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

Abstract

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.

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective

“…The multimetric approach can give relevant and essential information on exposure scenarios, but the lack of associated occupational exposure limit (OEL) values and the ever-expanding knowledge gap on human health effects of 2D materials have led to the use of precautionary principles in exposure control and risk management. One suggested approach is the utilization of safe-by-design principles to cover the whole life cycle of the product, from innovation, development, and production to end-of-life …”

Physico-Chemical Approaches to Investigate Surface Hydroxyls as Determinants of Molecular Initiating Events in Oxide Particle Toxicity

“…The bioanalytical tests discussed here, in addition to previous spectroscopic and analytical results, may be used collectively to unravel the molecular nature of the interaction of OxPs with biosystems. Both cell membranes and biomolecules, including phospholipids (PLs) and proteins, are important targets in the interaction of OxPs with living cells and such interaction may possibly trigger toxic outcomes [14,[91][92][93].…”

“…OxPs exist in a plethora of chemical, structural, dimensional, and morphological variants (Figure 1), which in turn differentiate them for their key toxicologically relevant parameters, such as surface reactivity, micromorphology, and biopersistence. Such intrinsic variability has posed a huge concern for the toxicological assessment, predictivity, and safe design of (nano)materials and hindered the definition of structure-activity relationships (SAR) to model the biological hazard [14,15]. Currently, the most robust paradigm in particle toxicology includes the simultaneous presence of three key properties that derive from a combination of bulk and surface characteristics.…”

Zero-Carbon and Carbon-Neutral Fuels: A Review of Combustion Products and Cytotoxicity

“…The toxic effects of emissions from biodiesel and its fuel blends involve cytotoxicity, oxidative stress, inflammatory response, and genotoxicity (carcinogenicity and mutagenicity) (Figure 2). In terms of cytotoxicity, cell morphological changes, the release of cytoplasmic components (e.g., LDH and AK), mitochondrial activity (e.g., MTT, MTS, XTT, and WST-1 assays), lysosomal integrity (neutral red uptake), adenosine triphosphate (ATP) levels, and the number of apoptosis and necrotic cells (trypan blue, propidium iodide and annexin staining) are often used as indicators of cytotoxicity or cell viability [156][157][158]. Biodiesel treatment increased the content of LDH and decreased cell viability [159].…”