1-hydroxy-4-[[4-[(methylsulphonyl)oxy]phenyl]amino]anthraquinone

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 September, 1993 to 25 November, 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:

1-hydroxy-4-[[4-[(methylsulphonyl)oxy]phenyl]amino]anthraquinone

EC Number:

216-475-4

EC Name:

1-hydroxy-4-[[4-[(methylsulphonyl)oxy]phenyl]amino]anthraquinone

Cas Number:

1594-08-7

Molecular formula:

C21H15NO6S

IUPAC Name:

4-[(4-hydroxy-9,10-dioxo-9,10-dihydroanthracen-1-yl)amino]phenyl methanesulfonate

Test material form:

not specified

Details on test material:

None

Specific details on test material used for the study:

Test substance
Code number: FAT - 36038/F
En-Nr.: 409753.32
Purity 69.4 %
Appearance: solid
Solubility: insoluble
Storage: room temperature
Expiration date: 09/98
Safety precautions: gloves and face masks

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Chemisch-pharmazeutische Fabrik D-7950 Biberach/Riss
- Weight at study initiation: 2280 to 2370 g
- Housing: housed individually in metal cages, identified by ear tattoo
- Diet: ad libitum, standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum, fresh water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30-70 %
- Photoperiod: 12 hours light cycle day

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye of each rabbit remained untreated and served as a control.

Amount / concentration applied:

0.1 ml (62 mg) of FAT 36038/F was placed into the conjunctival sac of the left eye of each animal.

Duration of treatment / exposure:

One single application

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 females rabbits

Details on study design:

0.1 ml (62 mg) of FAT 36038/F 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 36038/F according to the OECD scoring system. 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.

Scores for ocular lesions according to the OECD guideline 405:
*CORNEA
- Opacity: degree of density (area most dense taken for reading).
- No ulceration or opacity: 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible: 1
- Easily discernible translucent area, details of iris slightly obscured: 2
- Nacreous area, no details of iris visible, size of pupil barely discernible: 3
- Opaque cornea, iris not discernible through the opacity: 4

*IRIS
- Normal 0
- Markedly depended rugae , congestion , swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reaction to light (sluggish reaction is positive): 1
- No reaction to light, hemorrhage, gross destruction (any or all of these): 2

*CONJUNCTIVAE
Redness: (refers to palpebral and bulbar conjunctivae, cornea and iris)
- Blood vessels normal: 0
- Some blood vessels definitely hyperaemic (injected): 1
- Diffuse, crimson colour, individual vessels not easily discernible: 2
- Diffuse beefy red: 3

*Chemosis - lids and/or nictitating membranes.
- No swelling: 0
- Any swelling above normal (includes nictitating membranes): 1
- Obvious swelling with partial eversion of lids: 2
- Swelling with lids about half closed: 3
- Swelling with lids more than, half closed: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 male rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24h

Results 2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 male rabbits

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 male rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 male rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24h

Irritant / corrosive response data:

Reactions were observed within 48 hours after instillation of the test article, the observation period was extended to 7 days to determine the reversibility of the eye reactions.

Other effects:

None

Any other information on results incl. tables

Individual eye scores.

Animal N° 662/F	Cornea		Iris		Conjunctiva
	ce	te	ce	te	Redness ce te		Chemosisce te
After 1 hr.	0	0	0	1	0	1	0	1
After 24 hrs	0	0	0	0	0	1	0	0
After 48 hrs	0	0	0	0	0	1	0	0
After 72 hrs	0	0	0	0	0	0	0	0
Mean 24 -72 hours	0	0	0	0	0	0.67	0	0
After 7 days	0	0	0	0	0	0	0	0

Animal N° 016/F	Cornea		Iris		Conjunctiva
	ce	te	ce	te	Redness ce te		Chemosisce te
After 1 hr.	0	0	0	0	0	1	0	1
After 24 hrs	0	0	0	0	0	1	0	0
After 48 hrs	0	0	0	0	0	1	0	0
After 72 hrs	0	0	0	0	0	0	0	0
Mean 24 -72 hours	0	0	0	0	0	0.67	0	0
After 7 days	0	0	0	0	0	0	0	0

Animal N° 980/F	Cornea		Iris		Conjunctiva
	ce	te	ce	te	Redness ce te		Chemosisce te
After 1 hr.	0	0	0	0	0	1	0	1
After 24 hrs	0	0	0	0	0	1	0	0
After 48 hrs	0	0	0	0	0	1	0	0
After 72 hrs	0	0	0	0	0	0	0	0
Mean 24 -72 hours	0	0	0	0	0	0.67	0	0
After 7 days	0	0	0	0	0	0	0	0

ce = control eye

te = test eye

F = Female

Bodyweight (g):

Animal N°	662/F	016/F	980/F
At start of test	2320	2370	2280
After 3 days	2400	2440	2400
After 7 days (end)	2510	2580	2590

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 36038/F can be classified as non-irritant to rabbits eyes.

Executive summary:

The Acute Eye Irritation/Corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of FAT 36038/F in the albino rabbit eye and the associated mucous membranes. This test was based on the OECD Guideline No. 405, adopted February 24, 1987, by the OECD council, and on Annex V, part B of Council Directive 79/831/EEC (Commission Directive 92/69/EEC of July 31, 1992). The lids were 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. The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of FAT 36038/F according to the OECD scoring system. A slit-lamp was used to facilitate the evaluation. No corneal opacity was observed with any of the exposed animals. Slight irritation reactions with iris and chemosis was seen at 1 hour after the exposure, however these reactions were reversed by 24 hours. Slight conjunctival redness was seen in all three exposed animals, which was found to have reversed by 72 hours. Hence, based on the findings of the study, FAT 36038/F induced reactions of the iris and conjunctiva when instilled, into the conjunctival sac of albino rabbits' eyes. Because the mean values of the readings 24 to 72 hours after instillation are below the threshold of significance, FAT 36038/F can be classified as non-irritant.