Registration Dossier

Administrative data

Description of key information

FAT 40069/A 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:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959) of the US Association of Food and Drug Official (AFDO).
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Russian breed
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.5 to 2 kgs
- Housing: In order to prevent injuries by bites the rabbits were kept separately in V2A wire mesh cages
- Diet (e.g. ad libitum): ad libitum.
- Water (e.g. ad libitum): ad libitum.
Type of coverage:
occlusive
Preparation of test site:
shaved
Remarks:
on the whole back and flanks two days before treatment with an electric clipper
Vehicle:
other: PEG 400 (Polyethylene glycol)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
FAT 40069/A was applied to each side in quantities of 0.5 g. Before application a 50 % polyethylene glycol trituration (PEG 400) was made.
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6 rabbits (3 males and 3 females)
Details on study design:
Rabbits 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. 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, on the basis of the following evaluation scheme.

SCORING SYSTEM:

Erythema and Eschar Formation
- No erythema: 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 males and 3 females
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks:
Intact Skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0.5
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
None
Other effects:
None

Evaluation of the skin reactions:

Animal No. / Sex Skin Reaction 24 hours after application 72 hours after application
Intact skin sacrificed skin Intact skin sacrificed skin
1/M Erythema 0 0 0 0
Oedema 0 1 0 0
2/M Erythema 0 0 0 0
Oedema 2 2 0 1
3/M Erythema 0 0 0 0
Oedema 0 1 0 0
4/F Erythema 0 0 0 0
Oedema 0 0 0 0
5/F Erythema 0 0 0 0
Oedema 0 2 0 0
6/F Erythema 0 0 0 0
Oedema 1 1 0 0
Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40069/A is considered as non-irritant to the rabbit skin.
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 40069/A, on the skin of the rabbits according to the "Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959) of the US Association of Food and Drug Official (AFDO). Six rabbits (3 males and 3 females), Russian breed, 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 40069/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. In conclusion, The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 0.5. FAT 40069/A is to be considered as a 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:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: The procedure adopted was the technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Russian breed
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: V2A wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 g of the test substance
Duration of treatment / exposure:
One application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6 rabbits (3 males and 3 females)
Details on study design:
Amounts 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 on the basis of the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.

SCORING SYSTEM:
Cornea
A. Opacity-degree of density (area most dense taken for reading)
- No opacity: 0
- Scattered or diffuse area, details of iris clearly visible: 1
- Easily discernible translucent areas, details of iris slightly obscured: 2
- Opalescent areas, no details of iris visible, size of pupil barely discernible: 3
- Opaque, iris invisible: 4
B. Area of cornea involved
- One quarter (or less) but not zero: 1
- Greater than one quarter, but less than half: 2
- Greater than half, but less than three quarters: 3
- Greater than three quarters, up to whole area: 4
Total maximum = 80 (A x B x 5)

Iris
A. Values
- Normal: 0
- Folds above normal, congestion, swelling, circumcorneal injection (any or all 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
A x 5

Conjunctivae
A. Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
- Vessels normal: 0
- Vessels definitely injected above normal: 1
- More diffuse, deeper crimson red, individual vessels not easily discernible: 2
- Diffuse beefy red: 3
B. Chemosis
- No swelling: 0
- Any swelling above normal (includes nictitating membrane): 1
- Obvious swelling with partial eversion of lids: 2
- Swelling with lids about half closed: 3
- Swelling with lids about half closed to completely closed: 4
C. Discharge
- No discharge: 0
- Any amount different from normal (does not include small amounts observed in inner canthus of normal animals): 1
- Discharge with moistening of the lids and hairs just adjacent to lids: 2
- Discharge with moistening of the lids and hairs, and considerable area around the eye: 3
(A + B + C) x 2 Total maximum = 20

The total maximum is 80 for the cornea, 10 for the iris and 20 for the conjunctivae.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 females (eyes rinsed)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Basis:
animal #5
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
cornea opacity score
Basis:
animal #6
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
eyes rinsed
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
eyes rinsed
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
eyes rinsed
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal #4
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
not fully reversible within: 7d
Irritation parameter:
conjunctivae score
Basis:
animal #5
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7d
Irritation parameter:
conjunctivae score
Basis:
animal #6
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
eyes rinsed
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
eyes rinsed
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
eyes rinsed
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal #4
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
animal #5
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
animal #6
Remarks:
eyes not rinsed
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 female eyes rinsed and 3 female eyes not rinsed
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The results of the eye irritation test are summarized in tables 1 and 2. The total maximum is 80 for the cornea, 10 for the iris and 20 for the conjunctivae. The irritation index was found to be 10.8 for the cornea, 0 for the iris and 6.9 for the conjunctivae.

Eyes rinsed:

Days after application Rabbit 1 Female Rabbit 2 Female Rabbit 3 Female
Cornea Iris Conjuct. Cornea Iris Conjuct. Cornea Iris Conjuct.
1 0 0 10 0 0 10 0 0 12
2 0 0 6 0 0 10 0 0 10
3 0 0 0 0 0 0 0 0 0
4 0 0 0 0 0 0 0 0 0
7 0 0 0 0 0 0 0 0 0

Eyes not rinsed:

Days after application Rabbit 4 Male Rabbit 5 Male Rabbit 6 Male
Cornea Iris Conjuct. Cornea Iris Conjuct. Cornea Iris Conjuct.
1 20 0 18 10 0 16 30 0 18
2 30 0 12 5 0 12 45 0 12
3 40 0 12 0 0 10 45 0 10
4 30 0 8 0 0 6 40 0 6
7 20 0 8 0 0 0 10 0 0

Data represent values of calculated primary eye irritation index. Eyes not rinsed should not be taken into account for the overall hazard assessment.

Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40069/A is to be considered as a non-irritant to the eye of rabbits.
Executive summary:

A study was performed to determine the eye irritation potential of FAT 40069/A on rabbits according to the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). The substance was tested on 6 rabbits (3 males/3 females) of the Russian breed and only rabbits showing normal ophthalmic findings were included in the test. Amounts 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 primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 10.8 for the cornea, 0 for the iris and 6 .9 for the conjunctivae. The effects were observed to be completely reversible by the end of Day 7. FAT 40069/A is to be considered as a non-irritant to the eye of rabbits.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A study was carried out to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound, FAT 40069/A, on the skin of the rabbits according to the "Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959) of the US Association of Food and Drug Official (AFDO). The primary irritation index as the measure of the acute irritation to the skin of rabbits was found to be 0.5. The effects were observed to be completely reversable by the end of Day 7. FAT 40069/A is to be considered as a non-irritant to the skin of rabbits.

A study was performed to determine the eye irritation potential of FAT 40069/A in rabbits according to the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). The primary-irritation index, which serves as a measure of the acute irritation provoked by the substance, was found to be 10.8 for the cornea, 0 for the iris and 6 .9 for the conjunctivae.

The effects were observed to be completely reversible by the end of Day 7. FAT 40069/A is to be considered as a non-irritant to the eye of rabbits


Justification for selection of skin irritation / corrosion endpoint:
Basic data given, acceptable for assessment

Justification for selection of eye irritation endpoint:
Basic data given, acceptable for assessment

Justification for classification or non-classification

Based on the above stated assessment, FAT 40069/A is to be considered as a non-irritant to the skin and eyes of rabbits according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council.