regularly to protect crops. This study focused on mothers who were engaged in farm tasks and had children between the ages of 0 to 72 months, with the objective of reducing pesticide exposure. METHODS: This study was conducted from May 2020 to October 2020 in the Ban Fa and Ban Phi sub-districts in Ban Luang due to the high use of pesticides in these areas. A systematic random sampling technique was used to recruit 78 mothers exposed to pesticides. Thirty-nine mothers from Ban Fa district were randomly assigned to the intervention group and 39 from Ban Phi to the control group over a 3-month period. This study applied a pesticide behavioral change training program for the intervention group. To assess the effectiveness of the program, the study compared the results of a questionnaire regarding knowledge, attitude, and practice (KAP) and health beliefs related to pesticide exposure as well as the levels of acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) enzymes, biomarkers of exposure to pesticides, before and after the intervention using ANCOVA statistical test. Furthermore, to evaluate the effectiveness of the intervention program, a paired t-test was used to investigate the in-home pesticide safety assessment. RESULTS: After the intervention, we observed no significant change in AChE; however, a significant improvement in BChE (p < 0.05), a marker of short-term recovery, was observed. Pesticides can cause a reduction in AChE and BChE, however, after eliminating pesticides, BChE takes a shorter time (about 30-50 days) to recover than AChE (around 90-120 days). Therefore, increases in the measured concentrations of AChE and/or BChE suggest the presence of less chemicals from pesticides in the human body. The study also found a significant improvement in KAP and beliefs about chemical pesticide exposure after the intervention (p < 0.05). Furthermore, using a paired t-test, we found a significant increase in pesticide safety practices (p < 0.05) in the intervention group and a borderline significant increase regarding in-home safety (p = 0.051) in the control group. CONCLUSIONS: Based on the results, the constructs of the intervention program were effective and could be applied in other agricultural areas in less developed countries. However, due to time limitations during the COVID-19 pandemic, further studies should be conducted to enable data collection over a longer time, with a larger number of subjects providing the ChE levels for the non-agricultural season.

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.

Investigation of Prenatal Pesticide Exposure and Neurodevelopmental Deficits in Northern Thailand: Protocol for a Longitudinal Birth Cohort Study.

BACKGROUND: Prenatal exposure to pesticides has been linked to adverse neurodevelopmental outcomes. Gaps exist in the current literature about the timing and magnitude of exposures that result in these adverse outcomes. OBJECTIVE: The Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) cohort was established to investigate the impact of prenatal exposure to pesticides on early indicators of cognitive and motor skills, inhibitory control, emotion regulation, and memory that have been found to be important in the development of subsequent neurobehavioral and neurodevelopmental diseases. The overarching goal is to find earlier predictors of potential adverse neurologic outcomes in order to enable earlier interventions that could result in better outcome prognoses. METHODS: Recruitment of this prospective, longitudinal birth cohort began in July 2017 and was completed in June 2019 in Chom Thong and Fang, 2 farming districts in Chiang Mai Province in northern Thailand. Follow-up of the study participants is ongoing. During pregnancy, 7 questionnaires were administered. Time-resolved biospecimen samples were collected monthly (for urine) and during each trimester (for blood) during antenatal care visits. Medical records were abstracted. Infants were administered the NICU Network Neurobehavioral Scale (NNNS) test at 1 month of age. A total of 322 mother-child pairs completed the NNNS test. All children will be followed until 3 years of age and undergo a series of neurodevelopmental tests. We will complete several additional exposure related analyses. RESULTS: A total of 1298 women were screened, and of those, 394 (30.35%) women were enrolled. The mean gestational age at enrollment was 9.9 weeks (SD 2.6). Differences in literacy were observed between Chom Thong and Fang participants. In Fang, about 54 of 105 (51.4%) participants reported being able to read in Thai compared to about 206 of 217 (94.9%) participants in Chom Thong. The percentages were comparable for reporting to be able to write in Thai. CONCLUSIONS: This longitudinal birth cohort study will inform risk assessment standards for pregnant women in Thailand and other countries. Building awareness of how insecticide exposure during specific windows of pregnancy affects the neurodevelopmental trajectories of children in developing countries is a specific need recognized by the World Health Organization. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31696.

The relationship between prenatal exposure to organophosphate insecticides and neurodevelopmental integrity of infants at 5-weeks of age.

Introduction: Organophosphate (OP) insecticides are among the most abundantly used insecticides worldwide. Thailand ranked third among 15 Asian countries in its use of pesticides per unit hectare and fourth in annual pesticide use. More than 40% of Thai women of childbearing age work on farms where pesticides are applied. Thus, the potential for pregnant women and their fetuses to be exposed to pesticides is significant. This study investigated the relationship between early, mid, and late pregnancy maternal urine concentrations of OP metabolites and infant neural integrity at 5 weeks of age. Method: We enrolled women employed on farms from two antenatal clinics in the Chiang Mai province of northern Thailand. We collected urine samples monthly during pregnancy, composited them by early, mid and late pregnancy and analyzed the composited samples for dialkylphosphate (DAP) metabolites of OP insecticides. At 5 weeks after birth, nurses certified in use of the NICU Network Neurobehavioral Scale (NNNS) completed the evaluation of 320 healthy infants. We employed generalized linear regression, logistic and Poisson models to determine the association between NNNS outcomes and DAP concentrations. All analyses were adjusted for confounders and included creatinine as an independent variable. Results: We did not observe trimester specific associations between DAP concentrations and NNNS outcomes. Instead, we observed statistically significant inverse associations between NNNS arousal (ß = -0.10; CI: -0.17, -0.002; p = 0.0091) and excitability [0.79 (0.68, 0.92; p = 0.0026)] among participants with higher average prenatal DAP concentrations across pregnancy. We identified 3 NNNS profiles by latent profile analysis. Higher prenatal maternal DAP concentrations were associated with higher odds of being classified in a profile indicative of greater self-regulation and attention, but arousal and excitability scores below the 50th percentile relative to US normative samples [OR = 1.47 (CI: 1.05, 2.06; p = 0.03)]. Similar findings are also observed among infants with prenatal exposure to substances of abuse (e.g., methamphetamine). Discussion: Overall, the associations between prenatal DAP concentrations and NNNS summary scores were not significant. Further evaluations are warranted to determine the implications of low arousal and excitability for neurodevelopmental outcomes of attention and memory and whether these results are transitory or imply inadequate responsivity to stimulation among children as they develop.

Urinary Concentrations of Dialkylphosphate Metabolites of Organophosphate pesticides in the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE).

BACKGROUND: Measurements of urinary dialkyl phosphate (DAP) metabolites are often used to characterize exposures to organophosphate (OP) insecticides; however, some challenges to using urinary DAP metabolites as an exposure measure exist. OP insecticides have short biological half-lives with measurement in a single urine sample typically only reflecting recent exposure within the last few days. Because of the field staff and participant burden of longitudinal sample collection and the high cost of multiple measurements, typically only one or two urine samples have been used to evaluate OP insecticide exposure during pregnancy, which is unlikely to capture an accurate picture of prenatal exposure. METHODS: We recruited pregnant farmworker women in Chom Thong and Fang, two districts of Chiang Mai province in northern Thailand (N = 330) into the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. We collected up to 6 serial urine samples per participant during gestation and composited the samples to represent early, mid, and late pregnancy. We measured concentrations of urinary DAP metabolites in the composited urine samples and evaluated the within- and between-participant variability of these levels. We also investigated predictors of OP insecticide exposure. RESULTS: DAP metabolite concentrations in serial composite samples were weakly to moderately correlated. Spearman correlations indicated that composite urine samples were more highly correlated in Fang participants than in Chom Thong participants. The within-person variances (0.064-0.65) exceeded the between-person variances for DETP, DEP, ∑DEAP, DMP, DMTP, ∑DMAP, ∑DAP. The intraclass correlations (ICCs) for the volume-based individual metabolite levels (ng/mL) ranged from 0.10 to 0.66. For ∑DEAP, ∑DMAP, and ∑DAP the ICCs were, 0.47, 0.17, 0.45 respectively. We observed significant differences between participants from Fang compared to those from Chom Thong both in demographic and exposure characteristics. Spearman correlations of composite samples from Fang participants ranged from 0.55 to 0.66 for the ∑DEAP metabolite concentrations in Fang indicating moderate correlation between pregnancy periods. The ICCs were higher for samples from Fang participants, which drove the overall ICCs. CONCLUSIONS: Collecting multiple (∼6) urine samples during pregnancy rather than just 1 or 2 improved our ability to accurately assess exposure during the prenatal period. By compositing the samples, we were able to still obtain trimester-specific information on exposure while keeping the analytic costs and laboratory burden low. This analysis also helped to inform how to best conduct future analyses within the SAWASDEE study. We observed two different exposure profiles in participants in which the concentrations and variability in data were highly linked to the residential location of the participants.

Three Doses of Vitamin D and Cognitive Outcomes in Older Women: A Double-Blind Randomized Controlled Trial.

Vitamin D may affect cognitive performance, but previous studies are either short term or observational. We conducted a randomized controlled trial of vitamin D supplementation on domain-specific cognitive measures in postmenopausal women. Overweight/obese women with serum 25-hydroxyvitamin D (25OHD) levels less than 30 ng/mL were recruited. Vitamin D3 supplementation (600, 2,000, or 4,000 IU/d) was randomly assigned in a double-blinded manner for 1 year. Serum 25-hydroxyvitamin D, osteocalcin (total and undercarboxylated), amyloid beta, parathyroid hormone, and estradiol were analyzed before and after supplementation. Cognitive tests were administered after treatment. The women (58 ± 6 years; body mass index, 30.0 ± 3.5 kg/m2) had a baseline serum 25-hydroxyvitamin D level of 22.6 ± 5.8 ng/mL that increased to 30.2 ± 5.6, 36.0 ± 4.9, and 40.8 ± 7.0 ng/mL in the 600, 2,000, and 4,000 IU/d groups, respectively (p < .001). Participants taking 2,000 IU/d compared to other doses performed better in learning and memory tests (p < .05), yet the 4,000 IU/d group had a slower reaction time compared to the 600 IU/d group. Multiple regression indicated that serum undercarboxylated osteocalcin predicted tasks associated with reaction time and executive function, whereas body mass index and parathyroid hormone negatively predicted reaction time and executive function (p ≤ .01). These data suggest that vitamin D has differential effects on domain-specific cognitive measures and that a higher dose may negatively affect reaction time.

Chronic Exposure to Solvents Among Construction Painters: Reductions in Exposure and Neurobehavioral Health Effects.

OBJECTIVE: The aim of this study was to assess the neurobehavioral effects of lifetime solvent exposure by comparing the performance of painters and demographically comparable controls. METHODS: Performance of exposed painters (N = 133) was compared with unexposed tapers, glaziers, or carpenters (N = 78) on the following domains: motor/perceptual speed, visual contrast, attention, working memory/planning, and visual and verbal memory. Lifetime exposure was estimated with questionnaires, field measurements, and paint composition. RESULTS: After controlling for confounders, lifetime solvent exposure did not predict reduction in performance for overall domains of function. Lifetime solvent exposures predicted subtle alterations for individual tests of verbal learning, motor coordination, and visuospatial accuracy. CONCLUSION: Concentrations of solvents in paints have steadily declined during the working lifetime of subjects in this study. Although reduced performance was observed on individual tests, these alterations were not consistent across tests and unlikely to be of clinical significance.

Neurobehavioral effects of exposure to organophosphates and pyrethroid pesticides among Thai children.

The use of pesticides for crop production has grown rapidly in Thailand during the last decade, resulting in significantly greater potential for exposure among children living on farms. Although some previous studies assessed exposures to pesticides in this population, no studies have been conducted to evaluate corresponding health effects. Twenty-four children from a rice farming community (exposed) and 29 from an aquaculture (shrimp) community (control) completed the study. Participants completed a neurobehavioral test battery three times at 6 month intervals: Session I: preliminary orientation; Session II: high pesticide use season; Session III: low pesticide-use season. Only sessions II and III were used in the analyses. High and low pesticide use seasons were determined by pesticide use on rice farms. Urinary metabolites of organophosphates (OPs) and pyrethroids (PYR) were analyzed from first morning void samples collected the day of neurobehavioral testing. Rice farm participants had significantly higher concentrations of dialkylphosphates (DAPs) (common metabolites of OPs) and TCPy (a specific metabolite of chlorpyrifos) than aquaculture farm children during both seasons. But, TCPy was significantly higher during the low rather than the high pesticide use season for both participant groups. Rice farm children had significantly higher DCCA, a metabolite of PYR, than aquaculture participants only during the high exposure season. Otherwise, no significant differences in PYR metabolites were noted between the participant groups or seasons. No significant adverse neurobehavioral effects were observed between participant groups during either the high or low pesticide use season. After controlling for differences in age and the Home Observation for Measurement of the Environment (HOME) scores, DAPs, TCPy, and PYR were not significant predictors of adverse neurobehavioral performance during either season. Increasing DAP and PYR metabolites predicted some relatively small improvement in latency of response. However, due to the small sample size and inability to characterize chronic exposure, any significant differences observed should be regarded with caution. Moreover although not statistically significant, confidence intervals suggest that small to moderate adverse effects of pesticide exposure cannot be ruled out for some indicators of neurobehavioral performance.

Pyrethroid insecticide exposure in school-aged children living in rice and aquacultural farming regions of Thailand.

BACKGROUND: Pyrethroid insecticides (PYR) are commonly used in rice farms and household pest control in Thailand. No investigative study has yet been made regarding factors associated with PYR exposure among Thai children. OBJECTIVE: This study aimed to compare the levels of PYR exposure between children living in rice farms (high-intensity PYR used) and aquacultural areas (low-intensity PYR used) during the wet and dry seasons in Thailand, during which different amounts of PYR are applied. Environmental conditions and common activities of children were used to identify factors associated with PYR exposure. METHODS: A cross-sectional study was done during the wet and dry seasons, respectively. A total of 53 participants aged between 6 and 8 years old were recruited from rice farms and aquacultural areas. A parental-structured interview was used to gather information about PYR use, household environments, and participants' activities. First voided morning urine samples were collected for PYR urinary metabolites (ie, 3-phenoxybenzoic acid [3-PBA] and cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid [DCCA]) measurements. Hand wipe samples were collected during home visits, to measure PYR residues on the hands. RESULTS AND DISCUSSION: The concentrations of urinary PYR metabolites were not significantly different between participants who lived in rice farming and those who lived in aquacultural areas, during both wet and dry seasons. Both participant groups had slightly increased urinary PYR metabolites during the wet season compared with the dry season. The results from linear regression analysis revealed that some environmental conditions and activities or practices may be used to predict trends of PYR exposure. Frequency of PYR use in farms (ß=0.004) and households (ß=0.07), proximity to rice farms (ß=0.09), playing in rice farms (ß=0.11), and oral exposure from objects exposed to PYR (ß=0.08) were likely to be related to increased concentrations of PYR metabolites. These findings suggest that PYR use in rice farms and households may be significant sources of PYR exposure among children living in agricultural areas. However, a bigger sample size may be necessary in a subsequent study, to explore the association between long-term exposure to pesticide and its health effects on children.

Organophosphate pesticide exposure in school-aged children living in rice and aquacultural farming regions of Thailand.

Organophosphate pesticides (OPs) are widely used in agricultural sectors in Thailand. Previous studies have documented that children residing in agricultural areas have higher exposure to OPs than children living in other residential areas. The objective of this study was to quantify urinary biomarkers of OP exposure and determine the environmental conditions and activities that predict their levels among children living in Central Thailand farming regions. In October 2011, 53 6-8-year-old participants were recruited from Pathum Thani Province, Thailand. Twenty-four lived in rice farming communities at Khlong Luang District where OPs are the pesticides used frequently. Twenty-nine participants, living in aquacultural farming communities at Lum Luk Ka District where OPs are not used, were recruited to serve as controls for pathways of exposure (e.g., residential, dietary) other than occupational/paraoccupational exposures encountered in rice farming. Household environments and participants' activities were assessed using a parental structured interview. Urine samples (first morning voids) were collected from participants for OP urinary metabolite (i.e., dialkylphosphates [DAPs] and 3,5,6-trichloro-2-pyridinol [TCPy]) measurements. The levels of most urinary OP metabolites were significantly higher in participants who lived in a rice farming community than those who lived in an aquacultural farming community (P < .05). The results from linear regression analysis revealed that the frequency of OP application on rice farms (∑DAP: P = .001; TCPy: P = .001) and living in a rice farming community (∑DAP: P = .009; TCPy: P < .001) were significant predictors of urinary DAP metabolite levels in participants. Increasing TCPy levels were significantly related to proximity to rice farm (P = .03), being with parent while working on a farm (P = .02), playing on a farm (P = .03), and the presence of observable dirt accumulated on the child's body (P = .02). In conclusion, OP metabolite levels among children who live in rice farming communities were strongly influenced by farming activity, household environments, and child behaviors, suggesting that these are the primary pathways in which children living in these agricultural communities in Thailand were exposed to OPs.

Adaptation of a neurobehavioral test battery for Thai children.

BACKGROUND: Exposure to neurotoxicants is a world wide problem with significant health implications for child development. In spite of higher neurotoxicant exposures, many developing countries do not have established neuropsychological instruments. OBJECTIVE: This study evaluated the adaptation and reliability of a computer and examiner administered Behavioral Assessment and Research System (BARS) that includes tests of motor speed and dexterity, attention, memory, and visuospatial coordination for use in Thailand. MATERIAL AND METHODS: To assess test-retest and alternate form reliability, BARS was administered to 24 healthy, 6-8 year old urban Thai children during two testing sessions two weeks apart. A comparison group of 29 healthy, rural Thai children of similar age and sex completed the BARS as part of another study and comprised a comparison group. RESULTS: Test-retest reliabilities for tests without alternate forms ranged from 0.41 to 0.77, but reliabilities were lower for tests with alternate forms (0.11 to 0.83). Paired t-tests revealed few significant differences in group performance between test administrations. Performance of urban Thai participants was compared to 29 rural Thai participants of similar age and sex. Parental education was significantly greater for urban vs. rural participants, resulting in significant differences in performance on tests of motor speed. CONCLUSIONS: This study supports the use of BARS for epidemiologic studies of neurotoxicants in Thailand, but highlights the sensitivity of these tests to differences in parental education and the need for improved alternate test forms.

Alteration of peripheral blood monocyte gene expression in humans following diesel exhaust inhalation.

CONTEXT: Epidemiologic associations between acutely increased cardiorespiratory morbidity and mortality and particulate air pollution are well established, but the effects of acute pollution exposure on human gene expression changes are not well understood. OBJECTIVE: In order to identify potential mechanisms underlying epidemiologic associations between air pollution and morbidity, we explored changes in gene expression in humans following inhalation of fresh diesel exhaust (DE), a model for particulate air pollution. MATERIALS AND METHODS: Fourteen ethnically homogeneous (white males), young, healthy subjects underwent 60-min inhalation exposures on 2 separate days with clean filtered air (CA) or freshly generated and diluted DE at a concentration of 300 µg/m(3) PM(2.5). Prior to and 24 h following each session, whole blood was sampled and fractionated for peripheral blood mononuclear cell (PBMC) isolation, RNA extraction, and generation of cDNA, followed by hybridization with Agilent Whole Human Genome (4X44K) arrays. RESULTS: Oxidative stress and the ubiquitin proteasome pathway, as well as the coagulation system, were among hypothesized pathways identified by analysis of differentially expressed genes. Nine genes from these pathways were validated using real-time polymerase chain reaction (PCR) to compare fold change in expression between DE exposed and CA days. Quantitative gene fold changes generated by real-time PCR were directionally consistent with the fold changes from the microarray analysis. DISCUSSION AND CONCLUSION: Changes in gene expression connected with key oxidative stress, protein degradation, and coagulation pathways are likely to underlie observed physiologic and clinical outcomes and suggest specific avenues and sensitive time points for further physiologic exploration.

Agricultural Pesticide Management in Thailand: Situation and Population Health Risk.

As an agricultural country and one of the world's major food exporters, Thailand relies heavily on the use of pesticides to protect crops and increase yields. During the past decade, the Kingdom of Thailand has experienced an approximate four-fold increase in pesticide use. This increase presents a challenge for the Royal Thai Government in effectively managing and controlling pesticide use based upon the current policies and legal infrastructure. We have reviewed several key components for managing agricultural pesticides in Thailand. One of the main obstacles to effective pesticide regulation in Thailand is the lack of a consolidated, uniform system designed specifically for pesticide management. This deficit has weakened the enforcement of existing regulations, resulting in misuse/overuse of pesticides, and consequently, increased environmental contamination and human exposure. This article provides a systematic review of how agricultural pesticides are regulated in Thailand. In addition, we provide our perspectives on the current state of pesticide management, the potential health effects of widespread, largely uncontrolled use of pesticides on the Thai people and ways to improve pesticide management in Thailand.

Increased lead biomarker levels are associated with changes in hormonal response to stress in occupationally exposed male participants.

BACKGROUND: Lead (Pb) exposure has been associated with a host of pathological conditions in humans. In rodents Pb exposure has been shown to alter the hypothalamic-pituitary-adrenal (HPA) axis function. OBJECTIVE: We investigated the effects of lead on responses of the HPA axis to a psychosocial laboratory stressor administered to Pb-exposed workers. METHODS: Seventy male participants completed the Trier Social Stress Test (TSST). Serum cortisol (CORT) and plasma adrenocorticotropic hormone (ACTH) were assessed in response to and during recovery from the stressor. We measured Pb in blood, a biomarker of recent exposure, and in tibia bone by X-ray fluorescence (XRF), a biomarker of chronic exposure. RESULTS: The TSST induced statistically significant increases in ACTH and CORT in the participants. At baseline, ACTH was not significantly higher (p = 0.052) in participants with higher blood Pb concentration, but CORT was significantly lower in these participants (p = 0.016). Adjusted linear regression models indicated a positive association between blood and bone Pb and the increase in ACTH in response to stress. However, Pb was not strongly associated with changes in CORT in response to stress. Pb was also associated with the ACTH:CORT ratio at baseline and throughout the course of the protocol, suggesting an adrenal hyporesponsiveness in participants with higher Pb concentrations. CONCLUSION: The altered HPA-axis stress response observed in participants exposed to higher levels of Pb further supports the idea that lead may contribute to a host of biological dysfunctions beyond the classical neurotoxic effects.

Sleep and psychomotor vigilance in female shiftworkers.

The purpose of this study was to evaluate the relationships between sleep and psychomotor vigilance in female nurses and the changes in these variables over time. Participants comprised 16 staff registered nurses (10 day, 6 night; aged 30-65 years [M = 47.6; SD = 8.1]) who wore wrist actigraphs continuously and completed a 10-min psychomotor vigilance test (PVT-192, Ambulatory Monitoring, Inc., Ardsley, New York) and the Stanford Sleepiness Scale (SSS) in their homes before and after work for three consecutive 24-hr periods. Repeated measures ANOVA revealed that night nurses slept significantly less than day nurses, F(1, 15) = 26.06, p ≤ .001; M = 227.88 ± 37.03 min versus M = 365.75 ± 59.01 min, respectively, daily for three consecutive days. Night nurses napped more frequently and had more changes in the length of their main sleep periods than day nurses. Day nurses reported more wake episodes during main sleep periods. Night nurses were sleepier after work than day nurses; both groups had increased sleepiness after work for the first 2 days and similar psychomotor vigilance test results. These findings suggest that sleep deprivation, irregular sleep patterns, and sleepiness are significant issues for shiftworking nurses. Future study of the characteristics of sleep and sleepiness in a larger sample would be useful to evaluate the focus for interventions to improve sleep and alertness in shiftworking nurses.

Occupational solvent exposure and brain function: an fMRI study.

BACKGROUND: Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown. OBJECTIVES: We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers. METHODS: Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure. RESULTS: Solvent-exposed workers' performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices--areas serving working memory function and attention--was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers. CONCLUSIONS: This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology caused by prolonged exposure to solvent mixtures during construction work.