Page 77 - The Toxicology of Fishes

Toxicokinetics in Fishes 57

This chapter examines the topic of toxicokinetics in fish by first reviewing the anatomical, physiolog-
ical, and environmental determinants of chemical uptake and disposition. The goal of this chapter is to
link these structural and physiological determinants with empirical data and kinetic modeling approaches
that describe this composite behavior.

Basic Concepts
Fish as Wet Vertebrates

The basic requirements for life are the same for fish as other organisms. Life in water, however, presents
a number of challenges to fish that are not equitably shared by most terrestrial animals. Water has a high
specific heat capacity, which makes it impossible for all but the largest fish to maintain internal temper-
atures different from those of the immediate surroundings. Compared with air, water contains low levels
of dissolved gases. The solubilities of physiologically important gases in water also differ. These facts
necessitate both specialized gas-exchange surfaces and a different approach to acid–base balance. The
viscosity of water requires that fish employ specialized approaches to locomotion and expend consid-
erable energy to support respiration. A number of the adaptive physiological and structural modifications
that these challenges elicit either directly or indirectly influence xenobiotic toxicokinetics. As an example,
poikilothermy influences membrane structure and function, enzymatic isozyme profiles, cardiac output,
bile flow rate, and the intestinal passage rate.
Although the mechanisms available to fish for homeostasis are similar to those of other vertebrates,
the ways that they are used may or may not be the same. This is important to keep in mind when
comparing the kinetics of xenobiotics between fish and mammals, among fishes of diverse groups, and
even among individuals of the same species held under different environmental conditions. Table 3.1
lists some generalized structural and functional differences between fish and mammals (Cunningham,
1997; Evans, 1993; Ruckesbusch et al., 1991). It will become clear through the course of this chapter
that many of these differences influence xenobiotic absorption, distribution, and elimination in fishes.
Uptake of xenobiotics by fish may occur by inhalation, ingestion, or dermal exposure, as is the case
for their mammalian counterparts (Figure 3.1). Likewise, the excretion of xenobiotics by fish and
mammals occurs by diffusion or transport across respiratory and skin surfaces, as well as by urinary,
biliary, and fecal routes. Even with these commonalities, there are some obvious and not so obvious
differences between fish and mammals with regard to the nature of these pathways, the relative impor-
tance of each pathway, and xenobiotic movements at the exchange surfaces that separate the animal
from its environment.
Two of the more obvious differences between fish and mammals are that fish live in water and respire
using gills. The fact that the surrounding medium is water rather than air strongly influences the nature
of chemicals delivered to and eliminated at the gills. The mammalian lung, for example, is exposed
primarily to volatile chemicals and chemicals associated with or existing as particulates. In contrast, the
gill is commonly exposed to water-soluble chemicals, as well as nonpolar compounds adsorbed to
dissolved and particulate organic matter. Branchial uptake requires diffusion across the gill membranes,
which possess a hydrophobic core. For nonpolar compounds bound to organic matter in water, uptake
requires first that they dissociate from the organic material and traverse a polar water and mucus interface
before diffusing across a compatible hydrophobic membrane. The same phase transitions exist for
chemical excretion across the gills. In general, the gills play a much greater role in the absorption and
excretion of xenobiotics by fish than the lung plays in mammals.
The skin of mammals is dry, dead, and keratinized and does not possess a circulatory component.
When present, fur may further limit dermal uptake of xenobiotics in mammals. In contrast, the skin of
fishes is a living epidermis that is perfused by an underlying secondary circulation. In very small fish
or benthic species that are in constant contact with contaminated sediment, the skin becomes an important
exchange surface for xenobiotic compounds. The solvent fluid nature of water, combined with the
foregoing considerations, suggests that this route of exposure is more important for these fish than for
most mammals.