Registration Dossier

Administrative data

Description of key information

Skin irritation

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

The experimental dermal irritation study of read across 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.

 

The above result was further supported by the skin irritation study of another read across chemical reported by authoritative database on six humans to assess its skin irritation potential. The chemical was applied on skin ofeach subject at a dose of 1 to 5 μl DMPD/cm2.Local warming, reddening, blistering and itching (in an area that was 6 times larger than the point of application) occurred on the skin of treated subjects 15-30 minutes after the application of test chemical. Bleeding and pigment changes in the deeper skin layers were diagnosed on days 2 and 3. The healing process seemed to commence as of day 3; but 3 subjects exhibited skin symptoms for 2 further weeks.On the basis of observed effects, the test chemical was considered to be irritating to the skin of six humans.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally similar read across substances,it can be concluded that the testchemical is able to cause skin irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritating to eyes)”.

 

Eye irritation

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

The experimental socular irritation study of read across chemical acetate was assessed in rabbits according to Fed. Reg. 38, No. 187, § 1500.42, 1973 (Draize test) Guidelines. About 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 acetate can be considered to be irritating to rabbit eyes.

 

The above result was further supported by the eye irritation study of another read across chemical on human patients. The study reported the evaluation of 17 patients who were exposed to aerosolized test chemical. Approximately 10 lbs =(4.53kg) 4530000mg of test chemical 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 of 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 the test chemical can be considered as irritating to eyes.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally similar read across substances,it can be concluded that the testchemical is able 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 “Category 2 (irritating to eyes)”.

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:
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 2 skin irritation studies as- WoE-2 and WoE-3. Skin irritation study of test chemical was conducted on rabbits and humans to assess its skin irritating effects.
GLP compliance:
not specified
Specific details on test material used for the study:
IUPAC name: Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate Molecular weight: 515.7375Molecular formula: C33H45N3O2Smiles: CCN(CC)c1ccc(C{+}(c2ccc(N(CC)CC)cc2)(c2ccc(N(CC)CC)cc2).O{-}C(C)=O)cc1Inchl: 1S/C31H42N3.C2H4O2/c1-7-32(8-2)28-19-13-25(14-20-28)31(26-15-21-29(22-16-26)33(9-3)10-4)27-17-23-30(24-18-27)34(11-5)12-6;1-2(3)4/h13-24H,7-12H2,1-6H3;1H3,(H,3,4)/q+1;/p-1Physical state: Solid and liquidForm: Organic
Species:
other: 1.rabbit 2.human
Strain:
other: 1.Vienna White 2.Not applicable
Details on test animals and environmental conditions:
not specified
Type of coverage:
other: 1.occlusive 2.not specified
Preparation of test site:
other: 1.shaved 2.not specified
Vehicle:
other: 1.unchanged (no vehicle) 2.not specified
Controls:
not specified
Amount / concentration applied:
1. 100%2.1 to 5 μl /cm2
Duration of treatment / exposure:
1.4 h2.3 days
Observation period:
1.1, 2 and 8 days2.15-30 minutes after the application and on days 2 and 3
Number of animals:
1.22.6
Details on study design:
1.TEST SITE - Area of exposure: to the dorsal skin- % coverage: 2.5 x 2.5 cm
Irritation parameter:
other: 1.erythema score
Basis:
mean
Time point:
other: not specified
Reversibility:
not specified
Remarks on result:
other: Exact evaluation not possible due to staining of the skin by the substance
Irritation parameter:
other: 1.edema score
Basis:
mean
Time point:
24/48 h
Score:
2.6
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 3 days
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
1.Exact evaluation for erythema was not possible due to staining of the skin by the substance.The skin findings on the sacrificed animal was confirmed by gross pathological examination after incision of the skin.2.Local warming, reddening, blistering and itching (in an area that was 6 times larger than the point of application) occurred on the skin of treated subjects 15-30 minutes after the application of test chemical. Bleeding and pigment changes in the deeper skin layers were diagnosed on days 2 and 3. The healing process seemed to commence as of day 3; but 3 subjects exhibited skin symptoms for 2 further weeks.

1.

Observation Table:

Animal No.

4 hours

1 day

2 days

8 days

Reddening

Edema

Reddening

Edema

Reddening

Edema

Reddening

Edema

1

*

2e

*

3e

*

3e

*sSe

2e

2

*

2

*

3e

*

2e

*Se

1

S: scaling

s.S.: severe scaling

e: extending beyond the area of exposure

*Exact evaluation not possible due to staining of the skin by the substance.

2.Not specified

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate was considered to be irritating to the skin of humans and rabbits.
Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

The experimental dermal irritation study of read across 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.

 

The above result was further supported by the skin irritation study of another read across chemical reported by authoritative database on six humans to assess its skin irritation potential. The chemical was applied on skin ofeach subject at a dose of 1 to 5 μl DMPD/cm2.Local warming, reddening, blistering and itching (in an area that was 6 times larger than the point of application) occurred on the skin of treated subjects 15-30 minutes after the application of test chemical. Bleeding and pigment changes in the deeper skin layers were diagnosed on days 2 and 3. The healing process seemed to commence as of day 3; but 3 subjects exhibited skin symptoms for 2 further weeks.On the basis of observed effects, the test chemical was considered to be irritating to the skin of six humans.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally similar read across substances,it can be concluded that the testchemical is able to cause skin irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritating to eyes)”.

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:
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 2 eye irritation studies as- WoE-2 and WoE-3. An eye irritation study of test chemical was conducted on human and rabbits to assess its eye irritating effects.
GLP compliance:
not specified
Specific details on test material used for the study:
IUPAC name: Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate Molecular weight: 515.7375Molecular formula: C33H45N3O2Smiles: CCN(CC)c1ccc(C{+}(c2ccc(N(CC)CC)cc2)(c2ccc(N(CC)CC)cc2).O{-}C(C)=O)cc1Inchl: 1S/C31H42N3.C2H4O2/c1-7-32(8-2)28-19-13-25(14-20-28)31(26-15-21-29(22-16-26)33(9-3)10-4)27-17-23-30(24-18-27)34(11-5)12-6;1-2(3)4/h13-24H,7-12H2,1-6H3;1H3,(H,3,4)/q+1;/p-1Physical state: Solid and liquidForm: Organic
Species:
other: 1.Rabbit 2.human
Strain:
other: 1. albino 2.Not applicable
Details on test animals or tissues and environmental conditions:
1.TEST ANIMALS- Weight at study initiation:ca. 3 - 4 kg- Housing:One animal per cage- Diet (e.g. ad libitum): a standardized animal laboratory diet, ad libitum- Water (e.g. ad libitum): tap water ad libitum.- Acclimation period:at least 3 daysENVIRONMENTAL CONDITIONS- Temperature (°C):22 +/- 1°C- Humidity (%):55 +/- 10%- Photoperiod (hrs dark / hrs light):12 h light, 12 h darkness2.Age at study initiation: 16 males of mean age 39 years (25-50) and one female 40 year old.
Vehicle:
other: 1.unchanged (no vehicle) 2.not specified
Controls:
yes
Amount / concentration applied:
1.100 mg2.4530000 mg
Duration of treatment / exposure:
1.24 hours2.26 min
Observation period (in vivo):
1.72 hours2.24hrs
Number of animals or in vitro replicates:
1. 6 2.17 individuals
Details on study design:
1.The test substance was not washed out.Readings: 1 h, 24 h, 48 h and 72 h after instillation2.Not specified
Irritation parameter:
other: 1.cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
other: 1.iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
2
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
other: 1.chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
other: 2.overall irritation score
Basis:
mean
Time point:
24 h
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
1.Due to substance colouring, conjunctivae score was not assessed.2.Burning of the eyes (82%), excessive tearing (47%), nasal burning (41%), nasal itching (35%), chest pain/tightness (35%), rhinorhea (29%), cough (29%), dyspnea (29%), burning of the throat (24%). burning/ pruritic skin (24%), chest burning (12%), headache (6%), and nausea (6%).
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate was considered to be irritating to the eyes.
Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

The experimental socular irritation study of read across chemical acetate was assessed in rabbits according to Fed. Reg. 38, No. 187, § 1500.42, 1973 (Draize test) Guidelines. About 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 acetate can be considered to be irritating to rabbit eyes.

 

The above result was further supported by the eye irritation study of another read across chemical on human patients. The study reported the evaluation of 17 patients who were exposed to aerosolized test chemical. Approximately 10 lbs =(4.53kg) 4530000mg of test chemical 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 of 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 the test chemical can be considered as irritating to eyes.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally similar read across substances,it can be concluded that the testchemical is able 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 “Category 2 (irritating to eyes)”.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

The experimental dermal irritation study of read across 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.

 

The above result was further supported by the skin irritation study of another read across chemical reported by authoritative database on six humans to assess its skin irritation potential. The chemical was applied on skin ofeach subject at a dose of 1 to 5 μl DMPD/cm2.Local warming, reddening, blistering and itching (in an area that was 6 times larger than the point of application) occurred on the skin of treated subjects 15-30 minutes after the application of test chemical. Bleeding and pigment changes in the deeper skin layers were diagnosed on days 2 and 3. The healing process seemed to commence as of day 3; but 3 subjects exhibited skin symptoms for 2 further weeks.On the basis of observed effects, the test chemical was considered to be irritating to the skin of six humans.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally similar read across substances,it can be concluded that the testchemical is able to cause skin irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritating to eyes)”.

 

Eye irritation

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate. The studies are as mentioned below:

 

The experimental socular irritation study of read across chemical acetate was assessed in rabbits according to Fed. Reg. 38, No. 187, § 1500.42, 1973 (Draize test) Guidelines. About 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 acetate can be considered to be irritating to rabbit eyes.

 

The above result was further supported by the eye irritation study of another read across chemical on human patients. The study reported the evaluation of 17 patients who were exposed to aerosolized test chemical. Approximately 10 lbs =(4.53kg) 4530000mg of test chemical 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 of 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 the test chemical can be considered as irritating to eyes.

 

Based on the above summarized studies for target chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally similar read across substances,it can be concluded that the testchemical is able 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 “Category 2 (irritating to eyes)”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate and its structurally and functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical  is likely to cause skin and eye irritation. Hence Reaction mass of Methylium, tris[4-(diethylamino)phenyl]- & acetate can be classified under the category “Category 2 (irritating to eyes)” for skin and eye as per CLP.