A cutaneous full-thickness liquid sulfur mustard burn model in weanling swine: Clinical pathology and urinary excretion of thiodiglycol

Sulfur mustard (bis(2-chloroethyl)sulfide, HD) is a well-known blistering c hemical warfare agent. We have developed a cutaneous full-thickness HD burn model in weanling pigs for efficacy testing of candidate treatment regimen s. This report addresses clinical pathology findings and the urinary excret ion profile of a major HD metabolite (thiodiglycol, TDG) in this model. Six female Yorkshire pigs were exposed to HD liquid on the ventral surface for 2 h, generating six 3-cm diameter full-thickness dermal lesions per pig. B lood samples were collected throughout a 7-day observation period for hemat ology and serum chemistry examinations. Urine was collected in metabolism c ages. Routine urinalysis was performed and the urine analyzed for TDG using gas chromatography/mass spectrometry, Examination of clinical pathology pa rameters revealed subtle HD-related changes that are suggestive of a mild h emolytic episode. No other signs of clinically significant systemic toxicit ies were noted, including bone marrow suppression. Thiodiglycol was detecte d at the earliest time point tested (6-8 h post-exposure) at levels ranging from 0.66 to 4.98 mug ml(-1) with a mean of 2.14 mug ml(-1). Thiodiglycol concentrations were the highest for half of the animals at this earliest ti me point and at 24-48 h for the others. By the evening of day 3, the mean l evel had reached 50 ng ml(-1). Mean levels remained 10-40 ng ml(-1) for the remainder of the 7-day observation period, with the highest individual con centration noted during this period of 132ng ml(-1). Our results are in gen eral agreement with the TDG excretion profiles previously described for rod ent models and humans. Urinary excretion of absorbed HD in our weanling pig wound healing model appears to follow the same pattern as is seen in other laboratory animals models. In general, urinary excretion of TDG appears to peak within the first 1-4 days following exposure, with detectable levels after 1 week. Relatively high urinary TDG levels may thus indicate agent ex posure within the previous 96 h, Low levels significantly above natural bac kground levels may indicate either exposure to low levels of agent or expos ure that occurred more than 4 days prior to collection of the sample.