title: Direct exposure at the air-liquid interface: evaluation of an in vitro approach for simulating inhalation of airborne substances.
abstract: In toxicology, the strategies for testing the hazardous potential of substances are changing as a result of the ongoing progress in the development of in vitro methods and the demand of the authorities to reduce animal testing. Even in the complex field of inhalation toxicology with its high requirements on the technical implementation and cell culture models, the preconditions for using such methods are fulfilled. We here introduce a sophisticated technique that enables the stable and reproducible exposure of cultivated cells to airborne substances at the air-liquid interface by means of the CULTEX(®) Radial Flow System (RFS) module. The feasibility and suitability of the experimental setup is demonstrated by dose-response investigations of mainstream cigarette smoke and particulate matter of four substances in different lung epithelial cell lines. A dose-dependent cytotoxcity of the test substances was verified by applying different exposure times. The high reproducibility of the results indicate the reliability of the presented method and recommend the integration of such in vitro approaches in the field of inhalation toxicology by advancing their regulatory validation.
authors.affiliation: CULTEX Laboratories GmbH, Feodor-Lynen-Str. 21, 30625, Hannover, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rach
authors.forename: Jessica
authors.initials: J
authors.lastname: Budde
authors.forename: Niklas
authors.initials: N
authors.lastname: Möhle
authors.forename: Michaela
authors.initials: M
authors.lastname: Aufderheide
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000826:Animal Testing Alternatives / Q000295:instrumentation / Q000379:methods*; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D004867:Equipment Design; D005240:Feasibility Studies; D006801:Humans; D019570:Inhalation Exposure; D008954:Models, Biological; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity; D044367:Phase Transition; D015203:Reproducibility of Results; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D018675:Toxicity Tests / Q000295:instrumentation / Q000379:methods*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D014028:Tobacco Smoke Pollution
keywords: CULTEX® RFS module; air-liquid interface exposure; airborne particles; cigarette smoke; in vitro models; inhalation toxicology