Adverse respiratory effects in rats following inhalation exposure to ammonia: respiratory dynamics and histopathology

Abstract

Acute respiratory dynamics and histopathology of the lungs and trachea following inhaled exposure to ammonia were investigated. Respiratory dynamic parameters were collected from male Sprague–Dawley rats (300–350 g) during (20 min) and 24 h (10 min) after inhalation exposure for 20 min to 9000, 20,000, and 23,000 ppm of ammonia in a head-only exposure system. Body weight loss, analysis of blood cells, and lungs and trachea histopathology were assessed 1, 3, and 24 h following inhalation exposure to 20,000 ppm of ammonia. Prominent decreases in minute volume (MV) and tidal volume (TV) were observed during and 24 h post-exposure in all ammonia-exposed animals. Inspiratory time (IT) and expiratory time (ET) followed similar patterns and decreased significantly during the exposure and then increased at 24 h post-exposure in all ammonia-exposed animals in comparison to air-exposed controls. Peak inspiratory (PIF) and expiratory flow (PEF) significantly decreased during the exposure to all ammonia doses, while at 24 h post-exposure they remained significantly decreased following exposure to 20,000 and 23,000 ppm. Exposure to 20,000 ppm of ammonia resulted in body weight loss at 1 and 3 h post-exposure; weight loss was significant at 24 h compared to controls. Exposure to 20,000 ppm of ammonia for 20 min resulted in increases in the total blood cell counts of white blood cells, neutrophils, and platelets at 1, 3, and 24 h post-exposure. Histopathologic evaluation of the lungs and trachea tissue of animals exposed to 20,000 ppm of ammonia at 1, 3, and 24 h post-exposure revealed various morphological changes, including alveolar, bronchial, and tracheal edema, epithelial necrosis, and exudate consisting of fibrin, hemorrhage, and inflammatory cells. The various alterations in respiratory dynamics and damage to the respiratory system observed in this study further emphasize ammonia-induced respiratory toxicity and the relevance of efficacious medical countermeasure strategies.

Keywords:

• ammonia
• histopathology
• inhalation exposure
• plethysmography
• respiratory dynamics
• respiratory toxicology

Acknowledgements

Our special thanks to the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) program for support (IAA: AOD14021). Thanks to the USAMRICD Comparative Pathology Branch for all histopathology sample preparations and analysis and also to James Abraham for his illustrative and design expertise. M. W. P would like to express his deepest gratitude to Alfred M. Sciuto for being a remarkable mentor and impeccable team leader. K. S. and J. A. are supported by the Oak Ridge Associated Universities. The experimental protocol was approved by the Animal Care and Use Committee at the United States Army Medical Research Institute of Chemical Defense, and all procedures were conducted in accordance with the principles stated in the Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act of 1966 (P.L. 89-544), as amended. The views expressed in this article are those of the author(s) and do not reflect the official policy of the Department of the Army, Department of Defense, or the U.S. Government.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

Special thanks to the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) program for support (Chemical Affecting the Respiratory Tract ? Pulmonary Toxicant Gases, IAA: AOD14021-001-00000). K.S. and J.A. were supported in part by an appointment to the Internship/Research Participation Program for the US Army Medical Research Institute of Chemical Defense, administered by the Oak Ridge Institute for Science and Education through an agreement between the US Department of Energy and the USAMRICD.