Registration Dossier

Administrative data

Description of key information

Skin Irritation:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be irritating to skin and it can be further classified under the category “Category 2” as per CLP regulation

Eye Irritation:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be irritating to eyes and it can be further classified under the category “Category 2” as per CLP regulation.

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:
other: Weight of evidence approach based on structurally similar read across chemicals
Justification for type of information:
Weight of evidence approach based on structurally similar read across chemicals
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weight of evidence based on structurally similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal irritation potential of Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate- Molecular formula: C20H24N3OC2H3O2- Molecular weight: 381.473 g/mol- Smiles notation: [N+]=1(c2ccccc2C(C)(C)C1\C=N\NCc1ccc(cc1)OC)C.C(C)(=O)[O-]- InChl: 1S/C20H23N3O.C2H4O2/c1-20(2)17-7-5-6-8-18(17)23(3)19(20)14-22-21-13-15-9-11-16(24-4)12-10-15;1-2(3)4/h5-12,14H,13H2,1-4H3;1H3,(H,3,4)- Substance type: Organic- Physical state: Liquid (Yellow)
Species:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
undiluted
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
The study is based on weight of evidence approach from the read across values
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 8 days
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
signs of irritation observed
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be irritating to skin and it can be further classified under the category “Category 2” as per CLP regulation
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal irritation potential of  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate.

Primary dermal irritation study was performed in rabbits according to BASF TEST and Draize test methods to assess the irritation potential of the structurally similar read across chemical.

3 (2 male and 1 female) albino Vienna White rabbits were used for the study.0.5 ml undiluted sample was applied to intact and scarified back skin of rabbits under occlusion. The untreated skin sites served as control. The occlusive patches were removed after 4 hours and the test sites. The sites were observed for signs of irritation15-30 minutes after patch removal, then 48, 72 hours till 8 days. The reactions were scored according to Draize method.

The observed primary irritation score after 8 days was ≥3.9

Moderate to severe skin irritation along with tissue degeneration (necrosis) was noted in the rabbits.

Based on the scores and observations, the test chemical was considered to be moderate to strongly irritating to the rabbits’ skin.

This is supported by the experimental study performed for the structurally similar read across chemical according to OECD 404 Guidelines.

Undiluted test chemical was placed on a surgical gauze patch (2.5 cm x 2.5 cm) and applied to shaved dorsal skin of 2 Vienna White rabbits. The patch was covered with an occlusive dressing. The animals were exposed to the chemical for 4 hours. The animals were observed for signs of irritation at 1,2 and 8 days post exposure.

Exact evaluation for erythema was not possible due to staining of the skin by the substance. The skin findings on the sacrificed animal were confirmed by gross pathological examination after incision of the skin.

The edema formation exceeded beyond the area of exposure with mean score after 48 hours was 2.6 and was not reversible even after 8 days.

Based on the observations and scores, the test chemical was strongly irritating to the skin.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be irritating to skin and it can be further classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
other: Weight of evidence approach based on structurally similar chemicals
Justification for type of information:
Weight of evidence approach based on structurally similar chemicals
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on structurally similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the ocular irritation potential of Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate- Molecular formula: C20H24N3OC2H3O2- Molecular weight: 381.473 g/mol- Smiles notation: [N+]=1(c2ccccc2C(C)(C)C1\C=N\NCc1ccc(cc1)OC)C.C(C)(=O)[O-]- InChl: 1S/C20H23N3O.C2H4O2/c1-20(2)17-7-5-6-8-18(17)23(3)19(20)14-22-21-13-15-9-11-16(24-4)12-10-15;1-2(3)4/h5-12,14H,13H2,1-4H3;1H3,(H,3,4)- Substance type: Organic- Physical state: Liquid (Yellow)
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no data available
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
1. 0.1 ml2. no data available
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1. 8 days2. no data available
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
1. 32. no data available
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
signs of irritation observed
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore, Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be irritating to eyes and it can be further classified under the category “Category 2” as per CLP regulation.
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate.

Primary eye irritation study for test chemical was performed in albino Vienna White rabbits according to Draize method.

0.1 ml undiluted test chemical was instilled into the eyes of 3 albino Vienna White rabbits. The rabbits were observed from1, 24, 48, 72 hours till 8 days after application of test chemical. The ocular lesions observed were scored according to the method of Draize. The Mean score after 8 days was 46.

Based on the score, test chemical was considered to be moderately to severely irritating to eyes.

This is supported by the experimental study performed according to OECD 405 Guidelines to assess the the degree of ocular damage caused by the structurally similar chemical.

The test chemical was instilled into the eyes of rabbits and observed for signs of irritation (dose, duration, observation period not mentioned). The overall reactions were categorized -= not irritating and + = irritating.

Signs of irritation were observed when the test chemical was instilled to rabbit eyes, it can be considered to be irritating to eyes.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be irritating to eyes and it can be further classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal irritation potential of  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate.

Primary dermal irritation study was performed in rabbits according to BASF TEST and Draize test methods to assess the irritation potential of the structurally similar read across chemical.

3 (2 male and 1 female) albino Vienna White rabbits were used for the study.0.5 ml undiluted sample was applied to intact and scarified back skin of rabbits under occlusion. The untreated skin sites served as control. The occlusive patches were removed after 4 hours and the test sites. The sites were observed for signs of irritation15-30 minutes after patch removal, then 48, 72 hours till 8 days. The reactions were scored according to Draize method.

The observed primary irritation score after 8 days was ≥3.9

Moderate to severe skin irritation along with tissue degeneration (necrosis) was noted in the rabbits.

Based on the scores and observations, the test chemical was considered to be moderate to strongly irritating to the rabbits’ skin.

This is supported by the experimental study performed for the structurally similar read across chemical according to OECD 404 Guidelines.

Undiluted test chemical was placed on a surgical gauze patch (2.5 cm x 2.5 cm) and applied to shaved dorsal skin of 2 Vienna White rabbits. The patch was covered with an occlusive dressing. The animals were exposed to the chemical for 4 hours. The animals were observed for signs of irritation at 1,2 and 8 days post exposure.

Exact evaluation for erythema was not possible due to staining of the skin by the substance. The skin findings on the sacrificed animal were confirmed by gross pathological examination after incision of the skin.

The edema formation exceeded beyond the area of exposure with mean score after 48 hours was 2.6 and was not reversible even after 8 days.

Based on the observations and scores, the test chemical was strongly irritating to the skin.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be irritating to skin and it can be further classified under the category “Category 2” as per CLP regulation.

Eye Irritation:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate.

Primary eye irritation study for test chemical was performed in albino Vienna White rabbits according to Draize method.

0.1 ml undiluted test chemical was instilled into the eyes of 3 albino Vienna White rabbits. The rabbits were observed from1, 24, 48, 72 hours till 8 days after application of test chemical. The ocular lesions observed were scored according to the method of Draize. The Mean score after 8 days was 46.

Based on the score, test chemical was considered to be moderately to severely irritating to eyes.

This is supported by the experimental study performed according to OECD 405 Guidelines to assess the the degree of ocular damage caused by the structurally similar chemical.

The test chemical was instilled into the eyes of rabbits and observed for signs of irritation (dose, duration, observation period not mentioned). The overall reactions were categorized -= not irritating and + = irritating.

Signs of irritation were observed when the test chemical was instilled to rabbit eyes, it can be considered to be irritating to eyes.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that the target chemical will also tend to behave in a similar that of the read across substances. Therefore,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was estimated to be irritating to eyes and it can be further classified under the category “Category 2” as per CLP regulation.

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that 2-[[(4-methoxyphenyl)methylhydrazono]methyl]-1,3,3-trimethyl-3H-indolium acetate can be irritating to skin and eyes.

Hence by applying the weight of evidence approach,  Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate can be considered to be irritating to skin and eyes. It can be classified under the category “Category 2” as per CLP regulation.