Building species trait-specific nano-QSARs: Model stacking, navigating model uncertainties and limitations, and the effect of dataset size.

A strong need exists for broadly applicable nano-QSARs, capable of predicting toxicological outcomes towards untested species and nanomaterials, under different environmental conditions. Existing nano-QSARs are generally limited to only a few species but the inclusion of species characteristics into models can aid in making them applicable to multiple species, even when toxicity data is not available for biological species. Species traits were used to create classification- and regression machine learning models to predict acute toxicity towards aquatic species for metallic nanomaterials. Afterwards, the individual classification- and regression models were stacked into a meta-model to improve performance. Additionally, the uncertainty and limitations of the models were assessed in detail (beyond the OECD principles) and it was investigated whether models would benefit from the addition of more data. Results showed a significant improvement in model performance following model stacking. Investigation of model uncertainties and limitations highlighted the discrepancy between the applicability domain and accuracy of predictions. Data points outside of the assessed chemical space did not have higher likelihoods of generating inadequate predictions or vice versa. It is therefore concluded that the applicability domain does not give complete insight into the uncertainty of predictions and instead the generation of prediction intervals can help in this regard. Furthermore, results indicated that an increase of the dataset size did not improve model performance. This implies that larger dataset sizes may not necessarily improve model performance while in turn also meaning that large datasets are not necessarily required for prediction of acute toxicity with nano-QSARs.

Immunotoxic effects of metal-based nanoparticles in fish and bivalves.

There is a global research interest in metal nanoparticles (MNPs) due to their diverse applications, rapidly increasing use, and increased presence in the aquatic environment. Currently, most MNPs in the environment are at levels unlikely to cause overt toxicity. Sub-lethal effects that MNPs may induce, notable immunotoxicity, could however have significant health implications. Thus, deciphering the immunological interactions of MNPs with aquatic organisms constitutes a much-needed area of research. In this article, we critically assess the evidence for immunotoxic effects of MNPs in bivalves and fish, as key wildlife sentinels with widely differing ecological niches that are used as models in ecotoxicology. The first part of this review details the properties, fate, and fundamental physicochemical behavior of MNPs in the aquatic ecosystem. We then consider the toxicokinetics of MNP uptake, accumulation, and deposition in fish and bivalves. The main body of the review then focuses on immune reactions in response to MNPs exposure in bivalves and fish illustrating their immunotoxic potential. Finally, we identify major knowledge gaps in our current understanding of the implications of MNPs exposure for immunological functions and the associated health consequences for bivalves and fish, as well as the general lessons learned on the immunotoxic properties of the emerging class of nanoparticulate contaminants in fish and bivalves.

Do the joint effects of size, shape and ecocorona influence the attachment and physical eco(cyto)toxicity of nanoparticles to algae?

We systematically investigated how the combinations of size, shape and the natural organic matter (NOM)-ecocorona of gold (Au) engineered nanoparticles (ENPs) influence the attachment of the particles to algae and physical toxicity to the cells. Spherical (10, 60 and 100 nm), urchin-shaped (60 nm), rod-shaped (10 × 45, 40 × 60 and 50 × 100 nm), and wire-shaped (75 × 500, 75 × 3000 and 75 × 6000 nm) citrate-coated and NOM-coated Au-ENPs were used. Among the spherical particles only the spherical 10 nm Au-ENPs caused membrane damage to algae. Only the rod-shaped 10 × 45 nm induced membrane damage among the rod-shaped Au-ENPs. Wire-shaped Au-ENPs caused no membrane damage to the algae. NOM ecocorona decreased the membrane damage effects of spherical 10 nm and rod-shaped 10 × 45 nm ENPs. The spherical Au-ENPs were mostly loosely attached to the cells compared to other shapes, whereas the wire-shaped Au-ENPs were mostly strongly attached compared to particles with other shapes. NOM ecocorona determined the strength of Au-ENPs attachment to the cell wall, leading to the formation of loose rather than strong attachment of Au-ENPs to the cells. After removal of the loosely and strongly attached Au-ENPs, some particles remained anchored to the surface of the algae. The highest concentration was detected for spherical 10 nm Au-ENPs followed by rod-shaped 10 × 45 nm Au-ENPs, while the lowest concentration was observed for the wire-shaped Au-ENPs. The combined effect of shape, size, and ecocorona controls the Au-ENPs attachment and physical toxicity to cells.