Registration Dossier

Administrative data

Description of key information

FAT 36038 is a non-irritant to the skin as well as to the eyes.

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:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- The albino rabbit is the recommended species for skin irritation/corrosion studies.
- Animal strain: New Zealand white rabbits (Chbb:NZW)
- Breeder: Dr. K. Thomae GMBH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Acclimatisation period: at least 5 days

Group size and husbandry
The test was performed on 3 male rabbits, checked for normal skin conditions, weighing between 2320 to 2530 g. The animals were housed individually in metal cages, identified by ear tattoo, kept at a constant room temperature of 20 ± 3 °C, at a relative humidity of 30-70 % and on a 12 hours light cycle day. The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland - and fresh water. All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer. Analytical results are available at the animal supply office. The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewaesserschütz) are available to CIBA-GEIGY Limited, as well as the results of inhouse chemical analysis by the analytical laboratories of the Pharmaceutical Division, CIBA-GEIGY Limited.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: 0.5 % (w/v) Carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80.
Controls:
other: The contrelateral flank of each rabbit served as control.
Amount / concentration applied:
0.5 g of FAT 36038/F
Duration of treatment / exposure:
4 hours
Observation period:
72 hours; the skin reactions were evaluated 1, 24, 48, 72 hours after removing the gauze patches.
Number of animals:
3 male rabbits
Details on study design:
An area of at least 36 sq cm was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 sq cm) bearing 0.5 g of the test article was applied to the right flank of each animal. The skin area exposed directly to the test article was approx. 6 sq cm.
A control gauze patch was applied to the contralateral flank. Before application both patches were moistened with 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80.

The patches were loosely covered with an aluminum foil (approx. 36 sq cm) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).
The animals were checked daily for systemic symptoms and mortality (only findings reported).
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system.

SCORING SYSTEM:
Erythema and eschar formation
- No e rythema 0
- Very slight erythema (barely perceptible) 1
- Well defined erythema 2
- Moderate to severe erythema 3
- Severe erythema (beet redness) to slight eschar formation ( injuries in depth) 4
Total possible erythema score 4


Edema formation
- No edema 0
- Very slight edema (barely perceptible) 1
- Slight edema (edges of area well defined by definite raising) 2
- Moderate edema (raised approximately 1 mm) 3
- Severe edema (raised more than 1 mm and extending beyond area of exposure) 4
Total possible edema score 4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 rabbits males
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: slight erythema reactions in one animal only when applied to the clipped albino rabbit skin. The reactions were observed only one hour after removing the bandages.
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits males
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Under the experimental conditions employed FAT 36038/F induced slight erythema reactions in one animal only when applied to the clipped albino rabbit skin. The reactions were observed only one hour after removing the bandages.
Because no reactions were observed at 24 hours to 72 hours after removing the bandages, the test was ended after the 72 hours evaluation.
Other effects:
None

Individual Skin Reaction Scores:

Animal No. ERYTHEMA EDEMA
567/M   CF/TF 547/M   CF/TF 573/M   CF/TF 567/M   CF/TF 547/M   CF/TF 573/M   CF/TF
After 1 hour 0/1 0/0 0/0 0/0 0/0 0/0
After 24 hours 0/0 0/0 0/0 0/0 0/0 0/0
After 48 hours 0/0 0/0 0/0 0/0 0/0 0/0
After 72 hours 0/0 0/0 0/0 0/0 0/0 0/0
Mean 24-72 hours 0/0 0/0 0/0 0/0 0/0 0/0

CF = Control Flank

TF = test Flank

M = Male

Body Weights (g)

Animal no. 567/M 547/M 573/M
At start of test 2530 2320 2500
After 3 days (end) 2620 2390 2590
Interpretation of results:
GHS criteria not met
Conclusions:
FAT 36038/F can be classified as non-irritant to skin.
Executive summary:

An acute skin irritiation / corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of FAT 36038/F on the albino rabbit skin. This test was based on the OECD Guideline No. 404, adopted by the OECD council, and 79/831/EEC (Commission May 12, 1981, adapted July 17, 1992 on Annex V, part B of Council Directive Directive 92/69/EEC of July 31, 1992).

Three male rabbits were used for the experiment. An area of at least 36 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch bearing 0.5 g of the test article was applied to the right flank of each animal. A control gauze patch was applied to the contralateral flank. Before application both patches were moistened with 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80.

The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system.

Under the experimental conditions employed FAT 36038/F induced slight erythema reactions in one animal only when applied to the clipped albino rabbit skin. The reactions were observed only one hour after removing the bandages.

Because the mean values of the recordings 24 to 72 hours after application are scored zero, FAT 36038/F can be classified as non-irritant.

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:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Chemisch-pharmazeutische Fabrik D-7950 Biberach/Riss
- Weight at study initiation: 2280 to 2370 g.
- Housing: housed individually in metal cages, identified by ear tattoo
- Diet: ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum fresh water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30-70 %
- Photoperiod: 12 hours light cycle day

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye of each rabbit remained untreated and served as a control.
Amount / concentration applied:
0.1 ml (62 mg) of FAT 36038/F was placed into the conjunctival sac of the left eye of each animal.
Duration of treatment / exposure:
One single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 females rabbits
Details on study design:
0.1 ml (62 mg) of FAT 36038/F was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article.
The right eye remained untreated and served as a control.
The animals were checked daily for systemic symptoms and mortality (only findings reported).
The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of FAT 36038/F according to the OECD scoring system.
In order to determine the reversibility of the eye reactions additional evaluations of the ocular reactions were needed in this study. A slit-lamp was used to facilitate the evaluation.

Scores for ocular lesions according to the OECD guideline 405:
*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 depended rugae , congestion , swelling, moderate circumcorneal hyperaemia, or injection , any of these or combination of any thereof, iris still reaction to light (sluggish reaction is positive): 1
- No reaction to light, haemmorrhage, gross destruction (any or all of these): 2

*CONJUNCTIVAE
Redness: (refers to palpebral and bulbar conjunctivae, cornea and iris)
- Blood vessels normal: 0
- Some blood vessels definitely hyperaemic (injected): 1
- Diffuse, crimson colour, individual vessels not easily discernible: 2
- Diffusy beefy red: 3

*Chemosis - lids and/or nictating membranes.
- No swelling: 0
- Any swelling above normal (includes nictating 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:
chemosis score
Basis:
mean
Remarks:
3 male rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24h
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
3 male rabbits
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 male rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 male rabbits
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24h
Irritant / corrosive response data:
Reactions were observed within 48 hours after instillation of the test article, the observation period was extended to 7 days to determine the reversibility of the eye reactions.
Other effects:
None

Individual eye scores.

 Animal N° 662/F     Cornea     Iris           Conjunctiva
   ce  te  ce  te     Redness ce te     Chemosisce te
 After 1 hr.  0  0  0  1  0  1  0  1
 After 24 hrs  0  0  0  0  0  1  0  0
 After 48 hrs  0  0  0  0  0  1  0  0
 After 72 hrs  0  0  0  0  0  0  0  0
 Mean 24 -72 hours  0  0  0  0  0  0.67  0  0
 After 7 days  0  0  0  0  0  0  0  0

 Animal N° 016/F     Cornea     Iris           Conjunctiva
   ce  te  ce  te     Redness ce te     Chemosisce te
 After 1 hr.  0  0  0  0  0  1  0  1
 After 24 hrs  0  0  0  0  0  1  0  0
 After 48 hrs  0  0  0  0  0  1  0  0
 After 72 hrs  0  0  0  0  0  0  0  0
 Mean 24 -72 hours  0  0  0  0  0  0.67  0  0
 After 7 days  0  0  0  0  0  0  0  0

 Animal N° 980/F     Cornea     Iris           Conjunctiva
   ce  te  ce  te     Redness ce te     Chemosisce te
 After 1 hr.  0  0  0  0  0  1  0  1
 After 24 hrs  0  0  0  0  0  1  0  0
 After 48 hrs  0  0  0  0  0  1  0  0
 After 72 hrs  0  0  0  0  0  0  0  0
 Mean 24 -72 hours  0  0  0  0  0  0.67  0  0
 After 7 days  0  0  0  0  0  0  0  0

ce = control eye

te = test eye

F = Female

Bodyweight (g):

 Animal N°  662/F 016/F  980/F 
 At start of test  2320 2370  2280 
 After 3 days  2400 2440  2400 
 After 7 days (end)  2510 2580  2590 

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 36038/F can be classified as non-irritant to rabbits eyes.
Executive summary:

The Acute Eye Irritation/Corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of FAT 36038/F in the albino rabbit eye and the associated mucous membranes. This test was based on the OECD Guideline No. 405, adopted February 24, 1987, by the OECD council, and on Annex V, part B of Council Directive 79/831/EEC (Commission Directive 92/69/EEC of July 31, 1992).

The lids were held together for about one second in order to prevent loss of the test article. The right eye remained untreated and served as a control. The animals were checked daily for systemic symptoms and mortality. The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of FAT 36038/F according to the OECD scoring system. A slit-lamp was used to facilitate the evaluation.

No corneal opacity was observed with any of the exposed animals. Slight irritation reactions with iris and chemosis was seen at 1 hour after the exposure, however these reactions were reversed by 24 hours. Slight conjunctival redness was seen in all three exposed animals, which was found to have reversed by 72 hours. Hence, based on the findings of the study, FAT 36038/F induced reactions of the iris and conjunctiva when instilled, into the conjunctival sac of albino rabbits' eyes. Because the mean values of the readings 24 to 72 hours after instillation are below the threshold of significance, FAT 36038/F can be classified as non-irritant.  

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Several studies conducted to assess the skin irritation potential of Disperse Violet 57 are available. In the study considered to be the key one, the procedure adopted was based on the OECD Guideline No. 404, adopted by the OECD council, and 79/831/EEC (Commission May 12, 1981, adapted July 17, 1992 on Annex V, part B of Council Directive 92/69/EEC of July 31, 1992). Six rabbits (3 males/3 females) of the Russian breed were used in the occlusive patch test. FAT 36038 was applied to each side in quantities of 0.5 g. Before application both patches were moistened with 0.5 % (w/v) carboxy methylcellulose in 0.1 % (w/v) aqueous polysorbate 80.The gauze patches were removed 2 4 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it. The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 0. Therefore, FAT 36038 is to be considered as non-irritant to the skin of rabbits. Several other studies available and included in the dossier also point to Disperse Violet 57 being a non-irritant to the skin.

Eye irritation:

Several studies conducted to assess the eye irritation potential of Disperse Violet 57 are available. To assess the acute eye irritation potential of FAT 36038/F when exposed to rabbit eye, the key study was based on the OECD Guideline No. 405, adopted February 24, 1987, by the OECD council, and on Annex V, part B of Council Directive 79/831/EEC (Commission Directive 92/69/EEC of July 31, 1992). The substance was tested on 6 rabbits (3 males/3 females) of the Russian breed. Amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, their eyelids were held open for a few seconds. The right eye served as a control. The treated eyes of three rabbits were each rinsed with 10 ml lukewarm water about 30 seconds after treatment.The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of FAT 36038/F according to the OECD scoring system. A slit-lamp was used to facilitate the evaluation. The primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae. Therefore, FAT 36038 is to be considered as a non-irritant to the eye of rabbits. The test results from several other in vivo studies performed to assess the irritation potential, also suggest Disperse Violet 57 to be non-irritant to eyes of rabbit.

Justification for classification or non-classification

Based on the findings of the skin and eye irritation studies, the test substance does not need to be classified according to Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.