7-Cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Short-term toxicity to fish

Administrative data

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb - Aug 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method C.1 (Acute Toxicity for Fish)

Test guideline 3

Qualifier:

according to guideline

Guideline:

ISO 7346-1 (Determination of the Acute Lethal Toxicity of Substances to a Freshwater Fish [Brachydanio rerio Hamilton-Buchanan (Teleostei, Cyprinidae)] - Part 1: Static Method)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

EC Number:

807-111-0

Cas Number:

1211441-98-3

Molecular formula:

C23H30N8O

IUPAC Name:

7-cyclopentyl-N,N-dimethyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Test material form:

solid: bulk

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

Singular samples for possible analysis were taken from all test concentrations and the control according to the schedule.
Frequency at t=0 h and t=96 h
Volume 2.0 ml
Storage Samples were stored in a freezer until analysis.
Additionally, singular reserve samples of 2.0 ml were taken from all test solutions for possible analysis.

Test solutions

Vehicle:

yes

Details on test solutions:

Test concentrations LEE011-A4
10, 18, 32, 56 and 100% of a 0.45 μm filtered solution prepared at 100 mg/l.

Test medium
Adjusted ISO medium with a hardness of 180 mg CaCO3 per litre and a pH of 7.7 ± 0.3.

Test organisms

Test organisms (species):

Cyprinus carpio

Details on test organisms:

Carp (Cyprinus carpio, Teleostei, Cyprinidae) Linnaeus, 1758

Study design

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

96 h

Test conditions

Test temperature:

20-24°C

pH:

6.0-8.5

Dissolved oxygen:

oxygen > 60% of air saturation

Details on test conditions:

Note that aeration was introduced after 24 hours of exposure, as the oxygen concentration tended to drop below the optimum level for testing with carp, i.e. below 5 mg/l. All test conditions remained within the ranges prescribed by the protocol (pH: 6.0-8.5, constant within 1 unit; temperature 20-24°C, constant within 2°C; oxygen > 60% of air saturation).

Reference substance (positive control):

no

Remarks:

Controls: Test medium without test substance or other additives

Results and discussion

Effect concentrations

Effect concentrations 1

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

ca. 38 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Effect concentrations 2

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

> 43 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

The responses recorded in this test allowed for reliable determination of an LC50 and were in agreement with the results of the combined
limit/range-finding test. Besides the observed mortality no clinical signs were observed except for the fish that died in the 14 mg/l group that showed loss of equilibrium and discoloration one day before it died.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The 96h-LC50 was estimated to correspond to 38 mg/l based on actual measured exposure concentrations (95% confidence interval between 26 and 175 mg/l).