Andrea Miccoli

The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of "New Approach Methodologies" (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure-activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today's regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free "Next Generation Risk Assessment" (NGRA).

In the last three decades, the aquaculture sector has experienced a 527% growth, producing 82 million tons for a first sale value estimated at 250 billion USD. Infectious diseases caused by bacteria, viruses, or parasites are the major causes of mortality and economic losses in commercial aquaculture. Some pathologies, especially those of bacterial origin, can be treated with commercially available drugs, while others are poorly managed. In fact, despite having been recognized as a useful preventive measure, no effective vaccination against many economically relevant diseases exist yet, such as for viral and parasitic infections. The objective of the present review is to provide the reader with an updated perspective on the most significant and innovative vaccine research on three key aquaculture commodities. European sea bass (Dicentrarchus labrax), Nile tilapia (Oreochromis niloticus), and Atlantic salmon (Salmo salar) were chosen because of their economic relevance, geographical distinctiveness, and representativeness of different culture systems. Scientific papers about vaccines against bacterial, viral, and parasitic diseases will be objectively presented; their results critically discussed and compared; and suggestions for future directions given.

The energy transition requires large-scale storage to provide long-term supply and short-term grid stability. Though pumped hydro storage is widely used for this purpose, regions without natural topography do not have the potential for traditional high-head pumped hydro storage. To address this, multiple projects for low-head and seawater pumped hydro storage have been proposed, though few have been implemented. Here, we review the state of the art of the components of low-head seawater pumped hydro storage projects, for construction in shallow seas or integrated into coastal defenses. We reference all civil infrastructure components, in addition to legal, environmental/biological, and financial constraints, drawing knowledge from proposed, planned, and constructed tidal power and seawater pumped hydro storage projects worldwide. Combining this knowledge, we make a preliminary evaluation of the feasibility for low-head seawater pumped hydro storage in the North Sea. We find that an elevated storage basin is more economical than an excavated one in shallow bathymetry (10 m deep or less), while the reverse is true in deeper water. Corrosion and fouling prevention are already well developed due to implementation of these measures at tidal power plants. Dam construction is feasible if measures are taken to address piping, macro-instability (primarily from rapid drawdown), and bursting of the clay layer. Within the context of Europe, legal and environmental regulations may be the most formidable hurdles to such projects.

The increasing use of magnetic iron oxide nanoparticles (NPs) in biomedical applications has prompted extensive investigation of their interactions with biological systems also through animal models. A variety of toxic effects have been detected in NP-exposed fish and fish embryos, including oxidative stress and associated changes, such as lipid oxidation, apoptosis, and gene expression alterations. The main exposure route for fish is through food and the food web. This study was devised to investigate the effects of silica-coated NP administration through food in zebrafish (ZF, Danio rerio). Silica-coated magnetic NPs were administered to ZF through feed (zooplankton) from day 1 to 15 posthatching (ph). Larvae were examined 6 and 15 days ph and adults 3 and 6 months ph. A multidisciplinary approach, including morphometric examination; light, transmission electron, and confocal microscopy; inductively coupled plasma emission spectrometry; and real-time polymerase chain reaction, was applied to detect NP accumulation, structural and ultrastructural damage, and activation of detoxification processes in larvae and adults. Our findings document that the silica-coated NPs: (1) do not induce toxicity in ZF, (2) are excreted through feces, and (3) do not activate detoxification processes or promote tissue/cell injury.