Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Reactive Yellow 214 was found to be not irritating or corrosive to the skin and 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:
28 June 2006 to 10 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)
GLP compliance:
yes (incl. QA statement)
Remarks:
RCC Ltd, 4452 Itingen, Switzerland
Specific details on test material used for the study:
Identity: FAT 40826/A
Batch no.: TZ 5604 BOP 01/06
Expiration date: February 01, 2011
Purity: Content of organic part (Na-salt): approx. 78 %; Oligomers: 13 %; Main component: approx. 48 %
Solubility in water: Approx. >50 g/L at room temperature
Stability in water: Max. 7 days at room temperature
pH: 7.6 (1 g/L)
Aggregate state/physical form at room temperature: Solid (orange powder)
Storage conditions: At room temperature at about 20 °C, away from direct sunlight
Specific instructions: Store in desiccator
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan France, Zl Le Marcourlet, 03800 Gannat/France
- Age at treatment: 12-13 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 24/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
using electric clipper
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g test substance moistened with approximately 0.5 mL purified water.
Duration of treatment / exposure:
4 h
Observation period:
7 days
Number of animals:
1 male, 2 females
Details on study design:
TREATMENT
Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm² (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.5 g of FAT 40826/A was placed on a surgical gauze patch (ca. 4 cm x 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.

OBSERVATIONS
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 A73675.) using the same test item.

SCORING SYSTEM:
The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004 approximately 1, 24, 48 and 72 hours, as well as 7 days after the removal of the dressing, gauze patch and test item.
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:
- The test item did not elicit any skin reactions at the application site of any animal 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.
- Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
- Slight orange staining of the treated skin produced by the test item was observed in all animals from the 1- to the 48-hour reading and persisted in two animals until the 72-hour reading.
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
- A slight loss of weight (1.7 %) was noted during the acclimatization period in one animal. The animal recovered at the end of the observation period. The body weights of the other rabbits were considered to be within the normal range of variability.
Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40826/A is considered to be not irritating or corrosive to the rabbit skin.
Executive summary:

A GLP-compliant skin irritation study with FAT 40826/A was carried out according to OECD test guideline 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, as well as 7 days 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. The application of FAT 40826/A to the skin resulted in no signs of irritation. However, the test item caused slight orange staining of the treated skin in all animals. 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. Based on the study results, FAT 40826/A is considered to be "not irritating" to rabbit skin.

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:
11 July 2006 to 10 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:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Remarks:
RCC Ltd, 4452 Itingen, Switzerland
Specific details on test material used for the study:
Identity: FAT 40826/A
Batch no.: TZ 5604 BOP 01/06
Expiration date: February 01, 2011
Purity: Content of organic part (Na-salt): approx. 78 %; Oligomers: 13 %; Main component: approx. 48 %
Solubility in water: Approx. >50 g/L at room temperature
Stability in water: Max. 7 days at room temperature
pH: 7.6 (1 g/L)
Aggregate state/physical form at room temperature: Solid (orange powder)
Storage conditions: At room temperature at about 20 °C, away from direct sunlight
Specific instructions: Store in desiccator
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst / The Netherlands
- Age at treatment: 13-14 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 24/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
21 days
Observation period (in vivo):
up to 21 days
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
TREATMENT:
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 FAT 40826/A 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.

OBSERVATIONS:
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. No necropsy was performed on the animals sacrificed at termination of observation. The animals were killed by intravenous injection of Pentobarbitone into the ear vein at a dose of at least 1 mL/kg body weight and discarded.

SCORING SYSTEM:
The eye reactions was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004 at approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14, 17, and 21 days after administration. Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland)
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:
0.88
Max. score:
3
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 animal
Time point:
24/48/72 h
Score:
0.44
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
- No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals. Slight to moderate reddening of the conjunctivae was noted in all animals at the 1- and 24-hour reading and persisted as slight reddening in two animals until the 72-hour and 7 day reading. Slight swelling (chemosis) of the conjunctivae was observed in one animal at the 1- and 24-hour reading. Slight swelling to marked swelling with half closed lids was also noted in one animal from the 1- to the 48-hour reading. The reddening of the sclerea was not assessable in two animals for the first 24 hours after treatment due to staining produced by the test item and chemosis. When assessable one animal showed a slight reddening of the sclerea at the 48-hour reading. Slight to moderate ocular discharge was seen in two animals at the 1-hour reading and persisted as slight ocular discharge in one animal at the 24-hour reading. No abnormal findings were observed in the treated eye of any animal 10 days after treatment.
- No corrosion of the cornea was observed at any of the reading times.
Other effects:
- Slight to marked red staining was observed in all animals 1 hour after instillation and persisted as slight to marked yellow staining until the 17-day reading in two animals.
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
- The body weights of all rabbits were considered to be within the normal range of variability.

Individual eye score:

Animal No.

Time point

Corneal opacity

Area of Corneal Opacity

Iris

Conjunctiva

Sclera

 

Redness

Chemosis

1

After 24 h

0

0

0

1

0

0

2

0

0

0

1

1

n.a.

3

0

0

0

2

2

n.a.

1

After 48 h

0

0

0

0

0

0

2

0

0

0

1

0

0

3

0

0

0

1

1

1

1

After 72 h

0

0

0

0

0

0

2

0

0

0

1

0

0

3

0

0

0

1

0

0

  n.a. = not assessable due to staining and/or swelling produced by the test item

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40826/A is considered to be not irritating or corrosive to the rabbit eye.
Executive summary:

A GLP-compliant eye irritation study with FAT 40826/A was investigated according to OECD guideline 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, insofar as numerical scores were assessable. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.33, 1.00 and 0.33 for reddening and 0, 0.33 and 1 for Chemosis, respectively. The instillation of FAT 40826/A into the eye resulted in 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 10 days after treatment. Slight to marked red staining was observed in all animals 1 hour after instillation and persisted as slight to marked yellow staining until 17 days after treatment in two animals. 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. Thus, the test item did not induce significant or irreversible damage to the rabbit eye. Based on the study results, FAT 40826/A is considered to be "not irritating" to the rabbit eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:


A GLP-compliant skin irritation study with FAT 40826/A was carried out according to OECD test guideline 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, as well as 7 days 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. The application of FAT 40826/A to the skin resulted in no signs of irritation. However, the test item caused slight orange staining of the treated skin in all animals. 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. Based on the study results, FAT 40826/A is considered to be "not irritating" to rabbit skin.


 


Eye irritation:


A GLP-compliant eye irritation study with FAT 40826/A was investigated according to OECD guideline 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, insofar as numerical scores were assessable. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.33, 1.00 and 0.33 for reddening and 0.00, 0.33 and 1.00 for Chemosis, respectively. The instillation of FAT 40826/A into the eye resulted in 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 10 days after treatment. Slight to marked red staining was observed in all animals 1 hour after instillation and persisted as slight to marked yellow staining until 17 days after treatment in two animals. 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. Thus, the test item did not induce significant or irreversible damage to the rabbit eye. Based on the study results, FAT 40826/A is considered to be "not irritating" to the rabbit eye.

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study, Reactive Yellow 214 is not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.