CHEMICAL INCORPORATING PESTICIDES 2．SYNTHESIS OF NEW SUCCINIMIDO ORGANOPHOSPHATES AS POTENTIAL PESTICIDES

A series of succinimido-organophosphate analogueswas synthesized with maleic anhydride as starting material viamaleimide and its analogues as intermediates and characterized by IR,1HNMR and elementary analysis.

Pollutants, Snails, Oxidative-Stress, Organophosphates, Metals

Aquatic reservoirs remain the ultimate sink of chemical pollutants emanating from anthropogenic activities such as agriculture, mining and industry. Freshwater biota undoubtedly is at risk from the adverse effects of these water pollutants and there is therefore, a need to monitor effects of these chemical pollutants in order to safeguard the health of aquatic biota. We investigated the oxidative stress effects of chlorpyrifos and lead on the freshwater snail Helisoma duryi to assess the potential of using this enzyme system as a biondicator of exposure to environmental pollutants. Groups of snails were exposed to 5 ppb lead acetate and 25 ppb chlorpyrifos for 7 days after which half of the snails were sacrificed and the other half were allowed to recover in clean water and sacrificed after another 7 days. Post mitochondrial fractions were used to measure the activities of the following antioxidant enzymes: superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and diphosphotriphosphodiaphorase. Both pollutants enhanced the activities of all the antioxidant enzymes suggesting a defensive mechanism by the snail to combat the oxidative stress due to the organophosphate chlopryrifos and metal pollutant lead. There was a significant recovery of the antioxidant defense system of the snails allowed to recover in clean water shown by the reduced alteration of the antioxidant enzyme activities of the snails allowed to recover for 7 days. This suggests the need to minimize exposure of aquatic biota to chemical pollutants and remediate the polluted water reservoirs in order to safeguard the health of aquatic life.

Metal organophosphates:electronic structure tuning from inert materials to universal alkali-metal-ion battery cathodes

Organic cathodes for alkali-metal-ion batteries attract great attentions in recent years,but the ion storage sites are limited to some finite functional groups.This is because an organic cathode must have proper lowest unoccupied molecular orbitals(LUMO) to accept electrons at high potential.Herein,a novel type of organophosphate-based cathode has successfully been explored by tuning the LUMO energy level of organophosphates through metal ions with an inert electron pair.For the first time,the P=O of phytate(PA),N,N,N’,N’-ethylenediaminetetrakis(methylene phytate)(EDTMP),and diethylenetriaminepentakis(methyl phytate)(DTPMP) is activated by lead/bismuth(with 6s2electron pair) to storage Li/Na/K ions reversibly.Typically,density functional theory calculations indicate that the LUMO energy of Bi-PA is greatly reduced from-0.99(PA) to-4.61 eV,which shows the first discharge capacity of 173,182 and 206mAh·g-1and the reversibly capacity of 102,102 and 101mAh·g-1with the discharge platform of 2.4,2.1 and 2.4 V for Li/Na/K-ion battery cathodes,respectively.Similarly,with proper LUMO energy level,Pb-PA(-4.63 eV),Pb-EDTMP(-3.71 eV),and Pb-DTPMP(-4.45 eV) all exhibit admirable performance.This unique strategy of organic materials to alkali-metal-ion battery cathodes offers a new avenue for future energy storage systems.

Cerium dioxide as a new reactive sorbent for fast degradation of parathion methyl and some other organophosphates

Cerium dioxide was used for the first time as reactive sorbent for the degradation of the organophosphate pesticides para-thion methyl, chlorpyrifos, dichlofenthion, fenchlorphos, and prothiofos, as well as of some chemical warfare agents-nerve gases soman and O-ethyl S-[2-（diisopropylamino） ethyl] methylphosphonothioate （VX）. CeO2 specimens were prepared by calcination of basic cerous carbonate obtained by precipitation from an aqueous solution. The CeO2 samples containing certain amounts （1 wt.%-5 wt.%） of the neighboring lanthanides （La, Pr, Nd） were prepared in a similar way from pure lanthanide salts. It was shown that ceria accelerated markedly the decomposition of parathion methyl causing the cleavage of the P-O-aryl bond in the pesticide molecule. A similar reaction mechanism was proposed for the degradation of other organophosphate pesticides and nerve agents. The degradation times （reaction half-times） were in an order of minutes in the presence of CeO2, compared to hours or days under common environ-mental conditions. The reaction in suitable organic solvents allowed conversions of about 90%for parathion methyl loading of 20 mg pesticide/g CeO2 within 2 h with a reactant half-life in the order of 0.1 min. The key parameter governing the degradation efficiency of CeO2 was the temperature during calcination. At optimum calcination temperature （about 773.15 K）, the produced ceria retained a sufficiently high surface area, and attained an optimum degree of crystallinity （related to a number of crystal defects, and thus poten-tial reactive sites）. The presence of other lanthanides somewhat decreased the reaction rate, but this effect was not detrimental and permitted the possible use of chemically impure ceria as a reactive sorbent. A fast organophosphate degradation was demonstrated not only in non-polar solvents （such as heptane）, but also in polar aprotic solvents （acetonitrile, acetone） that are miscible with water. This opens new possibilities for designing more versatile decontamination strategies. The cleavage of phosphate ester bonds is of a great importance not only for the degradation of dangerous chemicals （chemical weapons, pesticides）, but also for interactions of ceria （es-pecially the nano-sized one） in biologically relevant systems.

Effect of pesticides on phosphorylation of tau protein,and its influence on Alzheimer’s disease

Alzheimer’s disease(AD)is a progressive and neurodegenerative illness which results in alterations in cognitive development.It is characterized by loss/dysfunction of cholinergic neurons,and formation of amyloid plaques,and formation of neurofibrillary tangles,among other changes,due to hyperphosphorylation of tau-protein.Exposure to pesticides in humans occurs frequently due to contact with contaminated food,water,or particles.Organochlorines,organophosphates,carbamates,pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment.The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein,and its cognitive implications in the development of AD.It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198,Ser199,Ser202,Thr205,Ser396 and Ser404.Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta,and protein phosphatase-2A.Moreover,it altered the expression of the microtubule associated protein tau gene,and changed levels of intracellular calcium.These changes affected tau protein phosphorylation and neuroinflammation,and also increased oxidative stress.In addition,the exposed subjects had poor level of performance in tests that involved evaluation of novelty,as test on verbal,non-verbal,spatial memory,attention,and problem-solving skills.

Chemical exposures and suspected impacton Gulf War Veterans

Gulf War Illness(GWI) encompass a spectrum of maladies specific to troops deployed during the Persian Gulf War(1990–1991). There are several hypothesized factors believed to contribute to GWI, including(but not limited to)exposures to chemical agents and a foreign environment(e.g., dust, pollens, insects, and microbes). Moreover, the inherent stress associated with deployment and combat has been associated with GWI. While the etiology of GWI remains uncertain, several studies have provided strong evidence that chemical exposures, especially neurotoxicants,may be underlying factors for the development of GWI. This mini style perspective article will focus on some of the major evidence linking chemical exposures to GWI development and persistence decades after exposure.

Pollution characteristics and risk assessment of organophosphate esters in aquaculture farms and natural water bodies adjacent to the Huanghe River delta

To date,little attention has been paid to the effects of organophosphate esters(OPEs)pollution on aquacultural environment and aquatic product safety.Huanghe(Yellow)River delta area is one of the largest aquaculture centers in China,where ecological security protection is crucial in the national strategy of China.To explore the pollution characteristics,bioaccumulation,and health risks of OPEs in aquaculture farms in the Huanghe River delta and natural water bodies in the adjacent seas,five species of organisms from different farm types nearby the Huanghe River delta,and the corresponding culture water and sediments were sampled in this study.The total concentrations of Σ_(13)OPEs in water,sediments,and organisms were 51.53-272.18 ng/L,52.63-63.17 ng/g dry weight(dw),and 46.82-108.90 ng/g dw,respectively.Among the five types of culture ponds,the water samples from the swimming crab and hairy crab culture ponds exhibited higher OPEs,the concentration of OPEs in the sediments from the few ponds was relatively balanced,and the OPEs in the organism from the holothurian ponds was higher.Tris(1,3-dichloro-2-isopropyl pho sphate)(TDCP)was the main contaminant in water samples and tripropyl phosphate(TPrP)in sediments and organisms.However,trisphenyl phosphate(TPhP)showed the strongest bioaccumulation ability,followed by 2-ethylhexyl diphenyl phosphate(EHDPP)and TPrP.The bioaccumulation capacities of the five species were as follows:prawn>holothurian>hairy crab>swimming crab>carp.These five types of organisms,as main seafood in human consumption,were at low risk of negative impacts of pollution.However,the risk from the mixture of organophosphate flame retardants(OPFRs)still requires more attention due to the increasing consumption and production in the world.

Biochemical indicators and the Peradeniya Organophosphate Poisoning scale in prediction and prognosis of organophosphorus poisoning:An observational prospective study

Objective:To study the value of some biochemical indicators and Peradeniya Organophosphate Poisoning scale in prediction and prognosis of organophosphorus poisoning.Methods:This was a hospital-based prospective,observational study.Various biochemical tests viz.complete blood count,random blood sugar,liver and renal function tests,creatine phosphokinase,and electrolytes were performed.Patients were assessed based on the Peradeniya Organophosphate Poisoning scale.All the patients were followed till the end point like recovery/death.Results:Out of the 100 patients,72%were males and 28%were females.The majority of the patients were farmers and 21 to 30 years of age.Suicidal was the most common manner(92,92%).Based on the Peradeniya Organophosphate Poisoning scale,47%were mild,34%moderate,and 19%severe.Serum creatinine,creatine phosphokinase,serum glutamic-oxaloacetic transaminase,serum glutamic pyruvic transaminase,and alkaline phosphatase levels showed a significant correlation with severity.Conclusions:Some biochemical indicators such as creatine phosphokinase,alkaline phosphatase can be used as prognostic markers of organophosphorus poisoning.The Peradeniya Organophosphate Poisoning scale can be used for assessing severity of the poisoning.

Genomic Instability Is a Mechanism for Diminished Male Fertility Following Chronic Dichlorvos Exposure

Background and Objectives: Chronic low-dose exposure to dichlorvos occurs in communities in Africa where the substance is used indiscriminately for a variety of purposes. This experiment used an animal model to evaluate genomic instability induced by this pattern of chronic exposure and its relationship with some measures of fertility in males. Methods: Seventy-five male Rattus norvegicus rats obtained for this experiment, were randomly allotted into five groups. Dichlorvos was given by oral gavage at doses of 0.28 mg/kg, 0.56 mg/kg and, 1.68 mg/kg, respectively, to three of the groups, on alternate days for 50 weeks. The remaining two groups received plain drinking water and cyclophosphamide as negative and positive controls, respectively. Samples were collected at 17, 34, and 50 weeks. Sperm count, sperm morphology and serum levels of follicle-stimulating hormone, luteinizing hormone, dihydrotestosterone, oestrogen and progesterone were determined. Furthermore, the frequency of micronucleated polychromatic erythrocytes was determined in bone marrow cells obtained from the femur. Results: The mean ranks of micronuclei frequency had an increasing trend. The frequency of micronucleated polychromatic erythrocytes (MnPCE) had a significant negative correlation with oestrogen (rs = -0.47, p = 0.00, n = 50), follicle-stimulating hormone (rs = -0.41, p = 0.00, n = 50) and progesterone (rs = -0.37, p = 0.01, n = 50) serum levels. A positive monotonic relationship also existed between micronuclei frequency and those of tubular necrosis, tubular vacuolation, and residual bodies. A positive significant moderate correlation was found between MnPCE and the proportion of immotile sperms (rs = 0.41, p = 0.00, n = 50). Conclusion: The nature of the correlations between micronuclei frequency and the proportion of immotile sperms, adverse histological changes and serum hormone levels found in this study suggest genomic instability as the possible mechanism for diminished fertility in males chronically exposed to dichlorvos.

混配农药中毒防治研究

首次在我国开展大规模的混配农药中毒流行病学调查,发现接触混配农药是当前发生农药中毒的重要危险因素,为针对性的预防提供了科学依据。毒理学研究证实多数农药混剂呈增毒效应或协同作用,且与其毒代动力学变化有密切关系,为今后开发高效、低毒的混配农药提供了毒理学依据。在国内外首次建立甲基对硫磷单克隆抗体酶联免疫测定法,并成功研制便携式血胆碱酯酶快速测定仪;这些检测接触、效应生物标志物的灵敏、特异、便捷的方法已试用于现场,并具有开发为产品的前景。同时还发现对氧磷酶基因在192位点的单核苷酸多态性,可能是甲基对硫磷免疫毒性作用的易感性生物标志物之一。在总结不同类别农药混配后所致中毒的临床表现特点和规律的基础上,修订现行的农药中毒诊断标准,增添了有机磷单剂及混剂中毒所致“中间期肌无力综合征”的新内容,将提高我国农药中毒的诊治水平。本研究主要成果达国内领先和国际先进水平。

自动固相微萃取(SPM E)GC-MS、GC-MS-MS法检测环境水中有机磷杀虫剂的研究

固相微萃取(solid-phase microextraction,SPME)是20世纪90年代发展起来的一种样品前处理技术,与传统的液-液提取、液-固提取相比,SPME更适用于提取、浓缩液态或气态的挥发性和半挥发性物质,SPME技术可将采样、萃取、浓缩和样本引入集中于一个步骤完成,尤其随着自动SPME与GC-MS等联用技术的日益完善,使SPME技术优点得到更充分的发挥.……

Screening of Total Organophosphate Pesticides in Agricultural Products with a Cellular Biosensor

Organophosphates belong to the most important pesticides used in agricultural practice worldwide. Although their analytical determinations are quite feasible with various conventional methods, there is a lack of efficient screening methods, which will facilitate the rapid, high-throughput detection of organophosphates in different food commodities. This study presents the construction of a rapid and sensitive cellular biosensor test based on the measurement of changes of the cell membrane potential of immobilized cells, according to the working principle of the Bioelectric Recognition Assay (BERA). Two different cell types were used, derived either by animal (neuroblastoma) or plant cells (tobacco protoplasts). The sensor was applied for the detection of a mixture of two organophosphate pesticides, diazinon and chlorpyrifos in two different substrates (tomato, orange). The pesticides in the samples inhibited the activity of cell membrane-bound acetylcholinesterase (AChE), thus causing a measurable membrane depolarization in the presence of achetylcholine (Ach). Based on the observed patterns of response, we demonstrate that the sensor can be used for the qualitative and, in some concentrations, quantitative detection of organophosphates in different substrates with satisfactory reproducibility and sensitivity, with a limit of detection at least equal to the official Limit of Detection (LOQ). The assay is rapid with a total duration of 3 min at a competitive cost. The sensitivity of the biosensor can be further increased either by incorporating more AChE-bearing cells per test reaction unit or by using cells engineered with more potent AChE isoforms. Standardization of cultured cell parameters, such as age of the cells and subculture history prior to cell immobilization, combined with use of planar electrodes, can further increase the reproducibility of the novel test.

Relationship between PON-1 enzymatic activity and risk factors for pesticide poisoning in farmers from the Cienega,Jalisco,Mexico

Paraoxonase-1(PON-1)is an enzyme that hydrolyzes organophosphate pesticides.The presence of polymorphisms in PON-1(L55M and Q192R)decreases its enzyme activity and increases the risk of central nervous system(CNS)toxicity in occupationally exposed farmers,leading to chronic degenerative diseases and death.We studied 103 farmers in the region of Cienega Jalisco,Mexico,which were exposed mainly to organophosphate pesticides.We used serum and plasma samples to assay PON-1 activity and perform polymorphism analysis(L55M and Q192R)using qPCR and TaqMan probes,respectively.For both polymorphisms,there was high percentage of heterozygosity(55 LL=0.19,LM=0.75,MM=0.06;192 QQ=0.12,QR=0.72,RR=0.16),while the allelic frequencies were more balanced(L=0.56,M=0.44;Q=0.48,R=0.52).There were no significant differences in enzyme activity of L55M polymorphism genotypes(LL=179.27;LM=192.11;MM=122.11;QQ=135.74;QR=187.90;RR=209;p>0.05).But there was a slight decrease in enzyme activity for the Q192R polymorphism genotypes.The genotype and alcohol consumption associated with slight increases in enzyme activity.However,genotype and tobacco consumption did not have a significant effect on PON-1 activity(μU/mL)(p>0.05).Overall,alcohol and tobacco consumption affected PON-1 enzyme activity(μU/mL)up to 21.1%.The data obtained in this study reveal that PON-1 activity is affected by genetic variants such as Q192R and alcohol consumption.This may influence the susceptibility of populations to organophosphate poisoning.

Examination of Urinary Chlorpyrifos Biomarker Concentrations and Heart Rate in a Sample of US Children and Adolescents

Objective: The purpose of the investigation is to determine if a relationship exists between heart rate and urinary biomarkers of chronic, subacute chlorpyrifos pesticide exposure in youth. Methods: Using 2001-2002 NHANES data, a sample of 1233 children ages 6 - 18 was grouped based on detection status of 3,5,6-trichloropyridinol (TCPy) in urine. Radial pulse and brachial pulse were recorded as measures of heart rate by physicians. T-tests and linear regression analyses were performed to test for associations between TCPy concentrations and heart rate. Results: None of the associations between TCPy levels and heart rate outcomes were found to be significant. Nonsignificant effects in the TCPy-detected groups included a slightly reduced heart rate in girls, as well as a slightly elevated heart rate in boys when compared to the undetected controls. Neither was there any significant observable difference in heart rate due to detection status in the sample overall. Conclusions: At this time, an effect on heart rate attributable to chronic, low-level chlorpyrifos exposure in youth cannot be determined. Children and adolescents detected did not demonstrate a substantial change in pulse measures when compared to controls. It is recommended that subsequent studies examine chlorpyrifos biomarkers as they may relate to other indicators of cardiovascular health.

Isolation and molecular characterization of a novel <i>pseudomonas putida</i>strain capable of degrading organophosphate and aromatic compounds

A bacterial strain designated in this study as POXN01 was found to be capable of degrading the synthetic organophosphorus pesticides paraoxon and methyl parathion. The strain was initially isolated through enrichment technique from rice field soil near Harlingen, Texas. Phylogenetic analysis based on 16S rRNA, gyrB and rpoD gene alignments identified the POXN01 isolate as a new strain of Pseudomonas putida, which is closely related to the recently discovered nicotine-degrading strain Pseudomonas putida S16. While being unable to metabolize nicotine, the POXN01 isolate was observed to actively proliferate using monocyclic aromatic hydrocarbons, in particular toluene, as nutrients. Search for the genetic determinants of paraoxon catabolism revealed the presence of organophosphorus-degrading gene, opd, identical to the one from Sphingobium fuliginis (former Flavobacterium sp. ATCC 27551). Assimilation of aromatic compounds likely relies on phc ARKLMNOPQ gene cluster for phenol, benzene and toluene catabolism, and on benRABCDKGEF cluster for benzoate catabolism. The observed versatility of POXN01 strain in degradation of xenobiotics makes it useful for the multi-purpose bioremediation of contaminated sites in both agricultural and industrial environmental settings.

Pesticide Biomonitoring in Florida Agricultural Workers

This descriptive study evaluates the blood serum levels of relevant pesticides in fern/ornamental and tomato agricultural workers in central and south Florida whose work activity is related to pesticide application or crop maintenance. The objectives of this study are to broadly evaluate pesticide absorption in agricultural workers, assess personal protective equipment (PPE) use and their potential relevance to pesticide absorption, and to evaluate the feasibility of using primary biomonitoring as a method of exposure assessment for long-term epidemiological investigations. Three rounds of sampling were conducted where 41 subjects provided serum samples analyzed for individual pesticides and responded to a survey regarding PPE use. Serum samples yielded quantifiable detections of DDE, Methiocarb, Malathion, Chlorpyrifos, and Endosulfan in select subjects. The personal protective equipment survey did not demonstrate association with positive serum samples. These results demonstrate that the evaluated workers are effectively protected against exposures known to result in acute toxicity. Biomonitoring for parent compounds and primary metabolites may have limited utility in long-term epidemiological studies to evaluate chronic toxicity where workers are exposed to a great diversity of workplace chemicals (fern/or- namental workers) compared to agricultural sectors where workplace chemical diversity is more limited (tomato workers).

Metal Nano Layer Coating for Improving the Detection and Recognition of Micro-Poisons Using Reflection Spectroscopic Measurement

Metal nano layer coating for increasing the sensitivity of spectroscopic measurements is proposed and experimentally demonstrated in this paper. The metal nano layer will attract the micro-poisons from any measured aqueous sample increasing the concentration of the micro-poison in the vicinity of the surface and significantly improves the sensitivity of the spectroscopic measurement. The demonstration was carried out using Fourier Transform Infra-Red (FTIR) operating in the MIR 400 cm-1 - 4000 cm-1 and 5 nm Gold layer which was grown on silicon oxide substrate. In the experimental demonstration Malathion organophosphate pesticide was used as micro-poison. The spectroscopic measurement proves that Malathion was attracted to the metal nano layer. Furthermore, the absorption lines of Malathion were detected and recognized. This proof of principle can be applied to any Internal Reflection Elements (IRE) and it can be used to purify any aqueous solutions and atmosphere from micro-poisons which will be attracted to the metal Nano layer.

Studies on the Purification and Characterization of Soybean Esterase,and Its Sensitivity to Organophosphate and Carbamate Pesticides

Soybean esterase, a cholinesterase-like enzyme, was purified by differential centrifugation firstly, then, ammonium sulfate precipitation, dialysis, and finally, DEAE-cellulose-32 ion-exchange chromatography after extracting it from soybean seeds with phosphate buffer （0.3 mol L^-1, pH 7.0）. The extract recovery rate of the purified enzyme was 8.18% and purification fold was 91.58. The soybean esterase appeared as two bands on the denaturing SDS-PAGE with molecular weights of 24 and 37.2 kDa, respectively, which proved that it is a dimer protein consisting of two subunits. The result of nondenaturing PAGE revealed that the soybean esterase is a single band with cholinesterase-like activity using α- naphthyl acetate as the substrate and fast blue B salt as coloring agent. The esterase showed very high sensitivity to 18 kinds of organophosphate pesticides and 6 kinds of carbamate pesticides with the lowest detective limits of 0.03125- 0.0625 and 0.03125-0.25 mg kg^-1, respectively, and can meet the demands of MRL specified by the most countries.

Clinical correlates of hypotension in patients with acute organophosphorus poisoning

BACKGROUND:The aim of the present study is to describe the clinical correlates of hypotension and its associated outcomes in patients with acute organophosphorus poisoning(AOPP).METHODS:In this retrospective cohort study,we analyzed data pertaining to 871 patients with AOPP who were treated at two hospitals.Data from hypotensive and non-hypotensive patients were compared to identify clinical correlates of hypotension.We also evaluated the association between clinical parameters(including hypotension)and in-hospital mortality.RESULTS:The incidence of hypotension in AOPP patients was 16.4%.Hypotensive patients showed signifi cantly higher in-hospital mortality(1.1%vs.39.9%,P<0.001).Advanced age(odds ratio[OR]1.25,95%confi dence interval[CI]1.08–1.44),history of diabetes(OR 2.65,95%CI 1.14–5.96),and increased white blood cell count(OR 1.06,95%CI 1.03–1.09),plasma cholinesterase(OR 0.91,95%CI 0.84–0.94),plasma albumin(OR 0.88,95%CI 0.85–0.92),serum amylase(OR 1.01,95%CI 1.01–1.02),and blood pH(OR 0.64,95%CI 0.54–0.75)were signifi cantly associated with hypotension.After adjusting for potential confounders,hypotension was associated with increased in-hospital mortality(hazard ratio 8.77–37.06,depending on the controlled variables).CONCLUSIONS:Hypotension is a common complication of AOPP and is associated with increased in-hospital mortality.Advanced age,history of diabetes,and changes in laboratory parameters were associated with hypotension in AOPP patients.

Effects of long-term exposure to TDCPP in zebrafish( Danio rerio )–Alternations of hormone balance and gene transcriptions along hypothalamus-pituitary axes

Background : TDCPP is one of the major chemical of organophosphate flame retardants(OPFRs) that has been detected ubiquitously in both the environment and biota. Previously we observed that it influenced the concentrations of sex and thyroid hormones in a sex-dependent pattern, leading to reproductive impairments after short-term exposure in zebrafish. Here we investigate the consequences of longerterm exposure to TDCPP on the hypothalamic-pituitary-gonad(HPG), hypothalamicpituitary-i nterrenal(HPI), and hypothalamic-pituitary-thyroid(HPT) axes of zebrafish( Danio rerio).Methods : A 120-day exposure test to 0.005, 0.05 and 0.5 mg/L TDCPP was initiated with fertilized eggs. Sex steroid hormones in the treated fishes were measured and transcriptional changes were analyzed.Results : In female fish, exposure to TDCPP resulted in increases in plasma cortisol,follicle stimulating hormone(FSH), luteinizing hormone(LH), 17β-estradiol(E2), cortisol, thyroxine(T4), and triiodothyronine(T3). Transcription of most target genes along HPG, HPI and HPT axes were increased by the exposure. While in male fish the exposure led to decreases in cortisol, FSH, LH, T4, T3, testosterone(T), and 11-ketotestosterone(11-KT). Transcription of genes along HPG, HPI and HPT axes,especially steroidogenic genes, were inhibited in male zebrafish. While, E2/T or E2/11-KT ratio was increased in both female and females. The sex-dependent changes in hormones might be due to differential responses to TDCPP induced stresses. An increase in cortisol level coincided with increases in E2 and THs in female fish, while in males decreases in cortisol as well as T, 11-KT and THs were observed. Long-term exposure to TDCPP at very low(μg/L) concentrations could disrupt hormone balances in a sex dependent way.Conclusion : This study revealed that TDCPP could affect endocrine axes – HPG, HPI and HPT – in zebrafish, and impair zebrafish development.