17 results on '"TCPy"'
Search Results
2. Biomarkers of chlorpyrifos exposure and effect in Egyptian cotton field workers
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Farahat, Fayssal M., Ellison, Corie A., Bonner, Matthew R., McGarrigle, Barbara P., Crane, Alice L., Fenske, Richard A., Lasarev, Michael R., Rohlman, Diane S., Anger, W. Kent, Lein, Pamela J., and Olson, James R.
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Chlorpyrifos -- Health aspects ,Textile workers -- Health aspects ,Biological markers -- Identification and classification -- Health aspects ,Environmental issues ,Health - Abstract
BACKGROUND: Chlorpyrifos (CPF), a widely used organophosphorus pesticide (OP), is metabolized to CPF-oxon, a potent cholinesterase (ChE) inhibitor, and trichloro-2-pyridinol (TCPy). Urinary TCPy is often used as a biomarker for [...]
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- 2011
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3. Biomarker of exposure for chlorpyrifos
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Chlorpyrifos -- Health aspects ,Biological markers -- Identification and classification ,Environmental issues ,Health - Abstract
Chlorpyrifos (CPF), a widely used organo-phosphorus pesticide (OP), is metabolized to CPF-oxon, a potent cholinesterase (ChE) inhibitor, and trichloro-2-pyridinol (TCPy). Urinary TCPy is often used as a biomarker for CPF [...]
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- 2011
4. Xenobiotic Exposure and Migraine-Associated Signaling: A Multimethod Experimental Study Exploring Cellular Assays in Combination with Ex Vivo and In Vivo Mouse Models
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Rasmussen, Rikke H., Christensen, Sarah L., Calloe, Kirstine, Nielsen, Brian Skriver, Rehfeld, Anders, Taylor- Clark, Thomas E., Haanes, Kristian A., Taboureau, Olivier, Audouze, Karine, Klaerke, Dan A., Olesen, Jes, and Kristensen, David M.
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Thermo Fisher Scientific Inc. ,Pollutants ,Scientific equipment and supplies industry ,Migraine ,Prevalence studies (Epidemiology) ,Ethylenediaminetetraacetic acid ,Epidemiology ,Neurophysiology ,Environmental issues ,Health ,European Community - Abstract
Background: Mechanisms for how environmental chemicals might influence pain has received little attention. Epidemiological studies suggest that environmental factors such as pollutants might play a role in migraine prevalence. Potential targets for pollutants are the transient receptor potential (TRP) channels ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), which on activation release pain-inducing neuropeptide calcitonin generelated peptide (CGRP). Objective: In this study, we aimed to examine the hypothesis that environmental pollutants via TRP channel signaling and subsequent CGRP release trigger migraine signaling and pain. Methods: A calcium imaging-based screen of environmental chemicals was used to investigate activation of migraine pain- associated TRP channels TRPA1 and TRPV1. Based on this screen, whole-cell patch clamp and in silico docking were performed for the pesticide pentachlorophenol (PCP) as proof of concept. Subsequently, PCP-mediated release of CGRP and vasodilatory responses of cerebral arteries were investigated. Finally, we tested whether PCP could induce a TRPA1-dependent induction of cutaneous hypersensitivity in vivo in mice as a model of migraine-like pain. Results: A total of 16 out of the 52 screened environmental chemicals activated TRPA1 at 10 or 100 [micro]M. None of the investigated compounds activated TRPV1. Using PCP as a model of chemical interaction with TRPA1, in silico molecular modeling suggested that PCP is stabilized in a lipidbinding pocket of TRPA1 in comparison with TRPV1. In vitro, ex vivo, and in vivo experiments showed that PCP induced calcium influx in neurons and resulted in a TRPA1-dependent CGRP release from the brainstem and dilation of cerebral arteries. In a mouse model of migraine-like pain, PCP induced a TRPA1-dependent increased pain response ([N.sub.total] = 144). Discussion: Here we show that multiple environmental pollutants interact with the TRPA1-CGRP migraine pain pathway. The data provide valuable insights into how environmental chemicals can interact with neurobiology and provide a potential mechanism for putative increases in migraine prevalence over the last decades. https://doi.org/10.1289/EHP12413, Introduction In 2016, the World Health Organization (WHO) found migraine to be the second largest cause of disability worldwide only exceeded by low back pain. (1) It is debated whether [...]
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- 2023
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5. Adult Organophosphate and Carbamate Insecticide Exposure and Sperm Concentration: A Systematic Review and Meta-Analysis of the Epidemiological Evidence
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Ellis, Lauren B., Molina, Karen, Robbins, C. Rebecca, Freisthler, Marlaina, Sgargi, Daria, Mandrioli, Daniele, and Perry, Melissa J.
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United States. Environmental Protection Agency -- International economic relations -- Analysis ,Carbamates -- Analysis ,Spermatozoa -- Analysis ,Non-governmental organizations -- Analysis ,Adults -- Analysis ,Epidemiology -- Analysis ,Insecticides -- Analysis ,Environmental issues ,Health ,World Health Organization - Abstract
Background: Evidence of the negative impacts of contemporary use insecticides on sperm concentration has increased over the last few decades; however, meta-analyses on this topic are rare. OBJECTIVES: This investigation assessed the qualitative and quantitative strength of epidemiological evidence regarding adult exposure to two classes of contemporary use insecticides--organophosphates (OPs) and N-methyl carbamates (NMCs)--and sperm concentration using robust and reproducible systematic review and meta-analysis methods. Methods: Three scientific databases (PubMed, Scopus, and Web of Science), two U.S. government databases (NIOSHTIC- 2 and Science.gov), and five nongovernmental organization websites were searched for relevant primary epidemiological studies published in any language through 11 August 2022. Risk of bias and strength of evidence were evaluated according to Navigation Guide systematic review methodology. Bias-adjusted standardized mean difference effect sizes were calculated and pooled using a three-level, multivariate random-effect meta- analysis model with cluster-robust variance estimation. Results: Across 20 studies, 21 study populations, 42 effect sizes, and 1,774 adult men, the pooled bias-adjusted standardized mean difference in sperm concentration between adult men more- and less-exposed to OP and NMC insecticides was -0.30 (95% CI: -0.49, - 0.10; [P.sub.Satt] Discussion: This comprehensive investigation found sufficient evidence of an association between higher OP and NMC insecticide exposure and lower sperm concentration in adults. Although additional cohort studies can be beneficial to fill data gaps, the strength of evidence warrants reducing exposure to OP and NMC insecticides now to prevent continued male reproductive harm. https://doi.org/10.1289/EHP12678, Introduction Studies conducted across a wide range of populations have found significant decreases in average sperm concentrations over the last century, (1-6) and the prospect of further declines threatens population-wide [...]
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- 2023
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6. Association of Prenatal Exposure to Organophosphate, Pyrethroid, and Neonicotinoid Insecticides with Child Neurodevelopment at 2 Years of Age: A Prospective Cohort Study
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Wang, Aizhen, Wan, Yanjian, Mahai, Gaga, Qian, Xi, Li, Yuanyuan, Xu, Shunqing, and Xia, Wei
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Pregnancy -- Analysis ,Infants -- Analysis ,Metabolites -- Analysis ,Pregnant women -- Analysis ,Insecticides -- Analysis ,Environmental issues ,Health - Abstract
Background: Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown. Objectives: We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure. Methods: Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (N = 1,041). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined. Results: Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI): -5.59, -0.74] and 3.06 points (95% CI: -5.45, -0.68) respectively in boys' MDI scores. Each 1-unit increase in that of trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI: -3.89, -0.58) in boys' MDI scores and 1.90 points (95% CI: -3.16, -0.64) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl- clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI: -5.47, -0.57) in MDI scores among the boys, and trans-DCCA contributed the most to the association (18%). Conclusions: Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings. https://doi.org/10.1289/EHP12097, Introduction Maternal exposure to environmental chemicals during pregnancy might impair fetal development and increase the future health risks of the children. (1-4) Organophosphates (OPPs), pyrethroids (PYRs), and neonicotinoids (NNIs) are [...]
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- 2023
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7. Disparities in Toxic Chemical Exposures and Associated Neurodevelopmental Outcomes: A Scoping Review and Systematic Evidence Map of the Epidemiological Literature
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Payne-Sturges, Devon C., Taiwo, Tanya Khemet, Ellickson, Kristie, Mullen, Haley, Tchangalova, Nedelina, Anderko, Laura, Chen, Aimin, and Swanson, Maureen
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British Petroleum Company PLC -- International economic relations ,Brain damage ,Environmental health ,Pollutants ,Pesticides ,Petroleum industry -- International economic relations ,Polychlorinated biphenyls ,Child welfare ,Environmental justice ,Epidemiology ,Combustion ,Air pollution ,Environmental issues ,Health - Abstract
Background: Children are routinely exposed to chemicals known or suspected of harming brain development. Targeting Environmental Neuro-Development Risks (Project TENDR), an alliance of >50 leading scientists, health professionals, and advocates, is working to protect children from these toxic chemicals and pollutants, especially the disproportionate exposures experienced by children from families with low incomes and families of color. Objective: This scoping review was initiated to map existing literature on disparities in neurodevelopmental outcomes for U.S. children from population groups who have been historically economically/socially marginalized and exposed to seven exemplar neurotoxicants: combustion-related air pollution (AP), lead (Pb), mercury (Hg), organophosphate pesticides (OPs), phthalates (Phth), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs). Methods: Systematic literature searches for the seven exemplar chemicals, informed by the Population, Exposure, Comparator, Outcome (PECO) framework, were conducted through 18 November 2022, using PubMed, CINAHL Plus (EBSCO), GreenFILE (EBSCO), and Web of Science sources. We examined these studies regarding authors' conceptualization and operationalization of race, ethnicity, and other indicators of sociodemographic and socioeconomic disadvantage; whether studies presented data on exposure and outcome disparities and the patterns of those disparities; and the evidence of effect modification by or interaction with race and ethnicity. Results: Two hundred twelve individual studies met the search criteria and were reviewed, resulting in 218 studies or investigations being included in this review. AP and Pb were the most commonly studied exposures. The most frequently identified neurodevelopmental outcomes were cognitive and behavioral/psychological. Approximately a third (74 studies) reported investigations of interactions or effect modification with 69% (51 of 74 studies) reporting the presence of interactions or effect modification. However, less than half of the studies presented data on disparities in the outcome or the exposure, and fewer conducted formal tests of heterogeneity. Ninety-two percent of the 165 articles that examined race and ethnicity did not provide an explanation of their constructs for these variables, creating an incomplete picture. Discussion: As a whole, the studies we reviewed indicated a complex story about how racial and ethnic minority and low- income children may be disproportionately harmed by exposures to neurotoxicants, and this has implications for targeting interventions, policy change, and other necessary investments to eliminate these health disparities. We provide recommendations on improving environmental epidemiological studies on environmental health disparities. To achieve environmental justice and health equity, we recommend concomitant strategies to eradicate both neurotoxic chemical exposures and systems that perpetuate social inequities. https://doi.org/10.1289/EHP11750, Introduction Evidence of disparities in pollutant and chemical exposures and disproportionate impacts of environmental hazards in communities of color and low-income communities is long standing and mounting. (1-5) Scholars on [...]
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- 2023
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8. Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations
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Meeker, John D., Cooper, Ellen M., Stapleton, Heather M., and Hauser, Russ
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Fireproofing agents -- Health aspects ,Metabolites -- Research ,Men -- Health aspects ,Dust -- Health aspects ,Environmental issues ,Health - Abstract
Flame retardant chemicals are commonly added to consumer products and raw materials to delay combustion and meet fire safety standards. Because many flame retardants are additive rather than chemically bonded [...]
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- 2013
9. Cholinesterase depression and its association with pesticide exposure across the agricultural season among Latino farmworkers in North Carolina
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Quandt, Sara A., Chen, Haiying, Grzywacz, Joseph G., Vallejos, Quirina M., Galvan, Leonardo, and Arcury, Thomas A.
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Pesticides -- Analysis -- Health aspects -- Research ,Cholinesterases -- Physiological aspects -- Research ,Agricultural laborers -- Health aspects ,Environmental issues ,Health - Abstract
BACKGROUND: Farmworkers can be exposed to a wide variety of pesticides. Assessing cholinesterase activity over time can be used to monitor exposure to organophosphorus and carbamate pesticides. OBJECTIVES: The goal [...]
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- 2010
10. The implications of using a physiologically based pharmacokinetic (PBPK) model for pesticide risk assessment
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Lu, Chensheng, Holbrook, Christina M., and Andres, Leo M.
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Pesticides -- Usage -- Health aspects ,Pharmacokinetics -- Models -- Research ,Risk assessment -- Methods ,Organophosphorus compounds -- Health aspects -- Research ,Environmental issues ,Health - Abstract
BACKGROUND: A physiologically based pharmacokinetic (PBPK) model would make it possible to simulate the dynamics of chemical absorption, distribution, metabolism, and elimination (ADME) from different routes of exposures and, in [...]
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- 2010
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11. A systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure
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Wigle, Donald T., Turner, Michelle C., and Krewski, Daniel
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Pesticides -- Complications and side effects -- Research ,Leukemia in children -- Risk factors -- Diagnosis -- Research -- Complications and side effects ,Environmental issues ,Health - Abstract
OBJECTIVES: We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure. DATA SOURCES: Searches of MEDLINE (1950-2009) and other electronic databases yielded 31 included studies. [...]
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- 2009
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12. Project TENDR: targeting environmental neuro-developmental risks. The TENDR consensus statement
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Hazardous substances -- Control -- Health aspects ,Pregnant women -- Care and treatment -- Research ,Developmental disabilities -- Prevention -- Risk factors -- Research ,Environmental issues ,Health - Abstract
SUMMARY: Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes--genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. APPROACH: Leading scientific and medical experts, along with children's health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children's brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children's risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. CONCLUSION: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential., A Call to Action The TENDR Consensus Statement is a call to action to reduce exposures to toxic chemicals that can contribute to the prevalence of neurodevelopmental disabilities in America's [...]
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- 2016
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13. Research
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Environmental health -- Research ,Organochlorine compounds -- Health aspects ,Nanotechnology -- Usage ,Environmental issues ,Health - Abstract
Aerosolized Nanomaterials in Environmental Studies Many laboratories are conducting research on engineered carbonaceous nanomaterials (CNMs) in environmentally relevant systems, but laboratory exposures during procedures used in this research have not [...]
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- 2010
14. Children's health in Latin America: the influence of environmental exposures
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Laborde, Amalia, Tomasina, Fernando, Bianchi, Fabrizio, Brune, Marie-Noel, Buka, Irena, Comba, Pietro, Corra, Lilian, Cori, Liliana, Duffert, Christin Maria, Harari, Raul, Iavarone, Ivano, McDiarmid, Melissa A., Gray, Kimberly A., Sly, Peter D., Soares, Agnes, Suk, William A., and Landrigan, Philip J.
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Latin America -- Health aspects -- Environmental aspects -- Social aspects ,Child health -- Environmental aspects -- Social aspects -- Research ,Environmental toxicology -- Health aspects -- Research ,Environmental issues ,Health - Abstract
Background: Chronic diseases are increasing among children in Latin America. Objective and Methods: To examine environmental risk factors for chronic disease in Latin American children and to develop a strategic initiative for control of these exposures, the World Health Organization (WHO) including the Pan American Health Organization (PAHO), the Collegium Ramazzini, and Latin American scientists reviewed regional and relevant global data. Results: Industrial development and urbanization are proceeding rapidly in Latin America, and environmental pollution has become widespread. Environmental threats to children's health include traditional hazards such as indoor air pollution and drinking-water contamination; the newer hazards of urban air pollution; toxic chemicals such as lead, asbestos, mercury, arsenic, and pesticides; hazardous and electronic waste; and climate change. The mix of traditional and modern hazards varies greatly across and within countries reflecting industrialization, urbanization, and socioeconomic forces. Conclusions: To control environmental threats to children's health in Latin America, WHO, including PAHO, will focus on the most highly prevalent and serious hazards-- indoor and outdoor air pollution, water pollution, and toxic chemicals. Strategies for controlling these hazards include developing tracking data on regional trends in children's environmental health (CEH), building a network of Collaborating Centres, promoting biomedical research in CEH, building regional capacity, supporting development of evidence-based prevention policies, studying the economic costs of chronic diseases in children, and developing platforms for dialogue with relevant stakeholders. http://dx.doi.org/10.1289/ehp.1408292, Introduction Physical, chemical, and biological hazards in the environment are responsible for > 24% of the global burden of disease and for 36% of all deaths in children worldwide (Pruss-Ustun [...]
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- 2015
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15. Early-life exposure to organophosphate pesticides and pediatric respiratory symptoms in the CHAMACOS cohort
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Raanan, Rachel, Harley, Kim G., Balmes, John R., Bradman, Asa, Lipsett, Michael, and Eskenazi, Brenda
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Respiratory symptoms -- Risk factors -- Research ,Children -- Health aspects ,Organophosphate pesticides -- Health aspects -- Research ,Environmental issues ,Health - Abstract
BACKGROUND: Although pesticide use is widespread, the possible effect of early- life exposure to organophosphate (OP) on pediatric respiratory health is not well described. OBJECTIVES: We investigated the relationship between early-life exposure to OPs and respiratory outcomes. METHODS: Participants included 359 mothers and children from the CHAMACOS birth cohort. Dialkyl phosphate (DAP) metabolites of OP pesticides, specifically diethyl (DE) and dimethyl (DM) phosphate metabolites, were measured in urine from mothers twice during pregnancy (mean = 13 and 26 weeks gestation) and from children five times during childhood (0.5-5 years). Childhood DAP concentrations were estimated by the area under curve (AUC). Mothers reported their child's respiratory symptoms at 5 and 7 years of age. We used generalized estimating equations (GEE) to examine associations of prenatal and childhood DAP concentrations with repeated measures of respiratory symptoms and exercise-induced coughing at 5 and 7 years of age, adjusting for child's sex and age, maternal smoking during pregnancy, secondhand tobacco smoke, season of birth, [PM.sub.2.5], breastfeeding, mold and cockroaches in home, and distance from highway. RESULTS: Higher prenatal DAP concentrations, particularly DE, were nonsignificantly associated with respiratory symptoms in the previous 12 months at 5 or 7 years of age [adjusted odds ratio (aOR) per 10-fold increase = 1.44; 95% CI: 0.98, 2.12]. This association was strongest with total DAP and DE from the second half of pregnancy (aOR per 10-fold increase = 1.77; 95% CI: 1.06, 2.95; and 1.61; 95% CI: 1.08, 2.39, respectively). Childhood DAP, DE, and DM concentrations were associated with respiratory symptoms and exercise-induced coughing in the previous 12 months at 5 or 7 years of age (total DAPs: aOR per 10-fold increase = 2.53; 95% CI: 1.32, 4.86; and aOR = 5.40; 95% CI: 2.10, 13.91, respectively). CONCLUSIONS: Early-life exposure to OP pesticides was associated with respiratory symptoms consistent with possible asthma in childhood. citation: Raanan R, Harley KG, Balmes JR, Bradman A, Lipsett M, Eskenazi B. 2015. Early-life exposure to organophosphate pesticides and pediatric respiratory symptoms in the CHAMACOS cohort. Environ Health Perspect 123:179-185; http://dx.doi.org/10.1289/ehp.1408235, Introduction Asthma is the most prevalent pediatric chronic disease [Pijnenburg 2012; World Health Organization (WHO) 2007], and is a leading cause of hospitalization in children (Mellon and Parasuraman 2004) and [...]
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- 2015
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16. Within-and between-child variation in repeated urinary pesticide metabolite measurements over a 1-year period
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Attfield, Kathleen R., Hughes, Michael D., Spengler, John D., and Lu, Chensheng
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Pesticides -- Health aspects ,Urine -- Health aspects -- Environmental aspects ,Biological markers -- Research ,Environmental issues ,Health - Abstract
BACKGROUND: Children are exposed to pesticides from many sources and routes, including dietary and incidental ingestion, dermal absorption, and inhalation. Linking health outcomes to these exposures using urinary metabolites requires understanding temporal variability within subjects to avoid exposure misclassification. OBJECTIVES: We characterized the within- and between-child variability of urinary organophosphorus and pyrethroid metabolites in 23 participants of the Children's Pesticide Exposure Study--Washington over 1 year and examined the ability of one to four spot urine samples to categorize mean exposures. METHODS: Each child provided urine samples twice daily over 7-to 16-day sessions in four seasons in 2003 and 2004. Samples were analyzed for five pyrethroid and five organophosphorus (OP) metabolites. After adjusting for specific gravity, we used a customized maximum likelihood estimation linear mixed-effects model that accounted for values below the limit of detection to calculate intraclass correlation coefficients (ICC) and conducted surrogate category analyses. RESULTS: Within-child variability was 2-11 times greater than between-child variability. When restricted to samples collected during a single season, ICCs were higher in the fall, winter, and spring than in summer for OPs, and higher in summer and winter for pyrethroids, indicating an increase in between-person variability relative to within-person variability during these seasons. Surrogate category analyses demonstrated that a single spot urine sample did not categorize metabolite concentrations well, and that four or more samples would be needed to categorize children into quartiles consistently. CONCLUSIONS: Urinary biomarkers of these short half-life pesticides exhibited substantial within-person variability in children observed over four seasons. Researchers investigating pesticides and health outcomes in children may need repeated biomarker measurements to derive accurate estimates of exposure and relative risks., Introduction Insect control in U.S. agriculture and residences is currently predominated by the widespread use of pesticides, amounting to > 90 million pounds annually (Grube et al. 2011). This results [...]
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- 2014
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17. Metabolic Effects of a Chronic Dietary Exposure to a Low-Dose Pesticide Cocktail in Mice: Sexual Dimorphism and Role of the Constitutive Androstane Receptor
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Lukowicz, Celine, Ellero-Simatos, Sandrine, Regnier, Marion, Polizzi, Arnaud, Lasserre, Frederic, Montagner, Alexandra, Lippi, Yannick, Jamin, Emilien L., Martin, Jean- Francois, Naylies, Claire, Canle, Cecile, Debrauwer, Laurent, Bertrand-Michel, Justine, Saati, Talal Al, Theodorou, Vassilia, Loiseau, Nicolas, Mselli-Lakhal, Laila, Guillou, Herve, and Gamet-Payrastre, Laurence
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Metabolites -- Research ,Metabolic diseases -- Genetic aspects -- Care and treatment -- Research ,Liquid chromatography -- Usage ,Body weight -- Physiological aspects -- Health aspects ,Mass spectrometry -- Usage ,Environmental issues ,Health ,European Union. European Food Safety Authority - Abstract
BACKGROUND: Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at nonrelevant doses or in combination with other risk factors such as high-fat diets. OBJECTIVES: We aimed to evaluate, in mice, the metabolic consequences of chronic dietary exposure to a pesticide mixture at nontoxic doses, relevant to consumers' risk assessment. METHODS: A mixture of six pesticides commonly used in France, i.e., boscalid, captan, chlorpyrifos, thiofanate, thiacloprid, and ziram, was incorporated in a standard chow at doses exposing mice to the tolerable daily intake (TDI) of each pesticide. Wild-type (WT) and constitutive androstane receptor-deficient ([CAR.sup.-/-]) male and female mice were exposed for 52 wk. We assessed metabolic parameters [body weight (BW), food and water consumption, glucose tolerance, urinary metabolome] throughout the experiment. At the end of the experiment, we evaluated liver metabolism (histology, transcriptomics, metabolomics, lipidomics) and pesticide detoxification using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Compared to those fed control chow, WT male mice fed pesticide chow had greater BW gain and more adiposity. Moreover, these WT males fed pesticide chow exhibited characteristics of hepatic steatosis and glucose intolerance, which were not observed in those fed control chow. WT exposed female mice exhibited fasting hyperglycemia, higher reduced glutathione (GSH):oxidized glutathione (GSSG) liver ratio and perturbations of gut microbiota-related urinary metabolites compared to WT mice fed control chow. When we performed these experiments on [CAR.sup.-/-] mice, pesticide-exposed [CAR.sup.-/-] males did not exhibit BW gain or changes in glucose metabolism compared to the [CAR.sup.-/-] males fed control chow. Moreover, [CAR.sup.-/-] females fed pesticide chow exhibited pesticide toxicity with higher BWs and mortality rate compared to the [CAR.sup.-/-] females fed control chow. CONCLUSIONS: To our knowledge, we are the first to demonstrate a sexually dimorphic obesogenic and diabetogenic effect of chronic dietary exposure to a common mixture of pesticides at TDI levels, and to provide evidence for a partial role for CAR in an in vivo mouse model. This raises questions about the relevance of TDI for individual pesticides when present in a mixture. https://doi.org/10.1289/EHP2877, Introduction The rates of metabolic disorders, including obesity and its complications, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD), have increased dramatically over the past three [...]
- Published
- 2018
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