lecture 12 toxicology
TRANSCRIPT
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
utio
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
XIF
ICA
TIO
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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