Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate

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 performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

84/449/EEC

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate

EC Number:

278-575-4

EC Name:

Sodium N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-hydroxynaphthalene-2-carboxamidate

Cas Number:

76918-62-2

Molecular formula:

C18H13N3O3.Na

Details on test material:

- Name of test material (as cited in study report): Naphtolon-Natrium TRF 8

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, breeding colony
- Age at study initiation: 3 months to 5 months
- Weight at study initiation: 2.9 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Altromin 2123) ad libitum, appr. 15 g hay daily
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

24 hours
rinsing with physiol. saline 24 h post instillation

Observation period (in vivo):

72 post instillation

Number of animals or in vitro replicates:

1

Details on study design:

Application of the substance to the conjunctival sac of the left eye of the animal, the right eye served as control.

REMOVAL OF TEST SUBSTANCE
- Washing: Washing with physiological saline at approx. 37 °C 24 h after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution (24, 48 and 72 h after administration) took place

TOOL USED TO ASSESS SCORE: 0.01 % solution of fluorescein sodium, under UV light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 h

Score:

4

Max. score:

4

Reversibility:

other: not reversible within observation period of 72h

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 hours

Max. score:

2

Remarks on result:

other: examination not possible

Results 3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 hours

Score:

4

Max. score:

4

Reversibility:

other: not reversible within observation period of 72h

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 hours

Score:

3

Max. score:

3

Reversibility:

other: not reversible within observation period of 72h

Irritant / corrosive response data:

The conjuntciva was diffuse red coloured and showed swelling with lids more than half closed at all times. It was discoloured grey and parts were ablated. The iris was not discernible through the opaque cornea (examination of iris score not possible). The cornea was rough and ablation of parts was observed. The animal showed continuing signs of severe irritation effects and therefore was humanely killed after 72 hours.

Other effects:

In the beginning light yellow, later on white mucous eye discharge was observed.

Any other information on results incl. tables

Evaluation Interval	Cornea	Conjunctiva			Iris
	Opacity	Redness	Chemosis	Discharge
1 h	4	2	4	X	Examination of iris score not possible
24 h	4	3	4	X
48 h	4	3	4	X
72 h	4	3	4	x

Applicant's summary and conclusion

Interpretation of results:

highly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The test item induced severe damage to the eye. Based upon these findings, the test item is considered to cause "serious damage" to the rabbit eye.

Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD test guideline no. 405. The test item was applied by instillation into the conjunctival sac of the left eye of a single young adult New Zealand White rabbit, the right eye served as control. The duration of treatment was 24 hours. The scoring of eye reactions was performed 30 - 60 min, 24, 48 and 72 hours after application. The mean scores were calculated across 3 scoring times (24, 48 and 72 hours after application) for iris, cornea, conjunctiva redness, and conjunctiva chemosis, separately.

After application the conjuntciva was diffuse red coloured and showed swelling with lids more than half closed at all times. It was discoloured grey and parts were ablated. The iris was not discernible through the opaque cornea (examination of iris score not possible). The cornea was rough and ablation of parts was observed. In the beginning light yellow, later on white mucous eye discharge was observed. The animal showed continuing signs of severe irritation effects and therefore was humanely killed after 72 hours.

Thus, the test item induced severe damage to the eye. Based upon these findings, the test item is considered to cause "serious damage" to the rabbit eye.