Page 93 - The Toxicology of Fishes

Toxicokinetics in Fishes 73

100

80
UPTAKE EFFICIENCY (%) 60

40

20

0
4 4.5 5 5.5 6 6.5 7 7.5 8 8.5
CHEMICAL LOG K OW
FIGURE 3.9 Dependence of dietary absorption efficiency on chemical log K ow . Solid circles represent values summarized
by Gobas et al. (1988). The solid line was generated using the fugacity model presented by Gobas et al. (1988).

models developed by Barber et al. (1991) and Clark et al. (1990) were used to simulate dietary uptake
of PCBs by fish. Both models predicted that dietary uptake will decrease with increasing chemical body
burden due to a decrease in the concentration gradient for uptake.
A few studies have examined the effect of dosage on the oral bioavailability of more water-soluble
xenobiotics in fish. The bioavailability of the antibiotic oxolinic acid in rainbow trout was reported to
be 14.3% (Cravedi et al., 1987), 13.6% (Bjorklund and Bylund, 1991), 38.1% (Cravedi et al., 1987),
and 91% (Kleinow et al., 1994) after oral administration of the drug at 100, 75, 20, and 5 mg/kg,
respectively. These results suggest that the bioavailability of oxolinic acid is higher at lower dosages.
Other studies with Atlantic salmon (Salmo salar) indicated no difference in bioavailability when fish
were administered oxolinic acid in feed at 9 and 26 mg/kg (Hustvedt et al., 1991). The bioavailability
of sulfadimethoxine in rainbow trout decreased slightly when the dosage was increased threefold from
42 to 126 mg/kg (Kleinow et al., 1992).
Studies with oxolinic acid in yellowtail (Seriola quinqueradiata) showed that oral bioavailability was
inversely related to particle size (Endo et al., 1987). The bioavailability of the sodium salt of sulfadi-
methoxine was nearly double that of the non-salt form (63 to 34%) (Kleinow et al., 1992). In each case,
bioavailability appears to have been controlled in part by solubility considerations.

Physiological Impacts on Gastrointestinal Absorption
Relatively little information is available regarding the direct effects of GIT structure and function on
dietary uptake of xenobiotics by fish. It is evident from nutritional studies, however, that pH gradients,
gastrointestinal passage times, blood-flow patterns, and other aspects of digestive physiology vary with
temperature and feeding frequency, as well as meal composition and size. Work with the mammalian
GIT also indicates that these physiological features influence the absorption of xenobiotics.

Digestion—Approximately 15% of teleost fishes lack a true stomach (Grondel et al., 1987). Significant
longitudinal pH gradients are not observed in these agastric species. The stomach pH of gastric species
generally ranges from 1 to 4 (Bowen, 1981; Moriarty, 1973; Payne, 1978), and that of the intestine
ranges from 6.5 to 9 (Fish, 1960; Nagase, 1964). Regional pH in the GIT may be an important determinant
of absorption for some xenobiotics (Guarino et al., 1988). This would be especially true for weak organic
acids and bases. In addition, pH can impact xenobiotic integrity, suggesting that differences in this regard
may exist between gastric and agastric species.