3-PBA Concentrations Research Articles

Association of urinary metabolites of non-persistent pesticides with serum sex hormones among the US females: NHANES 2013–2014

BackgroundEvidence indicated the possibility of non-persistent pesticides disrupting the homeostasis of sex hormones. However, few studies have focused on this relationship in females. We aimed to explore the relationship between non-persistent pesticide exposure and sex hormones among the US females from the National Health and Nutrition Examination Survey 2013–2014. MethodsA total of 790 females, including girls (6–11 years), female adolescents (12–19 years), and adult females (>19 years), were enrolled in this study. Age stratified associations of individual non-persistent pesticide metabolites and their mixtures with sex hormones were analyzed by weighted multiple linear regression and Bayesian kernel machine regression (BKMR) using spot urinary non-persistent pesticide measurement, including 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloropyridinol (TCPY), para-nitrophenol (PNP) and 3-phenoxybenzoic acid (3-PBA), and three serum sex hormones [total testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG)]. ResultsIn girls, weighted multivariate linear regression indicated that both 2,4-D and PNP were negatively associated with TT, and TCPY was inversely associated with SHBG. In female adolescents, TCPY was negatively associated with TT and E2, and 3-PBA was negatively associated with SHBG; positive associations were detected both in 2,4-D with SHBG, and in PNP with TT. In adult females, a higher concentration of 3-PBA was associated with higher levels of TT. The BKMR model showed that in female adolescents, the concentrations of pesticide metabolite mixtures at or above the 55th percentile were negatively related to the levels of E2 compared with their mixtures at 50th percentile, and an inverse U-shaped exposure-response function between PNP and E2 was found. ConclusionsAssociations between the four non-persistent pesticide metabolites and serum sex hormones were identified in the US females from NHANES 2013–2014 and these associations were age dependent, especially in adolescents. Large-scale cohort studies are needed to confirm these findings and elucidate the potential biological mechanisms.

The association of prenatal and childhood pyrethroid pesticide exposure with school-age ADHD traits.

Pyrethroid insecticides are commonly used in residential settings, and their use has increased rapidly. Although research has been scarce, they have been reported to be associated with impaired neurodevelopment. Moreover, susceptible exposure windows and the long-term effects of pyrethroids have not been investigated. We examined the association between pyrethroid exposure and attention-deficit/hyperactivity disorder (ADHD) symptoms over time, with exposure windows spanning from the prenatal period to school-age. Using 524 mother-child pairs, we measured urinary concentrations of 3-phenoxybenzoic acid (3-PBA), a major pyrethroid metabolite, and asked parents to fill-out the ADHD Rating Scale IV (ARS). We used Poisson regression to identify the susceptible periods of pyrethroid exposure, by correlating various 3-PBA exposure windows (prenatal, ages 2, 4, 6 and 8) with ADHD symptoms at ages 6 and 8. Doubling of prenatal and age 2 3-PBA concentrations was associated with increased ADHD symptoms at age 6 (2.7% change, 95% confidence interval [CI]: 0.3, 5.2; 5.2% change [95% CI: 0.5, 10.2], respectively). The 3-PBA concentrations at age 4 and age 6 were linked with ADHD symptoms at age 8 (2.7% change [95% CI: 0.3, 5.3]; 3.3% change [95% CI: 0.2, 6.4], respectively). There were no clear sex-specific patterns in association. Both prenatal and early-childhood exposure to 3-PBA were found to be associated with ADHD symptoms. Exposure during pregnancy, and at ages 2 to 6 were found to be susceptible periods for pyrethroid neurotoxicity at ages 6 and 8.

Environmental Pyrethroid Exposure and Cognitive Dysfunction in U.S. Older Adults: The NHANES 2001-2002.

Pyrethroid compounds are widely used in household insecticides and agricultural pesticides. Recent studies, however, report that pyrethroid exposures affect neurobehavioral function in animals and may be associated with adverse neurocognitive development in children. This study aimed to examine the association between pyrethroid exposure and cognitive dysfunction in older adults using a well-defined general population. We analyzed data from 336 individuals, aged 60–84 years, who participated in the National Health and Nutrition Examination Survey 2001–2002. We used urinary 3-phenoxybenzoic acid (3-PBA) concentration as a biomarker of pyrethroid exposures and assessed cognitive function with the digit–symbol coding test. The geometric means (±geometric standard errors) of creatinine-uncorrected and corrected urinary 3-PBA were 0.30 (±0.87) μg/L and 0.36 (±0.89) μg/g. After adjusting for sociodemographic factors, higher 3-PBA concentrations (> vs. ≤0.30 μg/g creatinine (median)) were associated with lower scores of cognitive function (−3.83 95% confidence interval: −7.11, −0.54). Significance was persistent after additionally adjusting for physical activity and smoking pack-year (−3.76 95% CI: −7.16, −0.36) and further adjusting for BMI and presence of hypertension and diabetes (−3.82 95% CI: −6.92, −0.71). Our findings suggest that pyrethroid exposure is associated with cognitive dysfunction in older adults.

Associations between 3-phenoxybenzoic acid levels and hematological measures in adults: Korean National Environmental Health Survey 2012–2014

BACKGROUND AND AIM: Pyrethroid insecticides have been widely used for pest control in agriculture and residential spaces due to their high insecticidal effectiveness and low toxicity to humans. Several animal studies suggested that exposure to pyrethroids may induce bone marrow toxicity, resulting in inhibiting blood cell production. However, no studies have reported the effect of pyrethroid insecticide exposure on hematological changes in humans without occupational exposure. This study aimed to investigate the effect of 3-phenoxybenzoic acid (3-PBA) concentrations in urine on hematological parameters in Korea's representative adult population. METHODS: We analyzed data from 6,296 Korean adults recruited in the Korean National Environmental Health Survey (2nd round, 2012–2014). A multiple linear regression analysis was used to evaluate the association of urinary 3-PBA levels with eight hematological profiles of white blood cell (WBC), red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), platelet, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). RESULTS:Urinary 3-PBA levels showed a negative association with WBC, RBC, Hb levels and a positive association with MCV levels. The association varied by sex and age. The adverse effects of 3-PBA levels on hematological parameters were more pronounced among men aged 60 years and older. Among this age group, 3-PBA concentrations were negatively associated with WBC, RBC, Hb, Hct, and MCHC levels in men. However, among adults aged below 60 years, no associations were found between 3-PBA concentrations and any of hematological measure in either male or female. The associations remained significant on sensitivity analysis after controlling other urinary chemicals. CONCLUSIONS:This is the first study reporting evidence that 3-PBA concentration in urine, at levels found in a Korean population, may influence blood cell counts. This novel finding merits further investigation to understand the impact of 3-PBA on human blood function and population health. KEYWORDS: Pesticides, Environmental epidemiology, Biomarkers of exposure, Epidemiology, Big data

Prenatal exposure to organophosphate and pyrethroid insecticides and the herbicide 2,4-dichlorophenoxyacetic acid and size at birth in urban pregnant women

BackgroundOrganophosphate insecticides and the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) are used to protect crops or control weeds. Pyrethroids are used to manage pests both in agriculture and in residences, and to reduce the transmission of insect-borne diseases. Several studies have reported inverse associations between exposure to organophosphates (as a larger class) and birth outcomes but these associations have not been conclusive for pyrethroids or 2,4-D, specifically. We aimed to investigate the association between birth outcomes and urinary biomarkers of pyrethroids, organophosphates and 2,4-D among healthy pregnant women living in New York City. MethodsWe quantified urinary biomarkers of 2,4-D and of organophosphate and pyrethroid insecticides from 269 women from two cohorts: a) Thyroid Disruption And Infant Development (TDID) and b) Sibling/Hermanos cohort (S/H). We used weighted quantile sum regression and multivariable linear regression models to evaluate the associations between a mixture of urinary creatinine-adjusted biomarker concentrations and birth outcomes of length, birthweight and head circumference, controlling for covariates. We also used linear regression models and further classified biomarkers concentrations into three categories (i: non-detectable; ii: between the limit of detection and median; and iii: above the median) to investigate single pesticides’ association with these birth outcomes. Covariates considered were delivery mode, ethnicity, marital status, education, income, employment status, gestational age, maternal age and pre-pregnancy BMI. Analyses were conducted separately for each cohort and stratified by child sex within each cohort. ResultsIn TDID cohort, we found a significant inverse association between weighted quantile sum of mixture of pesticides and head circumference among boys. We found that the urinary biomarkers of organophosphate chlorpyrifos, TCPy, and 2,4-D had the largest contribution to the overall mixture effect in the TDID cohort among boys (b = −0.57, 95%CI: −0.92, −0.22) (weights = 0.81 and 0.16 respectively) but not among girls. In the multivariable linear regression models, we found that among boys, for each log unit increase in 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of organophosphate chlorpyrifos) in maternal urine, there was a −0.56 cm decrease in head circumference (95%CI: −0.92, −0.19). Among boys in the TDID cohort, 2,4-D was associated with smaller head circumference in the second (b = −1.57; 95%CI: −2.74, −0.39) and third (b = −1.74, 95%CI: −2.98, −0.49) concentration categories compared to the first. No associations between pyrethroid and organophosphate biomarkers and birth outcomes were observed in girls analyzed in WQS regression or individually in linear regression models in TDID cohort. In the S/H cohort, head circumference increased with higher concentrations of 3-phenoxybenzoic acid (3-PBA, a biomarker of several pyrethroids) (b = 0.53, 95%CI: 0.03, 1.04) among boys and head circumference was lower among girls in the high compared to low category of 2,4-D (b = −2.27, 95%CI: − 3.98, −0.56). Birth length was also positively associated with the highest concentration of 2,4-D compared to the lowest among boys (b = 4.01, 95%CI: 0.02,8.00). ConclusionsWeighted quantile sum of pesticides was negatively associated with head circumference among boys in one cohort. Nonetheless, due to directional homogeneity assumption in WQS no positive associations were detected. In linear regression models with individual pesticides, concentrations of TCPy were inversely associated with head circumference in boys and higher concentrations of 2,4-D was inversely associated with head circumference among girls; 2,4-D concentrations were also associated with higher birth length among boys. Concentrations of 3-PBA was positively associated with head circumference among boys.

Urinary metabolites of non-persistent pesticides and serum hormones in Spanish adolescent males

ObjectiveTo assess the relationship of urinary concentrations of ethylenethiourea (ETU), the main degradation product of ethylene bis-dithiocarbamate fungicides, 3-phenoxybenzoic acid (3-PBA), a common metabolite of many pyrethroids, and 1-naphthol (1N), a metabolite of the carbamate insecticide carbaryl, with hormone concentrations in adolescent males; and to examine interactions between pesticide metabolites and polymorphisms in xenobiotic metabolizing enzymes, including CYP2C19 and CYP2D6, in relation to hormone concentrations. MethodsA cross-sectional study was conducted in 134 males from the Spanish Environment and Childhood (INMA)-Granada cohort. Urine and serum samples were collected from participants during the same clinical visit at the age of 15–17 years. First morning urine void was analyzed for concentrations of ETU, 3-PBA, and 1N. Serum was analyzed for concentrations of reproductive hormones (testosterone, 17β-estradiol [E2], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Müllerian hormone [AMH], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), insulin growth factor 1 (IGF-1), adrenocorticotropic hormone (ACTH), and cortisol. CYP2C19 G681A and CYP2D6 G1846A polymorphisms were determined in blood from 117 participants. Multiple linear regression, interaction terms, and stratified analyses were performed. ResultsUrinary ETU was detected in 74.6% of participants, 1N in 38.1%, and 3-PBA in 19.4%. Positive associations between detectable 3-PBA and TT3 and between detectable 1N and DHEAS were found, and marginally-significant associations of 1N with reduced E2 and FSH were observed. Poor CYP2C19 and CYP2D6 metabolizers (GA and AA genotype carriers) showed a greater increase in DHEAS for detected versus undetected 1N compared with GG genotype carriers. Poor CYP2D6 metabolizers (1846 GA and AA genotypes) evidenced increased cortisol for detected versus undetected ETU. ConclusionsThe associations observed between urinary pesticide metabolites and altered thyroid and reproductive hormones are novel and should be verified in studies with larger sample size. Further research on gene-environment interactions is warranted to establish individual susceptibility to pesticides and the risk of adverse health effects.

Synthetic pyrethroids common metabolite 3-phenoxybenzoic acid induces caspase-3 and Bcl-2 mediated apoptosis in human hepatocyte cells

Synthetic pyrethroids are a group of insecticides frequently used in public health and agriculture, and 3-PBA is a common metabolite of them. Although the liver is the primary organ responsible for metabolizing many compounds including pesticides, to the authors’ knowledge there have been no studies on the direct hepatotoxic effects of 3-PBA. Therefore, this study aimed to investigate the possible hepatotoxic effects of 3-PBA on a Human Hepatoma Cell Line (HepG2) and the underlying apoptotic mechanisms. Firstly, an LC50 of 1041.242 µM was calculated for 3-PBA by using the WST-1 test with concentrations ranging between 1 µM and 10 mM. Following that, the HepG2 cells in the experimental group were exposed to 3 different concentrations of 3-PBA (1/5 LC50, 1/10 LC50 and 1/20 LC50) for 24 hours. The apoptotic mechanism was evaluated by using flow cytometry, and immunofluorescence assays for Caspase 3 and Bcl-2. In the flow cytometry assay, the total number of apoptotic cells increased in a dose dependent manner (p < 0.05). In the immunofluorescence assay, the Caspase 3 protein showed strong immunoreactivity in the experimental groups, while the reaction to the Bcl-2 protein was minimal. These results demonstrated that 3-PBA has a significant hepatotoxic effect on HepG2 cells and induces apoptosis via the regulation of Caspase-3 and Bcl-2. Furthermore, our results could further the understanding of the fundamental molecular mechanisms of 3-PBA hepatotoxicity. More studies are needed to determine the effects of long-term exposure to 3-PBA and also the molecular mechanisms underlying hepatotoxicity.

Pyrethroid exposure among children residing in green versus non-green multi-family, low-income housing.

Background:There is growing concern about children’s chronic low-level pesticide exposure and its impact on health. Green building practices (e.g. reducing leakage of the thermal and pressure barrier that surrounds the structure, integrated pest management, improved ventilation) have the potential to reduce pesticide exposure. However, the potential impact of living in green housing on children’s pesticide exposure is unknown.Objective:To address this question, a longitudinal study of pyrethroid metabolites (3-phenoxybenzoic acid [3-PBA], 4-fluoro-3-phenoxybenzoic acid [4-F-3-PBA], trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid [trans-DCCA]) in first morning void urine, collected from 68 children from New Orleans, Louisiana residing in green and non-green housing was conducted.Methods:Children were followed for one year with three repeated measures of pesticide exposure. Generalized Estimating Equations examined associations between housing type (green v non-green) and urinary pyrethroid metabolite concentrations adjusting for demographic and household factors over the year.Results:Ninety-five percent of samples had detectable concentrations of 3-PBA (limit of detection [LOD]: 0.1 μg/L); 8% of 4-F-3-PBA (LOD: 0.1 μg/L), and 12% of trans-DCCA (LOD: 0.6 μg/L). In adjusted models, green housing was not associated with statistically significant differences in children’s 3-PBA urinary concentrations compared to non-green housing.Significance:In this study, green building practices had no impact on children’s pyrethroid urinary concentrations. Further studies with larger sample sizes are needed to confirm these findings.

Concentrations of urinary biomarkers and predictors of exposure to pyrethroid insecticides in young, Polish, urban-dwelling men

Pyrethroid insecticides are a class of pesticides with multiple agricultural and residential applications. However, widespread use of these chemicals may pose a threat to human health. Biomarkers of pyrethroid exposure are frequently detected in populations around the world, but some groups may be underrepresented. Moreover, there is an ongoing debate on factors contributing to pyrethroid burden in humans. To address these problems, we measured urinary biomarkers of pyrethroid exposure in urine samples from 306 young men living in urban area of Łódź, Poland, and gathered questionnaire data to identify predictors of exposure. Limit of detection (LOD) of gas chromatography–mass spectrometry (GC–MS) method was 0.1 ng/mL for all quantified pyrethroid metabolites, namely cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA), and 3-phenoxybenzoic acid (3-PBA). Detection rate ranged from 32% (cis-DBCA) to 76% (trans-DCCA). Concentrations of urinary biomarkers in studied sample were in lower range of these observed in similar studies, with unadjusted geometric means (GMs) of most prevalent biomarkers, trans-DCCA and 3-PBA, equal to 0.268 and 0.228 ng/mL, respectively. As for questionnaire data, the statistical analysis revealed that non-dietary factors, especially dog ownership and pesticide use on household pets, contribute significantly to urinary trans-DCCA and 3-PBA concentrations (p ≤ 0.009). Moreover, a few dietary sources of exposure were identified, such as seeds and nuts consumption for 3-PBA (p < 0.001) and vegetable juice intake for trans-DCCA (p = 0.015). Multivariate analyses further highlighted the importance of non-dietary factors in pyrethroid exposure. Compared to other works, our results confirm widespread exposure to pyrethroids observed in other studies and stress the role of residential pyrethroid use in pyrethroid burden in humans.

Erratum: Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort.

Erratum: Maternal Peripartum Serum DDT/E and Urinary Pyrethroid Metabolite Concentrations and Child Infections at 2 Years in the VHEMBE Birth Cohort.

Urinary 3-phenoxybenzoic acid (3-PBA) concentration and pulmonary function in children: A National Health and Nutrition Examination Survey (NHANES) 2007-2012 analysis.

Epidemiological studies have reported association of urinary 3-phenoxybenzoic acid (3-PBA), a major metabolite of pyrethroid insecticides (PYRs), with respiratory disease. However, knowledge regarding its effect on pulmonary function in susceptible children is limited. This study aimed to assess the associations between environmental 3-PBA concentrations and pulmonary function in children aged 6-17 years. Using data on 1174 children aged 6-17 years from the U.S. National Health and Nutrition Examination Survey (NHANES) 2007-2012, the exposure to PYRs was assessed by measuring urinary 3-PBA concentrations and pulmonary function was assessed by spirometry. Multivariable linear regression and generalized linear models (GLMs) were used to examine the associations between 3-PBA concentrations and pulmonary function in children, controlling for confounders. We found that 3-PBA concentrations were inversely associated with forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) in the pediatric population (p-trends<0.05). When stratified by age (6-10 and 11-17years) and gender (boys and girls), the adverse effects of PYR exposures on pulmonary function were more pronounced among boys aged 11-17 years. Among this age group, 3-PBA concentrations were negatively associated with FEV1, FVC, forced expiratory flow between 25% and 75% of FVC (FEF25-75%), and PEF. However, among children aged 6-10years, no associations were found between 3-PBA concentrations and any of the pulmonary function measures, in either boys or girls. Our findings suggest that environmental PYR exposures may adversely affect children's pulmonary function, with the strongest associations among 11-17 years old boys.

Variability of urinary pyrethroid biomarkers in Chinese young-aged men and women over one year.

Pyrethroids are a class of the most commonly used insecticides. The urinary metabolites are usually used as biomarkers of pyrethroid exposures in humans. In this study, the temporal variability of urinary pyrethroid biomarkers was investigated among 114 Chinese young-aged adults who provided up to 4-11 urine samples over one year. The detection rates of four urinary pyrethroid biomarkers, 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F-3PBA), trans-2,2-(dichloro)-2-dimethylvinylcyclopropane carboxylic acid (trans-DCCA) and cis-2,2-(dichloro)-2-dimethylvinylcyclopropane carboxylic acid (cis-DCCA) were 100%, 8%, 69% and 44%, respectively. The intraclass correlation coefficient (ICC) estimates for 3PBA indicated poor reproducibility (<0.15) in the spot urine samples of young-aged adults over a week, month and year. Log-transformed 3PBA used the least number of random spot urine samples (≥4) per person, which would provide a reliable biomarker estimate (ICC≥0.40) over a year. As the predictors of the top 33% yearly average 3PBA concentrations, the sensitivity and specificity of 3PBA ranged from 0.25 to 0.89, 0.58 to 0.96, respectively. Based on the results of this study, we recommend at least 4 urine samples collected 3 months apart for prospective assessment of pyrethroid exposure in the epidemiological studies to estimate exposure-response relationships between pyrethroids and health outcomes with relative long-term exposure periods.

In utero pyrethroid pesticide exposure in relation to autism spectrum disorder (ASD) and other neurodevelopmental outcomes at 3 years in the MARBLES longitudinal cohort

BackgroundWe assessed the relationships between prenatal pyrethroid pesticide exposure and autism spectrum disorders (ASD) or non-typical development (non-TD) at 3 years. MethodsParticipants were mother-child pairs (n = 201) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Because familial recurrence risk is high, MARBLES enrolls pregnant women with a family history of ASD. Children from these pregnancies were clinically assessed at 3 years of age and classified into 3 outcome categories: ASD, typically developing (TD), or non-TD (neither TD or ASD). Repeated maternal second and third trimester urine samples were analyzed for pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). Multinomial logistic regression was used to obtain relative risk ratios (RRR) linking 3-PBA concentrations averaged across each trimester and over pregnancy with child's outcome: ASD or non-TD vs. TD. Models were adjusted for specific gravity, maternal pre-pregnancy BMI, prenatal vitamin use, birth year, home-ownership, and pregnancy concentrations of TCPy (3,5,6-trichloro-2-pyridinol, a metabolite of chlorpyrifos). ResultsThe median specific gravity corrected 3-PBA concentration of all samples was 1.46 ng/mL. Greater second trimester 3-PBA concentrations were associated with a relative risk ratio (RRR) for ASD of (RRR: 1.50 (95% CI 0.89 to 2.51), p = 0.12). There were no differences between non-TD and TD. ConclusionsThis study found no evidence for differences in 3-PBA comparing non-TD with TD. A modestly elevated RRR was found comparing second trimester urinary 3-PBA concentrations for ASD versus TD; however, the confidence interval was wide and hence, these findings cannot be considered definitive.

Urinary Metabolites of Pyrethroid Insecticide in Relation to GABA Level and Hand Wipes Sample of Young Children in Urban Area, Bangkok Thailand

Exposure to pyrethroids were commonly used in households affects the nervous system in children. Data on pyrethroids exposure were related to neurotransmitter gamma-aminobutyric acid (GABA) is unknown. This study was investigated relationship between 3-PBA metabolite and GABA concentration, hand wipes and determine factors related to pyrethroids metabolite among young children in urban areas. Children aged 2-3 years were provided urine sample (n = 80), and their mothers completed a questionnaire. Urine samples were analyzed for the 3-PBA metabolite and hand wipes samples were analyzed pyrethroids contamination. Both were analyzed by gas chromatography (GC/MS). GABA was analyzed from urine sample using an enzyme-linked immunosorbent assay kit (ELISA). Spearman correlations were used to determine relationship between 3-PBA metabolite and GABA concentrations, hand wipes sample and binary logistic regression were used to determine association between 3-BPA metabolite and factor variables. Our results were presented that an increase of 3-PBA metabolite concentration was significantly correlated with low GABA concentration in urine children sample (rs = -0.230, p-value 0.004). Moreover, the increase of 3-PBA metabolite was significantly associated with increase hand wipes sample (including cypermethrin and allethrin) (rs = 0.226, p-value &lt; 0.05). In addition, genders and always walk bare feet inside household in a day were significantly associated with increased 3-PBA metabolite concentration (p-value = 0.041, OR = 0.333, 95%CI 0.116 - 0.956) and (p-value = 0.009, OR = 6.789, 95%CI 1.597 - 28.854), respectively. Hence, these factors could affect the levels of the neurotransmitter GABA in pyrethroids-exposed children. We suggest that should be provided education, awareness and management to reduce the risk from long-term PYR insecticide exposure of children living in households. Key words: 3-PBA metabolite, GABA, hand wipes sample, children, households

Exposure to pyrethroid pesticides and ovarian reserve

IntroductionSynthetic pyretroids are among the most common pesticides currently used worldwide. Animal studies suggest that exposure to pyrethroids could dysregulated the function of the ovary, mainly follicular development and/or synthesis of the reproductive hormone. Nevertheless data regarding the effect of exposure on female ovarian function is limited. So the aim of the present study is to assess the effect of exposure to synthetic pyrethroids on ovarian reserve. Materials and MethodsThe study population consists of 511 females aged 25–39 years attending infertility clinics for diagnostic purposes, because of couples’ infertility. Validated gas chromatography ion-tap mass spectrometry method was used to assess the urinary concentrations of pyrethroid metabolites (CDDCA (cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid), TDDCA (trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid), 3PBA (3-phenoxybenzoic acid) and DBCA (cis-2,2-dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid)). Ovarian reserve was assessed using parameters of ovarian reserve (antral follicle count and concentrations of hormones: AMH (anti-Mullerian hormone), FSH (follicle stimulating hormone) and E2 (estradiol)). ResultsIn the present analysis the association was found between urinary concentrations of 3-PBA and levels of AMH (p = 0.03), FSH (p = 0.04) and antral follicle count (p = 0.02). Urinary level of CDCCA, TDCCA and DBCA was not associated with any examined parameters of ovarian reserve. ConclusionsSynthetic pyrethroids may affect female ovarian reserve. As this is the first, preliminary study the results need confirmation in a further detailed investigations.

Longitudinal exposure to pyrethroids (3-PBA and trans-DCCA) and 2,4-D herbicide in rural schoolchildren of Maule region, Chile

BackgroundSeveral studies showed that early exposure to pesticides affects the development and health of children. In Maule, there is previous evidence of the high exposure to organophosphate pesticides (OP) of schoolchildren. However, to date, there are no studies assessing exposure to pyrethroids and the herbicide 2,4-D.Objetive.To evaluate children's exposure to pyrethroids insecticides 3-phenoxybenzoic acid (3-PBA), trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA) and 2,4 dichlorophenoxyacetic acid (2,4-D) herbicides. MethodLongitudinal study with 48 schoolchildren from two rural schools in the Maule region, Chile. Urinary metabolites of pyrethroids 3-PBA, Trans-DCCA and 2,4-D herbicides were evaluated in 2016 and 2017. Mann-Whitney U for repeated measurements and Spearman's rho correlation tests were used for data analysis. Also, we used a system of impulsive differential equations for mathematical modeling. ResultsAll the schoolchildren assessed had more than two pesticide urinary metabolites in both years, with the 3-PBA metabolite being the most frequent. There was an increase in concentrations of urinary 3-PBA in November 2017, compared to 2016 (from 0.69 μg/L to 1.90 μg/L). In 2016, the specific metabolites of 3-PBA were correlated with Trans-DCCA, 2,4-D, chlorpyrifos, diazinon, and para-nitrophenol. In 2017, 3-PBA was correlated with 2,4-D, and Trans-DCCA. The concentrations of 3-PBA of Chilean children were higher than studies conducted in the USA that found an association of prenatal exposure to these metabolites with cognitive difficulties. ConclusionsWe found high concentrations of pyrethroid metabolites among all the schoolchildren assessed, which may impact on their health and development. These insecticides had received no attention from the scientific community in Chile, and neither from the government agencies, despite the increased use of these chemicals in recent years. This is the first study in South America that confirms the exposure to pyrethroids and herbicides through biomarkers in human population living near farm fields.

Residential pyrethroid insecticide use, urinary 3-phenoxybenzoic acid levels, and attention-deficit/hyperactivity disorder-like symptoms in preschool-age children: The Environment and Development of Children study

Previous animal studies have reported that pyrethroids can cause dopamine system abnormalities and attention-deficit/hyperactivity disorder (ADHD) phenotypes. However, epidemiological studies investigating the associations between pyrethroid exposure and ADHD are limited. We aimed to investigate the association between pyrethroid exposure and ADHD-like symptoms among preschool-age children. We used data from 385 children at 4 years of age participating in the Environment and Development of Children (EDC) study. We evaluated pyrethroid exposure through questionnaires and urinary 3-phenoxybenzoic acid (3-PBA) concentrations. We assessed ADHD-like symptoms using the Korean ADHD rating scale (K-ARS). We conducted negative binomial regressions to evaluate the associations between pyrethroid exposure and ADHD-like symptoms. Residential use of insecticide adhesive (β = 0.42, 95% CI: 0.11, 0.74) and insecticide spray (β = 0.33, 95% CI: 0.08, 0.59) was associated with an increase in log-transformed creatinine-adjusted urinary 3-PBA concentrations. Residential insecticide adhesive use was associated with a 51.6% increase in K-ARS scores (95% confidence interval [CI]: 6.3, 116.1) among boys, when compared with non-users. When compared with creatinine-adjusted 3-PBA levels <0.50 μg/g creatinine, creatinine-adjusted 3-PBA levels ≥3.80 μg/g creatinine were associated with a 58% increase in K-ARS scores (95% CI: 0.1, 150.5) among boys. We found associations of residential pyrethroid insecticide use and urinary 3-PBA concentrations with K-ARS scores among preschool-age boys. Since the present study explored cross-sectional associations in preschool-age children, the possibility of reverse causality cannot be dismissed. Further studies implementing a cohort study design are warranted.

Effect of pyrethroid insecticides exposure in relation to pyrethroid metabolite and GABA concentration of young children, Bangkok Thailand

Exposure to pyrethroids (PYR) commonly used in households affects nervous system in children. Data on pyrethroids exposure related to neurotransmitter gamma-aminobutyric acid (GABA) is unknown. This study aims to investigate a relationship between urinary pyrethroids metabolite and GABA concentration, and determine factors related to pyrethroids metabolite among young children in urban areas in Bangkok, Thailand. Urine samples (n = 80) were collected from children aged 2–3 years in April – May 2019 and their mothers completed a questionnaire. Urinary metabolite, 3-phenoxybenzoic acid (3-PBA), was analyzed by gas chromatography (GC/MS) and GABA was measured by enzyme-linked-immunosorbent assay kit (ELISA). The result showed that median concentration of 3-PBA metabolite was 1.46 µg/mL and GABA median concentration was 355.11 ng/mL. The 3-PBA concentration was negatively correlated with GABA concentration (rs= −0.230, p < 0.05). 3-PBA concentration were significantly associated with personal exposure factors, use of insecticide coil, frequency of PYR insecticide use, and frequency of floor-cleaning (p < 0.05). Daily use of insecticide coil in households can cause children exposure to PYR while walking bare feet. Consequently, these factors may affect neurotransmitter GABA level in PYR exposed children. This study suggest that should give education and awareness to reduce risk of PYR insecticide exposure to children living in households.

Pyrethroid exposure, attention and executive function in 6-year old children from the Infants′ Environmental Health Study (ISA)

OPS 55: Pesticides and neurological outcomes, Room 412, Floor 4, August 26, 2019, 1:30 PM - 3:00 PM Background: Pyrethroid insecticides may impair children’s neurodevelopment but little evidence from prospective studies is available. In Costa Rica, pyrethroids are widely used for vector control. We examined whether prenatal and current pyrethroid exposure was associated with impaired attention and executive function in children from the Infants Environmental Health Study (ISA). Methods: To evaluate attention and executive function, we applied the Conners Continuous Performance Test (CPT-II) and Dimensional Change Card Sort (DCCS in 6-year old children (mean 6.4 ± 0.4 years) (n=268). We obtained repeated urine samples during pregnancy and 5-6 years of age, determined 3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylicacid (DCCA) and 3-phenoxybenzoicacid(3-PBA), and summed concentrations of both. We subsequently ran separate linear regression models for log-10 transformed mean prenatal, and mean child metabolite concentrations and CPT-II, and ran separate logistic regression model for DCCS. We adjusted a priori for child age, child sex, HOME score, and maternal education. We also ran analysis stratified by sex. Results: Median (p25-p75) prenatal and current specific gravity-adjusted summed DCCA and 3PBA were 2.4 (1.3-3.9) µg/L and 6.4 (3.8-10.5) µg/L, respectively. Prenatal summed DCCA and 3PBA concentrations were associated with increased CPT-II T-scores of error commissions for boys (ß= 4.5, 95%CI -0.1, 9.1, per ten-fold increase in exposure), but not for girls (ß= -5.1, 95%CI -11.9, 1.8), or all children (1.6, 95%CI -2.3, 5.6). Prenatal summed DCCA and 3PBA were associated with lower scores of DCCS for all children (OR=0.25; 95% 0.1-0.9). Current DCCA and 3PBA concentrations were not associated with measures of attention or executive function.Conclusion: Children aged six years with higher prenatal exposure to pyrethroids had poorer executive function as compared to children with lower prenatal exposure. Boys with higher prenatal exposure also had poorer attention, whereas girls did not. Prenatal exposure to pyrethroid may affect children’s neurodevelopment, some effects may be stronger in boys.

Prenatal exposure to DDT and pyrethroids and humoral response to vaccines among South African children from an area sprayed for malaria control

OPS 60: Social factors and environmental health across the world, Room 210, Floor 2, August 27, 2019, 1:30 PM - 3:00 PM Background/Aim: Animals studies strongly suggest that exposure to insecticides such as DDT and pyrethroids may inhibit immune response to vaccines. However, few human studies have investigated this question and none have done so in communities where insecticides are used to control malaria as part of Indoor Residual Spraying programs. These communities experience high exposure to insecticides and may be particularly susceptible to their toxic effects due to poverty, malnutrition and poor health. Our objective was thus to evaluate whether prenatal exposure to DDT and pyrethroids was associated with reduced immune response to vaccines at age 3.5 and 5 years among South African children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) birth cohort study. Methods: Between August 2012 and December 2013, we enrolled 752 women when they presented for delivery at Tshilidzini hospital in the city of Thohoyandou. We collected urine and blood samples at delivery for the measurement of pyrethroid metabolites and DDT via gas chromatography-mass spectrometry, respectively. At age 3.5 and 5 years, we measured measles, tetanus and Haemophilus influenzae b (Hib)-specific antibody titers in serum via enzyme-linked immunosorbent assay (ELISA). Results: Percentages of fully-vaccinated children with antibody titers below protective levels were 5.6% for measles, 31.1% for tetanus and 29.1% for Hib. Prenatal exposure to pyrethroids was associated with elevated risks of low measles (but not tetanus and Hib) antibody titers at 3.5 years. Each 10-fold increase in maternal urinary concentrations of 3-PBA, trans-DCCA and cis-DCCA was associated with relative risks of 1.85 (95%CI=0.98, 3.49), 1.84 (95%CI=1.09, 3.09) and 2.43 (95%CI=1.38, 4.29), respectively. No associations were found with DDT and DDE. Associations with antibody titers at age 5 will also be presented. Conclusion: Results suggest that prenatal exposure to pyrethroids may inhibit immune response to vaccines among South African children.