Application of in vivo microdialysis for studying the efficacy of protective preparations against sulfur mustard penetrating the skin

Subcutaneous microdialysis was employed for monitoring thiodiglycol (2,2'-thiodiethanol, TDG) levels with the aim of characterizing the transdermal penetration of topically applied liquid sulfur mustard (2,2'-dichlorodiethylsulfide, SM) in rats. TDG levels, evaluated in 20 min dialysates collected over a 6 h sampling period, were plotted against time after pooling. Linear correlation was identified between the SM dose and the mean areas under the 0-60 min or the whole curve (AUC(0-60) and AUC, respectively) as well as mean peak concentrations (C-max) in the range of 1.0-3.0 mu l applied volume (7.2-21.7 nmol). A commercially available barrier cream, a perfluoropolyether oil and a vaseline based ointment containing zinc oxide were subsequently tested as topical protectants. Each preparation was layered on the skin surface prior to the application of 2.0 mu l SM. The evaluation of the efficacy of the preparations was based on obtained AUC(0-60), AUC and C-max values. A statistical comparison of these parameters with those obtained when 2.0 mu l SM was applied without pretreatment indicated that the barrier cream and the perfluoropolyether oil significantly (P < 0.01) reduced the amount of penetrating SM within the sampling period. In addition, the perfluoropolyether oil almost completely prevented the penetration of SM for 20 min. Pretreatment with the ointment did not prove to be an effective countermeasure as its administration resulted in no significant reduction in AUC(0-60), AUC and C-max values. Copyright (C) 2007 John Wiley & Sons, Ltd.