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.

BACKGROUND: Biocides 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 METHODS: We 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. RESULTS: Urinary 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. CONCLUSIONS: These study findings suggest that biocides at levels found in Korean children and adolescents affect atopic dermatitis.

Association between pyrethroid exposure and osteoarthritis: a national population-based cross-sectional study in the US.

BACKGROUND: With the restriction of organophosphorus and other insecticides, pyrethroids are currently the second most-used group of insecticides worldwide due to their advantages such as effectiveness and low toxicity for mammalian. Animal studies and clinical case reports have documented associations between adverse health outcomesand exposure to pyrethroids. At present, the association between chronic pyrethroid exposure and osteoarthritis (OA) remains elusive. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 and 2007-2014 were used to explore the associations of pyrethroid exposure and OA. Urinary level of 3-phenoxybenzoic acid (3-PBA) in urine samples was used to evaluate the exposure of pyrethroid, and OA was determined on the basis of self-reported physician diagnoses. Multivariable logistic regression models were used to investigate the association between pyrethroid exposure and OA. RESULTS: Among the 6528 participants, 650 had OA. The weighted geometric mean of urinary volume-based 3-PBA concentration were 0.45 µg/L. With adjustments for major confounders, compared to participants in the lowest quartile of urinary volume-based 3-PBA, those in the highest quartilehad higher odds of OA (odds ratio, 1.39; 95% confidence interval: 1.01, 1.92). There was no nonlinear relationship between urinary volume-based 3-PBA and OA (P for non-linearity = 0.89). CONCLUSION: High urinary 3-PBA concentration was associated with increased OA odds in the US adults. Pyrethroid exposure in the population should be monitored regularly.

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.

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.

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.

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.

Mixtures modeling identifies heavy metals and pyrethroid insecticide metabolites associated with obesity.

We aim to examine the association between chemical mixtures and obesity. Blood and urinary levels of tween-six chemicals were measured in adults who participated in the KoNEHS. We identified the associations of chemicals with obesity using linear regression models. Weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were conducted as secondary analyses. Of the 3,692 participants included in the analysis, 18.0% had obesity. In the logistic regression model, mercury (Hg), lead (Pb), and 3PBA levels were associated with obesity, and significant trends were observed for these chemical tertiles (p < 0.001). Hg, Pb, and 3PBA levels were also associated with BMI. The WQS index was significantly associated with both obesity (OR = 2.15, 95% CI: 2.11-2.20) and BMI (ß = 0.39, 95% CI: 0.37-0.51). The qgcomp index also found a significant association between chemicals and both obesity (OR = 1.70, 95% CI: 1.56-1.85) and BMI (ß = 0.40, 95% CI: 0.39-0.41). Hg, Pb, and 3PBA were the most heavily weighed chemicals in these models. In BKMR analysis, the overall effect of the mixture was significantly associated with obesity. Hg, Pb, and 3PBA showed positive trends and were observed as the most important factors associated with obesity. Given increasing exposure to chemicals, there is a need to investigate the associations between chemical exposures, either separately or together, and incident obesity risk factors in well-characterized cohorts of different populations, and to identify potential approaches to chemical exposure prevention.

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 1 s (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 11-17 years) 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 6-10 years, 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.

Construction and characterization of a class-specific single-chain variable fragment against pyrethroid metabolites.

Pyrethroids are insecticides that are widely used in rural and urban areas worldwide. After entering the environment, pyrethroids are rapidly metabolized or degraded by various biological or abiotic methods. In this study, a single-chain variable fragment (scFv) which could simultaneously detect three pyrethroid metabolites was constructed based on a hybridoma raised against 3-phenoxybenzoic acid (3-PBA). By molecular docking, it showed that there were hydrogen bonds, hydrophobic interactions, CH-π interaction, and cation-π interaction between 3-PBA and its scFv. All the contact residues contributing to hydrogen bonds are located in VH-CDR2 or its neighboring region, and two of them were mutants of the closest germline sequence. Based on competitive ELISA, the half maximal inhibitory concentration (IC50) of the scFv for 3-PBA, 3-phenoxybenzaldehyde (PBAld), and 3-phenoxybenzyl alcohol (PBAlc) were calculated to be 0.55, 0.59, and 0.63 µgmL-1, respectively. The scFv also showed 23.91%, 13.41%, 1.15%, 1.00%, and 0.56% cross-reactivity with phenothrin, deltamethrin, fenvalerate, beta-cypermethrin, and fenpropathrin. The broad specificity of the scFv may be due to its hapten design. The scFv could be employed in class-specific immunoassays for pyrethroid metabolites with phenoxybenzyl (PB) group. It is also potentially used for characterizing degradation of pyrethroids or detecting PBAlc (PBAld) alone, and the detection results should be confirmed by other selective methods. KEY POINTS: • A scFv which can simultaneously detect 3-PBA, PBAlc, and PBAld was constructed. • Antibody informatics and binding mode of the scFv were obtained. • The reason for its broad specificity was discussed. • It could be used to monitor single or multi-pyrethroid metabolites with PB group.

An Innovative Nanobody-Based Electrochemical Immunosensor Using Decorated Nylon Nanofibers for Point-of-Care Monitoring of Human Exposure to Pyrethroid Insecticides.

A novel ultrasensitive nanobody-based electrochemical immunoassay was prepared for assessing human exposure to pyrethroid insecticides. 3-Phenoxybenzoic acid (3-PBA) is a common human urinary metabolite for numerous pyrethroids, which broadly served as a biomarker for following the human exposure to this pesticide group. The 3-PBA detection was via a direct competition for binding to alkaline phosphatase-embedded nanobodies between free 3-PBA and a 3-PBA-bovine serum albumin conjugate covalently immobilized onto citric acid-decorated nylon nanofibers, which were incorporated on a screen-printed electrode (SPE). Electrochemical impedance spectroscopy (EIS) was utilized to support the advantage of the employment of nanofibrous membranes and the success of the immunosensor assembly. The coupling between the nanofiber and nanobody technologies provided an ultrasensitive and selective immunosensor for 3-PBA detection in the range of 0.8 to 1000 pg mL-1 with a detection limit of 0.64 pg mL-1. Moreover, when the test for 3-PBA was applied to real samples, the established immunosensor proved to be a viable alternative to the conventional methods for 3-PBA detection in human urine even without sample cleanup. It showed excellent properties and stability over time.

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

BACKGROUND: Owing 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. OBJECTIVES: This 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. METHODS: Data 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. RESULTS: Urinary 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. CONCLUSION: Urinary 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.

Environmental pyrethroid exposure and thyroid hormones of pregnant women in Shandong, China.

BACKGROUND: Pyrethroid insecticides have been extensively used in China and worldwide, while their effects on thyroid functions are rarely explored, especially in susceptible pregnant women. OBJECTIVE: To assess the association between 3-phenoxybenzoic acid (3PBA), a major urinary metabolite of pyrethroids, and thyroid hormone levels in pregnant women in China. METHODS: Three hundred and seventy-four pregnant women were recruited during the admission for delivery (third trimester of pregnancy) in a local hospital in Shandong, China during December 2011 to December 2013. Pyrethoids exposure was assessed by examining urinary metabolite of 3PBA levels. Thyroid hormones were detected by measuring serum concentrations of thyroid stimulating hormones (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4) and free thyroxine (FT4). Multiple linear regression models were used to investigate the associations between 3PBA concentrations and thyroid hormones levels. RESULTS: The detection frequency of 3PBA was 90.4%, with a median concentration of 1.14 µg/g creatinine. After adjusted for potential confounders, we found a significant negative relationship between 3PBA and serum FT3 (ß = -0.06, 95% CI = -0.11 to -0.01) as well as an inverse dose dependent association (p for trend = 0.023). No significant association was found between 3PBA concentrations and other thyroid hormones. CONCLUSIONS: Our findings indicated that pyrethroid exposure was widespread and negatively associated with serum FT3 concentrations in pregnant women in northern China. Given to the widespread of pyrethroid exposure and critical role thyroid homeostasis plays during pregnancy, more studies are warranted to explore their relationships as well as underlying mechanisms.

Development of a Highly Sensitive Direct Competitive Fluorescence Enzyme Immunoassay Based on a Nanobody-Alkaline Phosphatase Fusion Protein for Detection of 3-Phenoxybenzoic Acid in Urine.

3-Phenoxybenzoic acid (3-PBA) is a human urinary metabolite of many pyrethroid insecticides and can be used as a biomarker to monitor human exposure to these pesticides. A rapid and sensitive direct competitive fluorescence enzyme immunoassay (dc-FEIA) for detecting 3-PBA on the basis of a nanobody (Nb)-alkaline phosphatase (AP) fusion protein was developed. The anti-3-PBA Nb-AP fusion protein was expressed and purified. The 50% inhibitory concentration (IC50) and linear range of dc-FEIA were 0.082 and 0.015-0.447 ng/mL, respectively, with a detection limit of 0.011 ng/mL. The IC50 of dc-FEIA was improved by nearly ten times compared with those of one-step and three-step direct competitive enzyme-linked immunosorbent assay (dc-ELISA). Spiked urine samples were detected by both dc-FEIA and liquid chromatography-mass spectrometry (LC-MS), and the results showed good consistency between the two analysis methods, indicating the reliability of dc-FEIA based on the Nb-AP fusion protein for detecting 3-PBA in urine.

Kinetic time courses of lambda-cyhalothrin metabolites after dermal application of Matador EC 120 in volunteers.

A controlled kinetic study was conducted in volunteers dermally exposed to the widely used lambda-cyhalothrin pyrethroid pesticide to document the time courses of relevant biomarkers of exposure, in order to better assess biomonitoring data in workers. Matador® EC120 formulation (120 g/l) was applied on 40 cm2 of the forearm at a 0.25 mg/kg dose of lambda-cyhalothrin and left without occlusion or washing for 6 h. The application site was then washed thoroughly with soap and water. The kinetic time courses of cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) metabolites were determined in plasma and urine up to 84 h post-application. Results show that the fraction of lambda-cyhalothrin absorbed in the body was rapidly cleared following dermal contact. According to CFMP and 3-PBA plasma profiles, calculated mean apparent absorption half-lives (t1/2) were 3 and 7.3 h, respectively, and corresponding mean apparent elimination t1/2 were 11.2 and 7.6 h. These differences suggest some metabolism at the site-of-entry and storage of metabolites by the dermal route. Toxicokinetic parameters calculated from urinary profiles confirm the values of absorption and elimination rates. Metabolites were almost completely excreted over the 84-h period post-application and, on average, 0.12 and 0.08% of the applied lambda-cyhalothrin dose was recovered in the urine as CFMP and 3-PBA, respectively, indicating a low dermal absorption fraction of this pyrethroid. This study showed the potential use of CFMP and 3-PBA biomarkers for the assessment of dermal exposure to lambda-cyhalothrin pyrethroid.

Phytotoxicity of pyrethroid pesticides and its metabolite towards Cucumis sativus.

Pyrethroid pesticides residues have been frequently detected in soils and have been recognized to contribute to soil toxicity. The phytotoxic impact of pesticides was evaluated in Cucumis sativus (C. sativus) seeds. Percentage of seed germination, root elongation, shoot length and leaf length were considered as endpoints to assess the possible acute phytotoxicity of soil by the exposure to pyrethroid pesticides (cypermethrin, deltamethrin and cyhalothrin) and its metabolite phenoxybenzoic acid (3-PBA), in a concentration range between 50 and 500µgkg-1. For germination percentage, it was only observed a negative impact when seeds were exposed to the metabolite. Cypermethrin showed impact in the three studied endpoints of seed development, while deltamethrin merely affected the root length. Concerning pigments content, it can be said that chlorophylls and total carotenoids median values increased for cypermethrin and deltamethrin. This increase was more pronounced to deltamethrin in joint effect with the organic solvent dimethyl sulphoxide (DMSO). When exposed to cyhalothrin and 3-PBA, no statistically significant differences were observed for C. sativus seeds to all the assessed endpoints of seed development and the investigated pigments content. This research brings new data concerning the relative sensitivity of C. sativus seeds to pyrethroids pesticides commonly found in agricultural facilities, as well as critical understanding and development of using C. sativus for phytotoxicity assessments efforts for pesticide exposures.

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.

Documenting the kinetic time course of lambda-cyhalothrin metabolites in orally exposed volunteers for the interpretation of biomonitoring data.

Lambda-cyhalothrin is a pyrethroid pesticide largely used in agriculture. Exposure assessment can be performed by measuring key urinary metabolites. For a proper use of biomonitoring data, it is however important to gain information on the toxicokinetics of these key biomarkers of exposure. A human volunteer study was performed to document the plasma and urinary time courses of major lambda-cyhalothrin metabolites. Seven volunteers ingested 0.025mgkg-1 body weight of lambda-cyhalothrin. Blood samples were withdrawn prior to dosing and at fixed time periods over the 72 h-period following ingestion and complete urine voids were collected pre-exposure and at pre-established intervals over 84h post-dosing. The cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA) metabolites were quantified in these samples. Plasma concentrations of CFMP and 3-PBA increased rapidly after ingestion, with average peak values at 3.1 and 4.0h post-dosing, respectively; subsequent elimination phase showed a rapid decay with a mean half-life (t½) of ≈5.3 and 6.4h for CFMP and 3-PBA, respectively. Urinary rate time courses displayed a profile similar to the plasma concentration-time curves with corresponding mean t½ of ≈4.2 and 5.9h. In the 84-h period post-treatment, on average 21% of lambda-cyhalothrin dose were excreted in urine as CFMP as compared to 30% as 3-PBA. Overall, CFMP and 3-PBA metabolites were confirmed to be major metabolites of lambda-cyhalothrin and exhibited similar kinetics with short half-lives; they thus both appear as useful biomarkers of exposure to lambda-cyhalothrin in humans.

Time courses and variability of pyrethroid biomarkers of exposure in a group of agricultural workers in Quebec, Canada.

PURPOSE: Cypermethrin is a pyrethroid pesticide widely used in agriculture. Exposure can be assessed through biomonitoring. However, interpretation of results requires a proper knowledge of the toxicokinetics of the exposure biomarkers of interest. This study aimed at characterizing typical urinary time courses of biomarkers of exposure to cypermethrin in farm workers in Quebec following an exposure episode, distribution of values and variability, and predictors of elevated excretion levels. METHODS: Workers provided total voids before seasonal spraying and during three consecutive days following an exposure period. Personal factors, professional tasks, and exposure conditions were documented by questionnaire. The urinary metabolites cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (DCCA) and 3-phenoxybenzoic acid (3-PBA) were quantified. RESULTS: Time courses showed significant variations of metabolite levels through time, although a clear profile typical of an acute exposure episode was not observed for several workers. However, maximum urinary levels in most exposed workers were generally reached 18-32 h following the onset of an exposure episode. Group comparison showed that applicators had higher excretions than workers performing inspection, harvest, or weeding. CONCLUSIONS: Time-dependent variations in excretions indicate the importance of serial urinary collections for a proper interpretation of a worker exposure pattern. In the context of group comparison, the alternative based on observed time courses and peak levels in most exposed workers would be the collection of urine samples prior to an exposure episode, at the end-of-shift after exposure onset and following morning void. When spot samples can only be collected for population exposure assessment, Monte Carlo simulations showed that iterative random selection of single urinary values from individual time courses observed in this study to predict distribution of values in the group of workers converged to similar central tendencies.

Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers compared with previously available kinetic data following permethrin exposure.

Biomonitoring of pyrethroid exposure is largely conducted but human toxicokinetics has not been fully documented. This is essential for a proper interpretation of biomonitoring data. Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers have been documented and compared with previously available kinetic data following permethrin dosing. Six volunteers ingested 0.1 mg kg(-1) bodyweight of cypermethrin acutely. The same volunteers were exposed to permethrin earlier. Blood samples were taken over 72 h after treatment and complete timed urine voids were collected over 84 h postdosing. Cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (trans- and cis-DCCA) and 3-phenoxybenzoic acid (3-PBA) metabolites, common to both cypermethrin and permethrin, were quantified. Blood and urinary time courses of all three metabolites were similar following cypermethrin and permethrin exposure. Plasma levels of metabolites reached peak values on average ≈ 5-7 h post-dosing; the elimination phase showed mean apparent half-lives (t½ ) for trans-DCCA, cis-DCCA and 3-PBA of 5.1, 6.9 and 9.2 h, respectively, following cypermethrin treatment as compared to 7.1, 6.2 and 6.5 h after permethrin dosing. Corresponding mean values obtained from urinary rate time courses were peak values at ≈ 9 h post-dosing and apparent elimination t½ of 6.3, 6.4 and 6.4 h for trans-DCCA, cis-DCCA and 3-PBA, respectively, following cypermethrin treatment as compared to 5.4, 4.5 and 5.7 h after permethrin dosing. These data confirm that the kinetics of cypermethrin is similar to that of permethrin in humans and that their common biomarkers of exposure may be used for an overall assessment of exposure.