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EC number: 470-130-4 | CAS number: 697235-49-7
- 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
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
- Study period:
- 2008-09-02 to 2008-10-14
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- adopted 1997-07-21
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- , 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- signed 2007-01-19
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- -
- EC Number:
- 470-130-4
- EC Name:
- -
- Cas Number:
- 697235-49-7
- Molecular formula:
- Hill formula: C16H15NO4 CAS formula: C16H15NO4
- IUPAC Name:
- 2-((3-(4-Hydroxyphenyl)propanoylamino)benzoic acid
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Physical state: white to light yellow powder
- Molecular formula: C16H15NO4
- Molecular weight: 285.3 g/mol
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories GmbH, Borchen, Germany
- Age at start of acclimatisation: 8 - 10 weeks
- Weight at study initiation: males: mean value 38.9 g (SD ± 1.2 g); females; mean value 31.2 g (SD ± 2.6 g)
- Assigned to test groups randomly: yes
- Housing: single; Makrolon Type I, with wire mesh top (EHRET GmbH, Emmendingen, Germany); granulated soft wood bedding (Harlan Laboratories GmbH, Borchen, Germany)
- Diet (ad libitum): pelleted standard diet (Harlan Laboratories GmbH, Borchen, Germany)
- Water (ad libitum): tap water (Gemeindewerke, Rossdorf, Germany)
- Acclimation period: minimum 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Relative humidity: 30 - 70% (the aim was 50-60%)
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: the test item was formulated in 30% DMSO/70% PEG 400
- Justification for choice of solvent/vehicle: the vehicle was chosen to its relative non-toxicity for the animals. furthermore, the vehicle does not react with the test substance - Details on exposure:
- All animals received a single standard volume of 10 mL/kg bw orally.
- Duration of treatment / exposure:
- 1 day
- Frequency of treatment:
- once
Doses / concentrations
- Remarks:
- Doses / Concentrations:
500, 1000 and 2000 mg/kg
Basis:
actual ingested
- No. of animals per sex per dose:
- 6 males and 6 females (except for the highest dose level: 12 males and 12 females)
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide monohydrate
- Route of administration: orally, once
- Doses / concentrations: 40 mg/kg bw (dissolved in deionised water)(volume administered: 10 mL/kg bw
Examinations
- Tissues and cell types examined:
- 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.
Ten animals (5 males, 5 females) per test group were evaluated. The remaining 6th animal of each sex in the respective test group is usually evaluated in case an animal dies in its test group spontaneously. - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
It is generally recommended to use the maximum tolerated dose or the highest dose that can be formulated and administered reproducibly or 2000 mg/kg as the upper limit for non-toxic test items.
The maximum tolerated dose level is determined to be the dose that causes toxic reactions without having major effects on survival within 48 hours.
The volume to be administered should be compatible with physiological space available.
TREATMENT AND SAMPLING TIMES
At the beginning of the treatment the animals (including the controls) were weighed and the individual volume to be administered was adjusted to the animals body weight. The animals received the test item, the vehicle or the positive control substance once. Twelve animals, six males and six females, were treated per dose group and sampling time. The animals of all dose groups (excepted the positive control) were examined for acute toxic symptoms at intervals of around 1 hour, 2 - 4 hours 6 hours, 24 hours and 48 hours after administration of the test item.
Sampling of the bone marrow was done 24 and 48 hours after treatment, respectively (48 hours only for high dose group).
DETAILS OF SLIDE PREPARATION:
The animals were sacrificed using CO2 followed by bleeding. The femora were removed, the epiphyses were cut off and the marrow was flushed out with foetal calf serum. The cell suspension was centrifuged at for 10 minutes and the supernatant was discarded. A small drop of the re-suspended cell pellet was spread on a slide. The smear was air-dried and then stained with May-Grünwald (Merck, Darmstadt, Germany)/Giemsa (Merck, Darmstadt, Germany). Cover slips were mounted with EUKITT (Kindler, Freiburg, Germany). 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.
ACCEPTANCE CRITERIA:
The study was considered valid as the following criteria are met:
- the negative controls are in the range of our historical control data.
- the positive controls are in the range of our historical control data.
- at least 5 animals per group and sex can be evaluated
- PCE to erythrocyte ratio should not be less than 20 % of the negative control. - Evaluation criteria:
- A test item is classified as mutagenic if it induces either a dose-related increase or a clear increase in the number of micronucleated polychromatic erythrocytes in a single dose group. Statistical methods (nonparametric Mann-Whitney test (Krauth, 1971)*) will be used as an aid in evaluating the results. However, the primary point of consideration is the biological relevance of the results.
A test item that fails to produce a biological relevant increase in the number of micronucleated polychromatic erythrocytes is considered non-mutagenic in this system.
*Reference
- Krauth, J. (1971): Locally most powerful tied rank test in a Wilcoxon situation, Annals of Mathematical Statistics, 42, 1949 - 1956. - Statistics:
- Please refer to "Evaluation criteria" above
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- please refer tp "Additional information on results" below
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- PRE-EXPERIMENT FOR TOXICITY
- Dose range: 2000 mg/kg bw
- Clinical signs of toxicity in test animals:
a) ruffled fur:
1- 6 hours after administration: all animals
24 and 30 hours: 2 animals
b) excitement:
1 - 4 hours: one animal
On the basis of these data 2000 mg/kg bw were estimated to be suitable.
TOXIC SYMPTOMS IN THE MAIN EXPERIMENT
2000 mg/kg bw: all animals had ruffled fur 1 to 6 hours after administration. 12 animals had ruffled fur 24 hours after administration.
1000 mg/kg bw: 5 animals had ruffled fur 1 to 4 hours after administration. 6 animals had ruffled fur 6 hours after administration.
Neither the animals treated with the low dose nor the vehicle control treated animals expressed any toxic reactions.
RESULTS OF DEFINITIVE STUDY
The mean number of polychromatic erythrocytes was not decreased after treatment with the test item as compared to the mean value of PCEs of the vehicle control indicating that the test item did not have any cytotoxic properties in the bone marrow.
In comparison to the corresponding vehicle controls there was no statistically significant or biologically relevant enhancement in the frequency of the detected micronuclei at any preparation interval and dose level after administration of the test item. The mean values of micronuclei observed after treatment with the test item were below or near to the value of the vehicle control group.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
In conclusion, the test item did not induce micronuclei as determined by the micronucleus test in the bone marrow cells of the mouse.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not mutagenic.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as mutagenic.
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