Table of Contents
Advances in Toxicology
Volume 2014 (2014), Article ID 185201, 11 pages
Research Article

Investigations of the Biological Effects of Airborne and Inhalable Substances by Cell-Based In Vitro Methods: Fundamental Improvements to the ALI Concept

Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Straße 1, 30625 Hannover, Germany

Received 24 July 2014; Accepted 11 October 2014; Published 12 November 2014

Academic Editor: Defeng Wu

Copyright © 2014 Detlef Ritter and Jan Knebel. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The state of the art for cell-based in vitro investigations of airborne and inhalable material is “air-liquid interface” (ALI) technology. Cell lines, primary cells, complex 3D models, or precision-cut lung slices (PCLS) are used to represent the lung or skin by way of an in vitro barrier model. These models have been applied in toxicity or pharmacological testing. However, contrasting with a clear demand for alternative methods, there is still no widely accepted procedure for cell-based in vitro testing of inhalable substances. In the light of this, an analysis was undertaken of common drawbacks of current approaches. Hence, the pivotal improvements aimed at were the cellular exposure environment, overall performance and applicability, operability of online investigations during exposure and routine setup. It resulted in an improved device (P.R.I.T. ExpoCube) based on an “all-in-one-plate” concept including all phases of the experiment (cell culture, exposure, and read-out) and all experimental groups (two test gas groups, controls) in one single commercial multiwell plate. Verification of the concept was demonstrated in a first experimental series using reference substances (formaldehyde, ozone, and clean air). The resulting ALI procedure enables the application of inhalable substances and mixtures under highly effective exposure conditions in routine utilization.