Pulmonary and Systemic Effects of Acute Chlorine Exposure in a Preclinical Model

Background and Purpose: Chlorine is a highly reactive and toxic gas produced in large quantities in industry. Accidental exposures occur frequently, highlighting a need for effective countermeasures. Animal models provide important insights into the injury mechanisms and serve as preclinical models for drug development and advancement. Here we describe a rat model of chlorine inhalation using near lethal dose (LD50) concentrations to characterize the physiological and systemic effects of exposure and to establish a platform for longitudinal therapeutic assessment. Methods: Sprague Dawley rats were exposed to 500 or 600 ppm of chlorine for 45 min and transferred to room air. Pulse oximetry was performed every 2h till 8h and then at 24h after exposure. At the predetermined timepoints (3, 6, and 24h), body weights were recorded and animals were euthanized for arterial blood collection from the descending aorta for arterial blood gas (ABG) measurements. Before bronchoalveolar lavage fluid (BALF) collection, the right upper lung (RUL) was clamped and excised for determination of lung wet-to-dry weight ratios. Lungs were then perfused, collected, and frozen. Additional endpoints included heart weight, spleen weight, complete blood cell count (CBC), BALF total cell counts, protein and LDH concentration in BALF supernatant. Cardiac injury markers, NTpro-BNP was measured in the plasma. Separate animals were processed for histological evaluations. Results: A single acute chlorine (500 or 600 ppm) exposure caused about 50% mortality and excessive respiratory distress in survivors. Exposed animals exhibited increased clinical scores, reduced heart rate and decreased tissue oxygenation. ABG analysis revealed hypoxemia accompanied by respiratory and metabolic acidosis (or compensated respiratory acidosis) at all time points. Systemic inflammation was indicated by decrease in monocyte and lymphocyte counts along with increased eosinophils and neutrophils in the blood. Lung injury and edema were confirmed by significantly increased BALF protein, LDH concentrations, higher lung wet-to-dry weight ratios, and increase in total BALF cell counts at all time points measured. Histopathological evaluation of lung H&E sections revealed marked injury to the airway and alveolar regions. Cardiac involvement was evident from increased heart-to-body weight ratios, increased plasma NT-proBNP, and ultrastructural damage observed by electron microscopy. Conclusions: This study establishes a robust preclinical rat model that reproduces the systemic and physiological effects of acute chlorine exposure. Using two near LD50 concentrations we demonstrate severe respiratory distress, systemic inflammation, cardiopulmonary damage and altered pulmonary physiology in the exposed animals. This model provides a valuable platform that can guide future mechanistic studies and evaluation of novel therapeutics. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.