Fifty rats were treated with topical nasal steroids with and without the preservative benzalkonium chloride in their right nostril twice daily for 21 days, while the left nostrils were exposed to 0.9% NaCl. By cutting the noses serially in frontal sections, the structure of the mucosal lining of all parts of the nose could be investigated. Areas with squamous cell metaplasia were observed in all nostrils exposed to topical steroids containing benzalkonium chloride. Such alterations were not observed in any nasal cavities exposed to the topical nasal steroid without the preservative or to 0.9% NaCl. In conclusion, benzalkonium chloride appears to be potentially toxic to the mucosa in vivo.
Human respiratory mucosa and human granulocytes were exposed to topical nasal steroids in vitro. The preparations containing benzalkonium chloride and benzalkonium chloride alone destroyed the mucosa within 10 days. The same preparations also inhibited human neutrophil actin polymerization, degranulation and oxidative burst in vitro in a time and concentration dependent manner. Preparations without benzalkonium chloride, as well as the steroid compounds themselves, did not have these effects. It is concluded that benzalkonium chloride has toxic effects on human respiratory mucosa and human neutrophils in vitro.
Human respiratory mucosa was exposed to oxymetazoline nasal spray in varying concentrations and for varying periods of time in vitro. The drug destroyed the tissue in a concentration- and time-dependent manner. In the experiments with various concentrations of the spray, some tissue fragments retained their viability throughout the experiment. This number increased parallel to a decrease in concentrations of the test substance. All the tissue fragments exposed to undiluted nose spray underwent severe destructive alterations during the exposure period. These alterations appeared first and were most extensive in those exposed for the longest periods of time. It has previously been demonstrated that the toxic effect of oxymetazoline nasal spray in vitro is probably due to the preservative benzalkonium chloride. The apparent lack of consistency between the toxic effects of benzalkonium chloride in vitro and in vivo is discussed, with special reference to protective systems absent in vitro but present in vivo.
The aim of this study was to investigate the morphological effects of decongestive drops and sprays on human respiratory mucosa in vitro. Precultured fragments of adenoid tissue in a specially designed tissue culture system were exposed to decongestive preparations for 10 minutes once a day for 10 days. Tissue exposed to preparations preserved with benzalkonium chloride and tissue exposed to benzalkonium chloride alone underwent severe morphological alterations. Unpreserved decongestive substances did not have this effect. Benzalkonium chloride is a well-documented toxic substance in several respects. Supported by previous studies, it may seem unfortunate to use it as an additive in decongestive preparations.
Fragments of human adenoid tissue were transferred to a nonadhesive, stationary organ culture system. The culture period was 40 days. In culture, beating cilia could be observed at the surface of the fragments. Light microscopy, scanning electron microscopy, and transmission electron microscopy showed that the tissue fragments were covered by a multilayered, pseudostratified, ciliated epithelium. Beneath the epithelium was a basement membrane. At the start of the culture period, the central parts of the fragments were dominated by lymphocytes. These lymphocytes gradually disappeared and were replaced by a collagen‐containing stroma with scattered fibroblasts. The tissue fragments can be used as an organ culture model for normal respiratory mucosa.
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