Pulmonary Irritation After Inhalation Exposure to Benzalkonium Chloride in Rats

Abstract

Background: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) with a C 8 to C 18 chain length of alkyl groups. Since BAC exerts toxic effects on microorganisms, it has been used as an effective germicide and preservative, mostly in cosmetic industry and medicine. However, the toxic potential of BAC may be hazardous to humans, due to the common use of preparations containing BAC as a preservative. Material and Methods: To assess the possible toxic effects of BAC, two-stage experiments were performed on female Wistar rats. At first, LC 50 after a single exposure to BAC aerosol was determined. Then, the animals were exposed to BAC aerosol at 30 mg/m 3 for 6 h, and for 3 days (6 h/day). The controls were unexposed rats. Directly after BAC exposure and 18 h afterwards,, BALF concentrations were measured of total protein, Clara cell protein, matrix metalloproteinase-9 (MMP-9), hyaluronic acid (HA), immunoglobulin E (IgE) and cytokines (TF-α, IL-6 and MIP-20), lactate dehydrogenase (LDH) and GSH-S-transferase (GST). Results: The LC 50 value for exposed rats was ca. 53 mg BAC in m 3 air for 4 h. All the rats survived single and repeated inhalation exposure to 30 mg/m 3 BAC. After single and repeated exposure, lung weight, total protein, HA and LDH activity in BALF of exposed rats were higher than in controls while CC16 levels were decreased. A significantly higher BALF concentration of IL-6 and IgE was noted in animals exposed to single and repeated doses. BALF concentrations of MMP-9, TNF-α, and MIP-2 in exposed rats were similar to those in control animals. Conclusion: BAC may be classified to class I acute inhalation toxicity. It showed a strong inflammatory and irritant activity on the lungs after 6h inhalation and stimulated dynamic patterns of IL-6 and IgE production and protein infiltration from blood vessels to BALF. Continued exposure resulted in cellular destruction, a statistically significant increase in LDH activity and a continuous decrease in CC16 concentration in BALF.

Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

“…In an inhalation study performed in mice, it was found that inhalation of BAC at higher concentrations induced deep lung effects and also lung inflammation [25]. In previous years we assessed toxic effects of BAC to the respiratory system and changes in the concentrations of catecholamines in the brain of rats exposed by inhalation to BAC aerosol [26,27]. The present study is an extension of our earlier works assessing the toxic effects of exposure to aerosol of BAC water solution in laboratory animals under conditions of repeated inhalation exposure.…”

Altered pulmonary defense system in lung injury induced by didecyldimethylammonium chloride in mice

“…Our findings in the present study indicated that topically applying DDAC to the lung alters lung antioxidant and antimicrobial defense systems, amplifying inflammatory responses by systemic administration of an exogenous stimulus, LPS. One of the QACs, BAC, induced pulmonary injury after inhalation (Swiercz et al, 2008) or oral administration (mediated by aspiration of a small amount into the bronchi) (Xue et al, 2004) in rats. These data, however, did not demonstrate the precise toxic effects on respiratory systems by QAC.…”

Safety of a Preservative-Free Acidified Saline Nasal Spray

“…[8][9][10] Data also suggest toxic effects of phenylcarbinol, another common preservative. [11][12][13] Despite the evidence showing that benzalkonium chloride and other preservatives can be damaging to human and animal tissues, preservatives are in widespread use in overthe-counter and prescription preparations.…”