title: The Slug Mucosal Irritation (SMI) assay: a tool for the evaluation of nasal discomfort.
abstract: In this research project, the Slug Mucosal Irritation (SMI) assay was applied to predict nasal discomfort, investigating the correlation between responses in slugs and humans. Several SMI experiments and a Human Nose Irritation Test (HNIT) were performed with five NaCl solutions (0.4%, 1.3%, 2.6%, 5.4% and 10.4%) and two benzalkonium chloride solutions (BAC 0.02% and BAC 0.05%). In the HNIT, subjective evaluation of clinical discomfort was performed by 24 participants at several time points. Analyzes reveal that (1) a significant positive association existed between immediate stinging reaction reported by the participants and the mean total mucus production of the slugs (Spearman's Rank correlation=0.963, p<0.001); (2) NaCl 0.4% was best tolerated in both tests; (3) a concentration-response effect was observed for NaCl and BAC solutions; (4) NaCl 10.4% induced the highest mucus production in the slugs and received higher sting scores for immediate discomfort in the HNIT; (5) stinging sensations decreased rapidly in time and (6) based on these results a new classification prediction model for nasal applications was established. In conclusion, the SMI assay is a promising evaluation method for clinical nasal discomfort. Screening (prototype) formulations with this assay allows formula optimization prior to a clinical trial.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. Joke.Lenoir@UGent.be
authors.forename: Joke
authors.initials: J
authors.lastname: Lenoir
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Els
authors.initials: E
authors.lastname: Adriaens
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001548:Benzalkonium Compounds / Q000633:toxicity*; D001681:Biological Assay / Q000379:methods; D018592:Cross-Over Studies; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D049851:Gastropoda; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D008297:Male; D009093:Mucus / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects*; D015203:Reproducibility of Results; D016037:Single-Blind Method; D012965:Sodium Chloride / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods; D055815:Young Adult
chemical_list: D001548:Benzalkonium Compounds; D007509:Irritants; D012965:Sodium Chloride
keywords: Benzalkonium chloride; Human Nose Irritation Test; NaCl; Nasal discomfort; Slug Mucosal Irritation assay