Species-Specific Activation of Transient Receptor Potential Ankyrin 1 by Phthalic Acid Monoesters

Biol Pharm Bull. 2022 Dec 1;45(12):1839-1846. doi: 10.1248/bpb.b22-00645. Epub 2022 Oct 13.


Phthalic acid (PA) diesters are widely used in consumer products, as plasticizers, and are ubiquitous environmental pollutants. There is a growing concern about their adjuvant effect on allergic diseases. Although its precise mechanism remains unknown, possible involvement of transient receptor potential ankyrin 1 (TRPA1) has been suggested. Hence, in this study, the activation of human and mouse TRPA1s by a series of PA di- and monoesters was investigated using a heterologous expression system in vitro. Consequently, it was found that monoesters activated human TRPA1, where EC50 values were in the order of mono-hexyl > mono-heptyl > mono-n-octyl > mono-2-ethylhexyl > mono-isononyl and mono-isodecyl esters. Significant species differences in TRPA1 activation by PA monoesters were also discovered; PA monoesters activated human TRPA1 but not mouse TRPA1 in a concentration-dependent manner up to 50 µM. These findings suggest that PA esters may exert TRPA1-dependent adverse effects on humans, which have never been demonstrated in experimental animals.

Keywords: adjuvant effect; nociceptive receptor; phthalic acid ester; species difference; transient receptor potential ankyrin 1.

MeSH terms

  • Animals
  • Humans
  • Mice
  • Phthalic Acids* / toxicity
  • Plasticizers
  • Species Specificity
  • TRPA1 Cation Channel* / metabolism


  • phthalic acid
  • Phthalic Acids
  • Plasticizers
  • TRPA1 protein, human
  • Trpa1 protein, mouse
  • TRPA1 Cation Channel