Toxicogenomics in a soil sentinel exposure to Zn nanoparticles and ions reveals the comparative role of toxicokinetic and toxicodynamic mechanisms

Abstract

A critical question for read across of the hazards of nanomaterials is the degree to which their mechanisms of action differ from those of their bulk chemical constituents. It has been established that metal and metal oxide nanoparticles (NPs) can be accumulated by invertebrate species. Moreover, it has been hypothesised that the observed toxicity resulting on exposure to these nanomaterials is most likely to be associated with the releases of ions from external or internal dissolution leading ultimately to toxicity. However, mechanistic confirmation of the similar modes of action for metal oxide nanomaterials and metal ions in studies invertebrates are largely lacking. Therefore, here we present a toxicogenomic study using exposed individuals of the earthworm Eisenia fetida from a single genetic lineage. We compared gene expression and pathway responses through RNA-seq analysis at equitoxic concentrations (EC₅₀ for reproduction) of ZnO NPs and ionic Zn. We found similar transcriptomic effects for both Zn forms with genetic signatures of tight control of cytosolic Zn concentrations through expression changes of genes encoding several Zn transporters. Activation and regulation of JUN, MAP and JNK kinases indicated a cellular response to the increased Zn concentrations of both forms with compound binding terms also enriched. Our results illustrate the need to consider both toxicokinetic and toxicodynamic mechanisms in the development of adverse outcome pathways for nanomaterials.