High-throughput screening (HTS)-based spectrophotometric direct peptide reactivity assay (Spectro-DPRA) to predict human skin sensitization potential

Toxicol Lett. 2019 Oct 10:314:27-36. doi: 10.1016/j.toxlet.2019.07.014. Epub 2019 Jul 8.

Abstract

Some cosmetic ingredients can act as a chemical hapten to induce an immune response; therefore, evaluating the sensitizing potential of cosmetic ingredients is essential. We previously developed a novel in chemico direct peptide reactivity assay involving a spectrophotometric evaluation (Spectro-DPRA) for animal skin sensitization tests (local lymph node assay; LLNA). Based on previous research, we expanded the test materials to confirm the effectiveness of the Spectro-DPRA method for predicting the animal skin sensitization potential, and further determined the feasibility of the method for estimating the human skin sensitization potential. Spectro-DPRA showed 83.1% or 89.1% accuracy compared to a conventional LLNA or prediction based on human data, respectively, with a combination model using both a cysteine peptide and lysine peptide cut-off. To identify the effect of the lipophilicity of a chemical on predicting the skin sensitization potential, we applied our prediction model to chemicals with a Log Pow range of -1 to 4. Overall predictability was increased, and the accuracy compared to the LLNA and human data was 91.5% and 94.9%, respectively, in the combination cut-off prediction model. In conclusion, Spectro-DPRA serves as an easy, rapid, and high-throughput in chemico screening method with high accuracy to predict the human skin sensitization potential of chemicals.

Keywords: Animal alternative; Peptide reactivity; Skin sensitization; Spectrophotometric.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Animal Testing Alternatives / methods*
  • Animals
  • Cysteine
  • Feasibility Studies
  • High-Throughput Screening Assays*
  • Humans
  • Local Lymph Node Assay
  • Lysine
  • Molecular Structure
  • Oligopeptides / chemistry*
  • Reproducibility of Results
  • Risk Assessment
  • Skin / drug effects*
  • Skin / immunology
  • Skin Irritancy Tests / methods*
  • Spectrophotometry
  • Structure-Activity Relationship

Substances

  • Oligopeptides
  • Lysine
  • Cysteine