Hydrogen bis[2-(3-chlorophenyl)-2,4-dihydro-4-[[2-hydroxy-5-mesylphenyl]azo]-5-methyl-3H-pyrazol-3-onato(2-)]chromate(1-)

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)  was assessedin various experimental studies which were conducted on rabbits and rats for target chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    and its structurally similar read across substancealuminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}, Chromium complex of 1-phenyl-3-methyl 4-(2'hydroxy-3'-sulfo-5'-chlorophenylazo) 5 -hydroxypyrazole(Acid Red 180)[CAS: 6408 -26 -0] and 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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    was assessedin various experimental studies which were conducted on rabbits for target chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    and its structurally similar read across substancealuminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}, 4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one (CAS No: 3520-72-7) and 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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    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: chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate)
SMILES:CC1C{-}(N=Nc2cc(S(C)(=O)=O)ccc2O{-}.[Cr]{3+}2.C{-}3(C(C)=NN(c4cccc(Cl)c4)C3=O)N=Nc3cc(S(C)(=O)=O)ccc3O{-}.2)C(=O)N(c2cccc(Cl)c2)N=1
InChI:1S/2C17H14ClN4O4S.Cr/c2*1-10-16(17(24)22(21-10)12-5-3-4-11(18)8-12)20-19-14-9-13(27(2,25)26)6-7-15(14)23;/h2*3-9,23H,1-2H3;/q2*-1;+3/p-1/b2*20-19+;
Molecular Formula: C34H26Cl2CrN8O8S2.H
Molecular Weight: 862.669 g/mole

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:

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 in treated rabbits.

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

(((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "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 ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anion by Substance Type

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 by Protein binding by OECD

Domain logical expression index: "d"

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: "e"

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: "f"

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 of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 amides 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 >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes 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 >> 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 SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals AND Transition Metals by Groups of elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alkaline Earth by Groups of elements

Domain logical expression index: "k"

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 16 - Sulfur S AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At AND Group 6 - Trans.Metals Cr,Mo,W by Chemical elements

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Carbonyl compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Carboxylic acid amide by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Carboxylic acid ester by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Primary alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as CO2 derivative (general) by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 782 Da

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 863 Da

Interpretation of results:

other: not irritating

Conclusions:

The chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated results, chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor. The chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated to be not irritating to the skin of New Zealand White rabbits.  Based on the estimated results, chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) can be considered to be not irritating to skin and can be 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:

(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:

chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) /71598-35-1/275-660-8
Name: chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate)
SMILES:CC1C{-}(N=Nc2cc(S(C)(=O)=O)ccc2O{-}.[Cr]{3+}2.C{-}3(C(C)=NN(c4cccc(Cl)c4)C3=O)N=Nc3cc(S(C)(=O)=O)ccc3O{-}.2)C(=O)N(c2cccc(Cl)c2)N=1
InChI:1S/2C17H14ClN4O4S.Cr/c2*1-10-16(17(24)22(21-10)12-5-3-4-11(18)8-12)20-19-14-9-13(27(2,25)26)6-7-15(14)23;/h2*3-9,23H,1-2H3;/q2*-1;+3/p-1/b2*20-19+;
Molecular Formula: C34H26Cl2CrN8O8S2.H
Molecular Weight: 862.669 g/mole

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1ml

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

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 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "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" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anion by Substance Type

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 by Protein binding by OECD

Domain logical expression index: "d"

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: "e"

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: "f"

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 of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones 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 SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro 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 SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group All log Kow < -3.1 AND (!Undefined)Group All log Kow > 9 AND (!Undefined)Group All Melting Point > 200 C AND Group All Aqueous Solubility < 0.000005 g/L AND Group All Aqueous Solubility < 0.00002 g/L AND Group All Molecular Weight > 650 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group All log Kow < -3.1 AND (!Undefined)Group All log Kow > 9 AND (!Undefined)Group All Melting Point > 200 C AND Group All Aqueous Solubility < 0.000005 g/L AND Group All Aqueous Solubility < 0.00002 g/L AND Group All Molecular Weight > 650 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow > 1.5 OR Group CNS log Kow > 3.6 by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aryl AND Aryl halide AND Azo AND Fused carbocyclic aromatic AND Phenol AND Pyrazolone AND Sulfone AND Unsaturated heterocyclic amine AND Unsaturated heterocyclic fragment by Organic Functional groups

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Carboxylic acid prim. amide by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as CO2 derivative (general) OR Diarylether OR Ether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Anion AND Aromatic compound AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Cation AND Halogen derivative AND Heterocyclic compound by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 629 Da

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 864 Da

Interpretation of results:

other: not irritating

Conclusions:

The chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated to be not irritating to the eyes of New Zealand White rabbits. Based on the estimated results, chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) can be considered to be not irritating to eyes.

Executive summary:

The ocular irritation potential of chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor. The chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) was estimated to be not irritating to the eyes of New Zealand White rabbits. Based on the estimated results, chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) can be considered to be not irritating to eyes and can be classified under the category “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 chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits, guinea pigs and rats for target chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) and its structurally similar read across substancesaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}, Chromium complex of 1-phenyl-3-methyl 4-(2'hydroxy-3'-sulfo-5'-chlorophenylazo) 5 -hydroxypyrazole(Acid Red 180)[CAS: 6408 -26 -0] and 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;

 

 

A study was designed and conducted by Sustainability Support Services (Europe) AB, 2017 on three New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5} that supported the above mentioned results. The animals were prepared 24 hours prior to application of test product. The furs from the dorsal area of trunk of animals were removed with electric clippers exposing an area measuring approximately 6 cm2 of body surface area of animal. The care was taken such that abrasion penetrated the Stratum corneum only and not dermis. 500gm (0.5g) of test compound was applied on a small area (approximately 6 cm2) of intact skin site. Each site of application was covered with impervious dressing which was secured in position with adhesive tape. The intact skin site of application of each animal was observed for signs of erythema and oedema at 60 min., 24, 48 and 72 hours after application and the responses were scored according to Draize method. The Primary Irritation Index (PII) foraluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}after 14 days of observation was 0.0.Alsoaluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}Bdid not produce pain and any clinical signs of toxicity throughout the examination period of 14 days. Hence, under the test conditions, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}can be concluded to be not irritating to New Zealand White rabbit skin.

 

 

The COMMISSION OF THE EUROPEAN COMMUNITIES {Scientific Committee on Cosmetology (seventh series),1988} reported experimental study for read across substance Chromium complex of 1-phenyl-3-methyl 4-(2'hydroxy-3'-sulfo-5' chlorophenylazo) 5-hydroxypyrazole [CAS: 6408 -26 -0] on guinea pig skin. 1% aqueous solution of the test chemical in 1% methylcellulose was applied on the skin of guinea pigs 3 times on day 1, and 3 times on day 2. The guinea pigs were evaluated daily for dermal reactions. No dermal reactions were observed even after repeated daily exposures to the test chemical. Hence, Chromium complex of 1-phenyl-3-methyl 4-(2'hydroxy-3'-sulfo-5'-chlorophenylazo) 5 -hydroxypyrazole(Acid Red 180)[CAS: 6408 -26 -0] can be considered to be not irritating to guinea pig skin.

 

The above results were further supported by the experimental study reported by European Commission (EC) - Scientific Committee on Cosmetology (SCC) {COMMISSION OF THE EUROPEAN COMMUNITIES; Brussels, Luxembourg, 1988} 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.

 

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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    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 chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     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 chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     andits structurally similar read across substancealuminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex {CAS No: 15790-07-5}, 4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one (CAS No: 3520-72-7) and 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 chemicalchromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1).The chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) is estimated to be not irritating to eye of New Zealand White rabbits.

 

An ocular irritation study was conducted by Sustainability Support Services (Europe) AB, 2017 on three New Zealand white rabbits in accordance with OECD 405 to assess the irritation parameter of read across chemical aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5). About 0.1g of the undiluted test chemical was instilled in the conjunctival sac of rabbits after gently pulling the lower lid away from the eyeball. The other eye which remained untreated served as a control. The ocular lesions were evaluated at 1, 24, 48 and 72 hours after the treatment. The grades of ocular reactions (conjunctiva, cornea and iris) were recorded at each observation. To determine the reversibility of the effect the animals were observed normally for 21 days. Any other lesions in the eye viz pannus, staining were observed and scored accordingly. Examination of reactions was facilitated by use of biomicroscope and hand slit lamp. Individual animal weights before and during the study was observed. The overall irritation index of aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) was 0.0 after 72 hours. Also aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) did not produce any clinical signs of toxicity throughout the examination period of 21 days. Hence, under the test conditions, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5)can be concluded  to be not irritating to New Zealand White rabbit eyes.

 

 

The above results were further supported by the experimental studies reported by European Commission (EC) - Scientific Committee on Cosmetology (SCC) {COMMISSION OF THE EUROPEAN COMMUNITIES; Brussels, Luxembourg, 1988} of read across chemicals 4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one (CAS No: 3520-72-7) and C.I. Pigment Red 3(CAS No: 2425-85-6) as below;

In case of 4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one (CAS No: 3520-72-7), 100 mg undiluted test chemical was instilled into the eyes of rabbits and observed for effects till 7 days. Slight irritation effects were observed which were fully recovered within 7 days. Hence, 4,4'-[(3,3'-dichloro[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[2,4-dihydro-5 -methyl-2-phenyl-3H-pyrazol-3-one was considered to be not irritating to rabbit eye.

 

In an ocular irritation study of chemical C.I. Pigment Red 3(CAS No: 2425-85-6), the undiluted 100mg of C.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 the rabbits’ eye.

 

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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)    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 chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1)     and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) is unlikely to cause skin and eye irritation. Hence chromium(3+) ion hydrogen bis(1-(3-chlorophenyl)-4-[(E)-2-(5-methanesulfonyl-2-oxidophenyl)diazen-1-yl]-3-methyl-1H-pyrazol-5-olate) (CAS No: 71598-35-1) can be classified under the category “Not Classified” for skin and eye as per CLP.