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EC number: 807-621-3 | CAS number: 1428450-95-6
- 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
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Basic data given: This micronucleus assay is part of a 90-day repeated dose toxicity study performed according to OECD 408. The test item was assessed for its cumulative toxicity when administered daily to rats by gavage for a period of 90 days and for its potential to induce the formation of micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of Wistar rats. No positive control was used.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- In this study, the animals were treated orally by gavage for period of at least 90 days; no positive control
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- N-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-2-methylpropanamide
- EC Number:
- 807-621-3
- Cas Number:
- 1428450-95-6
- Molecular formula:
- C13H14N2O3S
- IUPAC Name:
- N-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-2-methylpropanamide
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories B.V., Horst, The Netherlands
- Age at study initiation: 7 weeks
- Weight at study initiation: 212 - 256 g (males), 140 - 160 g (females)
- Housing: Animals were housed in groups of 3 or 4 in Makrolon type-4 cages with wire mesh tops and standard softwood bedding including paper enrichment.
- Diet: Pelleted standard HarlanTeklad 2914C rat / mouse maintenance diet, ad libitum
- Water: Community tap water, ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES:
From: 29 Nov 2012
To: 28 Feb 2013
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: PEG 300
- Batch no.: BCBJ2013V - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The dose formulations were prepared weekly. The test substance was weighed into a glass beaker on a tared balance and the vehicle added. The mixtures were stirred using a magnetic stirrer. Homogeneity of the test substance in the vehicle was maintained during the daily administration period using a magnetic stirrer.
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
50, 200, 800 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 7
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- none
Examinations
- Tissues and cell types examined:
- Tissue: bone marrow
Cell type: bone marrow cells - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: This micronucleus assay is part of 90 day repeated dose toxicity study. The dose levels were selected based on a previous dose range finding toxicity study.
TREATMENT AND SAMPLING TIMES: 24 hours after the last treatment of the animals, animals were sacrificed and the right femurs were removed.
DETAILS OF SLIDE PREPARATION: The epiphyses were cut off and the marrow was flushed out with warmed fetal calf serum (FCS), using a syringe. The nucleated cells were separated from the erythrocytes using the method of Romagna. Briefly, the cell suspensions were passed through a column consisting of α-Cellulose (Sigma) and Cellulose (Sigmacell type 50). The columns were then washed with Hank´s buffered saline. The cell suspension was centrifuged at 1500 rpm (390 x g) for 10 minutes and the supernatant was discarded. The pellet was resuspended in a small drop of FCS and spread on slides. The smears were air-dried, fixed in methanol and stained with May-Grünwald /Giemsa. Cover slips were mounted with EUKITT. At least one slide was made from each bone marrow sample.
METHOD OF ANALYSIS: Evaluation of the slides was performed using NIKON microscopes with 100x oil immersion objectives. At least 4000 immature erythrocytes per animal should be scored for the incidence of micronucleated immature erythrocytes. At least 2000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei. To describe a cytotoxic effect the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and expressed in polychromatic erythrocytes per 2000 erythrocytes. The analysis was performed with coded slides. - Evaluation criteria:
- A test item can be classified as mutagenic if it induces either a dose-related increase in the number of micronucleated polychromatic erythrocytes or a statistically significant positive response for at least one of the test points.
A test item producing neither a dose-related increase in the number of micronucleated polychromatic erythrocytes nor a statistically significant positive response at any of the test points, is considered non-mutagenic in this system.
This can be confirmed by means of the nonparametric Mann-Whitney test, if necessary. However, both biological and statistical significance should be considered together.
Acceptance Criteria
The study is considered valid if the following criteria show that:
- at least 5 animals per group and sex are evaluable
- PCE to erythrocyte ratio should not be less than 20% of the negative control.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- not examined
- Additional information on results:
- RESULTS
- Induction of micronuclei: In comparison to the corresponding vehicle controls, there was no statistically significant or biologically relevant enhancement of the frequency of the detected micronuclei in males and females at any dose level. The mean values of micronuclei observed after treatment with the test item were below or near the value of the respective vehicle control group (see Table 1+2) and within the historical control data (see Table 3).
- Ratio of PCE/NCE: The ratio between polychromatic and normochromatic erythrocytes was determined in the same sample to evaluate any cytotoxic effect due to treatment with the test substance and reported as the number of PCEs per 2000 erythrocytes. After treatment with the test substance, the mean number of PCEs per 2000 erythrocytes was not decreased as compared to the mean value of PCEs per 2000 erythrocytes of the vehicle control, thus indicating that the test substance did not induce cytotoxic effects in the bone marrow of exposed rats.
Any other information on results incl. tables
Table 1: Males
Test group |
Dose [mg/kg bw/day] |
PCEs with micronuclei [%] |
Range |
PCE per 2000 erythrocytes |
Vehicle (PEG 300) |
0 |
0.314 |
1-11 |
948 |
Test item |
50 |
0.350 |
1-17 |
965 |
Test item |
200 |
0.357 |
0-11 |
954 |
Test item |
800 |
0.257 |
3-9 |
1008 |
Table 2: Females
Test group |
Dose [mg/kg bw/day] |
PCEs with micronuclei [%] |
Range |
PCE per 2000 erythrocytes |
Vehicle (PEG 300) |
0 |
0.414 |
0-21 |
1039 |
Test item |
50 |
0.364 |
4-11 |
1144 |
Test item |
200 |
0.250 |
1-7 |
1095 |
Test item |
800 |
0.393 |
2-23 |
1135 |
Table 3: Historical controls 2006-2011
Micronuclated cells |
Males |
Females |
Total |
Males |
Females |
Total |
Mean ± SD [%] |
0.184± 0.054 |
0.160± 0.053 |
0.175± 0.055 |
2.154± 0.820 |
1.034± 0.432 |
1.723± 0.884 |
Range of mean group [%] |
0.085- 0.320 |
0.058- 0.283 |
0.058- 0.320 |
0.670- 4.058 |
0.470– 2.875 |
0.470– 4.058 |
Range (individual animal data) |
0-12 |
0-12 |
0-12 |
8-136 |
5-74 |
5-136 |
No. of Experiments |
51 |
35 |
51 |
49 |
32 |
49 |
The values included in the historical control data base were obtained from single time application using differentroutes(e.g. orally, intravenously, intraperitoneally).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: negative
Under the experimental conditions reported, the test substance did not induce micronuclei in the bone marrow of the rats exposed to the test substance for 90 days as part of a 90-day repeated dose toxicity study. Therefore, test substance is considered to be non-mutagenic in this micronucleus assay.
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