Perfluoroalkyl acids (PFAAs) are the first mostly ionic compounds that are of major concern due to their accumulative behavior. The discussion about their risk is ongoing considering the increasing production of structurally similar alternatives.

Here we conducted model calculations based on equilibrium distribution coefficients that allow studying the distribution of PFAAs and their alternatives in various mammalian organs through comparison to empirical measurements in humans and rats. The calculations rely on experimentally determined distribution coefficients of a series of PFAAs and four of their alternatives to physiological matrices such as structural proteins, storage lipids, membrane lipids, albumin, and fatty acid binding protein (FABP). The relative sorption capacities in each organ were calculated from the combination of distribution coefficients and physiological data. The calculated distribution of PFAAs and alternatives within the organs showed that albumin and membrane lipids and to a lesser extent also structural proteins have the highest relative sorption capacities for the compounds. Sorption to FABP is only relevant in the distribution of short‐chain PFAAs. Storage lipids play a minor role for the distribution of all studied compounds. Our calculated distribution of PFAAs was evaluated by comparison to reported PFAA concentrations in various organs.