main component 1 (isomer 1): 2-{6-fluoro-4-[3-(2,5-disulfo-phenylazo)-4-hydroxy-2-sulfonapht-7-ylamino]-1,3,5-triazin-2-ylamino}-3-{6-fluoro-4-[3-(1,5-disulfonaphth-2-ylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-propane sodium salt;main component 1 (isomer 2): 2-{6-fluoro-4-[3-(2,5-disulfo-phenylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-3-{6-fluoro-4-[3-(2,5-disulfo-phenylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-propane sodium salt;main component 2: 2,3-bis-{6-fluoro-4-[3-(2,5-disulfo-phenylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-propane sodium salt;main component 3: 2,3-bis-{6-fluoro-4-[3-(1,5-disulfonaphth-2-ylazo)-4-hydroxy-2-sulfonaphth-7-ylamino]-1,3,5-triazin-2-ylamino}-propane sodium salt

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 October 1996 to 12 December 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

422-610-1

EC Name:

-

Molecular formula:

multi constituent

IUPAC Name:

tetracosasodium 2-[(1E)-2-[6-({4-[(1-{[4-({6-[(1E)-2-(2,5-disulfonatophenyl)diazen-1-yl]-5-hydroxy-7-sulfonatonaphthalen-2-yl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}propan-2-yl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)-1-hydroxy-3-sulfonatonaphthalen-2-yl]diazen-1-yl]benzene-1,4-disulfonate 2-[(1E)-2-[6-({4-[(2-{[4-({6-[(1E)-2-(2,5-disulfonatophenyl)diazen-1-yl]-5-hydroxy-7-sulfonatonaphthalen-2-yl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}propyl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)-1-hydroxy-3-sulfonatonaphthalen-2-yl]diazen-1-yl]naphthalene-1,5-disulfonate 3-[(1E)-2-[6-({4-[(1-{[4-({6-[(1E)-2-(4,8-disulfonatonaphthalen-2-yl)diazen-1-yl]-5-hydroxy-7-sulfonatonaphthalen-2-yl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}propan-2-yl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)-1-hydroxy-3-sulfonatonaphthalen-2-yl]diazen-1-yl]naphthalene-1,5-disulfonate 5-[(1E)-2-[6-({4-[(2-{[4-({6-[(1E)-2-(2,5-disulfonatophenyl)diazen-1-yl]-5-hydroxy-7-sulfonatonaphthalen-2-yl}amino)-6-fluoro-1,3,5-triazin-2-yl]amino}propyl)amino]-6-fluoro-1,3,5-triazin-2-yl}amino)-1-hydroxy-3-sulfonatonaphthalen-2-yl]diazen-1-yl]naphthalene-1,6-disulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): FAT 40'557/A
- Lot/batch No.: PV 1
- Purity: Approx. 65%
- Expiry date: 30 September 2002
- Stability of Test Article: Stable under storage condition
- Storage: At room temperature away from light.

Specific details on test material used for the study:

Identity: FAT 40557/A
Batch-no.: PV1
Purity: 65 %
Appearance: Solid powder, red-brown
Stability of test article: stable at storage conditions; expiration date: September 30, 2002
Expiration date: 30 September, 2002
Storage conditions: At room temperature at about 20 °C, away from direct sunlight.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Birkendorferstrasse 65, D - 88397 Biberach / Riss
- Age at start treatment: 15 weeks
- Weight at start acclimatization: Male: 2.8 kg, Females: 2.6-2.7 kg
- Weight at start treatment: Male: 2.9 kg, Females: 2.6-2.7 kg
- Housing: Individually in stainless steel cages with an automatic cleaning system, equipped with feed hoppers, drinking water bowls and wood for gnawing.
- Diet: Pelleted standard Kliba 341 rabbit maintenance diet (batches 70/96 and 71/96) ad libitum from Kliba Mühlen AG, CH-4303 Kaiseraügst.
- Water: Community tap water from Itingen, ad libitum.
- Acclimation period: Four days under laboratory conditions after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 40-70 (values above 70 % during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

The test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article.

Observation period (in vivo):

up to 21 days

Number of animals or in vitro replicates:

3; 1 male, 2 females

Details on study design:

The eyes of the animals were examined for intactness once, one day prior to test article administration. Only those animals with no signs of ocular injury or irritation were used on the test. At treatment, 0.1 g of the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The right eye remained untreated and served as the reference control. The eyes of each animal were examined 1, 24, 48 and 72 hours, as well as 7, 14 and 21 days after administration for ocular irritation.

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

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 d

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

Irritation: Slight to moderate reddening and slight swelling of the conjunctivae were noted in all animals. These findings were reversible after 7 days. Slight to moderate watery discharge was also seen in all animals, but was reversible after 48 hours.
Corrosion: No corrosion of the cornea was observed at any of the measuring intervals. FAT 40557/A showed a primary irritation score of 1.33, when applied to the conjunctival sac of the rabbit eye.

Other effects:

Viability/mortality/clinical signs: No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
Coloration: Orange or light orange staining of the cornea, sclera and conjuctiva by the test article was observed. Staining of the conjunctivae persisted up to and including the end of the observation period.
Body weights: The body weight of the animals was within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the persistent staining of the conjunctivae up to and including the end of the observation period, FAT 40557/A is considered as irritant to eyes.

Executive summary:

In a GLP-compliant eye irritation study, performed according to OECD guideline 405, FAT 40557/A (0.1 g) was placed in the conjunctival sac of the left eye of three New Zealand White rabbits. The eyes were examined up to 21 days. There were no mortality observed while orange or light orange staining of the cornea, sclera and conjunctivae by the test article was observed. Staining of the conjunctivae persisted up to and including the end of the observation period. The test substance showed a mean chemosis score of 1 after 1 and 24 hours. A conjunctivae score of 2 was observed after 1 hour and a conjunctivae score of 1 was observed after 24, 48 and 72 hours. The chemosis and conjunctivae score were 0.00 at the other time points as were the cornea and iris scores during the whole observation period. No corrosion of the cornea was observed at any of the measuring intervals. However orange staining of the conjunctivae persisted up to and including the end of the observation period. Based on the persistent staining of the conjunctivae up to and including the end of the observation period, FAT 40557/A is considered as irritant to eyes.