Effects of longterm intranasal administration of benzalkonium chloride on rat nasal respiratory mucosa: a histological study

The preservative benzalkonium chloride [BZC] is widely used, not only for nasal drops, but also for eye drops and cosmetics, the objective of this study was to evaluate the histological changes after long-term administration of BZC on rat nasal respiratory mucosa. Sixty-six rats were used. Six were used as a control group and received saline nasal drops, the rest were divided into four groups, fifteen in each. The first group received nasal drops of a low concentration of BZC [0.025%] that is commonly used in nasal drops and sprays. The second group received steroid-mixed [0.15%] low concentration BZC solution. The third group received a high concentration of BZC solution [0.1%] that was reported to induce dermatitis. The fourth group received a steroid-mixed [0.15%] high concentration solution. Symptomatic changes were observed. After 1, 2 and 4 weeks of administrations, five animals from each group were sacrificed by decapitation. Small specimens were taken from the anterior part of the nasal septum for electron microscopy and the heads were decalcified. Noses were cut perpendicular to the hard palate into three levels: anterior, middle and posterior. Sections were stained with H and E. Epithelial height was measured using the image analysr. Sneezing and rubbing the nose with the forelegs were observed in the experimental groups. Light microscopic study revealed histological changes in the anterior level in all groups. After the first week, there was proliferation of goblet cells, degeneration and squamous metaplasia. After the second week, intraepithelial glands were formed together with cellular infiltration and vascular congestion. After the fourth week, tubular glands developed invading the lamina propria. Epithelial height of the anterior level demonstrated significant increase in all groups when compared to the control group. Electron microscopic study revealed the presence of abnormal spaces between epithelial cells. So, it could be concluded that BZC, even in low concentration and mixed with steroid, could produce nasal lesions, together with symptomatic changes. Hence, there is a strong need to develop a preservative without side effects or nasal applications without preservatives