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Topical nitrogen mustard exposure causes systemic toxic effects in mice
Dinesh G Goswami1, Dileep Kumar1, Neera Tewari-Singh1
1Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Summary
Topical exposure to nitrogen mustard (NM) causes severe skin injury and systemic toxicity, including significant weight loss and mortality in mice. NM also damages the spleen, small intestine, and kidneys, highlighting its broad toxic effects.
Area of Science:
- Toxicology
- Dermatology
- Systemic effects of chemical exposure
Background:
- Vesicating agents like sulfur mustard (SM) and nitrogen mustard (NM) are known skin irritants.
- Previous research indicates SM exposure can damage multiple organ systems.
Purpose of the Study:
- To investigate the systemic effects of topical nitrogen mustard (NM) exposure.
- To characterize the toxicological impact of NM on mouse skin and internal organs.
Main Methods:
- Topical application of 3.2mg NM to SKH-1 hairless mouse skin.
- Assessment of skin injury, body weight, mortality, and hematological parameters.
- Histopathological examination of spleen, small intestine, and kidneys.
Main Results:
- NM exposure caused significant skin injury, body weight loss, and 40-80% mortality.
- NM altered white blood cell counts and reduced spleen size.
- Damage was observed in the small intestine (epithelial integrity, villi) and kidneys (glomerular capillaries, increased BUN/creatinine ratio).
Conclusions:
- Topical NM exposure induces severe systemic toxicity beyond skin damage.
- NM affects the hematopoietic system, spleen, gastrointestinal tract, and kidneys.
- Findings contribute to understanding vesicant toxicity and developing countermeasures.
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