title: Mechanism of action of lung damage caused by a nanofilm spray product.
abstract: Inhalation of waterproofing spray products has on several occasions caused lung damage, which in some cases was fatal. The present study aims to elucidate the mechanism of action of a nanofilm spray product, which has been shown to possess unusual toxic effects, including an extremely steep concentration-effect curve. The nanofilm product is intended for application on non-absorbing flooring materials and contains perfluorosiloxane as the active film-forming component. The toxicological effects and their underlying mechanisms of this product were studied using a mouse inhalation model, by in vitro techniques and by identification of the binding interaction. Inhalation of the aerosolized product gave rise to increased airway resistance in the mice, as evident from the decreased expiratory flow rate. The toxic effect of the waterproofing spray product included interaction with the pulmonary surfactants. More specifically, the active film-forming components in the spray product, perfluorinated siloxanes, inhibited the function of the lung surfactant due to non-covalent interaction with surfactant protein B, a component which is crucial for the stability and persistence of the lung surfactant film during respiration. The active film-forming component used in the present spray product is also found in several other products on the market. Hence, it may be expected that these products may have a toxicity similar to the waterproofing product studied here. Elucidation of the toxicological mechanism and identification of toxicological targets are important to perform rational and cost-effective toxicological studies. Thus, because the pulmonary surfactant system appears to be an important toxicological target for waterproofing spray products, study of surfactant inhibition could be included in toxicological assessment of this group of consumer products.
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark stl@nrcwe.dk.
authors.forename: Søren T
authors.initials: ST
authors.lastname: Larsen
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark Polytech Nice-Sophia, University of Nice, Biot, France.
authors.forename: Constantin
authors.initials: C
authors.lastname: Dallot
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Larsen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Rose
authors.affiliation: Department of Biomedical Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Steen S
authors.initials: SS
authors.lastname: Poulsen
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Asger W
authors.initials: AW
authors.lastname: Nørgaard
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Jitka S
authors.initials: JS
authors.lastname: Hansen
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Jorid B
authors.initials: JB
authors.lastname: Sørli
authors.affiliation: National Research Centre for the Working Environment, Copenhagen, Denmark.
authors.forename: Gunnar D
authors.initials: GD
authors.lastname: Nielsen
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Foged
mesh_terms: D000818:Animals; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors; D012833:Siloxanes / Q000633:toxicity
chemical_list: D011663:Pulmonary Surfactants; D012833:Siloxanes
keywords: Waterproofing spay product; inhalation; lung toxicity; pulmonary surfactant