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Abstract: The comprehensive individual field-measurements on non-dietary exposure collected in the Children''s-Post-Pesticide-Application-Exposure-Study (CPPAES) were used within MENTOR/SHEDS-Pesticides, a physically based stochastic human exposure and dose model. In this application, however, the model was run deterministically. The MENTOR/SHEDS-Pesticides employed the CPPAES as input variables to simulate the exposure and the dose profiles for seven children over a 2-week post-application period following a routine residential and professional indoor crack-and-crevice chlorpyrifos application. The input variables were obtained from a personal activity diary, microenvironmental measurements and personal biomonitoring data obtained from CPPAES samples collected from the individual children and in their homes. Simulation results were compared with CPPAES field measured values obtained from the children''s homes to assess the utility of the different microenvironmental data collected in CPPAES, i.e. indicator toys and wipe samplers to estimate aggregate exposures that can be result from one or more exposure pathways and routes. The final analyses of the database involved comparisons of the actual data obtained from the individual biomarker samples of a urinary metabolite of chlorpyrifos (TCPy) and the values predicted by MENTOR/SHEDS-Pesticides using the CPPAES-derived variables. Because duplicate diet samples were not part of the CPPAES study design, SHEDs-Pesticides simulated dose profiles did not account for the dietary route. The research provided more confidence in the types of data that can be used in the inhalation and dermal contact modules of MENTOR/SHEDS-Pesticides to predict the pesticide dose received by a child. It was determined that we still need additional understanding about: (1) the types of activities and durations of activities that result in non-dietary ingestion of pesticides and (2) the influence of dietary exposures on the levels of TCPy found in the urine. [Copyright &y& Elsevier]

Abstract: Thyroid hormones are vital to a host of human physiological functions in both children and adults. Exposures to chemicals, including chlorpyrifos, have been found to modify thyroid signaling at environmentally relevant levels in animal studies. The aim of this study was to examine circulating T4 and TSH levels in relation to urinary concentrations of 3, 5, 6-trichloro-2-pyridinol (TCPY), a metabolite of the organophosphorus insecticides chlorpyrifos and chlorpyrifos-methyl, using data from individuals 12years and older from the U.S. National Health and Nutrition Examination Surveys (NHANES). NHANES datasets from 1999 to 2000 and 2001–2002 were combined, and individuals with thyroid disease, those taking thyroid medications, and pregnant women were excluded (N=3249). Multivariable linear regression models for relationships between log-transformed urinary TCPY and serum total T4 or log (TSH) were constructed adjusting for important covariates. Models were stratified by sex and a categorical age variable (12–18, 18–40, 40–60, and >60years). In male participants, an interquartile range (IQR) increase in urinary TCPY was associated with statistically significant increases in serum T4 of 3.8% (95th CI 0.75 to 7.0) among those 12–18years of age and 3.5% (95th CI 0.13 to 7.0) in the 18–40year age group, relative to median T4 levels using unweighted models. An IQR increase in TCPY was also associated with decreases in TSH of 10.7% (−18.7–2.05) among men 18–40years old and 20.0% (95th CI −28.9 to −9.86) among men >60years old. Conversely, urinary TCPY was positively associated with TSH in females >60years of age. Further research to confirm these findings, elucidate mechanisms of action, and explore the clinical and public health significance of such alterations in thyroid hormones is needed. [Copyright &y& Elsevier]

Globally, human exposures to organophosphate (OP) insecticides may pose a significant burden to the health of mothers and their developing fetuses. Unfortunately, relevant data is limited in certain areas of the world concerning sources of exposure to OP insecticides in pregnant populations. To begin to address this gap in information for Puerto Rico, we studied repeated measures of urinary concentrations of 10 OP insecticide metabolites among 54 pregnant women from the northern karst region of the island. We also collected demographic data and self-reported information on the consumption of fruits, vegetables, and legumes in the past 48 h before urine collection and home pest-related issues. We calculated the distributions of the urinary biomarkers and compared them to women of reproductive age from the general U.S. population. We also used statistical models accounting for correlated data to assess within-subject temporal variability of the urinary biomarkers and to identify predictors of exposure. We found that for all but two metabolites ( para -nitrophenol [PNP], diethylthiophosphate [DETP]), 50th or 95th percentile urinary concentrations (the metric that was used for comparison was based on the biomarker's detection frequency) of the other eight metabolites (3,5,6-trichloro-2-pyridinol [TCPY], 2-isopropyl-4-methyl-6-hydroxy-pyrimidine, malathion dicarboxylic acid, diethylphosphate, diethyldithiophosphate, dimethylphosphate, dimethylthiophosphate [DMTP], dimethyldithiophosphate) were somewhat lower in our cohort compared with similarly aged women from the continental United States. TCPY, PNP, DETP, and DMTP, which were the only urinary metabolites detected in greater than 50% of the samples, had poor reproducibility (intraclass correlation coefficient range: 0.19–0.28) during pregnancy. Positive predictors of OP insecticide exposure included: age; marital or employment status; consumption of cherries, grape juice, peanuts, peanut butter, or raisins; and residential application of pesticides. Further research is needed to understand what aspects of the predictors identified influence OP insecticide exposure during pregnancy. [ABSTRACT FROM AUTHOR]

To examine the association between urinary metabolites of organophosphate (OP) pesticides and serum concentrations of thyroid and reproductive hormones in male adolescents and to assess the potential effect of interactions between OP pesticides and paraoxonase 1 (PON1) polymorphisms on hormone levels. Study subjects (N = 117) were male 16- to 17-year-olds from the Environment and Childhood (INMA)-Granada cohort in Spain. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos/chlorpyrifos-methyl, 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), a metabolite of diazinon, and diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP), non-specific metabolites of OP pesticides, were measured in a spot urine sample from each subject and adjusted for creatinine. Levels of reproductive hormones (total testosterone [TT], estradiol [E 2 ], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Müllerian hormone [AMH], insulin growth factor 1 [IGF-1], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), and PON1 Q192R and L55M polymorphisms were determined in blood drawn during the same clinical visit. Multiple linear regression models showed that detectable levels of TCPy were associated with an increase in DHEAS and decreases in E 2 , FSH, and AMH; detectable IMPy with increases in E 2 , DHEAS, FSH, AMH, and prolactin and decreases in SHBG and LH; and detectable DETP with marginally-significant increases in TT and TT3 and decreases in FSH, AMH, and prolactin. The effect of IMPy and DETP on DHEAS and TT levels, respectively, was higher in subjects that carried the PON1 55MM genotype, while the effect of TCPy, IMPy, and DETP on thyroid hormone levels was higher in PON1 192QR/RR or 55MM genotype carriers. In male adolescents, non-occupational exposure to OP pesticides was associated with several changes in reproductive and thyroid hormone levels, and the magnitude of some associations was greater in adolescents genetically more susceptible to OP pesticide exposure who carry the PON1 55MM genotype. Unlabelled Image • OP pesticides are potential endocrine disruptors that may affect hormone levels. • We assessed the link between OP urinary metabolites and hormones in boys. • We also examined the interaction between OP metabolites and PON1 polymorphisms. • OP exposure was associated with altered reproductive and thyroid hormone levels. • Some associations were greater in subjects carrying the PON1 55MM genotype. [ABSTRACT FROM AUTHOR]

Human exposure to pesticides is widespread and has received much attention in recent years because of its link to adverse health outcomes. Measurement of urinary concentrations of pesticides and their metabolites is often used in the assessment of body burdens of these chemicals. However, pesticides and their metabolites can be present in blood circulatory system, although little is known on serum levels of pesticides. In this study, we aimed to examine the occurrence and profile of four organophosphate (OP), five pyrethroid (PYR) insecticides, two phenoxy acid (PA) herbicides, 14 neonicotinoid (neonic) insecticides and six dialkylphosphate metabolites in serum from 25 individuals diagnosed with osteoarthritis in Jeddah, Saudi Arabia. 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), 3,5,6-trichloro-2-pyridinol (TCPY), 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, 3-phenoxybenzoic acid, N -desmethyl acetamiprid, dimethylphosphate (DMP) and dimethylthiophosphate (DMTP) were detected in ≥80% of the serum samples analyzed. Metabolites of OPs, DMTP (median concentration: 2.14 ng/mL), DMP (1.04 ng/mL) and TCPY (0.84 ng/mL), collectively accounted for 67–83% of the total serum pesticide concentrations. Serum concentrations of pesticides were similar to or lower than those reported in urine. Our preliminary evidence suggests that serum can be used as a matrix for the assessment of exposure to OPs, PYRs, PAs and neonics. Unlabelled Image • Thirty-one pesticides and their metabolites were measured in human serum. • Eight out of 31 pesticides were detected in ≥80% of the serum samples. • Metabolites of organophosphates, DMP, DMTP and TCPY, were dominant in serum. • Serum can be used as a matrix to assess pesticide exposures. [ABSTRACT FROM AUTHOR]

Organophosphate insecticides have been widely used for >30 years, and are reported to be associated with various age-related chronic diseases. While shortening of telomere length has been considered as a marker of cellular aging, only a few small studies have been conducted to examine any difference of telomere length in workers exposed to organophosphates versus controls. Epidemiologic studies of the dose-response associations between environmental organophosphate exposure and telomere length in the general population are few. This study aimed to evaluate the association between levels of organophosphate insecticide exposure and telomere length in the general population. We analyzed data for 1724 participants aged 20 years or more from the National Health and Nutrition Examination Survey 1999–2002. Organophosphate insecticide exposure was estimated using measures of urinary concentrations for 3,5,6-trichloro-2-pyridinol (TCPY) and six non-specific dialkyl phosphate metabolites, e.g., diethyl thiophosphate (DETP). Multiple linear regression was conducted to assess the association between organophosphate exposure and telomere length. After controlling for sociodemographic and physical factors and urinary creatinine, participants in the second quartile for urinary TCPY had 0.06 (95% CI: 0.02–0.10) T/S ratio shorter telomere length than those in the lowest quartile. By contrast, participants in the second and third tertiles of urinary DETP had 0.08 (95% CI: 0.02–0.14) and 0.06 (95% CI, 0.01–0.11) T/S ratio longer telomere length than those in the lowest tertile. For other five metabolites, there was no association with telomere length. Levels of environmental exposures to certain organophosphate insecticides may be linked to altered telomere length in adults in the general population. Although our findings may need to be replicated, we provide the first evidence that environmental exposure to organophosphates may contribute to the alteration of telomere length, which is potentially related to biological aging and to the development of various chronic diseases. Unlabelled Image • Exposures to organophosphate insecticides may be linked to altered telomere length. • Their associations depended on the particular organophosphate metabolite. • TCPY was associated with shorter telomere length. • DETP was associated with longer telomere length. • This is the first epidemiological evidence for their associations in general adults. [ABSTRACT FROM AUTHOR]

Pesticides offer many benefits for humanity and agriculture, but at the same time pose a potential risk to human health because of their widespread use and high biological activity. Human biomonitoring (HBM) studies are the main tool to investigate human exposure to pesticides and other chemicals, but face limitations such as sampling biases, long time to complete and high costs. Wastewater-based epidemiology (WBE) is an alternative approach that is centered on the chemical analysis of biomarkers of (pesticide) exposure in urban wastewater. The present study used WBE to assess human exposure to selected classes of pesticides, triazines, pyrethroids and organophosphates, in Norway. Untreated wastewater samples were collected from four cities, covering approximately 20% of the Norwegian population. The highest population weighted mass loads (mg/day/1000 inhabitants) were for alkyl phosphates and the lowest for triazines. Some differences were observed for the two metabolites, 2-isopropyl-6-methyl-4-pyrimidinol (IMPY) and 3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (DCCA), which were higher in the rural city of Hamar. WBE figures were comparable with HBM findings for the specific metabolite of chlorpyrifos and chlorpyrifos methyl (3,5,6-trichloro-2-pyridinol; TCPY) but were different for the alkyl phosphates. Pyrethroid intake was calculated and was lower than the acceptable daily intake in all the cities, indicating low risk for human health. This is the most extensive WBE study performed to date to assess national human exposure to pesticides. This study demonstrated that WBE has the potential to be a useful complementary biomonitoring tool for assessing population-wide exposure to pesticides, overcoming some of the limitations of HBM. Unlabelled Image • Wastewater-based epidemiology was used to assess population exposure to pesticides. • The study covered 20% of the Norwegian population. • Some spatial differences were found for pyrethroids and organophosphates. • Levels of 3,5,6-trichloro-2-pyridinol were comparable to those found in human urine. • No potential risk for human health was assessed for pyrethroids. [ABSTRACT FROM AUTHOR]

Several studies have suggested that exposure to organophosphorus (OP) pesticides is detrimental for health, and in particular for children where moderate doses may have a negative impact on the neurodevelopment. This study surveys levels of the 6 non-specific urinary metabolites (dialkyl phosphates (DAPs)) of OP pesticides in Norwegian mothers (n = 48) and their children (n = 54), and examines the diurnal variation in concentrations as well as associations with consumption of specific food products. The highest median concentration measured in urine was found for dimethyl thiophosphate (5.3 and 5.5 ng/mL SG ; specific gravity corrected) for both children and mothers, respectively, followed by diethyl phosphate (3.8 and 5.3 ng/mL SG , respectively). The intra-class correlation coefficients of DAPs among mothers were moderate (0.49–0.68), and consumption of fruit explained between 8% and 55% of the variations in the mothers' and their children's urinary DAP concentrations. [ABSTRACT FROM AUTHOR]