Urinary 3-PBA Research Articles

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.

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.

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.

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.

Association between pyrethroid pesticide exposure and hearing loss in adolescents

BackgroundHearing loss in adolescents is a serious public health problem with a high prevalence. Pyrethroids are one of the most widely applied insecticides that have been linked to neurotoxicity. However, there is no study about the effect of pyrethroid insecticide exposure on the auditory system in the general population. ObjectiveTo investigate the association between pyrethroid pesticide exposure and hearing loss in adolescents in the United States. MethodsA total of 720 adolescents aged 12–19 years who participated in the National Health and Nutrition Examination Survey (NHANES, 2007–2010) were considered. 3-phenoxybenzoic acid (3-PBA), a urinary metabolite, was applied as a biomarker to assess pyrethroid exposure. Hearing loss in adolescents was defined as a pure-tone average (PTA) > 15 dB in either ear. Multivariate linear and logistic regression analyses were conducted to examine the associations of urinary 3-PBA with PTA hearing thresholds and risk of hearing loss, respectively. ResultsThe weighted geometric mean of 3-PBA levels in urine was 0.32 μg/g creatinine, and 7.62% of adolescents had hearing loss. After adjusting for age, sex, race/ethnicity, BMI, serum cotinine, annual family income and exposure to loud noise/music, linear regression analyses found that Ln-transformed 3-PBA was positively correlated with increase of hearing thresholds in either left (β = 0.61, 95% CI: 0.20–1.01) or right ear (β = 0.52, 95% CI: 0.16–0.89). Logistic regression analyses showed that adjusted odds ratio (OR) for hearing loss in adolescents with the highest tertile (≥0.52 μg/g creatinine) of 3-PBA were 3.12 (95% CI: 1.42–6.83) compared with the lowest tertile (<0.18 μg/g creatinine), with significant linear trends across tertiles. ConclusionPyrethroid pesticide exposure was positively associated with hearing loss in U.S. adolescents. This study provides new evidence for the association between pyrethroid exposure and auditory function.

Urinary 3-phenoxybenzoic acid levels and the association with thyroid hormones in adults: Korean National Environmental Health Survey 2012–2014

BackgroundOwing to insecticidal activity at low doses with relatively low toxicity in humans, synthetic pyrethroids have been used widely for pest control in agricultural and domestic settings. Pyrethroids are suspected for potential endocrine disruption. However, the thyroid disrupting effects of pyrethroids, particularly in humans, is relatively underexplored. ObjectivesThis study aimed to report 3-phenoxybenzoic acid (3-PBA) concentrations in urine, and assess its association with serum thyroid hormone (TH) levels in a representative adult population of Korea. MethodsData obtained from representative Korean adults recruited in the Korean National Environmental Health Survey (2nd round, 2012–2014) were analyzed. Urinary 3-PBA levels were associated with serum thyroxine (T4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH) levels among the Korean adult population. ResultsUrinary 3-PBA levels among Korean adults were >3 times higher than those reported in Canada and the United States. Urinary 3-PBA levels showed negative association with serum T4, and this pattern was not changed after stratification by sex. For T3, the association varied by sex and exposure levels. Male demonstrated the same inverse association between urinary 3-PBA and T3, but female did not show such association. Among adults in the lower half of urinary 3-PBA levels, the association with T3 was significant, while that among the remainder was marginal. The association with T4 remained significant on sensitivity analysis, after controlling for other urinary chemicals. ConclusionUrinary 3-PBA levels in the general Korean adult population were found to be generally higher than those of other countries, and were associated with decreased TH levels. Considering the importance of THs, the public health implications of pyrethroid insecticide exposure warrant further studies.

The relationship of urinary 3-phenoxybenzoic acid concentrations in utero and during childhood with adiposity in 4-year-old children

BackgroundPyrethroid pesticides are reported to be the most commonly used residential insecticides worldwide. We aimed to investigate the relationship between prenatal and postnatal 3-phenoxybenzoic acid (3-PBA) concentrations, and growth and adiposity parameters in 4-year-old children. MethodWe obtained data from 578 children who participated in the prospective Environment and Development of Children (EDC) study at around 4 years of age (45–55 months) between August 2008 and July 2011. Anthropometric measurements were obtained at age 4 years. Prenatal and postnatal urinary 3-PBA concentration was measured in maternal urine samples at around 20 weeks of gestation, and in the 4-year-old children, respectively. ResultThe detection frequency of urinary 3-PBA (geometric mean concentration) was 98–99% (0.98 μg/g Cr) in maternal urine, and almost 99–100% (1.34 μg/g Cr) in 4-year-old children. Prenatal urinary3-PBA concentration was not associated with height, weight, or body mass index (BMI) z-scores at 4 years of age, regardless of sex. Postnatal urinary3-PBA concentration was not related to height z-scores, but was positively associated with weight z-scores with marginal significance among only girls (p = 0.058). Analyzed by sex, there was a significant relationship between postnatal urinary 3-PBA concentration and BMI z-scores (p = 0.015) among girls, after adjusting for covariates. ConclusionChildhood urinary 3-PBA concentration measured at 4 years of age was positively associated with BMI z-scores in 4-year-old girls, but prenatal urinary 3-PBA concentration at midterm pregnancy exhibited no association.

Association of urinary 3-phenoxybenzoic acid level with pulmonary function reduction in an urban elderly population with repeated measures data

Pyrethroids are a class of man-made insecticides associated with various adverse health outcomes including respiratory problems. However, there were limited evidences on the relation between 3-phenoxybenzoic acid (3-PBA) as a metabolite of pyrethroids and pulmonary function, particularly among elderly population who have declining pulmonary function. Therefore, we collected urine samples and performed pulmonary function test (PFT) repeatedly in a total of 559 Korean elderly living in Seoul as an urban area. After measurement of urinary 3-PBA levels, cross-sectional relations of visit-to-visit variation in 3-PBA level on visit-to-visit variation in PFT parameters were evaluated using linear mixed effect models and generalized additive mixed models after adjustment for age, sex, body mass index, smoking status, education, visit episode, and phthalate metabolite levels. The Korean elderly were highly exposed to pyrethroids with 30.2% of elderly people with 3-PBA level over reference value derived on the 95th percentile of representative samples (2 ng/mL). Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25–75) as PFT parameters showed significant reductions by an increase of 3-PBA level (FEV1, β = −1.48, p-value < 0.01; FVC, β = −1.14, p-value < 0.01; and FEF25-75, β = −1.11, p-value = 0.03). The negative associations of 3-PBA level with FEV1, FVC, and FEF25-75 were found only for females (FEV1, β = −1.64, p-value < 0.01; FVC, β = −1.47, p-value < 0.01; and FEF25-75, β = −1.06, p-value = 0.07), but not for males. However, the longitudinal effect of 3-PBA level on the trajectory of FEV1, FVC, and FEF25-75 declines in females was not found. Community-level exposure to pyrethroids was associated with pulmonary function reduction in elderly population, indicating that more stringent control of pyrethroids is necessary to protect the elderly who have declining pulmonary function.

Environmental pyrethroid exposure and diabetes in U.S. adults

Pyrethroid insecticides have been used widely as replacements for organophosphate insecticides over the past decades. While several animal studies suggest that exposure to pyrethroids can alter glucose homeostasis, there is only limited evidence of the association between environmental pyrethroid exposure and diabetes risk in human populations. Therefore, we examined the National Health and Nutrition Examination Survey (NHANES) 2007–2010 data to determine the association between environmental pyrethroid exposure and the prevalence of diabetes in the general U.S. population. Using data on 2796 participants aged 20–79 years from NHANES 2007–2010, we estimated odds ratios (ORs) and 95% confidence intervals (CI) of the association between diabetes and urinary metabolite concentration of pyrethroids using logistic regression. The weighted prevalence of diabetes was 10.3%. The weighted geometric means and detection rate of 3-phenoxybenzoic acid (3-PBA), the most common nonspecific pyrethroid metabolite, were 0.41 μg/L (95% CI: 0.38, 0.45) and 72.0%, respectively. After adjusting for sociodemographic, behavioral, and metabolic factors, we found a significant dose-response relationship between urinary 3-PBA as quartile and prevalent diabetes (p-trend=0.007). Compared to the lowest quartile of 3-PBA, the highest quartile had OR of 2.18 (95% CI: 1.18, 4.03) for diabetes. Our finding suggests pyrethroid insecticides as a potential risk factor for diabetes. Further studies should be conducted to confirm our finding and to determine if this association is causal.

Brain Activity in Farm Workers Occupationally Exposed to Pesticides in Costa Rica

Background: Exposure to pesticides has been associated with neurobehavioral deficits and structural brain anomalies in animals and humans. We examined the association between pesticide exposure and brain activity in 48 farm workers from the Zarcero County, Costa Rica. Methods: In May-August 2016, we collected urine samples from each worker and quantified concentrations of urinary metabolites for mancozeb (ethylenethiourea, ETU), chlorpyrifos (trichloropyridinol, TCPy), and pyrethroids (3-phenoxybenzoic acid, 3-PBA). We assessed brain activity throughout bilateral prefrontal cortices using functional near-infrared spectroscopy (fNIRS) while participants completed tasks related to verbal working memory (Sternberg test), executive function (Wisconsin Card Sort Test), and attention (go/no-go test). We estimated exposure-outcome associations using linear regression models adjusted for age and education. Results: Median (P25-P75) urinary ETU, TCPy, and 3-PBA creatinine-adjusted concentrations were 1.0 (0.5-1.8), 7.2 (3.3-13.6), and 1.4 (0.7-1.7) &amp;#956;g/L, respectively. We observed that higher urinary TCPy and 3-PBA creatinine-adjusted concentrations were associated with decreased working memory-related brain activity in all eight regions of interest. For example, brain activity at the most posterior region in the prefrontal cortex of the left hemisphere decreased 2.3 (-4.1, -0.5) and 3.3 (-5.5, -1.1) per two-fold increase in urinary TCPy and 3-PBA creatinine-adjusted concentrations, respectively. We also found that executive function-related brain activity at the most posterior region in the prefrontal cortex of the left hemisphere decreased 2.3 (-4.5, -0.1) and 3.6 (-6.7, -0.4) per two-fold increase in urinary ETU and 3-PBA creatinine-adjusted concentrations, respectively. Conclusion: Our findings indicate that farm workers with higher pesticide exposure levels may be under-recruiting neural resources compared to those with lower exposure levels.

Effects of 3-PBA on Complete Blood Count (CBC) and Liver Enzyme in Human: The Second Korean National Environmental Health Survey (KONEHS)

Pyrethroid were synthetic analogues insecticides as pyrethrins. They are known to be effective in insects because they are degraded by rapid metabolism in mammals. However, health effects that occur are not clearly known in human. In this study, we evaluated the effect of exposure of low concentrations of insecticide, rather than high concentration exposure, on human health.This study was performed on 5474 adults aged 19 years and older based on the Second Korean National Environmental Health Survey(KoNEHS 2012&amp;#8211;2014). We used regression analysis to examine the effects of 3-PBA(phenoxybenzoic acid, as metabolite of pyrethroid) levels in urine on the complete blood count(CBC; white blood cell, red blood cell, hemoglobin, and platelet) and liver enzymes(AST, ALT, &amp;#915;-GPT). As clinical laboratory values are different according to sex, they are stratified. Thus, urinary 3-PBA/Cr, liver enzymes were transformed logarithmically due to their skewed distribution.Geometric mean concentrations of urinary 3-PBA were 1.94&amp;#956;g/L/Cr in total, 1.59&amp;#956;g/L/Cr in men, and 2.41&amp;#956;g/L/Cr in female, respectively. Association between log-transformed urinary 3-PBA and liver enzymes were not statistically significant. However, association between log-transformed urinary 3-PBA and RBC and hemoglobin were statistically significant, respectively (adjusted coefficient&amp;#61;-0.018(0.009), p&amp;#61;0.0425;-0.043(0.025) p&amp;#61;0.0791). After stratification, there was a negative association between log-transformed urinary 3-PBA and RBC and hemoglobin only for male group (adjusted coefficient&amp;#61;-0.024(0.035), p&amp;#61;0.0385;-0.097(0.011) p&amp;#61;0.0064).Low concentrations of pyrethroid exposure showed a statistically significant decrease in RBC and hemoglobin in humans. Liver enzymes, however, tended to increase, although not statistically significant. The results of this study need to educate the public about not being exposed to pesticides, and in order to do so, we must try to find these exposure factors in our living environment.

Urinary 3-Phenoxybenzoic Acid Concentrations In Utero and in Childhood: Association with BMI Z-Score in 4-Year-Old Children

BackgroundPyrethroids, a class of ubiquitous insecticides, have been considered as endocrine-disrupting chemicals. The use of pesticides has increased over the past few decades, which raise concerns on possibility of health effects, particularly in children. However, only a few studies have been conducted to examine the relationship between 3-phenoxybenzoic acid (3-PBA) and children&amp;#8217;s health effects. Because exposure to 3-PBA may affect children&amp;#8217;s growth, we aimed to evaluate the association between prenatal and postnatal 3-PBA concentrations and body mass index in 4-year-old Korean children.MethodWe used the data from 578 children (309 boys and 269 girls; 45&amp;#8211;55 months) at 4 years of age who were born from women who participated in the Environmental and Development in Children (EDC) cohort study from August 2008 to July 2011. Urinary 3-PBA concentration from mother at around 20 weeks of gestation and 4-year-old children was measured as prenatal and postnatal 3-PBA exposure, respectively.ResultThe geometric mean of BMI z-score of 4-year-old children was 1.308 and 95 percentile of BMI z-score was 1.389. Urinary 3-PBA was detected in 98.9-99.8% of prenatal and postnatal urine samples. The relationship between 3-PBA exposure at 4-year-old and BMI z-score of 4-year-old children was positively significant (p-value&amp;#61;0.0426). After sex stratification, the association remained significant among girls (p-value&amp;#61;0.0041), but not among boys. However, there is no association between prenatal 3-PBA exposure and BMI z-score at 4 years of age(p-value&amp;#61;0.6210).ConclusionChildhood adiposity measured as BMI Z-score was associated with urinary 3-PBA concentrations in children at 4 years of age.KeywordsPyrethroid, 3-phenoxybenzoic acid, BMI Z-score, childrenFunding&amp;#8217;sThis research was supported by a grant (18162MFDS121) from Ministry of Food and Drug Safety in 2018 and Center for Environmental Health through the Ministry of Environment.

Pyrethroid Pesticide Exposure and Risk of Primary Ovarian Insufficiency in Chinese Women.

Pyrethroids are a class of widely used insecticides. Female animal studies suggested that pyrethroid exposure impaired ovarian function, which resulted in similar symptoms of primary ovarian insufficiency (POI). However, it is still unknown whether this association applies to women. In this case-control study, a total of 172 POI patients and 247 control women were recruited in Zhejiang, China. The urinary concentrations of metabolites of pyrethroids, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), as well as the serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Mullerian hormone (AMH) were determined. The associations of pyrethroid metabolites with POI and POI-related hormones were accessed using unconditional logistic regression. Higher urinary levels of 3-PBA were significantly associated with increased risk of POI [adjusted odds ratio (OR) = 2.344, 95% CI: 1.193-4.607 for the highest vs lowest quartile of 3-PBA, p = 0.013]. Stratified analyses showed that each log increase in urinary 3-PBA concentration was significantly associated with an induction in odds of 51.0% being in the highest quartile of FSH and 28.6% being in the highest quartile of LH levels, whereas a 25.9% reduction in odds of being in the highest quartile of AMH levels (All p for trend <0.05). To our knowledge, this is the first case-control study to report an association of pyrethroid exposure with increased risk of POI in women.

Screening-level Biomonitoring Equivalents for tiered interpretation of urinary 3-phenoxybenzoic acid (3-PBA) in a risk assessment context

3-Phenoxybenzoic acid (3-PBA) is a common metabolite of several pyrethroid pesticides of differing potency and also occurs as a residue in foods resulting from environmental degradation of parent pyrethroid compounds. Thus, 3-PBA in urine is not a specific biomarker of exposure to a particular pyrethroid. However, an approach derived from the use of Biomonitoring Equivalents (BEs) can be used to estimate a conservative initial screening value for a tiered assessment of population data on 3-PBA in urine. A conservative generic urinary excretion fraction for 3-PBA was estimated from data for five pyrethroid compounds with human data. Estimated steady-state urinary 3-PBA concentrations associated with reference doses and acceptable daily intakes for each of the nine compounds ranged from 1.7 μg/L for cyhalothrin and deltamethrin to 520 μg/L for permethrin. The lower value can be used as a highly conservative Tier 1 screening value for assessment of population urinary 3-PBA data. A second tier screening value of 87 μg/L was derived based on weighting by relative exposure estimates for the different pyrethroid compounds, to be applied as part of the data evaluation process if biomonitoring data exceed the Tier 1 value. These BE values are most appropriately used to evaluate the central tendency of population biomarker concentration data in a risk assessment context. The provisional BEs were compared to available national biomonitoring data from the US and Canada.

Association of pyrethroids exposure with onset of puberty in Chinese girls

Pyrethroids, a class of ubiquitous insecticides, have been considered as endocrine-disrupting chemicals (EDCs). Female animal studies suggested that early-life pyrethroids exposure might delay puberty onset. However, it remains unclear whether this association applies to human populations. A total of 305 girls at the ages of 9–15 years old were recruited in Hangzhou, China in this study. The concentration of the common metabolite of pyrethroids, 3-phenoxybenzoic acid (3-PBA), was analyzed in urine samples to reflect the exposure level of pyrethroids. The associations of 3-PBA with pubertal stages were evaluated using a multinomial logistic regression model. The geometric mean level of 3-PBA was 1.11 μg/L (1.42 μg/g for creatinine-adjusted concentration). There was a significant 45% reduction in odds of being in breast stage 3 (B3) per one-unit increase in the log-transformed 3-PBA levels [OR = 0.55 (95%CI: 0.31–0.98), p = 0.042]. A similar negative association was found between urinary 3-PBA levels with later onset by pubic hair stage 2 (P2) [OR = 0.56 (95%CI: 0.36–0.90), p = 0.015]. Similar negative association was also observed between urinary 3-PBA levels and pubertal onset indicated by menarche [OR = 0.51 (95%CI: 0.28–0.93), p = 0.029]. For the first time to our knowledge, this work reveals that pyrethroids exposure may increase the risk of delayed pubertal onset in girls.

Maternal Exposure to Pyrethroid Insecticides during Pregnancy and Infant Development at 18 Months of Age

The possible association between maternal exposure to pyrethroid insecticides (PYRs) during pregnancy and infant development was explored. Levels of exposure to PYRs was assessed by metabolite (3-phenoybenzoic acid, 3-PBA) concentration in maternal spot urine sampled in the first trimester of index pregnancy, and infant development was assessed at 18 months of age using the Kinder Infants Development Scale (KIDS), which is based on a questionnaire to the caretaker. The relationship between KIDS score and maternal urinary 3-PBA levels was examined by a stepwise multiple regression analysis using biological attributes of the mother and infant, breast feeding, and nursing environment as covariates. The analysis extracted 3-PBA and the nursing environment as significant to explain the KIDS score at 18 months of age with positive partial regression coefficients. Inclusion of fish consumption frequency of the mother during pregnancy as an independent variable resulted in the selection of fish consumption as significant, while the two variables were marginally insignificant but still with a positive coefficient with the KIDS score. The result suggested a positive effect of maternal PYR exposure on infant development, the reason for which is not clear, but an unknown confounding factor is suspected.

Predictors of Urinary 3-Phenoxybenzoic Acid Levels in 50 North Carolina Adults.

Limited data are available on the non-chemical stressors that impact adult exposures to pyrethroid insecticides based on urinary biomonitoring. The urinary metabolite, 3-phenoxybenzoic acid (3-PBA), is commonly used to assess human exposure to a number of pyrethroids. In a further analysis of published study data, we quantified urinary 3-PBA levels of 50 adults over a single, 24-h sampling period and examined the associations between the biomarker measurements and selected non-chemical stressors (demographic, lifestyle, and dietary factors). A convenience sample of 50 adults was recruited in North Carolina in 2009–2011. Participants collected individual urine voids (up to 11) and filled out activity, food, and pesticide use diaries over a 24-h sampling period. Urine voids (n = 326) were analyzed for 3-PBA concentrations using high-performance liquid chromatography-tandem mass spectrometry. 3-PBA was detected in 98% of the 24-h composited urine samples. The geometric mean urinary 3-PBA level was 1.68 ng/mL in adults. Time spent outside (p = 0.0006) was a highly significant predictor of natural log-transformed (ln) urinary 3-PBA levels, while consumption of coffee (p = 0.007) and breads (p = 0.019) and ln creatinine levels (p = 0.037) were significant predictors of urinary 3-PBA levels. In conclusion, we identified specific factors that substantially increased adult exposures to pyrethroids in their everyday environments.

Urinary Metabolites of Organophosphate and Pyrethroid Pesticides and Neurobehavioral Effects in Chinese Children.

Organophosphate (OP) and pyrethroid (PYR) pesticides are widely used in China. However, few studies have investigated the neurobehavioral outcomes of Chinese children exposed to low levels of OP and PYR. We investigated urinary metabolite levels and their association with exposure characteristics and the neurobehavior of children. For all children, biomarker measurements were made in the same interval relative to neurobehavioral testing. We analyzed the morning urine samples of 406 children aged 3-6 years from Nanjing, China. The Kruskal-Wallis and Wilcoxon rank sum tests were used to identify the associations between urinary metabolite levels and exposure characteristics. Multiple linear regression models were used to test the associations between urinary metabolite levels and neurobehavioral test scores after adjusting for covariates (e.g., sex, age, and education expense). The detection of 3,5,6-trichloropyridinol (TCP) and 3-phenoxybenzoic acid (3-PBA) in the urine was positively associated with living areas adjacent to agricultural fields and using indoor mosquito repellent incense. These two metabolites were negatively associated with the soaking time of fruits and vegetables. When treated as dichotomous variables, TCP was significantly associated with arithmetic test scores in adjusted models, and 3-PBA was significantly associated with the scores on the Chinese Binet and arithmetic tests. When treated as a continuous variable, higher urinary 3-PBA levels were significantly associated with lower cancellation test scores. Our findings suggest that exposure to organophosphate and pyrethroid pesticides may have a significant impact on children's working memory and verbal comprehension.

Association between urinary 3-phenoxybenzoic acid and body mass index in Korean adults: 1(st) Korean National Environmental Health Survey.

BackgroundAccording to US-EPA report, the use of pyrethrins and pyrethroids has increased during the past decade, and their area of use included not only in agricultural settings, but in commerce, and individual household. It is known that urinary 3-PBA, major metabolite of pyrethroid, have some associations with health effect in nervous and endocrine system, however, there’s no known evidence that urinary 3-PBA have associations with obesity.MethodWe used data of 3671 participants aged above 19 from the Korean National Environmental Health Survey in 2009–2011. In our analysis, multivariate piece-wise regression and logistic regression analysis were used to investigate the association between urinary 3-PBA (3-Phenoxybenzoic Acid) and BMI.ResultLog-transformed level of urinary 3-PBA had significantly positive association with BMI at the low-level range of exposure (p < 0.0001), and opposite associations were observed at the high level exposure (p = 0.04) after adjusting covariates. In piece-wise regression analysis, the flexion point that changes direction of the associations was at around 4 ug/g creatinine of urinary 3-PBA. As quintiles based on concentration of urinary 3-PBA increased to Q4, the ORs for prevalence of overweight (BMI ≥ 23 kg/m2) were increased, and the OR of Q5 was lower than that of Q4 (OR = 1.810 for Q4; OR = 1.483 for Q5). In the analysis using obesity (BMI ≥ 25 kg/m2) as outcome variable, significant associations were observed between obesity and quintiles of 3-PBA, however, there were no differences between the OR of Q5 and that of Q4 (OR = 1.659 for Q4; OR = 1.666 for Q5).ConclusionOur analysis suggested that low-level of pyrethroid exposure has positive association with BMI, however, there is an inverse relationship above the urinary 3-PBA level at 4 ug/g creatinine.Electronic supplementary materialThe online version of this article (doi:10.1186/s40557-015-0079-7) contains supplementary material, which is available to authorized users.