N-(4-amino-9,10-dihydro-3-methoxy-9,10-dioxo-1-anthryl)benzenesulphonamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(4-amino-9,10-dihydro-3-methoxy-9,10-dioxo-1-anthryl)benzenesulphonamide

EC Number:

274-040-4

EC Name:

N-(4-amino-9,10-dihydro-3-methoxy-9,10-dioxo-1-anthryl)benzenesulphonamide

Cas Number:

69563-51-5

Molecular formula:

C21H16N2O5S

IUPAC Name:

N-(4-amino-3-methoxy-9,10-dioxo-9,10-dihydroanthracen-1-yl)benzenesulfonamide

Test material form:

other: solid

Details on test material:

None

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 9300102
- Expiration date of the lot/batch: July, 1998

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Weight at study initiation: between 2220 to 2490 g
- Housing: The animals were housed individually in metal cages.
- Diet (e.g. ad libitum):The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water (e.g. ad libitum):Fresh water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20 ± 3
- Humidity (%):30-70
- Photoperiod (hrs dark / hrs light):12 hours light cycle day.

Test system

Vehicle:

water

Controls:

other: The right eye remained untreated and served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (46 mg)

Duration of treatment / exposure:

The test substance was not flushed out of the eye.

Observation period (in vivo):

1, 24, 48, and 72 hours

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

Method
0.1 ml (46 mg) of FAT 36034/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 36034/D according to the OECD scoring system (Appendix 1). In order to determine the reversibility of the eye reactions additional evaluations of the ocular reactions were needed in this study. A slit-lamp was used to facilitate the evaluation. The irritant/corrosive potency of FAT 36034/D was classified according to Council Directive 67/548/EEC, adapted to technical progress by Commission Directive 93/21/EEC

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Any other information on results incl. tables

Because reactions were observed within 72 hours after instillation of the test article , the observation period was extended to 7 days to determine the reversibility of the eye reactions.

Individual eye scores

Animal No 002/F

Time point	Cornea (ce/te)	Iris (ce/te)	Conjunctiva
			Redness (ce/te)	Chemosis (ce/te)
After 24 hours	0/0	0/0	0/0	0/0
After 48 hours	0/0	0/0	0/1	0/0
After 72 hours	0/0	0/0	0/1	0/0
Mean (24-72 Hrs)	0/0	0/0	0/0.67	0/0

 

Animal No 092/F

Time point	Cornea (ce/te)	Iris (ce/te)	Conjunctiva
			Redness (ce/te)	Chemosis (ce/te)
After 24 hours	0/0	0/0	0/1	0/0
After 48 hours	0/0	0/0	0/1	0/0
After 72 hours	0/0	0/0	0/1	0/0
Mean (24-72 Hrs)	0/0	0/0	0/1	0/0

 

Animal No 040/F

Time point	Cornea (ce/te)	Iris (ce/te)	Conjunctiva
			Redness (ce/te)	Chemosis (ce/te)
After 24 hours	0/0	0/1	0/1	0/0
After 48 hours	0/0	0/0	0/1	0/0
After 72 hours	0/0	0/0	0/1	0/0
Mean (24-72 Hrs)	0/0	0/0.33	0/1	0/0

ce = control eye

te = test eye

Reversibility of any observed effect: Changes fully reversible within 7 days.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 36034/D can be classified as non-irritant.

Executive summary:

An acute eye irritation/corrosion key study was performed in NZW rabbits to determine the irritant or corrosive potency of FAT 36034/D on the NZW rabbit eye and the associated mucous membranes. This test was based on the OECD guideline No. 405, adopted May 12, 1981, by the OECD council and as well as followed the GLP guidelines. The substance was tested at the concentration of 94% purity. Under the experimental conditions applied FAT 36034/D induced reactions of the cornea, iris and conjunctiva when instilled into the conjunctival sac of albino rabbit eyes. Because the mean values (0.89 for conjunctiva/redness; and 0.11 for iris) of the readings 24 to 72 hours after instillation are below the threshold of significance, FAT 36034/D can be classified as non-irritant according to Council Directive 67/548/EEC, adapted to technical progress by Commission Directive 93/21/EEC.