Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl]azo]-4-[[4-[(2-chloro-5-sulphonatophenyl)amino]-6-fluoro-1,3,5-triazin-2-yl]amino]benzenesulphonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 October 1992 to 14 December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl]azo]-4-[[4-[(2-chloro-5-sulphonatophenyl)amino]-6-fluoro-1,3,5-triazin-2-yl]amino]benzenesulphonate

EC Number:

278-154-5

EC Name:

Disodium 2-[[5-carbamoyl-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridyl]azo]-4-[[4-[(2-chloro-5-sulphonatophenyl)amino]-6-fluoro-1,3,5-triazin-2-yl]amino]benzenesulphonate

Cas Number:

75268-65-4

Molecular formula:

C24H21ClFN9O9S2.2Na

IUPAC Name:

disodium 2-[(5-carbamoyl-1-ethyl-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridin-3-yl)diazenyl]-4-({4-[(2-chloro-5-sulfonatophenyl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)benzenesulfonate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Test article: FAT 40138/D
Trade name: Cibacron yellow F-4G
Batch No.: 275605.26
Purity: 79 %
Physical properties: powder, yellow
Storage conditions: room temperature
Validity: July, 1993

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animal strain: New Zealand white rabbits (Chbb:NZW)
Breeder : Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7 950 Biberach/Riss
Acclimatisation period: at least 5 days

The test was performed on 3 female rabbits, checked for normal skin conditions, weighing between 2330 to 2650 g. The animals were housed individually in metal cages, identified by ear tattoo, kept at a constant room temperature of 20±3 °C, at a relative humidity of 30-70 % and on a 12 hours light cycle day. The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland - and fresh water. All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer. Analytical results are available at the animal supply office.

The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesser schütz) are available to CIBA-GEIGY Limited, as well as the results of in-house chemical analysis by the analytical laboratories of the Pharmaceutical Division, CIBA-GEIGY Limited. The body weight was recorded at start and on days 3 and 7 of the test.

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: A control gauze patch was applied to the contralateral flank.

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3 females

Details on study design:

An area of at least 36 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm ) bearing 0.5 g of the test article was applied to the right flank of each animal. A control gauze patch was applied to the contralateral flank. Both patches were moistened before application with distilled water. The patches were loosely covered with an aluminum foil (approx. 36 cm²) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg). The animals were checked daily for systemic symptoms and mortality (only findings reported). The skin reactions were evaluated 1, 24, 48, 72 hours, and 7 days after removing the gauze patches according to the OECD scoring system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

for all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Because reactions were observed within 72 hours after removing the bandages, the observation period was extended to 7 days to determine the reversibility of the skin reactions. According to the EEC classification of the results obtained 24 to 72 hours after removing the bandages FAT 40138/D can be classified as non-irritant in albino rabbits.
The skin reactions observed were reversible until the end of the observation period on day 7.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40138/D can be considered as non-irritant to rabbit skin.

Executive summary:

The skin irritation potential of FAT 40138/D was evaluated in a study condcuted according to OECD Guideline 404 and in compliance with GLP. The test was performed on 3 female adult New Zealand White rabbits weighing 2330 to 2650 g. An area of at least 36 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm ) bearing 0.5 g of the test article was applied to the right flank of each animal. A control gauze patch was applied to the contralateral flank. Both patches were moistened before application with distilled water. The patches were loosely covered with an aluminum foil (approx. 36 cm²) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg). The skin reactions were evaluated 1, 24, 48, 72 hours, and 7 days after removing the gauze patches according to the OECD scoring system. Under the conditions of the present experiment FAT 40138/D was found to cause slight erythema (score 1) to one rabbit till 72 hours, while no erythema was observed with remaining two rabbits. No edema was observed with any of the treated animals. Hence, based on the study results, FAT 40138/D can be considered as non-irritant to rabbit skin.