Building confidence in skin sensitisation potency assessment using new approach methodologies: report of the 3rd EPAA Partners Forum, Brussels, 28th October 2019

Regul Toxicol Pharmacol. 2020 Nov:117:104767. doi: 10.1016/j.yrtph.2020.104767. Epub 2020 Aug 28.

Abstract

Skin sensitising substances that induce contact allergy and consequently risk elicitation of allergic contact dermatitis (ACD) remain an important focus regarding the replacement of animal experimentation. Current in vivo methods, notably the local lymph node assay (LLNA) refined and reduced animal usage and led to a marked improvement in hazard identification, characterisation and risk assessment. Since validation, regulatory confidence in the LLNA approach has evolved until it became the first choice assay in most regulated sectors. Currently, hazard identification using the LLNA is being actively replaced by a toolbox of non-animal approaches. However, there remains a need to increase confidence in the use of new approach methodologies (NAMs) as replacements for LLNA sensitiser potency estimation. The EPAA Partners Forum exchanged the current state of knowledge on use of NAMs in various industry sectors and regulatory environments. They then debated current challenges in this area and noted several ongoing needs. These included a requirement for reference standards for potency, better characterisation of applicability domains/technical limitations of NAMs, development of a framework for weight of evidence assessments, and an increased confidence in the characterisation of non-sensitisers. Finally, exploration of an industry/regulator cross-sector user-forum on skin sensitisation was recommended.

Keywords: Hazard assessment; In vitro alternatives; Potency measurement; Skin sensitisation.

Publication types

  • Review

MeSH terms

  • Allergens / toxicity*
  • Animal Testing Alternatives / methods
  • Animal Testing Alternatives / standards*
  • Animals
  • Belgium / epidemiology
  • Congresses as Topic / standards*
  • Dermatitis, Allergic Contact / diagnosis
  • Dermatitis, Allergic Contact / epidemiology
  • Humans
  • Local Lymph Node Assay*
  • Research Report / standards*
  • Risk Assessment / methods
  • Risk Assessment / standards
  • Skin / drug effects*

Substances

  • Allergens