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

Objectives: The preservatives benzalkonium chloride (BZC) and potassium sor bate (PS) are widely used, not only for nasal drops, but also for eyedrops and cosmetics. However, there have been many case reports that consider les ions such as dermatitis or conjunctivitis to be the results of irritation i nduced by BZC or PS, Methods: We evaluated the histological changes after t he long-term administration of BZC or PS on rat nasal respiratory mucosa, F orty 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 sp rays, The second subgroup received a high-concentration preservative soluti on that was reported to induce dermatitis in humans. The third and fourth s ubgroups received a steroid mixed preservative solution of low and high con centrations, respectively. The control group was administrated normal salin e. After each group received 1, 2, and 4 weeks of topical administration, t he symptomatic and histological changes on H&E stain were observed. Results : Sneezing and nasal rubbing with forelegs were observed in almost all subg roups by the seventh day of treatment. The preservatives induced nasal lesi ons, including intraepithelial glandular formation, inflammatory cell infil tration, vascular hyperplasia, and edematous change. The symptomatic and hi stological changes were pronounced with the prolonged duration of administr ation. 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 preser vative that can be safely and widely used and a nasal spray without preserv atives.