Registration Dossier

Skin irritation

The dermal irritation potential of test chemical was assessed in various experimental studies conducted for test chemical and its structurally similar read across chemical. Based on the available data for the key and supporting studies, it can be concluded that the test chemical is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye irritation

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical. Based on the summarized studies for target chemical and its structurally similar read across substances,it can be concluded that the testchemical is unable to cause ocular irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category Not Classified”.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewd journals

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

To assess the dermal irritation potential of test chemical in humans

GLP compliance:

not specified

Species:

other: humans

Strain:

other: not applicable

Details on test animals or test system and environmental conditions:

No data

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: Petrolatum

Controls:

not specified

Amount / concentration applied:

4% in petrolatum

Duration of treatment / exposure:

48 hr

Observation period:

48 hr

Number of animals:

25 subjects

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation observed

Interpretation of results:

other: not irritating

Conclusions:

The test chemical was not irritating to human skin after 48 hours exposure.

Executive summary:

A skin irritation study was performed on humans to assess the irritation potential of test chemical.

The test chemical was tested 4% in petrolatum in 25 human volunteers in 48 hours closed patch test.

No signs of irritation were observed after 48 hours of exposure.

Hence, the test material was considered not irritating to human skin.

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:

Data is from experimental studies for read across chemicals

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

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:

The ocular irritation potential of test chemical was assessed on the basis of various summarized studies which were conducted on rabbits and represented as study 1, 2 and 3 for WoE-2,WoE-3 and WoE-4 respectively.

GLP compliance:

no

Species:

rabbit

Strain:

other: Study 1: SPF albino; Study 2:albino; Study 3: Not Applicable

Details on test animals or tissues and environmental conditions:

Study 1: No Data Available:
Study 2: not specified
Study 3: not specified

Vehicle:

other: Study 1: unchanged (no vehicle); Study 2:unchanged (no vehicle) Study 3: not specified

Controls:

yes

Amount / concentration applied:

Study 1: 100% (0.1 ml ; undiluted)
Study 2: 100%
Study 3: 8%

Duration of treatment / exposure:

Study 1: 1, 48, 72 h and 7 days
Study 2: Not specified
Study 3: not specified

Observation period (in vivo):

Study 1: 7 days
Study 2: Not specified
Study 3: not specified

Number of animals or in vitro replicates:

Study 1: four female SPF alibino rabbits
Study 2: Not specified
Study 3: not specified

Details on study design:

Study 1: Not specified
Study 2: Not specified
Study 3: not specified

Irritation parameter:

other: Study 1:overall irritation score

Basis:

mean

Time point:

7 d

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

other: Study 2:overall irritation score

Basis:

mean

Time point:

other: Not specified

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

other: Study 3: overall irritation score

Basis:

mean

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No indication of ocular reaction were observed.

Interpretation of results:

other: Not irritating

Conclusions:

Based on the result obtained from these studies available for the structurally read across chemical, it can be estimated that the test chemical is unable to cause ocular irritation and thus can be considered as not irritating.

Executive summary:

The ocular irritation potential of test chemical was assessed on the basis of various summarized studies available for the structurally read across chemicals which were conducted on rabbits and humans. These studies have been summarized as below;

Study 1:

The ocular irritation study of test chemical was conducted in four female SPF albino rabbits to assess the irritation potential of test chemical. A dose volume of 0.1 ml was instilled into one eye. The untreated eye of each animal served as a control. Observations were made at 1, 48, 72 h and 7 days after treatment. At 24 h after dosing, corneal opacity was scattered or diffuse on more than one quarter but less than one half of the cornea. Application of fluorescein confirmed this finding. The conjunctiva were still diffuse, crimson red with individual vessels not easily discernible, swelling was still noted as well as an abnormal discharge. At 48 h after dosing, the scattered or diffuse area of opacity was still noted on one quarter or less of the cornea, even after instillation of fluorescein. The conjunctiva was still diffusely red; the individual vessels were not easily discernible and abnormal swelling still present. At 72 h after dosing, the conjunctival vessels were still injected and following the instillation of fluorescein a scattered or diffuse area of opacity on one quarter or less of the cornea was noted. By 7 days after dosing the animals were free of any signs of eye irritation. Since the observed effects were cleared within the observation period of 7 days, the test chemical was considered as not irritating to the eyes of treated rabbits.

Study 2:

The test chemical was evaluated to determine its eye irritation potential on rabbits. When the undiluted test chemical was instilled into the eyes of treated rabbits, no known signs of ocular lesions were observed. Hence the test material was considered to be not irritating to the eyes.

Study 3:

The primary eye irritation study of test chemical was conducted on human subjects to determine the adverse effects caused by the test chemical. The human subjects were exposed to solutions of 8% of test chemical. Although no corneal involvement was observed in this study, no information was provided as to the time for the eye irritation to clear. As no signs of eye irritation was observed, the test chemical was considered to be not irritating to the eyes.

Based on the result obtained from these studies available for the structurally read across chemical, it can be estimated that the test chemical is unable to cause ocular irritation and thus can be considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation:

Various studieshas been investigated for the test chemical to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in-vivo experiments conducted for target chemicaland its structurally similar read across substancesthat have been summarized as below;

A skin irritation study was performed on humans to assess the irritation potential of test chemical. The test chemical was tested 4% in petrolatum in 25 human volunteers in 48 hours closed patch test. No signs of irritation were observed after 48 hours of exposure. Hence, the test material was considered not irritating to human skin.

The above result was supported by a patch test performed on humans to assess the irritation potential of similar read across chemical. Undiluted test chemical was applied to the skin of 20 human volunteers for 24 hours. Since the test chemical did not induce skin irritation, it was considered as not irritating to human skin after 24 hours exposure.

The overall results were further supported by a Preliminary irritation screen conducted for a modified Draize sensitization study in Hartley strain albino guinea pigs to assess the irritation potential of similar read across chemical. The test compound was applied topically at a concentration of20%. No irritation was noted at the tested concentration. Thus the test material was considered to be not irritating to the skin of Guinea pigs.

Based on the above summarized studies for target chemical and its structurally similar read across substances,it can be concluded that the testchemical is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye irritation

The ocular irritation potential of test chemical was assessed on the basis of various summarized studies available for the structurally read across chemicals which were conducted on rabbits and humans. These studies have been summarized as below;

Study 1:

The ocular irritation study of test chemical was conducted in four female SPF albino rabbits to assess the irritation potential of test chemical. A dose volume of 0.1 ml was instilled into one eye. The untreated eye of each animal served as a control. Observations were made at 1, 48, 72 h and 7 days after treatment. At 24 h after dosing, corneal opacity was scattered or diffuse on more than one quarter but less than one half of the cornea. Application of fluorescein confirmed this finding. The conjunctiva were still diffuse, crimson red with individual vessels not easily discernible, swelling was still noted as well as an abnormal discharge. At 48 h after dosing, the scattered or diffuse area of opacity was still noted on one quarter or less of the cornea, even after instillation of fluorescein. The conjunctiva was still diffusely red; the individual vessels were not easily discernible and abnormal swelling still present. At 72 h after dosing, the conjunctival vessels were still injected and following the instillation of fluorescein a scattered or diffuse area of opacity on one quarter or less of the cornea was noted. By 7 days after dosing the animals were free of any signs of eye irritation. Since the observed effects were cleared within the observation period of 7 days, the test chemical was considered as not irritating to the eyes of treated rabbits.

Study 2:

The test chemical was evaluated to determine its eye irritation potential on rabbits. When the undiluted test chemical was instilled into the eyes of treated rabbits, no known signs of ocular lesions were observed. Hence the test material was considered to be not irritating to the eyes.

Study 3:

The primary eye irritation study of test chemical was conducted on human subjects to determine the adverse effects caused by the test chemical. The human subjects were exposed to solutions of 8% of test chemical. Although no corneal involvement was observed in this study, no information was provided as to the time for the eye irritation to clear. As no signs of eye irritation was observed, the test chemical was considered to be not irritating to the eyes.

Based on the result obtained from these studies available for the structurally read across chemical, it can be estimated that the test chemical is unable to cause ocular irritation and thus can be considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

The skin and eye irritation potential of test chemical and its structurally and functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical is not likely to cause skin irritation and eye damage. Hence the test chemical can be classified under the category “Not Classified” for skin and eye as per CLP.