Modeling the Uptake and Disposition of Hydrophobic Organic Chemicals in Fish Using a Physiologically Based Approach

Abstract

The development of physiologically based toxicokinetic (PBTK) models for hydrophobic chemicals in fish requires: 1) an understanding of chemical efflux at fish gills; 2) knowledge of the factors that limit chemical exchange between blood and tissues; and, 3) a mechanistic description of chemical uptake from the diet. Recently obtained data suggest that existing models of chemical flux at, fish gills can be used to predict branchial elimination of hydrophobic compounds. Empirical relationships derived from these data are sufficient to estimate equilibrium blood:water partitioning from chemical log KOW. Empirical relationships that predict tissue:water partitioning, and by extension tissue:blood partitioning, are not as well established. Factors that limit dietary uptake of hydrophobic compounds by fish are evaluated in PBTK models for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2′,5,5′tetrachlorobiphenyl (TCB). A diffusion and/or desorption limitation appears to operate along the entire length of the fish gastrointestinal tract. This observation is consistent with earlier work which suggested that dietary assimilation efficiency declines at very high log KOW values, although more research is needed using realistic diets. The utility of this information for interpreting chemical residues in field-collected animals is discussed.