PRINCIPLES OF TOXICOLOGY

36 ABSORPTION, DISTRIBUTION, AND ELIMINATION OF TOXIC AGENTS
Absorption
Distribution
Generally, a toxicant must be considered absorbed in order to have an effect, but this is not always
true. Some toxicants are locally toxic or irritating. For example, acid can cause serious damage to the
skin even though it is not absorbed through the skin.
Although a distinction is made in Figure 2.1 between the target tissue and the central compartment
that includes the blood, in some instances the blood itself represents the target tissue. Carbon monoxide,
for example, combines with hemoglobin to form carboxyhemoglobin, whose presence in the blood
reduces the availability of oxygen to the tissues. Hemolytic agents such as arsine are also active in the
blood compartment, and blood is their target tissue. But most often the target tissue is a tissue other
than the blood.
Significance of the Target Tissue
Elimination
Exposure Absorption
Disposition Tissue Dose
Tissue Interaction Effect
Figure 2.1 An overview of the absorption and disposition of a foreign compound. From the blood, the chemical
is both eliminated and distributed to the target tissue, where it exerts its effect.
The target tissue or target organ is not necessarily the tissue in which the toxicant is most highly
concentrated. For example, over 90 percent of the lead in the adult human body is in the skeleton, but
lead exerts its effects on the kidney, the central and peripheral nervous systems, and the hematopoietic
system. It is well known that chlorinated hydrocarbons tend to become concentrated in body fat stores,
but they are not known to exert any effects in these tissues. Whether distribution and/or storage
processes such as these are actually protective—that is, whether they act to lower the concentration of
toxicant at its site of action—is not always clear. There is experimental support for the idea that certain
highly localized and specialized sequestration mechanisms, such as incorporation of lead into intranuclear
lead inclusion bodies or binding of cadmium to the tissue protein metallothionein, do indeed
function as protective mechanisms. Whatever the case with regard to their function, however, the
existence of sequestration mechanisms for many compounds means that the bulk movement of a
toxicant through the body, or its kinetic behavior as reflected in plasma and tissue concentrations, must
be interpreted with care. The concentration or amount of the biologically active form of the toxicant
at sites in the target tissue controls the action—the dynamic behavior—of the toxicant.