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Sensory irritation to methylparaben is caused by its low metabolism in the skin

Rie Ninomiya1, Takafumi Nishijima1, Masahiro Aoshima2

  • 1Safety Science Research Laboratories, Kao Corporation, Odawara, Japan.

The Journal of Dermatology
|March 23, 2023
PubMed

Insights

Sensitive skin may result from reduced metabolism of cosmetic ingredients like methylparaben (MP). Lower MP hydrolysis in sensitive skin leads to irritation, unlike its byproduct, p-hydroxybenzoic acid (PHBA).

Area of Science:

  • Dermatology
  • Biochemistry
  • Toxicology

Background:

  • Sensitive skin exhibits sensory irritation from common cosmetic and pharmaceutical ingredients.
  • Methylparaben (MP), a widely used preservative, is a known sensory irritant that undergoes hydrolysis in the skin.

Purpose of the Study:

  • To investigate the relationship between methylparaben (MP) sensory irritation and its hydrolysis in the skin.
  • To identify the specific enzymes involved in MP metabolism and their role in sensitive skin.

Main Methods:

  • Ex vivo pig skin models were used to study MP percutaneous penetration and hydrolysis.
  • Human stinging tests and intracellular calcium assays in TRPA1-expressing cells evaluated the irritancy of MP and its hydrolysis product, p-hydroxybenzoic acid (PHBA).
  • Carboxylesterase (CES) activity was assessed in sensitive and non-sensitive human skin biopsies using specific inhibitors.

Main Results:

  • Topically applied MP was rapidly hydrolyzed to PHBA in ex vivo skin.
  • MP, not PHBA, induced sensory irritation and increased intracellular calcium in TRPA1-expressing cells.
  • MP hydrolytic activity was significantly lower in sensitive skin compared to non-sensitive skin, with CES1 identified as the primary enzyme responsible for MP metabolism.

Conclusions:

  • Reduced metabolism of topical agents, specifically lower MP hydrolysis by CES1, contributes to skin sensory irritation and the development of sensitive skin.
  • MP itself is the primary irritant, not its hydrolysis product PHBA.
  • Targeting skin metabolism pathways may offer new strategies for managing sensitive skin conditions.
Keywords:
carboxylesterasemethylparabenp-hydroxybenzoic acidsensitive skinsensory irritation

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