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Environmental Science & Technology Jan 2021Eleven organophosphate esters (OPEs) were detected in surface water and sediment samples from yearly sampling (2013-2018) in the Canadian Arctic. In water samples,...
Eleven organophosphate esters (OPEs) were detected in surface water and sediment samples from yearly sampling (2013-2018) in the Canadian Arctic. In water samples, ∑chlorinated-OPEs (Cl-OPEs) concentrations exceeded ∑non-chlorinated-OPEs (non-Cl-OPEs) with median concentrations of 10 ng L and 1.3 ng L, respectively. In sediment samples, ∑Cl-OPEs and ∑nonchlorinated-OPEs had median concentrations of 4.5 and 2.5 ng g, respectively. High concentrations of OPEs in samples from the Mackenzie River plume suggest riverine discharge as an OPE source to the Canadian Arctic. The prevalence of OPEs at other sites is consistent with long-range transport. The OPE inventory of the Canadian Arctic Ocean representative of years 2013-2018 was estimated at 450-16,000 tonnes with a median ∑OPE mass of 4100 tonnes with >99% of the OPE inventory estimated to be in the water column. These results highlight the importance of OPEs as water-based Arctic contaminants subject to long-range transport and local sources. The high OPE inventory in the water column of the Canadian Arctic Ocean points to the need for international regulatory mechanisms for persistent and mobile organic contaminants (PMOCs) that are not covered by the risk assessment criteria of the Stockholm Convention.
Topics: Arctic Regions; Canada; China; Environmental Monitoring; Esters; Flame Retardants; Oceans and Seas; Organophosphates
PubMed: 33305563
DOI: 10.1021/acs.est.0c04422 -
Revista Brasileira de Parasitologia... 2012Acaricide resistance has become widespread in countries where cattle ticks, Rhipicephalus (Boophilus) microplus, are a problem. Resistance arises through genetic changes... (Review)
Review
Acaricide resistance has become widespread in countries where cattle ticks, Rhipicephalus (Boophilus) microplus, are a problem. Resistance arises through genetic changes in a cattle tick population that causes modifications to the target site, increased metabolism or sequestration of the acaricide, or reduced ability of the acaricide to penetrate through the outer protective layers of the tick's body. We review the molecular and biochemical mechanisms of acaricide resistance that have been shown to be functional in R. (B.) microplus. From a mechanistic point of view, resistance to pyrethroids has been characterized to a greater degree than any other acaricide class. Although a great deal of research has gone into discovery of the mechanisms that cause organophosphate resistance, very little is defined at the molecular level and organophosphate resistance seems to be maintained through a complex and multifactorial process. The resistance mechanisms for other acaricides are less well understood. The target sites of fipronil and the macrocyclic lactones are known and resistance mechanism studies are in the early stages. The target site of amitraz has not been definitively identified and this is hampering mechanistic studies on this acaricide.
Topics: Acaricides; Animals; Drug Resistance; Organophosphates; Pyrethrins; Rhipicephalus
PubMed: 22534937
DOI: 10.1590/s1984-29612012000100002 -
Revista Espanola de Quimioterapia :... Sep 2021The most relevant information on the clinical uses of tedizolid from studies published in the last 18 months is presented in this brief review. The most important data... (Review)
Review
The most relevant information on the clinical uses of tedizolid from studies published in the last 18 months is presented in this brief review. The most important data indicate better tolerance and safety profile of long-term therapeutic regimes in off-label indications, such as osteoarticular infections and those caused by mycobacteria. Its lower risk of hazardous interactions compared to linezolid should be emphasized. Furthermore, tedizolid in its combination with rifampicin shows a more favourable way of acting as demonstrated in vitro and in vivo studies. A recent trial also opens the door for its potential use in nosocomial pneumonia caused by Gram-positive bacteria.
Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Organophosphates; Oxazoles; Oxazolidinones; Tetrazoles
PubMed: 34598418
DOI: 10.37201/req/s01.06.2021 -
Expert Opinion on Drug Metabolism &... Mar 2017Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Although tedizolid shares many similar properties with... (Comparative Study)
Comparative Study Review
Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Although tedizolid shares many similar properties with linezolid, another oxazolidinone used to treat ABSSSI, the two antibiotics have several key differences. Areas covered: This review provides a detailed summary of the overall pharmacodynamics, pharmacokinetics, clinical efficacy, and safety of tedizolid for the treatment of ABSSSI. Expert opinion: Compared to other antibiotics used for ABSSSI, tedizolid has several advantages. Tedizolid has a long half-life, allowing for once daily dosing. Tedizolid also has broad spectrum of activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, Coagulase-negative Staphylococci, and Enterococci - including isolates demonstrating resistance to linezolid. It is available in both oral and intravenous formulations, and, has outstanding oral bioavailability, allowing for oral-step down therapy. There is also some evidence that, tedizolid has fewer significant interactions with serotonin reuptake inhibitors or monoamine oxidase inhibitors than linezolid. Finally, thrombocytopenia may occur less often with tedizolid than linezolid. However, these benefits must be weighed against the financial cost of tedizolid and the availability of alternative antibiotic choices.
Topics: Animals; Anti-Bacterial Agents; Biological Availability; Drug Interactions; Half-Life; Humans; Organophosphates; Oxazoles; Skin Diseases, Bacterial; Soft Tissue Infections
PubMed: 28140693
DOI: 10.1080/17425255.2017.1290080 -
Romanian Journal of Morphology and... 2020Organophosphate (OP) use remains largely available worldwide despite more strict regulatory measures, in agriculture, parks or households, leading to a daily low-dose...
Organophosphate (OP) use remains largely available worldwide despite more strict regulatory measures, in agriculture, parks or households, leading to a daily low-dose exposure. The systemic dysfunction appears partly due to acetylcholinesterase inhibition, exhibiting a primary toxic effect on the endocrine system but also on the liver and kidneys, which are responsible for products metabolization and elimination. Prolonged OP exposure can be responsible for histopathological (HP) changes that can either evolve or worsen pre-existing conditions. We conducted an experimental study including six male Wistar rats divided into two groups (four rats in the study group and two in the control group). The subjects in the first group were administered 100 mg∕kg Chlorpyrifos half median lethal dose (LD50) at baseline and at 48 hours, under general anesthesia. Organ harvesting was achieved after one week. HP modifications were discovered in all kidney samples, with dystrophic changes and vacuolization of mesangial cells, dilation of renal tubules and epithelial atrophy. Congestion of vascular structures also occurred. The liver samples showed severe alteration in both vessels and hepatocytes. Adrenal gland impairment was confirmed through an increase in vacuole number in all areas, while a decrease in colloid content was noted in the thyroid gland simultaneously with a modified foamy aspect. This study is the first to certify the extent of organ injury induced by OP exposure, describing both glomerular and tubular involvement in the kidneys, liver necrosis and endocrine disturbances.
Topics: Animals; Male; Organophosphates; Rats; Rats, Wistar
PubMed: 33544793
DOI: 10.47162/RJME.61.2.11 -
Environment International Jun 2019Given the ongoing studies on the adverse effects of organophosphate ester (OPE) flame retardants and plasticizers on human health, there is an increasing scientific... (Review)
Review
Given the ongoing studies on the adverse effects of organophosphate ester (OPE) flame retardants and plasticizers on human health, there is an increasing scientific interest in the risk of exposure to OPEs via dietary intake. Using peer-reviewed literature published up to 2018, this review surveyed and compiled the available and reported data on the concentrations and distributions of 30 OPEs based on their occurrence in various food samples from around the world. Regardless of sampling locations or food categories, 22 OPEs were detectable in at least one of analyzed sample, and there were clear variations in OPE levels among samples from different locations or food categories. For instance, cereals and fats/oils were the most contaminated by OPEs in China and Belgium, whereas fats/oils and desserts were the main polluted products in Sweden. In contrast, vegetables, fruits, fluid dairy products, and cereals were reported as the primary categories of food polluted by OPEs in Australia. Animal-based food categories such as eggs, fish and meat were the least contaminated, whereas the highest median OPE concentrations were found in meat and fish from the United State. The levels and distribution patterns of OPEs in foodstuffs demonstrated a tremendous difference even when collected from the same country and the same food item. Rice from China had the highest tris(2‑chloroethyl) phosphate (TCEP, mean: 29.8 ng/g dw) levels, whereas 2‑ethylhexyl‑diphenyl phosphate (EHDPP, mean: 4.17 ng/g ww), triphenyl phosphate (TPHP, mean: 26.14 ng/g ww), tris(2-chloroisopropyl) phosphate (TCIPP, mean: 0.87 ng/g ww) and tributyl phosphate (TNBP, median: 0.55 ng/g ww) concentrations were the highest in the same food category from Sweden, Belgium, Australia, and the United States, respectively. These discrepancies may be due to a variety of reasons such as differences in OPE physico-chemical properties, extent of usage, uptake, metabolic pathways, industrial food manufacturing processes, OPE level differences as a function of habitat, and accumulation and degradability of OPEs in different species. It is worth noting that, due to its worldwide usage in food packaging materials, EHDPP was more prominently found in processed food compared to non-processed food. Based on reported OPE levels in various foods, this review conducted a preliminary assessment of human exposure to OPEs through dietary intake, which suggested that the OPE estimated daily intake (EDI) for humans was around 880 ng/kg bw/day (95th percentile). This value was well below the corresponding OPE health reference dose given by the U.S. EPA (≥15,000 ng/kg bw/day). Even so, dietary exposure to OPEs via food intake may be not negligible based on some important factors such as dilution effects, cooking processes, and the contribution of as yet unknown means of OPE exposure. Overall, this review highlights several gaps in our understanding of OPEs in foodstuffs: 1) the investigation of contamination levels of OPEs in foodstuffs should be extended to other regions, especially North America and European countries, where OPEs are widely used and frequently detected in environmental samples, and 2) newly identified OPE derivatives/by-products, e.g., OP diesters and hydroxylated metabolites, which have been reported as end-products of OPE enzymatic metabolism or degradation through aqueous hydrolysis, and which may co-exist with parent OPEs, could also be screened with precursor OPEs in foodstuffs in future studies.
Topics: Dietary Exposure; Environmental Pollutants; Flame Retardants; Humans; Organophosphates; Plasticizers
PubMed: 30901640
DOI: 10.1016/j.envint.2019.03.009 -
Nature Chemistry Apr 2021Electrochemical techniques have long been heralded for their innate sustainability as efficient methods to achieve redox reactions. Carbonyl desaturation, as a...
Electrochemical techniques have long been heralded for their innate sustainability as efficient methods to achieve redox reactions. Carbonyl desaturation, as a fundamental organic oxidation, is an oft-employed transformation to unlock adjacent reactivity through the formal removal of two hydrogen atoms. To date, the most reliable methods to achieve this seemingly trivial reaction rely on transition metals (Pd or Cu) or stoichiometric reagents based on I, Br, Se or S. Here we report an operationally simple pathway to access such structures from enol silanes and phosphates using electrons as the primary reagent. This electrochemically driven desaturation exhibits a broad scope across an array of carbonyl derivatives, is easily scalable (1-100 g) and can be predictably implemented into synthetic pathways using experimentally or computationally derived NMR shifts. Systematic comparisons to state-of-the-art techniques reveal that this method can uniquely desaturate a wide array of carbonyl groups. Mechanistic interrogation suggests a radical-based reaction pathway.
Topics: Aldehydes; Alkenes; Electrochemical Techniques; Ethers; Ketones; Models, Chemical; Organophosphates; Oxidation-Reduction; Silanes
PubMed: 33758368
DOI: 10.1038/s41557-021-00640-2 -
Environmental Research Sep 2022Organophosphate esters (OPE) are flame retardants and plasticizers used in a wide range of consumer products. Despite their widespread use, few studies have...
Organophosphate esters (OPE) are flame retardants and plasticizers used in a wide range of consumer products. Despite their widespread use, few studies have characterized pediatric exposures. We assessed variability and predictors of OPE exposures in a cohort panel study of 179 predominantly Black school-aged children with asthma in Baltimore City, MD. The study design included up to four seasonal week-long in-home study visits with urine sample collection on days 4 and 7 of each visit (n = 618). We quantified concentrations of 9 urinary OPE biomarkers: bis(2-chloroethyl) phosphate (BCEtp), bis(1-chloro-2-propyl) phosphate, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-benzyl phosphate (DBuP), di-benzyl phosphate, di-o-cresylphosphate, di-p-cresylphosphate (DPCP), di-(2-propylheptyl) phthalate (DPHP), 2,3,4,5-tetrabromo benzoic acid. We assessed potential predictors of exposure, including demographic factors, household characteristics, and cleaning behaviors. We calculated Spearman/tetrachoric correlations and intraclass correlation coefficients (ICCs) to examine within-week and seasonal intra-individual variability, respectively. We assessed OPE predictors using linear models for continuous log concentrations (BDCPP and DPHP) and logistic models for odds of detection (BCEtP, DBuP, DPCP), with generalized estimating equations to account for repeated measures. For all OPEs, we observed moderate within-week correlations (r: 0.31-0.63) and weak to moderate seasonal reliability (ICC: 0.18-0.38). BDCPP and DPHP concentrations were higher in the summer compared to other seasons. DPHP concentrations were lower among males than females (%: -53.5%; 95% CI: -62.7, -42.0) and among participants spending >12 h/day indoors compared to ≤12 h (%: -20.7%; 95% CI: -32.2, -7.3). BDCPP concentrations were lower among children aged 8-10 years compared to 5-7 years (%: -39.1%; 95% CI: -55.9, -15.9) and higher among children riding in a vehicle on the day of sample collection compared to those who had not (%: 28.5%; 95% CI: 3.4, 59.8). This study is the first to characterize within-week and seasonal variability and identify predictors of OPE biomarkers among Black school-aged children, a historically understudied population.
Topics: Biomarkers; Child; Esters; Female; Flame Retardants; Humans; Male; Organophosphates; Phosphates; Reproducibility of Results
PubMed: 35346652
DOI: 10.1016/j.envres.2022.113192 -
Scientific Reports May 2023In recent decades, the detrimental effects of environmental contaminants on human health have become a serious public concern. Organophosphate (OP) pesticides are widely...
In recent decades, the detrimental effects of environmental contaminants on human health have become a serious public concern. Organophosphate (OP) pesticides are widely used in agriculture, and the negative impacts of OP and its metabolites on human health have been demonstrated. We hypothesized that exposure to OPs during pregnancy could impose damaging effects on the fetus by affecting various processes. We analyzed sex-specific epigenetic responses in the placenta samples obtained from the mother-child PELAGIE cohort. We assayed the telomere length and mitochondrial copy numbers using genomic DNA. We analyzed H3K4me3 by using chromatin immunoprecipitation followed by qPCR (ChIP‒qPCR) and high-throughput sequencing (ChIP-seq). The human study was confirmed with mouse placenta tissue analysis. Our study revealed a higher susceptibility of male placentas to OP exposure. Specifically, we observed telomere length shortening and an increase in γH2AX levels, a DNA damage marker. We detected lower histone H3K9me3 occupancy at telomeres in diethylphosphate (DE)-exposed male placentas than in nonexposed placentas. We found an increase in H3K4me3 occupancy at the promoters of thyroid hormone receptor alpha (THRA), 8-oxoguanine DNA glycosylase (OGG1) and insulin-like growth factor (IGF2) in DE-exposed female placentas. H3K4me3 occupancy at PPARG was increased in both male and female placentas exposed to dimethylphosphate (DM). The genome-wide sequencing of selected samples revealed sex-specific differences induced by DE exposure. Specifically, we found alterations in H3K4me3 in genes related to the immune system in female placenta samples. In DE-exposed male placentas, a decrease in H3K4me3 occupancy at development-related, collagen and angiogenesis-related genes was observed. Finally, we observed a high number of NANOG and PRDM6 binding sites in regions with altered histone occupancy, suggesting that the effects were possibly mediated via these factors. Our data suggest that in utero exposure to organophosphate metabolites affects normal placental development and could potentially impact late childhood.
Topics: Child; Animals; Mice; Humans; Female; Male; Pregnancy; Histones; Organophosphates; Placenta; Insecticides; Mother-Child Relations
PubMed: 37198424
DOI: 10.1038/s41598-023-35113-8 -
International Journal of Environmental... Feb 2023Paraoxonase-1 (PON1) is a calcium-dependent, HDL-bound serum hydrolase active toward a wide variety of substrates. PON1 displays three types of activities, among which... (Review)
Review
Paraoxonase-1 (PON1) is a calcium-dependent, HDL-bound serum hydrolase active toward a wide variety of substrates. PON1 displays three types of activities, among which lactonase, paraoxonase, arylesterase and phosphotriesterase can be distinguished. Not only is this enzyme a major organophosphate compound detoxifier, but it is also an important constituent of the cellular antioxidant system and has anti-inflammatory and antiatherogenic functions. The concentration and activity of PON1 is highly variable among individuals, and these differences can be both of genetic origin and be a subject of epigenetic regulation. Owing to the fact that, in recent decades, the exposure of humans to an increasing number of different xenobiotics has been continuously rising, the issues concerning the role and activity of PON1 shall be reconsidered with particular attention to growing pharmaceuticals intake, dietary habits and environmental awareness. In the following manuscript, the current state of knowledge concerning the influence of certain modifiable and unmodifiable factors, including smoking, alcohol intake, gender, age and genotype variation on PON1 activity, along with pathways through which these could interfere with the enzyme's protective functions, is presented and discussed. Since exposure to certain xenobiotics plays a key role in PON1 activity, the influence of organophosphates, heavy metals and several pharmaceutical agents is also specified.
Topics: Humans; Aryldialkylphosphatase; Epigenesis, Genetic; Antioxidants; Smoking; Organophosphates; Life Style
PubMed: 36833509
DOI: 10.3390/ijerph20042813