TY - JOUR
T1 - Mechanism of Action of Lung Damage Caused by a Nanofilm Spray Product
AU - Larsen, Søren T.
AU - Dallot, Constantin
AU - Larsen, Susan W
AU - Rose, Fabrice
AU - Poulsen, Steen Seier
AU - Nørgaard, Asger W
AU - Hansen, Jitka S
AU - Sørli, Jorid B
AU - Nielsen, Gunnar D
AU - Foged, Camilla
N1 - © The Author(s) 2014. Published by Oxford University Press on behalf of Toxicological Sciences.
PY - 2014/5/25
Y1 - 2014/5/25
N2 - 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. Key Words: Waterproofing spay product; lung toxicity; inhalation; pulmonary surfactant.
AB - 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. Key Words: Waterproofing spay product; lung toxicity; inhalation; pulmonary surfactant.
U2 - 10.1093/toxsci/kfu098
DO - 10.1093/toxsci/kfu098
M3 - Journal article
C2 - 24863969
VL - 140
SP - 436
EP - 444
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 2
ER -