Urinary 3-phenoxybenzoic Acid Research Articles

A Novel Approach to Integrate Human Biomonitoring Data with Model Predicted Dietary Exposures: A Crop Protection Chemical Case Study Using Lambda-Cyhalothrin.

The appropriate use of human biomonitoring data to model population chemical exposures is challenging, especially for rapidly metabolized chemicals, such as agricultural chemicals. The objective of this study is to demonstrate a novel approach integrating model predicted dietary exposures and biomonitoring data to potentially inform regulatory risk assessments. We use lambda-cyhalothrin as a case study, and for the same representative U.S. population in the National Health and Nutrition Examination Survey (NHANES), an integrated exposure and pharmacokinetic model predicted exposures are calibrated to measurements of the urinary metabolite 3-phenoxybenzoic acid (3PBA), using an approximate Bayesian computing (ABC) methodology. We demonstrate that the correlation between modeled urinary 3PBA and the NHANES 3PBA measurements more than doubled as ABC thresholding narrowed the acceptable tolerance range for predicted versus observed urinary measurements. The median predicted urinary concentrations were closer to the median measured value using ABC than using current regulatory Monte Carlo methods.

A novel biomonitoring method to detect pyrethroid metabolites in saliva of occupationally exposed workers as a tool for risk assessment

Saliva is valuable in exposure assessment having been successfully used for drug and environmental pollutant detection, providing a surrogate measure of plasma concentrations. Pyrethroid biomarkers have not previously been assessed in saliva, although are prime candidates for saliva detection. This study’s objectives were to (1) develop a liquid-liquid extraction (LLE) method to quantify six pyrethroid metabolites using gas chromatography/ion trap mass spectrometry and (2) assess its application for an occupationally exposed population. Several solvents and mixing protocols were optimized for metabolite recovery. The optimized method was applied to a population of pest control operators (PCOs) and compared against a urine sample before and after a full workday using pesticides. A questionnaire collected demographic information, occupational history, and occupational and non-occupational exposure data. LLE recoveries ranged from 85–104% and 72–88% for toluene and dichloromethane using slow mixing, and 49–103% for methyl tert-butyl ether by fast mixing. Urinary 3-Phenoxybenzoic acid (3PBA) was detected in 100% of pre- and post-work urine samples. Three PCOs had increased urinary pyrethroid metabolite levels post-work. Salivary 3PBA was present below detection limit in two of the three PCO’s post-work saliva samples, demonstrating that salivary 3PBA could be measured in PCOs after the workday. This study presents preliminary findings of a potential, low-risk biomonitoring technique that may be utilized in future occupational pyrethroid exposure and risk assessment research.

Exposure to biocides and its association with atopic dermatitis among children and adolescents: A population-based cross-sectional study in South Korea

BackgroundBiocides have emerged as a contributor to the rising cases of atopic dermatitis among children and adolescents. Previous animal studies suggested that phenols, parabens, and pyrethroid insecticides present in these products might play a role in atopic dermatitis. However, there's limited epidemiological evidence confirming the individual or combined effects of exposure to these chemicals on atopic dermatitis in young populations. This study aimed to investigate the association between phenol, paraben, and pyrethroid metabolite levels in urine and atopic dermatitis among Korean children and adolescents MethodsWe analyzed 556 preschool children (3–5 years), 701 schoolchildren (6–11 years), and 731 adolescents (12–17 years) enrolled in the 4th Korean National Environmental Health Survey (KoNEHS) (2018–2020). We used logistic regression and Bayesian kernel machine regression to evaluate the association between atopic dermatitis and individual or mixed exposure to urinary triclosan (TCS), parabens (methylparaben, ethylparaben, propylparaben, and butylparaben), and 3-phenoxybenzoic acid (3-PBA) levels. ResultsUrinary TCS levels were positively associated with atopic dermatitis in schoolchildren. When stratified by sex, male schoolchildren exhibited an increasing prevalence of atopic dermatitis as their urinary TCS and 3-PBA levels increased. The combined effect of biocide mixtures on atopic dermatitis was also significantly increased in male schoolchildren, with TCS as the main contributor. ConclusionsThese study findings suggest that biocides at levels found in Korean children and adolescents affect atopic dermatitis.

Associations of pyrethroid exposure with skeletal muscle strength and mass.

This study aimed to examine the associations of pyrethroid exposure with handgrip strength and skeletal muscle mass and potential modification effects in US adults. The data from the National Health and Nutrition Examination Survey was used. Handgrip strength was determined with a handgrip dynamometer, and we quantified muscle mass by using the appendicular skeletal muscle index (ASMI). Urinary 3-Phenoxybenzoic Acid (3-PBA), a validated biomarker for pyrethroid exposure, was used in the primary analysis. After adjusting for other covariates, participants exposed to the highest tertile of 3-PBA exposure had significantly lower handgrip strength (β = -1.88, 95% CI: -3.29, -0.23, P = 0.026) than those exposed to the lowest tertile of 3-PBA. Similarly, the 3-PBA exposure was marginally significantly associated with ASMI (Tertile 3 vs. Tertile 1: β = -0.07, 95% CI: -0.14, -0.01, P = 0.056). Significant interactions were found between 3-PBA and body mass index (BMI) on handgrip strength and ASMI (P interaction < 0.05), which indicated a potential moderation effect of BMI on the associations. In conclusion, pyrethroid exposure was adversely associated with handgrip strength and skeletal muscle mass, especially in overweight and obese populations. Further studies are warranted to confirm our results and to explore the potential mechanisms.

Obesity modifies the association of environmental pyrethroid exposure with glucose homeostasis in the US general adults

Environmental pyrethroids are concerning due to their widespread residues and potential implications on human health. We aimed to assess the association of pyrethroid exposure with glucose homeostasis and examine the interaction between obesity and pyrethroid exposure. A total of 4233 US general adults from the National Health and Nutrition Examination Survey with measured urinary pyrethroid metabolites, fasting plasma glucose (FPG), fasting insulin (FINS), and glycated hemoglobin A1c (HbA1c) were included in the study. The homeostasis model assessment (HOMA2) calculator was utilized to assess insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS), and beta-cell function (HOMA2-β). We estimated the associations of pyrethroid metabolites with glucose homeostasis parameters (FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β) using multivariate linear regression models and restricted cubic spline models and further assessed the interaction between obesity and pyrethroid metabolites on glucose dyshomeostasis. Urinary 3-phenoxybenzoic acid (3-PBA) was the most detected pyrethroid metabolite (81%) with a median concentration of 0.43 (interquartile range 0.20–1.01) μg/g urinary creatinine. Compared with the participants in the lowest quartile, those in the highest quartile of 3-PBA had a 1.93% (95% confidence interval: 0.46%, 3.42%), 6.69% (1.96%, 11.64%), 1.60% (0.64%, 2.57%), 7.06% (2.33%, 12.01%), −6.59% (−10.72%, −2.28%), and 1.10% (−2.69%, 5.04%) alteration in FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β, respectively. The restricted cubic spline model displayed a linear positive association between 3-PBA and FPG, FINS, HbA1c, and HOMA2-IR, and a negative association with HOMA2-IS (all P for overall <0.05 and P for non-linear >0.05). Additionally, the association between urinary 3-PBA and FPG was modified by general obesity (P for interaction <0.05), with a more pronounced association observed in obese participants than in non-obese participants. Our findings suggested that pyrethroid exposure was associated with glucose dyshomeostasis. General obesity significantly heightened the association between pyrethroid exposure and increased FPG level.

Pyrethroid and Chlorpyrifos Pesticide Exposure, General Intellectual Abilities, and Executive Functions of School Children from Montevideo, Uruguay.

Children's developing brains are susceptible to pesticides. Less is known about the effect of exposure to chlorpyrifos and pyrethroids on executive functions (EF). We measured urinary 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos, and urinary 3-phenoxybenzoic acid (3-PBA), a general, nonspecific metabolite of pyrethroids in first-grade children from Montevideo, Uruguay (n = 241, age 80.6 ± 6.4 months, 58.1% boys). EFs were assessed with the Intra-dimensional/Extra-dimensional shift (IED), Spatial Span (SSP), and Stockings of Cambridge (SOC) tests from the Cambridge Neuropsychological Test Automated (CANTAB) Battery. General intellectual ability (GIA) was assessed using the Woodcock-Muñoz Cognitive battery. Median (range) urinary TCPy and 3-PBA levels were 16.7 (1.9, 356.9) ng/mg of creatinine and 3.3 (0.3, 110.6) ng/mg of creatinine, respectively. In multivariable generalized linear models, urinary TCPy was inversely associated with postdimensional errors on the IED task β [95% CI]: -0.11 [-0.17, -0.06]. Urinary 3-PBA was inversely associated with the total number of trials -0.07 [-0.10, -0.04], and the total number of errors -0.12 [-0.18, -0.07] on the IED task. When TCPy and 3-PBA were modeled together, the associations did not differ from single-metabolite models. We found no evidence of effect modification by blood lead level (BLL). Pesticide exposure may affect EF performance in urban children.

Detections of organophosphate and pyrethroid insecticide metabolites in urine and sweat obtained from women during infrared sauna and exercise: A pilot crossover study.

Synthetic pesticides such as organophosphates and pyrethroids are commonly used worldwide yet the metabolic and long-term human health effects of these environmental exposures are unclear. Urinary detections of metabolites involving both classes of insecticides have been documented in various global populations. However, reports documenting similar detections in human sweat are sparse. In this study, the concentrations of four insecticide metabolites were measured using liquid chromatography coupled with tandem mass spectrometry in repeated sweat and urine collections (n=85) from 10 women undergoing three interventions (control, infrared sauna and indoor bicycling) within a single-blinded randomised crossover trial. The Friedman test with post-hoc two-way analysis of variance, the related-samples Wilcoxon signed rank test and the Spearman's rank-order correlation test were used to analyse the results. Organophosphate metabolites were detected in 84.6% (22/26) and pyrethroids in 26.9% (7/26) of the collected sweat samples (pooled per individual, per intervention). Urinary concentrations of three of the four metabolites marginally increased after infrared sauna bathing: 3,5,6-trichloro-2-pyridinol (z=2.395, p=0.017); 3-phenoxybenzoic acid (z=2.599, p=0.009); and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (z=2.090, p=0.037). Urinary 3-phenoxybenzoic acid also increased after exercise (z=2.073, p=0.038) and demonstrated the most temporal variability (days to weeks) of any of the urinary metabolites. Definitive sweat/urine correlations were not demonstrated. These results indicate metabolites from organophosphate and pyrethroid pesticides can be detected in human sweat and this raises intriguing questions about perspiration and its role in the metabolism and excretion of synthetic pesticides.

Evaluating how occupational exposure to organophosphates and pyrethroids impacts ADHD severity in Egyptian male adolescents

BackgroundAttention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in attention and hyperactivity/impulsivity that cause impairments to daily living. An area of long-standing concern is understanding links between environmental toxicants, including pesticides, and the development or worsening of ADHD. ObjectivesThe present study evaluated associations between occupational pesticide exposure, specifically organophosphate (OP) pesticides, chlorpyrifos (CPF) and the pyrethroids (PYR) alpha-cypermethrin (αCM) and lambda-cyhalothrin (λCH), and symptoms of ADHD in a longitudinal study among Egyptian adolescent males. MethodsParticipants (N = 226, mean age = 17) were Egyptian adolescent males who either applied pesticides or were non-applicators. Urinary trichloro-2-pyridinol (TCPy) was measured as a specific metabolite biomarker of exposure to chlorpyrifos. Urinary 3-phenoxybenzoic acid (3-PBA) was measured as a general metabolite biomarker of exposure to pyrethroids, while urinary cis-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA) was measured as a specific biomarker of exposure to αCM and lambda cyhalothric acid (λCH acid) measured as a specific biomarker of exposure to λCH. Ordinal logistic regression models controlling for age were used to determine the likelihood of ADHD development (measured via parent-reported ADHD symptoms) as the level of biomarkers of pesticide exposure increased. ResultsCis-DCCA was the only biomarker associated with higher likelihood ADHD symptoms (> 0.60 vs. 0–0.17 μg/g creatinine; OR = 2.82, 95% CI: 1.29–6.14). All participants reported clinical levels of ADHD symptoms when compared to national norms used in the United States. TCPy, trans-DCCA and λCH acid were not associated with risk of ADHD symptoms after controlling for levels of cis-DCCA. No other metabolites were associated with the number of ADHD symptoms. There were no interaction effects found for exposure to both OPs and Pyrethroids. DiscussionThe results suggest that exposure to the pyrethroid αCM is associated with more ADHD symptoms. Methodological and cultural considerations in need of further study are discussed.

Effects of Pesticide Intake on Gut Microbiota and Metabolites in Healthy Adults.

Animal experiments have indicated that pesticides may affect gut microbiota, which is responsible for the production of short-chain fatty acids (SCFAs) and polyamines. Here, we present a preliminary observation of the relationship between pesticide exposure and fecal SCFAs and polyamines in Japanese adults. In total, 38 healthy adults aged 69 ± 10 years (mean ± SD) were recruited and subjected to stool and spot urine tests. Urinary dialkylphosphates (DAP), 3-phenoxybenzoic acid, and glyphosate were assayed as pesticide exposure markers of organophosphorus insecticide (OP), a pyrethroid insecticide, and glyphosate, respectively. Significant negative correlations (p < 0.05, Spearman’s rank correlation coefficient) were found between urinary DAP, fecal acetate (r = −0.345), and lactate (r = −0.391). Multiple regression analyses revealed that urinary DAP was a significant explanatory variable of fecal acetate concentration (p < 0.001, β = −24.0, SE = 4.9, t = −4.9) with some vegetable intake (adjusted R-square = 0.751). These findings suggest that OP exposure is independently associated with lower fecal acetate levels, which may contribute to human health in middle-aged and older adult groups. Given that the human gut environment has long-term effects on the host, studies on wide-range age groups, including children, are necessary.

Urinary pyrethroid metabolite and hearing threshold shifts of adults in the United States: A cross-sectional study.

Hearing loss (HL) is a global health problem with a high prevalence and profound socioeconomic impact. Pyrethroids are one of the most commonly used insecticides. Although previous studies have reported the relationship between pyrethroids and neurotoxicity, little is known about the effect of pyrethroid exposure on the auditory system among the general population. This study is aimed to investigate the association of pyrethroid exposure with hearing threshold shifts of adults in the United States. A total of 726 adults, aged from 20 to 69 years from the 2011–2012 National Health and Nutrition Examination Survey (NHANES) data were included in the study. Urinary 3-phenoxybenzoic acid (3-PBA), a general pyrethroid metabolite, was used as a biomarker for pyrethroid exposure. HL was defined as a pure-tone average (PTA) at 0.5, 1, 2, 4 kHz ≥ 20 dB in the better ear. Analyses by using multivariate linear regressions were conducted to explore the associations of urinary 3-PBA with PTA hearing threshold shifts. There were no statistically significant correlations between Ln-transformed 3-PBA and either low-frequency or high-frequency hearing thresholds after adjusting for age, gender, race/ethnicity, education level, firearm noise exposure, occupational noise exposure, recreational noise exposure, serum cotinine, BMI, hypertension, and diabetes. However, associations of 3-PBA with both low-frequency and high-frequency hearing thresholds depended on age (P interaction < 0.0396 and 0.0017, respectively). Positive associations between Ln-transformed 3-PBA and both low-frequency and high-frequency hearing thresholds were observed in participants aged 20–39 years after adjusting confounders (β = 1.53, 95% CI: 0.04–3.01, and β = 3.14, 95% CI: 0.99–5.29, respectively) with the highest tertile (≥ 0.884 μg/g creatinine) of 3-PBA compared with the lowest tertile (< 0.407 μg/g creatinine). The possibility of interaction between 3-PBA and age on the hearing threshold shifts indicated that pyrethroid insecticides were prone to be more toxic to auditory system in younger adults than in older ones. Further studies will be required to confirm these findings.

A systematic review of human biomonitoring studies of 3-phenoxybenzoic acid, a urinary biomarker pyrethroid insecticide exposure, 1997 to 2019

Pyrethroid insecticides are used, for example, in agriculture, indoor environments, and mosquito control programs, resulting in human exposure. Urinary 3-phenoxybenzoic acid (3-PBA) is a nonspecific biomarker for exposure to many pyrethroids. This systematic review identified human biomonitoring studies with 3-PBA that characterize environmental pyrethroid exposures in children and adolescents, pregnant women, and adults or occupational pyrethroid exposures relative to the National Health and Nutrition Examination Survey (NHANES) populations in the United States (US). PubMed, Embase, and SciFinder were searched for "3-phenoxybenzoic acid”, CAS No. 3739–38–6, and urine or urinary or urine level. Duplicate studies and studies meeting the exclusion criteria were removed from the search results based on predetermined exclusion criteria. This screening process identified 57 papers. Twenty-one, thirteen, twenty-two, and eleven manuscripts reported urinary 3-PBA levels in children, pregnant women, environmentally exposed adults, and occupationally exposed adults, respectively. Median 3-PBA levels ranged from 0.2 to 4.7 µg/g creatinine in children (1999–2016), 0.23–1.55 µg/g creatinine in pregnant women (1997–2014), and 0.11–3.34 µg/g creatinine in environmentally exposed adults (1999–2017). 3-PBA levels in occupationally exposed adults were significantly higher than in environmentally exposed populations, ranging from 0.43 to 14 µg/g creatinine (2004–2017). 3-PBA levels in children and adults from the general North American population increased significantly with the sampling year. A decrease in 3-PBA levels was noted in the adult cohorts from PR China and Japan. 3-PBA levels in most studies appeared to be comparable to levels in the NHANES populations; however, some smaller studies had high pyrethroid exposures. Factors contributing to higher 3-PBA levels in the general population included primarily dietary exposures and residential and agricultural pyrethroid applications. These findings demonstrate that pyrethroid exposures are near-ubiquitous worldwide and, in some regions, appear to increase over time. Thus, exposures to pyrethroid insecticides represent a continuing public health concern.

Urinary 3-phenoxybenzoic acid (3-PBA) levels and changes in hematological parameters in Korean adult population: A Korean National Environmental Health Survey (KoNEHS) 2012-2014 analysis.

Pyrethroid insecticides have been broadly used as pest control in agriculture and residential spaces, exerting high effectiveness of insecticidal property and relatively low toxicity to humans. Several animal studies suggested that exposure to pyrethroids may induce hematological abnormalities, thereby altering the number of blood cells and resulting in blood disorders. However, no epidemiologic study has reported on the effect of pyrethroid insecticide exposure on hematological changes, except for occupational exposure. This study aimed to investigate the effect of urinary 3-phenoxybenzoic acid (3-PBA) concentrations on hematological parameters in a representative South Korean adult population. We analyzed data from 6296 adults enrolled in the Korean National Environmental Health Survey (2012-2014). We employed multiple linear regression analysis to evaluate the association of urinary 3-PBA levels with eight hematological profiles: white blood cells (WBCs), red blood cells (RBCs), hemoglobin, hematocrit, platelets, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). The urinary 3-PBA levels were negatively associated with WBC, RBC, and hemoglobin levels and positively associated with MCV levels. The direction and magnitude of the association between the 3-PBA and hematological parameters varied according to sex and age. The adverse effects of 3-PBA on hematological parameters were distinctive among males aged 60 years and older. In this age group, 3-PBA levels were negatively associated with the WBC, RBC, hemoglobin, hematocrit, and MCHC levels among males. This study is the first to verify that urinary 3-PBA concentrations at the levels found in a Korean population are associated with blood parameters. This finding merits further investigation to understand the impact of 3-PBA on human blood function and public health.

Association between Urinary 3-Phenoxybenzoic Acid Concentrations and Self-Reported Diabetes in Korean Adults: Korean National Environmental Health Survey (KoNEHS) Cycle 2~3 (2012~2017)

Association between Urinary 3-Phenoxybenzoic Acid Concentrations and Self-Reported Diabetes in Korean Adults: Korean National Environmental Health Survey (KoNEHS) Cycle 2~3 (2012~2017)

Urinary concentrations and determinants of pyrethroid metabolites in pregnant women from non-rural areas of Yunnan, China.

The study assesses the levels of urinary pyrethroid pesticide (PYR) in women during early pregnancy. The factors associated with exposure are also determined. A total of 480 pregnant women from non-rural areas visiting hospital for prenatal examination during early pregnancy were enrolled. A self-designed, structured questionnaire was used to collect data on potential factors of PYR exposure. Urinary PYR metabolite levels were quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The majority of urine samples (98.8%) contained one or more PYR metabolite, although only a few women self-reported pesticide exposure. Urinary 3-phenoxybenzoic acid (3PBA) levels were close to those reported in certain developed countries. However, the levels of 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA) and 4-fluoro-3-phenoxybenzoic acid (4F3PBA) were higher than those reported in previous studies. Urinary PYR levels were positively associated with exposure to pesticides, consumption of bananas and oranges, the number of fruit types the women regularly ate, being multiparous, and cooked frequently. They were negatively associated with early pregnancy body mass index (BMI), unemployment, frequent intake of apples, and washing fruits and vegetables with soda or hot water. Pregnant women in non-rural areas were extensively exposed to low levels of PYRs. Dietary intake may be the primary pathway of exposure. The presented findings highlight the importance of using appropriate methods to reduce pesticide residues in food.

Association between pesticide exposure and sleep health among a representative sample of US adults: evidence from NHANES 2009\u20132014

BackgroundData suggest that pesticides interact with the melatonin receptor, which may influence sleep. However, the link between pesticides and sleep remains unexplored among the general adult population. This study evaluated unstratified and sex-stratified associations between urinary pesticide exposure (N = 4,478) and self-reported acute household pesticide exposure (N = 14,956), with sleep health outcomes within a nationally representative sample of US adults.MethodsData from the National Health and Nutrition Examination Surveys (NHANES) 2009–2014 were combined for analysis of aim 1 and aim 2. Urinary pesticide metabolite concentrations served as biomarkers of pesticide exposure. Acute household pesticide exposure (if any chemical products were used in the home in the past seven days to control pests) was self-reported (yes/no). Insufficient sleep duration (< 7 h/night) and trouble sleeping (yes/no) were self-reported. Log-binomial regression models that accounted for complex survey weights and adjusted for confounders were used to compute prevalence ratios and 95% CI.ResultsLog urinary 3-phenoxybenzoic acid (3-PBA) was related to a higher probability of insufficient sleep [1.09 (95% CI: 1.00, 1.20), p = 0.04] and trouble sleeping [1.14 (95% CI: 1.02, 1.27), p = 0.02] among males. Self-reported acute household pesticide exposure was associated with a higher probability of insufficient sleep duration [1.16 (95% CI: 1.02, 1.32), p = 0.03] and trouble sleeping [1.20 (95% CI: 1.01, 1.44), p = 0.04] in the unstratified sample. Sex-stratified findings showed that associations between acute household pesticide exposure and trouble sleeping only persisted among males [1.69 (95% CI: 1.27, 2.24), p < .001].ConclusionsIn summary, acute pesticide exposure may be detrimental to adult sleep health, particularly among US males.

Pyrethroids exposure induces obesity and cardiometabolic diseases in a sex-different manner

People in the United States and around the world are widely exposed to pyrethroid pesticides. However, little is known about the effect of pyrethroids exposure on obesity in adults. This study examined the association between pyrethroids exposure and obesity in males and females and the role of obesity in the association of pyrethroids exposure with diabetes and cardiovascular disease (CVD). We used data from the National Health and Nutrition Examination Survey 1999–2002 and 2007–2014. Multivariate linear regression and logistic regression models were fitted to assess the association between urinary 3-Phenoxybenzoic Acid (3-PBA, a validated biomarker for pyrethroids exposure used in the primary analysis) and obesity. Mediation analyses were performed to investigate the mediation role of obesity on the associations of 3-PBA with diabetes and CVD. In this analysis, 7896 participants aged 20 years and above were included, of which 1235 (32.2%) males and 1623 (39.9%) females were diagnosed as obese. There was a significant interaction between sex and 3-PBA (Pinteraction = 0.004) for the risk of obesity. Among females, participants in the highest tertile of urinary 3-PBA had higher odds of obesity (OR = 1.22, 95% CI: 1.00, 1.48) compared to those in the lowest tertile after adjusting for covariates. Among males, the association was not statistically significant. Similar trends were found in the associations of log-transformed urinary 3-PBA level with body mass index in males and females. Further, we found that, in males and females, obesity explained the effect of 3-PBA exposure on diabetes by 1.1% (P = 0.850) and 13.6% (P = 0.004), as well as cardiovascular diseases by 5.9% (P = 0.785) and 25.0% (P = 0.016), respectively. In conclusion, 3-PBA was significantly associated with a higher risk of obesity, especially in females. In addition, obesity partially mediated the associations of 3-PBA exposure with diabetes and CVD.

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.

Prenatal maternal pesticide exposure in relation to sleep health of offspring during adolescence

Study objectivesThe neurobiological processes involved in establishing sleep regulation are vulnerable to environmental exposures as early as seven weeks of gestation. Studies have linkedin utero pesticide exposure to childhood sleep-disordered breathing. However, the impact of in utero pesticide exposure on the sleep health of adolescents remains unexplored. Materials and methodsData from 137 mother-adolescent pairs from a Mexico City cohort were analyzed. We used maternal urinary 3-phenoxybenzoic acid (3-PBA, pyrethroid metabolite) and 3, 5, 6-trichloro-2-pyridinol (TCPy, chlorpyrifos metabolite) from trimester three to estimate in utero pesticide exposure. Among adolescents, we obtained repeated measures of objectively assessed sleep duration, midpoint, and fragmentation using wrist-actigraphy devices for 7 consecutive days in 2015 and 2017. Unstratified and sex-stratified associations between maternal urinary 3-PBA and TCPy and adolescent sleep measures were examined using generalized linear mixed models (GLMMs). We also examined the interactive effects of maternal pesticide exposure and offspring sex on sleep outcomes. Results3-PBA and TCPy were detected in 44.4% and 93% of urine samples, respectively. Adjusted findings demonstrated that higher exposure to maternal TCPy was associated with longer sleep duration and later sleep timing. Findings from interaction tests between maternal pesticide exposure and offspring sex were not statistically significant, although adjusted sex-stratified findings showed that the association between TCPy with duration and midpoint was evident only among female offspring. To illustrate, those in the highest tertile of exposure had a 59 minute (95% CI: 12.2, 104.8) (p, trend = 0.004) longer sleep duration and a 0.6 hour (95% CI: 0.01, 1.3) (p, trend = 0.01) later sleep midpoint. We found no significant associations between 3-PBA and sleep outcomes. ConclusionWithin a cohort of mother-adolescent pairs, we found associations between maternal prenatal pesticide exposure and longer sleep duration and later sleep timing among adolescent offspring. Further, this association may be female-specific.

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.

Household insecticide use and urinary 3-phenoxybenzoic acid levels in an elder population: a repeated measures data

BackgroundPyrethroids are associated with adverse health consequences, even at low-dose exposures. However, there is limited evidence on pyrethroids exposure levels among vulnerable elder population and on their exposure sources.ObjectiveWe tried to determine pyrethroids exposure levels among Korean elders and their exposure sources.MethodsWe measured levels of 3-phenoxybenzoic acid (3-PBA), a pyrethroids metabolite, in urines repeatedly collected from 1239 Korean rural and urban elders; we also explored exposure sources for pyrethroids using questionnaire data.ResultsOur participants had high levels of 3-PBA with 446 (36.0%) of elders with 3-PBA level over 2 ng/mL of 95th percentile of the German representative populations. After adjustment for sex, age, smoking status, visit episode, and surveyed season using linear mixed effect models, household insecticide spray use was significantly associated with 3-PBA level (β = 0.03 and p = 0.02) and the association was apparent only for females (β = 0.03 and p = 0.03). In the analyses for nonlinear relationships using generalized additive mixed models, there was a J-shape change in 3-PBA level by insecticide spray use (p < 0.01 both in total population and in females).SignificanceHousehold insecticide spray was a predominant exposure source for pyrethroids at community level among Korean elders, warning more stringent control for frequently exposed environmental factors for pyrethroids including insecticide spray.