Dr.

Yusof Omar, MD

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1. 2. 3. 4.

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

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TOXICOLOGY The qualitative and quantitative study of the adverse effects of toxicants on biological/living organisms. TOXICANT A toxic substance chemical, physical agents etc.

TOXICITY Property of the toxicants describing its health risk effect.

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TOXICANTS

Chemical agents

Physical agents

Chemical properties

Examples: Biological, dust, fibers, noise and radiation

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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

Integrates the exposure by all sources (occupational and non-occupational)

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DISEASES (Temporary/permanent)
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TOXIC EFFECT Storage; or Elimination: excretion Yusof - 2010 1. 2.

LIVER DETOXIFICATION: Toxic/Nontoxic effect

HUMAN

Uptake & distribution: Internal dose

Route Of Entry

EXPOSURE

TOXICANT

Exposure: route of entry

Ingestion

Inhalation

Skin absorption

Injection

Integrates the exposure by all routes

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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)

Toxic dose (TD)

Lethal dose (LD)

-Safe, reversible
-e.g eye irritation

e.g Brain damage

- Death

Dose
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Dose (D)

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b) Quantum effect
Individual resistance

100

% of population
50

50% of population intoxicated at ED50

ED50
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Dose
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Relative Toxicity Index: LD50

100 % of population affected

50

LD50 = 50% died

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

Allergic reaction, Carcinogenic, Mutagenic, Teratogenic

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 Local effects
Irritant Sensitivity/ allergic Corrosive

Systemic effects
Depend on system affected Teratogenic Carcinogenic Mutagenic

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 Types of Classification : i. Physicochemical properties/characteristics ii. Health effects.

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).

 Contamination with this substances can cause skin or tissue damage .

 Cause limited health effect.

lethal dose : LD50 : 200-500 mg/kg , oral (mice). LD50 :400-2000mg/kg, skin ( mice) . LD50 : 2-20 mg/liter , inhalation (mice).

 skin or mucousal rashes after repeated exposure.

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