title: Assessment of inhaled acute ammonia-induced lung injury in rats.
abstract: This study examined acute toxicity and lung injury following inhalation exposure to ammonia. Male Sprague-Dawley rats (300-350 g) were exposed to 9000, 20,000, 23,000, 26,000, 30,000 or 35,000 ppm of ammonia for 20 min in a custom head-out exposure system. The exposure atmosphere, which attained steady state within 3 min for all ammonia concentrations, was monitored and verified using a Fourier transform infrared spectroscopy (FTIR) gas analyzer. Animals exposed to ammonia resulted in dose-dependent increases in observed signs of intoxication, including increased chewing and licking, ocular irritation, salivation, lacrimation, oronasal secretion and labored breathing. The LCt50 of ammonia within this head-out inhalation exposure model was determined by probit analysis to be 23,672 ppm (16,489 mg/m(3)) for the 20 min exposure in male rats. Exposure to 20,000 or 23,000 ppm of ammonia resulted in significant body weight loss 24-h post-exposure. Lung edema increased in all ammonia-exposed animal groups and was significant following exposure to 9000 ppm. Bronchoalveolar fluid (BALF) protein concentrations significantly increased following exposure to 20,000 or 23,000 ppm of ammonia in comparison to controls. BAL cell (BALC) death and total cell counts increased in animals exposed to 20,000 or 23,000 ppm of ammonia in comparison to controls. Differential cell counts of white blood cells, neutrophils and platelets from blood and BALF were significantly increased following exposure to 23,000 ppm of ammonia. The following studies describe the validation of a head-out inhalation exposure model for the determination of acute ammonia-induced toxicity; this model will be used for the development and evaluation of potential therapies that provide protection against respiratory and systemic toxicological effects.
authors.affiliation: a Analytical Toxicology Division , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Perkins
authors.affiliation: a Analytical Toxicology Division , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wong
authors.affiliation: a Analytical Toxicology Division , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Tressler
authors.affiliation: a Analytical Toxicology Division , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Coggins
authors.affiliation: a Analytical Toxicology Division , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: a Analytical Toxicology Division , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Devorak
authors.affiliation: a Analytical Toxicology Division , US Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Sciuto
mesh_terms: D000641:Ammonia / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury / Q000473:pathology*; D008297:Male; D009504:Neutrophils; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000641:Ammonia
keywords: Ammonia; inhalation exposure; lung injury; pulmonary edema; respiratory toxicology; toxic industrial chemical