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

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: 84/449/EEC.B.

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 / tissue source

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.

Test system

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

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

Results 3

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

Results 4

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.

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

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.