Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride . The studies are as mentioned below:

 

A study was designed and conducted to determine the dermal reaction profile of read across chemical in Wistar 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 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. 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. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.

 

The above result was supported by the skin irritation study of another read across chemical by a peer reviewed journal on rabbits’ ear to indicate the Comedogenicity and irritancy of test compound. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control. The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The test chemical falls under Grade 0 (no irritation observed).Hence it can be concluded that the test chemical was not irritating to rabbit ears.

 

Based on the above summarized studies for target chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

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 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride . The studies are as mentioned below:

 

An eye irritation study was carried out by safety assessment report on Himalayan albino rabbits to assess the irritation potency of read across chemical. 0.1 g of test substance was instilled into the conjunctival sac of the left eye of six Albino-Himalaya rabbits. The right eye remained untreated and served as reference control. Scoring of irritation was performed 1, 7, 24, 48 and 72 hours after application with a magnifying glass. After 24 hours all eyes were rinsed with physiological saline. Because of colour interference, an exact judgement was not possible in the area of the cornea (1 and 7 hours after post application). The overall irritation score after 72 hours was as follows: Cornea = 0.00, iris = 0.00, conjunctiva redness = 0.67, conjunctiva chemosis = 0.06. Hence it can be considered that the test chemical was not irritating to rabbit eyes.

 

The above result was further supported by an ocular irritation study of another read across chemical in New Zealand White rabbits reported by the safety assessment report. The study was performed as per OECD 405 Guidelines. 3 male New Zealand White rabbits, thirteen to sixteen weeks old were used for the study. The eyes of each animal were examined prior to administration instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation. One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed. Approximately 70 mg of the test substance, the weight occupying a volume of 0.1 ml, was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated as control. Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48, and 72 hours) after instillation. Additional observations were made for two animals four days after treatment. : Observation of the eyes was aided by the use of a handheld light. Ocular irritation was assessed on the cornea, iris, conjunctivae, and chemosis. There were no signs of toxicity or ill health in any rabbit during the observation period. No corneal damage or iridial inflammation was observed. Transient hyperemia of blood vessels to a diffuse crimson coloration of the conjunctivae with slight swelling or partial eversion of the eyelids was observed in all animals. These responses had resolved completely by two days after instillation. Since, the effects were completely resolved by 2 days, the test chemical can be considered to be not irritating to New Zealand White rabbit eyes.

Based on the above summarized studies for target chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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 similar read across chemicals
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
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 rats and rabbits to assess its skin irritating effects.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material : Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride- Molecular formula : C35H46ClN5O4- Molecular weight : 636.232 g/mol-Smiles notation: C(CCOC(\C(=C\c1ccc(cc1)N(CC)CC)C#N)=O)[N+](C)(C)CCOC(\C(=C\c1ccc(cc1)N(CC)CC)C#N)=O.[ClH-]- InChl : 1S/C35H46N5O4.ClH/c1-7-38(8-2)32-16-12-28(13-17-32)24-30(26-36)34(41)43-22-11-20-40(5,6)21-23-44-35(42)31(27-37)25-29-14-18-33(19-15-29)39(9-3)10-4;/h12-19,24-25H,7-11,20-23H2,1-6H3;1H/q+1;/p-1/b30-24+,31-25+;- Substance type: Organic- Physical state: Liquid
Species:
other: 1.rat 2.rabbit
Strain:
other: 1.Wistar 2.New Zealand White
Details on test animals or test system and environmental conditions:
1.TEST ANIMALS- Sex:Male and Female- Source: In-House Bred at sa-FORD, Animal Facility- Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant- Age at study initiation: no data available- Weight at study initiation:Male:Minimum: 240 g and Maximum: 280 g;Female:Minimum: 222 g and Maximum: 239 g (Prior to Treatment)- Housing:Three animals were housed per polycarbonate cage of size 37 [cm] x 21 [cm], height 20 [cm].- Bedding:All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) Batch No.: SPAR – 32/2016- Diet (e.g. ad libitum): All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No: 040316.- 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 7 days prior to test item application.- Identification: During Acclimatization, animals were marked temporary by permanent marker, on their tails. After acclimatization, the animals were marked by toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number experimental start date, dosing date and completion date.- Randomization: Animals were selected manually. No computer generated randomization program was used- Room 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. ENVIRONMENTAL CONDITIONS - Temperature (°C): Minimum: 19.80 °C ; Maximum: 22.80 °C - Humidity (%): Minimum: 47.10%; Maximum: 68.60% - Air changes (per hr): More than 12 changes per hour - Photoperiod (hrs dark / hrs light): 12 hour light and 12 hour dark2.TEST ANIMALSSource: No dataAge at study initiation: No dataWeight at study initiation: 3 kg Fasting period before study: No dataHousing: singly housed, in suspended cagesDiet (e.g. ad libitum): Purina Rabbit Chow, ad libitumWater (e.g. ad libitum): water, ad libitumAcclimation period: No dataENVIRONMENTAL CONDITIONS Temperature (°C): No data Humidity (%):No data Air changes (per hr): No data Photoperiod (hrs dark / hrs light): 12 hour light and 12 hr dark cycleIN-LIFE DATES: From: No data To: No data
Type of coverage:
other: 1.occlusive 2.Entire inner surface of one ear
Preparation of test site:
other: 1.clipped 2.A colony of rabbits that had genetically good ears and which were free from mites were used for the assay
Vehicle:
other: 1.water 2.propylene glycol
Controls:
not specified
Amount / concentration applied:
1.limit dose of 2000mg/kg moistened with 0.2 ml distilled water2.Dose of 1ml of the test material was applied once daily for five days per week for 2 weeks.
Duration of treatment / exposure:
1.24 hours2.2 weeks
Observation period:
1.14 days2.2 weeks
Number of animals:
1.5 male and 5 female rats2.3 rabbits
Details on study design:
1.TEST SITE - Area of exposure: dorsal area - % coverage: no data available - Type of wrap if used: This porous gauze dressing was covered with a non-irritating tape REMOVAL OF TEST SUBSTANCE - Washing (if done):yes - Time after start of exposure: After the 24-hour application period, the dressings were removed and the skin was gently wiped with distilled water. OBSERVATION TIME POINTS(indicate if minutes, hours or days) : All animals were observed for dermal irritation and signs of toxicity at approximately 1, 2, 3 and 4 hours after treatment on day 0 and once daily during test days 1 14SCORING SYSTEM: - Method of calculation: no data available2.TEST SITEArea of exposure: Ear% coverage: A dose of 1ml of the test chemical is applied and spread once daily to the entire inner surface of one ear five days per week for 2 weeks.Type of wrap if used: No dataREMOVAL OF TEST SUBSTANCEWashing (if done): No dataTime after start of exposure: No dataSCORING SYSTEM: The irritancy produced by repeated application of a chemical or skin care product on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows: 0 = No irritation1 = few scales, no Erythema2 = diffuse scaling, no Erythema3 = Generalized scaling with Erythema4 = Scaling, Erythema and Edema5 = Epidermal necrosis and slough
Other effects / acceptance of results:
no data available
Irritation parameter:
other: 1.overall irritation score
Basis:
mean
Time point:
14 d
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
other: 2.overall irritation score
Basis:
mean
Time point:
14 d
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
1.No local signs of toxicity (e.g.: Abrasion, Alopecia, Erythema, Oedema, Scale Formation etc.) were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period2.No erythema observed
Other effects:
1.No mortality was observed at limit dose of 2000 mg/kg body weight of test item during the 14 day observation period. Mean body weight of male and female animals was observed with gain on day 7 and 14 as compared to day 0. The external and internal gross pathological observation of all terminally sacrificed animals did not show any pathological abnormality.No systemic signs of toxicity were observed at limit dose of 2000 mg/kg body weight of test item during the experimental period.2.No erythema observed

1.

Individual Animal Clinical Signs, Symptoms and Local Signs/Skin Reactions

 

Dose:2000 mg/kg body weight

Animal

No.

Sex

Hour(s) - Day 0

Day

1

2

3

4

1

2

3

4

5

6

7

01

Male

1

1

1

1

1

1

1

1

1

1

1

02

1

1

1

1

1

1

1

1

1

1

1

03

1

1

1

1

1

1

1

1

1

1

1

04

1

1

1

1

1

1

1

1

1

1

1

05

1

1

1

1

1

1

1

1

1

1

1

06

Female

1

1

1

1

1

1

1

1

1

1

1

07

1

1

1

1

1

1

1

1

1

1

1

08

1

1

1

1

1

1

1

1

1

1

1

09

1

1

1

1

1

1

1

1

1

1

1

10

1

1

1

1

1

1

1

1

1

1

1

 

Animal

No.

Sex

Day

8

9

10

11

12

13

14

01

Male

1

1

1

1

1

1

1

02

1

1

1

1

1

1

1

03

1

1

1

1

1

1

1

04

1

1

1

1

1

1

1

05

1

1

1

1

1

1

1

06

Female

1

1

1

1

1

1

1

07

1

1

1

1

1

1

1

08

1

1

1

1

1

1

1

09

1

1

1

1

1

1

1

10

1

1

1

1

1

1

1

Key: 1 = Normal

Individual Animal Body Weight (g) andBody Weight Changes(%)

 

Dose:2000 mg/ kg bodyweight                                                                                                         

Animal No.

Sex

Dose

(mg)*

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

01

Male

480

240

250

269

4.17

12.08

02

546

273

291

322

6.59

17.95

03

532

266

275

296

3.38

11.28

04

560

280

292

311

4.29

11.07

05

498

249

257

294

3.21

18.07

06

Female

470

235

239

253

1.70

7.66

07

478

239

243

258

1.67

7.95

08

444

222

226

241

1.80

8.56

09

450

225

226

240

0.44

6.67

10

454

227

228

238

0.44

4.85

    Key:* =Based on the day 0 body weight

Individual Animal Mortality Record

 

Dose:2000 mg/kg body weight

       Animal No.

Sex

Days of Observation (0 to 14)

Morning Observations

Evening Observations

01

Male

No mortality and morbidity

No mortality and morbidity

02

No mortality and morbidity

No mortality and morbidity

03

No mortality and morbidity

No mortality and morbidity

04

No mortality and morbidity

No mortality and morbidity

05

No mortality and morbidity

No mortality and morbidity

06

Female

No mortality and morbidity

No mortality and morbidity

07

No mortality and morbidity

No mortality and morbidity

08

No mortality and morbidity

No mortality and morbidity

09

No mortality and morbidity

No mortality and morbidity

10

No mortality and morbidity

No mortality and morbidity


Summaryof Animal Body Weight (g) and Body Weight Changes (%)

 

Dose:2000 mg/kg body weight

Sex

Body Weight (gram)

Body Weight Changes (%)

Day 0

Day 7

Day 14

Day 0-7

Day 0-14

Male

Mean

261.60

273.00

298.40

4.33

14.09

SD

16.68

19.20

20.03

1.35

3.60

n

5

5

5

5

5

Female

Mean

229.60

232.40

246.00

1.21

7.14

SD

7.13

8.02

8.92

0.70

1.45

n

5

5

5

5

5

Keys:SD= Standard deviation, n = Number of animals

2.

 Table Ingredients and their Comedogenicity and Irritancy

Test chemical

Comedogenicity*

[Grade 0-5]

Irritancy**

[Grade 0-5]

test chemical

2

0

 

*Comedogenicity or the ability of test substance to produce follicular hyperkeratosis

** Irritancy or ability of test substance to produce surface epithelial irritation


 

Interpretation of results:
other: not irritating
Conclusions:
The test chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride was considered to be irritating to the skin of rabbits and rats.
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 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride . The studies are as mentioned below:

 

A study was designed and conducted to determine the dermal reaction profile of read across chemical in Wistar 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 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. 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. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.

 

The above result was supported by the skin irritation study of another read across chemical by a peer reviewed journal on rabbits’ ear to indicate the Comedogenicity and irritancy of test compound. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control. The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The test chemical falls under Grade 0 (no irritation observed).Hence it can be concluded that the test chemical was not irritating to rabbit ears.

 

Based on the above summarized studies for target chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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:
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 similar read across chemicals
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
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 rabbits to assess its eye irritating effects.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material : Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride- Molecular formula : C35H46ClN5O4- Molecular weight : 636.232 g/mol-Smiles notation: C(CCOC(\C(=C\c1ccc(cc1)N(CC)CC)C#N)=O)[N+](C)(C)CCOC(\C(=C\c1ccc(cc1)N(CC)CC)C#N)=O.[ClH-]- InChl : 1S/C35H46N5O4.ClH/c1-7-38(8-2)32-16-12-28(13-17-32)24-30(26-36)34(41)43-22-11-20-40(5,6)21-23-44-35(42)31(27-37)25-29-14-18-33(19-15-29)39(9-3)10-4;/h12-19,24-25H,7-11,20-23H2,1-6H3;1H/q+1;/p-1/b30-24+,31-25+;- Substance type: Organic- Physical state: Liquid
Species:
rabbit
Strain:
other: 1.Himalayan 2.New Zealand White
Details on test animals or tissues and environmental conditions:
1. Not specified 2.- Sex: Male- Age at study initiation: Thirteen to sixteen weeks old- Weight at study initiation: 3.0 - 3.6 kg
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
1.0.1 g2.0.1 ml (70 mg)
Duration of treatment / exposure:
1.24 hours2.One dosage per 72 hour observation period.
Observation period (in vivo):
1.3 days2.Examination of the eyes was made after 1 hour and 1,2,3 days (equivalent to 24, 48, and 72 hours) after instillation.
Number of animals or in vitro replicates:
1.62.3 male rabbits
Details on study design:
1.TEST SITEArea of exposure: Conjunctival sac of the left eye % coverage: Not applicableType of wrap if used: Not applicableREMOVAL OF TEST SUBSTANCE- Washing (if done): After 24 hours all eyes were rinsed with physiological saline- Time after start of exposure: 24 hoursSCORING SYSTEM: Scoring of irritation was performed 1, 7, 24, 48 and 72 hours after application with a magnifying glass.2.TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: Observation of the eyes was aided by the use of a handheld light. Ocular irritation was assessed on the cornea, iris, conjunctivae, and chemosis.Observations: Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48, and 72 hours) after instillation. Additional observations were made for two animals four days after treatment.
Irritation parameter:
other: 1.overall irritation score
Basis:
mean
Time point:
72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
other: 2.overall irritation score
Basis:
mean
Time point:
24/48 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
1. Because of colour interference, an exact judgement was not possible in the area of the cornea (1 and 7 hours after post application).2.No corneal damage or iridial inflammation was observed.Transient hyperemia of blood vessels to a diffuse crimson coloration of the conjunctivae with slight swelling or partial eversion of the eyelids was observed in all animals. These responses had resolved completely by two days after instillation.
Other effects:
1. Not specified2.There were no signs of toxicity or ill health in any rabbit during the observation period

1.

Table 1: Overall Irritation Score

Irritation parameter

Mean score after 72 hours

Cornea opacity

0.00

Iris

0.00

Conjunctiva redness

0.67

Conjunctiva chemosis

0.06

 

2.Not specified

Interpretation of results:
other: not irritating
Conclusions:
The test chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride was considered to be not irritating to the eyes of rabbits.
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 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride . The studies are as mentioned below:

 

An eye irritation study was carried out by safety assessment report on Himalayan albino rabbits to assess the irritation potency of read across chemical. 0.1 g of test substance was instilled into the conjunctival sac of the left eye of six Albino-Himalaya rabbits. The right eye remained untreated and served as reference control. Scoring of irritation was performed 1, 7, 24, 48 and 72 hours after application with a magnifying glass. After 24 hours all eyes were rinsed with physiological saline. Because of colour interference, an exact judgement was not possible in the area of the cornea (1 and 7 hours after post application). The overall irritation score after 72 hours was as follows: Cornea = 0.00, iris = 0.00, conjunctiva redness = 0.67, conjunctiva chemosis = 0.06. Hence it can be considered that the test chemical was not irritating to rabbit eyes.

 

The above result was further supported by an ocular irritation study of another read across chemical in New Zealand White rabbits reported by the safety assessment report. The study was performed as per OECD 405 Guidelines. 3 male New Zealand White rabbits, thirteen to sixteen weeks old were used for the study. The eyes of each animal were examined prior to administration instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation. One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed. Approximately 70 mg of the test substance, the weight occupying a volume of 0.1 ml, was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated as control. Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48, and 72 hours) after instillation. Additional observations were made for two animals four days after treatment. : Observation of the eyes was aided by the use of a handheld light. Ocular irritation was assessed on the cornea, iris, conjunctivae, and chemosis. There were no signs of toxicity or ill health in any rabbit during the observation period. No corneal damage or iridial inflammation was observed. Transient hyperemia of blood vessels to a diffuse crimson coloration of the conjunctivae with slight swelling or partial eversion of the eyelids was observed in all animals. These responses had resolved completely by two days after instillation. Since, the effects were completely resolved by 2 days, the test chemical can be considered to be not irritating to New Zealand White rabbit eyes.

Based on the above summarized studies for target chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride . The studies are as mentioned below:

 

A study was designed and conducted to determine the dermal reaction profile of read across chemical in Wistar 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 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. 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. The overall irritation score of the substance was obtained to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days observation period after patch removal. Hence, it was concluded that the test substance was non-Irritating to the skin of rats under the experimental conditions tested.

 

The above result was supported by the skin irritation study of another read across chemical by a peer reviewed journal on rabbits’ ear to indicate the Comedogenicity and irritancy of test compound. The test chemical was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control. The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The test chemical falls under Grade 0 (no irritation observed).Hence it can be concluded that the test chemical was not irritating to rabbit ears.

 

Based on the above summarized studies for target chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

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 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride . The studies are as mentioned below:

 

An eye irritation study was carried out by safety assessment report on Himalayan albino rabbits to assess the irritation potency of read across chemical. 0.1 g of test substance was instilled into the conjunctival sac of the left eye of six Albino-Himalaya rabbits. The right eye remained untreated and served as reference control. Scoring of irritation was performed 1, 7, 24, 48 and 72 hours after application with a magnifying glass. After 24 hours all eyes were rinsed with physiological saline. Because of colour interference, an exact judgement was not possible in the area of the cornea (1 and 7 hours after post application). The overall irritation score after 72 hours was as follows: Cornea = 0.00, iris = 0.00, conjunctiva redness = 0.67, conjunctiva chemosis = 0.06. Hence it can be considered that the test chemical was not irritating to rabbit eyes.

 

The above result was further supported by an ocular irritation study of another read across chemical in New Zealand White rabbits reported by the safety assessment report. The study was performed as per OECD 405 Guidelines. 3 male New Zealand White rabbits, thirteen to sixteen weeks old were used for the study. The eyes of each animal were examined prior to administration instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation. One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed. Approximately 70 mg of the test substance, the weight occupying a volume of 0.1 ml, was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated as control. Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48, and 72 hours) after instillation. Additional observations were made for two animals four days after treatment. : Observation of the eyes was aided by the use of a handheld light. Ocular irritation was assessed on the cornea, iris, conjunctivae, and chemosis. There were no signs of toxicity or ill health in any rabbit during the observation period. No corneal damage or iridial inflammation was observed. Transient hyperemia of blood vessels to a diffuse crimson coloration of the conjunctivae with slight swelling or partial eversion of the eyelids was observed in all animals. These responses had resolved completely by two days after instillation. Since, the effects were completely resolved by 2 days, the test chemical can be considered to be not irritating to New Zealand White rabbit eyes.

Based on the above summarized studies for target chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride  and its structurally and functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical  is unlikely to cause skin and eye irritation. Hence Reaction mass of 1-Propanaminium, 3-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]-N-[2-[[2-cyano-3-[4-(diethylamino)phenyl]-1-oxo-2-propen-1-yl]oxy]ethyl]-N,N-dimethyl- & chloride can be classified under the category “Not Classified” for skin and eye as per CLP.