Registration Dossier

Administrative data

Description of key information

Skin Irritation:

The skin irritation study of test chemical was conducted in Russian breed rabbits. The test chemical was applied to each side in quantities of 0.5 g (500mg). Before application a 50 % polyethylene glycol trituration (PEG 400) was made. The gauze patches were removed 24 hours after the application. The primary irritation index of test chemical was evaluated to be 0.0 out of maximum score of 8. Since the treated rabbits did not develop any signs of skin irritation, the test chemical was considered to be not irritating to the skin. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye Irritation:

An eye irritation study of test chemical was conducted in six (3 males/3 females) Russian breed rabbits. Amounts of 0.1 g of the test substance were introduced into the conjunctival sac of the left eye with a spatula. Since there were no evidence of any signs of ocular lesions, the test chemical was considered to be not irritating to the rabbits’ eye. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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:
May 1974
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental report
Qualifier:
according to guideline
Guideline:
other: The patch-test 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).
Principles of method if other than guideline:
The skin irritation study of test chemical was conducted in Russian breed rabbits.
GLP compliance:
yes
Species:
rabbit
Strain:
other: Russian breed
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Six rabbits (3 males/3 females) of the Russian breed
- Weight at study initiation: 1.5 to 2 kgs
- Housing: V2A wire cages
- Diet (e.g. ad libitum): food (NAFAG, Gossau SG, rabbit food)
- Water (e.g. ad libitum): water ad libitum
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 g (500mg)
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6 (3 males/3 females)
Details on study design:
TEST SITE
- Area of exposure: back
- % coverage: 2.5*2.5 cm
- Type of wrap if used: 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.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data available
- Time after start of exposure: no data available

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : The reaction of the skin was appraised upon removal and 72 hours after it.

SCORING SYSTEM:
- Method of calculation: The primary irritation index as the measure of the acute skin irritation provoked by the substance is defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compounds producing combined averages (primary irritation indexes) of 2 or less are only mildly irritating; whereas those with indexes from 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0
Max. score:
8
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Not Irritating to skin
Other effects:
No Data Available
Interpretation of results:
other: Not irritating
Conclusions:
The primary irritation index as the measure of the acute irritation to the skin of rabbits was observed to be 0. Therefore the test chemical can be considered as non-irritant to the skin of rabbits.
Executive summary:

The skin irritation study of test chemical was conducted in Russian breed rabbits. 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. The test chemical was applied to each side in quantities of 0.5 g (500mg). 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. The primary irritation index as the measure of the acute skin irritation provoked by the substance was defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compounds producing combined averages (primary irritation indexes) of 2 or less are only mildly irritating; whereas those with indexes from 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants.

The primary irritation index of test chemical was evaluated to be 0.0 out of maximum score of 8. Since the treated rabbits did not develop any signs of skin irritation, the test chemical was considered to be not irritating to the 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:
May 1974
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental report
Qualifier:
according to guideline
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).
Principles of method if other than guideline:
An eye irritation study of test chemical was conducted in Russian breed rabbits.
GLP compliance:
yes
Species:
rabbit
Strain:
other: Russian breed
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: The substance was tested on 6 rabbits (3 males/3 females) of.the Russian breed, which were kept separately in V2A wire cages
- Diet (e.g. ad libitum): fed on NAFAG, Gossau SG, rabbit food and water ad libitum
- Only rabbits showing normal ophthalmic findings were included in the test.
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
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 treated eyes of three rabbits were each rinsed with 10 ml lukewarm water about 30 seconds after treatment
Observation period (in vivo):
The reactions were appraised with a slit-lamp after 24 hours and after 2, 3, 4 and 7 days
Number of animals or in vitro replicates:
6 (3 males/3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes of three rabbits were each rinsed with 10 ml lukewarm water about 30 seconds after treatment.

Procedure : 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.
TOOL USED TO ASSESS SCORE: slit lamp.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
110
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The irritation index was found to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae.
The total maximum is 80 for the cornea, 10 for the iris and 20 for the conjunctivae

 

 

 

 

Interpretation of results:
other: Not irritating
Conclusions:
The primary-irritation index (overall irritation score), which serves as a measure of the acute irritation provoked by the substance, was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae. Therefore the test chemical was considered as non-irritant to the eye of rabbits.
Executive summary:

An eye irritation study of test chemical was conducted in six (3 males/3 females) Russian breed rabbits. The study was performed as per 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). 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 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 total maximum scores are as follows: 80 for the cornea, 10 for the iris and 20 for the conjunctivae. The irritation index was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae out of maximum score of 110. Since there were no evidence of any signs of ocular lesions, the test chemical was considered to be not irritating to the rabbits’ eye.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

The skin irritation study of test chemical was conducted in Russian breed rabbits. 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. The test chemical was applied to each side in quantities of 0.5 g (500mg). 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. The primary irritation index as the measure of the acute skin irritation provoked by the substance was defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compounds producing combined averages (primary irritation indexes) of 2 or less are only mildly irritating; whereas those with indexes from 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants.The primary irritation index of test chemical was evaluated to be 0.0 out of maximum score of 8. Since the treated rabbits did not develop any signs of skin irritation, the test chemical was considered to be not irritating to the skin.

 

Eye Irritation:

An eye irritation study of test chemical was conducted in six (3 males/3 females) Russian breed rabbits.  The study was performed as per 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).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 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 total maximum scores were as follows: 80 for the cornea, 10 for the iris and 20 for the conjunctivae.The irritation index was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae out of maximum score of 110. Since there were no evidence of any signs of ocular lesions, the test chemical was considered to be not irritating to the rabbits’ eye.

Justification for classification or non-classification

The results obtained from these studies indicates that the test chemical is unlikely to cause skin and eye irritation. Hence the test chemical can be classified under the category “Not Classified” for skin and eye as per CLP.