An integrated approach to testing and assessment to support grouping and read-across of nanomaterials after inhalation exposure
Braakhuis, Hedwig M. and Murphy, Fiona and Ma-Hock, Lan and Dekkers, Susan and Keller, Johannes and Oomen, Agnes G. and Stone, Vicki (2021) An integrated approach to testing and assessment to support grouping and read-across of nanomaterials after inhalation exposure. Applied in Vitro Toxicology, 7 (3). pp. 112-128. ISSN 2332-1539 (https://doi.org/10.1089/aivt.2021.0009)
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Abstract
Introduction: Here, we describe the generation of hypotheses for grouping nanoforms (NFs) after inhalation exposure and the tailored Integrated Approaches to Testing and Assessment (IATA) with which each specific hypothesis can be tested. This is part of a state-of-the-art framework to support the hypothesis-driven grouping and read-across of NFs, as developed by the EU-funded Horizon 2020 project GRACIOUS. Development of Grouping Hypotheses and IATA: Respirable NFs, depending on their physicochemical properties, may dissolve either in lung lining fluid or in acidic lysosomal fluid after uptake by cells. Alternatively, NFs may also persist in particulate form. Dissolution in the lung is, therefore, a decisive factor for the toxicokinetics of NFs. This has led to the development of four hypotheses, broadly grouping NFs as instantaneous, quickly, gradually, and very slowly dissolving NFs. For instantaneously dissolving NFs, hazard information can be derived by read-across from the ions. For quickly dissolving particles, as accumulation of particles is not expected, ion toxicity will drive the toxic profile. However, the particle aspect influences the location of the ion release. For gradually dissolving and very slowly dissolving NFs, particle-driven toxicity is of concern. These NFs may be grouped by their reactivity and inflammation potency. The hypotheses are substantiated by a tailored IATA, which describes the minimum information and laboratory assessments of NFs under investigation required to justify grouping. Conclusion: The GRACIOUS hypotheses and tailored IATA for respiratory toxicity of inhaled NFs can be used to support decision making regarding Safe(r)-by-Design product development or adoption of precautionary measures to mitigate potential risks. It can also be used to support read-across of adverse effects such as pulmonary inflammation and subsequent downstream effects such as lung fibrosis and lung tumor formation after long-term exposure.
ORCID iDs
Braakhuis, Hedwig M., Murphy, Fiona ORCID: https://orcid.org/0000-0001-7925-0632, Ma-Hock, Lan, Dekkers, Susan, Keller, Johannes, Oomen, Agnes G. and Stone, Vicki;-
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Item type: Article ID code: 83594 Dates: DateEvent17 September 2021Published9 September 2021Published Online1 September 2021AcceptedSubjects: Medicine > Therapeutics. Pharmacology
Geography. Anthropology. Recreation > Environmental SciencesDepartment: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 21 Dec 2022 10:05 Last modified: 11 Nov 2024 13:43 URI: https://strathprints.strath.ac.uk/id/eprint/83594