title: Topical benzoic acid induces the increased biosynthesis of prostaglandin D2 in human skin in vivo.
abstract: BACKGROUND
  Benzoic acid is one of the most commonly used preservatives in cosmetics, foodstuffs, and drug preparations. Nonetheless, products containing this compound frequently induce cutaneous erythema. Previous studies have suggested that prostaglandins may mediate the cutaneous vasodilation because ingestion of cyclooxygenase inhibitors before the application of benzoic acid markedly diminishes this symptom. However, the prostaglandin responsible has not been conclusively determined. Recently we showed that cutaneous erythema similar to that associated with application of venzoic acid is induced by the topical administration of another preservative, sorbic acid, and is mediated by the increased biosynthesis of prostaglandin (PG)D2 in the skin. This study was designed to determine whether the cutaneous vasodilation induced by benzoic acid is mediated by this prostaglandin in humans.
  
  
  METHODS
  Benzoic acid (10% in petrolatum) was applied to the forearms of healthy volunteers. Blood was obtained from the antecubital vein draining the treated site and assayed for vasodilating prostaglandins and histamine.
  
  
  RESULTS
  Topical application of benzoic acid to four volunteers resulted in a 29- to 8000-fold increase in plasma levels of PGD2 and a 72- to 370-fold increase in levels of 9 alpha,11 beta-PGF2, the stable plasma metabolite of PGD2, in blood drawn from the antecubital vein draining the treated sites. In contrast, there were no changes in plasma levels of other vasodilating prostaglandins, PGE2 or prostacyclin (PGI2). Increases in levels of PGD2 and 9 alpha,11 beta-PGF2 were not found in blood drawn simultaneously from veins in the contralateral arm, indicating the increased biosynthesis of PGD2 from the site of benzoic acid application. Increased formation of PGD2 in response to topical application of benzoic acid was dose dependent over a concentration range of 0.01% to 15%. The increased synthesis of PGD2 was not accompanied by a release of histamine, suggesting that PGD2 was not derived from the mast cell.
  
  
  CONCLUSIONS
  PGD2 mediates the vasodilation associated with topical application of benzoic acid.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Downard
authors.forename: L J
authors.initials: LJ
authors.lastname: Roberts
authors.forename: J D
authors.initials: JD
authors.lastname: Morrow
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D019817:Benzoic Acid; D005260:Female; D005520:Food Preservatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D015230:Prostaglandin D2 / Q000096:biosynthesis* / Q000502:physiology; D012016:Reference Values; D012867:Skin / Q000378:metabolism*; D012879:Skin Physiological Phenomena; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001565:Benzoates; D005520:Food Preservatives; D019817:Benzoic Acid; D015230:Prostaglandin D2