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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 929-209-3 | CAS number: -
- 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
- Study period:
- 02/2022 - 09/2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The information for this endpoint study record was obtained from an experimental study. The OECD GLP criteria were met and the methods applied are fully compliant with OECD TG 474.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
- Report date:
- 2022
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- 4'-Ethyl-2,3-difluorbiphenyl-4-boronic acid
- EC Number:
- 929-209-3
- Cas Number:
- 1123312-95-7
- Molecular formula:
- C14 H13 B F2 O2
- IUPAC Name:
- 4'-Ethyl-2,3-difluorbiphenyl-4-boronic acid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Details on species / strain selection:
- Ninth Addendum to OECD Guidelines for Testing of Chemicals, Section 4, No. 474 “Mammalian Erythrocyte Micronucleus Test“, adopted July 29, 2016, recommends using mice. The mouse is an animal which has been used for many years as a suitable experimental animal in cytogenetic investigations. There is an abundance of available data, which may aid the interpretation of the results of the in vivo micronucleus test. In addition, the mouse is an experimental animal in many physiological, pharmacological and toxicological studies. Data from such experiments may also be useful for the design and performance of the micronucleus test
Source: Charles River, 97633 Sulzfeld, Germany
Number of animals: 5 males per dose group (7 males for 1 MTD dose group)
Initial age at start of
acclimatisation: 6 - 12 weeks
Age at start of treatment: Minimum 7 weeks - Sex:
- male
- Details on test animals or test system and environmental conditions:
- Housing: 5 animals of identical sex per cage
Cage type: IVC cage (Polysulphone), Type II L
Bedding: Altromin saw fiber bedding (Batch: 0131)
Feed: Free access to Altromin 1324 (Batch: 0939) maintenance diet for rats and mice
Air change: At least 10 x per hour
Water: Free access to tap water, sulphur acidified to pH value of approx. 2.8 (drinking water, municipal residue control, micro-biologically controlled at frequent intervals)
Environment: Temperature 22 ± 3 °C
Relative humidity 55 ± 10%
Artificial light 6:00 - 18:00
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- 0.25% aqueous hydroxypropyl methylcellulose (Methocel®) as vehicle of the test item was used as negative control. All control animals were handled in an identical manner to the test group subjects.
The sampling time for the negative control was 44 h after final treatment.
Name: 0.25% aqueous hydroxypropyl methylcellulose
Route and frequency of administration: oral, twice
Volume administered: 10 mL/kg bw
Name: Aqua ad iniectabilia
Supplier: Deltamedica
Batch No.: 2006003
Physical State/Colour:liquid/colorless
Storage: ambient, at room temperature
Expiry date: May 2023
Name: hydroxypropyl methylcellulose (Methocel®)
Supplier: Colorcon
Batch No.: D180I7S002
Storage: ambient, at room temperature
Expiry date: 27 July 2023 - Details on exposure:
- The animals received the test item twice at a 24 h interval by the oral route. Four hours before treatment all animals were under fasting condition.
- Duration of treatment / exposure:
- administrations on 2 consecutive days by oral gavage.
- Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Remarks:
- Top dose selection is based on results of the dose range finding experiment performend as pre test using 1000, 500, and 250 mg/kg bw.
- Dose / conc.:
- 125 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5 M
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Name: CPA; Cyclophosphamide
CAS No.: 50-18-0
Supplier: Sigma
Catalogue No.: C0768
Batch No.: MKCL2547
Dissolved in: physiological saline
Dosing: 40 mg/kg bw
Route and frequency of
administration: ip, single
Volume administered: 10 mL/kg bw
Expiry date: October 2022
Examinations
- Tissues and cell types examined:
- Clinical observation, Blood cell analysis
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
A preceding study on toxicity was performed with the same strain and under identical conditions as in the main study. The maximum dose that was applied was 1500 mg/kg bw for females and 1000 mg/kg bw for males based on data concerning toxicity of the test item provided by the sponsor and animal welfare aspects. The maximum volume which was administered was 10 mL/kg bw. The animals received the test item once.
The use of the maximum tolerated dose is generally recommended. In cases where the test item cannot be dissolved or evenly suspended in any of the well-known vehicles, the highest dose which can be formulated and administered reproducibly is used. The volume to be administered is compatible with physiological space available.
The maximum tolerated dose is defined as the highest dose that will be tolerated without evidence of study-limiting toxicity, relative to the duration of the study period (for example, by inducing body weight depression or hematopoietic system cytotoxicity, but not death or evidence of pain, suffering or distress necessitating humane euthanasia).
Animals treated with the highest dose (1 MTD) showed toxic effects with reduction of spontaneous activity, hunched posture, prone position, ataxia, constricted abdomen, piloerection and half eyelid closure up to 4 h after each application. 24 h after the final application all animals had fully recovered. Mice treated with 125 mg/kg bw/day (0.5 MTD) showed the same signs of toxicity as displayed for the 1 MTD dose group animals except for ataxia. These signs of toxicity were in total less intensely developed than in the 1 MTD group animals. 24 h after the final application all animals had fully recovered. The animals treated with 50 mg/kg bw/day (0.2 MTD) showed no signs of toxicity after the treatment with the test item.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
Sampling of the peripheral blood was carried out on animals 44 h after final treatment.
METHOD OF ANALYSIS:
Cell suspensions flow cytometry
OTHER: - Evaluation criteria:
- Providing that all acceptability criteria are fulfilled, a test item is considered clearly negative if, in all experimental conditions examined:
- none of the treatment groups exhibits a statistically significant increase in the frequency of micronucleated immature erythrocytes compared with the concurrent negative control,
- there is no dose-related increase at any sampling time when evaluated with an appropriate trend test,
- all results are inside the distribution of the historical negative control data (e.g. Poisson-based 95% control limits), and
- bone marrow exposure to the test item occurred. - Statistics:
- Poisson-based 95% control limits
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- reduction of spontaneous activity, hunched posture, prone position, ataxia, constricted abdomen, piloerection and half eyelid closure up to 4 h after each application. 24 h after the final application all animals had fully recovered.
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Dose Formulation Analysis Results
The quantification of the test item formulations showed that measured concentrations lay below the expected nominal concentrations and below the acceptance criterion. This could be due to the preparation method of the test item that resulted in a suspension of the test item with the presence of small particles. Albeit all formulations were shown to be homogenous, the presence of particles and the use of relatively small volumes for formulation analysis could be the cause for the discrepancy.
The test item formulations for the pre-experiment to determine the maximum tolerated dose and for the main experiment were prepared following the same procedure and were applied to the animals as suspensions under continuous stirring.
Additionally, the clinical signs of systemic toxicity of the animals of the highest dose group (1 MTD, 250 mg/kg) in the main experiment were consistent with the observations of the pre-experiment indicating that the doses applied in both experiments were consistent. The application of a higher dose would have led to a level of systemic toxicity contradicting animal welfare.
Thus in both experiments of this study the maximum tolerated dose of the test item was applied according to OECD 474 and the criteria for selection of the maximum dose were fulfilled and the study is considered acceptable and valid.
Bioanalysis
For analytical purposes blood samples of additional three male animals were obtained two hours after the final application of the maximum tolerated dose of the test item.
The analysis of the blood plasma showed that the test material could be detected in all samples demonstrating systemic bioavailability after oral administration which is considered as evidence for exposure of bone marrow to the test item.
For further details on results incl. historical control please refer to study report attached as a confidential attachment.
Any other information on results incl. tables
Dose Group |
Concentration [mg/kg bw/day] |
Sampling time [h] |
Rel. PCE |
Proportion rel. PCE to Control [%] |
MN [%] |
NC |
0 |
44 |
2.48 |
100 |
0.25 |
CPA |
40 |
44 |
0.47 |
19.0 |
1.95 |
0.2 MTD |
50 |
44 |
1.85 |
74.6 |
0.20 |
0.5 MTD |
125 |
44 |
1.59 |
64.1 |
0.19 |
1 MTD |
250 |
44 |
1.90 |
76.6 |
0.24 |
Applicant's summary and conclusion
- Conclusions:
- In conclusion, it can be stated that during the study described and under the experimental conditions reported, the test item did not induce structural and/or numerical chromosomal damage in the immature erythrocytes of the mouse.
Therefore, Art. 277455 (PY-2-B(OH)2) is considered to be non-mutagenic with respect to clastogenicity and/or aneugenicity in the mammalian erythrocyte micronucleus test.
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.