NH GI C TNH

NH GI MI QUAN H LIU LNG PHN NG

(DOSE-RESPONSE RELATIONSHIPS)

1. Tng quan v phng php 2. Cc thng s nh gi

TNG QUAN V PHNG PHP

c hc mi trng (environmental toxicology) hoc c hc sinh thi (ecotoxicology) l khoa hc nghin cu v tc ng ca c cht trong mi trng ti sinh vt v con ngi. Ni dung ca c hc mi trng:

Ngun gc pht sinh

Con ng xm nhp

Phn ng ca i tng

Mc tiu c hc mi trng:

Xc nh tc nhn gy nh hng
D on, nh gi nguy c xut ngn nga, gim thiu tc ng tiu cc
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TNG QUAN V PHNG PHP

Tc nhn gy c: l bt k cht ho hc no gy nhng hiu ng xu ti sc kho hoc gy cht cho sinh vt. Tt c cc cht ho hc u c tnh c (Paracelsus, 1538)

Theo c tnh sinh hc

c cht (toxicant)

Theo bn cht gy c
c bn cht (natural toxicity) c liu lng (dose toxicity)

Theo tim nng hot tnh

c tim tng (Potential toxicity) c hot tnh (Actual toxicity)

Theo tc ng/ tnh nng

c cp tnh

c t (toxin)

c mn tnh

TNG QUAN V PHNG PHP

Da theo mc bn vng
Khng bn (1 2 tun: Hu c, cacbonat) Bn trung bnh (3 18 thng: hu c P, N, S) Bn vng (2 5 nm: hu c clo) Rt bn (>5 nm vnh vin: kim loi nng)

Da theo c quan b tc ng
Gy nh hng h thn kinh (Cl2, O3, mui KLN, formon, F) Gy c mu (Zn, P)

Gy c nguyn sinh cht (Hg, S)

Gy c h enzym (P, F, Na2SO4) Gy m (HCCl3, CCl4, ete) Gy kch ng (kim, axit, mui kim loi nng)
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TNG QUAN V PHNG PHP

Da theo kh nng gy ung th ( ngi)

Nhm 1: Tc nhn gy ung th Nhm 2A: Tc nhn c th gy ung th (mang tnh tnh hung) Nhm 2B: Tc nhn c l gy ung th (bng chng cha y ) Nhm 3: Tc nhn khng th phn loi da trn kh nng gy ung th Nhm 4: Tc nhn c l khng gy ung th

TNG QUAN V PHNG PHP

Mt s thut ng khc
c ho sinh (Biochemical toxicity) c hnh vi (Behavioral toxicity) c dinh dng (Nutritional toxicity) Cht gy ung th (Carcinogenesis) Cht gy t bin (Mutagenesis) c c quan (organ toxicity) Tc ng ti cc enzym, t bo cht Tc ng n biu hin, thn kinh Tc ng n sinh trng, pht trin Tng sinh trng t bo bt thng

Tc ng ln vt cht di truyn Tc ng n 1 c quan chc nng

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PHNG PHP NH GI C TNH

Cn c vo mi quan h gia cc /b/gi tr th nghim Phng php dy (n yu t) Nng /liu lng: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 ppm Phng php ma trn (2 yu t)
Nng / Thi gian 1 gi 2 gi 3 gi 4 gi 5 gi 24 gi 1 2 3 4 5 6 7 8 9 10 7

PHNG PHP NH GI C TNH

Cn c sn phm/kt qu ca th nghim c tnh

Th nghim cp tnh (Acute Toxicity) LD50 LC50 TL50 EC50 LOAEL NOAEL

Th nghim tch lu sinh hc Tn ng sinh hc Th nghim x l Sinh vt tch lu

Th nghim mn tnh (Acute Toxicity) MATC Th nghim kh nng gy ung th Th nghim c sinh sn

SINH VT TH NGHIM
c cp tnh Sinh vt tch t c mn tnh

SINH VT TH NGHIM
Mt s sinh vt thng s dng

Daphnia Fathead minnows Rats/Mice

D quan st v d nui quy m phng th nghim

Ph bin, thng dng

C nhiu dn liu v c im sinh l, sinh sn R tin, d kim trong t nhin Vng i ngn
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Animal Cell cultures

Algal cell cultures Duckweed Mealworms Earthworms Frogs/tadpoles

MI QUAN H LIU LNG PHN NG

o Liu lng: l n v tip xc ca mt ho cht i vi sinh

vt c biu din bng nng hoc liu lng tip xc:

o Nng tip xc: khi lng/th tch mi trng tip xc o Liu lng tip xc: khi lng/th trng; khi lng/din tch b

mt tip xc

o Phn ng: l biu hin ca mt hoc mt vi b phn hoc

ton b c th sinh vt trc nhng cht gy kch thch

o Mi quan h gia liu lng v phn ng: nh lng nh

hng ca vic tip xc cht c vi nhng biu hin ca sinh vt th nghim

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MI QUAN H LIU LNG PHN NG

Mi quan h c biu din bng hm hi quy gia liu lng v phn ng ca sinh vt A. th tn sut B. th tch lu

Phn ng ph thuc liu lng Liu lng ngng: im bt u xut hin phn ng c: ph thuc dc ca ng cong

S dng so snh gia cc cht c hoc nh gi mt cht c

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MI QUAN H LIU LNG PHN NG

Khng c php gi nh a ra mi quan h liu lng phn ng Cc gi thit Phn ng quan st c ch do tc nhn ch nh gy nn Mc phn ng tng quan vi liu lng Phn ng c chn phi c o lng chnh xc thng tin nh lng

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MI QUAN H LIU LNG PHN NG

Cc thut ng lin quan

Phn trm tch lu ca phn ng (%)

100

Threshold dose Hyper-susceptible Cc c th nhy cm

Ceiling effect Hypo-susceptible Cc c th chng chu

Liu lng (mg/kg)

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MI QUAN H LIU LNG PHN NG

Liu nh hng (Effective dose, ED): phn ng mong i c quan st thy vi liu cho Liu c (Toxic Dose, TD): Liu lng m ti s nhim c biu hin c th th nghim Liu gy cht (Lethal dose, LD): gy nn phn ng t vong cho cc c th th nghim

Cc k hiu ED50,

TD50, LD50, ED99, TD10, LD10

c ngha % s c th th nghim c phn ng liu th nghim

Phn trm tch lu ca phn ng (%)

Cc thut ng lin quan

Liu lng (mg/kg)

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PHNG PHP NI SUY

Xc nh LD, ED trong nghin cu c tnh Phng php chuyn dng s liu

Trung bnh 34.13%

13.6%

2.13%

-2

-1

2
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lch chun (SD - Standard deviations)

PHNG PHP NI SUY

Xc nh LD, ED trong nghin cu c tnh Phng php chuyn dng s liu

ng cong phn b thng thng

Chuyn dng s liu 50% c th phn ng

% tch lu ca phn ng

EC50
Liu lng

Log(Liu lng)
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V D GI TR LD50 CA MT S CHT
Sodium Chloride 2,4-D (thuc dit c) DDT Caffeine Nicotine Strychnine sulfate (thuc dit chut) Botulinum toxin 4000 mg/kg 368 mg/kg 135 mg/kg 127 mg/kg 24 mg/kg 3 mg/kg 0,01 g/kg

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MI QUAN H LIU LNG PHN NG

Mc khng c nh hng c th quan st (No Observable Effects Level, NOEL) Mc khng c nh hng c hi c th quan st (No Observable Adverse Effects Level, NOAEL) Mc c cho l khng c nh hng c hi (Suggested No Adverse Response Level, SNARL) Gii hn nh hng c th quan st thp nht (Lowest Observable Effect Limit, LOEL) Gi tr gii hn ngng (Threshold Limit Value, TLV)

Phn trm tch lu ca phn ng (%)

Cc thut ng lin quan

Liu lng (mg/kg)

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VAI TR CA NGNG C
Cc gi tr quan trng NOEC/NOEL LOEC/LOEL

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VAI TR CA NGNG C

c mn tnh: MATC (nng c cc i c th chp nhn) NOEC(NOEL) < MATC < LOEC(LOEL)

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PHNG PHP NH GI (SO SNH 2 CHT C)

mnh l mt khi nim tng i so snh cc c cht da trn cng phn trm tch lu ca phn ng (vd: LD50). Tnh hiu qu: mt c cht c tnh hiu qu cao khi quan h liu phn ng c dc ln hn trn mt khong di. Tnh c o ngc: th c im ct nhau. iu ny xy ra khi mt c cht trong mt khong ca liu khng lun lun mnh hn mt c cht khc.

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BI TP V D
Nng % sng st 0 mg/l (i chng) 100 1 100 3 90 10 30 30 20 100 0

Th nghim c cp tnh trn Daphnia magna

p s:

NOEC: 1 mg/l LOEC: 3 mg/l 1 < MATC < 3 mg/l LC50 = 8,18 mg/l
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THO LUN PHNG PHP

Nng 0 mg/l (i chng) 1 3 10 30 100 100 100 90 30 20 0 % sng st 100 100 90 100 90 80 20 40 30 20 10 0 100 100 90 30 10 0 100 100 80 20 30 0

p s:

NOEC: t-test 1 pha LOEC: t-test 1 pha NOEC < MATC < LOEC mg/l LC50 = LC50 trung bnh
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THO LUN PHNG PHP

NOEC: t-test 1 pha Gi thuyt Ho: Trung bnh th nghim = 0 i thuyt H1: Trung bnh th nghim 0 LOEC: t-test 1 pha Gi thuyt Ho: Trung bnh th nghim = 0 i thuyt H1: Trung bnh th nghim 0 NOEC v LOEC mc ngha v s bc t do ng vi s php th/php lp li i vi 1 cht c hoc 1 nn th nghim So snh NOEC v LOEC mc ngha gia hai cht c hoc 2 nn th nghim: s dng t-test 2 pha Gi thuyt Ho: NOEC/LOEC (1) = NOEC/LOEC (2) i thuyt H1: NOEC/LOEC (1) NOEC/LOEC (2)

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XIN CHN THNH CM N

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