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

Skin irritation / corrosion

Administrative data

Endpoint:

skin 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Erythema could not be scored due to staining of the skin by the test substance.

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

Species:

rabbit

Strain:

New Zealand White

Remarks:

Albino, SPF-Quality

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: Approx. 12 weeks
- Weight at study initiation: 2287 - 2600 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
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1992-11-24 To: 1992-11-27

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- The powdery test substance was applied with the aid of a patch. The patch was moistened with distilled water, immediately before application, to ensure close contact of the test substance to the animal's skin.

Duration of treatment / exposure:

4 h

Observation period:

72 h (Observations were made 1, 24, 48 and 72 hours after exposure)

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Approximately 24 hours before treatment, the dorsal fur was shaved with electric clippers
- Area of exposure: approximately 150 square centimeters (10 cm X 15 cm).
- Type of wrap if used: moistened Scotchpak-non-woven patch, mounted on Micropore tape. The dressing was wrapped around the abdomen and secured with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the remaining test substance was removed using a tissue moistened with tap-water and subsequently a dry tissue
- Time after start of exposure: 4h

SCORING SYSTEM: Draize
- ERYTHEMA AND ESCHAR FORMATION
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to slight eschar formation (injuries in depth)

- OEDEMA FORMATION
0 No oedema
1 Very slight oedema (barely perceptible)
2 Slight oedema (edges of area well defined by definite raising)
3 Moderate oedema (raised approximately 1 mm)
4 Severe oedema (raised more than 1 mm and extending beyond area of exposure)

Results and discussion

In vivo

Results

Irritation parameter:

edema 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:

- Erythema: Erythema could not be scored due to staining of the skin by the test substance.
- Microscopic findings: No abnormalities were detected in either the treated skin-sites and reference control skin-sites by microscopical examination. The absence of microscopical detectable lesions in the skin, 72 hours after exposure, indicate that no or negligible irritation has occurred during the study period.
- Corrosion: There was no evidence of a corrosive effect on the skin.

Other effects:

Toxicity symptoms / mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table 1: Individual findings

Observation time	Rabbit no. 4266		Rabbit no. 4268		Rabbit no. 4270
	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1 Hour	-	0	-	0	-	0
24 Hours	-	0	-	0	-	0
48 Hours	-	0	-	0	-	0
72 Hours	-	0	-	0	-	0
Mean Value	-	0.0	-	0.0	-	0.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The facts that no oedema was observed during the study and microscopical examination of the treated skin sites after 72 hours revealed no abnormalities indicate that the test substance is not irritanting to skin.

Executive summary:

A GLP conform in vivo study was performed to assess the acute dermal irritation/corrosion potential of the test substance (purity 97.5%) in White New Zealand rabbits according to the OECD guideline 404. Three male rabbits were exposed to 0.5 g of the test substance that was applied onto shaved skin using a semi-occlusive dressing. After 4 hours, the remaining test substance was removed. Observations were made 1, 24, 48 and 72 hours after exposure. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. No oedema in the treated skin-areas of the rabbits were observed. Erythema could not be scored due to red staining of the skin by the test substance. However, microscopical examination revealed no abnormalities in either the treated skin-sites and reference control skin-sites 72 hours after exposure. The absence of microscopical detectable lesions in the skin indicate that no or negligible irritation has occurred during the study period. Therefore, the test substance is considered as non-irritating when applied to intact rabbit skin.