Page 76 - The Toxicology of Fishes

56 The Toxicology of Fishes

Physiologically Based Toxicokinetic Models..............................................................................105
Model Structure ..................................................................................................................106
Routes of Exposure ............................................................................................................110
Hepatic and Renal Elimination ..........................................................................................117
Model Parameterization......................................................................................................118
Utility of Physiologically Based Fish Models...................................................................122
Noncompartmental Analysis...............................................................................................124
Bioconcentration, Bioaccumulation, and Biomagnification..................................................................126
Bioconcentration...........................................................................................................................127
Steady-State Exposures ......................................................................................................127
Kinetic Modeling................................................................................................................127
QSAR Models.....................................................................................................................128
Bioaccumulation...........................................................................................................................128
Bioaccumulation Referenced to Water...............................................................................128
Mechanism of Biomagnification ........................................................................................129
Bioaccumulation Referenced to Sediment.........................................................................129
Equilibrium Partitioning Theory of Bioaccumulation from Sediments ............................ 130
Kinetic Models for Chemical Accumulation from Sediment............................................131
Food Web Models of Bioaccumulation in a Sediment–Water System ............................. 131
Fugacity-Based Models ......................................................................................................134
References..............................................................................................................................................134

Introduction
Fish are intimately linked to their aqueous habitat. They respire, osmoregulate, achieve acid–base balance,
and obtain their thermal character in relation to the surrounding water. In addition, water serves as a
common conduit for many essential life processes. Most fish eat, drink, urinate, defecate, swim, obtain
sensory information, reproduce, and spatially orient within a single surrounding and contiguous medium.
The structural and physiological adaptations that allow fish to thrive in an aqueous environment also
strongly impact their interactions with xenobiotic substances. The solvent properties of water and its
contrasting character relative to many important contaminants further shape these interactions.
Absorption, distribution, biotransformation, and excretion of xenobiotics by fish are important deter-
minants of chemical toxicity. These processes influence whole-organism dose–response relationships by
altering the effective concentration over time at a target site. The degree to which any individual process
alters the concentration and activity of a toxicant depends on the character of the toxicant and attributes
of the exposed organism. The role that individual organs play in each process and the molecular
susceptibility of specific tissues and organs provide the basis for specific toxicities.
Most of the literature dealing with the movement of chemicals into, through, and out of living systems
addresses drugs and their behavior. The term pharmacokinetics is used to describe the study of such
movements, particularly as they vary in time. Toxicokinetics deals with the movement of toxicants or
compounds that are present at toxic concentrations. This distinction aside, the two terms are synonymous;
thus, toxicokinetics refers to the study of time-dependent absorption, distribution, biotransformation, and
excretion of toxic substances with the goal of providing a description of the chemical concentration time
course at the site of action. Most of the toxicokinetic studies published to date have been conducted
using well-known mammalian laboratory species. Although they utilize many of the same basic tenets
employed in these mammalian efforts, studies with fish may require customized mathematical modeling
formats and experimental approaches due to structural, physiological, and lifestyle differences.
The processes of absorption, distribution, biotransformation, and excretion also determine the extent
to which xenobiotics bioconcentrate and bioaccumulate in fish. Bioconcentration refers to the uptake
and accumulation of chemicals directly from water. Bioaccumulation is a more inclusive term that
describes chemical uptake and accumulation from all sources: water, diet, and sediments. Bioconcen-
tration and bioaccumulation, particularly of persistent compounds, serve as indicators of past exposure
for the animal; as indicators of potential exposure for higher trophic levels, including the human
consumer; and as markers of potential toxicity.