Oil sand-derived process water is comprised of mixtures of many different toxic compounds. Recent modelling studies have been developed to assess oil sand ecotoxicity caused by naphthenic acids (NA). The hydrocarbon block method was used to described the ecotoxicity of NA mixtures using a database of physico-chemical properties for individual hydrocarbons. Chemical speciation and biota partitioning models are used to characterize the toxicity of ionizable compounds. An analysis of model predictions has suggested that high MW and compounds from the higher Z families contribute significantly to the ecotoxicity of oil sand-derived process water. However, the current modelling method overpredicts the toxicity of the highest residual fractions, which suggests that the bioavailability of the highest MW compounds is limited. Further model refinement is needed to evaluate NA compounds across a wide range of MW and Z families.