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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” 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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate was estimated to be irritating to eyes and it can be further classified under the category “Category 1” 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 based on structurally similar read across chemicals
Justification for type of information:
Weight of evidence 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 Methanaminium, N-[4-[[4-(dimethylamino)phenyl]phenylmethylene]-2,5-cyclohexadien-1-ylidene]-N-methyl- & acetate
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material:Reaction mass of Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate- Molecular formula: C25H28N2O2- Molecular weight: 388.508 g/mole- Smiles : [N+](=C1/C=CC(\C=C1)=C(\c1ccccc1)c1ccc(cc1)N(C)C)(\C)C.C(C)(=O)[O-]- Inchl: 1S/C23H25N2.C2H4O2/c1-24(2)21-14-10-19(11-15-21)23(18-8-6-5-7-9-18)20-12-16-22(17-13-20)25(3)4;1-2(3)4/h5-17H,1-4H3;1H3,(H,3,4)/q+1;/p-1- Substance type: Organic- Physical state: maroon lustrous liquid
Species:
rat
Strain:
other: 1. Sprague Dawley, 2. Wistar
Details on test animals and environmental conditions:
no data available
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
1. 2000mg/kg2. 20% suspension of test chemical
Duration of treatment / exposure:
1. 4 hours2. no data available
Observation period:
1. 14 days2. no data available
Number of animals:
1. 102. 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:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation observed
Interpretation of results:
other: not irritating
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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” 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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate.

A study was designed and conducted to determine the dermal reaction profile of the structurally similar read across chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. Ten rats (5 male and 5 female) were used for conducting dermal irritation /corrosion study. 

The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item. 

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Also, the erythema and edema score of rats was calculated as 0. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

  Hence, it was concluded that the test chemical was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and classified as “Category- Not Classified” as per CLP Classification.

 

This is supported by the results of a skin irritation study was carried out on rats to assess the irritation potency of other structurally similar read across chemical.20% suspension of test chemical was applied to the skin of Wistar rats and observed for signs of irritation (duration not mentioned).

No visible erythema or edema was observed on the skin of Wistar rats when exposed to 20% test chemical.

Hence, test chemical can be considered not irritating to 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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

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:
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
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
other: Weight of evidence approach based on 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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: Reaction mass of Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate- Molecular formula: C25H28N2O2- Molecular weight: 388.508 g/mole- Smiles : [N+](=C1/C=CC(\C=C1)=C(\c1ccccc1)c1ccc(cc1)N(C)C)(\C)C.C(C)(=O)[O-]- Inchl: 1S/C23H25N2.C2H4O2/c1-24(2)21-14-10-19(11-15-21)23(18-8-6-5-7-9-18)20-12-16-22(17-13-20)25(3)4;1-2(3)4/h5-17H,1-4H3;1H3,(H,3,4)/q+1;/p-1- Substance type: Organic- Physical state: maroon lustrous liquid
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. 100 mg of the undiluted test chemical2. 1% test chemical 3. Undiluted test chemical
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
1. 72 hours2. 3 days 3. 7 days
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
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
Time point:
72 h
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Severe irritation was observed
Interpretation of results:
Category 1 (irreversible effects on the eye) 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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate was estimated to be irritating to eyes and it can be further classified under the category “Category 1” 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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate

The ocular irritation potential of the structurally similar was assessed in rabbits according to Fed. Reg. 38, No. 187, § 1500.42, 1973 (Draize test) Guidelines. 100 mg of the undiluted test chemical was instilled into one eye of the 6 albino rabbits. The untreated eye served as control. The animals were exposed to the test chemical for 24 hours, and the treated eyes remained unwashed throughout the study. Rabbits were observed for signs of irritation 1 h, 24 h, 48 h and 72 h after instillation of the test chemical. The ocular reactions at 24 and 72 hours were scored according to method of Draize.

Conjunctivae score was not assessed due to staining of the test chemical. The effects observed in the rabbit eyes were not reversible even after 72 hours. The mean scores for corneal opacity, iris and chemosis after 24, 72 hours of observation were 3.3, 1.9, 3.2 respectively.

Based on the scores, the test chemical can be considered to be irritating to rabbit eyes.

The above result is supported by the experimental study performed for other structurally similar read across chemical. 1% test chemical was instilled in conjunctival sac of 2 rabbits thrice in a day. The histopathological appearance of normal conjunctiva obtained from control rabbit was compared with the treated eyes. Both the rabbits developed conjunctival congestion and discharge next day. After 3 days of instillation there was some necrosis of the conjunctiva. Conjunctival biopsies obtained from affected rabbits showed variable thinning of epithelial lining with total loss of goblet cells and subepithelial capillary congestion with neutrophilic infiltration.

In experimental studies on rabbits, the test chemical caused gross destruction of goblet cells and thinning of the conjunctival epithelium.

Hence, the test chemical can be considered to be a severe eye irritant.

These studies are supported by the results of Draize test performed to determine the degree of ocular damage caused by another structurally similar chemical. Undiluted test chemical was instilled in the eyes of 1 rabbit and observed for signs of irritation till 7 days. The reactions observed were scored according to Draize method. Mean scores are calculated for each animal from gradings at 24, 48, and 72 h after instillation of the test chemical and these “severity scores” are then used to determine the classification of the test chemical.

The study was terminated after day 1 since color staining of the cornea was observed.

Based on these observations, the test chemical was considered to highly irritating and causing irreversible damage to rabbit eyes, was classified under the category “Category 1”.

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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate was estimated to be irritating to eyes and it can be further classified under the category “Category 1” as per CLP regulation.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate.

A study was designed and conducted to determine the dermal reaction profile of the structurally similar read across chemical in Sprague Dawley rats. The study was performed as per OECD Guidelines 402 and complying to the GLP procedures. Ten rats (5 male and 5 female) were used for conducting dermal irritation /corrosion study. 

The animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item. 

The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Also, the erythema and edema score of rats was calculated as 0. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

Hence, it was concluded that the test chemical was Non-Irritating to the skin of Sprague Dawley rats under the experimental conditions tested and classified as “Category- Not Classified” as per CLP Classification.

This is supported by the results of a skin irritation study was carried out on rats to assess the irritation potency of other structurally similar read across chemical.20% suspension of test chemical was applied to the skin of Wistar rats and observed for signs of irritation (duration not mentioned).

No visible erythema or edema was observed on the skin of Wistar rats when exposed to 20% test chemical.

Hence, test chemical can be considered not irritating to 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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” 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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate.

The ocular irritation potential of the structurally similar was assessed in rabbits according to Fed. Reg. 38, No. 187, § 1500.42, 1973 (Draize test) Guidelines. 100 mg of the undiluted test chemical was instilled into one eye of the 6 albino rabbits. The untreated eye served as control. The animals were exposed to the test chemical for 24 hours, and the treated eyes remained unwashed throughout the study. Rabbits were observed for signs of irritation 1 h, 24 h, 48 h and 72 h after instillation of the test chemical. The ocular reactions at 24 and 72 hours were scored according to method of Draize.

Conjunctivae score was not assessed due to staining of the test chemical. The effects observed in the rabbit eyes were not reversible even after 72 hours. The mean scores for corneal opacity, iris and chemosis after 24, 72 hours of observation were 3.3, 1.9, 3.2 respectively.

Based on the scores, the test chemical can be considered to be irritating to rabbit eyes.

The above result is supported by the experimental study performed for other structurally similar read across chemical. 1% test chemical was instilled in conjunctival sac of 2 rabbits thrice in a day. The histopathological appearance of normal conjunctiva obtained from control rabbit was compared with the treated eyes. Both the rabbits developed conjunctival congestion and discharge next day. After 3 days of instillation there was some necrosis of the conjunctiva. Conjunctival biopsies obtained from affected rabbits showed variable thinning of epithelial lining with total loss of goblet cells and subepithelial capillary congestion with neutrophilic infiltration. In experimental studies on rabbits, the test chemical caused gross destruction of goblet cells and thinning of the conjunctival epithelium.

Hence, the test chemical can be considered to be a severe eye irritant.

These studies are supported by the results of Draize test performed to determine the degree of ocular damage caused by another structurally similar chemical. Undiluted test chemical was instilled in the eyes of 1 rabbit and observed for signs of irritation till 7 days. The reactions observed were scored according to Draize method. Mean scores are calculated for each animal from gradings at 24, 48, and 72 h after instillation of the test chemical and these “severity scores” are then used to determine the classification of the test chemical.

The study was terminated after day 1 since color staining of the cornea was observed. Based on these observations, the test chemical was considered to highly irritating and causing irreversible damage to rabbit eyes, was classified under the category “Category 1”.

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 Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate was estimated to be irritating to eyes and it can be further classified under the category “Category 1” 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 Reaction mass of Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate can be not irritating to skin and irritating to eyes.

Hence by applying the weight of evidence approach, Reaction mass of Methanaminium, N-​[4-​[[4-​(dimethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​methyl-​ & acetate can be considered to be not irritating to skin and severely irritating to eyes. It can be classified under the category “Not Classified” for skin irritation and “Category 2” for eye irritation as per CLP regulation.