Disposition of pentachlorophenol in rainbow trout ( Salmo gairdneri): effect of inhibition of metabolism

The accumulation kinetics of pentachlorophenol (PCP) were investigated in rainbow trout ( Salmo gairdneri) in the absence and presence of 25 mg/1 salicylamide, an inhibitor of PCP metabolism. After exposure to 5 μg/1 PCP over 1–96 h, the amount of PCP in the whole fish, its concentration in water and the total amount of metabolites (water, whole fish and bile) were measured. Equations for these variables, based on a two compartment pharmacokinetic model, were fitted simultaneously to the data using the computer program NONLIN, which uses an iterative nonlinear least squares technique. Salicylamide decreased the metabolic clearance of PCP, which resulted in an increase in the bioconcentration factor (BCF); this increase was partially offset by a salicylamide-induced decrease in the apparent volume of distribution of PCP. A clearance-volume compartment model permitted partitioning of the BCF in terms of the underlying physiologic and biochemical processes (uptake clearance, metabolic clearance and apparent volume of distribution). With this approach the BCF can be categorized as either dependent (e.g., PCP) or independent of uptake and metabolism (elimination) based on the relative sizes of the clearances for uptake and metabolism. Inhibition of PCP metabolism resulted in a loss of its dependence on uptake and metabolism. The BCF estimated as the apparent volume of distribution may be useful for assessment of the risk associated with exposure and bioaccumulation potential, as elimination is generally quite variable among aquatic species.