3-PBA Levels Research Articles

Exposure to biocides and their potential exposure sources among adults: A nationwide population-based study in South Korea

Biocides are present in personal care (including preservatives or antibacterials), pest control, and disinfectant products (including non-agricultural insecticides, fungicides, and disinfectants), and their long-term exposure may induce adverse health effects in humans. Therefore, in this study, we assessed the exposure levels and major exposure predictors of biocides among nationally representative Korean adults. The target group included adults (≥19 years) participating in the Korean National Environmental Health Survey (KoNEHS) 2015–2020. We employed survey-weighted multiple regression analysis and conditional inference trees analysis to assess the associations between demographic characteristics, behavioral sources (including personal care product use, pesticide use, and dietary patterns), and urinary levels of phenol (triclosan [TCS]), parabens (methyl paraben [MP], ethyl paraben [EP], propyl paraben [PP], and butyl paraben [BP]), and the pyrethroid insecticide metabolite (3-phenoxybenzoic acid [3-PBA]). Urinary EP, BP, and 3-PBA levels were higher in South Korean adults compared with those in Western countries. Major exposure predictors for MP, EP, and PP included the use of personal care products such as sunscreen, makeup, and hair care products in KoNEHS 2018–2020. Major exposure predictors for TCS and BP were vegetable consumption, and those for 3-PBA were mosquitocide use during summer in KoNEHS 2018–2020. However, these predictors were not observed in KoNEHS 2015–2017. Collectively, our findings suggest that biocide exposure predictors vary according to changes in product use and diet habits of individuals. Therefore, developing strategies to mitigate biocide exposure based on the demographic and behavioral characteristics of the general population is imperative.

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.

Applicability of Food Monitoring Data for Assessing Relative Exposure Contributions of Pyrethroids in Retrospective Human Biomonitoring Risk Estimations.

The use of pyrethroids is very broad and shows increasing trends. Human biomonitoring studies represent the best approach for realistic risk estimations, but their interpretation requires a tiered approach. A previous HBM4EU study indicated levels in European children groups just around the threshold for concern, requiring further refinement. The main difficulty is that several pyrethroids with different toxicity potencies generate the same urinary metabolites. As diet is the main pyrethroid source for the general population, EU food monitoring data reported by EFSA have been used to estimate the relative contribution of each pyrethroid. The main contributors were cypermethrin for DCCA and 3-PBA and lambda-cyhalothrin for CFMP. Urinary levels predicted from food concentration according to the EFSA diets were mostly within the range of measured levels, except 3-PBA and CFMP levels in children, both below measured levels. The predicted lower levels for 3-PBA can be explained by the very low Fue value, initially proposed as conservative, but that seems to be unrealistic. The discrepancies for CFMP are mostly for the highest percentiles and require further assessments. The refined assessments included the revision of the previously proposed human biomonitoring guidance values for the general population, HBM-GV Gen Pop, following recent toxicological reevaluations, and the estimation of hazard quotients (HQs) for each individual pyrethroid and for the combined exposure to all pyrethroids. All HQs were below 1, indicating no immediate concern, but attention is required, particularly for children, with HQs in the range of 0.2-0.3 for the highly exposed group. The application of probabilistic methods offers assessments at the population level, addressing the variability in exposure and risk and providing relevant information for Public Health impact assessments and risk management prioritization.

Associations of semen quality with pyrethroids in semen and urine samples of men with oligozoospermia: A cross-sectional study in Samsun, Turkey.

Pyrethroids (PYRs) may act as endocrine disrupters and lead to infertility. The aim of the study was to analyze the levels of anti-androgenic PYRs (cypermethrin, deltamethrin, and permethrin) and 3-phenoxy benzoic acid (3-PBA), a general metabolite of PYRs, in both semen and urine samples of men with oligozoospermia. The PYRs and 3-PBA metabolite levels in the semen and urine samples of the men were analyzed through GC-MS. The results indicated that the levels of PYRs in the semen samples of the infertile group were significantly higher than those of the fertile group. It was determined that cypermethrin exposure was associated with changes in sperm count and total sperm motility, while permethrin, deltamethrin, and 3-PBA levels were associated with changes in sperm morphology. It was determined that there was a significant negative correlation between semen deltamethrin levels and sperm morphology and sperm count. In addition, exposure of these patients to deltamethrin (range; 1.53-8.02µg/l) and having farmer parents were determined to increase the risk of infertility. In conclusion, the findings of this study showed that exposure to environmental PYRs may adversely affect semen quality, especially in terms of sperm morphology, in men with oligozoospermia.

Assessing the impact of coexposure on the measurement of biomarkers of exposure to the pyrethroid lambda-cyhalothrin in agricultural workers.

There are few published data on the impact of combined exposure to multiple pesticides (coexposure) on levels of biomarkers of exposure in workers, which may alter their toxicokinetics and thus the interpretation of biomonitoring data. This study aimed to assess the impact of coexposure to two pesticides with shared metabolism pathways on levels of biomarkers of exposure to pyrethroid pesticides in agricultural workers. The pyrethroid lambda-cyhalothrin (LCT) and the fungicide captan were used as sentinel pesticides, since they are widely sprayed concomitantly in agricultural crops. Eighty-seven (87) workers assigned to different tasks (application, weeding, picking) were recruited. The recruited workers provided two-consecutive 24-h urine collections following an episode of lambda-cyhalothrin application alone or in combination with captan or following tasks in the treated fields, as well as a control collection. Concentrations of lambda-cyhalothrin metabolites - 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-cyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) - were measured in the samples. Potential determinants of exposure established in a previous study, including the task performed and personal factors were documented by questionnaire. Multivariate analyses showed that coexposure did not have a statistically significant effect on the observed urinary levels of 3-PBA (Exp(β) (95% confidence interval (95% CI)): 0.94 (0.78-1.13)) and CFMP (1.10 (0.93-1.30). The repeated biological measurements ("time variable") - defined as the within-subjects variable - was a significant predictor of observed biological levels of 3-PBA and CFMP; the within-subjects variance (Exp(β) (95% (95% CI)) for 3-PBA and CFMP was 1.11 (1.09-3.49) and 1.25 (1.20-1.31). Only the main occupational task was associated with urinary levels of 3-PBA and CFMP. Compared to the weeding or picking task, the pesticide application task was associated with higher urinary 3-PBA and CFMP concentrations. In sum, coexposure to agricultural pesticides in the strawberry fields did not increase pyrethroid biomarker concentrations at the exposure levels observed in the studied workers. The study also confirmed previous data suggesting that applicators were more exposed than workers assigned to field tasks such as weeding and picking.

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.

Assessment of Preschool Children's Exposure Levels to Organophosphate and Pyrethroid Pesticide: A Human Biomonitoring Study in Two Turkish Provinces.

Pesticides are products developed to prevent, destroy, repel or control certain forms of plant or animal life that are considered to be pests. However, now they are one of the critical risk factors threatening the environment, and they create a significant threat to the health of children. Organophosphate (OP) and pyrethroid (PYR) pesticides are widely used in Turkey as well as all over the world. The main focus of this presented study was to analyze the OP and PYR exposure levels in urine samples obtained from 3- to 6-year-old Turkish preschool children who live in the Ankara (n:132) and Mersin (n:54) provinces. In order to measure the concentrations of three nonspecific metabolites of PYR insecticides and four nonspecific and one specific metabolite of OPs, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses were performed. The nonspecific PYR metabolite 3-phenoxybenzoic acid (3-PBA) found in 87.1% of samples (n = 162) and the specific OP metabolite 3,5,6-trichloro-2-pyridinol (TCPY) found in 60.2% of samples (n = 112) were the most frequently detected metabolites in all urine samples. The mean concentrations of 3-PBA and TCPY were 0.38 ± 0.8 and 0.11 ± 0.43ng/g creatinine, respectively. Although due to the large individual variation no statistically significant differences were found between 3-PBA (p = 0.9969) and TCPY (p = 0.6558) urine levels in the two provinces, significant exposure differences were determined both between provinces and within the province in terms of gender. Risk assessment strategies performed in light of our findings do not disclose any proof of a possible health problems related to analyzed pesticide exposure in Turkish children.

Association of 3-Phenoxybenzoic Acid Exposure during Pregnancy with Maternal Outcomes and Newborn Anthropometric Measures: Results from the IoMum Cohort Study

The aims of this study were to characterize the exposure of pregnant women living in Portugal to 3-phenoxybenzoic acid (3-PBA) and to evaluate the association of this exposure with maternal outcomes and newborn anthropometric measures. We also aimed to compare exposure in summer with exposure in winter. Pregnant women attending ultrasound scans from April 2018 to April 2019 at a central hospital in Porto, Portugal, were invited to participate. Inclusion criteria were: gestational week between 10 and 13, confirmed fetal vitality, and a signature of informed consent. 3-PBA was measured in spot urine samples by gas chromatography with mass spectrometry (GC-MS). The median 3-PBA concentration was 0.263 (0.167; 0.458) µg/g creatinine (n = 145). 3-PBA excretion was negatively associated with maternal pre-pregnancy body mass index (BMI) (p = 0.049), and it was higher during the summer when compared to winter (p < 0.001). The frequency of fish or yogurt consumption was associated positively with 3-PBA excretion, particularly during the winter (p = 0.002 and p = 0.015, respectively), when environmental exposure is low. Moreover, 3-PBA was associated with levothyroxine use (p = 0.01), a proxy for hypothyroidism, which could be due to a putative 3-PBA-thyroid hormone antagonistic effect. 3-PBA levels were not associated with the anthropometric measures of the newborn. In conclusion, pregnant women living in Portugal are exposed to 3-PBA, particularly during summer, and this exposure may be associated with maternal clinical features.

A time differentiated dietary intervention effect on the biomarkers of exposure to pyrethroids and neonicotinoids pesticides

Tailoring medical models to the right person or risk subgroups delivered at the right time is important in personalized medicine/prevention initiatives. The CIRCA-CHEM randomized 2x2 crossover pilot trial investigated whether the consumption of fruits/vegetables within a time-restricted daily window would affect urinary biomarkers of exposure to neonicotinoids (6-chloronicotinic acid, 6-CN) and pyrethroids (3-phenoxybenzoic acid, 3-PBA) pesticides, a biomarker of oxidative damage (4-hydroxynonenal, 4-HNE) and the associated urinary NMR metabolome. A statistically significant difference (p < 0.001) in both creatinine-adjusted 6-CN and 3-PBA levels was observed between the two-time dietary intervention windows (morning vs. evening). In the evening intervention period, pesticides biomarker levels were higher compared to the baseline, whereas in the morning period, pesticide levels remained unchanged. Positive associations were observed between pesticides and 4-HNE suggesting a diurnal chrono-window of pesticide toxicity. The discovery of a chronotoxicity window associated with chrono-disrupted metabolism of food contaminants may find use in personalized medicine initiatives.

Exploratory analysis of the association between pyrethroid exposure and rheumatoid arthritis among US adults: 2007-2014 data analysis from the National Health and Nutrition Examination Survey (NHANES).

Previous studies indicate that pesticide use may play an important role in the occurrence and development of rheumatoid arthritis (RA); however, little is known about the effect of specific pesticides on RA. The objective of this study was to evaluate whether pyrethroid exposure was linked to RA in adults. Data were originated from the 2007-2014 National Health and Nutrition Examination Survey (NHANES). The levels of pyrethroid exposure were assessed by 3-phenoxybenzoic acid (3-PBA) concentrations in urine samples. We built multivariate logistic regression models to assess associations between pyrethroid exposure and RA among US adults. A restricted cubic spline plot (three knots) was applied to test whether there was a nonlinear relationship between exposure to pyrethroid pesticides and the prevalence of RA. Finally, 4384 subjects were included in our analysis with 278 RA patients. In crude model, higher level of 3-PBA (creatinine-adjusted) was positively associated with RA (OR: 1.51, 95% CI: 1.07, 2.15). After adjustment for sex, race/ethnicity, education, body mass index, family poverty income, level of education, marital status, smoking status, alcohol usage, physical activity, hypertension, and urinary creatinine, the highest (vs lowest) quartile of 3-PBA was associated with an increased prevalence of RA (OR: 1.23, 95% CI: 0.86, 1.79). Significantly positive associations between 3-PBA concentration and RA were observed in the population aged between 40 and 59years and with lower level of education. The restricted cubic spline plot presented an increase in trend and indicated that pyrethroid exposure was linearly associated with occurrence of RA (p for nonlinearity = 0.728). In conclusion, our study indicated that pyrethroid pesticide exposure was associated with an increased risk of RA. Higher levels of pyrethroid exposure were linearly associated with increased prevalence of RA in adults. Certainly, our findings are in great need of further corroboration by prospective studies with strict design.

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.

Association between pyrethroid exposure and risk of depressive symptoms in the general US adults.

This study aimed to investigate the association between pyrethroid exposure and the risk of depressive symptoms in adults in the USA. Data of participants aged ≥20 years (n = 6455) from the National Health and Nutrition Examination Survey (NHANES, 2007-2014) were included. 3-Phenoxybenzoic acid (3-PBA), an adequately detected pyrethroid metabolite, was used as a biomarker to assess pyrethroid exposure. Depressive symptoms were defined as the Patient's Health Questionnaire (PHQ-9) total score ≥10 or use of antidepressant. Multivariable logistic regression analyses were performed to examine the association between urinary 3-PBA levels and the risk of depressive symptoms. In this study, 1150 participants (weighted frequency, 18.45%) developed depressive symptoms. Participants in the highest tertile have a higher risk of depressive symptoms than those in the lowest tertile of urinary 3-PBA and weighted OR of 1.28 (95% CI, 1.00-1.63, P=0.019). There was a nonlinear association between urinary 3-PBA and depressive symptoms (P for nonlinearity = 0.034). Mediation analysis showed the mediating effect of trouble sleeping on the association of urinary 3-PBA with depressive symptoms was 28.8% (P = 0.006). Our findings indicate that pyrethroid exposure is associated with the increased risk of depressive symptoms, and trouble sleeping may mediated this association. Further studies should be conducted to validate our findings and elucidate their underlying mechanisms.

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.

Associations between pyrethroid exposure and serum sex steroid hormones in adults: Findings from a nationally representative sample

BackgroundPyrethroids have been considered as potential endocrine-disrupting chemicals and have been shown to be associated with endocrine-related health outcomes. However, limited studies directly explored the link between pyrethroid exposure and sex hormones in the general population. ObjectivesTo explore the associations between exposure to pyrethroids and serum sex steroid hormones in adults. MethodsWe evaluated the cross-sectional associations in 1235 adults aged ≥20 years who had been assigned to the National Health and Nutrition Examination Survey (NHANES) 2013–2014. The urinary concentration of 3-phenoxybenzoic acid (3-PBA) was applied as a biomarker of human pyrethroid exposure levels. Information on sex steroid hormones, including total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) in serum were measured. Free androgen index (FAI) and the ratio of TT to E2 (TT/E2) were also calculated. The percent changes with 95% confidence intervals (CIs) for a doubling of 3-PBA concentrations in the serum sex hormone levels were estimated using generalized linear regression models. ResultsThe overall median concentrations of creatinine-adjusted 3-PBA were 0.58 μg/g creatinine, and 90.0% of adults had a detectable level of 3-PBA. In females, every two-fold increase in 3-PBA was associated with 4.34% (95% CI: 1.58%, 7.18%) higher levels of TT and 4.05% (95% CI: 7.03%, 1.16%) higher levels of SHBG, respectively. In males, a doubling in 3-PBA was associated with 3.02% (95% CI: 1.21%, 4.86%) increase in SHBG but 1.85% (−3.59%, −0.07%) decrease in FAI, respectively. In addition, significant non-linear associations of 3-PBA with SHBG in both males and females and TT in females were observed. ConclusionsEnvironmental pyrethroid exposure was associated with altered sex hormones in adults. This study provides important epidemiological evidence for the association of pyrethroids with endocrine disruption.

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.

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.

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

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.

Environmental exposure to pyrethroid pesticides in a nationally representative sample of U.S. adults and children: The National Health and Nutrition Examination Survey 2007–2012

Pyrethroids are an important class of insecticides, and thousands of tons of these compounds are used in the United States every year. This study characterized exposures to pyrethroids and assessed demographic, socioeconomic, and lifestyle factors that modulate pyrethroid exposure using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2012, a nationally representative survey of the non-institutionalized population of the United States. Urinary levels of commonly used biomarkers of pyrethroid exposure, including 3-phenoxybenzoic acid (3-PBA), 4-fluoro-3-phenoxybenzoic acid (F-PBA), and cis-dibromovinyl-dimethylcyclopropane carboxylic acid (DBCA), were determined by liquid chromatography-tandem mass spectrometry. The detection rate of 3-PBA, a nonspecific metabolite of several pyrethroids, was 78.1% in adults (N = 5233) and 79.3% in children (N = 2295). The detection rates of all other pyrethroid metabolites were <10%. The median urinary level of 3-PBA in adults was 0.47 μg/L (interquartile range, 0.14–1.22 μg/L). For children, the median urinary level was 0.49 μg/L (interquartile range, 0.17–1.29 μg/L). Age, gender, family income-to-poverty ratio (PIR), levels of physical activity, alcohol intake, and body mass index were associated with 3-PBA levels in adults. In children, age, gender, race/ethnicity, and PIR were associated with 3-PBA levels. 3-PBA levels also differed significantly across NHANES cycles, with higher levels observed in NHANES 2011–2012. Geometric mean 3-PBA levels in U.S. adults were 0.41 μg/L in NHANES 2007–2008, 0.41 μg/L in NHANES 2009–2010, and 0.66 μg/L in NHANES 2011–2012. In U.S. children, geometric mean 3-PBA levels were 0.40 μg/L in NHANES 2007–2008, 0.46 μg/L in NHANES 2009–2010, and 0.70 μg/L in NHANES 2011–2012. These results demonstrate that pyrethroid exposures remain a current environmental health concern and lay the foundation for further preclinical and epidemiological studies assessing human health risks associated with pyrethroids.

Impact of pesticide coexposure: an experimental study with binary mixtures of lambda-cyhalothrin (LCT) and captan and its impact on the toxicokinetics of LCT biomarkers of exposure.

This study aimed at gaining more insights into the impact of pesticide coexposure on the toxicokinetics of biomarkers of exposure. This was done by conducting an in vivo experimental case-study with binary mixtures of lambda-cyhalothrin (LCT) and captan and by assessing its impact on the kinetic profiles of LCT biomarkers of exposure. Groups of male Sprague-Dawley rats were exposed orally by gavage to LCT alone (2.5 or 12.5mg/kg bw) or to a binary mixture of LCT and captan (2.5/2.5 or 2.5/12.5 or 12.5/12.5mg/kg bw). In order to establish the temporal profiles of the main metabolites of LCT, serial blood samples were taken, and excreta (urine and feces) were collected at predetermined intervals up to 48h post-dosing. Major LCT metabolites were quantified in these matrices: 3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic (CFMP), 3-phenoxybenzoicacid (3-PBA), 4-hydroxy-3-phenoxybenzoicacid (4-OH3PBA). There was no clear effect of coexposure at the low LCT dose on the kinetics of CFMP and 3-PBA metabolites, based on the combined assessment of temporal profiles of these metabolites in plasma, urine and feces; however, plasma levels of 3-PBA were diminished in the coexposed high-dose groups. A significant effect of coexposure on the urinary excretion of 4-OH3PBA was also observed while fecal excretion was not affected. The temporal profiles of metabolites in plasma and in excreta were further influenced by the LCT dose. In addition, the study revealed kinetic differences between metabolites with a faster elimination of 3-PBA and 4-OH3BPA compared to CFMP. These results suggest that the pyrethroid metabolites CFMP and 3-PBA, mostly measured in biomonitoring studies, remain useful as biomarkers of exposure in mixtures, when pesticide exposure levels are below the reference values. However, the trend of coexposure effect observed in the benzyl metabolite pathway (in particular 4-OH3BPA) prompts further investigation.