Implementation of growth curves in a generic physiologically based kinetic model with a case study of perfluorooctanesulfonic acid (PFOS) in beef cattle, sheep, and chicken

Perfluorooctanesulfonic acid (PFOS) is an environmental contaminant with a long half-life in animals. Risk assessment of PFOS in livestock and food tissue can be conducted with physiologically-based kinetic (PBK) models. For fast-growing livestock, changes in body weight affect the kinetics of PFOS primarily through tissue dilution, which needs to be considered when using a PBK model. A generic PBK model was used to predict tissue concentrations of PFOS in cattle, sheep, and chickens. The primary excretion routes were feces and urine, which were affected by enterohepatic circulation and saturable tubular reabsorption, respectively. Animal weight gain was modeled using the sigmoidal Richards curve. Model performance was validated by comparing simulations, with or without growth, to independent literature data. Blood and plasma concentrations of independent cattle and chicken data were accurately predicted. Liver and kidney concentrations were overpredicted by up to five-fold and three-fold, respectively, in cattle, and twelve-fold for liver in chickens. Liver concentrations in sheep were accurately predicted. Muscle concentrations were overpredicted in cattle by up to three-fold. Predictions using constant body weights differed from the growth PBK predictions by up to 80%, 12%, and 60% in cattle, sheep, and chicken tissue, respectively. Integration of growth in the PBK model led to improved accuracy in concentration predictions. Tissue concentration predictions could be improved using reliable partition coefficient estimates. The presented model closed gaps in previously developed models by integrating growth and PFOS-specific processes such as enterohepatic circulation and tubular reabsorption.