Antiviral Effect of Chlorine Dioxide against Influenza Virus and Its A…
페이지 정보
본문
Antiviral Effect of Chlorine Dioxide against Influenza Virus and Its Application for Infection Control
Taiko Pharmaceutical Co., Ltd, 3-34-14 Uchihonmachi, Suita, Osaka, 564-0032 Japan
Abstract: Influenza is a respiratory tract infection, causing pandemic outbreaks. Spanish flu (A/H1N1), a pandemic oc- curred between 1918 and 1919, tolled patients and fatalities of 500 million and 50 million, respectively. Recently, human infection with highly pathogenic avian influenza A/H5N1 and swine influenza [Pandemic (H1N1) 2009] was reported. Because of the population explosion and busy global aircraft traffics, Pandemic (H1N1) 2009 is rapidly spreading world- wide. In addition, it is seriously concerned that H5N1 influenza pandemic would emerge in the very near future. The pandemic will cause the freeze of social activity and the crisis of business continuity, having a serious impact on the global economy consequently. It is fervently desired that efficient methods of infection control against influenza pandemic be developed.
Chlorine dioxide (ClO2) has a strong antiviral effect, and can disinfect the surface of object and the air in space. In recent
study on interaction between ClO2 and protein, ClO2 oxidatively modified tyrosine and tryptophan residues, and the pro-
tein was structurally denatured. Since hemagglutinin and neuraminidase of influenza virus A/H1N1 were inactivated by the reaction with ClO2, it is likely that denaturation of the proteins caused inactivation of the virus. A low concentration
(0.03 ppm) of ClO2 gas, where people can stay for a long period of time without any harmful effect, prevented the death
of mice caused by infection of influenza virus delivered as aerosol. We review current information based on the efficiency of ClO2 solution and gas, and also discuss the application of ClO2 against influenza pandemics outbreak.
Keywords: Chlorine dioxide, influenza, pandemic.
4. SAFETY OF CHLORINE DIOXIDE
4.1. Chlorine Dioxide Solution
ClO2 has been used to disinfect the tap water in the
U.S.A., and a review article was published by EPA [51]. Hereinafter, we extracted the content of this report.
As a result of oral administration of ClO2 solution for 90
days in rats, the lowest-observed-adverse-effect level (LOAEL) was 25 ppm (2 mg/kg/day). Also, from another experiment in which ClO2 solution was orally administered
for two years in rats, the no-observed-adverse-effect level (NOAEL) was 10 ppm (1.3 mg/kg/day) [51-53]. In an ex- periment in which African green monkeys were orally ad- ministered with ClO2 solution for six weeks, NOAEL was 30
ppm (3.5 mg/kg/day) and LOAEL was 100 ppm (9.5 mg/kg/ day) [51, 54]. Also, a human study was conducted and there was no toxic signs observed after oral intake of tap water containing 5 ppm of ClO2 for 12 weeks [51, 55]. As to the
metabolism of ClO2, an investigation was made by a single
oral administration of radiolabeled 36ClO2 in rats, which re-
vealed that the plasma 36Cl level reached the peak two hours
after the administration, and 30% of the radioactivity was excreted in urine by 72 hours after the administration [51, 56]. Approximately 80% of 36Cl were in the form of Cl-, and
most of the remaining radioactivity was ClO2-, with a small
amount of ClO3- [57].
4.2. Chlorine Dioxide Gas
Dalhamn performed an inhalation toxicity study in rats [58]. Some rats died after the exposure of as high as 260 ppm of ClO2 gas for two hours. On the other hand, after the
exposure of ClO2 gas at 0 or 0.1 ppm (average level during
ten weeks, ranging from 0.05 to 0.3 ppm) for five hours a day and seven days a week for ten weeks, neither death nor any toxic signs were observed. Our ClO2 products have an
advantage of controlling the concentration of ClO2 below 0.1
ppm in the space. This low concentration is lower than the weighted average of eight hours per day allowed by OSHA as the long term exposure, the weighted average of ten hour labor allowed by the National Institute for Occupation Safety and Health (NIOSH, U.S.A.) [59], and the standard level for eight hours a day for 40 hours a week allowed by the Ameri- can Conference of Governmental Industrial Hygienist (ACGIH, U.S.A.) [60]. From these findings, it may be as- sumed that there is little toxicity concern about the use of the low concentration of ClO2 gas below 0.1 ppm.