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)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Source: Ferenc Sandor breeder , Kartal, Hungary
- Age at study initiation: adult albino male rabbits
- Weight at study initiation: 2541-2702 g
at study termination: 2971-3380 g
- Housing: individually in metal cages.
- Diet (e.g. ad libitum): ad libitum, PURISTAR standard diet (AGRIBRANDS EUROPE)
- Water (e.g. ad libitum): ad libitum, potable water from automatic self-service water system
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70 %
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the contralateral eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of test item in pure state, as a single dose

Duration of treatment / exposure:

The eyes were not rinsed after the administration of the test item.

Observation period (in vivo):

1, 24, 48, 72 hours and 7, 14, 21 days after the application.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
no removal

SCORING SYSTEM:
by Draize (1959) and OECD 405

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

for each animal

Time point:

other: 1, 24, 48, 72h

Score:

2 - 3

Max. score:

3

Reversibility:

not fully reversible within: 3 weeks

Remarks on result:

other: chemosis, redness, discharge (yellowish white purulent)

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

for each animal

Time point:

other: 1, 24, 48, 48h

Score:

2 - 4

Max. score:

4

Reversibility:

not fully reversible within: 3 weeks

Remarks on result:

other: opacity of the cornea (opacity degree and extension)

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

for each animal

Time point:

other: 1, 24, 48, 72h

Score:

0 - 1

Max. score:

1

Reversibility:

fully reversible within: 1 week

Remarks on result:

other: redness

Irritant / corrosive response data:

1 hour after the treatment the observed highest irritation index: 83.
24 hours after the treatment the observed highest irritation index: 63.
48 hours after the treatment the observed highest irritation index: 63.
72 hours after the treatment the observed highest irritation index: 63.
One week after the treatment the observed highest irritation index: 34.
Two weeks after the treatment the observed highest irritation index: 30.
Three weeks after the treatment the observed highest irritation index: 14.
72 hour mean irritation index: 0. 00

Other effects:

The general state and behaviour of animals were normal during the whole study.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Remarks:

Migrated information

Conclusions:

In conclusion the test item proved to be heavily irritant. The observed symptoms can be evaluated as irreversible alterations.The test item can be classified into Category 1 for eye irritation.