Modeling the Toxicokinetics of Suspensions of Soluble Metallic Nanomaterials

Proper risk assessment of the many new nanoforms (NFs) that are currently being developed and marketed is hindered by constraints in time and resources for testing their fate and (eco) toxicity profile. This problem has also been encountered in conventional chemical risk assessments, where the definition of related chemical groups can facilitate risk assessment for all class members. Whereas grouping and read-across methods are well established, such approaches are in the early stages of development for NFs. In this study, a modeling framework was developed for grouping NFs into distinct classes regarding the contribution of released ions to suspension-induced toxicity. The framework is based on combining dissolution rate constants of NFs with information about the toxicokinetics of the NFs and the dissolution products formed. The framework is exemplified for the specific case of suspension toxicity of metallic NFs (silver and copper). To this end, principles of mixture toxicity and dose-response modeling are integrated to derive threshold values for the key NF properties determining suspension toxicity: size, shape, and chemical composition. The threshold values thus derived offer a possible solution for the high-throughput screening of NFs according to their morphological and compositional properties in a regulatory context.