Development of an oral mucosal irritation test using a three-dimensional human buccal oral mucosal model

Seiya Aizawa, Hidenori Yoshida, Kazuhiko Umeshita, Shinichi Watanabe, Yutaka Takahashi, Shinji Sakane, Hitoshi Sakaguchi, Shinsuke Kataoka

 The oral mucosa can become irritated by oral care products and lip cosmetics. Therefore, it is important to determine the irritation potential of their ingredients and products during safety evaluations. We developed a method for oral mucosal irritation test using EpiOral, which is a three-dimensional cultured model. Exposure of sodium lauryl sulphate (SLS) to EpiOral showed a dose-dependent decrease in cell viability. Under 120 min exposure conditions, SLS irritation was detected when 60% cell viability was set as a criterion. Evaluation of the irritancy of SLS and four other raw materials used in oral products at three laboratories under the above conditions confirmed good transferability of the test. Focused on the similarity of the oral and eye mucous, 32 chemicals categorised by the UN-GHS eye-irritation classification were evaluated to ensure the reliability of our criteria at these laboratories. The concordance rate between the UN-GHS classification and our test results was 100% for irritants and 60% for non-irritants. The good intra-laboratory reproducibility of our test was confirmed from the evaluation results of negative and positive controls, and the good inter-laboratory reproducibility was confirmed from the results of 32 chemicals. These findings showed that oral mucosal irritation can be evaluated using EpiOral. 


EpiOral (ORL-200), Oral mucosal irritation, Oral irritation assay, UN-GHS eye irritation category, Cat 1, Cat 2A, Cat 2B, No category, Inter-lab reproducibility, intra-lab reproducibility, histology, removal of superficial layers, oral mucosal score, prediction model, assay transferability

Materials Tested

betaine, 1-Octanol, 2-Aminoethanol, 2-Bromopropane, 2-Ethyl-1-hexanol, 2-Heptanone, 2-Methoxyethyl acrylate, 2-Methyl-1-pentanol, 3,3-Dimethylpentane, 3-Methoxy-1,2-propanediol, 4-Methyl-2-pentanone, Benzalkonium chloride, Cetylpyridinium bromide, Cyclohexanol, Ethyl-2-methylacetoacetate, Glycerol, Glycolic acid, Imidazole, Isopropyl acetoacetate, Methylcyclopentane, N,N-Diethyl-m-toluamide, n-Hexanol, Polyethylene glycol, Promethazine hydrochloride, Propylene glycol, Pyridine, Sodium deoxycholate, Sodium hydroxide (1%), Sodium hydroxide (10%), Sodium lauryl sulfate, SLS, SDS, Triton X-100 (10%), Triton X-100 (5%), Tween 20

Request a copy of this paper, click here.