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 chemical warfare agent. We have developed a cutaneous full-thickness HD burn model in weanling pigs for efficacy testing of candidate treatment regimens. This report addresses clinical pathology findings and the urinary excretion 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. Blood samples were collected throughout a 7-day observation period for hematology and serum chemistry examinations. Urine was collected in metabolism cages. Routine urinalysis was performed and the urine analyzed for TDG using gas chromatography/mass spectrometry. Examination of clinical pathology parameters revealed subtle HD-related changes that are suggestive of a mild hemolytic episode. No other signs of clinically significant systemic toxicities were noted, including bone marrow suppression. Thiodiglycol was detected at the earliest time point tested (6-8 h post-exposure) at levels ranging from 0.66 to 4.98 microg ml(-1) with a mean of 2.14 microg ml(-1). Thiodiglycol concentrations were the highest for half of the animals at this earliest time 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 the remainder of the 7-day observation period, with the highest individual concentration noted during this period of 132 ng ml(-1). Our results are in general agreement with the TDG excretion profiles previously described for rodent 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 exposure within the previous 96 h. Low levels significantly above natural background levels may indicate either exposure to low levels of agent or exposure that occurred more than 4 days prior to collection of the sample.
Graham
J S
JS
US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA.
Reid
F M
FM
Smith
J R
JR
Stotts
R R
RR
Tucker
E S
ES
Shumaker
S M
SM
Niemuth
N A
NA
Janny
S J
SJ
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002057:Burns, Chemical / Q000150:complications / Q000473:pathology*; D003879:Dermatologic Agents / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D008954:Models, Biological; D009151:Mustard Gas / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics / Q000652:urine*; D013552:Swine
D015415:Biomarkers; D003879:Dermatologic Agents; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; C047519:2,2'-thiodiethanol; D009151:Mustard Gas