Skin sensitization risk assessment model using artificial neural network analysis of data from multiple in vitro assays

Kyoko Tsujita-Inoue, Morihiko Hirota, Takao Ashikaga, Tomomi Atobe, Hirokazu Kouzuki, Setsuya Aiba

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

The sensitizing potential of chemicals is usually identified and characterized using in vivo methods such as the murine local lymph node assay (LLNA). Due to regulatory constraints and ethical concerns, alternatives to animal testing are needed to predict skin sensitization potential of chemicals. For this purpose, combined evaluation using multiple in vitro and in silico parameters that reflect different aspects of the sensitization process seems promising.We previously reported that LLNA thresholds could be well predicted by using an artificial neural network (ANN) model, designated iSENS ver.1 (integrating in vitro sensitization tests version 1), to analyze data obtained from two in vitro tests: the human Cell Line Activation Test (h-CLAT) and the SH test. Here, we present a more advanced ANN model, iSENS ver.2, which additionally utilizes the results of antioxidant response element (ARE) assay and the octanol-water partition coefficient (Log. P, reflecting lipid solubility and skin absorption). We found a good correlation between predicted LLNA thresholds calculated by iSENS ver.2 and reported values. The predictive performance of iSENS ver.2 was superior to that of iSENS ver.1. We conclude that ANN analysis of data from multiple in vitro assays is a useful approach for risk assessment of chemicals for skin sensitization.

Original languageEnglish
Pages (from-to)626-639
Number of pages14
JournalToxicology in Vitro
Volume28
Issue number4
DOIs
Publication statusPublished - 2014 Jun

Keywords

  • Antioxidant response element, ARE
  • Artificial neural network
  • H-CLAT
  • Risk assessment
  • SH test
  • Skin sensitization

ASJC Scopus subject areas

  • Toxicology

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