The Mode of Absorption, Distribution, and Elimination of Toxic Materials

Toxicology supports health risk assessments that generate exposure limits for chemicals. A toxic effect is presumed proportional to the concentration of the proximal toxicant at the target site of action. Uptake, distribution, metabolism and excretion of a toxicant explain the action of the agent and the variation in potency between exposure circumstances, species, and agents with similar mode of action. The proximal toxicant may be the parent compound or a product of metabolism of the toxic agent. Portals for entry into the body in the occupational environment are primarily inhalation and skin absorption. The most prominent determinants of absorption are physical state, particle size and lipid solubility. The liver is the most prominent organ for metabolism of toxicants, oxidation by Cytochrome P450 enzymes the most prominent metabolic pathway for activation and detoxification. Excretion pathways include exhalation of volatile compounds, transport of polar compounds to urine by the kidney and transport of lipid soluble compounds to feces via bile. Examples of agents and detailed discussion of the structure of organ systems are given. Keywords: Cytochrome P450; uptake; distribution; xenobiotics; exposure limits