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Environment International Oct 2021Over the course of the continual phase-outs of toxic halogenated flame retardants (HFRs), there has been an increasing demand for organophosphate esters (OPEs) in global... (Review)
Review
Over the course of the continual phase-outs of toxic halogenated flame retardants (HFRs), there has been an increasing demand for organophosphate esters (OPEs) in global FR markets. OPE-FRs have largely been identified as OP triesters, which have a basic chemical structure of O = P(OR). In addition to OP triesters, OPEs can refer to another class of related substances, namely, OP diesters that have a typical chemical structure of O = P(OR)(OH)). OP diesters are known as biotic or abiotic degradation products of OP triesters. In recent years, environmental scientists have proven that OP diesters widely exist in a variety of environmental matrices and biotic samples around the world, implying the potential risks from OP diester exposure to biota and humans in the environment. Here, we have reviewed the scientific literature for studies involving OP diesters and up to the end of 2020. The aim of the present review is to assess the present understanding of the physicochemical properties, sources (industrial production and degradation), environmental occurrence of OP diesters, and adverse effects to exposed organisms. Based on the literature in the Web of Science core collection, we found that at least 23 OP diesters have been reported as contaminants in various environments or as degradation products of OP triesters. The physicochemical properties of OP diesters vary depending on their specific chemical structures. OP diesters containing halogen atoms and aryl groups seem to be more persistent (with greater estimated half-life (t) values) in environmental matrices. There were multiple sources of OP diesters, including industrial production and biotic or abiotic degradation from OP triesters. Specifically, we found that ten OP diesters are produced somewhere in the world, and the total annual output was estimated to be 17,050 metric tons (this number is underestimated due to the limitation of the available information). In addition, the wide application of OP triesters worldwide makes the degradation of OP triesters another critical source of OP diesters to the environment and to organisms. Current monitoring studies have demonstrated that some OP diesters were detectable in the human body (via both blood and urine samples), indoor dust, wastewater, or sewage sludge worldwide. The highest concentrations of diphenyl phosphate (DPHP) in human urine have been reported as high as 727 ng/mL (children (aged 0-5 years) urine samples from Australia). In addition, adverse effects following direct or indirect exposure to 11 OP diesters in organisms (including animals, bacteria, and algae) have been reported, and the recorded adverse outcomes following exposure to OP diesters included developmental toxicity, alteration of gene expression, and disturbance of nuclear receptor activity. Biomonitoring studies regarding human samples have frequently reported statistically significant associations between the concentrations of OP diesters and markers of human health (mainly related to reproductive toxicity). Finally, on the basis of current knowledge on OP diesters, we propose prospects for related research directions in future studies.
Topics: Animals; Child; Dust; Environmental Monitoring; Esters; Flame Retardants; Humans; Organophosphates; Sewage; Wastewater
PubMed: 34146766
DOI: 10.1016/j.envint.2021.106691 -
International Journal of Environmental... Jul 2022Organophosphate esters (OPEs) are widely used as an additive in flame retardants, plasticizers, lubricants, consumer chemicals, and foaming agents. They can accumulate...
Organophosphate esters (OPEs) are widely used as an additive in flame retardants, plasticizers, lubricants, consumer chemicals, and foaming agents. They can accumulate in aquatic organisms from water (waterborne exposure) and food (dietary exposure). However, the bioaccumulation characteristics and relative importance of different exposure routes to the bioaccumulation of OPEs are relatively poorly understood. In this study, were exposed to fo typical OPEs (tris(2-chloroethyl) phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(2-butoxyethyl) phosphate (TBOEP), and triphenyl phosphate (TPHP)), and their toxicokinetics under waterborne and dietary exposure routes were analyzed. For the waterborne exposure route, the bioconcentration factors (BCFs) increased in the order of TBOEP, TCEP, TDCPP, and TPHP, which were consistent with their uptake rate constants. TPHP might have the most substantial accumulation potential while TBOEP may have the smallest potential. In dietary exposure, the depuration rate constants of four OPEs were different from those in the waterborne experiment, which may indicate other depuration mechanisms in two exposure routes. The biomagnification factors (BMFs) of fur OPEs were all below 1, suggesting trophic dilution in the transfer of four OPEs from to . Except for TBOEP, the contributions of dietary exposure were generally lower than waterborne exposure in under two exposure concentrations. This study provides information on the bioaccumulation and contribution of OPEs in via different exposure routes and highlights the importance of considering different exposure routes in assessing the risk of OPEs.
Topics: Animals; Bioaccumulation; Daphnia; Environmental Monitoring; Esters; Flame Retardants; Organophosphates; Phosphates; Zooplankton
PubMed: 35954739
DOI: 10.3390/ijerph19159382 -
Ecotoxicology and Environmental Safety Sep 2022Organophosphate flame retardants (OPFRs) are increasingly and widely used as substitutes for brominated flame retardants in daily life. The chemical structure of OPFRs... (Review)
Review
Organophosphate flame retardants (OPFRs) are increasingly and widely used as substitutes for brominated flame retardants in daily life. The chemical structure of OPFRs is very similar to that of organophosphorus pesticides, leading to concerns about their neurotoxicity. A few epidemiological studies have been published with inconsistent results on this topic, and a systematic scoping review is needed to provide an overview or map of the current evidence on the relationship of OPFRs with neurodevelopmental toxicity. Therefore, MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) were systematically searched for articles published in the last two decades. Nine eligible articles were included in the present systematic scoping review for adherence to the predefined PECOS (population, exposure, comparison, outcome, study design) statement. Six studies were conducted in the USA, and the remaining three studies were conducted in Austria, Norway and China. A total of 2 581 children (1 203 females and 1 378 males) were included. Half of the included studies focused on the adverse effects of OPFR exposure on cognition in children, while others primarily focused on the behaviors of children. In summary, the current evidence suggests inverse associations between early-life exposure to OPFRs and the childhood intelligence quotient and internalizing behavior and positive relationships of OPFR exposure with externalizing behavior. However, some differences in the timing of sample collection for exposure measurements, in the individual OPFR metabolites available, in the neurodevelopmental scales for outcome measurement, and in the statistical methods used to analyze the data are noted. In addition, further studies are warranted to evaluate some important issues, such as sex differences in the association, exposure-sensitive periods, and cumulative exposure risk assessment.
Topics: Child; Epidemiologic Studies; Female; Flame Retardants; Humans; Male; Organophosphates; Organophosphorus Compounds; Pesticides
PubMed: 35988382
DOI: 10.1016/j.ecoenv.2022.113973 -
Cell Reports Jan 2023Advanced mass spectrometry methods have detected thousands of post-translational phosphorylation and acetylation sites in bacteria, but their functional role and the...
Advanced mass spectrometry methods have detected thousands of post-translational phosphorylation and acetylation sites in bacteria, but their functional role and the enzymes catalyzing these modifications remain largely unknown. In addition to enzymatic acetylation, lysine residues can also be chemically acetylated by the metabolite acetyl phosphate. In Escherichia coli, acetylation at over 3,000 sites has been linked to acetyl phosphate, but the functionality of this widespread non-enzymatic acetylation is even less clear than the enzyme-catalyzed one. Here, we investigate the role of acetyl-phosphate-mediated acetylation in E. coli central metabolism. Out of 19 enzymes investigated, only GapA and GpmA are acetylated at high stoichiometry, which inhibits their activity by interfering with substrate binding, effectively reducing glycolysis when flux to or from acetate is high. Extrapolating our results to the whole proteome, maximally 10% of the reported non-enzymatically acetylated proteins are expected to reach a stoichiometry that could inhibit their activity.
Topics: Escherichia coli; Acetylation; Organophosphates; Protein Processing, Post-Translational; Glycolysis
PubMed: 36640332
DOI: 10.1016/j.celrep.2022.111950 -
Journal of Nanobiotechnology Aug 2023Organophosphate (OP)-induced delayed neurological damage is attributed to permanent neuropathological lesions caused by irreversible OP-neurocyte interactions, without...
BACKGROUND
Organophosphate (OP)-induced delayed neurological damage is attributed to permanent neuropathological lesions caused by irreversible OP-neurocyte interactions, without potent brain-targeted etiological antidotes to date. The development of alternative therapies to achieve intracerebral OP detoxification is urgently needed.
METHODS
We designed a brain-targeted nanoreactor by integrating enzyme immobilization and biomimetic membrane camouflaging protocols with careful characterization, and then examined its blood-brain barrier (BBB) permeability both in vitro and in vivo. Subsequently, the oxidative stress parameters, neuroinflammatory factors, apoptotic proteins and histopathological changes were measured and neurobehavioral tests were performed.
RESULTS
The well-characterized nanoreactors exerted favourable BBB penetration capability both in vitro and in vivo, significantly inhibiting OP-induced intracerebral damage. At the cellular and tissue levels, nanoreactors obviously blocked oxidative stress, cellular apoptosis, inflammatory reactions and brain histopathological damage. Furthermore, nanoreactors radically prevented the occurrence of OP-induced delayed cognitive deficits and psychiatric abnormality.
CONCLUSION
The nanoreactors significantly prevented the development of OP-induced delayed neurological damage, suggesting a potential brain-targeted etiological strategy to attenuate OP-related delayed neurological and neurobehavioral disorders.
Topics: Humans; Organophosphates; Organophosphate Poisoning; Brain; Antidotes; Nanotechnology
PubMed: 37550745
DOI: 10.1186/s12951-023-02039-2 -
Current Opinion in Microbiology Apr 2010Recent reports support the long-standing hypothesis that acetyl phosphate, a physiologically relevant small molecule, can serve as a phosphoryl donor to a subset of... (Review)
Review
Recent reports support the long-standing hypothesis that acetyl phosphate, a physiologically relevant small molecule, can serve as a phosphoryl donor to a subset of two-component response regulators that regulate diverse cellular processes. Since acetyl phosphate is a central metabolite, this ability would link nutritional status to global signaling. This review will first introduce acetyl phosphate and its pathway. It will then summarize the most compelling evidence supporting the hypothesis and list predicted properties of an acetyl phosphate-sensitive pathway. Next, it will describe emerging evidence that acetyl phosphate and/or its pathway can influence diverse cellular processes across a broad spectrum of bacteria. Finally, the review will explore the possibility that other metabolites can function in a capacity similar to acetyl phosphate.
Topics: Bacteria; Bacterial Infections; Bacterial Proteins; Gene Expression Regulation, Bacterial; Humans; Organophosphates; Phosphorylation; Signal Transduction; Virulence
PubMed: 20117041
DOI: 10.1016/j.mib.2010.01.002 -
Environment International Aug 2019Exposure of e-waste workers to eight halogenated and five organophosphate ester flame retardant chemicals (FRs) was studied at a Canadian e-waste dismantling facility....
Exposure of e-waste workers to eight halogenated and five organophosphate ester flame retardant chemicals (FRs) was studied at a Canadian e-waste dismantling facility. FR concentrations were measured in air and dust samples collected at a central location and at four work benches over five-24 hour periods spanning two weeks. The highest concentrations in air from workbenches were of BDE-209 (median 156 ng m), followed by Tris(2-chloroethyl) phosphate (TCEP, median 59 ng m). Dust concentrations at the workbenches were higher than those measured at the central location, consistent with the release of contaminated dust during dismantling. Dust concentrations from the workbenches were also dominated by BDE-209 (median 96,300 ng g), followed by Triphenyl phosphate (TPhP, median 47,000 ng g). Most FRs were in coarse particles 5.6-18 μm diameter and ~30% were in respirable particles (<~3 μm). Exposure estimates indicated that dust ingestion accounted for 63% of total FR exposure; inhalation and dermal absorption contributed 35 and 2%, respectively. Some air and dust concentrations as well as some estimated exposures in this formal facility in a high-income country exceeded those from informal e-waste facilities located in low and middle income countries. Although there is demonstrated toxicity of some FRs, FR exposure in the e-waste industry has received minimal attention and occupational limits do not exist for most FRs.
Topics: Canada; Dust; Electronic Waste; Female; Flame Retardants; Halogenated Diphenyl Ethers; Halogenation; Humans; Male; Occupational Exposure; Organophosphates
PubMed: 31125732
DOI: 10.1016/j.envint.2019.04.056 -
Environmental Health Perspectives Apr 2023Amniogenesis is a key event in biochemical pregnancy, and its failure may result in human embryonic death. However, whether and how environmental chemicals affect...
BACKGROUND
Amniogenesis is a key event in biochemical pregnancy, and its failure may result in human embryonic death. However, whether and how environmental chemicals affect amniogenesis remain largely unknown.
OBJECTIVES
The objective of the present study was to screen chemicals that may disrupt amniogenesis in an amniotic sac embryoid model and to investigate the potential mechanism of amniogenesis failure, with a focus on organophosphate flame retardants (OPFRs).
METHODS
This study developed a high-throughput toxicity screening assay based on transcriptional activity of octamer-binding transcription factor 4 (). For the two positive OPFR hits with the strongest inhibitory activity, we used time-lapse and phase-contrast imaging to assess their effects on amniogenesis. Associated pathways were explored by RNA-sequencing and western blotting, and potential binding target protein was identified through a competitive binding experiment.
RESULTS
Eight positive hits exhibiting expression were identified, with 2-ethylhexyl-diphenyl phosphate (EHDPP) and isodecyl diphenyl phosphate (IDDPP) showing the strongest inhibitory activity. EHDPP and IDDPP were found to disrupt the rosette-like structure of the amniotic sac or inhibit its development. Functional markers of squamous amniotic ectoderm and inner cell mass were also found disrupted in the EHDPP- and IDDPP-exposed embryoids. Mechanistically, embryoids exposed to each chemical exhibited abnormal accumulation of phosphorylated nonmuscle myosin (p-MLC-II) and were able to bind to integrin ().
CONCLUSION
The amniotic sac embryoid models suggested that OPFRs disrupted amniogenesis likely by inhibiting the pathway, thus providing direct evidence associating OPFRs with biochemical miscarriage. https://doi.org/10.1289/EHP11958.
Topics: Pregnancy; Female; Humans; Organophosphates; Flame Retardants; Biphenyl Compounds; Phosphates
PubMed: 37027338
DOI: 10.1289/EHP11958 -
Toxicology Apr 2022Diazinon is an organophosphate pesticide that has a history of wide use. Developmental exposures to organophosphates lead to neurobehavioral changes that emerge early in...
Diazinon is an organophosphate pesticide that has a history of wide use. Developmental exposures to organophosphates lead to neurobehavioral changes that emerge early in life and can persist into adulthood. However, preclinical studies have generally evaluated changes through young adulthood, whereas the persistence or progression of deficits into middle age remain poorly understood. The current study evaluated the effects of maternal diazinon exposure on behavior and neurochemistry in middle age, at 1 year postpartum, comparing the results to our previous studies of outcomes at adolescence and in young adulthood (4 months of age) (Hawkey 2020). Female rats received 0, 0.5 or 1.0 mg/kg/day of diazinon via osmotic minipump throughout gestation and into the postpartum period. The offspring were tested on a battery of locomotor, affective, and cognitive tests at young adulthood and during middle age. Some of the neurobehavioral consequences of developmental DZN seen during adolescence and young adulthood faded with continued aging, whereas other neurobehavioral effects emerged with aging. At middle age, the rats showed few locomotor effects, in contrast to the locomotor hyperactivity that had been observed in adolescence. Notably, though, DZN exposure during development impaired reference memory performance in middle-aged males, an effect that had not been seen in the younger animals. Likewise, middle-aged females exposed to DZN showed deficient attentional accuracy, an effect not seen in young adults. Across adulthood, the continued potential for behavioral defects was associated with altered dopaminergic function, characterized by enhanced dopamine utilization that was regionally-selective (striatum but not frontal/parietal cortex). This study shows that the neurobehavioral impairments from maternal low dose exposure to diazinon not only persist, but may continue to evolve as animals enter middle age.
Topics: Animals; Behavior, Animal; Diazinon; Female; Insecticides; Male; Organophosphates; Organophosphorus Compounds; Rats
PubMed: 35452779
DOI: 10.1016/j.tox.2022.153189 -
Environmental Science and Pollution... Jul 2013Emerging contaminants in wastewater and sewage sludge spread on agricultural soil can be transferred to the human food web directly by uptake into food crops or...
Emerging contaminants in wastewater and sewage sludge spread on agricultural soil can be transferred to the human food web directly by uptake into food crops or indirectly following uptake into forage crops. This study determined uptake and translocation of the organophosphates tris(1-chloro-2-propyl) phosphate (TCPP) (log Kow 2.59), triethyl-chloro-phosphate (TCEP) (log Kow 1.44), tributyl phosphate (TBP) (log Kow 4.0), the insect repellent N,N-diethyl toluamide (DEET) (log Kow 2.18) and the plasticiser N-butyl benzenesulfonamide (NBBS) (log Kow 2.31) in barley, wheat, oilseed rape, meadow fescue and four cultivars of carrot. All species were grown in pots of agricultural soil, freshly amended contaminants in the range of 0.6-1.0 mg/kg dry weight, in the greenhouse. The bioconcentration factors for root (RCF), leaf (LCF) and seed (SCF) were calculated as plant concentration in root, leaf or seed over measured initial soil concentration, both in dry weight. The chlorinated flame retardants (TCEP and TCPP) displayed the highest bioconcentration factors for leaf and seed but did not show the same pattern for all crop species tested. For TCEP, which has been phased out due to toxicity but is still found in sewage sludge and wastewater, LCF was 3.9 in meadow fescue and 42.3 in carrot. For TCPP, which has replaced TCEP in many products and also occurs in higher residual levels in sewage sludge and wastewater, LCF was high for meadow fescue and carrot (25.9 and 17.5, respectively). For the four cultivars of carrot tested, the RCF range for TCPP and TCEP was 10-20 and 1.7-4.6, respectively. TCPP was detected in all three types of seeds tested (SCF, 0.015-0.110). Despite that DEET and NBBS have log Kow in same range as TCPP and TCEP, generally lower bioconcentration factors were measured. Based on the high translocation of TCPP and TCEP to leaves, especially TCPP, into meadow fescue (a forage crop for livestock animals), ongoing risk assessments should be conducted to investigate the potential effects of these compounds in the food web.
Topics: Animal Feed; Crops, Agricultural; DEET; Daucus carota; Environmental Monitoring; Flame Retardants; Food Chain; Food Contamination; Hordeum; Organophosphates; Plant Roots; Plasticizers; Risk Assessment; Seeds; Sewage; Soil; Soil Pollutants; Sulfonamides; Triticum
PubMed: 23250727
DOI: 10.1007/s11356-012-1363-5