毒理學(xué)學(xué)科發(fā)展報告

毒理學(xué)學(xué)科進(jìn)展報告XXXXXX一、引言21世紀(jì)以來，毒理學(xué)續(xù)進(jìn)展、推動社會文明進(jìn)步的重要科技力氣。二、本學(xué)科的進(jìn)展概況“”2050年月起步，90年月中期至今是我國毒理學(xué)的快速進(jìn)展期。隨著我國公共衛(wèi)生體系的構(gòu)目前我國毒理學(xué)學(xué)科體系已差不多形成。放射毒理、軍事毒理、法醫(yī)毒理、藥物毒理、食品毒理、獸醫(yī)藥毒理、藥物依靠毒理、納米與型材料毒理、生物毒素毒理、中毒與救治等。在外源環(huán)境污染物、工業(yè)與農(nóng)業(yè)化學(xué)品、藥品、食品、化裝品、安康相關(guān)產(chǎn)品、型材料如納米材料等的安全性評判和危急度治理諸多方面發(fā)揮了不行替代的作用。特地是近年來，毒理學(xué)學(xué)問和科學(xué)技術(shù)在核、化、生突發(fā)大事的應(yīng)急處置行國際公約、禁毒，在處理日本遺留化學(xué)武器、集體中毒、環(huán)境污染等重大大事中，發(fā)揮了關(guān)鍵性作用。在以后涉及國家安全、經(jīng)濟(jì)進(jìn)展戰(zhàn)略、人類安康事業(yè)和社會和諧穩(wěn)固等特地多重大問題上，毒理學(xué)科技力氣將會發(fā)揮更大的作用。三、近年來本學(xué)科的要緊進(jìn)展和成就〔一〕毒理學(xué)根底爭論進(jìn)展隨著國家對毒理學(xué)領(lǐng)域科研投入的增長，我國毒理學(xué)根底爭論水平不斷提SCI400時學(xué)術(shù)論文質(zhì)量也在不斷提高，國際阻礙力逐步擴(kuò)大。靶器官毒性機(jī)理比較準(zhǔn)確地描述了外源化學(xué)物對整體動物或體外原代培育組織細(xì)胞的靶器官毒數(shù)據(jù)和科學(xué)依據(jù)。環(huán)境內(nèi)分泌干擾物日益增多的爭論資料說明，人類多種生殖系統(tǒng)疾病與外源化學(xué)物〔或藥物〕(EDCs)，特地是一些長久性有機(jī)污染物，可導(dǎo)致性分化特地、生殖道畸形、生精障礙、性功能特地、死〔畸〕胎和自然流預(yù)措施爭論供給了重要理論依據(jù)。生物標(biāo)志物1ppm水平中起到了重要作用。氧化應(yīng)激損害機(jī)制，開展了中藥和自然藥物的抗氧化力的測定和評判。DNA損害修復(fù)DNA了DNA-PK復(fù)合物在DNA損害修復(fù)和細(xì)胞有絲分裂調(diào)劑通路間的“cross-talk”作p53ApakDNA損害反響中的調(diào)控p53Axin的多蛋白復(fù)合體通過其組分的動態(tài)變化操縱p53的活性，從而打算細(xì)胞選擇或凋亡或周期阻滯的命運；在鑒定的DNA修復(fù)反響基因的功能爭論取得突破，如提醒JWA在DNA氧化損害修復(fù)反響中NatureCellBiology、CancerResearch、JBC、NucleicAcidsResearch上發(fā)表。表觀遺傳效應(yīng)進(jìn)展，如在結(jié)晶型NiS、BaP以及電離輻射等因素誘發(fā)細(xì)胞惡性轉(zhuǎn)化模型中，提醒NO在輻射旁效應(yīng)中的分子調(diào)劑作用等。(二)應(yīng)用毒理學(xué)爭論進(jìn)展建設(shè)與應(yīng)用方面，均取得了顯著成效。疼惜環(huán)境安全“致突變、致癌、致畸變”等特地毒性作用與機(jī)制；環(huán)境化學(xué)污染物對人體安康產(chǎn)生危害的規(guī)律及爭論領(lǐng)域涉及大氣環(huán)境毒理學(xué)、土壤環(huán)境毒理學(xué)、水環(huán)境毒理學(xué)等。促進(jìn)職業(yè)安全效應(yīng)標(biāo)志物和易感性標(biāo)志物。保證食品安全90天喂養(yǎng)試驗》等食品安全性毒理學(xué)評判的標(biāo)準(zhǔn)和理爭論和安全性評判技術(shù)整體水平顯著提高，并逐步與國際接軌。保證藥品安全2023年的“魚腥草”大事、“欣弗”2023年的“刺五加”“茵梔黃”2023年的“糖脂寧”大事、“雙黃連”大事和“甲氨蝶呤注射液”污染大事。為此我國加強(qiáng)了藥物安全監(jiān)2023年已有39〔GL認(rèn)證，藥物毒理和安全性評判爭論逐步與國際標(biāo)準(zhǔn)化治理接軌。材料安全21世紀(jì)以來，材料如納米材料不斷涌現(xiàn)，其生物安全性引起人們關(guān)——安全性的爭論在我國起步不久，但在國家科技部“973”工程等的資助下，差不多定了良好的根底。(三)治理毒理學(xué)爭論進(jìn)展理學(xué)。近年來在國內(nèi)制定和公布的很多公共衛(wèi)生與環(huán)境生態(tài)疼惜的政策和法令2080近幾年又加緊起草、公布和實施了一系列毒理學(xué)試驗指導(dǎo)原則和標(biāo)準(zhǔn)程序。試驗動物工作的標(biāo)準(zhǔn)化是保證國內(nèi)GLP試驗室與國際接軌的必要條件。我國化的規(guī)定和要求，有意識地加強(qiáng)了替代、削減和優(yōu)化原則〔3Rs〕的貫徹，重視了動物福利，有效地防止了因試驗動物質(zhì)量而對藥品安全性評判所造成的阻礙。另一方面，國內(nèi)的GLP試驗室也依據(jù)國際慣例，連續(xù)建立本機(jī)構(gòu)的“動物治理與使用委員會〔IACUC〕”，實行動物試驗的倫理審查制度。至20232090行國際通用的良好試驗室標(biāo)準(zhǔn)〔GLP〕。SFDA明確規(guī)定，一類藥及注射劑的非臨床安全性評判爭論，必需由通過《藥物非臨床爭論質(zhì)量治理標(biāo)準(zhǔn)〔GLP〕》認(rèn)證檢查的試驗室完成。國內(nèi)局部GLP中心通過了OECD成員國的GLP檢查。在國家科技部“十一五”GLP體系開頭建立，202310GLP試驗室考核。2023年環(huán)試的技術(shù)水平、今后實現(xiàn)國際上化學(xué)品測試數(shù)據(jù)互認(rèn)奠定了堅實的根底。四、促進(jìn)本學(xué)科進(jìn)展的建議固的重要性將會得到進(jìn)一步的表達(dá)。〔一〕擴(kuò)展毒理學(xué)領(lǐng)域、滿足日益增長的社會需求于預(yù)防醫(yī)學(xué)下設(shè)的“衛(wèi)生毒理學(xué)”學(xué)科，全部的招生、教學(xué)、人才培育和人才評判及工業(yè)、農(nóng)業(yè)、林業(yè)、海洋〔事〕CDC以及相關(guān)科研院所“衛(wèi)生毒理學(xué)”學(xué)科明顯存在局限性，其不能包含環(huán)境毒理學(xué)、生態(tài)毒理學(xué)、藥物毒理學(xué)、獸醫(yī)毒理學(xué)等特地有必要樹立起“大毒理學(xué)”的概念，將目前的衛(wèi)生毒理學(xué)專業(yè)擴(kuò)展為毒理學(xué)專業(yè)，以一級學(xué)科的規(guī)模設(shè)置各分支學(xué)科專業(yè)，賜予毒理學(xué)學(xué)科更大的進(jìn)展空間和領(lǐng)多建立了國家“毒理學(xué)家資格認(rèn)證”樂觀響應(yīng)。國際毒理學(xué)聯(lián)合會〔IUTOX〕也正在樂觀推動該項工作的國際間互學(xué)人才培育和學(xué)科隊伍建設(shè)的重要舉措。〔二〕建立中國國家毒理學(xué)打算、營造毒理學(xué)創(chuàng)環(huán)境劃〔NTP〕和歐洲化學(xué)品治理局〔ECHA〕體會，結(jié)合我國實際，盡快建立有中國特色的毒理學(xué)爭論和安全性評判機(jī)制和和諧機(jī)構(gòu)，即中國國家毒理學(xué)打算〔CNTP〕，由政府有關(guān)部門聯(lián)合推行，發(fā)揮全國性專業(yè)學(xué)術(shù)團(tuán)體如中國毒理學(xué)合作，建立公用信息庫，盡可能做到資源共享，包括技術(shù)與信息的共享?！踩掣谞幷撆c應(yīng)用并重，提升毒理學(xué)科技創(chuàng)力量些重大需求問題，而且又能大大促進(jìn)根底爭論的系統(tǒng)深入?；パa(bǔ)的國家級科研團(tuán)隊，組織實施毒理學(xué)領(lǐng)域重大科研打算的協(xié)同攻關(guān)爭論。治理毒理學(xué)與安康危急度評定爭論工作。當(dāng)效勞于社會經(jīng)濟(jì)建設(shè)和人類安康事業(yè)。ToxicologyToxicologyisthesciencethatstudiestheadverseeffectsofchemical,physical,orbiologicalagentsonlivingorganismsandtheecosystem,includingtheprevention,treatmentofameliorationofsuchadverseeffects.Asanintegrateddiscipline,toxicologyhasthecharacteristicsofmultivariateandintegration,involvesbasicacademicresearch,applicationresearchanddevelopment, andmanagementservice.Enteringthe21stcentury,toxicologyhasalreadybecomeanimportantscientificresourceandtechnicalpowerformaintainingenvironmentfriendlyandecologicalbalance, protecting life safety and health living, maintaining social sustainabledevelopment,andpromotingsocialcivilizationandprogress.OutlineofthedevelopmentoftoxicologyinChinaToxicologyhasalongdevelopmenthistorysameasthedevelopmenthistoryofthetraditionalChinesemedicineinChina.AsearlyastheancientperiodoffirestormmonarchYanEmperor,thereisrecordaboutthatShennongtastedahundredgrasses,met70toxicantsandpoisoningsononeday.Themoderntoxicologysciencestartedfrom1950”sinChina;ithasbeen experiencingarapiddevelopmentstagefromthemid1990”s.Atthepresent,anumberofnewtechnologytheoriesandbranchdisciplineshaveemergedintoxicologyacademicsystem,suchastoxicologicalgenomics,poisoningmetabonomics,poisoninganddynamics,nanotoxicology.Therearethreemainfieldswithintoxicology,i.e.,descriptivetoxicology,mechanistictoxicology,andregulatorytoxicology.Uptonow,therehavedevelopedvariousspecialtysubdisciplinesundertoxicologyinChina,theyareindustrialtoxicology,foodtoxicology,drugaddictiontoxicology,clinicaltoxicology,biochemistryandmolecular toxicology, feed toxicology, genetic toxicology, reproductive toxicology, environmental toxicology, ecotoxicology, biotoxintoxicology, analytical toxicology, veterinary toxicology, military radiotoxicology,regulatorytoxicology,intoxicationandremedy,medicinetoxicology,neurotoxicology,andNanotoxicology.Inrecentyears,thestrengthoftoxicologyscienceandtechnologyhasbeeninrapid growing, the scope of scientific research, teaching and management constantlyexpanding.Alongwiththeincreasingofbudgetinvestedinthefieldoftoxicology,theabilityofinnovationintoxicologyhasboostedinChina.Ontheonehand,toxicologicalbasicresearchlevelisraisingandtheinternationalimpactissteadilyincreasing.Ontheotherhand,theappliedtechnologiesandplatformsoftoxicologyhavebeenrapidlydevelopedfortheanalyticaltestingandriskevaluationofchemicalsincludingenvironmentalpollutants,residuesinallkindsofproducts,andmedicines.Thetoxicologyachievementshaveplayedanirreplaceableroleintheevaluationofsafetyandriskmanagementofexogenousenvironmentalpollutants,industrialchemicals,medicine,food,cosmetics,health-relatedproducts,andnewmaterials,suchasnanomaterials,etc.Especiallyinrecent years,theknowledgeandtechnologiesoftoxicologyhavebeensuccessfullyappliedtotheemergencydisposalandmedicalrescueforthepreventionagainstthepotentialpublicemergenciesofradiological,chemical,biologicalevents,tothesecurityofthe2023OlympicGamesinBeijingandthe2023WorldExpoinShanghai,toperformtheinternationalconventionsfordrugcontrol,andtoprocesstheleftchemicaltoxicagentsbyJapanese,majoreventsofenvironmentalpollution,etc.ThemainprogressandachievementoftoxicologyinChinaTheprogressoftoxicologicalbasicresearchThebasicresearchleveloftoxicologyisconstantlyupgradinginChina.ThequantityandqualityofresearcharticlespublishedininternationaljournalswithgoodreputationbyChinesetoxicologistsincreaseyearafteryear,andnowitreachesnearly400SCIpapersperyear.Forthetargetorganstoxicityandmechanism,inadditiontotheapplicationofthetraditionalexperimentalmodelsandmethodsfortheresearchoftargetorganstoxicitiesinvivoandinvitro,italsoadoptsandestablishesaseriesofadvancedtarget-organtoxicologyresearchmodelsandmethodsinrecentyears.Thetoxiccharacteristics,strength,andreversiblemechanismsoftargetorganstoxicitieshavebeenwidelystudiedandelucidatedintheanimalmodelsorinvitroculturedprimarytissue cells for various exogenous chemicals, including industrial environmentalpollutants,foodcontaminantsandbiologicalproducts,Chineseandwesternmedicines,andnewmaterials.FortheEnvironmental-endocrineDisruptingChemicals(EDCs),theincreasingresearchdataindicatethatvarioushumandiseasesofreproductivesystemarerelatedtotheexposureofexogenouschemicalsordrugs.Withtheresearchstrategiesforthecombinationofinvitrostudyandwholeanimalstudy,laboratorialexperimentalstudyandpopulationcohortstudyinsite,ChineseinvestigatorshavesystematicallystudiedthefeaturesandrelatedmechanismsofreproductivetoxicityofmultipleEDCs.IthasbeenprovedthatanumberofEDCs,especiallysomeofthepersistentorganicpollutants (POPs), led to broad reproductive disorders, including differentiationabnormalities,genitaldeformity,spermdefect,sexualabnormalities,birthdefect,deadfetus,andspontaneousabortion.Thesestudiedhaveprovidedimportantdatafortheriskevaluationandpopulationinterventionresearchofthereproductivetoxicity.Biomarkerisoneoftheimportantfieldsinthetoxicologyresearch.Inrecentyears,Chineseinvestigatorshavefoundmultiplebiomarkers(contactmarkersoreffectivemarkers)relatedtotheexposuresofanumberofchemicalsortoxicants.Forexample,1-itrogen-6-ethylene(deoxidizing)adeninewasrevealedasthecontactbiomarkerforevaluatingtheoccupationalexposurelevelofworkerstovinylchloride.Chinese and American investigators jointly initiated a cooperative project molecularepidemiologystudyonoccupationalbenzeneexposureworkers;theprojectaimstoelucidatethecomplexrelationshipbetweenthebenzeneexposureandtheearlychangesofmetabolicproductsandhematologyindex.TheirdatahaveplayedadirectroleforpromotingtheOccupationalHealth&SafetyAdministration,USAtodecreasethe occupationalbenzeneexposure limitation to1ppmlevel.Chineseinvestigatorsalsofoundthebodycontactmarkersoreffectmarkersfortheinteractionbetweenhumanandchemicals.ThetechnologyofgeneanalysishasalsobeenbroadlyemployedtothesusceptibilitystudiesoftheenvironmentalpollutantsandchemicalsinChina.Oxidativestressdamageisamajormechanismoftheacuteandchronicinjuriesinducedbyawiderangeofchemicals,radiation,andbiologicalfactors.Inrecentyears,Chineseinvestigatorshavemadeagreatprogressinthisfield.Aseriesofadvancedplatformsofoxidativestressandantioxidantresearchhavebeenestablished.Theoxidativestressdamageanditsmechanismshavebeenelucidatedforsomechemicals.Atheoryofantioxidantcompoundchainhasbeenproposed.AntioxidantcompoundsandtheiractivitieshavebeenscreenedandevaluatedusingthetraditionalChinesemedicinesandnaturecompounds.FortheDNAdamagerepair,aseriesofprogresseshavebeenachievedintheareaofDNAdamagerepairandcellularresponses.TheinvolvementandmechanismsofmultipleDNArepairgeneshavebeenelucidatedonthecellularresponsestovariouschemicalsandionizingradiation.IthasbeenrevealedthatDNA-PKcomplexregulatesthemitoticprogressingandspindlestabilityinresponsetoionizingradiation,andplaysa“cross-talk”rolebetweenthepathwaysofDNArepairandmitoticcheckpoint.Apak(ATMandp53-associatedKZNFprotein)hasbeendemonstratedasanegativeregulatorofp53-mediatedapoptosisanditdisplaysthedualroleofATMinp53regulationaftertheinductionofDNAdamage.Axinhasbeenfoundtobeacriticaldeterminantinp53-dependenttumorsuppressioninwhichPirh2andTip60havedifferentrolesintriggeringcell-cyclearrestorapoptosisdependingontheseverityofgenotoxicstress.JWA,anoxidativeDNAdamageresponsivegene,wasshownasanovelregulatorofXRCC1inthebaseexcisionrepairproteincomplextofacilitatetherepairofDNAsingle-strandbreaks.AseriesofpapersbasedonaboveresultshavebeenpublishedinthejournalsofNatureCellBiology,CancerResearch,Oncogene,JBC,andNucleicAcidsResearch.EpigeneticisarapidlygrowingresearchfieldthatfocusesontheheritablealterationsingeneexpressioncausedbymechanismsotherthanchangesinDNAsequence.Recently,theepigeneticeffectinducedbyenvironmentalfactorshasbecomeanexcitingtopicinthetoxicologyfieldinChina.Theassociationofepigenetic changes and the genomic instability during the progressing ofcarcinogenesisinducedbychemicals,suchasthecrystallizationtypeNiSandBaP,andionizingradiationhasbeenbroadlystudied.EpigeneticsilencingofMGMTwasobservedinNiS-treatedcells,andwhichis associatedwithDNAhypermethylation,histonemodifications,andDNMT1upregulation.Nano-particleSiO(2)wasalsodemonstrated to induce a global hypoacetylation implying a global epigeneticresponse,whichincludesconsequentialdecreasedlevelsofDNMT1,DNMT3a,andmethyl-CpGbindingprotein2(MBD2).Thebystandereffectandgenomicinstabilityinducedbyionizingradiationhasalsobeenconsideredasanepigeneticeffect.ThegapjunctionandoxidativestressandROS,forexampleNO,weredemonstratedrespondingtobystandereffect.TheprogressofappliedtoxicologyresearchInrecentyears,Chinesetoxicologistshavemaderemarkableachievementsontheconstructionoftoxicologicalplatformsandtechnologieswhichmeetthesocialneedsforsafetyaspectsofdomesticenvironment,food,pharmaceuticalandoccupationalissues.Intheareaofenvironmentalsafetymaintenance,theachievementsreflectedonthedetectionofenvironmentalpollutants,determinationofthemetabolic,generaltoxicityandmechanisminvitroandanimalexperiments,andriskevaluation.Theachievementsalsoincludetheassessmentmethodsandmeasuresforearlydetectionandearlypreventionofhumantoxicityeffectsforenvironmentalpollutants.Theresearchareasincludetheatmosphericenvironmenttoxicology,soilenvironmenttoxicology,andwatertoxicology,etc.Toxicologyachievementspromoteoccupationalsafety.Themaingoalistounderstandthehealthhazardsofindustrialchemicals,andpreventandcontroltheoccupationaldisease.Inrecentyears,agreatprogresshasbeenmadeontheneurotoxiceffectsandmechanismoflead,organicsolvent,polymercompounds,andsoon,aswellasthecorrespondingbiological markersofexposures.Multipletoxiceffectivemarkersandsusceptibilitymarkershavebeenfoundinthebiomarkerstudiesofoccupationalcontactworkers.Inthefoodsafetyaspects,Chinesegovernmentandadministrativeauthoritieshaverecentlyissuedaseriesofadministrativelawsorregulationstandardsbasedonthefundamentaldataoffoodtoxicologystudies.Forexample,theyinclude“thesafetyevaluationandtoxicologicaltestingrequirementsoffoodcontainersandpackagingmaterials”,“thesafetyevaluationproceduresfornewresourcefood”,and“thesafetydetectionof90daysfedratsforthetransgenicplantsandtheirfoodproducts”.Aseriesoffoodsafetymonitoring,warning,andevaluatingmethodsandplatformshavebeenconstructed,whichhavegreatlyimprovedthetechnologyleveloffoodsafetyevaluationandmonitoring,anditresultsinthatthefieldgraduallyconnectsandmatcheswiththeinternationalpractices.Toxicologyplaysanirreplaceableroleintheguaranteefordrugsafety.Inrecentyears,muchmoreeffortshavebeenmadeonthetoxicologyresearchandsafetysupervisionofwesternmedicinesandtraditionalChinesemedicines.Ithasbeenstrengthened on the administration of animal experiments, construction andmanagementofprofessionaldrugtoxicologyresearchorganization.Manyprogresseshavebeenmadeonthe establishmentandapplicationoftoxicitypathologicaldiagnosistechnologyandothernewtechnologiesandmethodsondrugstoxicologyresearch.Uptotheyearof2023,39GLPcentersfordrugtoxicologyresearchandsafetyevaluationhavebeenauthorizedbySFDA.ThedrugtoxicologyresearchandsafetyevaluationinChinahasbeengraduallyconnectedandmatchedwiththeinternationalstandardizationandmanagementsystem.Thetoxicologyandsafetyevaluationofnewmaterialsandproducts,especiallythenanomaterialsbecomesanewresearchfield,andprogressesrapidlyinChina,whichevenledtotheestablishmentofnanotoxicology,anewspecialtysubdisciplineoftoxicology.ThenanotoxicologyresearchinChinareachesattheinternationaladvancedlevelinmanyaspects.TheprogressofregulatorytoxicologyresearchRegulatorytoxicologyisarapidlygrowinganddevelopingfieldoftoxicologyinChina.Inrecentyears,aseriesofpolicies,law,andregulatoryinregardtothemanagement of domestic public health and the environmental and protectionhavebeenissued,andmostofthesedocumentsarelargelyformulatedonthebasisofthebasicscientificdata,andthetheoriesachievedthroughthesolidtoxicologyresearch.Aseriesoftestsguidingprinciplesandstandardprocedureshavebeenissuedandimplementedforthepurposes oftoxicologyresearchandriskmanagement offood,medicines,andchemicals.Amongthem,theinternationalizationofthestandardizationandmanagementwithrespecttotheexperimentalanimalsistheguaranteeforthedomesticGLPlaboratorytoconnectwiththeinternationalpractice.Allsortsofrelevantregulationsanddocumentshavebeenformulatedandissued,includingtheexperimentalanimalclassification,raisemanagement,andenvironmentalconditionsandfacilitiesforanimalexperiments,etc.Theprinciplesinvolvingreplacement,reduction, and implementation of animal use and animal welfare have beenstrengthened.Accordingtotheinternationalpractices,domesticGLPcentershavealsoestablishedtheirownInstitutionalAnimalCareandUseCommittees(IACUC),andexecuteethicalcensorshipofanimaltesting.Bytheyearof2023,27agencies/centers have pass