tert-Butyl 4-({6-[7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino}pyridin-3-yl)piperazine-1-carboxylate

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb - June 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Guideline:

OECD Guideline 201 (Alga, Growth Inhibition Test)

Qualifier:

according to guideline

Guideline:

EU Method C.3 (Algal Inhibition test)

Qualifier:

according to guideline

Guideline:

ISO 8692 (Water Quality - Fresh Water Algal Growth Inhibition Test with Scenedesmus subspicatus and Selenastrum capricornutum)

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

Samples for possible analysis were taken from all test concentrations and the control according to the schedule.
Frequency at t=0 h, t=24 h and t=72 h
Volume 2.0 ml
Storage Samples were stored in a freezer until analysis.

Vehicle:

yes

Details on test solutions:

The standard test procedures required generation of test solutions, which contained completely dissolved test substance concentrations or stable and homogeneous mixtures or dispersions. The testing of concentrations that would disturb the test system was prevented as much as possible (e.g. film of the test substance on the water surface). No correction was made for the purity/composition of the test substance.
The batch of LEE011-A3 tested was a beige powder and was not completely soluble in test medium at the loading rate initially prepared.
Preparation of test solutions started with a loading rate of 100 mg/l applying a 2-day period of magnetic stirring followed by a filtration through a 0.45 μm membrane filter (Supor membrane disk filter, Pall Corporation). The obtained Water Soluble Fraction (WSF) was used as the highest test
concentration. The lower test concentrations were prepared by subsequent dilutions of the WSF in test medium. The final test solutions were all clear and colourless.
After preparation, volumes of 50 ml were added to each replicate of the respective test concentration. Subsequently, 1 ml of an algal suspension was added to each replicate providing a cell density of 104 cells/ml.

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Details on test organisms:

Species Pseudokirchneriella subcapitata, strain: NIVA CHL 1
Source In-house laboratory culture.

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

72 h

Test temperature:

21-24°C

pH:

6.0-9.0

Reference substance (positive control):

no

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

> 0.05 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: maximum soluble concentration in test medium

Key result

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

> 0.05 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: maximum soluble concentration in test medium

Details on results:

0.050 is maximum soluble concentration in test medium.

Validity criteria fulfilled:

yes

Conclusions:

Under the conditions of the present study with Pseudokirchneriella subcapitata, LEE011-A3 did notinhibited growth rate and yield of this fresh water algae species at any of the tested concentrations.
The EC50 for both growth rate (72h-ERC50) and yield inhibition (72h-EYC50) was beyond the range tested, e.g. exceeded the maximum soluble concentration in the test medium.
The 72h-NOEC for both growth rate and yield inhibition was 0.050 mg/l, which was considered the maximum soluble concentration in the test medium.
Due to the very low solubility of LEE011-A3 in the test medium, concentration levels that might be toxic for algae could not be reached.

Description of key information

Under the conditions of the present study with Pseudokirchneriella subcapitata, LEE011-A3 did notinhibited growth rate and yield of this fresh water algae species at any of the tested concentrations.

The EC50 for both growth rate (72h-ERC50) and yield inhibition (72h-EYC50) was beyond the range tested, e.g. exceeded the maximum soluble concentration in the test medium.

The 72h-NOEC for both growth rate and yield inhibition was 0.050 mg/l, which was considered the maximum soluble concentration in the test medium.

Due to the very low solubility of LEE011-A3 in the test medium, concentration levels that might be toxic for algae could not be reached.