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Description of key information

Test substance is to be considered as a non-irritant to the skin and eye of rabbits.

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:
27 April 1994 to 22 June 1994
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:
other: Annex V, part B of Council Directive 79/831/EEC (Commission Directive 92/69/EEC of July 31, 1992)
GLP compliance:
yes
Specific details on test material used for the study:
- Source and lot/batch number of test material: P.04.36
- Expiration date of the lot/batch: 11/98
- Appearance: Solid
- Storage conditions: room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GMBH Chemisch-Pharmazeutische Fabrik D-88397 Biberach
- Weight at study initiation: 2230 to 2330 g
- Housing: metal cages
- Diet: rabbit pellet - Nafag No. 814, Gossau, Switzerland ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.5 g of the test article
Duration of treatment / exposure:
4 h
Observation period:
The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system
Number of animals:
3 male rabbits
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 animal
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 animal
Time point:
24/48/72 h
Score:
0
Max. score:
4

The skin reactions observed were reversible until the end of the observation period.

Individual skin reaction scores:

 

Mean Reaction Score

Time after exposure

hours

Erythema

Edema

 

Animal 1

Animal 2

Animal 3

Animal 1

Animal 2

Animal 3

24

1

0

1

0

0

0

48

1

0

0

0

0

0

72

0

0

0

0

0

0

 

Because the mean values of the recordings 24 t o 72 hours after application are below the threshold of significance (2 score for erythema or edema) FAT 40066/C can be classified as non-irritant according to council Directive 67/548/EEC, adapted to technical progress by Commission Directive 93/21/EEC.

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40066/C is to be considered as a non-irritant to the skin of rabbits.
Executive summary:

A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40066/C, on the skin of the New Zealand White rabbits. The study was carried out according to OECD guideline 404. An area of at least 36 cm2 was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm2) 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 cm2. A control gauze patch was applied to the contralateral flank. Before application both patches were moistened with distilled water. The patches were loosely covered with an aluminum foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape.

One animal from treatment group showed erythema till 48 h and one another animal till 24h observation perion. There were no edema observed.

Because the mean values of the recordings 24 t o 72 hours after application are below the threshold of significance FAT 40066/C can be clasified as non-irritant to the skin of rabbits.

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:
27 April 1994 to 22 June 1994
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:
other: part B of Council Directive 79/831/EEC (Commission Directive 92/69/EEC of July 31, 1992
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
- Source and lot/batch number of test material: P.04.36
- Expiration date of the lot/batch: 11/98
- Appearance: Solid
- Storage conditions: room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GMBH Chemisch-Pharmazeutische Fabrik D-88397 Biberach
- Weight at study initiation: 2050 to 2830 g.
- Housing: metal cages
- Diet:: standard rabbit pellet - Nafag No. 814, Gossau, Switzerland ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day.
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 ml (82 mg) of FAT 40066/C was placed into the conjunctival sac of the left eye of each animal.
Duration of treatment / exposure:
The lids were then held together for about one second in order to prevent loss of the test article.
Observation period (in vivo):
24, 48, and 72 h
Number of animals or in vitro replicates:
3 (one female and two male rabbits)
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:
mean
Remarks:
6 animal
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
6 animal
Time point:
24/48/72 h
Score:
0
Max. score:
4

Individual eye score:

Animal No.

Time point

Corneal opacity

Iris

Conjunctiva

 

Redness

Chemosis

1

After 24 h

0

0

1

0

2

0

0

1

0

3

0

0

1

0

1

After 48 h

0

0

0

0

2

0

0

0

0

3

0

0

0

0

1

After 72 h

0

0

0

0

2

0

0

0

0

3

0

0

0

0

 

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40066 is considered to be a non-irritant to the eyes.
Executive summary:

In a study performed according to OECD guideline 405 to determine the eye irritation potential of FAT 40066/C, the test substance was instilled in the eyes of 1 male and 2 female rabbits and observations for irritation were recorded at the time points of 24 hours, 48 hours 72 hours. 0.1 ml (82 mg) of FAT 40066/C 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.

The corneal opacity, iiris and chemosis score was "0" while redness was seen in all animals at 24 h but get reversed within 48 h. There were no mortality or adverse effects were seen in the study.

Under the experimental conditions FAT 40066/C can be classified as non-irritant according to Council Directive 67/548/EEC, adapted to technical progress by Commission Directive 93/21/EEC.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:


A study was performed to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40066/C, on the skin of the New Zealand White rabbits. The study was carried out according to OECD guideline 404.An area of at least 36 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm²) 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 cm². A control gauze patch was applied to the contralateral flank. Before application both patches were moistened with distilled water. The patches were loosely covered with an aluminum foil (approx. 36 cm2) and held in place for 4 hours by an adhesive tape. One animal from treatment group showed erythema till 48 h and one another animal till 24 h observation period. There were no edema observed. Because the mean values of the recordings 24 to 72 hours after application are below the threshold of significance FAT 40066/C can be classified as non-irritant to the skin of rabbits. 


In another supporting study, the skin irritation study with FAT 40066/A was carried out in Russian breed rabbits according to appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). Six rabbits (3 males/3 females) of the Russian breed, weighing 1.5 to 2 kgs, were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape. FAT 40066/A was applied to each side in quantities of 0.5 g. Before application a 50 % polyethylene glycol trituration (PEG 400) was made. The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and 72 hours after it. There were no erythema observed during the observation period while edema was observed in 5 animals which was reversed within 72 h. So, based on the study findings, FAT 40066/A is considered as non-irritant to skin of rabbits.


Eye Irritation:


In a study performed according to OECD guideline 405 to determine the eye irritation potential of FAT 40066/C, the test substance was instilled in the eyes of 1 male and 2 female rabbits and observations for irritation were recorded at the time points of 24 hours, 48 hours, and 72 hours. 0.1 ml (82 mg) of FAT 40066/C 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. The corneal opacity, iris and chemosis score was "0" while redness was seen in all animals at 24 h but get reversed within 48 h. There were no mortality or adverse effects seen in the study. Under the experimental conditions FAT 40066/C can be classified as non-irritant according to Council Directive 67/548/EEC, adapted to technical progress by Commission Directive 93/21/EEC.


In another supporting study, carried out basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO in Russian breed rabbits, six animals (3 male and 3 female) were used in the study. Total of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. After application, the 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 reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days. The corneal opacity, iris and chemosis score was "0" in all animals including eyes rinsed and not rinsed. Redness was seen in animals whose eyes were not rinsed but it got reversed after 48 h. So, based on the study results, FAT 40066/A is considered non-irritant to eyes of rabbit.

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study, the test substance does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 to be irritating to the skin as well eyes.

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