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EC number: 206-735-5 | CAS number: 371-40-4
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1999-07-05 to 1999-07-19
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- adopted July 21, 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
- Version / remarks:
- EPA 712-C-98-226, August 1998
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- 3,5-difluoroaniline
- EC Number:
- 206-752-8
- EC Name:
- 3,5-difluoroaniline
- Cas Number:
- 372-39-4
- Molecular formula:
- C6H5F2N
- IUPAC Name:
- 3,5-difluoroaniline
- Test material form:
- other: solid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: RCC Ltd. Biotechnology & Animal Breeding Division, CH-4414 Füllinsdorf
- Age at study initiation: 8-12 weeks
- Weight at study initiation: males 40 g, females 32.1 g
- Assigned to test groups randomly: yes
- Housing: Single, animals were kept conventionally; Cage type: Makrolon Type 1, with wire mesh top; Bedding: granulated soft wood bedding
- Diet: Pelleted standard diet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: min. 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 21 +/- 3 °C
- Humidity: 30-78 %
- Photoperiod: Artificial light from 6.00 am to 6.00 pm
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle used: DMSO
- Amount of vehicle: 4 mL/kg bw
- Purity: 99.5% - Frequency of treatment:
- Once
- Post exposure period:
- 24, 48 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
62.5, 125 and 250 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 84 (42 males /42 females)
6 males/ 6 females to each test group - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Route of administration: Intraperitoneally, once
- Doses: 40 mg/kg bw
- Volume: 10 mL/kg bw
Solution prepared on day of administration
Examinations
- Tissues and cell types examined:
- Bone marrow cells oft he mouse
2000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
Based on the pre-experiment of toxicity maximum tolerated dose estimated to be 250 mg/kg bw .
Pre-Experiment for Toxicity
A preliminary study on acute toxicity was performed with two or five animais per sex and group, respectively, under identical conditions as in the mutagenicity study concerning: animal strain; vehicle; route, frequency of administration, and application volume.
The animals were treated intraperitoneally with the test article and examined for acute toxic symptoms 1h, 6h, 24h, and 48h after treatment.
The pre-experiments were not conducted under GLP-regulations. However, the experimental performance was in accordance to the SOP for pre-experiments. The results will be archived together with the data and materials of the present study.
TREATMENT AND SAMPLING TIMES
Sampling of the bone marrow was done 24 and 48 hours after treatment, respectively.
DETAILS OF SLIDE PREPARATION:
The animals were sacrificed by cervical dislocation. The femora were removed, the epiphyses were cut off and the marrow was flushed out with fetal calf serum, using a syringe. The cell suspension was centrifuged at 1500 rpm (390 x g) for 10 minutes and the supernatant was discarded. A small drop of the resuspended cell pellet was spread on a slide. The smear was air-dried and then stained with May-Grünwald/Giemsa. Cover slips were mounted with EUTKITT. 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 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 as quotient PCEs/NCEs. The analysis was performed with coded slides. Five animals per group were evaluated as described. - Evaluation criteria:
- Acceptance Criteria
The study is considered valid as the following criteria are met:
- the vehicle controls are in the range of our historical control data (0.3 - 2.6 0/00) PCEs with micronuclei.
- the positive controls show statistically significant increased values (the upper range of the historical range of 9.5 - 23.6 0/00 PCEs with micronuclei was slightly exceeded [23.9 0/00]).
- more than 80 % of animals are evaluable
Evaluation of Results
A test article is 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 artiele 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.
However, both biological and statistical significance should be considered together. - Statistics:
- Statistical significance at the five per cent level (p <0.05) was evaluated by means ofthe non-parametric Mann-Whitney test.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Remarks:
- maximum tolerated dose estimated to be 250 mg/kg bw
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 200-400 mg/kg bw
- Solubility: in DMSO
- Clinical signs of toxicity in test animals (maximum tolerated dose 250 mg/kg bw): Reduction of spontaneous activity, eyelid closure, apathy, abdominal position, death (two female animals at 48 h)
- Evidence of cytotoxicity in tissue analyzed: No
RESULTS OF DEFINITIVE STUDY
- Ratio of PCE/NCE: 62.5 mg/kg bw: 1.14; 125 mg/kg bw: 1.17; 250 mg/kg bw: 1.08
- Statistical evaluation: Mann-Whitney test 250 mg test item at 24 h p=0.8264; 40.00 mg CPA/kg bw at 24 h <0.0001
The mean values of micronuclei observed after treatment with the test item were in the same range as compared to the vehicle control groups and within the laboratory's historical negative control range.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
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