Lung Damage in Mice after Inhalation of Nanofilm Spray Products: The Role of Perfluorination and Free Hydroxyl Groups

Abstract

Exposures to two commercial nanofilm spray products (NFPs), a floor sealant (NFP 1) and a coating product for tiles (NFP 2), were investigated for airway irritation, airway inflammation, and lung damage in a mouse inhalation model. The particle exposure was characterized by particle number, particle size distribution, and gravimetric analysis. BALB/cJ mice were exposed for 60 min to the aerosolized products at 3.3–60 mg/m3 (105–106 fine particles/cm3) measured in the breathing zone of the mice. Lung inflammation and lung damage were assessed by study of bronchoalveolar lavage fluid (BALF) cytology, protein in BALF, and histology. Mass spectral analysis showed that NFP 1 and NFP 2 contained hydrolysates and condensates of a perfluorosilane and alkylsilane, respectively. NFP 1 induced a concentration-dependent decrease of the tidal volume lasting for at least 1 day. Exposure concentrations above 16.1 mg/m3 (2.1 × 106 fine particles/cm3) gave rise to significant increases of protein level in BALF and reduced body weight, and histological examination showed atelectasis, emphysema, and hemorrhages. A narrow interval between the no-effect level (16.1 mg/m3) and the lethal concentrations (18.4 mg/m3) was observed. The alkylsilane-based product (NFP 2) had no effect at the concentrations studied. Experiments with different types of perfluorinated silanes and alkylsiloxanes showed that the toxic effects did not arise solely from the perfluorination. The number of free hydroxyl groups in the silanes/alkylsiloxanes was also critical for the toxicity.

Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials

“…The accumulation of inflammatory cells, such as neutrophils and macrophages, was observed in this centrilobular space, and the accumulation of nanomaterials and macrophages with phagocytosis of nanomaterials accompanied this inflammation [14,15]. As nanomaterials were observed mainly in centrilobular lesions just after the end of the inhalation exposure [16][17][18][19], we think that there is not much difference in distribution between intratracheal instillation and inhalation. However, some inflammatory lesions were observed not only deep in the alveolar wall but also in the subpleural area [17,18].…”

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

“…The respiration is monitored and, based on changes in the shape of the breathing curve, it can be assessed whether a chemical affects the upper, conducting or lower airways; effects can be directly translated to the human situation due to comparable neural functions (Alarie, 1973). Inhalation of certain types of aerosolized impregnation spray products by mice has shown to lead to an irreversible reduction in both tidal volume and expiratory flow rate (Nørgaard et al, 2010. These effects have been proposed to be driven by interaction between the impregnation product and the pulmonary surfactant.…”

“…The disrupted pulmonary surfactant may lead to liquid blocking of the terminal airways, which increases airway resistance. Furthermore, disruption of pulmonary surfactant may lead to development of atelectasis (Nørgaard et al, 2010). Atelectasis may progress to tissue damage and edema, and product testing may cause lethal lung damage (Hubbs et al, 1997;Nørgaard et al, 2010;Pauluhn et al, 2008).…”

“…Furthermore, disruption of pulmonary surfactant may lead to development of atelectasis (Nørgaard et al, 2010). Atelectasis may progress to tissue damage and edema, and product testing may cause lethal lung damage (Hubbs et al, 1997;Nørgaard et al, 2010;Pauluhn et al, 2008). We have recently shown that a tile-coating product, "Stain repellent super", which caused respiratory distress in 39 people in Greenland, also inhibits the function of pulmonary surfactant in vitro using the Langmuir balance, i.e., the classical method for studying lung surfactant properties (Duch et al, 2014), substantiating that this endpoint has relevance for effects in humans.…”

Can We Trust Real Time Measurements of Lung Deposited Surface Area Concentrations in Dust from Powder Nanomaterials?

“…A well-studied surface cleaning and maintenance product Multicover (Nanocover, Denmark) was applied for 10 seconds from a distance of 20 cm onto a metal sheet (Norgaard et al, 2009;Norgaard et al, 2010). Approximately 5 minutes after spraying a nucleation event took place, which formed nm-size droplet particles anticipated to be due to nucleation through limonene oxidation that slowly grew in size through condensation.…”