Page 103 - The Toxicology of Fishes

Toxicokinetics in Fishes 83

10

ELIMINATION RATE CONSTANT (1/day) 0.01
1

0.1

0.001
2 3 4 5 6 7 8 9
CHEMICAL LOG K
OW
FIGURE 3.13 Dependence of elimination rate in guppies on chemical log K ow : solid squares, chlorinated benzenes; solid
circles, chlorinated benzenes/biphenyls; open squares, chlorinated benzenes/naphthalenes; open circles, brominated ben-
zenes/biphenyls and chlorinated biphenyls. (Adapted from Erickson, R.J. and McKim, J.M., Aquat. Toxicol., 18, 175–198,
1990.)

branchial elimination of four PCBs with log K values ranging from 5.8 to 8.2. All four compounds
ow
were eliminated at low, but measurable rates. An analysis of these data suggested that a near-equilibrium
condition was established between chemical in venous blood entering the gills, including dissolved and
bound forms, and dissolved chemical in expired branchial water. At the other end of the spectrum,
organic chemicals such as detergents (Schmidt and Kimerle, 1981) and drugs with low (<1) log K
ow
values, or those that are ionized at the pH of fish blood (Maren et al., 1968), tend not to be eliminated
across the gills but are eliminated in urine or bile.

Biliary and Fecal Elimination
Several hepatic and intestinal processes in fish may contribute to the elimination of xenobiotic chemicals.
Compounds incompletely absorbed from the diet will be eliminated in feces. The absorbed fraction will
be transferred to the liver and subjected to a variety of elimination pathways, including biotransformation
and biliary secretion. Parent compounds and their metabolites in bile may be reabsorbed or expelled
with the feces (Statham et al., 1976). Lipophilic xenobiotics that are poorly metabolized or cleared by
renal and biliary routes can be transferred from blood to the intestinal lumen (Ingebrigtsen and Solbakken,
1985; Ingebrigtsen et al., 1988; Kleinow et al., 1996). Passive diffusion is an important mechanism for
this process, although active transport (Leu and Huang, 1995) and exfoliation of intestinal cells may
contribute.

Contribution of the Liver
The liver in fishes is a major site for amino acid homeostasis, glucose regulation, lipid processing,
hormone metabolism, and the production of numerous plasma constituents, including albumin-like
proteins and fibrinogen (Hinton et al., 2001). The liver also plays an important role in the excretion of
xenobiotic compounds. The excretion of xenobiotics by the hepatic parenchyma depends on chemical
uptake by hepatocytes, the formation and secretion of bile, and the transport of these compounds into
bile. In this excretory process, hepatic and intestinal biotransformation often plays a pivotal role by
producing polar anionic metabolites that are readily acted upon by the transport mechanisms of the liver.