1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N'-bis(mixed Ph, tolyl and xylyl) derivs.

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 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:

 

A patch test for read across chemical was performed by peer reviewed journal in 32 patients with an established p-aminoazobenzene allergy.The test was conducted on a group of 32 patients with presumable allergic contact dermatitis and all with a positive patch teat reaction to p-aminoazobenzene (0.25% pet). The group consisted of 20 women (mean age 39.9 years) and men (mean age 46.6 years). 11 patients had previously also shown sensitization to PPD (Para-phenyldiamine). 30 patients with an allergic contact dermatitis but negative to p-aminoazobenzene and PPD were also tested with the same patch test series. A patch with test chemical was placed in small squares (about 1.0 cm²) and wetted with 1 drop of tap water, water was used to imitate the circumstances (wet hands or sweating of hands). By this procedure a slight but visible yellow stain on the skin was found at the test site after 2 days of application, indicating liberation of the dyes.The chemical did not elicit a positive patch test reaction in any one of the 32 patients’ positive to p-aminoazobenzene nor in the 30 control subjects. Hence the test chemical was considered to be not sensitizing.

 

The above result was further supported by the Draize-Shelanski repeated insult patch test conducted by authoritative database on 200 human subjects for another read across chemical.In this study, the chemical applied to the subjects volvar forearms (200 subjects) as an aqueous solution for 10 alternate days, for 24-hour periods, followed by a 14-day rest period. Challenge batches were then applied under occlusion to fresh skin sites on the subjects scapular backs for 24 hours. The colour did not produce either irritation or allergic responses during the induction phase nor contact dermatitis in the challenge period. Thereforethe test chemical was considered to be not sensitizing in a Draize-Shelanski repeated insult patch test conducted on 200 human subjects.

 

Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) 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 patch tests on humans.

GLP compliance:

not specified

Type of study:

patch test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material : 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N'-bis(mixed Ph, tolyl and xylyl) derivs.
- Molecular formula: C17H18ClN7O9S2
- Molecular weight: 563.954g/mol
- Substance type: Organic
- Physical state: solid
-Smiles: N1(c2ccc(cc2)S(=O)(=O)O)N=C(C(O)=O)[C@@H](\N=N\c2ccc(cc2)S(=O)(=O)O)C1=O.C(=N)(N)N.Cl
-InChI: 1S/C16H12N4O9S2.CH5N3.ClH/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;2-1(3)4;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);(H5,2,3,4);1H/b18-17+;;

Species:

other: Human

Strain:

other: not applicable

Sex:

male/female

Route:

epicutaneous, occlusive

Vehicle:

other: 1.White petrolatum 2.White petrolatum

Concentration / amount:

1.2%
2.No data available

Day(s)/duration:

1. 2 days 2. 24 hours

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: 1.White petrolatum 2.Aqueous solution

Concentration / amount:

1. 2%
2.Not specified

Day(s)/duration:

1. 2days 2.24 hours

Adequacy of challenge:

not specified

No. of animals per dose:

1.32 patients
2.200 subjects

Details on study design:

1. A patch contain test chemical was placed in a small squares (about 1.0 cm2) and wetted with 1 drop of tap water, water was used to imitate the circumstances (wet hands or sweating of hands). By this procedure a slight but visible yellow stain on the skin was found at the test site after 2 days of application, indicating liberation of the dyes.

2. MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: no data
- Exposure period:24 hours
- Test groups: 200 subjects
- Control group: no data
- Site: volvar forearms
- Frequency of applications:
- Duration: 10 alternate days
- Concentrations: no data

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: after 14 days
- Exposure period: 24 hours
- Test groups: 200 subjects
- Control group:
- Site: scapular backs
- Concentrations: no data
- Evaluation (hr after challenge): after 24 hours

Challenge controls:

1.30 patients with an allergic contact dermatitis but negative to p- p-aminoazobenzene and PPD were also tested with the same patch test series.
2.Not specified

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

2%

No. with + reactions:

0

Total no. in group:

32

Clinical observations:

The chemical did not elicit a positive patch test reaction in any one of the 32 patients’ positive to p-aminoazobenzene nor in the 30 control subjects.

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Not specified

No. with + reactions:

0

Total no. in group:

200

Clinical observations:

None of the subjects showed any signs of contact sensitization.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

1.The chemical did not elicit a positive patch test reaction in any one of the 32 patients’ positive to p-aminoazobenzene nor in the 30 control subjects.
2.None of the subjects showed any signs of contact sensitization.

Interpretation of results:

other: not sensitizing

Conclusions:

The test chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N'-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) was considered to be not sensitizing to the skin.

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 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:

 

A patch test for read across chemical was performed by peer reviewed journal in 32 patients with an established p-aminoazobenzene allergy.The test was conducted on a group of 32 patients with presumable allergic contact dermatitis and all with a positive patch teat reaction to p-aminoazobenzene (0.25% pet). The group consisted of 20 women (mean age 39.9 years) and men (mean age 46.6 years). 11 patients had previously also shown sensitization to PPD (Para-phenyldiamine). 30 patients with an allergic contact dermatitis but negative to p-aminoazobenzene and PPD were also tested with the same patch test series. A patch with test chemical was placed in small squares (about 1.0 cm²) and wetted with 1 drop of tap water, water was used to imitate the circumstances (wet hands or sweating of hands). By this procedure a slight but visible yellow stain on the skin was found at the test site after 2 days of application, indicating liberation of the dyes.The chemical did not elicit a positive patch test reaction in any one of the 32 patients’ positive to p-aminoazobenzene nor in the 30 control subjects. Hence the test chemical was considered to be not sensitizing.

 

The above result was further supported by the Draize-Shelanski repeated insult patch test conducted by authoritative database on 200 human subjects for another read across chemical.In this study, the chemical applied to the subjects volvar forearms (200 subjects) as an aqueous solution for 10 alternate days, for 24-hour periods, followed by a 14-day rest period. Challenge batches were then applied under occlusion to fresh skin sites on the subjects scapular backs for 24 hours. The colour did not produce either irritation or allergic responses during the induction phase nor contact dermatitis in the challenge period. Thereforethe test chemical was considered to be not sensitizing in a Draize-Shelanski repeated insult patch test conducted on 200 human subjects.

 

Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) 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 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0). The studies are as mentioned below:

 

A patch test for read across chemical was performed by peer reviewed journal in 32 patients with an established p-aminoazobenzene allergy.The test was conducted on a group of 32 patients with presumable allergic contact dermatitis and all with a positive patch teat reaction to p-aminoazobenzene (0.25% pet). The group consisted of 20 women (mean age 39.9 years) and men (mean age 46.6 years). 11 patients had previously also shown sensitization to PPD (Para-phenyldiamine). 30 patients with an allergic contact dermatitis but negative to p-aminoazobenzene and PPD were also tested with the same patch test series. A patch with test chemical was placed in small squares (about 1.0 cm²) and wetted with 1 drop of tap water, water was used to imitate the circumstances (wet hands or sweating of hands). By this procedure a slight but visible yellow stain on the skin was found at the test site after 2 days of application, indicating liberation of the dyes.The chemical did not elicit a positive patch test reaction in any one of the 32 patients’ positive to p-aminoazobenzene nor in the 30 control subjects. Hence the test chemical was considered to be not sensitizing.

 

The above result was further supported by the Draize-Shelanski repeated insult patch test conducted by authoritative database on 200 human subjects for another read across chemical.In this study, the chemical applied to the subjects volvar forearms (200 subjects) as an aqueous solution for 10 alternate days, for 24-hour periods, followed by a 14-day rest period. Challenge batches were then applied under occlusion to fresh skin sites on the subjects scapular backs for 24 hours. The colour did not produce either irritation or allergic responses during the induction phase nor contact dermatitis in the challenge period. Thereforethe test chemical was considered to be not sensitizing in a Draize-Shelanski repeated insult patch test conducted on 200 human subjects.

 

Based on the above summarized studies for target chemical 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) 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 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) 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 1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, reaction products with guanidine hydrochloride N,N’-bis(mixed Ph, tolyl and xylyl) derivs. (CAS No: 71077-14-0) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.