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.

An in vitro method for predicting inhalation toxicity of impregnation spray products

“…The observed effects were comparable to those found in live rats and indicated that the spray products damaged the surfactant film. We have shown inhibition of pulmonary surfactants using the Langmuir technique (Duch et al, 2014;Larsen et al, 2014) and the interactions have been demonstrated using porcine (HL-10 (Vermehren et al, 2006) and Curosurf ® (Bernhard et al, 2000)) as well as bovine (Alveofact ® (Gunther et al, 2002)) pulmonary surfactant formulations. Results from these relatively diverse pulmonary surfactant formulations were in overall agreement, suggesting that pulmonary surfactant inhibition is a robust and reliable endpoint.…”

“…The method has recently been used to test the toxic effect of a specific nanofilm impregnation product and the effect of the solvent on the product toxicity . In addition, a strong correlation was observed between the CS and the Langmuir balance (Larsen et al, 2014). The Langmuir balance measures the surface pressure of spread films on a liquid subphase.…”

Waterproofing spray-associated pneumonitis: review of 29 cases and comparisons with acute eosinophilic pneumonia and hypersensitivity pneumonitis

“…In our study, patients with WAP had alveolitis and/or alveolar hemorrhage on histopathological examination, and macrophages constituted the dominant cell type in the BALF. In a past report, the mechanism underlying WAP, namely, the inhalation of fluororesin in a waterproof spray, induces macrophage infiltration and thickening of the alveolar septum, increased airway resistance, and reduced expiratory flow rate in mice [45,46]. These mechanisms might induce the macrophage domination in the BALF findings of patients with WAP.…”

Acute Inhalation Toxicity After Inhalation of ZnO Nanoparticles: Lung Surfactant Function Inhibition In Vitro Correlates With Reduced Tidal Volume in Mice

“…The fast and irreversible response resembles the effects previously observed after exposing mice to impregnation spray products, 33 for which the mechanism of toxicity was shown to be the inhibition of LS function. 15,16,18 However, the acute effects of ZnO NP inhalation may also be triggered by other mechanisms in the lungs, such as stimulation of nerves, disruption of barrier function, and triggering inflammation.…”

“…Disruption of LS function has been linked to acute inhalation toxicity, for example, for impregnation products where disruption of LS function correlates with an irreversible decrease in tidal volume of the exposed mice. 15 -18…”