Hypochlorous acid is not an exotic chemical. It is the same oxidizing compound that neutrophils, the front-line cells of the innate immune system, generate to kill invading microbes, and formulated versions of it have long been used in wound care and topical antisepsis. Laboratory studies have demonstrated activity against bacteria, viruses, fungi, and spores, and under appropriate conditions the molecule decomposes into simple products without leaving persistent toxic residue. What has been missing is human data for a very different exposure route: dry-fog disinfection, in which the liquid is dispersed as an aerosol of fine particles that fills an entire room, potentially contacting the respiratory tract, eyes, skin, and mucous membranes of anyone present. Tolerability data from creams and wound irrigations cannot simply be extrapolated to repeated inhalation.

The trial, conducted at MTZ Clinical Research in Warsaw between May 5 and June 25, 2025, was designed as a stepwise safety evaluation. Volunteers aged 18 to 65 were enrolled into two independent cohorts and randomized one-to-one to hypochlorous acid or 0.9 percent sodium chloride. The investigational product was an aqueous solution containing 300 parts per million active chlorine, corresponding to 0.03 percent, with a pH between 4.5 and 5.5, dispersed at 20 milliliters per cubic meter. In the short repeated exposure cohort, participants underwent three three-minute exposures per day for three consecutive days, totaling 27 minutes of exposure. In the prolonged cohort, a separate group received one 60-minute exposure daily for nine consecutive days, accumulating 540 minutes in total. The prolonged cohort was initiated only after the principal investigator reviewed the safety profile of the short cohort.

The engineering behind the fog was as carefully specified as the clinical assessments. A prototype dry-fog system developed at the Military University of Technology in Warsaw used a 3-kilowatt compressor, a 50-liter compressed-air reservoir, and automatic pressure control operating at 2 bar. The generated aerosol had particles smaller than 9 micrometers, with a predominant fraction of roughly 5 micrometers, small enough to remain suspended and penetrate the airways. In the short cohort, exposures took place inside a 31.8-cubic-meter tent erected in a hospital ward, with six floor-level nozzles directed upward at 45 degrees; each cycle aerosolized 636 milliliters of solution, a nominal active chlorine dose of 6.0 milligrams per cubic meter. In the prolonged cohort, exposures occurred in a 47.3-cubic-meter hospital room, with 946 milliliters aerosolized per cycle at the same nominal dose. After each session, ventilation ducts discharged residual aerosol outside the building.

Chlorine gas levels were measured indicatively after aerosol generation, when no participants were present, using a portable electrochemical detector with a detection limit of 0.05 parts per million. In both cohorts the measured gaseous chlorine concentration was 0.19 parts per million, approximately 0.55 milligrams per cubic meter. The authors note that this detector quantified only gaseous chlorine and did not capture the total hypochlorous acid contained in aerosol particles, an important distinction when interpreting the exposure dose participants actually received.

Safety monitoring was unusually comprehensive for a pilot study of this size. Investigators tracked adverse events, vital signs, hematology, and routine biochemistry, and measured serum concentrations of six inflammatory cytokines: interleukin-1 beta, interleukin-6, interleukin-8, interleukin-10, interleukin-12, and tumor necrosis factor alpha. Local tolerability was assessed with laryngological examination including rhinoscopy, nasal cytology evaluating epithelial morphology and inflammatory cells, and conjunctival examination graded on a four-point scale. In the prolonged cohort, laryngological assessments were performed daily throughout the nine exposure days, and participants returned for follow-up visits up to 20 days after their final session.

The results split cleanly by exposure regimen. In the short cohort, adverse events were reported in 9 of 20 participants receiving hypochlorous acid versus 3 of 20 receiving saline, a difference of 45 percent versus 15 percent that did not reach statistical significance. Events in this cohort were mild or moderate, and the most frequent were headache or migraine, reported by five hypochlorous acid participants. Notably, hematological abnormalities such as leukopenia and neutropenia occurred in both treatment groups, which the authors interpret as a nonspecific pattern rather than a clear drug-related signal. In the prolonged cohort, the contrast was stark: 13 of 20 hypochlorous acid participants reported adverse events compared with none of the 20 saline participants, a difference that was highly statistically significant. Every event in this cohort was mild, and only two were classified as definitely related to the exposure. The most common categories were mucosal irritation, gastrointestinal symptoms such as nausea, and neurological symptoms such as headache or dizziness.

The deeper safety assessments told a calmer story. Cytokine concentrations fluctuated over time, including modest numerical changes in interleukin-1 beta and interleukin-8, but final exposure-day values did not differ significantly between groups, and the authors found no consistent pattern suggesting sustained systemic inflammatory activation. Vital signs remained stable, with isolated between-group differences that were small, inconsistent, and judged not clinically meaningful. Routine laboratory tests revealed no clinically relevant organ-toxicity signal. On local examination, no clinically significant laryngological abnormalities were observed in either cohort. Transient mucosal redness appeared sporadically in the prolonged cohort, affecting between 5 and 10.5 percent of hypochlorous acid participants on individual assessment days, but without edema, discharge, pain, or need for treatment, and similar isolated findings occurred in saline participants. Mild conjunctival abnormalities were transient and occurred at similar frequencies in both groups, with no persistence at follow-up.

The trial builds on a preclinical foundation that the authors describe in detail. In vitro dry-fog experiments using the same 300-ppm solution showed no significant cytotoxic or genotoxic effects under short-exposure conditions, although higher concentrations or longer repeated exposure were associated with cytotoxic and genotoxic effects in cell models. Before the first human exposure, a study at Jagiellonian University Medical College exposed 238 Wistar rats to hypochlorous acid aerosol at 300 ppm and 20 milliliters per cubic meter, observing no unequivocal indicators of acute toxicity, respiratory tract injury, or hepatic or renal damage. Low-concentration gaseous hypochlorous acid also did not impair the viability or ciliary activity of human respiratory epithelial cells in laboratory models. The new trial extends these experimental observations into controlled human exposure data.

The authors are careful about what the study does and does not establish. As an exploratory pilot with 80 participants, no formal sample size calculation, and an open-label design that may have influenced reporting of mild subjective symptoms, it cannot detect rare adverse events or small between-group differences, and no adjustment for multiple comparisons was applied. All participants were healthy adults aged 18 to 65, so the findings cannot be generalized to children, older adults, or people with asthma, chronic obstructive pulmonary disease, cardiovascular disease, immunosuppression, or heightened mucosal sensitivity. Follow-up was limited to 10 days after short exposure and 20 days after prolonged exposure, leaving delayed or cumulative effects unexplored. Real-world healthcare environments also differ from the study conditions in room size, ventilation, fogging device, concentration, and timing of human re-entry. Within those boundaries, the message is measured: under the controlled conditions tested, aerosolized hypochlorous acid dry fog was generally well tolerated in healthy adults, with prolonged exposure producing more frequent but mild, transient, non-serious symptoms and no evidence of persistent local injury or systemic toxicity.

Subject of Research: Short-term safety and local tolerability of repeated aerosolized hypochlorous acid dry-fog exposure in healthy adults

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

Article References: Sanak, T., Zakrzewska, M., Bil, J., Krzowski, Ł., Witkowski, G., & Mierczyk, Z. (2026). Short-term safety and local tolerability of repeated exposure to aerosolized hypochlorous acid dry fog in healthy adults: a randomized controlled pilot study. Frontiers in Public Health, 14, Article 1970564. https://doi.org/10.3389/fpubh.2026.1970564

Image Credits: AI Generated

DOI: 10.3389/fpubh.2026.1970564

Keywords: hypochlorous acid, dry fog, disinfection, aerosol exposure, occupational health, randomized controlled trial, healthcare-associated infections, local tolerability, adverse events, cytokines, pilot study, Short-term