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 Ho 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 tin metabolite (thiodiglycol, TDG) in this model, Si x female Yorkshire pigs were exposed to HD liquid on the ventral surface fo r 2 h, generating six 3-cm diameter full-thickness dermal lesions per pig. Blood samples were collected throughout a 7-day observation period for hema tology and serum chemistry examinations. Urine was collected in metabolism cages, Routine urinalysis was performed and the urine analyzed for TDG usin g gas chromatography/mass spectrometry. Examination of clinical pathology p arameters revealed subtle HD-related changes that are suggestive of a mild hemolytic episode. No other signs of clinically significant systemic toxici ties were noted, including bone marrow suppression. Thiodiglycol was detect ed at the earliest time point tested (6-8 h post-exposure) at levels rangin g 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 t ime point and at 24-48 h for the others, By the evening of day 3, the mean level had reached 50 ng ml(-1). Mean levels remained 10-40 ng ml(-1) for th e remainder of the 7-day observation period, with the highest individual co ncentration noted during this period of 132 ng ml(-1). Our results are in g eneral agreement with the TDG excretion profiles previously described for r odent models and humans, Urinary excretion of absorbed HD in our weanling p ig wound healing model appears to follow the same pattern as is seen in oth er laboratory animals models, In general, urinary excretion of TDG appears to peak within the first 1-4 days following exposure, with detectable level s after 1 week. Relatively high urinary TDG levels may thus indicate agent exposure within the previous 96 h. Low levels significantly above natural b ackground levels may indicate either exposure to low levels of agent or exp osure that occurred more than 4 days prior to collection of the sample. Pub lished in 2000 by John Wiley & Sons, Ltd.