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

Endpoint summary

Description of key information

The test substance is neither a skin irritant nor an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

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

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.

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.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean score

Time point:

24/48/72 h

Score:

0

Max. score:

4

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 October 1992 to 17 December 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

other: 84/449/EEC.B.

GLP compliance:

yes

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animal strain: New Zealand white rabbits (Chbb:NZW)
Breeder: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
Acclimatisation period: at least 5 days

The test was performed on 3 male rabbits, checked for normal eye conditions, weighing between 2610 to 2710 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 Gewaesserschutz) 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 (all animals) and on day 14 (animals No. 587 and No. 677) of the test.

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye was not treated and served as an untreated control.

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

One second (The lids were held together for about one second in order to prevent loss of the test article).

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3 males

Details on study design:

0.1 ml (100 mg) of FAT 40138/D was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article. The right eye remained untreated and served as a control. The animals were checked daily for systemic symptoms and mortality (only findings reported). The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of FAT 40138/D according to the OECD scoring system. In order to determine the reversibility of the eye reactions further evaluations were carried out during this study. A slit-lamp was used to facilitate the evaluation. The irritant/corrosive potency of FAT 40138/D was classified according to the Commission Directive 83/467/EEC.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0.22

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

1.11

Max. score:

3

Reversibility:

fully reversible within: 14 d

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0.56

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Mild irritation reactions of the iris and conjunctiva were observed within 72 hours after instillation of the test article in two animals and within 10 days in third animal. The observation period was extended to 7 days for one animal and to 14 days in animals two animals to determine the reversibility of the eye reactions. A slight loss of weight was noticed in animal No. 1 on day 3.

Individual Animal score: Eyes rinsed

Days after Application	Rabbit 1				Rabbit 2				Rabbit 3
	Cornea	Iris	Conjunctivae	Chemosis	Cornea	Iris	Conjunctivae	Chemosis	Cornea	Iris	Conjunctivae	Chemosis
1	0	0	1	1	0	1	1	1	0	1	2	1
2	0	0	1	0	0	0	1	1	0	0	1	1
3	0	0	1	0	0	0	1	0	0	0	1	0

 

Interpretation of results:

GHS criteria not met

Conclusions:

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

Executive summary:

The eye irritation potential of the test substance was evaluated in a study conducted according to OECD Guideline 405. The test was performed on 3 male New Zealand White rabbits. The test material in an amount of 0.1 ml was placed into the conjunctival sac of the left eye of the rabbits and after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test substance. The right eye was not treated and served as an untreated control. The ocular reactions were examined 1, 24, 48, and 72 h after substance instillation and again during the following observation period by means of a slit-lamp. Mild irritation reactions of the iris and conjunctiva were observed within 72 h after instillation of the test article in two animals and within 10 days in third animal. A slight loss of weight was noticed in animal No. 1 on day 3. Because the mean values of the readings 24 to 72 h after instillation are below the threshold of significance, FAT 40138/D can be classified as non-irritant according to the Commission Directive 83/467/EEC.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In vivo Skin irritation:

Three studies to evaluate the skin irritation potential of FAT 40138 are available. In a key study, the skin irritation potential of FAT 40138/D was evaluated according to OECD Guideline 404 and in compliance with GLP. The test was performed on 3 female adult New Zealand White rabbits. 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. 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. Similarly, two other supporting studies conducted with FAT 40138/A and FAT 40138/C also support the conclusion that the substance is not a skin irritant.

 

In-vivo Eye irritation:

Three studies to evaluate the eye irritation potential of FAT 40138 are available. In a key study, the eye irritation potential of the test substance was evaluated in a study conducted according to OECD Guideline 405. The test was performed on 3 male New Zealand White rabbits. The test material in an amount of 0.1 ml was placed into the conjunctival sac of the left eye of the rabbits and after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test substance. The right eye was not treated and served as an untreated control. The ocular reactions were examined 1, 24, 48, and 72 h after substance instillation and again during the following observation period by means of a slit-lamp. Mild irritation reactions of the iris and conjunctiva were observed within 72 h after instillation of the test article in two animals and within 10 days in third animal. A slight loss of weight was noticed in animal No. 1 on day 3. Because the mean values of the readings 24 to 72 h after instillation are below the threshold of significance, FAT 40138/D can be classified as non-irritant according to the Commission Directive 83/467/EEC. Similarly, two other suppoerting studies conducted with FAT 40138/A and FAT 40138/C also support the conclusion that the substance is not a eye irritant.

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study, the test substance does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 to be irritating to the skin as well as eyes.