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Lg c c 8       :@Os3? wb_ 6 j  TToxicityThe ability of a chemical to cause a deleterious effect to a biological system. 2Zg Rg 8  P    3[t&k%k___PPT10i.@+D=' = @B +" 6.(    FQs3?u`SMO&{ 3"jdPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!ǩbd drs/shapexml.xmlU?6 ;\eY}ɁՈ/sASY1E $u+2u.nm}$;_rC TG߻x/91 )R= 1bʬ7)~y=iCDF,]T#]!8,JƘjha%gbrJb`n:b C 8*y' äSB1UTVWBE#AJp/O?YhD@M"BZ8wPϣirs82>Qox 注|gwU<ŠD;)Fyf6+sA:ɩ J.^^8|Ƞ[\ FQk^\,k3Suf⎬f$ q!вԙptEԠ>MٞjLYnv'946Ou=z`]׫84nW!k_dh7nmdm]|=@q`v­^`6SNS,= r$LA?%ЊWQw\؉Ë#--s TRVraŴ%/2{[xv1sbJfO˯C9گ`MEkyg9tz!k@#BPPHI*ixd?{#FRۜa„ D׃w͜Z(͠nyTX}R'ڌ7q2BD;J`"[EJ*n ) ?Uw;+L jPK!nwdrs/downrev.xmlDMK1EBCx7felZD(B?p IN./r.g\+z ~Z 4\+8֓9 I"_xG>"C8ԕRFma8wS&%]+b&6,vjIN튏jsZm'o/  zM/jc<ޮИDAAv˦PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!ǩbd )drs/shapexml.xmlPK-!nwWdrs/downrev.xmlPKYK:2___PPT9   TOXICOLOGY - CHAPER 1G    ,  J`Ws3?opGrS`SMO&{ 4"óPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!EN drs/shapexml.xmlVOo6wx-K,AruhP@R"a(z(N; q4#%%nÐ إ{{<|+R?C9Yb4uGQ 3i.BO갚ʁ\Mm&"Zbu *a-WI(XA%J\ptvU-R:Er8.țǛ~_?soNB782>`=9,b:Md0OC7zI&pA4,GWt?ImDϳ},J' "!F:,p8sd 7=ǃ,Xa_KѻD@YKgH>.IPݷ8졝~35UV[<|Ft`ЁF~0U>f0Vbxaض &v!')^.[^ xynsnYcEIny4e͉uo0,vM.[$4Զ3w>u=ctgi]׫a aNN&`ESPMIβ qx0Jݡ&n82=-#7OY8+VuiG*uY4d_1ܸH+vNrhaxB7[qln/Y \9T XkX[;5}`R ۱*Q _?@qL `1<0ꎱ !G&62,kSW:o1+=6reSi`z ^Len_~j~>`$d,APK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!EN )drs/shapexml.xmlPK-!wdrs/downrev.xmlPKWF>___PPT9   *0G G    v  :A ~? [a 5< ~b  :A?? VGr 7 w1 3[t&k%k80___PPT10.YN"" ""!(      p^s3Q[`SMO&{ 2" î PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!t?C#drs/shapexml.xmlZOo6w tT˲lFv뭀[uZb-tq;Ӱ6+5#)va[&(y$ߣ)rrƤ#'b{~<<4K b)/$հRɊT%K,FSJjlT0zf;Rl^ISKI-c넡G8-{/o^ۯGb)]iAKIqk ؕZfr: GȟG8Ǐ? ;tvz0̞֡{K"KP"QDf kUz ș3 Qۓƣ?~;v(z}﷬V@^eFgQ f"9UowV7Ypmݪƌ2i!6h뇃n%geM*۪f\v%غ;]1*8|@ Dt~eN5SX,/Jg&4/G%1շk*G\}!Tӻ X6B(Oj:hSzebYJ%1ULB=-g&a[Yh f\鹾mMbi k| *g7Ϭ 3 {~%@0^%Kb~(2!茏婝 Gvʂ*"oWX<dnnSerhrF SܮVN $V`"ݪd5XOr% +34ܲ4I`Zj_^i6Z͍g'd)M@d8yr쑒r8^hՔYhDYY9zlw.!yv$+_4Cا"+7lǸ|̶/W) - +즬c#&SyI MIb´4A.nZ]lӸChǎ/3q\LToxic agents may be classified in terms of their target organs: liver toxicants; kidney toxicants; neurotoxic agents: Uses: Drugs, pesticides, food additivities, industrial chemicals Sources: hazardous wastes, pollutants, natural toxins. labeling requirements : explosive, flammable, oxidizer. 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awv HbP"Sf6 A:ũ *f.^Mȡ[5F YqMCE4Xݸf-f%4 q&b}h9ptMԠ-op5Ƭx۩Q#vwpus.7íAKNŐeSdh\5wmd|7U$&Pܚ EDKۜؤXG;{TyC@ȅ0aN* p "9vsKK/m!J6V.gs3~ђ;Z> !0i Ɗ:@f&Z6N+2@f_P躬FDHmC cx 0KCJ=-LDiJ1ȑOl`[Az`3<2a\\~S PnA8!LmM0ω"P/F[ і-;]oA7PK!Gdrs/downrev.xmlDJ@E0+@i}.xF8f}}҄?pFeO%!X:UYёm"]2u(Q󃥞_-WC}^N[yh= Jx543[s$[6͖?PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!_Pz )drs/shapexml.xmlPK-!G[drs/downrev.xmlPK]K:2___PPT9   TOXICOLOGY - CHAPER 1    &  J s3?opGrS`SMO&{ 4"óPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!"hN drs/shapexml.xmlVn6?-Yl#vF`)VMI{/r(Ez= Rrdsh7zYh8޼N_JlT1NȡLrSx9\g@ISeŃ].mH() @^Ũl8C!44N7$b+K*cHR-x t0q=j`ͮLߵ$?Y f@)+!a ]aB,h6,F981"Z0&iY>LO.v Vb9qa (x#-a>Jd4ċ`ko|,=\# ( So0_m8M*+b UCXm>M{ir c5̈́˝uʸ[`]4^E-xPxdQuil4r{&^8]C_]U0+Mi#,J d^1گ9S}= F \?%5ZYSi:`6`ccEZӯ s;3)DnmU Bm֌kJ-j3ʷ \5paW|`+BU˂x`~4S|>ALb!w>t=߯gQGQ*KTn2gICǴyC40SͰĠާHNj'|?b]Pwj7PK!i,bdrs/downrev.xmlDQK0߅p*8nlpmn&)IoAj4؇YYmTk3*e+X-'7 *#؈ c_H*͆lSW;o(<]t!PkӃ_5WӷAt]UJ̰G?~62+Q;~UG =BrKPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!"hN )drs/shapexml.xmlPK-!i,bdrs/downrev.xmlPKEWF>___PPT9   **        s 4 ys3 wb_ 5"~PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!Hdrs/shapexml.xmlXn6;%Yvl#"vkyASY칇bkz E_i_Cn ȭ Cr~3YՋmцI"Lsy0RR/vU T`P*+AD] r٪$SLhP[w[Qb3Hn3(OcHLϏ:Il'J;N%yȦ= eI:I% y?mݻ /q3փJfut?ȩ,U Z2rZy7|{mF/1֡MtnW-s :rDP4xZ*0l3Y4?km{a; {@:񵆗 /}H+j4^s1J*%+2X2m TטHTxҮN'e׺Lrg>ؘJ􎳧6$W!PA$^ZosBZ%p(eٜ,f1Qd*uDUJQ ##+"Pӵx USцo+HcIJu5XΠDN|9 >l 暮R.z+" 0Ϧ/ QOC>{ )nBoC/8 ?X٤:]3 3GP {V{ I] AsL `>b݉tb#C BPd1\Oc)m'YKC=-ZՏU\=R~&|2?^_@DxK~+/R+A;oC$ %d r PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!H)drs/shapexml.xmlPK-!ppdrs/downrev.xmlPKs|A B:2___PPT9  Adverse effects are defined as pathological lesions, or biochemical, metabolic or genetic changes that affect the performance of the organism, impair the ability to adapt to environmental alteration, or cause changes in the genetic information transmitted to offspring. ve e e 3'e e 3e      s 4s3 wb_ 6" PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!Ԗkdrs/shapexml.xmlXn6;kDYn-F=/hP@ҎŞ{(cz/P}})Vp- ak(g|3tzsdReb-LGY1RB_1_~A9P%B ϵ.sWL\ZȜhN)bB r]I&!i9F'ˉDYF'M2`+}t8vZB E}8tb(|~?{w;-|41x;Q*RGSiFYv6ߏQ?N8NЍ{8>9<ؘ3b X V "LTMw"'ql "wnHrBZKa}hEAԻ1R* Cj* rW"2 (VrE~+Wz8{ nSy r"#  |9  ?1JXzFf$UJc1V=-%3F FlDC=NZ1-TI'T%k+1bn7J͖^=;[<[YXgZa 4?ɬ"UM"pXY^| @_ϝ FXj w(VIөmIh^IBaZ.Ϯvh23Ӹ(&(R+'P-.LhyU/U,1-3ʎ^yujni4k Z…1S˖H_,%B;r DENF%21)LyLDUR~V0Ἕ <O?'}7l͌8nqLnb0"&pig?~oo-` )E).OݺKM:OwNG.'PC!W!jWxLY`ńjd.{>lxi V`sn3Կ T{u3WwX%eM==nM|[njꒉy3vc"Iy'f*I[a{7Lmő|0܍2ĕӆkϷG!"kl3WS̵;eEpQAcK,SwbLR{<%m}E U*X=B~򦘔܍_/ "f,. & 7z!Wܒi9PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!Ԗk)drs/shapexml.xmlPK-!drs/downrev.xmlPKN NF>___PPT9  <f Nonadverse effects may be deduced as the absence of biological changes that impair the capacity of the organism to adapt and compensate for maintaining homeostasis, or enhance the susceptibility of the organism to the deleterious effects of other environmental influences, or have a significant impact on the well-being, growth, development, and life span. fg" e e e 3e 8S     cpRX,)80___PPT10.)O{"#  e"]"@E"(      ds30e0e, h 1"oiPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!!T2 drs/shapexml.xmlVn6;Z˲( ;@ST E $uBE@ߢ)9fsh C͐3}3C=Ԓ c+2S"E3*&XTV"wҷ?plCYYѝsͬ׳|'jfF(Jmj4׽+cjKxԫY)Rfm/n׆TEFJ߾K6s°pٛ*oΡ}ѿP-&]bGa^/x_PK!'drs/downrev.xmlDQK0C/RtFe2lK$%v>;|d{1Rw nfrםk|잮ADF(zu~\+i b KCRw"Zrewb҃ 5՗UP7Xdǫ|}J./biA6}t)(Hn4Y\PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!!T2 )drs/shapexml.xmlPK-!'Zdrs/downrev.xmlPK^^  :2___PPT9  TYPES OF TOXIC EFFECTS 6c $c " (  n   p@s3,Q[`SMO&{ 2  8The nature and magnitude of toxic effects depend on many factors such as  the physicochemical properties of the chemical ; its toxicokinetics, adaptive and protective mechanisms. 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XON-L`68MC7zН#7 i0LA?6јHj#zueAP"GD= 608B7; t:FqbDN=(kRB~3}/'T-{h CM,zt bσLPh< }/o`F1T G hK3ށD8.҂2аpZ٥л){F+䰧\%h!$ Õ+KaNO0L镾d ]w6˅ gvvMϠe5 9zubЍ5 >[k v+ LBw/ -kN{UE@UdIևorbFm;3:͡/|]]s&uz?L!3&x_?@qL `1<0ꎱ !G&62,kSW:o1+=6reSi`z ^Len_~j~>`$d,APK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!iD )drs/shapexml.xmlPK-!wdrs/downrev.xmlPKWF>___PPT9   *0G G     3[t&k%k80___PPT10.6l+  j*b*$J*(  $}  $  ds30e0e, h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!!#drs/shapexml.xmlU͎6;ZK^6V֎0F9Eي)R ivs_ǢWoCX|ptP`ϵLI|KJS> $0ʂ %yJܐ7iƦ pXq͸3lkj.T%t5XupiEZQ4մdWrjInAUOIk %]$p鯨EL)*%?gIA hy2 p޿f=澄w9xMuŴ2L=U.T'mol6ʆ,'aGp82n|:Js>D fm9o{P YG4I6d++8AE$Q2\GW>l7jj0UQ ۞nj]3[T4)I~\]O533%R#*YOowVmhSv cW(M~|XT/|%{A*Y6U5 A{Nb%ZsS楒ɩA>7Tqݖ;ɼ{\5 aKf=a_/Mf8-q|biLG5߭Nb*wmʋoQ\;?`V0;@)2B&atL4ro٥D"H \9HFq3(nϵ Չ9 D-RJۣ\BTY%CEQ*ܦRsՒugf,9s3أ[ŝɾ%`()Cn?՟Ba70Bi`慂.> w'$Jf"Œj _##̎|D޳#Oi&_PK!$3kdrs/downrev.xmlDAK@a؍=HݖP*4 4 c{x͗@!)d ^Q}Nc)8RlWPq#>2ֆ,ƉɥlENghxHpiJK {ZՏU7hݛ WE^J]^=>Sz vwhu)(Hn4Y\PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!!#)drs/shapexml.xmlPK-!$3kdrs/downrev.xmlPKq!^  :2___PPT9  ;TOXIC EFFECTS DIVIDED ACCORDING TO GENERAL LOCUS OF ACTION << ;    $  ps3,Q[`SMO&{ 2"_ Y PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!r drs/shapexml.xmlYn6?eEql#"Fn`qATFTv,z轇MFIq)Pt ԩc3"}bUdɥJO I9EDߜ^<\ǟvTUEY~ѹURɜLhKKY0hU+.4Ә[wZ=Pb9Hr,I6>%oÏᏟ">_ҵX0 n=܎D28qŐ4yq= ayofow֗WƆv#+,*SEL,XA^=8—=o^vQ" !tdhT&#(Q~)rnjLZ*a {àwP:wpՠ]4n=c4Bp7\Iw &9%+`a7 r0,E1,s6a"Ս8(a(Z1=*1ƗJ*}ɊVɜU*%0s8Z8] }O E:L". m %XdbGԫX~S29Nnе>Tv]8Reʔ ws&.@B$÷M܍qJƉ&Ka{>>5O6bTwDC<;>2dd"˯1C9Y19jluD5@%#rorQdE-#rὙaA:ʮ"{?dv D9%\Ĕ$!7ef9}lXejY&5nւMq\ؔy63 /kkTix-F|$3N-幁r"ك\C4$^昼>'J&,ߠc4^5< @ jqpڤSPAd)R?xY5 д6_@Ⱥͳ\*w H;SߚQ jArXѼ !m whogx>Vim:=I[R?eUVpb8l5H^Av˦PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!r )drs/shapexml.xmlPK-!vIdrs/downrev.xmlPKN^ :2___PPT9  Local toxic effects refer to those that occur at the site of first contact between the biological system and the toxicant. This type of toxic responses is usually restricted to the tissues with direct contact to the agent. 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(drs/downrev.xmlPK*K:2___PPT9   \G   # $ Js3?opGrS`SMO&{ 4"êPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!E drs/shapexml.xmlV͎6;ZKljJ[#<MQke)R ) z(sO=m萒ϡp8}3yxW1gK*!r"_EFQ3iT'_~q\Tffu6Z׳@ :5VYa Sy9%Uk᠊ *\rtvU/R:er8ۿ鯛׿}ߜ6]đK-$A֓2F/,HF,t3n2n y0`8~eN3"i?*Jj $t@a pMa4rl&g &tO_ 04:z0kRB+QSx9\u2yai`M4^gƳᡛYV(=l_?@qL `1<0ꎱ !G&62,kSW:o1+=6reSi`z ^Len_~j~>`$d,APK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!E )drs/shapexml.xmlPK-!wdrs/downrev.xmlPKWF>___PPT9   *0G G     3[t&k%k80___PPT10.`7!  8!0!,!(  ,  ,  d@s30e0e, h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!t drs/shapexml.xmlU͎6;Zlʁˆ7瀦([1E $r+X -:$ 5͛cс)H*ˆ *Flr FiCDE,'?t!,֘nnYK]-UK &Lb P$aKJVRY 5Ui!_,ɄB>07+E~j^t^59\I1-Ӡ)H" t6yr=b U̕ʢmZ6uPy@q+we~ϓlf`>ve x(<)pz/O@9"f%ï{PBBEw.4 `Ȝ: 43 s&t<̒!GLj7O2pt=>x0dsM:G)Y%qCkq̺9:kxBSf枳Sf wBx)$c!d S9#"(15MA퍬ŧlڬ̉Mxof̣N_Z#*XJ1X}O֫sExkFP;g^KafʚhE*["6{A{Xu KjЁ[hh#bP ?jg5LsOzz?P]W*ws!kx'ʧ"(uoV~q(8LV1, wLh>0[;cec!WZȕ01e?azl(^w oRpvr(f.dp+oMe_: f `yr߳̌5P/DencՄBn?n7䅂>>@no)"|Dv] 8ZEHIy '-roPK!rdrs/downrev.xmlDMK@Eaxv!;-A*UtaR){f^3̇34.tys9d1RLw u v׷ 8xG N`:?[b46܉ qD9R֐4\>Zc'ucA.FZ]~0P|[oxצVb@0M?|W{]cb [6͖ W?PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!t )drs/shapexml.xmlPK-!rdrs/downrev.xmlPK q^  :2___PPT9  gALLERGIC REACTIONS     ,  p s3,Q[`SMO&{ 2  Chemical Allergy is an immunologically mediated adverse reaction to a chemical resulting from previous sensitization to that chemical or to a structurally similar one. hypersensitivity is most often used to describe this allergic state Allergic reaction and sensitization reaction also describe this situation when pre-exposure of the chemical is required to produce the toxic effect. A molecule that must combine with an endogenous protein to elicit an allergic reaction is called a hapten. 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d U6c^ n׸JVqnm:CREA;GMDGS#\sB fgd>.<&TM1Q8S9]5/ [@\^M:t+sLY:%@s@JkKiGzTu}wܪxp-%rmgPm+ j_PK!:5drs/downrev.xmlDN1E&CHh @!5ٰ{L3뤭0 ]ܛss޶L> Fiõ35I,9]xC2"A8䨠˥ UCuĩ;8o1k=^ܶ1Ң`GSm|U!y+&e&7n D>wǿUh+Hn4Y\PK!,AhQdrs/_rels/shapexml.xml.relsJ1; " =xC2?&iy{#"X<3ϰz'.Ơ` (hl|_@TʰwrXZS^lʢ)!+XJIRfDeK y g۾ۀfXSjG}#$v6. fIC n$9:2___PPT9  hUnlike allergy, 1 the idiosyncratic reaction can occur on first exposure to the medication, 2 it affects only very few individuals.HE333E333zE333      L    %    3[t&k%k___PPT10.D B(+T^DH' = @B D' = @BA?%,( < +O%,( < +D:' = @B%(D' = @B%(Dp' =A@BB*BB0B%(D' =1:Bvisible*o3>+B#style.visibility<*<%(D' =-g6B fade*<3<*<D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<*<D' =+4 8?bCB#ppt_y+.1BCB#ppt_yB*Y3>B ppt_y<*<+8+0+< +$ ##P@"(  @O  @  d`s30e0e h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!qnyfdrs/shapexml.xmlUK6 x-zʁHmcaěsAQ"rm9/X萒=IAjcс)]I* *Jl.iCDA,'٫_nn\z$xgL3}Mw&J6L&j7i& 1~C&3p%fDok"h1_ϗPdʎfM"BE:OUU?fYYe yqEO,([FO6z8R\oK,*ei}Ye~T]ԏ2iz|4IƛЋ`1e0Z~w9_ހ=h=zYIח ^B C݅P%)!sj$S0TtLp Mh2/v֐89.dqnjmCX3F q m!"8ǚ #"(IpZO@G[#tlt Թ6sGdz9$kV9*Q*Ρ:(% !9ձrybʒQLJ0O/p{$rqcɆ F)T?SPݷ`no 9aXE驸j~5;:tu3PK!;drs/downrev.xmlDQk02f:uFب"Xw͵67%ɴ/a>;|YoZq"  +[ˤBfۛ fڞyC"T"BgˤeMvı[g0*#ܴr$4p|cm<(\P~ "Pc/PZx2JA?._􁜂m)/PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!qnyf)drs/shapexml.xmlPK-!;drs/downrev.xmlPKF^  :2___PPT9  dContents  $   @  ps3Q[`SMO&{ 2]m}f B:___PPT9 TOXIC AGENTS AND THEIR CLASSIFICATION ADVERSE EFFECTS TARGET ORGAN AND SELECTIVE TOXICITY DOSE, RESPONSE AND DOSE-RESPONSE RELATIONSHIP COMMON INDEX OF TOXICITY EVALUATING THE DOSE-RESPONSE RELATIONSHIP b@  , 8g  %c  ug  T7 m +    @ F`s3?u`SMO&{ 3"uoPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!ؘm}  drs/shapexml.xmlVOo6w xK,BNqzh5S@Үކvi4cMmb8iCs0 {|gvG[t)E#&KL;H"r¥`)3NtI1uib'f *b`Z1̈́!U~ܫH)L)+ѫL2Oq ?zӧ?~E}8B3Smȿ W56L, ',2ȟD2yY? y؏ZAP\./. ,JjY*,^@D .7A_^dCߋxE٩7@q8 &E[\/b\ EDSug>cx!!_(;pq8s$zkK: pp>q4 6J }o(hArjJL>9*d X1jd |4:֝YS!hm@o 7mJF)QE4P;{;KbP"Sf6sA:ũ *.^Mȡ[5%F YqCCE4LD݁B ZKhn{El#s`b^S+ΨA[f>mkLXPSw h m鵻9W7;b3?܊qT Y4N@㺹pl&IȮ7UYH2Na_Aip3uk&Ws.MH-nsbbQs'afN* p "9vuKK/m!gJy ]Z.lwဓu \R 50 ij(tmpc+d5+nʊit^kYQM6?Oź4tA㈑#~ }`3<2a\a~S ՐoA8!Qmu0ψ"P9I[EE/;]-B7_PK!Gdrs/downrev.xmlDJ@E0+@i}.xF8f}}҄?pFeO%!X:UYёm"]2u(Q󃥞_-WC}^N[yh= Jx543[s$[6͖?PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!ؘm}  )drs/shapexml.xmlPK-!Gbdrs/downrev.xmlPKdK:2___PPT9   TOXICOLOGY - CHAPER 1     @ J s3?opGrS`SMO&{ 4"5 / PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!NZdrs/shapexml.xmlYMo6tT냒%N+`AgZc-Qra P0`vˀ]"=$[I.ml1%y4ю(u랩kG<}AhViqOY?y5/2u:Ed)-e9[d"%a'`%Jm^'1w0?B} t˞_o{ׯ^Fcc'(kYud $I[?C{Cbhc0&ڎ?vruE]=72X)8Y-{Qv"XʰH = Cd{ƮeYn`;;;JZ@aLW<d'@W'YtT4^t vC-`k𥽓Ho԰.Iׁu60 ¨# p<Z&sQYvc49Q_,*1 j,h=k}bG#c7 ;rFȪ|x{;bMgfhȒx.z*l&}Nְb4~_r`_pntM0`x& (IYoI{saoj;7S]qɄ)bz-\@IjT!ߨ Mh0Ɉ0?QE28ӵg"0`<4a7,q6Dgtx D51 ðijt,i946W]kjK&dzoe9oT,?PK!@ drs/downrev.xmlDQK0C/ťN]]6D0.)kd]7sb5C㬀IldcM,D[gIHVˋҝ]T,Al(Q+9&a:;8o0 nZ>nAcG/d";;lsjx~iu+QR@1ρoC$/ %d |PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!NZ)drs/shapexml.xmlPK-!@  drs/downrev.xmlPK$ E[JB___PPT9$  *Fx" dg g    @` cpRX,)___PPT10i.O]+D=' = @B +"|!    `Dg (  D  D  ds30e0e, h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!% * drs/shapexml.xmlUˮ6?d+c #l)Pk;:eя+п!%W"H39gftT u](& Le&}W*3* 9󚼙m5+e=3w:57\Q/@;D˞:Ak!4b3`lDark8Fh؜f*;+ncfwN(cLqqoA?ly+QpOBn,$&mz0*/L) d ^fm΂(|u俛{%KW ǦBfMb$n֗1˒i9]ʙ޻\I3uG6F3 L|tb9r]1k[1)]!x2i|~哸ֻ9̅?9V7LQ 1tw&x0),ұCY#8(8!\awX ͇ n"|]1RE= ōX T@F .{Q\o>+(+RRB _VH\V쟎H݀F< yΙ};8Kٲxk rʀ/ ;pp8X6?('l(lE5֪Zr[񖪫ɿPK!7%drs/downrev.xmlLMO0DHk֡DCUTׁ\z8jlG8j4؇YimTkDdu2…W ʕ;ے*6"Al ARZ0u=7ST n:9˲iASk:tEƛ^opW_Ux{3O "4W^ asV"{L%PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!% * )drs/shapexml.xmlPK-!7%drs/downrev.xmlPK{_^  :2___PPT9  x$TARGET ORGAN AND SELECTIVE TOXICITY %% $   D  ps3,Q[`SMO&{ 2   BSelective damage to certain organs or tissues by a systemically distributed chemical is termed organ- or tissue-specific toxicity; the organs damaged are referred to as target organs of toxicity of the particular chemical. 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WaϸJC`QI {+KaNO0L鵾d ]w6˥ vMϠe5 9f}bЍ5K>;k v+ LBw[/ jN{uE@UdEևorbFm;3:͡/Ȯ]s&Mz7L!w3ƛ&x4"kVrȉM+}{'c4ϡ uKW&=zTtn{'>ZǷo~FNPj6eLJX* yAx%룒D9 RZM:Ǽ̳l%חQRw"[+ 0SPK!wdrs/downrev.xmlDj1!\R3ejD+u\'w&!I9|om#:vm .Rp>_?@qL `1<0ꎱ !G&62,kSW:o1+=6reSi`z ^Len_~j~>`$d,APK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!yE )drs/shapexml.xmlPK-!wdrs/downrev.xmlPKWF>___PPT9   *0G G     3[t&k%k___PPT10i.jP+C+D=' = @B +$ !##\#(  \P  \  d@s30e0e h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!|zfdrs/shapexml.xmlU͎6;ZY쵍[YoEQ6cHʵW[dH=iAj}37Zӆ+jT\nS>&KdI,'f?43 ,ͬIfXM̕j]tM,6l43LZb!P-x05E } P7"7( NduּV`s@ N1 +>'LNTx+m%tU=̎T/agmbXQ64>$/>@pn\rmONrI R\J%x>z$:v2 灞gfu+Ԯdc *B!Ol`䅂NA 5}{U_ h|FMO5=US_PH4PK!;drs/downrev.xmlDQk02f:uFب"Xw͵67%ɴ/a>;|YoZq"  +[ˤBfۛ fڞyC"T"BgˤeMvı[g0*#ܴr$4p|cm<(\P~ "Pc/PZx2JA?._􁜂m)/PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!|zf)drs/shapexml.xmlPK-!;drs/downrev.xmlPKF^  :2___PPT9  dContents  $   \  ps3Q[`SMO&{ 2]m}f B:___PPT9 TOXIC AGENTS AND THEIR CLASSIFICATION ADVERSE EFFECTS TARGET ORGAN AND SELECTIVE TOXICITY DOSE, RESPONSE AND DOSE-RESPONSE RELATIONSHIP COMMON INDEX OF TOXICITY EVALUATING THE DOSE-RESPONSE RELATIONSHIP b@  , ]g  0c  Eg  T7 m +    \ Fs3?u`SMO&{ 3"wqPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!d  drs/shapexml.xmlV?6 ;\ %YɁ8_悦([5E $u+2u,nm};"7ۏ=gS"TfX%Mc RF_uQ u*kca隕DɊ ˥*Zu*4pTNq$#0%vjDvs,F/޾퟿p ̴i" &LWڪ"4.KA"yha2ӰރxHs(ʂ*enΨ,;2 :MA|_x<޷EwK/&8L .:.PAТ~"KW3I7Ha18Ӗ9NԎU2|kK: !q6J 8VF7 Hfy䓣BPLvGua ?jh~6~]mRYKuĈ: #ztgyo %"(I05fk0Ξm<_@$j |W'P U _Ak7d86X4LLLȥ0cwhI4,Q5+C΁ EE+: |4{1aCV sh m5픫v]oҸ]\Aw*, 'C@㺾pl& lˢ?@W8dڛ^Aip3sk& .MH-n}b`Q 'aaN* p "9UvȾsKK/m!JY ]Z.lwဓu ZR550 iѧj,ϡmgpk4+d nit^kYQE6=?OŪ0tA㈑~㇟ }`3<1aX_aO~S UoFA8!QMu0͉"P9ISEE/;]-TB;_FPK!Gdrs/downrev.xmlDJ@E0+@i}.xF8f}}҄?pFeO%!X:UYёm"]2u(Q󃥞_-WC}^N[yh= Jx543[s$[6͖?PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!d  )drs/shapexml.xmlPK-!Gddrs/downrev.xmlPKfK:2___PPT9   TOXICOLOGY - CHAPER 1     \ J@s3?opGrS`SMO&{ 4"8 2 PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK! 7Zdrs/shapexml.xmlYMo6tTK2%KF"uiH&i2 CÀwi.vYMl%K ĔH/ND;fEg|[L]c<1?OBӵRP>I@?e`2c^"w:ed)-e9[dEJN^qAJmn'1w0?lE{g5NS,{/_uo^zyӏiI)jYud6xI 5*< 3esHFhw 뾐[n?*գy#^""+ei'[,uj9 TP;3Gh4vYqm5ݮaA0~wvw7fZR8f'@W'YtT6^t va-%ZB)\RK'"thPÖz&.ltteGlFa@u,۩&Yvc49@/X$1 j,h۽ocov?a@ 7zΨ; U=/v,rŚ&~%\N'T )c t8!jZ:jAʾem {g?]d^$A=97ܛXBKp=|L@8-UH7BD*72"Od3|#DTL!eVڳ"0ht-yKh"n(qz6vϬWix DOyz$!x9>ͣ&I;8yJvMDM4g<WDj')T&ksb׌jĪ`GCPGʍ!Vp5RV EHUͨ*̸i4B|D'yuu-<+tLbZ&陽XDːq`i!FKZ R, ި/Lo`[ #wv*NXQKdBl!DZfF:AM[fƔE|$bCJ+π cIͲHW:L 5[oj?p*ȭAMBUFZ!3oIjԜ j|&Qs[9 j>,T@?%%凨W@2ph@TViff*NP I(D=3nS>-(hmVj\M{]w rܩY;PK!@ drs/downrev.xmlDQK0C/ťN]]6D0.)kd]7sb5C㬀IldcM,D[gIHVˋҝ]T,Al(Q+9&a:;8o0 nZ>nAcG/d";;lsjx~iu+QR@1ρoC$/ %d |PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-! 7Z)drs/shapexml.xmlPK-!@  drs/downrev.xmlPK' E[JB___PPT9$  *Fx" dg g    @` cpRX,)___PPT10i.Oo+D=' = @B +"$ C$;$`#$(  `d  `  ds30e0e h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!6}tdrs/shapexml.xmlU͎HGwhu1›Hhmphw[mW*)o궙!.vUUoGt)E{WFLPb7H"r¥` >1Nxs]OtГ:;ckcWftT1pT[VL3a@ )+qke%zsX+T 1?dŽfMN\g1'Ԩ2wi4R(G|4쏖a.Nb%,*ea|Y%e~Tދ]wq{Xo3#g iSBVp[]KLk0Y9du=! אvQPK!ödrs/downrev.xmlDQk0p{D"b\k[lnJiܯ_|ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!$z drs/shapexml.xmlVOo6w x[$A"Nqzh5S@Үކvi4cMmb8iCs0{|ϧv%G[t!E.FLPb77H"2¥` 3 aGUWTNG+>KUKTi& 1䝠ۍ;%))W3e%z)Td 1㯷|~맏2b;3զ2E^AZ;KhN`]IM.áeOσ^zU"kc/( 9#S1Qkw œC ` BmXBmul0\+j]5hKߵOS?mY#fw9f]l[14nW!и<'۾ɨdכ(U$'ί459L&N>Ivb C@ȹ0Z3e' z* ;rxq`߻%vp3%ene+fhɋ^WZ. 4Scyf3 pk] XN(DtSL+ ]˒*"n ð* ],842]+! #G?ӧ?߳.IR}dRxT7r3F?Y<`jjlFzy4R-T/hiܱ*r yt5PK!Gdrs/downrev.xmlDJ@E0+@i}.xF8f}}҄?pFeO%!X:UYёm"]2u(Q󃥞_-WC}^N[yh= Jx543[s$[6͖?PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!$z )drs/shapexml.xmlPK-!G]drs/downrev.xmlPK_K:2___PPT9   TOXICOLOGY - CHAPER 1    % ` J@s3?opGrS`SMO&{ 4"òPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!$bmM drs/shapexml.xmlVn6;%Yl#.`F}l)"XPz*c/ݷ !%%N6vSax37P/9svTLgr('bU^_%n9JcLpUE/΋*x^EPdMsDA9BXRr5FyF3L\fɖ1j!yˇn Aܣ{=U<`#9[m$ ,7;]7 I%پ6VjY?"ψJ!4#Q@a `c6AAðQ4F&5 s(YWi0u~(KSA6L).^J`ݷyCk8g;TYnqoGAJ ПV6]RI 44f 7q,/xvR #I0QRTa"{.%%Eл< KI~,RB^q0a(j[Q yxHĈhYÔMҲ\OO.v c9qi + FVY [|Y / .)XTp=,$L ~|ChĆ70>/1TAfD;; a}|=oR cUɫuʸ[\`]4^{e)xPทe9:x2n7aE^$fZ8鎓7Wb`ͭ~$Y. 3+Fǵ;bzjהp=g#qH^2 \̭ 殃+f9V9>ͭŲ#. ,3ws1BV1!gfܔ_܈PjPQ].م >ԍ) W,lMʶ=eK1*炾q.E9r ̅2ym{M(_V&%k,hi$?|xӃ> _ NB~3_%X7K$SIcѼ!X})_ΰĠާVINj'|?b]Pw^TPK!i,bdrs/downrev.xmlDQK0߅p*8nlpmn&)IoAj4؇YYmTk3*e+X-'7 *#؈ c_H*͆lSW;o(<]t!PkӃ_5WӷAt]UJ̰G?~62+Q;~UG =BrKPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!$bmM )drs/shapexml.xmlPK-!i,bdrs/downrev.xmlPKEWF>___PPT9   **     . ` :s3? wb_ 5  *2 Internal (absorbed) dose is the actual quantity of a toxicant that is absorbed into the organism and distributed systemically throughout the body.zF       ` :`s3? wb_ 6[ dO 3 Delivered (target organ) dose refers to the amount of toxicant that gets to the target organ, causing a measurable effect.~bF   z    cpRX,)80___PPT10.:."" !!d!(  dc  d  d`s30e0e h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!78|tdrs/shapexml.xmlU[:~?R*ˆ6T@IO%Be\9)>pJ;ao݇jZ0Ό}3իCў)]J" *Rl&iCDN,Gɋ걮\z\'xkL=}M"BL"j׊i& 1~}"p%zD+<FT~|`I`t<(g ֧/iY9B 3uW2p ["60lFPށ#5'v j~`ƊǦg3~]޳Y3P͚VL5,6gbHSDkP:]S0Ppޯ_YiͯaqD"^i, ݫvF;%0zaMAEe[)) '2G+٤B%P>ђ}T jىy`ƊQLRt06O'p{ r{Y}`G FZՏTws{LЇ>'&;WD`):rn{@uvQPK!ödrs/downrev.xmlDQk0p{D"b\k[lnJiܯ_|ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!Vz drs/shapexml.xmlVn7;kVU` 4`s.(.WڊK.HJ[So=5z$hrwmO8پhǔ.Hqpcy)V)~yyC!"'\ ߜ#]#8,Nژzif'f *b`VZ1̈́!U~ҫH)Lݢ++\2Oq _?}|oPGȈL6o"yi=p,*S:I" $/'7O, QzU"b/J9ɢ()qA@}==ϣ zq6ɼ8{A4.bdO\7b\ EDSgnt>cx!!+;pq8sd/TTזt@AJ a'1 m< $H"@A#J p6Y+m3䨐5bŨq8Ѹ\XwBf%OY~k} @xs.6:`_j#qB,><ŠD;)F5pm憳hW*xAr5 "nWm&(g5Y.-2 32q )̹;$(VPŢV5Sv}=֘nv h m鵻픫v]n Ҹ]\Bw*, '#@㪹pl&l?BW8dڛ^Bip3sk& .MH-nsbbQ 'aaN* p "9vwKK/m!J6V.gs3~ђ;Z> !0i Ɗ:@v&ZN+2@fuY1.+t%+"0چ+#AaX3RzZc̕c#ǟ fxd °TY-܌݃q2BO;ښ`"E^+nK-K?Zwl ߂n^?]PK!Gdrs/downrev.xmlDJ@E0+@i}.xF8f}}҄?pFeO%!X:UYёm"]2u(Q󃥞_-WC}^N[yh= Jx543[s$[6͖?PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!Vz )drs/shapexml.xmlPK-!GZdrs/downrev.xmlPK\K:2___PPT9   TOXICOLOGY - CHAPER 1    $ d J s3?opGrS`SMO&{ 4"ñPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!l9_TL drs/shapexml.xmlVn6;gv#04eH9TŢ=S{y)9q9 Cp4:+R'?C9/*uQfB/z_~q^vU\u."+Z`u&Ja/r(%Uk᠂5ϋ9A(Si,rJ'_$ 8?no~/޿W'qD:OXH{ldi 4rSD`u4㠕06qHj+z8eQD %2}FDYڨ V6~#n}Fpuxo"5z PƯ`@Y *'1׏2}rx)ua=ǁ>)rL=ڐ:PR+ VOP5;MJv4 8q5n&XJ_R(Ama[x94gTV]Cbo$R0JY y@{G"jXӝ͆%0''ADˊL}nRmb/`۪/`dU%Gͮ|vq1Xʛ ȵu}+ H”+̗0Nlx 㳒CdJ̧nS~sazw2y7ÝBw qиj2w3&Y|>qG0Gx0Ncs}ot }/a+֛G+M1tX h+'vMzp{Fs\=I%5ZYSi:`6`ccIZ,?Яrs;S)DfmU!By6kMȍH {ۅ\]`SNh09𚅍S۶,|&U^P\7Υ(0GNP&F"5YG(YaGK3'o~!Q$A5:U]ju>K?9էK }JjVK*ߪo}G;=*{PK!i,bdrs/downrev.xmlDQK0߅p*8nlpmn&)IoAj4؇YYmTk3*e+X-'7 *#؈ c_H*͆lSW;o(<]t!PkӃ_5WӷAt]UJ̰G?~62+Q;~UG =BrKPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!l9_TL )drs/shapexml.xmlPK-!i,bdrs/downrev.xmlPKEWF>___PPT9   **      d :s3? wb_ 7a  ]Speaking of dose, the route, duration and frequency of exposure also should be indicated. The major routes by which toxic agents gain access to the body are the gastrointestinal tract, lungs, skin, and other parenteral routes. The exposure of animals to chemicals is usually divided into four categories: acute, subacute, subchronic, and chronic. l^ ((]    cpRX,)80___PPT10.Z",!   hl (  h  h  ds30e0e h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!D drs/shapexml.xmlUK6x-zX~X9 `,xs^Pe+H\A =q/2d#{kP3͌nkT n|PNDQm>g9Jc^`&8MЉ*fOT5\j$hu3 Q&Zˬc*?4esf4P!9W !HFC4pO53f F1ZڤKؤΔ?E2 xwj,W[*^jd[H 9-q9xtgMroK^ɱNd0Q| [`rb[p!FP Y0pdO RZ4G|]GjnW1*;ظD݊GO%oaF N +{>lt3AȭqwMfjCJSi^av0ް! rĬ:߬C RE%5̞oq:YXWRD VERns@c'ͷ-KJ̻Ԯxck JL _.BAq ꅂ>>`nn`~t}h@ Ƌ5|+i=_F[:/^Q}PK!drs/downrev.xmlDAK@aX-RD&l]_A|9N؇ (R9J>^@Hbs'\)7(>V "!'&>:T [ #׳nEtLpqMVCC=7\}_%JYLt)ܺ^wxy1nAExv>}_ԳA?>|k6"{L%PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!D )drs/shapexml.xmlPK-!drs/downrev.xmlPK F^  :2___PPT9  v"Four categories of animal exposure## "   h  ps3Q[`SMO&{ 2qb >6___PPT9 Acute exposure is defined as exposure to a chemical for less than 24 h. Subacute exposure refers to repeated exposure to a chemical for 1 month or less. Subchronic for 1 to 3 months, chronic for more than 3 months. xu":""@" """"   h Fs3?u`SMO&{ 3"qkPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!tz drs/shapexml.xmlV?6 ;\ -Y}Ɂu8_悦([5E $e+2u.nm};"7 ۏ=gS"Y#& b R_uQtУ*kcQ隕DɊ ˥*Zu*4pTNF-* R˿w?}zWԃ#dfM7d8wV1~Aҟ$ixAo8 eЋZ~4\^fm ~YeA27gTe&k\oe8N^#/L&Ͻd0{ &h2|>x;㋎@lk h"O8upj&F~#=}s2'8)ڱJF\OumI ~1:8 SSIAQ*PE}8լ6/|rTb8].;!ӂBP[Z,Z_7^/ @*kBC- :Y1RĘU3õYgO 6/NU V5sp(Dݪ΅5LP\d,gd&qr)ZKhn{M |+s`bQQ+ΩA;f}=HXPUwZ}'zr{.b i.;Cuq]yO}QneQH2q]^Aip3sk&W .MH-n}bcQ 'aaN* p "9UvȾuKK/m!J6V.g}3jђ;Z>5!0i:@ v&N#2@PP(FW5%UDHmC u{~7w ê0t|tMf3?xϦ6`o_l'&=?KoJQj}>'#d񴃩 &9QhJ4R4qǶ-hCPK!Gdrs/downrev.xmlDJ@E0+@i}.xF8f}}҄?pFeO%!X:UYёm"]2u(Q󃥞_-WC}^N[yh= Jx543[s$[6͖?PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!tz )drs/shapexml.xmlPK-!G^drs/downrev.xmlPK`K:2___PPT9   TOXICOLOGY - CHAPER 1    % h J`s3?opGrS`SMO&{ 4"òPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!M drs/shapexml.xmlVAo6 xK$;FrqhP@Ү㢇a(z(N; q4#%'N إ =}G=Tҥ)|rQ<Ͻ>F \ +㯿:FXA1t*dRUP]tj4بNEJ!Xꩲ=]O*)1-onݟooۘ6mP  Tyf8,/ѡ8声ɀ**z$dQTI- s@eՑEQRi U:I0(^ {2nw:.Půb&`뉤z'>cx!!+`=pyMw &ϩvܒPSJEaJqŇ1ذuC%~p)8t87u6ϙ|rRJb8h(ma2/9* һI~l/RRm1/(Dq/ڟߛ1|$y qRLjgOMұ>];XE ƙ3) hYM-hs2m[\,fd"2u )-InzI4JPަŬ5Rv#cCߝkgW|5ޚ9q;8 2o7gAMAM'pw%u=da t :2W54yKzU9(`rU2@o77f{9 |+snR, a{{vr,.w\Aֱn/[7}.TIY8[WfP˚ [~#r+RK^BmVn.v.\0kn(P^MDimw|yY1N+t&+"0“](V˜T%@K4s^!V{ BzA6=꽨T£XK$SIcdBp03E@I֭ZOR~Q}[uNAv_PK!i,bdrs/downrev.xmlDQK0߅p*8nlpmn&)IoAj4؇YYmTk3*e+X-'7 *#؈ c_H*͆lSW;o(<]t!PkӃ_5WӷAt]UJ̰G?~62+Q;~UG =BrKPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!M )drs/shapexml.xmlPK-!i,bdrs/downrev.xmlPKEWF>___PPT9   **      cpRX,)80___PPT10.P"" !!p!(  p  p  d`s30e0e h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!%Kdrs/shapexml.xmlUn8/ x](eٱEZsAQ͚".z_cя[`CJ4Uy7ݼ>T6\z1IU&`DD(|d妞biu04t*bT$J+bQoZ3ä% U"zQX. R^igѻJ#^$8H JI`vɏ.4<3Fʲ(.8 ^"Y4/l F]hJ5=GT+J{EU䔅>y?n{:Ot.M0HAE0}&{> `vu̵$PfΜw^%TiRg$[d5d ChOFd-la =8:is۞ii]3[@ #VOq }mC@p7o*]pmrݥʸ op/=z[:qum$%n({hl\='EI(c 3|@^rw9ubE4q_ұANu/tPAυgPK!Kdrs/downrev.xmlDQK0Co.ݐ)u٘1Xpmڲ&$q >7[ '򡳬`<@Vw(AL .`1a홷tb#C ].e[2F`oxNpIMCZշQ\ӫ[>eޣRwD!]Y^_ԇV0qX]|"y-&KPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!%K)drs/shapexml.xmlPK-!Kdrs/downrev.xmlPKF^  :2___PPT9  5Two Different Types of Response ---Graded and Quantal66"+5   p  ps3Q[`SMO&{ 2p  WThe graded (or variable) response involves a continual change in effect with increasing dose. Graded responses may be a deleterious action observed in a single individual where the severity (or magnitude) of the effect changes with the dose.4"gg  p Fs3?u`SMO&{ 3"oiPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!==\z drs/shapexml.xmlVOo6w xK$FNqzhP@Үކvi4cMmb8iCs0{|gvG[t)E#&KJ;H"r¥`)3aGuԣ^O5>5WHUKՊi& 1^EJ`Jl\Y^n y#߿׻>+2b;3ӦrE^CZ;Khɲp_dE4E8~zU2bϢJ9ɢ()qA@}3M&x7񳁗 'I2}>D[\7b\ ETSg."}BBPwpN;g;fS;VhWꩮ- AGa>IB? 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P (      d`t30e0e h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!o.gdrs/shapexml.xmlUю8}_u24(VB#T+q ű#۰@>q/ 03U s9kS(U\2rRQ$OȁzjhV Y[[ [-ּJU\—+]R^* Z*E+j{JB;:(D$Dɯ_AtvnlS™ͳ>SEB>fѸ; Vq8ƃp]Ll]>ސi!Ng9EY0SeKyx9w~3qOa=~kǓߍO5m3̆D emߜy^b)7 q;/uIB%WZPA$[X GGna/: L*;8iSC[Z>@&!N_ ؓ>X1Q"!!OBRz|*/l+i i!80إ=p.wⓀےG7ĮZ F-Vh<6 :l\Ƈ;*b+Oɑˊ9TllH{ӽ(y=F)Ȍo/A-ۄHtVTKo`õ$` XB.8}B(ܤV*vVh{p;WY!R(QdgRRUݷi'a<9sCӴˆƭؾ')~-?ºli33M}pvQ>uK砳r7F-TSgIgHzQw݀7FPK!Gjdrs/downrev.xmlDAK@a؍ENKKi/4 fgڦzz|v>NnF(ʙVjT$:'pٔr㎲Ck rBhbsCհ0r=K[)ZOgD[j%=4cgeoQb/-j#ˋa*OWwZW09}l(D-&KгPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!o.g)drs/shapexml.xmlPK-!Gjdrs/downrev.xmlPKF^  :2___PPT9  @Major Assumptions in Establishing the Dose-Response RelationshipAA"+@     pt3Q[`SMO&{ 2f B:___PPT9 UThe response is due to the chemical administered, a cause-and-effect relationship. The magnitude of the response is in fact related to the dose. There exists both a quantifiable method of measuring and a precise means of expressing the toxicity. 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I \oQ;/Ş}^BΔm\w}5jђ<;@Tsbu?FN=;,ϡGЭvm5+dv oit^kYQE6>t#`\V˔K4sEc{6C<(6GV+GuS. 3B?YjlFzxb+/lHQWPK!Wkdrs/downrev.xmlDQK0C^ĥ2.c0CV_ۦ)IoAfɇֱ| nQx"1)Rfv>XF$BPn N]ŘoxIpE-ŖӃv ͐Շ^/+>nھ4W^v}WZ#z>a$d,APK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!msh  )drs/shapexml.xmlPK-!Wkadrs/downrev.xmlPKdt K:2___PPT9   Toxicology - Chaper 1    +  Jt3?opGrS`SMO&{ 4"øPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!ۉxSN drs/shapexml.xmlVn6?%Yl#"rF`i*VMI{m/r(Ez= Rrds(6-z8h潙N_lJ欩T O1TE&D;k a}4e{ ?0}x ,jˀ෿ObӃX(fpDE.QMCU ͭeՖԫykh|>Cw?ՊMݷbӚO+?C=*LU PK!Bdrs/downrev.xmlDMK1E!<،}-R(V$tAop˽˙/Gۋc2!M*>?ַO R&Μ`SxNK5!C-ej4[JؕR.1vRE:崪fҒqAS7:ToVFE_AdxjEm|F(eŭKPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!ۉxSN )drs/shapexml.xmlPK-!Bdrs/downrev.xmlPKWF>___PPT9   **     b  :A?? VGr 2`   : t3? wb_ 9  Various ways of presenting dose-response data The abscissa /bsjsY/ is a log dosage of the chemical. The ordinate of the top panel is mortality frequency producing a bell-shaped curve; In the middle panel a sigmoidal curve is produced when the ordinate is percent mortality; In the bottom panel the response is linearized when the mortality is in probit units.n-33 ;gK n   DTj[}1cOr80___PPT10.p{?  (    Ft3?u`SMO&{ 3"uoPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!msh  drs/shapexml.xmlUOo6w xF"vqzh5S@Үކvi4cMmb;iCs&'~=ۖm҅ O2+m_ޤ^#m%x4~6j+V ^S }_%+>KUKuWi& 1~=$#0%6jD63,1F~ݟ}@8Blk4A+Hsg Uii yq0e<ҨӿNI齱ސ*ry1/( 9eMA|_ipq:N/y:}6^\D Gg@lk h"-pTҕnc"G{ /$s|.eNq6c6c *ڒ"HDAJu^ :~/ @F njVJL>9*d %X1jd|.;!ӂBP[Z -Z_7^Ư @*KB'x1h"FP;{;O$O0(ANQ53\q mT]b%QS/N:BdЭ\-F X~C}ELX܁\ s-f%4 q^q }h9p1tEgԠ P4{1fCV vsh m5vҸ[\Aw*, 'C@㺾pl&ȮeQH2N~M459L [X'XG;{T! I \oQ;/Ş}^BΔm\w}5jђ<;@Tsbu?FN=;,ϡGЭvm5+dv oit^kYQE6>t#`\V˔K4sEc{6C<(6GV+GuS. 3B?YjlFzxb+/lHQWPK!Wkdrs/downrev.xmlDQK0C^ĥ2.c0CV_ۦ)IoAfɇֱ| nQx"1)Rfv>XF$BPn N]ŘoxIpE-ŖӃv ͐Շ^/+>nھ4W^v}WZ#z>a$d,APK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!msh  )drs/shapexml.xmlPK-!Wkadrs/downrev.xmlPKdt K:2___PPT9   Toxicology - Chaper 1    ,  J.s3?opGrS`SMO&{ 4"ùPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!ڌTN drs/shapexml.xmlVn6?%Yl#"vF`)*VMI{m/r(Ez= Rrds(6-z8h潙N_lJ欩T OXSeM.mDHFq/݂ݎ3xj) 8^8hw"? YI_RlT I<5Qk?EZ0\ jzkR7ۚs^0RYC{Uz~.xg`G` ' IѲV)=[F ʼ?`rbqi (x3΅]Àh~]ËBOP.{.>̱$ ~^`~ ShĆ7PU"S5g~= ?0?ַO R&Μ`SxNK5!C-ej4[JؕR.1vRE:崪fҒqAS7:ToVFE_AdxjEm|F(eŭKPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!ڌTN )drs/shapexml.xmlPK-!Bdrs/downrev.xmlPKWF>___PPT9   **     b  :A?? VGr 1*3Q   :s3? wb_ 5 =  <Grated dose-response relationship for an essential substance<     :`4s3? wb_ 6R  x:For substances that are required for normal physiological function and survival (e.g., vitamins and essential trace elements such as chromium, cobalt, and selenium), the shape of the  graded dose-response relationship in an individual over the entire dose range is actually U-shaped.    DTj[}1cOr80___PPT10.ͭR!  }e(  !   d+s30e0eX h 1}#   i Hormesis          p,s30e0eXQ[`SMO&{ 2~3  6Nonnutritional substances, Toxic at high doses, Produce beneficial or stimulatory effects (e.g., of growth, reproduction, survival, or longevity) at low doses. "hormesis" also may result in a U-shaped dose-response curve. 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ӇRQ[ (> ~ 1=?bG!]?AQԯJՔ?Tj[_mY=pLWۿfʳVlZZ}qVIo`j7PK!Bdrs/downrev.xmlDMK1E!<،}-R(V$tAop˽˙/Gۋc2!M*>?ַO R&Μ`SxNK5!C-ej4[JؕR.1vRE:崪fҒqAS7:ToVFE_AdxjEm|F(eŭKPK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!PVN )drs/shapexml.xmlPK-!Bdrs/downrev.xmlPKWF>___PPT9   **      DTj[}1cOr80___PPT10.ح`$_($ /#'##(  O    d@,s30e0e h 1"PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!{;yfdrs/shapexml.xmlU͎FG;X}<0Ƭd%4B9jmu7Xy_!hnEn9DvUUo\RɄ$O! 2BI7n뱩\f\'dkm=t +Us ]tE-zө57\Zjt*ZJ2+yX+$vwX2FV}#.mix_r ɢ*VFd{qS/cf7a:q:hi/i/MG'ҙv|Η7P؂֢IRdM~PJTh} UL6$ NP1!1 nQX#G 8GMg*?9j3WMkh>@&!^?T=X1W"!0OB2z=[UaIإ.]ۓ6yh}7 ^: 842<65 _ =/m9]ʙ޹F %_ɨ [5l`V{Y!5s9 nnvS/^^pQ;-]>k~.ѣ1E;,7obi"xC}UV6 (8!\a|ކ;,OQgy+HtU;̎Tk/`ǵX$`,!a]RQ>@n7{J+Ux9/=9%-{JB:|1Jԛ h5A=xQpVi-{秕}OPP~>:  f5?W[~-'\+)zjZ濠zOG.ԓPK!;drs/downrev.xmlDQk02f:uFب"Xw͵67%ɴ/a>;|YoZq"  +[ˤBfۛ fڞyC"T"BgˤeMvı[g0*#ܴr$4p|cm<(\P~ "Pc/PZx2JA?._􁜂m)/PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!{;yf)drs/shapexml.xmlPK-!;drs/downrev.xmlPKF^  :2___PPT9  dContents  $     p)s3Q[`SMO&{ 2]m}f B:___PPT9 TOXIC AGENTS AND THEIR CLASSIFICATION ADVERSE EFFECTS TARGET ORGAN AND SELECTIVE TOXICITY DOSE, RESPONSE AND DOSE-RESPONSE RELATIONSHIP COMMON INDEX OF TOXICITY EVALUATING THE DOSE-RESPONSE RELATIONSHIP x@  , g  c  g  ,g  T7 m +     F@1s3?u`SMO&{ 3"tnPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!  drs/shapexml.xmlVOo6w x؈\n0#NMQHڵ]n;mvi[쑒'ahN&#~ٮh˔.Hqpcy)V)~uyiCDN,{_#]#8,Nژzif'f *b`VZ1̈́!U~ҫH)L++\2Oq ?zӧ?~E!#33mȿ W56L, ',2؟"zY^lF[=HFT1˼!H>*Zʪ'qM|r$o|2hH0dp:=b~[Z-&r:t=Fw~#=s1'81ڱJFBUOumI~1ڧ8~tji%AY Q@nXZi'G+FÙlUº2+9* %m`)tACG0n!,ގSS JDPbjT fa=5HGsx8UWXE •I9t&h3A9+rqhhFwœCK` BmXAoul0\,jj]95hKlۧ-c +vjpnp^L9`V %tbȲp24;ɶo2jٛMUV{S|X{K( nfn̈́jŢ imNlR,=! 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Rz̅) Q8Ej@{)wH zcі j IA$hP_r|HM̹PgDU;RI\Zy8}30MY wDLR 2IJa.Pj!ICug=epA2Z1+QKLXJt|s>'Y#6"Q:,?g'?KX7o*R xkyzhtK?p&`O؅85'aSXɇn#赻p LMԳBC k=ЕL>Z> 붋+UfM!fN ^ϡ䀍'w9",c<qђj~E4sQlhpIkjwg;63v]-0nMw߳rʁ 3tʱiZ" 3tu6zl-*L3/V"CyI8߄XHX8#eLP.u뛼VNxMٸqLukr9e>aQd Y r|U# !$TI&:WTzxqt%YT(k#@_-{,*Y̞@`-2'$ON5|JsJ9fƤJrNHd$Mй@>=?y>Si%:D9 Q(ebEf:Q<`%fL)dZhU09;k`y2[`5[n;2[0-6;Ŭբ*56Szm-[ӑ^Lp{dk[#fuղ̇fLw*cY:k.=ЎПSktUس81k<5լׅzݖvoM&̆ԫ 4k0Kq76~hz]v=Ymi5lywsi5m83LI;c ZT_];,~B|*p*Pu+W ڳͦm>kϷs抺xZp:ËcĻ}b'mFRvZk齰"_%P<|[HWV.Q94ۼ-Ӻi _cxVؐʲdvnI[>ы`&B.Kȍ{k>k?5~0OrJ%e?U(b_PK!zdrs/downrev.xmlDN0DHHܨC uą$K :N=rft8RֳYrDL[Ϥ` KӱJ%*0)u60|GS:ᮕXJvw ^~C)]/]+uy1nA$s5,?,7E9>dM)drs/shapexml.xmlPK-!z drs/downrev.xmlPK Vp2B:2___PPT9  aHomework: Introduce some famous toxic events in history Content requirements: time, place, event process, causes and consequences of the events, the thoughts about the events; Formation requirement: it should be presented in the form of PPT with distinct hierarchy and clear expressions, avoiding large paragraphs of text, Pictures and short videos are favoured. One group consist of 2-3students introduce one event. Discussion is to be followed.H / `c `    3[t&k%k80___PPT10.!|Pƨt. {-s-[-(  0    rs30e0eRectangle 2"ÄPK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!׀ drs/shapexml.xmlVn6}:(dَȅD]75%VCIN~ža߰M!%;n`C})^^{νWxwϔ.Ip'K?'6TKb4y1zk1SO{=XE^!UE j۫LjpQ{a?UdP~]<& " ZĖ3/:e{ԦsE? vF1a2J#?G$h*p0doFL1ɫ!}*3%,Y&,2c˫e .b"I|ap,`~~"Ea>o--evJϱ RAb2RÎ\CpQ@Cy框|4$INhN@j}o{z%2lgpEqnq$[`?bNJ-h TxŸE4Xӝ;/$ '&)=8o,JO Bڬz#.wSɊƍ3}X)rL6GŸYqK7ǎ/ˑi]Dݹ-0sw 06ؚlX5"Cź,&]gxaQ=ǚ8uHXtpiw^[ېF!OMvX4ǣ"عp&ȸY)]Tֻ*+ s$&k 7K~k{9!Ook41Ҿ Tyr,1ehI9YL|O)/ٯ ՌmVJy Z ` )qȓCP jCGԍ^ hllv5UA3`zsc&=?>ۻI8Bեv)J a؞y8d43=}`C* ӵk;*k]S6kjATo0]Qs]EXE'QA"PK!$drs/downrev.xmlDQK0߅ptRecnRen?ܵ$p[FӉo-+ĕ- {> k, yX-'W ̵=2"B稠 ϥUCı;Yg0j#t6I2i`O(ؽ._iaEvDD17G7 i |pޣDhMA.PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!׀ )drs/shapexml.xmlPK-!$rdrs/downrev.xmlPKy8jj  F>___PPT9  Relationship to other sciences, & $!"$     s3d@ϷRectangle 3#"   PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!c cdrs/shapexml.xmlY[o6~@up-uī^`)XekHS'E>J$5;|xxHw(ϻ`B\I &d\'Yk0cLy?_jl*ҌI&و7s%uiAea]\J/vTr},O'AoOc;H&1tTf*o#TEţ3;e҂w._kQGQ?N ^4"HQ&Nty:ˋZ\ Vcn7 w^(׆b JML y1 x K~4*ȱdoD)6d\}Tg/w1/t<ؼiKVpf^5ۼ}|5QY aaE(Ϛ#=̟[ {I,qoЁʺᮎr[NRumA$dL$ 9aUq;*iR>r]1GbpZQzR{A9B/Veev: F0VCnDM\7iywۣ0vit'Uvӫ9(N#+@Qɰ*)JH^aVTd|8v#$"\^; %-"i,qֵ':L,GG~<Y#jM h5ae~wmDO$C?:j|kYW9evO!S^+R0N8 {x8'fslf tdõzk *|1q^ۖyMe(KIa4~ܴ׾u.+K ;h.Ւ 9%= ~pō.9]]h2\[R EGWp2 \\s[yMSNR ^'wy>n }χ g/وBx;+ WiUGE}_ 'LMd'8^Db`g?x d?GU PK!/g ydrs/downrev.xmlDKO1&撸*>F Ab5ez.Ow&EKW  {> k-yFj5Pa2&g%}.`R;GUJLJz.).aa5WZ~ߔuG?^OE+y @Uz>Sm49PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!c c)drs/shapexml.xmlPK-!/g ydrs/downrev.xmlPK4^ :2___PPT9  FPharmacology and toxicology both study the effect of chemicals on living organisms and have often used identical methods. Pharmacology focused on chemicals with beneficial effects (drugs) at lower doses  Toxicology studied the adverse health effects occurring with the same chemicals at high doses. Today, the main interest of research in toxicology has shifted to studies on the long-term effects of chemicals after low-dose exposure, such as cancer or other irreversible diseases.  P&p*   )  n` s31?opGrS`SMO&{ 6E  z*(2      3  e,gFh 2"|PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!B-drs/shapexml.xmlUn6;%YR#vqeHv{m=詗ދAߦstHImYp~~sP gp%s1IU&oo`DD(r|d|E36 Ҍomƃ[Vs&aR&z3h43LZbQ-qfp'`JWR;^2C$?<ïߣɘ7?KMAB/zKhyET+*{FU=PU)tq@Q&3}>Qi< l4 E489@0s8"{Tq.;{ puG9C IHa< 0:(L$s!@SO4KG F4,ʲK4mL:( X3j}Ӑ="ػp,l.4cB)4/ѓǣ OŮ. 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Frequently, the perturbation of normal life processes by toxic chemicals enables us to learn more about the life processes themselves. The development of toxicology has expanded from a purely descriptive science to one that uses the whole range of methodology of experimental sciences to study the mechanisms.2 Z333  ___3f___PPT10i. >+D=' = @B +"  0 (  6  dPD+1?u`SMO&{ 4`   Toxicology - Chaper 1&%( 2  3  hpG+1?opGrS`SMO&{ 5`   *&%( 2     rp3+gֳgֳRectangle 2T$   Like medicine, toxicology is both a science and an art. 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J[3\thBht hg*60\8 SvRMA#G[Zxah 9WRN e7rac悔cEf/[OC>Ucyh; [k]A sXN(vSL+ ]˒*"A~|B`,V디 tMfGO>|f6}I;~+LJQj>'#d#&9Q*"iHHErǻUhgkPK!Gdrs/downrev.xmlDJ@E0+@i}.xF8f}}҄?pFeO%!X:UYёm"]2u(Q󃥞_-WC}^N[yh= Jx543[s$[6͖?PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-! b  )drs/shapexml.xmlPK-!Gbdrs/downrev.xmlPKdK:2___PPT9   TOXICOLOGY - CHAPER 1      J@+?opGrS`SMO&{ 4"7 1 PK![Content_Types].xmlJ0*miG]`Hm6 Xwt?. g#Wi3E).+7 >ON ޑ1ˋz "+R RhB.} /<^ITխ%rHK4uK~I0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!UZdrs/shapexml.xmlYMo6tTK2%KF"uiH&i2 CÀwi.vYMl%K ĔH/ND;fEg|[L]c<1?OBӵRP>I@?e`2c^"w:ed)-e9[dEJN^qAJmn'1w0?lE{g5NS,{/_uo^zyӏiI)jYud6xI 5*< 2#7{/ۏ vh`WHl!EY8bZ("2ΟvžAv ,蹾c /ЬuX+SU'Avt|EGe#I`M_@RrE 9 µq-(қ.-A5lGlFOKAKWPF{v`t]DzZoR90/Je7J EB f 8Inf?1aVuGȪ|x{;bMgfh̒x.z*0)c t8!jZ:jAʾemB~ 5OF-MbK3X{S˽h?+$N ׃h|R*D4rü/#TJ67BD;z_fř=+(CLגG&,BB=gh=|3oaHT)@D< {giNńOsN"]S Qe%6*U:IJ158(XQ0h_[@1 nF>A鴊@5[8قFȜOd6/g%^ILD1=W}h4N,-hIW[Vz9[]X,H?H6i̘b/Dа]^}hPiual4u7YJif{Ma8X5IjH 5 5 UA6$T5jn 5"2 ^AMctƒHN !N3Z^[R~za#wN CQ F*ml]W,35Uؽ= M2gqg 7)qo)HkS6%n ?6SצLܭ؝)| W,GmHh&$5 N֏U}Sn裪MqU@oPe)`,dL"D+ȁ :o)X6/lNjdznJbf5D9լJ_ɼsvdO,#ݑOwzRP9Zq} 8A7ϖpOB!&qw=Ϣk 559WAE|x6U-];b8Ra$_=Pq+$>cGYb&'"]b03R-4R]$Ib,`-&Fa%}:SVj{8K)C٦kv&y@){ qׯ09Me5Kܖݢ ˮ lIʍ߹dsQg%Ŏ&U?ӂjk]vդwu~W୬ ͝ e'PK!@ drs/downrev.xmlDQK0C/ťN]]6D0.)kd]7sb5C㬀IldcM,D[gIHVˋҝ]T,Al(Q+9&a:;8o0 nZ>nAcG/d";;lsjx~iu+QR@1ρoC$/ %d |PK-![Content_Types].xmlPK-!1_a ._rels/.relsPK-!UZ)drs/shapexml.xmlPK-!@  drs/downrev.xmlPK& E[JB___PPT9$  *Fx" dg g    @` cpRX,)80___PPT10.P@"  (  6  d6+1?u`SMO&{ 7`   Toxicology - Chaper 2&%( 2  3  hl+1?opGrS`SMO&{ 8`   *&%( 2  J   rg+gֳgֳRectangle 2wY7   4Toxicology is a science for the wellbeing of mankind5 5& 0!5    A ?j0205403Picture 11j0205403     vA ??j0303428Picture 28j0303428=   vA??j0303441Picture 29j03034416 gT  vA??j0336980Picture 30j0336980S ~   ___3f___PPT10i.ˀ+D=' = @B +"< 0(  )  rSs31?Rectangle 6`P   v kSuktf[     /  rFs31?Rectangle 7`   |*        l0e0eRectangle 2   H   Zs30e0e5%Rectangle 3 @   R    ̙3380___PPT10.%<HX J y q pY (     j0e0e{^opGrVP`SMO&{ 1   [   `\s30e0e5%Yl`SMO&{ 2 @   mOne could define a poison as any agent capable of producing a deleterious response in a biological system, seriously injuring function or producing death. This is not a useful working definition, however, for the simple reason that virtually every known chemical has the potential to produce injury or death if it is present in a sufficient amount (dose). At sufficiently high doses, any chemical may be described as toxic. The importance of dose is clearly seen with molecular oxygen or dietary metals. Oxygen at a concentration of 21% in the atmosphere is essential for life, but 100% oxygen at atmospheric pressure causes massive lung injury in rodents and often results in death. Some metals such as iron, copper, and zinc are essential nutrients. When they are present in insufficient amounts in the human diet, specific disease patterns develop, but in high doses they can cause fatal intoxications. Therefore, all toxic effects are products of the amount of chemical to which the organism is exposed and the inherent toxicity of the chemical; they also depend on the sensitivity of the biological system. The toxicity of a chemical could be defined as the ability to cause a deleterious effect to a biological system.N " 6     FJs3?u`SMO&{ 3`P   v kSuktf[       J`Rs3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.xֳ  y q Y (     j0e0e{^opGrVP`SMO&{ 1   [   Ks30e0e5%Yl`SMO&{ 2 @   mOne could define a poison as any agent capable of producing a deleterious response in a biological system, seriously injuring function or producing death. This is not a useful working definition, however, for the simple reason that virtually every known chemical has the potential to produce injury or death if it is present in a sufficient amount (dose). At sufficiently high doses, any chemical may be described as toxic. The importance of dose is clearly seen with molecular oxygen or dietary metals. Oxygen at a concentration of 21% in the atmosphere is essential for life, but 100% oxygen at atmospheric pressure causes massive lung injury in rodents and often results in death. Some metals such as iron, copper, and zinc are essential nutrients. When they are present in insufficient amounts in the human diet, specific disease patterns develop, but in high doses they can cause fatal intoxications. Therefore, all toxic effects are products of the amount of chemical to which the organism is exposed and the inherent toxicity of the chemical; they also depend on the sensitivity of the biological system. The toxicity of a chemical could be defined as the ability to cause a deleterious effect to a biological system.N " 6     F@Ts3?u`SMO&{ 3`P   v kSuktf[       JUs3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.P@& ې _ W ? (     j0e0e{^opGrVP`SMO&{ 1   A   ?s30e0e5%Yl`SMO&{ 2 @   SOne could define a poison as any agent capable of producing a deleterious response in a biological system, seriously injuring function or producing death. This is not a useful working definition, however, for the simple reason that virtually every known chemical has the potential to produce injury or death if it is present in a sufficient amount (dose). At sufficiently high doses, any chemical may be described as toxic. The importance of dose is clearly seen with molecular oxygen or dietary metals. Oxygen at a concentration of 21% in the atmosphere is essential for life, but 100% oxygen at atmospheric pressure causes massive lung injury in rodents and often results in death. Some metals such as iron, copper, and zinc are essential nutrients. When they are present in insufficient amounts in the human diet, specific disease patterns develop, but in high doses they can cause fatal intoxications. Therefore, all toxic effects are products of the amount of chemical to which the organism is exposed and the inherent toxicity of the chemical; they also depend on the sensitivity of the biological system. The toxicity of a chemical could be defined as the ability to cause a deleterious effect to a biological system.6]# 6     F Qs3?u`SMO&{ 3`P   v kSuktf[       J Vs3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.@ l R J 2 (     j0e0e{^opGrVP`SMO&{ 1   4   Ys30e0e5%Yl`SMO&{ 2 @   F& Ferrous sulfatekxxN Morphine sulfateTaU Phenobarbital sodium Picrotoxin(g2]k } Strychnine sulfatekxxju(g֜wx Nicotine<\SN d-TubocurarineR{{kx Hemicholinium-3 Tetrodoxin[ƀx Dioxin (TCDD) Botulinum toxinkFg̃k } *LD50 is the dosage (mg/kg body weight) causing death in 50 percent of exposed animals. IP SC and IV stand for intraperitonealyT, subcutaneous, and intravenous injection, respectively6ho                         X      8    F@^s3?u`SMO&{ 3`P   v kSuktf[       J@@s3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.Zдa\ (     j0e0e{^opGrVP`SMO&{ 1       `s30e0e5%Yl`SMO&{ 2 @   v cYnSf[irv(uSR^V S\kirR:N`$]Nkir SbuN-NvSe0-NSO0RBR0Bg(0bT0oRNT0^_irI{a$sXalgir SbuN-Nc>ev^l0^4lT^#n0ُNalgirSǏzzl04l0WXbߘir qSSN{|eP^b$ߘT-N gkbR Sb)Y6qk }0ߘTS(TNuvk }NSߘT-N NTe\'`8h }0*  O    F s3?u`SMO&{ 3`P   v kSuktf[       J@s3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.  b Z PB (     j0e0e{^opGrVP`SMO&{ 1   D   s30e0e5%Yl`SMO&{ 2 @   VThe toxic responses that form the study of toxicology span a broad biologic and physiologic spectrum (broad range of potentially adverse effects). The nature and magnitude of toxic effects depend on many factors such as the physicochemical properties of the chemical and its toxicokinetics, adaptive and protective mechanisms. The latter factors include physiological mechanisms such as adaptive enzyme induction, DNA repair, and others. Effects of interest may range from something relatively minor such as irritation or tearing, to a more serious response like acute and reversible liver or kidney damage, to an even more serious and permanent disability such as cirrhosis0sYrosjs0lxS of the liver or liver cancer. H"8       Fs3?u`SMO&{ 3`P   v kSuktf[       Js3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.φ)N ph(     j0e0e{^opGrVP`SMO&{ 1   j   s30e0e5%Yl`SMO&{ 2 @   |0cirrhosis[sY rYsjs]lxS     F`s3?u`SMO&{ 3`P   v kSuktf[       J`s3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.3 2*(     j0e0e{^opGrVP`SMO&{ 1      s30e0e5%Yl`SMO&{ 2 @   &Immediate toxic effects can be defined as those that occur or develop rapidly after a single administration of a substance, whereas delayed toxic effects are those that appear long after the initiation and/or cessation of exposure to the toxicant. Carcinogenic effects of chemicals usually have a long latency period, often 20 to 30 years in humans. An example is vaginal 4Scancer during adulthood resulting from in utero exposure to diethylstilbestrol (DES)]p̖Z.Tv  T       Fs3?u`SMO&{ 3`P   v kSuktf[       J@s3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.ME ֢ H @ ( (     j0e0e{^opGrVP`SMO&{ 1   *   `s30e0e5%Yl`SMO&{ 2 @   <Some toxic effects of chemicals are reversible, and others are irreversible. Reversible toxic effects are used for adverse effects that diminish once exposure to a toxicant is stopped. The degree of reversibility of toxicity depends on a number of factors, including the extent of exposure (time and amount of toxicant), the type of injury and the capacity of the affected tissue to regenerate or repair injury. For example, kidney damage by xenobiotics is often reversible, after survival of the acute phase of the intoxication, without further consequence due to the high capacity of the kidney for cell proliferation and thus the capacity to repair organ damage. Irreversible toxic effects are often caused by the covalent binding of toxic chemicals to biological macromolecules. Under extreme conditions, the modified macromolecule is not repaired; after excretion of the toxic agent, the effect persists. Further exposure to the toxic agent will produce additive effects. Carcinogenic and teratogenic effects of chemicals, once they occur, are usually considered irreversible toxic effects. Injury to the central nervous system is largely irreversible since the differentiated cells of the nervous system cannot divide and dead cells cannot be replaced.     F`s3?u`SMO&{ 3`P   v kSuktf[       J s3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10. v E =  % (       j0e0e{^opGrVP`SMO&{ 1   '    s30e0e5%Yl`SMO&{ 2 @   9Some toxic effects of chemicals are reversible, and others are irreversible. Reversible toxic effects are used for adverse effects that diminish once exposure to a toxicant is stopped. The degree of reversibility of toxicity depends on a number of factors, including the extent of exposure (time and amount of toxicant), the type of injury and the capacity of the affected tissue to regenerate or repair injury. For example, kidney damage by xenobiotics is often reversible, after survival of the acute phase of the intoxication, without further consequence due to the high capacity of the kidney for cell proliferation and thus the capacity to repair organ damage. Irreversible toxic effects are often caused by the covalent binding of toxic chemicals to biological macromolecules. Under extreme conditions, the modified macromolecule is not repaired; after excretion of the toxic agent, the effect persists. Further exposure to the toxic agent will produce additive effects. Carcinogenic and teratogenic effects of chemicals, once they occur, are usually considered irreversible toxic effects. Injury to the central nervous system is largely irreversible since the differentiated cells of the nervous system cannot divide and dead cells cannot be replaced.      Fs3?u`SMO&{ 3`P   v kSuktf[        Js3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.6ćlN /   ( (  ( (  j0e0e{^opGrVP`SMO&{ 1    (  @s30e0e5%Yl`SMO&{ 2 @   Local toxic effects refer to those that occur at the site of first contact between the biological system and the toxicant. Local effects may be produced by skin contact with a corrosive agent(P'`ir(), by inhalation of irritant gases, or by ingestion of tissue-damaging materials. This type of toxic responses is usually restricted to the tissues with direct contact to the agent. Systemic toxic effects are characterized by the absorption of the chemical and distribution from the port of entry to a distant site where toxic effects are produced. Except for highly reactive xenobiotics, which mainly act locally, most chemicals act systemically. For some materials, both effects can be demonstrated. If the local effect is marked, there may also be indirect systemic effects.: 8  F    ( Fs3?u`SMO&{ 3`P   v kSuktf[      ( Js3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10. Å 0l(  0 0  j0e0e{^opGrVP`SMO&{ 1   n 0  `s30e0e5%Yl`SMO&{ 2 @    Chemical allergy is an immunologically mediated adverse reaction to a chemical resulting from previous sensitization to that chemical or to a structurally similar one. The term  hypersensitivity is most often used to describe this allergic state, but  allergic reaction and  sensitization reaction also describe this situation when pre-exposure of the chemical is required to produce the toxic effect. Once sensitization has occurred, allergic reactions may result from exposure to very low doses of chemicals, and therefore population-based dose-response curves for allergic reactions have seldom been obtained. For a given allergic individual, however, allergic reactions are dose-related. Sensitization reactions are sometimes very severe and may be fatal. Most chemicals and their metabolic products are not sufficiently large to be recognized by the immune system as foreign substance and thus must first combine with an endogenous protein to form an antigen (or immunogen). A molecule that must combine with an endogenous protein to elicit an allergic reaction is called a hapten(JSbS . The haptenprotein complex (antigen) is then capable of eliciting the formation of antibodies, and usually at least 1 or 2 weeks is required for the synthesis of significant amounts of antibodies. Subsequent exposure to the chemical results in an antigen-antibody interaction, which provokes the typical manifestations of allergy. These may affect various organ systems and range in severity from skin disturbance to fatal anaphylacticǏOev shock. The pattern of allergic response differs in various species. In humans, involvement of the skin (e.g., dermatitisvp, urticariahu, and itching) and of the eyes (e.g., conjunctivitis~p) is most common.B    |     4      0 Fs3?u`SMO&{ 3`P   v kSuktf[      0 J s3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.Hz) 08(  8 8  j0e0e{^opGrVP`SMO&{ 1    8   s30e0e5%Yl`SMO&{ 2 @   Idiosyncratic [.jdiYsjK'krtjk] Reactions Chemical idiosyncrasy refers to an abnormal reactivity to a chemical. The response observed is usually qualitatively similar to that observed in most individuals but may take the form of extreme sensitivity to low doses or extreme insensitivity to high doses of the chemical. This response is genetically determined, and a good example would be sensitivity to nitrates due to deficiency in NADH-methemoglobin reductase.     8 Fs3?u`SMO&{ 3`P   v kSuktf[      8 Js3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10. JBpH*(  H H  j0e0e{^opGrVP`SMO&{ 1   , H  s30e0e5%Yl`SMO&{ 2 @   >Most chemicals that produce systemic toxicity do not cause a similar degree of toxicity in all organs; instead, they usually elicit their major toxicity in only one or two organs. Selective damage to certain organs or tissues by a systemically distributed chemical is termed organ- or tissue-specific toxicity; the organs damaged are referred to as target organs of toxicity of the particular chemical. The target organ of toxicity is often not the site of the highest concentration of the chemical. The target organ most frequently affected in systemic toxicity is the CNS. Next in order of frequency of involvement in systemic toxicity are the circulatory system; the blood and hematopoietic system; visceral organsQvsuch as the liver, kidney, and lung; and the skin. Muscle and bone are least often the target tissues for systemic effects. With substances that have a predominantly local effect, the frequency with which tissues react depends largely on the portal of entry.YgNykir;NNu@\k\O(u HNDdeQMOnQ[;N_c$Ov~~ Selective toxicity means that a chemical produces injury to one kind of living matter without harming another form of life even though the two may exist in intimate contact. The living matter that is injured is termed the uneconomic form (or undesirable), and the matter protected is called the economic form (or desirable). They may be related to each other as parasite and host or may be two tissues in one organism. This biological diversity interferes with the ability of toxicologists to predict the toxic effects of a chemical in one species (humans) from experiments performed in another species (laboratory animals). However, by taking advantage of the biological diversity, it is possible to develop agents that are lethal for an undesired species and harmless for other species.}{"J"!'T        H Fs3?u`SMO&{ 3`P   v kSuktf[      H Js3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.@q== @8P (  P P  j0e0e{^opGrVP`SMO&{ 1    P  `s30e0e5%Yl`SMO&{ 2 @   ,Most chemicals that produce systemic toxicity do not cause a similar degree of toxicity in all organs; instead, they usually elicit their major toxicity in only one or two organs. Selective damage to certain organs or tissues by a systemically distributed chemical is termed organ- or tissue-specific toxicity; the organs damaged are referred to as target organs of toxicity of the particular chemical. The target organ of toxicity is often not the site of the highest concentration of the chemical. The target organ most frequently affected in systemic toxicity is the CNS. Next in order of frequency of involvement in systemic toxicity are the circulatory system; the blood and hematopoietic system; visceral organsQvsuch as the liver, kidney, and lung; and the skin. Muscle and bone are least often the target tissues for systemic effects. With substances that have a predominantly local effect, the frequency with which tissues react depends largely on the portal of entry.YgNykir;NNu@\k\O(u HNDdeQMOnQ[;N_c$Ov~~ Selective toxicity means that a chemical produces injury to one kind of living matter without harming another form of life even though the two may exist in intimate contact. The living matter that is injured is termed the uneconomic form (or undesirable), and the matter protected is called the economic form (or desirable). They may be related to each other as parasite and host or may be two tissues in one organism. This biological diversity interferes with the ability of toxicologists to predict the toxic effects of a chemical in one species (humans) from experiments performed in another species (laboratory animals). However, by taking advantage of the biological diversity, it is possible to develop agents that are lethal for an undesired species and harmless for other species.}{"J"!>T        P Fs3?u`SMO&{ 3`P   z kSuktf[       P Js3?opGrS`SMO&{ 4`   *      ̙3380___PPT10.Y3, B:l"(  l l  j0e0e{^opGrVP`SMO&{ 1   $ l  s30e0e5%Yl`SMO&{ 2 @   6   l Fs3?u`SMO&{ 3`P   v kSuktf[      l Js3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.4Vto  t(  t t  j0e0e{^opGrVP`SMO&{ 1    t  s30e0e5%Yl`SMO&{ 2 @   dThe graded response: ϑS^ Quantal all-or-none (S^T         t Fs3?u`SMO&{ 3`P   v kSuktf[      t Js3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10. *iR @8p (     j0e0e{^opGrVP`SMO&{ 1   "    t30e0e5%Yl`SMO&{ 2 @   4\abscissa/bsjsY/*jPWhordinate/TdjnYt/*jPWh 0- p             Ft3?u`SMO&{ 3`P   v kSuktf[       Jt3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.̭j% (     j0e0e{^opGrVP`SMO&{ 1      @s30e0e5%Yl`SMO&{ 2 @   MThat is, at very low doses, there is a high level of adverse effect, which decreases with an increasing dose. T his region of the dose-response relationship for essential nutrients is commonly referred to as a deficiency. As the dose is increased to a point where the deficiency no longer exists, no adverse response is detected and the organism is in a state of homeostasis. However, as the dose is increased to abnormally high levels, an adverse response (usually qualitatively different from that observed at deficient doses) appears and increases in magnitude with increasing dose. M     F1s3?u`SMO&{ 3`P   v kSuktf[       J5s3?opGrS`SMO&{ 4`   |*      ̙3380___PPT10.̭@Z^% zrZ(     j0e0e{^opGrVP`SMO&{ 1   \   5s30e0e5%Yl`SMO&{ 2 @   n"For example, chronic alcohol consumption is well recognized to increase the risk of esophageal cancer, liver cancer, and cirrhosis of the liver at relatively high doses, and this response is dose-related. However, there is substantial clinical and epidemiologic evidence that low to moderate consumption of alcohol reduces the incidence of coronary heart disease and stroke. There are other agents that display hormesis for which the benefit of low doses is less intuitive. A number of studies on animals and humans have suggested that low doses of ionizing radiation decrease cancer incidence and mortality while high doses lead to increased cancer risk. There is some evidence that hormesis may be applicable to a variety of types of chemical toxicants as a generalized phenomenon to certain extent. 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The science of toxicology is defined as the observational and data-gathering phase; whereas the art of toxicology consists of the utilization of the data to predict outcomes of exposure in human and animal population.Medicine: a science and an art ContentsPowerPoint 演示文稿]Maximum tolerated dose (MTD) studies are used to set the doses for short and long-term toxicology studies in animals and to determine safe starting doses for first-in-man clinical trials. 10% body weight loss is usually used as an index. 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