Short-term safety and local tolerability of repeated exposure to aerosolized hypochlorous acid dry fog in healthy adults: a randomized controlled pilot study

Background Hypochlorous acid (HOCI) is an oxidizing chlorine-based compound with broad antimicrobial activity and potential application as a dry-fog disinfectant in healthcare environments. However, human safety data for repeated exposure to aerosolized HOCI remain limited. This study evaluated the short-term safety and local tolerability of aerosolized HOCI dry fog under controlled conditions. Methods This prospective, randomized, open-label pilot study included healthy adult volunteers aged 18–65 years. Participants were enrolled into two independent exposure cohorts and randomized 1:1 to aerosolized HOCI or aerosolized 0.9% sodium chloride. The investigational product was a 300-ppm HOCI solution dispersed as dry fog at 20 mL/m 3 . In the short repeated exposure cohort, participants underwent three 3-min exposures per day for 3 consecutive days. In the prolonged repeated exposure cohort, participants underwent one 60-min exposure per day for 9 consecutive days. Safety assessments included adverse events, vital signs, hematology, routine biochemistry, serum cytokines, laryngological examination with rhinoscopy, nasal cytology, and conjunctival assessment. Results Eighty participants were randomized, 40 in each exposure cohort. No serious adverse events occurred, and no participant discontinued the study because of an adverse event. In the short repeated exposure cohort, adverse events were reported in 9/20 participants receiving HOCI and 3/20 receiving sodium chloride (45% vs. 15%; p = 0.082). In the prolonged repeated exposure cohort, adverse events were reported in 13/20 participants receiving HOCI and 0/20 receiving sodium chloride (65% vs. 0%; p < 0.001). All adverse events in the prolonged exposure cohort were mild; two were classified as definitely related to HOCI exposure. No persistent laryngological or conjunctival abnormalities were observed. Cytokine concentrations showed no consistent exposure-related pattern or sustained systemic inflammatory activation. Vital signs and routine laboratory parameters showed no clinically relevant systemic toxicity signal. Conclusion Under the controlled exposure conditions tested, aerosolized HOCI dry fog was generally well tolerated in healthy adults. Prolonged repeated exposure was associated with more frequent non-serious, mild adverse events, but without serious adverse events, persistent local irritation, systemic inflammatory activation, or clinically meaningful laboratory toxicity.