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A Medical Research and Evaluation Facility (MREF) and Studies Supportingthe Medical Chemical Defense Program

Authors: Carl T. Olson; Michele M. Danne; James A. Blank; James E. Estep; BATTELLE MEMORIAL INST COLUMBUS OH
 
Abstract: Vesicants, such as sulfur mustard (HD), have several routes of exposure, including dermal, ocular, and pulmonary. The most hazardous effects of HD are manifested in the respiratory tract following inhalation of HD vapor. Acute lung edema will result when the pulmonary system is exposed to sufficiently high levels of HD (Eisenmenger et al., 1991). One research objective of the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) is to assess the risk of pulmonary HD exposure and to identify early markers of exposure. HD is a highly reactive compound that is unstable in biological fluids, making it difficult to quantify the dose received deep in the lungs after an aerosol exposure. Previous investigators found that, following an inhalation exposure, clinical manifestations of HD-induced injury were found primarily in the upper airway passages (Papirmeister et al., 1991). Literature references indicate that intravenous and subcutaneous HD exposures of rodents can be used to study pulmonary toxicity, thus circumventing the need for generating HD vapor for inhalation (Maisonneuve et al.; 1993 Maisonneuve et al., 1994; Elsayed et al., 1992). Data in the literature also demonstrate that subcutaneous injection of the monofunctional HD analog, butyl 2-chloroethyl sulfide, induces free radical-mediated oxidative pulmonary damage in mice (Elsayed et al., 1992). As part of a USAMRICD Study, Protocol No. 1-04-97-000-A- 741, lung specimens from rats that had been intravenously exposed to HI) were sent to Battelle's Medical Research and Evaluation Facility (MREF) and assessed for activation of nuclear factor kappa B (NF-kB), a transcription factor involved in the inflammatory response. NF-kB is a ubiquitous transcription factor of particular importance in the early amplification of the inflammatory response. NF-kB is normally present in the cell as inactive cytosolic complexes of NF-kB and the inhibitory protein called I-kB.

Limitations: APPROVED FOR PUBLIC RELEASE
Description: Final rept. Task 97-47
Pages: 42
Report Date: DEC 1999
Contract Number: DAMD17-89-C-9050
Report Number: A566273
Keywords relating to this report:
AEROSOLS
ARMY RESEARCH
CHEMICAL WARFARE
DEFENSE SYSTEMS
EXPOSURE(PHYSIOLOGY)
HAZARDS
HD AGENT
INFLAMMATION
LUNG
MEDICAL RESEARCH
MUSTARD AGENTS
PREVENTIVE MEDICINE
PULMONARY EDEMA
RATS
RESPIRATORY SYSTEM
RESPONSE(BIOLOGY)
SUBCUTANEOUS TISSUE
SULFUR
TOXICITY
VESICANTS
WOUNDS AND INJURIES
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