Absorption is the transfer of a chemical from the site of exposure, usually an external or internal body surface, into the systemic circulation.
Toxicants are removed from the systemic circulation by biotransformation, excretion, and storage at various sites in the body.
Excretion is the removal of xenobiotics from the blood and their return to the external environment via urine, feces, or exhalation, etc.
The disposition of a chemical or xenobiotic is defined as the composite actions of its absorption, distribution, biotransformation, and elimination. The quantitative characterization of xenobiotic disposition is termed pharmacokinetics or toxicokinetics. Figure 5–1 is a pictoral overview of the processes that determine disposition, which are likely to occur simultaneously. The toxicity of a substance in most circumstances directly depends on the dose, where “dose” is defined as the amount that ultimately reaches the site or sites of action (tissue, cell, or molecular target). Therefore, the disposition of a chemical determines its concentration at the site of action such that the concerted actions of absorption, distribution, and elimination also determine the potential for adverse events.
Summary of the disposition of toxicants as determined by absorption, distribution, and excretion in the body. Black lines represent major pathways of absorption into the body, blue designates distribution, and green lines identify pathways of final excretion (elimination) from the body, with the exception of enterohepatic circulation, which is designated in red.
The skin, lungs, and alimentary canal are the main barriers that separate higher organisms from an environment containing many chemicals (Fig. 5–1). Toxicants must cross one or several of these incomplete barriers to exert deleterious effects, except for caustic and corrosive chemicals (acids, bases, salts, oxidizers) that act directly at the point of contact. A chemical absorbed into the bloodstream or lymphatics through any of the major barriers is distributed, at least to some extent, throughout the body, including the target organ or target tissue where it produces damage. A chemical may have one or several target organs, and, in turn, several chemicals may have the same target organ or organs. However, it cannot be assumed that the tissue of highest concentration is also the target organ where toxicity will be observed.
Poor absorption of a toxicant resulting from a low amount absorbed or from a low rate of absorption will limit or prevent toxicity because a chemical may never attain a sufficiently high concentration at a potential site of action to cause toxicity. A well absorbed chemical that is rapidly biotransformed or eliminated from an organism is less likely to cause toxicity because rapid excretion prevents it from reaching a sufficiently high concentration at a site of action.
Toxicants usually pass through cells, such as the stratified epithelium of the skin, the thin ...