4-(oxiran-2-ylmethoxy)-9H-carbazole

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:

guideline study

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)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-[(oxiran-2-yl)methoxy]-9H-carbazole

EC Number:

610-764-2

Cas Number:

51997-51-4

Molecular formula:

C15H13NO2

IUPAC Name:

4-[(oxiran-2-yl)methoxy]-9H-carbazole

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Carvedilol 4th intermediate (Oxiranylmethoxy carbazole)
- Physical state: chamois powder
- Lot/batch No.: 2000/2
- Expiration date of the lot/batch: 02.2002
- Storage condition of test material: dry, cool place, protected from light

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Breeder: Ferenc Sándor, Address: Vörös Hadsereg street 131, H-2173 Kartal, Hungary
- Age at study initiation: adult
- Weight at study initiation: 2655-2952 g
at tstudi termination: 2757-3040 g
- Housing: individually in metal cages
- Diet (e.g. ad libitum): ad libitum, PURISTAR standard diet for rabbits produced by AGRIBANDS Europe
- Water (e.g. ad libitum): ad libitum, tap water for human consumption from automatic self-supplying watering system
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30-70 %
- 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 Carvedilol 4th intermediate (Oxiranylmethoxy carbazole) in pure state in a single dose

Duration of treatment / exposure:

The eyes of the test animals were not washed out after the application of the test item.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 (male)

Details on study design:

REMOVAL OF TEST SUBSTANCE
The eyes of the test animals were not washed out after the application of the test item.

SCORING SYSTEM:
Draize (1959)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

other: 1, 2, 3

Time point:

other: 1 h, 24 h, 48 h, 72 h

Score:

0 - 14

Max. score:

20

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

cornea opacity score

Basis:

other: 1, 2, 3

Time point:

other: 1 h, 24 h, 48 h, 72 h

Score:

0

Max. score:

80

Results 3

Irritation parameter:

iris score

Basis:

other: 1, 2, 3

Time point:

other: 1 h, 24 h, 48 h, 72 h

Score:

0

Max. score:

10

Results 4

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 78 and 72 hours after the application

Score:

11.33

Max. score:

110

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

One hour after treatment the vessels were more diffuse in two animals (No.: 09601 and 09599) and the vessels were diffuse, beefy red in the third case (No.: 09452). Any swelling above the normal occurred in one rabbit (No.: 09452) and chemosis was not found in the other two cases (No.: 09601 and 09599). Discharge with moistening of the lids and hairs on considerable area around the eye was found in every animal. Corneal and iris alterations were not found during the study.

One hour after the treatment the observed highest irritation index was 14.

24 hours after treatment the vessels were definitely injected above the normal in all animals. Discharge with moistening of the lids and hairs just adjacent to lids was found in two cases (No.: 09452 and 09599) and any amount of discharge differed from the normal in the third case (No.: 09601). Chemosis did not occur in any case.

24 hours after the treatment the observed highest irritation index was 6.

48 and 72 hours after treatment every animal was symptom-free.

72 hours after the treatment the study was terminated, since no primary irritation symptoms occurred.

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion, the test item CARVEDILOL 4th INTERMEDIATE applied to the rabbits' eye mucosa proved to be "SLIGHTLY IRRITANT". The observed symptoms can be evaluated as fully reversible alterations.