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PloS One 2019We investigated a potential use of a 3D tetraculture brain microphysiological system (BMPS) for neurotoxic chemical agent screening. This platform consists of neuronal...
We investigated a potential use of a 3D tetraculture brain microphysiological system (BMPS) for neurotoxic chemical agent screening. This platform consists of neuronal tissue with extracellular matrix (ECM)-embedded neuroblastoma cells, microglia, and astrocytes, and vascular tissue with dynamic flow and membrane-free culture of the endothelial layer. We tested the broader applicability of this model, focusing on organophosphates (OPs) Malathion (MT), Parathion (PT), and Chlorpyrifos (CPF), and chemicals that interact with GABA and/or opioid receptor systems, including Muscimol (MUS), Dextromethorphan (DXM), and Ethanol (EtOH). We validated the BMPS platform by measuring the neurotoxic effects on barrier integrity, acetylcholinesterase (AChE) inhibition, viability, and residual OP concentration. The results show that OPs penetrated the model blood brain barrier (BBB) and inhibited AChE activity. DXM, MUS, and EtOH also penetrated the BBB and induced moderate toxicity. The results correlate well with available in vivo data. In addition, simulation results from an in silico physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) model that we generated show good agreement with in vivo and in vitro data. In conclusion, this paper demonstrates the potential utility of a membrane-free tetraculture BMPS that can recapitulate brain complexity as a cost-effective alternative to animal models.
Topics: Acetylcholinesterase; Animals; Brain; Cell Line; Cell Survival; Imaging, Three-Dimensional; Mice; Microfluidics; Neurotoxins; Organophosphates; Receptors, GABA; Receptors, Opioid; Time Factors; Toxicity Tests
PubMed: 31703066
DOI: 10.1371/journal.pone.0224657 -
Environment International Feb 2023As a substitute for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardant triphenyl phosphate (TPhP) is widely used in our daily products and diffusely...
As a substitute for polybrominated diphenyl ethers (PBDEs), organophosphate flame retardant triphenyl phosphate (TPhP) is widely used in our daily products and diffusely exists in our living surroundings, but there is a paucity of information concerning its neurodevelopmental toxicity. Herein, we investigated the effects of TPhP exposure on developmental parameters, locomotor behavior, oxidative stress, apoptosis and transcriptional levels in zebrafish at different developmental stages, so as to explore the effects of TPhP exposure on zebrafish neural development and the underlying molecular mechanisms. TPhP concentration gradient exposure reduced the survival rate, hatchability, heart rate, body length and eye distance of zebrafish embryos/larvae, and caused malformations of zebrafish larvae. TPhP also leads to abnormal locomotor behaviors, such as reduced swimming distance and swimming speed, and impaired panic avoidance reflex to high light stimulation. TPhP caused ROS accumulation in 96 hpf larvae and induced Nrf2-antioxidant response in zebrafish. In addition, TPhP further activated mitochondrial signaling pathways, which affected apoptosis in the zebrafish eye region, resulting in visual impairment. Neurodevelopmental (mbpa, syn2a, foxo3a and pax6a), Retinoid acid metabolism (cyp26a1, raraa, rbp5, rdh1, crabp1a and rbp2a) and apoptosis-related genes (bcl2a, baxa and casp9) revealed the molecular mechanism of abnormal behavior and phenotypic symptoms, and also indicated that 96 hpf larvae are more sensitive than 7 dpf larvae. Thus, in the present study, we revealed the neurotoxic effects of TPhP at different early life stages in zebrafish, and zebrafish locomotor behavior impairments induced by TPhP exposure are attributed to co-regulation of visuomotor dysfunction and neuro-related genes. These results suggest that the safety of TPhP in organisms and even in humans needs to be further studied.
Topics: Animals; Flame Retardants; Organophosphates; Swimming; Zebrafish
PubMed: 36657258
DOI: 10.1016/j.envint.2023.107745 -
Environment International Dec 2021Human exposure to OPEs is pervasive and should be of great concern due to associations with adverse health effects, especially in susceptible populations. In this study,...
Human exposure to OPEs is pervasive and should be of great concern due to associations with adverse health effects, especially in susceptible populations. In this study, body burdens and exposure pathways of OPEs were investigated for 76 healthy elderly people in Jinan, China based on the measured OPE and metabolite concentrations in human bio-samples (whole blood and urine) and paired environmental matrices (air and dust), as well as food frequency questionnaire. Eight of 16 OPEs and 5 of 11 metabolites were detected in > 50% of whole blood and urine samples, respectively. Tri(1-chloro-2-propyl) phosphate (TCIPP), tris(2-chloroethyl) phosphate (TCEP), tri-phenyl phosphate (TPHP), and 2-ethylhexyl di-phenyl phosphate (EHDPP) were frequently detected and abundant in whole blood, while their corresponding metabolites were detected at low frequencies or levels in urine. The reduced metabolic and/or excretory capacity of elderly people may be an important reason, implying a higher health risk to them. Fourteen OPEs had over 50% detection frequencies in indoor air and dust, while 6 di-esters in indoor dust. Tris(2-ethylhexyl) phosphate (TEHP) in indoor dust and tri-n-butyl phosphate (TnBP) in indoor air were positively correlated with paired levels in blood but not with their metabolites (BEHP and DnBP) in urine. Combined with the direct intakes of BEHP and DBP from dust, blood is indicated as more suitable biomarker for TEHP and TnBP exposure. High consumption frequencies of several foods were associated with higher blood concentrations of three OPEs and urinary levels of four di-OPEs, indicating the importance of dietary exposure pathway. Estimated daily total intakes of OPEs via inhalation, dust ingestion, and dermal absorption ranged from 2.78 to 42.0 ng/kg bw/day, which were far less than the reference dosage values. Further studies were warranted to explore the potential health effects of OPE exposure in the elderly populations.
Topics: Aged; Air Pollution, Indoor; Body Burden; China; Dust; Environmental Monitoring; Esters; Flame Retardants; Humans; Organophosphates
PubMed: 34365320
DOI: 10.1016/j.envint.2021.106803 -
Environment International Apr 2023Contaminants of emerging concern such as organophosphate flame retardants (OPFRs) are associated with atmospheric fine particles (PM), which pose the greatest health...
Investigating the associations between organophosphate flame retardants (OPFRs) and fine particles in paired indoor and outdoor air: A probabilistic prediction model for deriving OPFRs in indoor environments.
Contaminants of emerging concern such as organophosphate flame retardants (OPFRs) are associated with atmospheric fine particles (PM), which pose the greatest health risk in the world. However, few surveys have explored the interaction between PM and OPFRs in residential paired indoor/outdoor environments. 11 priority OPFRs and PM were investigated across 178 paired indoor and outdoor air samples taken from 89 children's households in southern Taiwan, across cold and warm seasons. This involved exploring their associations with building characteristics, interior materials, and human activities. We developed a probabilistic predictive model for indoor OPFRs based on the indoor/outdoor (I/O) ratio of contaminants and an air quality index. The significant associations of paired indoor/outdoor OPFRs and PM were explored. The indoor level of OPFRs was greater than that of outdoor households, contrasting with PM. The I/O OPFRs ratio was higher than 1 (except for TEHP, EHDPP, and TCP), which suggests that the sources of OPFRs were primarily emitted from indoors. Indoor TCEP was significantly positively associated with indoor and outdoor PM. The OPFR level detected in apartments was higher than in houses due to the greater decoration, furniture and electronic devices. However, this was not the case for PM. TCIPP was the dominant compound in paired indoor and outdoor air. The indoor OPFR predictive model obtained a high accuracy with an R value of 0.87. The material used in mattresses, the use of purifiers and heaters, and the total material area were the main influencing factors for indoor OPFRs in households. These findings could provide important evidence of the interaction between paired indoor/outdoor OPFRs and PM and interior equipment in different building types. In addition, it could prevent the potential risks posed by indoor/outdoor air pollutants and eliminate OPFR emissions through the selection of better construction and building materials.
Topics: Child; Humans; Organophosphates; Flame Retardants; Air Pollution, Indoor; Air Pollutants; Particulate Matter; Environmental Monitoring
PubMed: 36931197
DOI: 10.1016/j.envint.2023.107871 -
Molecules (Basel, Switzerland) Jul 2021The field of gas chromatography-mass spectrometry (GC-MS) in the analysis of chemical warfare agents (CWAs), specifically those involving the organophosphorus-based... (Review)
Review
Analysis of Organophosphorus-Based Nerve Agent Degradation Products by Gas Chromatography-Mass Spectrometry (GC-MS): Current Derivatization Reactions in the Analytical Chemist's Toolbox.
The field of gas chromatography-mass spectrometry (GC-MS) in the analysis of chemical warfare agents (CWAs), specifically those involving the organophosphorus-based nerve agents (OPNAs), is a continually evolving and dynamic area of research. The ever-present interest in this field within analytical chemistry is driven by the constant threat posed by these lethal CWAs, highlighted by their use during the Tokyo subway attack in 1995, their deliberate use on civilians in Syria in 2013, and their use in the poisoning of Sergei and Yulia Skripal in Great Britain in 2018 and Alexei Navalny in 2020. These events coupled with their potential for mass destruction only serve to stress the importance of developing methods for their rapid and unambiguous detection. Although the direct detection of OPNAs is possible by GC-MS, in most instances, the analytical chemist must rely on the detection of the products arising from their degradation. To this end, derivatization reactions mainly in the form of silylations and alkylations employing a vast array of reagents have played a pivotal role in the efficient detection of these products that can be used retrospectively to identify the original OPNA.
Topics: Alkylation; Fluorobenzenes; Gas Chromatography-Mass Spectrometry; Humans; Hydrolysis; Methylation; Nerve Agents; Organophosphates; Organophosphorus Compounds; Organothiophosphorus Compounds; Sarin; Soman
PubMed: 34361784
DOI: 10.3390/molecules26154631 -
Dental Materials Journal May 2010The aim of the present study was to evaluate the bonding durability of resin-based luting cement to partially stabilized tetragonal zirconia (Y-TZP) achieved by...
The aim of the present study was to evaluate the bonding durability of resin-based luting cement to partially stabilized tetragonal zirconia (Y-TZP) achieved by combination treatment of tribochemical (TBC) treatment and two different phosphate acid ester monomers. Two phosphate acid ester monomers (EP: Epricord opaque primer, AZ: AZ primer) were applied to each surface modification followed by application of resin-based luting cement (Rely-X ARC). Bonding specimens were placed in deionized water at 37 degrees C and stored for 24 h. The other groups were subjected to 30,000 cycles of a thermal stress for the durability test. Shear bond tests were done using a universal testing machine at 1 mm/min. Shear bond strengths of combination treatments using EP and AZ on TBC treatment after thermal stress showed no significant difference (p>0.05) compared with those of storage after 24 h. Combination treatment using phosphoric acid ester monomer could achieve a durable bond.
Topics: Bisphenol A-Glycidyl Methacrylate; Composite Resins; Dental Bonding; Dental Etching; Dental Porcelain; Dental Stress Analysis; Friction; Materials Testing; Methacrylates; Organophosphates; Phosphonoacetic Acid; Polyethylene Glycols; Polymethacrylic Acids; Resin Cements; Shear Strength; Yttrium; Zirconium
PubMed: 20484831
DOI: 10.4012/dmj.2009-099 -
International Journal of Environmental... Aug 2022This study investigates associations between house characteristics and chemical contaminants in house dust, collected under the nationally representative Canadian House...
This study investigates associations between house characteristics and chemical contaminants in house dust, collected under the nationally representative Canadian House Dust Study (2007−2010). Vacuum samples (<80 µm fraction) were analysed for over 200 synthetic organic compounds and metal(loid)s. Spearman rank correlations between contaminant concentrations in dust and presence of children and pets, types of flooring, heating styles and other characteristics suggested a number of indoor sources, pointing to future research directions. Numerous synthetic organics were significantly associated with reported use of room deodorizers and with the presence of cats in the home. Hardwood flooring, which is a manufactured wood product, emerged as a source of metal(loid)s, phthalates, organophosphate flame retardants/plasticizers, and obsolete organochlorine pesticides such as ∑DDT (but not halogenated flame retardants). Many metal(loid)s were significantly correlated with flame-retardant compounds used in building materials and heating systems. Components of heating appliances and heat distribution systems appeared to contribute heat-resistant chemicals and alloys to settled dust. Carpets displayed a dual role as both a source and repository of dust-borne contaminants. Contaminant loadings (<80 µm fraction) were significantly elevated in heavily carpeted homes, particularly those located near industry. Depending on the chemical (and its source), the results show that increased dust mass loading may enrich or dilute chemical concentrations in dust. Research is needed to improve the characterisation of hidden indoor sources such as flame retardants used in building materials and heating systems, or undisclosed ingredients used in common household products, such as air fresheners and products used for companion animals.
Topics: Air Pollution, Indoor; Canada; Dust; Environmental Monitoring; Flame Retardants; Metals; Organophosphates
PubMed: 36011971
DOI: 10.3390/ijerph191610329 -
International Journal of Environmental... Jan 2022Organophosphate (OP) pesticides are associated with numerous adverse health outcomes. Pesticide use data are available for California from the Pesticide Use Report...
Organophosphate (OP) pesticides are associated with numerous adverse health outcomes. Pesticide use data are available for California from the Pesticide Use Report (PUR), but household- and individual-level exposure factors have not been fully characterized to support its refinement as an exposure assessment tool. Unique exposure pathways, such as proximity to agricultural operations and direct occupational contact, further complicate pesticide exposure assessment among agricultural communities. We sought to identify influencing factors of pesticide exposure to support future exposure assessment and epidemiological studies. Household dust samples were collected from 28 homes in four California agricultural communities during January and June 2019 and were analyzed for the presence of OPs. Factors influencing household OPs were identified by a data-driven model via best subsets regression. Key factors that impacted dust OP levels included household cooling strategies, secondary occupational exposure to pesticides, and geographic location by community. Although PUR data demonstrate seasonal trends in pesticide application, this study did not identify season as an important factor, suggesting OP persistence in the home. These results will help refine pesticide exposure assessment for future studies and highlight important gaps in the literature, such as our understanding of pesticide degradation in an indoor environment.
Topics: Agriculture; Dust; Environmental Exposure; Housing; Humans; Organophosphates; Pesticides
PubMed: 35055689
DOI: 10.3390/ijerph19020862 -
Ecotoxicology and Environmental Safety Jun 2024Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting...
BACKGROUND
Organophosphate esters (OPEs) are used extensively as flame retardants and plasticizers. Laboratory studies have shown that OPEs exhibit osteotoxicity by inhibiting osteoblast differentiation; however, little is known about how OPEs exposure is associated with bone health in humans.
OBJECTIVES
We conducted a cross-sectional study to investigate the association between OPEs exposure and bone mineral density (BMD) in adults in the United States using data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES).
METHODS
Multivariate linear regression models were used to assess the association between concentrations of individual OPE metabolites and BMDs. We also used the Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models to estimate joint associations between OPE mixture exposure and BMDs. All the analyses were stratified according to gender.
RESULTS
A total of 3546 participants (median age, 40 years [IQR, 30-50 years]; 50.11% male) were included in this study. Five urinary OPE metabolites with a detection rate of > 50% were analyzed. After adjusting for the potential confounders, OPE metabolite concentrations were associated with decreased total-body BMD and lumbar spine BMD in males, although some associations only reached significance for bis(1-chloro-2-propyl) phosphate (BCPP), dibutyl phosphate (DBUP), and bis(2-chloroethyl) phosphate (BCEP) (β = -0.013, 95% CI: -0.026, -0.001 for BCPP and total-body BMD; β = -0.022, 95% CI: -0.043, -0.0001 for DBUP and lumbar spine BMD; β=-0.018, 95% CI: -0.034, -0.002 for BCEP and lumbar spine BMD). OPE mixture exposure was also inversely associated with BMD in males, as demonstrated in the BMKR and qgcomp models.
CONCLUSIONS
This study provides preliminary evidence that urinary OPE metabolite concentrations are inversely associated with BMD. The results also suggested that males were more vulnerable than females. However, further studies are required to confirm these findings.
Topics: Humans; Adult; Male; Bone Density; Female; Middle Aged; United States; Nutrition Surveys; Cross-Sectional Studies; Organophosphates; Esters; Flame Retardants; Environmental Exposure; Environmental Pollutants
PubMed: 38714086
DOI: 10.1016/j.ecoenv.2024.116414 -
Journal of Clinical Microbiology Jun 2017Tedizolid is a new oxazolidinone with improved and intracellular potency against , including multidrug-resistant strains, and some species of nontuberculous...
Tedizolid is a new oxazolidinone with improved and intracellular potency against , including multidrug-resistant strains, and some species of nontuberculous mycobacteria (NTM) compared with that of linezolid. Using the current Clinical and Laboratory Standards Institute (CLSI)-recommended method of broth microdilution, susceptibility testing of 170 isolates of rapidly growing mycobacteria showed equivalent or lower (1- to 8-fold) MIC and/or MIC values for tedizolid compared with that for linezolid. The tedizolid MIC values for 81 isolates of subsp. and 12 isolates of subsp. were 8 μg/ml and 4 μg/ml, respectively, compared with linezolid MIC values of 32 μg/ml for both. The MIC values for 20 isolates of were 2 μg/ml for tedizolid and 4 μg/ml for linezolid. Twenty-two isolates of had tedizolid and linezolid MICs of 2 μg/ml and 16 μg/ml, respectively. One hundred forty-two slowly growing NTM, including 7/7 , 7/7 , and 7/11 of other less commonly isolated species, had tedizolid MICs of ≤1 μg/ml and linezolid MICs of ≤4 μg/ml. One hundred isolates of complex and eight isolates had tedizolid MICs of 8 μg/ml and linezolid MICs 32 and 64 μg/ml, respectively. Nine isolates had MICs of 4 μg/ml and 16 μg/ml for tedizolid and linezolid, respectively. These findings demonstrate a greater potency of tedizolid than linezolid against NTM and suggest that an evaluation of tedizolid as a potential treatment agent for infections caused by selected NTM is warranted.
Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Nontuberculous Mycobacteria; Organophosphates; Oxazoles
PubMed: 28330892
DOI: 10.1128/JCM.00274-17