TRNG I HC BCH KHOA H NI VIN KHOA HC V CNG NGH MI TRNG --------- - - --------

Bi ging

C HC MI TRNG

GV: ThS. on Th Thi Yn

H Ni - 2006 CHNG 1: GII THIU CHUNG

1. c hc (Toxicology) L ngnh hc nghin cu v kha cnh nh tnh v nh lng 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 hng ca chng. Ngnh c hc ch bt u c xy dng t u th k 19 c lin quan cht ch n ngnh dc l (nghin cu tc dng ca thuc ln c th). c hc l khoa hc ca cc nh hng 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. Mt s nhm ca c hc - c hc mi trng - c hc ca thuc tr su - c hc thu sinh - c hc thn kinh 2. c hc mi trng (environmental toxicology) 2 - c hc cng nghip - c hc dinh dng - c hc lm sng

Hai khi nim c hc mi trng (environmental toxicology) v c hc sinh thi (ecotoxicology) rt gn nhau trong i tng nghin cu v mc ch. i khi ngi ta ng nht chng. c hc mi trng l mt ngnh nghin cu quan h cc tc cht c hi trong mi trng t nhin (ngun gc, kh nng ng dng, s xut hin, o thi, hu dit) v phng thc hot ng ca chng trong mi trng. c hc mi trng hng v mi quan h gia tc cht, cu trc ca tc cht nh hng 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 trng (Butler, 1978). Mc tiu chnh ca c hc sinh thi l to ra nhng chun mc ban u thit lp tiu chun cht lng mi trng, nh gi v d on nng trong mi trng, nguy c cho cc qun th t nhin (trong c c con ngi) b tc ng mnh bi s nhim mi trng. C mt s s khc nhau c bn gia c hc v c hc sinh thi. c hc thc nghim thng 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 ngi. Ngc 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 tng tc phc tp. Mc ch ca c hc l bo v sc kho con ngi 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. 3. Cht c, tnh c 3

3.1. Cht c 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 sinh hc, gy ri lon chc nng sng bnh thng, dn n t rng thi bnh l hoc gy cht. Liu lng hoc nng ca mt tc nhn ho hc hoc vt l s quyt nh n c phi l cht c hay khng. V 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 ". Tt c mi th u c th l cht c, ch c iu liu lng s quyt nh mt cht khng phi l cht c (Everything is a poison. Nothing is without poison. Theo dose only makes. That something is not a poison - Paracelsus bc s Thu s, 1528) 3.2. Tnh c 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. 4. Phn loi. C rt nhiu c s khc nhau phn loi cc tc nhn c, tu theo mc ch nghin cu v i tng nghin cu. C th k mt vi cch phn loi nh sau: - Phn loi theo ngun gc cht c. - Phn loi theo nng , liu lng. - Phn loi theo bn cht ca cht c. - Phn loi theo mi trng tn ti cht c (t, nc, khng kh) - Phn loi theo ngnh kinh t, x hi: c cht trong nng nghip, cng nghip, y t, qun s

- Phn loi theo tc dng sinh hc n thun (tc dng kch ng, gy ngt, d ng, ung th, t bin gen, qui thai) - Phn loi da vo nguy c gy ung th ngi. Theo bn cht ca cht c cc loi tc nhn c th gy c gm cc loi ho cht (t nhin v tng hp, hu c v v c), tc nhn vt l (bc x, vi sng) tc nhn sinh hc c t ca nm mc, vi khun, ng, thc vt. Da trn nhng chng c r rng nghin cu trn cc ho cht c kh nng gy ung th trn ngi, IARC (c quan nghin cu ung th quc t ) phn cc ho cht theo 4 nhm c kh nng gy ung th. Nhm 1: Tc nhn l cht gy ung th ngi Nhm 2A: Tc nhn c th gy ung th ngi Nhm 2B: Tc nhn c l gy ung th ngi Nhm 3: Tc nhn khng th phn loi da trn tnh gy ung th ngi Nhm 4: Tc nhn c l khng gy ung th ngi Vic phn nhm cc yu t mang tnh khoa hc da trn nhng thng tin, s liu tin cy, chng c thu c t nhng nghin cu ngi v ng vt th nghim. 5. Nguyn l chung: Mi quan h gia nng (liu lng) p ng/phn ng ca c th. Liu lng (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 lng (hay th tch) trn th trng 1 (mg, g, ml/kg c th) hoc trng lng (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 lng hoc th tch trn mt th tch khng kh nh ppm, hay mg, g/m3 khng kh. Nng trong nc: mg/l = ppm hay ug/l = ppb.

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 cng ca p ng thng lin quan n cng 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 thng l hm s ca liu lng v mi quan h ny c gi l mi quan h liu lng - p ng. Mt tc ng c hi, gy tn thng, hoc c c tnh l mt s thay i v hnh thi, sinh l, s pht trin, sinh trng 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 trng. 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 tng 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 ap ng lin quan n s th th tham gia v thi gian tng 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. 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 hng 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 tng 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 thng 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 tng 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 ngi 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 (thng 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 vt qua lp mng t bo, qua cc lp phospholipit bng mt qu trnh vn chuyn b ng (khng tiu hao nng lng) hay vn chuyn ch ng (tiu hao nng lng). C nhiu loi p ng c sinh ra sau cc tng 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 ngay hoc sau mt thi gian, c th mt hoc nhiu b phn, c th c li hoc c hikt qu cui cng c th l kch thch hoc km hm. Tuy nhin, bn cht i thnh ca t bo khng b ho cht lm bin i, v d t bo c th khng 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 lng 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 thng v liu lng c din t theo dng s hc hoc logarit.
Khong tcng Khonggia tngtc ngca Khong t c ng t i a

100

50

EC50

logdose (mg/kg)

6. c trng ca tnh c - Trong mi trng 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 ngng gy c ring i vi mi tc ng trn c th th khc nhau. - Mi cht c c mt ngng gy c ring i vi mi tc ng trn c th. Liu lng cht c vt qua ngng chu ng ti a ca c th, c th gy cht. V d: SO2 0,03 mg/m3: kch thch mi: 3mg/m3: ho: 30mg/m3: cht Tnh c tng theo liu lng cht c - C 2 dng nhim c: cp tnh v mn tnh 7. c tnh cp, c tnh mn

Ref: /3/p.80-90: /5/p.31, p.96 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. Thng xy ra khi nng tc cht c hi cao nn s c th b nhim c khng ln. nh gi c tnh cp v ngng c ngi ta dng cc i lng sau LD50 (median lethal dose): liu lng gy cht 50% s sinh vt th nghim. Thng 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, thng p dng nh gi c tnh ca cht c dng lng, ho tan trong nc hay nng hi, bi trong khng kh nhim. n v mg/l dung dch c. Ngi ta thng 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 tng th nghim b cht. Nu nh hng gy c ch cc chc nng sinh hc quan trng th nng cht c tng ng c 50% p ng gi l IC50 (median inhibition concetraion). EC50 (effective concentration)/ED50 (effective dose): nng /liu lng cht c gy ra cc nh hng sinh hc khc nhau cho 50% i tng 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 trng bi i lng 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 lng, thi gian tc ng v cc iu kin th nghim khng i.

LD50 (con ng Mc c Rt c c C hi phi nhim: ming, chut, mg/ kg BW) 25 25 - 200 200 - 2000

LD50 (con ng phi nhim: da chut hoc th mg kg BW) 50 50 - 400 400 - 2000

LD50 (con ng phi nhim: h hp, chut - mg lit 4h) 0,25 0,251 1-5

Ngun: Worksafe Australia, 1994 c tnh mn: do c cht c th tch lu trong c th sng nu thng xuyn tip xc nn mt nng nht nh (di ngng), cha gy cht hay nhng nh hng bt thng (nh /v nhim c cp) m lu di s gy nhng bnh tt nguy him, gy t bin gen, ung th, gy nh hng ln tnh di truyn hay nh hng ln thai nhi. Nhng tc cht c, c kh nng tch lu dn trong c th, c th gy tc hi v lu di nh trn l cht c c nh mn tnh. Nhim c mn tnh thng do hm lng cht c thp v c kh nng tch lu trong cc c quan trong c th. S lng c th b nhim c mn thng nhiu hn so vi nhim c cp, thi gian tip xc di hn. Nhim c mn thng kh pht hin kh xc nh nguyn nhn. Trong nghin cu c tnh mn, thng mc tiu l xc nh gi tr ngng, hay mc tip xc vi cht c cha th gy ra bt c nh hng bt li c th nhn thy c. im cui ca nhim c khng phi l im cht ca vt th nghim nhng c nhng nh hng kh thy. y chnh l vng gii hn gia mc nh hng quan st c (observed effect level) v mc nh hng khng quan st dc (no observed effect level - NOEL). NOEL gn xp x vi min ngng c mn. NOEC tng 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 hng thp nht quan st c, LOEL, l mc tip xc vi cht c t nht m khng gy ra nhng nh hng c bit no

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(xem hnh 1-2). Gi tr ngng c th chn l im gia ca NOEL l LOEL. Gi tr ngng ch ra s tch bit ca nh hng t gi tr nng khng gy nh hng. NOAEL/NOAEC (no observed adverse effect level/concentration) liu nng ho cht cao nht khng gy cc nh hng bt li cho sinh vt chu tc ng. LOAEL/LOAEC (low observed adverse offect level/concentration) liu nng ho cht bt u quan st thy nh hng c hi cho SV th nghim.

100
LOEL NOEL

50

Nng(nv tu)

Hnh 1-2: Gin th hin khi nim NOEL v LOEL

Khi nghin cu trn c, gi tr ngng cng c gi l nng cht c cc i c th chp nhn c MATC. Do chi ph cao khi tin hnh cc th nghim c tnh trong thi gian di nn Mount v Stephan (1967) ngh dng mt h s p dng (AF) th hin mi quan h gia c tnh cp v c tnh mn: AF = MATC/LC50 AF l mt thng s khng th nguyn, 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 cha bit MATC, nhng 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 thu sinh th n cng c th p dng cho mt loi khc. L thuyt

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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 . MATC 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. 8. Cc yu t nh hng n c tnh Mc gy c ca mt tc cht c hi ln c th sinh vt ph thuc rt nhiu yu t, c mi trng xung quanh ln trng thi ca c th b tc ng, c trng 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 d chuyn qua mng t bo v nng ti c quan tip nhn. Trong qu trnh bin i sinh hc, c th thng chuyn i cc ui tan trong m thnh dng d b loi b. Cc iu kin tip xc. - Liu l ng/n ng t i v tr ti p xc s quy t nh m c c a s p ng.

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- Con ng tip xc rt quan trng, v d khi ht phi methylene chloride s sinh ra cc khi u, nhng 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, nhng 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 nhng khng h gy tc hi vi loi khc. V d B-naphthamine gy u bng quang ca linh trng, chut chi,ch nhng li khng sao chut bch v chut ch. - B phn b tc ng cng khc nhau cc loi khc nhau. V d dibutylnitrosamine gy u gan chut cng v chut lang nhng 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 ging mang tnh nh lng v s p ng ca cc loi thng l ging nhau hn l khc nhau. - Tui tc ca loi b tc ng cng nh hng n pngs. 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 thc c th (trng lng, din tch b mt, cu to c th, kh nng chuyn ho sinh hc) - S khc bit v gii tnh cng nh hng 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 thng h tit niu do hydrocarbon bay hi, sau sinh u thn. S khc bit v gii tnh thng xut hin khi trng thnh. C th c l do s iu khin ca hormon. Tnh trng sc kho khi xy ra s phi nhim (tip xc) iu kin dinh dng ca c th v tnh trng bnh tt c nh hng ti phn ng ca c th vi ho cht. Ch n ung protein v cc nguyn t vi lng c th bo v c th chng li cht c. S

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thiu ht vitamin c th ko di thi gian tc ng ca ho cht. 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 hng 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 trng khi xy ra s tip xc (cc phn ng cho) S trong tc cho (tng tc hn hp ca mt hay nhiu loi ho cht) gy nn s thay i p ng v mt nh tnh v nh lng 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 tng tc cho. - Sinh hc: nh hng 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 tng tc cho ho hc c th xut hin bn ngoi c th (trong khng kh, nc, 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: = cc hiu ng ring l hoc > cc hiu ng ring l hoc < cc hiu ng ring l S thch nghi, chng chu c coi nh l s p n suy gim i vi mt ho cht sau khi tip xc mt nng di ngng. C s cho s chng chu l vic to ra cc enzym thch hp tham gia vo s chuyn ho sinh hc ca ho cht. Cu hi n tp:

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1. nh ngha c hc, c hc mi trng, cht c, nh hng c hi? 2. Bn cht ca tng tc gia tc nhn ho hc v sinh hc l g? 3. Th th l g? Bn cht ca mi quan h gia ho cht v th th l g? C phi tt c cc mi quan h s gy ra p ng hay khng? 4. Cc th th to ra p ng th no? 5. Liu ngng l g? Gi tr LD50, LD50 l g? 6. Nhng yu t no nh hng ti p ng? 7. Cc khc bit ch yu gia c hc v c hc sinh thi l g? 8. ngha ca NOEL trong c hc sinh thi?

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CHNG 2: CHT C TRONG MI TRNG 1. Gii thiu cc loi cht c trong mi trng. 1.1. Cc cht c trong mi trng khng kh. 1.2. Cc cht c trong mi trng nc. 1.3. Cc cht c trong mi trng t. 2. Tc ng sinh thi ca cht c. 2.1. Qu trnh lan truyn ca cht c trong mi trng. 2.2. Tc ng ca cht c trong mi trng khng kh. 2.3. Tc ng ca cht c trong mi trng nc. 2.4. Tc ng ca cht c trong mi trng t.

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CHNG 3: PHNG THC CHT C VO C TH 1. Gii thiu Phn ng ca c th (response) i vi mt cht c ho hc ph thuc trc tip vo liu lng ho cht c chuyn n b phn tip nhn. Cn hiu r s tip xc (s phi nhim) v liu lng. - S tip xc (exposure): l vic c mt ca mt cht l i vi c th (xenobiotic) trong c th sinh vt. n v ca s tip xc l ppm hoc n v khi lng/m3 khng kh, lt nc, kg thc phm. S tip xc qua da thng biu din theo nng /din tch b mt c th. - Liu lng (dose): l lng cht ngoi sinh (cht l i vi c th) tip cn b phn ch v gy ra phn ng ho hc gia cht c v cc hp cht ni sinh trong b phn ch . n v biu din liu lng thng l khi lng cht c/kg trng lng c th hay m2 b mt c th. Khi xy ra tip xc cht c phi t mi trng vo c th, vn chuyn ti t bo qua b mt c th (da, phi, ng tiu ho), qu trnh gi l hp th hay ni mt cch c th hn l hp th t mi trng vo mu hoc h bch cu. T h thng tun hon, cc cht c i n mt vi hay tt c cc c quan trong c th. Qu trnh ny gi l phn b. S vn chuyn cht c t h tun hon vo cc m cng gi l s hp th. N tng t nh s vn chuyn ho cht t b mt c th n h tun hon. V th, ta phi xt c 2 kiu hp th. 1/ Chuyn t b mt c th vo mu (hay bch huyt). 2/ Chuyn t mu vo cc m. S loi b cht c khi c th gi l bi tit. Qu trnh ny thc hin c nh cc hot ng c bit ca thn (to ra nc tiu), gan (to ra mt) v phi (th ra cc hp cht bay hi).

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2. Hp th Qu trnh vn chuyn ca ho cht t ni tip xc s c chuyn vo h tun hon .

Cht c b mt c th (VD: da, phi h tun hon (mu, bch cu))

Cht c phi i mt s mng t bo trc khi i su vo c th n cc t chc c quan 2.1. Mng t bo: Hu ht cc trng hp, cht c phi xuyn qua mng t bo, i n v tr mc tiu to ra phn ng sinh hc. Hnh v Hnh 3-1: Cu trc lp mng t bo Hnh 3-2 l s mt t bo ng vt. Mt phn ca mng t bo ny c phng i hnh 3-3, biu din cc phospholipid v protein cu to nn mng t bo. Hnh v Hnh 3-2: Mt t bo ng vt Hnh v Hnh 3-3: Mt phn nh mng t bo ng vt phng to Phn mng t bo c cu trc bi cc si phospholipid v protein. Cc phn t phospholipid c biu din bng cc hnh trn c ui di, cc phn t protein c i din bng cc si zic zc mang in tch + v Hnh 3-3 minh ha mt phn t phospholipid l phosphatidylcholine distearate (trong thc t c rt nhiu loi phn t tng t trong mng t bo) v u phn t phn cc, tan trong nc, ui khng phn cc, tan trong m. Hnh v

18

CH3 | CH3-N-CH3 | CH2 | O | O-P=O | O | CH2 | CH2 O | |O = C | (H2C) 16 | H3C O | C=O | (CH2)16 | CH3

Phn u phn t phospholipid (phn cc tan trong nc)

ui phn t phospholipid (khng phn cc tan trong m)

Hnh 3-4: Cu trc ca mt loi phn t phospholipit Cu trc ny c ngha rt quan trng trong hp th v bi tit. N nh mt lp mng du trong mi trng nc. Cc protein hnh cu trong mng di chuyn t do dc theo b mt ca mng. Mt s phn t protein i xuyn qua mng to mt knh a nc trong mng lipid. Cc phn t nh tan trong nc v cc ion c th khuyt tn qua mng theo knh ny, cn cc phn t tan trong m li khuych tn qua phn phospholipid ca mng. Cc phn t tan trong nc, kch thc ln khng th d dng i qua mng m phi thng qua cc c ch vn chuyn c bit. Protein c th i qua, c trong bi tit ln hp th.

19

Do phn ln din tch mng t bo l phospholipid nn cc phn t a m vt qua mng nhanh hn. Cc phn t a nc, kch thc, ch xuyn qua mng nh knh protein. Con ng chnh cc c cht trong mi trng i vo h tun hon l thng qua da, phi v h tiu ho. Tc hp th. - Tc hp th s tng khi nng cht c trong mu hoc cc c quan tng. - S hp th ho cht qua mng t bo ph thuc kch thc phn t, h s phn b octanol/nc K (K = nng ho cht trong pha octanol/ nng cng ho cht trong nc). C ch hp th: - Khuyt tn th ng. - Lc. - Vn chuyn c bit. - Vch xp. Hu ht cc cht c vt qua t bo bi c ch khuyt tn th ng n gin ny. Tc khuyt tn ph thuc vo: - Gradient nng ca cht c khi qua mng. - Kh nng tan trong du: dng ion, tan t trong du: dng khng ion, tan nhiu trong du. i vi acid: pKa - pH = log (khng ion/ion). i vi bazz: pKa - pH = log (ion/khng in). v d i vi acid benzoic (pKa = 4) v anilin (pHa = 5).
pH
1 2 3 4 5 6 7

Benzoi c COOH

% Nonioniz
99. 9 99 90 50 10 1

% Aniline Nonioniz NH3+

0. 1 1 10 50 90 99

COO_

20

NH2

0. 1

FOR WEAK ACIDS [nonionized ] pKa - pH = log [ionized ]

Benzoic acid pKa 4 Stomach pH 2 4 - 2 = log

[nonionized ] [ionized ] [nonionized ] 2 = log [ionized ] [nonionized ] 102 = log [ionized ] [nonionized ] 100 = log [ionized ]

Ratio favors absorption Intestine pH 6

[nonionized ] [ionized ] [nonionized ] -2 = log [ionized ] [nonionized ] 10-2 = [ionized ] [nonionized ] 1 = [ionized ] 100

4 - 6 = log

21

FOR WEAK BASES [ionized ] pKa - pH = log [nonionized ]

Aniline pKa 5 Stomach pH 2

5 - 2 = log [nonionized ] 3 = log [nonionized ] 103 = log [nonionized ] 100 = log [nonionized ] Intestine pH 6 5 - 6 = log [nonionized ] -1 = log [nonionized ] 10-1 = [nonionized ]
[ionized ] 1 = 10 [nonionized ] [ionized ] [ionized ] [ionized ] [ionized ] [ionized ] [ionized ]

[ionized ]

Ratio favors absorption

22

2.2. Hp th c cht qua da Cc hp cht dnh trn da c th c 4 phn ng sau: - Da v cc t chc m c tc dng nh hng ro cn chng li s xm nhp ca c cht gy tn thng c th. - c cht c th phn ng vi b mt da v gy vim da, d ng. - c cht xm nhp qua da, kt hp vi cc t chc protein gy cm ng da. - c cht xm nhp vo c th qua da vo mu. C 2 ng xm nhp qua da l qua lp mng t bo biu b, qua tuyn b v cc tuyn khc. Hnh v tr18 (cu trc lp da) Hp th di da: Cht c lp biu b epidermis lp h b demis Lp biu b: l lp ngoi cng ca da gm cc t bo phng khng nhn hoc cht cha keratin (protein si). Cc t bo ny bao ly nhau to thnh lp mng bn vng, do dai, cc si keratin c ph mt lp m mng. Lp biu b hn ch tc hp th cht c. Cc cht c phn cc khuych tn qua b mt ngoi ca cc si leratin ca lp sng hydrat ho. Cc cht c khng phn cc ho tan v khuyt tn qua mng lp lipid khng thm nc gia cc si motein. Tc khuyt tn tng quan vi ho tan trong lipid v t l nghch vi khi lng phn t. Trc khi vo h tun hon, cht c phi i qua mt s lp t bo. Tc vn chuyn ny ph thuc dy ca da, tc dng mu hiu qu ca huyt thanh. T bo bch cu v cc yu t khc. Tc hp th nhanh, nng c cht trong mu cng cao. 2.3. Hp th c cht qua phi. Cc cht c tip xc khi ht th s hp th qua phi. Cc kh c tan c trong nc, khi vo phi s ho tan trong dch nhy ca ng h

23

hp v c th tch t , gy tc hi ngay ti khu vc . Cc kh tan trong m khuyt tn qua mng ph nang vi tc ph thuc h s phn b m/nc K50 v kh nng ho tan ca kh trong mu. Phi ngi c din tch tip xc rng, ngoi ra li c mt h thng mao mch phong ph dng mu i qua phi nhanh, to iu kin thun li cho s hp th cc cht c trong khng kh qua ph nang vo mao mch. Hnh v tr19 (h h hp) Ht 1 < d < m: gy tc hi phn di ca h h hp lng ng trong kh qun ph qun. Ht d > 10 m: tc hi n phn trn ca ph nang v ph qun (phn mi v kh qun). Ht d < 1m: chui vo ti ph nang (ti phi, m phi) n ti mng phi. Cc ht mc phn trn ca h h hp thng c thi ra qua vic ho, ht hi hoc i khi nut vo theo h tiu ho. Khong 1/2 s ht bi s b y ra trong mt ngy, tu thuc vo bn cht ca cht c. Cc ht mc phn di ca h h hp c th i ti tn mng phi. Cc ht kh tan nht b loi b lu nht. Cc ht tan c, nm trong ph nang s khuyt tn trc tip vo mu i qua phi: cc ht khng tan s xm nhp vo cc khong trng v theo mu i n cc c quan khc trong c th. 2.4. Hp th c cht qua h tiu ho Cc cht c c th i vo h tiu ho thng qua thc n. S hp th cht c din ra dc theo ng i ca qu trnh tiu ho, cc vng hp th c trng l d dy (c tnh acid yu, khng ion ho, hp th tt cht thn m) v rut (tnh baz yu). Qu trnh hp th xy ra t ming n trc trng. Ni chung cc hp cht c hp thu trong cc phn ca h tiu ho, ni c nng cao nht v dng d ho tan trong m nht. Cc cht tan trong m d dng vo mu v c phn b n cc t bo, gy nh hng ln b phn tip

24

nhn hoc tch lu lu di trong c th. Cc cht tan trong nc tc ng n cc c quan tip nhn v b o thi ra ngoi (khng tch t). Cc cht c c cu trc v in ly tng t nh cc cht dinh dng th d dng b vn chuyn qua mng rut vo mu. Ni dung c cht hp th qua ng tiu ho t. Ngoi ra c tnh ca nhiu cht cn gim i khi qua h tiu ho v tc dng ca dch d dy (acid) v dch tu (kim). 2.5. Tc hp th Nh ta bit mc c tu thuc vo nng cht c. Hu ht cc trng hp, s hp th xy ra nh qu trnh khuyt th c th hin hin bng hm s m cy ng hc bc nh sau: Log C = log C - k1/2/3 Vi C = nng cht ngoi sinh ti thi im hp th C0 = nng ban u ca cht l ti im tip xc K hng s tc ca hp th, tng ng 0.693. T1/2 = bn thi gian hp th khi C = 1/2C0
3. PHN B

Sau khi vo huyt tng qua hp th hay qua tnh mch cht c s c phn b i khp c th. Tc phn phi cht c ph thuc vo h thng cc mch mu ti cc c quan . S phn b cht c cn ph thuc vo kh nng lu gi cht c ca cc t bo. Cc v tr lu gi c th l: + Cc protein ca huyt tng. + M ca c th. + Xng. + Gan v thn. p ng ca c th khi b cht c xm nhp tu thuc vo nng cht c t do trong huyt tng. Lin kt protein l lin kt ion, cu ni hyro, hay lin kt Van der Waals, nn yu v thun nghch.

25

Cc cht c c kh nng lin kt bn vng vi protein ca mu, tch t ti mt s c quan trong c th v s tr nn rt nguy him. Cc cht ny thay th cc thnh phn lin kt ca huyt tng mt vi v tr, dn n thay i nhim v, xo trn chc nng hay hot tnh ca huyt tng. Mt s thuc tr su nh DDT, PCB clodan tan nhiu trong m v c th tch lu qua qu trnh ho tan vt l n gin. Xng cng l ni tch lu cc hp cht nh Pb, stronti florua. Cc cht c ny c th c o thi qua qu trnh trao i ion b mt tinh th xng hay qua qu trnh ho tan ca cc tinh th xng.
CHT C VO C TH

Super Hydrphbic Rtkhng Hydrophobic (0phncc tram) Polar (Phncc) Hydrophili c (anc)

T ch l u t r ong cc c quan m Pha I : chuyn ho si nh hc hoc l oi b c t nh Phn ng xy ho, kh, t hu phn Pha I I : chuyn ho si nh hc hoc l oi b c t nh Phn ng l i n hi p Hydr ophi l i c Bi t i t

4. QU TRNH CHUYN HO CHT C/TRAO I CHT

26

Sau khi cht c c phn phi n cc c quan trong c th th s xy ra qu trnh chuyn ho cht c. Chuyn ho cht c trong c th thc cht l qu trnh sinh ho chuyn cc cht c thnh cc cht hot ng hay bt hot. Qu trnh ny thng xy ra gan, thn hay cc c quan khc ca c th, nhng mc gii hn khc nhau. c tnh chung nht ca qu trnh ny l cc sn phm ca n thng phn cc hn so vi cc cht ban u, do s thun li cho qu trnh tip theo l o thi cht c vo nc tiu hay mt. Mt chuyn ho sinh hc c th dn n nhng thay i v c tnh c nh sau: - Chuyn ho mt hp cht hot ng thnh khng hot ng. - Chuyn mt cht khng hot ng sang dng hot ng. - Chuyn mt cht khng hot ng sang mt dng khng hot ng khc. - Chuyn mt cht hot ng sang dng hot ng khc. S chuyn ho:

Cht c Kh c Khng c Bi t i t Khng i Gc hot t nh Gy t c ng l n c t h Chuyn ho

Ti n c chuyn t hnh dng c

Qu trnh chuyn ho (trao i) theo 2 giai on: Giai on I gm cc phn ng lm cho cht c hot ng hn chuyn thnh cc dn xut vi cc nhm chc thch hp cho cc phn ng giai on II. Giai on II

27

phn ng gn cc nhm phn cc cao ln c cht, nhm h tr qu trnh bi tit bng thn v gan. Pha 1 trao i cht: gm cc phn ng oxy ho, kh v thu phn. Phn ng oxy ho: Oxi ho cc cht tan trong m c tr gip bi cc enzym ny cn c cc tn khc nh l oxydaza chc nng hn h, microsomal hydroxylaza, cytechrom P450. Tn chung cho c nhm l cytochrom P-450 monooxygenaza. Mt s phn ng c xc tc bi enzym nonmicrosomal. V d [5] [3] Oxi ho cc hp cht tan trong nc.
AD H ALD H

NAD+

NADH+

NAD+H2ONADH H+

xi ho amin monoamine (MAO) ti ty th v diamine (DAO) ti t bo cht.

HO CH CH2 NH MAO CH3 HO | OH epinephn ne HO HO CH2NH2

HO HO

CH CH2 CH CH3 | |

CH CH NH2CH3 | ||

HC= O

MAOB Benzyltam ine

+NH3+

28

Mt s khc c xc tc bi cc enzym microsomal. y l cc phn ng chuyn ho sinh hc quan trng, c th lm gia tng hay lm gim tnh c ca cc hp cht l. Phn ng tng qut: nadph = nicotinamide adenine inucleotie phosphate [4] p.85 NADPH + O2 + ho cht ho cht OH + H2O + NADP+ S ni tip cc bc trong phn ng xy ho xc tc bi cytochrom P-150 monooxygenaza c minh ha nh sau: [5 f4, p531 [4] p85 Vit tt: microsomal flavoprotein: NADPH dng kh nicotinamide adenine dinucleotide phosphate; P-450 (Fe+) : cytochrom P- 450. XENOBITIC HO-X Pv450- Fe X-P450-Fe -++

HO-X-P450-FE

NADH +

Oxidized Cytochrome b5 Reuce Cytochrome b5

NADPH Ha NADP

2 HO

Oxidized Cytochrome b5 NADP + NADPH Cytochrome NADPH Reductase

NAD +

Cc bc trong s oxy ho xc tc bng h cytochrom P-450 moncoxyenaza Mt vi v d: |5| f5, p531 |4| p86,87 Hinh tr24

29

Trong hu ht cc trng hp, s oxy ho cc xenobiotic (cht ngoi sinh) thn m l s hydoroyl ho, tc l thm nhm OH vo sn phm cui cng. Epoxi ho l mt trng hp c bit, cng mt phn t oxy vo ni i C = C. Phn ng kh: kh cht c (gm cc loi halogen hu c, ceton, hp cht nitro, azo) thnh hp cht alcohol, amin R-NH2. Phn ng thng xy ra trong gan. V d [5] figure 2. a. Nitro reduction

NO2

NO

NOQH

NH2

Nitrobenz ene

Nitrobenz ene

Phenyl hydroxylami ne

Aniline

b. Azo reduction
CH3 N=N CH3 NH2 N=N || HH Hydrazo divative H3C + NH3 NH3 Amineproduct H2N CH3

O Aminoaztluene

c. Disufide reduction S S || || (C2H5)2 NCS - SCN (C2H5)2 Disulfiram S || 2 (C2H5)2 NCSH

Dimethylithido carbamic acid

30

d. Alehye reduction
CHO
p Chlorobenzaldeh

Cl

2 CHOH

p Chlorobenzaldeh

e. Sulfoxide reduction
S || O Cl

(C2H5)2PSCH2S
Carbophenothion sulfxide

S ||

(C2H5)2PSCH2S
Carbophenothion

Cl

Phn ng thu phn: xy ra mt s c quan nh gan, thn, huyt tng, vi s tham gia ca nhiu loi cnzym khc nhau. Cc loi tc cht c th b thu phn l ester, hydrazde, carbamate, epoxide v amide, bng cch b gy cc hp cht trn v thm phn t nc vo, vo cu ni ester mt s v d: [5] f1, p529 [4] p89. NH2 | H2O | C O || Hnh v tr 26 Pha 2 lin hp Phn ng pha 2 l s kt hp mt cht ni ..tan trong nc vo tc cht xm nhp (cht ngoi sinh). Cc phn ng pha mt p dng i vi cc hp cht tan trong m v c xem nh l gn mt "cnh tay" vo phn t pha 2 c th nm vo. "Cnh tay" ny thng l cc nhm hydroxyl, ni m cc enzem lin hp s gn mt phn t ng hay acid | COOH NH2 | + HO N

31

vo thnh mt sn phm cui tan trong nc v c th c bi tit bng gan, thn. Kt qu ca cc phn ng lin hp l to thnh cc dng enzym ca gluctronide ethereal sulfate, mercapturic acid thng qua s lin hp vi glutthione, amino acid cty amin v cc hp cht methyl. Hnh v tr 27 V d: Lin hip acid glucuronic, sulfate, acetyl ho, tng hp acid mercapturic [5] p.533,534 [4] voll p.90.95 Phn ng tng qut ca s lin hp acid glucuronic l: UDPGA + RX Trong : GT R-X-GA + UDP UDPGA = uridine diphoshogluccuronic acid X = OH - COOH, NH2 GT = glucuronyltransferase

32

CH2OH O OH
OH

UTP

CH2OH O OH
OH OH

O | HN | O N

O P OH

OPOPOCH2 O OHOH

DGlucose1phosphate

UDPDglucose(UDPG)

enzyme UDPG + 2NAD + H2O

+

COOH O O OPO POCH2 OH O

OH OH

HN

O | | N

UTP = uridine triphospha Enzyme = UDP deny Hinh tr 28 cn Phn ng tng qut ca lin hp sulfat: PAPS + R-XH R-X-SO3H + PAP Trong : X = OH hay NH2

OHOH

PAPS = 3-phosphoadenoyl - 5 - phosphosulfate PAP = 3, 5 - adenosine diphosphat Acetyl ho: R - NH2 + CH3 - C - SCoA R- N - C-CH3 + CoA-SH || | || O H O Amin acetyl CoA N-acetyl amin R: C mch thng hoc nhn thm Tng hp acid mereapturie: Chuyn ho RX - glutathione R-S- glutathlone

33

Peptid R- S - glutathione Hnh tr 29 Sn phm ca phn ng lin hp rt quan trng trong gii c. Trong gan v cc m trong c th cha sn rt nhiu cc tc nhn to phn ng lin hp. Nhng nu nhu cu qu ln, vt qu kh nng cung cp th cc sn phm ca pha 1 s t do phn ng vi cc phn t trong t bo nh nc, acid nucleic, protein iu ny gii thch ti sao tn ti gi tr ngng c. Lng cht c nh hn gi tr ngng s c loi b an ton khi c th, nhng nu nng vt qu mc ngng th tc o thi cht c khng nhanh, cht c s li lu di trong c th.
5. O THI CHT C

R-S - mereapturate

R: mch thng hoc vng thm

Cc cht c c bi tit ra ngoi theo nhiu cch nh gan, thn, tuyn m hi, nc bt, nc mt, sa m, nhng quan trng nht l thn. 5.1. Qua thn, nc tiu: Nhiu cht ho hc c loi b ti thn do chng b chuyn ho sinh hc thnh cc sn phm ho tan nhiu trong nc khi chng b bi tit qua nc tiu. Cc cht c c th c loi vo nc tiu qua con ng lc ca tiu cu th ng, khuych tn qua ng th ng v s tit ra ng ch ng. Sau khi cht c (hay sn phm chuyn ho ca chng) c lc qua nc tiu cu, cc cht c h s phn b m / nc cao (tan trong m) s c hp th li, cc cht tan trong nc v cc ion s b o thi qua bng i v ra theo nc tiu. S bi tit ch ng cc cht c c th t c thng qua 2 c ch bi tit ng, mt c ch cho anion hu c (acid) v mt c ch cho cc cation hu c (baz). Cc protein c lin kt vi cht c khng b o thi

34

bi s lc ca tiu cu hoc s khuych tn th ng, c th b o thi qua qu trnh bi tit ch ng ny. 5.2. Qua ng gan, mt, rut. y l con ng ch yu loi b cc cht c (cc cht d sinh ho) qua c th. Cc cht cn rn (phn) bao gm thc n khng tiu ho, mt phn cht dinh dng, cc cht d sinh ho c trong thc phm hoc thuc, d l cc cht khng c c th hp th. Gan c v tr thun li trong vic loi b cc cht c xm nhp qua ng rut. Cht c qua d dy - rut s vo mu i qua ng rut, ti gan trc khi vo h tun hon. Do vy gan c th tch mt s cht c trong mu, ngn chn s phn b ca chng i khp c th. S bi tit qua mt ng vai tr quan trng trong vic o thi 3 loi hp cht c khi lng phn t ln hn 300: cc anion v cc phn t khng b oxy ho, c nhm phn cc v cc nhm a m. Cc cht c khi lng phn t nh b o thi yu qua mt, c l l do chng b hp th li khi i qua. Cc cht o thi qua mt thng c chia thnh 3 nhm theo t l nng ca chng trong mt v huyt tng: Nhm A: t l gn bng 1: Na, K, glucoza, Tali, Ce v Co. Nhm B t l mt / huyt tng > 1: acid mt, pylirubin, sunfobrom phtalein, Pb, As, Mn. Nhm C t l < 1: imulin, albumin, Zn, Fe, Au, Cr. S bi tit qua rut: mt s cht ho hc (digitoxin, dinitrobenzamit, hexaclobenzen, ochratoxin A) c thi ra phn khng qua qu trnh bi tit mt v cng khng phi i trc tip t ming, cc ho cht ny c chuyn trc tip t mu vo rut v ra phn. 5.3. Qua hi th: Cc cht tn ti pha kh trong c th, cc cht lng d bay hi nm cn bng vi pha kh ca chng trong ti phi, c loi b ch yu qua phi.

35

5.4. Cc tuyn bi tit khc: Tuyn sa: Loi b cht c trong tuyn sa rt quan trng v cht c c th theo sa m truyn cho con hay t ng vt truyn sang con ngi. Cc cht c (nht l cc cht thn m) d dng i vo tuyn sa do s khuych tn n gin. Do tuyn sa l mt tuyn bi tit quan trng cc cht c khi c th. Tuyn m hi ( qua a): Cc cht c tan trong nc d dng b bi tit qua da bi tuyn m hi. Quan th thai: Ngi m b ng c, b cc bnh truyn nhim rt d truyn sang cho thai nhi qua con ng rau thai. Ngc li thai nhi cng bi tit cht c khi c th, n qua rau thai i vo mu m. Nc bt: Mt s ngi nhim c ch c biu hin vng li u chn rng b xm en hoc b vim. l do cht c b o thi ra theo tuyn nc bt. * Tc o thi ph thuc vo: - Tc kh hot tnh sinh ho. - Tc bi tit .. Hu ht cc cht c c o thi khi t bo, mu, c th vi tc ph thuc vo nng ca chng trong mu v qu trnh trao i cht bin cht c thnh cht tan trong nc (theo phng trnh ng hc bc 1), nht l khi cht c c nng thp. Cc cht c c nng cao. Enzym trao i cht c th bo ho, do tc qu trnh trao i l khng i. Nu cht c a m, s bi tit trc tip gp kh khn v tc o thi s l bc zero (l mt hng s, khng ph thuc nng trong mu) cho n khi nng cht c thp hn mc bo ho. Tm li: - Cc tc cht c tan trong nc, sau khi vo c th thng c loi ra nhanh chng nn t c c hi tham gia vo qu trnh chuyn ho sinh hc trong c th.

36

- Cc tc cht c tan trong m khng th b loi ra khi c th ( tr cc cht d bay hi), nn chng li trong cc c quan cho n khi tham gia vo qu trnh chuyn ho v bin i thnh cc dn xut tan trong nc. - Cc cht c c th b bin i c tnh nh qu trnh trao i nht. Cc phn ng pha 1 thng lm tng c tnh v l giai on gn cc nhm a nc cho phn ng pha 2. - Cc cht c c th tham gia mt hay nhiu cch trao i cht, cch no nhanh hn th quan trng hn trong loi b cht c khi c th. - Vic tip xc vi cht c qua khng kh, thc phm hoc nc c th vn chuyn cc cht c vo mu, h tun hon v cc m ca c th. - Cc cht a m thng b hp th nhanh hn cht a nc v mng t bo mang tnh *** hn l tnh nc. - Cc cht c sau khi c phn b n cc m c th tch lu ti v lin kt vi cc protein trong mu. - C th ch loi b c cc cht tan trong m qua nc tiu v mt cc cht tan trong m nn bay hi c s b loi b bng phi. - Nng ca cht c trong mu s quyt nh phn ln nng ca chng trong hu ht cc m. Cu hi: 1. Ti sao ngi ta ndng ctanol cp cu ngi b ng c metanol. 2. Cc mn a nc no thng c b xung vo lin kt vi cht c trong phn ng chuyn ho pha 2. 3. Trong cc cht sau: cht no lm tan nhiu trong nc. Cht no lm nhiu trong m ben.zen, hean, metanlo, acid benzoic. CCL4 4. Ti sao cc cht tan nhiu trong m li rt t b loi theo nc tiu.

37

CHNG 4: TC NG CA CHT C I VI C TH CON NGI Cc cht c sau khi li trong c th hay chuyn ho sinh hc hc c th to nn cc phn ng c i vi c th. Cc phn ng ny th hin hai cp: s cp ( l cc phn ng nhim c cp tnh ) v th cp ( l cc phn ng min c mn tnh.). Cc biu hin nhim c cp th hin ngay sau khi tip nhn t vi pht n vi gi. Cc tc ng th cp ca cht c ln c th con ngi kh pht hin ngay. Phi sau mt thi gian mi quan st thy cc du hiu nhim c mn tnh nh xut hin bnh tt ( nguy him, nan y nh ung th) - C th suy gim kh nng min dch, t bin ghen, sinh thi 1. Phn ng s cp: Nhim c cp [5] O.269 Phn ng ca c th qua 3 buc: - Phn ng ca c cp: L phn nh ng ca ngi nhn hay c quan tip nhn ca cht c . - Phm ng sinh hc: l phn ng ca cc phn t sinh hc vi cht c. - Cc phn ng sau phn sinh hc nh phn ng sinh l, hnh vi. Cht c ( hoc tin c). ' Ni tip nhn

P. s cp: P. sinh hc

Thay i cu trc ni nhn Ngn cn hot ng ca enzym ' - Gy ri loi mng t bo - Gy nhim qua trnh tng hp enzyn - Ri lon qu trnh chuyn ho lipit, carbon. - Ngn cn h hp - Nhiu qu trnh tng hp protein

Cc phn ng khc V hnh vi, sinh l.

38

Tng, gim nhit c th Nhp p mch khng u (tng hoc gim) H hp khng u, nh hng h thn kinh, Gy o gic. T bo cht V d: Hi Benzen vo mu n cc t bo c th v lin kt vi acid nuleic (ADN). y l nh hng khng thun nghch. - Tc ng gy ngt ca CO: CO + HbO HbO CoHb+ OA2: Tc ng c tnh thun nghch. . Do nh hng bi tc nhn khng vn chuyn O2 nn gy thiu oxy trong mu, dn n no thiu oxy chuyn sang tri, sinh HbO, gim c. Cc Biu hin v nh hng sinh hc ca phn ng sinh hc: a. Tn thng chc nng ca enzime do lin kt enzime v coenzime, lm thay i mng t bo do cht c t ti mng t bo, gy tn thng cho cc c quan trong c th. b. Can thip vo chuyn ho carbon: nh hng n qu trnh nng lng. c. Tng tch t lipit ( gan nhim m) d. Ngn cn qu trnh ho hc do tiu th oxy cho qu trnh oxi ho sinh thi lm nh hng n qu trnh cung cp nng lng. e. Lm dng hay can thip vo qu trnh tng hp sinh hc cc protin do phn ng ca cht c i vi ADN thay i cu trc ADN . f. Can thip vo qu trnh iu hnh trung gian ca cc hocmon trong c th. 2. Phn ng th cp. Do tip xc trong thi gian di vi cht c gy ra cc nhim c mn do c th dn n cc dng nh gy ung th lm suy gim kh nng min dch t bin gien qui thai Ngoi ra cn c cc nh hng sm gim hot ng cc cc c quan. Nu tng lng oxy vo mu, cn bng s dch

39

hn nh: au bng, au gan, thn. S c v h tun hon, nh hng trn h thn kinh trung ng v ngoi bin C th quan st c cc phn ng ny thng qua cc biu hin ca huyt mch, huyt p du, mu da thay i, s tng m hay kh ca da, xut hin nhng mi l, ri lon th gic, thch gim, khu gic, bnh thn kinh, hn m, co git - t bin: l s thay i cu trc AND do tip xc lu di vi cht c. t bin ny c th dn n ung th hay qu thai. V vy cht c gy t bin c xp vo loi cht c nguy him V D 11g,Pb. - Qui thai: Do cht c n t bo trng v tinh trng, gy bin i cu trc ca cc c quan trong thai nhi. Cui cng tr sinh ra b khuyt tt hay di tt. C ch sinh ho rt phc tp v a dng, biu hin : + Cht c ngn cn enz i ti t bo. + Hn ch hay thay i mt s phn quan trng trong qu trnh th thai. + Ngn cn vic cung cp nng lng cho thai nhi trong giai on hnh thnh. + Thay i qu trnh thm thu cht dinh dng qua mng rau thai. - Ung th: do cht c i vo c th, lm thay i qu trnh pht trin ca t bo lin kt vi t bo, c bit l AND lm nh hng n vic kim sot bn sao ca t bo, dn n cc m ung th. Tc cht gy ung th thng l cc ho cht hu c mch vng thm, Asen . Cht c Loi c Xm nhp qua n ung H hp 60mg/kg, ngy 8.1.10

As A 1,76mg/kg,ngy (Thuc tr su, dit nm xc tc, tb, quang in) CCL4 B2 0,13 Ca A *** DDT B 0,34

40

iedrin PCB Phenyl Clorua vinyl

B2 B2

0,58 7.7 1.66.10

0,295

41

CHNG 5: C TNH CA MT S CHT C MI TRNG

PHN A: CHT C HO HC

1. Cht c ho hc dng v c 1.1. Mt s kim loi nng. Cc yu t nh hng n c tnh ca kim loi nng. - Tng tc vi kim loi vi cht trong c th: c th lm tng hay gim c tnh ca kim loi ring. V D.cd v Zn tng tc.Cd thay th Zn trong mt s enz-kim; Pb thay th Ca v c ch s vn chuyn sau phn chia t bo. - Hnh thnh phc kim loi - protein: KLN lin kt vi protein, nn s nm li lu trong c th, tch t nhiu ln n ngng gy c. - Tui v tnh trng pht trin; Ngi gi d nhim c hn ngi tr kho, tr em d nhim c Pb hn ngi ln. - Cch sng: Ngi ht thuc nhiu d ng c./ nhim HLN hn bnh thng, cn trong bia ru lm hng chc nang gan, dn n hn ch chuyn ho KLN. - Dng v loi ho cht : V d Cr6+ c hn Cr3+ - Trng thi min dch ca mi c th c hc ca mt s KLN: 1.1.1. Thu ngn Hg v cc hp cht ca thu ngn. Ngun gc , phn b trong mi trng. - Trong cc qung t nhin 80 ppb. - Trong cng nghip, nguyn nhin liu, v d oxid thu ngn dng l cht xc tc trong CN, trong sn chng h bm trn tu thuyn i bin. - Hg2CL2 Chlorua thu ngn I cn gi l lm thuc a ty giun c th gy ng c. - HgCl2 Chlorua thu ngn II c tc dng mn ngoi tc dng gy c.

42

- Ngoi ra cn nhiu hp cht thu ngn v c v hu c, Hp cht thu ngn hu c c hn v c. Cc dng thu ngn: - Hg nguyn t tn ti dng lng nhit phng. - Hi Hg, c hn trng nguyn t. - Mui Hg c 2 loi: Hg(1) v Hg(II), dng Hg2+ c hn dng Hg+ - Methyl thu ngn l dng thy ngn hu c gy c nht. ng xm nhp - Hg v hp cht c th vo c th qua mi ng - Hg v cc hp cht khng ion ho c thhp th qua da, d yu. - Trong cng nghip, Hg v hp cht thng c hp thu qua h h hp ( nht l cc hp cht thu ngn bay hi, git Hg ri ri) Cc hnh thi ho hc ca Hg v tnh c: - Hg nguyn cht khng c, tr, khi xm nhp qua h tiu ho th n s c bi tit v c nhng chuyn ho do dch tiu ho gy au bng, nhim c. - Hi Hg rt c, hp th qua ng h hp, p sut hi trn b mt cao, khi ht phi d dng vo mu, ln no gy ng c cp hoc cc bnh thn kinh (phn lit h thng TK). Phi hp thu c hn 90% hi thu ngn sinh ra. - Hg22+ : t c, Hg2Cl2 Chlorua thu ngn (I) khng tan trong rut. - Hg2-: c, khng vn chuyn c qua mng sinh hc, nn kh n c cc t bo sinh hc, tc dng vi S trong c th nh acid amin cha S, protein, ngn cn chuyn ho ca protein. - Hg hu c (RHg+) rt c, d vn chuyn qua mng sinh hc, tan trong m v cc thnh phn lipit, lu tr trong cc t bo, kt hp vi S lm cn tr qu trnh vn chuyn enz, gim nng lng t bo v lm ri lon cc xung thn kinh, nh hng: + Gy ri lon h thn kinh, dn n bnh thn kinh phn lp.

43

+ Ri lon nhim sc th, lm t NST hay ngn cn vic phn chia t bo, nh hng di truyn. - CH3Hg c th chuyn t m sang tr s sinh do m b nhim c dn n phn ly nhim sc th, ngn cn s phn chia t bo v a tr s mang bnh TK phn lp. - R2Hg t c, vo h tiu ho, nh mi trng acid li chuyn thnh RHg+. - Trong thu quyn - Trong kh quyn: Hg + 2CH3 (CH3)2 Hg
2+ Hg

Hg

(CH3) 2Hg
+ (CH3) 2Hg

t ch t sinh hc

- Trong a quyn:

Hg CH3Hg+ (CH3)2Hg Hg Hg2+ Hg2 2+ HgS

C ch nhim c C ch chuyn ho Hg (II)vc Hghe nh vi khun tng mtan him kh c trong nc. Qu trnh chuyn ho ny s rt thun li vi coEnz c cha Coban. HgCL2 Vi khun Methylcobalamin CH3HgCl + Cl

CH3 Co

+ Hg2+

CH3Hg Co

+Cl

RHg tan trong nc khi pH gim C ch dy chuyn thc phm, tch t Hg;

44

Hg2+ VK ym kh CH3Hg+ + SV tri ni (ph du) 10-1ppm Ln g Ngi nhim c Hg S tch t Hg trong c th ngn cn hot ng ca enz bng cch thay th gc SH. SH enzim SH +Hg enzim
2+

8ppm

Su b Chim

C nh C ln

10-3ppm 1ppm 20ppm/1vk.

S Hg+2H+

S Khng hot ng Ngn cn qu trnh hot ng ca protein do to thnh phc khng hot ng (tng t qu trnh ng t asen ca protein). Ngn cn qu trnh to hng cu. Biu hin nhim c mn tnh hi Hg. - Tit nc bt nhiu v vim li (li sng ty , d chy mu, i khi thy ng vin Hg trn li). - Rung c (bt u t ngn tay, mi mt, li, mi, tip theo l ch vit, ri n cc chi - ging bnh Parkinson). - Thay i hnh vi c nhn (mt t ch, c khuynh hng hay ci ln v chnh mng lao ng, d cu gt, o ln nhp ng, ri lon v ni). - Mt tr nh - Suy nhc nghim trng. - M sng v o gic Sn phm ca qu trnh methyl ho thu ngn trong t nhin thng l monomethyl thu ngn hay methylmercury. N i vo chui th n trong

45

nc qua mt xch u tin l plankton ri n c n c. C n tht n c n c nn tip tc nhim Hg v tch t lng thu ngn tng ln. Cui cng con ngi n c nhim c s b ng c. Tu theo lng Hg vo c th m biu hin ng c s tng dn: - T lit hay nga c xung quanh ming, mi, u ngn chn, ngn tay. - Kh nut v kh pht m cc . - Km nhy cm, mt mi, bt lc, kh tp trung tr c. - Gim thnh gic, th gic - Co cng v run - Hn m v cht
100 80 60 40 20 1025 50100200 61640 76156312 * T ngn chn, tay, ming *Mtthngbng * Kh nut, kh pht m *ic Cht

MgHgvocth MgHgvocth

Phng nga: - Thay Hg bng cc cht khc, nu c - Chng Hg bay hi bng thng gi hp l. - Tm cch gim mi tip xc vi Hg, nht l vi nhng ngi nhim. - Kim sot thng xuyn lng Hg c trong mi trng khng kh ni lm vic. iu tr: Gii c Hg v c bng thuc c hiu BAL ( British Antilewite) = 2,3 dimercapto propanol. Cht ny c cha 2 nhm thiol- SH nn c i lc

46

vi Hg, lin kt vi Hg ang phong b enzym (enz. Cn thit cho c th c nhm thiol) v gii phng enz. Tuy nhin BAL ch tc dng trong nhim c cp, khng c hiu qu trong nhng trng hp c bt.

SH CH2 - OH CH - SH CH2 - SH BAL

SH

+ HgCl2

S ___ Hg ___ S + 2HCl enz. b bt hot bi Hg CH2 - OH CH - S + H_S_S_H

Enz. C nhm thiol + S_Hg_S

CH - S CH2 - S Hp cht BAL-Hg Enz. c phc hi (thi qua nc tiu)

1.1.2. Hp cht ca asenic (As) trong t HxA sO4(3-x).

Asen tn ti trong cc qung cc dng sau trong t nhin: Dng asenat c HxAsO4(3-x) AsO3(3-x) CH3As (O) (OH)2 (CH3)2 As(O)(OH) Kh vi sinh kim loi mu. H3AsO3 + H2O H3AsO4 + H2+ As3+ c. S dng trong cc thuc dit nm, cn trng. As cn c th i vo mi trng t cc ngun: - T nhin (chng hn ng t, ni la, xi mn , chy rng hay cc hot ng ca con ngi). - t nhin liu ho thch (du m, than ) - Cng nghip sn xut giy - Sn xut xi mang - Khai hong 47 kh ho vi sinh metyl asen dimetyl asen Nng khong 2-10mg/kg qung, tn ti dng qung phosphat

As c dng trong - Lm bng ng thau v lm pho hoa, trong sn xut thu tinh, gm s. - Thm vo thc n gia sc tng trng nhanh. - Trong thuc dit cn trng v dit c. - bo qun g (kt hp vi Cu v Cr) Tnh c: - Ph thuc vo dng ho hc v trng thi vt l ca hp cht. Asen v c c coi l c nht i vi sc kho con ngi. - As(V) l dng ch yu trong nc mt, trong khi nc ngm ch tm thy As (III). - Trong c th As b chuyn ho thnh dng methyl. Methyl Asen (III) c th gy ra nhng nh hng c bit c vi nhng tip xc. - Cng nhn tip xc vi bi asen thng b vim da, vim mng kt. Tip tc ht phi bi Asen s c th gy thng xoang mi. - n ung c cha mt lng tng i cao Asen s gy nn cc bnh nh sau: + Bnh trn cc mch mu ngoi vi (bnh en chn, nhiu nht Bngladet) + Bnh a (da c mu, sng ho, ung th da). + Lm suy yu chc nng gan. + Ung th cc c quan ni tng(Bng quang, gan, thn) + Tiu ng. C ch tc ng ca Asen - Ngn cn hot ng ca enzim trong c th bng cch thay th cc nhm SH- trong cu trc Enz (nh vi Hg), to thnh hp cht km hm, ngng chuyn ho ca Enz. SH enzim SH O SH A s-O + 2OH As-O enzim O S Khng hot ng sinh hc

48

49

- Lm ng t cc protein do to thnh phc O O CH2-SH As - O + CH2 CH-SH (CH2)3 C=O Protein Glyceraldehyde3-phosphat S-CH2 O - As CH2 S-CH (CH2)3 C=O protein 1,2- diphosphat glycerat

AsO3

CH2-OH-C-OH C=O O- AsO3

Thu phn T pht

Khng to Thnh ATP

nh hng ln sinh vt: LD50 chut 4,5mg/kg (As2O3), ngi 5-50mg/ kg [Ca3 (AsO4)2] Nhim c cp: gy co git, au, cht ngay sau vi pht Nhim c mn: vim da c nt en, chm en nh, mng chn en, d gy: ung th, thn da. 1.1.3. Ch v cc dng hp cht ca ch Ngun gc t nhin: Qung PbS, PbCl2, Pb3(PO4), PbCO3 ln trong nhiu loi qung. Hm lng Pb trong a quyn thp. Pb ng th 5 trong s dng sau Fe, Cu, Al, Zn. Khi c s dng dng nguyn cht: Trong sn kh, pin, xng, nha, linh kin in t, men, s v cc thit b chng phng x. Acetat ch: sn xut mui ch Antimon ch: l cht mu trong sn, m, thu tinh, snh s. Asenat ch: thuc tr su, chng mt Borat ch: cht lm kh cc loi vecni, nh bng sn, cht m ln snh s. Ngun tip xc:

50

- Sn pha ch (c) - Kh bi, nht l nhng th ng dn v dng xng pha ch - Nhim bn trong nc ung t cc ngun t nhin hay do chy trong ng ng lm bng hp kim ch. - Khi pht x t cc khu cng nghip c dng ch trong nguyn liu v cht t. - Men s, thu tinh, thit b chng phng x. - t nhim ch, pH>5 Pb c gi li trong t, nng cho php trong t 100- 1100ppm (mg/l) Ch pht tn vo mi trng theo cc ng sau; - Khng kh: do chy t xng pha ch PbClBr (PbCl2, PbBr2), khi thi t cc l luyn kim, m khai thc PbO, PbSO4. - Nc: Ch yu dng Pb2+, tan tu thuc pH. Tiu chun nc ung 15-50ppb Pb. - t: do sn, vt liu xy dng, cht thi rn cng nghip(bao b, t, xe my) bi lng. pH>5 ch c gi li tt trong t. Lng ch cho php trong t 100-11000ppm. Tc ng sinh ho: Ch i vo c th do: cng nhn lm vic trong mi trng cha Pb, nc ung chy trong ng ch, khi pH thp, Pb trong ng ng tan vo nc, ht th khng kh nhim, ht thuc, dng thc phm nhim ch ( thc phm trng trn t c Pb). S dng cc dng c Pb. u tin Pb c hp thu vo c th do n ung. Sau tch tr li trong c th nh l cht thay th Ca trong cu trc xng ca c th. Phn cn li i vo ma; 10% nm trong huyt tng v i n cc m ca c th. Thi gian lu gi Pb trong mu khong 25 ngy, sau o thi dn. Thi gian lu trong cc m khong 40 ngy, trong xng 25 nm. Tc ng ca Pb n h thn kinh trung ng: - Lm suy yu chng trnh lin kt t bo - t bo

51

- Lm nhiu cc sung TK do t bo TK dnh cht vi cc phn t khc - Ngn cn cc hot ng ca no do s thay th nhm SH trong Enz dn n ri lon thn kinh, tc ng ln cc dy thn kinh ngoi vi d n t lit. Pb c ch mt s hot ng ca mt s Enz c nhm SH, lm gim qu trnh tng hp Hemoglobin, gy ln 3 thay i sinh ho c bit: gim hng cu, tng ALA ( acid denta amino lavevulinic), sinh hng cu non. Ph v c ch trao i cht ca Ca bng cch ng khi Ca ttrong cc knh dn Ca, thay th Ca trong bm Ca - Na ATRP Trong thn: gy vim thn mn tnh, Nhn bit qua: hng cu gim, c ALA trong nc tiu Biu hin nhim c ch v c: Nhim c cp: hm lng cao gy au bng, to bn, nn ma, ri lon tiu ho. suy sp c th nhanh, vim thn hay vim gan thn (i t, protein niu, m huyt tng, t vong trc ngy th 4). Khi mi ngy tip sc mt lng ch cao (>10mgPb/ngy) trong vi tun s gy nhim c nng. n 1gPb/ln s cht ngay. - Nhim c mn: thng do c tnh ngh nghip thng xuyn phi tip xc vi Pb, s lng tip xc nhiu, Pb>0.2mg. Biu hin: u tin: vng v, ri lon, d b kch thc, mt ng, chn rng c ng vin en do Pb + hp cht S h/cht mu tm en, lng chn rng, v tanh kim loi trn ming. Sau: thiu mu, xm da, tc dng ln t bo mu lm thay i thm qua mng, lm tng lng kali b mt, hu qu l tui th b rt ngn Ri lon hot ng ca Fe trong mu, dn n tng lng Fe trong huyt tng Vim no: thng tr em ngi ln thng xuyn tip sc vi xng pha Pb

52

C Pb mu > 0.5 ppm: thiu mu, ri lon chc nng C Pb > 0.8 ppm: ri loan thn kinh v chc nng thn

- Ch + Tr em nhim c nhanh do kh nng hp th nhanh v s tc ng n h TKTW + C th thiu Ca, Fe 3+ s to iu kin d rng cho vic hp th Pb v c th lm trm trng triu chng ng c. + Tr s sinh nhim c Pb t m s chm pht trin tr nh, hng thn, ph hoi h thn kinh trung ng v cc t bo mu. Nhim c Pb t hu c (tetrraethyl Pb): Cp: nhit c th gim, huyt p gim, m sng, co git. Nhm nhim ch hu c thng gy ra bnh i vi h thn kinh trung ng, nht l bnh no biu hin qua - Ri lon tinh thn, hoang tng - Run c , tng phn x, gin ng t - Suy nhc c th, thn nhit gim, nhp tim chm, huyt p gim Bnh ny thng gy ra t vong, mt s trng hp khi th tin trin rt chm, cc triu chng gim v mt sau 6 - 7 tun. c/ Phong chng nhim c Pb: Phng bnh: - Bo m an ton mi trng loa ng, m bo khng r r hay hin hin ch trong khng kh ni lm vic - iu tra xc nh khu vc nhim c Pb cao (t, nc, khng kh). - Xc nh k hoch phng nga nhim c Pb thng qua vic cch li khng ngi tip xc ngun c Pb - Thay th cm s dng cc dng, vn chuyn xng du c Pb. - Gio dc cng ng hiu tc hi ch ng phng chng iu tr:

53

- Ty Pb. Dng canxi chelat, y Pb ra khi c ch thng qua con ng bi tit nc tiu. 1.1.4 Cadimi a. Ngun gc: - T nhin: thnh phn v tri t, qung km, trong trm tch nc sng, bin - Dng trong cng nghip: + pin CdNi, c qui + Hp cht mu Cd, sn + hp kim trong qu trnh hn nhm + Lp ph Cd, m in (m Ni) + n hi, t bo quang in + Thanh iu khin phn ng - Dng trong nng nghip: trong phn bn, thuc dit nm b. Trao i cht Cd vo c th ngi s gy hi,ch mt phn nh b o thi ngay. Bi v Cd thay th Zn trong thionein - kim (metanollothionein - mt loai protein c cha Zn). Chc nng chnh ca tyonyn -kim l mc iu chnh cc kim loi dng cht trong c th, c bit l Zn v Cu. Cd c kt hp cht tr vi tyonyn - kim do c ch ca h tng t nh Zn. 80 90% Cd vo c th c gi li trong c th bng cch ny. Phc cht Cd - tyonyn kim c chuyn n thn v c lc qua tiu cu ti hp th bi cc t bo ca u niu qun, y protein b b gy, gi phng cc ion t do. Cc ion ny li gip cc t bo ca u niu qun sinh thm tyonyn kim . C c toynyn- kim ny kt hp mt ln na vi Cd. Phc Cd- tyonyn kim l cht c i vi thn.

54

Thi gian bn phn gii ca Cd rt lu, t 7-30 nm v bi tit rt chm. Tuyn bi tit chnh l qua thn, ch khi thn b tn thng v hot ng km th Cd s ra thng nc tiu vi bt k lng no. Cd thng tch t trong thn v gan, ch mt lng nh gii hn l trong cc m mm.
Cd 2+ trong c th

Trao i Zn 2+ , thay th Zn 2+ Cyclodien

C l C l C l

C( CCl )2

C l C C C C

Chlorinated Benzen
C l

TDCT c chlor hay c dng, nht l cc nc ang pht trin v dit su bnh tt, bn trong mi trng, phn hu chm, gi r. Cc du hiu v triu chng ng c cp tnh v c tnh mn sau khi tip xc vi mt vi loi TDCT C CHLOR Loi thuc Dichlorodiphenylethane DDT DDD (Rothane) DMC (Dimite) Dicofol (Kelhane) Methoxychlor Chlorbenzylate Du hiu cp Du hiu mn Cng ming, kh iu St cn, chn n, thiu khin vn ng, bc mu i khc thng, hoa run mt, chng mt, au c bp yu, tnh trng u, bun nn, nn, qu kch thch, hi hp.

mt mi, ngt lm. Hexachlorrocyclohexane Bun nn, au u, Lindal nn, cng thng qu, (ng phn gamam)

55

Benzene phn) Cyclodien Endrin Telodrin Isodrin Endosulfan Heptachlor Aldrin Dieldrin Chlordane Toxaphene

kh chu, ln cn co au u, chng mt, qu kch ng, co c tng cn, ri lon tm thn bao gm mt ng, cng thng, d cu, Mt cm gic, co ng kinh

(hn hp cc ng git

au ngc, au khp, da ni mn, mt iu ho vn ng, khng kt hp c cc hot ng, ni lp. Cng thng d cu, mt tr nh, nhn kh khn khng th tp trung, suy nhc c bp, run tay, suy nhc nghim trng s sinh tinh.

Chlordecone (Kepone Hirex

B. Loi c ch Cholinesterraza: gm 2 nhm c phosphat v carbamat Du hiu v triu chng b ng c c lin quan n s tch t ca cc acetylcholin (ACh) t do, khng lin kt, mt vt truyn tn hiu thn kinh ti cui dy TK, c nhim v chm dt cc tc ng sinh hc gy ra bi ACh. Ach c cha trong khoang ca mt mng trc khp t bo TK, ni c cc dng xung in sinh hc gii phng n cho ra dng hot

56

ng. Tip theo, ACh di chuyn qua khp TK (khong trng gia cc im cui dy thn kinh hay hch) kch thch c quan tip nhn ti mng sau khp TK, v cc xung TK tip tc din ra. Sau khi truyn tn hiu n c quan tip nhn kiu kch thch cholin, ACh nhanh chng b thu phn bi hot ng ca enzym acetylcholine esterase (ACHE) sinh ra cholin bt hot (Ch) v acetic acid (Aa). Mt enzym khc, acetyl coenzyme A (ACEA) lin kt vi Aa v Ch quay li ACh. Xem hnh sau:

C ch gy c ca nhm c phosphat v carbamat tng t nh nhau. Gm 3 giai on: - Tng tc ti vng hot ng ca ACh to 1 phc khng bn. - Thu phn phc ny v gii phng cc cu t R hay Z sinh ra mt phosphoryl (/v c phospho) hay carbamyl (/v carbamatester) c ch AChE. - Loi phosphoryl (hay carbamyl) ca AChE thot ra AChE t do hot ng v c th ph hng ACh, vt truyn tn hiu thn kinh. Nhiu phc hp phosphoryl-AChE, khng c giai on 3, duy tr c ch khng th o ngc, dn n triu chng ng c nng bi v c nhiu ACh bn. Ngc li, phc carbaryl-AChE d dng phn ly cho ra AChE t do thot ra. C. Pyrethroid ester

57

- c tng hp da trn c tnh ca acid pyrethric v acid chrysanthemic - L cht c thn kinh - Ester tng hp c th c chia lm 2 phn nhm chnh da vo cu trc v du hiu ng c: + Hi chng I: gn ging ng c DDT. + Hi chng I CS: cha nhm cyano (CN), gy mt thng bng, co git, nga, t lit, au u, bun nn, co c, mt mi. II. Thuc dit c (Herbicide) Nhiu loi nht, c tnh cho con ngi thp, tuy nhin c hp cht bispyridyl, c bit l paraquat th rt c. Kh nng gy ung th, t bin gen, sinh qui thai hay ung th cn ang nghi ng v ang c nghin cu. c tnh c th l do ln nguyn liu c, hay do sinh ra cc sn phm ph. Trong , c bit n nhiu nht l 2,3,7,8 - TCDD ln trong thng phm 2,4,5 - T. Hu ht chng l cc acid mnh, amin, ester hay phenol nn c th gy d ng da, pht ban, vim da d ch tip xc lng nh, pha long. C nhng nhim th cp i vi nhng c th qu nhy cm khi tip xc vi thuc qua da hoc h hp (dng sol kh), biu hin qua d ng. Cc tip xc ngh nghip, lp li theo ma, c th dn n tc hi nghim trng. Mn, chlor hay "weed bump" lin quan n tip xc vi chlorine dioxin hay furan. Hot ng ca n l trao i cht trong tuyn b nhn di da. Paraquat L cht c i vi phi, nu i vo c th qua h tiu ho (do t t hay tai nn) th s trng c trong vng 3 - 4 tun, vi s gim nhanh oxy huyt, c bit l chtdo ngt.

58

C ch: paraquat tm cc c quan c nng oxy cao nh phi, phn ng to H2O gy tn thng lp mng ca phi, dn n khng trao i kh O2/CO2. Gy hoi t gan, thn v c tim. Diquat c cu trc tng t paraquat, khng c vi phi nhng gy hi gan, thn. III. Thuc dit nm (Fungicide) L cc loi thuc thng dng trc v sau thu hoch ngn chn s pht trin ca nm khi iu kin nhit v m thch hp. Thng gy c cp tnh i vi con ngi, LD50 800 - 1000mg/kg trng lng c th. Tip xc thng xuyn vi da c th gy d ng, xng ty hoc vim da. L cht c i vi t bo cht (gy t bin). Cc loi thuc dit nm ch yu l: 1. Dithiocarbamate: chng hot ng qu nhiu ca hch tuyn gip, l cht gy t bin, qui thai v ung th cho ng vt. Tng tc vi alcohol gy c cho c th, c ch tng t nh thuc cha nghin ru. Do nn trnh dng alcohol khi dng dithiocarbamate. 2. Organomecurial: Gy c cho gan, thn v c bit l h thn kinh (c trung ng v ngoi vi). Bo thai v tr s sinh rt nhy cm vi loi thuc ny. Chng tan trong m nn c th tn lu v tch lu trong chui thc n, c l ngun tch lu giu nht. IV. Thuc dit loi gm nhm (Roenticide) Kim sot s lng loi gm nhm rt quan trng trc v sau v ma bo v ma mng cng nh khng ch bnh tt. C ch gy c ca thuc thng nht cho cc loi, ch c liu lng hay tnh ngon ming i vi mt loi ny l yu t gim c tnh cho loi khc.

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Nu n phi (do c tnh t t hay tai nn) th rt nguy him v liu cao, cc biu hin ng c rt nghim trng, thm ch c th e do n tnh mng. C mt vi loi thuc gii c. Mt vi loi: 1. Zinc Phosphide (Zn3P2): L loi thuc r, v hiu qu. Khi n phi, n s phn ng vi nc sinh ra phosphine (PH 3), l mt cht khng bn, phn ng vi mng t bo gy tn thng nim mc, mng t bo trong ng rut, trong thn, gan, phi. Him khi b tai nn loi ny v nng cao (>5000mg), nu nn ra c th bnh nhn c th sng st, k c khi liu nut l 25 000 - 100 000mg. 2. Fluoroaceta / Flouroacetatamide: Khng mi, v, hp thu tt qua ng rut v c ch enzym lin quan n trao i cht ca glucose. Flouroacetat gy c qua ng ming cho chut = 0.2mg/kg cho ngi = 10mg/kg. 3. Alpha Naphthyl thiourea (ANTU): Phi c hot ho trong cc m gy phn ng v gy c ngay lp tc, dn n tch dch trong phi, gy tn thng cc mch mu nh. 4. Coumarin / Indadiones: L cht chng ng, gy trn mu trong mi, ng rut, u gi, khuu tay. V. Quan trc vic tip xc v x l ng c 1. Quan trc: 2 phng php trc tip v gin tip: a. Trc tip: - Dng c o gn trn o cng nhn hay vng da d c tip xc. - Thit b ly mu gm: ng plastic c cha vt liu hp thu ni vi bm ht mu vng kh ht th, thi gian bm ht t 1-4 gi, tc 0.2 - 1 lt/pht. Sau a ng i ra gii bng dung mi thch hp ri phn tch bng GC hay LC. Hoc dng ming vi c tm cht hp thu hay gn dng c o trc tip ln o cng nhn ang lm vic.

60

b. Quan trc gin tip: thng dng trong thc t, c 2 phng php l ly mu mt im v nhiu im. - Ly mu mt im: o t cc sn phm bi tit nh nc tiu, phn, nc bt sau cui thi gian lm vic. Xc nh cc cht trao i cht c bi tit ra. - Ly mu nhiu im: Ly t mt vi loi dch ca c th nh mu, m, trong cc sn phm trao i cht hoc cc enzim b c ch tm hiu mc tn cng ca cc c quan. Cng c th o tc dn truyn thn kinh nh gi mc b hi ca h thn kinh (trc TK, tu) cng nh nh gi kh nng nhn thc. 2. Phng nga nhim c thuc BVTV - Hun luyn phng php s dng an ton v hiu qu thuc, k thut phun thuc ng, c bo h lao ng. - Dng cc loi thuc d phn hu trong t nhin. - C nhng nguyn tc nghim khc khi s dng - Quan trc cc sn phm (v ma, nng phm)
2.2. DUNG MI HU C

Cc dung mi hu c l dd. Tan trong m hoc nc. Trong c th, chng c th tri qua qu trnh chuyn ho sinh hc hay khng i dung mi tan trong m s tch t chn lc trong cc c quan thn m, gm c h thn kinh. Dung mi tan trong nc vo c th qua knh a nc v phn b rng ri khp c th. Tt c cc dung mi hu c u c hp thu vo c th qua phi di dng hi. Ngoi ra cc dung mi a m c th vo qua da. Cc dung mi khng chuyn ho trong c th s c bi tit nguyn vn qua kh th hoc trong nc tiu. T nhng dung mi c th chuyn ho sinh hc trong c th, cc sn phm trao i cht ca chng xut hin trong nc tiu hay mu. iu ny c dng quan trc trn phng din sinh hc ni lm vic.

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Th nghim cho thy khi cho alcohol cng vi ng ng ca benzen th chuyn ho sinh hc ca dung mi b chm li. Lng etanol nhiu hn hn, gip cho alcol cnh tranh ly mt enzym, nn trao i cht ca dung mi b chm li. Dung mi s chuyn ho li khi t l tng i dung mi / etanol ph hp. nh hng ca alcohol ln qu trnh trao i cht ca dung mi khng n gin nh th nghim trong phng. Etanol l mt cht iu khin enzim, tip xc thng xuyn, lin tc s lm tng hot ng ca men P450, xc tc s oxy ho nhiu dung mi. V th gia sc c ung nhiu etanol trong thi gian di s chuyn ho cc dung mi nhanh hn bnh thng. C gi thit cho rng cc cng nhn nghin ru nng bi thi dung mi nhanh hn nhng ngi khc. V th c th ni etanol cng thm nh hng ln h thn kinh trung ng khi tip xc vi dung mi. 2.2.1. Benzen L im khi ngun cho nhiu qu trnh tng hp trong cng nghip ho cht. Trc y, n vn c dng rng ri nh mt dung mi, nhng do c ca n nn benzen b cm dng nu nng cao hn 1%. C nhiu bo co nghin cu cho thy vic tip xc vi benzen s tc ng ln h gien v c th dn ti nguy c ung th. Benzen lin quan n bnh bch cu v mt s dng ung th khc nh ung th thn. Ngi ta pht hin thy c s sai lch nhim sc th v gy ri AND nhng cng nhn c tip xc vi benzen, v th c th ni benzen l cht c i vi h gien. a. Ngun tip xc: - Trong cng nghip ho cht v tng hp ho hc - Chng ct benzen t than , du m. - Trong cc ngnh vn dng benzen l dung mi, nh sn, vecni, cao su, nha, mc in, ch to da mm. - Nhin liu cha benzen.

62

b. Qu trnh trao i cht

Ngi ta hp thu benzen ch yu qua ht th v c th qua da, nhng t. Khong 40% benzen c thi nguyn vn ra ngoi qua nc tiu v khng kh th ra. Mt phn tham gia qu trnh trao i cht trong c th. Benzen tham gia chuyn ho sinh hc u tin v ch yu gan, thng qua h thngcytochrom P-450 ZEI, ngoi ra cn tu xng. Nh trong hnh v, cc bc chuyn ho benzen nh sau: - u tin, oxy ho to thnh cc hydroxyl vng. - Cc sn phm trung gian tip theo l h cn bng gia oxit benzen v dng oxepin (dng hot ng nht) - M vng benzen hoc ti dng epoxide hoc dihdrodiol chuyn trans, trans-muconaldehyde thnh acid t,t-muconic. - Epoxide sp xp li khng cu enzim to ra phenol

63

- Cc phenol tri qua qu trnh hydroxyl ho to ra hydroquinon v catechol - Cc catechol cng c th c to thnh do mt chui cc phn ng k tip, bt u t hydrat ho oxit benzen to ra hidydrodiol nh enzim dehydrogenaza-phenol. - Hydroquinon, catechol, v cc sn phm hydroxyl ho tip theo l 1,2,3 - trihydroxy benzen c th gn vi cc gc ether sulfat hoc acid glucuronic. Thi gian bn phn gii khong 12 gi. c tnh ca benzen ch th hin khi to ra cc dng trao i cht ca benzen. Cc dng trao i cht hot ng nh hydroquinon, catechol, acid t,t-muconic v phenol to ra gan s tch t trong tu xng. y l ni benzen th hin c tnh v gy ung th ch yu. c. Biu hin nhim c Cp: cm gic ngy ngt, au u, nn ma. Nu khng c cp cu ra khi trng thi hn m th c th t vong v suy h hp. Kinh nin: thi gian u khng c triu chng v nhim c kinh nin. Nhng triu chng thng khng c bit v khng r mc tn hi nghim trng ti tu xng. Triu chng: ri lon tiu ho nh, lo o, chy mu nim mc v d ng trn da. Bnh ph bin ca nhim c mn benzen: thiu mu, gim bch cu. Do tu xng b gim huyt tng, nu vn tip tc tip xc vi benzen th s b thiu huyt tng trm trng, dn n ph v cc thnh phn t bo. S c hi ny cn tr s t hp AND. Ngi tip xc thng xuyn vi benzen thng b ri lon nhim sc th, bch cu. d. Phng nga - Thay th dn tin ti khng dng benzen trong nguyn, nhin liu, khng tip xc trc tip vi benzen.

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- Cc cng ngh bt buc cn c benzen phi c thit k khp kn hn ch tip xc. e. iu tr ng c Cp cu: a ra khi ni nhim, h hp nhn to, cho ngi cacbogen, cho thuc tr tim, khng dng adrenalin v c th gy rung tm tht. iu tr: cha c thuc c tr, ch yu l iu tr triu chng. Phi cho ngng tip xc vi benzen (ngh lm) v a n c quan y t. f. Quan trc benzen trong khng kh v nc tiu Benzen c xp vo danh sch cc cht gy ung th nn vic quan trc s tip xc vi benzen trong mi trng v sinh gii l rt cn thit. N gm c cc ch s sinh hc nh mc benzen trong mu, nc tiu. Cc ch s ny cho ta bit mc tip xc v lng tch t bn trong ca tng c th, c nhng d phng cho tnh trng sc kho. Vn quan trc s c mt ca benzen trong mi trng v cc ch s sinh hc nh acid t,t-muconic trong nc tiu c nhiu ngi quan tm. Pht hin v nh lng benzen trong khng kh Xc nh dng trao i cht ca benzen, acid t,t-muconic trong nc tiu o creatinine trong nc tiu 2.2.2. Toluen Toluen l mt trong nhng dung mi c s dng nhiu nht trong cng nghip. Toluen c trong sn, nha, keo dn v l dung mi cho cao su v trong cng ngh in nh. Trong tt c cc cng ngh c toluen cn c thng kh tt m bo gim thiu lng tip xc vi n. Khi chuyn ch cn trnh ri rt. Toluen l dung mi hay gy ra kht kht. nhit thng, toluen cho ra nhng hi rt d chy, n. Do vy nu mt thng toluen cn ct hay hn m dng n la th phi lau sch ht toluen.

65

Trao i cht: toluen c hp thu qua phi v mt lng gii hn qua da. Tan trong m, n tch t trong cc c quan a m. Thi gian bn phn r sinh hc l t 3 - 4 gi, khi khng cn tip xc vi toluen th n bi tit rt nhanh. Khong 10% lng toluen c thi ra ngoi qua ng h hp, phn cn li ch yu chuyn ho thnh acid acid huppuric, mt lng nh thnh o-cresol v p-cresol. c tnh: 1000ppm: cm gic long chong, au u lin min. Cao hn: ngt lm, gy cc bnh tm thn, o gic. Nng thp gy mt mi v c v cm gic au m trong mi ca lm vic Toluen khng tc ng n tu xng, khng gy hi cho gan. Khng tc ng n h thn kinh ngoi bin, trong nhng iu kin tip xc bnh thng th khng c du hiu lm tn hi n no, nhiu ni ngi ta thy rng toluen t keo dn gy suy tiu no v gn y l cc ca b thiu nng tr tu. t t do keo dnh thng l do lon nhp tim, do ct c tim lun chuyn catecholamin, tuy nhin nguyn nhn thc s phc tp hn nhiu.
2.3. CC HP CHT HU C BN, TN LU LU DI TRONG MI TRNG (POPS)

12 POP (Persistent Organic Pollutants) quan trng nht c th gii quan tm l: aldrin, chlordane, dieldrin, DDT, endrin, HCB, heptachlor, mirex, PCB, toxaphene, dioxin, furan. 2.3.1. PCB (polychlorinated biphenyls) PCB l mt lot hp cht do chlor ho biphenyl. C khong 209 hp cht PCB khc nhau. Chng l cht in mi tt, bn ho hc, bn nhit, khng bt chy, tng i t bay hi, h s cch in cao. Chng c dng trong cng nghip t 1929, lm cht cch in trong bin th, t in, trong cht do, cht dnh, trong cht lng truyn nhit, giy in khng carbon.

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T 1929 n 1977, M sn xut 610.000 tn PCB cc loi. Trong nm 1979 M cm sn xut v tiu th cc sn phm PCB. Cc nc cng nghip pht trin cng thc hin. H thng nht thay th PCB bng cht khc t c hn. Tuy nhin cng c hn khuynh hng a PCB sang tiu th cc nc km pht trin. Hin nay, tng lng PCB hin c trn ton cu c tnh khong 2 triu tn. Nhim c: PCB c th c trong thnh phn hu c trong t, trong trm tch y sng, trong m sinh vt, dung mi hu c. c tnh ca PCB quyt nh bi s lng v v tr ca nguyn t cht lng trong cu trc. S tch t ca PCB trong c th ph thuc vo mc cht lng ho ca nhm biphenyl. Nhim c ch yu: ng n ung, thng qua c, tht gia sc, rau, go. Nhim c cp: t ngi b do p sut hi ca PCB thp. Biu hin: sng m mt, i mu mng tay, mt mi, chong, bun nn. LC50 /v ng vt: 2 - 10g/ kg c th. LC50 c: 0,015mg/l nc, i vi c heo xanh: 2,74mg/l nc, vi c nh rt nhy cm vi PCB, nng ppb lm nhim c trng c, ph n mng trng lm trng khng n c. Nhim c mn: tnh bn ca PCB lm nh hng n tuyn gip khi PCB tch t lu di trong c th, gy ri lon chc nng gan v h tiu ho, c th dn n ung th gan, d dy, gim kh nng min dch ca c th, gy cc bnh v da. Nhng ngi tip xc thng xuyn vi PCB c th xut hin mn chloracne (nhng thng tn v da). Trong trng hp nng, bnh nhn cm thy rt au, bin dng mt v ko di dai dng. Cc nh hng khc giai on ngn, khng phi ung th ca PCB i vi ngi nhim c th c nh lm gim cn, min dch km, nh hng ti h thn kinh, gy au u, hoa mt, cng thng, mt mi, suy

67

nhc Cc biu hin kinh nin cng c th li hu qu ti gan, v hot ng ca enzym Sn phm chy khng hon ton ca PCB bao gm polychlorinated dibenzofurans (PCDs) v polychlorinated dibenzo-p-dioxins (PCDDs), c hai u c hn PCB v gy ra nhng nh hng ti sinh sn, qui thai, nh hng c tnh lp li, c kh nng gy ung th. Chc chn rng, PCB l mt trong s cc hp cht bn nht tng c bit, khi i vo mi trng chng phn hu rt chm, chng rt d chuyn v lu li lu di trong nhng cht m c trong nc ngt v nc mn, k c c sau a vo c th ngi n. PCB tch t trong trm tch y, do s c cc ng vt y v vi sinh vt tiu th. Chim sn mi li n cc loi ng vt y ny v tr thnh ngun mang cht c quan trng. PCB c ch hormon estrogen, dn n c ch lng ng canxi trong qu trnh hnh thnh v trng, dn n v yu v non. PCB c ch hormon androgen c th lm o ngc cc c tnh sinh sn ca chim c, v cc loi ng vt khc. 2.3.2. HCB (hexachlorbenzen) Sn phm thng mi ca HCB bt u nm 1933, ch yu bao ngoi ht ging la m, thay th cho thuc tr nm c thu ngn c. N cng c dng bo v g, cht ph gia polimer, trong nhum, sn xut pho hoa, cht ph gia lm chy chm. T 1978, cc sn phm nh thuc dit nm, bo v g, bn trong c HCB khng c dng M. Tuy nhin c nhng sn phm vn c lng HCB khng mong mun do qu trnh chlor ho hydrocarbon (tetrachloroethylene v cc loi thuc tr su khc). V d trong thuc dit nm quintozn c cha 1-6% HCB. Mt ngun khc sinh ra HCB l t qu trnh thiu cc cht thi c hi v rc sinh hot. 2.3.3. Dioxin
C OCH2COOH C C OCH2COOH

68

2,4-Dichlorophenoxyacetic acid (2,4-D)

2,4,4- Trichlorophenoxyacetic (2,4,5-T)

Hai loi cht dit c trn lm vng l cy trong vng. Chng cng dng khng ch cc thc vt nc trong h, ao, h cha. Dioxin l cht cc k c i vi cc c quan trong c th con gni (LC 50 rt thp). N khng c trong t nhin, l sn phm ph trong tng hp 2,4,5- T, dn n tc hi rt nghim trng khi s dng. Dioxin cng l cht sinh ra khi t cc vt c cha hp cht hu c ca Chlor. C rt nhiu ng phn ca dioxin nhng c nht l 2,3,7,8- tetrachlodibezodioxin (TCDD) C l C l O C l C l

O 2,3,7,8- Dioxin

2,3,7,8 - TCDD bn trong acid, baz, ho tan trong nc thp, phn hu nhanh nhit > 8000C. Qu trnh t cc hp cht PCB khng kim sot nhit c th sinh ra dioxin v furan. C 3 c cht trn u gy mn, pht ban trn da v ko di nhiu tun. Dioxin cn gy nn cc khi u trong c th vt th nghim v ngi. C khong 25 ng phn ca PCB c tnh cht ging dioxin. C khong 17 ng phn ca dioxin v furan c cu trc l nguyn t Cl v tr 2,3,7,8; cc ng phn ny c c tnh cao nht v c kh nng tch t sinh hc. Dioxin v Furan l 2 cht c gy nhiu bnh nguy him v lm bin i nhiu cu trc cng nh cc chc nng ca cc c quan trong c th

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sng v n tc ng nh nhng hoc mon sinh trng. C khong 75 ng phn ca dioxin v 135 ng phn ca Furan. Cc ngun sinh ra Furan v Dioxin: - Sn xut bt giy: trong cng on ty trng bng chlor, nc thi sau ty c cha dioxin - Sn xut thuc bo v thc vt: dy chuyn sn xut th s ch gia cng, pha trn v ng gi sn phm, khng khng ch c lng dioxin hin tng trong mt vi loi thuc tr su; c bit l 6 loi ( b cm lu hnh nhiu nc) trong nhm thuc Chlor hu c lng cao dioxin v ng dng. - Qu trnh s dng qu liu thuc BVTV: nhiu ni vn dng nhng loi thuc trong danh mc thuc cm v phun vi nng cao, dn n h lng tn lu trong sn phm cng nh trong t v ngm xung nc ngm, gy ng c cp v nh hng lu di. Bi nh bit, dioxin l cht c i sn di, tn lu lu bn trong t nhin do lng tch t sinh hc ca n trong t nhin rt nguy him, nht l cho con ngi. - Chy rng, t ci, rm r v cht t thi rn, ligin s kt hp vi Chlor sinh ra dioxin. - Tn d t v tr kh ho hc trong chin tranh, li nhiu hu qu cho nhn dn trong vng b ri cht c ho hc nh nhng bnh nan y, sinh qui thai, cc nh hng di truyn Cc phng php x l dioxin v Furan thng dng l phng php ho hc 9dng chlorua vi, KMnO4 phn hu), phng php quang ho ( chlor ho), phng php vi sinh X l ngun nc thi ca sn xut thuc BVTV, thng thy phn c cht trong nc thi vi KMnO4, sau l Ozon. ngn nga s to ra dioxin tron qu trnh t cht thi rn, bung t phi t trn 13000C, v sau c bung thu hi v x l Dioxin v Furan trong khi. 70

Phn b v chuyn ho: l cht tan trong m v tn lu rt lu. C th sinh vt khng th t o thi dioxin m ch c th tch t ngy cng nhiu v pht bnh. Dioxin thm vo mu v c vn chuyn ti cc m m. Tai y, n tch t li hoc ho tan trong m i vi c th nam, ngoi cch dioxin t phn hu theo chu k bn hu th khng cn cch no khc o thi khi c th. Vi n dioxin c th c o thi qua thai ( li di chng lu di cho cc th h ) hay qua sa. Biu hin nhim c cp (khi nhim lng nh): au bng nhc u, bun nn, tiu chy, song cc triu chng ny s qua nhanh chng, mi nguy him thc s l li hu qu lu di. Tc hi lu di: khi mt lng dioxin ln 9100pg/kg) vo c th s tc ng ln ntron thn kinh, to mt xung tn hiu bt thng i vi h thn kinh trung ng, dn n chng mt, nhc u, mt. Dioxin cn tc ng ln h tiu ho, ph hu v lm bin i men tiu ho, tc ng ln cc t bo c chc nng hp th cht dinh dng trong thnh rut, lm cho ngi nhim b au bng, bun nn, tiu chy. V lu di, dioxin tch t trong c th, tn lu trong cc m m, cc c quan ni tng, cc nguyn t cht lng trong phn t dioxin s tc ng ln cu trc nhim sc th v h gen gy t bin gen, ph hu cu trc nhim sc th v cu trc di truyn, sinh qui thai v d tt bm sinh. Ngoi ra tc ng vo h gen, dioxin cn lm gim kh nng khng ca c th. Ngng c: LOEL (hm lng c th bt u c phn ng) ca dioxin 0.01pg/kg. Nu 1 ngi, 1 ngy nhim 1pg/kg th sau 5-10 nm hm lng trung bnh trong c th 223pg/kg. 2.4. CC HO CHT GY RI LON NI TIT (EDCENDOCRINE DISRUPTING CHEMICAL). 2.4.1. Gii thiu chung: a. Khi nim:

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Ho cht gy ri lon h ni tit (EDCs) l cc ho cht ngoi sinh can thip, cn tr chc nng hot ng bnh thng ca ni tit t (hormon) khi lt vo c th. Cc nh khoa hc pht hin ra rng mt s ho cht trong mi trng c kh nng lm suy yu qu trnh sinh sn ca cc loi ng vt v gy ra cc khi u c tnh bi v chc nng ni tit t bnh thng b ri lon khi nhim phi cc ho cht ni trn. EDCs l cc ho cht c th cn tr v nh hng n h thng sinh sn ca con ngi v ng vt, gy ra cc u c tnh. Khi b nhim cc ho cht , s sng ca con ngi v ng vt s b nh hng nghim trng, lin quan n s sng cn, km theo cc hu qu nghim trng cho cc th h tng lai m chng ta kh lng trc c. b. Cc ho cht nh hng n estrogen (hormon n) Cc tuyn ni tit ra hng lot cc hormon trong c th con ngi. Trong s cc hormon, androgen (kch t tnh c) c ch tit bi tinh hon, estrogen (kch t ng dc) c ch tit bi bung trng, hormon sinh trng (tuyn yn), v insulin (tuyn tu). Con ngi c cc ng vt c xng sng c nhiu im chung v tn gi cc ni tit v thnh phn ho hc c cc hormon ca chng - c bit l cchormon steroid (estrogen, androgen, hormon tuyn thng thn) Cc cng trnh tp trung nghin cu cc ho cht gy nh hng n chc nng bnh thng ca estrogen, v mt s l do: - Nhiu trng hp ung th c pht hin trong cc c quan sinh sn ca ph n c lin quan n vic s dng DES (mt loi estrogen tng hp dng trnh xy thai, dng nhiu trong khong 1960-1970) - Nhiu nh khoa hc pht hin cc tp tnh sinh dc bt thng ca mt s loi ng vt hoang d, c th b gy ra do vic dng DDT hoc cc ho cht gy nhim mi trng khc c c tnh ging estrogen.

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- Mt nh khoa hc M cng b hin tng nonylphenol b r r ra ngoi t cc thit b th nghim khi th nghim vi cc t bo ung th v (MCF-7) c tc dng ging estrogen yu. Tuy nhin khng th nhn nhn c th gy ri lon chc nng hormon hon ton l do cc ho cht c chc nng ging estrogen gy ra. C th l do nhng ho cht khc lm ri lon chc nngca cc hormon khc na. 2.4.2. Ni tit t (hormon) a.Vai tr ca hormon Hormon c tit t cc tuyn ni tit trc tip vo mu. Hormon ng vai tr rt quan trng trong vic phn lp cc m ca ng vt, s sinh trng ca chng, s pht trin cc chc nng sinh sn v iu ho s cn bng bn trong c th. Cc hormon khc nhau tc ng ln cc c quan v cc m khc nhau trong c th. Hormon c tc ng v vi cng tng giai on ca chu k sng. Hormon c tit ra t cc tuyn ni tit khi chng c ih v chng s chuyn ng trong cc mch mu thc hin cc tc ng c c th i hi ti cc c quanhc cc m ca c th. Mt s hormon c dng kch hot v truyn tn hiu trc tip hoc gin tip ti DNA trong nhn, kch thch s sinh ra cc protein c th. Cc hormon sau s b ho tan v bin mt. Qu trnh hot ng ng ca chc nng hormon tht phc tp, cho n nay vn cha c mt gii thch no tht y l ti thi im no cc ho cht gy ri lon ni tit b lt vo c th, c th nh hng ln chc nng bnh thng ca h ni tit. b. Hormon lm vic th no? Hormon c phn loi th thnh hormon steroid, amino acidinductive v peptide (protein) tu theo thnh phn ho hc ca chng. Chng c vn chuyn trong mu dng t do v c gn vi cc cht mang l protein. Khi n cc c quan hoc cc m thch hp cc hormon s gn

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kt vi cc c quan th cm trong t bo (trng hp hormon steroid v amono acid-inductive) v cc c quan nhn cm trn b mt ca t bo (trng hp hormon peptidehc hormon protein), c kch hot v tng tc vi DNA. Hot ng ca hormon c kim sot mt mc rt n nh bng c ch c phn hi. Khi nng ca mt hormon tng n mt mc nht nh th c ch phn hi. + Cc hormon phi c tng hp trong cc tuyn ni tit. + Cc hormon phi c lu gi trong cc tuyn ni tit v s c gii phng ra khi c yu cu. + Cc hormon khi c gii phng ra s c chuyn qua ng mu vo c quan ni tng ch (a ch yu cu) hoc b tiu hu trong gan hoc b thi ra khi c th qua ng thn. + Cc ni tit t (hormon) nhn ra cc c quan th cm c gn kt vi chng v thc hin chc nng kch hot. + Cc hormon sau chuyn tn hiu n cc nhim sc th DNA to ra cc protein hoc kim sot s phn chia t bo. Nu mt ho cht gy ri lon ni tit tc ng ln bt k qu trnh no trn y th s ph v chc nng bnh thng ca hormon hoc chc nng thng thng s b thay th. C khong 7 ho cht hin nay ang b nghi ng c tim nng gy ri lon ni tit. Phn ln cc cht u c nhn nh l c chc nng ri lon cc ni tit t qua vic gn kt vi cc c quan th cm (c ni n ti bc 4 trn). Ngoi cc cht ny, dioxin v cc hp cht thic hu c cng c coi l cc ho cht ngn cn qu trnh 5. Cc styren c coi l cc ho cht lm cn tr s tng hp hormon trong tuyn yn v gy ri lon c ch phn hi. Nh vy chng ngn cn qu trnh (1) v (3). c. Cc c ch mang tnh ho hc i vi vic gy ri lon chc nng ni tit t.

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* Cc c ch gy ri lon ni tit t. Tuy cha c gii thch r rng v c ch ho cht gy ri lon ni tit v v cc chc nng ni tit t bnh thng, nhng c th hiu nh sau: Khi mt hormon steroid c tng hp trong tuyn ni tit v i n c quan ni tng ch, n s gn vi c quan th cm v to ra DNA tng hp thnh mt protein c th. Loi hormon ny xc nh loi c quan th cm m n gn kt. Ho cht gy ri lon ni tit gn kt vi mt c quan th cm v dn n gen s thu nhn tn hiu sai. PCB, DDT nonylphenol v bisphenol A tc ng ging hormon, gn kt vi cc c quan th cm estrogen v lm sai lc tnh nng sinh sn ca con ci. DDE (mt dn xut ca DDT) v vinclozin (ho cht nng nghip) gn kt vi c quan th cm andrro gen (kch t tnh dc) v ngn cn chc nng . Cc nh khoa hc bo co v s tn ti ca cc ho cht gy s sn sinh cc protein chc nng bngcch kch hot cc gen qua tc ng ln ng truyn tn hiu trong t bo m khng gn trc tip vi cc c quan th cm hormon. V d dioxin khng trc tip gn vi c quan th cm estrogen hoc vi c quan nhn cm androgen m chng gy nh hng ln chc nng estrogen mt cch gin tip qua vic gn vi mt protein trong t bo v kch hot cc gen. * Kch t ng dc thc vt - Phytoestrogen C khong 20 loi kch t phytoestrogen l cc ho cht sinh ra bi thc vt v c cc hiu ng nh kch t ng dc estrogen. Khi mt ho cht nh vy c ng vt tiu th, n s nh hng n qu trnh tng hp estrogen v c th tc ng ging estrogen hoc khng estrogen. Lng phytoestrogen c hp th qua n ung ln hn nhiu ln so vi lng hp cht c chlor c a vo c th v sinh ra cc hiu ng dng estrogen. d. nh hng c hi ca EDC

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Cc bo co v tc ng bt li ln c, chim, cc loi b st v ng vt hoang d bao gm chc nng sinh sn khng bnh thng, tp tnh sinh sn bt thng, mt tnh c v hiu qu n trng gim. S lng cc bo co v hin tng trn tng cao t ngt t u nhng nm 1990. Ngi ta nghi ng nguyn nhn trc tip l do s dng DDT v nonylphenol. Cc bo co v nhng nh hng c hi ln sc kho con ngi. - DES - diethylstilbestrol l loi thuc c dng rng ri trong qu kh trnh xy thai gy ra bnh ung th v v cc u c tnh khc. - Khi tc tip xc dioxin vi lng l 126 pg/kg/ngy pht trin bnh vim mng trong d con. N ng ch v ch ra s mt chc nng ca estrogen do dioxin. - Nm 1992 c bo co nu ln s tinh trng ca nam gii an Mch gim i trong sut 50 nm qua. - PCB v Dioxin c mt nhm nghin cu kt lun l gy ri lon tuyn yn. Tuy nhin cng cn rt nhiu vn cn cha r cc EDC nhng co th kt lun mt cch chc chn rng EDC gy ri lon chc nng hormon ca con ngi v ng vt trong mi trng. 67 ho cht b nghi ng l cc ho cht gy ri lon ni tit c Cc mi trng Nht Bn cng b thng 7/1997 (xem danh sch phn ph lc) PHN B: C T SINH VT c t nm (mycotoxin) in hnh aflatoxin Aflatoxin l sn phm trao i cht ca nm trn/trong lng thc hoc thc n gia sc. Chng l loi c t nm c tm hiu v tp trung nghin cu nhiu nht v lin quan n nhiu bnh khc nhau trn ngi v vt nui. S hin din ca aflatoxin l mt yu t mi trng, n ph thuc vng a l, cch thc trng trt v chn nui, s d ly nhim nm

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trong v ma, khi ct gi v trong qu trnh ch bin. Aflatoxin c tp trung nghin cu nhiu hn cc c t nm khc v n gy c tnh cp nguy him trn ngi v l tc nhn gy ung th. Nhiu nc phi a ra quy nh gii hnlng Aflatoxin trn nhng hng ho c dng nh lng thc v thc n gia sc. 1. Gii thiu: Trong nm 1960, hn 100.000 con g ty nh ln ra cht trong vi thng. T xut hin tn "bnh g ty X" iu tra k lng th pht hin nguyn nhn l do thc n t lc ca Braxin c nhim c v c th sinh ra t nm. Sau ngi ta t tn loi c t l Aflatxin. Pht hin ny pht trin nhn thc v mi nguy him tim tng ca cc cht ny bi v s nhim c trong lng thc v thc n s gy bnh tt, thm ch gy cht ngi v gia sc. C 4 loi Aflatoxin chnh B1, B2, G1, G2 trong lng thc v thc n cng thm 2 loi: M1, M2 trong sa b c n c nhim aflatoxin M. Aflatoxin B do pht hunh quang xanh dng di n UV, G: pht hunh quang xanh l - vng. Cc c t ny c Cu trc gn tng t nhau. Cng thc phn t ca Aflatoxin c xc nh qua phn tch nguyn t v khi ph nh sau: B1: C17H12O6 B2: C17H14O6 G1: C17H12O7 G2: C17H14O7 Aflatoxin B2 v G2 l dn xut thm 2 hydro vo B1 v G1. Trong khi aflatoxin M1 l 4-hydroxy aflatoxin B1 v aflatoxin M2 l 4-dihydroxy aflatoxin B2. Aflatoxin B1 l dng hay gp nht trong cc mu b nhim mc. Nu khng c dng aflatoxin B1 th cng khng gp G1. 2. Ngun gc: Aflatoxin thng c trong cy trng trc v gt. Nhim sau thu hoch thng trong kho do m thch hp cho nm mc pht trin. Cn

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trng v chut b ph hoi cng gip cho mc d dng xm nhp vo cc hng nng phm ang ct tr. c pht hin thy trong sa, ph mt, ng, lc, ht bng, nhiu nht l trong ng, lc, ht bng, t hoc khng b ph hu di iu kin n thng thng v trong tit trung. Tuy nhin rang lc th gim hm lng aflatoxin. 3. Aflatoxin v sc kho con ngi. Con ngi nhim aflatoxin do n lng thc c nhim nm. S tip xc ny kh trnh khi v nm pht trin trong lng thc v rt kh phng nga. Thm ch thc n nhim nm nng vn khng b cm lu hnh cc ch cc nc km pht trin. Nhim c cp aflatoxin xy ra nhiu nc thuc th gii th ba nh Ouganda, n , i Loan. Biu hin ng c: nn, au bng, ph phi, co git, hn m v c th cht do ph no, ng m trn gan, thn, tim. iu kin gia tng nhim c cp aflatoxin /v con ngi lin quan n lng gii hn trong lng thc v mi trng, ng thi do thiu h thng qui nh quan trc v kim sot aflatoxin. Bi v Aflatoxin, c bit l B1 l tc nhn gy ung th trn vt th nghim, ngi ta cng quan tm n s pht trin ca nm trn cy trng v cc loi hng ho khc. 1998, IARC xp Aflatoxin B1 vo nhm cc tc nhn gy ung th cho ngi. Tc ng ca aflatoxin ph thuc tui tc, gii tnh, ch dinh dng v tm sut tip xc. 4. Kim sot v qun l Aflatoxin. A. Kim sot bng qui nh. Nhim bn Aflatoxin c coi l khng th trnh khi trong lng thc v thc n gia sc, ngay c trong iu kin sn xut tt. FDA a ra mt hng dn qui nh lng c th chp nhn Aflatoxin trong lng thc ca con ngi v thc n gia sc.

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- Con ngi: 20ppb tng Aflatoxin, vi lng chp nhn c trong sa l 0,5 ppb aflatoxin M1. - Trong thc ng gia sc: 20ppb tng aflatoxin. Tuy nhin rt kh c tnh chnh xc nng aflatoxin trong mt s lng ln mu, do khng th xc nh nng aflatoxin chc chn 100%. B. Chnh sch loi tr c tnh. Bi v khng th phng nga nhim aflatoxin, nn mt s phng n tr c c a ra, bao gm phng php tch vt l, bt hot nhit, chiu x, trch dung mi, hp thu bng cch ho tan, bt hot vi sinh v ln men. Cc phng php ho hc cng c p dng: - Ph hu cu trc sau x l ho hc: nhiu nhm ho cht c th ph huy cu trc hay lm bt hot Aflatoxin. Tuy nhin hu ht khng p dng c do khng an ton hoc li cht c khc hoc khng bo m dinh dng ca lng thc. C 2 cch c ch l ammonia ho v phn ng vi sodium bisulfite. Nhiu th nghim cho thy dng ammonia ho c th loi c c tnh ca Aflatoxin trong ng v cc hng ho khc. C ch; thu phn vng lacton v o ngc ho hoc ca Aflatoxin B1 cho ra mt s sn phm c c tnh gim. cch khc, phn ng vi sodium bisulfite di cc iu kin khc nhau v nhit , nng , thi gian cho ra cc sn phm tan trong nc. - Thay i c tnh bng cch ch n; c ca t nm c th b tc ng mnh bi ch n thay i phn ng thng thng ca c th ng vt i vi cc cht ny. Cc yu t ny gm thnh phn dinh dng (V d : protein, cht bo, vitamin) cht ph tr ( v d cht khng sinh, cht bo qun) v cc yu t khc c th tng tc vi nh hng ca Aflatoxin ln gia sc. - Thay i chp hp thu Aflatoxin: thm mt cht hp thu v c, chng hn nh hydrat sodium calcium aluminosilicate (HSCAS) vo ch

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n ca gia sc. HSCAS c th lin kt v thu hi cc Aflatoxin trong ng rut ca gia sc, kt qu l kh c tnh ca Aflatoxin. 4. Tnh c: Th hin khc nhau rt nhiu loi ng vt. C Cu vng, vt, g ty, ln, th, ch l nhng ging rt nhy cm, trong khi cu li c kh nng chng chu ln nht. Ngoi ra mc gy c cng tu thuc vo tui, gii tnh, tnh trng dinh dng, kiu dng ho cht. Nhn chung Aflatoxin c hn cho cc ng vt non, con c b nhim c nng hn con gi. Biu hin u tin ca nhim c l km n v st cn. Gan l c quan mc tiu ch yu. Tiu thu gan b hoi t thoi ho m. Tng sinh trng tit mt. Bn cnh gan, mt s c quan khc cng b nh hng nghim trng: phi b sung huyt, thnh thong, b hoi t c tim v thn LD50 ng vt T/nghim = 0,5-10mg/kg trng lng c th. - Hot tnh ung th: bt u c bo co nm 1961 trn th nghim vi chut cho n cng bt lc vi g ty mc bnh. Aflatoxin B 1 l cht c nguy c gy ung th gan nhiu nht. Aflatoxin G1 cng l cht gy ung th mnh. Aflatoxin U1 to cc t bo carcinoma c hi v chut, nhng mc t hn nhiu so vi afflatoxin B1. Aflatoxin B2 c hot tnh gy ung th, nhng yu hn 100 ln so vi aflatoxin B1. - Hot tnh gy qui thai: aflatoxin B1 sau khi vo chut c thai s gy ra chm pht trin thai l biu hin th cp ca tnh c aflatoxin, s suy gan m dn n st cn ca bo thai. - nh hng gy ung thu ngi: trong qun th nghin cu, ung th gan xut hin nhiu nht. 5. Cc phng php phn tch Aflatoxin trong lng thc: c 2 cch ho hc v sinh hc. - Phng php ho hc: chit bng aceton, metanol, chloroform, sau lm sch bng sc k ct v nh lng bng sc k lp mng 2 chiu hoc HPLC.

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- Phng php th nghim sinh hc: th nn nhiu h thng sinh hc khc nhau: h thng enzim ngoi t bo, nui cy t bo xc nh s c mt ca aflatoxin hoc nhy vi aflatoxin. PHN C: TC NHN VT L. Bc x ion ho bao gm: - Bc x ion ho trc tip: l cc ht mang in (electron, proton, ht), c ng nng gy ra hin tng ion ho do va chm. - Bc x ion ho gin tip: l cc ht khng mang in (neutron) va cc photon (tia X) c th gii phng cc ht ion ho trc tip hoc c th gy ra cc bin i ht nht (phn ng ht nhn). Cht c phng x: c hai ngun cht thi phng x m ph bin nht l t nh my nng lng ht nhn, m qung Uranium, cht thi bnh vin C 3 loi tia phng x nh hng ln con ngi l alpha, gamma. Mc gy c hi tu thuc loi tia. Cht phng x s gy ra tnh trng thiu mu, suy nhc c th, mt mi, rng tc, c thu tinh th, ni ban da, ung th, hoc gy nhng t bin trong qu trnh hnh thnh t bo, bin i gien lm nh hng n c mt th h tng lai. Liu hp thu D: nhng thay i ho hc v sinh hc xy ra trong cc b phn b chiu x tu thuc vo nng lng m bc x nhng cho b phn b chiu x hn l lng ion m bc x to ra trong khng kh. Liu hp th c th cho bt k loi bc x ion ho no. n v c bit ca liu hp thc l Rad (radiation absorbed dose). 1 rad = 10-2J/kg. Liu tng ng H: l tch s ca D, Q v N ti im quan st trong t chc: H = D.Q.N Trong , H liu tng ng, D liu tng ng tnh bng rad,

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Q- h s cht quy nh s thay i ca hiu ng sinh hc ca mt liu hp th chn trc do tnh cch chuyn nng lng theo ng i ca cc ht in tch to ra do chiu xa. N- Tp hp cc h s bin i khac. Liu tng ng c cng th nguyn nh liu hp thu, do c th dng n v Rad hay J.Kg-1, nhng do tm quan trng ca an ton phng x, H cn c n v ring. l Rem hay Sievert (n v SI) 1Sv = 100 rem Liu gii hn tip xc: Gii hn liu tng ng c tc hi, tip xc hng nm i vi cng ng (hoc 1 tp th) l 5 mSv (0,5rem). Liu tng ng tip xc i vi tng b phn trong c th ngi b chiu x l 50 mSv/ nm (5rem/ nm). nh hng ca tia phng x: Tia phng x khi chiu t ngoi vo b mt c th gi l tc dng ngoi chiu. Cht phng x xm nhp vo c th qua ng h hp, tiu ho, ti cc c quan, sau gy tc dng chiu x th gi l tc dng ni chiu. Tc dng ny nguy him hn tc dng trn. Nn nhn nhim phng x c th hai dng: nhim x cp tnh v mn tnh. Cp tnh: Pht bnh rt nhanh sau khi nhim phng x vi ngy hoc vi gi. Khi c th b nhim x ton thn mt liu trn 300 Rem, c cc triu chng: - Ri lon cc chc nng thn kinh trung ng, c bit l v no, cm gic mt mi. - Da b bng ch tia chiu x i qua. - C quan to mu b tn thng nng n. - Lin kt ho hc ca AND trong t bo b b gy.

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- Suy nhc c th dn n cht. Nhim x cp tnh ch xy ra trong cc v n ht nhn, s c trung tm nguyn t, t gp trong cc iu kin sn xut v nghin cu. Mn tnh: Cc triu chng xut hin vi nm n vi chc nm sau khi b nhim x. Turk (1984) cho bit khi con ngi hay sinh vt tip xc vi ngun phng x t 100-250 Rad th khng cht, nhng mt mi, nn ma, rng tc,xut hin cc mm mng ca bnh ung th.
TI LIU THAM KHO

1. Hong Vn Bnh, c cht hc cng nghip. Ti liu nghip v 11/1996 2. L Huy B ( ch bin), c hc mi trng, NXB H Quc gia TP. HCM, 2000 3. Eros Bacci, Ecotoxicology of organic Contaminants, Lewis Publisher.1994 4. M. Ruchirawat. Enviromental toxicology Chulabhorn research institute (ICETT), vol 1,2,3 5. Gary M. Rand. Fundamental of aquatic toxicology. Hemisphere Publishing Corporation 6. Jaakko Paasivirta Chemical E cotoxicalog Lewis Publishers 1991 7. Vin Chulabhorm.

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Ti liu ca kho o to v "pht hin cc cht nhim mi trng v quan trc cc tc ng n sc kho". i hc Khoa hc T nhin 5/1999 H Ni. 8. Phan Vn Duyt, An ton v sinh phng x, NXB y hc 1986. 9. Trnh Th Thanh c hc, Mi trng v sc kho con ngi. NXB i hc quc gia H Ni 2001 10. Mohamed Larbi Bouguerer, Nn nhim v hnh. NXB H Ni 2001 11. Ti liu c kho o to "c hc cc thuc vt hi v ho cht cng nghip: Bnh ngh nghip v an ton", thng 2/2003. 12/. Ti liu ca kho o to "Qun l v nh gi nhng ri ro cc ho cht mi trng", H Ni thng 12/2003. 13. Edward S.Rubin Introduction to Engineering and Environment MeGraw- Hill Intenational Edition 2001

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PH LC 2 TNG QUAN V POLYCHLORINATED BIPHENYL (PCB) PCBs l g: 1. Cu trc ho hc ca PCBs: a) V cu trc: - PCB c hai vng bnzn v t 1-10 nguyn t cht lng (nh v tr nh hnh v). - C 209 hp cht PCB. PCBs c to ra bi phn ng biphenyl v Clo qua mt xc tc. PCB l mt h cc hp cht hu c clo, bn ho hc, khng chy v khng d sinh ra hi. Chng khng tan trong nc nhng tan c trong du v cht bo. phn ng gia biphenyl v clo vi s c mt ca mt cht xc tc lm mt s nguyn t Hidro b thay th bi Clo. Qu trnh Clo ho ton b (thay th cc nguyn t H) c kim sot, iu khin bi tng s Clo c mt ban u v thi gian din ra phn ng. Sn phm ca phn ng l cc polyclorin biphenyl (vit tt l PCBs). Phn ng ca biphenyl vi clo sinh ra hn hp cc PCBs v ph thuc vo t l gia clo vi biphenyl, vo thi gian v vo nhit rn v tronng mt s l cht rn c im tan thp. Cc ng phn c th c chia thnh nhm tu thuc vo s nguyn t clo gn vo nguyn t biphenyl, V d, mt nguyn t Clo s sinh ra mt mono- clobiphenyl, hai nguyn t Clo sinh ra di- chobiphenyl, mi nguyn t Clo s tng ng to ra deca- clobiphenyl. Tn gi poly- chobiphenyl c dng ch tt c cc PCB. 2. Cc c tnh vt l ca PCBs Tnh cht chng: - L cht lng dng du, c nh sng - Tng t mt ong, nng - Nhn, sp.

85

- Khng chy. - Khng dn in - C im si cao. - Nng hn nc v c tnh tan nh. L tnh ca PCB tu thuc vo s nhm th Cl trong phn t PCB. PCB c 1,2,3 v 4 nhm th Chlo th nh nh du, PCB c 5 nhm Chlo th nng hn, nh dng mt ong. Cn li, hu ht c dng st hoc nh sp. Ni chung, PCBs l cht khng chy v khng tan trong nc. Chng c im si cao v dn in thp. Chng l nhng cht c bn ho, bn nhit. Cc c tnh ny khin PCBs c ng dng rng ri trong cng nghip, nh lm cht in mi, cht lu (hydraulic fluids), dung mi (solvent extender), cht lm chm chy, cht pha long v c, cht in mi, lm mc vit, thuc nhum, sn, v keo. V d PCB c tm thy trong loi giy t cabon, giy bo v hp cht hn x. 3. Lch s ca cc cht PCB. PCBs c pht hin t th k 19 v bt u c sn xut t 1929. PCB c ng dng rng ri nh cc c tnh u vit: khng chy, khng d b phn hu. PCBs c thay th cho cc loi cht cch nhit d chy trc y. Vic s dng PCB gim nguy c chy trong cc vn phng, to nh bnh vin, x nghip v trng hc.. PCB c xem nh loi ho cht k diu. Trong lut trc ki ca mt s thnh ph c quy nh cm s dng du m v yu cu tt c cc cng t, t in, bin p phi l loi dng PCBs. Khi s dng PCb trong cc thit b ny cho php cc t in tr ln nh hn v gim chi ph trang thit b. Cc Cng ty bo him yu cu cc thit b c PCB nhiu ni.

86

PCB c ng dng trong: cc bin p, t in, n in, cc motor, namchm PCB l thnh phn trong cc dy cp in, mch in, bm chn khng,cht dn nhit, cng tc, cu daov cc loi sn phm platic, sn, cht keo, giy carbon, mc PCBs i vo mi trng nh th no? Trc y, PCB thng c tu s dng kh bi (trn vi du dng kh bi). Vic chn lp cc loi rc thi PCB c xem nh hp php v khng c hi. PCBs i vo mi trng t cc pht thi ngu nhin nh: - R r, trn t thit b c cha PCB - T du thi - T cc nhin liu b nhim bn - T bi chn lp Khi t, PCB b phn hu thnh dioxin, dibenzenfuran. Cc cht ny chn PDBs nhiu. Mt c tnh ng ch na l khi t PCB khng chy hon ton (khi du thi c dng nh mt nhin liu). Ngoi ra, PCBs i vo mi trng t cc ngun thi khc nh; chy bin p, n cng t, thi t sn, mc in, keo dnh. NHNG NH HNG CA PCB TI SC KHO 1. u thp k 3: Nhiu ngi b nhim clo khi lm vic vi PCB 2. Nm 1966: PCBs c tm thy trong cc mu t mi trng 3. Nm 1968: Hin tng "yusho" ti Nht Bn. 4. Nm 1978: Bnh "yu - cheng" ti i Loan 5. nm 1999: ti B, 25 lt du my bin th cha PCB, lm nhim 107 tn m, lm nh hng ti hn 2500 gia cm, ln, gia sc.. v lm thit hi khong 1 t USD cho nc ny. Chi ph x l (PCB) c tnh mt khong 1000 USD.

87

1. Hin tng Yusho ti Nht bn: Yusho l tn gi ca bnh m do nhim PCB c trong du cm go(du ng cc) lm 1200 ngi ti Nht bn b nhim c. Yusho ln u c miu t bi cc nh khoa hc Nht bn nh mt bnh clo xut hin ti vng pha ty Nht Bn cui nm 1986. Nhng du hiu u tin nhim c l gia tng tit nc mt, sng m mt trn, da xut hin mu, c th cm thy m yu. Sau , cm thy bun noonm, nn, tiu chy, cc triu chng bnh thn kinh xut hin. Cc th nghim v hot ng ca gan ch ra, c nhng du hiu ca nhim c. Mt loi du t cm go c xem l ngun gc ca s pht sinh bt pht nhng bnh rt thng ny. Cc nghin cu su hn pht hin ra th du go ny b nhim PCB r r t mt b trao i nhit dng trong thit b ch bin du go ny. Hu qu l c trn 1600 ngi b nh hng ca tai nn khng may ny. 2. Bnh Yu- cheng ti i Loan. Bnh ny xy ra i Loan. Khong 2000 ngi n loi du go. Bnh ny do s phn hu sn phm ph (PCB c nguyn t Clo v tr 4). Mt on kho st ca i Loan, Nht Bn thng bo rng hin tng Yusho xut hin i Loan. Khong 1800 ngi i Loan mc phi nhng du hiu v triu chng tng xut hin Nht bn hn mt thp k trc y. Nhng phn tch th du go i Loan cho thy c cha t PCB v v furan hn li du Nht Bn. Tuy nhin, lng du tng cng tiu th nhng ngi mc bnh ti i Loan l khong 13 lt anh/ ngi (=1,14 lt/ ngi), cao hn 28 ounce (n v =~ 30g) so vi lng du tiu th trung bnh nhng ngi Nht. Cc nh nghin cu ngi Nht, i Loan vn ang tip tc phn tch cn bnh ny. 3. Nhng nh hng ca PCB ti sc kho.

88

Nhng nh hng cp tnh: chloracne (nhng thng tn nghim trng trn da), lm da ni mn, mt s iu khin/ ri lon. Cc nh hng lu di (mn tnh): pht sinh bnh, hu hoi gan, cc nh hng c tnh cht lp li v cng tng ln, c th dn ti ung th. c bit cc sn phm b nhim PCB phn hu (thnh cc dng khc) th mc c hi cn nguy him hn. Nhng nh hng ca PCB ti mi trng v sc kho (ngun: USEPA, c quan bo v mi trng M). Cc d liu ch ra rng mt s PCB c kh nng to ra cc nh hng c tnh cht lp li ng vt c v, thm ch mt liu m khng gy nhng du hiu khc ca c tnh. Nhng nh hng cho tr s sinh c biu hin qua th nghim trn cc loi ng vt mi sinh, m con m tip xc vi PCB trc khi sinh v qua sa. Cc nghin cu a tin hnh v ang tin hnh trn qun th ngi cng ch ra nhng du hiu tim tng tng t nh ng vt mi sinh. Trong mt s trng hp, mn chloracne (nhng thng tn v da) c th xut hin trn ngi tip xc thng xuyn vi PCB. Trong trng hp nng, bnh nhn cm thy rt au, bin dng mt v ko di dai dng. Cc nh hng khc giai on ngn, khng phi ung th ca PCB i vi ngi nhim c th c nh lm gim cn, min dch km, nh hng ti h thn kinh, gy au u, hoa mt, cng thng mt mi, suy nhc Cc biu hin kinh nin cng c th li hu qu ti gan, v hot ng ca enzym. Sn phm chaysko hon ton ca PCB bao gm polychlorinated dibenzofurans (PCDs) v polychlinated dibenzo- p-dioxins (PCDDs), c hai u c hn PCB v gy ra nhng nh hng ti sinh sn, qui thai, nh hng c tnh lp li, c kh nng gy ung th

89

Chc chn rng, PCB l mt trong s cc hp cht bn nht tng c bit, khi i vo mi trng chng phn hu rt chm, chng rt d chuyn v lu li lu di vo trong nhng cht m c trong nc ngt v nc mn, k c c sau a vo c th ngi n. PCB tch t trong trm tch y, do s c cc ng vt y v vi sinh vt tiu th. Chim sn mi li n cc loi ng vt y ny v tr thnh ngun mang cht c quan trng. PCB c ch hormon estrogen, dn n c ch lng ng canxi trong qu trnh hnh thnh v trng, dn n v yu v non. PCB c ch hormon androgen c th lm o ngc cc c tnh sinh sn ca chim c, v cc loi ng vt khc. Nhng lut l, quy nh v cc cam kt quc t v PCB. - Cng c Basel - Hi ngh v POP - Cc lut nh ca OECD - V nhiu iu lut, quy nh ti cc nc khc CC KH NNG X L V LOI B PCBS C th x l, loi b PCBs bng cch t nhit cao, bng cc phng php ho hc nhm kh clo v c th bng cc cch tip cn sinh hc khc. 1. X l nhit v cc chi tit k thut ca qu trnh x l nhit: X l nhit t hiu qu loi b ti 99,9999%PCB. Nhit v thi gian x l tng ng l 12000C v 2 giy (vi 3% oxi d). Cc yu cu ca h thng x l nhit gm c: mt h thng in t ngt, v thit b iu khin kh t, mt h thng lc kh t. 2. Mt s cc phng php khc loi b PCB khi du c th p dng nh: - Kh clo

90

- Thc hin cc qu trnh xc tc. - Nu chy cc loi mui. - Hydro ho. - p dng cc bin php in ho. - Oxi ho nc bng cc phng php cao cp. - p dng cc phng php sinh ho a) phng php ho hc kh Clo. ng dung: trong x l du trong cc my bin th. Nguyn tc c bn: l s dng cc cht phn ng da vo kim hoc Kali. Phng php ho hc: kh Clo c th gim mc PCB xung t hn 2 mg/kg (tng ng 2ppm). b) Phng php ho hc: - Qu trnh lm sch du c ng dng rng ri l phng php x l du da vo phn tn chun ca kim. - Nguyn tc: Kim s kt hp vi clo c trong cu trc nguyn t PCB. - Du sau khi kh clo c th ti s dng. c. Cng ngh kim: nhng thun li v kh khn. - u im: cng ngh n gin, kch c thit b gonk - Nhc im: + Vi cc loi du khng tinh khit (ln nc) cn phi tin hnh tin x l. + Tuy r, nhng chi ph x l ph thuc vo nng PCB. d. Cng ngh h quang Plasma. Nguyn l: Cc cht hu c b phn hu nhit ln khong 5000-150000C bi ngn la Plsm. Nhit Plasma sinh ra bng cch cho mt dng in xoay chiu i qua mt lung kh p sut thp. e. Cng ngh Plsm

91

Mt u im quan trng xa x l PCB theo cng ngh plasma (dng nhit cao) l sinh ra cc nguyn t c cu trc n gin v khng c hi. - u im: + H thng x l nh gn hn rt nhiu so vi l t. + Tc khi kh cao. - Nhc im: chi ph cao v du sau x l khng s dng li c. f. Phng php Hydro ho. Phng php x l ny thc hin 8000C, chuyn PCB thnh sn phm ph t c. - u im: c th x l PCB trong my bin p, cng t in cng mt h thng x l. - Nhc im: chi ph thit b cao, khng th ti to s dng du. 3. X l PCB trong cc my bin th. C 3 cch tip cn : Retrofilling, dng dung mi ra v hi kim loi, dng l t a. Phng php retrofilling. Du c ly ra khi my bin p, kh PCB v hi c bm vo bin p (s dng li). Kh PCB trong du bng phng php kh clo hoc cc qu trnh xc tc. Thun li: cc thit b linh ng, d di chuyn. Phng php retrofilling ny p dng cho my bin p loi ln. Ra dung mi - Tho v my bin p. - Ly ra tng b phn - Ra cc b phn bng dung mi, thu hi kim loi ti s dng. - Tip x l du theo cc phng php miu t nc phn trn, hoc c PCB bng chng ct phng php ny chuyn hm lwow3ngj

92

PCB thnh acid HCl (s dng acid ny cho cng nghip ho cht), hoc thiu t (PCB). Vn pht sinh khi p dng phng php ny l mt s cc b phn r (porous) kh loi b PCB. Hm lng PCB cn c tip tc x l theo mt trong cc cch sau: l t, chuyn sang dng acid HCl, x l bng kim, tuy nhin c th s t. 4. Cng t in: x l bng dung mi. vn l kh khn trong vic tch li ca cng t in Kt qu l phn ln nhng cng t in hin nay c t v x l theo cc cng on sau; - Chia cng t thnh nhiu phn, v, li ring. - Ti ch v kim loi. - Ra phn li bng dung dch. - S dng li phn li qua x l, (thu hi phi nhm) KT LUN 1. cc nc c sn cc l t, th cng ngh l t nhn chung c dng loi b PCB kh cc my bin p, cng t in v du thi. Tuy nhin, cc loi hnh cng ngh khc hin cng c th p c p dng x l cc thit b v vt liu cha PCB, c bit l bin php ny (p dng nhiu loi hnh cng ngh khc nhau) rt thch hp ti cc nc ang pht trin. 2. Cc my bin p c th c x l bng ra dung mi v cc phn kim loi trong my. Bin p c th c ti s dng. Cc cng t in c p nh, ra bng dung mi v phi nhm, phn v dng cho ti ch. Du dn in c th x l bng phng php ho hc v ti s dng. 3. Mt s cc vn cn tn ti m cha c cp n khi x l cc thit b v vt liu cha PCB l: du thi, dy cp in, nhiu vt liu khc b nhim PCB nh gng tay, qun o, r lau t b nhim PCB.

93

4. Cc phng php sinh ho cng c th c p dng cng vi cc k thut ph hp trong x l PCB.

94

PH LC 3 Bng 3: cc ho cht nghi ng c hiu ng ri lon ni tit. iu tra mi trn g

St t 1

Cc ho cht

Cng dng (sn phm khng d kin)

Gii hn

Dioxins v furans 2

Polychorina ted biphennayl (PCB)

Polyboromb i phenyl (PBB)

4 Hexachloro benzene (HCB)

Pentachloro phenol (PCP)

Lut nhim khng kh, lut lm sch cng cng v x l rc thi. POPs(ho cht gy nhim hu c tn d). Lut kim tra v quy nh sn xut Giy Cc loi ho cht cp I nm khng c 1974. cm sn xut nm 1972, lut carbon kim tra nhim nc, lut chng chu nhit gy nhim bin, lut v sinh trung cng cng v rc thi. Tiu chun bnh, ho cht lng mi trng v in nc ngm nhim t, nhim nc, POPs Ho cht lm chy chm Thuc Lut v kim tra v quy nh sn dit vi xut, ca cc ho cht cp I khun, nm 1974, khng c ng k nguyn Nht POPs. liu th ho cht tng hp hu c Ho cht Ht hiu lc s dng nm 1990. kh trng, Ho cht nng nghip nhim thuc dit nc, Lut kim tra ho cht c c, thuc v cht gy hi.

95

dit vi khun 6 2,4,5Trichloroph enoxyacetic acid 2,4Dichloroph e noxyacetic acid Thuc dit c Ht hiu lc 1975, lut kim tra ho cht c v ho cht gy hi, lut v sinh thc phm ng k Thuc dit c Thuc dit c, thuc nhum, ho cht ti nha thng Thuc dit c Thuc dit c Khng cn s dng 1975, lut an ton thc phm

Amtrole

9 10 11

Atrazinc Alachlor

ng k

Simazine (CAT) 12 Hexachloro cyclohexan e, Ethyl parathion Carbaryl

ng k, Lut phng chng nhim bin ng k lut phng chng nhim v nc ngm, nhim Thuc t, v nhim nc, lut lm dit c sch cng cng v rc thi. Lut lm sch nc Hexachlorocycloxane ht hn v Thuc tr cm bn nm 1971, ethyl parathion su khng cn s dng nm 1972 ng k, lut kim tra ho cht Thuc tr c v ho cht gy hi, lut v su sinh thc phm

13

96

14 Chlordane

Lut kim tra v quy nh sn xut.. Cc ho cht cp I nm Thuc tr 1981,ht hn nm 1986, lut kim su tra ho cht c v ho cht gy hi, POPs. chlordane Thuc tr Nonachlor khng c ng k ti su Nht heptachlor ht hn nm 1972 Ht hn nm s dng 1980 Thuc tr su Lut v kim tra v quy nh sn xut .. ca cc ho cht cp I Thuc tr nm 1981 ht hn v cm bn nm su 1971, lut v sinh thc phm, POPs thuc tr khng c ng k ti Nht su Thuc tr ang k, lut v sinh thc rp cy phm Lut v kim tra v quy nh sn xut ete ca cc ho cht cp I Thuc tr nm 1981, ht hn nm 1975. Ho su cht nng nghip tn d trong t, lut kim tra ho cht c v cc ho cht gy hi, POPs Lut v kim tra v quy nh sn xut.. ca cc ho cht ho hc nm 1981 ht hn nm 1975, Ho Thuc tr cht nng nghip tn d trong cy su trng, lut kim tra ho cht c v cc ho cht gy hi, lut v sinh thc phm POPs Thuc tr Lut v kim tra v quy nh sn su xut ca cc ho cht nm 1975,

15 16 17

Oxychlorda ne TrnNonachlor 1,2dibromo-3chloropropan e

18 DDT

19 20 21

DDE v DDD Kelthane (Dicofol)

Aldrin

22

Endrin

23

Dieldrin

97

24

Endosulfan (Benzoepin)

Thuc tr su

25 Heptachlor Thuc tr su

Cc ho cht ho hc ht hn nm 1975, cc ho cht ho hc nng nghip tn d trong t, lut kim tra ho cht c v cc ho cht gy hi, lut v sinh thc phm, lut kim tra sn phm cha ho cht c trong gia nh POPs Lut kim tra ho cht c v ho cht nguy hi, ho cht nng nghip nhim nc Lut v kim tra v quy nh sn xut ete ca cc ho cht ho hc nm 1986, ht hn nm 1975, lut kim tra ho cht c v cc ho cht gy hi POPs.

26 27 28 29 30 31 32

Heptachlor epoxide Malathion Methomyl Mthychler Mirex Nitrofen Toxapene (Camphechl or)

Heptachlor Thuc tr su Thuc tr su Thuc tr su Thuc tr su Thuc dit c Thuc tr su ng k, lut v sinh thc phm ng k, lut kim ho cht c v cc ho cht gy hi Ht hn nm 1960 khng c ng k ti Nht, POPs Ht hn nm 1982 khng c ng k ti Nht, POPs

33 Tributyltin

34

Triphenytin

Lut v kim tra v quy nh sn Sn chng xut ete ca cc ho cht TBTO r tu, ho cp I, cn tn 13 ho cht: cp cht kh IITB nm 1990,lut kim tra trng li c sn phm c hi trong gia nh Sn chng Lut v kim tra v quy nh sn r tu, ho xut ete ca cc ho cht cp Ii

98

35 36

Trifluralin

Alkvl phenol (t C5 nC9) Nonyl phenol 37 38

bisphenol A Di(2ethylhexyl) phthalate Bultybenzyl phthalate Di-n-butyl phthalate Decyclohex yl phthalate Diethyl phthalate Benzo(a)py rene Dichloroph enol

39

40

41

42

43 44

nm 1990, ht hn nm 1990, lut cht kh kim tra cc sn phm c hi trong trng li c gia nh Thuc dit ng k c Nguynliu Lut chng nhim bin th sn xut cc ho cht hot ng b mt sn phm phn hu Ha cht Lut v sinh an ton thc phm th nha Ho cht lm do nha Ho cht Lut chng nhim bin lm do nha Ho cht Lut chng nhim bin lm do nha Ho cht lm do nha Ho cht Lut chng nhim bin lm do nha Lut chng nhim bin Hp cht nhum trung gian Ho cht lm do Lut chng nhim bin

45 Diethylhexy l adipate

Lut chng nhim bin

99

46 Beenzophen one

47

4Nitrotoluen e

48 octachlorost yrene 49 50 51 Thuc tr su

Aldicarb Benomyl Kepone (Chlordeco ne) Manzeb (Mancozeb) Maneb Metiram Metribuzin Cypermethr in Esfenvalera t Fenvalerate

nha Ho cht th tng hp i vi sn phm thuc nc hoa Ho cht Lut chng nhim bin trung gian 2,4dinitrolueno (sn xut bi hp ho cht chlorine hu c) Khng ng k Nht Thuc dit ng k vi khun khng c ng k Nht Thuc tr su Thuc dit vi khun Thuc dit vi khun Thuc dit vi khun Thuc dit c Thuc tr su Thuc tr su Thuc tr ng k ng k ng k Ht hn nm 1975 ng k, lut kim sot ho cht c v c hi, lut an ton v sinh thc phm ng k, lut kim sot ho cht c v c hi, lut an ton v sinh thc phm ng k, lut kim sot ho

52 53 54 55 56

57

58

100

59 60 61 62 63 64 65 66

Permethrin Vinclozolol in Zineb Ziram Dipentyl phthalate Dihexylpht halate Dipropyl phthalate Styrens intermediat e nBytylbenzn e

cht c v c hi, lut an ton v sinh thc phm Thuc tr ng k, lut an ton v sinh su thc phm Thuc dit Ht hn nm 1998 vi khun Thuc dit ng k vi khun Thuc dit ng k vi khun khng sn xut Nht su khng sn xut Nht khng sn xut Nht Cao su tng hp Sp trung gian sn xut tinh th lng

67

101