2-(4-aminoanilino)-5-nitrobenzenesulphonic acid

Endpoint summary

Description of key information

Skin irritation:

Primary Skin irritation study was conducted in rabbits by GESTIS SUBSTANCE Database (2017) and BG Chemie (2000) for test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) to determine its skin irritating behavior in accordance with OECD guideline No. 404. The animals were subjected to a single 4- hour exposure to 500 mg of the test substance, mixed into a paste with water and applied semi-occlusively to the mechanically depilated skin of the flanks. The findings were scored after 1, 24, 48 and 72 hours as well as 7 days in accordance with the Draize method. The average irritation scores according to the Draize scoring for erythema and oedema were 0.0.Hence, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to skin of female albino rabbits.

Eye Irritation:

An eye irritation study was conducted in 6 rabbits by GESTIS SUBSTANCE Database (2017) for 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) to assess its eye irritation efficacy in accordance with OECD guideline 405. About 100 μl of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid was placed into the conjunctival sac of each rabbits and the results were recorded for 3 days. Slight reddening in only one of 6 animals was observed but this was reversible after 3 days. Since the observed eye effects were not persisted after 3 days ,the test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to rabbits’ eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from Authoritive database

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Primary Skin irritation study was performed in 3 female albino rabbits to determine the irritation potential of test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid according to OECD guideline no 404.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4-nitro-4’-aminodiphenylamine-2-sulfonic acid
- Molecular formula: C12H11N3O5S
- Molecular weight: 309.301 g/mol
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

other: HC:NZW

Details on test animals or test system and environmental conditions:

- Sex: Female
- Age at study initiation: adult
- Weight at study initiation: 3.2-3.3 kg

Type of coverage:

semiocclusive

Preparation of test site:

other: Mechanically depilated skin of flanks

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 hrs

Observation period:

1,24,48 and 72 hrs and day 7

Number of animals:

3 female rabbits

Details on study design:

SCORING SYSTEM: Draize method.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

None of the test animals produced skin reactions.

Interpretation of results:

other: Not irritating

Conclusions:

The average irritation scores according to the Draize scoring for erythema and oedema were 0.0.
Hence, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to skin of female albino rabbits

Executive summary:

Primary Skin irritation study was conducted for test chemical4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) to determine its skin irritating behavior in accordance withOECD guideline No. 404. The animals were subjected to a single 4- hour exposure to 500 mg of the test substance, mixed into a paste with water and applied semi-occlusively to the mechanically depilated skin of the flanks. The findings were scored after 1, 24, 48 and 72 hours as well as 7 days in accordance with the Draize method.

The average irritation scores according to the Draize scoring for erythema and oedema were 0.0.

Hence, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to skin of female albino rabbits

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:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from handbook or collection of data

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Ocular irritation study of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid was carried out in 6 rabbits in accordance with OECD guideline No. 405

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4-nitro-4’-aminodiphenylamine-2-sulfonic acid
- Molecular formula: C12H11N3O5S
- Molecular weight: 309.301 g/mol
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

100 µl

Duration of treatment / exposure:

3 days

Observation period (in vivo):

3 days

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

6

Details on study design:

TEST SITE
- Area of exposure: the conjunctival sac of eye
- % coverage: No data
- 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: No data

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 3 days

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Slight reddening in only one of 6 animals was observed but this was reversible after 3 days.

Interpretation of results:

other: not irritating

Conclusions:

4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to eye of rabbits.

Executive summary:

Eye irritation study was conducted in 6 rabbits for 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) to assess its eye irritation efficacy in accordance with OECD guideline 405. About 100 μl of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid was placed into the conjunctival sac of each rabbits and the results were recorded for 3 days. Slight reddening in only one of 6 animals was observed but this was reversible after 3 days.

Since the observed eye effects were not persisted after 3 days ,the test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to rabbits’ eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical -nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) and its structurally similar read across substances Diphenylamine (CAS No:- 122-39-4) and 4-nitro-N-phenylaniline (CAS No:- 836-30-6) which are summarized as below;

Primary Skin irritation study was conducted in rabbits by GESTIS SUBSTANCE Database (2017) and BG Chemie (2000) for test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) to determine its skin irritating behavior in accordance with OECD guideline No. 404. The animals were subjected to a single 4- hour exposure to 500 mg of the test substance, mixed into a paste with water and applied semi-occlusively to the mechanically depilated skin of the flanks. The findings were scored after 1, 24, 48 and 72 hours as well as 7 days in accordance with the Draize method. The average irritation scores according to the Draize scoring for erythema and oedema were 0.0.Hence, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to skin of female albino rabbits.

The above result was further supported by theAcute skin irritation study performed on 3 rabbits according to the OECD guideline No. 404 summarized byBG Chemie (2000) for test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2). In this acute skin irritation study, rabbits were exposed to 500 mg of chemical under semi-occlusive cover for 4 hrs following application to the mechanically depilated dorsal skin. Skin reactions were observed at 30 to 60 minutes and 24, 48 and 72 hours after the end of exposure. None of the rabbits showed any cutaneous reactions. Hence, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) was considered to be not irritating to the mechanically depilated dorsal skin of New Zealand albino rabbits.

These results were supported by the experiment data reported by GESTIS SUBSTANCE Database (2017) and European Union Risk Assessment Report (2008)on structurally similar read across substance Diphenylamine (CAS No:- 122-39-4).Thisskin irritation study was carried out in 2 albino rabbits and the test substance Diphenylamine was applied to the inner surface of the ears of each rabbit for the exposure period of 24 hours under occlusive condition. Skin reactions were up to 7 days.  No signs of irritation were observed during 7 days observation period. Hence, the test chemical Diphenylamine (CAS No: - 122-39-4) was considered to be not irritating to the inner surface of the rabbit’s ears.

Another Dermal irritation study was performed byGESTIS SUBSTANCE Database (2017) for anotherstructurally similar read across substance 4-nitro-N-phenylaniline (CAS No:- 836-30-6) .In this test, the rabbits were exposed to pulverized and moistened substance 4 -nitro-N-phenylaniline at concentration of 500mg and it was applied on intact and also scarified skin of each rabbits under semi occlusive conditions for 24 hours. None of the rabbits showed irritating effect at concentration of 500mg. Hence, the chemical 4-nitro-N-phenylaniline (CAS No: - 836-30-6) was considered to be not irritating to the rabbit’s skin.

Another skin irritation study was carried out in 6 rabbits byGESTIS SUBSTANCE Database (2017) andOECD SIDS (1988)to assess the irritation potency of same read across substance chemical 4-nitro-N-phenylaniline(CAS No:- 836-30-6). 4-nitro-N-phenylaniline was applied to abraded and non-abraded skin of each rabbits for the exposure period of 24 hours and later skin reactions were scored. Since the irritation index was observed to be 0.0 out of maximum score of 8.Hence, 4-nitro-N-phenylaniline (CAS No: - 836-30-6) was considered to be not irritating to the rabbit’s skin.

Based on the available data for the target substance4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2)and read across substancesDiphenylamine (CAS No:- 122-39-4) and 4-nitro-N-phenylaniline (CAS No:- 836-30-6), it can be concluded thatchemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2)is not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye Irritation:

In different studies,4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) and its structurally similar read across substancesDiphenylamine (CAS No:- 122-39-4) and 4-nitro-N-phenylaniline (CAS No:- 836-30-6).

An eye irritation study was conducted in 6 rabbits by GESTIS SUBSTANCE Database (2017) for 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) to assess its eye irritation efficacy in accordance with OECD guideline 405. About 100 μl of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid was placed into the conjunctival sac of each rabbits and the results were recorded for 3 days. Slight reddening in only one of 6 animals was observed but this was reversible after 3 days. Since the observed eye effects were not persisted after 3 days ,the test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to rabbits’ eye.

Another two Ocular irritation studies were performed by BG Chemie (2000) for test chemical 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) in accordance with OECD guideline No. 405 as follows;

In the first study, the rabbits were given a single instillation of 100 μl (approx. 50 mg) into the conjunctival sac of one eye, and the results were recorded after 1, 24, 48 and 72 hours as well as after 7 days. Evaluation was carried out in accordance with the Draize method. The average irritation scores according to the Draize scoring for cornea, iris and conjunctivae were 0.0. Hence, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) was considered to be not irritating to eyes of albino rabbits.

In next study, 100 mg of 4-nitro-4’-aminodiphenylamine-2-sulfonic acid was applied to the conjunctival sac of the left eye. The eyes were scored after 1, 24, 48 and 72 hours. Signs of irritation (clouding of the cornea, diffuse redness and marked swelling of the conjunctiva) were seen in 1 of the 3 treated animals, but the effects were reversible within 3 days. Since the eye irritating effects were cleared after 72 hours, 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2) was considered to be not irritating to eye of New Zealand white albino rabbits.

Above results were supported by experimental data reported by FAO and WHO (701. Diphenylamine PESTICIDE RESIDUES IN FOOD ‐ 1984) on structurally similar read across substance Diphenylamine (CAS No:- 122-39-4).In this ocular irritation test, 100 mg of undiluted diphenylamine was placed in 2 albino rabbit’s eye and observed for any ocular changes for 10 days. Only slight iritis and moderate conjunctivitis were observed, which cleared after ten days. Hence Diphenylamine (CAS No:- 122-39-4)was considered to be not irritating to the eyes of Albino rabbits.

Another eye irritation study was performed by NTRL (NTRL REPORT- OTS0557205; 09/28/82)for samestructurally similar read across substance Diphenylamine (CAS No:- 122-39-4) in New Zealand white albino rabbits.100 mg of undiluted diphenylamine was placed in Six rabbits without washing the treated eyes. An additional group of 3 rabbits received 100 mg of undiluted test chemical and then after 20 seconds the treated eye was flushed for 1 minute with lukewarm water. The test substance was allowed to fall on averted lower lid of one eye of each rabbit. The upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing to prevent loss of material. Readings for ocular lesions were scored at 24, 48 and 72 hours. In unwashed group, after 24 hour slight iritis and moderate conjunctivitis was observed in one rabbit and slight conjunctivitis in 5 rabbits. During the course of the observations period these effects cleared up gradually. After 10 days all treated eyes were normal again. In washed group, after 24 hours slight conjunctivitis was observed in all rabbits. After 7days all lesions had cleared. The irritation index after 10 days was 0.0.hence Diphenylamine (CAS No:- 122-39-4)was considered to be not irritating to the eyes of New Zealand white albino rabbits.

GESTIS SUBSTANCE Database (2017) andOECD SIDS (1988) carried out an eye irritation study for another read across substance 4-nitro-N-phenylaniline (CAS No:- 836-30-6) in 6 rabbits to assess its effects in rabbits’ eye. The pulverized test substance was administrated placed into the conjunctival sac of each rabbit at concentration of 100mg for 24 hours and observed for any ocular changes. The irritation index of 4-nitro-N-phenylaniline (CAS No: - 836-30-6) was observed to be 2.6 of 110 and it was unable to cause eye irritating effects. Hence, 4-nitro-N-phenylaniline (CAS No: - 836-30-6) was considered to be not irritating to the rabbits’ eyes.

Based on the available data for the target substance4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2)and read across substancesDiphenylamine (CAS No:- 122-39-4) and 4-nitro-N-phenylaniline (CAS No:- 836-30-6), it can be concluded thatchemical substance4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No:91-29-2)is not likely to cause eye irritation.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 chemical4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2)and its read acrosssubstancesDiphenylamine (CAS No:- 122-39-4) and 4-nitro-N-phenylaniline (CAS No:- 836-30-6)were observed in various studies. The results obtained from these studies indicates that the test chemical4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2) is not likely to cause skin and eye irritation. Hence 4-nitro-4’-aminodiphenylamine-2-sulfonic acid (CAS No: 91-29-2)can be classified under the category “Not Classified” for skin and eye as per CLP.