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A 7-day mouse model to assess protection from sulfur mustard (SM) skin injury

TitleA 7-day mouse model to assess protection from sulfur mustard (SM) skin injury
Publication TypeConference Proceedings
Year of Conference2003
AuthorsBabin M.C., Gazaway M.Y., Kiser R.C., Koplovitz I., Krogel N., Mitcheltree L.W., Moore D.M., Niemuth N.A., Ricketts K.M., Skvorak K., Sweeney R.E., Casillas R.P.
Conference NameProceedings of the 42nd Annual Meeting of the Society of Toxicology
Volume72 (S-1)
PublisherOxford University Press
Conference LocationSalt Lake City, UT
KeywordsSulfur Mustard

The mouse ear vesicant model (MEVM) has been successfully used as a screening tool to identify protective compounds against sulfur mustard [bis(2-chloroethyl)sulfide]-induced skin injury. The MEVM provides an edema response and histopathological endpoints as measurements of inflammation and tissue damage 24 h following a topical SM (0.16 mg) exposure. Compound effectiveness is defined as a statistically significant (p<0.05) reduction in these endpoints. To further evaluate compounds, the MEVM was modified for use as a 7-day model. Dose response studies were conducted with SM (0.01 mg to 0.16 mg) to determine the optimal dose for producing widespread necrosis at day 7. A modified Draize scoring system of 0-4 (no damage to extensive necrosis) was incorporated as an endpoint to evaluate the extent of ear tissue damage out to day 7. Draize results revealed an optimum SM dose of 0.08 mg. Edema response and the existing histopathological scoring system were not feasible endpoints in the 7-day model. Octyl homovanillamide (OHV), a protective compound in the MEVM, and 2 pharmacologically inactive analogs were tested as topical pretreatments 15 min prior to a 0.08 mg SM challenge. OHV significantly reduced Draize scores whereas the inactive analogs had no effect. OHV was also evaluated as a pretreatment 15 min before exposure to 0.06, 0.08, and 0.16 mg SM. OHV protection at day 7 was similar for the 0.06 and 0.08 mg doses but not effective against the severely necrotizing 0.16 mg SM dose.OHV also significantly reduced SM injury when a single topical 2 mmol dose was administered 10 min after SM challenge. These data support the use of the Mouse Ear Vesicant Treatment Model (MEVTM) for evaluating candidate antivesicant compounds. This work was supported by the US Army Medical Research and Materiel Command under Contract DAMD17-99-D-0010, Task Order 0002.

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