Pulmonary Toxicity of Perfluorinated Silane-Based Nanofilm Spray Products: Solvent Dependency

Abstract

A number of cases of pulmonary injury by use of aerosolized surface coating products have been reported worldwide. The aerosol from a commercial alcohol-based nanofilm product (NFP) for coating of nonabsorbing surfaces was found to induce severe lung damage in a recent mouse bioassay. The NFP contained a 1H,1H,2H,2H-perfluorooctyl trialkoxysilane (POTS) and the effects were associated with the hydrolyzed forms of the silane; increase in hydrolyzation resulted in faster induction of compromised breathing and induction of lung damage. In this study, the impact of the solvent on the toxicity of POTS has been investigated. BALB/cA mice were exposed to aerosolized water-based NFPs containing POTS, and solutions of hydrolyzed POTS in methanol, ethanol, and 2-propanol, respectively. No acute respiratory effect was observed at exposure concentrations up to 110 mg/m³ with an aqueous solution of POTS. However, exposure to POTS in methanol resulted in a decrease of the tidal volume--an effect that did not resolve within the recovery period. After 27 min of exposure, the tidal volume had decreased by 25%, indicating partial alveolar collapse. For POTS in ethanol and 2-propanol, a 25% reduction of the tidal volume was observed after 13 and 9 min, respectively; thus, the tidal volume was affected by increase of the chain length. This was confirmed in vitro by investigating lung surfactant function after addition of POTS in different solvents. The addition of vaporized methanol, 2-propanol, or acetone to aerosolized POTS in methanol further exacerbated the tidal volume reduction, demonstrating that the concentration of vaporized solvent participated in the toxicity of POTS.

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

“…3C). None of the products caused upper or lower airway irritation (data not shown and Nørgaard et al, 2010Nørgaard et al, , 2014.…”

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

“…We have worked with the acute airway effect of IPs for several years (Nørgaard et al, 2010(Nørgaard et al, , 2014Duch et al, 2014;Sørli et al, 2015b), and during this period, the in vivo bioassay has gone through several rounds of refinement. From the first sets of experiments (Nørgaard et al, 2010(Nørgaard et al, , 2014, we know that the toxic response to IPs is very uniform, and manifests as a rapid reduction in VT.…”

“…From the first sets of experiments (Nørgaard et al, 2010(Nørgaard et al, , 2014, we know that the toxic response to IPs is very uniform, and manifests as a rapid reduction in VT. Animals experiencing a toxic response to an IP are in a moribund state and will die within 24 h (Nørgaard et al, 2010).…”

“…The reduction of VT is irreversible and recovery does not occur (Nørgaard et al, 2010(Nørgaard et al, , 2014Duch et al, 2014;Sørli et al, 2015b). A severe reduction in VT during the experiment (> 50% reduction compared to baseline) can lead to death during exposure (Nørgaard et al, 2010(Nørgaard et al, , 2014Duch et al, 2014;Sørli et al, 2015b). Based on these observations, we reduced the group size in each experiment from n = 10 to n = 4-5 during range-finding, and to n = 5-7 for determination of the NOAEC.…”

“…The effect of the test substance is assessed based on changes in the breathing pattern during respiration (Alarie, 1973). Inhalation of some aerosolized IPs leads to an irreversible reduction in tidal volume (Nørgaard et al, 2010(Nørgaard et al, , 2014Duch et al, 2014;Sørli et al, 2015b). This effect has been proposed to be driven by interaction between the IP and the LS, which may lead to development of atelectasis (Nørgaard et al, 2010).…”