ABSTRACT: Impacts of engineered nanomaterial (ENM) exposure is known to be dependent upon physico-chemical characteristics of the material but is also significantly dependent upon the organism exposed, with unclear reasons for these differences. Although studies have identified some common mechanistic impacts across species (e.g., oxidative stress), these do not necessarily correlate to adverse outcomes, which may differ by orders of magnitude across species. Differences in toxicological response could potentially be due to species-specific biochemical mechanisms, magnitude of response of common pathways across species, or differences in the exposure and uptake of nanomaterials. In-depth analysis across studies is made difficult as multiple species are not often included in the same study, nanomaterials from multiple sources differ in their characteristics, and variation in exposure duration and media confounds the ability to draw synthetic conclusions from existing cross-species data. The current study examines mechanisms of response across model species Danio rerio, Daphnia magna, and Chironomus riparius to a single-source complex metal oxide, lithium cobalt oxide nanosheets. Each species has previously been shown to have differing sensitivities to NM exposure. RNA-sequencing was used to identify impacted pathways and physiological functions, revealing nanomaterial-specific biochemical responses not replicated by ion exposures, as has also been shown by standard toxicology tests, and importantly that nanomaterial uptake does not fully explain cross-species differences. Significant variation in biochemical response may explain differences, both in the magnitude of response of unifying mechanisms across species and novel pathways impacted in a sensitive or tolerant species. Analysis indicates both commonly identified responses to ENM, including stress, changes in energy metabolism, apoptosis, and immune functions and lesser-explored or novel responses involved in cardiovascular system, hormone, and central nervous system impacts. This comparison demonstrates new universal mechanisms of toxicity for this model ENM and provides insight into how biomolecular responses across species can play a role in varying sensitivity to nanomaterials in general.
