5H-dibenz[b,f]azepine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

other information

Study period:

May 05 to 15, 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and reported study, conducted according to internationally accepted technical guideline and in compliance with GLP in recognized industrial research organization.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

of 1987

Deviations:

yes

Remarks:

The volume of 0.1 g test material was too high for application. Therefore, only 0.06 to 0.072 g of test material was administered into the conjunctival sac of one eye per rabbit.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5H-dibenz[b,f]azepine

EC Number:

205-970-0

EC Name:

5H-dibenz[b,f]azepine

Cas Number:

256-96-2

Molecular formula:

C14H11N

IUPAC Name:

5H-dibenzo[b,f]azepine

Details on test material:

- Name of test material (as cited in study report): PBS 7049, iminostilben dry intermediate
- Supplier: Pharma Chemical Production
- Description: orange crystalline powder
- Expiration date of the lot/batch: 03/96
- Storage conditions: room temperature

Test animals / tissue source

Species:

rabbit

Strain:

other: Russian rabbit, Chbb:HM (SPF)

Details on test animals or tissues and environmental conditions:

- Animal supplier: Dr. K. Thomae, GmbH, Biberach (FRG)
- Initial Age (at dosing): 47 - 53 weeks.
- Number and sex of animals: 3 male rabbits.
- Weight on day of treatment (at dosing): Minimum 2.593 kg, maximum 2.805 kg.
- Housing: Individual housing in stainless steel cages.
- Diet (ad libitum): Commercially available pelleted standard diet (NAFAG No. 814, analysed by the
manufacturer, NAFAG, 9202 Gossau, Switzerland).
- Water (ad libitum): Tap water. (Periodically analysed)
- Acclimation period: At least 5 days under laboratory conditions.


ENVIRONMENTAL CONDITIONS

Air conditioned room:
- Temperature (°C): 20 ± 3°C
- Relative Humidity (%): 30 to 70%
- Photoperiod: 12 hrs artificial light/day

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

The volume of 0.1 g test material was too high for administration. Therefore, a single dose of only 0.06 to 0.072 g of unchanged test material was administered into the conjunctival sac of one eye per rabbit. The contralateral eye remained untreated to serve as a control.

Duration of treatment / exposure:

There was no mentioning in the report that eyes were rinsed after treatment. Consequently the treatment/exposure period was equivalent to the entire observation period following administration, which was 7 days, or lasted until removal of the test material by physiological mechanisms, whichever happened sooner.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

There was no mentioning in the report that eyes were rinsed after administration of the test material.

Eyes were evaluated according to the OECD scoring system at: Pretest (prior to treatment), 1, 24, 48 and 72 hours and 7 days after administration. Grades attained at 24, 48 and 72 hours after administration were included in the mean gradings of ocular lesions used for eye irritation/corrosion classification.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: Corneal ulceration or opacity was not evident

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Reversibility:

other: Iridal changes were not evident

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0.56

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

over 3 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Untreated control eyes were always free from ocular lesions in all animals. In addition at pre-dose, eyes foreseen for treatment were free from ocular lesions in all animals. In the eye treated with test material, one of the three animals did not show any ocular lesion throughout the study, the other two animals showed conjunctival redness grade 1 and chemosis grade 1. Conjunctival redness (grade 1) was seen at 1, 24, 48 and/or 72 hours after administration having fully reversed by 72 hours or 7 days in the two affected animals. Chemosis (grade 1) was seen at 1 and 24 hours after administration having fully reversed by 48 hours in both affected animals. Corneal and iridic lesions were not evident throughout the study.

Other effects:

There was no mortality. Systemic clinical signs or relevant changes in body weight were not evident.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

PBS 7049 had only minimal effects on the eye not necessitating any labelling regarding eye irritation according to EU classification rules [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008].

Executive summary:

PBS 7049 was tested for eye irritation according to OECD Guideline 405 and in compliance with GLP. Reliability grade 1 was assigned to the study.

 

Each of three Russian rabbits [Chbb:HM (SPF)] was treated by administration of a single dose of 60 to 72 mg test material to the conjunctival sac of one eye. The test material volume attained from 100 mg, usually dosed in such eye irritation studies, was too high for administration. The other eye served as a control in each animal. Eyes were evaluated for ocular lesions prior to dosing and at 1, 24, 48 and 72 hours and 7 days after administration. In addition, general clinical signs, mortality and bodyweights were recorded on a number of occasions.

 

There was no mortality. Systemic clinical signs or relevant changes in body weight were not evident. The only ocular lesions seen in the present study were conjunctival redness (grade 1) and chemosis (grade 1) in the treated eye in two of the three animals. The conjunctival redness finding was seen at 1, 24, 48 and/or 72 hours after administration having fully reversed by 72 hours or 7 days and the chemosis was seen at 1 and 24 hours after administration having fully reversed by 48 hours in the two affected animals. Corneal and iridic lesions were not evident throughout the study.

 

In conclusion, PBS 7049 had only minimal effects on the eye not necessitating any labelling regarding eye irritation according to EU classification rules [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008].