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1.
Sci Rep ; 13(1): 8003, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198424

RESUMO

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.


Assuntos
Histonas , Inseticidas , Criança , Animais , Camundongos , Humanos , Feminino , Masculino , Gravidez , Histonas/genética , Histonas/metabolismo , Organofosfatos/toxicidade , Organofosfatos/metabolismo , Placenta/metabolismo , Inseticidas/metabolismo , Relações Mãe-Filho
2.
Arch Toxicol ; 97(6): 1691-1700, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37145338

RESUMO

Novichoks represent the fourth generation of chemical warfare agents with paralytic and convulsive effects, produced clandestinely during the Cold War by the Soviet Union. This novel class of organophosphate compounds is characterised by severe toxicity, which, for example, we have already experienced three times (Salisbury, Amesbury, and Navalny's case) as a society. Then the public debate about the true nature of Novichoks began, realising the importance of examining the properties, especially the toxicological aspects of these compounds. The updated Chemical Warfare Agents list registers over 10,000 compounds as candidate structures for Novichoks. Consequently, conducting experimental research for each of them would be a huge challenge. Additionally, due to the enormous risk of contact with hazardous Novichoks, in silico assessments were applied to estimate their toxicity safely. In silico toxicology provides a means of identifying hazards of compounds before synthesis, helping to fill gaps and guide risk minimisation strategies. A new approach to toxicology testing first considers the prediction of toxicological parameters, eliminating unnecessary animal studies. This new generation risk assessment (NGRA) can meet the modern requirements of toxicological research. The present study explains, using QSAR models, the acute toxicity of the Novichoks studied (n = 17). The results indicate that the toxicity of Novichoks varies. The deadliest turned out to be A-232, followed by A-230 and A-234. On the other hand, the "Iranian" Novichok and C01-A038 compounds turned out to be the least toxic. Developing reliable in silico methods to predict various parameters is essential to prepare for the upcoming use of Novichoks.


Assuntos
Substâncias para a Guerra Química , Toxicologia , Animais , Substâncias para a Guerra Química/toxicidade , Substâncias para a Guerra Química/química , Organofosfatos , Dose Letal Mediana , Irã (Geográfico) , Toxicologia/métodos
3.
Toxicol In Vitro ; 90: 105607, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37149271

RESUMO

Triphenyl phosphate (TPhP) is one of the most commonly found organophosphorus flame retardants (OPFRs) in the environment and the general population. Continuous daily exposure to TPhP may adversely impact male reproductive health. However, few researches were conducted to investigate the direct effects of TPhP on the progress of sperm growth and development. In this study, mouse spermatocyte GC-2spd (GC-2) cells were selected as an in vitro model, the impact of oxidative stress, mitochondrial impairment, DNA damage, cell apoptosis and the related molecular mechanisms were investigated using high content screening (HCS) system. Our study indicated that cell viability was decreased significantly in a dose-dependent manner after TPhP treatment with the half lethal concentration (LC50) at 105.8, 61.61 and 53.23 µM for 24, 48 and 72 h. A concentration-related apoptosis occurrence was observed in GC-2 cells after TPhP exposure for 48 h. In addition, the elevated intracellular reactive oxygen species (ROS) and the total antioxidant capacity (T-AOC) also observed after exposing to 6, 30 and 60 µM of TPhP. Furthermore, based on the enhancement of pH2AX protein and alteration of nuclear morphology or DNA content, DNA damage might be induced by higher concentration of TPhP treatment. Simultaneously, alteration of mitochondrial structure, enhancement of mitochondrial membrane potential (MMP), reduction of cellular adenosine triphosphate (ATP) content, altered expression of Bcl-2 family proteins, release of cytochrome c and increase of caspase-3 and caspase-9 activity demonstrated that caspase-3 dependent mitochondrial pathway might play a key role in the process of GC-2 cell apoptosis. Taken together, these results showed that TPhP was a mitochondrial toxicant and apoptotic inducer, which might trigger alike responses in human spermatogenic cells. Therefore, the potential reproductive toxicity of TPhP should not be ignored.


Assuntos
Antineoplásicos , Retardadores de Chama , Humanos , Masculino , Animais , Camundongos , Caspase 3/metabolismo , Espermatócitos , Sêmen/metabolismo , Estresse Oxidativo , Organofosfatos/toxicidade , Antineoplásicos/farmacologia , Retardadores de Chama/toxicidade
4.
Mol Biol Rep ; 50(6): 5465-5479, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37155010

RESUMO

Organophosphate pesticides (OPs) are widely used in agriculture, healthcare, and other industries due to their ability to kill pests. However, OPs can also have genotoxic effects on humans who are exposed to them. This review summarizes the research on DNA damage caused by OPs, the mechanisms behind this damage, and the resulting cellular effects. Even at low doses, OPs have been shown to damage DNA and cause cellular dysfunction. Common phenomena seen in cells that are exposed to OPs include the formation of DNA adducts and lesions, single-strand and double-strand DNA breaks, and DNA and protein inter and intra-cross-links. The present review will aid in comprehending the extent of genetic damage and the impact on DNA repair pathways caused by acute or chronic exposure to OPs. Additionally, understanding the mechanisms of the effects of OPs will aid in correlating them with various diseases, including cancer, Alzheimer's, and Parkinson's disease. Overall, knowledge of the potential adverse effects of different OPs will help in monitoring the health complications they may cause.


Assuntos
Inseticidas , Intoxicação por Organofosfatos , Praguicidas , Humanos , Praguicidas/toxicidade , Organofosfatos/toxicidade , Reparo do DNA , Dano ao DNA
5.
Environ Health ; 22(1): 43, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37194087

RESUMO

Thermally degraded engine oil and hydraulic fluid fumes contaminating aircraft cabin air conditioning systems have been well documented since the 1950s. Whilst organophosphates have been the main subject of interest, oil and hydraulic fumes in the air supply also contain ultrafine particles, numerous volatile organic hydrocarbons and thermally degraded products. We review the literature on the effects of fume events on aircrew health. Inhalation of these potentially toxic fumes is increasingly recognised to cause acute and long-term neurological, respiratory, cardiological and other symptoms. Cumulative exposure to regular small doses of toxic fumes is potentially damaging to health and may be exacerbated by a single higher-level exposure. Assessment is complex because of the limitations of considering the toxicity of individual substances in complex heated mixtures.There is a need for a systematic and consistent approach to diagnosis and treatment of persons who have been exposed to toxic fumes in aircraft cabins. The medical protocol presented in this paper has been written by internationally recognised experts and presents a consensus approach to the recognition, investigation and management of persons suffering from the toxic effects of inhaling thermally degraded engine oil and other fluids contaminating the air conditioning systems in aircraft, and includes actions and investigations for in-flight, immediately post-flight and late subsequent follow up.


Assuntos
Poluição do Ar em Ambientes Fechados , Poluição do Ar , Humanos , Aeronaves , Organofosfatos , Literatura de Revisão como Assunto
6.
Ticks Tick Borne Dis ; 14(4): 102190, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37167772

RESUMO

The present study compared the efficacy of different methods to apply an acaricide formulation to control Rhipicephalus (Boophilus) microplus. To compare the methods, an acaricide blend containing three active ingredients (a pyrethroid and two organophosphates) was used. In experiment 1 (farm 1: Goiânia, GO, Brazil), three methods were tested: a backpack sprayer (BS), power sprayer (PS) and spray race (SR). In experiment 2 (farm 2: São José do Rio Pardo, SP, Brazil), two methods were tested: BS and PS. In both experiments, 10 cattle with similar tick burdens were used. On day 0 in both experiments, the animals were treated with the acaricide. On day +1 (only in experiment 1), +3, +7, +14, +21, +28 and +35 (only in experiment 2), tick counts were performed to determine the control efficacy. The time application, pressure (KPa), volume applied (L) and ergonomic aspects of each spraying system were also evaluated. The adult immersion test (AIT) using three different acaricide blends (combinations of pyrethroid + organophosphate) was performed to compare the susceptibility of strains of each farm. In experiment 1, all treatments significantly reduced (p < 0.05) the number of ticks on the animals, and PS resulted in the greatest acaricide efficacy since day +1. In experiment 2, both treatments (PS and BS) reduced (p < 0.05) the tick burden, and as observed in experiment 1, PS resulted in the best reduction. The application times were 4.5, 150 and 330 s, while pressures were 306.8, 4,826.3 and 220.6 KPa for SR, PS and BS, respectively. In the AIT, the efficacy values were between 99.8 and 100% for the tick strain form farm 1 (Goiânia), while for tick strain from farm 2 (São José do Rio Pardo), the efficacy was between 67.2 and 80.9%. We conclude that the sprayer methods chosen influences the efficacy of the acaricide. All sprayer methods were efficient for acaricide application; the best efficacy was obtained using the PS, while the SR resulted in good efficacy and lower application time. The strain from farm 2 was less susceptible to all acaricides tested.


Assuntos
Acaricidas , Doenças dos Bovinos , Piretrinas , Rhipicephalus , Infestações por Carrapato , Animais , Bovinos , Acaricidas/farmacologia , Piretrinas/farmacologia , Organofosfatos , Brasil , Doenças dos Bovinos/prevenção & controle , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária
7.
PLoS One ; 18(4): e0284786, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37083685

RESUMO

Organophosphate intoxication via acetylcholinesterase inhibition executes neurotoxicity via hyper stimulation of acetylcholine receptors. Here, we use the organophosphate paraoxon-ethyl to treat C. elegans and use its impact on pharyngeal pumping as a bio-assay to model poisoning through these neurotoxins. This assay provides a tractable measure of acetylcholine receptor mediated contraction of body wall muscle. Investigation of the time dependence of organophosphate treatment and the genetic determinants of the drug-induced inhibition of pumping highlight mitigating modulation of the effects of paraoxon-ethyl. We identified mutants that reduce acetylcholine receptor function protect against the consequence of intoxication by organophosphates. Data suggests that reorganization of cholinergic signalling is associated with organophosphate poisoning. This reinforces the under investigated potential of using therapeutic approaches which target a modulation of nicotinic acetylcholine receptor function to treat the poisoning effects of this important class of neurotoxins.


Assuntos
Intoxicação por Organofosfatos , Receptores Nicotínicos , Animais , Intoxicação por Organofosfatos/tratamento farmacológico , Paraoxon/uso terapêutico , Paraoxon/toxicidade , Inibidores da Colinesterase/uso terapêutico , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Acetilcolinesterase/metabolismo , Receptores Nicotínicos/genética , Neurotoxinas , Organofosfatos/toxicidade , Organofosfatos/uso terapêutico
8.
ACS Sens ; 8(4): 1510-1517, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37036422

RESUMO

Novichok is a recently identified class of neurotoxic organophosphorus compounds that have subsequently been banned by the Organization for Prohibition of Chemical Weapons (OPCW) as chemical warfare agents. Selective, rapid detection of Novichok remains a challenge. Several colorimetric paper-based detection devices have recently been developed for the rapid and selective detection of sarin, VX, and sulfur mustard. In this article, we present a similar colorimetric device designed specifically for the detection of Novichok, based on hydrazone derivatives from 2,4-dinitrophenylhydrazine (2,4-DNPH) impregnated on a glass fiber substrate. Results show that these compounds rapidly and selectively reveal the presence of Novichok agents to the naked eye. The low cost, ease of use, portability, and high selectivity to Novichok of this device complete the detection range of colorimetric paper-based sensors for chemical warfare agents.


Assuntos
Substâncias para a Guerra Química , Substâncias para a Guerra Química/análise , Hidrazonas/química , Colorimetria/métodos , Organofosfatos
9.
Neurotoxicology ; 96: 184-196, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37120036

RESUMO

In most airplanes, cabin air is extracted from the turbine compressors, so-called bleed air. Bleed air can become contaminated by leakage of engine oil or hydraulic fluid and possible neurotoxic constituents, like triphenyl phosphate (TPhP) and tributyl phosphate (TBP). The aim of this study was to characterize the neurotoxic hazard of TBP and TPhP, and to compare this with the possible hazard of fumes originating from engine oils and hydraulic fluids in vitro. Effects on spontaneous neuronal activity were recorded in rat primary cortical cultures grown on microelectrode arrays following exposure for 0.5 h (acute), and 24 h and 48 h (prolonged) to TBP and TPhP (0.01-100 µM) or fume extracts (1-100 µg/mL) prepared from four selected engine oils and two hydraulic fluids by a laboratory bleed air simulator. TPhP and TBP concentration-dependently reduced neuronal activity with equal potency, particularly during acute exposure (TPhP IC50: 10-12 µM; TBP IC50: 15-18 µM). Engine oil-derived fume extracts persistently reduced neuronal activity. Hydraulic fluid-derived fume extracts showed a stronger inhibition during 0.5 h exposure, but the degree of inhibition attenuates during 48 h. Overall, fume extracts from hydraulic fluids were more potent than those from engine oils, in particular during 0.5 h exposure, although the higher toxicity is unlikely to be due only to higher levels of TBP and TPhP in hydraulic fluids. Our combined data show that bleed air contaminants originating from selected engine oils or hydraulic fluids exhibit neurotoxic hazard in vitro, with fumes derived from the selected hydraulic fluids being most potent.


Assuntos
Aeronaves , Óleos , Animais , Ratos , Organofosfatos
10.
Chemosphere ; 331: 138805, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37121286

RESUMO

In this study, an investigation on the pollution status, distribution, and ecological risk to the aquatic organisms of six organophosphate tri-esters (tri-OPEs) and two organophosphate tri-esters (di-OPEs) in surface water in urban Hanoi, Vietnam were conducted. In 37 surveyed water samples (6 rivers and 17 lakes), all eight targeted OPEs were discovered with a detection frequency (DF) of 41-100% and the concentration varied largely from below the method detection limit (

Assuntos
Retardadores de Chama , Poluentes Químicos da Água , Animais , Rios/química , Água , Lagos , Vietnã , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Retardadores de Chama/análise , Ésteres , Organofosfatos , Medição de Risco , China
11.
Environ Int ; 175: 107936, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37088006

RESUMO

Drinks are an essential part of human diet, which makes them a source of human exposure to plasticizers such as organophosphate esters (OPEs). The current study provides new information about sixteen OPE levels in 75 different samples (tap water, packed water, cola drinks, juice, wine and hot drinks). Tap water mean levels (40.9 ng/L) were statistically higher than packed water mean levels (4.82 ng/L), mainly due to the contribution of tris(2-chloroisopropyl) phosphate (TCIPP) and tris(2-butoxyethyl) phosphate (TBOEP) that may come from PVC water pipes. Over 90% of samples presented at least one OPE, where regular cola drinks had the highest mean concentrations (2876 ng/L). There was a significantly higher presence of OPEs in added sugar beverages than sugar free drinks, especially for 2-ethylhexyl diphenyl phosphate (EHDPP), which might be related not only to packaging materials but to the added sugar content. Estimated daily intakes (EDIs) in normal and high-exposure scenarios were 2.52 ng/kg bw/day and 7.43 ng/kg bw/day, respectively. Human risk associated with beverages ingestion showed regular cola drinks, juice and tap water as the groups with the highest hazard quotients (HQs). Although OPE exposure was below to safety limits, it should be noted that EHDPP values for regular cola group must be cause of concern, and other routes of exposure such as food ingestion or air inhalation should be also considered.


Assuntos
Retardadores de Chama , Humanos , Retardadores de Chama/análise , Ésteres/análise , Organofosfatos/análise , Fosfatos , Bebidas , Monitoramento Ambiental , China
12.
J Hazard Mater ; 452: 131161, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37030217

RESUMO

Organophosphorus flame retardants (OPFRs) have been widely used in industrial and commercial applications. Unfortunately, the chemical constituents of OPFRs, organophosphate esters (OPEs), which have been proven to be carcinogenic and biotoxic, can release into the environment and pose potential risks to human health. This paper reviews the research progress of OPEs in the soil through bibliometric analysis and comprehensively elaborates on their pollution status, potential sources, and environmental behaviors. The OPE pollution is widely distributed in the soil at concentrations ranging from several to tens of thousands of ng/g dw. Some novel OPEs, newly discovered OPEs in the environment in recent years, are also detected. OPE concentrations vary substantially among landuses, and waste processing areas are important point sources of OPE pollution in the soil. Emission source intensity, physicochemical properties of compounds, and soil properties play important roles in the transfer process of OPEs in the soil. Biodegradation, especially microbial degradation, has potential application prospects in the remediation of OPE-contaminated soil. Brevibacillus brevis, Sphingomonas, Sphingopyxis, Rhodococcus, and other microorganisms can degrade some OPEs. This review helps clarify the pollution status of OPEs in the soil and highlights perspectives for future research.


Assuntos
Monitoramento Ambiental , Retardadores de Chama , Humanos , Retardadores de Chama/análise , Compostos Organofosforados , Solo , Organofosfatos/análise , Ésteres/análise , China
13.
Environ Pollut ; 327: 121576, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37028786

RESUMO

ANALYSIS: of air conditioner (AC) filter dust can reveal the level of organophosphate ester (OPE) pollution in indoor environments, but comprehensive research on this topic remains lacking. This study combined non-targeted and targeted analysis to screen and analyze 101 samples of AC filter dust, settled dust, and air obtained in 6 indoor environments. Phosphorus-containing organic compounds account for a large proportion of the organic compounds found in indoor environments, and OPEs might be the main pollutants. Using toxicity data and traditional priority polycyclic aromatic hydrocarbons for toxicity prediction of OPEs, 11 OPEs were prioritized for further quantitative analysis. The concentration of OPEs in AC filter dust was highest, followed in descending order by that in settled dust and that in air. The concentration of OPEs in AC filter dust in the residence was two to seven times greater than that in the other indoor environments. More than 56% of the OPEs in AC filter dust showed significant correlation, while those in settled dust and air were weakly correlated, suggesting that large amounts of OPEs collected over long periods could have a common source. Fugacity results showed that OPEs were transferred easily from dust to air, and that dust was the main source of OPEs. The values of both the carcinogenic risk and the hazard index were lower than the corresponding theoretical risk thresholds, indicating low risk to residents through exposure to OPEs in indoor environments. However, it is necessary to remove AC filter dust in a timely manner to prevent it becoming a pollution sink of OPEs that could be rereleased and endanger human health. This study has important implications for comprehensive understanding of the distribution, toxicity, sources, and risks of OPEs in indoor environments.


Assuntos
Poluição do Ar em Ambientes Fechados , Retardadores de Chama , Humanos , Monitoramento Ambiental , Ésteres/análise , Retardadores de Chama/análise , Organofosfatos/análise , Medição de Risco , Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , China
14.
Environ Sci Technol ; 57(16): 6435-6443, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37040548

RESUMO

Organophosphate esters (OPEs) are an emerging class of chemicals used in a variety of consumer products as flame retardants, plasticizers, and additives. While prior epidemiologic studies suggest that OPEs may impact respiratory health, results remain inconclusive. We examined associations between urinary biomarkers of OPEs and symptoms of respiratory morbidity in a panel study of 147 predominantly Black school-aged children with asthma living in Baltimore City, Maryland. The study consisted of up to four seasonal, week-long, in-home visits where urine samples and self-reported asthma symptoms were collected on days 4 and 7 (nsamples = 438). We quantified concentrations of nine urinary OPE biomarkers: bis(2-chloroethyl) phosphate (BCEtp), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n-butyl phosphate (DBuP), di-benzyl phosphate (DBzP), di-o-cresylphosphate (DOCP), di-p-cresylphosphate (DPCP), di-(2-propylheptyl) phthalate (DPHP), and 2,3,4,5-tetrabromo benzoic acid (TBBA). We estimated prevalence odds ratios (POR) of respiratory morbidity symptoms using logistic regression with generalized estimating equations to account for our repeated measure design. We assessed BDCIPP and DPHP as continuous (log2) concentrations and dichotomized exposure of BCEtP, DBuP, and DPCP (detect vs non-detect) based on their lower detection frequencies. We adjusted models for season, visit day, age, gender, caregiver education, health insurance type, exposure to household smoking, atopy, and PM2.5. Higher DPHP concentrations were significantly associated with odds of daytime symptoms (POR: 1.26; 95% CI: 1.04-1.53; p = 0.02) where daytime symptoms consisted of trouble breathing due to asthma, reporting bother caused by asthma, and/or limitation in activities due to asthma. DBuP detection was associated with use of rescue medication on the day of sample collection (POR: 2.36; 95% CI: 1.05-5.29; p = 0.04). We also observed several consistent, albeit non-significant (p > 0.05), positive associations for BCEtP and DPCP and respiratory morbidity measures. This is the first study to evaluate the relationship between OPE biomarkers and respiratory morbidity symptoms in children with asthma, and findings suggest that further studies are warranted to confirm whether these associations are causal.


Assuntos
Asma , Retardadores de Chama , Humanos , Criança , Organofosfatos , Fosfatos , Biomarcadores , Ésteres/urina
15.
Chemosphere ; 328: 138571, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37019402

RESUMO

Legacy and emerging organic pollutants pose an ever-expanding challenge for the marine environment. This study analysed a dated sediment core from Cienfuegos Bay, Cuba, to assess the occurrence of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), alternative halogenated flame retardants (aHFRs), organophosphate esters (OPEs), and phthalates (PAEs) from 1990 to 2015. The results evidence the continuing presence of historical regulated contaminants (PCBs, OCPs, and PBDEs) in the southern basin of Cienfuegos Bay. PCB contamination declined since 2007, likely in response to the gradual global phasing out of PCB containing materials. There have been relatively consistent low accumulation rates for OCPs and PBDEs at this location (in 2015 approximately 1.9 and 0.26ng/cm2/year, respectively, with 2.8ng/cm2/year for Σ6PCBs), with indications of recent local DDT use in response to public health emergencies. In contrast, sharp increases are observed between 2012 and 2015 for the contaminants of emerging concern (PAEs, OPEs, and aHFRs), and in the case of two PAEs (DEHP and DnBP) the concentrations were above the established environmental effect limits for sediment dwelling organisms. These increasing trends reflect the growing global usage of both alternative flame retardants and plasticizer additives. Local drivers for these trends include nearby industrial sources such as a plastic recycling plant, multiple urban waste outfalls, and a cement factory. The limited capacity for solid waste management may also contribute to the high concentrations of emerging contaminants, especially plastic additives. For the most recent year (2015), the accumulation rates for Σ17aHFRs, Σ19PAEs, and Σ17OPEs into sediment at this location were estimated to be 10, 46 000, and 750ng/cm2/year, respectively. This data provides an initial survey of emerging organic contaminants within this understudied region of the world. The increasing temporal trends observed for aHFRs, OPEs, and PAEs highlights the need for further research concerning the rapid influx of these emerging contaminants.


Assuntos
Retardadores de Chama , Hidrocarbonetos Clorados , Praguicidas , Bifenilos Policlorados , Bifenilos Policlorados/análise , Éteres Difenil Halogenados/análise , Retardadores de Chama/análise , Cuba , Baías , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Organofosfatos/análise , Plásticos , Monitoramento Ambiental
16.
Chemosphere ; 328: 138597, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37028719

RESUMO

The presence and distribution of thirteen organophosphate flame retardants (OPFRs) were investigated in indoor air and dust samples collected in Hanoi, Vietnam. The total OPFRs (Æ©OPFRs) concentrations in indoor air and dust samples were 42.3-358 ng m-3 (median 101 ng m-3) and 1290-17,500 ng g-1 (median 7580 ng g-1), respectively. The profile of OPFRs in both indoor air and dust indicated that tris(1-chloro-2-propyl) phosphate (TCIPP) was the most dominant compound with a median concentration of 75.3 ng m-3 and 3620 ng g-1, contributing 75.2% and 46.1% to Æ©OPFRs concentrations in indoor air and dust, respectively, followed by tris(2-butoxyethyl) phosphate (TBOEP), with a median concentration of 16.3 ng m-3 and 2500 ng g-1, contributing 14.1% and 33.6% to Æ©OPFRs concentrations in indoor air and dust, respectively. The levels of OPFRs in the indoor air samples and corresponding indoor dust samples showed a strong positive correlation. The total estimated daily intakes (EDItotal) of Æ©OPFRs (via air inhalation, dust ingestion, and dermal absorption) for adults and toddlers under the median and high exposure scenarios were 36.7 and 160 ng kg-1 d-1, and 266 and 1270 ng kg-1 d-1, respectively. Among the investigated exposure pathways, dermal absorption was a primary exposure pathway to OPFRs for both toddlers and adults. The hazard quotients (HQ) ranged from 5.31 × 10-8 to 6.47 × 10-2 (<1), and the lifetime cancer risks (LCR) were from 2.05 × 10-11 to 7.37 × 10-8 (<10-6), indicating that human health risks from exposure to OPFRs in indoor environments are not significant.


Assuntos
Poluição do Ar em Ambientes Fechados , Retardadores de Chama , Adulto , Humanos , Organofosfatos/análise , Monitoramento Ambiental , Retardadores de Chama/análise , Poeira/análise , Poluição do Ar em Ambientes Fechados/análise , Vietnã , Exposição Ambiental/análise
17.
Environ Health Perspect ; 131(4): 47007, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37027338

RESUMO

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 (Oct4). 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 Oct4 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 ß1 (ITGß1). CONCLUSION: The amniotic sac embryoid models suggested that OPFRs disrupted amniogenesis likely by inhibiting the ITGß1 pathway, thus providing direct in vitro evidence associating OPFRs with biochemical miscarriage. https://doi.org/10.1289/EHP11958.


Assuntos
Retardadores de Chama , Organofosfatos , Gravidez , Feminino , Humanos , Organofosfatos/toxicidade , Retardadores de Chama/toxicidade , Compostos de Bifenilo , Fosfatos
18.
Environ Health Perspect ; 131(4): 47009, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37042841

RESUMO

BACKGROUND: Organophosphate esters (OPEs) are common endocrine-disrupting chemicals, and OPE exposure may be associated with type 2 diabetes (T2D). However, greater knowledge regarding the biomolecular intermediators underlying the impact of OPEs on T2D in humans are needed to understand biological etiology. OBJECTIVES: We explored the associations between OPE exposure and glycometabolic markers among older Chinese adults 60-69 years of age to elucidate the underlying mechanisms using a multi-omics approach. METHODS: This was a longitudinal panel study comprising 76 healthy participants 60-69 years of age who lived in Jinan city of northern China. The study was conducted once every month for 5 months, from September 2018 to January 2019. We measured a total of 17 OPEs in the blood, 11 OPE metabolites in urine, and 4 glycometabolic markers (fasting plasma glucose, glycated serum protein, fasting insulin, and homeostatic model assessment for insulin resistance). The blood transcriptome and serum/urine metabolome were also evaluated. The associations between individual OPEs and glycometabolic markers were explored. An adverse outcome pathway (AOP) was established to determine the biomolecules mediating the associations. RESULTS: Exposure to five OPEs and OPE metabolites (trimethylolpropane phosphate, triphenyl phosphate, tri-iso-butyl phosphate, dibutyl phosphate, and diphenyl phosphate) was associated with increased levels of glycometabolic markers. The mixture effect analysis further indicated the adverse effect of OPE mixtures. Multi-omics analyses revealed that the endogenous changes in the transcriptional and metabolic levels were associated with OPE exposure. The putative AOPs model suggested that triggers of molecular initiation events (e.g., insulin receptor and glucose transporter type 4) with subsequent key events, including disruptions in signal transduction pathways (e.g., phosphatidylinositol 3-kinase/protein kinase B and insulin secretion signaling) and biological functions (glucose uptake and insulin secretion), may constitute the diabetogenic effects of OPEs. DISCUSSION: OPEs are associated with the elevated risk of T2D among older Chinese adults 60-69 years of age. Implementing OPE exposure reduction strategies may help reduce the T2D burden among these individuals, if the relationship is causal. https://doi.org/10.1289/EHP11896.


Assuntos
Diabetes Mellitus Tipo 2 , Retardadores de Chama , Resistência à Insulina , Idoso , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , População do Leste Asiático , Ésteres , Retardadores de Chama/análise , Organofosfatos/urina , Fosfatos
19.
Ecotoxicol Environ Saf ; 256: 114876, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37027944

RESUMO

Triphenyl phosphate (TPHP) is a widely used organophosphate flame retardant and has biological toxicity. Previous studies showed TPHP can restrain testosterone biosynthesis in Leydig cells, while the underlying mechanisms remain unclear. In this study, C57BL/6J male mice were exposed to 0, 5, 50, and 200 mg/kg B.W. of TPHP for 30 d by oral, as well as TM3 cells were treated with 0, 50, 100, and 200 µM of TPHP for 24 h. Results showed that TPHP induced testes damage, including spermatogenesis disorders and testosterone synthesis inhibition. Meanwhile, TPHP can cause apoptosis in testicular Leydig cells and TM3 cells, as evidenced by the increased apoptosis rate and decreased Bcl-2/Bax ratio. Moreover, TPHP disrupted mitochondrial ultrastructure of testicular Leydig cells and TM3 cells, reduced healthy mitochondria content and depressed mitochondrial membrane potential of TM3 cells, as well as inhibited mitochondrial fusion proteins mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (Opa1) expression, without effect on mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission 1 (Fis1) in testicular tissue and/or TM3 cells. Then, the mitochondrial fusion promoter M1 was used to pre-treat TPHP-exposed TM3 cells to determine the roles of mitochondrial fusion inhibition in TPHP-induced Leydig cells apoptosis. The results showed M1 pretreatment alleviated the above changes and further mitigated TM3 cells apoptosis and testosterone levels decreased, indicating TPHP induced TM3 cells apoptosis by inhibited mitochondrial fusion. Intriguingly, the intervention experiment of N-acetylcysteine (NAC) showed that TPHP-induced mitochondrial fusion inhibition is ROS dependent, because inhibition of ROS overproduction alleviated mitochondrial fusion inhibition, and subsequently relieved TPHP-induced apoptosis in TM3 cells. In summary, above data revealed that apoptosis is a specific mechanism for TPHP-induced male reproductive toxicity, and that ROS-mediated mitochondrial fusion inhibition is responsible for Leydig cells apoptosis caused by TPHP.


Assuntos
Células Intersticiais do Testículo , Dinâmica Mitocondrial , Camundongos , Animais , Masculino , Células Intersticiais do Testículo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Apoptose , Proteínas Mitocondriais/metabolismo , Organofosfatos/metabolismo , Testosterona/metabolismo
20.
Environ Sci Technol ; 57(18): 7109-7128, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37079500

RESUMO

Organophosphate flame retardants (OPFRs) are found in various environmental matrixes and human samples. Exposure to OPFRs during gestation may interfere with pregnancy, for example, inducing maternal oxidative stress and maternal hypertension during pregnancy, interfering maternal and fetal thyroid hormone secretion and fetal neurodevelopment, and causing fetal metabolic abnormalities. However, the consequences of OPFR exposure on pregnant women, impact on mother-to-child transmission of OPFRs, and harmful effects on fetal and pregnancy outcomes have not been evaluated. This review describes the exposure to OPFRs in pregnant women worldwide, based on metabolites of OPFRs (mOPs) in urine for prenatal exposure and OPFRs in breast milk for postnatal exposure. Predictors of maternal exposure to OPFRs and variability of mOPs in urine have been discussed. Mother-to-child transmission pathways of OPFRs have been scrutinized, considering the levels of OPFRs and their metabolites in amniotic fluid, placenta, deciduae, chorionic villi, and cord blood. The results showed that bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP) were the two predominant mOPs in urine, with detection frequencies of >90%. The estimated daily intake (EDIM) indicates low risk when infants are exposed to OPFRs from breast milk. Furthermore, higher exposure levels of OPFRs in pregnant women may increase the risk of adverse pregnancy outcomes and influence the developmental behavior of infants. This review summarizes the knowledge gaps of OPFRs in pregnant women and highlights the crucial steps for assessing health risks in susceptible populations, such as pregnant women and fetuses.


Assuntos
Retardadores de Chama , Organofosfatos , Lactente , Humanos , Feminino , Gravidez , Gestantes , Resultado da Gravidez/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Fosfatos
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