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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 fish
Administrative data
- Endpoint:
- fish early-life stage toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Oct 2013 - NOV 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted with the base (BAY 73-4605) 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:
- 2 014
- Report date:
- 2014
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 210 (Fish, Early-Life Stage Toxicity 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
- Analytical purity: 100.7%
- Lot/batch No.: BXR4Z07
Constituent 1
Sampling and analysis
- Analytical monitoring:
- yes
Test solutions
- Vehicle:
- yes
Test organisms
- Test organisms (species):
- Pimephales promelas
Study design
- Test type:
- flow-through
- Water media type:
- freshwater
- Limit test:
- no
- Total exposure duration:
- 28 d
- Remarks on exposure duration:
- post hatch (ph)
Results and discussion
Effect concentrationsopen allclose all
- Duration:
- 28 d
- Dose descriptor:
- NOEC
- Effect conc.:
- 0.007 µg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- mortality
- Duration:
- 28 d
- Dose descriptor:
- LOEC
- Effect conc.:
- 0.025 µg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- mortality
Any other information on results incl. tables
Table 1: Summary of survival, length and weight of fathead minnow exposed to Regorafenib in an ELS test over 28 days post hatch (ph)
Regorafenib [ug/L] nominal / extrapolated | Hatching rate [%] n=80 | Survival day 7 ph [% of hatched larvae] | Survival day 28 ph [% of hatched larvae] | Weight day 28 ph [mg] n=counted larvae | Length day 28 ph [mm] n=counted larvae | |
0 (control) | 98,8 | 84,9 | 24,48 (n=67) | 11,22 (n=67) | ||
0 (DMF) | 95,0 | 100 | 85,3 | 38,75 (n=65) | 12,04 (n=65) | |
0,03 / 0,01 | 93,8 | 98.5 | 89,3 | 19,86 (n=67) | 10,65 (n=67) | |
0.1 / 0,03 | 93,8 | 95,9 | 45,0 | 40,83 (n=34) | 12,51 (n=34) | |
0.3 / 0.08 | 85,0 | 96,9 | 38,2 | 29,39 (n=26) | 11,5 (n=26) | |
1.0 / 0.38 | 77,5 | 93,7 | 43,5 | 35,7 (n=27) | 12,0 (n=27) | |
3.0 / 1,39 | 73,8 | 94,3 | 39,4 | 14,17 (n=23) | 8,91 (n=23) |
Applicant's summary and conclusion
- Validity criteria fulfilled:
- yes
- Conclusions:
- The results of this study showed that regorafenib has effects on survival of fish (fathead minnow) at concentrations from 0.025 ¿g/L onwards.
Thus, the overall no observed effect concentration (NOEC) was 0.007 ¿g/L, the lowest observable effect concentration (LOEC) was 0.025 ¿g/L. - Executive summary:
The purpose of this study was to determine the aquatic toxicity of Regorafenib in the early-life-stage test on the fathead minnow (Pimephales promelas). Regorafenib is a multi-kinase inhibitor developed for tumor therapy. The study was conducted following the OECD guideline 210.
Freshly fertilized eggs (80 per treatment group, 4 replicates) from a laboratory culture of adult fathead minnow were used for each test solution of regorafenib and for the control group. For each group two separate glass vessels, each with 20 eggs, were introduced.
The eggs and larvae were exposed for a period of 28 days post-hatch (ph) to five test solutions of regorafenib with nominal concentrations of 0.03 ¿g/L, 0.1 ¿g/L, 0.3 ¿g/L, 1 ¿g/L und 3 ¿g/l. Additionally a tap water control and a solvent control (DMF) was used under the same conditions. For the preparation of the stock solutions, the test substance was dissolved in DMF.
Mortalities and visible abnormalities were recorded daily over the exposure phase. Hatching success and survival were recorded during the first phase of embryonic development as well as growth and survival during the larval stage until the end of the exposure period. The hydrographic parameters were recorded daily and after day 7 ph weekly.
Fish larvae hatched 6 days after the introduction of the eggs in all test solutions. The hatching success was >95% in both the water and solvent controls, and decreased concentration related in all test solutions from 94 to 74%. This was, however, not statistically significant. For weight increase, there was a decrease compared to control fish, however, this was also not statistically significant. The NOEC and LOEC for length increase was 0.34 ¿g/L and 1.39 ¿g/L.
The number of dead fish increased with increasing concentration. For post-hatch survival the NOEC was 0.007 ¿g/L and the LOEC was 0.025 ¿g/L.
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