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Description of key information

Acute oral Toxicity: 

The acute oral toxicity dose (LD50) for Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate was considered based on data available for the structurally and functionally similar read across chemicals. The LD50 value is between 300 -2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate can be classified as “category 4” for acute oral toxicity. 

Acute Inhalation Toxicity:

Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate has very low vapour pressure of 6.84E-12 Pa (5.13E-14 mm Hg). Also, the test chemical has a particle size distribution of 52-147 micron, so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for acute inhalation toxicity by inhalation route is considered for waiver.

Acute dermal Toxicity: 

The acute dermal toxicity dose (LD50) for Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate was considered based on data available for the structurally and functionally similar read across chemicals. The LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate cannot be classified for acute dermal toxicity. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
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 read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally and functionally similar read across chemicals
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 two acute oral toxicity studies as- 1.and 2. Acute Oral toxicity test was carried out to study the effects of the test chemicals on rodents
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
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:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
1.1650 mg/kg bw2.1030 mg/kg bw
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
1.Details on study design:- Other examinations performed: clinical signs2.not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 1 030 - < 1 650 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
1.50% mortality was observed at dose 1650 mg/kg bw2.50% mortality was observed at dose 1030 mg/kg bw
Clinical signs:
1.In clinical signs observations,changes in urine composition,behavioral excitement and convulsions or effect on seizure threshold were observed.2.not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
According to CLP regulation, the test chemical Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate can be classified as “category 4” for acute oral toxicity, as the LD50 value is between 300-2000 mg/kg bw.
Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate.The studies are as mentioned below:

1.Acute oral toxicity study was performed in rats using test chemical.50% mortality was observed at dose1650 mg/kg bw.In clinical signs observations,changes in urine composition,behavioral excitement and convulsions or effect on seizure threshold were observed.Hence,LD50 value was considered to be1650 mg/kg bw,when rats were treated with test chemical orally.

2.Acute oral toxicity study was performed in rats using test chemical.50% mortality was observed at dose1030 mg/kg bw. Hence,LD50 value was considered to be 1030 mg/kg bw,when rats were treated with test chemical orally.

Thus, based on the above summarised studies, Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate and it’s structurally and functionally similar read across substance, it can be concluded that LD50 value is between 300 -2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate can be classified as “category 4” for acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 650 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from authoritative database

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally and functionally similar read across chemicals
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 two acute dermal toxicity studies as- WoE 2.and WoE 3. Acute dermal toxicity test was carried out to study the effects of the test chemicals on rodents
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
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:
other: 1. rabbit 2. rat
Strain:
other: 1. not specified 2. Wistar
Sex:
male/female
Details on test animals and environmental conditions:
1. not specified2. TEST ANIMALS- Source: In-House Bred - Weight at study initiation: Male: Minimum: 248 g and Maximum: 271 g (Prior to Treatment)Female: Minimum: 202 g and Maximum: 249 g - Housing: Bedding : All cages were provided with corn cobs Husbandry : The animals were housed individually in polycarbonate cagesRoom Sanitation : The experimental room floor and work tops were swept and mopped with disinfectant solution every day. Cages and water bottle : All the cages and water bottles were changed at least twice every week.- Diet (e.g. ad libitum): animals were provided conventional laboratory rodent diet ad libitum - Water (e.g. ad libitum): Aqua guard filtered tap water was provided ad libitum via drinking bottles- Acclimation period: All animals were acclimatized to the test conditions for 6 days prior to administration of the test item.ENVIRONMENTAL CONDITIONS- Temperature (°C): Minimum: 19.80 °C Maximum: 23.20 °C- Humidity (%): Minimum: 50.60% Maximum: 63.20%- Air changes (per hr): More than 12 changes per hour- Photoperiod (hrs dark / hrs light): 12:12
Type of coverage:
other: 1. Dermal 2. occlusive
Vehicle:
other: 1. not specified 2. water
Details on dermal exposure:
1. not specified2. TEST SITE- Area of exposure: dorsal area of the trunk - % coverage: Approx. 10% of body surface area of rat- Type of wrap if used: porous gauze dressing and non-irritating tapeREMOVAL OF TEST SUBSTANCE- Washing (if done): residual test item was removed by using distilled water- Time after start of exposure: 24-hour exposure periodTEST MATERIAL- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight- Concentration (if solution): Individual rat was applied with an amount of test item moistened with 0.2 ml distilled water- Constant volume or concentration used: yes- For solids, paste formed: yesVEHICLE- Amount(s) applied (volume or weight with unit): 0.2ml
Duration of exposure:
1. not specified2. 24 hrs
Doses:
1. 5000 mg/kg bw2. 2000 mg/kg body weight
No. of animals per sex per dose:
1. not specified2. Five male and five female wistar rats
Control animals:
not specified
Details on study design:
1. not specified2. - Duration of observation period following administration: 14 days - Frequency of observations and weighing: individual animals were frequently observed at 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all animals were observed once a day during the 14 day observation period- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, body weight,organ weights, histopathology were observed
Statistics:
1. not specified2. not specified
Preliminary study:
1. not specified2. not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
1. No mortality was observed in treated rabbits at 5000 mg/kg bw.2. No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period
Clinical signs:
1. not specified2. All the animals were observed with normal clinical signs throughout the experimental period
Body weight:
1. not specified2. Mean body weight of male and female was observed with increase on day 7 and 14, as compared to day 0
Gross pathology:
1. not specified2. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality
Other findings:
1. not specified2. not specified
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation the test chemical Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw
Executive summary:

Data available for the structurally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate. The studies are as mentioned below:

1. Acute dermal toxicity study was conducted in rabbits by using test chemical at the concentration of 5000 mg/kg bw by dermal application. No mortality was observed in treated rabbits at dose 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

2. Acute dermal toxicity study of test chemical in Rats was performed as per OECD No. 402. 5 male and 5 female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, an amount of test item moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. All the animals were observed for mortality, clinical signs, body weight and gross pathology. No mortality was observed in any animal, normal clinical signs were observed. Mean body weight of male and female was observed with increase on day 7 and 14, as compared to day 0. No pathological abnormality was observed. Thus the LD50 value was considered to be >2000 mg/kg bw, when male and female wistar rats were treated with test chemical by dermal application.

Thus, based on the above summarised studies, Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate cannot be classified for acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from peer-reviewed journal.

Additional information

Acute oral Toxicity: 

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the acute oral toxicity of the test chemical Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate. The studies are as mentioned below:

1. Acute oral toxicity study was performed in rats using test chemical.50% mortality was observed at dose 1650 mg/kg bw. In clinical signs observations, changes in urine composition, behavioural excitement and convulsions or effect on seizure threshold were observed. Hence, LD50 value was considered to be 1650 mg/kg bw, when rats were treated with test chemical orally.

2. Acute oral toxicity study was performed in rats using test chemical.50% mortality was observed at dose1030 mg/kg bw. Hence, LD50 value was considered to be 1030 mg/kg bw, when rats were treated with test chemical orally.

Thus, based on the above summarised studies, Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate and it’s structurally and functionally similar read across substance, it can be concluded that LD50 value is between 300 -2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 3H-​Indolium, 2-​[[2-​(4-​methoxyphenyl)​-​2-​methylhydrazinyliden​e]​methyl]​-​1,​3,​3-​trimethyl-​ & acetate can be classified as “category 4” for acute oral toxicity.

Acute Inhalation Toxicity:

Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate has very low vapour pressure of 6.84E-12 Pa (5.13E-14 mm Hg). Also, the test chemical has a particle size distribution of 52-147 micron, so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point for acute inhalation toxicity by inhalation route is considered for waiver.

Acute dermal Toxicity: 

Data available for the structurally similar read across chemicals has been reviewed to determine the acute dermal toxicity of the test chemical Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate. The studies are as mentioned below:

1. Acute dermal toxicity study was conducted in rabbits by using test chemical at the concentration of 5000 mg/kg bw by dermal application. No mortality was observed in treated rabbits at dose 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with test chemical by dermal application.

2. Acute dermal toxicity study of test chemical in Rats was performed as per OECD No. 402. 5 male and 5 female healthy young adult rats were randomly selected and used for conducting acute dermal toxicity study. Rats free from injury and irritation of skin were selected for the study. 24 hours prior to dermal application of test item, approximately 10% of body surface area of each rat was clipped. A limit dose of 2000 mg/ kg body weight of test item moistened with 0.2 ml distilled water was applied by single dermal application and observed for 14 days after treatment. On test day 0, an amount of test item moistened with 0.2 ml distilled water was applied directly on the intact skin of clipped area of rats; the porous gauze dressing was put on to the intact skin of clipped area. This porous gauze dressing was covered with a non-irritating tape. After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. The skin reactions were assessed. All the animals were observed for mortality, clinical signs, body weight and gross pathology. No mortality was observed in any animal, normal clinical signs were observed. Mean body weight of male and female was observed with increase on day 7 and 14, as compared to day 0. No pathological abnormality was observed. Thus the LD50 value was considered to be >2000 mg/kg bw, when male and female wistar rats were treated with test chemical by dermal application.

Thus, based on the above summarised studies, Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above experimental studies on Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw for acute oral toxicity and LD50 value is >2000 mg/kg bw for acute dermal toxicity. Thus, comparing these values with the criteria of CLP regulation, Reaction mass of 3H-Indolium, 2-[[2-(4-methoxyphenyl)-2-methylhydrazinylidene]methyl]-1,3,3-trimethyl- & acetate can be classified as “category 4” for acute oral toxicity and cannot be classified for acute dermal toxicity. For acute inhalation toxicity wavier was added so, not possible to classify.