Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 244-169-0 | CAS number: 21049-70-7
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 2008-06-24 to 2008-11-04
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- signed by Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht Rheinland Pfalz (2005-10-21)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Sodium sulphite
- EC Number:
- 231-821-4
- EC Name:
- Sodium sulphite
- Cas Number:
- 7757-83-7
- IUPAC Name:
- disodium sulfite
- Details on test material:
- Please refer to the section "Confidential details on test material" below.
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Germany GmbH
- Age at study initiation: 5–8 weeks old (information from the breeder)
- Assigned to test groups randomly: yes, under following basis: the animals were assigned to the test groups according to a randomization plan prepared with an appropriate computer program.
- Weight at study initiation: mean 29.9 g
- Housing: individually, in Makrolon type M I cages, with Type Lignocel FS 14 fibres, dustfree bedding, supplied by SSNIFF, Soest, Germany
- Diet: Standardized pelleted feed (Maus/Ratte Haltung "GLP", Provimi Kliba SA, Kaiseraugst, Switzerland)
- Water: Drinking water from bottles was available ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 20-24 °C
- Humidity: 30-70 %
- Photoperiod: 12 hours dark / 12 hours light
Administration / exposure
- Route of administration:
- subcutaneous
- Vehicle:
- - Vehicle/solvent used: water
- Justification for choice of solvent/vehicle: due to the good solubility of the test substance in water, purified water was used as vehicle.
- Concentration of test material in vehicle: 25, 50, 100 mg/mL
- Amount of vehicle: 10 mL/kg bw - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS
- To achieve a solution of the test substance in the vehicle, the test substance preparation was shaken thoroughly. All test substance formulations were prepared immediately before administration.
- The stability of the test substance at room temperature in the vehicle purified water was determined analytically. For the determination of the test substance concentrations in the vehicle, 6 samples of each dose were taken from the test substance preparations. These were kept at room temperature until the treatment of the last animal (approximately 1 hour) and then were kept deep-frozen. The determination of the concentrations in the vehicle was carried out by means of iodometric titration. - Duration of treatment / exposure:
- single administration
- Frequency of treatment:
- once
- Post exposure period:
- 24 and 48 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
250, 500, 1000 mg/kg bw
Basis:
nominal conc.
- No. of animals per sex per dose:
- 5 mice
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (20 mg/kg bw) and Vincristine sulfate (0.15 mg/kg bw)
Examinations
- Tissues and cell types examined:
- Polychromatic erythrocytes of bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION
In a pretest for the determination of the acute subcutaneous toxicity, deaths were observed down to 1500 mg/kg bw. At 1000 mg/kg bw all animals (male and female) survived showing clinical signs. The clinical sign only observed was making rough of the administration area. However, there were no distinct differences in the symptoms between males and females. Thus, only male animals were used for the cytogenetic investigations. Therefore, a dose of 1000 mg/kg bw was selected as the high dose level in the present cytogenetic study. Further doses adminisered were 500 and 250 mg/kg bw.
DETAILS OF SLIDE PREPARATION
The two femora of the animals sacrificed by cervical dislocation were prepared by dissection and removing all soft tissues. After cutting off the epiphyses, the bone marrow was flushed out of the diaphysis into a centrifuge tube using a cannula filled with fetal calf serum (FCS) which was preheated up to 37 °C (about 2 mL/femur). The suspension was mixed thoroughly with a pipette and centrifuged at 300 x g for 5 min. The supernatant was removed and the precipitate was resuspended in about 50 µL fresh FCS. One drop of this suspension was dropped onto clean microscopic slides, using a Pasteur pipette. Smears were prepared using slides with ground edges. The preparations were dried in the air and subsequently stained.
METHOD OF ANALYSIS
In general, 2000 polychromatic erythrocytes (PCE) were evaluated for the occurrence of micronuclei from each animal of every test group, so in total 10000 PCEs were scored per test group. The normochromatic erythrocytes (= normocytes / NCE) were also scored. The following parameters were recorded:
- Number of polychromatic erythrocytes
- Number of polychromatic erythrocytes containing micronuclei
The increase in the number of micronuclei in polychromatic erythrocytes of treated animals as compared with the vehicle control group provides an index of a chromosome-breaking (clastogenic) effect or damage of the mitotic apparatus (aneugenic activity) of the test substance administered.
- Number of normochromatic erythrocytes
- Number of normochromatic erythrocytes containing micronuclei
The number of micronuclei in normochromatic erythrocytes at the early sacrifice interval shows the situation before test substance administration and may serve as a control value.
A test substance induced increase in the number of micronuclei in normocytes may be found with an increase in the duration of the sacrifice interval.
- Ratio of polychromatic to normochromatic erythrocytes
An alteration of this ratio indicates that the test substance actually reached the bone marrow, means the target determined for genotoxic effects.
- Number of small micronuclei (d < D/4) and of large micronuclei (d ≥ D/4)
[d = diameter of micronucleus, D = cell diameter]
The size of micronuclei may indicate the possible mode of action of the test substance, i.e. a clastogenic effect (d < D/4) or a spindle poison effect (d ≥ D/4). Slides were coded before microscopic analysis. Since the absolute values shown were rounded, but further calculation was based on unrounded values, there may be deviations in the relative values given. - Evaluation criteria:
- A finding is considered positive if the following criteria are met:
- Statistically significant and dose-related increase in the number of PCEs containing micronuclei
- The number of PCEs containing micronuclei has to exceed both the concurrent vehicle control value and the range of the historical vehicle control data.
A test substance is considered negative if the following criteria are met:
- The number of cells containing micronuclei in the dose groups is not statistically significant increased above the concurrent vehicle control value and is within the range of the historical vehicle control data. - Statistics:
- The statistical evaluation of the data was carried out using the program system MUKERN (BASF SE). The asymptotic U test according to Mann-Whitney (modified rank test according to Wilcoxon) was carried out to clarify the question whether there are statistically significant differences between the untreated control group and the treated dose groups with regard to the micronucleus rate in PCEs. The relative frequencies of cells containing micronuclei of each animal were used as a criterion for the rank determination for the U test. Statistical significances were identified as follows: * p < 0.05, ** p < 0.01. However, both biological relevance and statistical significance were considered together.
Results and discussion
Test results
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 1000, 1500 mg/kg bw
- Clinical signs of toxicity in test animals: deaths were observed down to 1500 mg/kg bw. At 1000 mg/kg bw all animals (male and female) survived showing clinical signs.
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): the number of normochromatic erythrocytes containing micronuclei did not differ to any appreciable extent in the vehicle control group or in the various dose groups at any of the sacrifice intervals.
Any other information on results incl. tables
Results:
Test group | Interval: 24 hours | Interval: 48 hours | ||||||
Polychromatic erythrocytes | Normocytes / total amount polychromatic erythrocytes | Cells with micronuclei (%) | Polychromatic erythrocytes | Normocytes / total amount polychromatic erythrocytes | Cells with micronuclei (%) | |||
Dose (mg/kg bw) | polychromatic | normochromatic | polychromatic | normochromatic | ||||
vehicle control | 10000 | 4767 | 0.9 | 1.5 | 10000 | 4834 | 0.9 | 0.4 |
250 | 10000 | 5469 | 0.8 | 0.5 | ||||
500 | 10000 | 5309 | 1.5 | 0.9 | ||||
1000 | 10000 | 4211 | 1.4 | 1.4 | 10000 | 7289 | 1.2 | 0.5 |
20, Cyclophosphamide | 5000 | 3833 | 10.3 | 1.8 | ||||
0.15, Vincristine | 5000 | 6097 | 48.4 | 1.3 |
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)