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684                                                        The Toxicology of Fishes




                       Introductory and Historical Perspectives
                       Understanding basic mechanisms of toxicological processes is integral to assessment of risk. In aquatic
                       toxicology, however, the mechanistic evaluation of environmental chemicals is a much younger area of
                       investigation than in mammalian systems and only recently has received significant attention. Prior to
                       the 1970s and 1980s, the development of standardized bioassays and routine environmental monitoring
                       served as the primary means to assess and regulate chemical contaminants. Subsequent to this era,
                       investigators in aquatic toxicology turned their attention from whole organism responses to those at the
                       cellular or organ system levels of biological organization.  This led to a proliferation of efforts and
                       information relating to clinical approaches utilizing hematology, histology, histochemistry, metabolism,
                       pharmacokinetics, and physiological or biochemical effects as measures of toxicity. In the l990s, these
                       approaches broadened with the increased use of molecular biology techniques that have greatly assisted
                       efforts to define and understand mechanisms of action. Since 2000, with the recent advances in -omic
                       methodologies, multiple endpoints have been identified as being modified by exposure to various stressors
                       with the potential development for stressor-specific responses. The results of mechanistic studies have
                       proven to be valuable to many applied areas of aquatic toxicology. In risk assessment, mechanistic data
                       have been useful in demonstrating that an adverse effect observed in the laboratory is directly related
                       to population-level effects. As costs associated with environmental compliance increase, regulators and
                       the regulated community, must make the most effective use of the funds and time allocated for reducing
                       environmental impacts. At present, assessment and regulatory decisions continue to be based primarily
                       on empirical measures that may be highly susceptible to change. Decisions based on a more complete
                       mechanistic understanding of chemical effects would be less likely to vary with technological trends.
                       Additionally, the more sensitive our assessment methodologies become, the earlier adverse effects of
                       environmental chemicals on aquatic ecosystems can be measured and, in turn, the more accurate the
                       evaluation of ecological risk.
                        Adverse effects to aquatic organisms begin with the release of a chemical into the environment. A
                       much relied upon means to evaluate ecological risk has been through environmental monitoring in which
                       chemical residues are assessed.  This approach has provided useful information but with significant
                       limitations, not the least of which are the time and costs associated with chemical residue analysis.
                       Although time and cost restraints are arguable issues, a more significant challenge associated with such
                       an approach is the inability to quantitatively evaluate the availability of a chemical from the environmental
                       matrix to the aquatic organism. Furthermore, metabolism or limitations in available technology may
                       render a chemical difficult, if not impossible, to detect in environmental or biological samples. Appli-
                       cation of biomarkers in environmental monitoring may resolve many of these challenges by providing
                       a measure of availability of an environmental chemical to an aquatic organism by providing a direct
                       measure of the response of an organism to chemical exposure. Regarding biological response to sublethal
                       concentrations of environmental chemicals, Depledge et al. (1993) noted that an essential criterion of
                       the biomarker approach is the identification of early onset changes in otherwise healthy organisms that
                       predict increased risk of development of chemically induced pathologies. Other potential uses are listed
                       in Table 16.1.


                               TABLE 16.1
                               Potential Uses for Biomarkers in Field Studies.
                               To demonstrate residency or exposure for the purposes of interpreting responses as site specific
                               To demonstrate or define the characteristics of an unknown chemical or chemical mixture
                               To demonstrate bioavailability (or lack thereof)
                               To examine the time course of uptake
                               To provide in vitro opportunities for understanding mechanisms
                               To prioritize sites, stressors, or samples for further sampling or analyses
                               To direct testing during fractionation procedures to isolate unknowns
                               To evaluate the time course or success of remediation
                               To conduct surveillance
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