2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

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 211 (Daphnia magna Reproduction Test)

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Vehicle:

no

Test organisms (species):

Daphnia magna

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

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

Validity criteria fulfilled:

yes

Conclusions:

Due to the low water solubility of Sorafenib tosylate 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 Sorafenib tosylate 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).

Description of key information

A guideline study according to OECD Guideline 211 (Daphnia magna Reproduction Test) was performed under GLP to assess the long-term toxicity of Sorafenib tosylate to Daphnia magna. A group of 10 Daphnia magna were used for each of the 5 test concentrations and 10 Daphnia for the water control. The Daphnia were held individually. The Daphnia were exposed to the test solution and the tap water control 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. 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 concentration and aliquots of the obtained solution were further diluted by the factor 1:3, 1:9, 1:27 and 1:81 with tap water in order to prepare the respective test concentrations. For each change, all test solutions were prepared freshly. Samples of the test solutions were taken weekly for concentration analysis by HPLC. The test substance was not detectable in most test solutions, due to the low water solubility of the test substance. Only at the two highest concentrations, detectable levels of the test substance were found. 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. Thus, the NOEC for cumulative offspring was 0.00086 mg/L and the LOEC was > 0.00086 mg/L (measured cocentration).

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

NOEC

Effect concentration:

>= 0.001 mg/L