Page 80 - The Toxicology of Fishes

60 The Toxicology of Fishes

exchange surfaces of fish. Conceptually similar processes operate within the fish, modulating exposure
to the sites of toxicity.
Water dissolves more substances and dissolves them more completely than any other liquid; never-
theless, some nonpolar substances are relatively insoluble in water. This solubility or insolubility is a
primary determinant of the distribution and availability of contaminants to aquatic organisms. In general,
polar compounds that are nonvolatile will remain freely dissolved in the water column. Alternatively, if
the compound is nonpolar and nonvolatile, it will partition to organic matrices in the water, reducing
the amount that is freely dissolved. In doing so, these chemicals may exhibit an apportioning equilibrium
that reflects their relative polarity. These characteristics influence not only toxicant availability to the
fish but also the primary routes of uptake.
Water in natural systems is a composite of H O and the materials dissolved and suspended in it.
2
Because these materials influence the complexation, binding, precipitation, and chemical form of many
compounds, water cannot be viewed as a uniform or generic medium. Water quality as it relates to
aquatic toxicology includes both biotic and abiotic components. Living organisms and organically derived
substances contribute to the biotic character of water. Abiotic factors include pH, hardness, alkalinity,
salinity, dissolved solids, and temperature. Collectively, water quality can influence the chemical form,
availability, and ultimately toxicity of chemicals in the aquatic environment. Often the influence of water
quality on toxicity is a collective action, with each characteristic exerting independent as well as
interdependent effects. A comprehensive discussion of chemical bioavailability, focusing on environ-
mental processes that control chemical uptake and accumulation by fish, is presented in Chapter 2.

Membranes and Xenobiotic Movement

Xenobiotic absorption, distribution, and elimination are dependent on transport across one or more
biological membranes. All known cellular membranes are composed of lipid bilayers arranged with
hydrophilic polar regions facing the outer surfaces and hydrophobic regions oriented toward the interior.
On either surface or traversing the entire width of the membrane are globular proteins. Hydrophobic
and electrostatic molecular interactions, along with the cytoskeleton, maintain the association of com-
ponents, regionalization, and structural integrity of the membrane. Throughout the fish, and even within
each cell, membranes may possess different morphological and biochemical attributes (Crockett and
Hazel, 1995; Schulthess and Hauser, 1995). External influences such as diet and temperature may also
alter membrane composition and character (Crockett and Hazel, 1995). Specific membranes may con-
tribute to the characteristic disposition of xenobiotics according to their particular properties. All mem-
branes, however, exhibit a basic structural similarity, which provides an operative model for their
interaction with xenobiotic chemicals.

Diffusion
A primary pathway for xenobiotic transport across lipid membranes is by passive diffusion. Moderately
nonpolar, lipid-soluble compounds diffuse easily across biological membranes. Polar and very nonpolar
compounds diffuse across membranes less easily, although for different reasons. Polar compounds have
limited access to the nonpolar portion of membranes, due to their low lipid solubility. In contrast, evidence
suggests that very nonpolar compounds may be sequestered by membranes, limiting their movement.
The net result of these interactions is that chemical transport from the external environment into plasma,
interstitial fluid, intracellular fluid, and even into cell organelles is dictated by the ability of the compound
to diffuse across membranes.
In general, the rate of diffusion across a membrane is directly proportional to the membrane–water
partition coefficient of a chemical (assuming that the membrane is bathed on both sides by an aqueous
medium), as well as its diffusion coefficient (for diffusion within the membrane) and the concentration
gradient (Hunn and Allen, 1974; Spacie and Hamelink, 1982). The diffusion coefficient is a function of
molecular size, conformation, and the presence or absence of particular functional groups. Specific to
each membrane is a molecular weight or size discrimination profile, and the passive diffusion of large
molecules may be prevented altogether. The membrane–water partition coefficient is a measure of the