****!!!!**** "guidelinevalue for chlorine dioxide was not needed as chlorine dioxide is reduced primarily to chlorite, chlorate and chloride in drinking-water, and to chlorite and chloride upon ingestion"

*****Poison Control Reports, etc.

Volume 3 of the Drinking Water and Health series examined the toxicity of several major disinfectants and many of the by-products formed during drinking water disinfection.

****!!!!****!!!! "Chlorine dioxide is used directly as a bleaching agent for cellulose, textiles, flour, leather, oils, and beeswax. It is also used in the purification of water and as a bactericide and antiseptic." "The annual statewide industrial emissions ... were estimated to be 1136 pounds of chlorine dioxide" "Case reports of human occupational exposure to chlorine dioxide have shown that 19 ppm was fatal to one worker and 5 ppm was definitely irritating. Seven out of 12 workers exposed regularly to chlorine dioxide at levels generally below 0.1 ppm (0.28 mg/m3) reported symptoms of ocular and respiratory irritation leading to slight bronchitis. However, the authors ascribed the bronchitis to occasional acute excursions of chlorine dioxide levels"

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

(2000)

OEHHA recommends an action level of 200 ug/L (ppb) chlorate in drinking water. " A concentration-dependent lag phase was seen before methemoglobin was formed, presumably reflecting time required for chlorate to enter or hemolyze RBCs. Other effects on RBCs included increased permeability to cations, increased resistance to hypotonic hemolysis, and prolonged filtration time through polycarbonate membranes. This suggests an increased RBC membrane rigidity due to membrane protein polymerization, as demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Simultaneously, erythrocyte enzymes were inactivated, primarily glucose-6-phosphate dehydrogenase."

****!!!!*** {Excellent summaries of studies of effects on health, legal limits, 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."

{OSHA CURRENT LIMITS} NIOSH REL: 0.1 ppm (0.3 mg/m3) TWA, 0.3 ppm (0.9 mg/m3) STEL. Current OSHA PEL: 0.1 ppm (0.3 mg/m3) TWA. 1989 OSHA PEL: 0.1 ppm (0.3 mg/m3) TWA, 0.3 ppm (0.9 mg/m3) STEL. 1993-1994 ACGIH TLV: 0.1 ppm (0.28 mg/m3) TWA, 0.3 ppm (0.83 mg/m3) STEL

********* {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."

2004 Sept.

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."

~2003. "Chlorine dioxide and chlorite (ions and salts) are strong oxidizers and react quickly in water or moist body tissues to form chloride ions. Consequently, chlorine dioxide and chlorite (ions and salts) are not detected in human tissues (e.g., blood, urine, fat, or breast milk). [Have some studies shown contradiction??]" " In water, chlorine dioxide is a strong oxidizer; **50–70%** of the chlorine dioxide that reacts with organic and inorganic compounds will immediately appear as chlorite (ClO2-) and chloride (Cl-) ions...chlorine dioxide does result in the formation of other DBPs (e.g., lower chlorinated organics, chlorate, and chlorite) which may be found in drinking water... ***Chlorine dioxide will decompose upon exposure to sunlight. The gas-phase absorption spectrum for chlorine dioxide is the same as in aqueous solution. The primary photochemical reaction of ClO2 in the gas phase corresponds to homolytic scission of one of the chlorine-oxygen bonds (i.e., ClO26ClO + O). Products of this initial reaction generate secondary products including doublet-state oxygen (O2*), chlorine (Cl2), and chlorine trioxide (Cl2O3) . If chlorine dioxide gas is diluted in air to below 15 volume percent, it can be relatively stable in darkness." "Chlorine dioxide alone will not hydrolyze in solution to any appreciable extent between pH 2 and 10. .." "Chlorite ions (ClO2-) are also effective oxidizing agents, although they react much slower than chlorine dioxide""Chlorine substitution in the products, however, is not entirely absent" "Under sunlight, some photolysis intermediates with long half-lives are capable of oxidizing bromide to from bromate."

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

1991. {Includes toxicology data} from IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 52. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon (FR): International Agency for Research on Cancer. "Mouse: Groups of 50 male and 50 female B6C3F1 mice, six weeks old, were given 0.0, 0.025 or 0.05% sodium chlorite (82–87% pure [impurities unspecified]) in the drinking-water for 80 weeks. Survival at 85 weeks was: males—control, 35/50; low-dose, 47/50; high-dose, 43/50; females—control, 47/50; low-dose, 50/50; high-dose, 50/50."

********!!!!!!********** {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.

***!!!!*** Current date. "PubChemCID 23668197" "125 to 250 parts per million as a slimicide in the manufacture of paper and paperboard that contact food"

***!!!!**** 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."