Nasal toxicity of benzalkonium chloride

Benzalkonium chloride (BAC) is added to nasal preparations to prevent microbial contamination. Adverse effects of BAC on human nasal mucosa should be evaluated.

The ciliotoxicity of BAC was assessed in isolated human nasal epithelia from 15 donors. The effects of nasal BAC 0.05% (4 x 200 microL/day for 8 days) on nasal saccharin transport time, inflammatory cells and cytokine levels in nasal secretions, and nasal symptom scores were assessed in a randomized, double-blind crossover trial in 16 healthy volunteers.

In vitro, BAC was ciliotoxic (p < 0.0001). In vivo, BAC did not alter saccharin transport time in healthy individuals (p > 0.8). No BAC-associated proinflammatory effects were observed. The staining index for myeloperoxidase was 4.8% in the placebo period and 6.3% (p = 0.42) in the BAC period. Also, nasal secretion levels of cytokines and the neuropeptide substance P revealed no BAC-associated differences. Concentrations for interleukin (IL)-6 in the placebo period were 41.5 pg/mL (0.9-91.7 pg/mL) and in the BAC period were 17.6 pg/mL (3.2-65.9 pg/mL; p = 0.46), and concentrations for substance P were 119 pg/mL (58-293 pg/mL) and 131 pg/mL (80-330 pg/mL; p = 0.31), respectively. Immediately after application, BAC caused nasal irritation (p = 0.001), a burning sensation (p = 0.0003), and hypersecretion (p = 0.006). Moreover, BAC caused a persistent sensation of nasal irritation (p < 0.01).

BAC in concentrations used in nasal preparations is ciliotoxic. In healthy individuals, the ciliotoxic effect of BAC is neutralized, probably by components of nasal secretions. No BAC-related proinflammatory effects have been observed. At higher doses than normally used therapeutically, BAC caused significant nasal irritation.