Development of a chronic respiratory toxicity assay using an in vitro human airway model

George, R. Jackson, Jr., Michelle Debatis, Mitchell Klausner, Anna G. Maione and Patrick J. Hayden

Knowledge of chronic respiratory toxicity potential is important for establishing safe use of chemicals and consumer products. The current work describes efforts to develop an alternative, non-animal method for determining chronic (subacute) respiratory toxicity using the EpiAirway™ in vitro human airway model. Initial acute toxicity experiments were conducted by exposing EpiAirway tissues to four concentrations of test chemicals via apical application using either aqueous or corn oil vehicles for three hours. After exposure, the test chemicals were rinsed off and the tissues were incubated for an additional 21 hours. An IC75 concentration (concentration required to reduce the endpoint value to 75% of vehicle exposed controls) was determined from the dose-response data using barrier function (determined by measuring transepithelial electrical resistance (TEER)) and tissue viability (MTT assay) as endpoints. Based on the determined acute IC75 value, EpiAirway tissues were exposed to additional serial dilutions of the test chemicals, using the IC75 as the baseline dose. Tissues were apically exposed for three hours, followed by rinsing, every Monday, Wednesday and Friday, with TEER measured prior to each dose application. Experiments were continued for at least 30 days to determine no-observed adverse-effect level (NOAEL) doses.


EpiAirway (AIR-100), respiratory toxicity, chronic exposure, long term culture, TEER, no-observed-adverse-effect level (NOAEL)

Materials Tested

formaldehyde, butylamine, oxalic acid, vinyl acetate, morpholine, methyl methacrylate, Dimethyl acetamide, ethanol

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