*****Poison Control Reports, etc.

{Method for testing levels of chlorine dioxide}

"Chlorine dioxide is generally effective for the deactivation of pathogenic microorganisms. It is less effective for the deactivation of rotaviruses and E. coli bacteria." [Note: Some ClO2 products are very economical] "The costs of chlorine dioxide depend upon the price of the chemicals that are used to produce chlorine dioxide."

{Workplace exposure limits, monitoring method, on-site screening techniques, etc}

****!!!!****!!!!** "**Sodium chlorite solutions should never be allowed to dry on fabrics** because this would result in a flammable combination" "The presence of chloride ions is essential for the formation of chlorine dioxide" "No significant amount of chlorine dioxide is formed in acidified chlorate solutions with various reducing agents when chloride has previously been removed from the reaction system by adding silver sulfate." "If chlorine dioxide generators are allowed to stand overnight, minor ClO2 formation consumes all of the chloride present in the reaction mass. When the supply of fresh raw materials is started the next morning, a specific chloride level must build up before chlorine dioxide can be produced at the desired rate" "Independent on the choice of reducing agent, the primary reaction for chlorine dioxide production is the reaction between chloric acid and hydrochloric acid to form chlorine dioxide and chlorine. Traces of Mn2+ and Ag+ ions catalyze the reaction" "In industrial chlorine dioxide production, sulfur dioxide, hydrochloric acid, or methanol are used as reducing agents. Other reducing agents are not economical" " solid sodium chlorite forms explosive mixtures with such oxidizable materials as sulfur, powdered coal, metal powders, or organic compounds." "t. At low pH (approximately 2), chlorite solutions contain chlorous acid that decomposes to form chlorine dioxide and chlorate... At pH 3 – 4, decomposition slows down. Alkaline solutions are stable, and dilute solutions can even be boiled without decomposition. Concentrated alkaline solutions of sodium chlorite slowly decompose when heated... The reaction of sodium chlorite with hypochlorite depends on pH [137]. At low pH, the reaction produces chlorine dioxide, whereas at high pH, chlorate is formed. The reaction with chlorine produces chlorine dioxide and sodium chloride" "Crystalline sodium chlorite is slightly hygroscopic without caking; it is stabilized with alkali for long-term storage" "The absorption of chlorine dioxide in caustic soda solution and the simultaneous reduction of chlorate to chlorite are achieved by a suitable reducing agent, such as hydrogen peroxide... The product is a 33 wt % solution of sodium chlorite, which is then converted to a dry solid containing ca. 80 wt % of sodium chlorite, the rest being stabilizers" "Sodium chlorite is a very efficient bleaching agent. Its oxidation potential allows a controlled bleaching that is not attainable with other bleaching agents"

*****!!!!****!!!** {Includes long list of research studies; regulations searches; patents; products from a broad range of manufacturers, and ingredients; etc}

****!!!!*** {Excellent summary of toxicity studies regarding health, and more}

***!!!!*** 2017 Jan "Since in aqueous solutions, sodium hypochlorite (NaOCl) and chlorine share the same anion (ClO-) and, thus, release the very same active substance (i.e. active chlorine, thought to consist of hypochlorite, hypochlorous acid and chlorine in equilibrium), read-across is possible for all the toxicological end-points." "In the acute inhalation toxicity study (Anonymous, 1970), inactivity and lacrimation were evident at the dose of 10.5 mg avCl/L (1 h exposure). No deaths occurred (LC0 >10.5 mg avCl/L). Thus, the LC50 was determined to be greater than 10.5 mg avCl/L." "...by a factor of 4 for dusts and mists according to Annex I, notes to Table 1.1, paragraph c). However, in the case of sodium hypochlorite which only exerts local effects at the ****side [site?] of first contact, it is expected that local irritative effects are rather concentration than time dependent. Hence, findings for 4-h exposure durations are expected to be similar to those observed after 1-h exposures. " "ystemic toxicity after inhalation exposure towards sodium hypochlorite would therefore occur only secondary to locally irritating effects mainly caused by the local oxidation and basic nature of hypochlorite and its solutions. The remaining sodium and chloride ions are physiologically essential elements and are required in the intermediary metabolism and can therefore not be regarded as typical xenobiotics when entering the body."

"Acute oral LD50 = 1.1 g/kg BW (LD50 as available Cl2) = 1100 mg/kg BW NaClO as av. Cl2" "Dermal LD50 > 20 g/kg bw...2 of 8 animals died on day 1 and 2 after application in the high dose group (20 g/kg bw)." "The LC0 value by inhalation in rat was found to be greater than 10.5 mg/l for 1 hour exposure... inhalation exposure of sodium hypochlorite is only possible if aerosols are formed"

*******!!!***!!!!*

1999 "studies have shown that pH has much less effect on pathogen inactivationfor viruses and cysts with chlorine dioxide than with chlorine in the pH range of 6 to 8.5. Unlikechlorine, studies on chlorine dioxide have shown the degree of inactivation of poliovirus 1 (Scarpinoet al., 1979) and Naegleria gruberi cysts (Chen et al., 1984) increase as the pH increases." "In the first disinfection mechanism, chlorine dioxide reacts readily with amino acids cysteine,tryptophan, and tyrosine, but not with viral ribonucleic acid (RNA)). From this research, it was concluded that chlorine dioxide inactivated viruses by altering theviral capsid proteins. However, chlorine dioxide reacts with poliovirus RNA and impairs RNA synthesis. It has also been shown that chlorine dioxide reacts with free fatty acids. At this time, it is unclear whether the primary mode ofinactivation for chlorine dioxide lies in the peripheral structures or nucleic acids. Perhaps reactions inboth regions contribute to pathogen inactivation.The second type of disinfection mechanism focuses on the effect of chlorine dioxide on physiologicalfunctions. It has been suggested that the primary mechanism for inactivation was the disruption ofprotein synthesis (Bernarde et al., 1967a). However, later studies reported the inhibition of proteinsynthesis may not be the primary inactivation mechanism. A more recent studyreported that chlorine dioxide disrupted the permeability of the outer membrane). The results of this study were supported by the findings of Olivieri et al. (1985) and Ghandbari et al. (1983), which found that the outer membrane proteins and lipids were sufficiently altered by chlorine dioxide to increase permeability"

***** {Includes chart of residuals in treated foods} "While the chlorite ion is stable in aqueous solution, under acidic conditions, chlorite forms a semi-stable intermediate, chlorous acid (HClO2). Chlorous acid disintegrates to chlorine dioxide (ClO2), which further degrades to chlorite (ClO2 ̄) and ultimately chloride (Cl ̄) is formed. The extent of each of the degradation pathways and thus the proportion of each of the oxy-chlorine species depends in part on the pH of the solution. Other factors such as temperature and alkalinity of the water also affect the composition of the oxy-chlorine constituents." "At a pH of 2.3, approximately 31% of chlorite (from sodium chlorite) is converted to chlorous acid" "The pH values at different concentrations of citric acid, phosphoric acid, and sodium hydrogen sulfate to prepare a 1000 mg/l sodium chlorite solution are presented in Figure 1" "The technical-grade of sodium chlorite used to prepare ASC is comprised of 80% of sodium chlorite, with sodium chloride, sodium carbonate, sodium hydroxide, sodium sulfate, and sodium chlorate making up the remainer of the composition." "Although levels of chlorine dioxide do not exceed 3 ppm in the solution initially, chlorine dioxide levels increase during aging of the solution." "Chlorine dioxide... is not present as a residue of the treated food-product." "Instead, the ASC solution is monitored for sodium chlorite concentration and pH, which are known to result in acceptable levels of chlorate, chlorite, and chlorine dioxide. Depending on the food application, the solution is characterized by a sodium chlorite concentration in the range of 50-150 mg/l and a pH of 2.8-3.2 or 500-1200 mg/l and a pH of 2.5-2.9."

********* {Includes graph comparing contact time effects for differing dosages.} {Includes chart of level testing methods} {Includes comparison chart of commercial chlorine dioxide generator equipment} "...it is stable in dilute solution in a closed container in the absence of light. " "In drinking water, chlorite (ClO2-) is the predominant reaction endproduct, with approximately 50 to70 percent of the chlorine dioxide converted to chlorite and 30 percent to chlorate (ClO3-) and chloride (Cl-)" "educing the temperature from 20°C to10°C reduced the disinfection effectiveness of chlorine dioxide on Cryptosporidium by 40 percent,which is similar to previous results for Giardia and viruses." "At neutral pH levels, the required doses may be morethan 20 mg/L." "mostly viral aggregates took 2.7 times longer to inactivate with chlorine dioxide than single state viruses" "clumps of... cysts were more resistant to chlorine dioxide" " CT required for 2-log inactivation [of Naegleriagruberi cysts] was much higher than normally employed for water treatment" "In water treatment processes that require high pH, such as softening, chlorine dioxide should beadded after the pH has been lowered" "The occurrence of photochemical decomposition of chlorine dioxide can affect the ultimateconcentrations of chlorine dioxide, chlorite, and chlorate in water treated with chlorine dioxide" "[Sodium chlorite] 25 percent solution [as formulated commercially] may not require any special protection except in cold climates" "The reactions produce chlorite and chlorate as endproducts (compoundsthat are suspected of causing hemolytic anemia and other health effects)" "chlorinedioxide dosage cannot exceed 1.4 mg/L to limit the total combined concentration ofClO2, ClO2-, ClO3-, to a maximum of 1.0 mg/L. Under the proposed DBP regulations,the MRDL for chlorine dioxide is 0.8 mg/L and the MCL for chlorite is 1.0 mg/L"

****!!!!*** Current date. {There are likely some errors in this info} "PubChem CID 24870. Structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more."

*****!!!!**** Current date. {Central page with many sub-linked documents}

*******!!!!****** (Current date) {Includes 20+ docs, including ones for 2006 RED}

****2018 Jan. {Very good technical info. Fumigation leaves no CD or by-product residue. Air treatments are more effective than Liquid. Includes several CD and SC trade names. Denied because of lack of public requests, available alternatives, etc.}

2000 Sept. {Evaluating RfC, RfD, carcinogenicity. Includes **injection report.} "what exists in water or the stomach is a mixture of these chemical species (i.e., chlorine dioxide, chlorite, chlorate) and possibly their reaction products with the gastrointestinal contents." "[after gavage dosing of rats] it was not clear from these reports whether the parent chlorine dioxide itself or the chlorite, chlorate, or chloride ion degradation products were absorbed"

2000 Sept. "No studies examining the toxicity of inhaled chlorite were located,,,Under ambient conditions, airborne chlorite is likely to exist as a particulate, whereas inhalation exposure to chlorine dioxide is as a gas. Based on their physical and chemical properties, it is anticipated that inhaled chlorine dioxide and chlorite would have very different modes of exposure. Therefore, the potential hazards associated with exposure to these two chemicals are also very different."

The daily drinking water consumption for the 10 kg child and 70 kg adult are assumed to be 1 L/day and 2 L/day

2008 May ******* {in-depth info on concentrations, safety, efficacy & time for CD and other disinfectants} "The use of chlorine dioxide at 20 mg/l resulted in little or no difference in numbers of total aerobic bacteria on beef compared with using potable water. " "The reaction of the bromide ion (Br−) with chlorine dioxide is thermodynamically unfavourable. However, with intense sunlight and high concen-trations of chlorine dioxide, chlorine dioxide does oxidize the bromide ion to hypobromite (BrO−) and bromate (BrO3−)"

{Includes Chlorine Dioxide info.} "Chlorine dioxide kills microorganisms directly by disrupting transport of nutrients across the cell wall." "Chlorine dioxide is a very reactive compound and breaks down quickly in the environment (ATSDR, 259 2004a). In air, sunlight rapidly causes chlorine dioxide to break down into chlorine gas and oxygen. When 260 used as a disinfecting agent, however, the product of chlorine dioxide is primarily chlorite. Although 261 chlorite in water may move into groundwater, reactions with soil and sediments may reduce the amount of 262 chlorite reaching groundwater. The toxic action of chlorite is primarily in the form of oxidative damage to 263 red blood cells at doses as low as 10 mg/kg of body weight. Toxic reaction products are not known to 264 occur when chlorite is mixed with organic materials."

*****This IRIS assessment for Chlorine dioxide consists of hazard identification and dose-response assessment data and provides support for EPA risk management decisions.

********!!!!!!********** {Safe levels. 2000 is most recent date noted.} "...chlorine dioxide rapidly disappeared from the stored water (within 2-4 hours) and water chlorite concentrations concomitantly increased. Once absorbed, chlorine dioxide and chlorite are cleared from the blood at similar rates and are similarly distributed throughout the body .. Additionally, chloride is the major in vivo degradation product for chlorine dioxide, chlorite, and chlorate. The available data suggest that chlorine dioxide and chlorite have similar targets of toxicity and potencies. Therefore, the toxicity information for chlorite is relevant to deriving an RfD for chlorine dioxide." Integrated Risk Information System (IRIS)

Annotation record.

***!!!!**** 2002 " Some studies have been conducted via the oral route using aqueous solutions of chlorine dioxide. Several of these studies were conducted using “stabilized aqueous chlorine dioxide,” sometimes by maintaining a constant pH using sodium carbonate and sodium hydrogen carbonate. However, it is recognized that this would effectively lead to the formation of aqueous sodium chlorite (which can subsequently generate chlorine dioxide by acid dis-placement). These studies are felt to be less relevant than those using stabilized aqueous chlorine dioxide and are not summarized in this review. The reasons for this are that chlorine dioxide dissolves discretely in water (i.e., it does not dissociate into ions), forming a solution of around pH 5 or less, whereas an aqueous solution of sodium chlorite has a different, ionized composition and a pH of approximately 8. The explosive nature of this substance has limited the concentration of chlorine dioxide in aqueous solutions to a maximum of about 1% w/v" {******pg 4 -- ppm conversion info for air concentrations:} "0.1 ppm (0.28 mg/m3) 8-h time-weighted average (TWA) and 0.3 ppm (0.84 mg/m3) 15-min reference period" "It is predicted thatdermal exposure from contact with the aqueous solution in occupational settings will range from 0.1 to 5 mg/cm2 per day" "There are no quantitative human data, but chlorine dioxide is very toxic by single inhalation exposure in rats. There were no mortalities following exposure to 16 ppm (45 mg/m3) for 4 h, although pulmonary oedema and emphysema were seen in all animals exposed to 16–46 ppm (45–129 mg/m3) chlorine dioxide,the incidence increasing in a dose-related manner. The calculated mean LC50 was 32 ppm (90 mg/m3). In another study, ocular discharge, nosebleeds, pulmonary oedema, and death occurred at 260 ppm (728 mg/m3) for 2 h. Chlorine dioxide is toxic when administered in solution by a single oral dose to rats; at 40 and 80 mg/kg bodyweight, there were signs of corrosive activity in the stomach and gastrointestinal tract. The calculated oral LD50 was 94 mg/kg body weight."