PubH 462 - Environmental Toxicology and Health

Lecture Topic: Absorption, Distribution, and Elimination (Including Biotransformation)

Overview

• Today's lecture focuses on key aspects of toxicology: absorption, distribution, elimination, and biotransformation.
• Discussion of membrane transport and the phospholipid bilayer, essential for understanding how chemicals move through the body.
• Exploration of the toxicokinetics and toxicodynamics of chemicals in the body.

Membrane Transport

• Phospholipid Bilayer: Fundamental structure of membranes; understanding its characteristics helps explain chemical movement.
• Physical Properties of Chemicals: Importance of polarity; polar vs. non-polar chemicals.

Absorption

• Types of Absorption:
  • Skin absorption (dermal)
  • Respiratory absorption
  • GI Tract absorption

Distribution and Elimination

• Movement of chemicals once absorbed and pathways for elimination.
• Toxicokinetics: How chemicals travel to target sites.
• Toxicodynamics: Interaction with target molecules leading to possible damage.

Toxicokinetics vs. Toxicodynamics

• Toxicokinetics: Movement of the chemical to the site of toxicity.
• Toxicodynamics: Interaction with target molecules, leading to cellular dysfunction or disease.
• Steps in Toxicity:
  1. Delivery to target site.
  2. Reaction at the target site.
  3. Cellular dysfunction resulting in toxicity.

Case Studies

• Tetrahydrotoxin: Targets nerve cells; found in pufferfish; disrupts sodium channels.
• Melamine: Used in plastics; causes kidney damage when ingested; forms crystals in kidneys.

Factors Affecting Toxicity

• Host Factors:
  • Size, age, sex, species, and internal environment
• Chemical Factors:
  • Route and rate of administration
  • Interactions with other drugs

Toxicokinetics in Detail

• Absorption: Chemicals enter bloodstream via various routes.
• Distribution: Spreading of chemicals across the body.
• Elimination/Biotransformation: Chemicals are metabolized and/or stored before elimination.

Phospholipid Bilayer and Chemical Movement

• Phospholipids: Composed of polar heads and non-polar tails.
• Chemical Movement:
  • Hydrophilic vs. hydrophobic chemical behavior
  • Small molecules vs. large molecules

Factors Influencing Membrane Transport

• Chemical Charge: Charged molecules struggle to pass the bilayer.
• Molecular Size: Smaller molecules pass through more easily.
• Polarity: Polar molecules face difficulty moving through the bilayer.
• Membrane Composition & Thickness: Variability affects transport ease.

Conclusion

• Understanding these key elements provides a solid foundation for studying toxicology.
• Importance of biochemical properties and physiology in determining chemical behavior in biological systems.