title: Real-time detection of p-phenylenediamine penetration into human skin by in vivo Raman spectroscopy.
abstract: BACKGROUND
  Penetration, autoxidation and N-acetylation of p-phenylenediamine (PPD) have been studied in vitro and ex vivo. However, a clear understanding of in vivo PPD penetration and the formation of PPD derivatives is lacking.
  
  
  OBJECTIVE
  To obtain insights into the in vivo penetration, clearance and formation of PPD derivatives in human skin.
  
  
  METHODS
  Patch test chambers containing PPD 1% pet. were applied to the forearms of two human volunteers, with increasing application times. Non-invasive Raman microspectroscopy was used for detection of PPD (derivatives) in skin at several follow-up times.
  
  
  RESULTS
  Application of a PPD 1% pet. patch for 30 min resulted in substantial amounts of PPD in the stratum corneum of 90 mg PPD/g keratin. PPD contents were highest after three applications for 1 h each (330 mg PPD/g keratin), followed by single applications for 2 h 40 min, 2 h, and 23 h. The PPD half-time in the skin was 3 h. No spectral contributions of Bandrowski's base, monoacetyl-PPD and diacetyl-PPD were detected.
  
  
  CONCLUSIONS
  We have gained insights into the in vivo penetration of PPD in human skin by using non-invasive Raman spectroscopy. Penetration into the skin was fast, and the PPD concentrations detected in the stratum corneum were high. PPD was detected in both the stratum corneum and the viable epidermis. Oxidized or acetylated PPD derivatives could not be detected.
authors.affiliation: Department of Dermatology, University Medical Centre Groningen, University of Groningen, 9700, RB, Groningen, The Netherlands.
authors.forename: Laura Marjolijn
authors.initials: LM
authors.lastname: Pot
authors.affiliation: Department of Dermatology, University Medical Centre Groningen, University of Groningen, 9700, RB, Groningen, The Netherlands.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Coenraads
authors.affiliation: Department of Environmental Toxicology, University of Trier, D-54296, Trier, Germany.
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Blömeke
authors.affiliation: Department of Dermatology, Centre for Optical Diagnostics and Therapy, Erasmus MC, 3015, CE, Rotterdam, The Netherlands.|RiverD International B.V., 3029, AK, Rotterdam, The Netherlands.
authors.forename: Gerwin J
authors.initials: GJ
authors.lastname: Puppels
authors.affiliation: Department of Dermatology, Centre for Optical Diagnostics and Therapy, Erasmus MC, 3015, CE, Rotterdam, The Netherlands.|RiverD International B.V., 3029, AK, Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Caspers
mesh_terms: D000107:Acetylation; D000328:Adult; D004396:Coloring Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D010655:Phenylenediamines / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D012869:Skin Absorption; D013059:Spectrum Analysis, Raman
chemical_list: D004396:Coloring Agents; D010655:Phenylenediamines; C029728:4-phenylenediamine
keywords: Raman spectroscopy; in vivo; p-phenylenediamine (PPD); penetration; skin