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 Reaction mass of Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate will also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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 Reaction mass of Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate will also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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 chemicals
Justification for type of information:
Weight of evidence approach based on structurally similar chemicals
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
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 dermal irritation potential of Reaction mass of Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: Reaction mass of Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate
- Molecular formula: C29H36N2O2
- Molecular weight: 444.615 g/mole
- Substance type: Organic
- Physical state: maroon lustrous liquid
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
no data available
Type of coverage:
not specified
Preparation of test site:
other: intact and avraded skin
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
1. undiluted
2. 0.5 g
Duration of treatment / exposure:
1.4hours
2. no data available
Observation period:
1. 72 hours
2. no data available
Number of animals:
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:
other: no data available
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 4-{[4-(diethylamino)phenyl](phenyl)methylidene}-N,N-diethylcyclohexa-2,5-dien-1-iminium acetatewill also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.
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 of4-{[4-(diethylamino)phenyl](phenyl)methylidene}-N,N-diethylcyclohexa-2,5-dien-1-iminium acetate

 

The dermal irritation potential of the test chemical was assessed in rabbits. The study was performed as per 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.

This is supported by an experimental study performed to assess the skin irritation potential of the structurally similar read across chemical. 0.5 g of the test chemical was applied to the intact and abraded skin of rabbits (duration of exposure not mentioned).

The test chemical was very slightly irritating to intact and abraded rabbit skin. Hence, it can be considered to be skin irritant.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that4-{[4-(diethylamino)phenyl](phenyl)methylidene}-N,N-diethylcyclohexa-2,5-dien-1-iminium acetatewill also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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 based on similar chemicals
Justification for type of information:
Weight of evidence based on similar chemicals
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
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 4-{[4-(diethylamino)phenyl](phenyl)methylidene}-N,N-diethylcyclohexa-2,5-dien-1-iminium acetate
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: Reaction mass of Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate
- Molecular formula: C29H36N2O2
- Molecular weight: 444.615 g/mole
- Substance type: Organic
- Physical state: maroon lustrous liquid
Species:
other: rabbits and humans
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
The study is based on weight of evidence approach from the read across values
Duration of treatment / exposure:
The study is based on weight of evidence approach from the read across values
Observation period (in vivo):
The study is based on weight of evidence approach from the read across values
Duration of post- treatment incubation (in vitro):
The study is based on weight of evidence approach from the read across values
Number of animals or in vitro replicates:
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
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 that4-{[4-(diethylamino)phenyl](phenyl)methylidene}-N,N-diethylcyclohexa-2,5-dien-1-iminium acetatewill also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.
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 of4-{[4-(diethylamino)phenyl](phenyl)methylidene}-N,N-diethylcyclohexa-2,5-dien-1-iminium acetate.

 

The study reports the evaluation of 17 patients who were exposed to aerosolized structurally similar chemical.

Approximately 10 lbs =(4.53kg) 4530000mg of powder was spilled onto the floor of a vehicle maintenance shop. A cleanup crew began to sweep up the powder from the floor . This resulted in an aerosol of test chemical dust that dispersed throughout the building contaminating the hair , skin, eyes, and clothing of most of the shop employees. Sixteen of the patients (94%) complained of symptoms such as redness, burning sensation..etc. One patient (6%) denied any symptoms despite being exposed to the dust for 15 minutes without a surgical mask. The most frequently reported symptom was burning o f the eyes which occurred in 82% of the patients. Four of the patients (24%) were placed on humidified oxygen because of respiratory symptoms. Five of the patients (29%) underwent irrigation of their eyes secondary to eye burning. After being discharged from the hospital, follow up was maintained. Ten of the patients (59%) reported that their symptoms had resolved within 4 hours of their exposure to the dust. One patient (6%) reported that his symptoms lasted 12 hours and 2 patients (12%) reported their symptoms lasted 24 hours. Three of the patients (18%) could not remember the duration of their symptoms.

Burning of eyes was observed in 82% of the patients. Based on these effects test chemical may be considered as irritating to eyes.

This is supported by a study was performed to assess the ocular irritation potential of the other structurally similar chemical. The test chemical was instilled into rabbit eyes and effects were observed (duration and dose not mentioned). Signs of irritation were observed in animals.

Hence, the test chemical can be considered to be irritating to rabbit eyes.

The above results are further supported by the experimental study performed in rabbits according to Fed. Reg. 38, No. 187, § 1500.42, 1973 (Draize test) Guidelines to assess the ocular irritation of another structurally similar chemical. 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.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that4-{[4-(diethylamino)phenyl](phenyl)methylidene}-N,N-diethylcyclohexa-2,5-dien-1-iminium acetatewill also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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 Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate.

 

 

The dermal irritation potential of the test chemical was assessed in rabbits. The study was performed as per 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.

This is supported by an experimental study performed to assess the skin irritation potential of the structurally similar read across chemical. 0.5 g of the test chemical was applied to the intact and abraded skin of rabbits (duration of exposure not mentioned).

The test chemical was very slightly irritating to intact and abraded rabbit skin. Hence, it can be considered to be skin irritant.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that Reaction mass of Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate will also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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 Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate

The study reports the evaluation of 17 patients who were exposed to aerosolized structurally similar chemical.

Approximately 10 lbs =(4.53kg) 4530000mg of powder was spilled onto the floor of a vehicle maintenance shop. A cleanup crew began to sweep up the powder from the floor . This resulted in an aerosol of test chemical dust that dispersed throughout the building contaminating the hair , skin, eyes, and clothing of most of the shop employees. Sixteen of the patients (94%) complained of symptoms such as redness, burning sensation..etc. One patient (6%) denied any symptoms despite being exposed to the dust for 15 minutes without a surgical mask. The most frequently reported symptom was burning o f the eyes which occurred in 82% of the patients. Four of the patients (24%) were placed on humidified oxygen because of respiratory symptoms. Five of the patients (29%) underwent irrigation of their eyes secondary to eye burning. After being discharged from the hospital, follow up was maintained. Ten of the patients (59%) reported that their symptoms had resolved within 4 hours of their exposure to the dust. One patient (6%) reported that his symptoms lasted 12 hours and 2 patients (12%) reported their symptoms lasted 24 hours. Three of the patients (18%) could not remember the duration of their symptoms.

Burning of eyes was observed in 82% of the patients. Based on these effects test chemical may be considered as irritating to eyes.

This is supported by a study was performed to assess the ocular irritation potential of the other structurally similar chemical. The test chemical was instilled into rabbit eyes and effects were observed (duration and dose not mentioned). Signs of irritation were observed in animals.

Hence, the test chemical can be considered to be irritating to rabbit eyes.

The above results are further supported by the experimental study performed in rabbits according to Fed. Reg. 38, No. 187, § 1500.42, 1973 (Draize test) Guidelines to assess the ocular irritation of another structurally similar chemical. 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.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that Reaction mass of Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate will also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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 Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate can be irritating to skin and irritating to eyes.

Hence by applying the weight of evidence approach, Reaction mass of Ethanaminium, N-​[4-​[[4-​(diethylamino)​phenyl]​phenylmethylene]​-​2,​5-​cyclohexadien-​1-​ylidene]​-​N-​ethyl-​ & acetate can be considered to be irritating to skin and eyes. It can be classified under the category “Category 2” for eye irritation as per CLP regulation.