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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.

Background: Few studies exist on environmental risk factors for respiratory infections in Thai school children. Aim: To study associations between home and outdoor environment and respiratory infections among school children in Northern Thailand in dry and wet season. Methods: A repeated questionnaire survey among the children (N = 1159). Data on ambient temperature and relative air humidity (RH) and PM10 and ozone was collected from nearby monitoring stations. We used logistic regression to calculate odds ratios (OR). Results: 14.1% had current respiratory infections (last 7 days), 32.1% had any respiratory infection last 3 months, and 26.1% had any respiratory infection last 12 months with antibiotic treatment. Students with diagnosed allergy (7.7%) and diagnosed asthma (4.7%) had more often respiratory infections (ORs 1.40-5.40; p < 0.05). Current respiratory infections were more common in dry (18.1%) than in wet season (10.4%) (p < 0.001) and was associated with indoor mould (OR 2.16; p = 0.024) and outdoor RH (OR 1.34 per 10% RH; p = 0.004.) in the total material. In wet season, mould (OR 2.32; p = 0.016), window pane condensation (OR 1.79; p = 0.050), water leakage (OR 1.82; p = 0.018), environmental tobacco smoke (ETS) (OR 2.34; p = 0.003) and outdoor RH (OR 2.70 per 10% RH; p = 0.01) were risk factors for current respiratory infections. In dry season, mould (OR 2.64; p = 0.004) and outdoor RH (OR 1.34 per 10% RH; p = 0.046) were associated with current respiratory infections. Irrespectively of season, biomass burning inside or outside the home was a risk factor for respiratory infections (ORs 1.32-2.34; p < 0.05). Living in a wooden house decreased the risk of respiratory infections (OR 0.56: p = 0.006). Conclusions: Dry season, high outdoor RH, household dampness, indoor mould and ETS can increase childhood respiratory infections. Living in a traditional wooden house can reduce respiratory infections, possibly due to better natural ventilation. Smoke from biomass burning can increase childhood respiratory infections in northern Thailand.

Objective: There are few studies on fractional exhaled nitric oxide (FeNO) among children in subtropical areas. We studied associations between FeNO and respiratory symptoms, reported diagnosed allergies and indoor and outdoor environmental factors in first grade junior high school students (N = 270) in upper northern Thailand. Methods: Data on demographics, health and home environment were collected by a questionnaire distributed in dry season (February-March 2018). FeNO was measured when the research team visited the school. Daily outdoor pollution data (PM10 and ozone) were collected from the nearest monitoring station 3 days (lag 3) and 7 days (lag 7) before the FeNO measurements. Two-level (student, school) linear mixed models were used to analyze associations, adjusting for gender and family education level. Results: In total, 29.6% had elevated FeNO level (>20 ppb) and 7.8% reported any allergy diagnosed by a doctor. Male gender (p = 0.02), diagnosed allergy (p = 0.001), especially to cat (p = 0.001) and house dust mite (HDM) allergies (p = 0.001) were associated with FeNO. Eye symptoms (p = 0.01), rhinitis symptoms (p = 0.03) and dyspnea (p = 0.05) in the last 3 days were associated with FeNO. Household indoor mold (p = 0.03), gas cooking (p = 0.03) and PM10 (lag 3 and lag 7) were negatively (protective) associated with FeNO. Conclusions: Diagnosed allergy, especially to cat and HDM, can be associated with increased FeNO. Indoor mold and gas cooking can be associated with lower FeNO. Ocular, nasal and dyspnea symptoms reported by students in dry season in northern Thailand can be associated with FeNO, a biomarker of Th2 driven airway inflammation.

Radon exposure is the second leading cause of lung cancer, after smoking. In upper northern Thailand (UNT), lung cancer incidence was frequently reported by Thailand National Cancer Institute. Besides smoking, radon exposure may also influence the high lung cancer incidence in this region. Indoor radon concentrations were measured in 192 houses in eight provinces of UNT. Indoor radon concentrations ranged from 11 to 405 Bq m−3 and estimated annual effective dose ranged from 0.44 to 12.18 mSv y−1. There were significant differences in indoor radon concentrations between the houses of lung cancer cases and healthy controls (p = 0.033). We estimated that 26% of lung cancer deaths in males and 28% in females were attributable to indoor radon exposure in this region. Other factors influencing indoor radon levels included house characteristics and ventilation. The open window-to-wall ratio was negatively associated with indoor radon levels (B = −0.69, 95% CI −1.37, −0.02) while the bedroom location in the house and building material showed no association. Indoor radon hence induced the fractal proportion of lung cancer deaths in UNT.

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

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 DERR1-10.2196/31696

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.

Several studies indicated organophosphate (OP) and neonicotinoid (NEO) insecticides are endocrine disruptors, however, data are scarce. This cross-sectional study recruited 143 male farmworkers aged 18–40 years in Fang district, Chiang Mai province, northern Thailand. OP exposure was assessed by measuring urinary dialkylphosphate (DAPs) using a gas-chromatography flame photometric detector. Urinary NEOs, their metabolites (NEO/m) and serum steroid hormones were measured using liquid chromatography–tandem mass spectrometry. Characteristics of participants were determined by face-to-face interviews. DAPs and five NEO/m were detected in more than 60% of samples. The concentration of diethylphosphate was highest among DAP metabolites (geometric mean concentration (GM: 23.9 ng/mL) and the concentration of imidacloprid (IMI) was highest among NEO/m (GM: 17.4 ng/mL). Linear regression models showed that the IMI level was positively associated with testosterone, dehydrocorticosterone (DHC) and dehydroepiandrosterone (DHEA) levels. Imidacloprid-olefin and DHEA levels were positively associated. Thiamethoxam (THX) were inversely associated with DHC and deoxycorticosterone levels. Clothianidin (CLO), THX and N-desmethyl-acetamiprid levels were positively associated with the androstenedione level. CLO and THX levels were inversely associated with the cortisone level. In conclusion, the association between NEO insecticides exposure and adrenal androgens, glucocorticoids and mineralocorticoids, suggest potential steroidogenesis activities. Our findings warrant further investigation.

We performed a repeated questionnaire study on home environment and health (six medical symptoms) in 1159 junior high school students (age 12.8 ± 0.7 years) in upper northern Thailand in wet and dry seasons. Data on outdoor temperature, relative humidity (RH), and air pollution were collected from nearest monitoring station. Odds ratios (OR) were calculated by multi-level logistic regression. Most common symptoms were rhinitis (62.5%), headache (49.8%), throat (42.8%), and ocular symptoms (42.5%). Ocular symptoms were more common at lower RH and rhinitis more common in dry season. Water leakage (28.2%), indoor mold (7.1%), mold odor (4.1%), and windowpane condensation (13.6%) were associated with all six symptoms (ORs: 1.3-3.5). Other risk factors included cat keeping, environmental tobacco smoke (ETS), other odor than mold odor, gas cooking, and cooking with biomass fire. Biomass burning inside and outside the home for other reasons than cooking was associated with all six symptoms (ORs: 1.5-2.6). Associations between home environment exposure and rhinitis were stronger in wet season. In conclusion, dampness-related exposure, windowpane condensation, cat keeping, ETS, gas cooking, and biomass burning can impair adolescent health in upper northern Thailand. In subtropical areas, environmental health effects should be investigated in wet and dry seasons.

Multiple pesticides are used in vegetable and fruit cultivation worldwide, including in Thailand. A survey series on pesticide residues in vegetable and fruit samples sourced from markets in urban and rural areas of upper northern Thailand during 2007–2013. Sixteen different vegetables (n = 412) and 11 different fruits (n = 301) were analyzed for 43 pesticide residues including 20 organophosphates (OP), 6 synthetic pyrethroids, 12 carbamates, 2 abamectins, imidacloprid, dithiocarbamates, and carbendazim. Out of the 412 vegetable samples, 235 (57%) had pesticide residues and 185 (45%) had pesticide residues that exceeded the maximum residue limits (MRLs). For the fruit samples, 245 (81%) of the 301 samples had pesticide residues and 165 (55%) had pesticide residues that exceeded the MRLs. The vegetable and the fruit samples had multiple synthetic pyrethroid residues and higher levels of residues than OP and other pesticides. Among the OP pesticides, chlorpyrifos was the most frequently detected pesticide. Residue detection in the rural samples was higher than that in the urban samples. The present study found very high numbers of samples to be above the MRLs: 45% of the vegetable samples and 55% of the fruit samples. Therefore, multi-residue methods are proposed as a regular monitoring system to ensure coverage of the multiple pesticides that are commonly used in agriculture and secure the national food safety policy.

Exposure to insecticides may result in various health problems. This study investigated the association between haematological parameters and exposure to a mixture of organophosphate (OP) and neonicotinoid (NEO) insecticides among male farmworkers in Fang district, Chiang Mai province, northern Thailand. Concentrations of urinary dialkylphosphates, non-specific metabolites of OPs, and NEOs and their metabolites and haematological parameters were measured in 143 male farmworkers. The Bayesian kernel machine regression model was employed to evaluate the associations. Exposure to a mixture of insecticides was significantly associated with the mean corpuscular haemoglobin concentration (MCHC) when the concentrations of all the compounds and their metabolites were at the 60th percentile or higher compared with the 50th percentile. Furthermore, exposure to clothianidin (CLO) showed a decreasing association with MCHC when all the other insecticides were at their mean concentrations. CLO was the most likely compound to reduce MCHC, and this was confirmed by sensitivity analysis. These findings suggest that exposure to NEO insecticides, especially CLO, affects the haematological status relating to haemoglobin parameters.

Smoke haze from biomass burning has been a crisis in northern Thailand. There have been plenty of reports on ambient PM 10 and PAHs but not on individual exposure during smoke haze episodes. The present study aimed to quantify urinary 1-OHP, a predominant biomarker of PAH exposure, among 200 rural school children in Om Koi and Mae Chaem districts, Chiang Mai Province, northern Thailand. Questionnaires for information regarding environmental exposure and health diaries were given out. Urine samples were collected to measure 1-OHP using high-performance liquid chromatography-fluorescence detection, HPLC-FLD (HP1100 Series/HP1046A). Proficiency testing materials were obtained from the participation of German External Quality Assessment Scheme (G-EQUAS, Erlangen, Germany) and analyzed as part of the method validation of our urinary 1-OHP method. The median urinary 1-OHP level in the school children from Om Koi District was significantly higher than that in Mae Chaem District (0.70 versus 0.24 μmol/mol cr). The present study showed the evidence that urinary 1-OHP level among school children from the selected study sites during haze episode in northern Thailand is higher than those reported in other region of Thailand and other countries.

The use of pesticides for crop production has grown in developing nations, especially in Thailand. As a result, agricultural workers are exposed to higher concentrations of organophosphate and pyre...

Organophosphate (OP) pesticides are widely used for crop protection in many countries including Thailand. Aside from causing environmental contamination, they affect human health especially by over-stimulating of the neurotransmission system. OP pesticides, as with other non-persistent pesticides, degrade quickly in the environment as well as are metabolized quite rapidly in humans. Assessing human exposures to these compounds requires analytical methods that are sensitive, robust, and most importantly, suitable for specific laboratory settings. The aim of this study was to develop and validate an analytical method for measuring 11 OP pesticide residues in human plasma and breast milk. Analytes in both plasma and breast milk samples were extracted with acetone and methylene chloride, cleaned-up using aminopropyl solid phase extraction cartridges, and analyzed by gas chromatography with flame photometric detection. The optimized method exhibited good linearity, with the coefficients of determination of 0.996–0.999 and