Page 3: Guidelines for Canadian Drinking Water Quality: Guideline Technical Document – Chlorite and Chlorate
Chlorite and chlorate in drinking waterFootnote 1
Part II. Science and Technical Considerations
4.0 Identity, use and sources in the environment
Chlorite (ClO2-) and chlorate (ClO3-) are anions that can form salts (e.g., with sodium). Chlorine dioxide (ClO2) is a greenish to reddish-yellow gas at ambient temperature and pressure (Gates, 1989; Lewis, 1993). Due to its volatile and reactive nature, chlorine dioxide must be generated on site and has a very limited shelf life. The main properties of sodium chlorite and sodium chlorate as well as chlorine dioxide are given in Table 1.
|Properties/values||Chlorite (sodium)||Chlorate (sodium)||Chlorine dioxide|
Table 1 Footnotes
|Form||White crystal/powder||White or colourless, crystals or granules||Greenish to yellow-reddish gas at ambient temperature and pressure|
|Melting point||Decomposes at > 180°C||248°C||-59.6°C|
|Boiling point||NA (decomposes at > 180°C)||Decomposes at > 265°C||10.9°C|
|Density||2.47 at 25°C||2.49 at 25°C||1.64 at 0°C|
|Vapour pressure||not applicable||not applicable||142.13 kPa (1066 mm Hg) at 20°C|
|Water solubility||405 g/L at 20°C
Very soluble (dissociates into sodium and chlorite ions)
|960 - 1000 g/L
Very soluble (dissociates into sodium and chlorate ions)
|3.01 g/L at 25°C high solubility|
|Octanol/water partition coefficient (log Kow)||-7.18||-7.18||-3.22|
Chlorine dioxide is used as a disinfectant or biocide in municipal water treatment for purification and for taste, odour and colour control. It is a strong oxidizing agent (oxidation power relative to chlorine = 0.94) in water, used to help control tastes and odours in drinking water and as an alternative disinfectant to chlorine. Chlorine dioxide is typically used as a primary disinfectant, but some utilities have carried a chlorine dioxide residual into the distribution system to maintain water quality (Volk et al., 2002). However, the use of chlorine dioxide as a secondary disinfectant is not recommended. Chlorine dioxide disinfection requires less contact time and lower dose levels than chlorine for comparable coliform reductions (Aieta et al., 1980). The taste and odour threshold for chlorine dioxide is 0.4 mg/L (U.S. NRC, 1987).
Chlorine dioxide is also used in industrial and wastewater water treatment; in pulp mills (slime control and paper machines); in the food processing and textile industry; as a bleaching agent for cellulose, wood pulp, fats and oils, textiles and beeswax; and as a room or equipment disinfectant and steriliser (U.S. NRC, 1987; U.S. EPA, 2000; Budavari et al., 2001; ATSDR, 2004).
Sodium chlorite is used for on-site production of chlorine dioxide. It has also been used as a bleaching agent in the production of paper, textiles and straw products, in the manufacture of waxes, shellacs and varnishes, in disinfectant formulations, in sterilization, and in etching printed circuit boards (U.S. EPA, 2000; ATSDR, 2004; WHO, 2004).
Sodium chlorate is used in the manufacture of dyes, matches and explosives, for tanning and finishing leather, and in formulations of herbicides and defoliants (WHO, 2004).
4.1 Behaviour in water systems
Studies have shown that approximately 70% of the applied chlorine dioxide will eventually form chlorite, while about 10% will form chlorate (Volk et al., 2002). Although chlorine dioxide is an unstable gas that decomposes rapidly in air, it is readily soluble in water (ATSDR, 2004). Aqueous solutions of chlorine dioxide are subject to partial photodecomposition (White, 1992). Solutions of chlorine dioxide alone will not undergo any appreciable hydrolysis when the pH is kept between 2-10 (ATSDR, 2004). In an alkaline solution, a mixture of chlorite and chlorate ions is formed fairly rapidly (Cotton et al., 1999).
Chlorine dioxide does not react with water or ammonia but oxidizes the bromide ion to hypobromide and bromate in the presence of intense sunlight and at high concentrations. Generally, chlorine dioxide does not react with primary amines but will react slowly with secondary and tertiary amines, producing secondary aliphatic amines without the formation of N-oxides (White, 1992). ATSDR (2004) also reported that "chlorine-free" chlorine dioxide does not form trihalomethanes (THMs) from reaction with humic and fulvic acids; however, other chlorinated organics may be formed. However, it must be noted that secondary disinfection with chlorine will result in the formation of low levels of chlorinated disinfection by-products (CDBPs).
Chlorite and chlorate ions have been shown to undergo reduction by bacteria under anaerobic conditions. Anaerobic degradation is an important process in anoxic groundwater. However, no quantitative information was located on the biodegradation rate of chlorate or chlorite ions in the environment. However, the rate of chlorate ion degradation appears to be rapid under anaerobic conditions in waste-water treatment facilities (Logan, 1998).
The major route of environmental exposure to chlorite and chlorate is through drinking water. Chlorite and chlorate ions are often found in drinking water where chlorine dioxide is used in the treatment process. It is the generation technology and, to a lesser degree, the generator "tuning" that will determine the types and quantities of by-products or unreacted precursors, such as chlorite, chlorate and perchlorate (ClO4-) ions, that may be found in the final chlorine dioxide feed (Gordon, 2001). Formation of chlorate ion in water may also occur through the photolytic decomposition of pre-existing chlorine dioxide and chlorite by sunlight and fluorescent lighting (Griese et al., 1992).
Chlorine dioxide is used by very few Canadian water treatment plants; Quebec is one of the few provinces where chlorine dioxide is being used. The concentrations of chlorine dioxide, chlorite and chlorate ions were measured in 8 systems in Quebec (Aranda-Rodriguez et al., 2004; Health Canada, 2005) in winter and summer 2003. Samples were collected at the treatment plant outlet (T), and at three different locations along the distribution system (D1, D2 and D3). A range and average of concentrations for all locations are found in Table 2:
|Chemical||Season||Range of concentrations observed, in mg/L (average)|
Table 2 Footnotes
|Summer||<0.01 - 0.63
|not analyzed||not analyzed||not analyzed|
Chlorine dioxide, chlorite and chlorate may occur in foodstuffs as a result of their use in flour processing, as a decolorizing agent for carotenoids and other natural pigments (chlorine dioxide), as a bleaching agent in the preparation of modified food starch (sodium chlorite), as an indirect additive in paper and paperboard products used for food packaging (sodium chlorite) and as a defoliant, desiccant and fungicide in agriculture (sodium chlorate) (U.S. EPA, 1983; CMA, 1989; U.S. FDA, 1990).
Although the formation of chlorate is most often associated with the use of chlorine dioxide, the treatment of drinking water with either sodium hypochlorite (NaOCl) or calcium hypochlorite (Ca(OCl)2) can also increase the concentration of chlorate in finished water. The long-term storage of hypochlorite solutions may lead to its decomposition and the formation of chlorate. The formation of chlorate ion in a hypochlorite solution is influenced by storage conditions such as pH, temperature, length of time in storage, presence of ultraviolet light, concentration of solution and presence of transition metals. Solid forms of hypochlorite are not affected by this decomposition (Gordon et al., 1995).
Chlorate and chlorite ions are very water soluble and are known to occur in drinking water supplies disinfected with chlorine dioxide. Based on the physical-chemical properties of chlorate and chlorite ions, and given the lack of data regarding their presence in food, air, soil and consumer products, chlorate and chlorite are not expected to be present in significant levels in environmental media other than drinking water. As a result, drinking water is assumed to be the primary source of exposure to chlorate and chlorite for the general population, and an allocation factor of 80% for drinking water has been determined as most appropriate for risk assessment.
6.0 Analytical methods
The analysis of chlorite, chlorate and chlorine dioxide in water is commonly based on spectrophotometric or colorimetric, electrochemical, and chromatographic techniques. The main methods for the analysis of chlorite, chlorate in water are summarized in Appendix A. When available, method detection limits (MDL), practical quantitation limits (PQL), potential interferences and relevant application remarks, including interferences, are provided. However, users should refer to the full method description for detailed information on specific interferences and scope of application of methods.
6.1 Chlorite - U.S. EPA approved methods
The U.S. Environmental Protection Agency (EPA) has approved three methods for the determination of chlorite in drinking water: (1) EPA Method 300.0, Revision 2.1 (U.S. EPA, 1999b), (2) EPA Method 300.1, Revision 1.0 (U.S. EPA, 1998), and (3) Standard Method 4500-ClO2 E (APHA et al., 1998).
EPA Method 300.0, Revision 2.1 is a chromatographic method in which a small volume of sample is introduced into an ion chromatograph. The anions of interest are separated and measured using a system composed of a guard column, analytical column, suppressor device and a conductivity or ultraviolet/visible (UV/VIS) detector. EPA Method 300.1, Revision 1.0 is similar, but uses a superior analytical column to improve the sensitivity of analysis.
Standard Method 4500-ClO2 E is an amperometric method approved for chlorite and chlorine dioxide, but also capable of determining chlorate and chlorine in water. The method uses successive titrations at varying pH ranges with either phenyl arsine oxide or sodium thiosulphate as the titrant. The application of potassium bromide as a reducing agent at one stage of the titration will minimize the oxidation of iodide to iodine by oxygen at a low pH, while the addition of potassium iodide crystals will prevent the reduction of iodate to iodine. At the low pH ranges necessary for chlorite and chlorate determination, this method is susceptible to interferences from manganese, copper and nitrite. This method is useful when a knowledge of the various fractions (chlorine, chlorine dioxide, chlorite and chlorate) is desired. This method is typically used for daily monitoring of chlorite at the treatment plant. However, it requires specialized equipment and a great deal of analytical skill. It must be noted that the final calculations to determine chlorite concentrations are subject to large cumulative errors when using this method (Gates, 1998).
6.2 Chlorate - U.S. EPA approved methods
The U.S. EPA has approved two methods for the determination of chlorate in drinking water: (1) EPA Method 300.0, Revision 2.1 (U.S. EPA, 1999b) and (2) EPA Method 300.1, Revision 1.0 (U.S. EPA, 1998). These methods are briefly described in section 6.1.
6.3 Chlorine dioxide - U.S. EPA approved methods
The U.S. Environmental Protection Agency (EPA) has approved the following three methods for the determination of chlorine dioxide in drinking water: (1) Standard Method 4500-ClO2 C (APHA et al., 2005), (2) Standard Method 4500-ClO2 D (APHA et al., 1998), and (3) Standard Method 4500-ClO2 E (APHA et al., 2005). This method can be used for daily monitoring of the chlorine dioxide feed dose at the treatment plant.
Standard Method 4500-ClO2 C is an amperometric method approved for chlorine dioxide but also capable of determining chlorite, chlorine and chloramines in water. The method uses successive titrations at varying pH ranges with phenyl arsine oxide as the titrant. This method is susceptible to interferences from iodide, bromide, ferriccyanide, chromate, dichromate and ferric ion.
Standard Method 4500-ClO2 D is an extension of the N,N-diethyl-p-phenylenediamine (DPD) colorimeteric method for the determination of free chlorine. When used for the determination of chlorine dioxide, the free chlorine is suppressed by the addition of glycine prior to addition of the DPD reagent.
Standard Method 4500-ClO2 E is described in Section 6.1, and can be used for daily monitoring of the chlorine dioxide feed dose at the treatment plant.
6.4 Other available methods
The U.S. EPA has also proposed, but not yet approved, three methods for the determination of chlorite and/or chlorate in drinking water: (1) EPA Method 317.0, Revision 2.0 (U.S. EPA, 2001a), (2) EPA Method 326.0, Revision 1.0 (U.S. EPA, 2002) and (3) EPA Method 327.0, Revision 1.0 (U.S. EPA, 2003b).
EPA Methods 317.0, Revision 2.0 and 317.0, Revision 1.0 are alternative chromatographic techniques for chlorite and chlorate using post column reactions to increase specificity and sensitivity of the method.
EPA Method 327.0, Revision 1.0 (U.S. EPA, 2003b), is a UV/VIS spectrophotometric method for measuring chlorine dioxide and chlorite in drinking water. It uses the colour indicator Lissamine Green B and is capable of determining chlorite at levels typically found in drinking water. The reagent Lissamine Green B/horseradish peroxidase is added to the water sample, where the horseradish peroxidase helps catalyse the conversion of chlorite to chlorine dioxide. The chlorine dioxide then oxidizes the Lissamine Green B and reduces its absorbance, which is proportional to the original chlorite concentration and is measured by a spectrophotometer at 633 nm.
Flow injection analysis can also be used for the detection of chlorine dioxide, chlorite and chlorate in drinking water (Novatek, 1991). Chloramines and other oxidants may interfere with this method. This method can be automated and thus provide on-line monitoring. Wang et al. (2001) have modified this method to analyse low concentrations of chlorine dioxide in the presence of chlorine and other anions and has a detection limit of 20 µg/L.
Other methods developed for the analysis of chlorine dioxide include DPD test kits. These test kits are based on the colorimetric method of Standard Method 4500-ClO2 G and are typically used for field determination of residual chlorine dioxide. These methods are applicable to concentrations greater than 0.1 mg/L of chlorine dioxide. Manganese, and other chlorine related oxidants may interfere with this method.
A method using Acid ChromeViolet K (ACVK) (Masschelein, 1989) for the determination of chlorine dioxide is based on the oxidation and resulting decoloration of ACVK (Alizarin violet 3R, color index 6170) at 548 nm using a spectrophotometer.
The iodometric titration method (APHA Method 4500-ClO2 B), gives a very precise measure of chlorine dioxide (APHA et al., 2005). However, it does not allow speciation of the various chlorine species; therefore, the method is more suitable for standard chlorine dioxide solutions (APHA et al., 2005).
7.0 Treatment technology
Up to 70% of the applied chlorine dioxide can eventually form chlorite (Volk et al., 2002). Given that chlorite reacts with free chlorine to form chlorate ion which is very difficult to remove (Gallagher et al., 1994; U.S. EPA, 1999a), two strategies are recommended to minimize initial chlorite formation: (1) the control of treatment processes to reduce disinfectant demand; and (2) the control of the chlorine dioxide generation processes to ensure maximum purity of chlorine dioxide. Current commercial chlorine dioxide generators may be broadly classified as chlorite based, chlorate based or electrochemical systems.
There are four available treatment options to control chlorite ion concentrations in drinking water at the municipal scale: (1) tuning of the chlorine dioxide generator; (2) activated carbon; (3) iron reducing agents; and (4) sulphur reducing agents. These are described briefly below:
- Chlorine dioxide generator tuning: Chlorine dioxide generator design and performance have a large impact on the amount of chlorite ion formed during chlorine dioxide production. Precise operation ("tuning"), proper maintenance and the generation technology employed with the chlorine dioxide generator have a large bearing on the chlorine dioxide production efficiency and the rate at which chlorite and other undesirable by-products, such as chlorate, hydrogen peroxide and perchlorate, are formed and fed into the water with the chlorine dioxide dose. The onsite production of chlorine dioxide can be technically challenging for the operator. Minor leaks can lead to potentially dangerous white crystalline material which can be ignited if it contacts strong reducing agents or if it is subjected to spark, flame, friction or compression. Any spills should be immediately flushed with copious amounts of water (Gates, 1998).
A properly tuned generator will yield high purity chlorine dioxide, thus limiting the presence of contaminants that can carry through into the distribution system and increase the total concentration of chlorate and chlorite (Gordon, 2001). Proper balance and control of chlorine dioxide generators are required to prevent the formation and carry-through of impurities such as chlorate ion, perchlorate ion and chlorine (Gordon, 2001).
- Activated carbon: Activated carbon will remove chlorite ion through adsorption and chemical reduction. Early chlorite breakthrough has been reported in granular activated carbon (GAC) filters when the adsorptive sites have been exhausted, likely by competing compounds, such as natural organic matter, and only the reduction mechanism remains. The performance of GAC filters for chlorite removal is further complicated by the oxidation of chlorite to chlorate, which may occur if free chlorine is present in the feed water. Short bed life, high operating costs and the potential for chlorate formation make GAC an impractical choice for chlorite removal at the municipal scale (Dixon and Lee, 1991).
- Iron reducing agents: Ferrous iron (Fe2+) will chemically reduce chlorite ion, thereby lowering its concentration in water. Chlorate ion will form only if the pH drops below 5, which can occur at localized application points where acidic reducing agents such as ferrous chloride are added to the water. Good application and rapid mix and/or pH adjustment to neutral pH 7 may prevent the occurrence of micro-regions of low pH and the subsequent formation of chlorate (Griese et al., 1992). When the pH exceeds 7, the subsequent reaction of chlorite and ferrous iron forms insoluble ferric hydroxide, which may be beneficial by aiding clarification when used in conjunction with filtration to capture the solids (Iatrou and Knocke, 1992). However, if the pH exceeds 9, elevated dissolved oxygen and dissolved organic carbon levels impede the effectiveness of ferrous iron and require increased ferrous dosages to attain adequate chlorite removal. Ferrous iron dosing of 3.5-4.0 mg/mg chlorite provides efficient removal of chlorite ion (Hurst and Knocke, 1997). Any residual chlorite will react with chlorine to form chlorate and should be removed before secondary disinfection with chlorine. Ferrous iron, when used as a treatment options for chlorite removal and fed in excess of the demand, can hinder efficiency of secondary disinfection (U.S. EPA, 2001b). Ferrous iron used for chlorite reduction may lead to levels of iron in the treated water which exceed the aesthetic guideline level of 0.3 mg/L.
- Sulphur reducing agents: Sulphur agents such as thiosulphate, metabisulphite and sulphite will reduce chlorine dioxide and chlorite ion, thereby lowering their concentrations in water. Although benchscale studies demonstrated that thiosulphate is effective at reducing chlorine dioxide and chlorite, and does not form chlorate as a by-product, it requires a long contact time and the reaction is pH dependent. This may limit the effectiveness of thiosulphate for municipal-scale (Griese et al., 1991). In the presence of dissolved oxygen, sulphite and metabisulphite will reduce chlorite to form chloride ion and the undesirable chlorate ion and, as such, are not recommended for the removal of chlorite in drinking water.
Chlorine dioxide and chlorite ion will react with free chlorine to form chlorate ion. Once chlorate ion is present in water, it is very persistent and very difficult to remove (Gallagher et al., 1994; U.S. EPA, 1999a). Chlorate can also be formed during the generation of chlorine dioxide. Currently, there is no known practical and economical treatment available to remove chlorate ion once it has been formed in drinking water. As much as 35% of the chlorate found in a distribution system can be attributed to the performance (tuning) of the chlorine dioxide generator. If chlorite ion is present in water and is not removed, it will react with any applied free chlorine to produce chlorate and chloride ions. In order to control this persistent by-product, it is important to minimize its formation during the chlorine dioxide generation process and/or to remove the chlorite ion before adding secondary disinfection with chlorine (Gallagher et al., 1994).
The formation of chlorate ion in a hypochlorite solution is influenced by storage conditions such as pH, temperature, length of time in storage, presence of ultraviolet light, concentration of solution and presence of transition metals (Gordon et al., 1995). Hypochlorite solutions should:
- contain less than 1500 mg chlorate/L;
- have a pH greater than 12;
- be used within a relatively short time frame after delivery (within 3 months);
- be stored in a cool dry location where the temperature does not exceed 30°C, away from sunlight; and
- contain less than 0.08 mg/L of transition metals (AWWA, 2004).
Manufacturers are able to produce bleach that has a lower initial concentration of chlorate; utilities should specify hypochlorite solutions with a chlorate concentration as low as possible to ensure that they will meet the proposed guideline for chlorate in finished water .
Municipal treatment of drinking water is designed to reduce contaminants to levels at or below guideline value. As a result, the use of residential-scale treatment devices on municipally treated water is generally not necessary but primarily based on individual choice. Since chlorine dioxide would not be used to disinfect individual water systems, it is not likely that chlorite or chlorate would be present in individual surface water or groundwater sources. Some residential-scale treatment devices may remove chlorite, but none is currently certified for this use.
Health Canada does not recommend specific brands of drinking water treatment devices, but it strongly recommends that consumers look for a mark or label indicating that the device has been certified by an accredited certification body as meeting the appropriate NSF International (NSF)/American National Standards Institute (ANSI) standards. These standards have been designed to safeguard drinking water by helping to ensure the material safety and performance of products that come into contact with drinking water. Certification organizations provide assurance that a product conforms to applicable standards and must be accredited by the Standards Council of Canada (SCC). The following organizations have been accredited by the SCC to certify drinking water devices and materials as meeting NSF/ANSI standards:
- Canadian Standards Association International;
- NSF International;
- Water Quality Association;
- Underwriters Laboratories Inc.;
- Quality Auditing Institute and
- International Association of Plumbing & Mechanical Officials.
(An up-to-date list of accredited certification organizations can be obtained from the SCC).
Where point-of-entry or point-of-use treatment technology is being considered at the residential scale, chlorite removal options are limited solely to adsorption through a GAC filter. However, there are currently no certified drinking water treatment devices that specifically remove chlorite ion. NSF International has developed several standards for residential water treatment devices designed to reduce the concentrations of various types of contaminants in drinking water. However, chlorite is currently not included in any NSF/ANSI standard.
Research is ongoing in the private and public sectors to test and adopt efficient methods for the reduction of chlorite in drinking water. Products that use adsorption technology such as activated carbon lose removal capacity through usage and time and need to be replaced. Consumers should verify the expected longevity of the adsorption media in their treatment device as per the manufacturer's recommendations and service it when required, understanding that research shows breakthrough occurs earlier for chlorite than for other chlorine compounds.
Because chlorate ion is very difficult to remove from drinking water, there is no known residential-scale treatment technology available at the present time to remove it from residential tap water once it has been formed (Gallagher et al., 1994).
8.0 Kinetics and metabolism
8.1 Absorption and metabolism
Chlorite ion, chlorate ion and chlorine dioxide are rapidly absorbed from the gastrointestinal tract in rats. No particular organ appears to selectively concentrate the dose following exposure to chlorite ion, chlorate ion and chlorine dioxide (Abdel-Rahman, 1985). Following oral ingestion, chlorine dioxide was rapidly converted into chloride ion and, to a lesser extent, chlorite and chlorate by monkeys (Abdel-Rahman et al., 1982; Bercz et al., 1982). It was transformed mainly into chloride in rats, smaller amounts appearing as unchanged chlorite.
Following oral administration of chlorine dioxide to rats, the plasma levels of chlorine dioxide peaked after 1 hour. The plasma half-life was 44 hours (U.S. NRC, 1982).
The distribution of 36Cl-labelled chlorite ion (10 mg/L solution) and chlorate ion (5 mg/L solution) was studied in rats following oral administration. The amounts found in various fluids and tissues (as a percentage of the initial dose) after 72 hours for chlorite ion were as follows: 0.55% in plasma, 0.63% in packed cells, 0.64% in whole blood and a total of about 3% in kidneys, lungs, stomach, duodenum, ileum, liver, spleen, bone marrow, testes, skin and carcass, with the highest concentrations found in the testis, skin, stomach and lungs (0.4% each). Chlorate was distributed in the tissues as follows: 0.68% in plasma, 0.23% in packed cells and 0.57% in whole blood, with a total of 3.6% in kidneys, lungs, stomach, duodenum, ileum, liver, spleen, bone marrow, testes, skin and carcass and with the highest concentrations (0.4% each) in kidney, lung, stomach, testis and skin (Abdel-Rahman et al., 1982).
Rats excreted 30% of an oral dose of 36Cl-labelled chlorine dioxide in the urine after 72 hours. About 27% of the chlorine label was in the form of chloride and 3% in the form of chlorite ion. An additional 9% was excreted in the faeces. Of the labelled chlorite ion administered orally to rats, 40% was excreted in the urine as chloride after 72 hours. No chlorate ion was found after ingestion of chlorine dioxide or chlorite. When labelled chlorate ion was administered orally to rats, approximately 38% of the labelled material was excreted in the urine; 20% was in the form of chloride, 4% was in the form of chlorite ion and 13% was in the form of chlorate ion. The authors concluded that once these compounds are ingested, they are rapidly degraded in the body to chloride and consequently are not considered to be of toxicological concern following chronic exposure in drinking water (Abdel-Rahman et al., 1980b, 1984a, 1984b). Excretion of chlorite, chlorate and chlorine dioxide is mainly via the urine, smaller amounts being excreted in faeces (Abdel-Rahman et al., 1982, 1985).
9.0 Health effects
9.1 Effects in humans
9.1.1 Acute and short-term toxicity
Because of its use as a herbicide, a large number of cases of chlorate poisoning have been reported (U.S. NRC, 1987). Symptoms include methaemoglobinaemia, anuria, abdominal pain and renal failure. For an adult human, the oral lethal dose is estimated to be as low as 20 g of sodium chlorate, or 230 mg chlorate/kg bw (U.S. NRC, 1982).
Six different doses of chlorine dioxide (0.1, 1, 5, 10, 18 and 24 mg/L), chlorite ion (0.01, 0.1, 0.5, 1.0, 1.8 and 2.4 mg/L) and chlorate ion (0.01, 0.1, 0.5, 1.0, 1.8 and 2.4 mg/L) in drinking water were administered to each of 10 male volunteers (Lubbers et al., 1981). Each volunteer ingested 1000 mL of the water in two portions. The study involved a series of six sequences of 3 days each. Serum chemistry, blood count and urinalysis parameters were monitored. A treatment-related change in group mean values for serum uric acid was observed with chlorine dioxide exposure, which the authors concluded was not physiologically detrimental. The highest dose tested, 24 mg/L (about 0.34 mg/kg bw per day), can be identified as a single-dose no-observed-adverse-effect level (NOAEL) for chlorine dioxide. Changes in group mean values for serum urea nitrogen, creatinine and urea nitrogen/creatinine ratio were observed in the chlorite exposure groups, which the authors concluded were not adverse physiological effects. Very slight changes in group mean serum bilirubin, iron and methaemoglobin were observed in the chlorate exposure groups, but the authors concluded that they were not adverse physiological effects. A NOAEL of 2.4 mg/L (0.034 mg/kg bw per day) was identified for both chlorite ion and chlorate ion (Lubbers et al., 1981).
The same male volunteers drank 0.5 L of water containing 5 mg/L of chlorine dioxide each day for approximately 12 weeks and were then observed for 8 weeks. Serum chemistry, blood counts and urinalysis revealed no abnormalities, except for a slight change in blood urea nitrogen, which the authors concluded was of doubtful physiological or toxicological significance. This exposure, equivalent to 0.036 mg/kg bw per day, can be considered a NOAEL (Lubbers et al., 1981).
In a prospective study of 197 persons, a portion of the population of a rural village exposed for 12 weeks to a chlorine dioxide-treated water supply (containing 0.25-1.1 mg chlorine dioxide/L and 0.45-0.91 mg free chlorine/L) experienced no significant changes in haematological parameters, serum creatinine or total bilirubin (CMA, 1989).
9.1.2 Reproductive effects
A cross-sectional study was conducted of 548 births at Galliera Hospital in Genoa and 128 births at Chiavari Hospital in Chiavari (Italy) during 1988-1989 to mothers residing in each city (Kanitz et al., 1996). Women in Genoa were exposed to filtered water disinfected with chlorine dioxide (Brugneto River wells, reservoir and surface water) and/or chlorine (Val Noci reservoir). Women residing in Chiavari used untreated well water. Water source and type of disinfectant were recorded, as well as family income, mother's age, smoking, alcohol consumption, education level and birth outcomes (low birth weight, preterm delivery, body length, cranial circumference and neonatal jaundice). Neonatal jaundice was almost twice as likely (odds ratio 1.7; 95% confidence interval 1.1-3.1) in infants whose mothers used surface water disinfected with chlorine dioxide as in infants whose mothers used untreated well water. Chlorinated surface water did not produce a similar effect. Smaller cranial circumference and body length were associated with water from surface water sources disinfected with chlorine or chlorine dioxide. Risks of low birth weight (#2500 g) were also increased in infants whose mothers used drinking water disinfected with either chlorine or chlorine dioxide, but they were not statistically significant. For preterm delivery (#37 weeks), there were small but non-significant increased risks associated with chlorine or chlorine dioxide disinfection. This study suggests possible risks associated with surface water disinfected with either chlorine or chlorine dioxide, but the results should be interpreted very cautiously. No information was collected to assess the mothers' water consumption (including use of bottled water) or nutritional habits, and the age distribution of the mothers was not considered. In addition, there are concerns about incomplete ascertainment of births and whether the populations may be different in aspects other than the studied water system differences. Exposures to surface water and groundwater sources are compared in this study; however, no information is presented about other possible water quality differences. No conclusion can be drawn from this study, since some of the effects were not statistically significant and also because numerous biases were found (Kanitz et al., 1996).
9.2 Effects on experimental animals and in vitro
9.2.1 Acute toxicity
A summary of the available acute oral toxicity studies for sodium chlorite, sodium chlorate, and chlorine dioxide is provided in Table 3.
|Compound||Oral LD50 (mg/kg bw)||Clinical observations|
Table 3 Footnotes
|Sodium chlorite||105-165Table 3 Footnote 1,Table 3 Footnote 2||350Table 3 Footnote 1||not available||300Table 3 Footnote 1||not available|
|Sodium chlorate||1200Table 3 Footnote 3||3600Table 3 Footnote 3||7200Table 3 Footnote 3||6100Table 3 Footnote 3||not available|
|Chlorine dioxide||292Table 3 Footnote 4||not available||not available||not available||Somnolence and respiratory stimulation|
Acute effects were also seen one hour after dogs ingested 0.5-2 g sodium chlorate/kg bw; the dogs vomited and their methaemoglobin levels increased. Chlorate ion was observed in the blood and urine. Dogs who received the highest dose (between 1 and 2 g/kg bw) developed tachycardia and depression. They also exhibited cyanosis and died between 12 and 24 hours later (Sheahan et al., 1971).
9.2.2 Short-term exposure
In a recent study, doses of 0, 10, 25 or 80 mg sodium chlorite/kg bw per day were administered daily by gavage to male and female Crl: CD (SD) BR rats (15 per sex per group) for 13 weeks (equivalent to 0, 7.4, 18.6 or 59.7 mg chlorite/kg bw per day). The highest dose produced death in a number of animals (Harrington et al., 1995). It also resulted in morphological changes in erythrocytes and significant decreases in haemoglobin concentrations. A non-significant reduction in red blood cell counts was observed at 10 mg/kg bw per day in male rats, with further decreases being observed at 80 mg/kg bw per day. Red blood cell counts were significantly depressed in female rats at doses of 25 mg/kg bw per day and above. As would be expected where haemolysis is occurring, splenic weights were increased. Adrenal weights were increased in females at 25 and 80 mg/kg bw per day, whereas statistically significant changes were observed only at 80 mg/kg bw per day in males. Histopathological examination of necropsied tissues revealed squamous cell epithelial hyperplasia, hyperkeratosis, ulceration, chronic inflammation and oedema in the stomach of 7 of 15 males and 8 of 15 females given 80 mg/kg bw per day doses. This effect was observed in only 2 of 15 animals at the 25 mg/kg bw per day dose and not at all at the 10 mg/kg bw per day dose. The NOAEL for this study was determined to be 7.4 mg chlorite/kg bw per day for stomach lesions and increases in spleen and adrenal weights (Harrington et al., 1995).
In an study of oxidative damage to erythrocytes, rats were exposed to chlorite ion at 0, 1, 5, 10, 25 or 50 mg/kg bw per day for 30-90 days in their drinking water. Haematological parameters were monitored, and the three highest concentrations produced transient anaemia. At 90 days, red blood cell glutathione levels in the 10 mg/kg bw per day group were 40% below those of controls, and there was at least a 20% reduction in rats receiving 5 mg/kg bw per day. A NOAEL of 1 mg/kg bw per day was identified (Heffernan et al., 1979). While providing useful information on the toxicity of chlorite, the design of this study would not make it suitable as a basis for setting a drinking water guideline, because the effects were transient and occurred at only two dose levels.
Both A/J and C57L/J mice were exposed to sodium chlorite at about 0, 0.15, 1.5 or 15 mg/kg bw per day in their drinking water for 30 days. At a dose of 15 mg/kg bw per day, increases in glucose-6-phosphate dehydrogenase, mean corpuscular volume and osmotic fragility were observed; however, no increases were seen at lower doses. There was a significant difference between strains for both glucose-6-phosphate dehydrogenase and osmotic fragility (Moore et Calabrese, 1982). The NOAEL for this study was 1.5 mg/kg bw per day, based on blood changes.
African green monkeys (five males and seven females) were used to study the thyroid effects of chlorite when administered for 30-60 days as sodium chlorite at concentrations of 0, 25, 50, 100, 200 and 400 mg/L (equivalent to 0, 4, 7.5, 15, 30 or 58.4 mg/kg bw per day) (U.S. NRC, 1987; Bercz, 1992). Chlorite did not induce thyroid depression. Chlorite induced a dose-dependent oxidative stress, which resulted in a decrease in haemoglobin and erythrocyte count and an increase in methaemoglobin, which is interpreted as oxidative stress on haematopoiesis. There was a statistically significant dose-dependent increase in alanine aminotransaminase, but the authors indicated that the change was not clinically important. The blood changes during the study reversed before the end of the administration of chlorite, further indicating that only mild clinical changes had occurred. No NOAEL or LOAEL was determined in this study. However, based on a review by the U.S. EPA (2000), the data were not presented in a manner that would allow identification of threshold doses for these effects.
In another study, male rats and white leghorn chickens were given chlorite in drinking water at approximately 0, 4.28, 42.8 and 428 mg/kg bw per day (chickens) and 0, 3.42, 34.2 and 342 mg/kg bw per day (rats) for 4 months. A decrease in osmotic fragility of erythrocytes and in the morphology of erythrocytes was observed in both species in all treatment groups (Abdel-Rahman et al., 1980a)
No evidence of adverse toxicity except for minor signs of anaemia at the highest dose was observed in rats orally administered sodium chlorate by gavage at doses of 0, 10, 100 or 1000 mg/kg bw per day for 13 weeks (Bio/Dynamics, Inc., 1987b).
Beagle dogs (four per sex per dose) were exposed by gavage to sodium chlorate at doses of 0, 10, 60 or 360 mg/kg bw per day for 3 months. Haematological changes were limited to a slight elevation in methaemoglobin level in high-dose animals, but this appeared to be within normal limits and was not judged to be treatment-related. No other effects were observed. A NOAEL of 360 mg/kg bw per day in dogs was identified (Bio/Dynamics, Inc., 1987a).
Sprague-Dawley rats (14 per sex per dose) were exposed by gavage to sodium chlorate at doses of 0, 10, 100 or 1000 mg/kg bw per day for up to 3 months. At the highest dose, haematological changes indicative of anaemia included decreases in erythrocyte count, haemoglobin concentration and erythrocyte volume fraction (haematocrit). No other effects were observed. A NOAEL of 100 mg/kg bw per day was identified (Bio/Dynamics Inc., 1987b).
In a 90-day study, concentrations of chlorate at 0, 30, 100 or 510 mg/kg bw per day in males and 0, 42, 164 or 800 mg/kg bw per day in females in drinking water were provided to Sprague-Dawley rats. Body weight gain was sharply curtailed in both sexes at the highest concentration. These effects were generally paralleled by smaller organ weights (except for brain and testes). Some decreases in haemoglobin, haematocrit and red blood cell counts were observed at this same dose. Pituitary lesions (vacuolization in the cytoplasm of the pars distalis) and thyroid gland colloid depletion were observed in both the mid- and high-dose groups of both sexes. A NOAEL of 30 mg/kg bw per day was identified (McCauley et al., 1995).
African green monkeys (five males and seven females) were used to study the thyroid effects of chlorate when administered for 30-60 days as sodium chlorate at concentrations of 0, 25, 50, 100, 200 and 400 mg/L (0, 4, 7.5, 15, 30 or 58.4 mg/kg bw per day) (Bercz, 1992; IPCS, 2000). Chlorate did not induce thyroid depression. Chlorate did not induce a dose-dependent oxidative stress, as was observed in the case of chlorite. No NOAEL or LOAEL was determined in this study.
In another study, male rats and white leghorn chickens were given chlorate in drinking water at approximately 4.28, 42.8 and 428 mg/kg bw per day (chickens) and 3.42, 34.2 and 342 mg/kg bw per day (rats) for 4 months. A decrease in osmotic fragility of erythrocytes and in the morphology of erythrocytes was observed in both species in all treatment groups (Abdel-Rahman et al., 1980a).
188.8.131.52 Chlorine Dioxide
Drinking water containing chlorine dioxide at 0, 1.5 or 15 mg/kg bw per day was administered to mice (10 per dose) for 30 days with no apparent effects on blood parameters. The NOAEL for this study was 15 mg/kg bw per day (Moore and Calabrese, 1982).
Twelve African green monkeys were exposed to water containing chlorine dioxide at doses of 0, 30, 100 or 200 mg/L (0, 3.5, 9.5 or 11 mg/kg bw per day) using a rising-dose protocol (Bercz et al., 1982). Each dose was maintained for 30-60 days, except for the high dose exposure group which was terminated after 1 week due to signs of dehydration and an excess of nitrogenous bodies in the blood as a result of kidney insufficiency. A slight suppression of thyroid function (decreased thyroxine) was observed in monkeys receiving 100 mg/L. No other effects were noted (Bercz et al., 1982). A review by IPCS (2002) found that the two highest concentrations were both equivalent to about 9 mg/kg bw per day due to impaired palatability leading to reduced water intake.. The suppression of thyroid function was not supported by the few data available. Overall, at 200 mg/L, there were clear indications of irritation of the oral cavity, leading to palatability problems. At 100 mg/L (approximately 9 mg/kg bw per day) or less, there were no clear effects among these primates over an 8-week exposure period (IPCS, 2002).
Six monkeys were treated for 8 weeks with drinking water containing chlorine dioxide at 4.6 mg/kg bw per day. Thyroxine level was reduced after 4 weeks of treatment but rebounded after a further 4 weeks. In the same study, drinking water containing chlorine dioxide was administered to male rats (12 per dose) at 0, 10 or 20 mg/kg bw per day. A dose-dependent decrease in thyroxine levels was observed after 8 weeks of treatment; there was no rebound. The LOAEL in this study was identified as 10 mg/kg bw per day (Harrington et al., 1986). According to IPCS (2002), there was no consistent pattern for effects on the thyroid.
Sprague-Dawley rats (10 per sex per dose) were exposed to chlorine dioxide in drinking water for 90 days at dose levels of 0, 2, 4, 6 or 12 mg/kg bw per day for males and 0, 2, 5, 8 or 15 mg/kg bw per day for females. Water consumption was decreased in both sexes at the three highest dose levels, probably because of its reduced palatability. Food consumption was decreased in males receiving the highest dose. Goblet cell hyperplasia was significantly increased in the nasal turbinates of females given 8 or 15 mg/kg bw per day and of males at all doses. Inflammation of the nasal cavity was observed in males at 2 mg/kg bw per day and in both sexes at higher doses. However, the authors mentioned that these lesions were likely caused by inhalation of chlorine dioxide vapours at the drinking water sipper tube or from off-gassing of the vapours after drinking rather than by ingestion of the drinking water. The authors concluded that the lowest dose (2 mg/kg bw per day) was a LOAEL (Daniel et al., 1990).
In another study, male rats and white leghorn chickens were given chlorine dioxide in drinking water at approximately 0, 4.28, 42.8 and 428 mg/kg bw per day (chickens) and 0, 3.42, 34.2 and 342 mg/kg bw per day (rats) for 4 months. A decrease in osmotic fragility of erythrocytes and in the morphology of erythrocytes was observed in both species in all treatment groups (Abdel-Rahman et al., 1980a).
9.2.3 Long-term exposure and carcinogenicity
A one year study was conducted to examine the effects of chlorine dioxide and its metabolites on the formation of chloroform, H-thymidine incorporation in organs, and hepatic microsomal enzyme activities in rats. Male Sprague-Dawley rats were given double-distilled water containing chlorine dioxide at 0, 1, 10 or 100 mg/L (corresponding to 0, 0.1, 1 and 10 mg/kg bw per day), chlorite at 1 or 10 mg/L (corresponding to 0.1 and 1 mg/kg bw per day) or chlorate at 1 or 10 mg/L (corresponding to 0.1 and 1 mg/kg bw per day) for 1 year . Blood chloroform levels were decreased in the chlorine dioxide-treated groups at 2, 10 and 12 months treatment. In addition, the chlorite and chlorate treatment groups showed similar decreases in blood chloroform concentration after 1 year of treatment. However, no significant chloroform values in liver, kidney, spleen, testes, and brain were observed in any treatment group in the same time period. I (Suh et al., 1984).
Sprague-Dawley rats (four males per group) were given different concentrations of chlorine dioxide (0, 1, 10, 100 or 1000 mg/L), chlorite ion (10 or 100 mg/L) or chlorate ion (10 or 100 mg/L) in double-distilled water 20 hours per day, 7 days per week, for a year (Abdel-Rahman et al., 1984a). Control animals received double-distilled water. Rats were administered methyl 1',3'-3H-thymidine at 0.5 µCi/g bw intraperitoneally after treatment with 10 and 100 mg chlorine dioxide/L, 10 and 100 mg chlorite/L and 10 mg chlorate/L in daily drinking water. Nuclei of liver, kidney, testes and mucosa of small intestines were taken for determination of thymidine incorporation. Decreased osmotic fragility in the red blood cells was observed in all treatment groups. At 2 months, blood glutathione content decreased significantly in all treatment groups except the 100 mg chlorine dioxide/L group. At 4 months, glutathione content decreased only in the 1 and 10 mg chlorine dioxide/L groups and in the 100 mg chlorite/L group. At 9 months, decreased glutathione was observed in both the chlorite and chlorate groups, while it was significantly increased in the 100 mg chlorine dioxide/L groups. Changes were observed in the blood cell compartment after 7 months, but not before this period. The red blood cell counts were significantly increased in the 100 mg chlorine dioxide/L group, while they were decreased in the 10 mg chlorate/L group. Haematocrit was increased in the 100 and 1000 mg chlorine dioxide/L treatment groups and decreased in the 10 mg chlorate/L group. The mean corpuscular haemoglobin concentration was increased in the 10 mg chlorine dioxide/L and the 10 and 100 mg chlorite/L groups. After 9 months, red blood cell counts, haematocrit and haemoglobin were decreased in all treatment groups. All three compounds inhibited the incorporation of 3H-thymidine into nuclei in rat testes, whereas chlorite inhibited its incorporation in the liver and chlorine dioxide (100 mg/L) in the kidney. The incorporation of 3H-thymidine in small intestinal nuclei was increased at both 10 and 100 mg chlorine dioxide/L and at 10 mg chlorite/L. The treatment with all three compounds decreased rat body weights in all groups after 10 and 11 months of treatment (Abdel-Rahman et al., 1984a).
The effect of sodium chlorite in drinking water at 0, 1, 2, 4, 8, 100 or 1000 mg/L (equivalent to doses of 0, 0.09, 0.18, 0.35, 0.7, 9.3 or 81 mg/kg bw per day) on the survival and postmortem pathology of albino rats (seven per sex per dose) was examined in a 2-year study. The life span of the animals was not significantly affected at any dose. No effects were observed in animals exposed to 0.7 mg/kg bw per day or less. Animals exposed to 9.3 or 81 mg/kg bw per day exhibited treatment-related renal pathology; the author concluded that this was the result of a non-specific salt effect (Haag, 1949). In a review by TERA (1998), adverse renal effects were seen at doses of 8.3 and above, even though according to the author they may have been non specific, and based on these renal effects, this study identified a NOAEL of 0.7 mg/kg bw per day. According to the review by TERA (1998), this study had limited value, since an insufficient number of animals were tested per group, the pathology was conducted on a small number of animals and the author did not adequately evaluate more sensitive parameters.
In a carcinogenicity study in which sodium chlorite was administered to B6C3F1 mice (50 per sex per dose) at concentrations of 0, 250 or 500 mg/L (equivalent to 0, 36 or 71 mg chlorite ion/kg bw per day) in drinking water for 80 weeks, there was no significant increase in tumours compared with controls at a dose of 36 mg chlorite ion/kg bw per day. Although treated male mice exhibited an increased incidence of lung and liver tumours, tumour rates were within historical ranges for control mice, increases in the liver tumours did not display a typical dose-response pattern and significant increases were seen only for benign tumours (Kurokawa et al., 1986). This study was not conducted for the entire life span of the animals and was not considered adequate based on Organisation for Economic Co-operation and Development (OECD) guidelines.
Chlorite ion was given to Sprague-Dawley rats (four males per group) in drinking water for 12 months (7 days per week) at dose levels of 0, 1 or 10 mg/kg bw per day, based on a reference body weight of 0.523 kg and a drinking water intake of 0.062 L/day (Couri and Abdel-Rahman, 1980; Abdel-Rahman et al., 1984b). There were significant decreases in body weight gain at 10 mg/kg bw per day at all measuring periods; body weight gain was also decreased in the 1 mg/kg bw per day group at 10 and 11 months. No changes were observed in erythrocyte count, haematocrit or haemoglobin levels. Mean corpuscular haemoglobin concentration was increased at both exposure levels after 7 months of exposure, but not after 9 months. Osmotic fragility was significantly decreased at 1 and 10 mg/kg bw per day after 7 and 9 months of exposure. DNA synthesis (as measured by 3H-thymidine incorporation) was decreased in the liver and the testes at 1 and 10 mg/kg bw per day, decreased in the intestinal mucosa at 10 mg/kg bw per day and increased in the intestinal mucosa at 1 mg/kg bw per day. Blood glutathione reductase activity was significantly increased at 1 and 10 mg/kg bw per day after 6 months of exposure and decreased at 1 mg/kg bw per day after 12 months. Blood glutathione peroxidase was not altered after 6 months of exposure, but was decreased in both groups after 12 months. Significant decreases in blood glutathione levels were observed in both groups. Blood catalase activity was decreased after 6 months of exposure in the 1 and 10 mg/kg bw per day groups and increased in the 1 mg/kg bw per day groups after 12 months. The lack of consistent dose-response, small numbers of animals and small magnitude of effects complicate the interpretation of the results (Couri and Abdel-Rahman, 1980; Abdel-Rahman et al., 1984b).
There are no studies of the carcinogenic potential of chlorate administered alone. Sodium and potassium chlorate were evaluated as promoters of renal tumours in N-ethyl-N-hydroxyethylnitrosamine-initiated F344 rats. Sodium but not potassium chlorate caused an increase in the number of renal tumours, but the effect was not statistically significant due to the small number of animals used (Kurokawa et al., 1986).
Chlorate ion was administered to Sprague-Dawley rats (four males per group) in drinking water for 12 months (7 days per week) at dose levels of 0, 1 or 10 mg/kg bw per day based on a reference body weight of 0.523 kg and a drinking water intake of 0.062 L/day. After 6 months, blood glutathione peroxidase was increased in the 10 mg/kg bw per day group only. A decrease in catalase activity was observed in the 10 mg/kg bw per day group. After 6 and 12 months, a significant increase in blood glutathione levels was observed at both dose levels compared with the control groups (Couri and Abdel-Rahman, 1980).
184.108.40.206 Chlorine dioxide
Chlorine dioxide was given to Sprague-Dawley rats (four males per group) in drinking water for 12 months (7 days per week) at dose levels of 0, 0.1, 1, 10 or 100 mg/kg bw per day, based on a reference body weight of 0.523 kg and a drinking water intake of 0.062 L/day. After 12 months of exposure, the erythrocyte glutathione reductase levels in treated rats were similar to those of the controls, but the levels of erythrocyte glutathione peroxidase were significantly increased at 10 and 100 mg/kg bw per day. Erythrocyte glutathione concentrations were significantly decreased at 0.1, 1 and 10 mg/kg bw per day after 6 months and at 100 mg/kg bw per day after 12 months of exposure. Erythrocyte catalase levels were increased in the 100 mg/kg bw per day group after 6 and 12 months of exposure and decreased in the 0.1 and 1 mg/kg bw per day group after 6 months of exposure (Couri and Abdel-Rahman, 1980).
Chlorine dioxide was also given to Swiss mice in drinking water for 12 months (7 days per week) at dose levels of 0, 0.18, 1.8, 18 or 180 mg/kg bw per day. Glutathione peroxidase levels were decreased at 18 mg/kg bw per day and increased at 180 mg/kg bw per day after 12 months of exposure, and glutathione levels were decreased at 1.8 and 18 mg/kg bw per day after 12 months. Catalase levels were increased in the 1.8, 18 and 180 mg/kg bw per day groups after 12 months of exposure. The inconsistent relationship between the dose and the magnitude of the alterations in the glutathione-dependent system makes interpretation of the results of this study difficult. In addition, it is not clear if these effects are biologically significant. Therefore, no NOAEL or LOAEL could be determined (Couri and Abdel-Rahman, 1980).
Chlorine dioxide was given to white male leghorn chicken (four per group) in drinking water for 10 months (7 days per week) at concentrations of 0, 10, 100 or 1000 mg/L. An increase of 70% in the activity of glutathione reductase was observed at all concentrations. Glutathione peroxidase activity was significantly decreased at the highest concentration; however, catalase activity was increased in the same group. Glutathione peroxidase activity varied inversely with the concentration of chlorine dioxide in drinking water (Couri and Abdel-Rahman, 1980).
Chlorine dioxide was administered in drinking water to rats (seven per sex per dose) at concentrations of 0, 0.5, 1, 5, 10 or 100 mg/L (equivalent to dose levels of 0, 0.07, 0.13, 0.7, 1.3 and 13 mg/kg bw per day) for 2 years. At the highest dose level, survival rate was substantially decreased in both sexes, and mean life span was reduced compared with that for control animals. No correlation was observed between treatment and histopathological findings (Haag, 1949). A NOAEL of 1.3 mg/kg bw per day was identified, although according to TERA (1998), this 1949 study has serious limitations.
Sodium chlorite produced an increase in revertants in Salmonella typhimurium strain TA100 in both the presence and absence of metabolic activation (Ishidate et al., 1984). No chromosomal abnormalities were seen in either the mouse micronucleus test or a cytogenetic assay in mouse bone marrow cells following gavage dosing with chlorite (Meier et al., 1985).
A positive result was obtained in a micronucleus test in bone marrow from male ddY mice after a single intraperitoneal injection of sodium chlorite at 0, 7.5, 15, 30 or 60 mg/kg bw. A statistically positive response was observed at 15 and 30 mg/kg bw only: 0.38% and 1.05%, respectively, compared with 0.18% for the control group (Hayashi et al., 1988).
Chlorate has long been known to select nitrate reductase-deficient mutants of Aspergillus nidulans (Cove, 1976). However, it has been demonstrated that there is also a mutagenic effect of chlorate in Chlamydomonas reinhardtii and Rhodobacter capsulatus. Chlorate failed to induce mutations in the BA-13 strain of Salmonella typhimurium. The positive mutagenic effects were separated from simple selection of nitrate reductase mutants by incubating cells in nitrogen-free media; lack of nitrogen prevents cell division during the treatment period. In the case of C. reinhardtii, significant increases in mutants were observed at concentrations of 4-5 mmol/L and above (Prieto and Fernandez, 1993).
No chromosomal abnormalities were seen in either the micronucleus test or a cytogenetic assay in mouse bone marrow cells following gavage dosing with chlorate (Ishidate et al., 1984).
220.127.116.11 Chlorine dioxide
In vitro, chlorine dioxide was mutagenic in Salmonella typhimurium strain TA100 in the absence of a metabolic activation system (S9) (Ishidate et al., 1984). No sperm head abnormalities were observed in male mice following chlorine dioxide gavage (Meier et al., 1985). In an in vitro cytogenetics assay, Chinese hamster ovary (CHO) cells were treated with 0, 2.5, 5, 10, 15, 30 or 60 µg 0.2% chlorine dioxide/mL in phosphate-buffered saline solution without metabolic activation (-S9). A second experiment was conducted with CHO cells treated at 0, 6, 13, 25, 50 or 75 µg/mL with metabolic activation (+S9). In the first experiment (without metabolic activation), cell toxicity was observed at 60 µg/mL, and there was an absence of mitotic cells at 30 µg/mL. At 2.5-15 µg/mL, there was a dose-related, statistically significant increase in the number of metaphases with chromosome aberrations. In the second experiment (with metabolic activation), cell toxicity and absence of mitotic cells were observed at 75 µg/mL. A statistically significant increase in the number of metaphases with chromosome aberrations was noted at 50 µg/mL (Ivett and Myhr, 1986). In a mouse lymphoma forward mutation assay (using L5178Y TK+/-), cells were treated with 0-65 µg chlorine dioxide/mL in phosphate-buffered saline with and without metabolic activation (S9). Without S9, marked toxicity was observed at the highest concentration used, 37 µg/mL. The relative growth at the next two concentrations (15 and 24 µg/mL) was 13-18%. There was a dose-related increase in mutant frequency. With S9, marked toxicity was observed at the highest concentration, 65 µg/mL, and there was also a dose-related increase in mutant frequency, indicating positive results both with and without metabolic activation in this test system (Cifone and Myhr, 1986).
In in vivo studies, no chromosomal abnormalities were seen in either the micronucleus test or a cytogenetic assay in mouse bone marrow cells following gavage dosing with chlorine dioxide (Meier et al., 1985). CD-1 mice (five per sex) received a single intraperitoneal injection of 0, 2, 5 or 15 mg chlorine dioxide/kg bw in a bone marrow cytogenetic assay. Bone marrow cells were analysed for chromosome aberrations at 6, 24 and 48 hours. There were no clear effects on the mitotic index, but two males receiving approximately 15 mg chlorine dioxide/kg bw died, and other signs of toxicity were also observed at the highest dose level. There were no increases in the frequency of chromosome aberrations among treated animals at any of the sacrifice times compared with controls (Ivett and Myhr, 1984). Groups of five male ICR mice received a single intraperitoneal injection of approximately 0, 9, 21, 28 or 39 mg aqueous chlorine dioxide/kg bw. Following subcutaneous implantation of bromodeoxyuridine and 26 hours after chlorine dioxide administration, approximately 25 bone marrow metaphase cells from each animal were assessed for sister chromatid exchange. All animals showed hyperactive behaviour after administration of chlorine dioxide. Overall, there were no significant increases in sister chromatid exchange among any of the chlorine dioxide-treated groups (Ivett and Myhr, 1984).
In a dominant lethal assay in rats administered up to 20 mg aqueous chlorine dioxide/kg bw intraperitoneally, no mutagenic effects on male germ cells were observed (Moore and Myhr, 1984).
9.2.5 Reproductive and developmental toxicity
In a series of three experiments, sodium chlorite was administered to male rats (12 per dose) in drinking water for 66-76 days at concentrations of 0, 0.075, 0.75, 7.5 or 27 mg chlorite/kg bw per day. No compound-related abnormalities were observed on histopathological examination of the reproductive tract. Abnormal sperm morphology and decreased sperm motility were seen at the two highest dose levels, but no sperm effects were observed at 0.75 mg/kg bw per day, which can be identified as the NOAEL (Carlton et al., 1987).
In another part of the same study, male rats were bred with female rats treated at 0, 0.075, 0.75 or 7.5 mg chlorite/kg bw per day dose levels. Males were exposed for 56 days and females for 14 days prior to breeding and throughout the 10-day breeding period. Females were also exposed throughout gestation and lactation until the pups were weaned on day 21. There was no evidence of any adverse effects on conception rates, litter size, day of eye opening or day of vaginal opening. Decreases in the concentrations of triiodothyronine and thyroxine in blood were observed on postnatal days 21 and 40 in male and female pups exposed to 7.5 mg/kg bw per day. Based on reproductive effects, the NOAEL was 0.75 mg/kg bw per day (Carlton et al., 1987).
CMA (1996) and Gill et al. (2000) conducted a two-generation study in which Sprague-Dawley rats (30 per sex per dose) received drinking water containing 0, 35, 70 or 300 mg sodium chlorite/L for 10 weeks and were then paired for mating. Males were exposed throughout mating, then sacrificed. Exposure for the females continued through mating, pregnancy and lactation until necropsy following weaning of their litters. Twenty-five males and females from each of the first 25 litters to be weaned in a treatment group were chosen to produce the F1 generation. The F1 pups were continued on the same treatment regimen as their parents. At approximately 14 weeks of age, they were mated to produce the F2a generation. Because of a reduced number of litters in the 70 mg/L F1-F2a generation, the F1 animals were remated following weaning of the F2a generation to produce the F2b generation. The corresponding chlorite dose, as calculated by EPA and reported in a review by TERA (1998), for the F0 animals were 0, 3.0, 5.6 or 20.0 mg chlorite/kg bw per day for males and 0, 3.8, 7.5 or 28.6 mg chlorite/kg bw per day for females. For the F1 animals, doses were 0, 2.9, 5.9 or 22.7 mg chlorite/kg bw per day for males and 0, 3.8, 7.9 or 28.6 mg chlorite/kg bw per day for females. There were reductions in water consumption, food consumption and body weight gain in both sexes in all generations at various times throughout the experiment, primarily in the 70 and 300 mg/L groups; these were attributed to lack of palatability of the water. At 300 mg/L, reduced pup survival, reduced body weight at birth and throughout lactation in F1 and F2, lower thymus and spleen weights in both generations, lowered incidence of pups exhibiting a normal righting reflex, delays in sexual development in males and females in F1 and F2 and lower red blood cell parameters in F1 were noted. Significant reductions in absolute and relative liver weights in F0 females and F1 males and females, reduced absolute brain weights in F1 and F2 and a decrease in the maximum response to auditory startle stimulus on postnatal day 24 but not on postnatal day 60 were noted in the 70 and 300 mg/L groups. Minor changes in red blood cell parameters in the F1 generation were seen at 35 and 70 mg/L, but these appear to be within normal ranges based on historical data. The NOAEL and LOAEL in this study, as reported by TERA (1998), were 35 mg/L (2.9 mg/kg bw per day) and 70 mg/L (5.9 mg/kg bw per day), based on lower auditory startle amplitude, decreased absolute brain weight in the F1 and F2 generations and altered liver weights in two generations.
Two groups of female A/J mice were treated with sodium chlorite in drinking water at doses of 0 and 100 ppm (equivalent to 0 and 22 mg/kg bw per day - according to U.S. EPA, 2000) from day 1 of gestation and throughout lactation; 21 control and 12 exposed dams had litters. Conception rates were 56% for controls and 39% for treated mice. The body weights of pups at weaning were reduced (14% below the controls) in treated mice (Moore and Calabrese, 1982), so that 22 mg/kg bw per day (the only dose tested) is the LOAEL for this study (U.S. EPA, 2000).
Fetuses from maternal Sprague-Dawley rats exposed to chlorite ion via drinking water at levels of 1 or 10 mg/L for 2.5 months prior to mating and throughout gestation were examined. There was an increase in the incidence of anomalies at both concentrations; however, because the treatment groups were small (6-9 females per group), the effects were not considered statistically significant (Suh et al., 1983).
New Zealand white rabbits (16 per group) were treated with 0, 10, 26 or 40 mg chlorite ion/kg bw per day in their drinking water from day 7 to day 19 of pregnancy to study developmental toxicity. The animals were necropsied on day 28. Food consumption was depressed at the two highest doses, and water consumption was depressed at all doses, but more notably at the two highest doses. Mean fetal weights were slightly lower at the two highest doses as well, with a slightly higher incidence of incomplete ossification of some bones. There were no dose-related increases in defects identified. Minor skeletal anomalies were observed as the concentration of chlorite in water was increased and maternal food consumption was depressed (Harrington et al., 1995).
Groups of female Sprague-Dawley rats (12 per group) were exposed for 9 weeks to drinking water containing 0, 3 or 6 mg chlorite/kg bw per day beginning 10 days prior to breeding with untreated males and until the pups were sacrificed at 35-42 days post-conception. From day 31 to day 42 post-conception, six litters of each treatment group were assessed for the development of exploratory activity. Pups exposed to a dose of 6 mg/kg bw per day exhibited a consistent and significant depression in exploratory behaviour on post-conception days 36-39, but not on day 40. Exploratory activity was comparable between treated and control groups after post-conception day 39. Based on behavioural effects, the NOAEL and LOAEL were identified as 3 and 6 mg/kg bw per day, respectively (Mobley et al., 1990).
No studies were available examining the reproductive or embryotoxic potential of chlorate. Sodium chlorate was administered to pregnant CD rats by gavage at doses of 0, 10, 100 or 1000 mg/kg bw per day on days 6-15 of gestation. There were no maternal deaths in treated animals or treatment-related effects on maternal body weight gain, food consumption, clinical observations, number of implantations or gross necropsy. Examination of fetuses on day 20 revealed no effects on fetal weight or sex ratio, and no external, visceral or skeletal abnormalities were detected. In this study, a developmental NOAEL of 1000 mg/kg bw per day in rats was identified (Bio/Dynamics, Inc., 1987c).
18.104.22.168 Chlorine dioxide
A one-generation study was carried out with chlorine dioxide administered to Long-Evans rats by gavage at doses of 0, 2.5, 5 or 10 mg/kg bw per day to male rats (12 per group) for 56 days prior to and through mating to female rats (24 per group) that were dosed from 14 days prior to mating and through pregnancy. Fertility measures were not significantly different among the dose groups. There were no dose-related changes in sperm parameters (i.e., concentration, motility, progressive movement or morphology). Thyroid hormone levels were altered significantly, but not in a consistent pattern. The only significant difference was depressed vaginal weights in female pups whose dams had been treated with 10 mg/kg bw per day. Based on this one change, the NOAEL was considered to be 5 mg/kg bw per day (Carlton et al., 1991).
The developmental neurotoxic potential of chlorine dioxide was evaluated in a study in which it was administered to male and female Sprague-Dawley rat pups by oral intubation at 14 mg/kg bw per day on postnatal days 1-20. Forebrain cell proliferation was decreased on postnatal day 35, and there were decreases in forebrain weight and protein content on postnatal days 21 and 35. Cell proliferation in the cerebellum and olfactory bulbs was comparable to that in untreated controls, as were migration and aggregation of neuronal cells in the cerebral cortex. Histopathological examination of the forebrain, cerebellum and brain stem did not reveal any lesions or changes in these tissues. In this study, a LOAEL of 14 mg/kg bw per day (the only dose tested) was identified (Toth et al., 1990).
Female Sprague-Dawley rats received chlorine dioxide at approximately 0, 0.07, 0.7 or 7 mg/kg bw per day in drinking water (Suh et al., 1983). After approximately 10 weeks of exposure, females were mated with untreated males and continued to receive chlorine dioxide throughout gestation. On day 20 of gestation, the dams were euthanized, their uteri were removed and weighed and fetuses were examined; half of the fetuses were examined for skeletal and half for visceral abnormalities. There were no clinical signs of toxicity and no exposure-related mortalities among the dams. There was a slight, but statistically significant, reduction in body weight gain among dams at 0.7 and 7 mg/kg bw per day during pregnancy (about 14% reduction compared with controls). There was a slight reduction in the mean number of implants per dam in the two highest dose groups, which was statistically significant at 7 mg/kg bw per day (10.3 per dam compared with 12.3 per dam in controls), with a similar change in the number of live fetuses. This may be related to maternal toxicity at these two exposure levels, as there was a slight reduction in body weight gain among dams. The incidence of litters with anomalous fetuses was unaffected by treatment (5/6, 4/6, 6/6 and 7/8 among animals receiving 0, 0.07, 0.7 and 7 mg/kg bw per day, respectively) (Suh et al., 1983).
Female Sprague-Dawley rats (13-16 per dose) were supplied with drinking water containing 0, 1, 3 or 14 mg/kg bw per day from 2 weeks before mating through gestation and lactation until pups were weaned on postnatal day 21. No significant effect on the body weight of either the dams or the pups was observed at any dose tested. At 14 mg/kg bw per day for the pregnant dams, a significant depression of serum thyroxine and an increase in serum triiodothyronine were observed in the pups at weaning, but not in the dams. Neurobehavioural exploratory and locomotor activities were decreased in pups born to dams exposed to 14 mg/kg bw per day but not in pups born to those exposed to 3 mg/kg bw per day, which was considered a NOAEL (Orme et al., 1985).
In a companion study, Sprague-Dawley rat pups were exposed directly (by gavage) to 14 mg chlorine dioxide/kg bw per day on postnatal days 5-20. In this study, serum thyroxine levels were depressed, a somewhat greater and more consistent delay in the development of exploratory and locomotor activity was seen and pup body weight gain was reduced. The decrease in serum triiodothyronine levels was not statistically significant. Based on decreased pup development and decreased thyroid hormone levels, a LOAEL of 14 mg/kg bw per day (the only dose tested) was identified (Orme et al., 1985).
Cell number was significantly depressed in the cerebellum of 21-day-old rat pups born to Sprague-Dawley dams supplied during gestation and lactation with water containing about 14 mg chlorine dioxide/kg bw per day. A group of 12 rat pups dosed directly by gavage with 14 mg/kg bw per day had depressed cell numbers in both the cerebellum and forebrain at postnatal day 11 and displayed decreased voluntary running-wheel activity at postnatal days 50-60, despite the fact that chlorine dioxide treatments were terminated at 20 days of age. These data suggest that chlorine dioxide is capable of influencing brain development in neonatal rats. In this study, a LOAEL of 14 mg/kg bw per day, the only dose tested, was identified (Taylor and Pfohl, 1985).
10.0 Classification and assessment
Based on the available data, chlorite has been classified in Group VIA (inadequate data for evaluation of carcinogenicity to humans) (Health Canada, 1994). This concurs with the conclusions by IARC (1991) -- Group 3, not classifiable as to its carcinogenicity to humans -- and by U.S. EPA (2005)-- not classifiable as to human carcinogenicity because of inadequate data in humans and animals (U.S. EPA, 1996).
Subchronic studies in animals (cats, mice, rats and monkeys) indicate that chlorite and chlorate cause haematological changes (osmotic fragility, oxidative stress, increase in mean corpuscular volume), stomach lesions and increased spleen and adrenal weights (Heffernan et al., 1979; Bercz et al., 1982; Moore and Calabrese, 1982; Bio/Dynamics, Inc., 1987b; Harrington et al., 1995; McCauley et al., 1995).
No carcinogenicity studies were found for chlorite in the literature. The chronic study on mice with chlorite (Kurokawa et al., 1986) was not conducted for the entire life span of the animals and was not considered adequate based on OECD guidelines. Although haematological effects were observed in the rat study (Couri and Abdel-Rahman, 1980; Abdel-Rahman et al., 1984b), a consistent dose-effect relationship was not found; a small number of animals and the small magnitude of effects complicate the interpretation of the results. Minor blood changes were observed in the two-generation study used to derive the guideline (CMA, 1996; Gill et al., 2000; TERA, 1998), confirming the effects found in subchronic studies with rats.
Neurobehavioural effects (lowered auditory startle amplitude, decreased brain weight and decreased exploratory activity) are the most sensitive endpoints following oral exposure to chlorite (Mobley et al., 1990; CMA, 1996; Gill et al., 2000). The LOAEL identified in the Mobley et al. (1990) developmental toxicity study is approximately 6 mg chlorite/kg bw per day. Mobley et al. (1990) also found significant decreases in exploratory activity at 3 mg/kg bw per day, but the difference between activity in this group and the controls was small. Nevertheless, the NOAEL for neurobehavioural effects from this study is 3 mg chlorite/kg bw per day. In the two-generation study in rats from CMA (1996), a similar NOAEL of 2.9 mg/kg bw per day was identified based on lower startle amplitude, decreased absolute brain weight in the F1 and F2 generations and altered liver weights in two generations. Both these studies were conducted using the drinking water route, which makes them relevant for the present assessment.
The CMA (1996) study was selected for a number of reasons. It was conducted with sufficient numbers of animals of both sexes at multiple dose levels showing a range of effects and with numerous endpoints. The endpoint is toxicologically significant, and the rat species is widely used to parallel reproductive and developmental effects in humans. In this study, the male rats were also exposed to sodium chlorite during the mating period. Therefore, a more complete assessment of the adverse effects is covered in this study, which makes it more appropriate to select as the critical study for the development of a guideline. There are sufficient data available to estimate a tolerable daily intake (TDI) for chlorite, based on this two-generation study where the NOAEL of 2.9 mg/kg bw per day was identified (CMA, 1996; TERA, 1998). The TDI has been derived based on this study as follows:
- 2.9 mg/kg bw per day is the NOAEL based on lower startle amplitude, decreased absolute brain weight and altered liver weights in a two-generation study in rats,
- 100 is the uncertainty factor (×10 for interspecies variation; ×10 for intraspecies variation).
This TDI is consistent with results from human volunteer studies.
Because chlorite is classified in Group VIA, the MAC for chlorite in drinking water is derived from the TDI as follows:
- 0.029 mg/kg bw is the TDI, as calculated above,
- 70 kg bw is the average body weight of an adult,
- 0.80 is the proportion of total daily intake allocated to drinking water (as drinking water is the major source of exposure),
- 1.5 L/day is the average daily consumption of drinking water for an adult.
There are no data available to assess the carcinogenicity of chlorate; as such, chlorate has been classified in Group VIB -- no data available for evaluation of carcinogenicity to humans (Health Canada, 1994). IARC has not classified the carcinogenicity of chlorate.
The chronic and carcinogenicity studies, and the developmental and reproductive studies do not provide sufficient information to derive a guideline for chlorate. In addition, in human volunteers, a chlorate dose of 0.036 mg/kg bw per day for 12 weeks did not result in any adverse effects (Lubbers et al., 1981). Although the database for chlorate is less extensive than that for chlorite, a well-conducted 90-day study in rats was available, which identified a NOAEL of 30 mg/kg bw per day based on thyroid gland colloid depletion at the next higher dose of 100 mg/kg bw per day (McCauley et al., 1995).
A TDI for chlorate can therefore be derived as follows:
- 30 mg/kg bw per day is the NOAEL based on thyroid gland colloid depletion in a 90-day study in rats,
- 1000 is the uncertainty factor (×10 for interspecies variation; ×10 for intraspecies variation; ×10 to account for the short duration of the study).
This TDI is consistent with results from human volunteer studies.
Because chlorate is classified in Group VIB, the MAC for chlorate in drinking water is calculated from the TDI as follows:
- 0.03 mg/kg bw is the TDI, as calculated above,
- 70 kg bw is the average body weight of an adult,
- 0.80 is the proportion of total daily intake allocated to drinking water (as drinking water is the major source of exposure),
- 1.5 L/day is the average daily consumption of drinking water for an adult.
10.3 Chlorine dioxide
Chlorine dioxide has been shown to impair neurobehavioural and neurological development in rats exposed perinatally. Significant depression of thyroid hormones has also been observed in rats and monkeys exposed to it in drinking water studies. However, a MAC has not been proposed for chlorine dioxide because of its rapid reduction to chlorite (and, to a lesser extent, chlorate). As well, the MAC for chlorite is considered adequately protective for potential toxicity from chlorine dioxide; the NOAEL of 2.9 mg/kg bw per day used to derive the TDI for chlorite is similar to the lowest NOAELs observed for effects of chlorine dioxide on neurobehavioural and neurological development and on thyroid hormone levels.
WHO has not established a guideline for chlorine dioxide in drinking water because of its rapid breakdown and because the chlorite provisional guideline value is protective for potential toxicity from chlorine dioxide. The U.S. EPA has established a Maximum Residual Disinfectant Level (MRDL), based on a weight-of-evidence evaluation including information on chlorite and adverse reproductive and developmental effects.
The taste and odour threshold for chlorine dioxide is 0.4 mg/L (U.S. NRC, 1987), which is lower than the MACs derived for chlorite and chlorate.
Chlorite, chlorate and chlorine dioxide can be found in drinking water that is treated using chlorine dioxide as the primary disinfectant instead of the much more commonly used chlorine. Chlorate can also be found in drinking water that has been treated with hypochlorite solutions (as a source of chlorine) that have been inadequately stored or used, or that fail to meet quality specifications. Both disinfection methods are very effective in reducing waterborne disease; however, both also have the potential to produce harmful by-products, and these should be minimized without compromising the effectiveness of disinfection of the water.
Because chlorine dioxide is used by very few Canadian water treatment plants, the risk of exposure to chlorine dioxide, chlorite and chlorate is not expected to be significant for the average Canadian. Although more Canadians could be exposed through the use of hypochlorite solutions, the quality of the solution, as well as its appropriate storage and use, can greatly reduce any potential exposure. There is no epidemiological or experimental evidence to show that chlorite, chlorate and chlorine dioxide are human carcinogens. However, other health effects were observed in rigorous experimental studies, which warrant the establishment of guidelines for chlorite and chlorate. Despite neurological and hormonal effects observed in experimental animals, a guideline for chlorine dioxide was deemed unnecessary because of its rapid reduction to chorite, making human exposure via drinking water unlikely. It was determined that study results on chlorite are considered representative of the potential health risks related to exposure to chlorine dioxide hence there is no need to develop a separate guideline for chlorine dioxide. Instead, a maximum feed dose is suggested for chlorine dioxide, to ensure that consumers are not exposed to concentrations of chlorine dioxide or its disinfectant by-products that could pose health risks.
As part of its ongoing guideline review process, Health Canada will continue to monitor new research in this area and recommend any change(s) to this Guideline Technical Document that it deems necessary.
Decreased brain weight, decreased reaction to loud noise and altered liver weights in the first two generations of offspring in Sprague-Dawley rats were considered significant effects of chlorite exposure in one study. This study was used to derive the TDI of 0.029 mg/kg bw and is consistent with results from human volunteer studies. The MAC of 1 mg/L is easily measured in drinking water using a number of U.S. EPA analytical methods. Although it is possible to remove chlorite from treated drinking water using methods such as activated carbon and sulphur and iron reducing agents, the recommended approach is to reduce the production of chlorite in the disinfection process by optimizing the efficiency of the chlorine dioxide generator. Chlorite levels lower than the MAC of 1 mg/L are considered achievable using these strategies.
Subchronic chlorate exposure was associated with smaller body and organ weights, blood abnormalities and pituitary and thyroid abnormalities in one study using Sprague-Dawley rats. The TDI derived from this study was very close to that of chlorite, at 0.03 mg/kg bw, and is consistent with results from human volunteer studies. A MAC of 1 mg/L is easily measured in drinking water using several U.S. EPA analytical methods, including variations of the methods used to detect chlorite. Unlike the case with chlorite, however, there are no known treatments available to reduce chlorate ion once it has been formed in drinking water. Where hypochlorite solutions are used in treatment, caution should be taken to prevent chlorate formation. Furthermore, excess chlorite can react to produce additional chlorate; so it is important to maintain appropriate tuning of the chlorine dioxide generator to reduce the production of chlorite and chlorate. Excess chlorite must be removed before secondary disinfection with chlorine to avoid formation of chlorate in the distribution system. The chlorate MAC of 1 mg/L is considered achievable using this method.
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