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Ch

ng CH C

I T NG QUT V 1. ch c 1.1. Khi ni m

L ngnh hc nghin cu v kha cnh nh tnh v nh l-ng tc hi ca cc tc nhn ho hc, vt l v sinh hc ln h thng sinh hc ca sinh vt sng (J.E Borzelleca). Theo B sch gio khoa Brockhaus. c hc l ngnh khoa hc v cht c v cc nh h-ng ca chng. Ngnh c hc ch bt u -c xy dng t u th k 19 c lin quan cht ch n ngnh d-c l (nghin cu tc dng ca thuc ln c th). c hc l khoa hc ca cc nh h-ng c ca ho cht ln cc c th sng. N bao gm cc cht nh-: dung mi hu c, kim loi nng, thuc tr su, m phm, cc thnh phn trong thc n, cc cht ph gia thc phm (Textbook on Toxicology). c hc l khoa hc v cht c, l ngnh khoa hc c bn v ng dng. c hc l mn khoa hc xc nh cc gii hn an ton ca cc tc nhn ho hc. (Casarett v Doull 1975). c hc -c nh ngha bi J.H. Duffus nh- l mn khoa hc nghin cu v mi nguy him thc s hoc tim tng th hin nhng tc hi ca cht c ln cc t chc sng. Cc h sinh thi: v mi quan h gia cc tc hi vi s tip xc, v c ch tc ng, s chun on, phng nga v cha tr ng c. Tm li, c hc l mn khoa hc nghin cu v nhng mi nguy him ang xy ra hay s xy ra ca cc c cht ln c th sng. 1.2. Phn lo i

Hai khi nim c hc mi tr-ng (environmental toxicology) v c hc

sinh thi (ecotoxicology) rt gn nhau trong i t-ng nghin cu v mc ch. i khi ng-i ta ng nht chng. c hc mi tr-ng l mt ngnh nghin cu quan h cc tc cht c hi trong mi tr-ng t nhin (ngun gc, kh nng ng dng, s xut hin, o thi, hu dit ) v ph-ng thc hot ng ca chng trong mi tr-ng. c hc mi tr-ng h-ng v mi quan h gia tc cht, cu trc ca tc cht nh h-ng c hi ca chng i vi cc c th sng. c hc sinh thi l ngnh khoa hc quan tm n cc tc ng c hi ca cc tc nhn ho hc v vt l ln cc c th sng. c bit l tc ng ln cc qun th v cng ng trong h sinh thi. Cc tc ng bao gm: con -ng xm nhp ca cc tc nhn ho l v cc phn ng gia chng vi mi tr-ng (Butler, 1978). Mc tiu chnh ca c hc sinh thi l to ra nhng chun mc ban u thit lp tiu chun cht l-ng mi tr-ng, nh gi v d on nng trong mi tr-ng, nguy c cho cc qun th t nhin (trong c c con ng-i) b tc ng mnh bi s nhim mi tr-ng. C mt s s khc nhau c bn gia c hc v c hc sinh thi. c hc thc nghim th-ng tin hnh th nghim trn ng vt c v v cc s li dng -a ra cc gii hn an ton ch cho mt mc tiu tip cn, l con ng-i. Ng-c li mc tiu ca c hc sinh thi l bo v ton b sinh quyn, bao gm hng triu loi khc nhau, -c t chc theo qun th, cng ng, cc h sinh thi lin h vi nhau qua nhng mi t-ng tc phc tp. Mc ch ca c hc l bo v sc kho con ng-i trong cng ng mc tng c th. Cn mc ch ca c hc sinh thi khng phi l bo v tng c th m bo tn cu trc v chc nng ca cc h sinh thi. 2. Ch t 2.1. c Khi ni m

Cht c (cht nguy hi) l bt c loi vt cht no c th gy hi ln ti c th sng v h sinh thi, lm bin i sinh l, sinh ho, ph v cn bng
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sinh hc, gy ri lon chc nng sng bnh th-ng, dn n t rng thi bnh l hoc gy cht. Tt c mi cht u c th l cht c, ch c iu liu l-ng/nng ca chng s quyt nh chng c phi l cht c hay khng. Nh- vy tt c cc cht u c th l cht c tim tng. Theo J.H.Duffus "mt cht c l cht khi vo hoc to thnh trong c th s gy hi hoc git cht c th ". 2.2. Phn lo i a. Phn loi theo c tnh sinh hc: cht c c th l cht c v c th l c t c cht (toxicant) ch vai tr tc nhn ha hc gy c ca n c t (toxin) ch vai tr v bn cht sinh hc ca c cht b. Phn loi theo bn cht c bn cht (Natural toxicity) c nhng cht c vi mt liu l-ng rt nh cng gy c. c liu l-ng (Dose toxicity) l nhng cht mt liu l-ng nh khng gy c thm ch cn l dinh d-ng. Nh-ng khi v-t qu mt liu l-ng nht nh i vi mt sinh vt trong mt thi k nht nh s gy hiu ng c. Nh- vy tt c cc cht u l cht c tim tng c. Phn loi theo tim nng hot tnh Tc nhn gy c gm cc tc nhn ha hc ( t nhin, nhn to, hu c, v c); tc nhn vt l (tc nhn c th, bc x, vi sang); tc nhn sinh hc (c t ca vi khun, nm, thc vt, ng vt). Tc nhn gy c tim tng (Potential toxicity) Tc l chng c kh nng gy ng c cho sinh vt nh-ng hi ti ch-a th hin. N ch biu hin c tnh khi c iu kin mi tr-ng thch hp.
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Tc nhn gy c hot tnh (Actual toxicity) Tc cc tc nhn gy c ang dng hot ng, th hin tnh c, gy hi cho c th sinh vt. d. Phn loi theo dng, th tn ti Cc dng th hin ca cc tc nhn gy c c th l khng kh, n-c, thc phm, d-c phm, m phm v sn phm tiu th qua tip xc da. e. Phn loi theo tnh nng Dng cp tnh: nguy cp, c th gy cht tc thi, ngn hn, th-ng i vi liu cao hoc nng cao v s t ng-i b nh h-ng nh- khi lm ha cht, thot cht c hi ra khng kh. Dng mn tnh: m tn ti trong c th sinh vt v qun th, di hn, th-ng i vi liu l-ng v nng thp, xy ra cho s ng-i ng hn hoc rt lu (th-ng i vi liu l-ng v nng rt nh, nhiu ng-i mc phi nh- tr-ng hp nhim c thc phm, nhim kim loi nng hoc nhim n-c). Cn c th phn theo nhin cch khc nhau na ty theo mc ch nghin cu S nhim c c th xy ra trong nh, ni lm vic hoc bt c ni no. 3. Tnh c 3.1. Khi nim L tc ng ca cht c i vi c th sng. N ph thuc vo nng ca cht c v qu trnh tip xc. Kim tra tnh c l tin hnh nhng xt nghim -c tnh nhng tc ng bt li ca cc tc nhn ln cc t chc c quan trong c th trong iu kin tiu chun. 3.2. c tr-ng ca tnh c

Trong mi tr-ng c nhiu c cht cng tn ti th tnh c s thay i. Phn ng thu -c c th khuch i c (1+1=2), thm ch khuch i gp bi (1+1>5). Cng c th mang tnh tiu c (1+1<1 nay 1+1=0) Tnh c ca mt cht tc ng ln cc c quan khc nhau th khc nhau. Tnh c ca cc cht khc nhau tc ng ln cng mt c quan trong c th th khc nhau. Mi cht c c mt ng-ng gy c ring i vi mi tc ng trn c th th khc nhau. Mi cht c c mt ng-ng gy c ring i vi mi tc ng trn c th. Liu l-ng cht c v-t qua ng-ng chu ng ti a ca c th, c th gy cht. VD: SO2 0,03 mg/m3: kch thch mi: 3mg/m3: ho: 30mg/m3: cht Tnh c tng theo liu l-ng cht c C 2 dng nhim c: cp tnh v mn tnh 4. c cp tnh v c tnh mn 4.1. c tnh cp: L tc ng gy cht mt nhm sinh vt sau mt thi gian tip xc ngn (24h - 96h) vi mt tc cht c. Th-ng xy ra khi nng tc cht c hi cao nn s c th b nhim c khng ln. nh gi c tnh cp v ng-ng c ng-i ta dng cc i l-ng sau LD50 (median lethal dose): liu l-ng gy cht 50% s sinh vt th nghim. Th-ng p dng cho nhm sinh vt trn cn. n v mg/kg ng vt. LC50 (median lethal concentration) nng gy cht 50% sinh vt th nghim, th-ng p dng nh gi c tnh ca cht c dng lng, ho tan trong n-c hay nng hi, bi trong khng kh nhim. n v mg/l dung dch c.
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Ng-i ta th-ng dng cc ch s thi gian i km vi gi tr LD, LC chng hn nh- LD50/24h hay LC50/48h ch khong thi gian i t-ng th nghim b cht. Nu nh h-ng gy c ch cc chc nng sinh hc quan trng th nng cht c t-ng ng c 50% p ng gi l IC50 (median inhibition concetraion) EC50 (effective concentration)/ED50 (effective dose): nng /liu l-ng cht c gy ra cc nh h-ng sinh hc khc nhau cho 50% i t-ng th nghim. TDx nu mt liu ho cht ch gy tc ng bt li n sc kho ca X% sinh vt th nghim ch khng gy cht th l cht c v -c c tr-ng bi i l-ng TD. LT50 (lethal time) thi gian cn thit 50% vt th nghim b nhim c v cht. Nghin cu ny i hi khng ch cc iu kin v tc cht c, nng / liu l-ng, thi gian tc ng v cc iu kin th nghim khng i. T chc Y t th gii (WHO) da vo gi tr LD50 phn loi c tnh ca c cht. Gi tr LD50 ca mt cht cng nh, c tnh ca cht cng cao. C nhiu quy -c phn loi cht c da vo LD50 ca chng nh- sau Nhm I: rt c, LD50 < 100 mg/kg Nhm II: c cao, LD50 = 100 -300 mg/kg Nhm III: c va, LD50 = 300 1000 mg/kg Nhm IV: c t, LD50 > 1000 mg/kg Trong mi tr-ng n-c, c tnh ca ha cht i vi thy sinh -c nh gi bi LC50. Gi tr ny cng thp, c tnh cng cao.
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Nu giai on cui th nghim khng gy cht ng vt th nghim m cc nng (liu l-ng) th nghim dn n cc tc ng khc nhau i vi 50% vt th nghim gi l liu nh h-ng 50% ED50 (median effective dose) hay nng 50% (Rand v Petrocelli, 1985) Gi tr EC50 hay LD50 th-ng -c thc hin trong vng 24 n 96 gi v -c th nghim trn mt loi cht nht nh. V d nh- th nghim trn ngun n-c o h, thuc bo vt thc vt, mt loi cht in hnh trong n-c thi cng nghip... xc nh nng v ng-ng an ton. Thi gian cng th-ng -c ghi cng vi liu l-ng gy cht : LD50 48h hay EC50 24h. Mt ph-ng php nghin cu khc l do thi gian cn thit xc nh 50% sinh vt th nghim c khn ng c bit (VD nh- cht). Ph-ng php ny i hi phi gi mc ca cc tc ng chn lc lun khng i v theo di trong thi gian th nghim xc nh thi im 50% vt th nghim cht, hay 50% vt th nghim sng st. Thi gian gi l median lethal time LT50 thi gian cht 50%. Do t vong l mt yu t d cc nh trong cc phn hi nn th nghim c cp tnh thng th-ng nht l th nghim nng gy cht cp tnh; trong , 50% phn hi l thng s ch v hm l-ng c t s dng v 96h (hay t hn) l thi gian ng c tiu chun (do n l thi gian cn cho s ng c gy cht cp tnh). Thng s dng cho c cp tnh th-ng -c s dng cho c v cc ng vt khng x-ng ln l 96h hay LC50. Tuy nhin, do t vong khng d xc nh cho cc sinh vt khng x-ng, mt thng s khc, EC50 (nng nh h-ng trung bnh), th-ng -c s dng hn l LC50. Anh h-ng -c s dng -c tnh EC50 cho mt s ng vt khng x-ng sng (chng hn daphnia, u trng rui nhu) l s bt ng, -c xc nh l khng di chuyn. Cc tc ng th-ng -c s dng -c tnh EC50 cho cua, tm bin, tm ng l s bt ng v mt cn bng, -c xc nh l mt kh nng duy tr t- th bnh th-ng. 4.2. c mn tnh
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c tnh mn: do c cht c th tch lu trong c th sng nu th-ng xuyn tip xc nn mt nng nht nh (d-i ng-ng), ch-a gy cht hay nhng nh h-ng bt th-ng (nh- /v nhim c cp) m lu di s gy nhng bnh tt nguy him, gy t bin gen, ung th-, gy nh h-ng ln tnh di truyn hay nh h-ng ln thai nhi. Nhng tc cht c, c kh nng tch lu dn trong c th, c th gy tc hi v lu di nhtrn l cht c c tnh mn tnh. Nhim c mn tnh th-ng do hm l-ng cht c thp v c kh nng tch lu trong cc c quan trong c th. S l-ng c th b nhim c mn th-ng nhiu hn so vi nhim c cp, thi gian tip xc di hn. Nhim c mn th-ng kh pht hin kh xc nh nguyn nhn. Trong nghin cu c tnh mn, th-ng mc tiu l xc nh gi tr ng-ng, hay mc tip xc vi cht c ch-a th gy ra bt c nh h-ng bt li c th nhn thy -c. im cui ca nhim c khng phi l im cht ca vt th nghim nh-ng c nhng nh h-ng kh thy. y chnh l vng gii hn gia mc nh h-ng quan st -c (observed effect level) v mc nh h-ng khng quan st -c (no observed effect level NOEL). NOEL gn xp x vi min ng-ng c mn. NOEC (No obesered effect concentration) t-ng t nh- NOEL n l nng cao nht ca mt cht c khng to ra mt phn ng r rt vt th nghim. Mc nh h-ng thp nht quan st -c, LOEL, l mc tip xc vi cht c t nht m khng gy ra nhng nh h-ng c bit no (xem hnh 1-2). Gi tr ng-ng c th chn l im gia ca NOEL l LOEL. Gi tr ng-ng ch ra s tch bit ca nh h-ng t gi tr nng khng gy nh h-ng. NOAEL/NOAEC (no observed adverse effect level/concentration) liu nng ho cht cao nht khng gy cc nh h-ng bt li cho sinh vt chu tc ng.
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LOAEL/LOAEC (low observed adverse offect level/concentration) liu nng ho cht bt u quan st thy nh h-ng c hi cho SV th nghim.

100
LOEL NOEL

50
Nng (n v tu )

Hnh 1-2: Gin th hin khi nim NOEL v LOEL Trong cc th nghim tm ra c mn tnh, nng ng-ng gy ra cc tc ng c hi ng k th-ng -c gi l nng gy c cc i c th chp nhn -c MATC (maximum allowable toxicant concentration). MATC l nng l thuyt nm trn nng cao nht khng gy ra nh h-ng (NOEC) v nm d-i nng gy c thp nht (LOEC), do NOEC < MATC < LOEC. Trong vic thit lp mi quan h gia c cp tnh v c mn tnh, mt thng s -c -a ra s dng, l yu t p dng (AF application factor), th hin mi quan h gia c tnh cp v c tnh mn. l mt thng s khng th nguyn, thun ty ha hc, -c tnh bng nng ng-ng ca c mn tnh chia cho nng gy c cp tnh. AF = MATC/LC50 Yu t p dng AF -c xem nh- l di nng . V d nu MATC nm trong khong 0.5 - 1mg/l v LC50 = 10mg/l th AF = 0.05 - 0.1 Nu ch-a bit MATC, nh-ng bit NOEC, LOEC v LC50 th AF nm trong khong NOEC/LC50 v LOEL/LC50. Theo l thuyt AF kh n nh cho mt ho cht. Do khi AF ca mt ho cht -c xc nh cho mt loi
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thu sinh th n cng c th p dng cho mt loi khc. L thuyt ny cho php -c tnh v nng c tnh mn ca mt ho cht ln cc loi khng th tin hnh cc th nghim do khng c thng tin v cc yu cu cn thit duy tr i sng sinh vt. C th dng AF tnh MATC ca loi khc vi gi tr c tnh cp. MATC = AF * LC50 Chng hn, AF ca mt ho cht i vi c l t 0.05 - 0.1, AF ny c th p dng tnh MATC ca mt loi gip xc nh- l tm, khi bit LC50 ca n l 1mg/l, MATC ca ho cht ny i vi tm l: MATC = AF*LC50 = 0.05 0.1 * 1mg/l c tnh bn cp: l tc ng ca cht c ln c th lm cho c th phn ng li sau khi tip xc vi cht c trong khong thi gian bng 10% thi gian sng ca ng vt b nhim c cp. 5. Cc yu t nh h-ng ti c tnh Mc gy c ca mt tc cht c hi ln c th sinh vt ph thuc rt nhiu yu t, c mi tr-ng xung quanh ln trng thi ca c th b tc ng, c tr-ng ging loi, gii tnh, s thch nghi, kh nng khng hoc mn cm ca cc c th. * Bn cht ca ho cht: tnh cht ho hc, vt l quyt nh hot tnh sinh hc - Bn cht ho hc ca ho cht quyt nh th th c bit v bn cht lin kt. - Tnh cht ho l v tan trong m s quyt nh tc v phm vi di chuyn qua mng t bo v nng ti c quan tip nhn. Trong qu trnh bin i sinh hc, c th th-ng chuyn i cc ui tan trong m thnh dng d b loi b. * Cc iu kin tip xc.
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- Liu l-ng/nng ti v tr tip xc s quyt nh mc ca s p ng. - Con -ng tip xc rt quan trng, v d khi ht phi methylene chloride s sinh ra cc khi u, nh-ng nu nut n th li khng sinh u. - Thi gian tip xc: ngn gy cc tc hi c th khc phuc, di, gy cc tc hi nguy him, khng th khc phc. V d nhim c ngn alcohol gy mt kh nng lc m ca gan, nh-ng v lu di s gy s gan. * Ging, loi, gii tnh, tui v cc yu t di truyn. - Mt cht c th rt c vi loi ny nh-ng khng h gy tc hi vi loi khc. V d B-naphthamine gy u bng quang ca linh tr-ng, chut chi, ch nh-ng li khng sao chut bch v chut tr. - B phn b tc ng cng khc nhau cc loi khc nhau. V d dibutylnitrosamine gy u gan chut cng v chut lang nh-ng li gy u bng quang v thc qun chut nht. - S khc bit loi c th bao gm khc bit v tr tc ng, s chuyn ho sinh hc, tnh trng sinh l. Tuy vy s khc bit loi mang tnh nh l-ng v s p ng ca cc loi th-ng l ging nhau hn l khc nhau. - Tui tc ca loi b tc ng cng nh h-ng n s nhim c. V d parathiol gy c nhiu cho chut mi sinh hn l chut ln. C s ca s khc bit ny lin quan n kch th-c c th (trng l-ng, din tch b mt, cu to c th, kh nng chuyn ho sinh hc ) - S khc bit v gii tnh cng nh h-ng n p ng. V d khi tip xc vi DDT lu di, chut c nhy cm hn chut ci 10 ln. Chut c nhy cm nht vi tn th-ng h tit niu do hydrocarbon bay hi, sau sinh u thn. S khc bit v gii tnh th-ng xut hin khi tr-ng thnh. C th c l do s iu khin ca hormon. * Tnh trng sc kho khi xy ra s phi nhim (tip xc)
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iu kin dinh d-ng ca c th v tnh trng bnh tt c nh h-ng ti phn ng ca c th vi ho cht. Ch n ung protein v cc nguyn t vi l-ng c th bo v c th chng li cht c. Vi c th ang mc bnh gan phi s kch thch cc tc hi ca cht c ln gan v phi. Cc bnh v thn s nh h-ng ti s bi tit cht c v ko di thi gian tc ng ca chng trong c th. *S c mt cng lc cc ho cht trong c th hoc mi tr-ng khi xy ra s tip xc (cc phn ng cho) Trong s tc cho (t-ng tc hn hp ca mt hay nhiu loi ho cht) gy nn s thay i p ng v mt nh tnh v nh l-ng so vi p ng ring l ca tng loi ho cht. S tip xc v p ng c th l ng thi hoc ni tip. S thay i c tnh c th tng ln hay gim i. 2 loi t-ng tc cho. - Sinh hc: nh h-ng ca ho cht ln s nh v v hot tnh th th ca loi ho cht khc. - Ho hc cc phn ng gia cc loi ho cht to nn cc cht c hot tnh hay mt hot tnh. Cc t-ng tc cho ho hc c th xut hin bn ngoi c th (trong khng kh, n-c, thc phm) hoc bn trong c th lin quan n s nh v sinh hc (bao gm s hp th, phn b, chuyn ho sinh hc, bi tit, ng hc) v hot tnh ca th th. Tc ng ca 2 hay nhiu loi ho cht xy ra mt lc c th: = 7 cc hiu ng ring l hoc > cc hiu ng ring l hoc < cc hiu ng ring l 6. Nguyn l chung: Mi quan h gia nng (liu l-ng) p ng/phn ng ca c th.
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Liu l-ng (dose) l mt n v ca vic tip xc cc tc nhn gy hi ln mt c th sng. N -c th hin qua n v trng l-ng (hay th tch) trn th trng 1 (mg, g, ml/kg c th) hoc trng l-ng (hay th tch) trn mt n v din tch b mt tip xc ca c th (mg, g, ml/m2 b mt c th). Nng trong khng kh c th -c biu din qua n v ca khi l-ng hoc th tch trn mt th tch khng kh nh- ppm, hay mg, g/m3 khng kh. Nng trong n-c: mg/l = ppm (part per million) hay ug/l = ppb ( part per billion) S p ng/phn ng (Response) l phn ng ca c th hay mt hoc mt vi b phn ca c th sinh vt i vi mt kch thch ca cht c (Duffus). S kch thch c th gm nhiu dng v c-ng ca p ng th-ng lin quan n c-ng kch thch; kch thch cng mnh th s p ng trong c th cng ln. Khi cht kch thch l mt ho cht th p ng th-ng l hm s ca liu l-ng v mi quan h ny -c gi l mi quan h liu l-ng - p ng. Mt tc ng c hi, gy tn th-ng, hoc c c tnh l mt s thay i v hnh thi, sinh l, s pht trin, sinh tr-ng v tui th ca mt c th, gy ra s suy yu ca cc hot ng c bn hoc suy yu kh nng khng li nhng cht c, hoc tng s mn cm vi tc ng c hi ca mi tr-ng. C quan tip nhn (receptor) l mt im nhy cm hoc d p ng, nm ti t bo chu tc ng ca tc nhn kch thch. N cn -c gi l th th. Cc th th trn b mt -c gi l loi I. Trong t bo cht gi l loi II, trong nhn gi l loi III. Kt qu ca t-ng tc gia tc nhn v c quan tip nhn l s khi u ca mt chui cc s kin sinh ho v nh im l p ng ta nhn thy. S p ng lin quan n s th th tham gia v thi gian t-ng tc gia ho cht v th th. S th th tham gia li lin quan n i lc ca chng vi tc nhn nng ca ho cht, thi gian tc ng. S p ng ph thuc vo s phc hp ho cht - th th -c to thnh.
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Cc th th phi lin kt vi ho cht, tri qua mt s phn ng to ra p ng. Khi liu ho cht tng ln, s lin kt vi th th cng tng ln, s p ng cng tng. Lin kt gia ho cht v c quan tip xc c th l ng ho tr, hydrogen, hay lc Van der Walts. Bn cht ca lin kt trn s nh h-ng n thi gian tn ti phc ho cht - c quan tip nhn v thi gian sinh ra cc hiu ng. Lin kt ng ho tr th t-ng i khng thun nghch (khng phc hi -c) cn lin kt ion, hydro v Van der Walts th thun nghch (phc hi -c). mt c quan tip nhn c th gy ra mt p ng th u tin n phi gn vi ho cht tc ng. Lin kt ny th-ng l lin kt khng ng ho tr v thun nghch. Tip heo, cc c quan tip nhn -c hot ho, qu trnh ny -c gi l chuyn ho tn hiu, to ra cc hot tnh ni lc. Sau l hng lot cc hin t-ng v sau cng l to ra p ng ca c th. Qu trnh ny gi l qu trnh lin kt gia c quan tip nhn - p ng. Con -ng xm nhp ca cc ho cht vo c th con ng-i v ng vt qua ming (tiu ho), -ng th (h hp) v qua da (tip xc cc b) Ho cht tip xc vi c th, i vo mu. Trong mu, ho cht c th tn ti dng t do hay lin kt vi protein (th-ng vi albumin). Ho cht c th ri mu n cc c quan ni -c chuyn ho sinh hc (v d gan), hay tch tr (cc m m) hay bi tit (thn) hay pht ra mt p ng (no). Ho cht phi v-t qua lp mng t bo, qua cc lp phospholipit bng mt qu trnh vn chuyn b ng (khng tiu hao nng l-ng) hay vn chuyn ch ng (tiu hao nng l-ng). C nhiu loi p ng -c sinh ra sau cc t-ng tc ho cht - b phn tip nhn. N bao gm s thay i hnh dng trng thy hoc khng trng thy, hoc nhng thay i trong cc chc nng sinh l hoc sinh ho. Cc p ng c th khng c hiu nh- s vim nhim, hoi t c th c hiu nh- t bin gen, khuyt tt, ung th-. Cc p ng c th nhn thy
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ngay hoc sau mt thi gian, c th mt hoc nhiu b phn, c th c li hoc c hi kt qu cui cng c th l kch thch hoc km hm. Tuy nhin, bn cht ca t bo kh ng b ho cht lm bin i, v d t bo c th kh ng b bin i thnh t bo bi tit. S bin i c bn hay tc ng c hi mc t bo l cn bng ni sinh b dch chuyn Mi quan h liu l-ng p ng biu din s lin quan gia tc dng v p ng quan st -c ti mt qun th no y. Chng -c th hin trn th vi ln ca p ng nh- bnh th-ng v liu l-ng -c din t theo dng s hc hoc logarit.
Khong tc ng Khong gia tng tc ng Khong tc ng ti a

100

50
EC50

log dose (mg/kg)

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