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EC number: 608-209-4 | CAS number: 284461-73-0
- 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
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- Nanomaterial surface chemistry
- Nanomaterial dustiness
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- Nanomaterial pour density
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- 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
Link to relevant study record(s)
- Endpoint:
- fish early-life stage toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 2008-2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- Sorafenib tosylate was used as an analogue.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Analytical monitoring:
- yes
- Vehicle:
- yes
- Test organisms (species):
- Pimephales promelas
- Test type:
- flow-through
- Water media type:
- freshwater
- Limit test:
- no
- Total exposure duration:
- 33 d
- Duration:
- 28 d
- Dose descriptor:
- EC10
- Effect conc.:
- 0 mg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- mortality
- Validity criteria fulfilled:
- yes
- Conclusions:
- The results of this study showed that Sorafenib tosylate has effects on growth and survival of fish
(fathead minnow) at concentrations from 1.0 µg/L onwards. Thus, the overall no observed effect concentration (NOEC) was <1.0 µg/L, the lowest observable effect concentration (LOEC) was 1.0 µg/L. The lowest EC10 for survival was 0.17 µg/L. - Executive summary:
The eggs and larvae were exposed to three test solutions of sorafenibtosylate with nominal
concentrations of 6, 17 and 50 µg (nominal) per liter tap water and additionally to a vehicle
(dimethylformamide, DMF) and a control for a period of 28 days post hatch (ph). For the
preparation of the stock solution, the test substance was dissolved in DMF.
The stock solution was mixed with tap water and delivered continuously to the tanks.
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 weekly.
The oxygen concentration in the test vessels was >60 % of air saturation value, the
temperature was maintained at 24 ± 2 ºC and the pH-value between 6.5 and 8.5.
Samples for the concentration analysis in the test solutions were taken at the start of the exposure
and weekly thereafter. The determination of Sorafenib tosylate in the test solutions was carried
out by HPLC/MS.
The endpoint survival was statistically evaluated by the computer program
TOXRat Professional XT, length and weight was evaluated by PROVANTIS (NOEC, LOEC)
and TOXRat Professional XT (ECx).
Then analytical results gave mean measured concentrations of 1, 2.4 and 14.8 µg/L.
Hatching and short-term survival (day 5 ph) was not affected by the test substance while
mortality of the larvae (day 28 ph) increased clearly with increasing concentration of
sorafenibtosylate. Additionally, the growth of the treated fish decreased with increasing
concentration of the test substance.
A significant substance-related effect on growth and survival of the treated fish compared to the
control could be observed. The NOEC (survival) was <1.0 µg/L and the LOEC (survival) was
1.0 µg/L, the EC10 for survival was 0.17 µg/L. The NOEC for length and weight was 2.4 µg/L,
the LOEC was 14.8 µg/L. The EC10 was 0.47 µg/L for weight and 0.32 µg/L for length.
Accordingly, 0.17 µg/L was the toxicity threshold for sorafenib tosylate.
Reference
Fish larvae hatched 4 days after the introduction of the eggs in all test solutions. The hatching success was > 66 % in all test and control solutions. The number of dead fish increased with increasing concentration. From the second highest concentration on, fish growth (weight and length) decreased. The NOEC and LOEC for weight and length was 2.4 µg/L and 14.8 µg/L, respectively, for survival the NOEC was < 1.0 µg/L and the LOEC was 1.0 µg/L and for hatchability NOEC and LOEC were 14.8 µg/L.
In order to define a threshold for toxic effects, the EC10 for weight and length inhibition was determined with 0.47 µg/L and 0.32 µg/L, respectively, for survival (28 dph) was 0.17 µg/L.
Description of key information
A guideline study according to OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test) was performed under GLP to assess the long-term toxicity of Sorafenib tosylate to fish Pimephales promelas. The eggs and larvae were exposed to three test solutions with nominal concentrations of 6, 17 and 50 µg (nominal) per liter tap water and additionally to a vehicle (dimethylformamide, DMF) and a control for a period of 28 days post hatch (ph). For the preparation of the stock solution, the test substance was dissolved in DMF. The stock solution was mixed with tap water and delivered continuously to the tanks. 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. Samples for the concentration analysis in the test solutions were taken at the start of the exposure. The analytical results by HPLC/MS gave mean measured concentrations of 1, 2.4 and 14.8 µg/L. A significant substance-related effect on growth and survival of the treated fish compared to the control could be observed. The NOEC (survival) was <1.0 µg/L and the LOEC (survival) was 1.0 µg/L, the EC10 for survival was 0.17 µg/L. The NOEC for length and weight was 2.4 µg/L, the LOEC was 14.8 µg/L. The EC10 was 0.47 µg/L for weight and 0.32 µg/L for length. Accordingly, 0.17 µg/L was the toxicity threshold for the test substance.
Key value for chemical safety assessment
Fresh water fish
Fresh water fish
- Dose descriptor:
- LC10
- Effect concentration:
- 0 mg/L
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