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BASIC TOXICOLOGY

Fathiyah Safithri

FK-UMM

2010

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DEFINISIIlmu tentang racunIlmu yang mempelajari asal, mekanisme dan efek

buruk agen kimia atau fisik dan radiasi padaorganisme hidup atau sistem biologis lain.

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KLASIFIKASI Sistem klasifikasi sangat bervariasi

Bds tujuan / bidang aplikasi (forensik, klinik,lingkungan, okkupasional, dll)

Bds sistem organ yg dipengaruhi (kardiovaskular,renal, neuro. Dll)

Bds metode riset yg digunakan utk mempelajaritoksisitas (molekular, biokemis, behavioral, dll)

Bds kemampuan menimbulkan toksisitas (ringansedang, berat, ekstrim, super)

Bdr struktur kimia (aromatik amine, halogenatedhydrocarbon, dll)

dll

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Forensic toxicology kombinasi kimiaanalitik dan toksikologi dasar yang memperhatikanaspek medikolegal

Clinical toxicology fokus pada penyakityang disebabkan atau secara unik berhubungandengan substansi toksik

RUANG LINGKUP KEDOKTERAN

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berhub dg bhn kimia disekitar tempat kerja

terutama identifikasi agent

kondisi tempat kerja aman, absorbsi bahan kimiaberlebih dapat dicegah

guideline konsentrasi bahan kimia di udara yangpasti aman (establish) ada daftar bahan kimiayg direkomendasikan memenuhi threshold limit

values (TLVs). Guideline selalu di evaluasi newinformation

Occupational Toxicology

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Toksikologi Lingkungan

berhubungan dg dampak kimia sbg polutan di lingkunganorganisme hidup udara, tanah, air, dll

target utama manusia, spesies lain target biologikpotensial

Polusi udara produk industri

pengembangan teknologi

peningkatan urbanisasi

Polusi tanah dan air pestisida

Pengolahan makanan residu bahan kimia padaproduk makanan

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Ecotoxicology toksikologi ekosistem

Bioaccumulation = the accumulation of a contaminant ortoxin in or on an organism

from all sources (e.g., food, water, air).

Biomagnification = the increase in concentration of

toxin as it passes through successive levels of the food web

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Food Web =A summary of the feedingrelationships within an ecological community.

ORGANIC DEBRIS

Osprey

Water Plants

Sucker

Bay

Shrimp

Trout

Plankton

Silverside

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TERMINOLOGI Toksisitas : derajat keracunana atau injury yg

ditimbulkan oleh suatu bahan kimia. Toksisitastergantung pd dosis, lama paparan dan rute / jln

masuk, struktur dan bentuk bahan kimin tsb, dan faktorindividual

Agen toksik : bahan kimia yg dpt merusak /membunuh manusia, hewan atau tumbuhan, yangberasal dari produk alam, mis tumbuhan, hewan,

bakteri, jamur, logam berat (arsen), dll Toksikan : .berasal dari aktivitas manusia. Mis logam

berat (arsen)

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LD50 (mg/kg) Examples

Supertoxic < 0.01 dioxin, botulism,mushrooms

Extreme. Toxic 15g water, table sugar

Klasifikasi berdasarkan Potensi dlm

menimbulkan Toksisitas

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Testing Toxicity

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Parameter utk menentukan dosis toksik

hewan coba

Dosis toksik tiap spesies berbeda

Luas permukaan tubuh (Surface area) lebih

akurat Berat badan

dosis toksik pd tikus stl dihitung bdsperbandingan BB tikus-manusia = hanya 1/10

dari dosis toksik yg diterima manusia

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UJI TOKSISITAS AKUT : LD50, LC50 SUBKRONIS

KRONIS KHUSUS : teratogenisitas, karsinogenisitas,

mutagenitas

Uji toksisitas yg digunakan tgt tujuan & lamapemakaian bhn kimia yg akan diuji Obat anti cacing : uji toksisitas akut Obat anti hipertensi, anti DM : uji toksisitas kronis,

karsinogenisitas, teratogenisitas

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UJI TOKSISITAS AKUT ACUTE EXPOSURE

= Dosis bahan kimia tunggal atau dlm

waktu pendek(umumnya < 1 hari ) Hewan coba : tikus, mencit jantan atau betina

Pemeriksaan penyebab kematian hewan cobadalam kurun waktu 14 hari

Diamati : BB, prilaku, konsumsi makanan, dll Informasi: LD50 / LC50, target organ,

reversibility, dose-response

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Dose-Response Curve

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The Median Lethal Dose (LD50)

Dosis bahan kimia yg menimbulkan kematian pd 50%populasi hewan coba. Dosis diberikan dlm bbrp metode

Satuan :

mg/kg

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The Median Lethal Concentration (LC50)

Konsentrasi bahan kimia dlm lingkungan

(umumnya udara / air) yg menyebabkankematian pd 50% populasi hewan coba ygdipapar dlm periode waktu tertentu.

Satuan : mg/L atau ppm

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UJI TOKSISITAS SUBKRONIS Gejala / tanda toksik tampak setelah dipapar

berulang selama < usia harapan hidup

(90 hr) Diamati : BB, konsumsi makanan, gangguan

respirasi, kardiovaskuler, perubahan motorikdan prilaku, dll

Pd akhir hr ke-90 darah dan organdikumpulkan utk dianalisa

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UJI TOKSISITAS KRONIS Gejala /tanda toksik tampak setelah

dipapar berulang dg bhn kimia pd dosis

tertentu selama usia harapan hidup Mice : 18 - 24 bulan

Rats : 2 - 2.5 tahun

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PARAMETER DALAM MENILAI KEAMANAN

ZAT KIMIA DLM MAKANAN

Zat kimia yg baru disintesis dan mau digunakan

uji toksisitas.

Parameter yg digunakan :

a.NoAEL ( No Observed Adverse Effect Level )

b.LOAEL (Lowest ObservedAdverse Effect Level )

c. ADI (Acceptable Daily Intake)d. MPC (Maximal Permissible Concentration)

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NoEL =NOAEL

(No Observed Adverse Effect Level)

= Jumlah atau konsentrasi suatu zat kimia

terbesar (yg ditemukan melalui penelitian atauobservasi) yg tidak menimbulkan kelainanburuk, perubahan morfologi atau fungsi organ,pertumbuhan, perkembangan, maupun

mengurangi lama hidup hewan coba. Menunjukkan batas dimana efek / respon

toksik tertentu mulai terlihat (threshold dose)

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Masing masing efek / respon toksik mempunyaithreshold dose

Efek toksik Asetil salisilic acid a.l : perdarahan GIT,

tinnitus & asidosis sistemik. Threshold dose perdarahanGIT =1-2 tablet pd dewasa, tinnitus = 20-30 tab,asidosis sistemik = 40-50 tab

Efek / respon toksik berupa Kanker dpt tjd tanpa

menunggu tercapainyathreshold dose non

threshold response (satu molekul sdh cukup utkmenimbulkan efek toksik berupa Ca)

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LOAEL

(Lowest Observed Adverse Effect Level )

= Jumlah atau konsentrasi suatu zat kimia terkecil

(yg ditemukan melalui penelitian atau

observasi) yg menimbulkan kelainan buruk,perubahan morfologi atau fungsi organ,pertumbuhan, perkembangan, maupunmengurangi lama hidup hewan coba.

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ADI

(acceptable daily intake)

= Dosis suatu zat kimia terbesar yang

dinyatakan dalam satuan mg/kg BB/hari ygdapat diberikan setiap hari seumur hidup dandapat diperkirakan tidak menimbulkan efekkesehatan yg buruk pada manusia,

berdasarkan pengetahuan yg ada waktu itu

NOEL/100 = ADI (mg/kg BB/hari)

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MPC(maximal permissible concentration)

= konsentrasi zat kimia yg diperbolehkan berada dalammakanan tertentu

ADI x Berat badan (kg)MPC = -------------------------- = . ppm

faktor makanan (kg)

Faktor makanan : konsumsi rata2 suatu makanan tertentu(kg/orang/hr)

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Toksikokinetika

Racun

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Intravaskuler Ekstravaskuler

Distribusi Eliminasi

Metabolisme Ekskresi

Reseptor di

organ / sel target

Metabolit toksik Metabolit non-toksikEfek toks ik

Sirkulasi Darah

RACUN

(senyawa induk)

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Timbulnya respon / efek toksik suatu senyawa, tgt pd :

1. kondisi manusia2. kondisi pemajanan (exposure)3. mekanisme kerja bhn toksik4. wujud dan sifat efek toksik

Route of entry : Intravaskuler : i.v, i.a, i.k Ekstravaskuler (ada fase absorbsi): p.o, i.m, i.p, s.c,

inhalasi, dermal

Absorbsi : menent kecepatan & kdr toksikan dlm sirkulasiDistribusi : menent kecepatan & kdr toksikan di tempat kerja /organ target

Eliminasi : menent kadar dan durasi toksikan di organ target

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Primary Routes of ExposureThere are three primary routes by which

organisms are exposed

Oral

Dermal

Inhalation

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Oral Exposure

Any exposure which occurs when the chemical is taken inthrough the mouth and passes through the gastrointestinaltract

ADME (target organadverse effect is dependent upon the

concentration of active compound at the target site forenough time ),

Not all organs are affected equally,greater susceptibility of the target organ,

higher concentration of active compound Liver, Kidney Lung, Neurons, Myocardium, Bone marrow

Racunygadadi GIT tidakakanmenyebabkanefek toksikselamabelumdiabsorbsi, kecuali jk racunbersifat kaustik

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Dermal Exposure

Animal back

Examination: erithema,edema, corrosive action

Barier kulit yg menyulitkan absorbsi toksikan :

- Lapisan terluar kulit adalah sel mati

- Sel terluar epidermis dipadati keratin

- Suplai darah jelek

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Inhalation Exposure

Occurs when a chemical is breathed

into the lungs through the nose ormouth

Significant route of exposure for

aquatic organisms

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What is a Response / Effect ? Respon (gejala) / efek akibat bahan toksik

dapat dilihat dari tingkat molekuler,

sellular, organ, atau tingkat organisme Respon /efek dapat diklasifikasikan a.l :

Local vs. Systemic Reversible vs. Irreversible

Immediate vs. Delayed Graded vs. Quantal

(degrees of the same damage v/s all or none)

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Wah, aman apa nggak

ya ???..