Registration Dossier

Administrative data

Description of key information

Skin

The primary skin irritation potential of FAT 93503/A was investigated in the OECD Guideline 404 (Acute Dermal Irritation/Corrosion) study. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing by the number of data points. The primary irritation score was 0.00 (max. 8.0). Local signs (mean values from 24 to 72 h) consisted of grade 0.00 erythema and grade 0.00 oedema. No corrosive effects were noted on the treated skin of any animal at any measuring interval. In conclusion, the test article is considered to be "not irritating" to rabbit skin.

Eye:

The primary eye irritation potential of FAT 93503/A was investigated in the OECD Guideline 405 (Acute Eye Irritation / Corrosion) study. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing the resulting total by the number of data points. The primary irritation score was 0.56 (max. 13). The eye reactions (mean values from 24 to 72 h) consisted of grade 0.00 corneal opacity, grade 0.00 iris, grade 0.56 redness of the conjunctivae and grade 0.00 chemosis of the conjunctivae. All eye reactions were fully reversible within 72 h after treatment. No corrosion was observed at any of the measuring intervals. In conclusion, FAT 93503/A is considered to be "not irritating" to the rabbit 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:
25 January, 2000 to 3 February, 2000
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)
Remarks:
Swiss GLP
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 99 Labor Mischung 1
- Expiration date of the lot/batch: January 2005

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight.
- Stability of the test substance in the solvent/vehicle: Stable in bi-distilled water for at least 24 h.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: elevage scientifique des Dombes, F-01400 Chatillon sur Chalonne/France
- Age: 15 weeks (males), 16 weeks (females)
- Weight: 2.7 - 3.0 kg
- Housing:Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood (RCC Ltd, Füllinsdorf) and hay sticks
for gnawing.
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature:22 ± 3 °C
- Humidity: 35-54 %
- Air changes: air conditioned with 10-15 air changes per hour
- Photoperiod: light cycle of 12 hours light and 12 hours dark. Music was played during the light cycle.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: Test item was moistened with bi-distilled water before application.
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g/animal
The test article was moistened with bi-distilled water.
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
1 male and 2 females
Details on study design:
Approximately 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 approximately 24 h before treatment, and regrown fur was again clipped. 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 93503/A were put on a surgical gauze patch (ca. 2.5 cm x 2.5 cm). This gauze patch was applied to approximately 6 cm² of 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.

SCORING SYSTEM:
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 (beet 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
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:
IRRITATION:
Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 0.00. Local signs (mean values from 24 to 72 h) consisted of grade 0.00 erythema and grade 0.00 oedema.

CORROSION:
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
VIABILITY/MORTALITY AND CLINICAL SIGNS:
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

COLORATION:
Light red staining by the test article of the treated skin was observed throughout the reading intervals.

BODY WEIGHTS:
The body weight of all rabbits were considered to be within the normal range of variability.
Interpretation of results:
GHS criteria not met
Conclusions:
FAT 93503/A is considered to be not irritating to the rabbit skin.
Executive summary:

The purpose of this primary skin irritation study was to assess the possible irritation potential when a single dose of the test article is placed on the skin of rabbits for approximately 4 h. This study was performed according to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion). 0.5 g FAT 93503/A was applied topically to 6 cm² intact left flank of three young adult New Zealand White rabbits (1 male and 2 females). The duration of exposure was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 h, after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 h) were used in calculating the respective mean values for each type of lesion. No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing by the number of data points. The primary irritation score was 0.00 (max. 8.0). Local signs (mean values from 24 to 72 h) consisted of grade 0.00 erythema and grade 0.00 oedema. Light red staining by the test article of the treated skin was observed throughout the measuring intervals. No corrosive effects were noted on the treated skin of any animal at any measuring interval. In conclusion, the test article 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:
22 February, 2000 to 3 March, 2000
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)
Remarks:
Swiss GLP
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 99 Labor Mischung 1
- Expiration date of the lot/batch: January 2005

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Test system: New Zealand White Rabbit, SPF.
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne / France.
- Age at study initiation: 14 weeks (male) and 14 to 15 weeks (females).
- Weight at study initiation: approximately 3.0 to 3.2 kg.
- Housing: Individually in stainless steel cages equipped with feed hoppers.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 66/99) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf ad libitum.
- Acclimation period: Seven days under laboratory conditions after health examination. only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 28-52 %
- Air changes: Air-conditioned with 10-15 air changes per hour.
- Photoperiod: Light cycle of 12 h light and 12 h dark. Music was played during the light cycle.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 g (per animal) of FAT 93503/A was weighed and applied undiluted as it was delivered by the sponsor.
Duration of treatment / exposure:
single application
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
1 male and 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM:Grading of Ocular Lesions.
CORNEA.
- 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 circumcomeal 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 color, 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 animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 animal
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Remarks:
Male (animal no 19)
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Remarks:
Female (animal no 20)
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Remarks:
Female (animal no 21)
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
IRRITATION:
Application of the test article to healthy rabbit conjunctivae resulted in a primary irritation score of 0.56. The eye reactions (mean values from 24 to 72 h) consisted of grade 0.00 corneal opacity, grade 0.00 iris, grade 0.56 redness of the conjunctivae and grade 0.00 Chemosis of the conjunctivae. Hyperemic conjunctival blood vessels were noted in all animals at the 1-hour examination and persisted through 48 h (one animal), increased in severity at 24 h before diminishing to clear by 72 h (one animal) or disappeared at the 24-h examination (one animal). Slight conjunctival swelling was seen in two animals at the 1-h examination. Slightly to moderately reddened sclera was observed in all animals at the 1-h reading and persisted with less severity in one animal through 48 h. All eye reactions were clear within 72 h after treatment.

CORROSION:
No corrosion of the cornea was observed at any of the reading times.
Other effects:
VIABILITY/MORTALITY AND CLINICAL SIGNS:
- No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

COLORATION
Red to light red staining of the treated eyes by the test article was observed during the entire reading period.
Red remnants of the test article in eye or conjunctival sac were observed at the 1-h reading.

BODY WEIGHTS
Except the slight loss of body weight of the animal no. 21 (Female) between the treatment start and the end of the study, the body weight of the rabbits were considered to be within the normal range of variability. This loss of body weight was considered to be incidental.
Interpretation of results:
GHS criteria not met
Conclusions:
FAT 93503/A is considered to be not irritating to the rabbit eye.
Executive summary:

The purpose of this primary eye irritation study was to assess the possible irritation potential when a single dose of the test article is placed in the conjunctival sac of rabbit eyes. The study was conducted according to the OECD Guideline 405 (Acute Eye Irritation / Corrosion). The primary irritation potential of FAT 93503/A was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 h after test article application. The scores of each animal at the following reading times (24, 48 and 72 h) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing the resulting total by the number of data points. The primary irritation score was 0.56 (max. 13). The eye reactions (mean values from 24 to 72 h) consisted of grade 0.00 corneal opacity, grade 0.00 iris, grade 0.56 redness of the conjunctivae and grade 0.00 chemosis of the conjunctivae. Hyperemic conjunctival blood vessels were noted in all animals at the 1-h examination and persisted through 48 h (one animal), increased in severity at 24 h before diminishing to clear by 72 h (one animal) or disappeared at the 24-h examination (one animal). Slight conjunctival swelling was seen in two animals at the 1-h examination. Slightly to moderately reddened sclera was observed in all animals at the 1-h reading and persisted with less severity in one animal through 48 h. All eye reactions were clear within 72 h after treatment. Red to light red staining of the treated eyes by the test article was observed during the entire reading period. Red remnants of the test article in eye or conjunctival sac were observed at the 1-h reading. No corrosion was observed at any of the measuring intervals. In conclusion, FAT 93503/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

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study Disperse Red 302 does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.