Long-term use of preservatives on rat nasal respiratory mucosa: Effects of benzalkonium chloride and potassium sorbate

Objectives: The preservatives benzalkonium chloride (BZC) and potassium sorbate (PS) are widely used, not only for nasal drops, but also for eyedrops and cosmetics. However, there have been many case reports that consider lesions such as dermatitis or conjunctivitis to be the results of irritation induced by BZC or PS, Methods: We evaluated the histological changes after the long-term administration of BZC or PS on rat nasal respiratory mucosa, Forty rats were used for the BZC group and 40 rats for PS group. Animals in each group were divided into four subgroups, The first subgroup received a low-concentration preservative solution that was commonly used for nasal sprays, The second subgroup received a high-concentration preservative solution that was reported to induce dermatitis in humans. The third and fourth subgroups received a steroid mixed preservative solution of low and high concentrations, respectively. The control group was administrated normal saline. After each group received 1, 2, and 4 weeks of topical administration, the symptomatic and histological changes on H&E stain were observed. Results: Sneezing and nasal rubbing with forelegs were observed in almost all subgroups by the seventh day of treatment. The preservatives induced nasal lesions, including intraepithelial glandular formation, inflammatory cell infiltration, vascular hyperplasia, and edematous change. The symptomatic and histological changes were pronounced with the prolonged duration of administration. Similar results were observed in the steroid mixed-solution groups. In the PS steroid mixed-solution group, however, symptoms and nasal lesions were reduced with the prolonged duration of administration. Conclusion: It is our finding that even a low concentration solution of preservative can lead to nasal lesion, Hence there is a strong need to develop both a preservative that can be safely and widely used and a nasal spray without preservatives.