Benzenesulfonic acid, 2-[2-[5-(aminocarbonyl)-1-ethyl-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-3-pyridinyl]diazenyl]-4-[[4-chloro-6-[[4-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]amino]-1,3,5-triazin-2-yl]amino]-, sodium salt (1:2)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 April 1993 to 04 May 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study condcuted to EU & OECD test guidance in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Details on test material:

See below

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Chemisch Pharmazeutische
- Age at study initiation: 3 -5 months
- Weight at study initiation: 3.4 - 3.7 kg
- Housing: in fully air-condtioned rooms, seperate cages (arranged in a battery)
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet, ad libitum and hay (approx 15g daily)
- Water (e.g. ad libitum): deionised, chlorinated water from automatic water dispenser, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 (±3C)
- Humidity (%): 55 (±20%)
- Photoperiod (hrs dark / hrs light): Lighting time 12 hours per day

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

About 24 hours before the start of the study the test eyes gf all animals were examined under UV light for corneal lesions after instillation of one drop of a 0.01 % fluorescein-sodium solution. Only animals without ocular abnormalities were used for the study.
100 mg Reaktiv-Gelb F-66 923 FW was applied once to the conjunctival sac of the left eye of 3 rabbits. The untreated eyes served in each case as a control.
24 hours after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein-sodium solution took place, the treated eyes were washed out thoroughly with physiological saline at approx. 37 °C.
The eyes were examined 1, 24, 48 and 72 hours after application of the test substance. At 24 and 72 hours as well as after 7 days, the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01 % fluorescein-sodium solution. Lesions in cornea, iris or conjunctivae were graded numerically. All other changes or toxic effects were recorded. Since effects were still present in the eyes after 72 hours, further examinations were carried out after 7 days.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: overall 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: overall 24, 48, 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

other: overall 24, 48, 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: overall 24, 48, 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: overall 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: overall 24, 48, 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible

Results 7

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

other: overall 24, 48, 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: overall 24, 48, 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: overall 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: overall 24, 48, 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible

Results 11

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

other: overall 24, 48, 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: overall 24, 48, 72 hours

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

7 days p.a. the irritations were reversible.

Other effects:

From one hour up to 48 hours p.a. the conjunctiva of the animals showed slight to obvious swelling with partial eversion of lids. Additionally, up to 72 hours p.a. evident hyperaemie to diffuse deeper crimson coloured reddenings were noted. From 24 up to 72 hours p.a. bleedings on the nictating membrane of the animals were observed.
Additional a clear from the substance discoloured discharge was observed.

Any other information on results incl. tables

Rabbit Eye Irritation Test - Readings

Animal Number	Sex	Eye Used	Init Pain Reaction	Irrigat’n	Elapsed Time	Cornea		Iris	Conjunctiva
						Opacity	Area		Redness	Chemosis	Discharge
67	F	Left	None	24 Hrs	1.0 Hrs	0	0	0	2	2	2
					1 Day	0	0	0	2	1	0
					2 Days	0	0	0	2	0	0
					3 Days	0	0	0	2	0	0
					7 Days	0	0	0	0	0	0
69	M	Left	None	24 Hrs	1.0 Hrs	0	0	0	2	1	2
					1 Day	0	0	0	2	1	0
					2 Days	0	0	0	2	0	0
					3 Days	0	0	0	2	0	0
					7 Days	0	0	0	0	0	0
85	F	Left	None	24 Hrs	1.0 Hrs	0	0	0	1	2	2
					1 Day	0	0	0	1	1	0
					2 Days	0	0	0	1	1	0
					3 Days	0	0	0	1	0	0
					7 Days	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Testing of Reaktiv-Gelb F-66 923 FW for primary eye irritation in the rabbit showed, that the substance is slightly irritating to eye. The substance does not trigger the criteria for classification.

Executive summary:

Testing for primary irritation in the rabbit eye provides information on ocular lesions after a single application of the test substance to the conjunctival sac of the eye and serves as a basis for classification and labelling. The present study was conducted in compliance with EEC Directive B.5. 'Acute toxicity Eye Irritation' of the Directive 84/449/EEC and OECD Guidelines for Testing of Chemicals, 405 "Acute Eye Irritation/Corrosion",in compliance with GLP.  

From one hour up to 48 hours p.a. the conjunctiva of the animals showed slight to obvious swelling with partial eversion of lids. Additionally, up to 72 hours p.a. evident hyperaemie to diffuse deeper crimson coloured reddenings were no­ted. From 24 up to 72 hours p.a. bleedings on the nictating membrane of the animals were observed.

7 days p.a. the irritations were reversible.

Additional a clear from the substance discoloured discharge was observed.

 

Testing of Reaktiv-Gelb F-66 923 FW for primary eye irritation in the rabbit showed, that the substance is slightly irritating to eye.

 

The substance does not trigger the criteria for classification.