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BASIC TOXICOLOGY

Fathiyah Safithri
FK-UMM
2011

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DEFINISI toksikologi

Ilmu tentang racun

Ilmu yang mempelajari asal, mekanisme


dan efek buruk agen kimia atau fisik dan
radiasi pada organisme 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 mempelajari
toksisitas (molekular, biokemis, behavioral, dll)
Bds kemampuan menimbulkan toksisitas (ringan
sedang, berat, ekstrim, super)
Bdr struktur kimia (aromatik amine, halogenated
hydrocarbon, dll)
dll

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TOKSIKOLOGI DLM LINGKUP
KEDOKTERAN
Forensic toxicology kombinasi kimia analitik dan
toksikologi dasar yang memperhatikan aspek medikolegal

Clinical toxicology fokus pada penyakit yang


disebabkan atau secara unik berhubungan dengan substansi
toksik

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Occupational Toxicology
berhub dg bhn kimia disekitar tempat kerja
terutama identifikasi agent
kondisi tempat kerja aman, absorbsi bahan kimia
berlebih dapat dicegah
guideline konsentrasi bahan kimia di udara yang
pasti aman (establish) ada daftar bahan kimia
yg direkomendasikan memenuhi threshold limit
values (TLVs). Guideline selalu di evaluasi new
information

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Toksikologi Lingkungan
berhubungan dg dampak kimia sbg polutan di lingkungan
organisme hidup udara, tanah, air, dll
target utama manusia, spesies lain target biologik
potensial
Polusi udara produk industri
pengembangan teknologi
peningkatan urbanisasi
Polusi tanah dan air pestisida
Pengolahan makanan residu bahan kimia pada
produk makanan

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Ecotoxicology toksikologi ekosistem

Bioaccumulation = the accumulation of a contaminant or


toxin 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 feeding
relationships within an ecological community.

Osprey

Sucker

Trout

Silverside
Bay
Shrimp
Water Plants
Plankton ORGANIC DEBRIS

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TERMINOLOGI
Toksisitas : derajat keracunana atau injury yg
ditimbulkan oleh suatu bahan kimia. Toksisitas tergantung
pd dosis, lama paparan dan rute / jln masuk, struktur dan
bentuk bahan kimin tsb, dan faktor individual

Agen toksik : bahan kimia yg dpt merusak /


membunuh manusia, hewan atau tumbuhan, yang berasal
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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Klasifikasi berdasarkan Potensi
dlm menimbulkan Toksisitas
LD50 (mg/kg) Examples
Supertoxic < 0.01 dioxin, botulism,
mushrooms
Extreme. Toxic <5 heroin, nicotine
Very Toxic 5-50 morphine, codeine
Toxic 50-500 DDT, H2SO4,
Caffeine
Mod. Toxic 500-5g aspirin, wood alcohol
Slight. Toxic 5g-15g ethyl alcohol, soaps
Non-Toxic >15g water, table sugar

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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 bds
perbandingan 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 & lama


pemakaian 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 coba
dalam 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 menyebabkan
kematian pd 50% populasi hewan coba yg
dipapar 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 motorik
dan prilaku, dll
Pd akhir hr ke-90 darah dan organ
dikumpulkan 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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Classification for Carcinogenicity

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Classification for Carcinogenicity

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Test for Mutagenicity
for measuring heritable alterations in phenotype
and/or genotype. These include tests for detecting the
Mutation loss or alteration of a gene product and change of
function through forward or reverse mutation,
tests recombination, and gene conversion; they may involve
the nuclear genome, the mitochondrial genome, and
resident viral or plasmid genomes.

Chromoso for detecting changes in chromosomal number


mal (aneuploidy), structural chromosomal
effects aberrations, sister-chromatid exchanges,
tests micronuclei and dominant-lethal events.

Cell that monitor the production of preneoplastic


transforma or neoplastic cells in culture and are
tion tests significant because they attempt to simulate
essential steps in cellular carcinogenesis.

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Toksikokinetika
Racun

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RACUN
(senyawa induk)

Intravaskuler Ekstravaskuler

Sirkulasi Darah

Distribusi Eliminasi

Reseptor di
organ / sel target Metabolisme Ekskresi

Efek toksik
Metabolit toksik Metabolit non-toksik

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Timbulnya respon / efek toksik suatu senyawa, tgt pd :
1. kondisi manusia
2. kondisi pemajanan (exposure)
3. mekanisme kerja bhn toksik
4. 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 sirkulasi


Distribusi : 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 Exposure
There 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
in through the mouth and passes through the GIT
ADME (target organ adverse effect is dependent
upon the concentration of active compound at the
target site for enough 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
Racun yg ada di GIT tidak akan menyebabkan efek
toksik selama belum diabsorbsi, kecuali jk racun
bersifat kaustik atau sangat iritatif utk GIT

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Dermal Exposure

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 or
mouth

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EFEK / RESPON TOKSIK

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DEFINISI EFEK TOKSIK
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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EFEK TOKSIK

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TOXIC RESPONSE

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Spectrum of biological response to
environmental pollutant exposure

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TOXIC RESPONSE

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Wah, aman apa nggak
ya ???..

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