Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making

Risk of lung damage from inhaled chemicals or substances has long been assessed using animal models. However, New Approach Methodologies (NAMs) that replace, reduce, and/or refine the use of animals in safety testing such as 2D and 3D cultures are increasingly being used to understand human-relevant...

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Main Authors: Joanne Wallace, Mary C. McElroy, Mitchell Klausner, Richard Corley, Seyoum Ayehunie
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/18/1/113
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author Joanne Wallace
Mary C. McElroy
Mitchell Klausner
Richard Corley
Seyoum Ayehunie
author_facet Joanne Wallace
Mary C. McElroy
Mitchell Klausner
Richard Corley
Seyoum Ayehunie
author_sort Joanne Wallace
collection DOAJ
description Risk of lung damage from inhaled chemicals or substances has long been assessed using animal models. However, New Approach Methodologies (NAMs) that replace, reduce, and/or refine the use of animals in safety testing such as 2D and 3D cultures are increasingly being used to understand human-relevant toxicity responses and for the assessment of hazard identification. Here we review 2D and 3D lung models in terms of their application for inhalation toxicity assessment. We highlight a key case study for the Organization for Economic Cooperation and Development (OECD), in which a 3D model was used to assess human toxicity and replace the requirement for a 90-day inhalation toxicity study in rats. Finally, we consider the regulatory guidelines for the application of NAMs and potential use of different lung models for aerosol toxicity studies depending on the regulatory requirement/context of use.
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institution Kabale University
issn 1424-8247
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series Pharmaceuticals
spelling doaj-art-c5f569c872e9442b8f8a7907e490be212025-01-24T13:45:26ZengMDPI AGPharmaceuticals1424-82472025-01-0118111310.3390/ph18010113Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision MakingJoanne Wallace0Mary C. McElroy1Mitchell Klausner2Richard Corley3Seyoum Ayehunie4Charles River Laboratories, Edinburgh EH33 2NE, UKCharles River Laboratories, Edinburgh EH33 2NE, UKMatTek Corporation, Ashland, MA 01721, USAGreek Creek Toxicokinetics Consulting LLC, Boise, ID 83714, USAMatTek Corporation, Ashland, MA 01721, USARisk of lung damage from inhaled chemicals or substances has long been assessed using animal models. However, New Approach Methodologies (NAMs) that replace, reduce, and/or refine the use of animals in safety testing such as 2D and 3D cultures are increasingly being used to understand human-relevant toxicity responses and for the assessment of hazard identification. Here we review 2D and 3D lung models in terms of their application for inhalation toxicity assessment. We highlight a key case study for the Organization for Economic Cooperation and Development (OECD), in which a 3D model was used to assess human toxicity and replace the requirement for a 90-day inhalation toxicity study in rats. Finally, we consider the regulatory guidelines for the application of NAMs and potential use of different lung models for aerosol toxicity studies depending on the regulatory requirement/context of use.https://www.mdpi.com/1424-8247/18/1/1132D and 3D lung modelsinhaled chemical safety assessmentin vitrohumanratcomputational modeling
spellingShingle Joanne Wallace
Mary C. McElroy
Mitchell Klausner
Richard Corley
Seyoum Ayehunie
Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making
Pharmaceuticals
2D and 3D lung models
inhaled chemical safety assessment
in vitro
human
rat
computational modeling
title Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making
title_full Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making
title_fullStr Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making
title_full_unstemmed Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making
title_short Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based Decision Making
title_sort two and three dimensional culture systems respiratory in vitro tissue models for chemical screening and risk based decision making
topic 2D and 3D lung models
inhaled chemical safety assessment
in vitro
human
rat
computational modeling
url https://www.mdpi.com/1424-8247/18/1/113
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AT marycmcelroy twoandthreedimensionalculturesystemsrespiratoryinvitrotissuemodelsforchemicalscreeningandriskbaseddecisionmaking
AT mitchellklausner twoandthreedimensionalculturesystemsrespiratoryinvitrotissuemodelsforchemicalscreeningandriskbaseddecisionmaking
AT richardcorley twoandthreedimensionalculturesystemsrespiratoryinvitrotissuemodelsforchemicalscreeningandriskbaseddecisionmaking
AT seyoumayehunie twoandthreedimensionalculturesystemsrespiratoryinvitrotissuemodelsforchemicalscreeningandriskbaseddecisionmaking