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Environmental Science and Pollution... Nov 2023Human health is adversely affected by exposure to organophosphate (OP) pesticides. This study aims to investigate the correlation between urinary OP metabolites and the...
Human health is adversely affected by exposure to organophosphate (OP) pesticides. This study aims to investigate the correlation between urinary OP metabolites and the prevalence of asthma. In cross-sectional studies, data from the National Health and Nutrition Examination Survey (NHANES) projects conducted between 2003-2008, 2011-2012, and 2015-2018 were analyzed. Multiple logistic regressions and restricted cubic spline (RCS) regressions were utilized to examine the relationship between four urinary OP metabolites, namely dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl phosphorothioate (DMTP), and diethyl phosphorothioate (DETP), and the prevalence of asthma. Additionally, quantile g-computation (QG-C) regression was employed to evaluate the association between urinary OP metabolites (both individual and combined exposures) and asthma prevalence. The results showed that a total of 9316 adults, including 1298 participants with asthma, were included in the analysis. The median age of the participants was 47.37 years, and 50.27% were female. In the comprehensive model, the third tertile of DMP and DEP exhibited a positive association with asthma prevalence compared to the first tertile (odds ratio [95% confidence interval]: 1.26 [1.01-1.57], P = 0.036; and 1.25 [1.07-1.51], P = 0.008, respectively). Moreover, a linear relationship was observed between DMP, DEP, and asthma prevalence (P for nonlinearity = 0.320 and 0.553, respectively). The QG-C regression revealed a positive association between the mixture of urinary OP metabolites and asthma prevalence (OR = 1.04 [1.01-1.07], P = 0.025), with DEP contributing the most substantial effect (weight = 0.564). Our findings suggest that exposure to OP pesticides is associated with an increased prevalence of asthma, with DEP demonstrating the strongest impact.
Topics: Humans; Adult; Female; Middle Aged; Male; Cross-Sectional Studies; Nutrition Surveys; Pesticides; Organophosphorus Compounds; Insecticides; Organophosphates; Environmental Exposure
PubMed: 37847364
DOI: 10.1007/s11356-023-30174-8 -
The Science of the Total Environment Dec 2023Triphenyl phosphate (TPhP) is an organophosphate flame retardant widely distributed in the environment. The neurodevelopmental toxicity of TPhP has been observed in...
Triphenyl phosphate (TPhP) is an organophosphate flame retardant widely distributed in the environment. The neurodevelopmental toxicity of TPhP has been observed in animals and humans. Previously, we found that prenatal TPhP exposure disturbed placental tryptophan metabolism, impaired neurodevelopment in male offspring, and induced abnormal neurobehavior; however, the underlying mechanisms are unknown. In this study, using the trophoblast cell line JEG-3, we found that TPhP altered gene and protein expression in the tryptophan metabolism pathway, inhibited the tryptophan-serotonin pathway, and activated the tryptophan-kynurenine pathway. Meanwhile, TPhP induced oxidative stress by activating monoamine oxidase A (MAOA), promoting inflammatory factors including nuclear factor kappa-B (NFκB), interleukin-6, and tumor necrosis factor α. The NFκB inhibitor sulfasalazine could alleviate the effects of TPhP on tryptophan metabolism disturbance. The MAOA inhibitor clorgyline or the antioxidant N-acetylcysteine can mitigate oxidative stress and eliminate TPhP-induced inflammatory factors and tryptophan metabolism disturbances. The data above suggest that TPhP disturbed tryptophan metabolism by activating NFκB through MAOA-mediated oxidative stress. Finally, using the mouse intrauterine exposure model, the results confirmed that TPhP induced oxidative stress, activated inflammatory factors, disturbed tryptophan metabolism, and increased the levels of the tryptophan metabolites serotonin, kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid in the placenta during the second trimester of pregnancy. Overall, TPhP can disturb placental tryptophan metabolism by activating the inflammatory factor NFκB, which was induced by MAOA-induced oxidative stress. The results of this study confirm that indirect exposure to xenobiotic compounds at an early life stage can impair offspring development and provide a novel perspective on the neurodevelopmental toxicity of TPhP.
Topics: Humans; Animals; Mice; Male; Female; Pregnancy; Tryptophan; NF-kappa B; Reactive Oxygen Species; Kynurenine; Placenta; Monoamine Oxidase; Cell Line, Tumor; Serotonin; Organophosphates; Flame Retardants
PubMed: 37659542
DOI: 10.1016/j.scitotenv.2023.166688 -
Environment International Oct 2023Organophosphate esters (OPEs), used as flame retardants and plasticizers, are chemicals of concern for maternal and infant health. Prior studies examining temporal...
BACKGROUND
Organophosphate esters (OPEs), used as flame retardants and plasticizers, are chemicals of concern for maternal and infant health. Prior studies examining temporal trends and predictors of OPE exposure are primarily limited by small sample sizes.
OBJECTIVES
Characterize temporal trends and predictors of OPE exposure biomarkers.
METHODS
We determined urinary concentrations of eight biomarkers of OPE exposure at three timepoints during pregnancy for participants in the LIFECODES Fetal Growth Study (n = 900), a nested case-cohort recruited between 2007 and 2018. We examined biomarker concentrations, their variability during pregnancy, and temporal trends over the study period. In addition, we identified sociodemographic and pregnancy characteristics associated with biomarker concentrations. Analyses were conducted using both the within-subject pregnancy geometric means and biomarker concentrations measured at individual study visits.
RESULTS
Five OPE biomarkers were detected in at least 60% of the study participants. Biomarkers were not strongly correlated with one another and intraclass correlation coefficients, measuring within-subject variability during pregnancy, ranged from 0.27 to 0.51. Biomarkers exhibited varying temporal trends across study years. For example, bis(1-chloro-2-propyl) phosphate (BCIPP) increased monotonically, whereas bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), displayed non-monotonic trends with concentrations that peaked between 2011 and 2014. We observed associations between sociodemographic characteristics and OPE biomarkers. In general, concentrations of most OPE biomarkers were higher among participants from racial and ethnic minority populations, participants who were younger, had higher pre-pregnancy body mass index (BMI), and less than a college degree. We observed consistent results using either averaged or visit-specific biomarker concentrations.
SIGNIFICANCE
We observed widespread exposure to several OPEs and OPE biomarkers displayed varying temporal trends in pregnant people from 2007 to 2018. Concentrations of most OPE biomarkers varied according to sociodemographic factors, suggesting higher burdens of exposure among participants with higher pre-pregnancy BMI, those belonging to racial and ethnic minority populations, and lower educational attainment.
Topics: Pregnancy; Female; Humans; Flame Retardants; Plasticizers; Ethnicity; Minority Groups; Esters; Organophosphates; Phosphates; Biomarkers
PubMed: 37708814
DOI: 10.1016/j.envint.2023.108194 -
Journal of Hazardous Materials Feb 2024Polyfluoroalkyl phosphate esters (PAPs) are emerging substitutes for legacy per- and polyfluoroalkyl substances (PFAS), which are widely applied in consumer products and... (Review)
Review
Polyfluoroalkyl phosphate esters (PAPs) are emerging substitutes for legacy per- and polyfluoroalkyl substances (PFAS), which are widely applied in consumer products and closely related to people's daily lives. Increasing concern has been raised about the safety of PAPs due to their metabolism into perfluorooctanoic acid (PFOA) and other perfluorinated carboxylates (PFCAs) in vivo. This review summarizes the current knowledge on PAPs and highlights the knowledge gaps. PAPs dominated the PFAS profiles in wastewater, sludge, household dust, food-contact materials, paper products, paints, and cosmetics. They exhibit biomagnification due to their higher levels in top predators. PAPs have been detected in human blood worldwide, with the highest mean levels being found in the United States (1.9 ng/mL) and China (0.4 ng/mL). 6:2 diPAP is the predominant PAP among all identified matrices, followed by 8:2 diPAP. Toxicokinetic studies suggest that after entering the body, most PAPs undergo biotransformation, generating phase Ⅰ (i.e., PFCAs), phase II, and intermediate products with toxicity to be verified. Several epidemiological and toxicological studies have reported the antiandrogenic effect, estrogenic effect, thyroid disruption, oxidative damage, and reproductive toxicity of PAPs. More research is urgently needed on the source and fate of PAPs, human exposure pathways, toxicity other than reproductive and endocrine systems, toxic effects of metabolites, and mixed exposure effects.
Topics: Humans; Fluorocarbons; Organophosphates; Biotransformation; Carboxylic Acids; Phosphates
PubMed: 37984148
DOI: 10.1016/j.jhazmat.2023.133018 -
Journal of Hazardous Materials Oct 2023The list of organophosphate esters (OPEs) reported in the environment continues to expand as evidenced by the increasing number of OPE studies in the literature.... (Review)
Review
The list of organophosphate esters (OPEs) reported in the environment continues to expand as evidenced by the increasing number of OPE studies in the literature. However, there remains a general dearth of information on more recently produced and used OPEs that are proving to be emerging environmental contaminants. The present review summarizes the available studies in a systematic framework of the current state of knowledge on the analysis, environmental fate, and behavior of emerging OPEs. This review also details future directions to better understand emerging OPEs in the environment. Firstly, we make recommendations that the current structural/practical abbreviations and naming of OPEs be revised and updated. A chemical database (CDB) containing 114 OPEs is presently established based on the suspect list from the current scientific literature. There are 12 established OPEs and a total of 83 emerging OPEs that have been reported in human and/or biota samples. Of the emerging OPEs more than 80% have nearly 100% detection frequencies in samples of certain environmental media including indoor air, wastewater treatment plants, sediment, and fish. In contrast to OPEs considered established contaminants, most emerging OPEs have been identified more recently due to the more pervasive use of high-resolution mass spectrometry (HRMS) based approaches and especially gas or liquid chromatography coupled with HRMS-based non-target analysis (NTA) of environmental sample fractions. Intentional/unintentional industrial use and non-industrial formation are sources of emerging OPEs in the environment. Predicted physical-chemical properties in silico of newer, molecularly larger and more oligomeric OPEs strongly suggest that some compounds such as bisphenol A diphenyl phosphate (BPA-DPP) are highly persistent, bioaccumulative and/or toxic. Limited information on laboratory-based toxicity data has shown that some emerging OPEs elicit harmful effects such as cytotoxicity, development toxicity, hepatotoxicity, and endocrine disruption in exposed humans and mammals. Established, and to a much lesser degree emerging OPEs, have also been shown to transform and degrade in biota and possibly alter their toxicological effects. Research on emerging OPE contaminants is presently limited and more study is warranted on sample analysis methods, source apportionment, transformation processes, environmental behavior, biomarkers of exposure and toxicity.
Topics: Animals; Humans; Esters; Flame Retardants; Organophosphates; Environmental Monitoring; Phosphates; China; Mammals
PubMed: 37523961
DOI: 10.1016/j.jhazmat.2023.132095 -
Toxicological Sciences : An Official... May 2024Exposure to the organophosphate esters (OPEs), used as flame retardants and plasticizers, is associated with a variety of adverse health effects including an increase in...
Exposure to the organophosphate esters (OPEs), used as flame retardants and plasticizers, is associated with a variety of adverse health effects including an increase in the incidence of fatty liver diseases. The goal of this study was to investigate the effects of six OPEs, all detected in Canadian house dust, on the phenotype and function of HepG2 liver cells. We used high-content imaging to investigate the effects of these OPEs on cell survival, mitochondria, oxidative stress, lipid droplets, and lysosomes. Effects on the autophagy/lipophagy pathway were evaluated using confocal microscopy. The triaryl OPEs (isopropylated triphenylphosphate [IPPP], tris(methylphenyl) phosphate [TMPP], and triphenyl phosphate [TPHP]) were more cytotoxic than non-triaryl OPEs (tris(2-butoxyethyl) phosphate [TBOEP], tris(1-chloro-2-propyl) phosphate [TCIPP], and tris(1,3-dichloro-2-propyl) phosphate [TDCIPP]). Exposure to most OPEs increased total mitochondria, reduced reactive oxygen species, and increased total lipid droplet areas and lysosomal intensity. Potency ranking was done using the lowest benchmark concentration/administered equivalent dose method and toxicological prioritization index analyses to integrate all phenotypic endpoints. IPPP, TBOEP, and TPHP ranked as the most potent OPEs, whereas TMPP, TCIPP, and TDCIPP were relatively less bioactive. Confocal microscopic analysis demonstrated that IPPP reduced the colocalization of lipid droplets (PLIN2), lysosomes (LAMP1), and autophagosomes (p62), disrupting autophagy. In contrast, TBOEP rescued cells from bafilomycin A1-induced inhibition of autophagy and/or increased autophagic flux. Together, these data demonstrate that OPEs have adverse effects on HepG2 cells. Further, OPE-induced dysregulation of autophagy may contribute to the association between OPE exposure and adverse effects on liver lipid homeostasis.
Topics: Humans; Flame Retardants; Plasticizers; Hep G2 Cells; Organophosphates; Autophagy; Oxidative Stress; Phenotype; Cell Survival; Lipid Droplets; Lysosomes; Esters
PubMed: 38518089
DOI: 10.1093/toxsci/kfae034 -
Water Research Jul 2023Organophosphate esters (OPEs), as an important class of new pollutants, have been pervasively detected in global aquatic products, arousing widespread public concern due... (Review)
Review
Organophosphate esters (OPEs), as an important class of new pollutants, have been pervasively detected in global aquatic products, arousing widespread public concern due to their potential bioaccumulative behavior and consequent risks. With the continuous improvement of living standards of citizens, there have been constant increment of the proportion of aquatic products in diets of people. The levels of OPEs exposed to residents may also be rising due to the augmented consumption of aquatic products, posing potential hazards on human health, especially for people in coastal areas. The present study integrated the concentrations, profiles, bioaccumulation, and trophic transfer of OPEs in global aquatic products, including Mollusca, Crustacea, and fish, evaluated health risks of OPEs through aquatic products in daily diets by Mont Carol Simulation (MCS), and found Asia has been the most polluted area in terms of the concentration of OPEs in aquatic products, and would have been increasingly polluted. Among all studied OPEs, chlorinated OPEs generally showed accumulation predominance. It is worth noting that some OPEs were found bioaccumulated and/or biomagnified in aquatic ecosystems. Though MCS revealed relative low exposure risks of residents, sensitive and special groups such as children, adolescents, and fishermen may face more serious health risks than the average residents. Finally, knowledge gaps and recommendations for future research are discussed encouraging more long-term and systematic global monitoring, comprehensive studies of novel OPEs and OPEs metabolites, and more toxicological studies to completely evaluate the potential risks of OPEs.
Topics: Animals; Child; Humans; Adolescent; Environmental Monitoring; Ecosystem; Esters; Organophosphates; Risk Assessment; China; Flame Retardants
PubMed: 37224669
DOI: 10.1016/j.watres.2023.120083 -
Neurobiology of Disease Oct 2023Acute organophosphate (OP) intoxication can trigger seizures that progress to status epilepticus (SE), and survivors often develop chronic morbidities, including...
Acute organophosphate (OP) intoxication can trigger seizures that progress to status epilepticus (SE), and survivors often develop chronic morbidities, including spontaneous recurrent seizures (SRS). The pathogenic mechanisms underlying OP-induced SRS are unknown, but increased BBB permeability is hypothesized to be involved. Previous studies reported BBB leakage following OP-induced SE, but key information regarding time and regional distribution of BBB impairment during the epileptogenic period is missing. To address this data gap, we characterized the spatiotemporal progression of BBB impairment during the first week post-exposure in a rat model of diisopropylfluorophosphate-induced SE, using MRI and albumin immunohistochemistry. Increased BBB permeability, which was detected at 6 h and persisted up to 7 d post-exposure, was most severe and persistent in the piriform cortex and amygdala, moderate but persistent in the thalamus, and less severe and transient in the hippocampus and somatosensory cortex. The extent of BBB leakage was positively correlated with behavioral seizure severity, with the strongest association identified in the piriform cortex and amygdala. These findings provide evidence of the duration, magnitude and spatial breakdown of the BBB during the epileptogenic period following OP-induced SE and support BBB regulation as a viable therapeutic target for preventing SRS following acute OP intoxication.
Topics: Rats; Animals; Blood-Brain Barrier; Rats, Sprague-Dawley; Organophosphates; Status Epilepticus; Seizures; Brain
PubMed: 37797902
DOI: 10.1016/j.nbd.2023.106316 -
Environmental Science & Technology Jul 2023The present article critically and comprehensively reviews the most recent reports on smart sensors for determining glyphosate (GLP), an active agent of GLP-based... (Review)
Review
The present article critically and comprehensively reviews the most recent reports on smart sensors for determining glyphosate (GLP), an active agent of GLP-based herbicides (GBHs) traditionally used in agriculture over the past decades. Commercialized in 1974, GBHs have now reached 350 million hectares of crops in over 140 countries with an annual turnover of 11 billion USD worldwide. However, rolling exploitation of GLP and GBHs in the last decades has led to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide of farm and companies' workers. Intoxication with these herbicides dysregulates the microbiome-gut-brain axis, cholinergic neurotransmission, and endocrine system, causing paralytic ileus, hyperkalemia, oliguria, pulmonary edema, and cardiogenic shock. Precision agriculture, i.e., an (information technology)-enhanced approach to crop management, including a site-specific determination of agrochemicals, derives from the benefits of smart materials (SMs), data science, and nanosensors. Those typically feature fluorescent molecularly imprinted polymers or immunochemical aptamer artificial receptors integrated with electrochemical transducers. Fabricated as portable or wearable lab-on-chips, smartphones, and soft robotics and connected with SM-based devices that provide machine learning algorithms and online databases, they integrate, process, analyze, and interpret massive amounts of spatiotemporal data in a user-friendly and decision-making manner. Exploited for the ultrasensitive determination of toxins, including GLP, they will become practical tools in farmlands and point-of-care testing. Expectedly, smart sensors can be used for personalized diagnostics, real-time water, food, soil, and air quality monitoring, site-specific herbicide management, and crop control.
Topics: Animals; Conservation of Natural Resources; Smart Materials; Plants, Genetically Modified; Agriculture; Herbicides; Glyphosate
PubMed: 37384557
DOI: 10.1021/acs.est.3c01269 -
Ecotoxicology and Environmental Safety Feb 2024Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the...
Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
Topics: Female; Animals; NF-E2-Related Factor 2; Zebrafish; Ferroptosis; Acetylcholinesterase; Flame Retardants; Kelch-Like ECH-Associated Protein 1; Reactive Oxygen Species; Organophosphorus Compounds; Oxidative Stress; Organophosphates; Xanthophylls
PubMed: 38219622
DOI: 10.1016/j.ecoenv.2024.115960