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

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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 201 (Alga, Growth Inhibition Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Vehicle:

no

Test organisms (species):

Desmodesmus subspicatus (previous name: Scenedesmus subspicatus)

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

72 h

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

> 0.001 mg/L

Basis for effect:

growth rate

Sorafenib tosylate had no concentration-depended inhibitory effect on the growth of Desmodesmus subspicatus. The ErC50 (growth rate) was > 0.000536 mg/L on the basis of measured concentrations. The NOEC/growth rate was 0.000536 mg/L, the LOEC was > 0.000536 mg/L.

Due to the low solubility of the test substance, the exact test concentrations in the test vessels could not be determined.

Validity criteria fulfilled:

yes

Conclusions:

Sorafenib tosylate was considered to be not toxic to the green algae Desmodesmus subspicatus, since the NOEC was higher than the solubility limit.

Executive summary:

The test substance Sorafenib tosylate was incubated in an aqueous solution including nutrients with an algae population of Desmodesmus subspicatus for a test duration of approximately 72 hours in an electronically controlled dosing and incubation apparatus. The nutrient solution was made up of mainly ammonium, phosphates and some trace elements. For the preparation of the test solutions a suspension with a nominal loading of 100 mg/L, sorafenibtosylate, was suspended in water, ultrasonified for approximately 30 min and constantly stirred for approximately 24 hours. This suspension was filtered through a glass-fiber filter. The resulting solution was used for the preparation of the test solutions. The highest concentration was a 1:1.25 dilution obtained by adding nutrient solution and inoculum, the further concentrations were obtained by dilutions of 1:5, 1:10, 1:25, 1:50 and 1:100 with demineralized water, nutrient solution and inoculum. Additionally, a control solution was prepared with demineralized water without test material. A sample was taken for the concentration analysis by HPLC-MS (stock solution) before the test solutions were prepared. The concentration of sorafenibtosylate in the stock solution was 0.00067 mg/L. The further test concentrations were extrapolated from the result of the HPLCMS- analysis. There were between 0.0007 and 0.536 µg/L. The algae were exposed to each concentration in triplicate. Six vessels were prepared for the control. The algae were incubated under standardized conditions (continuous light, controlled temperature). As a parameter for the growth of the algae population, the fluorescence of the algae cells was measured with a fluorescence-photometer. The growth rate was calculated on the basis of the fluorescence and served as basis for evaluation.

 

Sorafenib tosylate had no concentration-depended inhibitory effect on the growth of Desmodesmus subspicatus. The ErC50 (growth rate) was > 0.000536 mg/L on the basis of measured concentrations. The NOEC/growth rate was ¿ 0.000536 mg/L, the LOEC was > 0.000536 mg/L.

Description of key information

A guideline study according to OECD Guideline 201 (Algae, Growth Inhibition Test) was performed under GLP to assess the toxicity of Sorafenib tosylate to Algae Desmodesmus subspicatus. The test substance was incubated in an aqueous solution including nutrients with an algae population of Desmodesmus subspicatus for a test duration of approximately 72 hours in an electronically controlled dosing and incubation apparatus. Additionally, a control solution was prepared with demineralized water without test material. The algae were exposed to each concentration in triplicate. Six vessels were prepared for the control. For the preparation of the test solutions a suspension with a nominal loading of 100 mg/L of the test substance was suspended in water, ultrasonified for approximately 30 min and constantly stirred for approximately 24 hours. This suspension was filtered through a glass-fiber filter. The resulting stock solution was used for the preparation of the test solutions. The test concentrations were obtained by dilutions of 1:1.25, 1:5, 1:10, 1:25, 1:50 and 1:100 with demineralized water, nutrient solution and inoculum. A sample was taken for the concentration analysis by HPLC-MS (stock solution) before the test solutions were prepared. The concentration of the test substance in the stock solution was 0.00067 mg/L, due to the low solubility of the test substance. The further test concentrations were extrapolated from the result of the HPLCMS- analysis and were between 0.0007 and 0.536 µg/L. The test substance had no concentration-depended inhibitory effect on the growth of Desmodesmus subspicatus. The EC50 (growth rate) was > 0.000536 mg/L on the basis of measured concentrations. The NOEC/growth rate was 0.000536 mg/L, and the LOEC was > 0.000536 mg/L. The test substance was considered to be not toxic to the green algae Desmodesmus subspicatus, since the NOEC was higher than the solubility limit.

Key value for chemical safety assessment

EC50 for freshwater algae:

0.001 mg/L