Governance of advanced materials: Shaping a safe and sustainable future.

The past few decades of managing the uncertain risks associated with nanomaterials have provided valuable insights (knowledge gaps, tools, methods, etc.) that are equally important to promote safe and sustainable development and use of advanced materials. Based on these insights, the current paper proposes several actions to optimize the risk and sustainability governance of advanced materials. We emphasise the importance of establishing a European approach for risk and sustainability governance of advanced materials as soon as possible to keep up with the pace of innovation and to manage uncertainty among regulators, industry, SMEs and the public, regarding potential risks and impacts of advanced materials. Coordination of safe and sustainable advanced material research efforts, and data management according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles will enhance the generation of regulatory-relevant knowledge. This knowledge is crucial to identify whether current regulatory standardised and harmonised test methods are adequate to assess advanced materials. At the same time, there is urgent need for responsible innovation beyond regulatory compliance which can be promoted through the Safe and Sustainable Innovation Approach. that combines the Safe and Sustainable by Design concept with Regulatory Preparedness, supported by a trusted environment. We further recommend consolidating all efforts and networks related to the risk and sustainability governance of advanced materials in a single, easy-to-use digital portal. Given the anticipated complexity and tremendous efforts required, we identified the need of establishing an organisational structure dedicated to aligning the fast technological developments in advanced materials with proper risk and sustainability governance. Involvement of multiple stakeholders in a trusted environment ensures a coordinated effort towards the safe and sustainable development, production, and use of advanced materials. The existing infrastructures and network of experts involved in the governance of nanomaterials would form a solid foundation for such an organisational structure.

The State of the Art and Challenges of In Vitro Methods for Human Hazard Assessment of Nanomaterials in the Context of Safe-by-Design.

The Safe-by-Design (SbD) concept aims to facilitate the development of safer materials/products, safer production, and safer use and end-of-life by performing timely SbD interventions to reduce hazard, exposure, or both. Early hazard screening is a crucial first step in this process. In this review, for the first time, commonly used in vitro assays are evaluated for their suitability for SbD hazard testing of nanomaterials (NMs). The goal of SbD hazard testing is identifying hazard warnings in the early stages of innovation. For this purpose, assays should be simple, cost-effective, predictive, robust, and compatible. For several toxicological endpoints, there are indications that commonly used in vitro assays are able to predict hazard warnings. In addition to the evaluation of assays, this review provides insights into the effects of the choice of cell type, exposure and dispersion protocol, and the (in)accurate determination of dose delivered to cells on predictivity. Furthermore, compatibility of assays with challenging advanced materials and NMs released from nano-enabled products (NEPs) during the lifecycle is assessed, as these aspects are crucial for SbD hazard testing. To conclude, hazard screening of NMs is complex and joint efforts between innovators, scientists, and regulators are needed to further improve SbD hazard testing.

Integrative approach in a safe by design context combining risk, life cycle and socio-economic assessment for safer and sustainable nanomaterials.

Moving towards safe and sustainable innovations is an international policy ambition. In the on-hand manuscript, a concept combining safe by design and sustainability was implemented through the integration of human and environmental risk assessment, life cycle assessment as well as an assessment of the economic viability. The result is a nested and iterative process in form of a decision tree that integrates these three elements in order to achieve sustainable, safe and competitive materials, products or services. This approach, embedded into the stage-gate-model for safe by design, allows to reduce the uncertainty related to the assessment of risks and impacts by improving the quality of the data collected along each stage. In the second part of the manuscript, the application is shown for a case study dealing with the application of nanoparticles for Li-Ion batteries. One of the general conclusions out of this case study is that data gaps are a key aspect in view of the reliability of the results.

Toward Rigorous Materials Production: New Approach Methodologies Have Extensive Potential to Improve Current Safety Assessment Practices.

Advanced material development, including at the nanoscale, comprises costly and complex challenges coupled to ensuring human and environmental safety. Governmental agencies regulating safety have announced interest toward acceptance of safety data generated under the collective term New Approach Methodologies (NAMs), as such technologies/approaches offer marked potential to progress the integration of safety testing measures during innovation from idea to product launch of nanomaterials. Divided in overall eight main categories, searchable databases for grouping and read across purposes, exposure assessment and modeling, in silico modeling of physicochemical structure and hazard data, in vitro high-throughput and high-content screening assays, dose-response assessments and modeling, analyses of biological processes and toxicity pathways, kinetics and dose extrapolation, consideration of relevant exposure levels and biomarker endpoints typify such useful NAMs. Their application generally agrees with articulated stakeholder needs for improvement of safety testing procedures. They further fit for inclusion and add value in nanomaterials risk assessment tools. Overall 37 of 50 evaluated NAMs and tiered workflows applying NAMs are recommended for considering safer-by-design innovation, including guidance to the selection of specific NAMs in the eight categories. An innovation funnel enriched with safety methods is ultimately proposed under the central aim of promoting rigorous nanomaterials innovation.

Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer.

Low invasive tests with high sensitivity for colorectal cancer and advanced precancerous lesions will increase adherence rates, and improve clinical outcomes. We have performed an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-(TOF) MS)-based metabolomics study to identify faecal biomarkers for the detection of patients with advanced neoplasia. A cohort of 80 patients with advanced neoplasia (40 advanced adenomas and 40 colorectal cancers) and 49 healthy subjects were analysed in the study. We evaluated the faecal levels of 105 metabolites including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. We found 18 metabolites that were significantly altered in patients with advanced neoplasia compared to controls. The combinations of seven metabolites including ChoE(18:1), ChoE(18:2), ChoE(20:4), PE(16:0/18:1), SM(d18:1/23:0), SM(42:3) and TG(54:1), discriminated advanced neoplasia patients from healthy controls. These seven metabolites were employed to construct a predictive model that provides an area under the curve (AUC) median value of 0.821. The inclusion of faecal haemoglobin concentration in the metabolomics signature improved the predictive model to an AUC of 0.885. In silico gene expression analysis of tumour tissue supports our results and puts the differentially expressed metabolites into biological context, showing that glycerolipids and sphingolipids metabolism and GPI-anchor biosynthesis pathways may play a role in tumour progression.