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EC number: 692-722-3 | CAS number: 835621-07-3
- 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
Long-term toxicity to aquatic invertebrates
Administrative data
- Endpoint:
- long-term toxicity to aquatic invertebrates
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Nov 2012 - Jan 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted with the base (BAY 73-4506) according to OECD guideline under GLP
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 211 (Daphnia magna Reproduction Test)
- Deviations:
- no
- Principles of method if other than guideline:
- not relevant
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 4-(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}-3-fluorophenoxy)- N-methylpyridine-2-carboxamide
- IUPAC Name:
- 4-(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}-3-fluorophenoxy)- N-methylpyridine-2-carboxamide
- Details on test material:
- - Name of test material (as cited in study report): Regorafenib (BAY 73-4506)
- Analytical purity: 100%
- Lot/batch No.: BXR4Z07
Constituent 1
Sampling and analysis
- Analytical monitoring:
- yes
Test solutions
- Vehicle:
- yes
Test organisms
- Test organisms (species):
- Daphnia magna
Study design
- Test type:
- semi-static
- Water media type:
- freshwater
- Limit test:
- no
- Total exposure duration:
- 21 d
Results and discussion
Effect concentrationsopen allclose all
- Duration:
- 21 d
- Dose descriptor:
- NOEC
- Effect conc.:
- 24.7 µg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- reproduction
- Duration:
- 21 d
- Dose descriptor:
- NOEC
- Effect conc.:
- 10.5 µg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- immobilisation
- Duration:
- 21 d
- Dose descriptor:
- LOEC
- Effect conc.:
- 57.6 µg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- reproduction
- Duration:
- 21 d
- Dose descriptor:
- LOEC
- Effect conc.:
- 24.7 µg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- immobilisation
Any other information on results incl. tables
Table 1: Cumulative number of off-spring and number of brood per surviving animals after 21 days of exposure to Regorafenib (mean values ± standard deviation)
Nominal | Number of surviving | No. of off-spring per | Number of broods per |
concentration of | animals | surviving parent | surviving parent |
BAY 73-4506 | (survival / total) | animals | animal |
[microg/L] | [MV ± SD] | [MV ± SD] | |
0 (control) | 10/10 | 74.0 ± 7.4 | 4.8 ± 0.6 |
0 (vehicle control) | 8/10 | 68.3 ± 13.0 | 4.4 ± 0.7 |
2.6 | 9/10 | 71.0 ± 10.6 | 4.7 ± 0.5 |
5.5 | 9/10 | 67.8 ± 14.7 | 4.8 ± 0.4 |
10.5 | 9/10 | 68.4 ± 5.1 | 5.1 ± 0.3 |
24.7 | 4/10 | 64.8 ± 18.0 | 4.8 ± 0.5 |
57.6 | 1/10 | 33.0 | 3.0 |
Applicant's summary and conclusion
- Validity criteria fulfilled:
- yes
- Conclusions:
- Regorafenib had a concentration related mortality and effects on reproduction in Daphnia magna. The most sensitive NOEC for chronic
immobilization was 10.5 microg/L, the LOEC was 24.7 microg/L. - Executive summary:
The purpose of this study was to determine the chronic toxicity of the compound Regorafenib (BAY 73-4506) on reproduction of Daphnia magna in the context of evaluating the risk to the aquatic environment. Regorafenib is developed for cancer therapy.
The study was conducted in agreement with the guideline of the OECD, no. 211. Due to the low water solubility of Regorafenib, the study was conducted with DMF as vehicle.
10 Daphnia magna were used for each of the 5 test concentrations of Regorafenib and 10 for the dilution water control and the vehicle control. The Daphnia were exposed to the test solution, the vehicle control and the tap water for a period of 21 days (start of treatment = day 1) under semistatic conditions, i.e. the solutions were renewed three times a week. The Daphnia were held individually. The number of living off-spring was recorded at each change of test solution 3 times per week, immobilization of parent animals was recorded daily.
For the preparation of the stock solution an amount of 100 mg Regorafenib was dissolved in 100 mL DMF by stirring. Aliquots of the obtained stock solution were further diluted with tap water and DMF in order to prepare the appropriate test concentrations: 6.3 microg/L, 12.5 microg/L, 25 microg/L, 50 microg/L and 100 microg/L. The vehicle control and the test solutions contained 0.1 mL DMF/L in water.
The test temperature was in the range of 19.9°C to 21.6°C. The pH was in a range between 7.6 and 8.6, and the oxygen concentration between 7.7 and 9.7 mg/L. The light/dark rhythm was adjusted to 16 hours/8 hours.
Samples for the concentration analysis by HPLC/MS-detection were taken weekly from the test and control solutions and samples from the stock solution were taken at the beginning and at the end of the study.
The mean number of off-spring per parent animal varied between 74.0 and 33.0, the number of broods varied between 4.8 and 3.0 showing a dose dependence. The first brood in the control and the vehicle control group was recorded at day 9 (mean) of the exposure.
Regorafenib had a concentration related mortality and effects on reproduction in Daphnia magna.
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