toksikologi dasar
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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
atausangat iritatif utkGITCreate PDF files without this message by purchasing novaPDF printer (http://www.novapdf.com)
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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 ???..