Use of methyl salicylate as a simulant to predict the percutaneous absorption of sulfur mustard

Exposure to chemical vesicants such as sulfur mustard (HD) continues to be a threat to military forces requiring protectant strategies to exposure to be evaluated. Methyl salicylate (MS) has historically been the simulant of choice to assess HD exposure. The purpose of this study was to compare the percutaneous absorption and skin deposition of MS to HD in the isolated per fused porcine skin flap (IPPSF). The HD data were obtained from a previousl y published study in this model wherein 400 mug cm(-2) of [C-14]-MS or [C-1 4]-HD in ethanol were topically applied to 16 IPPSFs and experiments were t erminated at 2, 4 or 8 h. Perfusate was collected at increasing time interv als throughout perfusion, Radioactivity was determined in perfusate and ski n samples. Perfusate flux profiles were fitted to a bi-exponential model Y( t) = A(e(-ht) - e(-dt)) and the area under the curve (AUC), peak flux and t ime to peak flux were determined. Sulfur mustard had more pronounced and ra pid initial flux parameters (P < 0.05). The AUCs determined from observed a nd model-predicted parameters were not statistically different, although th e mean HD AUC was 40-50% greater than MS. The HD skin and fat levels were u p to twice those seen with MS, but had lower stratum corneum and residual s kin surface concentrations (P < 0.05). Compared with other chemicals studie d in this model, HD and MS cutaneous disposition were very similar, support ing the use of MS as a dermal simulant for HD exposure. Copyright (C) 2001 John Wiley & Sons, Ltd.