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

Abstract

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 perfused porcine skin flap (IPPSF). The HD data were obtained from a previously published study in this model wherein 400 microg cm(-2) of ](14)C[-MS or ](14)C[-HD in ethanol were topically applied to 16 IPPSFs and experiments were terminated at 2, 4 or 8 h. 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 the area under the curve (AUC), peak flux and time to peak flux were determined. Sulfur mustard had more pronounced and rapid initial flux parameters (P < 0.05). The AUCs determined from observed and model-predicted parameters were not statistically different, although the mean HD AUC was 40--50% greater than MS. The HD skin and fat levels were up to twice those seen with MS, but had lower stratum corneum and residual skin surface concentrations (P < 0.05). Compared with 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.

Chemical Agent Simulant Release from Clothing Following Vapor Exposure

“…8 MeS has similar physical properties to sulfur mustard, a vesicant. 9 A chemical closely resembling nerve agents would have been preferred, but compounds such as methyl phosphonates are too toxic to handle outside of closed laboratory environments and fume hoods, which was felt to be an unrealistic environment for these tests. The MIST Program investigators reached the same conclusions.…”

Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

“…Please note that the studies of Riviere et al (2001) and Duncan et al (2002) were performed in the years following publication of NRC/BAST (1997), and members of the Standing Committee would not have had access to these more recent data comparing MeS and agent absorption through the skin of swine.…”

“…Methyl salicylate (MeS) has long been considered an appropriate simulant for agent HD due to similar physical properties (water solubility, vapor pressure, and molecular weight) and fabric penetration characteristics, as well as its known safety for human topical use (Riviere et al 2001). Further, its rapid hydrolysis and metabolism to salicylic acid and derivatives in the body of mammals allows ready monitoring of MeS in blood serum as a measure of systemic absorption (Duncan et al 2002).…”

“…Further, its rapid hydrolysis and metabolism to salicylic acid and derivatives in the body of mammals allows ready monitoring of MeS in blood serum as a measure of systemic absorption (Duncan et al 2002). Recent studies comparing percutaneous absorption and skin deposition of HD to MeS in the isolated perfused porcine skin flap has determined that the cutaneous disposition of HD and MeS are very similar (Riviere et al 2001). The Riviere et al (2001) work demonstrates that MeS simulates the HD dose acquisition process and strongly supports the use of MeS as a dermal simulant for agent HD exposure and hazard assessment.…”

“…Recent studies comparing percutaneous absorption and skin deposition of HD to MeS in the isolated perfused porcine skin flap has determined that the cutaneous disposition of HD and MeS are very similar (Riviere et al 2001). The Riviere et al (2001) work demonstrates that MeS simulates the HD dose acquisition process and strongly supports the use of MeS as a dermal simulant for agent HD exposure and hazard assessment. Topical application of MeS to 4 skin sites (skin of the ear, perineum, inguinal crease, epigastrium) on the domestic pig have identified the following rank order for MeS permeation: ear > perineum > inguinal crease ³ epigastrium (Duncan et al 2002).…”