Registration Dossier

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 known 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 results and applying the weight of evidence approach, the test chemical can be considered 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”.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Remarks:

a

Justification for type of information:

data is from authoritative database

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

To estimate the dermal irritation potential of the test chemical.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

no data available

Duration of treatment / exposure:

no data available

Observation period:

no data available

Number of animals:

no data available

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: no data available

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritation were estimated

Other effects:

no data available

Table showing skin irritation estimation by three different models i.e, Leadscope, battery and SciQSAR &CASE Ultra,the average skin irritation results was given by the fourth model i.e, Battery model.

	Exp	Battery	CASE Ultra	Leadscope	SciQSAR
Severe Skin Irritation in Rabbit		NEG_IN	NEG_IN	NEG_IN	NEG_IN

Where,IN = inside applicability domain

Interpretation of results:

other: not irritating

Conclusions:

No Severe skin irritation effects of the test chemical were estimated in rabbit skin by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database.Hence, the test chemical can be considered to be not irritating to skin.

Executive summary:

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 known when the test chemical wasexposed to rabbit skin.

Hence, the test chemical can be considered to be not irritating to 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:

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 for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

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 are referred as study 1,2

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

1. 0.1 gram
2.100 mg (undiluted)

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

1. 14 days
2. 48 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

1. 6
2. 6

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No signs of irritations observed

Interpretation of results:

other: not irritating

Conclusions:

Based on the available results and applying the weight of evidence approach, the test chemical can be considered 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”.

Executive summary:

Various studies have been reviewed to determine the extent of ocular damage caused by the test chemical in living organisms. These include in vivo experimental studies for the test chemicals. The results are summarized below:

An eye irritation study was conducted on six rabbits to assess the adverse effects caused by the test chemical.

The test chemical was administered undiluted at a dose of 0.1 gram into one eye of each of six rabbits, with the other eye serving as an untreated control. The treated eye of each rabbit was scored for irritation at 1, 2, 3, 4, 7, and 14 days following test article administration. The control eye was used for comparison.

The maximum irritation score of 5.3/110.0 was obtained 1 day after administration of the test article. Ocular Irritation was seen in all rabbits during the study, but only three rabbits exhibited positive reactions. Complete recovery from all signs of ocular irritation was evident in two rabbits by the 2nd day, in five rabbits by the 4th day, and in all rabbits by the final scoring interval.

Since all the ocular lesions cleared upto 14 days, the test chemical was considered to be not irritating to the rabbits’ eye.

This is supported by another ocular irritation study conducted on six albino rabbits for the test chemical. When chemical was applied at a concentration of 100 mg (undiluted) to one eye of each of six albino rabbits, slight irritation of the iris and conjunctiva was observed , which was 9.0 of a total score of 110 after one hour and 4.5 after 24 hours. All symptoms had disappeared 48 hours after application.

Thus on the basis of observed results, the test chemical was considered to be not irritating to the eyes of albino rabbits.

Based on the available results and applying the weight of evidence approach, the test chemical can be considered 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”.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation:

Various studies have been reviewed to determine the degree of dermal irritation caused by the test chemical in living organisms. These include in vivo experimental studies for the test chemicals. The results are summarized below:

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 known when the test chemical was exposed to rabbit skin.

Hence, the test chemical can be considered to be not irritating to skin.

This estimated result is supported a study designed and conducted to determine the dermal reaction profile of the test chemical in Wistar rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.

1 female for the dose range finding study, followed by additional 2 females rats for main study.

Based on the individual body weight, the test item at the dose of 2000 mg/kg body weight was weighed on an aluminum foil and made as a paste in Milli-Q water and applied directly to the clipped skin (clipping was done approximately 24 hour prior to application) of the animal to cover about 10% of the body surface of the animal (semi-occlusive). The area of application was covered with cotton gauze (size: Females: 8 x 5 cm of 6 ply) and it was secured in position by adhesive tape wrapped around the torso. The test item contact period with the skin was for 24 hours.

After the 24 hours contact period, the adhesive tape and cotton gauge was removed and the applied area was washed with deionized water and wiped dry using clean towels.

All the rats were observed for clinical signs of toxicity and mortality for 14 days post application. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test item using the Draize criteria. There were no clinical signs of toxicity and mortality.

There was no skin reaction observed at test item applied area. The mean erythema and edema scores were 0.0 at all observation times. Hence, it was concluded that the test chemical was Non-Irritating to the skin of Wistar rats under the experimental conditions tested and classified as “Category-Not Classified” as per CLP Classification.

The above results are supported by an acute skin irritation test conducted on the intact dorsal skin of rabbits according to OECD guidelines 404 to assess the irritation potential of the test chemical.

50% aqueous solution of the test substance was applied in an area of 2.5 cm x 2.5cm on the upper third of the back of the 3 (1 male and 2 female) Vienna White rabbits. The test animals were exposed for 4 hours and readings were taken 30 -60 minutes after the removal of test patches and 24, 48 and 72 hours after the beginning of application. Untreated skin sites of the same animal were treated as negative control.

Observations were made for appearance of any symptoms of Erythema and Edema on the tested skin sites. However, none of the observations taken at different intervals showed any clinical signs of Erythema and Edema. Based on the results, the test chemical was considered to be not irritating to skin.