Annual Review TOXICOKINETICS IN AQUATIC SYSTEMS: MODEL COMPARISONS AND USE IN HAZARD ASSESSMENT

Toxicokinetic models are not constrained by assumptions of equilibrium as are thermodynamic (equilibrium-partitioning) models and are more accurate predictors of toxicant accumulation for non-steady-state exposures and multiple uptake routes. Toxicokinetic models-compartmentbased models, physiological-based models, and energetics-based models-are reviewed and the different mathematical formalisms compared. Additionally, the residue-based toxicity approach is reviewed. Coupling toxicokinetic models with tissue concentrations at which toxicity occurs offers a direct link between exposure and hazard. Basing hazard on tissue rather than environmental concentrations avoids the errors associated with accommodating multiple sources, pulsed exposures, and non-steady-state accumulation. Keywords-Kinetic models Bioaccumulation Tissue residue effects Sediment contamination Hazard assessment INTRODUCTION identifying components dominating toxicant mass Assessment and of toxicant effects on balance. This approach has been best refined using aquatic organisms require evaluation of the extent the fugacit~ concept and applied to describe the imof organism exposure. Exposure assessment estabportance of sediment as a toxicant source [3] and lishes the relationship between environmental taxtoxicant distributions within ecosystems [4,5]. icant concentrations and organism accumulation Although there is a continued focus on equilibwhile accounting for environmental and biological rium-~artitioning models within regulatory agenfactors that modify exposure. ~f the relationships cies, it is clear that the environment is complex and between the amount of toxicant accumulated and variable. Therefore, to obtain more accurate prethe resulting effects are known, then the hazard for dictions and assessments, kinetic models are needed a particular exposure regime can be established. to predict n0n-steady-state, nonequilibrium accuAquatic exposure assessments and predictions mulation from temporally and spatidy varying exhave employed mainly steady-state and equilibriumposures when the simplifying assumptions of the partitioning models. Early efforts, using simple kiequilibrium-partitioning models are inappropriate, netic models, were designed to provide estimates of for example, when multiple sources contribute sigsteady-state accumulation from water exposures nificantly [1,2] These steady-state estimates were then utiKinetic models have been used successfully in lized in hazard assessments based on thermodypharmacology for decades. Such permit namic limits equilibrium). such models prediction of the onset of drug action and allow the have been employed with good success for evalmonitoring of drug clearance and termination of uation of general conditions, describing toxicant effects. Further, these kinetic models describe distribution among ecosystem components and changes in tissue concentrations resulting from absorption, distribution, metabolism, and elimination. In aquatic toxicology, kinetic models have the *To whom correspondence may be addressed. potential to provide the same level of predictive res-