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466epithelial cells and eventually emphysema occurs7). Therefore, although the effectiveness of ozone has been proven, its use, especially in terms of concen-trations and exposure periods, should be carefully controlled to avoid adverse effects. Chlorine dioxide Chlorine dioxide inactivates many viruses. For instance, the inactivation activity of chlorine dioxide against feline calicivirus and influenza A virus was 0.05 ppmv for 5 h, and the reduction of virus was to a level of 10-5 8). Inactivation of viruses by chlorine dioxide aqueous solution was also demonstrated. Sanekata et al. found that human influenza virus, measles virus, canine distemper virus, human herpes virus, human and canine adenoviruses, and canine parvovirus were inactivated by chlorine dioxide aqueous solution9). Hepatitis A virus was completely inactivated after 10 min in a 7.5 mg/L aqueous solution of chlorine dioxide10). The cause of inactivation of the virus was related to the complete loss of antigenicity of the virus and the loss of the 5’ non-translated region of its genome10, 11). Chlorine dioxide is a relatively stable free radical12, 13) that denatures proteins by oxidizing their tyrosine and tryptophan residues14-16). Ogata et al demonstrated that chlorine dioxide is effective against the SARS- CoV-2 and the mechanisms of action that inhibits the binding of the spike protein of the SARS-CoV-2 on ACE2 through the action of chlorine dioxide has been verified17).Akamatsu et al. demonstrated the safety of a low concentration of chlorine dioxide in an animal experiment. Rats exposed to whole-body inhalation of 0.1 ppmv chlorine dioxide for six months with a two-week recovery period showed no differences in body weight gain, food intake, water intake, rela-tive organ weight, blood biochemistry data, and hematology examination data compared with control rats not exposed to chlorine dioxide18). In their experiment, rats were exposed to chlorine dioxide for 24 hours/day and 7 days/week. Further-more, the concentration of gas was precisely controlled within ± 25% of the target concentra-tion18). Their result strongly suggests that chlorine dioxide at or below 0.1 ppmv can be used safely to disinfect room air in the presence of humans for a long period. A concentration of 0.1 ppmv chlorine dioxide was effective at inactivating virus in room air19-21). The US Department of Labor of the Occu-pational Safety and Health Administration (OSHA) stated that the permissible exposure concentration of chlorine dioxide for humans for an 8-hour time-weighted average was 0.1 ppmv22). Dalhamn reported a no-observed adverse-effect-level (NOAEL) of 0.1 ppmv in rats exposed to chlorine dioxide for 5 hours/day for 10 weeks23). Therefore, chlorine dioxide can be used effectively and safely at relatively low concentrations against viruses and bacteria.Ultraviolet (UV) UV light and photochemical reactions have been used to inactivate viruses. Regarding UV light irra-diation, 254 nm light is usually used24, 25). While this method is quite useful for inactivating viruses floating in room air or stuck on objects in a room, its disadvantages include that it cannot inactivate virus in the blind spots of a room where UV light does not penetrate. Furthermore, humans cannot be present because UV irradiation causes cata-racts26) and dermal neoplasms27). There are other similar methods that can inactivate viruses. For instance, viruses are inactivated by photochemical reactions using titanium oxide28). However, this method is useful predominantly to inactivate viruses stuck on objects. Furthermore, it has not been proven to be effective at inactivating virus floating in room air or away from object surfaces.Hypochlorous acid (HClO)Aerosol sprays are also used to disinfect room air containing pathological viruses. For this purpose, hypochlorous acid in water is frequently used as a spray to inactivate avian influenza virus, Newcastle disease virus, and coronavirus29, 30). An aqueous solution of sodium hypochlorite (NaClO) was also used as a spray to disinfect viruses31, 32). However, both hypochlorous acid and sodium hypochlorite solution sprays are primarily used to disinfect viruses on the surfaces of objects. While useful, they are rarely used to disinfect room air, and their effectiveness at inactivating viruses floating in room air has not been demonstrated quantitatively. Ventilation The mechanical or natural ventilation of room air is a simple, effective, and inexpensive way to mini-mize the airborne transmission of respiratory

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