Toxicology

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 $ickness% 0athieu 8oseph +onaventure Or5!a - 9ather o modern to#ico!ogy - autopsy materia! and chemica! ana!ysis as proo o poisoning .9orensic to#ico!ogy/ 0agendie - 0O7 o emetine and strychnine C!aude +ernard - Experi!ental !edicine Oswa!d "chmiedeerg - trained (:* students ;!!enog - to#icity o %g and ' +ernardino &ama<
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&is - reAuency o occurrence o adverse efect upon e#posure %a
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III$ 7&;7" O9 TOXICOLOGY ($ ;#peri ;#perimen menta! ta! To#ico o#ico!og !ogy y  - investigation o to#ic efect o sustance on io!ogica! system - use o !iving organism .mice, rat, rait/ B L46* L46* - sma! sma!!es !estt dose dose that that i!! i!!s s 6* 6* o the popu!ation, any route e#cept inha!ation B LC6* LC6* - sma!! sma!!est est con concen centra tratio tion n that that i!!s i!!s 6* 6* o the popu!ation - administered through inha!ation, aAuatic e#posure B TL1 TL1 - Thr Thres esho ho!d !d Lim Limit it 1a! 1a!ue ue - ma#imum amount o drug considered sae - !ow TL1 D more dangerous B ;46* ;46* - dose dose whic which h produ produces ces the the desi desire red d efect efect in 6* o su@ect >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 sei
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Cho!inergics

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"ympathomime tics

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Opiates

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II$ '&I=CI'L;" 'oison - >Corpus 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 •

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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/

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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

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&emote efects - the efect is produced in an area other than the site o app!ication ;#amp!eH 7tropine 'O

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 +!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/

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EFFECT

EXAMPLE

TYPE

Irritants

=eurotic Carcinogenic 7sphy#iants

Lacrimators

"ternutators 7sthenics =arcotics

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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
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"peci5c efect

POISON

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Cause tissue necrosis on contactH caustic efect 7fect C=" "timu!ate pro!ieration o cancer ce!!s Cause dyspnea cause comp!ete suspension o  respiration "timu!ate the Fow o tears rom the !acrima! g!ands "timu!ate e#cessive snee;#haustive? 'roduce menta! weaness M depression, stupor, coma, respiratory depression

7cid M a!a!i

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%a!!ucinogens =itorsamines 7Fato#in CO, 0ethane

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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/

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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

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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 en
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Immediate vs 4e!ayed &esponse  Immediate - to#icity with n : hours ;#amp!eH 7naphy!actic "hoc - worst orm o a!!ergy - !ower +' vasodi!ation, ronchoconstrict Corrosive %:"O

1$ CL7""I9IC7TIO= O9 TOXIC 7G;=T"

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 Topica!, percutaneous, derma! - sin 'arentera! 4uration o e#posure  7cute - :hrs,  .Inha!ation/ "uacute - ( month or !ess "uchronic - ( to 3 months Chronic - more than 3 months 9reAuency o ;#posure .Porp!ace/ 7cute - sing!e episodeE incident "uchronic - repeated!y over wees or months Chronic - months or years

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&eversi!e vs Irreversi!e To#ic efects  &eversi!e - afected organ undergoes repair ;#amp!eH 'aracetamo! afects !iver .regenerating ai!ity/

Irreversi!e - afected organ does not undergo repair

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;#amp!eH ;thano! afects rain ce!!s .diferentiated ce!!s/

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Loca! vs "ystemic  Loca! - occurs at the site o 5rst contact ;#H 7cids - coagu!ative necrosis +ase - !iAueactive necrosis Gases .Ch!orine gas/ - !ung tissue

"ystemic - ata! since the poison is asored and distriuted in the ody -&eAuires asorption and distriution o to#icant to entry point

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;#H Tetraethy! Lead - rom sin to C=" and other organs •

 Target organ - oten not the site o highest concentration o chemica! Order o reAuency o invo!vement in systemic to#icity C=" Circu!atory system +!ood M hematopoietic system 1iscera! Organs .Liver, idney, !ungs, sin/ 0usc!e M +one - se!dom target tissue or systemic efect −

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1III$ 97CTO&" 799;CTI=G T%; ;99;CT O9 'OI"O= ($ 'oison-re!ated a$ &oute o administration - 'rincip!eH In@ected poison .I1-asored comp!ete!y/ is more to#ic than ora!!y administered poison .'O-( st pass efect/

- ;#H "aponins -

'O .used as tonics/ I1 . to#ic, hemo!ytic agents/

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Concentration - 'rincip!eH %igh doseE conc D high to#icity c$ "o!ui!ity - vehic!e  - 'rincip!eH %igh !ipid so!ui!ity D high to#icity - ;#H =erve gases .7sored via sin M inha!ation/ :$ 'atient-re!ated a$ 7ge o patient - 'ediatricH !iver .other organ system/ are not u!!y deve!oped D high to#icity - GeriatricH decrease metao!i0onday 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

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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$