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The isolated perfused lung (IPL) as a screening tool for aerosol products

: Fischer, Monika; Dasenbrock, Clemens; Koch, Wolfgang

Naunyn-Schmiedebergs archives of pharmacology 386 (2013), Supplement 1, S.S22
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <79, 2013, Halle/Saale>
Zeitschriftenaufsatz, Konferenzbeitrag
Fraunhofer ITEM ()

The use of aerosol products containing surface active agens frequently results in adverse, sometimes even severe, health effects in consumers. Upon use of waterproofing sprays in particular, severe cases of acute lung injury have been reported repeatedly. It is hypothesized that impairment of the pulmonary surfactant by deposition of inhaled respirable particles of the active compound is one of the main causes of the acute lung injury. Since the inhalation toxicity cannot be predicted a priori based on the physical and chemical properties of the formulation, proper test strategies are required to ensure consumer safety.
We propose to combine screening tests addressing both, exposure and acute lung toxicity. The exposure potential of the spray product is characterized by determining the release fraction of the active compound in the respirable particle size range under conditions relevant for the product application. This is carried out by spraying defined quantities of the product into a control volume and measuring the concentration of health related size fractions. This procedure takes into account spray ageing, especially size reduction of the droplets due to solvent evaporation.
The isolated perfused lung is proposed as a model for testing acute toxicity. Ventilated rat lungs are exposed to aged aerosols with proper particle size of approximately 1 m MMAD generated from the liquid spray formulation. Lung compliance and lung resistance are continuously monitored during exposure. Dose dependent deviations from the controls are used as read-out parameters. The results and in particular the comparison of the results with those of the corresponding animal experimental studies have shown that the isolated perfused lung can be used to screen for substances that exhibit acute inhalation toxicity. So, the test in the isolated lung could be performed before any testing of a surface active substance in living animals is undertaken, to allow formulations exhibiting acute lung toxicity to be identified and discarded in advance. Using the isolated perfused lung as screening method may help avoid acute animal inhalation studies in the future in line with the "3-Rs" principles.