Registration Dossier

Administrative data

Description of key information

Skin Irritation

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, no severe skin irritation effects were estimated when the test chemical was exposed to rabbit skin. Hence, the test chemical can be considered to be not irritating to skin.

Eye Irritation

Based on the available data for the test chemicals and applying the weight of evidence approach, the test chemical was not irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, test chemical 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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Weight of evidence approach based on various test chemicals
Justification for type of information:
Weight of evidence approach based on various test chemicals
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on various test chemicals
Principles of method if other than guideline:
Weight of evidence approach based on various test chemicals
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
other: 1. no data available; 2. occlusive; 3. Entire inner surface of one ear
Preparation of test site:
other: 1. no data available; 2. intact and slightly scarified skin; 3. colony of rabbits that had genetically good ears and which were free from mites were used for the assay
Vehicle:
other: 1. no data available; 2. 50 % polyethylene glycol trituration (PEG 400); 3. the test chemical was mixed with propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated
Controls:
not specified
Amount / concentration applied:
1. no data available
2. 500 mg (0.5g) in 50 % polyethylene glycol trituration (PEG 400)
3. the test chemical was mixed with propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration).
Duration of treatment / exposure:
1. no data available
2. 24 hours
3. once for five days per week for two weeks
Observation period:
1. no data available
2. 24 and 72 hours
3. 2 weeks
Number of animals:
1. no data available
2. 6 rabbits
3. Three rabbits
Details on study design:
The data is based on weight of evidence approach based on various test chemicals
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
14 d
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation observed
Interpretation of results:
other: not irritating
Conclusions:
Based on the available data for the test chemicals and applying the weight of evidence approach, the test chemical was not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.
Executive summary:

The skin irritation potential of the test chemical was assessed based on the available results from the various test chemicals. The studies include experimental as well as estimated results for the test chemicals.

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, no severe skin irritation effects were estimated when the test chemical was exposed to rabbit skin. Hence, the test chemical can be considered to be not irritating to skin.

The estimated result is supported by the skin irritation study conducted on six rabbits to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the

test chemical on the skin of the rabbits. The test was performed according to procedure adopted was 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).

Six rabbits (3/sex) of 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 chemical was applied to the each side at a dose of 500 mg (0.5g) in 50 % polyethylene glycol trituration (PEG 400). The gauze patches were removed 24 hours after the application.The reaction of the skin was appraised upon removal and after 72 hours.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. Compound producing combined averages (primary irritation indexes) of 2 or less were only mildly irritating; whereas those with indexes from 2 to 5 were moderate irritants, and those with scores above 6 were considered severe irritants.

The primary irritation index of the test chemical was estimated to be 0. Hence, the test chemical was considered to be not irritating to the rabbits’ skin.

These results are further supported by a study performed using a single rabbit ear to indicate the Comedogenicity and irritancy of the test chemical. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control.

The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

 0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

The test chemical falls under Grade 0 (no irritation observed).Hence it can be concluded that the test chemical was not irritating to rabbit ears.

Based on the available data for the test chemicals and applying the weight of evidence approach, the test chemical was not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Weight of evidence approach based on various test chemicals
Justification for type of information:
Weight of evidence approach based on various test chemicals
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on various test chemicals
Principles of method if other than guideline:
Weight of evidence approach based on various test chemicals
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
1. 0.1g of the test chemical
2. 2 instillation of 0.2 ml of a 10% aqueous suspension of the test chemical
Duration of treatment / exposure:
1. single
2. 5 times per week for 4 weeks.
Observation period (in vivo):
1. 24 hours and after 2,3,4 and 7 days
2. 4 weeks
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
1. 6(3/sex)
2. no data available
Details on study design:
The data is based on weight of evidence approach based on various test chemicals
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation observed
Interpretation of results:
other: not irritating
Conclusions:
Based on the available data for the test chemicals and applying the weight of evidence approach, the test chemical was not irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.
Executive summary:

The eye irritation potential of the test chemical was assessed based on the available results from the various test chemicals.

An ocular irritation study was conducted to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the test chemical on the eye of the rabbits. The study was performed according to 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).

About (0.1g) of the test chemical were introduced into the conjunctival sac of the left eye of six rabbits (3/sex) of Russian breed 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.

The primary irritation index of the test chemical was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae. Hence, the test chemical was considered to be not irritating to the rabbits’ eye.

This is supported by the results of another study performed to investigate the local eye irritative effects caused when the rabbits were exposed to the test chemical.

 Each rabbit received 2 installation of 0.2 ml of a 10% the test chemical aqueous suspension into the conjunctival sac of rabbits 5 times per week for 4 weeks.

The chemical produced only minimal irritative effects after 2 hours which could not confirmed the irritation potential. Hence, on the basis of findings, the test chemical can be considered as not irritating to the rabbits’ eye.

Based on the available data for the test chemicals and applying the weight of evidence approach, the test chemical was not irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.a

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 potential of the test chemical was assessed based on the available results from the various test chemicals. The studies include experimental as well as estimated results for the test chemicals.

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, no severe skin irritation effects were estimated when the test chemical was exposed to rabbit skin. Hence, the test chemical can be considered to be not irritating to skin.

The estimated result is supported by the skin irritation study conducted on six rabbits to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the test chemical on the skin of the rabbits. The test was performed according to procedure adopted was 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).

Six rabbits (3/sex) of 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 chemical was applied to the each side at a dose of 500 mg (0.5g) in 50 % polyethylene glycol trituration (PEG 400). The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and after 72 hours. 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. Compound producing combined averages (primary irritation indexes) of 2 or less were only mildly irritating; whereas those with indexes from 2 to 5 were moderate irritants, and those with scores above 6 were considered severe irritants.

The primary irritation index of the test chemical was estimated to be 0. Hence, the test chemical was considered to be not irritating to the rabbits’ skin.

These results are further supported by a study performed using a single rabbit ear to indicate the Comedogenicity and irritancy of the test chemical. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control.

The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

 0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough.

The test chemical falls under Grade 0 (no irritation observed).Hence it can be concluded that the test chemical was not irritating to rabbit ears.

Based on the available data for the test chemicals and applying the weight of evidence approach, the test chemical was not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Eye Irritation:

The eye irritation potential of the test chemical was assessed based on the available results from the various test chemicals.

An ocular irritation study was conducted to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the test chemical on the eye of the rabbits. The study was performed according to 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).

About (0.1g) of the test chemical were introduced into the conjunctival sac of the left eye of six rabbits (3/sex) of Russian breed 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.

The primary irritation index of the test chemical was estimated to be 0 for the cornea, 0 for the iris and 0 for the conjunctivae. Hence, the test chemical was considered to be not irritating to the rabbits’ eye.

This is supported by the results of another study performed to investigate the local eye irritative effects caused when the rabbits were exposed to the test chemical.

Each rabbit received 2 instillation of 0.2 ml of a 10% aqueous suspension of the test chemical into the conjunctival sac of rabbits 5 times per week for 4 weeks.

The chemical produced only minimal irritative effects after 2 hours which could not confirmed the irritation potential. Hence, on the basis of findings, the test chemical can be considered as not irritating to the rabbits’ eye.

Based on the available data for the test chemicals and applying the weight of evidence approach, the test chemical was not irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Justification for classification or non-classification

The results of the experimental studies from the various test chemicals indicate a possibility thatthe test chemicalcan be not irritating to skin and eyes.

Hence, by applying the weight of evidence approach,the test chemical can be considered to be not irritating to skin and eyes. It can be classified under the category “Not Classified” as per CLP regulation.