3-(diethylamino)-7-imino-7H-[1]benzopyrano[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile

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 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1). The studies are as mentioned below:

 

The peer reviewed journal conductedskin sensitization study for read across substance in 10 female guinea pigs by using modified FCA and guinea pig maximization test.In the induction phase, the test compound was dissolved in FCA, 15 mg in 4 ml. Then physiological saline was added and an emulsion was prepared by mixing the material by mean of a 5ml syringe, until emulsification was completed.The intradermal injections of 6 X 0.10-0.15 ml of this emulsion was applied in a semi-circle arc on clipped and shaved shoulder from left to right in such a way that whole quantity of emulsion was used up for 10 animals. This procedure was repeated on 5^thand 9^thday. , leaving a gap of 2-3 cm between the rows of injection.After induction phase of 11 days, animals were challenged by applying 0.05ml of test chemical in a subirritant concentration, with further dilution to the clipped and shaved skin of the right flank of the treated animals, allowing 5 mins for drying. Control animals were also used.Mean Observations were made after 24, 48 and 72 hours. As no sensitization effects were observed, the test material can be concluded as non-sensitizing to the female guinea pigs.

 

The above result was further supported by the skin sensitization study reported by safety assessment reportfor another read across chemicalin guinea pigs. In this study, the test animals were treated dermally with 10% solution of test chemical during induction. After induction, treated animals were dermally exposed to challenge concentration of 1 or 2% solutions of test chemical. Since the test animals failed to induce any cutaneous reaction at challenge concentrations, the test chemical was considered as not sensitizing to guinea pigs.

 

Based on the above summarized studies for target chemical 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1) 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

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 test was conducted on guinea pigs to determine the potential of skin sensitization caused by the chemical.

GLP compliance:

not specified

Type of study:

other: 1. Modified FCA method and Guinea pig maximization test 2.Not specified

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material : 3-(diethylamino)-7-imino-7H-[1]benzopyrano[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile
- Molecular formula : C23H19N5O
- Molecular weight : 381.437 g/mol
- Smiles notation : c12cc3c4nc5ccccc5n4c(=N)c(C#N)c3oc1cc(N(CC)CC)cc2
- InChl : 1S/C23H19N5O/c1-3-27(4-2)15-10-9-14-11-16-21(29-20(14)12-15)17(13-24)22(25)28-19-8-6-5-7-18(19)26-23(16)28/h5-12,25H,3-4H2,1-2H3
- Substance type : Organic
- Physical state : Solid

Details on the study design:

1.TEST ANIMALS
- Source: No data available
- Age at study initiation: No Data available
- Weight at study initiation:280-350 g
- Housing: animals were kept 3 to a cage
- Diet (e.g. ad libitum):altromin ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: No Data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22-24⁰C
- Humidity (%):50-55%
- Air changes (per hr): No Data available
- Photoperiod (hrs dark / hrs light): Under artificial illumination for 10 hours a day


2.not specified

Species:

guinea pig

Strain:

other: 1.Pirbrigjht white strain 2.not specified

Sex:

female

Details on test animals and environmental conditions:

not specified

Route:

intradermal

Vehicle:

other: FCA and saline

Concentration / amount:

15 mg

Day(s)/duration:

5th and 9th day

Adequacy of induction:

other: WoE-1

Route:

other: Dermal

Vehicle:

not specified

Concentration / amount:

10%

Day(s)/duration:

not specified

Adequacy of induction:

other: WoE-2

No.:

#1

Route:

epicutaneous, open

Vehicle:

other: Acetone

Concentration / amount:

0.05ml

Day(s)/duration:

72 hours

Adequacy of challenge:

other: WoE-1

No.:

#1

Route:

other: Dermal application

Vehicle:

not specified

Concentration / amount:

1 or 2%

Day(s)/duration:

not specified

Adequacy of challenge:

other: WoE-2

No. of animals per dose:

1. Induction route-10
Challenge route-10

1.No data available.

Details on study design:

1.MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 8
- Exposure period:9 days
- Test groups: 10 guinea pigs
- Control group: 10 guinea pigs
- Site: Intradermal induction -Intraderma injection of 6x0.10-0.15 ml of emulsion were applied.The emulsion was applied in a semicircular arc on clipped and shaved shoulder area (4Х6 cm) from left to right.
- Frequency of applications: repeated on 5th and 9th days
- Duration: 9 days
- Concentrations: 15 mg in 4 ml FCA

B. CHALLENGE EXPOSURE
- No. of exposures: multiple times
- Day(s) of challenge: 11 days after induction, animals were challenged.
- Exposure period:5 mins
- Test groups: 10 guinea pigs
- Control group: 10 guinea pigs
- Site: clipped and shaved skin of the right flank of treated animals.
- Concentrations:0.05ml
- Evaluation (hr after challenge): after 24, 48 and 72 hr.

2.
MAIN STUDY
A. INDUCTION EXPOSURE

- Concentrations: 10%

B. CHALLENGE EXPOSURE
- Concentrations: 1or 2%
-

Challenge controls:

1.No data available.
2.not specified

Statistics:

1.Mean response was computed as the quotient of the sum of the observe reaction and the number of the trated animals

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

0.05 ml

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization was observed in treated group.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

1.No skin sensitization was observed in treated group.
2.

1.

Sensitizer	Challenged with	Concentration	24 hour	48 hour	72 hour	24 hour	48 hour	72 hour
			+++ ++ + (+) 0 - - - - 10	+++ ++ + (+) 0 - - - - 10	+++ ++ + (+) 0 - - - - 10	0	0	0

2. Not specified

Interpretation of results:

other: not sensitising

Conclusions:

The test chemical 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1) was considered to be not sensitizing to the 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 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1). The studies are as mentioned below:

 

The peer reviewed journal conductedskin sensitization study for read across substance in 10 female guinea pigs by using modified FCA and guinea pig maximization test.In the induction phase, the test compound was dissolved in FCA, 15 mg in 4 ml. Then physiological saline was added and an emulsion was prepared by mixing the material by mean of a 5ml syringe, until emulsification was completed.The intradermal injections of 6 X 0.10-0.15 ml of this emulsion was applied in a semi-circle arc on clipped and shaved shoulder from left to right in such a way that whole quantity of emulsion was used up for 10 animals. This procedure was repeated on 5^thand 9^thday. , leaving a gap of 2-3 cm between the rows of injection.After induction phase of 11 days, animals were challenged by applying 0.05ml of test chemical in a subirritant concentration, with further dilution to the clipped and shaved skin of the right flank of the treated animals, allowing 5 mins for drying. Control animals were also used.Mean Observations were made after 24, 48 and 72 hours. As no sensitization effects were observed, the test material can be concluded as non-sensitizing to the female guinea pigs.

 

The above result was further supported by the skin sensitization study reported by safety assessment reportfor another read across chemicalin guinea pigs. In this study, the test animals were treated dermally with 10% solution of test chemical during induction. After induction, treated animals were dermally exposed to challenge concentration of 1 or 2% solutions of test chemical. Since the test animals failed to induce any cutaneous reaction at challenge concentrations, the test chemical was considered as not sensitizing to guinea pigs.

 

Based on the above summarized studies for target chemical 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1) 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 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1). The studies are as mentioned below:

 

The peer reviewed journal conductedskin sensitization study for read across substance in 10 female guinea pigs by using modified FCA and guinea pig maximization test.In the induction phase, the test compound was dissolved in FCA, 15 mg in 4 ml. Then physiological saline was added and an emulsion was prepared by mixing the material by mean of a 5ml syringe, until emulsification was completed.The intradermal injections of 6 X 0.10-0.15 ml of this emulsion was applied in a semi-circle arc on clipped and shaved shoulder from left to right in such a way that whole quantity of emulsion was used up for 10 animals. This procedure was repeated on 5^thand 9^thday. , leaving a gap of 2-3 cm between the rows of injection.After induction phase of 11 days, animals were challenged by applying 0.05ml of test chemical in a subirritant concentration, with further dilution to the clipped and shaved skin of the right flank of the treated animals, allowing 5 mins for drying. Control animals were also used.Mean Observations were made after 24, 48 and 72 hours. As no sensitization effects were observed, the test material can be concluded as non-sensitizing to the female guinea pigs.

 

The above result was further supported by the skin sensitization study reported by safety assessment reportfor another read across chemicalin guinea pigs. In this study, the test animals were treated dermally with 10% solution of test chemical during induction. After induction, treated animals were dermally exposed to challenge concentration of 1 or 2% solutions of test chemical. Since the test animals failed to induce any cutaneous reaction at challenge concentrations, the test chemical was considered as not sensitizing to guinea pigs.

 

Based on the above summarized studies for target chemical 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1) 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 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1) 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 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.