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1.
Sci Total Environ ; 771: 144752, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33540161

RESUMO

Organophosphate esters (OPEs) are common additives in a wide range of commercial and industrial products. Elevated and prolonged exposure to OPEs may induce several adverse effects. This is concerning as they are ubiquitous in air, indoor dust, drinking water, and other environmental matrices. However, information on the presence of OPEs in foodstuffs and consequent health risks remains scant. This review critically evaluates available information on levels and sources of OPEs in food, discusses the relative significance of diet as a pathway of human exposure, identifies knowledge gaps, and suggests directions for future research. For toddlers, dermal uptake from dust ingestion appears the predominant pathway of exposure to chlorinated OPEs, as well as ethylhexyl diphenyl phosphate (EHDPP) and triphenyl phosphate (TPHP). In contrast, diet appears the main pathway of exposure to all eight OPEs considered for adults, and for tri n-butyl phosphate (TnBP), tris 2-ethylhexyl phosphate (TEHP), and tris (2-butoxyethyl) phosphate (TBOEP) for toddlers. While summed exposures via all pathways are within reference dose (RfD) values, they do not include high-end exposure estimates, and for highly-exposed individuals, the margin between exposure and RfD values is smaller. Moreover, our exposure estimates are based on a meta-analysis of multiple exposure assessments conducted over a range of points in space and time. There is an urgent need for assessments of human exposure to OPEs that examine all relevant pathways in a spatially and temporally-consistent fashion. Given food is an important exposure pathway to OPEs, regular monitoring of their presence as well as their metabolites (that may have toxicological significance) in foodstuffs is recommended. While dermal uptake from indoor dust appears an important human exposure pathway, no evaluations exist of exposure via dermal uptake from OPE-containing products such as foam-filled furniture. This review also highlights very few data exist on OPEs in drinking water.


Assuntos
Retardadores de Chama , Adulto , China , Poeira/análise , Ingestão de Alimentos , Exposição Ambiental/análise , Monitoramento Ambiental , Ésteres/análise , Retardadores de Chama/análise , Humanos , Organofosfatos/análise , Organofosfatos/toxicidade
2.
Environ Toxicol Pharmacol ; 83: 103600, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33508468

RESUMO

Tris (2-chloroethyl) phosphate (TCEP) has been received great concerns because of its increasing presence in various environmental compartments and toxicity. In the present study, zebrafish embryos were exposed to environmentally relevant concentrations of TCEP (0.2, 2, 20, 200 µg/L) from 3 to 120 h post-fertilization (hpf). The results showed that TCEP exposure (20, 200 µg/L) led to developmental toxicity including decreased body length and delay of hatching. Treatment with TCEP significantly decreased whole-body thyroxine (T4) levels and mRNA level of thyroglobulin (tg), and enhanced transcriptions of genes sodium/iodide symporter (nis), thyroid hormone receptor α (trα) and ugt1ab involved in thyroid synthesis and metabolism, respectively. Additionally, TCEP altered the transcription of α1-tubulin, gap43 and mbp related to nervous system development, even at relatively low concentrations. Overall, our results revealed that TCEP exposure can lead to developmental toxicity, thyroid endocrine disruption and neurotoxicity on early developmental stages of zebrafish.


Assuntos
Disruptores Endócrinos/toxicidade , Retardadores de Chama/toxicidade , Organofosfatos/toxicidade , Teratogênios/toxicidade , Animais , Embrião não Mamífero , Larva , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
3.
Chemosphere ; 263: 127703, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32854002

RESUMO

Organophosphate ester flame retardants (OPFRs) are used to prevent ignition and spreading of fire. They are present in various human matrices suggesting adult, fetal, and neonate exposure. Endocrine related effects have been observed in vivo, but information at the molecular level is lacking for some OPFRs. Also, a better understanding of potential contribution from chemical substructures is needed. The aim of this study was to screen OPFRs for endocrine disruptive potential in vitro and in silico. We selected eleven substances to represent some OPFRs with 1) little information on endocrine activity and others to represent 2) varied chemical substructures. We used in vitro assays for androgen receptor (AR), aryl hydrocarbon receptor (AhR), and Nrf2 activity, effects on steroidogenesis, and transthyretin (TTR) binding, as well as in silico models covering estrogen, thyroid, and CYP3A4 induction related endpoints. Ten OPFRs affected AR and AhR activity, seven affected TTR binding, and five affected 17ß-estradiol levels. Several substances had IC50-values below 10 µM and exhibited efficacious effects. These included TPHP, CDP, TMPP, TIPPP, and EHDPP for AR antagonism, suggesting that the degree of arylation and the size of the substance can play a role for the activity. Chlorinated OPFRs had low/no effect on TTR binding. No clear trend was observed for AhR and steroidogenesis, but all arylated OPFRs were predicted to have alert for estrogen receptor binding in an in silico model with metabolism simulator included. Collectively, our data suggest that OPFRs have endocrine disruptive potential warranting further studies to enable human risk assessment.


Assuntos
Retardadores de Chama , Adulto , Simulação por Computador , Ésteres , Estrogênios , Retardadores de Chama/toxicidade , Humanos , Recém-Nascido , Organofosfatos/toxicidade
4.
Chemosphere ; 262: 127724, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32805653

RESUMO

Earthworms are common organisms in soil toxicity-testing framework, and endogeic species are currently recommended due to their ecological role in agroecosystem. However, little is known on their pesticide metabolic capacities. We firstly compared the baseline activity of B-esterases and glutathione-S-transferase in Allolobophora chlorotica and Aporrectodea caliginosa. Secondly, vulnerability of these species to pesticide exposure was assessed by in vitro trials using the organophosphate (OP) chlorpyrifos-ethyl-oxon (CPOx) and ethyl-paraoxon (POx), and by short-term (7 days) in vivo metabolic responses in soil contaminated with pesticides. Among B-esterases, acetylcholinesterase (AChE) activity was abundant in the microsomal fraction (80% and 70% of total activity for A. caliginosa and A. chlorotica, respectively). Carboxylesterase (CbE) activities were measured using three substrates to examine species differences in isoenzyme and sensitivity to both in vitro and in vivo exposure. CbEs were mainly found in the cytosolic fraction (80% and 60% for A. caliginosa and A. chlorotica respectively). GST was exclusively found in the soluble fraction for both species. Both OPs inhibited B-esterases in a concentration-dependent manner. In vitro trials revealed a pesticide-specific response, being A. chlorotica AChE more sensitive to CPOx compared to POx. CbE activity was inhibited at the same extent in both species. The 7-d exposure showed A. chlorotica less sensitive to both OPs, which contrasted with outcomes from in vitro experiments. This non-related functional between both approaches for assessing pesticide toxicity suggests that other mechanisms linked with in vivo OP bioactivation and excretion could have a significant role in the OP toxicity in endogeic earthworms.


Assuntos
Inibidores Enzimáticos/toxicidade , Oligoquetos/efeitos dos fármacos , Oligoquetos/enzimologia , Organofosfatos/toxicidade , Praguicidas/toxicidade , Poluentes do Solo/toxicidade , Acetilcolinesterase/metabolismo , Animais , Carboxilesterase/metabolismo , Citosol/enzimologia , Ecotoxicologia/métodos , Esterases/metabolismo , Glutationa Transferase/metabolismo , Oligoquetos/metabolismo , Paraoxon/análogos & derivados , Paraoxon/toxicidade , Solo/química , Especificidade da Espécie , Testes de Toxicidade
5.
Chemosphere ; 263: 127997, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32846289

RESUMO

The environmental safety of flame retardants has attracted growing attention. Alkyl organophosphorus flame retardants (OPFRs) have been prevalently applied, but the potential risk and the structure effects of different alkyl chain lengths OPFRs on aquatic microalgae remain unknown. This study investigated the biological response of five alkyl-OPFRs to Chlorella pyrenoidosa by computational simulation together with biological approaches. The reduced docking energy had a significantly positive correlation (R2 = 0.9) with the cell inhibition alongside the incremental chain length of alkyl-OPFRs. Molecular docking simulations suggested that the toxicity of alkyl-OPFRs would be highly correlated to their molecular structures. Coincidently, the reactive oxygen species, superoxide dismutase and malondialdehyde were triggered by 85%, 92% and 155% (based on the control group), after exposure to the longest chain length tributyl phosphate (TBPC12), respectively. Furthermore, combining the ultrastructure scrutiny with the photosynthesis analysis, TBPC12 was also found to significantly inhibit the chlorophyll biosynthesis (43%) and restrain the photosynthetic efficiency (26%) when compared with the control group. Overall, this is the first study to comprehensively reveal the biological effects of different alkyl-OPFRs on microalgae via the combination of computational simulation and cellular responses, providing a novel insight into targeted predicting the aquatic ecological risks of OPFRs.


Assuntos
Chlorella/efeitos dos fármacos , Retardadores de Chama/toxicidade , Organofosfatos/toxicidade , Produtos Biológicos , Carbono , Retardadores de Chama/análise , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Organofosforados/toxicidade , Espécies Reativas de Oxigênio
6.
Ecotoxicol Environ Saf ; 207: 111263, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916532

RESUMO

Tris(2-chloroethyl) phosphate (TCEP) is an organophosphate flame retardant that used in textiles, industrial materials, and furniture to delay the spread of fire after ignition. TCEP has been detected in the tissues and eggs of fish and birds. However, there are no studies regarding the effects of TCEP on avian embryos. In the present study, we investigated the developmental toxicity of TCEP exposure on chicken embryos in a shell-less incubation system, which enables in situ observation. Chicken embryos were treated with graded doses of TCEP (50, 250, and 500 nmol/g egg) on incubation day 0. The survival rate, morphological biometrics, heart rate, and length and branch number of extraembryonic blood vessels were measured on incubation days 3-9. Survival rates were reduced from incubation day 3 and were significantly decreased until day 9. Body length, head + bill length and eye diameter were significantly reduced by TCEP exposure. Regarding skeletal effects, spine length was decreased in a dose-dependent manner on day 9. Body weight on day 9 significantly reduced in all TCEP treatment groups. These results suggest that TCEP exposure to >50 nmol/g egg retards development in chicken embryos. TCEP exposure to 500 nmol/g egg significantly increased heart weight to body weight ratio in the embryos. More than 250 nmol/g egg of TCEP significantly reduced the heart rate of embryos in the early developmental stage. The formation of extraembryonic blood vessels and the number of erythrocytes were significantly reduced even with 50 nmol/g egg of TCEP. These findings suggest that TCEP exposure specifically affects the cardiovascular system in chicken embryos, which leads to developmental delay. The results of this study also demonstrate that the shell-less incubation system can be used to continuously monitor the effects of chemicals on developing avian embryos.


Assuntos
Retardadores de Chama/toxicidade , Compostos Organofosforados/toxicidade , Animais , Embrião de Galinha , Galinhas , Organofosfatos/toxicidade , Fosfatos
7.
Chemosphere ; 268: 129375, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33360147

RESUMO

Prenatal exposure to organophosphate flame retardants (OPFRs) has been associated with adverse pregnancy outcomes including low birth weight and preterm birth. However, no study has addressed the impacts of OPFRs exposure on spontaneous abortion (SAB) and fetal chromosome abnormalities. We examined whether prenatal exposure to OPFRs was associated with increased risk of SAB and fetal chromosome abnormalities. A total of 272 pregnant women, including 136 SAB cases and 136 healthy controls, were enrolled in this case-control study. Urinary concentrations of 3 OPFRs metabolites (diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCIPP) and bis (1-chloro-2-propyl) phosphate (BCIPP)) were measured using ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). More than 70% of the urine samples detected quantifiable levels of 3 OPFRs metabolites. Concentrations of BCIPP were significantly higher in SAB cases than in healthy controls. Higher urinary BCIPP levels were associated with increased risk of SAB. Per unit increase in ln-transformed BCIPP concentrations was associated with 103% (OR = 2.03, 95% CI, 1.57, 2.63) increase in the odds of SAB. While higher BDCIPP levels were associated with increased risk of fetal chromosome abnormalities and the corresponding OR associated with a unit increase in ln-transformed BDCIPP concentrations were 2.34 (95% CI, 1.14, 4.81). Our results suggested the potential developmental toxicity and teratogenicity of some OPFRs.


Assuntos
Aborto Espontâneo , Retardadores de Chama , Nascimento Prematuro , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia , Estudos de Casos e Controles , Ésteres , Feminino , Retardadores de Chama/toxicidade , Humanos , Recém-Nascido , Organofosfatos/toxicidade , Gravidez , Espectrometria de Massas em Tandem
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(10): 1152-1160, 2020 Oct 06.
Artigo em Chinês | MEDLINE | ID: mdl-33115204

RESUMO

Organophosphate ester (OPEs) has been widely used as a substitute of brominated biphenyl ethers and other brominated flame retardant (BFRs), and their health effects and environmental impacts are widely concerned. This article systematically reviews the common types, metabolites, environmental occurrences, exposure pathways, levels, toxic effects and biomarkers of OPEs, in order to explore the relationships between OPEs exposures and biomarkers, to reveal the potential mechanisms of health effects, and to provide references and scientific basis for the health effects of OPEs exposure in China.


Assuntos
Biomarcadores , Retardadores de Chama , Organofosfatos , China , Monitoramento Ambiental , Ésteres , Retardadores de Chama/toxicidade , Organofosfatos/toxicidade
9.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 250-254, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981281

RESUMO

Objective: To investigate the potential toxic effects and mechanisms of Tris(1; 3-dichloro-2-propyl) phosphate (TDCIPP) on thyroid in female SD rats.Methods: Thirty-two 3-weeks-old female SD rats were randomly divided into normal group(treated with corn oil ), and low/moderate/high-dose group treated with TDCIPP (dissolved in corn oil )(n=8). All rats were treated with corn oil or TDCIPP (50, 100, 250 mg/(kg·d)) once a day during a 21-day period. All rats were sacrificed after the last administration. Serum thyroid stimulating hormone (TSH), 3,3',5-triiodothyronine (T3), 3,3',5,5'-tetraiodothyronine (T4), free 3,3',5,5'-tetraiodothyronine (FT4) were detected with ELISA kit. Morphology of thyroid was observed with hematoxylin and eosin (HE) staining. Expressions of genes and proteins correlate with thyroid were measured respectively by real-time fluorescence quantitative PCR and Western blot. Results: Compared with control group, morphology of thyroid showed follicles irregular arrangement, hypocolloid, and follicular hyperplasia in TDCIPP treatment groups. The levels of serum TSH in low-dose TDCIPP group and T3 in high-dose TDCIPP group were significantly higher than those in control group(P<0.05). Thyroid stimulating hormone receptor (TSHR) mRNA expression was decreased distinctly in low-dose TDCIPP group, while the expression of thyroperoxidase (TPO) mRNA was increased notably in moderate and high-dose TDCIPP groups(P<0.05,P<0.01). Compared with control group, the level of TRß protein was decreased significantly in moderate and high-dose TDCIPP groups, while the expressions of udp-glucuronosyl-transferases (UGTs) and cytochrome-p450-3A1 (CYP3A1) proteins were upregulated notably in TDCIPP treatment groups(P<0.05). Conclusion: Treated with 50 mg/(kg·d) TDCIPP can cause thyroid hyperplasia, change the levels of thyroid hormones, and disturb thyroid function, therefore, it has toxic effects on the thyroid.


Assuntos
Organofosfatos , Glândula Tireoide , Hormônios Tireóideos , Animais , Feminino , Organofosfatos/toxicidade , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Disgenesia da Tireoide/induzido quimicamente , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue
10.
Environ Sci Process Impacts ; 22(9): 1809-1827, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32760963

RESUMO

Regulations and the voluntary activities of manufacturers have led to a market shift in the use of flame retardants (FRs). Accordingly, organophosphate ester flame retardants (OPFRs) have emerged as a replacement for polybrominated diphenyl ethers (PBDEs). One of the widely used OPFRs is tris(2-chloroethyl) phosphate (TCEP), the considerable usage of which has reached 1.0 Mt globally. High concentrations of TCEP in indoor dust (∼2.0 × 105 ng g-1), its detection in nearly all foodstuffs (max. concentration of ∼30-300 ng g-1 or ng L-1), human body burden, and toxicological properties as revealed by meta-analysis make TCEP hard to distinguish from traditional FRs, and this situation requires researchers to rethink whether or not TCEP is an appropriate choice as a new FR. However, there are many unresolved issues, which may impede global health agencies in framing stringent regulations and manufacturers considering the meticulous use of TCEP. Therefore, the aim of the present review is to highlight the factors that influence TCEP emissions from its sources, its bioaccessibility, threat of trophic transfer, and toxicogenomics in order to provide better insight into its emergence as an FR. Finally, remediation strategies for dealing with TCEP emissions, and future research directions are addressed.


Assuntos
Poluentes Atmosféricos/análise , Retardadores de Chama/análise , Organofosfatos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Monitoramento Ambiental , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/análise , Humanos , Organofosfatos/toxicidade , Fosfatos
11.
Ecotoxicol Environ Saf ; 205: 111126, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32823070

RESUMO

Triphenyl phosphate (TPP) has been found in various environmental media and in biota suggesting widespread human exposure. However, there is still insufficient information on the hepatotoxicity mechanisms of health risk exposed to TPP. In this study, TPP could induce human normal liver cell (L02) apoptosis, injury cell ultrastructure and elevate the levels of reactive oxygen species (ROS). The integrated multi-omic (transcriptomic, proteomic, and metabolomic) analysis was used to further investigate the mechanisms. Transcriptomic analysis revealed that TPP exposure markedly affected cell apoptosis, oncogene activation, REDOX homeostasis, DNA damage and repair. Additionally, proteomic analysis found that the related proteins associated with apoptosis, oxidative stress, metabolism and membrane structure were affected. And metabolomic analysis verified that the related metabolic pathways, such as glycolysis, citrate cycle, oxidative phosphorylation, lipid and protein metabolism, were also significantly disrupted. Based on the multi-omic results, a hypothesized network was constructed to discover the key molecular events in response to TPP and illustrate the mechanism of TPP-induced hepatotoxicity in L02 cells. Therefore, molecular responses could be elucidated at multiple biological levels, and multi-omic analysis could provide scientific tools for exploring potential mechanisms of toxicity and chemical risk assessment.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Poluentes Ambientais/toxicidade , Redes e Vias Metabólicas/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Organofosfatos/toxicidade , Transcriptoma/efeitos dos fármacos , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Perfilação da Expressão Gênica , Humanos , Metabolômica , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Espécies Reativas de Oxigênio/metabolismo
12.
Environ Res ; 188: 109859, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32846645

RESUMO

BACKGROUND: Organophosphate pesticides (OP) are widely used for both agricultural and domestic purposes. Epidemiological studies suggest neurotoxicity in children after exposure to organophosphates pesticides (OP) at low levels but possible mechanism is still unclear. OBJECTIVES: We aimed at investigating the effects of prenatal exposure to OPs on inhibitory control of 10-12 year-old-children assessed by a motor inhibition task during functional magnetic resonance imaging (fMRI). METHODS: Ninety-five children from the PELAGIE cohort (Brittany-France, from 2002) underwent a fMRI examination during which inhibition was assessed by a Go/No-Go task. Task performance was assessed by average response latency, commission rate and composite performance score (PS). Whole brain activation was estimated by modeling the hemodynamic response related to inhibition demand and successful inhibition. OP exposure was assessed by measuring six dialkylphosphate (DAP) metabolites in the urine of women in early pregnancy (<19 WG). Concentrations were summed to obtain overall levels of diethylphosphate (DE), dimethylphosphate (DM) and total non-specific metabolites (DAP), standardized to homogenize sampling conditions and categorized into levels of exposure: low (reference), moderate or high. Regression models were adjusted for potential cofounders considered by restriction and statistical criteria. RESULTS: Moderate levels of DAP were associated with a decreased commission rate (ß = -6.65%, p = 0.04), indicating improved performance. Increasing levels of DM and DE were associated with decreased brain activity in the left inferior and bilateral superior frontal regions during successful inhibition. We did not observe any differential activation related to inhibitory demands. DISCUSSION: These results suggest that prenatal OPs may be associated with altered pattern of brain activity in regions related to inhibition among children and need to be confirmed by additional studies.


Assuntos
Inseticidas , Praguicidas , Criança , Exposição Ambiental/análise , Feminino , França/epidemiologia , Humanos , Inseticidas/toxicidade , Imagem por Ressonância Magnética , Organofosfatos/toxicidade , Compostos Organofosforados/toxicidade , Praguicidas/toxicidade , Gravidez
13.
Artigo em Inglês | MEDLINE | ID: mdl-32629972

RESUMO

Approximately 33% of U.S. soldiers from the first Gulf War suffer from a multi-system disorder known as the Gulf War Illness (GWI). GW veterans suffer from a cluster of symptoms that prominently include fatigue and can include mood-related symptoms. Compared to traditional antidepressants, ketamine (KET) produces a fast-onset and long-lasting antidepressant response, but assessments of KET for GWI-related depression are lacking. The etiology of GWI is multi-factorial and exposure to organophosphates (OP) during deployment is one of the factors underlying GWI development. Here, male Sprague-Dawley rats were repeatedly exposed to an OP DFP and three months later these rats, when assessed on a battery of rodent behavioral assays, displayed signs consistent with aspects of GWI characteristics. When treated with a sub-anesthetic dose of KET (3, 5, or 10 mg/kg, i.p.), DFP-treated rats exhibited a significant improvement in immobility time, open-arm exploration, and sucrose consumption as early as 1 h and much of these effects persisted at 24-h post-KET injection. KET's stereoisomers, R-KET and S-KET, also exhibited such effects in DFP rats, with R-KET being the more potent isomer. Our studies provide a starting point for further assessment of KET for GWI depression.


Assuntos
Ketamina , Organofosfatos , Síndrome do Golfo Pérsico , Animais , Modelos Animais de Doenças , Ketamina/toxicidade , Masculino , Organofosfatos/toxicidade , Síndrome do Golfo Pérsico/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Estereoisomerismo
14.
Environ Sci Technol ; 54(14): 8900-8908, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32643373

RESUMO

Scarce attention has been paid to the immunotoxicity of organophosphate flame retardants (PFRs), which poses a challenge to the systematic assessment of their health risks. In this study, a battery of in vitro immunotoxicity screening assays, including adhesion, phagocytosis, and 48 cytokine/chemokine production, was measured after exposing THP-1-derived macrophages to six selected common PFRs (TPHP, TDCPP, TNBP, TOCP, TCEP, and TBOEP) at a noncytotoxic concentration (≤50 µM). Our results showed that TPHP and TBOEP partially attenuated the adhesion and phagocytosis of the THP-1 mφs and that TDCPP caused a functional loss of phagocytosis, implying the potential immunosuppression. In contrast, TNBP and TOCP may cause an immunostimulation by significantly promoting cell adhesion and enhancing phagocytic efficiency. Additionally, the results from a cytokine/chemokine secretion analysis revealed the proinflammatory properties of TDCPP, TPHP, and TBOEP. TOCP was thought to disrupt the inflammatory balance by inhibiting both proinflammatory and antiinflammatory cytokines. TCEP showed no effect on adhesion or phagocytosis and little modulation of cytokine release at this experimental concentration. Overall, this study supports that PFRs can be immunotoxic to macrophages in different ways and provides evidence for developing more sensitive in vitro immunotoxicity bioassay methods.


Assuntos
Retardadores de Chama , Retardadores de Chama/toxicidade , Humanos , Macrófagos , Organofosfatos/toxicidade , Compostos Organofosforados , Fagocitose
15.
Environ Sci Technol ; 54(15): 9519-9528, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32609501

RESUMO

Although the bioaccumulation of organophosphate flame retardants (OPFRs) in aquatic organisms has been investigated, little information is available about their bioaccumulation in mammals following chronic inhalation exposure. To address this knowledge gap, C57BL/6 mice were exposed to 7 PM2.5-associated OPFRs via the trachea to study their bioaccumulation, tissue distribution, and urinary metabolites. Low (corresponding to the real PM2.5 concentrations occurring during winter in Guangzhou), medium, and high dosages were examined. After 72 days' exposure, ∑OPFR concentrations in tissues from mice in the medium dosage group decreased in the order of intestine > heart > stomach > testis > kidney > spleen > brain > liver > lung > muscle. Of the OPFRs detected in all three exposure groups, chlorinated alkyl OPFRs were most heavily accumulated in mice. We found a significant positive correlation between the bioaccumulation ratio and octanol-air partition coefficient (KOA) in mice tissues for low log KOW OPFR congeners (log KOW ≤ 4, p < 0.05). Three urinary metabolites (di-p-cresyl phosphate: DCrP, diphenyl phosphate: DPhP, dibutyl phosphate: DnBP) were detected from the high dosage group. These results provide important insights into the bioaccumulation potential of OPFRs in mammals and emphasize the health risk of chlorinated alkyl OPFRs.


Assuntos
Retardadores de Chama , Animais , Biomarcadores , Exposição Ambiental , Retardadores de Chama/análise , Retardadores de Chama/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Organofosfatos/análise , Organofosfatos/toxicidade , Material Particulado
16.
Artigo em Inglês | MEDLINE | ID: mdl-32668751

RESUMO

BACKGROUND: Organophosphate pesticides (OPs) are one of the most commonly used classes of insecticides in the U.S., and metabolites of OPs have been detected in the urine of >75% of the U.S. POPULATION: While studies have shown that OP exposure is associated with risk of neurological diseases and some cancers, the relationship between OP exposure and breast cancer risk is not well understood. METHODS: The aim of this rapid review was to systematically evaluate published literature on the relationship between OP exposure and breast cancer risk, including both epidemiologic and laboratory studies. Twenty-seven full-text articles were reviewed by searching on Pubmed, EMBASE, and Cochrane databases. RESULTS: Some human studies showed that malathion, terbufos, and chlorpyrifos were positively associated with human breast cancer risk, and some laboratory studies demonstrated that malathion and chlorpyrifos have estrogenic potential and other cancer-promoting properties. However, the human studies were limited in number, mostly included agricultural settings in several geographical areas in the U.S., and did not address cumulative exposure. CONCLUSIONS: Given the mixed results found in both human and laboratory studies, more research is needed to further examine the relationship between OP exposure and breast cancer risk, especially in humans in non-agricultural settings.


Assuntos
Neoplasias da Mama , Inseticidas , Praguicidas , Animais , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Feminino , Humanos , Inseticidas/toxicidade , Organofosfatos/toxicidade , Compostos Organofosforados , Praguicidas/toxicidade , Estudos Prospectivos
17.
Environ Toxicol ; 35(12): 1326-1333, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32662595

RESUMO

Organophosphate flame retardants (OPFRs) have become a growing concern due to their potential environmental and health risk. However, limited studies have described the toxicity, particularly neurotoxicity of alkyl and aromatic OPFRs. This study investigated the neurotoxicity of alkyl tri-n-butyl phosphate (TnBP) and aromatic tricresyl phosphate (TCP) to rat adrenal pheochromocytoma (PC12) cells for 24 h. Viability detection showed dose-response toxicity effect of TCP and TnBP to PC12 cells. The half-maximal inhibitory concentration of 24 h (24 h-IC50 ) of TCP and TnBP were 2415.61 and 338.09 µM, respectively. Both TnBP and TCP significantly changed the acetylcholinesterase (AChE) activity, and TnBP is more likely to cause neurotoxicity to PC12 cells compared to TCP. Also, The results of LDH and caspase-3 activity detection as well as Hoechst staining suggested that cell apoptosis induced by TCP and TnBP may be the primary pathway. These findings provide a toxicity data of aromatic and alkyl-substituted OPFRs to PC12 cells, and a new insight into the toxicity of OPFRs on health risk assessment.


Assuntos
Apoptose/efeitos dos fármacos , Retardadores de Chama/toxicidade , Neurônios/efeitos dos fármacos , Organofosfatos/toxicidade , Tritolil Fosfatos/toxicidade , Acetilcolinesterase/metabolismo , Animais , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neurônios/enzimologia , Neurônios/patologia , Células PC12 , Ratos
18.
Chemosphere ; 260: 127631, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32688321

RESUMO

Restrictions on the production and use of some highly toxic and persistent flame retardants has resulted in the increased use of alternative phosphate flame retardants that are less-well characterized. The brominated organophosphate ester flame retardant, tris(tribromoneopentyl) phosphate (CAS 19186-97-1, molecular formula C15H24Br9O4P, molecular weight 1018.47 g/mol, acronym TTBrNP) is a compound with potential to bioaccumulate and disrupt endocrine functions. To determine the toxicity of TTBrNP, two Canadian native amphibian species, Lithobates sylvaticus and L. pipiens, were acutely (embryos and Gosner stage 25 (GS25) tadpoles) or sub-chronically (GS25-41 tadpoles) exposed to the following nominal concentrations of TTBrNP: 0 (water and solvent controls), 30.6, 61.3, 122.5 and 245.0 µg/L. Note, measured concentrations declined with time (i.e., 118%-30% of nominal). There was high survival for both species after acute and sub-chronic exposures, where 75%-100% survived the exposures, respectively. There were no differences in the occurrence of abnormalities or hatchling size between controls and TTBrNP treatments for either species exposed acutely as embryos or tadpoles. Furthermore, after 30 d of sub-chronic exposure of L. pipiens tadpoles to TTBrNP there were no effects on size, developmental stage, liver somatic index or sex ratio. Bioconcentration factors were low at 26 ± 3.1 L/kg ww in tadpoles from all treatments, suggesting biotransformation or limited bioavailability via aquatic exposures. Thus, using two species of anurans at different early larval stages, we found TTBrNP up to 245 µg/L to have no overt detrimental effects on survival or morphological responses that would suggest fitness-relevant consequences.


Assuntos
Retardadores de Chama/toxicidade , Organofosfatos/toxicidade , Animais , Bioacumulação , Canadá , Halogenação , Larva , Ranidae/fisiologia
19.
Epilepsia ; 61(6): e54-e59, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32359085

RESUMO

Organophosphate (OP) compounds constitute a class of highly toxic molecules, characterized by irreversible cholinesterase (ChE) inhibition. Being either pesticides or chemical warfare agents, they present a major health issue in some countries, as well as a terrorist or military threat. Prompted by the need for suitable animal models to test novel medical countermeasures, we developed a new convulsive mouse model of OP poisoning using diisopropylfluorophosphate (DFP). Using electrocorticography (ECoG), we analyzed seizure and status epilepticus (SE) occurrences, as well as relative power of ECoG frequency band modifications after DFP injection in male Swiss mice. Next, we investigated DFP effect on ChE inhibition. Histological changes on neuronal activity and neuronal damage were examined by c-Fos immunolabeling and Fluoro-Jade C staining. We showed that mice exposed to DFP presented electrocorticographic seizures that rapidly progressed to SE within 20 minutes. Lasting >8 hours, DFP-induced SE was associated with major power spectrum modifications in seizing DFP animals compared to control animals. Seizures and SE development were concomitant with profound ChE inhibition and induced massive neuronal degeneration. Presenting all hallmarks of convulsive OP poisoning, we showed that our mouse model is valuable for studying pathophysiological mechanisms and preclinical testing of newly available therapeutic molecules.


Assuntos
Lesões Encefálicas/induzido quimicamente , Modelos Animais de Doenças , Isoflurofato/toxicidade , Organofosfatos/toxicidade , Convulsões/induzido quimicamente , Estado Epiléptico/induzido quimicamente , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Lesões Encefálicas/fisiopatologia , Inibidores da Colinesterase/toxicidade , Eletrocorticografia/efeitos dos fármacos , Eletrocorticografia/métodos , Masculino , Camundongos , Convulsões/fisiopatologia , Estado Epiléptico/fisiopatologia
20.
Chemosphere ; 256: 127066, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32434091

RESUMO

Tri(1,3-dichloropropyl) phosphate (TDCPP) potentially damages the thyroid system in humans and animals. However, knowledge of its toxic effects and underlying mechanisms is limited. The present study was conducted to determine the thyroid hormone-disrupting effects of TDCPP and its major metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP) in rat pituitary cell lines (GH3). TDCPP and BDCPP, that mimic the thyroid hormone (TH), promoted GH3 cell proliferation and modulated the progression of the cell cycle at 20 and 200 µmol/L, respectively. Similar to T3, TDCPP and BDCPP also significantly upregulated c-fos and downregulated Tshß gene expression. Although the binding affinity of these chemicals for thyroid receptor ß (TRß) was not measured, significant competition between these chemicals to bind to the membrane thyroid hormone receptor (integrin αvß3) was found, suggesting that TDCPP and BDCPP were strongly bound to integrin αvß3. Results from a molecular docking analysis provided further evidence of strong binding affinities of TDCPP and BDCPP for integrin αvß3, and the ligand binding site of Arg-Gly-Asp (RGD) was identified. Real-time PCR also supported the supposition that, after binding to integrin αvß3, TDCPP and BDCPP may induce the activation of the extracellular signal-regulated protein kinase (ERK1/2) signal transduction pathway. Taken together, our data suggest that TDCPP and BDCPP have the ability to mimic THs and that the underlying mechanism might be associated with their interactions with integrin αvß3 and the activation of the ERK1/2 pathway, providing new insight into the mechanism of TDCPP- and BDCPP-induced cytotoxicity.


Assuntos
Organofosfatos/toxicidade , Hormônios Tireóideos/metabolismo , Testes de Toxicidade , Animais , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Integrina alfaVbeta3/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno , Simulação de Acoplamento Molecular , Oligopeptídeos , Organofosfatos/metabolismo , Compostos Organofosforados , Ratos , Transdução de Sinais , Glândula Tireoide/efeitos dos fármacos
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