Section 10: Key Points

What We've Covered
This section made the following main points:

• Absorption is the process by which toxicants gain entrance into the body.
• Ingested and inhaled materials are considered outside the body until they cross the cellular barriers of the gastrointestinal tract or respiratory system.
• The likelihood of absorption depends on the:
  • Route of exposure.
  • Concentration of the substance at the site of contact.
  • Chemical and physical properties of the substance.
• Exposure routes include:
  • Primary routes:
    • Gastrointestinal (GI) tract
      • Mouth and esophagus — poorly absorbed under normal conditions due to short exposure time (nicotine and nitroglycerin are notable exceptions).
      • Stomach — significant site for absorption of weak organic acids, but weak bases are poorly absorbed.
      • Intestine — greatest absorption of both weak bases and weak acids, particularly in the small intestine.
      • Colon and rectum — very little absorption, unless administered via suppository.
    • Respiratory tract
      • Mucociliary escalator — movements of the cilia push mucus and anything contained within up and out into the throat to be swallowed or removed through the mouth.
      • Pulmonary region — most important site for absorption with about 50 times the surface area of the skin and very thin membranes.
    • Skin
      • Epidermis and stratum corneum — the only layer important in regulating the penetration of a skin contaminant.
      • Toxicants move across the stratum corneum by passive diffusion.
      • If a toxicant penetrates through the stratum corneum, it enters lower layers of the epidermis, dermis, and subcutaneous tissue, which are far less resistant to further diffusion.
  • Other exposure routes:
    • Injections
    • Implants
    • Conjunctival instillations (eye drops)
    • Suppositories
• Cell membranes surround all body cells and are made up of a phospholipid bilayer in which each molecule contains a:
  • Polar (hydrophilic, or attracted to water) phosphate head
  • Lipophilic (attracted to lipid-soluble substances) lipid tail
• Xenobiotics must pass across cell membranes to enter, move within, and leave the body. This movement can be either:
  • Passive transfer (most common) — simple diffusion or osmotic filtration with no cellular energy or assistance required.
  • Facilitated transport — similar to passive transport, but a carrier-mediated transport mechanism and thus faster and capable of moving larger molecules.
  • Active transport — movement against the concentration gradient (from lower to higher concentrations), requiring cellular energy from ATP.
  • Endocytosis — the cell surrounds the substance with a section of its cell wall, separating from the membrane and moving into the interior of the cell.

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The concept of distribution