Module 3: Toxicology - Section 2: General Principles of Toxicology

TOX2.4: Absorption

ABSORPTION:

Both the concentration and lipid solubility of the toxic substance determine the rate of absorption. Increased blood flow and large surface areas of exposure increase the rate of absorption. Common routes of absorption are the astrointestinal tract, respiratory tract and skin or dermal system.

Most toxic substances that are ingested are absorbed in the small intestine. However the most common route of exposure is the respiratory tract with most gaseous and volatile substances being inhaled. The degree of water solubility and ionization of the toxic substance determines its point of absorption in the respiratory tract. Relatively acidic substances such as aspirin are in an ionized state in alkaline environments and non-ionized in acidic environments, hence aspirin is well absorbed in the stomach.

Dermal absorption is dependent on the degree of contact of the toxic agent and its lipid solubility. Aspects such as hydration of the dermis, open lesions and thickness of the skin affect the extent of absorption. The greatest rate of dermal absorbtion is in the axilla and perineum and in areas of dermatitis.

The above diagram reflects the route of maximum absorption over time showing that the most effective route of absorbtion is via the respiratory route, (for small enough particulates to enter the lower respiratory tract), followed by the gastrointestinal tract with the least effective route being through the skin.

Gastrointestinal tract

A great many chemicals are absorbed when ingested. Gastrointestinal absorption may be deliberate as in the case of poisoning or secondary due to hand mouth contact or mucocilliary clearance from the upper respiratory tract. The gut has a large surface area and relatively high rate of blood supply. This means that absorbed substances are quickly moved and a concentration gradient between the gut lumen and the blood is maintained to ensure high levels of absorption. Diet and transit time can both affect the rate or effectiveness of absorbtion.

Bacteria in the gut can also biotransform and increase toxicity for certain chemicals e.g. nitrates are reduced to nitrites by E. coli (R-O-NO₂ to R-O-NO) which may result in methemoglobinemia (and may react with secondary amines to form nitrosoamines). This occurs primarily in infants with low acidity in their stomachs and the elderly with achlorhydria.

Skin

The skin is both a "barrier" and a significant route of absorption. Passive diffusion is the major mechanism of absorbtion and correlates with the partition coefficient or lipid solubility of an agent. Abrasion of the skin and dermatitis greatly increase permeability. In general, the stratum corneum is relatively impermeable (palms and soles have thick, but fractured and very permeable stratum corneum). The scrotum has very thin and permeable stratum corneum. Organic solvents pass readily across the skin and may act as vehicles for absorbtion of pesticides.

Lungs

The lungs have a surface area of 50 to 100 m² with great proximity of the alveolar capillary vasculature to the alveolar air space maximizing gas exchange. Water solubility and particle size determine the depth of penetration of a substance with water soluble substances largely going into solution in the mucous lining of the upper respiratory tract The particle size of the chemical determines site of deposition (aerodynamic diameters) in the airway:

• 5 mm - particulate is deposited in the nasopharynx (sneezed or swallowed)
• 2-5 mm - particles settle by inertia in the branch points of the tracheobronchial tree and largely cleared by the mucociliary blanket inertia and ingested
• 1 mm - particles reach the alveoli and may be absorbed into the blood or exhaled.

Absorbtion of a substance to particulate such as sulfur dioxide adhering to coal soot particulate may enhance both depth of penetration and residence time.

Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
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