Absorption - Pesticide Biotransformation and Disposition - page 42

Stomach contents
(pH 1.0)

Nonionized/ionized ratio
favors absorption

Blood (pH 7.4)

Nonionzed
[1]

lonized
[0.43]

Ionized
[54,000]

Nonionized
[1]

Nonionized
[1]

lonized
[460]

Intestinal contents
(pH 5.3)

Nonionized/ionized ratio
does not favor absorption

Figure 3.4 Proportion of nonionized and ionized forms of 2,4-D (p K a  2.6) in the stomach and intes-
tinal contents (adapted from Hodgson et al., 1991). Only the nonionized form crosses cell membranes.

be metabolized before reaching the systemic circulation. This first-pass metabolism
decreases the systemic availability (bioavailability) of the parent compound. Some
highly lipophilic compounds such as organochlorine pesticides are absorbed into the
lymphatic system in a manner similar to the absorption of nutritional fats ( Turner and
Shanks, 1980 ). Absorption into the lymphatic system bypasses delivery to the liver and
the potential for first-pass metabolism.
Many of the in vivo oral absorption studies in laboratory animals have demonstrated
that oral absorption of many pesticides can be significantly greater than absorption fol-
lowing skin exposure. This is especially applicable to the pyrethroid class of insecticides,
which do not readily penetrate skin and usually have a dermal bioavailability of less
than 10% in human skin. Deltamethrin is rapidly absorbed ( T max  1.0 h) and its abso-
lute oral bioavailability was 18% in rats given doses in the range of 0.2-10 mg/kg by
oral gavage in glycerol formal ( Kim et al., 2007 ). Permethrin was less rapidly absorbed
( T max  3.52 h) and had a greater absolute bioavailability ( F  61%) in the same strain
of rats ( Anadon et al., 1991 ). Many of the organophosphates are readily absorbed,
although the data suggest that pesticide formulation can result in absorption varying
from 20% to as much as 70% according to several human studies ( Eaton et al., 2008;