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

Endpoint summary

Description of key information

The test substance was found to be not irritating or corrosive to the skin, but caused irreversible damage to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 October 1996 to 12 December 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

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
Stability in Water: At least 48 hours
Expiration date: 30 September, 2002
Storage conditions: At room temperature at about 20 °C, away from direct sunlight.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Birkendorferstrasse 65, D - 88397 Biberach / Riss
- Age at treatment: 15 weeks
- Weight at start acclimatization: Males: 2.7 kg, Females: 2.6 - 2.9 kg
- Weight at start of treatment: Males: 2.8 kg, Females: 2.6 - 3.0 kg
- Housing: Individually in stainless steel cages with an automatic cleaning and drinking system equipped with feed hoppers, drinking water bowls and wood for gnawing.
- Diet: Pelleted standard Kliba 341, batch 70/96 rabbit maintenance diet ("Kliba", Kliba Muehle AG, CH-4303 Kaiseraugst), ad libitum
- Water: Community tap water from Itingen ad libitum
- Acclimation period: Four days under test 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

In life phase: October 21-24, 1996

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Test material was applied moistened in distilled water

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

up to 72 hours

Number of animals:

3 (1 male and 2 females)

Details on study design:

Approximately 24 hours before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100 square centimetres (10 cm x 10 cm). The skin of the animals was examined once, 1 day prior to test article administration. On the day of treatment, 0.5 g of the test article was applied to approximately 6 cm² of the intact skin of the clipped area. It was covered with a 2.5 cm x 2.5 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The test article was applied in such a position as to preclude oral ingestion after removal of the dressing. Four hours after the application, the dressing was removed and the skin was flushed with lukewarm tap water. The skin reaction was assessed at 1, 24, 48 and 72 hours intervals after the removal of the dressing, gauze patch and test article.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Irritation: FAT 40577/A showed a primary irritation score of 0.00 when applied to healthy intact rabbit skin. Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema.
Corrosion: No irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.

Other effects:

Coloration: Initial orange staining, later fading to pale orange staining of the treated skin by the test article was observed.
Body weights: The body weight gain of all rabbits was within the normal range of variability.
Toxic symptoms/mortality: No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 40557/A was found to be not irritating or corrosive.

Executive summary:

In a GLP-compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied, semi-occlusive, to the skin of three New Zealand White rabbits for 4 hours. After 4 hours, the treated skin was flushed with water and observation were made for an additional 72 hours. The test substance showed a primary irritation score (24, 48, 72 hours) of 0.00 and local signs (24, 48, 72 hours) consisted of an erythema and edema score of 0.00 at all time points. No corrosive effect was evident on the skin. There were no mortality however clinical observation such as initial orange staining, later fading to pale orange staining of the treated skin by the test article was observed. Based on the study results, the test substance was found to be not irritating or corrosive.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

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.

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

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.

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

In a GLP-compliant skin irritation study, performed according to OECD guideline 404, the test substance (moistened, 0.5 g) was applied, semi-occlusive, to the skin of three New Zealand White rabbits for 4 hours. After 4 hours, the treated skin was flushed with water and observation were made for an additional 72 hours. The test substance showed a primary irritation score (24, 48, 72 hours) of 0.00 and local signs (24, 48, 72 hours) consisted of an erythema and edema score of 0.00 at all time points. No corrosive effect was evident on the skin. There were no mortality however clinical observation such as initial orange staining, later fading to pale orange staining of the treated skin by the test article was observed. Based on the study results, the test substance was found to be not irritating or corrosive.

 

Eye irritation/corrosion:

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.

Justification for classification or non-classification

Based on the findings in the skin irritation study, the test substance does not considered to be classified however, based on the findings in the eye irritation study, the test substance need to be classified as eye irritant according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.