Bisbenzimidazo[2,1-b:2',1'-i]benzo[lmn][3,8]phenanthroline-8,17-dione

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:

According to OECD TG 405 and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

according to the Swiss Ordinance relating to GLP [RS 813.016.5]

Test material

Test material information

Constituent 1

Reference substance name:

Bisbenzimidazo[2,1-b:2',1'-i]benzo[lmn][3,8]phenanthroline-8,17-dione

EC Number:

224-597-4

EC Name:

Bisbenzimidazo[2,1-b:2',1'-i]benzo[lmn][3,8]phenanthroline-8,17-dione

Cas Number:

4424-06-0

Molecular formula:

C26H12N4O2

IUPAC Name:

bisbenzimidazo[2,1-b:2',1'-i]benzo[lmn][3,8]phenanthroline-8,17-dione

Test material form:

solid: nanoform

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32-36, 88353 Kisslegg, Germany (SPF breed)
- Age at study initiation: 11 to 12 weeks (male and females)
- Weight at study initiation (animal#77 male/#78 female/#79 female at the first day of treatment): 2264/2654/2511 g
- Housing: individually in stainless steel cages equipped with feed hoppers and drinking water bowles.
- Diet: pelleted standard Provimi Kliba 3418 rabbit maintenance diet; ad libitum
- Water: community tap water; ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70 %
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye remained untreated and served as control respectively

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
The pH of a 1 % (w/w) suspension was measured in RCC study No A13195 and was found to be 7.12.

Duration of treatment / exposure:

single instillation (not rinsed after instillation)

Observation period (in vivo):

1, 24, 48, 72 h and 7 d after instillation

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

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

- Instillation: 100 mg of the undiluted substance

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed after instillation

SCORING SYSTEM: according to OECD TG 405. Additionally, ocular discharge, reddening of sclerae and staining of conjunctivae, sclerae and cornea by the test item was assessed.

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic -lamp


The eyes are examined and the grade of ocular reaction is recorded at 1, 7, 24, 48, 72 h and 7 d.

The mean scores were calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: # 77, 78, 79 each

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Reversibility inapplicable since no signs of irritation (cornea) at any time

Results 2

Irritation parameter:

iris score

Basis:

animal: # 77, 78, 79 each

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Reversibility inapplicable since no signs of irritation (iris) at any time

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: # 77

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: initial signs of irritation (conjunctiva) were fully reversible within 24 h

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal: # 78

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal: # 79

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

chemosis score

Basis:

animal: # 77, 78, 79 each

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: initial signs of irritation (chemosis) were fully reversible within 24 h

Irritant / corrosive response data:

No corrosion of the cornea was observed at any of the reading times.

Other effects:

After one hour there were still remnants in the eye or the conjunctival sac in all three animals. Slight discharge was observed in all animals at the 1 h readings. Orange staining was noted 1 h up to 48 h.

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:

All (initial) signs of irritation noted were fully reversible within 72 h. According to the classification criteria of Regulation (EC) No 1272/2008 the test material is not irritating to eyes under these test conditions.

Executive summary:

The test material was subject to a primary eye irritation/corrosion test in 3 New Zealand White rabbits according to OECD 405. No corneal or iridial effects were observed. Conjunctival redness was observed in all animals at one hour after instillation of the test item (scores (redness): 1-1-2) and persisted up to the 48 hour examination in one of these animals. Slight to moderate reddening of the sclerae was present in all animals at the 1 hour reading. Slight ocular discharge was noted at the same time in all animals. As no abnormal findings were observed in the treated eye of any animal 72 hours after treatment or later and the mean values of the observed eye responses fall well below the critical values for classification according to the criteria of Regulation (EC) No 1272/2008, the test material is not irritating to eyes and has not to be classified for eye irritation.