Benzalkonium chloride accumulates and causes toxicity in the heart and pancreas following the repeated inhalation exposures.

Benzalkonium chloride (BKC) is used as a disinfectant and preservative in aerosolized formulations, including various household cleaning products. Although primary organ toxicity of BKC has been reported, secondary organ toxicity after inhalation exposure remains unclear. This study evaluated the biodistribution of radiolabeled [14C] BKC using quantitative whole-body autoradiography in rats. Autoradiography after a single intranasal administration revealed significant accumulation and prolonged retention of radioactivity in the heart and pancreas, suggesting potential secondary organ toxicity following inhalation. To assess potential toxic effects without confounding pulmonary inflammation, rats were administered repeated intratracheal instillations (10 times, 3-day intervals) at non-inflammatory doses of 50 and 100 μg/rat. Despite the absence of pulmonary toxicity, BKC accumulation in the heart caused inflammation in the pericardium and myocardium, accompanied by transcriptomic alterations linked to mitochondrial dysfunction, reactive oxygen species (ROS) generation, inflammation, and cell death. Additionally, pancreas tissues exhibited histopathological changes, including acinar cell vacuolization, and gene expression changes associated with ROS generation, inflammation, and disrupted glucose regulation. These findings suggest that repeated inhalation exposure to BKC can damage the heart and pancreas at pulmonary non-toxic and occupationally relevant doses due to accumulation in these secondary organs, warranting further research to clarify hazards and mechanisms.