CONTENT • Toxicology • Principle of toxicity • Poisons • Xenobiotics • Duration of poisons • MOA • Transport • Reference TOXICOLOGY Toxicology is defined as the science of poisons with Its • Distribution • Effect on human body • Mechanisms of action It also includes the study of the effects of physical agents such as radiation and heat BASIC PRINCIPLES OF TOXICITY: 1. Poisons • Paracelsus in the 16th century that “all substances are poisons” • The right dosage differentiates a poison from a remedy. • Therapeutic drugs with potentially harmful effects. BASIC PRINCIPLES OF TOXICITY: 2. Xenobiotic • The exogenous chemicals in the environment that may be absorbed by the body through 1. inhalation 2. ingestion 3. skin contact BASIC PRINCIPLES OF TOXICITY: 3. Duration of poisons: Chemicals may be excreted or accumulate: Urine Feces expired air Bone Fat Brain other tissues BASIC PRINCIPLES OF TOXICITY: 4. Mechanisms of action: • Chemicals may act at the site of entry, or they may be transported to other sites • Some agents are not modified on entry in the body • but most solvents and drugs are metabolized to form - water-soluble products - activated metabolites BASIC PRINCIPLES OF TOXICITY: • The metabolic reaction occur in two phases •Phase-I reaction: chemical can undergo 1. Hydrolysis 2. Oxidation 3. Reduction • It involved cytochrome p-450 enzyme system located in the ER of • Liver primarily • Skin • Lung • GI mucosa BASIC PRINCIPLES OF TOXICITY: • In Phase-I reaction two metabolites are form 1. Water soluble Metabolite (excret in urine) 2. Active Metabolite • The active Metabolite can enter to phase two reaction. •phase II reactions: • Active metabolite of phase-I undergo 1. Glucuronidation (conjugation of glucuronic acid which make insoluble substance soluble) 2. Sulfation (addition of sulfate) 3. Methylation (addition of methyl) 4. conjugation with glutathione • Water-soluble compounds are readily excreted. CONT….. • In both reaction ROS can produce, as a byproduct, which can cause cellular damage MECHANISMS OF ACTION DIAGRAMMATICAL VIEW metabolism BASIC PRINCIPLES OF TOXICITY: 5. Transport • Most solvents and drugs are lipophilic • It transport in the blood by lipoproteins • penetration through lipid components of cell membranes SUMMARY • Poisons enter to the body • Absorbed into bloodstream • When the poisons is soluble then the liver can excret out the substance • If the poisons is insoluble then the substance is stored by liver and then lead to toxicity. • Reference: Robbins BASIC PATHOLOGY (TENTH EDITION) • Page no: 301

1. P R E P A R E D B Y : S H A F Q A T H U S S A I N
D I S C I P L I N E : M L T
M A R D A N C O L L A G E O F M E D I C A L T E C H N O L O G I E S ( B K M C )
TOXICITY OF CHEMICAL
AND PHYSICAL AGENTS

2. CONTENT
• Toxicology
• Principle of toxicity
• Poisons
• Xenobiotics
• Duration of poisons
• MOA
• Transport
• Reference

3. TOXICOLOGY
Toxicology is defined as the science of poisons with
Its
• Distribution
• Effect on human body
• Mechanisms of action
It also includes the study of the effects of physical
agents such as radiation and heat

4. BASIC PRINCIPLES OF TOXICITY:
1. Poisons
• Paracelsus in the 16th century that “all substances
are poisons”
• The right dosage differentiates a poison from a
remedy.
• Therapeutic drugs with potentially harmful effects.

5. BASIC PRINCIPLES OF TOXICITY:
2. Xenobiotic
• The exogenous chemicals in the environment that
may be absorbed by the body through
1. inhalation
2. ingestion
3. skin contact

6. BASIC PRINCIPLES OF TOXICITY:
3. Duration of poisons:
Chemicals may be excreted or accumulate:
Urine
Feces
expired air
Bone
Fat
Brain
other tissues

8. BASIC PRINCIPLES OF TOXICITY:
4. Mechanisms of action:
• Chemicals may act at the site of entry, or they may
be transported to other sites
• Some agents are not modified on entry in the body
• but most solvents and drugs are metabolized to
form
- water-soluble products
- activated metabolites

9. BASIC PRINCIPLES OF TOXICITY:
• The metabolic reaction occur in two phases
•Phase-I reaction: chemical can undergo
1. Hydrolysis
2. Oxidation
3. Reduction
• It involved cytochrome p-450 enzyme system located in the
ER of
• Liver primarily
• Skin
• Lung
• GI mucosa

10. BASIC PRINCIPLES OF TOXICITY:
• In Phase-I reaction two metabolites are form
1. Water soluble Metabolite (excret in urine)
2. Active Metabolite
• The active Metabolite can enter to phase two reaction.
•phase II reactions:
• Active metabolite of phase-I undergo
1. Glucuronidation (conjugation of glucuronic acid which
make insoluble substance soluble)
2. Sulfation (addition of sulfate)
3. Methylation (addition of methyl)
4. conjugation with glutathione
• Water-soluble compounds are readily excreted.

11. CONT…..
• In both reaction ROS can produce, as a by-
product, which can cause cellular damage

12. MECHANISMS OF ACTION
DIAGRAMMATICAL VIEW
metabolism

13. BASIC PRINCIPLES OF TOXICITY:
5. Transport
• Most solvents and drugs are lipophilic
• It transport in the blood by lipoproteins
• penetration through lipid components of cell
membranes

14. SUMMARY
• Poisons enter to the body
• Absorbed into bloodstream
• When the poisons is soluble then the liver can excret
out the substance
• If the poisons is insoluble then the substance is
stored by liver and then lead to toxicity.

15. • Reference: Robbins BASIC PATHOLOGY (TENTH
EDITION)
• Page no: 301