The kinetics of accumulation of pentachlorophenol (PCP) at various pH values were investigated to explore how pH-dependent accumulation might influence PCP toxicity. Goldfish (Carassius auratus) were exposed to 5 μg PCP/L in a static system buffered with 7.5 mM bicine orN,N-bis(2-hydroxyethyl)-2-aminoethane sulfonic acid (BES) at pH 7.0, 8.0, or 9.0. The amount of PCP in the fish, concentration of PCP in water, and the total amount of metabolites in the system were measured after exposure of fish from 1 to 96 hr. Equations for these variables based on a two compartment pharmacokinetic model were fitted simultaneously to the data using NONLIN, which uses an iterative nonlinear least squares technique. Uptake clearance, metabolic clearance, and apparent volume of distribution of PCP decreased as pH increased. The decrease in PCP accumulation with increased pH was not due solely to a pH-induced decrease in uptake. In addition, the distribution of PCP within the fish was altered by changes in the external pH. The pH-associated changes in distribution may have altered access of PCP to sites of metabolism, thereby altering the metabolic clearance. The pH-related changes in the pharmacokinetics of PCP resulted in a decrease in its bioconcentration factor with an increase in pH and account both for the decreased capacity of the fish to accumulate PCP and for its reduced LC50.
