Evaluation of a non-animal toolbox informed by adverse outcome pathways for human inhalation safety
In general, PoDs occurred at higher concentrations than the corresponding human exposure values for the majority of the low-risk chemical-exposure scenarios. For all the high-risk chemical-exposure scenarios, there was a clear overlap between the PoDs and lung deposited mass and C<sub>max</sub> for the benchmark inhaled materials and therapeutic drugs, respectively. Our findings suggest that combining computational and <i>in vitro</i> new approach methodologies (NAMs) informed by adverse outcome pathways (AOPs) associated with pulmonary toxicity can provide relevant biological coverage for chemical lung safety assessment.
Authors
- Joanne Wallace (ORCID: https://orcid.org/0000-0002-6951-7070)
- Anthony M. Bowden
- Renato Ivan de Ávila (ORCID: https://orcid.org/0000-0001-6795-304X)
- Samuel Constant (ORCID: https://orcid.org/0000-0002-0931-2663)
- Danilo Basili (ORCID: https://orcid.org/0000-0003-4830-7848)
- A. Middleton (ORCID: https://orcid.org/0000-0002-9508-4117)
- Bernadett Boda (ORCID: https://orcid.org/0000-0002-4563-4088)
- Vivek Patel (ORCID: https://orcid.org/0000-0001-7209-3531)
- Helen Barlow
- Ouarda Saib
- Iris Müller (ORCID: https://orcid.org/0000-0001-8542-0175)
- Holger Behrsing
- Maria Teresa Baltazar (ORCID: https://orcid.org/0000-0002-3854-5685)
- Patrik Engi
- Tymoteusz Pietrenko
- Mathura Theiventhran
Institutions
- Unilever (United Kingdom) (GB)
- University of Bedfordshire (GB)
- Charles River Laboratories (United Kingdom) (GB)
- Institute for In Vitro Sciences (US)
Publication Details
- Journal
- Frontiers in Toxicology
- Published
- 2025-02-21
- DOI
- https://doi.org/10.3389/ftox.2025.1426132
- Citations
- 4
- Primary Topic
- Inhalation and Respiratory Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 6.07