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EC number: 816-285-7 | CAS number: 1263133-33-0
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
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
- Qualifier:
- according to guideline
- Guideline:
- other: MAFF Japan Notification No. 12-Nousan-8147 Guideline No. 2-1-19-3 (2000)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- other: Mouse micronucleus assay
Test material
- Reference substance name:
- Reference substance 002
- Cas Number:
- 1263133-33-0
- Test material form:
- solid
- Details on test material:
- Purity: 97.04%
Impurities: Not reported
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: Crl:CD1(ICR)
- Details on species / strain selection:
- Mice have been shown to exhibit micronuclei indicative of broken chromosomes (clastogenic effects) or spindle effects (aneugenic effects) in response to known mutagens and were therefore used in this assay. The Crl:CD1(ICR) mouse was selected based on extensive experience with this strain at DuPont Haskell and its suitability for genetic toxicology studies.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories International, Inc. (Raleigh, North Carolina, U.S.A.)
- Age at study initiation: ~ 8 weeks old
- Weight at study initiation: Males: Solvent Control group: 31.2 g; Low-dose group: 31.1 g; Mid-dose group: 31.0 g; High-dose group: 31.6 g; and Positive control group: 31.0 g Females: Solvent Control group: 24.3 g; Low-dose group: 24.0 g; Mid-dose group: 24.2 g; High-dose group: 24.3 g; and Positive control group: 24.7 g
- Assigned to test groups randomly: Yes
- Fasting period before study: Not mentioned
- Housing: All animals were housed in solid-bottom cages with Enrich-o’Cobs™ (i.e., enrichment-containing bedding).
- Diet (e.g. ad libitum): PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002
- Water (e.g. ad libitum): Tap water
- Acclimation period: At least 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26ºC (68-79ºF)
- Humidity (%): 30-70%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- 0.1% Tween-80 in 0.5% aqueous methylcellulose
- Duration of treatment / exposure:
- All animals were given a single dose by oral gavage.
- Frequency of treatment:
- All animals were given a single dose by oral gavage.
- Post exposure period:
- No
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 mg/kg bw (total dose)
- Dose / conc.:
- 1 000 mg/kg bw (total dose)
- Dose / conc.:
- 2 000 mg/kg bw (total dose)
- No. of animals per sex per dose:
- The vehicle control and the low- and mid-dose groups contained 10 animals/sex. The high-dose group contained 14 animals/sex.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (CP)
Examinations
- Tissues and cell types examined:
- Bone marrow smears were prepared immediately after the sacrifice
- Evaluation criteria:
- Data were evaluated using scientific judgment taking into account both statistical and biological significance. Results not meeting the indicated criteria for positive or negative findings were evaluated on a case-by-case basis. Further investigation of an equivocal result was not required to obtain a conclusive finding.
The test substance was judged negative if the following conditions were met:
• No statistically significant dose-related increases in the group mean MN-RETs above the concurrent vehicle control value occurred at any concentration of the test substance.
• The MN-RET values of the test substance-treated animals were within reasonable limits of the laboratory historical control range.
The test substance was judged positive if the following conditions were met:
• The group mean MN-RETs was statistically significantly increased at one or more concentrations of the test substance compared to the concurrent vehicle control values.
• An accompanying statistically significant dose-response increase in MN-RETs was observed.
Micronucleus data was evaluated using scientific judgment taking into account both statistical and biological significance. The individual animal was considered the experimental unit. All micronucleus data analyses were one-tailed and conducted at a significance level of 5%. Data from the positive control group was not included in evaluating normality or variance homogeneity of distribution. - Statistics:
- Micronucleus data was evaluated using scientific judgment taking into account both statistical and biological significance. The individual animal was considered the experimental unit. All micronucleus data analyses were one-tailed and conducted at a significance level of 5%. Data from the positive control group was not included in evaluating normality or variance homogeneity of distribution.
For any treatment groups where the increase in MN-RETs was found to be statistically significant, the data were further analyzed for dose response using the Cochran-Armitage trend test.
For each treatment group, the mean and standard deviation of % RETs and % MN-RETs were calculated. Data were be transformed prior to analysis using an arcsine square root or Freeman-Tukey function. This transformation is appropriate for proportions since the distribution of the transformed data more closely approximates a normal distribution than does the non-transformed proportion.
No statistical analysis was conducted on body weights or clinical signs.
See the section below for the Methods of Statistical Analyses used.
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- No clinical signs of toxicity were observed at any timepoint at any dose level in male or female animals exposed to the test substance. No abnormalities were detected in the vehicle or positive control groups. No mortality occurred during the study.
No statistically significant increases in micronucleated PCE frequency were observed in any evaluated test substance-treated group of male or female animals at either timepoint (See Tables 1 and 2 in the following section for details).
A statistically significant depression in the frequency of PCE/total erythrocytes was observed in female mice at the 48 hour timepoint indicating target cell exposure. No other reductions in PCE frequency were detected at any other timepoint in either male or female animals exposed to the test substance.
The positive control groups exhibited a response consistent with the micronucleated PCE historical control data. There were no obvious changes in body weight or body weight gain in either male or female animals administered the test substance.
Any other information on results incl. tables
Table 1 - Micronucleus Evaluation for Male Mice
Parameter |
Solvent Control |
500 mg/kg Group |
1000 mg/kg Group |
2000 mg/kg Group |
Positive Control Group |
|||
PCEs/1000 Erythrocytes
24-hour
48-hour |
556 ± 14
565 ± 22 |
554 ± 43
a |
563 ± 28
a |
577 ± 16
562 ± 30 |
508* ± 17
b |
|||
PCE/NCE Ratio
24-Hour (Mean ± SD)
48-Hour (Mean ± SD) |
1.255 ± 0.071
1.306 ± 0.112 |
1.261 ± 0.229
a |
1.294 ± 0.149
a |
1.366 ± 0.092
1.289 ± 0.151 |
1.032* ± 0.068
b |
|||
MNPCE/2000 PCEs
24-Hour (Mean ± SD)
48-Hour (Mean ± SD) |
3.0 ± 1.2
2.2 ± 1.9 |
2.0 ± 1.0
a |
2.0 ± 1.0
a |
1.8 ± 0.8
2.6 ± 1.9 |
35.3* ± 9.4
b |
|||
* Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test
a = Not evaluated at this timepoint
b = Group not included at this timepoint
Table 2 - Micronucleus Evaluation for Female Mice
PCEs/1000 Erythrocytes
24-hour
48-hour |
566 ± 22
568 ± 11 |
568 ± 40
a |
557 ± 16
a |
557 ± 33
542* ± 12 |
516* ± 27
b |
|||
PCE/NCE Ratio
24-Hour (Mean ± SD)
48-Hour (Mean ± SD) |
1.311 ± 0.127
1.317 ± 0.061 |
1.333 ± 0.230
a |
1.258 ± 0.079
a |
1.265 ± 0.155
1.186* ± 0.059 |
1.070* ± 0.118
b |
|||
MNPCE/2000 PCEs
24-Hour (Mean ± SD)
48-Hour (Mean ± SD) |
2.8 ± 1.5
1.8 ± 1.5 |
1.6 ± 0.9
a |
1.8 ± 1.3
a |
3.2 ± 2.6
1.8 ± 0.8 |
26.6** ± 7.6
b |
|||
* Statistically significant difference from control at p < 0.05 by Dunnett/Tamhane-Dunnett test
** Statistically significant difference from control at p < 0.05 by Dunn's test and the Dunnett/Tamhane-Dunnett test
a = Not evaluated at this timepoint
b = Group not included at this timepoint
Applicant's summary and conclusion
- Conclusions:
- All criteria for a valid study were met. Under the conditions of this study, the test substance did not induce biologically relevant increases in micronucleated polychromatic erythrocytes in animal bone marrow. The test substance was concluded to be negative in this in vivo study.
- Executive summary:
The test substance was evaluated for its ability to induce micronuclei in bone marrow polychromatic erythrocytes (PCEs) in male and female Crl:CD1(ICR) mice. Based on range-finding results, doses of 0, 500, 1000, and 2000 mg/kg of the test substance were selected for the main study. Concurrent control groups were administered 0.1% Tween-80 in 0.5% aqueous methylcellulose as the vehicle (negative) control, or 40 mg/kg of cyclophosphamide [positive control] (OECD Guidelines for the Testing of Chemicals No 474; EPA OPPTS Guideline 870.5395; EC Directive 2008/32/EC Method B.12; and MAFF Japan Notification No. 12-Nousan-8147 Guideline No. 2-1-19-3).
All animals were given a single dose by oral intubation. The vehicle control and the low- and intermediate-dose groups contained 10 animals/sex. The high-dose group contained 14 animals/sex. The positive indicator group consisted of 5 animals/sex. Half of the animals in each test substance and untreated control group were sacrificed at each timepoint, approximately 24 or 48 hours post-dosing, respectively. The positive control group was sacrificed approximately 24 hours post-dosing. Bone marrow smears were prepared immediately after the sacrifices. Two thousand PCEs per animal were evaluated for micronuclei and 1000 total erythrocytes per animal were evaluated for bone marrow toxicity.
Aliquots of the vehicle control and each test substance concentration were taken to confirm homogeneity, dose concentrations, and stability. Homogeneity and target concentrations were verified, and the test substance was stable for the duration of the dosing period.
No clinical signs of toxicity were observed at any timepoint at any dose level in male or female animals exposed to the test substance. No abnormalities were detected in the vehicle or positive control groups. No mortality occurred during the study.
No statistically significant increases in micronucleated PCE frequency were observed in any evaluated test substance-treated group of male or female animals at either timepoint (See Tables 1 and 2 in the "Other information on results including tables" section for details).
A statistically significant depression in the frequency of PCE/total erythrocytes was observed in female mice at the 48 hour timepoint indicating target cell exposure. No other reductions in PCE frequency were detected at any other timepoint in either male or female animals exposed to the test substance.
The positive control groups exhibited a response consistent with the micronucleated PCE historical control data. There were no obvious changes in body weight or body weight gain in either male or female animals administered the test substance.
All criteria for a valid study were met. Under the conditions of this study, the test substance did not induce biologically relevant increases in micronucleated polychromatic erythrocytes in animal bone marrow. The test substance was concluded to be negative in this in vivo study.
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