TOKSIKOLOGI

Pendahuluan

Defenisi

Toksikologi: Ilmu yang mempelajari hal ikhwal racun terutama pengaruhnya pada makhluk hidup
Merupakan multidisipliner: Ilmu kimia, biokimia, biologi, faal, patologi, farmakologi, ilmu kesehatan masyarakat

Toxicology can be defined as that branch of science that deals with poisons, and a poison can be defined as any substance that causes a harmful effect when administered, either by accident or design, to a living organism.

By convention;

toxicology also
includes the study of harmful effects caused by physical phenomena, such as radiation of various kinds and noise.

Broader definitions of toxicology, such as the study of the detection, occurrence, properties, effects, and regulation of toxic substances,

Toxicity itself can rarely, if ever, be defined as a single molecular event but is, rather, a cascade of events starting with exposure, proceeding through distribution and metabolism, and ending with interaction with cellular macromolecules (usually DNA or protein) and the expression of a toxic end point.

The study of toxicology

to protect humans and the environment from the deleterious effects of toxicant
to facilitate the development of more selective toxicants such as anticancer and other clinical drugs and pesticides.

TOXICOLOGY
POISON * CHARACTERISTIC * ACTION OF DAMAGE * CLINICAL SIGN * THERAPEUTIC MANNER

SUBSTANCE

INDIVIDUAL PHYSIOLOGY LIFEABILITY

PATOLOGY DAMAGE OF ACTIONS LOCAL DAMAGEOF LOCAL CEL (SKIN, MUCOUS) LOCAL PAIN S/ SYSTEMIC TOXEMIA SYSTHEMIC ABSORPTION CIRCULATION ORGAN S/SPESIFIC CYANIDA RESPIRATION INSECTISIDE CNS STRYCHNIN .SPINAL CHORD

The definition of a poison, or toxicant

a qualitative biological aspect because a compound, toxic to one species or genetic strain, may be relatively harmless to another. For example: Carbon tetraclorida: potent hepatotoxicant in many species, is relative harmless to the chicken.

Toxicant Exposure

Entrance to Body Ingestion Skin Inhalation

Absorption into Blood Stream and Distribution to Body Tissues and Organs Storage Excretion

Toxicity

Metabolism

Perkembangannya toksikologi terbagi menjadi beberapa subdisiplin: - toksikologi klinik; diagnosis dan terapi keracunan - toksikologi forensik; medikolegal - toksikologi lingkungan; polusi atau pencemaran udara, air dan tanah, residu obat dan racun serta higiens industri dipelajari lebih rinci -toksikologi ekonomi; aspek ekonomi - toksikologi perang; aspek pertahanan&keamanan Toksikologi patologi:changes in subcellular,

Applied toxicology

1. Clinical toxicology: diagnosis and treatment of human poisoning Veterinary toxicology : diagnosis and treatment of poisoning in animals other than humans Forensic toxicology: medicolegal aspects, including detection of poisons in clinical Enviromental toxicology: movement of toxicants and their metabolites and degradation products in the enviroment and in food chains and with effect of such contaminants on individuals Industrial toxicology: a specific area of enviromental toxicology, part of industrial

Relative Toxicity:Are all substances toxic?

Sugar has an LD50 of 30,000 mg/kg Even water has a recognized LD50 of slightly greater than 80,000 mg/kg

PATBH paracelcus
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1493-1541: A. percobaan pada hewan merupakan cara yang paling baik dalam mempelajari respon tubuh terhadap racun B. efek suatu bahan pada tubuh dapat merupakan efek terapetik yang berguna dan efek toksik yang merugikan. Kedua macam efek itu timbul karena ada perbedaan dosis Doses make poison
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World War I Chlorine gas, mustard gas and other human pesticides Curies (Marie, Pierre and Irene) discover radium and radioactivity and their toxicities 1920s Arsenicals developed to treat syphillis

1962 Rachel Carsons Silent Spring and the beginning of the environmental movement Analytical capabilities to PPB (part per billion) levels Minimata Bay and Hg poisoning

Hubungan dosis dengan efek

- kuantitas racun yang masuk - cara - frekuensi - tipe dan derajad cidera serta waktu yang diperlukan untuk menimbulkan cidera tersebut

Ukuran toksisitas disebut dengan Potensi Potensi besar: <<< dosis----kematian/keracunan

Lethal dose

LD; ukuran toksisitas

Jumlah kematian yang timbul pada sekelompok hewan uji setelah diberi suatu dosis racun * ukuran yang bersifat komparatif dan relative yang dapat menggambarkan prakiraan rentag dan batas dosis yang aman digunakan Starting point; dalam penelitian toksikologik

Kurva respon; (lihat di e book)

Potensi toksisitas
1. Sangat toksis LD50 <1 mg/kgBB 2. Toksis sekali: 1-50 mg/kgBB 3. Toksis: 50-500 mg/kgBB 4. Tidak begitu toksis: 500-5000 mg/kg 5. Tidak toksis: 5-15 g/kg 6. Tidak membahayakan sama sekali: >15 g/kgBB

Margin of safety

Batas keamanan dinyatakan sebagai indek terapi

=Jarak antara dosis yang menimbulkan efek yang diharapkan (secara maksimal) dengan dosis yang mengakibatkan mulai timbul kematian (ED99 - LD1)

Indeks terapi
Perbandingan antara LD1 dengan ED99 Karena dosis letalis dan dosis efektif pada umumnya dinyatakan pada tingkat 50% maka indeks terapi itu dinyatakan oleh perbandingan antara LD50 dan ED50