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EC number: 233-162-8 | CAS number: 10049-04-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
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- Flash point
- Auto flammability
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- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
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- Nanomaterial pour density
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- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Carcinogenicity
Administrative data
Description of key information
Chlorine dioxide should not be considered as a substance with a carcinogenic potential.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- No data
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: No guideline or GLP compliance specified but the study is well conducted. No details on the animals conditions and the study is performed with water disinfected with chlorine dioxide.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Chlorine dioxide was administered orally at 0.5 mL three times a week for the first two weeks as part of the “initiation” phase of the assay. Two weeks after the final initiating dose, 1.0 µg of 12-tetradecanylphorbal-13-acetate (TPA; a known cancer promoter) in 0.2 mL acetone was administered by topical application to the dorsal skin of half of the experimental animals three times per week for 20 weeks, whereas the remaining animals received acetone only (0.2 mL/mouse) for the same duration. This was part of the “promotion” phase of the assay. Tumour incidence was observed at 30 experimental weeks.
- GLP compliance:
- not specified
- Species:
- mouse
- Strain:
- Sencar
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- No data
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 2 weeks initiation with the test material (ClO2 by oral route) 3 times/week followed by 20 weeks of topical administration of TPA in acetone or acetone alone.
- Frequency of treatment:
- Initiation phase: 3 times a week
Promotion phase: 3 times a week - Post exposure period:
- 8 weeks (the animals were observed for skin tumor incidence at 30 experimental weeks).
- Remarks:
- Doses / Concentrations:
Total volume applied = 0.5 mL
Basis: - No. of animals per sex per dose:
- 34 animals for the initiation and promotion (the full assay), 14 animals only for the initiation step.
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- Positive control: 500mg/kg urethane
- Observations and examinations performed and frequency:
- No data
- Sacrifice and pathology:
- no data
- Other examinations:
- After the sacrifice of the animals, skin tumor incidence on the back of the mouse was determined
- Statistics:
- No data
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Pathology: The treatment with vehicle control (2% Emulphor) yielded 0.09/9 tumors per animal/animals with tumor. The positive control group (500 mg/kg urethane) had 0.9 tumors per animal. Chlorine dioxide treated water did not induce tumors on the back of the mice (see table 7.7/1).
- Relevance of carcinogenic effects / potential:
- Chlorine dioxide was not considered as an initiator.Therefore, chlorine dioxide should not be considered as a substance with a carcinogenic potential since it is not implicated in the first step of the carcinogenesis.
- Conclusions:
- Chlorine dioxide did not initiate tumors in the mice.
- Executive summary:
In a carcinogenicity study, Chlorine dioxide was administered to Sencar mice in drinking water at dose levels of 0.5 mL three times a week for the first two weeks as part of the “initiation” phase of the assay. Two weeks after the final initiating dose, 1.0 µg of 12-tetradecanylphorbal-13-acetate (TPA, a known cancer promoter) in 0.2 mL acetone was administered by topical application to the dorsal skin of half of the experimental animals three times per week for 20 weeks, whereas the remaining animals received acetone only (0.2 mL/mouse) for the same duration. This was part of the “promotion” phase of the assay.
Tumor incidence was observed at 30 experimental weeks.
Concurrent vehicle (2% Emulphor) animals were used as a negative control and 500 mg/kg urethane was used as a positive control. The results obtained with these controls were considered as acceptable. Indeed, the treatment with vehicle control (2% Emulphor) yielded 0.09 tumor per animal, 9% of the animals presented tumors. The positive control group (500 mg/kg urethane) gave 0.9 tumours per animal, 65 % of the animals presented skin tumors.
Under the test conditions, skin tumours were not observed in the mice dosed by chlorine dioxide via drinking water followed by promoter skin administration. Therefore, Chlorine dioxide should not be considered as an initiator in the carcinogenic process.
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- No data
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: No guideline or GLP compliance specified but the study is well conducted. No details on the animals conditions and the study is performed with water disinfected with chlorine dioxide.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The rat liver foci assay is a short-term bioassay which determine the ability of a substance to initiate γ-glutamyltranspeptidase (GGT) positive foci, an indicator of preneoplastic liver changes. This enzyme found in many tissues, the most notable one being the liver, is involved in the transfer in the transfer of amino-acids across the cellular membrane and in leukotrien metabolism. It is involved in glutathion metabolism by transferring the glutamyl moiety to variety of acceptor molecules.
Rats were hepatectomised on day 0 (2/3 partial hepatectomy), and treated 24 hours later by oral administration of the test and control materials (positive and negative). One week later (day 7), the rats started to received 500 ppm sodium Phenobarbital (a known cancer promoter) in their drinking water for a total of 56 days. All animals were sacrificed at day 70. Frozen liver sections were prepared for the histochemical detection and quantification of GGT-positive foci. - GLP compliance:
- not specified
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- no data
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Details on exposure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 56 days
- Frequency of treatment:
- No data
- Post exposure period:
- 14 days: all animals were sacrificed at day 70.
- Remarks:
- Doses / Concentrations:
no data
Basis: - No. of animals per sex per dose:
- 10 rats per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- Positive control: 50 mg/kg bw diethylnitrosamine (DENA)
- Observations and examinations performed and frequency:
- No data
- Sacrifice and pathology:
- Histopathology: frozen liver sections were prepared for the histochemical detection and quantitation of GGT foci.
- Other examinations:
- No data
- Statistics:
- No data
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Histopathology: Chlorine dioxide did not initiate an incidence of GGT foci above that of the vehicle control group. The positive control diethylnitrosamine induced a high incidence of GGT foci, which indicated that the test was functioning properly (see table 7.7/1)
- Relevance of carcinogenic effects / potential:
- Chlorine dioxide was not considered as an initiator.Therefore, chlorine dioxide should not be considered as carcinogenic substance since it is not implicated in the first step of the carcinogenesis.
- Conclusions:
- Chlorine dioxide did not initiate an incidence of GGT foci in the rats.
- Executive summary:
In a carcinogenicity study, Chlorine dioxide was administered to hepatectomised rats (2/3 partial hepatectomy) by oral route. This is part of the “initiation” phase of the assay. One week later (day 7), the rats started to received 500 ppm sodium Phenobarbital (a known cancer promoter) in their drinking water for a total of 56 days. This is part of the “promotion” phase of the assay. All animals were sacrificed at day 70. Then, frozen liver sections were prepared for the histochemical detection and quantification of γ-glutamyltranspeptidase-positive foci, which are an indicator of preneoplatic liver changes.
Concurrent vehicle (2% Emulphor) animals were used as a negative control and 50 mg/kg Diethylnitrosamine (DENA) was used as a positive control. The results obtained with these controls were considered as acceptable. Indeed, the treatment with vehicle control (2% Emulphor) yielded 0.00 foci/cm3,whereas the positive control group gave 383 (+/- 97) foci/cm3.
Under the test conditions, GGT foci in the liver were not observed in the rats dosed by chlorine dioxide via drinking water followed by the promoter administration. Therefore, Chlorine dioxide should not be considered as an initiator in the carcinogenic process.
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- No data
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: No guideline or GLP compliance specified but the study is well conducted. No details on the animals conditions and the study is performed with water disinfected with chlorine dioxide.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Chlorine dioxide was administered to male and female mice orally three times a week for 8 weeks. 16 weeks after the last administration, the lung was examined for the presence of Adenoma.
- GLP compliance:
- not specified
- Species:
- mouse
- Strain:
- Strain A
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: 6 week old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
no data
IN-LIFE DATES: From: To: no data - Route of administration:
- oral: unspecified
- Vehicle:
- other: water sample in 2% Emulphor
- Details on exposure:
- No data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 3 times a week for 8 weeks.
- Frequency of treatment:
- 3 times a week.
- Post exposure period:
- 16 weeks.
- Remarks:
- Doses / Concentrations:
Total volume applied = 0.25 mL, the sample are 2000- or 4000-X concentrate
Basis: - No. of animals per sex per dose:
- 20 animals per dose per sex.
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- Positive control: 10 mg urethane in a single dose by gavage.
- Observations and examinations performed and frequency:
- No data
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes: After lung perfusion, the adenomas were counted independently by 2 technicians
HISTOPATHOLOGY: Yes : histological confirmation was performed on 10% of the positive specimens. - Other examinations:
- no data
- Statistics:
- No data
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- The body weight changes and the mortality data within the exposure groups and controls gave further indication that no-treatment-related effect was evident during the study.
See details for the lung adenoma results in Table 7.7/1. - Relevance of carcinogenic effects / potential:
- Chlorine dioxide was not considered as an initiator.Therefore, chlorine dioxide is not considered as carcinogenic substance as it is not implicated in the first step of the carcinogenesis.
- Conclusions:
- Chlorine dioxide did not induce lung adenoma in the mice.
- Executive summary:
In a carcinogenicity study, 0.25 mL of Chlorine dioxide water sample in 2% Emulphor was administered to male and female mice by oral route 3 times per week for 8 weeks at 2 concentrations: 2000 and 4000 X concentrate. After a 16 week post-exposure period, animals were sacrificed and examined for lung adenoma. 20 animals/dose/sex were used for this study.
Concurrent vehicle (2% Emulphor) animals were used as a vehicle control and 10 mg of urethane was used as a positive control. The results obtained with these controls were considered as acceptable. Indeed, the treatment with vehicle control (2% Emulphor) yielded 1 female/20 with tumors and 2 males/15 with tumors,whereas the positive control group gave all animals with tumors.
Under the test conditions, lung adenoma was not observed in the mice dosed by chlorine dioxide via drinking water.
Referenceopen allclose all
Table 7.7/1: Results of the Initiation/Promotion assay
Treatment |
Promotion (TPA) |
No. of animals with tumour, % |
Total tumours |
Tumours/animal |
Nondisinfected water |
Yes |
5/13 (16) |
5 |
0.16 |
No |
0/16 (0) |
0 |
0.00 |
|
Negative control (2% Emulphor) |
Yes |
3/35 (0) |
3 |
0.09 |
No |
0/37 (0) |
0 |
0.00 |
|
Positive control (Urethane 500 mg/kg) |
Yes |
13/20 (65) |
18 |
0.90 |
Water disinfected with Chlorine dioxide |
Yes |
4/34 (12) |
5 |
0.15 |
No |
0/14 (0) |
0 |
0.00 |
Table 7.7/1: Results of Carcinogenicity study
Sample |
Number of animals |
Mean ± SD no. of GGT-foci/cm3 |
Nondisinfected water |
9 |
21.0 ± 21.0 |
Negative control (2% Emulphor) |
7 |
0.00 |
Positive control (DENA 50 mg/kg) |
7 |
383 ± 97 |
Water disinfected with Chlorine dioxide |
7 |
0.00 |
Table 7.7/1: Results of Carcinogenicity study
Sample |
Female |
Male |
||||||
2000 X concentrate |
4000 X concentrate |
2000 X concentrate |
4000 X concentrate |
|||||
Animals with tumor |
Tumors per animal |
Animals with tumor |
Tumors per animal |
Animals with tumor |
Tumors per animal |
Animals with tumor |
Tumors per animal |
|
Nondisinfected water |
5/20 |
0.30 |
5/19 |
0.32 |
1/20 |
0.05 |
2/29 |
0.11 |
Chlorine dioxide treated water |
0/20 |
0.00 |
2/17 |
0.12 |
3/20 |
0.15 |
4/16 |
0.31 |
Negative control |
1/20 |
0.05 |
- |
- |
1/19 |
0.05 |
- |
- |
Vehicle control (2% Emulphor) |
1/20 |
0.05 |
- |
- |
2/15 |
0.13 |
- |
- |
Positive control (10 mg Urethane) |
19/19 |
11.47 |
- |
- |
20/20 |
11.55 |
- |
- |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Harmonised classification:
The classification entered in the Annex VI to the CLP Regulation for Chlorine dioxide is not harmonised for the carcinogenicity category.
Self-classification:
No self-classification is proposed.
Additional information
There is no concern for carcinogenicity resulting from exposure to chlorine dioxide based on:
- the three studies used as a weight of evidence approach showing that the chlorine dioxide was not an initiator of the carcinogenesis and didn't induce lung adenoma. Therefore, chlorine dioxide is not implicated in the first step of the carcinogenesis.
- Chlorine dioxide has not a widespread dispersive use or there is no evidence of frequent or long-term human exposure and,
- the substance is not classified as mutagen, as chlorine dioxide has no mutagenic potential (see § 7.6).
Therefore, chlorine dioxide should not be considered as a substance with a carcinogenic potential.
Moreover, regarding the chlorine dioxide classification as corrosive and fatal by inhalation, the workers wear appropriate Protective Personal Equipments (mask and gloves) at the workplace. Hence, the workers are not exposed to the chlorine dioxide frequently or for a long period of time. Therefore, it is not deemed useful to perform a carcinogenicity study on the chlorine dioxide.
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