Basic Toxicology

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PRINSIP-PRINSIP TOKSIKOLOGI Dr. dr. Nurdiana, Mkes TOKSIKOLOGI : mempelajari sifat-sifat racun zat kimia serta keamanannya terhadap mahluk hidup dan lingkungan What is a Poison? All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a remedy. Paracelsus (1493-1541) Xenobiotik ( Xeno = asing ) zat kimia baru uji toksisitas

Transcript of Basic Toxicology

Page 1: Basic Toxicology

PRINSIP-PRINSIP TOKSIKOLOGI Dr. dr. Nurdiana, Mkes

TOKSIKOLOGI : mempelajari sifat-sifat racun zat kimia serta keamanannya terhadap mahluk hidup dan lingkungan

What is a Poison? All substances are poisons;

there is none that is not a poison. The right dose differentiates a poison and a remedy.

Paracelsus (1493-1541)

Xenobiotik ( Xeno = asing ) zat kimia baru uji toksisitas

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UJI TOKSISITAS : AKUT

KRONIS

ACUTE EXPOSURE

- DOSIS BAHAN KIMIA TUNGGAL ATAU DL WAKTU PENDEK (PADA UMUMNYA KURANG DARI SATU HARI)-HEWAN COBA : TIKUS, MENCIT, JANTAN ATAU BETINA

-Pemeriksaan : kematian hewan coba dalam kurun waktu 14 hari.(weight, behavioral, lethargy, food consumption etc)

- Information: LD50,target organ, reversibility, dose-response

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Measures of Toxicity:The Median Lethal Dose

LD50

The amount (dose) of a chemical which produces death in 50% of a population of test animals to which it is administered by any of

a variety of methods

mg/kgNormally expressed as milligrams of substance

per kilogram of animal body weight

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Measures of Toxicity:The Median Lethal

ConcentrationLC50

The concentration of a chemical in an environment (generally air or water) which

produces death in 50% of an exposed population of test animals in a specified time

frame

mg/LNormally expressed as milligrams of substance

per liter of air or water (or as ppm)

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Fig. 16.5, p. 400

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ToxicityLD50 measured in mg/kg of body weightLD50 measured in mg/kg of body weight

LD50 (mg) 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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CHRONIC EXPOSURE

Subchronic ExposureToxic symptoms are expressed after

repeated applications for a timeframe less than half the life expectancy of the organism (90 days)

Examination: body weight, food consumtion, respiratory and cardiovascular distress, motor and behavioral abnormalities etc

At the end of the 90-day blood and organ collected for analysis

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Chronic Exposure

Expression of toxic symptoms only after repeated exposure to a chemical in doses regularly applied to the organism for a time greater than half of its life-expectancy

Mice : 18 m – 24 mRats : 2-2.5 y

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Pemeriksaan toksisitas tergantung tujuan dan lama penggunaan :

obat cacing penggunaan cepat perlu data toksisitas akut

obat hipertensi, obat kontrasepsi penggunaan lama/kronik perlu data karsinogenisitas, teratogenisitas

Uji toksikologi zat kimia :

-farmakokinetik ADME

-farmakodinamik EFEK YG PALING MENONJOL

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Contoh :

penggunaan obat baru risiko reaksi toksik (walaupun kecil 0,001 %)FDA zat x harus diberikan pd 15 000 org utk melihat manifestasi reaksi tdk dikehendaki

Frekuensi kejadian dipengaruhi :

Umur sex, ras, kehamilan, kelainan gen

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MENILAI KEAMANAN ZAT KIMIA

Zat kimia yg baru disintesis dan mau digunakan

uji toksisitas.

NEL

( No Effect Level )

Jumlah atau konsentrasi suatu zat kimia yg ditemukan melalui penelitian atau observasi yg tidak menimbulkan kelainan buruk, perubahan morfologi atau fs organ, pertumbuhan, perkembangan, maupun mengurangi 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 yg dapat diberikan setiap hari seumur hidup dan dapt diperkirakan tidak menimbulkan efek kesehatan yg buruk pada manusia, berdasarkan pengetahuan yg ada waktu itu

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

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MPC : maximal permissible concentration

konsentrasi zat kimia yg diperbolehkan berada dalam makanan tertentu

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

faktor makanan (kg)

Faktor makanan : konsumsi rata2 suatu makanan tertentu dlm kg/orang/hr

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Area toksikologi khusus yang penting utk 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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Toksikologi di tempat kerja (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, spesias 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.

ORGANIC DEBRIS

Osprey

Water Plants

Sucker

Bay Shrimp

Trout

Plankton

Silverside

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Measures of Toxicity

• Toxicity of chemicals is determined in the laboratory

• The normal procedure is to expose test animals– By ingestion, application to the skin, by

inhalation, gavage, or some other method which introduces the material into the body, or

– By placing the test material in the water or air of the test animals’ environment

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Measures of Toxicity

• Toxicity is measured as clinical “endpoints” which include :– Mortality (death)– Reproductive tox

(teratogenesis,reproduction performance,perinatal and postnatal tox)

– Carcinogenicity (ability to cause cancer), and,

– Mutagenicity (ability to cause heritible change in the DNA)

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What is a Response?

• Response (symptoms) could be on the molecular, cellular, organ, or organism level

(interference w/receptor,membrane function,cellular energy production, biomolc, calsium homeostasis etc)

• Local vs. Systemic • Reversible vs. Irreversible• Immediate vs. Delayed• Graded vs. Quantal degrees of the same damage vs. all or none

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Primary Routes of Exposure

There are three primary routes by which organisms are exposed to

pesticides

Oral

Dermal

Inhalation

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Primary Routes of Exposure:

Oral ExposureAny exposure which occurs when the chemical is taken in through the mouth and passes through the gastrointestinal tract

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

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Primary Routes of Exposure:

Dermal ExposureAnimal backExposure of the skin Examination: erithema,edema, corrosive action

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Primary Routes of Exposure:

Inhalation ExposureOccurs when a chemical is breathed into

the lungs through the nose or mouth

Significant route of exposure for aquatic organisms

Not of toxicological concern until it crosses from the lung into the body (unless the chemical is corrosive)

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UJI TOKSISITAS

Sebelum menguji suatu bahan telah ada :

Data identifikasi, sifat zat kimia dan rencana penggunaan

Hal-hal yang harus di : - bahan yang diuji

persiapkan - dosis

- hewan coba

- cara pemberian

- lama pemberian

- efek yang diamati organ, laboratorium

hasil

- pengunaan

-