Registration Dossier

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.

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 for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

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 or test system 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:

no adverse effect observed (not irritating)

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 for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

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:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

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.

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.