Distribution and Pharmacokinetics Models - Pesticide Biotransformation and Disposition - page 117

Dermal

iv, ip, sc, im Inhalation

Oral

Gastrointestinal
tract

Lung

Skin

Excretion

Excretion

Liver Blood

Metabolites

Target
organ(s)

Kidney

Excretion
Figure 6.1 Representation of the absorption, distribution, metabolism, and excretion of toxicants.

concentration in the target organ ( Figure 6.1 ). Absorption is the translocation of the
pesticide from an external source of exposure to the bloodstream. Once in the blood,
the chemical is distributed through the body and delivered to the tissues, where it may
leave the blood and enter the cells of the tissue, or remain in the blood and simply pass
through the tissue. In certain tissues, such as the liver, the chemical may be effectively
removed from the body by metabolism. Other tissues, such as the kidney and lung,
serve to eliminate xenobiotics from the body by excretion. Absorption, distribution,
metabolism, and excretion, which are collectively termed disposition, are all factors
that affect the concentration of a chemical in target tissues. Pharmacokinetics refers to
the mathematical description of the time course of chemical disposition in the body.
Metabolism and excretion are discussed in detail in other chapters of this work. This
chapter focuses on chemical distribution and the basic pharmacokinetic modeling
techniques used to mathematically describe chemical disposition.

DISTRIBUTION
Once in the bloodstream, the chemical is available for distribution throughout and
elimination from the body. Metabolism and excretion, which are components of elimi-
nation, are discussed in other chapters. This section focuses on distribution, the reversible
translocation of chemicals from one location to another in the body. Distribution of a
toxicant to and accumulation in the target organ may result in toxicity. Accumulation
at nontarget sites, on the other hand, results in storage of the pesticide away from the