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 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.
Riviere
J E
JE
Center for Cutaneous Toxicology and Residue Pharmacology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. Jim_Riviere@NCSU.EDU
Smith
C E
CE
Budsaba
K
K
Brooks
J D
JD
Olajos
E J
EJ
Salem
H
H
Monteiro-Riviere
N A
NA
D000279:Administration, Cutaneous; D000327:Adsorption; D000818:Animals; D019540:Area Under Curve; D002250:Carbon Radioisotopes; D046508:Culture Techniques; D003879:Dermatologic Agents / Q000493:pharmacokinetics*; D005404:Fixatives; D008954:Models, Biological; D009151:Mustard Gas / Q000493:pharmacokinetics*; D012459:Salicylates / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013552:Swine
D002250:Carbon Radioisotopes; D003879:Dermatologic Agents; D005404:Fixatives; D012459:Salicylates; C033069:methyl salicylate; D009151:Mustard Gas