有机溶剂的特性.ppt

SolventsandVaporsVolatileOrganicCompounds,,有機溶劑的特性,溶解性脂溶性（可溶解脂肪）愈強，去脂效能愈佳，對皮膚和神經系統的傷害也愈大可燃性可燃性高者作燃料，不可燃者則作滅火劑。揮發性蒸氣壓愈高，揮發性愈強，空氣中有機溶劑的濃度愈大，愈多經由呼吸道吸入人體。化學結構一般而言，結構相似者毒性可能相近，例如鹵化有機溶劑（四氯甲烷，三氯乙烯，四氯乙烯等），對肝皆具毒性。也可能差很多，2,4-diaminotoluenelivertumor/2,6-diaminotoluenenot,Themaindeterminantsofasolvent’sinherenttoxicitythenumberofcarbonatomlipophilicityvolatilitywhetheritissaturatedorhasdoubleortriplebondsbetweenadjacentcarbonatomsitsconfigurationstraightchain,branchchain,orcyclicthepresenceoffunctionalgroupsex.Amides/amines-potentsensitizeraldehyde-irritating,,,RouteofExposure,PrimaryrouteRespiratoryRelatedtovolatilityofsolventLipidsolubilityMACSecondaryrouteSkinIngestionaccident,Sourcesofexposure,Dailyactivity-workplace,gasstation,smoking,household,etc.Solventabuse-produceeuphoria,delusions,sedationandvisualandauditoryhallucinationEnvironmentalcontaminationmajorvolatileorganicsolventsVOCs,,,,OccupationalStandardsTWA,Thetime-weightedaverageisthetime-weightedaverageconcentrationforanormal8-hourworkdayor40-hourworkweek,towhichnearlyallworkersmayberepeatedlyexposed,dayafterday,withoutadverseeffect.Asshowninthefigure,timeweightedaveragespermitexcursionsabovethelimitprovidedthattheyarecompensatedbyequivalentexcursionsbelowthelimitduringtheworkweek,TWA,,ToillustratetheTWAula,assumethatasubstancehasan8-hourtime-weightedaveragePELof100ppm.AssumethatanemployeeissubjecttothefollowingexposureTwohoursexposureat150ppmTwohoursexposureat75ppmFourhoursexposureat50ppm.Substitutingthisinationintheula,wehaveTWA150275250481.25ppm8Since81.25ppmislessthan100ppm,the8-hourtime-weightedaveragelimit,theexposureisacceptable,Short-TermExposureLimitTLV-STEL,themaximumconcentrationtowhichworkerscanbeexposedcontinuouslyforashortperiodoftime15-minutewithoutsufferingfromirritation,chronicorirreversibletissuechange,ornarcosisofsufficientdegreetoincreaseaccidentproneness,impairself-rescue,ormateriallyreduceworkefficiency.,CeilingTLV-C,CeilingTLV-Cistheconcentrationthatshouldnotbeexceededeveninstantaneously.Forsomesubstances,forexampleirritantgases,onlytheTLV-ceilingmayberelevant.,GeneralAcuteToxicEffects,CNSdepressionHighlevelexposure中樞神經麻醉效果，例如乙醚麻醉一般而言，碳鏈愈長，含雙鍵、鹵素基（氯、溴、氟等）的溶劑中樞效果愈強。臨床上，暴露的人會頭暈、頭痛、噁心、嘔吐、嗜睡，平衡失調，像醉酒一般，除了影響健康外，勞工甚易發生工作意外。工作場所中常存在多種溶劑或混合物，彼此加強作用，危害比單一物質更大。-SubanestheticdosebehavioraltoxicityDermalandmucousirritation,Solvent-inducedchronicencephalopathyCSE,Nonspecificsymptomsheadache,fatigue,sleepdisorderswithorwithoutchangesinneuropsychologicaldysfunctionTypeISymptomsonlyType2ASustainedpersonalityormoodchangeType2BImpairmentinintellectualfunctionType3Dementia,刺激性或過敏性皮膚炎,有機溶劑具去脂性，能溶解皮膚表面油脂，引起皮膚炎。暴露濃度愈高，時間愈長，或溶劑封閉在手套內無法揮發，造成的傷害愈大。在工廠內有一個動作十分容易傷害皮膚，即是用溶劑來洗手，去除污垢。殊不知長期下來，油脂儘失，往往引起刺激性或過敏性皮膚炎。皮膚炎的臨床表現分急慢性兩種，急性呈紅，腫，慢性呈乾，裂的濕疹樣變化。,Biomarkersofsolvents,MeasurementsofbloodorurinelevelsofchemicalsfollowingexposurenothighlyspecificCharacterizationandquantitationofuniquemetabolitesinbodyfluidsMeasurementofcovalentbindingofreactivemetabolitestoproteins,lipids,ornucleicacidsChemicallyrelatedandspecificsofchromosomedamage,Metabolism,MetabolicinactivationdetoxificationtolueneMetabolicactivationbioactivationbenzeneP450isozymesexhibitspecies-,substrate-,andregion-selectivity,CYP2E11,2E1activeinbothhepaticandnon-hepatictissuessubstratepreference--mainlyforsimplealiphaticcompounds‘solvents’oxidizessmallstraight-chainorbranched-chaincompoundsnoringsalcoholsmethanol,ethanol,acetoneandketonebodies,short-chainfattyacidschlorinatedsolvents--chloro,trichloroethyleneTCE,carbontetrachloride,etc.oxidizesbenzenesingleunsubstitutedaromaticring,CYP2E12,Bioactivationaliphaticepoxidesandaldehydesarereactivemetabolitesliverdamagebenzeneepoxidemyelotoxicity--bonemarrowcelldamage--leukemiaslightlyinduciblebysmallaliphaticcompounds/alsoprolongsenzymeactivity‘EtOH-inducibleP450’ethanol--2-5xincreaseCYP2E1levels,Metabolites,Generationofbiologicreactiveintermediatesa.Inactivatedbyglutathione,ascorbicacidandothercellularantioxidantsb.covalentbindtocellularmacromolecules→inactivationofreceptorsandspecificproteins,damagetocellmembranes,orinitiationofmutagenicreactionsc.Metabolicsaturation-detoxicationpathway→bioactivationpathwayGenerationofreactiveoxygenspecies-freeradical,ROS,P450inducersandinhibitors,Inducers-ethanol,acetone,ketones,PAH,certaindrugsphenobarbital,phenytoin,diazepam,rifampicin,smokingInhibitors-disulfiram,3-amino-1,2,4-triazole,severalconstituentsoffoodsdiallylsulfide,dihydrocapsaicin,phenylethylisothiocyanateSuicideinhibitors1,2-dichloroethylenevs.CYP2E1,AlkanesandAlkenes,CarbonchainsSimpleStraightorbranchedGenerallyhighlyvolatileandlipophilicExamplesPentane,hexane,octanePaintthinners,enamels,varnishes,AlkanesandAlkenes,SolubilizeoremulsifyfatsRespiratoryEffectsIrritation/swellingofmucousmembranesBronchoconstrictionPulmonaryedemaCNSAnesthesiaandnarcosisSkinIrritationandswelling,HalogenatedHydrocarbons,GeneralStructure–HofhydrocarbonreplacedbyF,Cl,Br,INames–HalogennamedassubstituentgroupF–fluoroCl-chloroBr-bromoI-iodo–ExamplesdichloromethaneCH2Cl21,2-dibromoethaneCH2Br-CH2Br,HalogenatedHydrocarbons,Chloro,dichloromethane,carbontetrachlorideHeptatoxicity-fattyliverandnecrosis↑numbersofhalogens,size,easeofhomolyticcleavage→↑toxicity,Dichloromethanemethylenechloride,SolventforremovingpaintordegreasingRemovalofcaffeinefromcoffeeToxiceffectsCNSdepressionMetabolizedtoCOhypoxia,,Chloro,EarliestanestheticsAcuteeffectsAnesthesia,cardiacarrhythmiasChroniceffectsLiverdamageMetabolismtoreactivemetabolitePhosgeneCentrilobularnecrosis,fattyliverKidneydamage,CarbonTetrachloride,UsesSolvent,cleaningagent,fireextinguisherAntihelminthicforhumansExposureOccupationalFoundingroundwaterandwastesites,CarbonTetrachloride,ToxicityHepatotoxicsreactivemetabolitesCentrilobularnecrosis,fattyliver,2E1,InhibitmicrosomalATPaseactivitywithinminutesSinglecellnecrosis5-6hrMaximalcentrolobularnecrosis24-48h,CYP2E1inhibitorscanpreventCCl4toxicity,TCEhasmultipleeffectsSeveralsofcancer.neurotoxicity,immunotoxicity,developmentaltoxicity,livertoxicity,kidneytoxicity,andendocrineeffects.TCEactsthroughmultiplemetabolitesandmetabolicpathwaysCYP450metabolitesincludeTCA,DCA.GSTmetabolitesincludeDCVC..TCEactsthroughmultiplemodesofaction.,TrichloroethyleneTCE,KidneytumorsDCVCisbioactivatedinproximaltubularcellstoreactivethiolS-1,2-dichlorovinylthiolLivertumorsExpressionofCYP2E1inthehepatocytesTCAandDCALungcancerChloralhydrateaccumulationinClaracells,Tetrachloroethylene,widelyusedfordry-cleaningfabricsandmetaldegreasingoperationsliver,kidney,andcentralnervoussystemCNSfromacuteandchronicinhalationexposuretotetrachloroethyleneprobablycarcinogenictohumans,Alcohols,EthylalcoholSolvent,intoxicatingbeverageOccupationalexposureminorToxiceffectsCNSdepressionDisruptcellmembraneBlockNMDAreceptorsFetalalcoholsyndromeHepatotoxicMetabolismtoacetaldehydeROSMalnutrition,Possiblemechanismsofalcohol,↑membranefluidity→displacementofmembraneenzymeandalterationthefunctionofmembrane,thereticularactivatingsystemismostsensitiveblocktheNMDAreceptorinterferewithATP-gatedionchannel,Methanol,SolventIndustrialexposureToxicityPermanentblindnessDamagesretinaandopticnerveMetabolizedtoicacidAccumulatesintissues,,CO2H2O,,icacid,,,aldehyde,,,Methanol,Tetrahydrofolate,Alcoholdehydrogenase,Aldehydedehydrogenase,,,,Methanolintoxication,Neurologicsymptomsheadachedizzinessamnesiarestlessnessacutemanialethargyconfusioncomaconvulsions,OPHTHALMOLOGICTOXICITY,Target-retina-opticdiskandopticnerveOccurwhenserumpHdropsbelow7.2LowpHintracellularconcentrationofateImprovementofvisionwithcorrectionofacidosis,becauseatemovesoutofthecellateisaninhibitorofcytochromeoxidase,whichcouldinhibitATPationintheopticnerve,Treatment,EthanoltherapyHemodialysiseffectivelyremovesmethanolanditstoxicmetabolites4-methylpyrazole4-MP“Fomepizole”amorepotentinhibitorofalcoholdehyrogenaseFolatetherapySodiumbicarbonate,EthyleneGlycol,UsesHeatexchangers,antifreeze,hydraulicfluid,industrialsolventsExposureVaporormistGroundwaterAccidental,,Treatment–thesameasmethanol,AromaticHydrocarbons,Benzene,tolueneandxyleneMostcommonaromatichydrocarbonsfoundinpetroleumHighvolatilityLowwatersolubilityPrioritypollutants,Benzene,UsesPetroleumindustryStartingmaterialinchemicalsynthesisExposurePrimarilyworkplaceInhalationofbenzenevaporsSkinabsorption,BenzeneToxicity,MechanismChronicConversionofbenzenetoreactivemetaboliteBenzeneoxideQuinones,semiquinonesInitialreactionsLiverFinalreactionsBonemarrowCovalentlybindtoDNA,RNAandproteinsROS,,TolueneandXylene,UsesSynthesisofresins,plastics,gasolineadditivesPaints,thinners,glues,cleaningagentsExposureLowlevelIndustrialworkers,gasstationattendantsToluenemorelipophilicthanbenzene,TolueneandXyleneToxicity,AcuteCentralnervoussystemDepression,narcosisGastrointestinaldisturbancesChronicImpairedcognition,reactiontimesHearingloss,PossiblemechanismofCNSeffectsoftolueneChangemembranefluidityalteringintracellularcommunicationPartitionintohydrophobicregionsofproteinsalteringmembrane–boundenzymeactivityand/orreceptoractivityNeurotransmitterEnhanceGABAAreceptorAttenuateNMDAreceptor,nicotinicreceptorActivatedopaminesystems,,,PolycyclicAromaticHydrocarbonsPAHs,TwoormorefusedaromaticringsLargegroupofchemicalsPrioritypollutantsSourcesIncompletecombustionoforganicmaterialAutomobiles,manufacturing,PAHs,TransportReleasedintoatmosphereMovementDepositionSurfacewaterPlantsSedimentsGroundwater,PAHs,ExposureWidelydistributedinenvironmentSurfacewaterDepositionofairbornePAHsWastewaterdischarge,stormwaterrunoffIndustrialdischargesFoodGrilled/smokedmeatsLeafyvegetablesandgrainsTobaccosmoke,PAHs,ExposureInhalationOralSkinStoredinkidneyandliverLipophilicResistanttodegradationinenvironmentToxicityReactivemetabolitesPotentialcarcinogens,HEALTHEFFECTS,InadditiontoskincancerReportsindicatinghigherincidencesofRespiratorytracttumorsUppergastrointestinaltracttumorsDuetooccupationalexposureofPAHs,