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Updated: Sep 1, 2026
In vitro Cell Culture Model for Toxic Inhaled Chemical Testing
Published on: May 8, 2014
In vitro models of lung toxicity
1Toxicology and Pharmacology Department, Battelle Columbus Division, Columbus, Ohio 43201.
Abstract:
In vitro assays that emphasize cellular components critical to the host defense system have been developed to evaluate pulmonary toxicity and define deleterious changes in parenchymal cell populations. Assays that employ pulmonary alveolar macrophages (PAM) have demonstrated good correlation between macrophage toxicity and pulmonary fibrogenicity for many inorganic compounds. The PAM assays provide simple and inexpensive screens of potential respiratory tract toxicity. Many investigators screen chemicals for their ability to alter the mucosal epithelial cell conducting airways by performing tracheal organ cultures. The tracheal assays have also provided useful screens for Vitamin A analogues required for epithelial cell differentiation. Most recently, in vitro respiratory tract models have been extended to include whole-lung explants, an approach that allows for development of fibrosis and epithelial cell toxicity after in vitro exposure to inorganic and organic fibrogens. The whole-lung explant system appears to duplicate the in vivo response to a variety of lung toxins, including bleomycin, silica, and crocidolite asbestos. Together, these assays provide a description of potential toxicity to key components of the lung, emphasizing the pulmonary macrophage, conducting airways, and alveolar septae. It is expected that continued research in these models will enhance their predictive abilities and utility in risk assessment.
Insights
In vitro assays using lung cells like macrophages and whole-lung explants effectively screen for respiratory toxins. These methods predict pulmonary toxicity and fibrosis, aiding in risk assessment.
Area of Science:
- Toxicology
- Cell Biology
- Pulmonary Medicine
Background:
- In vitro assays are crucial for evaluating pulmonary toxicity.
- Pulmonary alveolar macrophages (PAM) and tracheal organ cultures are established models.
- Assessing lung toxicity requires models that mimic in vivo responses.
Purpose of the Study:
- To review and highlight in vitro assays for pulmonary toxicity assessment.
- To emphasize the utility of PAM, tracheal organ cultures, and whole-lung explants.
- To discuss the predictive value of these models in risk assessment.
Main Methods:
- Utilizing pulmonary alveolar macrophage (PAM) assays for toxicity and fibrogenicity screening.
- Employing tracheal organ cultures to assess effects on conducting airway epithelial cells.
- Developing and using whole-lung explant models to study fibrosis and toxicity from various fibrogens.
Main Results:
- PAM assays show strong correlation between macrophage toxicity and pulmonary fibrogenicity for inorganic compounds.
- Tracheal assays are effective for screening Vitamin A analogues impacting epithelial cell differentiation.
- Whole-lung explant models successfully replicate in vivo responses to toxins like bleomycin, silica, and asbestos.
Conclusions:
- Established and novel in vitro assays provide valuable insights into pulmonary toxicity.
- These models focus on critical lung components: macrophages, conducting airways, and alveolar septae.
- Continued research is expected to improve the predictive power of these assays for risk assessment.
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