The performance of an in vitro skin sensitisation test, IL-8 luc assay (OECD442E), and the integrated approach with direct peptide reactive assay (DPRA)

Yutaka Kimura, Mika Watanabe, Noriyuki Suzuki, Tomoko Iwaki, Kohji Yamakage, Koichi Saito, Yoshihiro Nakajima, Chizu Fujimura, Yoshihiro Ohmiya, Takashi Omori, Hajime Kojima, Setsuya Aiba

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

In all current in vitro skin sensitisation assays, DMSO is used to dissolve water-insoluble chemicals. However, our previous study suggested the superiority of the modified IL-8 Luc assay (mIL-8 Luc), in which X-VIVO™ 15 is used to dissolve chemicals, over the original assay using DMSO (oIL-8 Luc). In this study, to confirm the superiority of the mIL-8 Luc, we first increased the number of chemicals examined and demonstrated the superiority of the mIL-8 Luc, in which the mIL-8 Luc provided 87.6% of sensitivity, 74.2% of specificity, and 84.6% of accuracy. Next, to clarify the cause of false negative judgment by the mIL-8 Luc, we examined the effects of physical properties of chemicals on judgment. The results demonstrated that high molecular weight, high LogKo/w, or poor water solubility, did not cause false negative judgment. When it was accepted as an OECD test guideline, the criteria of the mIL-8 Luc to determine sensitisers were modified to further decrease false negative judgment by poor solubility. By applying the new criteria, the test guideline IL-8 Luc assay (tgIL-8 Luc) improved sensitivity but decreased specificity and increased the number of chemicals that cannot be judged. To overcome this problem, we examined a simple combination of the tgIL-8 Luc with direct peptide reactive assay (DPRA), which could improve specificity and decrease the number of the chemicals that cannot be judged. These data suggest that the tgIL-8 Luc is a promising in vitro skin sensitisation assay in combination with other in vitro or in chemico methods.

Original languageEnglish
Pages (from-to)741-749
Number of pages9
JournalJournal of Toxicological Sciences
Volume43
Issue number12
DOIs
Publication statusPublished - 2018

Keywords

  • Alternative method
  • Contact dermatitis
  • Luciferase assay
  • Sensitisation test
  • Skin sensitisation

ASJC Scopus subject areas

  • Toxicology

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