Page 91 - The Toxicology of Fishes

Toxicokinetics in Fishes 71

100

80
% ORAL BIOAVAILABLITY 60

40

20

0 2,4-D
BENZOIC ACID ORMETOPRIM CHLORPYRIFOS NAPHTHOL SULFADIMETHOXINE TETRACYCLINE

FIGURE 3.7 Oral bioavailability of seven chemicals in channel catfish, expressed as a percentage of the administered
dose. (Data are from Barron et al., 1991; Michel et al., 1990; Plakas and James, 1990; Plakas et al., 1990, 1992b; Stehly
and Plakas, 1992.)

Gastrointestinal Absorption of Xenobiotics
The absorption of xenobiotics from the GIT depends on a multiplicity of events in four general spheres
of interaction: (1) within the intestinal lumen, (2) at the absorptive surface, (3) within the enterocytes,
and (4) at the enterocyte–vascular interface. Physical, chemical, and biochemical events within the
intestinal lumen determine the chemical form and integrity of a compound and its availability for uptake
across the gut epithelium. Qualitative and quantitative characteristics of the diet play an especially
important role in this environment. On the apical surface of the enterocytes, physical and chemical
properties of the membrane and associated unstirred layer, as well as the transporter complement within
the membrane, significantly influence xenobiotic uptake. Within the enterocytes, biotransformation
enzymes, carrier molecules, and cellular components further impact xenobiotic concentration and move-
ment. Transport across the enterocyte basolateral membrane into blood is dependent on factors similar
to those operating at the apical membrane. The composition and flow rate of blood may also influence
uptake. Directly impacting all of these processes is the character of the xenobiotic and fish species under
consideration. The relative amount of an ingested compound that reaches the systemic circulation is
defined as dietary or oral bioavailability. Oral bioavailability may be expressed relative to 100%
(complete bioavailability) using the area under the blood concentration–time curve (AUC), referenced
to that of an intravascular dose (Gibaldi and Perrier, 1982). Oral bioavailability in fish is species and
chemical specific and varies widely (Figure 3.7).
Dietary uptake also may be characterized by measuring chemical residues in tissues after feeding fish
a defined ration of contaminated food. The uptake efficiency calculated in this manner is termed dietary
assimilation efficiency, and it reflects the net result of dietary uptake and subsequent elimination (Penry,
1998). A third means of characterizing dietary uptake is to estimate the efficiency with which ingested
compounds are absorbed across the GIT. Typically, this is done by fitting the whole-fish chemical
concentration data to a derivative form of the mass-balance equation that describes dietary uptake and
elimination (Bruggeman et al., 1984). This approach yields a dietary absorption efficiency constant, the