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Updated: May 30, 2025

In vitro Cell Culture Model for Toxic Inhaled Chemical Testing
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Two- and Three-Dimensional Culture Systems: Respiratory In Vitro Tissue Models for Chemical Screening and Risk-Based

Joanne Wallace1, Mary C McElroy1, Mitchell Klausner2

  • 1Charles River Laboratories, Edinburgh EH33 2NE, UK.

Pharmaceuticals (Basel, Switzerland)
|January 25, 2025
PubMed
Summary

New Approach Methodologies (NAMs), including 3D lung models, are replacing animal testing for inhalation toxicity assessment. A 3D model successfully replaced a 90-day rat study for the OECD, demonstrating human-relevant toxicity evaluation.

Keywords:
2D and 3D lung modelscomputational modelinghumanin vitroinhaled chemical safety assessmentratvalidation

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Area of Science:

  • Toxicology
  • In vitro toxicology
  • Inhalation toxicology

Background:

  • Traditional animal models are used for assessing lung damage from inhaled substances.
  • New Approach Methodologies (NAMs) are emerging to replace, reduce, and refine animal use in safety testing.
  • 2D and 3D cell cultures are key NAMs for understanding human-relevant toxicity.

Purpose of the Study:

  • To review the application of 2D and 3D lung models for inhalation toxicity assessment.
  • To highlight the use of NAMs in regulatory toxicology.
  • To discuss regulatory guidelines for NAMs in aerosol toxicity studies.

Main Methods:

  • Review of existing literature on 2D and 3D lung models for inhalation toxicity.
  • Case study analysis of a 3D model used for OECD regulatory assessment.
  • Discussion of regulatory frameworks for NAMs.

Main Results:

  • 3D lung models demonstrate potential for assessing human-relevant toxicity responses.
  • A specific 3D model successfully replaced a 90-day rat inhalation toxicity study for OECD evaluation.
  • NAMs offer viable alternatives to animal testing in hazard identification.

Conclusions:

  • 2D and 3D lung models are valuable tools for inhalation toxicity assessment.
  • NAMs, particularly 3D models, can meet regulatory requirements and reduce animal use.
  • The choice of lung model depends on specific regulatory needs and study context.