Registration Dossier

Administrative data

Description of key information

Skin Irritation

The results from these experimental studies lead to a possibility of the test chemical being not irritating to skin. By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, the test chemical can be classified under the category “Not Classified”.

Eye irritation

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also tend to behave in a similar

manner. Therefore, the test chemical was estimated to be not irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, the 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. The study 2,3,4 are referred as study 1,2,3
GLP compliance:
not specified
Species:
other: 1. rat; 2,3. rabbits
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
other: 1,3. undiluted; 2. propylene glycol at a 9 to 1 dilution
Controls:
not specified
Amount / concentration applied:
1. 200,100, 2000 mg/kg body weight
2. 10% concentration in propylene glycol at a 9 to 1 dilution
3. 0.5 ml undiluted
Duration of treatment / exposure:
1. 24 hours
2. 5 days per week for 2 weeks
3. not specified
Observation period:
1. 14 days
2. 14 days
3. 24, 48 and 72 hours
Number of animals:
1. 5 female rats
2. colonies of rabbits
3. 6 rabbits
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:
The results from these experimental studies lead to a possibility of the test chemical being not irritating to skin. By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, the test chemical can be classified under the category “Not Classified”.
Executive summary:

Various studies have been summarized to determine the extent of dermal irritation caused by the test chemical in living organisms. These results include in vivo experimental studies performed on rabbits, rats for the various test chemicals.

A study was designed and conducted to determine the dermal reaction profile of the test chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. 5 female nulliparous and non-pregnant Sprague Dawley rats were used for the study.

In the dose range finding study a single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered with the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours.

As the dose range finding study revealed no mortality or clinical signs at the maximum dose of 2000 mg/kg, the main study was initiated with two additional animals. The animals were administered with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals.

The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were found at the end of 14 days observation period after patch removal.

Hence, it was concluded that the test chemical was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and classified as “Category- Not Classified” as per CLP Classification.

This is supported by the results of a study performed on a 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). Colonies 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.

The above results are supported by a study performed to assess the skin irritation potential of the test chemical in rabbits. The test was performed according to the procedure outlined in the Journal Officiel de la Republique Francaise.

0.5 ml undiluted test chemical was applied under occlusion to the clipped skin of 6 albino rabbits. The reactions were scored at 24, 48 and 72 hours.

The Primary Irritation Index of undiluted test chemical was 0.0. Hence, the test chemical can be considered not irritating to rabbit skin.

The results from these experimental studies lead to a possibility of the test chemical being not irritating to skin. By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, the 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 read across chemicals
Justification for type of information:
Weight of evidence approach based on read across chemicals
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on read across chemicals
Principles of method if other than guideline:
Weight of evidence approach based on read across chemicals. The study 2,3 are referred as study 1,2
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
no data available
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1, 2, and 3 days
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
6
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 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 various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also tend to behave in a similar manner. Therefore, the test chemical was estimated to be not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation,the test chemicalcan be classified under the category “Not Classified”.
Executive summary:

Various studies have been summarized to determine the degree of ocular damage caused by the test chemical in living organisms. These results include in vivo experimental studies performed on rabbits for the various test chemicals.

 

An eye irritation study was carried out on rabbits to assess the irritation potency of the structurally similar read across chemical. 0.1 ml dose of the test chemical was placed into the conjunctival sac of one eye of 6 New Zealand White rabbits. The contralateral eye of each rabbit was considered the control. Observations were recorded 1, 2, and 3 days after the introduction of the test ingredient. The reactions were graded as determined by the Consumer Product Safety Act regulations. None of the six rabbits tested had any irritation of the cornea or iris. Four rabbits had slight conjunctivitis. Three of these continued to have the condition beyond the observation period, while one rabbit had conjunctival redness only on the first day of testing.

The Draize Maximum average score was calculated to be 2.3. The test chemical was considered to be not irritating to rabbit eyes.

The above results are supported by the experimental study for the test chemical. 0.1 ml undiluted test chemical was placed into the conjunctival sac of one eye of 6 [3 male and 3 female] New Zealand White rabbits. The treated eye received no further treatment. Observations were recorded 1, 2, and 3 days after the introduction of the test ingredient.

No corneal, conjunctival, or iridial irritation was noted over a 3-day observation period. Hence, the test chemical was considered to be not irritating to rabbit eyes.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also tend to behave in a similar manner. Therefore, the test chemical was estimated to be not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation,the test chemicalcan be classified under the category “Not Classified”.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

Various studies have been summarized to determine the extent of dermal irritation caused by the test chemical in living organisms. These results include in vivo experimental studies performed on rabbits, rats for the various test chemicals.

A study was designed and conducted to determine the dermal reaction profile of the test chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. 5 female nulliparous and non-pregnant Sprague Dawley rats were used for the study.

In the dose range finding study a single dose of 200 mg/kg body weight of the test item was administered to 1 female animal. No death or clinical signs of toxicity was observed during first 48 hours, hence, additional 1 female animal was administered with the dose of 1000 mg/kg body weight. Administration of 1000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours, hence, additional 1 female animal was administered at the dose of 2000 mg/kg body weight. Administration of 2000 mg/kg body weight did not reveal any clinical signs of toxicity or death during first 48 hours.

As the dose range finding study revealed no mortality or clinical signs at the maximum dose of 2000 mg/kg, the main study was initiated with two additional animals. The animals were administered with a dose of 2000 mg/kg body weight in sequential manner at 48 hours intervals.

The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were found at the end of 14 days observation period after patch removal.

Hence, it was concluded that the test chemical was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and classified as “Category- Not Classified” as per CLP Classification.

This is supported by the results of a study performed on a 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). Colonies 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.

The above results are supported by a study performed to assess the skin irritation potential of the test chemical in rabbits. The test was performed according to the procedure outlined in the Journal Officiel de la Republique Francaise.

0.5 ml undiluted test chemical was applied under occlusion to the clipped skin of 6 albino rabbits. The reactions were scored at 24, 48 and 72 hours.

The Primary Irritation Index of undiluted test chemical was 0.0. Hence, the test chemical can be considered not irritating to rabbit skin.

The results from these experimental studies lead to a possibility of the test chemical being not irritating to skin. By applying the weight of evidence approach, the test chemical can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, the test chemical can be classified under the category “Not Classified”.

Eye Irritation

Various studies have been summarized to determine the degree of ocular damage caused by the test chemical in living organisms. These results include in vivo experimental studies performed on rabbits for the various test chemicals.

An eye irritation study was carried out on rabbits to assess the irritation potency of the structurally similar read across chemical. 0.1 ml dose of the test chemical was placed into the conjunctival sac of one eye of 6 New Zealand White rabbits. The contralateral eye of each rabbit was considered the control. Observations were recorded 1, 2, and 3 days after the introduction of the test ingredient. The reactions were graded as determined by the Consumer Product Safety Act regulations. None of the six rabbits tested had any irritation of the cornea or iris. Four rabbits had slight conjunctivitis. Three of these continued to have the condition beyond the observation period, while one rabbit had conjunctival redness only on the first day of testing.

The Draize Maximum average score was calculated to be 2.3. The test chemical was considered to be not irritating to rabbit eyes.

The above results are supported by the experimental study for the test chemical. 0.1 ml undiluted test chemical was placed into the conjunctival sac of one eye of 6 [3 male and 3 female] New Zealand White rabbits. The treated eye received no further treatment. Observations were recorded 1, 2, and 3 days after the introduction of the test ingredient.

No corneal, conjunctival, or iridial irritation was noted over a 3-day observation period. Hence, the test chemical was considered to be not irritating to rabbit eyes.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also tend to behave in a similar

manner. Therefore, the test chemical was estimated to be not irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, the 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 that the test chemical can be not irritating to skin and eyes.

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