Jeftri 2022 JML Systematic Review ClO2 Disinfectant
Jeftri 2022 JML Systematic Review ClO2 Disinfectant
Jeftri 2022 JML Systematic Review ClO2 Disinfectant
JML | REVIEW
Author Affiliations
1. PAP Rashidah Sa'adatul Bolkiah Institute of Health Sciences, Universiti Brunei Darussalam, Gadong, Brunei Darussalam
2. School of Pharmacy, KPJ Healthcare University College, Nilai, Malaysia
3. Faculty of Pharmacy, University of Cyberjaya, Cyberjaya, Malaysia
4. College of Pharmacy, National University of Science and Technology, Muscat, Oman
5. Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Malaysia
6. College of Pharmacy, University of Science and Technology of Fujairah, Fujairah, United Arab Emirates
7. College of Medical Sciences, Azal University for Human Development, Sana'a, Yemen
ABSTRACT
The COVID-19 pandemic has tremendously increased the production and sales of disinfectants. This study aimed to
systematically review and analyze the efficacy and safety of chlorine dioxide as a disinfectant. The literature relating
to the use of chlorine dioxide as a disinfectant was systematically reviewed in January 2021 using databases such as
PubMed, Science Direct, and Google Scholar. Inclusion criteria were studies that investigated the use of chlorine
dioxide to assess the efficacy, safety, and impact of chlorine dioxide as a disinfectant. Out of the 33 included studies,
14 studies focused on the disinfectant efficacy of chlorine dioxide, 8 studies expounded on the safety and toxicity in
humans and animals, and 15 studies discussed the impact, such as water treatment disinfection using chlorine diox-
ide. Chlorine dioxide is a safe and effective disinfectant, even at concentrations as low as 20 to 30 mg/L. Moreover,
the efficacy of chlorine dioxide is mostly independent of pH. Chlorine dioxide can be effectively used to disinfect
drinking water without much alteration of palatability and can also be used to destroy pathogenic microbes, including
viruses, bacteria, and fungi from vegetables and fruits. Our review confirms that chlorine dioxide is effective against
the resistant Mycobacterium, H1N1, and other influenza viruses. Studies generally support the use of chlorine dioxide
as a disinfectant. The concentration deemed safe for usage still needs to be determined on a case-by-case basis.
obtained is provided in Supplementary information 1: Efficacy by 30% and 65%, respectively. Spraying disinfectant twice a day
of chlorine dioxide; Supplementary information 2: Safety of reduced the bacterial load by 74% and the fungal load by 38%.
chlorine dioxide and Supplementary information 3: Impact of Watamoto et al. reported that disinfection of dental instruments
chlorine dioxide on water (drinking water and wastewater). using 0.02% chlorine dioxide completely disinfected the instru-
ment within 10 minutes of application [15]. The chlorine diox-
ide solution at 0.02% concentration even removed HCV from
DISCUSSION the contaminated instruments. Thus, the authors suggested that
chlorine dioxide and ultrasonic disinfectants provide a suitable
Disinfection efficacy using chlorine dioxide alternative to other potentially toxic disinfectants. Moreover, Xue
et al. (2013) informed the effects of chlorine dioxide on human
The articles obtained for this section were published from rotavirus [16]. They found chlorine dioxide to be more effective
1998 to 2019. The most recent article evaluated the effectiveness than chlorine alone. The efficiency of disinfection is defined using
of chlorine dioxide as a sanitizer on mixed salad to reduce the the Ct value as the product of disinfectant concentration (milli-
presence of human norovirus [10]. The study evaluated the ef- gram per liter) and the contact time (min). A Ct value of chlorine
ficacy of a chlorine dioxide solution prepared using 2000 mg/L dioxide and chlorine of 1.21–2.47 mg/L and 5.55–5.59 min, re-
of chlorine gas dissolved in water. This chlorine dioxide solution spectively, were required at 20°C for a 4-log reduction of HRV.
was tested against various bacteria and found to be effective in Furthermore, Miura and Shibata (2010) described the effi-
5–20 mg/L with a 98.2% reduction in bacterial activity, where- cacy of chlorine dioxide against the influenza virus [17]. They
as the antiviral effects against H1NI and EV71 strains were ob- suggested that chlorine dioxide has strong disinfectant activity at
served at 46.39 mg/L and 84.65 mg/L, respectively. The pre- a concentration of 0.03%. Their review suggested that chlorine
pared chlorine dioxide solution was safe when tested in rabbits at dioxide, either in a solution or gaseous form, could be effectively
50 mg/L concentration. Moreover, 40 mg/L in drinking water used to control influenza due to its strong antiviral effects used to
did not show any toxic symptoms when tested for subchronic oral control H1N1 infections. Other articles that show the efficacy of
toxicity. The most similar article to this review was published by chlorine dioxide on bacteria were published by Valderrama et al.,
Ma et al., which evaluates the efficacy and safety of chlorine diox- Taylor et al. and Foschino et al., where Valderrama et al. reported
ide solution [11]. Chlorine dioxide was effective against the virus a 4-log unit reduction in the Listeria monocytogenes upon treat-
strain at 20 mg/L, reducing virus infectivity by at least 3-log units ment with 3 mg/L chlorine dioxide within 90 seconds [18–20].
after 1 min. Other studies focused on the efficacy of oxidizing However, the efficacy of chlorine dioxide was not the same for
disinfectants such as chlorine dioxide to inactivate murine noro- 20% CaCl2 brine solutions; this inefficacy could be due to the
virus [12] and on the inactivation of bacteria and viruses when a interference or presence of the divalent cations and organic ma-
low concentration of chlorine dioxide gas was used [13]. terials. Taylor et al. showed disinfecting properties of disinfectants
Three articles obtained from 2013 were published by Hsu on Mycobacterium avium, and Foschino et al. illustrated its killing
and Huang (2013), Watamoto et al. (2013), and Xue et al. (2013) effects on Escherichia coli [19, 20]. Zhu et al. distinctly narrated
[14–16]. Hsu and Huang (2013) focused on the disinfection effi- the preparation of solid chlorine dioxide-based disinfectant pow-
cacy of chlorine dioxide gas [14]. The study found that the one- der and its efficacy [21]. This disinfectant powder was diluted
time disinfection process reduced the fungal and bacterial loads with water before use and tested against Staphylococcus aureus and
Escherichia coli. The study concluded that vegetative forms of bac- ence of drinking water treatment on chlorine dioxide consump-
teria could be killed using 100 mg/L chlorine dioxide solution. tion [31, 32].
Moreover, the same concentration of chlorine dioxide effectively Lenes et al. assessed the removal and inactivation of influen-
disinfected the surface objects. The powder was found to be safe za viruses using a drinking water treatment, while Wondergem
and non-irritant. and van Dijk-Looijard evaluated the use of chlorine dioxide as
Gagnon et al. published an article in 2005 showing the effi- a post-disinfectant for drinking water [33, 34]. The remaining
cacy of chlorine dioxide in drinking water biofilms [22]. Their eight articles reported on water disinfection in general. These
study revealed that chlorine dioxide (0.5 mg/L) has greater ef- eight articles were published by Wen et al., Casini et al., Qiao
ficacy against heterotrophic bacteria than chlorite ions. The last et al., Heiner et al., Liu and Lin, Barbeau et al., Chauret et al.,
article to be mentioned was published in 2003 by Jean et al., fo- and Huber et al. for water disinfection in general [35–42]. Wen
cusing on the effectiveness of commercial disinfectants, including et al. evaluated the inactivation of fungal spores in groundwater
chlorine dioxide, to inactivate the Hepatitis A virus [23]. They in- disinfected using chlorine dioxide [35]. Casini et al. provided in-
vestigated six commercially available disinfectants, including 2% formation on the long-term effect of hospital water network dis-
stabilized chlorine dioxide solution against Hepatitis A virus in infection on Legionella and waterborne bacteria [36]. Qiao et al.
suspensions or on the food and other surfaces. Disinfectants were evaluated the inactivation of resistant Mycobacterium mucogenicum
more effective in suspensions compared to their efficacy against in water due to chlorine resistance [37]. Heiner et al. compared
the virus on food or other surfaces. Chlorine dioxide 30 mg/L a variety of field water disinfection tablets [38]. Liu and Lin
demonstrated a 0.96 and 1.01 viral reduction (log) at 4°C and studied the application of chlorine dioxide for water disinfection
22°C, respectively. [39]. Barbeau et al. showed the impact of water quality in natural
waters [40]. Chauret et al. showed the effect of disinfectants on
Safety and toxicity of chlorine dioxide disinfectant micro-organisms in the water distribution systems, and Huber
et al. illustrated the potential oxidation of chlorine dioxide during
on humans and animals
water treatment [41, 42].
The articles obtained were published from 1983 to 2019. A few of the articles may provide both qualitative and quan-
Eight articles described the safety and toxicity of chlorine dioxide titative data. However, most articles focus on qualitative data
disinfectants, with 4 of them including other subtopics. Three only. Most of the studies were done in a laboratory setting, in
out of 4 articles were obtained from the first subtopic, the efficacy a controlled manner. Not all of the studied articles provided in-
of chlorine dioxide, published by Ma et al., Miura and Shibata, formation on chlorine dioxide alone. Most studies also include
and Zhu et al. in 2017, 2010, and 2008, respectively [11, 17, 21]. other disinfectants where they compare the differences between
The other article was obtained from the third and final subtopics each disinfectant. Even if the articles include other disinfectants,
of this review, where it was added later on after full-text review, chlorine dioxide is the main disinfectant to be reviewed, and only
and it was published by Zhong et al. in 2019 [24]. The remain- the data including chlorine dioxide was compiled and compared
ing 4 articles focus on the safety and toxicity of chlorine dioxide in the different settings from each article. Additional data in the
specifically. Two of the articles published in 2005 by Ferraris et al. articles with less significance for this review were excluded.
and Svecevicius et al. explored the toxicity of chlorine dioxide on
rainbow trout [25, 26]. Ferraris et al. utilized the hepatocytes of Efficacy of chlorine dioxide
the rainbow trout fish, while Svecevicius et al. used the fish as a
whole for the study [25, 26]. Peter Bercz et al. published an article In general, the studied articles gathered came to the same
in 1986 showing the toxicity of chlorine dioxide on iodide metab- conclusion that chlorine dioxide is effective against micro-organ-
olism, which is part of the thyroid function in humans, and ani- isms tested [10–18, 20–23]. Not all of the concentrations used in
mals were used in this study [27]. Another article was published all of the studies were the same; therefore, it is better to evaluate
in 1983 by Duck H. Suh, showing the toxicity of chlorine dioxide whether or not chlorine had its effect on different types of mi-
present in drinking water on fetal development in rats [28]. cro-organisms. The only possible reason for using different con-
centrations of chlorine dioxide may be based on the guidelines on
Impact of water disinfection using chlorine dioxide the micro-organisms tested. As a result, most of the studies that
tested the efficacy of chlorine dioxide against viruses used a high-
Fifteen articles discussed the impact of water disinfection er concentration of chlorine dioxide compared to the concentra-
using chlorine dioxide, with 3 focusing on wastewater disinfec- tion used for bacteria and fungi [10–12, 15, 17, 23]. For bacteria
tion, 4 detailing drinking water disinfection, and 8 informing on and fungi, even the lowest possible concentration of chlorine di-
water disinfection in general. The articles obtained for wastewa- oxide gives an effect. As a result, even the lowest concentration
ter disinfection were published by Zhong et al., Akhlaghi et al., used shows a certain level of its effect, and the highest concentra-
and Alcalde et al. in 2019, 2018, and 2007, respectively [24, 29, tion gives a complete removal of micro-organisms [11, 13, 23].
30]. Zhong et al. explained disinfection by-products (DBPs) in When chlorine dioxide is compared with other disinfectants,
wastewater effluents treated by chlorine dioxide [24]. Akhlaghi it is better to keep in mind that most studies used a lower concen-
et al. compared data of chlorine dioxide and chlorine disinfec- tration of chlorine dioxide than other disinfectants [10, 16, 22,
tant in wastewater effluent, while Alcalde et al. gave information 23]. Even at a low concentration of chlorine dioxide used, it is ef-
on wastewater reclamation systems that use chlorine dioxide to fective against the tested micro-organisms. Another disinfectant,
disinfect water [29, 30]. The articles for drinking water disinfec- such as hypochlorite and peracetic acid, was used at a higher
tion were published by Lin et al., Sorlini et al., Lenes et al., and concentration which may be 2 to 3 times higher and have a high
Wondergem and van Dijk-Looijard in 2014, 2010, and 1991, efficacy [10]. Therefore, using chlorine dioxide lower than that
[31–34]. Lin et al. and Sorlini et al. published in 2014, and Lin and still being effective was considered more effective.
et al. studied the use of chlorine dioxide to inactivate zooplank- However, there are also some anomalies in the included
ton in drinking water treatment. Sorlini et al. indicated the influ- studies regarding the efficacy of chlorine dioxide. For example,
one study mentioned that chlorine dioxide does not have an ef- dizing organic matter as this may lead to the lower inactivation
fect as there was no significant difference before and after disin- rate of micro-organisms present in drinking water. This will lead
fection [22]. Another anomaly is that the use of chlorine dioxide to a possible presence of micro-organisms in the drinking water.
may lead to resistance, as there was evidence on Mycobacterium In addition, using aluminum sulfate to replace iron (III) chlo-
avium strains developing resistance to chlorine dioxide [19]. ride may be used in some water plants [32]. The reason for this
replacement is to reduce the concentration of chlorine dioxide
Chlorine dioxide toxicity in humans and animals used for water treatment.
The remaining studies highlighting water disinfection in
Chlorine dioxide is relatively safe for use based on the stud- general also proved that chlorine dioxide in water treatment
ies. The possibility of chlorine dioxide being cytotoxic to humans plants had a positive impact. As mentioned by one of the stud-
is low [11]. Each study states the maximum concentration of ies, the inactivation rate of fungal spores was increased when
chlorine dioxide that is safe for use, and usually, levels beyond chlorine dioxide was used, suggesting a positive impact on water
the maximum concentration of chlorine dioxide may show some treatment [35]. Similar to the result of using chlorine dioxide in
cytotoxicity. The maximum concentration of chlorine dioxide drinking water, chlorine dioxide is more efficient than chlorine
differs from one animal to another. The chlorine dioxide con- as a water disinfectant. One of the articles also highlights that
centrations that may become toxic are size or weight-related. chlorine dioxide only acts as a partial barrier, especially in the
The reason for this hypothesis was that one of the animals, the case of pharmaceutical oxidation reactions [42]. Other informa-
African monkeys, can tolerate a higher concentration of chlorine tion regarding the use of chlorine dioxide for water disinfection
dioxide compared to rats, which are smaller in terms of physical that deviates from the general result of the studies includes the
size [17]. resistance of micro-organisms, palatability of water, and insuffi-
When chlorine dioxide was compared with another disinfec- cient evidence on the impact of using chlorine dioxide. The use
tant such as chlorine, it was proven that both disinfectants were of chlorine dioxide and possibly a longer time frame of using
safe for use. However, when chlorine and chlorine dioxide were chlorine dioxide may lead to resistance. This was proven by two
mixed, it had a higher cytotoxicity level, especially on fish [24]. studies, with evidence on specified micro-organisms that were
Therefore, using chlorine and chlorine dioxide is possible, but more likely to develop resistance against chlorine dioxide [35,
advisable to avoid using them as a disinfectant in water contain- 37]. As chlorine dioxide derives from chlorine, there is a possi-
ing aquatic animals. Disinfectant by-products (DBPs) released by bility of developing resistance to chlorine dioxide, for example,
chlorine dioxide have a higher toxicity level compared to chlo- mycobacteria. As mentioned by the study, the compositions of
rine dioxide based on the results. It is worth noting that between mycobacteria cell membrane might lead to chlorine resistance
chlorite and chlorate, chlorate has a higher possibility of being [37]. Therefore, it may also affect chlorine dioxide resistance.
toxic [24, 28]. Therefore, it is advisable to avoid using chlorine The palatability of water is not preferred when chlorine dioxide
dioxide disinfectant that is less stable to reduce the production of is used alone. To improve this palatability of water, an additional
disinfectant by-products (DBPs). reagent such as ascorbic acid would help. Even with the addition
of ascorbic acid, the most preferred one is not chlorine dioxide
Water disinfection using chlorine dioxide and ascorbic acid. However, when comparing using chlorine di-
oxide alone and using chlorine dioxide with ascorbic acid, it is
Not all studies suggest that using chlorine dioxide has a preferable to add ascorbic acid [38].
positive impact on water disinfection. Three studies on chlorine The current best disinfectant used for drinking water was
dioxide on wastewater effluents generally reported a positive chlorine dioxide compared to chlorine. Moreover, the method
impact. This positive impact was based on the importance of of water disinfection is also important to ensure the availability
chlorine dioxide in the water treatment of wastewater as using of palatable water to the target population. Especially for small-
only chlorine as a disinfectant for water treatment is insufficient er areas or countries where the budget is limited, some methods
[24, 29, 35, 39, 42]. This supports the use of chlorine dioxide such as the infiltration-percolation system could be more efficient
owing to its higher efficacy compared to chlorine. One of the in cost saving. However, this water disinfection method should be
studies suggested that chlorine alone may increase the produc- monitored and adjusted from time to time in the long-term run
tion of disinfectant by-products (DBPs). When chlorine was used of using chlorine dioxide to ensure that there is enough evidence
together with chlorine dioxide, the production of these disinfec- to fully support the use of chlorine dioxide.
tant by-products (DBPs) was much lower and less likely to have
a toxic effect [24].
In four studies on the use of chlorine dioxide in drinking wa- CONCLUSIONS
ter, chlorine dioxide also had a positive impact on drinking water
disinfection [31, 32, 34, 38]. The studies indicate that chlorine This review analyzed the efficacy, safety, and influence of
dioxide used for drinking water treatment is beneficial. The study chlorine dioxide on water disinfection. The referred literature
also supports chlorine dioxide in the water treatment with the supports chlorine dioxide as a safe and efficient disinfectant.
additional effect of inactivating influenza viruses such as H5N1 Generally, chlorine dioxide is recommended as a disinfectant
and H1N1 and other disinfectants to allow full water disinfection since it kills microorganisms even at low concentrations. Chlorine
against harmful micro-organisms [33]. dioxide could be used as a disinfectant during the COVID-19
In addition, these studies also provide alternatives for wa- pandemic. Studies also support the use of chlorine dioxide in
ter disinfection plants to increase the efficacy of chlorine dioxide water treatment, especially in delivering microbial-safe drinking
for drinking water treatment [31, 32]. To make full use of chlo- water. The use of chlorine dioxide is a newer water disinfection
rine dioxide as a disinfectant for drinking water, some chemicals technology; adequate management of the method is essential to
should be avoided or could be added. The chemical that should make it cost-effective and ensure high efficacy and safety for hu-
be avoided with chlorine dioxide in water treatment is an oxi- mans and animals.
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