1-Propanesulfonamide, N-[3-[[5-bromo-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-02-21 to 2011-02-25

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

yes

Remarks:

The study used nominal concentration that was far in excess of the water solubility of the test substance.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

Deviations:

yes

Remarks:

The study used nominal concentration that was far in excess of the water solubility of the test substance.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N-{3-[5-bromo-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide

EC Number:

806-756-5

Cas Number:

1262985-24-9

Molecular formula:

C24 H16 Br Cl2 F2 N3 O4 S

IUPAC Name:

N-{3-[5-bromo-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide

Test material form:

other: solid

Details on test material:

Solid
Water solubility: <1 mg/L
Purity: >99% (w/w)
Expiry date: 30 June 2011

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

HPLC analyses of the test substance concentrations were conducted in the definitive test at the beginning of the test and after 24 h and 48 h of incubation, respectively.

Test solutions

Vehicle:

no

Details on test solutions:

Prior to the definitive test a non-GLP range finding test with a nominal concentrations of 100 mg/L was performed.
Since no significant effects were observed in this range finding test, only a limit test with the nominal concentration of 100 mg/L was performed as a definitive test. Due to the limited water solubility of the test substance, only the water accommodated fraction was tested.
This water accommodated fraction was prepared by addition of the respective amount of an acetonic stock solution to an empty glass vessel. After complete evaporation of the solvent, the aerated Daphnia medium was added. The test solution was moderately stirred overnight followed by filtration
(MILLIPORE AP15 glass fibre filter). The resulting water accommodated fraction was used in the test.
100 mL of the filtered test solutions were filled in one of the two replicate test vessels. The solution was aerated by stirring for about 0.5 h. 02 concentration and pH was measured. The pH was adjusted if necessary. Afterwards, half of the solution (50 mL) was filled in the 2nd replicate test vessel.

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

Daphnia maqna (Straus, 1820).
Young daphnia with an age of < 24 hours were selected for the test.
Renewal of the cultures: After 7 days of cultivation half of the medium twice a week.
Temperature o f medium: 20 °C constant within +/-2°C
Feeding: Daily except at weekends.
Illumination: 16 h per day
Medium: Continuously aerated Elendt M4 medium prepared with deionised water (conductivity <1.5 uS/cm).

Study design

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Test conditions

Test temperature:

20°C +/- 2°C

pH:

7.0-8.0

Dissolved oxygen:

5.6-6.1

Details on test conditions:

Test type: Static
Test duration: 48 hours
Test vessels: 100 ml, all-glass
Medium: I Continuously aerated Elendt M4 medium; prepared with deionised water (conductivity <1.5 uS/cm
Number of daphnia: 40 per concentration
Loading: 20 per vessel containing 50 ml medium
Light: 16 hours photoperiod daily
Daphnia, aged less than 24 h, were acclimatised to the test medium for about 1 h before introduction into the formulated test media

Reference substance (positive control):

yes

Remarks:

potassium dichromate

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 0.1 mg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

mobility

Effect concentrations 2

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

< 0.1 mg/L

Nominal / measured:

meas. (TWA)

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

Using the water accommodated fraction of the test item no toxic effects (:>1 0% immobilization) were observed after 24 and 48 h of exposure. No
toxic effects were also observed in the control after 24 and 48 h of exposure.
Based on the analytically determined concentrations the 24 and 48 h EC50 values were >0.1 mg/L.
The no-observed-effect concentration (NOEC) for 24 and 48 h of incubation based on the analytically determined concentrations were <0.1 mg/L.
100% immobilization was not detected.

Results with reference substance (positive control):

Periodically acute reference tests were conducted with potassium dichromate

Reported statistics and error estimates:

The median effective concentration (EC50 value) is the concentration estimated to immobilize 50% of the Daphnia after 24 or 48 h of exposure. Those individuals not able to swim within 15 s after gentle agitation of the test vessel are considered to be immobile.
The EC values at 24 and 48 h of exposure will be calculated from the percentage response (number of immobile Daphnia) and the logarithms of the corresponding nominal test substance concentrations.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Remarks:

The study used nominal concentration that was far in excess of the water solubility of the test substance.

Conclusions:

Under the test conditions no toxic effects (>10% immobilization) were obserwed.

Executive summary:

INTRODUCTION: The acute toxicity of the test item to Daphnia magna was investigated under static exposure conditions over a period of 48 h. The applied nominal test concentrations was 100 mg/L. 40 individual Daphnia divided in 2 test vessels were exposed to the test substance.

METHOD: HPLC analyses of the test substance concentrations were conducted at the beginning of the test and after 24 h and 48 h of exposure, respectively.

RESULTS: Using the water accommodated fractions no toxic effects (>10% immobilization) were observed at 24 and 48 h of exposure, respectively. No toxic effects were also observed in the control after 24 and 48 h of exposure. 100% immobilization was not detected. The test substance was not quantified in any of the test solutions, all results were <0.1 mg/L.

CONCLUSION: Under the test conditions no toxic effects (>10% immobilization) were obserwed.