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Administrative data

Description of key information

Skin Irritation:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswill also tend to behave in a similar manner that of the read across substances. Therefore,1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswas estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswill also tend to behave in a similar manner that of the read across substances. Therefore,1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswas estimated to be irritating to eyes. It can be classified under the category “Category 2” as per CLP regulation.

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:
other: Weight of evidence based on structurally similar read across chemicals
Justification for type of information:
Weight of evidence based on structurally similar read across chemicals
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
other: Weight of evidence approach based on similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal irritation potential of 1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates
- Molecular formula: C26H34N8O8
- Molecular weight: 586.597 g/mol
- Smiles notation: CC(=O)O{-}.N{+}c1ccc(N=Nc2cccc(N=Nc3ccc(N{+}.O{-}C(C)=O)cc3N{+}.O{-}C(C)=O)c2)c(N{+}.O{-}C(C)=O)c1
- Substance type: Organic
- Physical state: Solid
Species:
other: rat and rabbits
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
1.
2. 2000 mg/kg
Duration of treatment / exposure:
24 hours
Observation period:
1. 24 and 72 hours
2. 14 days
Number of animals:
1. 6 (3/sex)
2. 10 (5/sex)
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation observed
Interpretation of results:
other: not irritating
Conclusions:
Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswill also tend to behave in a similar manner that of the read across substances. Therefore,1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswas estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal irritation potential of 1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates.

 

The skin irritation study was conducted to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound on the skin of the rabbits.

The study was performed as per the patch-test technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). Six rabbits (3/sex) of Russian breed were used for the study.

 In this test, each rabbits were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The chemical was applied to the each side at a dose of 500 mg (0.5g) in 50 % polyethylene glycol trituration (PEG 400). The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and after 72 hours.

The primary irritation index as the measure of the acute skin irritation provoked by the substance was defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compound producing combined averages (primary irritation indexes) of 2 or less were only mildly irritating; whereas those with indexes from 2 to 5 were moderate irritants, and those with scores above 6 were considered severe irritants. The primary irritation index of chemical was estimated to be 0. Hence, the test chemical was considered to be not irritating to the rabbits’ skin.

This result is supported by a study designed and conducted to determine the dermal reaction profile of the other structurally similar chemical in Sprague Dawley 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 animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

The test chemical 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. Also, the erythema and edema score of rats was calculated as 0. 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.

Thus it can be concluded that the test chemical can be considered to be not irritating to skin and classified under "Not Classified" category.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswill also tend to behave in a similar manner that of the read across substances. Therefore,1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswas estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

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:
other: Weight of evidence based on structurally similar chemicals
Justification for type of information:
Weight of evidence based on structurally similar chemicals
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
other: Weight of evidence based on structurally similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the ocular irritation of 1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: 1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates
- Molecular formula: C26H34N8O8
- Molecular weight: 586.597 g/mol
- Smiles notation: CC(=O)O{-}.N{+}c1ccc(N=Nc2cccc(N=Nc3ccc(N{+}.O{-}C(C)=O)cc3N{+}.O{-}C(C)=O)c2)c(N{+}.O{-}C(C)=O)c1
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
72 hours
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
6
Details on study design:
The study is based on weight of evidence approach from the read across values
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Signs of irritation observed
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswill also tend to behave in a similar manner that of the read across substances. Therefore,1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswas estimated to be irritating to eyes. It can be classified under the category “Category 2” as per CLP regulation.
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates.

 

 

A study was performed in rabbits to determine the ocular irritation potential of the structurally similar chemical.

 

6 New Zealand white rabbits were used for the study. Both eyes of each animal were examined with Fluorescein Sodium Ophthalmic solution U.S.P. 96 hours before testing and only those animals without observable eye defects or irritation were used. 0.1 ml undiluted test chemical was instilled into the conjunctival sac of 6 New Zealand White rabbits. The lids were held closed for 1-second for even distribution of the test substance. The other eye served as an untreated control. The eyes were not washed following instillation of the test material. The animals were immobilized in a suitable animal restrainer 1 hour subsequent to treatment. After the initial examination at 24 hours all eyes were washed with sufficient clean tap water at body temperature to remove the residual test sample. All eyes were further examined by placing one drop of Fluorescein Sodium Ophthalmic solution U.S.P. on the cornea. After 5 minutes the excess fluorescein was flushed out with sufficient tap water. Fluorescein Sodium in 2% aqueous solution when applied topically to the eye is used as an ophthalmic diagnostic aid for the detection of corneal lesions, injured areas of the cornea appear greenish yellow following application of fluorescein. The eyes were examined and the grade of ocular reaction was recorded at 1, 24, 48 and 72 hours, using the scale for scoring ocular lesions as outlined by Lehman. The evaluation of the data was done in accordance with Section 191.12 Chapter 1, Title 21, Code of Federal Regulations under the FHSA.

 

Since the results from the initial test were unsatisfactory to classify the substance according to F.H.S.A Guidelines, an additional group of 6 rabbits were selected and tested using the same procedure to obtain suitable information to classify the test chemical. The eyes of animals of Group II were examined with fluorescein approximately 4 hours prior to treatment.

 

A maximum average score of 10.2 was recorded at 24 hours in the initial test. This score was not sufficient to classify the test chemical as per F.H.S.A Guidelines, so a confirmatory test was performed using 6 additional rabbits. In the confirmatory test, ocular damage in the form of erythema, chemosis, discharge and corneal opacity was observed. Minimal to slight conjunctival irritation (6 anims18) and corneal opacity (5 animals) persisted through 72 hours post-treatment.

A maximum average score of 30.3 was recorded at 24 hours.

Based on the observations and score in the confirmatory test, the test chemical can be considered to be irritating to eyes.

 

 

This result is supported by a study performed in rabbits to determine the ocular irritation potential of the other structurally similar chemical.

 

6 New Zealand white rabbits were used for the study. Both eyes of each animal were examined with Fluorescein Sodium Ophthalmic solution U.S.P. 96 hours before testing and only those animals without observable eye defects or irritation were used. 0.1 ml (72 mg) of the test chemical was instilled into the conjunctival sac of 6 New Zealand White rabbits. The lids were held closed for 1-second for even distribution of the test substance. The other eye served as an untreated control. The eyes were not washed following instillation of the test material. The animals were immobilized in a suitable animal restrainer 1 hour subsequent to treatment. After the initial examination at 24 hours all eyes were washed with sufficient clean tap water at body temperature to remove the residual test sample. All eyes were further examined by placing one drop of Fluorescein Sodium Ophthalmic solution U.S.P. on the cornea. After 5 minutes the excess fluorescein was flushed out with sufficient tap water. Fluorescein Sodium in 2% aqueous solution when applied topically to the eye is used as an ophthalmic diagnostic aid for the detection of corneal lesions, injured areas of the cornea appear greenish yellow following application of fluorescein. The eyes were examined and the grade of ocular reaction was recorded at 1, 24, 48 and 72 hours, using the scale for scoring ocular lesions as outlined by Lehman. The evaluation of the data was done in accordance with Section 191.12 Chapter 1, Title 21, Code of Federal Regulations under the FHSA.

Moderate eye damage in the form of slight to moderate erythema, well defined chemosis, slight to moderate accumulation of watery to watery-mucoid discharge and corneal opacity in 6/6 test eyes of a moderate degree involving approximately 1/4 of the corneal surface (2 animals); greater than 1/4, but less than 1/2 (3 animals), and greater than 1/2, but less than 3/4 (1 animal) were observed within 24 hours of exposure to the test chemical. Only slight improvement in the condition of the test eyes was observed by 72 hours. All animals still showed a slight to moderate degree of corneal opacity. A maximum average score of 30.5 was recorded at 24 hours.

Based on the observations and scores, the test chemical can be considered to be irritating to eyes.

 

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswill also tend to behave in a similar manner that of the read across substances. Therefore,1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswas estimated to be irritating to eyes. It can be classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal irritation potential of1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates.

 

The skin irritation study was conducted to determine the primary-irritation index, which serves as a measure of the acute irritation, provoked by the compound on the skin of the rabbits.

The study was performed as per the patch-test technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). Six rabbits (3/sex) of Russian breed were used for the study.

 In this test, each rabbits were shaved on the whole back and flanks two days before treatment with an electric clipper. The shaven skin on the left side was slightly scarified immediately before treatment. A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The chemical was applied to the each side at a dose of 500 mg (0.5g) in 50 % polyethylene glycol trituration (PEG 400). The gauze patches were removed 24 hours after the application. The reaction of the skin was appraised upon removal and after 72 hours.

The primary irritation index as the measure of the acute skin irritation provoked by the substance was defined as the average of all the ratings found after 24 and 72 hours on the intact and slightly scarified skin. Compound producing combined averages (primary irritation indexes) of 2 or less were only mildly irritating; whereas those with indexes from 2 to 5 were moderate irritants, and those with scores above 6 were considered severe irritants. The primary irritation index of chemical was estimated to be 0. Hence, the test chemical was considered to be not irritating to the rabbits’ skin.

 

This result is supported by a study designed and conducted to determine the dermal reaction profile of the other structurally similar chemical in Sprague Dawley 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 animals were kept in their cages for at least 5 days prior to administration for acclimatization to the laboratory condition and after acclimatization period, animals were randomly selected. Approximately 24 hours before application, the hair of each rat was closely clipped from the trunk (dorsal surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 10% of the body surface area. The test item was applied directly onto the exposed skin of the animal, taking care to spread the test item evenly over the entire area of approximately 10% of the total body surface area or as much of the area as can reasonably be covered. The test item was held in contact with the skin using a porous gauze dressing and non irritating tape around the animal to cover the exposure site for first 24 hours exposure period. Elizabethan collar was placed on each animal for first 24 hours after application of the test item. These collars prevent ingestion of test item. Following 24 hours of exposure, the wrapping was removed and the test site wiped free of excess test item. Distilled water was used to remove residual test item.

The test chemical 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. Also, the erythema and edema score of rats was calculated as 0. 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.

Thus it can be concluded that the test chemical can be considered to be not irritating to skin and classified under "Not Classified" category.

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswill also tend to behave in a similar manner that of the read across substances. Therefore,1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates was estimated to be not irritating to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

 

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the ocular irritation potential of1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates.

 

 

A study was performed in rabbits to determine the ocular irritation potential of the structurally similar chemical.

 

6 New Zealand white rabbits were used for the study. Both eyes of each animal were examined with Fluorescein Sodium Ophthalmic solution U.S.P. 96 hours before testing and only those animals without observable eye defects or irritation were used. 0.1 ml undiluted test chemical was instilled into the conjunctival sac of 6 New Zealand White rabbits. The lids were held closed for 1-second for even distribution of the test substance. The other eye served as an untreated control. The eyes were not washed following instillation of the test material. The animals were immobilized in a suitable animal restrainer 1 hour subsequent to treatment. After the initial examination at 24 hours all eyes were washed with sufficient clean tap water at body temperature to remove the residual test sample. All eyes were further examined by placing one drop of Fluorescein Sodium Ophthalmic solution U.S.P. on the cornea. After 5 minutes the excess fluorescein was flushed out with sufficient tap water. Fluorescein Sodium in 2% aqueous solution when applied topically to the eye is used as an ophthalmic diagnostic aid for the detection of corneal lesions, injured areas of the cornea appear greenish yellow following application of fluorescein. The eyes were examined and the grade of ocular reaction was recorded at 1, 24, 48 and 72 hours, using the scale for scoring ocular lesions as outlined by Lehman. The evaluation of the data was done in accordance with Section 191.12 Chapter 1, Title 21, Code of Federal Regulations under the FHSA.

 

Since the results from the initial test were unsatisfactory to classify the substance according to F.H.S.A Guidelines, an additional group of 6 rabbits were selected and tested using the same procedure to obtain suitable information to classify the test chemical. The eyes of animals of Group II were examined with fluorescein approximately 4 hours prior to treatment.

 

A maximum average score of 10.2 was recorded at 24 hours in the initial test. This score was not sufficient to classify the test chemical as per F.H.S.A Guidelines, so a confirmatory test was performed using 6 additional rabbits. In the confirmatory test, ocular damage in the form of erythema, chemosis, discharge and corneal opacity was observed. Minimal to slight conjunctival irritation (6 anims18) and corneal opacity (5 animals) persisted through 72 hours post-treatment.

A maximum average score of 30.3 was recorded at 24 hours.

Based on the observations and score in the confirmatory test, the test chemical can be considered to be irritating to eyes.

 

 

This result is supported by a study performed in rabbits to determine the ocular irritation potential of the other structurally similar chemical.

 

6 New Zealand white rabbits were used for the study. Both eyes of each animal were examined with Fluorescein Sodium Ophthalmic solution U.S.P. 96 hours before testing and only those animals without observable eye defects or irritation were used. 0.1 ml (72 mg) of the test chemical was instilled into the conjunctival sac of 6 New Zealand White rabbits. The lids were held closed for 1-second for even distribution of the test substance. The other eye served as an untreated control. The eyes were not washed following instillation of the test material. The animals were immobilized in a suitable animal restrainer 1 hour subsequent to treatment. After the initial examination at 24 hours all eyes were washed with sufficient clean tap water at body temperature to remove the residual test sample. All eyes were further examined by placing one drop of Fluorescein Sodium Ophthalmic solution U.S.P. on the cornea. After 5 minutes the excess fluorescein was flushed out with sufficient tap water. Fluorescein Sodium in 2% aqueous solution when applied topically to the eye is used as an ophthalmic diagnostic aid for the detection of corneal lesions, injured areas of the cornea appear greenish yellow following application of fluorescein. The eyes were examined and the grade of ocular reaction was recorded at 1, 24, 48 and 72 hours, using the scale for scoring ocular lesions as outlined by Lehman. The evaluation of the data was done in accordance with Section 191.12 Chapter 1, Title 21, Code of Federal Regulations under the FHSA.

Moderate eye damage in the form of slight to moderate erythema, well defined chemosis, slight to moderate accumulation of watery to watery-mucoid discharge and corneal opacity in 6/6 test eyes of a moderate degree involving approximately 1/4 of the corneal surface (2 animals); greater than 1/4, but less than 1/2 (3 animals), and greater than 1/2, but less than 3/4 (1 animal) were observed within 24 hours of exposure to the test chemical. Only slight improvement in the condition of the test eyes was observed by 72 hours. All animals still showed a slight to moderate degree of corneal opacity. A maximum average score of 30.5 was recorded at 24 hours.

Based on the observations and scores, the test chemical can be considered to be irritating to eyes.

 

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetateswill also tend to behave in a similar manner that of the read across substances. Therefore,1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates was estimated to be irritating to eyes. It can be classified under the category “Category 2” as per CLP regulation.

 

Justification for classification or non-classification

The results of the experimental studies from the structurally similar read across substances indicate a possibility that 1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates can be not irritating to skin, but causes irritation to eyes.

Hence by applying the weight of evidence approach, 1,3-Benzenediamine, coupled with diazotized m-phenylenediamine, acetates can be considered to be not irritating to skin but irritating to eyes. It can be classified under the category “Not Classified” for skin irritation and “Category 2” for eye irritation as per CLP regulation.

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