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)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

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: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Name: Clopidogrel 5th intermediate (K-salt)
Batch No: CL-141
Appearance: almost white, crystalline powder
Storage: at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TOXICOOP LTD.
- Age at study initiation: 7 weeks old
- Weight at study initiation: 203 - 226 g
- Fasting period before study: 24 hours
- Housing: 3 animals/cage type MAKROLON II; laboratory bedding
- Diet (e.g. ad libitum): ad libitum (exept after test item administration for 3 hours)
- Water (e.g. ad libitum): tap water ad libitum in MAKROLON type drinking bottles
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.3 -24.2 ºC
- Humidity (%): 26.0-51.8 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1 % aquesous MC (methylcellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5 g/ 5ml and 3 g/30 ml
- Amount of vehicle (if gavage): 20 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

Doses:

200 mg/kg bw and 2000 mg/kg bw

No. of animals per sex per dose:

3 male /3 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: 6 hours after the treatment, and thereafter twice a day.
weighing: before treatment (1st day), on the 8th day, on the 14th day
- Necropsy of survivors performed: yes (macroscopic)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality

Clinical signs:

other: Females in the 2000 mg/kg dose group show moderate CNS depressive symptoms 3 hours after treatment (moderate somnolence) and during the first 6 hours. All animals were symptom-free on the second day of the study.

Gross pathology:

No pathological macroscopic findings due to test item could be detected at termical sacrifice.
In one male in the 2000 mg/kg dose group hydronephrosis occured in kidneys which is a common alteration observed sporadically in experimental rats.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item administered by oral route to Wistar rats was above 2000 mg/kg so the test item is not classified according to EU regulations.