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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
Biodegradation in water and sediment: simulation tests
Administrative data
- Endpoint:
- biodegradation in water: sediment simulation testing
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- May 2011 - Feb 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted with the base (labelled, BAY 73-4605 14-C) 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:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 308 (Aerobic and Anaerobic Transformation in Aquatic Sediment Systems)
- Deviations:
- no
- Principles of method if other than guideline:
- not relevant
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]-3-fluorophenoxy}-Nmethylpyridine- 2-[14C]carboxamide
- IUPAC Name:
- 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]-3-fluorophenoxy}-Nmethylpyridine- 2-[14C]carboxamide
- Details on test material:
- - Name of test material (as cited in study report): Regorafenib
- Analytical purity: 98.7%
- Lot/batch No.: GCM 1569-1-14C
- Radiochemical purity (if radiolabelling): 99.2%
- Specific activity (if radiolabelling): 2.47 MBq/mg
Constituent 1
- Radiolabelling:
- yes
Study design
- Oxygen conditions:
- aerobic
- Inoculum or test system:
- natural water / sediment
- Duration of test (contact time):
- 100 d
Initial test substance concentration
- Initial conc.:
- 200 other: uL
- Based on:
- test mat.
Results and discussion
% Degradation
- % Degr.:
- < 10
- Parameter:
- radiochem. meas.
- Sampling time:
- 100 d
Half-life of parent compound / 50% disappearance time (DT50)
- Compartment:
- water
- DT50:
- < 1 d
- Type:
- (pseudo-)first order (= half-life)
- Temp.:
- 20 °C
Any other information on results incl. tables
Table 1: Mass balance of [14C]- regorafenib in two sediments after 100 days [% of initially introduced radioactivity]
Sediment system | Water | Sediment | CO2 | Total mass balance |
Nordhafen | 0,4 | 112,5 | 0,3 | 113,3 * |
Tegeler See | 2 | 101,2 | 0,9 | 104,1 |
* Rounding resulted in slight differences to the individual values
Applicant's summary and conclusion
Validity criteria
- Validity criteria fulfilled:
- yes
- Conclusions:
- [14C]-regorafenib was removed rapidly from the water fraction and bound to the sediment in both sediment-systems.
Because of the lack of relevant biodegradation, the test item is assumed to accumulate in the sediment. - Executive summary:
The aerobic water/sediment metabolism (CO2 development) and the distribution of regorafenib (BAY 73-4506) was studied in two aerobic water/sediment-systems under laboratory conditions. Regorafenib is developed for cancer therapy. It is assumed that unlabeled regorafenib and 14C-labelled regorafenib behave identically in an aquatic sediment-system. Because the use of 14C-labelled test item is required in the study design, 14C-labelled regorafenib was employed and the results of this study utilized for the assessment. The study was conducted in agreement with the test guideline OECD no. 308, aerobic part.
The 14C-labelled test item regorafenib was incubated in an aerobic system, which contained intact lake sediment and overlaying water. Two types of sediments were used, one with higher organic carbon content and fine particle size (sediment-system 1, Nordhafen), the other with lower content of organic carbon and coarse grain size (sediment-system 2, Tegeler See). The substance was incubated over a period of 100 days. For the preparation of the test vessels 50 g of intact sediment and 150 g sample water were filled in each washing flask and 200 ¿L (equivalent to 0.1 MBq) of a stock solution (total radioactivity: 5 MBq/10 mL ethanol) were applied. In order to absorb evolving 14CO2 a trap of soda lime was put on each washing flask. 18 test vessels were prepared for each sedimentsystem. Samples for analysis were taken after 2, 15, 29, 43, 64 and 100 days. Three test vessels for each time point were removed for analysis. On these days temperature, oxygen content and pH value were determined in one of the replicates. Additionally after day 15 the oxygen content was measured weekly in one vessel and in all test vessels when samples were taken. Radioactivity of [14C]-regorafenib in the test system (water, sediment and 14CO2 trap) was quantified by liquid scintillation counting (LSC). The concentration of extractable [14C]-regorafenib and of occurring transformation products were analysed by radio-HPLC. The distribution of [14C]-regorafenib to the sediment compartment and the disappearance from the water fraction was determined by plotting the radioactivity over time. The disappearance time (DT50) was determined by empirical extrapolation. The mass balance (recovery of radioactivity) was calculated by summing the total radioactivity determined in soda lime, in the aqueous fraction and in the sediment.
After 100 days [14C]-regorafenib remained only to about 0.4 and 2 % in the water phase of sediment location 1 and 2, respectively. After less than one day more than 50 % of the test item were removed from the water fraction. Ultimate biodegradation was low and accounted for 0.3 and 0.9 % of the radioactivity in sediment 1 and 2, respectively. The total mass balance ranged from 81.4 to 118.8 % of the total radioactivity (0.1 MBq) in sediment-system ¿Nordhafen¿ and from 67.5 to 114.7 % of the total radioactivity (0.1 MBq) in sediment-system ¿Tegeler See¿ without showing major differences between the sediment-systems.
The extraction of water and sediment did not show significant (>10%) transformation of regorafenib and no non-extractable radioactivity was found in sediments.
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