Registration Dossier

Administrative data

Description of key information

Skin irritation:

The dermal irritation potential of target chemical was assessed in various in-vivo experimental studies.Based on the available studies,it can be concluded that the test chemical 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 target chemical was assessed in various in-vivo experimental studies.Based on the available studies,it can be concluded that the test chemical is unable to cause eye irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it 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:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
Data is from Danish QSAR
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
The data predicted using the Danish (Q)SAR Database
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
not specified
Duration of treatment / exposure:
not specified
Observation period:
not specified
Number of animals:
not specified
Details on study design:
not specified
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: not specified
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
not specified
Other effects:
not specified

Table showing skin irritation estimation by four different models i.e, Battery,SciQSAR ,CASE Ultra

and Leadscope.The average skin irritation results was given by the first model i.e, Battery model.

DK

Battery

Ultra Leadscope

Leadscope

SciQSAR

Skin irritation in

rabbit

NEG_IN

NEG_IN

NEG_IN

INC_OUT

Domain

IN

IN

IN

OUT

 

Where,

IN = inside applicability domain

OUT = outside applicability domain

Interpretation of results:
other: not irritating
Conclusions:
No severe skin irritation effects of the test chemical were estimated in rabbit skin by three different models i.e, Battery, Leadscope and CASE Ultra used within Danish QSAR database.
Executive summary:

Skin irritation effects were estimated by three different models i.e, Battery, Leadscope 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.

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 of test substances
Justification for type of information:
Data for the target chemical is summarized based on the available studies
Reason / purpose:
read-across source
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 eye irritation studies as- WoE-2, WoE-3 and WoE-4.
An eye irritation studies were condcuted on rabbits to assess its ocular effects.
Species:
other: 2.rabbit 3.rabbit 4.rabbit
Strain:
other: 2.not specified 3.not specified 4.New Zealand White
Details on test animals or tissues and environmental conditions:
2.not specified
3.not specified
4.no data available
Vehicle:
other: 2.0.05 %aqueous sodium sulphite (0.1mL pH 7.0) 3.unchanged (no vehicle) 4.Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3.
Controls:
other: 2.not specified 3.not specified 4.Other eye acted as control in all the groups
Amount / concentration applied:
2.2.5% (0.1mL)
3.undiluted
4.2.5%(w/v) Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3.
Duration of treatment / exposure:
2.10 seconds
3.no data available
4.10 seconds
Observation period (in vivo):
2.1 hr, Days 1, 2, 3, 4, and 7.
3.no data available
4.No data
Number of animals or in vitro replicates:
2.3
3.no data available
4.3
Details on study design:
2.Washing (if done): eye was rinsed with 50 mL of lukewarm water
SCORING SYSTEM: Draize scoring system
3.no data available
4.SCORING SYSTEM: Categorized as + or - according to whether extrapolation of the result would be expected to give a positive or negative test for eye irritation based on the definition in the Code of Federal Regulations, Test for Eye Irritants (Title 16, Sec. 1500.42).

REMOVAL OF TEST SUBSTANCE
Washing (if done): 50 ml of lukewarm water (37°C)
Time after start of exposure: 10 seconds after instillation
Irritation parameter:
other: 2.overall irritation score
Basis:
mean
Time point:
7 d
Reversibility:
not fully reversible within:
Remarks on result:
no indication of irritation
Irritation parameter:
other: 3.overall irritation score
Basis:
mean
Time point:
other: no data available
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
other: 4.overall irritation score
Basis:
mean
Time point:
24 h
Reversibility:
fully reversible within: 24 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
2.No ocular lesions were observed in treated rabbits.
3.no irritation observed
4.occasional transient mild conjunctival inflammation was observed
Interpretation of results:
other: Not irritating
Conclusions:
The Test chemical was considered to be not irritating to the eyes of treated rabbits.
Executive summary:

Various studies were performed on rabbits to assess the ocular irritation potential of test chemical which have been summarized as follows:

An eye irritation study was conducted to assess its eye irritation potential of test chemical. The test material was installed onto the eyes of rabbits in the concentration 0.1 mL of a 2.5% w/v in aqueous sodium sulphite (pH 7.0) for 10 sec. After 10 seconds the eye was rinsed with 50 mL of lukewarm water. The treated eyes were evaluated and scored by Draize scoring system at 1 hr and then at Days 1, 2, 3, 4, and 7. Since none of the treated rabbit produced any ocular lesions, the test chemical was considered to be not irritating to the rabbits’ eye.

An eye irritation study was performed to assess the irritation potential of test chemical in rabbits. The study was performed according to a standardized rabbit eye test (OECD 405). Undiluted test chemical was instilled into rabbit eyes and effects were observed (duration not mentioned). Undiluted test chemical caused only slight eye irritation, which can be considered as not irritating.

The irritant effects on rabbit eye mucosa, was assessed for test chemical in rabbits.The procedure for the eye tests was based on that prescribed in the Code of Federal Regulations (Title 16, Sec. 1500.42). Test chemical was prepared as a 2.5% (w/v) solution or suspension. (Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3). Eleven groups of three rabbits were used to test solutions, each of which was instilled into one eye of each of three rabbits. The reactions were scored and categorized as + or - according to whether extrapolation of the result would be expected to give a positive or negative test for eye irritation based on the definition in the Code of Federal Regulations, Test for Eye Irritants (Title 16, Sec. 1500.42). None of the three animals treated with test chemical showed any response to treatment, and although occasional transient mild conjunctival inflammation was observed. The reactions did not persist for more than 24 hr.Thus, test chemical was considered to be not irritating to rabbit eyes.

The results obtained from these studies lead to a conclusion that Test chemical is indeed not irritating to eye. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can 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:

In different studies, the test chemical has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in-vivo experimental conducted in different subjects. The predicted data using the Danish QSAR database has also been compared with the experimental data and summarized as below:

Skin irritation effects were estimated by three different models i.e, Battery, Leadscope 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.

The above study is further supported by another study available for structurally similar read across substance, in which, Patch test was performed on humans in accordance with IMDG code (2002) to assess the irritation potential of test chemical. 50 mg/patch was applied under occlusive conditions to the inner arm of 5 male volunteers for 4 hours.The test site was observed for erythema and edema till 14 days post dosing.Test chemical was not irritating to the skin of humans in 6hr patch test. Hence, test chemical can be considered not irritating to skin.

Both the above studies were again supported by study available for functionally similar read across substance. The skin irritation study of test chemical was performed in humans to determine its irritation potential. During the test, 10% in petrolatum of test sample was administrated to the skin of human subject for 48 hours under closed patch. No known cutaneous reaction was observed after 48 hours. Therefore, the test chemical can be considered as non irritant on human skin.

All these studies lead to a conclusion that Test chemical is indeed not irritating to skin. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical cannot be classified for skin irritation.

Eye irritation:

Various studies were performed on rabbits to assess the ocular irritation potential of test chemical which have been summarized as follows:

An eye irritation study was conducted to assess its eye irritation potential of test chemical. The test material was installed onto the eyes of rabbits in the concentration 0.1 mL of a 2.5% w/v in aqueous sodium sulphite (pH 7.0) for 10 sec. After 10 seconds the eye was rinsed with 50 mL of lukewarm water. The treated eyes were evaluated and scored by Draize scoring system at 1 hr and then at Days 1, 2, 3, 4, and 7. Since none of the treated rabbit produced any ocular lesions, the test chemical was considered to be not irritating to the rabbits’ eye.

An eye irritation study was performed to assess the irritation potential of test chemical in rabbits. The study was performed according to a standardized rabbit eye test (OECD 405). Undiluted test chemical was instilled into rabbit eyes and effects were observed (duration not mentioned). Undiluted test chemical caused only slight eye irritation, which can be considered as not irritating.

The irritant effects on rabbit eye mucosa, was assessed for test chemical in rabbits.The procedure for the eye tests was based on that prescribed in the Code of Federal Regulations (Title 16, Sec. 1500.42). Test chemical was prepared as a 2.5% (w/v) solution or suspension. (Suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3). Eleven groups of three rabbits were used to test solutions, each of which was instilled into one eye of each of three rabbits. The reactions were scored and categorized as + or - according to whether extrapolation of the result would be expected to give a positive or negative test for eye irritation based on the definition in the Code of Federal Regulations, Test for Eye Irritants (Title 16, Sec. 1500.42). None of the three animals treated with test chemical showed any response to treatment, and although occasional transient mild conjunctival inflammation was observed. The reactions did not persist for more than 24 hr.Thus, test chemical was considered to be not irritating to rabbit's eyes.

The results obtained from these studies lead to a conclusion that Test chemical is indeed not irritating to eye. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical was observed in various studies. The results obtained from these studies indicate that the chemical is not likely to cause skin and eye. Hence the test chemical cannot be classified for skin and eye irritation as per CLP.