Registration Dossier

Administrative data

Description of key information

Skin 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, it was considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, the test chemical cannot be classified for skin irritation.

 

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, it was considered to be not irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, the test chemical cannot be classified for eye irritation.

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:
experimental data from various test chemicals
Justification for type of information:
Data is summarized based on the available information from various test chemicals.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
WoE report is based on 2 skin irritation studies as- WoE-2 and WoE-3.
Skin irritation study of test chemical was conducted on rabbits to assess its skin irritating effects.
GLP compliance:
no
Species:
other: 2. rabbit 3. Human
Strain:
other: 2. New Zealand White 3. Not applicable
Details on test animals and environmental conditions:
2. - Age at study initiation: adult
3. No data available
Type of coverage:
other: 2. occlusive 3. not specified
Preparation of test site:
other: 2. shaved (intact or abraded sites) 3. not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
2. 500 mg
3. No data available
Duration of treatment / exposure:
2. 4 hours
3. No data available
Observation period:
2. 24, 48 and 72 hours
3. No data available
Number of animals:
2. 6 (3 males and 3 females)
3. No data available
Details on study design:
2. - Area of exposure: shaved backs
SCORING SYSTEM: According to the criteria laid down in EC regulation 1272/2008/EC
3. No data available
Irritation parameter:
overall irritation score
Remarks:
Erythema and edema
Basis:
mean
Time point:
24/48/72 h
Score:
1
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
2
Irritation parameter:
overall irritation score
Basis:
mean
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
3
Irritant / corrosive response data:
2. A slight erythema (scoring value 1) was observed in all animals at the 24-hour reading and was still persistent in 1 out of 3 animals treated onto an intact skin and 2 out of 3 animals treated on an abraded area at the 72-hour reading. Only one animal with intact skin showed a slight oedema (soring value 1) at the 72-hour reading.
3. No skin irritation was observed in treated humans.
Other effects:
No data
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 considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, the test chemical cannot be classified for skin irritation.
Executive summary:

In different studies, the given test chemical has been investigated for the dermal irritation potential to a greater or lesser extent. The studies are summarized as below -

 

The dermal irritation test was conducted to determine the skin irritation potential of the given test chemical in adult New Zealand white rabbits (3 males and 3 females) using the 49 CFR Part 173.240 method from the US Hazardous Materials Regulations. the test method used was comparable to the OECD 404 guideline issued in 1981. During the study, the rabbits were dermally exposed to 500 mg of test chemical for 4 hours on prepared shaved backs. 3 animals received the test chemical onto an intact skin while the remaining received the test chemical onto an abraded area. The test substance was held in contact with the skin by means of an occlusive dressing. Cutaneous reactions were observed 24, 48 and 72 hours after removal of the dressing. The test substance caused slight erythema (scoring value 1) in all animals at the 24-hour reading and was still persistent in 1 out 3 animals treated onto an intact skin and 2 out 3 animals treated on an abraded area at the 72-hour reading. Only one animal with intact skin showed a slight oedema (soring value 1) at the 72-hour reading. Thus, according to the criteria laid down in EC regulation 1272/2008/EC and based on the observations, the test chemical was considered as non-irritant to the skin.

 

The above study was supported with another skin irritation test performed to determine skin irritation potential of the given test chemical. There was no evidence of skin irritation, when the chemical was applied dermally on human skin. Thus, the test chemical was considered to be not irritating to the skin of humans.

 

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 behave in similar manner and was considered to be not irritating to skin. Thus it cannot be classified for skin irritation.

 

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:
experimental data from various test chemicals
Justification for type of information:
Data is summarized based on the available information from various test chemicals.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
WoE report is based on 2 eye irritation studies as- WoE-2 and WoE-3.
Eye irritation study of test chemical was conducted rabbits to assess its eye irritating effects.
GLP compliance:
not specified
Species:
rabbit
Strain:
other: 2. not specified 3. Himalayan
Details on test animals or tissues and environmental conditions:
2. not specified
3. TEST ANIMALS
- Age at study initiation:4.5 to 5.5 months old
-Weight at study initiation:2.4 to 2.5 kg body weight
Vehicle:
not specified
Controls:
other: 2. The other untreated eye served as control. 3. The left untreated eye served as control
Amount / concentration applied:
2. 100 mg
3. 100mg
Duration of treatment / exposure:
2. 72 hours
3. 1 hours
Observation period (in vivo):
2. 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions.
3. 24 hours
Number of animals or in vitro replicates:
2. 3 (Male/female)
3. Total = 3
Details on study design:
2. TEST SITE
- Area of exposure: one eye
REMOVAL OF TEST SUBSTANCE
- Washing (if done): For 6 rabbits, the eyes were not rinsed after administration of the test item while a washing procedure was applied for 3 other animals.
3. TEST SITE
- Area of exposure: conjunctival sac of the right of each rabbit
REMOVAL OF TEST SUBSTANCE
- Washing (if done): One hour after the instillation the eyes were rinsed with 20 ml aqueous (0.9%) sodium chloride solution.
Irritation parameter:
chemosis score
Remarks:
For rinsed eye
Basis:
mean
Time point:
72 h
Score:
0.33
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
2
Irritation parameter:
conjunctivae score
Remarks:
For rinsed eye
Basis:
mean
Time point:
72 h
Score:
0.89
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
2
Irritation parameter:
iris score
Remarks:
For rinsed eye
Basis:
mean
Time point:
72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
2
Irritation parameter:
cornea opacity score
Remarks:
For rinsed eye
Basis:
mean
Time point:
72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
2
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Reversibility:
fully reversible within: 24 hours
Remarks on result:
no indication of irritation
Remarks:
3
Irritant / corrosive response data:
2. For rinsed eye : 0.33 for chemosis, 0.89 for redness of the conjunctiva, 0 for iris lesions and 0 for corneal opacity. Redness and chemosis were fully reversible within 10 and 3 days respectively.
3. One hour after the instillation the conjunctiva in all animals was reddened. This hyperaemic reaction was reversible after 24 hours. The cornea and iris were not affected. Systemic intolerance reactions were not observed.
Other effects:
2. not specified
3. No data
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 considered to be not irritating to eyes. Comparing the above annotations with the criteria of CLP regulation, the test chemical cannot be classified for eye irritation.
Executive summary:

The ocular irritation potential was assessed based on the available results from the various test chemicals.These studies have been summarized as below -

 

An acute ocular irritation study was conducted for the given test chemical to determine the potential to induce eye irritation in 9 rabbits according to methods similar to OPPTS 870.2400 and OECD 405 guidelines. During the study, a single dose of 100 mg of the test chemical was instilled into one eye, the other eye was not treated and served as control. For 6 rabbits, the eyes were not rinsed after administration of the test chemical while a washing procedure was applied for 3 other animals. Ocular reactions were observed 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were noted for each animal. Mean scores calculated over 24, 48 and 72 hours for the 6 animals without rinsing were 0.33 for chemosis, 0.89 for redness of the conjunctiva, 0 for iris lesions and 0 for corneal opacity. Redness and chemosis were fully reversible within 10 and 3 days respectively. Washing procedure did not change the ocular reactions. Thus, under these experimental conditions, test chemical was considered as non-irritant when administered by ocular route to rabbits.

 

The above study was supported by the results of an eye irritation study conducted to determine the irritation potential of the test chemical on 3 Himalayan rabbits. In a study, 100 mg of test chemical was instilled into the conjunctival sac of the right eye of 3 Himalayan rabbits (4.5 to 5.5 months old; 2.4 to 2.5 kg body weight). One hour after the instillation the eyes were rinsed with 20 ml aqueous (0.9%) sodium chloride solution. The left eye served as control. One hour after the instillation the conjunctiva in all animals was reddened. This hyperaemic reaction was reversible after 24 hours. The cornea and iris were not affected. Systemic intolerance reactions were not observed. Since the observed effects were reversible within 24 hours, the chemical was considered as not irritating to the eyes.

 

Based on the available data, it can be concluded that the given test chemical cannot cause irritation to rodent’s eyes. Comparing the above annotations with the criteria of CLP regulation, the test chemical cannot be classified for eye irritation.

 

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

In different studies, the given test chemical has been investigated for the dermal irritation potential to a greater or lesser extent. The studies are summarized as below -

 

The dermal irritation test was conducted to determine the skin irritation potential of the given test chemical in adult New Zealand white rabbits (3 males and 3 females) using the 49 CFR Part 173.240 method from the US Hazardous Materials Regulations. the test method used was comparable to the OECD 404 guideline issued in 1981. During the study, the rabbits were dermally exposed to 500 mg of test chemical for 4 hours on prepared shaved backs. 3 animals received the test chemical onto an intact skin while the remaining received the test chemical onto an abraded area. The test substance was held in contact with the skin by means of an occlusive dressing. Cutaneous reactions were observed 24, 48 and 72 hours after removal of the dressing. The test substance caused slight erythema (scoring value 1) in all animals at the 24-hour reading and was still persistent in 1 out 3 animals treated onto an intact skin and 2 out 3 animals treated on an abraded area at the 72-hour reading. Only one animal with intact skin showed a slight oedema (soring value 1) at the 72-hour reading. Thus, according to the criteria laid down in EC regulation 1272/2008/EC and based on the observations, the test chemical was considered as non-irritant to the skin.

 

The above study was supported with another skin irritation test performed to determine skin irritation potential of the given test chemical. There was no evidence of skin irritation, when the chemical was applied dermally on human skin. Thus, the test chemical was considered to be not irritating to the skin of humans.

 

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 behave in similar manner and was considered to be not irritating to skin. Thus it cannot be classified for skin irritation.

 

Eye irritation

The ocular irritation potential was assessed based on the available results from the various test chemicals.These studies have been summarized as below -

 

An acute ocular irritation study was conducted for the given test chemical to determine the potential to induce eye irritation in 9 rabbits according to methods similar to OPPTS 870.2400 and OECD 405 guidelines. During the study, a single dose of 100 mg of the test chemical was instilled into one eye, the other eye was not treated and served as control. For 6 rabbits, the eyes were not rinsed after administration of the test chemical while a washing procedure was applied for 3 other animals. Ocular reactions were observed 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions. The values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were noted for each animal. Mean scores calculated over 24, 48 and 72 hours for the 6 animals without rinsing were 0.33 for chemosis, 0.89 for redness of the conjunctiva, 0 for iris lesions and 0 for corneal opacity. Redness and chemosis were fully reversible within 10 and 3 days respectively. Washing procedure did not change the ocular reactions. Thus, under these experimental conditions, test chemical was considered as non-irritant when administered by ocular route to rabbits.

 

The above study was supported by the results of an eye irritation study conducted to determine the irritation potential of the test chemical on 3 Himalayan rabbits. In a study, 100 mg of test chemical was instilled into the conjunctival sac of the right eye of 3 Himalayan rabbits (4.5 to 5.5 months old; 2.4 to 2.5 kg body weight). One hour after the instillation the eyes were rinsed with 20 ml aqueous (0.9%) sodium chloride solution. The left eye served as control. One hour after the instillation the conjunctiva in all animals was reddened. This hyperaemic reaction was reversible after 24 hours. The cornea and iris were not affected. Systemic intolerance reactions were not observed. Since the observed effects were reversible within 24 hours, the chemical was considered as not irritating to the eyes.

 

Based on the available data, it can be concluded that the given test chemical cannot cause irritation to rodent’s eyes. Comparing the above annotations with the criteria of CLP regulation, the test chemical cannot be classified for eye irritation.

 

 

Justification for classification or non-classification

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, it was considered to be not irritating to skin and eye. Comparing the above annotations with the criteria of CLP regulation, it cannot be classified for skin and eye irritation.