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The Science of the Total Environment Sep 2024Children are exposed to endocrine disrupting chemicals (EDCs) through inhalation and ingestion, as well as through dermal contact in their everyday indoor environments....
Children are exposed to endocrine disrupting chemicals (EDCs) through inhalation and ingestion, as well as through dermal contact in their everyday indoor environments. The dermal loadings of EDCs may contribute significantly to children's total EDC exposure due to dermal absorption as well as hand-to-mouth behaviors. The aim of this study was to measure potential EDCs, specifically halogenated flame retardants (HFRs) and organophosphate esters (OPEs), on children's hands during preschool attendance and to assess possible determinants of exposure in preschool indoor environments in Sweden. For this, 115 handwipe samples were collected in winter and spring from 60 participating children (arithmetic mean age 4.5 years, standard deviation 1.0) and analyzed for 50 compounds. Out of these, 31 compounds were identified in the majority of samples. Levels were generally several orders of magnitude higher for OPEs than HFRs, and 2-ethylhexyl diphenyl phosphate (EHDPP) and tris(2-butoxyethyl) phosphate (TBOEP) were detected in the highest median masses, 61 and 56 ng/wipe, respectively. Of the HFRs, bis(2-ethyl-1-hexyl)-2,3,4,5-tetrabromobenzoate (BEH-TEBP) and 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) were detected in the highest median masses, 2.8 and 1.8 ng/wipe, respectively. HFR and/or OPE levels were found to be affected by the number of plastic toys, and electrical and electronic devices, season, municipality, as well as building and/or renovation before/after 2004. Yet, the calculated health risks for single compounds were below available reference dose values for exposure through dermal uptake as well as for ingestion using mean hand-to-mouth contact rate. However, assuming a high hand-to-mouth contact rate, at the 95th percentile, the calculated hazard quotient was above 1 for the maximum handwipe mass of TBOEP found in this study, suggesting a risk of negative health effects. Furthermore, considering additive effects from similar compounds, the results of this study indicate potential concern if additional exposure from other routes is as high.
Topics: Flame Retardants; Humans; Sweden; Child, Preschool; Organophosphates; Skin Absorption; Environmental Exposure; Endocrine Disruptors; Esters; Male; Female; Environmental Pollutants; Environmental Monitoring
PubMed: 38821289
DOI: 10.1016/j.scitotenv.2024.173635 -
The Science of the Total Environment Aug 2024Halogenated organophosphate esters (OPEs) are increasingly used as flame retardants to replace polybrominated diphenyl ethers (PBDEs), which have been phased out due to...
Halogenated organophosphate esters (OPEs) are increasingly used as flame retardants to replace polybrominated diphenyl ethers (PBDEs), which have been phased out due to their confirmed persistence, toxicity, and ability to undergo long range atmospheric transport. Non-halogenated OPEs are primarily used as plasticizers. While human exposure to PBDEs in the Canadian Arctic is well documented, it is not the case for OPEs. To assess the exposure to OPEs in Inuit living in Nunavik (northern Québec, Canada), we measured 16 metabolites of halogenated and non-halogenated OPEs in pooled urine samples from the last population health survey conducted in Nunavik, the Qanuilirpitaa? 2017 Inuit Health Survey (Q2017). Urine samples (n = 1266) were pooled into 30 pools by sex (female; male), age groups (16-19; 20-29; 30-39; 40-59; 60+ years old) and regions (Hudson Bay; Hudson Strait; Ungava Bay). Q2017 geometric means and 95 % confidence intervals were compared with data from the Canadian Health Measures Survey Cycle 6 (2018-2019) (CHMS). Halogenated OPEs were systematically detected and generally found at higher concentrations than non-halogenated OPEs in both Q2017 and CHMS. Furthermore, urinary levels of BCIPP and BDCIPP (halogenated) were lower in Q2017 compared to CHMS while concentrations of DPhP, DpCP and DoCP (non-halogenated) were similar between Q2017 and CHMS. Across the 16 metabolites measured in Q2017, BCIPHIPP (halogenated) had the highest levels (geometric mean: 1.40 μg/g creatinine). This metabolite was not measured in CHMS and should be included in future surveys. Overall, our results show that Inuit in Nunavik are exposed to lower or similar OPEs levels than the rest of the general Canadian population suggesting that the main current exposure to OPEs may be from consumer goods containing flame retardants and imported from the south rather than long-range atmospheric transport to the Arctic.
Topics: Humans; Inuit; Adult; Female; Male; Organophosphates; Middle Aged; Young Adult; Environmental Exposure; Flame Retardants; Quebec; Adolescent; Environmental Pollutants; Esters
PubMed: 38810742
DOI: 10.1016/j.scitotenv.2024.173563 -
PloS One 2024Ae. aegypti is the vector of important μ arboviruses, including dengue, Zika, chikungunya and yellow fever. Despite not being specifically targeted by insecticide-based...
BACKGROUND
Ae. aegypti is the vector of important μ arboviruses, including dengue, Zika, chikungunya and yellow fever. Despite not being specifically targeted by insecticide-based control programs in West Africa, resistance to insecticides in Ae. aegypti has been reported in countries within this region. In this study, we investigated the status and mechanisms of Ae. aegypti resistance in Niamey, the capital of Niger. This research aims to provide baseline data necessary for arbovirus outbreak prevention and preparedness in the country.
METHODS
Ovitraps were used to collect Ae. aegypti eggs, which were subsequently hatched in the insectary for bioassay tests. The hatched larvae were then reared to 3-5-day-old adults for WHO tube and CDC bottle bioassays, including synergist tests. The kdr mutations F1534C, V1016I, and V410L were genotyped using allele-specific PCR and TaqMan qPCR methods.
RESULTS
Ae. aegypti from Niamey exhibited moderate resistance to pyrethroids but susceptibility to organophosphates and carbamates. The kdr mutations, F1534C, V1016I and V410L were detected with the resistant tri-locus haplotype 1534C+1016L+410L associated with both permethrin and deltamethrin resistance. Whereas the homozygote tri-locus resistant genotype 1534CC+1016LL+410LL was linked only to permethrin resistance. The involvement of oxidase and esterase enzymes in resistance mechanisms was suggested by partial restoration of mosquitoes' susceptibility to pyrethroids in synergist bioassays.
CONCLUSION
This study is the first report of Ae. aegypti resistance to pyrethroid insecticides in Niamey. The resistance is underpinned by target site mutations and potentially involves metabolic enzymes. The observed resistance to pyrethroids coupled with susceptibility to other insecticides, provides data to support evidence-based decision-making for Ae. aegypti control in Niger.
Topics: Animals; Aedes; Insecticide Resistance; Pyrethrins; Niger; Insecticides; Mutation; Mosquito Vectors; Genotype; Larva; Insect Proteins
PubMed: 38809933
DOI: 10.1371/journal.pone.0304550 -
Polymers May 2024Decreasing oil resources creates the need to search for raw materials in the biosphere, which can be converted into polyols suitable for obtaining polyurethane foams...
Decreasing oil resources creates the need to search for raw materials in the biosphere, which can be converted into polyols suitable for obtaining polyurethane foams (PUF). One such low-cost and reproducible biopolymer is cellulose. There are not many examples of cellulose-derived polyols due to the sluggish reactivity of cellulose itself. Recently, cellulose and its hydroxypropyl derivatives were applied as source materials to obtain polyols, further converted into biodegradable rigid polyurethane foams (PUFs). Those PUFs were flammable. Here, we describe our efforts to modify such PUFs in order to decrease their flammability. We obtained an ester from diethylene glycol and phosphoric(III) acid and used it as a reactive flame retardant in the synthesis of polyol-containing hydroxypropyl derivative of cellulose. The cellulose-based polyol was characterized by infrared spectra (IR) and proton nuclear magnetic resonance (H-NMR) methods. Its properties, such as density, viscosity, surface tension, and hydroxyl numbers, were determined. Melamine was also added to the foamed composition as an additive flame retardant, obtaining PUFs, which were characterized by apparent density, water uptake, dimension stability, heat conductance, compressive strength, and heat resistance at 150 and 175 °C. Obtained rigid PUFs were tested for flammability by determining oxygen index, horizontal flammability test, and calorimetric analysis. Obtained rigid PUFs showed improved flammability resistance in comparison with non-modified PUFs and classic PUFs.
PubMed: 38794632
DOI: 10.3390/polym16101438 -
International Journal of Molecular... May 2024Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer's disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble...
Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer's disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show red blood cell (RBC) membrane-binding capacity and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Ab-treated RBCs. In RBCs following different treatments, the ATP, 2,3 DPG and cAMP levels and caspase 3 activity were determined by spectrophotometric and immunoassay. S1P rescued the inhibition of ATP release from RBCs triggered by Ab, through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.
Topics: Lysophospholipids; Sphingosine; Amyloid beta-Peptides; Erythrocytes; Humans; Cyclic AMP; Adenosine Triphosphate; Caspase 3; Alzheimer Disease; 2,3-Diphosphoglycerate; Signal Transduction
PubMed: 38791223
DOI: 10.3390/ijms25105184 -
Environmental Research Aug 2024Several studies have reported immune modulation by organophosphate (OP) pesticides, but the relationship between OP exposure and SARS-CoV-2 infection is yet to be...
Several studies have reported immune modulation by organophosphate (OP) pesticides, but the relationship between OP exposure and SARS-CoV-2 infection is yet to be studied. We used two different measures of OP pesticide exposure (urinary biomarkers (N = 154) and residential proximity to OP applications (N = 292)) to examine the association of early-childhood and lifetime exposure to OPs and risk of infection of SARS-CoV-2 using antibody data. Our study population consisted of young adults (ages 18-21 years) from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal cohort of families from a California agricultural region. Urinary biomarkers reflected exposure from in utero to age 5 years. Residential proximity reflected exposures between in utero and age 16 years. SARS-CoV-2 antibodies in blood samples collected between June 2022 and January 2023 were detected via two enzyme linked immunosorbent assays, each designed to bind to different SARS-CoV-2 antigens. We performed logistic regression for each measure of pesticide exposure, adjusting for covariates from demographic data and self-reported questionnaire data. We found increased odds of SARS-CoV-2 infection among participants with higher urinary biomarkers of OPs in utero (OR = 1.94, 95% CI: 0.71, 5,58) and from age 0-5 (OR = 1.90, 95% CI: 0.54, 6.95).
Topics: Humans; COVID-19; Female; Young Adult; Adolescent; Environmental Exposure; Pesticides; Male; SARS-CoV-2; California; Pregnancy; Adult; Antibodies, Viral; Biomarkers; Organophosphates; Longitudinal Studies
PubMed: 38788790
DOI: 10.1016/j.envres.2024.119214 -
Ecotoxicology and Environmental Safety Jul 2024Organophosphorus flame retardants, such as triphenyl phosphate (TPhP), exist ubiquitously in various environments owing to their widespread usage. Potential toxic...
Organophosphorus flame retardants, such as triphenyl phosphate (TPhP), exist ubiquitously in various environments owing to their widespread usage. Potential toxic effects of residual flame retardants on cultured non-fish species are not concerned commonly. TPhP-induced physiological and biochemical effects in an aquatic turtle were evaluated here by systematically investigating the changes in growth and locomotor performance, hepatic antioxidant ability and metabolite, and intestinal microbiota composition of turtle hatchlings after exposure to different TPhP concentrations. Reduced locomotor ability and antioxidant activity were only observed in the highest concentration group. Several metabolic perturbations that involved in amino acid, energy and nucleotide metabolism, in exposed turtles were revealed by metabolite profiles. No significant among-group difference in intestinal bacterial diversity was observed, but the composition was changed markedly in exposed turtles. Increased relative abundances of some bacterial genera (e.g., Staphylococcus, Vogesella and Lawsonella) probably indicated adverse outcomes of TPhP exposure. Despite having only limited impacts of exposure at environmentally relevant levels, our results revealed potential ecotoxicological risks of residual TPhP for aquatic turtles considering TPhP-induced metabolic perturbations and intestinal bacterial changes.
Topics: Animals; Turtles; Gastrointestinal Microbiome; Liver; Water Pollutants, Chemical; Flame Retardants; Organophosphates; Bacteria; Intestines; Antioxidants
PubMed: 38776782
DOI: 10.1016/j.ecoenv.2024.116488 -
Ecotoxicology and Environmental Safety Jul 2024Combined toxicity is a critical concern during the risk assessment of environmental pollutants. Due to the characteristics of strong hydrophobicity and large specific...
Combined toxicity is a critical concern during the risk assessment of environmental pollutants. Due to the characteristics of strong hydrophobicity and large specific surface area, microplastics (MPs) and nanoplastics (NPs) have become potential carriers of organic pollutants that may pose a health risk to humans. The co-occurrence of organic pollutants and MPs would cause adverse effects on aquatic organism, while the information about combined toxicity induced by organophosphorus flame retardants and MPs on human cells was limited. This study aimed to reveal the toxicity effects of co-exposure to triphenyl phosphate (TPHP) and polystyrene (PS) particles with micron-size/nano-size on HepG2 cell line. The adsorption behaviors of TPHP on PS particles was observed, with the PS-NP exhibiting a higher adsorption capacity. The reactive oxygen species generation, mitochondrial membrane potential depolarization, lactate dehydrogenase release and cell apoptosis proved that PS-NPs/MPs exacerbated TPHP-induced cytotoxicity. The particle size of PS would affect the toxicity to HepG2 cells that PS-NP (0.07 μm) exhibited more pronounced combined toxicity than PS-MP (1 μm) with equivalent concentrations of TPHP. This study provides fundamental insights into the co-toxicity of TPHP and PS micro/nanoplastics in HepG2 cells, which is crucial for validating the potential risk of combined toxicity in humans.
Topics: Humans; Hep G2 Cells; Polystyrenes; Nanoparticles; Membrane Potential, Mitochondrial; Apoptosis; Flame Retardants; Microplastics; Reactive Oxygen Species; Particle Size; Organophosphates; Water Pollutants, Chemical; Adsorption; Plastics
PubMed: 38776781
DOI: 10.1016/j.ecoenv.2024.116489 -
Environmental Toxicology and... Jun 2024Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its...
Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.7 macrophages. Moreover, chlorpyrifos induced intracellular ROS production, subsequently leading to lipid peroxidation. Chlorpyrifos reduced the activation of antioxidative enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Chlorpyrifos upregulated HO-1 expression and activated the Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation and Keap1 degradation. Chlorpyrifos exerted effects on the following in a dose-dependent manner: cytotoxicity, genotoxicity, lipid peroxidation, intracellular ROS production, antioxidative enzyme activity reduction, HO-1 expression, Nrf2 phosphorylation, and Keap1 degradation. Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced intracellular ROS generation, cytotoxicity, and genotoxicity. Thus, chlorpyrifos may induce cytotoxicity and genotoxicity by promoting intracellular ROS production and suppressing the antioxidative defense system activation in macrophages.
Topics: Chlorpyrifos; Animals; Mice; RAW 264.7 Cells; Reactive Oxygen Species; NF-E2-Related Factor 2; Macrophages; Kelch-Like ECH-Associated Protein 1; Insecticides; Cell Survival; Antioxidants; Lipid Peroxidation; Heme Oxygenase-1; Superoxide Dismutase; Catalase; Glutathione Peroxidase; Oxidative Stress; Membrane Proteins
PubMed: 38759849
DOI: 10.1016/j.etap.2024.104468 -
Phytomedicine : International Journal... Jul 2024The identification of a novel and effective strategy for the clinical treatment of acute leukemia (AL) is a long-term goal. Minnelide, a water-soluble prodrug of...
BACKGROUND
The identification of a novel and effective strategy for the clinical treatment of acute leukemia (AL) is a long-term goal. Minnelide, a water-soluble prodrug of triptolide, has recently been evaluated in phase I and II clinical trials in patients with multiple cancers and has shown promise as an antileukemic agent. However, the molecular mechanism underlying minnelide's antileukemic activity remains unclear.
PURPOSE
To explore the molecular mechanisms by which minnelide exhibits antileukemic activity.
METHODS
AL cells, primary human leukemia cells, and a xenograft mouse model were treated with triptolide and minnelide. The molecular mechanism was elucidated using western blotting, immunoprecipitation, flow cytometry, GSEA and liquid chromatography-mass spectrometry analysis.
RESULTS
Minnelide was highly effective in inhibiting leukemogenesis and improving survival in two complementary AL mouse models. Triptolide, an active form of minnelide, causes cell cycle arrest in G1 phase and induces apoptosis in both human AL cell lines and primary AL cells. Mechanistically, we identified Ars2 as a new chemotherapeutic target of minnelide for AL treatment. We found that triptolide directly targeted Ars2, resulting in the downregulation of miR-190a-3p, which led to the disturbance of PTEN/Akt signaling and culminated in G1 cell cycle arrest and apoptosis.
CONCLUSIONS
Our findings demonstrate that targeting Ars2/miR-190a-3p signaling using minnelide could represent a novel chemotherapeutic strategy for AL treatment and support the evaluation of minnelide for the treatment of AL in clinical trials.
Topics: Phenanthrenes; Animals; Humans; Diterpenes; MicroRNAs; Epoxy Compounds; Cell Line, Tumor; Mice; Apoptosis; Xenograft Model Antitumor Assays; Leukemia; Organophosphates; Antineoplastic Agents, Phytogenic
PubMed: 38759317
DOI: 10.1016/j.phymed.2024.155724