Riviere, C.E. Smith, K. Budsaba, J.D. Brooks, E.J. Olajos, H. Salem, and N.A. Monteiro-Riviere. (2000). Use of Methyl Salicylate as a Simulant to Predict the Percutaneous Absorption of Sulfur Mustard. The Toxicologist 54(1): Abstract # 715.

methyl salicylate - 00119-36-8; sulfur mustard - 00505-60-2

Exposure to chemical vesicants such as sulfur mustard (HD) continue to be a threat to military forces which requires that protectant strategies to exposure 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 perfused porcine skin flap (IPPSF). HD data were obtained from previously published study in this model (Toxicol. Appl. Pharmacol 135: 25-34, 1995). 400 mg/cm2 of 14C-MS or 14C-HD in ethanol were topically applied to 16 IPPSFs and experiments terminated at 2 hrs, 4 hrs or 8 hrs. Perfusate was collected at increasing time intervals throughout perfusion. Radioactivity was determined in perfusate and skin samples. Perfusate flux profiles were fitted to a bi-exponential model Y(t)=A(e-bt - e-dt) and AUC, peak flux and time to peak flux were determined. HD had more pronounced and rapid initial flux parameters. AUC determined from observed and model-predicted parameters were not statistically different, although mean HD AUC was 40 to 50% greater than MS. HD skin and fat levels were up to twice those seen with MS, but had lower stratum corneum and residual skin surface concentrations. Compared to other chemicals studied in this model, HD and MS cutaneous disposition were very similar, supporting the use of MS as a dermal simulant for HD exposure.