title: Effect of different alcohols on stratum corneum kallikrein 5 and phospholipase A2together with epidermal keratinocytes and skin irritation.
abstract: OBJECTIVE
  The aim of this exploratory study was to investigate the effect of ethanol, isopropanol and n-propanol on stratum corneum (SC) enzymes and keratinocytes in vitro together with their effects on skin condition and function.
  
  
  METHODS
  Activities of kallikrein 5 (KLK5) and phospholipase A2 (PLA2) as well as keratinocyte metabolic activity, interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were measured in vitro in the presence and absence of the different alcohols. We also measured transepidermal water loss (TEWL), skin capacitance, visual dryness and visual redness on the volar forearms of 25 Caucasian women following application of the alcohols 20 and 100 times per day over a period of 14 days in a clinical study.
  
  
  RESULTS
  Reduced activities of KLK5 and PLA2 were observed in the presence of the alcohols. The greatest denaturing effect was always observed for n-propanol (P < 0.001), and in the case of PLA2, the effect of isopropanol was greater than ethanol (P < 0.001). Equally, ethanol had the mildest effects on keratinocyte metabolic activity and cytokine secretion (P < 0.001) and n-propanol always produced the most severe changes in normal and differentiated keratinocytes. These in vitro findings supported the clinical results where the major effects were on the induction of skin irritation (increased dropout rates) and ranked the intolerance of the different alcohols as follows: n-propanol > isopropanol > ethanol. At the high application frequencies, the effect of the different alcohols on transepidermal water loss (TEWL) and skin capacitance was similar, but at the low application frequencies, n-propanol had a significant effect on TEWL and capacitance values (P < 0.05). Equally, n-propanol and isopropanol produced significantly more skin redness at the low application frequencies.
  
  
  CONCLUSIONS
  Clearly, isopropanol and n-propanol caused significant SC and keratinocyte perturbation in vitro together with damage to skin condition and function in vivo whereas ethanol did not. As a result, we show that ethanol-based sanitizers are better tolerated by skin, particularly in high-use settings, than other alcohols and should be the active ingredient of choice.
authors: GOJO Industries, Inc, PO Box 991, Akron, OH, 44309-0991, USA.
authors: T
authors: T
authors: Cartner
authors: School of Pharmacy, UCL, London, UK.
authors: N
authors: N
authors: Brand
authors: GOJO Industries, Inc, PO Box 991, Akron, OH, 44309-0991, USA.
authors: K
authors: K
authors: Tian
authors: GOJO Industries, Inc, PO Box 991, Akron, OH, 44309-0991, USA.
authors: A
authors: A
authors: Saud
authors: Carr Consulting, Wilmette, IL, USA.
authors: T
authors: T
authors: Carr
authors: School of Pharmacy, UCL, London, UK.
authors: P
authors: P
authors: Stapleton
authors: School of Pharmacy, UCL, London, UK.
authors: M E
authors: ME
authors: Lane
authors: School of Pharmacy, UCL, London, UK.|AVR Consulting Ltd., 26 Shavington way, Northwich, UK.
authors: A V
authors: AV
authors: Rawlings
mesh_terms: D000438:Alcohols / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects*; D054467:Phospholipases A2 / Q000378:metabolism*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000438:Alcohols; D054467:Phospholipases A2; C400147:KLK5 protein, human; D007610:Kallikreins
keywords: alcohol; cell culture; formulation/stability; skin barrier; stratum corneum