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Yusof Omar, MD
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Defintion; Fate of Toxins: Toxicokinetic and toxicodynamic; Measures of Concentration of Toxic Substances Factors Influencing Toxic Effect a) Toxicant characteristic b) Personal Factors Effect of Toxin 5. Health Effects
DrYusofCUCMS2012
DrYusofCUCMS2012
DrYusofCUCMS2012
DrYusofCUCMS2012
DrYusofCUCMS2012
TOXICOLOGY The qualitative and quantitative study of the adverse effects of toxicants on biological/living organisms. TOXICANT A toxic substance chemical, physical agents etc.
TOXICANTS
Chemical agents
Physical agents
Chemical properties
Types of toxicant
1. Particulates dust Nuisance-calcium , silicon Fibrogenic-silica, coal dust Fibers-asbestos, mineral wool Fumes-metal 2. Gaseous Oxon Carbon monoxide 3. Vapors Benzene Hexan 4. Liquids Phenol Elemental mercury Solids Organic - Coal Inorganic - Lead, Iron, Nickel
5.
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Tobacco smoke
Asbestos dust
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DISEASES (Temporary/permanent)
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HUMAN
Route Of Entry
EXPOSURE
TOXICANT
Inhalation
Skin absorption
Injection
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1. Most process occur in the liver; 2. Non-toxic/Toxic end product; 3. Process involved, examples: a) METABOLIC TANSFORMATIONS OXIDATION: Methanol Formaldehyde HYDROXYLATION: Benzene Phenol b) CONJUGATIONS Toluen + Glycine= Hippuric acid
Formic acid
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Before or after liver metabolism: Protein-Hg, Chromate +protein in tissue/blood Fat-High lipid soluble Bone- Pb etc
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1. 2. 3. 4. 5. 6.
Expired air: alcohol Alimentary canal: stools Kidney: Urine e.g. lead, benzene , phenol Saliva e.g. lead Sweat: Hg Breast milk: lead
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Quantity of toxicant taken by the human: Ingestion (mg/kg) Gaseous (ppm atau mg/m3)
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1. Dosage of toxicant with its health toxic effects. 2. Graph of Dose-response curve: a) Graded effect - Health effects Vs Dosage b) Quantum effect - Dosage Vs Physiological, biochemical or death.
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Toxicity
Effective dose(ED)
-Safe, reversible
-e.g eye irritation
- Death
Dose
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Dose (D)
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b) Quantum effect
Individual resistance
100
% of population
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ED50
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Dose
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50
LD50
Dos
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For ingestion route of exposure. ED50: effective dose for 50% of subjects (response is minor and reversible) TD90: toxic dose for 90% of subjects (irreversible) LD10 : lethal dose for 10% of subjects LD50/30 or an LD50/60 : a dose that without treatment will be lethal to 50% of the population within (respectively) 30 or 60 days. Unit: mg/kg body weight. N.B: One curve representing one agent.
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Inhalation or absorption routes of exposure. EC10: effective dose for 10% of subjects.(response is minor and reversible) TC50: toxic concentration for 50% of subjects (irreversible) LC90: lethal concentration for 90% of subjects. Unit: ppm or mg/meter cubic of the air.
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LD50 for DDT is 113 mg/kg and Ethyl alcohol is 1,400 mg/kg. Which toxicant has more toxicity?
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Toxicant characteristics
Individual susceptibility
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Age Gender Allergy Genetic Immunological status Dietary status Existence of chronic diseases
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Toxicant characteristics
Toxicant concentration Composition Physical state Duration of exposure Route of entry Method of exposure Latent period Reaction process Metabolism Detoxification and excretion Specific target organ Asbestos (lung)/ Cadmium (kidney)/ Solution, dust, gaseous, vapor sand solids. Acute/Chronic Inhalation, ingestion, absorption, penetration. Localized/Generalized Immediate effect/Delay Reversible/Irreversible Relationship between dose and effect.
Special effects
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Local effects
Irritant Sensitivity/ allergic Corrosive
Systemic effects
Depend on system affected Teratogenic Carcinogenic Mutagenic
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A. Very toxic Severe acute, severe chronic health effect or fatal Lethal dose: LD50 < 25 mg/kg , oral (mice). LD50<50 mg/kg, skin ( mice) . LD50<0.5 mg/ liter (4 hr), inhalation (mice).
B. TOXIC: Acute health effect Chronic health effect cancer, teratogenic or mutagenic Lethal dose: LD50 25-200 mg/kg , oral (mice). LD50 50-400 mg/kg , skin ( mice) . LD50 0.5-2 mg/ liter (4 hr), inhalation (mice).
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