Pulmonary Toxicity and Biodistribution of Sodium Fluoride in Male Rats Following Intratracheal Instillation and Nose-Only Inhalation Exposure

Pulmonary exposure to sodium fluoride (NaF) may occur in certain consumer-product and occupational settings, but its pulmonary toxicity and systemic biodistribution remain insufficiently characterized. This study investigated acute pulmonary inflammatory responses and biodistribution kinetics in rats following a single airway exposure to NaF. Non-radioactive NaF was administered in 7-week-old male Sprague-Dawley rats by intratracheal instillation at 0.75, 1.5, or 3.0 mg/rat, and pulmonary responses were evaluated at 1, 7, and 28 days using bronchoalveolar lavage fluid analysis and histopathology. Biodistribution was assessed using positron emission tomography/computed tomography (PET/CT) and organ gamma counting after administration of fluorine-18 radiolabeled sodium fluoride ([18F]NaF). NaF induced acute pulmonary inflammation characterized by increased neutrophils and eosinophils, elevated lactate dehydrogenase activity, and increased levels of tumor necrosis factor-alpha and eotaxin. These inflammatory responses gradually resolved by 7 and 28 days after exposure. PET/CT analysis showed rapid pulmonary clearance of NaF, with concurrent accumulation in bone and predominant urinary excretion within approximately 30 min after administration. These findings indicate that single airway exposure to NaF induces acute but reversible pulmonary inflammation despite rapid lung clearance, and call for evaluation under repeated or exposure-relevant conditions and in both sexes, as pulmonary toxicity was assessed only in male rats and only by intratracheal instillation.