Annals of Pharmacology and Pharmaceutics

Research Article
Published: 07 Mar, 2022

Concentrations of Chlorine Dioxide Gas in Room Air
During the Use of Its Generator and Spray
Norio Ogata* and Michiyo Shimokawa
Taiko Pharmaceutical Co., Ltd., Osaka, Japan

Abstract
Chlorine dioxide gas has strong bactericidal and virucidal activities against many microbes, and isfrequently used to disinfect microbes. However, its concentration should be controlled accurately
in rooms so that it remains effective enough to kill microbes, but is safe for humans. Therefore, it isimportant to know how much chlorine dioxide gas is delivered from commonly used domestic gasgenerating devices or spray units. The aim of this paper was to measure concentrations of chlorine
dioxide gas in room air delivered from a common market-sold gas-generating device (canister) and
its aqueous solution delivered by its spray unit. The chlorine dioxide gas concentration in room
air was measured after the canister was placed in a room or after the chlorine dioxide aqueous
solution was sprayed in a room. Particle diameters and their numbers in room air were alsomeasured after the use of the spray. The chlorine dioxide gas concentration was 0.007 ppmv to0.026 ppmv (volume ratio) 60 days after placing the canister in the room. The rate of decay
constant during 60 days was 5.6 day-1. When the chlorine dioxide aqueous solution was sprayed ina room, the gas concentration was 0.003 ppmv to 0.019 ppmv during 60 min with a rate of decay
constant of 12.7 min-1. The concentrations of chlorine dioxide gas were safe to humans present in
the room, and were sufficient to effectively inactivate microbes in the room. These results justify
the safe and effective use of chlorine dioxide gas-generating devices and spray units to disinfectmicrobes, such as SARS-CoV-2 and highly pathogenic avian influenza virus, in closed and poorly
ventilated areas without evacuating humans.
Keywords: Chlorine dioxide; Gas; Spray; Aerosol; Disinfection; SARS-CoV-2

Introduction
OPEN ACCESS*Correspondence:
Norio Ogata, Taiko Pharmaceutical Co.,
Ltd., 1-4-1 Nishihonmachi, Nishiku,
Osaka 550-0005, Japan,
E-mail: nogata7@yahoo.co.jp
Received Date: 02 Feb 2022
Accepted Date: 22 Feb 2022
Published Date: 07 Mar 2022
Citation:
Ogata N, Shimokawa M.
Concentrations of Chlorine Dioxide
Gas in Room Air During the Use of Its
Generator and Spray. Ann Pharmacol
Pharm. 2022; 7(1): 1205.
Copyright © 2022 Norio Ogata. This is
an open access article distributed under
the Creative Commons Attribution
License, which permits unrestricted
use, distribution, and reproduction inany medium, provided the original work
is properly cited.

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Chlorine Dioxide (ClO2) (CD) is yellow gas that is a relatively stable free radical at room
temperature [1-3]. It is usually generated by mixing an acid with sodium chlorite (NaClO2) [4]. It
has a strong oxidizing activity against many organic compounds, such as proteins [4], and it
oxidizes amino acids, such as tryptophan [4,5], and tyrosine [6], and denatures proteins [4]. The
oxidizing activity of CD inhibited the biological activities of microbes [1,3]. Indeed, Morino andhis coworkers clearly demonstrated that CD inactivated various microbes [7-12]. Furthermore, it
was demonstrated that CD inhibited the growth of influenza virus [13,14]. In addition, CD
protected mice from infection by influenza virus [13], and this antivirus activity was related tooxidation of a specific tryptophan residue in hemagglutinin, a viral protein required for binding toa host cell receptor [15]. It is also reported recently that CD inhibited binding of the spike proteinof the SARS-CoV-2 virus, an etiological virus of COVID-19 disease, to its human receptor,
angiotensin converting enzyme 2 [16-18]. In view of the current outbreaks of COVID-19 andhighly pathogenic avian influenza viruses, a safe and effective disinfection system for use in rooms
or closed spaces is strongly and urgently needed.
Various CD-generating devices are currently available including large disinfecting machines
for buildings and small devices for tabletop household use to disinfect room air. Other household
devices use CD aqueous solutions delivered as an aerosol from a spray unit (usually a bottle) in aroom. These devices are commonly sold. Although CD gas at appropriate concentrations is very
effective at inactivating microbes in the air [7-11,13,14,19-21], very high concentrations of CD are
harmful to animals including humans [22], and strict regulations regarding the concentration of CD
gas are needed when it is used in the presence of humans to avoid human intoxication [23].
Indeed, the American Occupational Safety and Health Administration (OSHA) states that thepermissible exposure limit (PEL) concentration of CD gas for human in terms of 8-h timeweighted average should be 0.1 ppmv (parts per million volume, a volume/volume ratio) [23].

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Results

Regarding the above-mentioned CD devices, it is unclear whether
CD gas concentrations generated from the above-mentioned devices
are reasonable, in terms of safety [24], and effectiveness against various
microbes [7-12]. The concentrations of CD gas generated from theabove-mentioned various devices should be high enough to inactivate
microbes in the ambient air of a room, but should be low enough to
be safe to humans present in the room during its use. Therefore, it isimportant to measure and demonstrate the gas concentrations of CD
in a room during the use of common CD-generating devices. Here,
we measured CD gas concentrations in a room generated from a CD
gas-generating canister and CD gas concentrations present in room
air soon after spraying a CD aqueous solution from a CD spraying
unit.

The CD gas concentration at 24.5 ± 0.7°C (average ± standard
deviation, n=39) two days after the commencement of the CD gas
generation from the canister is shown in Figure 1.
As shown in Figure 1, the CD gas concentration depended upon
the relative humidity of the room. A long-term change in the CD
gas concentration at 13.2°C and at 52% relative humidity is shownin Figure 2. The decay curve of this gas concentration was fitted toan exponential decay curve with a rate constant of decay of 5.6 day-1.
The CD gas concentration at 23.3ºC and 26% relative humidity
after spraying the CD aqueous solution is shown in Figure 3. When the
decay curve of the CD gas concentration was fitted to an exponential
decay curve, the rate constant of the decay was 12.7 min-1.

Materials and Methods
A tabletop CD gas generator and domestic use canister (CleverinG, 150 g) were obtained from Taiko Pharmaceutical Co., Ltd. (Osaka,
Japan). The canister contains a separated sachet of sodium dihydrogen
phosphate powder (as an acid) and a solution of sodium chlorite. The
CD gas generator canister starts to generate CD gas when the powder
is mixed with the solution. No gas is generated unless the powder
is mixed with the solution. The generation of the CD gas gradually
decreases after the mixing of the powder with the solution. The shelf
life of the CD shown on the label on the canister is two months
after mixing the powder with the solution. In this experiment, theconcentration of the CD gas was measured 2 days after mixing thepowder with the solution. Then, the CD gas concentration in a room
generated from the canister was measured at six evenly separated
points and at 0.2 m to 1.5 m height in a room of 3.40 by 4.83 m floor
size (16.4 m) and a 46.0 m3 room volume. The room contained asquare desk of 1.3 by 2.6 m in the center surrounded by six chairs. The
ventilation system in the room was turned off during the experiment.
Lights in the room were always on during the experiment. Humidity inthe room was controlled by a humidifier (Proscenia 808C, Shenzhen
Pisonis Technology, and Shenzhen, China) and dehumidifier (Iris
Ohyama DCE-6515, Sendai, Japan). One CD canister was placed in
the room. CD gas concentrations were measured using a Midas Gas
Detector ClO2 (Honeywell, New Jersey, USA).

The distribution of diameters of aerosol particles after using thespray unit of the CD aqueous solution in the room was next measured.
The diameters of the aerosols distributed in the room 2 min to 5 minafter spraying and their diameters are shown in Figure 4. It is worth
noting that a small peak of 1.0 µm to 2.0 µm diameter was found in

Figure 1: The short-term measurement of concentrations of chlorine dioxide
gas generated from a tabletop domestic canister placed in a room of 16.4 m2
floor size and 46.0 m3 volume at 25.9 ± 1.1°C (n=39). The relative humidity
was 27.4 ± 1.1% (n=13) (filled circles), 46.2 ± 1.4% (n=13) (triangles) or 60.4
± 2.6% (n=13) (open circles). The data were collected two days after thecommencement of the gas generation from the canister. Each data point
represents an average ± standard deviation of the measurements at six
different places in the room.

A spray unit (a bottle with a lever on its top for domestic use)
(Cleverin Spray, Taiko Pharmaceutical Co., Ltd.) contains 300 mL of
a 1.9 mmol/L (130 ppm (w/w)) aqueous solution of CD. An aerosol
is delivered from the orifice of the unit when the lever on the top issqueezed. One squeeze of the handle lever delivers 1.06 mL ± 0.01 mL(n=5) of the solution inside the bottle of the unit as an aerosol. The
CD gas concentration in the room 2 min to 5 min after the spraying
was measured as above at five evenly separated places in the room. To
measure the particle size and density (number of particles per unit
volume of air), a laser particle counter (Rion model KC-52, Tokyo,
Japan) was used. It aspirated 1 L of room air during a period of 21 s
into the device at each session of the measurement, and the diameterof each aerosol particle and density (counted number in 1 L of theaspirated room air) are displayed on the counter. Background dataobtained in the same room just before spraying CD were subtracted
from the measured data obtained after spraying. This counter wasplaced 1.2 m above the floor at five evenly separate places in the room
for the measurement. The fittings of the observed data, as a one-phase
exponential decay function, were performed using GraphPad Prism
software (GraphPad, San Diego, CA, USA).
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Figure 2: The long-term measurement of concentrations of chlorine dioxide
gas generated from a table-top canister (filled circles). The exponential
decay curve fitted to the data is shown by a broken line, with a rate constantof decay of 5.6 day-1. Each data point represents an average ± standard
deviation of the measurements at six different places in the room.

2

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unclear. One possibility is that water reacts or combines with gaseous
CD, and this CD water complex is the actual substance detected by
the analyzer.
According to the American OSHA, the PEL of CD gas is 0.1
ppmv [23]. As shown in Figures 1-3, the concentrations of CD gas
delivered from the domestic CD devices used in this study were
within the range of 0.01 ppmv to 0.06 ppmv. These results indicatethat these devices can be used within the safe limit of CD gas forhumans. However, CD gas in the range of 0.01 ppmv to 0.02 ppmv
was reported to be effective at inactivating viruses and bacteria [19].
These findings related to the safety of humans and effectivenessagainst microbes strongly suggest the usefulness of CD gas devices
for the prevention of serious microbial infectious diseases, such as
SARS-CoV-2 and highly pathogenic avian influenza virus, in clouded
and poorly ventilated arias.

Figure 3: The measurement of concentrations of chlorine dioxide gas in aroom after spraying the chlorine dioxide aqueous solution (filled circles). The
exponential decay curve fitted to the data is shown by a broken line with arate constant of decay of 12.7 min-1. Each data point represents an average ±standard error of measurements at six different places in the room.

The concentrations of the CD gas can remain within an effective[19], and non-toxic level to humans (≤ 0.1 ppmv) using the CDdomestic devices used in this study (Figures 1-3) [23]. It is
important to note that the shelf life of the CD gas devices should
always be considered (Figure 2). In this study, the concentration of
CD gas delivered in closed spaces was not precisely controlled. The
CD gas concentration decreased with time (Figures 1-3). Therefore,
it should be borne in mind that the CD gas devices should be
renewed before their shelf life expires so that the effective
concentration of CD gas delivered from the device is guaranteed to
be within the useful range. A large machine-type CD generating
device for buildings can generate and deliver CD gas using a feedback monitoring system so that an effective and safe concentrationof CD gas is maintained. The reason for the decreased concentrationof CD gas is unclear. One possibility is that the concentration of the
CD gas decreases after its reaction with various organic substances
floating in the room air or organic substances present on objects in
the room [4,25]. It is also possible that CD gas adheres to the surfaceof various objects in the room. The fact that CD absorbs light of
358.5 nm wave length with molar extinction coefficient of 1250 ± 3
M-1cm-1 [26], also suggests that a photochemical reaction of CD gas
with light in the room occurs and this may explain the decrease in
CD gas in the room, Indeed, the photodecomposition of CD withultraviolet light was reported by Cosson and Ernst [27].

Figure 4: Distribution of diameters and densities of aerosol particles ofchlorine dioxide aqueous solution delivered from a spray unit in a room. The
distribution of aerosol diameters from the spray unit was 2 min to 5 min after
spraying. The number of aerosol particles measured tended to decrease
after aspirating 1 L of room air as measured by a laser particle counter. Eachbar represents the average ± standard deviation of five measurements.

this distribution (Figure 4).

Discussion
We measured the CD concentration in the room after spraying
the CD aqueous solution as an aerosol (Figure 3). One squeeze of thespray unit delivered 1.06 mL ± 0.01 mL (n=5) of the CD aqueous
solution at a concentration of 1.9 mmol/L. After 21 squeezes were
performed in a 46.0 m3 room, 0.042 × 10-3 mol (1.9 × 10-3 × 1.06 × 10-3
× 21 = 0.042 × 10-3) of CD was calculated to be delivered as aerosol
particles. Using the ideal gas law, we calculated the volume V of CDgas delivered from the spray unit. It was calculated as follows usinga gas constant of 8.3145 J•K-1•mol-1, absolute temperature of (273 +
23.3) K and atmospheric pressure of 101325 Pa:

Conclusion
The CD gas generating device and CD spray unit used in thisstudy delivered sufficient CD gas concentrations that were effectiveat inactivating microbes in a room and safe for humans present in theroom. The results justify the use of CD-generating and CD spraying
devices for use in closed spaces without the need to evacuate humans.
Furthermore, the use of CD gas is the most effective method tocounteract the spread of serious infectious microbial diseases such as
SARS-CoV-2 and highly pathogenic avian influenza virus.

V= 0.042 × 10-3 × 8.3145 × (273+23.3)/101325 = 1.02 × 10-3 L.
Because this volume of CD gas was calculated to be present in a 46.0
m3 room, its concentration, in terms of ppmv, was 1.02 × 10-3 L/(46 × 103) L=0.022 ppmv. This value is in good agreement with theobserved result of 0.019 ppmv (Figure 3). It is to be noted that theconcentration of the CD gas differed markedly depending upon therelative humidity (Figure 1). However, why the CD gas concentrationdiffers so much depending upon the change in the relative humidity is

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Conflicts of Interest
All authors are employees of Taiko Pharmaceutical Co., Ltd.

Acknowledgement
This work was supported by Taiko Pharmaceutical Co., Ltd.
We are grateful for the contributions of Kazuhiko Taguchi, Kouichi
Taura and Genshi Izutsu.
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