title: Phenol-croton oil peel: establishing an animal model for scientific investigation.
abstract: BACKGROUND
  Phenol-croton oil formulas for facial peeling contain a mixture of phenol, croton oil, hexachlorophene foam (Septisol; Steris Corp., Mentor, OH), and water. For years, it was felt that the active ingredient of the solution was phenol, with the view that croton oil was little more than an irritant. Hetter reported, based on clinical experience, that the addition of tiny amounts of croton oil to any concentration of phenol caused a deeper peel. He also noted that the number of applications of a phenol-croton oil solution also enhanced the peel effects. To date, there have been no animal studies that confirm these clinical observations.
  
  
  OBJECTIVE
  The purpose of this study was to develop an animal model to further evaluate and refine the hypotheses of Hetter regarding the croton oil solution.
  
  
  METHODS
  At the Medical College of Wisconsin, Milwaukee, WI, using a porcine animal model, 40 different solutions of phenol, water, croton oil, hexachlorophene foam, and ethyl alcohol, in 8 groupings, were applied to the flank according to grids. On days 1, 8, and 22, clinical observations were made and punch biopsies were obtained from all grids, including controls. All tissue samples were examined by a blinded dermatopathologist.
  
  
  RESULTS
  The results were analyzed by both clinical and histologic observation. Solutions with any amount of croton oil added had a brisker inflammatory response than solutions without croton oil. The histologic examination of skin biopsies from the phenol-treated cells (with or without croton oil) demonstrated formation of sharply demarcated dermis with parallel collagen fiber bundles arranged horizontally when compared with the elastotic dermis of the control specimens. The depth of peel and time needed for healing were greater with 45 strokes than with 20 or 5 strokes. Replacing water with ethyl alcohol produced a less clinically significant peel.
  
  
  CONCLUSIONS
  Phenol peels more deeply with increasing concentrations. Peel depth increases with increasing concentration of croton oil. Multiple applications of croton oil in phenol increases the depth of peel. The porcine model is a satisfactory model for studying chemoexfoliative agents.
authors.affiliation: Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Dlarson@mcw.edu
authors.forename: David L
authors.initials: DL
authors.lastname: Larson
authors.forename: Firas
authors.initials: F
authors.lastname: Karmo
authors.forename: Greg P
authors.initials: GP
authors.lastname: Hetter
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage; D002615:Chemexfoliation / Q000379:methods*; D003436:Croton Oil / Q000627:therapeutic use*; D003879:Dermatologic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006582:Hexachlorophene / Q000008:administration & dosage; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D023421:Models, Animal; D019800:Phenol / Q000627:therapeutic use*; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000891:Anti-Infective Agents, Local; D003879:Dermatologic Agents; D004338:Drug Combinations; D019800:Phenol; D003436:Croton Oil; D006582:Hexachlorophene