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Archives of Toxicology Sep 2018Organophosphate triesters (PEFRs) are used increasingly as flame retardants and plasticizers in a variety of applications, such as building materials, textiles, and... (Review)
Review
Organophosphate triesters (PEFRs) are used increasingly as flame retardants and plasticizers in a variety of applications, such as building materials, textiles, and electric and electronic equipment. They have been proposed as alternatives to brominated flame retardants. This updated review shows that biomonitoring has gained incrementally greater importance in evaluating human exposure to PEFRs, and it holds the advantage of taking into account the multiple potential sources and various intake pathways of PEFRs. Simultaneous and extensive internal exposure to a broad range of PEFRs have been reported worldwide. Their metabolites, mainly dialkyl or diaryl diesters, have been used as biomarkers of exposure and have been ubiquitously detected in the urine of adults and children in the general population. Concentrations and profiles of PEFR urinary metabolites are seen to be variable and are highly dependent on individual and environmental factors, including age, country regulation of flame retardants, and types and quantities of emissions in microenvironments, as well as analytical procedures. Additional large biomonitoring studies, using a broad range of urinary diesters and hydroxylated metabolites, would be useful to improve the validity of the biomarkers and to refine assessments of human exposure to PEFRs.
Topics: Biomarkers; Environmental Exposure; Flame Retardants; Humans; Occupational Exposure; Organophosphates; Risk Assessment
PubMed: 30097699
DOI: 10.1007/s00204-018-2275-z -
Journal of Dental Research May 2009Self-etching primers have simplified the process of direct bonding of dental resins, by eliminating the rinsing step after etching in conventional bonding, for example....
Self-etching primers have simplified the process of direct bonding of dental resins, by eliminating the rinsing step after etching in conventional bonding, for example. Although it is generally assumed that all of the applied self-etching primer is incorporated into the resin, the possibility that a substantial amount remains free and extractable into a person's saliva has not been investigated. The aim of the present study was to examine this issue by bonding brackets to extracted teeth with self-etching primers under controlled conditions and determining the proportion of the applied phosphoric acid ester that is subsequently extractable by high-performance liquid chromatography. Approximately half of the applied acid ester was extractable and thus not integrated into the polymeric network following standard light curing. This was reduced to 40% when the curing time was doubled. Acid ester leaching was a rapid process that was essentially completed within an hour.
Topics: Acid Etching, Dental; Chromatography, High Pressure Liquid; Curing Lights, Dental; Dental Bonding; Dentin-Bonding Agents; Humans; Magnetic Resonance Spectroscopy; Materials Testing; Organophosphates; Orthodontic Brackets; Polymers; Resin Cements; Sodium Chloride; Time Factors
PubMed: 19493887
DOI: 10.1177/0022034509336646 -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carcinogenicity Tests; Carcinogens; Flame Retardants; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Organophosphates; Salmonella typhimurium
PubMed: 10476442
DOI: No ID Found -
Biochemistry. Biokhimiia Oct 2012Development of new ways of creating catalytic antibodies possessing defined substrate specificity towards artificial substrates has important fundamental and practical... (Review)
Review
Development of new ways of creating catalytic antibodies possessing defined substrate specificity towards artificial substrates has important fundamental and practical aspects. Low immunogenicity combined with high stability of immunoglobulins in the blood stream makes abzymes potent remedies. A good example is the cocaine-hydrolyzing antibody that has successfully passed clinical trials. Creation of an effective antidote against organophosphate compounds, which are very toxic substances, is a very realistic goal. The most promising antidotes are based on cholinesterases. These antidotes are now expensive, and their production methods are inefficient. Recombinant antibodies are widely applied in clinics and have some advantage compared to enzymatic drugs. A new potential abzyme antidote will combine effective catalysis comparable to enzymes with high stability and the ability to switch on effector mechanisms specific for antibodies. Examples of abzymes metabolizing organophosphate substrates are discussed in this review.
Topics: Animals; Antibodies, Catalytic; Organophosphate Poisoning; Organophosphates; Substrate Specificity
PubMed: 23157294
DOI: 10.1134/S0006297912100069 -
Environmental Research Jul 2018The metabolites of nine organophosphate ester (OPE) flame retardants were measured in 180 urine samples collected from a population (including adults and children) in...
The metabolites of nine organophosphate ester (OPE) flame retardants were measured in 180 urine samples collected from a population (including adults and children) in western Shanghai, China, using liquid chromatography-tandem spectrometry (LC-MS/MS). The total urinary concentrations of nine OPE metabolites ranged 100-23800 pg/mL, with a geometric mean (GM) value of 1450 pg/mL. The concentrations of alkyl-OPE metabolites (879 pg/mL) were approximately an order of magnitude higher than those of aryl-OPE (53.7 pg/mL) and chlorinated-OPE metabolites (52.7 pg/mL). Diphenyl phosphate (DPHP), diethyl phosphate (DEP), di-n-butyl phosphate (DNBP), bis(2-ethylhexyl) phosphate (BEHP), and bis(2-butoxyethyl) phosphate (BBOEP) were the dominant OPE metabolites found in urine. The results showed that an increase in age was associated with a significant decrease in urinary DPHP (r = -0.278, p < 0.01) and DNBP (r = -0.314, p < 0.01) concentrations. The highest concentrations of DPHP (GM = 80.7 pg/mL) and DNBP (GM = 16.9 pg/mL) were found in urine from people living in homes that were less than 10 years old. The urinary DNBP concentration was significantly associated with self-reported symptoms of allergy. Our result establishes baseline value for OPE exposure in a population in China for comparison in future studies.
Topics: Adult; Child; China; Chromatography, Liquid; Flame Retardants; Humans; Organophosphates; Tandem Mass Spectrometry
PubMed: 29604578
DOI: 10.1016/j.envres.2018.03.031 -
Biochimica Et Biophysica Acta Mar 2004Quantifying the rate of phosphate monoester dianion hydrolysis under physiological conditions has implications for designing transition state mimics and understanding... (Review)
Review
Quantifying the rate of phosphate monoester dianion hydrolysis under physiological conditions has implications for designing transition state mimics and understanding how catalysis is facilitated. Catalysis is energetically most efficient if the mechanistic pathway in solution is stabilised. Monoesters are believed to have a "dissociative" transition state that has little bonding to the nucleophile and leaving group. However, in many instances, it is suggested that enzymes catalyse monoester transfer through an associative (diester-like) pathway. This is perhaps easier to rationalise in terms of the active site residues available. For example, in the catalytic subunit of protein phosphatase 1 (PP1), these are metal ions and cationic side chains which might be expected to stabilise developing negative charge. By using multiple interactions simultaneously, cooperativity in catalysis may be achieved. However, this idea is difficult to demonstrate unambiguously in large, complex natural systems. This contribution examines the background reactivity of phosphate esters, and reports data showing that the substrates for serine/threonine phosphatases have slower intrinsic rate constants than any other enzyme substrates. Using model complexes, the characteristics of alternative (associative) mechanisms that have been proposed for the metallophosphatase catalysed reaction are explored. Finally, complementary catalytic groups are combined with this core complex to look for experimental evidence for possible cooperativity in this context.
Topics: Humans; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Metals; Models, Chemical; Organophosphates; Phosphoric Monoester Hydrolases; Phosphotransferases; Thermodynamics
PubMed: 15023368
DOI: 10.1016/j.bbapap.2003.11.031 -
IARC Monographs on the Evaluation of... 1990
Review
Topics: Animals; Carcinogens; Carcinogens, Environmental; Chemical Phenomena; Chemistry; Female; Flame Retardants; Mice; Mutagens; Organophosphates; Organophosphorus Compounds; Rats
PubMed: 2197455
DOI: No ID Found -
Occupational Medicine (Oxford, England) Mar 2004The ubiquitous organophosphates present a continuing health hazard in agriculture, public health eradication programmes and as chemical warfare agents. Despite... (Review)
Review
The ubiquitous organophosphates present a continuing health hazard in agriculture, public health eradication programmes and as chemical warfare agents. Despite significant progress in understanding the potential mechanisms of toxicity far beyond the commonly accepted mechanism of cholinesterase inhibition in intentional exposures, the precise health effects following occupational exposures are yet to be completely defined. A much greater understanding exists of the clinical features of organophosphate poisoning. These are characterized by a triphasic response involving an initial acute cholinergic phase, an intermediate syndrome (both associated with high mortality) and a disabling but non-lethal delayed polyneuropathy. The delayed polyneuropathy may occur in the absence of the cholinergic or intermediate phases. However, progress is still required in order to improve the quantification and assessment of occupational exposures and the implementation of appropriate preventive measures. Finally, evidence-based guidelines for appropriate or optimal therapeutic interventions following poisoning are required urgently and collaborative work with colleagues in developing countries, where the occurrence of organophosphate exposures is more frequent, may provide the answers.
Topics: Cholinesterases; Environmental Monitoring; Humans; Occupational Diseases; Occupational Exposure; Organophosphates; Polyneuropathies; Respiration
PubMed: 15020723
DOI: 10.1093/occmed/kqh018 -
Environmental Pollution (Barking, Essex... Feb 2024Organophosphate esters (OPEs), which are phosphoric acid ester derivatives, are anthropogenic substances that are widely used in commerce. Nevertheless, there is growing... (Review)
Review
Organophosphate esters (OPEs), which are phosphoric acid ester derivatives, are anthropogenic substances that are widely used in commerce. Nevertheless, there is growing public concern about these ubiquitous contaminants, which are frequently detected in contaminated water sources. OPEs are mostly emitted by industrial operations, and the primary routes of human exposure to OPEs include food intake and dermal absorption. Because of their negative effects on both human health and the environment, it is clear that innovative methods are needed to facilitate their eradication. In this study, we present a comprehensive overview of the existing characteristics and origins of OPEs, their possible impacts on human health, and the merits, drawbacks, and future possibilities of contemporary sophisticated remediation methods. Current advanced remediation approaches for OPEs include adsorption, degradation (advanced oxidation, advanced reduction, and redox technology), membrane filtration, and municipal wastewater treatment plants, degradation and adsorption are the most promising removal technologies. Meanwhile, we proposed potential areas for future research (appropriate management approaches, exploring the combination treatment process, economic factors, and potential for secondary pollution). Collectively, this work gives a comprehensive understanding of OPEs, providing useful insights for future research on OPEs pollution.
Topics: Humans; Water; Environmental Monitoring; Esters; Organophosphates; Water Pollution; China; Flame Retardants
PubMed: 38147949
DOI: 10.1016/j.envpol.2023.123218 -
Paediatric Drugs Oct 2019Triclofos sodium (TFS) has been used for many years in children as a sedative for painless medical procedures. It is physiologically and pharmacologically similar to... (Review)
Review
AIM
Triclofos sodium (TFS) has been used for many years in children as a sedative for painless medical procedures. It is physiologically and pharmacologically similar to chloral hydrate, which has been censured for use in children with neurocognitive disorders. The aim of this study was to investigate the safety and efficacy of TFS sedation in a pediatric population with a high rate of neurocognitive disability.
METHODS
The database of the neurodiagnostic institute of a tertiary academic pediatric medical center was retrospectively reviewed for all children who underwent sedation with TFS in 2014. Data were collected on demographics, comorbidities, neurologic symptoms, sedation-related variables, and outcome.
RESULTS
The study population consisted of 869 children (58.2% male) of median age 25 months (range 5-200 months); 364 (41.2%) had neurocognitive diagnoses, mainly seizures/epilepsy, hypotonia, or developmental delay. TFS was used for routine electroencephalography in 486 (53.8%) patients and audiometry in 401 (46.2%). Mean (± SD) dose of TFS was 50.2 ± 4.9 mg/kg. Median time to sedation was 45 min (range 5-245), and median duration of sedation was 35 min (range 5-190). Adequate sedation depth was achieved in 769 cases (88.5%). Rates of sedation-related adverse events were low: apnea, 0; desaturation ≤ 90%, 0.2% (two patients); and emesis, 0.35% (three patients). None of the children had hemodynamic instability or signs of poor perfusion. There was no association between desaturations and the presence of hypotonia or developmental delay.
CONCLUSION
TFS, when administered in a controlled and monitored environment, may be safe for use in children, including those with underlying neurocognitive disorders.
Topics: Child; Child, Preschool; Female; Humans; Hypnotics and Sedatives; Infant; Male; Nervous System Diseases; Organophosphates
PubMed: 31292919
DOI: 10.1007/s40272-019-00346-6