Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles
Lung cancer, one of the most common and deadly forms of cancer, is in some cases associated with exposure to certain types of particles. With the rise of nanotechnology, there is concern that some engineered nanoparticles may be among such particles. In the absence of epidemiological evidence, asses...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Toxicology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/ftox.2021.653386/full |
| _version_ | 1819322957741162496 |
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| author | Penny Nymark Hanna L. Karlsson Sabina Halappanavar Ulla Vogel Ulla Vogel |
| author_facet | Penny Nymark Hanna L. Karlsson Sabina Halappanavar Ulla Vogel Ulla Vogel |
| author_sort | Penny Nymark |
| collection | DOAJ |
| description | Lung cancer, one of the most common and deadly forms of cancer, is in some cases associated with exposure to certain types of particles. With the rise of nanotechnology, there is concern that some engineered nanoparticles may be among such particles. In the absence of epidemiological evidence, assessment of nanoparticle carcinogenicity is currently performed on a time-consuming case-by-case basis, relying mainly on animal experiments. Non-animal alternatives exist, including a few validated cell-based methods accepted for regulatory risk assessment of nanoparticles. Furthermore, new approach methodologies (NAMs), focused on carcinogenic mechanisms and capable of handling the increasing numbers of nanoparticles, have been developed. However, such alternative methods are mainly applied as weight-of-evidence linked to generally required animal data, since challenges remain regarding interpretation of the results. These challenges may be more easily overcome by the novel Adverse Outcome Pathway (AOP) framework, which provides a basis for validation and uptake of alternative mechanism-focused methods in risk assessment. Here, we propose an AOP for lung cancer induced by nanosized foreign matter, anchored to a selection of 18 standardized methods and NAMs for in silico- and in vitro-based integrated assessment of lung carcinogenicity. The potential for further refinement of the AOP and its components is discussed in relation to available nanosafety knowledge and data. Overall, this perspective provides a basis for development of AOP-aligned alternative methods-based integrated testing strategies for assessment of nanoparticle-induced lung cancer. |
| first_indexed | 2024-12-24T11:59:38Z |
| format | Article |
| id | doaj.art-ce263b46ff984df0adcd90a413d7017b |
| institution | Directory Open Access Journal |
| issn | 2673-3080 |
| language | English |
| last_indexed | 2024-12-24T11:59:38Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Toxicology |
| spelling | doaj.art-ce263b46ff984df0adcd90a413d7017b2022-12-21T16:56:23ZengFrontiers Media S.A.Frontiers in Toxicology2673-30802021-04-01310.3389/ftox.2021.653386653386Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by NanoparticlesPenny Nymark0Hanna L. Karlsson1Sabina Halappanavar2Ulla Vogel3Ulla Vogel4Institute of Environmental Medicine, Karolinska Institute, Stockholm, SwedenInstitute of Environmental Medicine, Karolinska Institute, Stockholm, SwedenEnvironmental Health Science and Research Bureau, Health Canada, Ottawa, ON, CanadaNational Research Centre for the Working Environment, Copenhagen, DenmarkDTU Health Tech, Technical University of Denmark, Kgs. Lyngby, DenmarkLung cancer, one of the most common and deadly forms of cancer, is in some cases associated with exposure to certain types of particles. With the rise of nanotechnology, there is concern that some engineered nanoparticles may be among such particles. In the absence of epidemiological evidence, assessment of nanoparticle carcinogenicity is currently performed on a time-consuming case-by-case basis, relying mainly on animal experiments. Non-animal alternatives exist, including a few validated cell-based methods accepted for regulatory risk assessment of nanoparticles. Furthermore, new approach methodologies (NAMs), focused on carcinogenic mechanisms and capable of handling the increasing numbers of nanoparticles, have been developed. However, such alternative methods are mainly applied as weight-of-evidence linked to generally required animal data, since challenges remain regarding interpretation of the results. These challenges may be more easily overcome by the novel Adverse Outcome Pathway (AOP) framework, which provides a basis for validation and uptake of alternative mechanism-focused methods in risk assessment. Here, we propose an AOP for lung cancer induced by nanosized foreign matter, anchored to a selection of 18 standardized methods and NAMs for in silico- and in vitro-based integrated assessment of lung carcinogenicity. The potential for further refinement of the AOP and its components is discussed in relation to available nanosafety knowledge and data. Overall, this perspective provides a basis for development of AOP-aligned alternative methods-based integrated testing strategies for assessment of nanoparticle-induced lung cancer.https://www.frontiersin.org/articles/10.3389/ftox.2021.653386/fulladverse outcome pathwaysnanoparticlesgenotoxicitylung cancernew approach methodologies |
| spellingShingle | Penny Nymark Hanna L. Karlsson Sabina Halappanavar Ulla Vogel Ulla Vogel Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles Frontiers in Toxicology adverse outcome pathways nanoparticles genotoxicity lung cancer new approach methodologies |
| title | Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles |
| title_full | Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles |
| title_fullStr | Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles |
| title_full_unstemmed | Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles |
| title_short | Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles |
| title_sort | adverse outcome pathway development for assessment of lung carcinogenicity by nanoparticles |
| topic | adverse outcome pathways nanoparticles genotoxicity lung cancer new approach methodologies |
| url | https://www.frontiersin.org/articles/10.3389/ftox.2021.653386/full |
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