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

Endpoint summary

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 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 irritation study of read across substance in guinea pigs. The10 female Pirbright-White guinea pigs were treated with an emulsion prepared from FCA and physiological saline but without the test chemical and applied on a semicircular arc on the clipped or shaved shoulder area (4*6 cm) from left to right in such a way that whole emulsion was used up for the animals.1 day before the challenge exposure, ten guinea pigs were treated with test chemical by applying different concentrations of the test chemical (10%, 3% and 1%) to the right flank. The results of the challenge exposure were observed after 24 hours. A (+) reaction was considered as threshold of irritation. The mean irritation index of chemical was 0.0 after 24 hours. Hence, the test material was considered to be not irritating to guinea pigs.

 

Above result was further supported by dermal irritation carried out byanother peer reviewed journal for another read across substance.The test uses a single rabbit ear to indicate the Comedogenicity and irritancy of test chemical. The 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 grades are summarized as follows:  0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough. The chemical falls under Grade 0 (no irritation observed). Hence it can be concluded that the test substance was not irritating to rabbit ears.

 

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 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 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 ocular irritation potential of the test substance was conducted by peer reviewed journal on rabbits. When the chemical was instilled into the conjunctival sac of each rabbit, none of the treated rabbit had developed any signs of ocular lesions. Hence the test chemical was considered to be not irritating to the rabbit’ eye.

 

The above result was further supported by another ocular irritation study reported by authoritative database for another read across chemical. In this test, each rabbit received undiluted chemical and were observed for any ocular lesions. Since the chemical did not induce any adverse effects, the test material was considered as not irritating to the rabbits’ eye.

 

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 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 guinea pigs 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 : 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

Species:

other: 1. guinea pig 2.Rabbit

Strain:

other: 1.Pirbright- White 2.New Zealand White

Details on test animals or test system and environmental conditions:

1.TEST ANIMALS
- Sex: female
- 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.TEST ANIMALS
Source: No data
Age at study initiation: No data
Weight at study initiation: 3 kg
Fasting period before study: No data
Housing: singly housed, in suspended cages
Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitum
Water (e.g. ad libitum): water, ad libitum
Acclimation period: No data
ENVIRONMENTAL 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 cycle

IN-LIFE DATES: From: No data To: No data

Type of coverage:

other: 1. open 2.Entire inner surface of one ear

Preparation of test site:

other: 1.clipped or shaved 2.A colony of rabbits that had genetically good ears and which were free from mites were used for the assay

Vehicle:

other: 1.FCA and Physiological saline 2.propylene glycol

Controls:

not specified

Amount / concentration applied:

1.10%, 3% and 1 %
2.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 hours
2.2 weeks

Observation period:

1.24 hours
2.2 weeks

Number of animals:

1.10
2.3 rabbits

Details on study design:

1.TEST SITE
- Area of exposure: clipped or shaved shoulder area (4*6 cm)
OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : The results were read 24 hours after challenge exposure with the test chemical
SCORING SYSTEM:
- Method of calculation:A (+) reaction was considered as threshold of irritation

2.TEST SITE
Area 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 data

REMOVAL OF TEST SUBSTANCE
Washing (if done): No data
Time after start of exposure: No data

SCORING 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 irritation
1 = few scales, no Erythema
2 = diffuse scaling, no Erythema
3 = Generalized scaling with Erythema
4 = Scaling, Erythema and Edema
5 = Epidermal necrosis and slough

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Score:

0

Max. score:

5

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

1.No skin irritation observed
2.No erythema observed

1.Table 1: Results of the study

Test chemical	Concentration	Irritation index
Test chemical	10%	0.0

The mean irritation index is the average of 3 readings

2.

 Table 1: 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 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1) was considered as not irritating to the skin.

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 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 irritation study of read across substance in guinea pigs. The10 female Pirbright-White guinea pigs were treated with an emulsion prepared from FCA and physiological saline but without the test chemical and applied on a semicircular arc on the clipped or shaved shoulder area (4*6 cm) from left to right in such a way that whole emulsion was used up for the animals.1 day before the challenge exposure, ten guinea pigs were treated with test chemical by applying different concentrations of the test chemical (10%, 3% and 1%) to the right flank. The results of the challenge exposure were observed after 24 hours. A (+) reaction was considered as threshold of irritation. The mean irritation index of chemical was 0.0 after 24 hours. Hence, the test material was considered to be not irritating to guinea pigs.

 

Above results were further supported by dermal irritation carried out byanother peer reviewed journal for another read across substance.The test uses a single rabbit ear to indicate the Comedogenicity and irritancy of test chemical. The 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 grades are summarized as follows:  0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough. The chemical falls under Grade 0 (no irritation observed). Hence it can be concluded that the test substance was not irritating to rabbit ears.

 

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 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.

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

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

not specified

Vehicle:

other: 1. not specified 2.unchanged

Controls:

not specified

Amount / concentration applied:

1.not specified
2. 100% (undiluted)

Duration of treatment / exposure:

not specified

Observation period (in vivo):

not specified

Duration of post- treatment incubation (in vitro):

not specified

Number of animals or in vitro replicates:

not specified

Details on study design:

not specified

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed in treated group.

Interpretation of results:

other: not irritating

Conclusions:

The test material 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 irritating to the rabbits' eye.

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 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 ocular irritation potential of the test substance was conducted by peer reviewed journal on rabbits. When the chemical was instilled into the conjunctival sac of each rabbit, none of the treated rabbit had developed any signs of ocular lesions. Hence the test chemical was considered to be not irritating to the rabbit’ eye.

 

The above result was further supported by another ocular irritation study reported by authoritative database for another read across chemical. In this test, each rabbit received undiluted chemical and were observed for any ocular lesions. Since the chemical did not induce any adverse effects, the test material was considered as not irritating to the rabbits’ eye.

 

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 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 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 irritation study of read across substance in guinea pigs. The10 female Pirbright-White guinea pigs were treated with an emulsion prepared from FCA and physiological saline but without the test chemical and applied on a semicircular arc on the clipped or shaved shoulder area (4*6 cm) from left to right in such a way that whole emulsion was used up for the animals.1 day before the challenge exposure, ten guinea pigs were treated with test chemical by applying different concentrations of the test chemical (10%, 3% and 1%) to the right flank. The results of the challenge exposure were observed after 24 hours. A (+) reaction was considered as threshold of irritation. The mean irritation index of chemical was 0.0 after 24 hours. Hence, the test material was considered to be not irritating to guinea pigs.

 

Above result was further supported by dermal irritation carried out byanother peer reviewed journal for another read across substance.The test uses a single rabbit ear to indicate the Comedogenicity and irritancy of test chemical. The 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 grades are summarized as follows:  0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough. The chemical falls under Grade 0 (no irritation observed). Hence it can be concluded that the test substance was not irritating to rabbit ears.

 

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 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 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 ocular irritation potential of the test substance was conducted by peer reviewed journal on rabbits. When the chemical was instilled into the conjunctival sac of each rabbit, none of the treated rabbit had developed any signs of ocular lesions. Hence the test chemical was considered to be not irritating to the rabbit’ eye.

 

The above result was further supported by another ocular irritation study reported by authoritative database for another read across chemical. In this test, each rabbit received undiluted chemical and were observed for any ocular lesions. Since the chemical did not induce any adverse effects, the test material was considered as not irritating to the rabbits’ eye.

 

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 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 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 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 3-(diethylamino)-7-imino-7H-chromeno[3’,2’:3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile (CAS No: 52372-39-1)  can be classified under the category “Not Classified” for skin and eye as per CLP.