Dr.Yusof Omar, MD

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1. Defintion;

2. Fate of Toxins: Toxicokinetic and toxicodynamic;

3. Measures of Concentration of Toxic Substances

4. 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

Chemical properties

Physical agents

Examples:

Biological, dust, fibers, noise and

radiation

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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

5. Solids

• Organic

- Coal

• Inorganic

- Lead, Iron, Nickel

Types of toxicant

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Integrates the exposure by all sources

(occupational and non-occupational)

Asbestos

dust

Tobacco

smoke

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TO

XIC

AN

T

HUMAN

Upta

ke &

distrib

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n:

Inte

rnal d

ose

TO

XIC

EFFEC

T

DIS

EA

SES (Te

mpora

ry/p

erm

anent)

Ro

ute

Of E

ntry

EX

PO

SU

RE

LIVER

DETO

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N:

Toxic/N

on

toxic e

ffect

Yusof - 2010

1. Storage; or

2. Elimination: excretion

Skin absorption

Injection

Inhalation

Ingestion

Exposure: route of entry

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 Formic acid

• HYDROXYLATION: Benzene Phenol

b) CONJUGATIONS

• Toluen + Glycine= Hippuric 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. Expired air: alcohol

2. Alimentary canal: stools

3. Kidney: Urine e.g. lead, benzene , phenol

4. Saliva e.g. lead

5. Sweat: Hg

6. 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

Dose (D)

Effective dose(ED)

-Safe, reversible

-e.g eye irritation

Toxic dose (TD)

e.g Brain damage

Lethal dose (LD)

- Death

Dose

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% of population

100

50

0 ED50 Dose

50% of population intoxicated at ED50

Individual resistance

b) Quantum effect

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% o

f p

op

ula

tio

n a

ffec

ted

100

50

0

LD50 Dos

Relative Toxicity Index: LD50

LD50 = 50% died

• 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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• Age • Gender • Allergy • Genetic • Immunological status • Dietary status • Existence of chronic diseases

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Toxicant

characteristics Individual

susceptibility

Toxicant concentration Relationship between dose and effect.

Composition

Physical state Solution, dust, gaseous, vapor sand solids.

Duration of exposure Acute/Chronic

Route of entry Inhalation, ingestion, absorption, penetration.

Method of exposure Localized/Generalized

Latent period Immediate effect/Delay

Reaction process Reversible/Irreversible

Metabolism

Detoxification and excretion

Specific target organ Asbestos (lung)/ Cadmium (kidney)/

Special effects Allergic reaction, Carcinogenic, Mutagenic, Teratogenic

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Toxicant characteristics

• 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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