Registration Dossier

Ecotoxicological information

Long-term toxicity to aquatic invertebrates

Administrative data

Endpoint:
long-term toxicity to aquatic invertebrates
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2008-2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 211 (Daphnia magna Reproduction Test)
Deviations:
no
Principles of method if other than guideline:
Not relevant
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: particulates
Details on test material:
test was performed with the tosylate salt of BAY 43-9006 (sorafenib tosylate=4-{4-[3-(4-Chloro-3-trifluoromethyl-phenyl)ureido]phenoxy}pyridine 2-carboxylic acid methylamide 4-methylbenzenesulfonate)

Sampling and analysis

Analytical monitoring:
yes

Test solutions

Vehicle:
no

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 concentrations
Duration:
21 d
Dose descriptor:
NOEC
Effect conc.:
>= 0.001 mg/L
Nominal / measured:
meas. (arithm. mean)
Conc. based on:
test mat.
Basis for effect:
reproduction

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Conclusions:
Due to the low water solubility of sorafenibtosylate the test substance was not detectable in most
test solutions.
Only weak effects were observed on the number of off-spring at the three highest concentrations.
No effects were observed on the surviving parent animals and the number of broods.
The NOEC for cumulative offspring was ¿ 0.00086 mg/L. The LOEC was > 0.00086 mg/L
(measured cocentration).
Executive summary:

Ten Daphnia magna were used for each of the 5 test concentrations of sorafenibtosylate and 10

for the dilution water control. The Daphnia were exposed to the test solution and the tap water

for a period of 22 days (start of treatment = day 1) under semi-static conditions, i.e. the solutions

were renewed three times a week. The Daphnia were held individually. The immobilization of

parent animals was recorded every day and the number of living off-spring was recorded at each

change of the test solution 3 times per week starting when the first brood was released.

The NOEC/LOEC of the number of off-spring and the number of broods were statistically

evaluated by the computer program TOXRat Professional XT.

For the preparation of the test solutions a solution with a nominal concentration of 100 mg/L was

ultrasonified for approximately 30 minutes and stirred for approximately 24 hours. This

suspension was filtered through a glass-fiber filter. This solution was used for the highest test

solution and also aliquots of the obtained solution were further diluted 1:3, 1:9, 1:27 and 1:81

with tap water in order to prepare the appropriate test concentrations.

For each change of test solutions the saturated solution and the dilutions were prepared freshly.

Samples of the test solutions were taken weekly for concentration analysis by HPLC

The test temperature was in the range of 19.7 °C to 20.1 °C. The pH was in a range between 7.6

and 8.4 and the oxygen concentration between 7.8 and 8.9 mg/L. The light/dark rhythm was

adjusted to 12 hours/12 hours.

Due to the low water solubility of sorafenibtosylate the test substance was not detectable in most test solutions. Only at the two highest concentrations, detectable levels were found. The NOEC for cumulative offspring was ¿ 0.00086 mg/L. The LOEC was > 0.00086 mg/L(measured cocentration).