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Inhalation Toxicology
The Globally Harmonized System (GHS) is a United Nations endorsed system for the classification of material hazards, including toxicity. The U.S. Environmental Protection Agency has also established a toxicity classification system. Current OECD testing guidelines (TGs 403, 433, 436) for inhalation toxicity outline the use of animals to determine LC-50 (concentration required to cause the death of 50% of test animals).
The EpiAirway in vitro tissue model is used to predict respiratory toxicity following exposure to inhaled test materials. The ED-25 value (dose required to reduce tissue viability by 25% relative to the vehicle control-treated tissues) is determined for test materials applied directly to the apical tissue surface to model exposure to mists and sprays. A prediction model was established based on ED-25 values to discriminate between respiratory irritants and non-irritants. The prediction model identified 100% of GHS Acute Inhalation Toxicity Category 1 and 2 chemicals (n=7 chemicals) and 66% of Category 3 and 4 chemicals (n=32 chemicals) as irritants. In addition, the prediction model labeled 64% of Category 5 and No Category chemicals (n=14 chemicals) as non-irritants.
Protocol
| Test Model | EpiAirway |
| Replicates | N=3 tissues per test condition |
| Exposure Time | 4-hour topical exposure of test chemical, followed by a 20 hour recovery period |
| Assay Controls | Negative Control – Sterile DI H2O or Corn oil Positive Control – 14mg/ml Formaldehyde |
| Endpoints | MTT Tissue Viability Assay |
| Data Delivery | ED-25 Values Predicted GHS or EPA Classification |
Download the EpiAirway Inhalation Toxicity Test Protocol
References
Multi Species 3D Airway Tissue Models for Translational Inhalation Toxicity. Jackson GR, Durand S, Coen K, Landry T, Klausner M, Kaluzhny Y, Armento A, Ayehunie S. Presented at the Society of Toxicology meeting, March, 2023, Nashville, TN.
Development and evaluation of in vitro inhalation model to predict acute respiratory toxicity of mists and volatile liquids. Kaluzhny Y, Jackson GR, Markus J, Kearney P, Letasiova S, Klausner M, Armento A. Presented at the Society of Toxicology meeting, March, 2023, Nashville, TN.
Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model. Jackson, G.R., Jr., Maione, A.G., Klausner, M., Hayden, P.J., 2018. Appl In Vitro Toxicol 4, 149-158.
Development of an in vitro cytotoxicity model for aerosol exposure using 3d reconstructed human airway tissue: application for assessment of e-cigarette aerosol. Neilson L, Mankus C, Thorne D, Jackson G, DeBay J, Meredith C. Toxicol In Vitro. 2015 Oct: 29(7):1952-62.
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