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INTRODUCTION TO TOXICOLOGY   TOXICOLO  TOXICOLOGY GY - poison, poison, adverse adverse efect, treatment treatment o disorder that they produce - adverse efect or unwanted efect o any agent on a io!ogica! system  TOXICOLO  TOXICOLOGI"T GI"T - trained trained to e#amine e#amine the nature nature o those efects and ssess the proai!ity o the occurrence I$ %I"TO&Y "mith 'apyrus - ()**+C use o charms against snae poison - Ebers Papyrus Papyrus - o!dest writing to nown poison .hem!oc, aconite, opium, etc/ - Book of Jobs - poison arrows 0ithridates I1, 2ing o 'ontus - (st deve!oped an antidote - too 3) ingredients as protection against assassination - survived every poisoning attempt %ippocrates - descrie e!ementa! concepts o ioavai!ai!ity and overdose 4ioscorides - gree pharmacist - 5rst attempt to c!assiy poisons - De Materia Medica - 6 vo!umes, )** p!ants, (*** medications 5rst systemic pharmacopeia "u!!a - issued Lex Cornelia .!aw Cornelia .!aw against poison/ "ocrates - poison victim e#ecuted y hem!oc  - coniine .active princip!e/ 0aimonides - treat posion rom snae, insects, dogs ioav o mi!, utter .de!ay asorp/ - Treatise on Poisons & Their antidotes Catherine de 0edici - tested to#ic concoction, onset, potency, speci5ity 'hi!ippus 7ureo!ous +omastus Theophrastus von %ohenheim 'arace!sus - De istoria Planataru! - poisonus p!ants - 7!! sustances now to man are poison there is none which is not a poison and on!y the dose determines its efect 'arace!sus - revo!utionary views on to#ico!ogy - "n Miner#s $ickness% 0athieu 8oseph +onaventure Or5!a - 9ather o modern to#ico!ogy - autopsy materia! and chemica! ana!ysis as proo o poisoning .9orensic to#ico!ogy/ 0agendie - 0O7 o emetine and strychnine C!aude +ernard - Experi!ental !edicine Oswa!d "chmiedeerg - trained (:* students ;!!enog - to#icity o %g and ' +ernardino &ama<0edian efective dose? B Therap Therapeut eutic ic Inde Inde# # - measur measure e saety saety ratio ratio o L46* to ;46* :$ C!inica! C!inica!EE 0edica! 0edica! To#ico! o#ico!ogy ogy - diagnosis and treatment o poisoning cases - with emphasis on medica! scinces, inc!uding signs and symptoms .to#idrome/ CLASS TOXIDROME 7nti 7ntich ch!o !oin iner ergi gic c 4ry, 4ry, hype hypert rthe herrmia, mia, mydriasis de!irium, Fushed sin 40++;L""E"L4G; - 4iarrhea, urination micturition radycardia ronchoconstriction emesis mydriasis tachycardia hypertension hyperthermia seiCorpus de!ecti? or ody o evidence - cause in@ury, disease, death 'oisoning - accidenta! e#posure  To#in  To#in - produce produced d y natura! sustance Xenoiotics - oreign sustance not ound in the ody Into#ication - to#icity associated with chemica! sustance Overdosage - intentiona! e#posure with intent o causing se! in@ury • • • • • • $ EXAMPLE 7tropine Organophosphat es, caramates 7mphetamine cocaine 0orphine %eroin ;nviron ;nvironment menta! a! To#i To#ico!o co!ogy gy - de!eteriou de!eterious s efect and impact o chemica!s .air,soi!,water/ .air,soi!,water/ present as po!!utants o environment to ring organism - ;#oto#ico!ogy - impact o to#ic in ecosystem 4eve!op 4eve!opmenta menta!! to#ico! to#ico!ogy ogy - adver adverse se efct efct due to to e#posure to chemica!s sustance .prenata!/ - Terato!ogy - study o deects conception to irth 6$ &egu!a &egu!atory tory to#ico! to#ico!ogy ogy - esta!i esta!ishme shment nt o standards or chemica!s )$ 4escript 4escriptive ive to#ico to#ico!ogy !ogy - conce concerne rned d with samp!ing samp!ing and to#icity testing which provide inormation or saety eva!uation and regu!atory reAuirements J$ 9oren 9orensic sic To# To#ico! ico!ogy ogy - medica! medica! and !ega! !ega! aspects aspects or poisoning or haru! efects o chemica!s to human K$ 0echanst 0echanstic! ic! to#i to#ico!o co!ogy gy - mechan mechanism ism y y which which chemica!s e#ert their to#ic efect on organism - To#icogenomics - app!ication o genomic, trascriptomic, $ Occupationa! To#ico!ogy - dea!s with chemica! ound in worp!ace - industria! andagricu!tura! worers usua!!y afected - industria! settingH ma@or route o poisoning .inha!ation/ • • 3$ • • • • $ • I1$ 'OI"O=I=G ;99;CT ($ Loca! ;fect - the impression made y the poison to the ody part it made contact - efect is continued to the area o administration ;#amp!eH Corrosive .7cids/ - %:"O on cornea Coagu!ative ."o!idi5cation   =ecrosis Caustic .7!a!i/ - %:"O on cornea LiAueactive .'eroration/ =ecrosis :$ → &emote efects - the efect is produced in an area other than the site o app!ication ;#amp!eH 7tropine 'O 3$ → →  +!urred vision Comine - the poison posses oth !oca! and remote efects ;#amp!eH 'hosphorousH Loca! .Cutaneous urns/ "ystemic.%epaticM&ena! ai!ure/ CantharidineH Loca! .1esicant - !istering/ "ystemic .7phrodisiac - irritant to genitourinary system/ $ EFFECT EXAMPLE TYPE Irritants =eurotic Carcinogenic 7sphy#iants Lacrimators "ternutators 7sthenics =arcotics • 1I$ ;1I4;=C;" O9 'OI"O=I=G ($ Circumstantia! - evidence rom various events ut not very re!ia!e :$ 'ost-mortem - ater an autopsy is perormed ater death - use o tissue organs or ody Fuid 3$ ;#perimenta! - administering suspected sustance to !iving anima! and noting the efect or symptoms $ Chemica! - detection o suspected sustance via ana!ysis o samp!e ody Fuid co!!ected 6$ "ymptomatic - poisoning signs and symptoms oserved 1II$ "';CT&0 O9 =4;"I&7+L; ;99;CT" ($ 7!!ergic reaction - chemica! a!!ergy  immuno!ogica!!y medicated adverse reaction to a chemica! resu!ting rom previous sensiti;#haustive? 'roduce menta! weaness M depression, stupor, coma, respiratory depression 7cid M a!a!i − %a!!ucinogens =itorsamines 7Fato#in CO, 0ethane − • • Cho!inergic, Caramates, Organophospahte s "trychnine, 1eratrine  Tuocurarine, =0 !ocers Opiods ;#amp!eH "ucciny!cho!ine - se!eta! musc!e re!a#ation .ester short acting/ - I&H 'ro!onged musc!e re!a#ation .!ong acting/ G)4' de5cient - CEI to su!a drugs ."u!onamides/, antima!aria! drugs .deve!oped hemo!ytic anemia/ 3$ • 1I$ C%7&7CT;&I"TIC" O9 ;X'O"&; ($ Concentration - %igh Conc D %igh To#icity "ing!e dose - more to#ic 0u!tip!e dose - !ess to#ic :$ &oute M "ite o ;#posure - descending order o efectiveness . inha!ation, intraperitonea!, "N, I0, I4, ora!, derma!/ Ingestion - GIT Inha!ation - !ungs • 4e!ayed - efect ater a !ong period o time .(*-3*yrs/ ;#amp!eH Carcinogens, Teratogens, 0utagens "moers - tar in cigarette .smoe/, components o en0onday disease? =icotineH a true poison, ut due to constant e#posure, the human ody has we!!to!erated the poison, increasing their thresho!d !eve!s d$ IdiosyncrasyE nnown cause - genetic deects may !ead to to#icity - ;#H G)4' de5cientH deve!op hemo!ytic anemia with su!onamides, Auinine, etc$