生物钟基因研究进展.ppt

Toxicology Chaper1 1 IntroductiontoToxicology Chapter1 Toxicology Chaper1 2 Thestudyoftheadverseeffectsofchemicalsonlivingorganismsandtheunderlyingmechanisms Toxicology Toxicology Chaper1 3 Likemedicine toxicologyisbothascienceandanart Thescienceoftoxicologyisdefinedastheobservationalanddata gatheringphase whereastheartoftoxicologyconsistsoftheutilizationofthedatatopredictoutcomesofexposureinhumanandanimalpopulation Toxicology Toxicology Chaper1 4 HistoryofToxicology Antiquity Eberspapyrus 1500B C BenChaoGongMu Mingdynasty Middleages Renaissance PoisonsandTheirAntidotes 1198 arsenic containingproductsAgeofenlightenment Parcelsus 1493 1548 Allsubstancesarepoisons thereisnonewhichisnotapoison Therightdosedifferentiatesapoisonfromaremedy Toxicology Chaper1 5 HistoryofToxicology Ageofenlightenment Orfila 1787 1853 thefirsttoxicologisttouseautopsymaterialandchemicalanalysissystematicallyaslegalproofofpoisoning OswaldSchmiedeberg 1838 1921 thefirsttoxicologisttotrain120studentswholaterpopulatedthemostimportantlaboratoriesofpharmacologyandtoxicologythroughouttheworld Toxicology Chaper1 6 HistoryofToxicology Mordentoxicology 1900 Developmentofearlyadvancesinanalyticmethods heavymetalsEarlymechanisticstudies drugs plantsIntroductionofnewtoxicantsandantidotes nitriteandthiosulfateforcyanide DDT 1944 organophophoruscompounds 1952 Developmentofnewbranches Toxicology Chaper1 7 Toxicology Chaper1 8 HistoryofToxicology TheSilentSpring RachelCarson 1962 Theearth svegetationisapartofaweboflifeinwhichthereareintimateandessentialrelationsbetweenplantsandtheearth betweenplantsandotherplants betweenplantsandanimals Sometimeswehavenootherchoicebuttodisturbtheserelationships butweshoulddosothoughtfully withfullawarenessthatwhatwedomayhaveconsequencesremoteintimeandplace Toxicology Chaper1 9 Threeerasofdevelopmentofexperimentaltoxicology Toxicology Chaper1 10 ToxicologyBranch Accordingtoobjectofstudy AnimalToxicologyHumanToxicologyPlantToxicologyInsectToxicologyLivestockToxicology Toxicology Chaper1 11 ToxicologyBranch Accordingtofieldofstudy EnvironmentalToxicologyFoodToxicologyOccupationalToxicologyClinicalToxicologyForensicToxicologyAnalyticToxicology Toxicology Chaper1 12 ToxicologyBranch Accordingtotargetorganofstudy LiverToxicologyKidneyToxicologyNeurotoxicologyImmunotoxicologyProductiveToxicologyHemotoxicolgy Toxicology Chaper1 13 ToxicologyBranch Accordingtomechanismofstudy CellularToxicologyMolecularToxicologyMembraneToxicologyBiochemicalToxicologyGeneticToxicology Toxicology Chaper1 14 ToxicologyBranch Accordingtoareaofstudy DescriptiveToxicologyMechanisticToxicologyRegulatoryToxicology Toxicology Chaper1 16 MainAreasofToxicologyStudy DescriptiveToxicology Totesttoxicityinexperimentalanimalstoprovideimportantcluestoachemical smechanismofaction Toyieldinformationthatcanbeusedtoevaluaterisksposedtohumansandtheenvironment Toxicology Chaper1 17 MainAreasofToxicologyStudy MechanisticToxicology Toidentifyandunderstandthecellular biochemicalandmolecularmechanismsbywhichchemicalsexerttoxiceffectsonlivingorganisms Todesignandproducesaferalternativechemicalsfortherapyofpoisoningandtreatmentofdiseases Toxicology Chaper1 18 MainAreasofToxicologyStudy RegulatoryToxicology Toperformtheriskassessmentofapotentialhazardtothehumanhealthandtheecosystem Toestablishstandardsfortheamountofchemicalspermittedinambientair industrialatmosphere anddrinkingwater Toxicology Chaper1 19 SpectrumofToxicDose Amongchemicalsthereisawidespectrumofdosesneededtoproducedeleteriouseffects seriousinjury ordeath However themeasuresofacutelethalitysuchasLD50maynotaccuratelyreflectthefullspectrumoftoxicityassociatedwithexposure e g carcinogenicorteratogeniceffects Toxicology Chaper1 20 Toxicology Chaper1 21 SpectrumofUndesiredEffects 1 AllergicreactionsChemicalallergyisanimmunologicallymediatedadversereactiontoachemicalandisdose relatedforagivenindividual Theincidenceofallergicasthmahasincreasedsubstantiallyinrecentyears Toxicology Chaper1 22 SpectrumofUndesiredEffects 2 IdiosyncraticreactionsReferringtoageneticallydeterminedabnormalreactivitytoachemical i g extremesensitivetolowdosesorextremeinsensitivetohighdoses Examplesofchemicalidiosyncrasyincludeexposurestosuccinylcholineandmethemoglobin inducingchemicals Toxicology Chaper1 23 SpectrumofUndesiredEffects 3 ImmediateversusdelayedtoxicityMostchemicalsproduceimmediatetoxiceffectsbutnotdelayedeffects Delayedtoxicitycanbeseenincarcinogenicchemicals years andorganophosphoruspesticides weeks suchasTOCPtoinhibittheneuropathytargetesterase NTE Toxicology Chaper1 24 SpectrumofUndesiredEffects 4 ReversibleversusirreversibletoxiceffectsTheabilityofexposedtissuetoregeneratelargelydetermineswheretheeffectsisreversibleorirreversible Carcinogenicandteratogeniceffectsareusuallyconsideredirreversibletoxiceffectsoncetheyoccur Toxicology Chaper1 25 SpectrumofUndesiredEffects 5 LocalversussystemictoxicityLocaleffectsoccuratthesiteoffirstcontactofchemicals e g ingestionofcausticsubstancesorinhalationofirritantmaterials Systemiceffectsrequireabsorptionanddistributionofatoxicantfromitsentrypointtoadistantsitetoproducedamages someoftheaffectedorgansarereferredtoasthetargetorgansofaparticularchemical OverviewofToxicologyStudy Xenobiotic TargetOrganism Community Population Ecosystem Absorption TargetTissue TargetCell Exposure Distribution Metabolism ClassicalToxicology Xenobiotic MembraneTransport OrganismToxicity TissueToxicity RegulatoryToxicology Excretion Epidemiology EnvironmentalToxicology TargetMolecule CellularandMolecularEvents CellularToxicity MolecularandCellularToxicology GeneticSusceptibilityBiomarkersRiskassessment MechanismsandtreatmentoftoxicityRiskcharacterization Biology Response Metabolism InformationResourceofToxicology HazardousChemicals andtheEnvironmentChemicalInformationIdentifychemical itssynonyms andCASfindchemicalstructure chemicalsurrogatebasedonstructuresimilarity Canbesearchedbyusingachemicalname CASNumber molecularformula ormolecularweighttoxnet nlm nih gov ChemID findwhichNationalLibraryofMedicine NLM databasescontaininformationonthechemical 2 ToxicologyInformationhttp toxnet nlm nih gov Summarizetoxicologicalstu