Distribution and Pharmacokinetics Models - Pesticide Biotransformation and Disposition - page 123

affinity of a tissue for a given chemical (tissue partition coefficient). Bone tissue, for
example, is a potential storage depot for heavy metals.
Storage with Repeated Exposures
Body burden is the term for the concentration (or amount) of chemical in the body at
any given time, and the biological half-life of a chemical is the time required to reduce
the concentration of the chemical in the body by one-half, in the absence of further
intake. Many pesticides are water soluble and easily excreted, or are readily metabolized
to more water-soluble compounds that are easily excreted. Lipophilic pesticides, such
as the organochlorines, however, are stored in fat and are not easily removed from the
body, and most people around the world carry a low body burden of organochlorine
pesticides ( Burgaz et al., 1994; Durham, 1969; Zatz, 1972 ). Repeated exposure to a
chemical may result in cumulative storage and an increased body burden. If the inter-
val between exposures is long relative to the biological half-life of the chemical, all
or most of it will be removed from the body prior to subsequent exposure, and it is
unlikely that the chemical will accumulate. If the interval between exposures is short
relative to the biological half-life, however, there will be a residual body burden from
the first exposure when the second exposure occurs, and so on, such that the chemical
accumulates in the body.
Cumulative storage of a chemical upon repeated exposure continues until a steady
state of storage is reached. Factors that influence storage include exposure level (dos-
age), time interval between exposures, duration of repeated exposures, interaction with
other chemicals, age, sex, species, disease status, and nutritional status. A mathematical
discussion of storage is presented later in this chapter.
PHARMACOKINETICS
Pharmacokinetics is the modeling and mathematical description of the time course
of chemical disposition (absorption, distribution, metabolism, and excretion). Although
urine and exhaled breath may be obtained from humans, blood is the only tissue that
can be readily and repeatedly sampled in humans. Pharmacokinetic models typically
describe the change in blood (or plasma) concentration of the chemical with time.
There are two basic approaches to characterizing the pharmacokinetics of a chemical
in the body: compartmental and noncompartmental. Compartmental pharmacokinetic
models represent the body as discrete compartments with mathematical descriptions
of the movement of a chemical between compartments, including the processes of
absorption and elimination. Compartmental models may be subdivided into classical
and physiologically based models. In contrast, the noncompartmental approach assumes
no compartmentalization of the body and applies the trapezoidal rule for calculat-
ing the area under the plasma concentration-time curve to characterize a chemical's
pharmacokinetics.