Mechanisms of toxicity of engineered nanoparticles: adverse outcome pathway for dietary silver nanoparticles in mussels

Over recent years, engineered nanoparticles (NPs) have been increasingly incorporated into many consumer products because they present novel physicochemical properties in comparison to their bulk counterparts. Metal-bearing NPs are used extensively and, among them, silver NPs (Ag NPs) have gained high commercial and scientific interest due to their unique optical, catalytical and antimicrobial properties. Applications of Ag NPs are increasing and so are concerns about their potential input into aquatic ecosystems and their environmental hazards. Due to their filter-feeding activity, mussels Mytilus spp. are sentinel species widely used in biomonitoring of environmental pollution and as suitable model organisms for characterizing the potential impact of NPs in marine environments. NPs are trapped by gills, the first organ vulnerable to particle interactions, and then directed to the digestive gland. NP accumulation, cellular fate and effects depend on their physicochemical characteristics. The application of biomarkers after waterborne exposure of mussels to Ag NPs revealed adverse effects such as destabilization of the lysosomal membrane in digestive cells, induction of antioxidant enzyme activities and lipid peroxidation in the digestive gland and gills, genotoxic effects in hemocytes as well as a concentration-dependent increase in malformed D-shell larvae, among others. Also, omic’s tools have identified molecular markers that can help to predict adverse outcome pathways from initiating events to higher level consequences. However, studies assessing the potential trophic transfer of Ag NPs remain scarce even though NPs may be prone to bioaccumulation and biomagnification along trophic chains. In this work we reviewed literature on the fate and toxicity of engineered NPs in aquatic organisms and discussed data showing that dietary exposure of marine mussels to Ag NPs at environmentally relevant concentrations caused deleterious effects at molecular, cellular and tissue levels, as well as on reproduction and offspring development. Proteomic and transcriptomic studies unveiled Ag NP responsive biological pathways, which were modulated by season, providing insights into the mechanisms of toxicity. Further, all the data were integrated in an adverse outcome pathway proposed for Ag NP impact in dietarily exposed mussels at different seasons.