Journal
SMALL
Volume 17, Issue 15, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202007628
Keywords
in vitro toxicity; lung fibrosis; nanoparticles; nanotoxicity; risk assessment
Categories
Funding
- Health Canada's Genomics Research and Development Initiative
- European Union [760813]
- SmartNanoTox [686098]
- Adolphe Merkle Foundation
- Swiss Federal Office of Public Health (FOPH)
- German Chemicals Industry Association (VCI, Verband der Chemischen Industrie e.V.)
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Faster, cheaper, more sensitive, and mechanisms-based animal alternatives are needed for safety assessment of nanomaterials, along with strategies to identify and prioritize alternative schemes and enable their validation and refinement. This review presents two strategies, the current nanotoxicology literature review and the adverse outcome pathways (AOPs) framework, to address these needs. Through analyzing frequently assessed toxicity measurements, AOPs of relevance to inhalation toxicity of NM, and specific AOPs for lung fibrosis, key events of toxicity for in vitro assay development are identified.
Faster, cheaper, sensitive, and mechanisms-based animal alternatives are needed to address the safety assessment needs of the growing number of nanomaterials (NM) and their sophisticated property variants. Specifically, strategies that help identify and prioritize alternative schemes involving individual test models, toxicity endpoints, and assays for the assessment of adverse outcomes, as well as strategies that enable validation and refinement of these schemes for the regulatory acceptance are needed. In this review, two strategies 1) the current nanotoxicology literature review and 2) the adverse outcome pathways (AOPs) framework, a systematic process that allows the assembly of available mechanistic information concerning a toxicological response in a simple modular format, are presented. The review highlights 1) the most frequently assessed and reported ad hoc in vivo and in vitro toxicity measurements in the literature, 2) various AOPs of relevance to inhalation toxicity of NM that are presently under development, and 3) their applicability in identifying key events of toxicity for targeted in vitro assay development. Finally, using an existing AOP for lung fibrosis, the specific combinations of cell types, exposure and test systems, and assays that are experimentally supported and thus, can be used for assessing NM-induced lung fibrosis, are proposed.
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