Inhalation exposure systems for the development of rodent models of sulfur mustard-induced pulmonary injury.
Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg x min/m(3) resulted in homogeneous lung injury with no nasal degeneration.
Weber
Waylon M
WM
Lovelace CounterACT Center of Excellence, Lovelace Respiratory Research Institute, Albuquerque, NM 87108, USA. wweber@lrri.org
Kracko
Dean A
DA
Lehman
Mericka R
MR
Irvin
Clinton M
CM
Blair
Lee F
LF
White
Richard K
RK
Benson
Janet M
JM
Grotendorst
Gary R
GR
Cheng
Yung-Sung
YS
McDonald
Jacob D
JD
D000336:Aerosols; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D019570:Inhalation Exposure; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D009151:Mustard Gas / Q000633:toxicity*; D010316:Particle Size; D010865:Pilot Projects; D051381:Rats; D011916:Rats, Inbred F344; D014420:Turbinates / Q000187:drug effects / Q000473:pathology; D014835:Volatilization
D000336:Aerosols; D002619:Chemical Warfare Agents; D009151:Mustard Gas