Bisbenzimidazobenzo[lmn][3,8]phenanthrolinedione

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

Remarks:

Study meets the requirements of OECD Guideline 405 and EU Method B.5 (84/449/EEC)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bisbenzimidazobenzo[lmn][3,8]phenanthrolinedione

EC Number:

232-340-2

EC Name:

Bisbenzimidazobenzo[lmn][3,8]phenanthrolinedione

Cas Number:

8005-56-9

Molecular formula:

C26H12N4O2

IUPAC Name:

bisbenzimidazobenzo[lmn][3,8]phenanthrolinedione

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Animal specifics:CHbb: NZW (SPF)
- Source: Chemisch pharmazeutische Fabrik Dr. K. Thomae, 88400 Biberach
- Age at study initiation: 3 months to 5 months
- Weight at study initiation: 2.7 kg to 3.1 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): 18° ± 3°C (air-condition)
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

One administration / 24 hours

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3 animals

Details on study design:

Application of the substance to the conjunctival sac of the left eye of each animal, the right eyes served as control respectively

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:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since on effects occured

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effects occured

Results 3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effects occured

Results 4

Irritation parameter:

conjunctivae score

Basis:

other: mean of each animal

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

1 hour up to 1 day p.a. the conjunctivae of the eyes showed definitely injectiones. 2 days p.a. all irritations were reversible.

Other effects:

Clear, from test substance discoloured discharge, was observed

Any other information on results incl. tables

Results table:

Animal	Evaluation interval (after application)	Opacity of cornea	Redness of conjunctiva	Chemosis of conjunctiva	Iris	eye discharge	Fluoresceinestaining
# 82	1 hour	0	1	0	0	1
# 83		0	1	0	0	1
# 87		0	1	0	0	1
# 82	24 hours	0	1	0	0	0	0
# 83		0	1	0	0	0	0
# 87		0	1	0	0	0	0
# 82	48 hours	0	0	0	0	0
# 83		0	0	0	0	0
# 87		0	0	0	0	0
# 82	72 hours	0	0	0	0	0	0
# 83		0	0	0	0	0	0
# 87		0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

The test item has not to be classified for eye irritation according to Regulation (EC) No 1272/2008.

Conclusions:

The test item has not to be classified for eye irritation according to Regulation (EC) No 1272/2008.

Executive summary:

A study according to OECD Guideline 405 and EU Method B.5 was performed to investigate the irritation potential to the rabbit eye.

100 mg of the test item was applied once to the conjunctival sac of the left eye of 3 rabbits. The untreated eyes served in each case as a control. The eyes were examined 1, 24, 48 and 72 hours after application of the test substance.

One and 24 hours after treatment the conjunctivae of the animals showed definitely injected blood vessels. Additionally, slight from substance coloured clear eye discharge were observed in the animals one hour after treatment.

Mean values from the 24h/48h/72h readings were calculated as follows:

Animal No:	1	2	3
Corneal opacity:	0.0	0.0	0.0
Iris:	0.0	0.0	0.0
Conjunctivae Redness	0.33	0.33	0.33
Conjunctivae Chemosis	0.0	0.0	0.0

48 hours after treatment all signs of irritation were reversible.

Based on that findings, the test item has not to be classified for eye irritation according to Regulation (EC) No 1272/2008.