Next generation risk assessment for skin sensitisation: A case study with propyl paraben

Regul Toxicol Pharmacol. 2021 Jul:123:104936. doi: 10.1016/j.yrtph.2021.104936. Epub 2021 Apr 24.


Skin sensitisation is a key adverse health effect to be addressed in the safety assessment of cosmetic ingredients. Regulatory demands have urged the development of Next Generation Risk Assessment (NGRA) using New Approach Methodologies (NAM) and Defined Approaches (DA) instead of animal models. An illustrative NGRA case study shall demonstrate if the use of propyl paraben at 0.2% in a face cream was safe for consumers. A sequential stacking tier testing DA based on NAM data predicted propyl paraben to be a non-sensitiser, while some NAM input data showed positive results. To increase confidence, structurally related parabens were considered, which revealed NAM and DA hazard predictions similar to those of propyl paraben, non-sensitiser classifications in animal models and very rare cases of human skin allergy. Based on a weight of evidence it was decided that propyl paraben should be considered a non-sensitiser leading to a favourable NGRA conclusion, in line with traditional risk assessment. Examination of an ab initio NGRA based on NAM and metabolism data resulted in a more conservative weak sensitiser consideration as point of departure, which still led to a favourable conclusion.

Keywords: Defined approaches; Hazard identification; New approach methodologies; Next generation risk assessment; Parabens; Risk characterisation; Skin sensitisation; Weight of evidence.

MeSH terms

  • Animals
  • Cosmetics
  • Dermatitis, Allergic Contact
  • Models, Animal
  • Parabens / toxicity*
  • Risk Assessment
  • Skin / drug effects*


  • Cosmetics
  • Parabens
  • propylparaben