Kesling Toksling

7/17/2019 Kesling Toksling

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Xenobiotik

P =4>40 4670< ?4<7 19?9> C3<407682

Xenobiotik Lingkungan Organisme Efek Biologis

+;487B 34@90 :437 ?20:4 >7:9A I%&'(#)*+*,- /'#,&*0,-D

4Q41C5670D 1404840 ?234@90D >2N40 ?234@90J

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$98?23

EMISI

EKOKINETIKA

FARMAKOKINETIKAPEMAPARAN

IMISI



Jenis-jenis

xenobiotik

Emisi:-

Point

- Area

-

Mobile

Sumber: Cunningham, 2008



Ekokinetika

! Proses biotik abiotik (fisik, kimia, danenzim)! Transportasi: jarak pendek dan jarak

jauh! Efek regional atau lokal

Tergantung: sumber, distribusi/transportasi, dan transformasi

! Mudah ditransportasi (gas, partikulat,aerosol dan cairan), kelarutan

! Persistensi di lingkungan! Reaktivitas (interaksi dengan

komponen lain) ! toksisitas,degradabilitas, distribusi

! biokonsentrasi, bioakumulasi dan

biomagnifikasi




Ekokinetika

$C;9?7;7146 :40 8C?7;7146B

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–

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828?340 A28?90<596 62; 12369690 C;2> 620L4N4 57874 L40< 6239A4

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Bioakumulasi - Biomagnifikasi




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Ekokinetika

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TRANSFORMASI

• +=%"!%#B

– [C1C57874 S "567:467

– "567:467 S h2:9567

– /7:3C;7676 S ;4700L4B 4;57;467D 5;C370467

•

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– E753CC3<407684

– !404840 :40 >2N40



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Imisi

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S 59;71

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Farmakokinetika

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Dosis vs konsentrasi?



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Efek

•

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Penyakit Non-Infeksi



Efek pada manusia

Efek pada organismetergantung:

- toleransi,

-

hipersensitivitas,

-

kumulasi

Pada:

sel, enzim, DNA, RNA,

organ target (hati, sistemsaraf, paru-paru, ginjal,

kulit)

Efek berdasarkan gejala:

-

Fibrosis

-

Granuloma

-

Demam-

Anfiksia

-

Alergi

-

Mutan, kanker, dan teratoma

-

Endocrine disrupture

-

Neurotoksik

Keracunan sistemik



Senyawa karsinogenik dalam kopi

k +@214;:2>L:2

k =20_4;:2>L:2

k =20_202

k =20_CK9340

k =20_Cl4mAL3202

k W4i27@ 4@7:

k W412@>C;

k XDTDYDe .7?20_401>34@202

k -1>40C;

•

-1>L;?20_202

k [C384;:2>L:2

k [9340

k [93K934;

k /L:3C<20 A23C^7:2

k /L:3Cn970C02

k &78C0702

k $1L3202

k !C;9202

k gL;202

Toksik: 100 cangkir kopi! LD kafein



Mekanisme dalam

menurunkan efek toksik•

Degradasi Metabolik dan Ekskresi

•

Mekanisme perbaikan kerusakan



Degradasi metabolik dan ekskresi

!

Sistem Ensimatik:-0678 I- 8753C6C8C04; ,cYZJ! 8209390540 2K25 1C5675

E484;74B 123;2145 :7 >4M

!

Ekskresi:-;7870467 :437 19?9> 82;4;97 A3C626 25653267

EC;259; OC;4M;B W"TD /W) :40 521C0! 25653267 82;4;97 676128 A2304K4640

'4348 :40 620L4N4 ;470 ?23;2?7>! 52370<41

$20L4N4R?4>40 123;4391! K90<67 <70H4;! 9370

!

Akumulasi senyawa toksik:#23964540 676128 O714;B <70H4;D ;48?90<D 9696



Sel Tumbuhan, Hewandan Mikroorganisma



Metabolisme Xenobiotic

!

o4;93 8214?C;7684 L40< 820<9?4> 61395193

57874 620L4N4 xenobiotic

!

h24567 57874 I?7C13406KC38467JB

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! A3C626 :21C567U5467

! !23H4:7 :4;48 b K462




•

[462 % B 8C:7U5467

•

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• [462 %%%B 8C:7U5467 ;40H9140 :40 25653267

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! 820<20:4;7540 ;70<590<40 7012304;

$20L4N4 AC;43! M:45 :4A41 82028?96

52@94;7 620L4N4T L40< :7A23;9540!

13406AC31 A3C1270




Fase I (Modifikasi)

•

E2;7?41540 ?23?4<47 20678Cytochrome P-450 I6DED EF;GD 6DEF;G/ `

:2A20:201 87^2: K90@MC0 C^7:462 6L6128!

123H4:7 :7 871C5C0:374 4149 32M59;98 20:CA;4684

• h24567B

–

"567:467D – h2:9567

– /7:3C;7676 Reaksi yang dikatalisa:

monooksigenase

RH + O2 + 2H+ + 2e – ! ROH + H2O



Reaksi monooksigenase

•

"567:467 4;7K4M5R43C84M5 ! 4;5C>C;

• )S:24;57;467 ?7;4 4:4 <9<96 hS)SW/b! hS)/ p

/W/"

•

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/W/"

• $S:24;57;467B A434MC0! A43C56C0

• "567:4MK :24870467 ?7;4 4:4 <9<96 hS)SW/b!

hS)/ p /W/"



Reaksi Oksidasi lain

•

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620L4N4 43C84M5 =20_202! [20C;

• "567:467 820<>467;540 /7:3C<20 ,23C567:4

I/T"TJ! 820L2340< 69?61341! ;954 57874



#$%& ' '

•

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• -0678B

–

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– .')/#%0%& ,)'*)$+')(

–

1&/0%' #+')(

–

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Metabolisme lipofilik Fase I dan II

Hasil konyugasi:

•

Polaritas tinggi

•

Lebih terlarut dalam air

•

Lebih mudah dieliminasi (ekskresikan)



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– '70H4;

–

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–

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! 1*'&'2*3"& 45$3# 60+*3"#')



Mekanisme perbaikan•

Perbaikan kerusakan pada individual sel sampaiDNA atau protein pada tingkat molekular, jaringan

dan organ.

•

Jika suatu sel terpapar secara teratur oleh senyawatoksik mekanisme perbaikan.

• Kulit, lapisan epitel saluran pencernaan, pembuluh

darah, paru2: laju reproduksi selular tinggi utkmengganti sel rusak pertumbuhan tdk terkendali

kanker/tumor

Kesling Toksling

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