Tetrasodium [2-({4-fluoro-6-[(2-{[4-fluoro-6-({5-(hydroxykappaO)-6-[(2-{[2-(hydroxy-kappaO)-5-sulfophenyl] diazenyl-kappaN1}-4,5-dimethoxyphenyl) diazenyl-kappaN2]-7-sulfo-2-naphthyl} amino)-1,3,5-triazin-2-yl] amino} propyl) amino]-1,3,5-triazin-2-yl} amino) benzene-1,4- disulfonato(6-)] cuprate(4-)

Endpoint summary

Description of key information

FAT 40825 was found to be non-irritant to skin. It caused staining to eyes and thus classified as Eye corrosive - 1.

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 - 03 May 2006;
Experiment completion date - 12 May 2006;
Study completion date - 12 May 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 (incl. QA statement)

Specific details on test material used for the study:

Identity: FAT 40825/A
Batch number: CHU 297 / BOP 04/05
Purity: Organic part (Na-salt): approx. 83.7 %; All coloured components: approx. 80.54 %; Main component: approx. 59.1 %.
Appearance: Solid, black powder
Storage conditions: At room temperature at about 20 °C
Expiration date: December 31, 2010

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: 13 - 14 weeks (male) 13 - 14 weeks (females)
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

HUSBANDRY:
Standard Laboratory Conditions: Air-conditioned with ranges for room temperature 17 - 23 °C, relative humidity 30 - 70 % and approximately 10 - 15 air changes per hour. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

Accommodation:
Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 (batch no. 77/05) were provided for gnawing.

Diet:
Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 85/05) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Water: Community tap water from Füllinsdorf, ad libitum.

Water:
Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after removal of the dressing

Number of animals:

3

Details on study design:

The primary skin irritation potential of FAT 40825/A 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 four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing.

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 weights: At start of acclimatization, on the day of application and at termination of observation.
NECROPSY: The animals were not sacrificed. No signs of irritation were observed on the treated skin following the application of the test item. For ethical reasons and in the interest of animal
welfare, the animals were therefore re-used for the eye irritation study (RCC Study A53818) using the same test item.

Grading of Skin Reactions:
ERYTHEMA AND ESCHAR FORMATION
No erythema...................... 0
Very slight erythema............. 1
Well-defined erythema...................... 2
Moderate to severe erythema.................... 3
Severe erythema (beef redness) or eschar formation (injuries in depth preventing erythema) reading..... 4

OEDEMA FORMATION
No oedema................................................. 0
Very slight oedema (barely perceptible)..................................... 1
Slight oedema (edges of area well-defined by definite raising)........................ 2
Moderate oedema (edges raised approximately 1 mm)........................... 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) ............4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 animals

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 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No erythema or edema was observed at any time point. All the scores at all time points was zero. Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. No staining produced by the test item of the treated skin was observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is considered to be "not irritating" to rabbit skin and shall not be classified according to the CLP regulation (Regulation EC No. 1272/2008).

Executive summary:

The primary skin irritation potential of FAT 40825/A was investigated according to OECD test guideline no. 404 in a GLP-certified laboratory. 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 four hours. The scoring of skin reactions 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. No erythema or edema was observed at any time point. All the scores at all time points was zero. Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. And the test item is considered to be "not irritating" to rabbit skin and shall not be classified according to the CLP Regulation (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 - 12 May 2006;
Experiment completion date - 07 June 2006;
Study completion date - 07 June 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 (incl. QA statement)

Specific details on test material used for the study:

Identity: FAT 40825/A
Batch number: CHU 297 / BOP 04/05
Purity: Organic part (Na-salt): approx. 83.7 %; All coloured components: approx. 80.54 %; Main component: approx. 59.1 %.
Appearance: Solid, black powder
Storage conditions: At room temperature at about 20 °C
Expiration date: December 31, 2010

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: 14 - 15 weeks (male) 14 - 15 weeks (females)
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

HUSBANDRY: Standard Laboratory Conditions: Air-conditioned with ranges for room temperature 17 - 23 °C, relative humidity 30 - 70 % and approximately 10 - 15 air changes per hour. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.
Accommodation: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 (batch no. 77/05) were provided for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 85/05) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
Water: Community tap water from Füllinsdorf, ad libitum.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

one second and the treated eyes were not rinsed after instillation.

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 weights: 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, 72 hours as well as 7, 10, 14, 17 and 21 days after administration.

Number of animals or in vitro replicates:

3

Details on study design:

The primary eye irritation potential of the test item was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 g 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, 10, 14, 17 and 21 days after test item instillation.
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately.

Grading of Ocular Lesions
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 deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)...................... 1
No reaction to light, hemorrhage, gross destruction (any or all of these)...................... 2

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with control eye)
Blood vessels normal...................... 0
Some blood vessels definitely hyperemic (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 (including 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

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animals

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 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0.778

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slight corneal opacity affecting the whole area was observed in all animals 1 hour after treatment. No abnormal findings were observed in the iris of any animal at any of the measurement intervals. Moderate reddening of the conjunctivae was noted in all animals at the 1- hour reading and persisted as slight reddening in two animals till 48 hours after application and in one animal until 72 hours after application. No swelling (Chemosis) of the conjunctivae was observed. Slight to moderate reddening of the sclerae was noted in all animals at the 1-hour reading and persisted in two animals till the 48- and in one animal till the 24-hour reading. Slight ocular discharge was noted in all animals at the 1-hour reading. No corrosion of the cornea was observed at any of the reading times.

Other effects:

Slight to marked black staining of the treated eyes produced by the test item was observed in all animals throughout the whole observation period. Black remnants of the test item were observable in the three rabbits from 1 hour to 72 hours after application. No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, the test article is irritant to the eye of rabbits (Stains the eyes ).

Executive summary:

The primary eye irritation potential of the test item was investigated according to OECD test guideline no. 405 in a GLP certified laboratory. The test item was applied by instillation of 0.1 g 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, 10, 14, 17 and 21 days after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. 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, 0.67 and 0.67 for reddening and 0.00 for chemosis for all three animals, respectively. The instillation of test item into the eye resulted in mild and early-onset ocular changes, such as corneal opacity, reddening of the conjunctivae and sclerae and discharge. Slight to marked black staining of the treated eyes was noted in all animals at the 1-hour reading and persisted as slight staining in all animals until the 21-day reading, the end of the observation period for all animals. Black remnants were observed in the eye or conjunctival sac of all the rabbits from 1 hour to 72 hours after application. No abnormal findings were observed in the 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 results of the study, the test article is irritant to the eye of rabbits (Stains the eyes).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The primary skin irritation potential of FAT 40825/A was investigated according to OECD test guideline no. 404 in a GLP- certified laboratory. 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 four hours. The scoring of skin reactions 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. No erythema or Edema was observed at any time point. All the scores at all time points was zero. Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed. And the test item is considered to be "not irritating" to rabbit skin and shall not be classified according to the CLP Regulation (Regulation EC No. 1272/2008).

 

Eye irritation/corrosion:

The primary eye irritation potential of the test item was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 g 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, 10, 14, 17 and 21 days after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. 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, 0.67 and 0.67 for reddening and 0.00 for chemosis for all three animals, respectively. The instillation of test item into the eye resulted in mild and early-onset ocular changes, such as corneal opacity, reddening of the conjunctivae and sclerae and discharge. Slight to marked black staining of the treated eyes was noted in all animals at the 1-hour reading and persisted as slight staining in all animals until the 21-day reading, the end of the observation period for all animals. Black remnants were observed in the eye or conjunctival sac of all the rabbits from 1 hour to 72 hours after application. No abnormal findings were observed in the iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No clinical signs were observed.

Justification for classification or non-classification

Based on the skin irritation / corrosion test result, the test substance shall not be classified for skin irritation/corrosion according to the CLP Regulation (Regulation EC No. 1272/2008). 

Based on the eye irritation / corrosion test result, the test substance shall be classified according to the CLP Regulation (Regulation EC No. 1272/2008) for eye damage, category 1.