2-cyano-2-[2,3-dihydro-3-(tetrahydro-2,4,6-trioxo-5(2H)-pyrimidinylidene)-1H-isoindol-1-ylidene]-N-methylacetamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

acceptable restrictions: occlusive conditions, 72 h reading missing, 8-day observation period

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive conditions, 72 h reading missing, limited documentation

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-cyano-2-[2,3-dihydro-3-(tetrahydro-2,4,6-trioxo-5(2H)-pyrimidinylidene)-1H-isoindol-1-ylidene]-N-methylacetamide

EC Number:

278-388-8

EC Name:

2-cyano-2-[2,3-dihydro-3-(tetrahydro-2,4,6-trioxo-5(2H)-pyrimidinylidene)-1H-isoindol-1-ylidene]-N-methylacetamide

Cas Number:

76199-85-4

Molecular formula:

C16H11N5O4

IUPAC Name:

2-cyano-N-methyl-2-[3-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)-2,3-dihydro-1H-isoindol-1-ylidene]acetamide

Details on test material:

- Test substance number: 80/345
- Physical state: solid, yellow
- Analytical purity: 88 %
- Stability: At least 2 years under normal conditions
- Expiration date of the lot/batch: October 1983

Test animals

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler Offenbach/Main, Germany
- Weight at study initiation: male 2.98 kg, female 3.72 kg
- Housing: one animal per cage of stainless steel with wire mesh walk floors, floor area: 40 cm x 51 cm,
- Diet (e.g. ad libitum): Ovator Solikanin 4 mm; Muskator-Werke, Duesseldorf , Germany (about 130 g per animal per day)
- Water (e.g. ad libitum): About 250 ml per animal per day: demineralized water (Monday-Friday), tap water (Saturday/Sunday)
- Acclimation period: About 8 days before the beginning of the study in the skin laboratory; same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): Conventional (about 30 - 70%)
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Test system

Type of coverage:

occlusive

Preparation of test site:

other: clipping of the fur at least 15 hours before beginning of the study

Vehicle:

water

Controls:

other: Untreated skin sites of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test substance is applied
- Concentration (if solution): 50 % aqueous formulation

Duration of treatment / exposure:

4 hours

Observation period:

8 days

Number of animals:

1 male, 1 female

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm, Upper third of the back or flank

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period with Lutrol and Lutrol/water (1:1)

SCORING SYSTEM: According to J. H. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health

READINGS: 30 - 60 minutes after removal of the test patches and 24 h, 48 h and 8 d after the beginning of application

ADDITIONAL EXAMINATIONS: After sacrifice the animals are examined by gross pathology. If there are clinical signs of necroses, these are confirmed by gross-pathological examination after incision of the skin.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable because no effects were observed

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable because no effects were observed

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable because no effects were observed

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable because no effects were observed

Irritant / corrosive response data:

No effects were observed 8 days after the treatment.

Other effects:

No other effects.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present experiment, the test material does not give indication of an irritant property to rabbit skin.

Executive summary:

To assess the acute skin irritation or corrosion potential of the test substance in vivo a skin irritation test in Vienna White rabbits similar to OECD guideline 404 was performed. The test item was applied by topical occlusive application of 0.5 g of the 50% test substance solution to the upper third of the back or flank of each of two rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 24 and 48 hours, as well as 8 days after removal of the dressing.

The test item did not elicit any skin reactions at the application site at any of the observation times (all scores 0). No clinical signs were observed.

Under the conditions of the present experiment, the test material does not give indication of an irritant property to rabbit skin.