Acute Respiratory Toxicity

Exposure of lung tissue to materials, inhaled or otherwise, may challenge the tissue leading to cell death or loss of viability. IIVS’s Respiratory Toxicology Program offers several pulmonary models that will allow the assessment of cytotoxicity or viability loss after tissue exposure to test articles. These acute toxicity endpoints are available for all pulmonary models utilized within Respiratory Toxicology.

Cytotoxicity Endpoint

Cytotoxicity manifests as a loss of membrane integrity and results in the release of intracellular constituents. Respiratory tissue exposed to a test material can have medium sampled at multiple time points following exposure. The medium will then be assayed for the presence of leakage markers such as lactate dehydrogenase (LDH) or adenylate kinase (AK); two hallmark leakage markers. Leakage marker analysis typically include a 100% marker release control to calculate % cytotoxicity.

Viability Endpoint

A loss of tissue viability can result in the diminished capability or functionality of tissue. Respiratory tissue exposed to a test material can be assayed at the terminal time point to assess a viability marker such as enzymatic activity or levels of ATP. Viability assays employed by IIVS include the MTT assay, WST-8 assay, and ATP content assay. Negative control tissues are used as the frame of reference when calculating % loss of viability. The viability of tissue is often measured in tandem with cytotoxicity to provide a well-formed depiction of tissue response to acute toxicity.

Histological Assessment

Pulmonary tissues undergo distinct changes upon loss of viability and cytotoxic events. Histological assessment of stained tissues is available, with focused viability determinations possible.

Talk to IIVS about your custom evaluation needs!  We can work with you if you have specific biochemical or histological cytotoxicity and viability markers in mind!

Example Figure: The inverse relationship of viability and cytotoxicity
Human PCLS exposed to Aminoflavone Prodrug: Acute damage is detected at Day 1 (cytokines) ultimately leads to severe alveolar damage by Day 7.