Apparent Khat chewers exposure to DDT in Ethiopia and its potential toxic effects: A scoping review.

Dichlorodiphenyltrichloroethane (DDT) is an insecticide, a member of dirty dozen persistent organic pollutants, used widely in the world until it was banned in the 1970s.The banning of DDT was strengthened by the Stockholm Convention in 2001. DDT is allowed only for malaria control in Ethiopia. However, farmers are misusing DDT and applying it to Khat (Catha edulis) farming. So, this review analyzes available data in the literature on the current trend, application, occurrence, fate and effects of DDT and its metabolites, dichlorodiphenyldichloroethane (DDD), dichlorodiphenyldichloroethylene (DDE), in the chewable parts of Khat. Generally, the concentration level of DDT, DDD, and DDE, designated as DDTs, is detected in different farmlands of Ethiopia. Some of the DDTs concentrations detected are very high (141.2-973 µg/kg (Gelemso), 194.4-999 µg/kg (Aseno) and 6253-8413.3 µg/kg (Gurage), and these concentrations may indicate increasing recent unmonitored application of DDT on Khat leaves. Some of the detected concentrations of DDT in the literature were above the maximum residue limit (MRL) set by FAO/WHO (100 µg/kg) and the European Commission 10 µg/kg in vegetables and 50 µg/kg in cereals. DDT exposure of Khat chewers linked to the concentration of DDT on Khat leaves and the amount of Khat consumed. DDT might pose health risks to chewers due to chronic toxicity, bioaccumulation, persistent and endocrine disruption properties.

Metabolic Consequences of the Water We Drink: A Study Based on Field Evidence and Animal Model Experimentation.

The effect of the chronic consumption of water contaminated with residual concentrations of DDT's metabolites (DDD-dichlorodiphenyldichloroethane and DDE-dichlorodiphenyldichloroethylene) found in the environment were evaluated on the biometric, hematological and antioxidant system parameters of the hepatic, muscular, renal and nervous tissues of Wistar rats. The results showed that the studied concentrations (0.002 mg.L-1 of DDD plus 0.005 mg.L-1 of DDE) could not cause significant changes in the hematological parameters. However, the tissues showed significant alteration in the activity of the antioxidant system represented by the increase in the activity of the enzymes gluthathione S-transferases in the liver, superoxide dismutase in the kidney, gluthathione peroxidase in the brain, and several changes in enzymatic activity in muscle (SOD, GPx and LPO). The enzymes alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) were also evaluated for the amino acids' metabolism in the liver, with ALT showing a significant increase in the exposed animals. In the integrative analysis of biomarkers (Permanova and PCOA), the studied concentrations showed possible metabolic changes and damage to cellular structures evidenced by increased oxidative stress and body weight gain among the treated animals. This study highlights the need for further studies on the impact of banned pesticides still present in soils that may induce adverse effects in organisms that may prevail in future generations and the environment.

Exposure to non-persistent pesticides and sexual maturation of Spanish adolescent males.

BACKGROUND: Several non-persistent pesticides are endocrine disrupting chemicals and may impact on sexual maturation. OBJECTIVE: To examine the association between urinary biomarkers of non-persistent pesticides and sexual maturation in adolescent males in the Environment and Childhood (INMA) Project. METHODS: The metabolites of several pesticides were measured in spot urine samples collected from 201 boys aged 14-17 years, including: 3,5,6-trichloro-2-pyridinol (TCPy), metabolite of chlorpyrifos; 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), metabolite of diazinon; malathion diacid (MDA), metabolite of malathion; diethyl thiophosphate (DETP) and diethyl dithiophosphate, non-specific metabolites of organophosphates; 3-phenoxybenzoic acid (3-PBA) and dimethyl cyclopropane carboxylic acid, metabolites of pyrethroids; 1-naphthol (1-NPL), metabolite of carbaryl; and ethylene thiourea (ETU), metabolite of dithiocarbamate fungicides. Sexual maturation was assessed using Tanner stages, self-reported Pubertal Development Scale, and testicular volume (TV). Multivariate logistic regression was employed to examine associations between urinary pesticide metabolites and the odds of being in Tanner stage 5 of genital development (G5) or pubic hair growth (PH5); stage ≥4 of overall pubertal development, gonadarche, and adrenarche; or having mature TV (≥25 mL). RESULTS: DETP concentrations>75th percentile (P75) were associated with lower odds of being in stage G5 (OR = 0.27; 95% CI = 0.10-0.70), detectable TCPy with lower odds of gonadal stage≥4 (OR = 0.50; 95% CI = 0.26-0.96), and intermediate detectable MDA concentrations (

Cellulose polymers with ß-amino ester pendant group: design, synthesis, molecular docking and application in adsorption of toxic metals from wastewater.

BACKGROUND: Cellulose polymers with multidentate chelating functionalities that have high efficiency for toxic metal ions present in water were designed, synthesized, and analyzed. The synthesis was carried out by reacting microcrystalline cellulose extracted from the solid waste of the olive industry with tert-Butyl acetoacetate (Cell-AA), produced cellulose with ß-ketoester functionality was then reacted with aniline and the amino acid glycine to produce Cell-ß-AN and Cell-ß-GL, respectively. RESULTS: The adsorption efficiency of the three polymers toward Pb(II) and various toxic metal ions present in sewage was evaluated as a function of adsorbent dose, time, temperature, pH value, and initial ion concentration to determine optimum adsorption conditions. The three polymers showed excellent efficiency toward about 20 metal ions present in a sewage sample collected from the sewer. The adsorption process follows the Langmuir adsorption isotherm model with a second-order of adsorption rate, the calculated qe values (2.675, 15.252, 20.856 mg/g) were close to the experimental qe values (2.133, 13.91, 18.786 mg/g) for the three polymers Cell-AA, Cell-ß-AG and Cell-ß-AN, respectively. Molecular Dynamic (MD) and Monte Carlo (MC) simulations were performed on the three polymers complexed with Pb(II). CONCLUSION: The waste material of the olive industry was used as a precursor for making the target cellulose polymers with ß-Amino Ester Pendant Group. The polymer was characterized by SEM, proton NMR, TGA, and FT-IR spectroscopy. The efficacy of adsorption was quantitative for metal ions present in a real sample of wastewater and the efficiency didn't drop even after 7 cycles of use. The results indicate the existence of strong complexation. The thermodynamic study results showed a spontaneous bonding between of Pb(II) and the polymers pendant groups expressed by the negative value of the Gibbs free energy.

Association of urinary metabolites of non-persistent pesticides with serum sex hormones among the US females: NHANES 2013-2014.

BACKGROUND: Evidence indicated the possibility of non-persistent pesticides disrupting the homeostasis of sex hormones. However, few studies have focused on this relationship in females. We aimed to explore the relationship between non-persistent pesticide exposure and sex hormones among the US females from the National Health and Nutrition Examination Survey 2013-2014. METHODS: A total of 790 females, including girls (6-11 years), female adolescents (12-19 years), and adult females (>19 years), were enrolled in this study. Age stratified associations of individual non-persistent pesticide metabolites and their mixtures with sex hormones were analyzed by weighted multiple linear regression and Bayesian kernel machine regression (BKMR) using spot urinary non-persistent pesticide measurement, including 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloropyridinol (TCPY), para-nitrophenol (PNP) and 3-phenoxybenzoic acid (3-PBA), and three serum sex hormones [total testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG)]. RESULTS: In girls, weighted multivariate linear regression indicated that both 2,4-D and PNP were negatively associated with TT, and TCPY was inversely associated with SHBG. In female adolescents, TCPY was negatively associated with TT and E2, and 3-PBA was negatively associated with SHBG; positive associations were detected both in 2,4-D with SHBG, and in PNP with TT. In adult females, a higher concentration of 3-PBA was associated with higher levels of TT. The BKMR model showed that in female adolescents, the concentrations of pesticide metabolite mixtures at or above the 55th percentile were negatively related to the levels of E2 compared with their mixtures at 50th percentile, and an inverse U-shaped exposure-response function between PNP and E2 was found. CONCLUSIONS: Associations between the four non-persistent pesticide metabolites and serum sex hormones were identified in the US females from NHANES 2013-2014 and these associations were age dependent, especially in adolescents. Large-scale cohort studies are needed to confirm these findings and elucidate the potential biological mechanisms.

Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach.

BACKGROUND: Numerous contemporary non-persistent pesticides may elicit neurodevelopmental impairments. Brain-derived neurotrophic factor (BDNF) has been proposed as a novel effect biomarker of neurological function that could help to understand the biological responses of some environmental exposures. OBJECTIVES: To investigate the relationship between exposure to various non-persistent pesticides, BDNF, and behavioral functioning among adolescents. METHODS: The concentrations of organophosphate (OP) insecticide metabolites 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), malathion diacid (MDA), and diethyl thiophosphate (DETP); metabolites of pyrethroids 3-phenoxybenzoic acid (3-PBA) and dimethylcyclopropane carboxylic acid (DCCA), the metabolite of insecticide carbaryl 1-naphthol (1-N), and the metabolite of ethylene-bis-dithiocarbamate fungicides ethylene thiourea (ETU) were measured in spot urine samples, as well as serum BDNF protein levels and blood DNA methylation of Exon IV of BDNF gene in 15-17-year-old boys from the INMA-Granada cohort in Spain. Adolescents' behavior was reported by parents using the Child Behavior Check List (CBCL/6-18). This study included 140 adolescents of whom 118 had data on BDNF gene DNA methylation. Multivariable linear regression, weighted quantile sum (WQS) for mixture effects, and mediation models were fit. RESULTS: IMPy, MDA, DCCA, and ETU were detected in more than 70% of urine samples, DETP in 53%, and TCPy, 3-PBA, and 1-N in less than 50% of samples. Higher levels of IMPy, TCPy, and ETU were significantly associated with more behavioral problems as social, thought problems, and rule-breaking symptoms. IMPy, MDA, DETP, and 1-N were significantly associated with decreased serum BDNF levels, while MDA, 3-PBA, and ETU were associated with higher DNA methylation percentages at several CpGs. WQS models suggest a mixture effect on more behavioral problems and BDNF DNA methylation at several CpGs. A mediated effect of serum BDNF within IMPy-thought and IMPy-rule breaking associations was suggested. CONCLUSION: BDNF biomarkers measured at different levels of biological complexity provided novel information regarding the potential disruption of behavioral function due to contemporary pesticides, highlighting exposure to diazinon (IMPy) and the combined effect of IMPy, MDA, DCCA, and ETU. However, further research is warranted.

Combining Culture-Dependent and Independent Approaches for the Optimization of Epoxiconazole and Fludioxonil-Degrading Bacterial Consortia.

Epoxiconazole (EPO) and fludioxonil (FLU) are two widely used fluorinated pesticides known to be highly persistent and with high ecotoxicological potential, turning them into pollutants of concern. This work aimed to optimize two degrading bacterial consortia, previously obtained from an agricultural soil through enrichment with EPO and FLU, by characterizing the contribution of their corresponding bacterial isolates to the biodegradation of these pesticides using both culture-dependent and independent methodologies. Results showed that a co-culture of the strains Hydrogenophaga eletricum 5AE and Methylobacillus sp. 8AE was the most efficient in biodegrading EPO, being able to defluorinate ca. 80% of this pesticide in 28 days. This catabolic performance is likely the result of a commensalistic cooperation, in which H. eletricum may be the defluorinating strain and Methylobacillus sp. may assume an accessory, yet pivotal, catabolic role. Furthermore, 16S rRNA metabarcoding analysis revealed that these strains represent a minority in their original consortium, showing that the biodegradation of EPO can be driven by less abundant phylotypes in the community. On the other hand, none of the tested combinations of bacterial strains showed potential to biodegrade FLU, indicating that the key degrading strains were not successfully isolated from the original enrichment culture. Overall, this work shows, for the first time, the direct involvement of two bacterial species, namely H. eletricum and Methylobacillus sp., in the biodegradation of EPO, while also offering insight on how they might cooperate to accomplish this process. Moreover, the importance of adequate culture-dependent approaches in the engineering of microbial consortia for bioremediation purposes is also emphasized.

Cellulose-Based Hectocycle Nanopolymers: Synthesis, Molecular Docking and Adsorption of Difenoconazole from Aqueous Medium.

The goal of this work was to develop polymer-based heterocycle for water purification from toxic pesticides such as difenoconazole. The polymer chosen for this purpose was cellulose nanocrystalline (CNC); two cellulose based heterocycles were prepared by crosslinking with 2,6-pyridine dicarbonyl dichloride (Cell-X), and derivatizing with 2-furan carbonyl chloride (Cell-D). The synthesized cellulose-based heterocycles were characterized by SEM, proton NMR, TGA and FT-IR spectroscopy. To optimize adsorption conditions, the effect of various variable such as time, adsorbent dose, pH, temperature, and difenoconazole initial concentration were evaluated. Results showed that, the maximum difenoconazole removal percentage was about 94.7%, and 96.6% for Cell-X and Cell-D, respectively. Kinetic and thermodynamic studies on the adsorption process showed that the adsorption of difenoconazole by the two polymers is a pseudo-second order and follows the Langmuir isotherm model. The obtained values of ∆G ° and ∆H suggest that the adsorption process is spontaneous at room temperature. The results showed that Cell-X could be a promising adsorbent on a commercial scale for difenoconazole. The several adsorption sites present in Cell-X in addition to the semi crown ether structure explains the high efficiency it has for difenoconazole, and could be used for other toxic pesticides. Monte Carlo (MC) and Molecular Dynamic (MD) simulation were performed on a model of Cell-X and difenoconazole, and the results showed strong interaction.

Urinary metabolites of non-persistent pesticides and serum hormones in Spanish adolescent males.

OBJECTIVE: To assess the relationship of urinary concentrations of ethylenethiourea (ETU), the main degradation product of ethylene bis-dithiocarbamate fungicides, 3-phenoxybenzoic acid (3-PBA), a common metabolite of many pyrethroids, and 1-naphthol (1N), a metabolite of the carbamate insecticide carbaryl, with hormone concentrations in adolescent males; and to examine interactions between pesticide metabolites and polymorphisms in xenobiotic metabolizing enzymes, including CYP2C19 and CYP2D6, in relation to hormone concentrations. METHODS: A cross-sectional study was conducted in 134 males from the Spanish Environment and Childhood (INMA)-Granada cohort. Urine and serum samples were collected from participants during the same clinical visit at the age of 15-17 years. First morning urine void was analyzed for concentrations of ETU, 3-PBA, and 1N. Serum was analyzed for concentrations of reproductive hormones (testosterone, 17ß-estradiol [E2], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Müllerian hormone [AMH], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), insulin growth factor 1 (IGF-1), adrenocorticotropic hormone (ACTH), and cortisol. CYP2C19 G681A and CYP2D6 G1846A polymorphisms were determined in blood from 117 participants. Multiple linear regression, interaction terms, and stratified analyses were performed. RESULTS: Urinary ETU was detected in 74.6% of participants, 1N in 38.1%, and 3-PBA in 19.4%. Positive associations between detectable 3-PBA and TT3 and between detectable 1N and DHEAS were found, and marginally-significant associations of 1N with reduced E2 and FSH were observed. Poor CYP2C19 and CYP2D6 metabolizers (GA and AA genotype carriers) showed a greater increase in DHEAS for detected versus undetected 1N compared with GG genotype carriers. Poor CYP2D6 metabolizers (1846 GA and AA genotypes) evidenced increased cortisol for detected versus undetected ETU. CONCLUSIONS: The associations observed between urinary pesticide metabolites and altered thyroid and reproductive hormones are novel and should be verified in studies with larger sample size. Further research on gene-environment interactions is warranted to establish individual susceptibility to pesticides and the risk of adverse health effects.

Microbial degradation of two highly persistent fluorinated fungicides - epoxiconazole and fludioxonil.

Biodegradation of two highly persistent fluorinated fungicides, epoxiconazole (EPO) and fludioxonil (FLU), by microbial consortia enriched from estuarine sediment and agricultural soil is reported. After an enrichment period of 6 months, four microbial consortia were able to completely remove and defluorinate the fungicides in co-metabolic conditions. Defluorination was biologically mediated and results suggest it is not a primary catabolic step, as fungicide removal was always faster than its defluorination. Three of the four enriched consortia had similar biodegradation performances in the absence of a co-substrate. Biodegradation kinetics revealed that microbial degradation followed a first-order kinetics, with cultures being capable of biodegrading concentrations up to 10 mg L-1 of EPO or FLU, in a maximum of 21 days. Estimated half-life values for these compounds were significantly lower than those reported in literature, highlighting the unique metabolic performance of the obtained consortia. Analysis of their microbial composition revealed that they integrate several bacterial species belonging to the Proteobacteria phylum, with the most common genera being Pseudomonas, Ochrobactrum and Comamonas. This is the first study providing clear evidence on the biodegradation of EPO and FLU, opening doors for the design of bioremediation technologies for the recovery of ecosystems polluted with such recalcitrant compounds.

Occupational exposure to pesticides and hematological alterations: A survey of farm residents in the South of Brazil / Exposição ocupacional a agrotóxicos e alterações hematológicas: Estudo transversal em moradores rurais do Sul do Brasil

Abstract This study sought to investigate the association of exposure to organochlorine (OC) and non-persistent pesticides with hematological parameters in an agricultural population in Southern Brazil. A cross-sectional study was conducted with a random sample of 275 farm workers and their families in Farroupilha-RS. A questionnaire was used to collect information on sociodemographic and lifestyle factors, duration, frequency and type of pesticide used, among others. Blood samples were collected and analyzed for serum concentration of 24 OC pesticides and hematological parameters. Associations were explored through linear regression, controlling for confounders. Lifetime use of chemical classes other than organophosphates and dithiocarbamates were associated with decreased number of lymphocytes, while subjects sampled in the high pesticide use season showed higher number of erythrocytes and hemoglobin level. Detectable serum levels of many OC pesticides were associated with lower counts of white blood cells, particularly eosinophils. Although mostly null associations were observed between pesticide use and hematological parameters, findings may suggest that OC pesticides could lead to hematological alterations among agricultural workers.

Resumo O objetivo deste estudo foi investigar a associação entre a exposição a organoclorados (OC) e agrotóxicos não persistentes e os parâmetros hematológicos em uma população agrícola de Farroupilha-RS. Foi utilizado um questionário para coletar informações sobre fatores sociodemográficos e de estilo de vida, duração, frequência e tipo de pesticidas utilizados, entre outros. Amostras sanguíneas foram coletadas e analisadas quanto a concentração sérica de 24 pesticidas OC e parâmetros hematológicos. As associações foram exploradas através de regressão linear, controlando por confundidores. O uso cumulativo de classes químicas diferentes de organofosforados e ditiocarbamatos associou-se com diminuição do número de linfócitos enquanto indivíduos que tiveram suas coletas sanguíneas realizadas na estação de maior uso de agrotóxicos tinham contagem de eritrócitos e hemoglobina maiores. Níveis séricos de diversos pesticidas organoclorados foram associados com contagens mais baixas de células brancas do sangue, particularmente eosinófilos. Embora as associações com o uso de agrotóxicos tenham sido, em geral, nulas, os resultados podem sugerir que os pesticidas OCs poderiam levar a alterações hematológicas entre os trabalhadores agrícolas.

Thyroid and reproductive hormones in relation to pesticide use in an agricultural population in Southern Brazil.

This study aimed to assess the association of short- and long-term exposure to pesticides with circulating levels of thyroid and reproductive hormones in an agricultural population in the South of Brazil. Serum specimens from 122 male and female adults residing in small agricultural properties were sampled both in the low and high pesticide use season. A comprehensive questionnaire was used to collect detailed information on recent and cumulative lifetime use of pesticides and other agricultural-related exposures. The difference in serum hormone levels between seasons was assessed by the T-test and Wilcoxon test for paired samples, and associations between pesticide exposure-related variables and hormone values were explored by multivariate linear regression analysis. Levels of total thyroxine (T4) and male testosterone were significantly reduced from the low to high pesticide use season. In the high exposure season, recent use of dithiocarbamate fungicides, not using full personal protection equipment, and use of manual equipment was associated with reduced levels of thyroid-stimulating hormone (TSH). Moreover, recent use of lambda-cyhalothrin (pyrethroid) was associated with reduced total T4 and increased male luteinizing hormone (LH), use of paraquat (herbicide) with reduced free triiodothyronine (T3), and use of phthalamide (fungicide) with increased male LH. We also found associations of lifetime years of agricultural work with reduced total T4 and increased male testosterone; and of lifetime agricultural work and use of various pesticide classes (i.e. insecticides, herbicides, organophosphate insecticides, dithiocarbamate fungicides, and pyrethroids), mancozeb (fungicide), and paraquat with slight changes in free or total levels of T4 and/or T3. Findings suggest that both short- and long-term exposure to agricultural pesticides may alter thyroid hormones and male testosterone levels among farm residents.

Non-persistent pesticides in breast milk in an agricultural area in Turkey.

BACKGROUND: Organophosphates, pythyreoids, carbamate pesticides and fungicides are heavily used in agriculture. They may have dangerous effects on newborn health especially on immune system and growth via prenatal transmission by placenta or postnatal transmission by breastfeeding. METHODS: In 2015, 144 non-persistent pesticides in 64 milk samples of 32 mothers were studied by OuEChERS method in liquid chromatography/tandem mass spectrometer in neonatal Intensive Care Unit in Adana, a city in Cukurova region which is an important agricultural area in Turkey. RESULTS: Pesticides were detected in milk samples of 11 mothers (34.3%) and 21 (32.8%) of milk samples. In five mothers, fungicides (in 5/10 samples propicanozole-PP, in 4/10 samples bromucanozole-BM), in five mothers, organophosphates (in 10/10 samples primyphosphomethyl-PPM), in one mother, both organophosphates and fungicide (in 1/2 samples PPM and in 1/2 samples buprimate) were detected. However, the estimated daily intakes (EDI) were less than acceptable daily intakes (ADI) for PPM, PP and BM, respectively. CONCLUSIONS: Although pesticides levels in human milk did not exceed the ADIs, we suggest monitoring pesticides in human breast milk especially for newborn health.

Pesticide exposure and thyroid function in an agricultural population in Brazil.

Although numerous pesticides may interfere with thyroid function, however, epidemiological evidence supporting this relationship is limited, particularly regarding modern non-persistent pesticides. We sought to evaluate the association of agricultural work practices, use of contemporary-use pesticides, and OC pesticides residue levels in serum with circulating thyroid hormone levels in an agricultural population. A cross-sectional study was conducted with a random sample of 275 male and female farm residents in Farroupilha, South of Brazil. Information on sociodemographics, lifestyle and agricultural work was obtained through questionnaire. Blood samples were collected on all participants and analyzed for cholinesterase activity, serum residues of OC pesticides, and levels of free T4 (FT4), total T3 (TT3) and TSH. Non-persistent pesticides exposure assessment was based on questionnaire information on current use of pesticides, and frequency and duration of use, among others. Associations were explored using multivariate linear regression models. Total lifetime years of use of fungicides, herbicides and dithiocarbamates in men was associated with increased TSH accompanied by decrease in FT4, with evidence of a linear trend. In addition, there was an association between being sampled in the high pesticide-use season and increased TSH levels. Conversely, farm work and lifetime use of all pesticides were related with slight decrease in TSH and increased TT3 and FT4, respectively. In general, pesticide use was not associated with thyroid hormones in women. Subjects with detected serum concentrations of ß-hexachlorocyclohexane, endrin, dieldrin, heptachlor epoxide B, γ-chlordane, transnonachlor, heptachlor, p,p'-dichlorodiphenylethane and endosulfan II experienced slight changes in TT3; however, associations were weak and inconsistent. These findings suggest that both cumulative and recent occupational exposure to agricultural pesticides may affect the thyroid function causing hypothyroid-like effects, particularly in men.

Exposure to non-persistent pesticides and thyroid function: A systematic review of epidemiological evidence.

Numerous pesticides are recognized for their endocrine-disrupting properties. Non-persistent pesticides such as organophosphates, dithiocarbamates and pyrethroids may interfere with thyroid function as suggested by animal studies. However, the influence of chronic exposure to these compounds on thyroidal functions in humans remains to be determined. The present study aimed to review epidemiological evidence for an association between exposure to non-persistent pesticides and circulating levels of thyroid hormones (thyroxin [T4] and triiodothyronine [T3]) and thyroid-stimulating hormone (TSH). A systematic review was conducted using MEDLINE, SCOPUS and Virtual Health Library (BVS) databases. Articles were limited to original studies and reports published in English, Portuguese or Spanish. Nineteen epidemiological studies were identified, 17 of which were cross-sectional, 14 were of occupationally exposed workers and 11 used exposure biomarkers. Fungicides and organophosphates (OP) insecticides were the most studied pesticides. Although methodological heterogeneity between studies was noted, particularly regarding study design, exposure assessment, and control of confounding, most of them showed associations with changes in T3 and T4, and/or TSH levels, while results from a few of these are consistent with experimental data supporting the findings that non-persistent pesticide exposure exerts hypothyroid-like effects. However, reporting quality was moderate to poor in 50% of the studies, particularly regarding method of selection of participants and discussion of external validity. Overall, current knowledge regarding the impact of non-persistent pesticides on human thyroid function is still limited. Given the widespread use of pesticides, future research should assess effects of exposure to currently-used pesticides in cohort studies combining comprehensive questionnaire-based assessment and biomarkers. Investigators need to pay particular attention to exposure during critical windows of brain development and exposure in agricultural populations.

Association of persistent organic pollutants and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia: A systematic review.

BACKGROUND: Over half of the people with diabetes in the world live in Asia. Emerging scientific evidence suggests that diabetes is associated with environmental pollutants, exposures that are also abundant in Asia. OBJECTIVE: To systematically review the literature concerning the association of persistent organic pollutants (POPs) and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia. METHODS: PubMed and Embase were searched to identify studies published up to November 2014. A secondary reference review of all extracted articles and the National Toxicology Program Workshop on the association of POPs with diabetes was also conducted. A total of 19 articles met the inclusion criteria and were evaluated in this review. RESULTS: To date, the evidence relating POPs and non-persistent pesticides with diabetes in Asian populations is equivocal. Positive associations were reported between serum concentrations of polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and several organochlorine pesticides (DDT, DDE, oxychlordane, trans-nonachlor, hexachlorobenzene, hexachlorocyclohexane) with diabetes. PCDD/Fs were also associated with blood glucose and insulin resistance, but not beta-cell function. There were substantial limitations of the literature including: most studies were cross-sectional, few studies addressed selection bias and confounding, and most effect estimates had exceptionally wide confidence intervals. Few studies evaluated the effects of organophosphates. CONCLUSIONS: Well-conducted research is urgently needed on these pervasive exposures to inform policies to mitigate the diabetes epidemic in Asia.

Case-control study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women.

BACKGROUND: Exposure to environmental chemicals may impair endocrine system function. Alaska Native (AN) women may be at higher risk of exposure to these endocrine disrupting chemicals, which may contribute to breast cancer in this population. OBJECTIVE: To measure the association between exposure to select environmental chemicals and breast cancer among AN women. DESIGN: A case-control study of 170 women (75 cases, 95 controls) recruited from the AN Medical Center from 1999 to 2002. Participants provided urine and serum samples. Serum was analyzed for 9 persistent pesticides, 34 polychlorinated biphenyl (PCB) congeners, and 8 polybrominated diethyl ether (PBDE) congeners. Urine was analyzed for 10 phthalate metabolites. We calculated geometric means (GM) and compared cases and controls using logistic regression. RESULTS: Serum concentrations of most pesticides and 3 indicator PCB congeners (PCB-138/158; PCB-153, PCB-180) were lower in case women than controls. BDE-47 was significantly higher in case women (GM=38.8 ng/g lipid) than controls (GM=25.1 ng/g lipid) (p=0.04). Persistent pesticides, PCBs, and most phthalate metabolites were not associated with case status in univariate logistic regression. The odds of being a case were higher for those with urinary mono-(2-ethylhexyl) phthalate (MEHP) concentrations that were above the median; this relationship was seen in both univariate (OR 2.16, 95% CI 1.16-4.05, p=0.02) and multivariable (OR 2.43, 95% CI 1.13-5.25, p=0.02) logistic regression. Women with oestrogen receptor (ER)-/progesterone receptor (PR)-tumour types tended to have higher concentrations of persistent pesticides than did ER+/PR+ women, although these differences were not statistically significant. CONCLUSIONS: Exposure to the parent compound of the phthalate metabolite MEHP may be associated with breast cancer. However, our study is limited by small sample size and an inability to control for the confounding effects of body mass index. The association between BDE-47 and breast cancer warrants further investigation.

Method for the quantification of current use and persistent pesticides in cow milk, human milk and baby formula using gas chromatography tandem mass spectrometry.

The aim of this study was to develop an analytical method for the quantification of organochlorine (OC), organophosphate (OP), carbamate, and pyrethroid insecticide residues in cow milk, human milk, and baby formula. A total of 25 compounds were included in this method. Sample extraction procedures combined liquid-liquid extraction, freezing-lipid filtration, dispersive primary-secondary amine cleanup, and solid-phase extraction together for effective extraction and elimination of matrix interferences. Target compounds were analyzed using gas chromatography with electron impact ionization-tandem mass spectrometry (GC-EI-MS/MS) in the multiple reaction monitoring (MRM) mode. Average extraction recoveries obtained from cow milk samples fortified at two different concentrations (10 ng/mL and 25 ng/mL), ranged from 34% to 102%, with recoveries for the majority of target compounds falling between 60% and 80%. Similar ranges were found for formula fortified at 25 ng/mL. The estimated limits of detection for most target analytes were in the low pg/mL level (range 3-1600 pg/mL). The accuracies and precisions were within the range of 80-120% and less than 15%, respectively. This method was tested for its viability by analyzing 10 human milk samples collected from anonymous donors, 10 cow milk samples and 10 baby formula samples purchased from local grocery stores in the United States. Hexachlorobenzene, p,p-dicofol, o,p-DDE, p,p-DDE, and chlorpyrifos were found in all samples analyzed. We found detectable levels of permethrin, cyfluthrin, and fenvalerate in some of the cow milk samples but not in human milk or baby formula samples. Some of the pesticides, such as azinphos-methyl, heptachlor epoxide, and the pesticide synergist piperonyl butoxide, were detected in some of the cow milk and human milk samples but not in baby formula samples.

[Exposure to persistent and non-persistent pesticides in a non-occupationally exposed population in Tenerife Island (Spain)]. / Exposición a plaguicidas persistentes y no persistentes en población no expuesta laboralmente de la isla de Tenerife.

OBJECTIVE: Chronic exposure to non-persistent pesticides (NPPs) is of concern because these substances have been associated with chronic diseases. However, few studies have addressed chronic exposure to NPPs in Spanish populations. METHODS: We determined the presence of 24 pesticide residues by gas chromatography/mass spectrometry in 363 serum samples obtained from non-occupationally exposed adults from Tenerife island in 2007. RESULTS: Most of the samples (99.45%) showed detectable residues (6 ± 2 pesticides per sample). The most frequently detected pesticides were pyrethrins (96.1%), organophosphates (93.9%) and organochlorines (92.3%). The neurotoxicants bifenthrin and malathion were detected in 81% of the samples and hexachlorobenzene DDT and buprofezin in more than 50%. Malation, an "environmental obesogen", was detected in 82%, and "endocrine disrupter" pesticides were present in 97.2% of the samples. CONCLUSIONS: Because there is clear, continuous and inadvertent exposure to NPPs that may be inducing adverse effects on human health, NPPs should be included in biomonitoring studies.

Dietary intakes of pesticides based on community duplicate diet samples.

The calculation of dietary intake of selected pesticides was accomplished using food samples collected from individual representatives of a defined demographic community using a community duplicate diet approach. A community of nine participants was identified in Apopka, FL from which intake assessments of organophosphate (OP) and pyrethroid pesticides were made. From these nine participants, sixty-seven individual samples were collected and subsequently analyzed by gas chromatography/mass spectrometry. Measured concentrations were used to estimate dietary intakes for individuals and for the community. Individual intakes of total OP and pyrethroid pesticides ranged from 6.7 to 996 ng and 1.2 to 16,000 ng, respectively. The community intake was 256 ng for OPs and 3430 ng for pyrethroid pesticides. The most commonly detected pesticide was permethrin, but the highest overall intake was of bifenthrin followed by esfenvalerate. These data indicate that the community in Apopka, FL, as represented by the nine individuals, was potentially exposed to both OP and pyrethroid pesticides at levels consistent with a dietary model and other field studies in which standard duplicate diet samples were collected. Higher levels of pyrethroid pesticides were measured than OPs, which is consistent with decreased usage of OPs. The diversity of pyrethroid pesticides detected in food samples was greater than expected. Continually changing pesticide usage patterns need to be considered when determining analytes of interest for large scale epidemiology studies. The Community Duplicate Diet Methodology is a tool for researchers to meet emerging exposure measurement needs that will lead to more accurate assessments of intake which may enhance decisions for chemical regulation. Successfully determining the intake of pesticides through the dietary route will allow for accurate assessments of pesticide exposures to a community of individuals, thereby significantly enhancing the research benefit realized from epidemiological exposure studies.