Page 37 - The Toxicology of Fishes

Bioavailability of Chemical Contaminants in Aquatic Systems 17

thiol groups tend to complex with amino acids and small peptides. Specific transport systems may exist
to move these complexes across the gut epithelium, thereby facilitating metal uptake. Simple diffusion
across the gastrointestinal epithelium may control the rate of uptake of some compounds. Uptake of
poorly diffusing chemicals may occur due to pinocytosis of proteins and associated bulk media (McLean
and Donaldson, 1990).
When used in the context of dietary uptake, the term bioavailability generally refers to the fraction
of chemical that is absorbed by an animal following the ingestion of a contaminated meal. Dietary
absorption efficiency may in theory be determined by measuring the difference in chemical mass in food
and feces (Penry, 1998). In practice, however, such measurements are difficult to make. More commonly,
researchers estimate absorption efficiency by measuring the amount of chemical retained by a fish after
feeding it a defined ration. This value is referred to as the dietary assimilation efficiency and represents
the net result of absorption and elimination, including biotransformation. To the extent that elimination
occurs during the course of such an experiment, dietary assimilation efficiency will be lower than true
absorption efficiency. For this reason, feeding studies designed to estimate absorption efficiency based
on accumulated chemical residues are most useful when the compound is eliminated from the animal
very slowly. In prolonged feeding studies, dietary assimilation efficiency is expected to decline as fish
accumulate chemical and approach a dynamic steady state.
Alternatively, researchers have used simple kinetic models and independently obtained estimates of
elimination rate (generally from depuration studies) to estimate dietary absorption efficiency (Bruggeman
et al., 1981; Niimi and Oliver, 1988). This method also relies on the use of measured whole-body
concentration data. By using a kinetic model, however, it is possible to account for the effect of chemical
elimination. The absorption efficiency constant determined in this manner does not change as fish
accumulate chemical; instead, the fish’s approach to steady state is determined by the balance between
uptake and elimination processes. A portion of the chemical eliminated by fish may be contained in
feces, but the contribution of these losses to total elimination is unknown. Using this approach, fitted
absorption efficiency constants may be subject to error when the elimination rate is very low and therefore
difficult to estimate.
Another way to characterize dietary uptake is to employ methods developed in pharmacokinetic studies
with mammals to estimate the oral bioavailability of drugs. In this procedure, the compound of interest
is administered in food, and samples are collected to characterize plasma concentrations of the chemical
over time. Later, after the first dose has been cleared, the animal is administered an equivalent amount
of compound as either an intravascular (i.v.) or intraperitoneal (i.p.) dose, which is considered to be
100% bioavailable. Oral bioavailability is then calculated as the ratio of the area under the plasma
concentration–time curve (AUC) for oral dosing to the AUC for i.v. or i.p. dosing. A variation on this
method involves the use of two groups of animals, one of which is dosed i.v. or i.p. and the other fed
a contaminated diet. Oral bioavailability determined in this manner may be thought of as the fraction
of the ingested dose that is absorbed across the GIT and enters the systemic circulation.
Feeding studies with fish have provided empirical dietary uptake data for a large number of organic
compounds as well as some metals. Based on a review of literature values for organic compounds, Gobas
et al. (1988) reported a dependence of absorption efficiency on chemical log K ; absorption efficiencies
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averaged about 50% for chemicals with log K values between 4 and 7 and then declined progressively
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at higher log K values. Other researchers have reported a lack of dependence of assimilation efficiency
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on chemical log K (Burreau et al., 1997). Dietary uptake of some metals by fish appears to be regulated,
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resulting in a less-than-proportional increase in whole-body concentration for a given increase in the
trace element concentration in food. This phenomenon has been observed for both essential (e.g., zinc)
and nonessential (e.g., cadmium) metals (Douben, 1989; Spry et al., 1988). The mechanisms by which
this regulation is accomplished remain poorly understood and could conceivably involve concentration-
dependent changes in absorption across the gut, although adaptive changes in elimination pathways are
also likely (Reinfelder et al., 1998).
Variability in estimated absorption efficiency values for fish may also be due in part to methodological
considerations. Feeding studies with fish are generally conducted by spiking test chemicals into prepared
diets. Less commonly, an effort is made to incorporate chemicals into live prey items. Limited data
suggest that organic chemicals incorporated into live prey are taken up more efficiently than the same