2-[(4-chloro-2-nitrophenyl)azo]-N-(4-ethoxyphenyl)-3-oxobutyramide

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was assessedin various experimental studies which were conducted on rabbits for target chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) and its structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0). The predicted data usingQSAR toolbox and Danish QSAR databasehas 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 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) 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 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was assessedin various experimental studies which were conducted on rabbits for target chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) and its structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0). 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 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) 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): 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide
- Molecular formula: C18H17ClN4O5
- Molecular weight: 404.808 g/mol
- Smiles notation: O=C(Nc1ccc(OCC)cc1)[C@@H](\N=N\c1c([N+](=O)[O-])cc(cc1)Cl)C(=O)C
- InChl: 1S/C18H17ClN4O5/c1-3-28-14-7-5-13(6-8-14)20-18(25)17(11(2)24)22-21-15-9-4-12(19)10-16(15)23(26)27/h4-10,17H,3H2,1-2H3,(H,20,25)/b22-21+
- 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:

48 hours

Number of animals:

No data available

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 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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 >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide 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 Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes 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 phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphates by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

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 No alert found by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg AND Group All Melting Point > 200 C AND Group CNHal Aqueous Solubility < 0.001 g/L AND Group CNHal Aqueous Solubility < 0.1 g/L AND Group CNHal log Kow > 3.8 AND Group CNHal Molecular Weight > 370 g/mol AND Group CNHal Molecular Weight > 380 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Group All log Kow > 9 OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "n"

Similarity boundary:Target: CCOc1ccc(NC(=O)C(C(C)=O)N=Nc2ccc(Cl)cc2N(=O)=O)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: CCOc1ccc(NC(=O)C(C(C)=O)N=Nc2ccc(Cl)cc2N(=O)=O)cc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: CCOc1ccc(NC(=O)C(C(C)=O)N=Nc2ccc(Cl)cc2N(=O)=O)cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.25

Domain logical expression index: "r"

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 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) 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): 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide
- Molecular formula: C18H17ClN4O5
- Molecular weight: 404.808 g/mol
- Smiles notation: O=C(Nc1ccc(OCC)cc1)[C@@H](\N=N\c1c([N+](=O)[O-])cc(cc1)Cl)C(=O)C
- InChl: 1S/C18H17ClN4O5/c1-3-28-14-7-5-13(6-8-14)20-18(25)17(11(2)24)22-21-15-9-4-12(19)10-16(15)23(26)27/h4-10,17H,3H2,1-2H3,(H,20,25)/b22-21+
- 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:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

No data available

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.

Estimation method: Takes mode value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((("a" and ("b" and ( not "c") )  )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and "u" )  and ("v" and "w" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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 >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Acyl halide 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 Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) 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 phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphates by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

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 No alert found by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Has superfragment AND O=C(R{*})C(C(=O)NR{*})N=NR{*} by Superfragments ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Aryl halide AND Azo AND Carboxamide AND Ether AND Ketone AND Nitrobenzene by Organic Functional groups

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkyl arenes by Organic Functional groups

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Aryl halide AND Azo AND Carboxamide AND Ether AND Ketone AND Nitrobenzene by Organic Functional groups

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Alkyl halide by Organic Functional groups

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Aryl halide AND Azo AND Carboxamide AND Ether AND Ketone AND Nitrobenzene by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Benzamide by Organic Functional groups

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Aryl halide AND Azo AND Carboxamide AND Ether AND Ketone AND Nitrobenzene by Organic Functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Urea derivatives by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Alpha-oxoamide [C(C(=O))C(=O)N] AND Amide, aliphatic attach [-C(=O)N] AND Amino, aliphatic attach [-N<] AND Amino-carbonyl compound [NCC(=O)-C] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Carbonyl, aliphatic attach [-C(=O)-] AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitro, aromatic attach [-NO2] AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] by Organic functional groups (US EPA)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Alpha-oxoamide [C(C(=O))C(=O)N] AND Amide, aliphatic attach [-C(=O)N] AND Amino, aliphatic attach [-N<] AND Amino-carbonyl compound [NCC(=O)-C] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Carbonyl, aliphatic attach [-C(=O)-] AND Chlorine, aromatic attach [-Cl] AND Chlorine, olefinic attach [-Cl] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitro, aromatic attach [-NO2] AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Carbonyl, one aromatic attach [-C(=O)-] by Organic functional groups (US EPA)

Domain logical expression index: "u"

Similarity boundary:Target: CCOc1ccc(NC(=O)C(C(C)=O)N=Nc2ccc(Cl)cc2N(=O)=O)cc1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.99

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.05

Interpretation of results:

other: not irritating

Conclusions:

The chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) 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 chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  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 chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  and its structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0).The predicted data using the OECD QSAR toolbox andDanish QSAR databasehas 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 chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) . The chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  is estimated to be not irritating to skin of New Zealand White rabbits.

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) . Based on estimation, no skin irritation reactions were observed in rabbits. Therefore, 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) was considered to be not irritating.

 

The above results were further supported by the patch test studies reported by OECD SIDS {OECD HPV Chemical Programme, SIDS Dossier, approved at SIAM 16 (27/05/2003)} for two read across chemicals C. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0) as follows;

The patch tests for both the chemicals were conducted on rabbits to determine the degree of skin irritation caused by the chemicals. When the test chemicals were applied on each rabbit for 24 hours under occlusive condition, no skin reactions were observed. Hence the chemicals C. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0) were considered as not irritating to the skin of rabbits.

 

Thus on the basis of available data for thetarget chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  and its structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0),it can be concluded thatchemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  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 chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  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 chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  its structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0).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 chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) . The chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  is estimated to be not irritating to eye of New Zealand White rabbits.

 

The OECD SIDS {OECD HPV Chemical Programme, SIDS Dossier, approved at SIAM 16 (27/05/2003)} reported an eye irritation study for read across chemical C. I. Pigment Yellow 12 (CAS no: 6358-85-6) on rabbits according to OECD Guide-line 405 “Acute Eye Irritation/Corrosion”. When chemical C. I. Pigment Yellow 12 was instilled into the eyes of each rabbit, no ocular lesions were observed. Hence the chemical C. I. Pigment Yellow 12 (CAS no: 6358-85-6) was considered as not irritating to the eye of rabbits.

 

The above results were further supported by another eye irritation study reported by OECD SIDS {OECD HPV Chemical Programme, SIDS Dossier, approved at SIAM 16 (27/05/2003)} on New Zealand White rabbits for read across chemical C. I. Pigment Yellow 13 (CAS no: 5102-83-0). In the given study, the undiluted 0.1ml of C. I. Pigment Yellow 13 was instilled into the left eye of each of six rabbits whereas other untreated eye served as control. The ocular lesions were scored at 1, 2, 4, 24, 48 and 72 hours in accordance with those depicted in "Illustrated Guide for Grading Eye Irritation by Hazardous Substances" issued by the Superintendent of Documents, Government Printing Office, Washington DC. After 1 hour a moderate to severe ptosis was present in all animals, which subsided over the next 2-3 hours. Since the observed effects were cleared and all the scores were 0.0 at 72 hours, the chemical C. I. Pigment Yellow 13 (CAS no: 5102-83-0) was considered to be not irritating to the New Zealand White rabbits’ eye.

 

Thus on the basis of available data for thetarget chemical2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  and its structurally similar read across substancesC. I. Pigment Yellow 12 (CAS no: 6358-85-6) and C. I. Pigment Yellow 13 (CAS no: 5102-83-0),it can be concluded thatchemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  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 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8) is unlikely to cause skin and eye irritation. Hence 2-[(E)-2-(4-chloro-2-nitrophenyl)diazen-1-yl]-N-(4-ethoxyphenyl)-3-oxobutanamide (CAS No: 52320-66-8)  can be classified under the category “Not Classified” for skin and eye as per CLP.