Tetra(sodium/potassium)-7-[(E)-{2-acetamido-4-[(E)-(4-{[4-chlor-6-({2-[(4-fluor-6-{[4-(vinylsulfonyl)phenyl]amino}-1,3,5-triazin-2-yl)amino]propyl}amino)-1,3,5-triazin-2-yl]amino}-5-sulfonato-1-naphthyl)diazenyl]-5-methoxyphenyl}diazenyl]-1,3,6-naphthalintrisulfonate

Endpoint summary

Description of key information

FAT 40827 is not a skin or eye irritant.

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:

Experiment start date - 28 June 2006; Experiment completion date - 06 July 2006; Study completion date - 24 August 2006.

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)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Identity: FAT 40827/A
Batch: T2 5572 BOP 01/06
Purity: determined in this study
Appearance: black sticky powder
Expiration date: 28.02.2011
Storage: at room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test System: Young Adult New Zealand White Rabbit (SPF)
Number of animals per test: 3 (Animals of both sexes were used)
Age at treatment: 11-12 weeks (male); 13-14 weeks (females)
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions after health examination. Only healthy animals were used for the study.
Allocation: Male no. 7 and Female Nos: 8 – 9

Conditions
Standard Laboratory Conditions.
Air-conditioned with ranges for room temperature of 17 - 23 °C and relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations were considered not to have any influence on the study and, therefore, these data were not reported but were retained at RCC. 12 hours artificial fluorescent light/12 hours dark, music during the light period.
Accommodation: Individually in stainless steel cages with feed hoppers, drinking water bowls. Wood blocks and haysticks 4642 were provided for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch 24/06) ad libitum.
Water: Community tap water, ad libitum.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

Viability/mortality: Daily from acclimatization of the animals to the termination of test.
Clinical signs: Daily from acclimatization of the animals to the termination of test.
Body weight: At start of acclimatization, on the day of application and at termination of observation.
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item)

Number of animals:

3

Details on study design:

Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm² (10cm × 10cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again. On the day of treatment, 0.5 g of test item was placed on a surgical gauze patch (ca. 4 cm × 4 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time. The scoring of skin reaction was performed 1, 24, 48 and 72 hours after removal of the dressing.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

Other effects:

No clinical signs of system toxicity were observed in the animals during the study and no mortality occurred. A slight red staining of the treated skin produced by the test item was observed in all animals 1 hour after removal of the dressing and persisted in one animal still at the 24-hour reading. Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin. The body weights of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not induce significant or irreversible damage to the skin.

Executive summary:

The primary skin irritation potential of test item was investigated according to OECD test guideline no. 404. The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White Rabbits. The duration of treatment was 4 hours. The scoring of skin reaction was performed 1, 24, 48 and 72 hours after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0. A slight red staining of the treated skin produced by the test item was observed in all animals 1 hour after removal of the dressing and persisted in one animal still at the 24-hour reading. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Based on the results of this test, it indicates that the test item shall not be classified in accordance with CLP (Regulation EC No.1272/2008).

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:

Experiment start date - 06 July 2006; Experiment completion date - 25 July 2006; Study completion date - 16 August 2006.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Identity: FAT 40827/A
Batch: T2 5572 BOP 01/06
Purity: determined in this study
Appearance: black sticky powder
Expiration date: 28.02.2011
Storage: at room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test System: Young Adult New Zealand White Rabbit (SPF)
Number of animals per test: 3 (Animals of both sexes were used)
Age at treatment: 11-12 weeks (male); 13-14 weeks (females)
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions after health examination. Only healthy animals were used for the study.
Allocation: Male no. 7 and Female Nos: 8 – 9

Conditions
Standard Laboratory Conditions.
Air-conditioned with ranges for room temperature of 17 - 23 °C and relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations were considered not to have any influence on the study and, therefore, these data were not reported but were retained at RCC. 12 hours artificial fluorescent light/12 hours dark, music during the light period.
Accommodation: Individually in stainless steel cages with feed hoppers, drinking water bowls. Wood blocks and haysticks 4642 were provided for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch 24/06) ad libitum.
Water: Community tap water, ad libitum.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g per animal

Observation period (in vivo):

Viability/mortality: Daily from acclimatization of the animals to the termination of test.
Clinical signs: Daily from acclimatization of the animals to the termination of test.
Body weight: At start of acclimatization, on the day of application and at termination of observation.
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after test article application.

Number of animals or in vitro replicates:

3

Details on study design:

The eyes of the animals were examined one day prior to test item administration.
Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.1 g of test item 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 test item. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed after instillation. The eyes of each animal were examined approximately 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after test article application.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.44

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The instillation of test item into the eye resulted in mild to moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 14 days after treatment, the end of the observation period for all animals. A slight black staining produced by the test item was visible in 2 animals 1 hour after application. The staining did not persist. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals.

Other effects:

No clinical signs were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not induce significant or damage to the rabbit eye.

Executive summary:

The primary eye irritation potential of test item was investigated according to OECD test guideline No.405. The test item was applied by instillation of 0.1g into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after test article application for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual 24/48/72h mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 1.67 and 1.67 for reddening, respectively and 0.00 in all three animals for chemosis. The instillation of test item into the eye resulted in mild to moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 14 days after treatment, the end of the observation period for all animals. A slight black staining produced by the test item was visible in 2 animals 1 hour after application. The staining did not persist. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No clinical signs were observed. Based on the result of this test, it indicates that the test item shall not be classified in accordance with CLP (Regulation EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two studies were conducted to assess the potential toxicity to skin and eyes of rabbits following guideline and GLP principles.

 

Skin irritation

The primary skin irritation potential of test item was investigated according to OECD test guideline no. 404. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0. A slight red staining of the treated skin produced by the test item was observed in all animals 1 hour after removal of the dressing and persisted in one animal still at the 24-hour reading. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the skin.

 

Eye irritation

The primary eye irritation potential of test item was investigated according to OECD test guideline No.405. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 1.67 and 1.67 for reddening, respectively and 0.00 in all three animals for chemosis. The instillation of test item into the eye resulted in mild to moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 14 days after treatment, the end of the observation period for all animals. A slight black staining produced by the test item was visible in 2 animals 1 hour after application. The staining did not persist. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

Justification for classification or non-classification

The test substance shall not be classified according to the CLP Regulation (Regulation EC No. 1272/2008) based on available in vivo data for skin and eye irritation/corrosion.