Pyrrolo[3,4-c]pyrrole-1,4-dione, 3,6-bis([1,1'-biphenyl]-4-yl)-2,5-dihydro-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

413-920-6

EC Name:

-

Cas Number:

88949-33-1

Molecular formula:

C30 H20 N2 O2

IUPAC Name:

3,6-bis({[1,1'-biphenyl]-4-yl})-1H,2H,4H,5H-pyrrolo[3,4-c]pyrrole-1,4-dione

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Substance type: Organic
- Physical state: Solid
- Lot/batch No.: Z-2281/1,2,4,5
- Expiration date of the lot/batch: April 01, 1997
- Storage condition of test material: at room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: Approx. 15 weeks
- Weight at study initiation: 2666 - 3022 grams
- Housing: individual
- Diet: Standard laboratory rabbit diet, approx. 100 g per day
- Water: Tap-water diluted with decalcified water, ad libitum
- Acclimation period: At least 5 days before start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1992-11-30 To: 1992-12-03

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

21 mg

Duration of treatment / exposure:

single

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

REMOVAL OF TEST SUBSTANCE: No

SCORING SYSTEM: Draize

- Cornea opacity degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent area, details of iris slightly obscured
3 Nacreous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

- Area of cornea affected:
0 No ulceration or opacity
1 One quarter or less but not zero
2 Greater than one quarter, but less than half
3 Greater than half, but less than three quarters
4 Greater than three quarters, up to whole area

- Iris:
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circum corneal hyperaemia, or injection, any of these or any combination thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or al 1 of these)

- Conjuctivae redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris):
0 Blood vessels normal
1 Some blood vessels definitely hyperaemic (injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse beefy red

- Conjuctivae chemosis: lids and/or nictitating membrane
0 No swelling
1 Any swelling above normal (includes nictitating membrane)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half closed
4 Swelling with lids more than half closed

- Conjuctivae discharge:
0 No discharge 0
1 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 Discharge with moistening of the lids and hairs, just adjacent to lilds
3 Discharge with moistening of the lids and hairs, in a considerable area around the eye

TOOL USED TO ASSESS SCORE: fluorescein
Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48h

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

- Irritation: Instillation of the test substance into one eye of each of the three male albino rabbits affected the conjunctivae in one animal. The irritation of the conjunctivae had resolved within 48 hours after instillation. A small amount of discharge was observed at the 24 hour observation in another animal. Eye irritation was not observed at all in the third animal during the study period. Treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals.
- Corrosion: There was no evidence of ocular corrosion.

Other effects:

- Colouration: Red/purple staining of the fur on the head, surrounding the treated eye, by the test substance was observed.
- Toxic symptoms / mortality: No toxic symptoms were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Individual Draize score calculation

Animal No.	Tissue	Hours after administration
		1	24	48	72
4218	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjunctivae	2	4	0	0
	Subtotal	2	4	0	0
4227	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjunctivae	0	2	0	0
	Subtotal	0	2	0	0
4299	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjunctivae	0	0	0	0
	Subtotal	0	0	0	0
Total		2	6	0	0
Mean total		0.7	2	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test substance is considered not irritanting to eyes.

Executive summary:

To assess the acute eye irritation/corrosion potential of the test substance (purity 97.5%), a GLP conform eye irritation test in White New Zealand rabbits was performed according to OECD guideline 405. Single samples of approximately 21 mg of the test substance were instilled into one eye of each of three male rabbits. Observations were made 1, 24, 48 and 72 hours after instillation. No signs of systemic intoxication were observed and no mortality occurred during the study period. Instillation of the test substance resulted in effects on the conjunctivae in two animals. Irritation of the conjunctivae was observed as slight redness and discharge in one animal each, which had completely resolved within 48 hours. No corneal opacity was observed over the entire study period and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage in any of the animals. Mean scores of the 24-72 h readings were 0.0 for both corneal opacity and iris, 0.33 for conjunctivae redness. Therefore, the test substance is considered non-irritating to the rabbit eye.