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

Endpoint summary

Description of key information

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization 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:

 

The skin sanitization study of read across chemical was conducted by a safety assessment report in 10 female guinea pigs to determine its sensitization potential. The study was conducted according to OECD 406 Guidelines.  For intradermal induction, the test animals received 6 injections (2 injections of a 0.1 ml Freund’s adjuvant/aqua dest 1:1, 2 injections of 0.1 ml of a 5% test substance formulation, 2 injections of a 0.1 ml 5% test substance formulation in Freund’s adjuvant/aqua dest 1:1). The intradermal induction with 5% test substance preparations caused moderate and confluent erythema and swelling or intense erythema and swelling in test group animals at 24 h after application. Percutaneous induction was carried out 1 week after intradermal induction. The test substance (25% in olive oil) and the vehicle were applied for 48 h to the animals under occlusive conditions. Incrustation, erythema and oedema were observed in test and control animals at 48 h after beginning of application. After the epicutaneous induction, incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test groups animals. A challenge with a 25% test substance preparation in olive oil was performed 14 days after the epicutaneous induction. No skin reactions could be observed neither in control group nor in the test group, 24 and 48 hours after removal of the patches. Olive oil, which was applied as a vehicle control to all animals, did not cause any skin reactions. Since no borderline results were observed, a 2nd challenge was not performed. Therefore, it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test.

 

The above result was further supported by the dermal sensitization study of another read across chemical in guinea pigs. The study was performed as per OECD 406 Guidelines. 10 female were used for and 5 female Himalayan spotted guinea pigs were used in the test and control groups respectively. In induction treatment, 10 females in test group, 5 females in control group were used. Animals were induced with intradermal induction of Freund´s Complete Adjuvant (FCA) and physiological saline (1:1), test item at 5% in 1 % CMC and 5 % dilution of the test item in 1% CMC in a 1:1 mixture with FCA / physiological saline on day 1. After 7 days, epidermal induction of sensitization (day 8) was conducted under occlusion with the test item at 50 % in 1 % CMC for 48 hours. The challenge was performed at day 22 by application of the test item at 10 % in 1 % CMC under occlusive patch for 24 h at a different part of the skin. Observations were made at 24 and 48 hours removal of the dressing. After challenge exposure, no skin reactions were observed. Hence, sodium the test chemical was considered to be non-sensitizing to the Himalayan spotted albino guinea pigs.

 

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 and functionally similar read across substances,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. 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 sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 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 sensitization studies as- WoE-2 and WoE-3. Skin sensitization of test chemical was determined by performing tests on guinea pigs.

GLP compliance:

not specified

Type of study:

other: 1.guinea pig maximisation test

Justification for non-LLNA method:

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:

guinea pig

Strain:

other: 1.not specified 2.Himalayan

Sex:

female

Details on test animals and environmental conditions:

1.- Age at study initiation: 327 – 375 g2.No data available.

Route:

other: 1.intradermal and epicutaneous

Vehicle:

olive oil

Concentration / amount:

INTRADERMAL INDUCTION: Test substance 5% in olive oil or 5% in Freund's adjuvant, 10.9% aqueous NaCl-solution (1:1)EPICUTANEOUS INDUCTION: Test substance 25 % in olive oil

Day(s)/duration:

24 hours, 6 exposures

Adequacy of induction:

not specified

Route:

other: 2.intradermal and epicutaneous

Vehicle:

CMC (carboxymethyl cellulose)

Concentration / amount:

Intradermal Induction:•Freund´s Complete Adjuvant (FCA) and physiological saline (1:1)• test chemical at 5% in 1 % CMC•5 % dilution of the test chemical in 1% CMC in a 1:1 mixture with FCA / physiological saline.Epidermal Induction:•50% in 1% CMC solution

Day(s)/duration:

Intradermal Induction: 7 days Epidermal Induction: 48 hour

Adequacy of induction:

not specified

Route:

other: 1.epicutaneous, occlusive

Vehicle:

olive oil

Concentration / amount:

CHALLENGE: Test substance 25 % in olive oil

Day(s)/duration:

24 hours

Adequacy of challenge:

not specified

Route:

other: 2.epicutaneous, occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Concentration / amount:

10%

Day(s)/duration:

24 and 48 hour

Adequacy of challenge:

not specified

No. of animals per dose:

1.20 Guinea pigs10: Test group10: Control group2.15 Guinea pigs10 females: test group, 5 females :control group

Details on study design:

1.MAIN STUDYA. 1.INDUCTION EXPOSURE- No. of exposures:6- Exposure period:24 hours- Test groups:10 Guinea pigs- Control group: Guinea pigs- Site: no data available- Frequency of applications:- Duration:24 hours- Concentrations: Test substance 5% in olive oil or 5% in Freund's adjuvant, 10.9% aqueous NaCl-solution (1:1)A.2. EPICUTANEOUS INDUCTION EXPOSURE- No. of exposures:1- Exposure period:48 hours- Test groups: 10 Guinea pigs- Control group: 10 Guinea pigs- Site: no data available- Frequency of applications:- Duration:48 hours- Concentrations: Test substance 25 % in olive oilB. CHALLENGE EXPOSURE- No. of exposures:1- Day(s) of challenge: 14 days after theepicutaneous induction- Exposure period: 24 hours - Test groups: 10 Guinea pigs- Control group: 10 Guinea pigs- Site:no data available- Concentrations: Test substance 25 % in olive oil- Evaluation (hr after challenge): 24 and 48 hours after removal of the patches.2.Details on study designRANGE FINDING TESTS:MAIN STUDYA.1. INDUCTION EXPOSURE: Intradermal Induction:- No. of exposures:1- Exposure period:7 days- Test groups:10 females- Control group:5 females- Site:- Frequency of applications:- Duration: 7 days- Concentrations: •Freund´s Complete Adjuvant (FCA) and physiological saline (1:1)• 5% in 1 % CMC•5 % dilution in 1% CMC in a 1:1 mixture with FCA / physiological salineA.2. INDUCTION EXPOSURE: Epidermal Induction- No. of exposures:1- Exposure period:48 hours- Test groups: 10 females- Control group: 5 females- Site:- Frequency of applications:- Duration: 48 hours- Concentrations: 50% in 1% CMC solutionB. CHALLENGE EXPOSURE- No. of exposures:1- Day(s) of challenge: on day 22- Exposure period:24 hours- Test groups: 10 females- Control group: 5 females- Site: different part of the skin- Concentrations: 10% in 1% CMC solution- Evaluation (hr after challenge): at 24 and 48 hours removal of the dressings

Challenge controls:

No data available

Reading:

other: 1.1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

25 % in olive oil

No. with + reactions:

0

Clinical observations:

moderate and confluent erythema and swelling or intense erythema, Incrustation and oedema

Remarks on result:

no indication of skin sensitisation

Reading:

other: 1.1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization was observed.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

1.moderate and confluent erythema and swelling or intense erythema, Incrustation and oedema.2.No skin sensitization was observed.

1.Since no borderline results were observed, a 2^ndchallenge was not performed.

2.Not specified

Interpretation of results:

other: not sensitizing

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 sensitizing on skin of guinea pigs.

Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization 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:

 

The skin sanitization study of read across chemical was conducted by a safety assessment report in 10 female guinea pigs to determine its sensitization potential. The study was conducted according to OECD 406 Guidelines.  For intradermal induction, the test animals received 6 injections (2 injections of a 0.1 ml Freund’s adjuvant/aqua dest 1:1, 2 injections of 0.1 ml of a 5% test substance formulation, 2 injections of a 0.1 ml 5% test substance formulation in Freund’s adjuvant/aqua dest 1:1). The intradermal induction with 5% test substance preparations caused moderate and confluent erythema and swelling or intense erythema and swelling in test group animals at 24 h after application. Percutaneous induction was carried out 1 week after intradermal induction. The test substance (25% in olive oil) and the vehicle were applied for 48 h to the animals under occlusive conditions. Incrustation, erythema and oedema were observed in test and control animals at 48 h after beginning of application. After the epicutaneous induction, incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test groups animals. A challenge with a 25% test substance preparation in olive oil was performed 14 days after the epicutaneous induction. No skin reactions could be observed neither in control group nor in the test group, 24 and 48 hours after removal of the patches. Olive oil, which was applied as a vehicle control to all animals, did not cause any skin reactions. Since no borderline results were observed, a 2nd challenge was not performed. Therefore, it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test.

 

The above result was further supported by the dermal sensitization study of another read across chemical in guinea pigs. The study was performed as per OECD 406 Guidelines. 10 female were used for and 5 female Himalayan spotted guinea pigs were used in the test and control groups respectively. In induction treatment, 10 females in test group, 5 females in control group were used. Animals were induced with intradermal induction of Freund´s Complete Adjuvant (FCA) and physiological saline (1:1), test item at 5% in 1 % CMC and 5 % dilution of the test item in 1% CMC in a 1:1 mixture with FCA / physiological saline on day 1. After 7 days, epidermal induction of sensitization (day 8) was conducted under occlusion with the test item at 50 % in 1 % CMC for 48 hours. The challenge was performed at day 22 by application of the test item at 10 % in 1 % CMC under occlusive patch for 24 h at a different part of the skin. Observations were made at 24 and 48 hours removal of the dressing. After challenge exposure, no skin reactions were observed. Hence, sodium the test chemical was considered to be non-sensitizing to the Himalayan spotted albino guinea pigs.

 

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 and functionally similar read across substances,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. 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 sensitising)

Additional information:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the skin sensitization 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:

 

The skin sanitization study of read across chemical was conducted by a safety assessment report in 10 female guinea pigs to determine its sensitization potential. The study was conducted according to OECD 406 Guidelines.  For intradermal induction, the test animals received 6 injections (2 injections of a 0.1 ml Freund’s adjuvant/aqua dest 1:1, 2 injections of 0.1 ml of a 5% test substance formulation, 2 injections of a 0.1 ml 5% test substance formulation in Freund’s adjuvant/aqua dest 1:1). The intradermal induction with 5% test substance preparations caused moderate and confluent erythema and swelling or intense erythema and swelling in test group animals at 24 h after application. Percutaneous induction was carried out 1 week after intradermal induction. The test substance (25% in olive oil) and the vehicle were applied for 48 h to the animals under occlusive conditions. Incrustation, erythema and oedema were observed in test and control animals at 48 h after beginning of application. After the epicutaneous induction, incrustation, partially open (caused by the intradermal induction) could be observed in addition to moderate and confluent erythema and swelling in all test groups animals. A challenge with a 25% test substance preparation in olive oil was performed 14 days after the epicutaneous induction. No skin reactions could be observed neither in control group nor in the test group, 24 and 48 hours after removal of the patches. Olive oil, which was applied as a vehicle control to all animals, did not cause any skin reactions. Since no borderline results were observed, a 2nd challenge was not performed. Therefore, it was concluded that the test substance does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test.

 

The above result was further supported by the dermal sensitization study of another read across chemical in guinea pigs. The study was performed as per OECD 406 Guidelines. 10 female were used for and 5 female Himalayan spotted guinea pigs were used in the test and control groups respectively. In induction treatment, 10 females in test group, 5 females in control group were used. Animals were induced with intradermal induction of Freund´s Complete Adjuvant (FCA) and physiological saline (1:1), test item at 5% in 1 % CMC and 5 % dilution of the test item in 1% CMC in a 1:1 mixture with FCA / physiological saline on day 1. After 7 days, epidermal induction of sensitization (day 8) was conducted under occlusion with the test item at 50 % in 1 % CMC for 48 hours. The challenge was performed at day 22 by application of the test item at 10 % in 1 % CMC under occlusive patch for 24 h at a different part of the skin. Observations were made at 24 and 48 hours removal of the dressing. After challenge exposure, no skin reactions were observed. Hence, sodium the test chemical was considered to be non-sensitizing to the Himalayan spotted albino guinea pigs.

 

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 and functionally similar read across substances,it can be concluded that the testchemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 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. From the results obtained from these studies it is concluded that the 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 is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.