Park HJ, et al. Allergy Asthma Immunol Res. 2017 Jul;9(4):329-339. https://doi.org/10.4168/aair.2017.9.4.329

Benzalkonium chloride (BAC) is a widely used disinfectant/preservative, and respiratory exposure to this compound has been reported to be highly toxic. Spray‐form household products have been known to contain BAC together with triethylene glycol (TEG) in their solutions. The purpose of this study was to estimate the toxicity of BAC and TEG mixtures to pulmonary organs using in vitro and in vivo experiments. Human alveolar epithelial (A549) cells incubated with BAC (1‐10 μg/mL) for 24 hours showed significant cytotoxicity, while TEG (up to 1000 μg/mL) did not affect cell viability. However, TEG in combination with BAC aggravated cell damage and inhibited colony formation as compared to BAC alone. TEG also exacerbated BAC‐promoted production of reactive oxygen species (ROS) and reduction of glutathione (GSH) level in A549 cells. However, pretreatment of the cells with N‐acetylcysteine (NAC) alleviated the cytotoxicity, indicating oxidative stress could be a mechanism of the toxicity. Quantification of intracellular BAC by LC/MS/MS showed that cellular distribution/absorption of BAC was enhanced in A549 cells when it was exposed together with TEG. Intratracheal instillation of BAC (400 μg/kg) in rats was toxic to the pulmonary tissues while that of TEG (up to 1000 μg/kg) did not show any harmful effect. A combination of nontoxic doses of BAC (200 μg/kg) and TEG (1000 μg/kg) promoted significant lung injury in rats, as shown by increased protein content and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluids (BALF). Moreover, BAC/TEG mixture recruited inflammatory cells, polymorphonuclear leukocytes (PMNs), in terminal bronchioles and elevated cytokine levels, tumor necrosis factor α (TNF‐α), and interleukin 6 (IL‐6) in BALF. These results suggest that TEG can potentiate BAC‐induced pulmonary toxicity and inflammation, and thus respiratory exposure to the air mist from spray‐form products containing this chemical combination is potentially harmful to humans.

Kim EJ, et al. Allergy Asthma Immunol Res. 2013 May;5(3):162-169. https://doi.org/10.4168/aair.2013.5.3.162

Benzalkonium chloride (BAC), a disinfectant, and triethylene glycol (TEG), an organic solvent/sanitizer, are frequently combined in commercially available household sprays. To assess the respiratory effect of this combination, Sprague-Dawley rats were exposed to an aerosol containing BAC (0.5%, w/v) and TEG (10%, w/v) for up to 2 weeks in a whole-body inhalation chamber. BAC (4.1-4.5 mg/m3, sprayed from 0.5% solution) promoted pulmonary cell damage and inflammation as depicted by the increase in total protein, lactate dehydrogenase, polymorphonuclear leukocytes, and macrophage inflammatory protein-2 in the bronchoalveolar lavage fluid, whereas TEG (85.3-94.5 mg/m3, sprayed from 10% solution) did not affect the lung. Rats exposed to the BAC/TEG mixture for 2 weeks showed severe respiratory symptoms (sneezing, wheezing, breath shortness, and chest tightness), but no lung damage or inflammation was observed. However, significant ulceration and degenerative necrosis were observed in the nasal cavities of rats repeatedly exposed to the BAC/TEG mixture. The mass median aerodynamic diameters of the aqueous, BAC, TEG and BAC/TEG aerosols were 1.24, 1.27, 3.11 and 3.24 μm, respectively, indicating that TEG-containing aerosols have larger particles than those of the aqueous and BAC alone aerosols. These results suggest that the toxic effects of BAC and BAC/TEG aerosols on the different respiratory organs may be associated with the difference in particle diameter, since particle size is important in determining the deposition site of inhaled materials.