Tetrasodium 2-[[8-[[3-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]benzoyl]amino]-1-hydroxy-3,6-disulphonato-2-naphthyl]azo]naphthalene-1,5-disulphonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Remarks:

source of read across

Adequacy of study:

key study

Study period:

From September 21 to October 04, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted February 24, 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Similar Substance 01

IUPAC Name:

Similar Substance 01

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne / France.
- Age at study initiation: 15 weeks old.
- Weight at study initiation: male ca 2.7 kg; females ca 2.7-2.8 kg.
- Housing: individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet: pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no.65/99).
- Water: community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 5 days, under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
- Health check: the eyes of the animals were examined one day prior to test article administration. Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 40 - 70 %
- Air changes: 10-15 air changes per hour.
- Photoperiod: 12 hour light/dark cycle.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g/animal (left eye only).

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

1 male and 2 females

Details on study design:

OBSERVATIONS
- Viability/Mortality: daily from delivery of the animals to the termination of test.
- Clinical signs: daily from delivery of the animals to the termination of test.
- Body weights: at start of acclimatization, on the day of application and at termination of observation.

TOOL USED TO ASSESS SCORE: eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel / Switzerland).

SCORING SYSTEM
The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC. July 31,1992 at approximately 1, 24, 48 and72 hours, as well as 7 days after administration.
When present, corrosion of and/or staining of sclera and cornea by the test article were recorded and reported.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 1

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 1

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal: 3/3

Time point:

24/48/72 h

Score:

< 2

Reversibility:

fully reversible within: 24 hours

Irritant / corrosive response data:

Application of the test article to healthy rabbit conjunctivae resulted in a primary irritation score of 0.56.
Hyperemic conjunctival blood vessels were noted in all animals at the 24-hour examination and persisted through 72 hours in one animal only. This latter was observed with a slight swelling of the conjunctivae at the 1-hour examination and with a slightly reddened sclera from the 24- to the 72-hour examination. Slight to moderate watery discharge was also observed in all animals at the 1-hour examination.
All eye reactions were reversible within 7 days after treatment.
Reddish-brown remnants in eye or conjunctival sac and around eye and/or on lids were observed until the 72-hour reading.
No corrosion of the cornea was observed at any of the reading times.

Other effects:

VIABILTY/MORTALITY AND CLINICAL SIGNS
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

BODY WEIGHTS
The body weight of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

Individual reactions

Animal N.	Reaction	After					Mean 24/48/72 hrs
		1 hr	24 hrs	48 hrs	72 hrs	7 days
76 male	Corneal opacity	0	0	0	0	0	0.00
77 female	Corneal opacity	0	0	0	0	0	0.00
78 female	Corneal opacity	0	0	0	0	0	0.00
76 male	Iris	0	0	0	0	0	0.00
77 female	Iris	0	0	0	0	0	0.00
78 female	Iris	0	0	0	0	0	0.00
76 male	Coniunctivae redness	0	1	0	0	0	0.33
77 female	Coniunctivae redness	0	1	0	0	0	0.33
78 female	Coniunctivae redness	0	1	1	1	0	1.00
76 male	Coniunctivae chemosis	0	0	0	0	0	0.00
77 female	Coniunctivae chemosis	1	0	0	0	0	0.00
78 female	Coniunctivae chemosis	1	0	0	0	0	0.00

Applicant's summary and conclusion

Interpretation of results:

other: not classified, according to the CLP Regulation (EC) No 1272/2008

Conclusions:

Non irritating

Executive summary:

The primary irritation potential of test item was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of data points. The primary irritation score was 0.56 (max. 13). Hyperemic conjunctival blood vessels were noted in all animals at the 24-hour examination and persisted through 72 hours in one animal only. This latter was observed with a slight swelling of the conjunctivae at the 1-hour examination.

Reddish-brown rernnants in eye or conjunctival sac and around eye and/or on lids were observed until the 72-hour reading. All eye reactions were reversible within 7 days after treatment. No corrosion was observed at any of the measuring intervals.

Conclusion

The mean values from gradings at 24, 48 and 72 hours were lower than 1 for corneal opacity, lower than 1 for iritis, lower than 2 for both conjunctival redness and chemosis, in all the tested animals. All the reactions recorded were reversible within 7 days. Therefore, the substance does not meet the criteria to be classified as eye irritating, according to the CLP Regulation (EC) No 1272/2008.