4-[(2,4-dimethylphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) was assessedin various experimental studies which were conducted on rabbits for target chemical4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) and its functionally similar read across substancesC.I. Pigment Red 3 (CAS No: 2425-85-6)andSodium 4-(3-hydroxy-5-methyl-4-phenylazopyrazol-2-yl)benzenesulphonate(CAS No:6359-82-6). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) is unable to cause skin irritation and thus 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

An ocular irritation potential of target chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) was assessedin various experimental studies which were conducted on rabbits for target chemical4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) and its structurally similar read across substanceEdaravone(CAS No:-89-25-8) and functionally similar read across substance C.I. Pigment Red 3(CAS No: 2425-85-6). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) is unable to cause eye damage and thus can be 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:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one
- Common name: Solvent Yellow 18
- Molecular formula: C18H18N4O
- Molecular weight: 306.367 g/mol
- Smiles notation: O=C1N(N=C(C)[C@@H]1\N=N\c1c(cc(cc1)C)C)c1ccccc1
- InChl: 1S/C18H18N4O/c1-12-9-10-16(13(2)11-12)19-20-17-14(3)21-22(18(17)23)15-7-5-4-6-8-15/h4-11,17H,1-3H3/b20-19+
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" or "e" or "f" or "g" )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Schiff base formation AND Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives AND Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  by Protein binding by OASIS v1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amides AND Hydrazines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amides OR Hydrazines by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Amides AND Hydrazines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Hydrazine OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "k"

Similarity boundary:Target: Cc1ccc(N=NC2C(C)=NN(c3ccccc3)C2=O)c(C)c1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: Cc1ccc(N=NC2C(C)=NN(c3ccccc3)C2=O)c(C)c1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds OR Halogenated Aromatic Hydrocarbon Type Compounds by Oncologic Primary Classification

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.34

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.02

Interpretation of results:

other: not irritating

Conclusions:

The chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) can be considered to be not irritating to skin and can be classified under the category ˋ 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:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one
- Common name: Solvent Yellow 18
- Molecular formula: C18H18N4O
- Molecular weight: 306.367 g/mol
- Smiles notation: O=C1N(N=C(C)[C@@H]1\N=N\c1c(cc(cc1)C)C)c1ccccc1
- InChl: 1S/C18H18N4O/c1-12-9-10-16(13(2)11-12)19-20-17-14(3)21-22(18(17)23)15-7-5-4-6-8-15/h4-11,17H,1-3H3/b20-19+
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed in treated rabbits.

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" or "d" or "e" or "f" or "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Schiff base formation AND Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives AND Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  by Protein binding by OASIS v1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amides AND Hydrazines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amides OR Hydrazines by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Amides AND Hydrazines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic azo AND SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitro by DNA binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.87

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 11.3

Interpretation of results:

other: not irritating

Conclusions:

The chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

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 chemical4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) 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 chemical4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) and its functionally similar read across substancesC.I. Pigment Red 3 (CAS No: 2425-85-6) and Sodium 4-(3-hydroxy-5-methyl-4-phenylazopyrazol-2-yl)benzenesulphonate(CAS No:6359-82-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) .The chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) is estimated to be not irritating to skin of New Zealand White rabbits.

 

The European Commission (EC) - Scientific Committee on Cosmetology (SCC) {COMMISSION OF THE EUROPEAN COMMUNITIES; Brussels, Luxembourg, 1988} reported skin irritation study of read across chemical C.I. Pigment Red 3 (CAS No: 2425-85-6) on rabbits.TheC.I. Pigment Red 3 was applied on abraded and non-abraded skin of each rabbits under occlusive condition. No indication of skin irritation was observed. Hence the chemical C.I. Pigment Red 3(CAS No: 2425-85-6) was considered to be not irritating to theabraded and non-abraded skin of rabbits under occlusive condition.

 

The above results were further supported by the experimental study reported by European Commission (EC) - Scientific Committee on Cosmetology (SCC) {Environment and Quality of Life - Reports (Seventh Series), European Commission (EC) - Scientific Committee on Cosmetology (SCC), 1988} for read across substance Sodium 4-(3-hydroxy-5-methyl-4-phenylazopyrazol-2-yl)benzenesulphonate (CAS No:6359-82-6) on intact and abraded skin of rabbits. When rabbits were exposed with 100 mg of undiluted Sodium 4-(3-hydroxy-5-methyl-4-phenylazopyrazol-2-yl)benzenesulphonate(CAS No:6359-82-6), no skin irritating effects were observed. Thus the chemicalSodium 4-(3-hydroxy-5-methyl-4-phenylazopyrazol-2-yl)benzenesulphonate(CAS No:6359-82-6) was considered to be not irritating to the rabbits’ skin.

 

Thus based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) is unable 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:

In different studies,the test chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) and its structurally similar read across substance Edaravone(CAS No:-89-25-8) and functionally similar read across substance C.I. Pigment Red 3(CAS No: 2425-85-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9).The chemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The Cosmetic Ingredient Review, CIR Expert Panel {Journal Of The American College of Toxicology, Volume 11, Number 4, 1992; Mary Ann Liebert, Inc., Publishers} conducted an eye irritation study in six albino (3/sex) rabbits for read across chemicalEdaravone(CAS No:-89-25-8).The test substance was applied into theconjunctival sac of the right eye of each rabbit at volume of 0.1 ml (0.66% solution of PMP in propylene glycol) and the left eye served as control. The eyes were not rinsed and examinedfor ocular lesionsafter24 hours and on days 2, 3, 4, and 7 using a cap lamp and also examined with a fluorescent lamp after injection of 2% sodium fluorescein solution.The ocular irritation index was observed to be 0.66/110 on day 1 and 0.00/110 0n the reaming days.As the ocular lesions were not persisted until 7 days observation period with ocular irritation index of 0.00, the test chemical Edaravone (CAS No:-89-25-8) was considered to be non-irritating to the eyes of albino rabbits.

 

The above results were further supported by an ocular irritation study of read across chemical C.I. Pigment Red 3 (CAS No: 2425-85-6) conducted on rabbits by European Commission (EC) - Scientific Committee on Cosmetology (SCC) {COMMISSION OF THE EUROPEAN COMMUNITIES; Brussels, Luxembourg, 1988}.The undiluted 100mg ofC.I. Pigment Red 3 was installed into the eye of each rabbits which produced Slight conjunctival changes only after one hour. Since the observed effects were cleared, the chemical C.I. Pigment Red 3(CAS No: 2425-85-6)was considered to be not irritating to therabbits’ eye.

 

Thus on the basis of available data for thetarget chemical4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) and its structurally similar read across substanceEdaravone(CAS No:-89-25-8) and functionally similar read across substance C.I. Pigment Red 3(CAS No: 2425-85-6),it can be concluded thatchemical 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) is unable 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 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9)and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 4-aminobenzene-1,2-dicarbonitrile is unlikely to cause skin and eye irritation. Hence 4-[(E)-2-(2,4-dimethylphenyl)diazen-1-yl]-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (CAS No: 6407-78-9) can be classified under the category “Not Classified” for skin and eye as per CLP.