Thieno[3,2-c]pyridine-5(4H)-acetic acid, .alpha.-(2-chlorophenyl)-6,7-dihydro-, methyl ester, (.alpha.S)-, (1R,4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate (1:1)

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study according to international accepted guidelines and GLP compliant.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[(1R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl]methanesulfonic acid; methyl (2S)-2-(2-chlorophenyl)-2-{4H,5H,6H,7H-thieno[3,2-c]pyridin-5-yl}acetate

EC Number:

601-680-7

Cas Number:

120202-68-8

Molecular formula:

C16H16ClNO2S.C10H16O4S

IUPAC Name:

[(1R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl]methanesulfonic acid; methyl (2S)-2-(2-chlorophenyl)-2-{4H,5H,6H,7H-thieno[3,2-c]pyridin-5-yl}acetate

Test material form:

solid: crystalline

Details on test material:

Test item: Clopidogrel camphorsulphonic acid salt (CAS: 120202-68-8)
Batch No.: 648038N (0090D94)
Physical state: Solid, crystalline powder
Colour: Almost white
Storage: At a temperature of 15 to 30 °C, protected from light and moisture

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

In the test the following nominal concentrations were applied: 9.62; 4.81; 3.21; 2.41; 1.60; 0.96; and 0.64 mg/L.
At the start of the test before adding the daphnids the concentration of the test item was determined in the remaining test solution of the concurrent test vessels at each dilution levels.
The concentration of the test item of pooled samples for each concentration was measured at the end.
Before the analysis the samples were filtered. The first 10 ml filtrates were disposed.

Test solutions

Vehicle:

yes

Details on test solutions:

The test organism was breaded and hold in Elendt M4 medium which was used also for preparing of saturated test item solution.

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

Test species: Daphnia magna Straus
Young daphnids were used in the test were less than 24 hours old and were not first brood progeny.
Age: < 24 hours neonates
Origin: National Institute of Environmental Health

Study design

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Test conditions

Test temperature:

21 ± 1 °C

pH:

At the beginning of the test before adding the daphnids the pH values were measured in the remaining test solution of the concurrent test vessels at each dilution levels.
At the end of the test the pH-values were also measured in each test vessels.
The pH of test solutions was not adjusted at the beginning of the test.

Dissolved oxygen:

At the beginning of the test before adding the daphnids the dissolved oxygen concentrations were measured in the remaining test solution of the concurrent test vessels at each dilution levels.
At the end of the test the dissolved oxygen concentrations were also measured in each test vessels.

Nominal and measured concentrations:

In the test the following nominal concentrations were applied: 9.62; 4.81; 3.21; 2.41; 1.60; 0.96; and 0.64 mg/L.
The measured concentrations at the start of the test : 8.84, 4.67, 3,06; 2.30, 1.46, 0.86, 0.58 mg/L.
The measured concentrations at the end of the test : 8.48, 4.58, 3.03, 2.30, 1.53, 0.87, 0.58 mg/L.

Details on test conditions:

At each concentration level four replicate test vessels were prepared. Each test vessel contained 5 daphnids in 50 ml test solution. The test vessels were covered with plastic lids and were kept in thermostat at 21 ± 1 °C with a 16/8 hours light/dark cycle. The controls were kept under the same conditions in Elendt M4 medium.
The pH values and dissolved oxygen concentrations were measured at the start and at the end of the test. The numbers of immobilised daphnids were counted at 24 and 48 hours after the start of test.

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

1.46 mg/L

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95 % CL

Effect concentrations 2

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

3.56 mg/L

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95 % CL

Details on results:

The two lowest test concentrations were not involved in the statistical evaluation of the effective concentrations (ECx) of the test item as these concentrations were out of the validated concentration range.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

According to this Daphnia sp., Acute Immobilisation Test for Clopidogrel camphorsulphonic acid salt the results indicated that the test item is hazardous to the aquatic environment [GHS Acute aquatic hazard Category Acute II. – 48 hr EC50 (for Crustacea) > 1 mg/L but ≤ 10 mg/L].