Development and optimization of a screening method for clinical discomfort using the Slug Mucosal Irritation test

Abstract

When discomfort is associated with application of a certain product, patients and consumers may be less likely to adhere to the prescribed regimen or continue using a product. From a medical perspective this may affect the outcome of a certain treatment. For cosmetic companies adverse sensory sensations related to a certain product withholds consumers from buying these products in the future. Except for animal and clinical tests, to date no study is able to demonstrate the ability of a single, alternative method to predict human discomfort. Thus, academic, pharmaceutical and cosmetic research and development agencies would benefit from the development of a quick, relevant, reproducible test method to screen new and existing chemicals, active ingredients, pharmaceutical formulations and cosmetics for their discomfort potential. In the past, the Slug Mucosal Irritation (SMI) test was developed as an alternative mucosal irritation test using slugs as test organisms. The slug’s mucosal tissue histologically resembles human mucosa. When it comes into contact with an irritating substance, the slug will produce mucus. Mucus production was therefore selected as the endpoint for irritation. Previous research of our group demonstrated a relation between an increased mucus production in slugs and an elevated incidence of stinging, itching and burning sensations in humans. During this PhD research project, a new protocol was developed based on the principles of the SMI test, specifically focusing on the evaluation of clinical discomfort. Its applicability and clinical relevance to predict ocular and nasal discomfort was demonstrated by means of clinical trials. Indications for its usefulness for the prediction of dermal discomfort were also found, but more research is needed. Concluding, the new test is a promising screening method for clinical discomfort