Deriving in vivo biotransformation rate constants and metabolite parent concentration factor/stable metabolite factor...

Growing concern for the biological fate of organic contaminants and their metabolites and the urge to connect in vitro and in vivo toxicokinetics have prompted researchers to characterize the biotransformation behavior of organic contaminants in biota. The whole body biotransformation rate constant (k_M ) is currently determined by the difference approach, which has significant methodological limitations. A new approach for determining k_M from the kinetic observations of the parent contaminant and its intermediate metabolites is proposed. In this method, k_M can be determined by fitting kinetic data of the parent contaminant and the metabolites to analytical equations that depict the bioaccumulation kinetics. The application of the proposed method is illustrated using worm bioaccumulation-biotransformation data collected from the literature. Furthermore, a metabolite parent concentration factor (MPCF) is also proposed to characterize the persistence of the metabolite in biota. Because both the proposed k_M method and MPCF build on the existing theoretical framework for bioaccumulation, they can be readily incorporated into standard experimental bioaccumulation protocols or risk assessment procedures or frameworks. Possible limitations, implications, and future directions are elaborated. Environ Toxicol Chem 2016;35:2903-2909. © 2016 SETAC.