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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
- Surface tension
- Flash point
- Auto flammability
- Flammability
- 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
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- 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
Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01 December 2011 - 06 February 2012
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP study conducted according to OECD Guideline 403 with restrictions: only 3 rats/sex are exposed at the highest concentrations by comparison with the other concentrations (5 rats/sex), 0.6 % aqueous chlorine dioxide (ClO2) solution, inherently stabilized without any explanation about the method used for stabilising the substance. Absence of any reported effects, due to the treatment, except the deaths of animals, according to dose levels. The physical state of the test atmosphere has not been characterized in the study. It is not clear whether or not the test atmosphere consists of gas of chlorine dioxide in liquid droplets. No justification for the selected concentration levels (achievable concentrations or anticipated effects from the acute toxicity by inhalation of gas)
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes
- Remarks:
- inspected on 25, 26, 27 & 28 November 2008 / signed on 12 November 2009
- Test type:
- standard acute method
- Limit test:
- no
Test material
- Reference substance name:
- Chlorine dioxide
- EC Number:
- 233-162-8
- EC Name:
- Chlorine dioxide
- Cas Number:
- 10049-04-4
- Molecular formula:
- ClO2
- IUPAC Name:
- Chlorine Dioxide
- Test material form:
- other: liquid
- Details on test material:
- - Name of test material (as cited in study report): 0.6 % aqueous chlorine dioxide (ClO2) solution, inherently stabilized
- Physical state: Yellow liquid
- Date of receipt: 25 October 2011
- Storage condition of test material: Stored in a refrigerator
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: CD / Crl:CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Sulzfeld, Germany.
- Age at study initiation: Males: approx. 8 weeks; Females: approx. 9 weeks
- Weight at study initiation: Males: 231-290 g; Females: 218-250 g
- Fasting period before study: Feeding was discontinued approx. 16 h before test item administration
- Housing: During the 14-day observation period the animals were kept by sex in groups of 2-3 animals in MAKROLON cages (type III plus)
- Diet: Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Drinking water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 55 ± 15 %
- Photoperiod: 12 h dark / 12 h light
Administration / exposure
- Route of administration:
- inhalation: mist
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Dynamic inhalation chamber (air changes/h (≥ 12 times))
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: Cylindrical exposure chamber (volume 40 L) which holds a maximum of 20 animals in pyrex tubes at the edge of the chamber in a radial position.
- Source and rate of air: Spray-jet was fed with compressed air (5.0 bar) from a compressor at a flow rate of 900 L/h and with the test item using an infusion pump at flow rates of 12, 20 and 50 mL/h. At the bottom of the exposure chamber, the air was sucked off at a lower rate than created by the spray-jet in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
- Air change: 22.5 changes per hour
- Method of conditioning air: A manometer and an air-flow meter were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected, if necessary.
- The oxygen content in the inhalation chamber was 21 % v/v. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube Oxygen 67 28 081). Carbon dioxide concentration did not exceed 1 %.
- Method of particle size determination: Analysis of the particle size distribution was carried out twice during the exposure period using a cascade impactor according to May, 1975.
- Treatment of exhaust air: Exhaust air was sucked through gas wash-bottles.
- Temperature, humidity, pressure in air chamber: The temperature (20.8-21.5 °C) and humidity (60.4-64.4 %) was checked and noted once every hour during the exposure period of the experiment.
TEST ATMOSPHERE
- Brief description of analytical method used: ClO2-concentrations in the inhalation chamber was determined by iodometric titration
- Aerosol samples were taken once every hour during the 4-hour exposure period. For that purpose, a probe was placed close to the animals’ noses and samples were collected by drawing 7.5 L air at a flow rate of 0.5 L/min for 15 minutes through 2 consecutive gas washing bottles containing approx. 50 mL 0.02 % potassium iodide solution (pH=2.0), each. The contents of both washing bottles were combined in an 1000 mL volumetric flask and filled up to the mark with water. An aliquot of 50 mL was used for the iodometric determination. Each sample was analysed twice.
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The mist from the exposure chamber was drawn through the cascade impactor for 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg).
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): In the inhalation chamber, close to the animals' noses, the spray-jet generated atmosphere had mass median aerodynamic diameters (MMAD) between 2.388 and 2.467 μm as determined with a cascade impactor. The Geometric Standard Deviations (GSD) of the MMAD were calculated as 2.69, 2.74 and 2.78. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 0.030, 0.047 and 0.074 mg/L air (iodometric determination).
The concentrations are acceptable based on the masse median aerodynamic diameter values of 2.388, 2.429 and 2.467 µm and the corresponding GSD values of 2.78, 2.74 and 2.69. This is inside the required range of 1-4 µm and 1.5-3, respectively as required by the OECD 403 guideline.
However,it is not reported if :
- these concentrations are the technical maximum achievable concentrations knowing that the measured concentrations as pure ClO2 are closed to the nominal concentrations which can be calculated taking into account both the air compressor flow rate (900L/h) and the ClO2 solution infusion pump flow rates (12, 20 et 50 mL/h).
- or if these concentrations are selected based on anticipated effects in rats as showed in the acute toxicity study by inhalation for the gas. - No. of animals per sex per dose:
- 3 animals/sex/dose at 0.074 mg/L air
5 animals/sex/dose at 0.030 and 0.047 mg/L air - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations: A careful clinical examination was made at least once daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Frequency of weighing: Individual body weights of animals were determined during the acclimatisation period on the day of exposure, prior to exposure and on test days 2, 4, 8 and 15 and at time of death if survival exceeded day 1. Changes in weight were calculated and recorded when survival exceeds one day. At the end of the test, the animals were weighed and sacrificed.
- Necropsy of survivors performed: Yes; Necropsy of all animals was carried out and all gross pathological changes were recorded.
Other examinations performed:
- The weight of the lungs was determined and recorded.
- No microscopic examination was carried out as no pathological findings were noted at necropsy. - Statistics:
- No data
Results and discussion
- Preliminary study:
- Not applicable
Effect levelsopen allclose all
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- 0.048 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Sex:
- female
- Dose descriptor:
- LC50
- Effect level:
- 0.04 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 0.041 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- - Premature death was observed in 3/3 males and 3/3 females at the concentration of 0.074 mg/L air
- Premature death was observed in 2/5 males and 2/5 females at the concentration of 0.047 mg/L air.
- None of 5 male and 1/5 female animals died prematurely at the concentration of 0.030 mg/L air. - Clinical signs:
- other:
- Body weight:
- All surviving animals gained the expected body weight.
- Gross pathology:
- No pathological findings were noted at necropsy.
- Other findings:
- None
Any other information on results incl. tables
Table 7.2.2/2: Summary of results
Symptoms/Criteria |
Chlorine dioxide |
|||||
0.074 mg/L air |
0.047 mg/L air |
0.030 mg/L air |
||||
Males (n=3) |
Females (n=3) |
Males (n=5) |
Females (n=5) |
Males (n=5) |
Females (n=5) |
|
Clinical signs: |
||||||
Ataxia |
+ 0’-3 h (3) |
+ 0’-3 h (3) |
+ 0’-60’ (5) |
+ 0’-60’ (5) |
+ 0’-30’ (5) |
+ 0’-30’ (5) |
Tremor |
+ 0’-60’ (3) |
+ 0’-60’ (3) |
+ 0’-60’ (5) |
+ 0’-60’ (5) |
+ 0’-30’ (5) |
+ 0’-30’ (5) |
Dyspnoea |
+-++ 0’-3 h (3) |
+-++ 0’-3 h (3) |
+ 0’-3 h (5) |
+ 0’-3 h (5) |
+ 0’-2 d (5) |
+ 0’-2 d (5) |
Mortality |
||||||
Within 3 h |
0 |
0 |
0 |
0 |
0 |
0 |
Within 24 h |
3 |
3 |
2 |
2 |
0 |
1 |
Within 7 days |
3 |
3 |
2 |
2 |
0 |
1 |
Within 14 days |
3 |
3 |
2 |
2 |
0 |
1 |
Mean body weight (g) |
||||||
Start |
265.3 |
246.3 |
236.2 |
227.2 |
278.8 |
235.6 |
After 7 days |
# |
# |
299.0 (+26.6) |
250.3 (+10.2) |
328.0 (+17.6) |
249.8 (+6.0) |
After 14 days |
|
|
335.0 (+43.9) |
268.0 (+19.3) |
354.2 (+28.6) |
259.0 (+11.2) |
Inhibition of body weight gain |
# |
# |
None |
None |
None |
None |
Necropsy findings |
None |
None |
None |
None |
None |
None |
+ = slight; ++ = moderate; ' = minutes; h = hours; d = days; 0' = immediately after end of administration; # = all animals died prematurely
Applicant's summary and conclusion
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- Chlorine dioxide solutions have to be classified as Category 4 (H332: Harmful if inhaled) for acute inhalation toxicity (ATI4) above a concentration limit of 0.82%.
- Executive summary:
In an acute inhalational toxicity study performed in accordance with GLP and OECD Guideline 403, groups of CD / Crl:CD(SD) rats were exposed to 0.6% aqueous chlorine dioxide (ClO2) solution, inherently stabilized *, at actual concentrations of 0.030, 0.047 and 0.074 mg/L air for 4 h by inhalation (mist) using a dynamic nose-only exposure chamber. The exposure concentrations were determined by iodometry.Animals were then observed for mortality, clinical signs and bodyweights for 14 days and necropsy was performed in all animals for macroscopical examination.
In the inhalation chamber, close to the animals' noses, the spray-jet generated atmosphere had mass median aerodynamic diameters (MMAD) between 2.388 and 2.467 μm as determined with a cascade impactor. The Geometric Standard Deviations (GSD) of the MMAD were calculated as 2.69, 2.74 and 2.78.
At the concentration of 0.074 mg/L air, slight ataxia, slight tremor and slight to moderate dyspnoea and premature death in all 3/3 male and 3/3 female animals. At the concentration of 0.047 mg/L air, slight ataxia, slight tremor and slight dyspnoea in all 5/5 male and 5/5 female animals. Two of 5 male and 2 of 5 female animals died prematurely. At the concentration of 0.030 mg/L air, slight ataxia, slight tremor and slight dyspnoea in all 5/5 male and 5/5 female animals. None of 5 male and 1/5 female animals died prematurely. All surviving animals gained the expected body weight. No pathological findings were noted at necropsy.
LC50 for males and females were 0.048 and 0.040 mg/L air/4 h, respectively. LC50 males and females combined (14 days): 0.041 mg/L air/4 h as pure ClO2. Therefore, based on the calculation method of CLP, the LC50value corresponds to 6.83 mg 0.6% ClO2 solution/L air/4h as pure ClO2 which is lower to the classification limit for a mist (5 mg/L) according to the CLP.
According to the study results, and applying the classification criteria for acute inhalation toxicity (5 mg/L for mist/aerosol), chlorine dioxide solutions have to be classified as category 4 for acute inhalation toxicity (ATI4) above a concentration limit of 0.82%, based on prorata of concentration according to CLP Regulation (EC) 1272/2008 (6.83 mg/L x 0.6% / 5 mg/L).
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