Registration Dossier

Skin Irritation:

The dermal irritation potential of Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated result; Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

The ocular irritation potential of Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result; Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium can be considered not irritating to the eyes and can be classified under the category “Not Classified” as per CLP regulation.

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 v3.4 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium
- Substance type: Organic

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:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.5g

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

no data available

Details on study design:

no data available

Other effects / acceptance of results:

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 signs of dermal irritation observed

Other effects:

no data available

Estimation method: Takes mode value from the 6 nearest neighbours
Domain logical expression:Result: In Domain

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

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 SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Schiff base formation with carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR Schiff base formation OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by Protein binding by OASIS v1.4 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD ONLY

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 ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 ONLY

Domain logical expression index: "i"

Similarity boundary:Target: CC1C{-}(N=Nc2cc(Cl)ccc2O{-}.[Cr]{2+}.O{-}c2ccc(Cl)cc2N=NC{-}2C(C)=NN(c3cccc(S(=O)(=O)O{-}.[Na]{+})c3)C2=O)C(=O)N(c2ccccc2)N=1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Similarity boundary:Target: CC1C{-}(N=Nc2cc(Cl)ccc2O{-}.[Cr]{2+}.O{-}c2ccc(Cl)cc2N=NC{-}2C(C)=NN(c3cccc(S(=O)(=O)O{-}.[Na]{+})c3)C2=O)C(=O)N(c2ccccc2)N=1
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 751 Da

Domain logical expression index: "l"

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

Interpretation of results:

other: not irritating

Conclusions:

Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated result; Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium can be considered not irritating to skin and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

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 v3.4 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium
- Substance type: Organic

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:

0.1 ml

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

7 days

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

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no signs of irritation observed

Other effects:

no data available

Estimation method: Takes mode value from the 10 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 ("j" and ( not "k") ) ) and ("l" and ( not "m") ) ) and ("n" and ( not "o") ) ) and ("p" and "q" ) )

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 SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Schiff base formation with carbonyl compounds (AN2) OR AN2 >> Schiff base formation with carbonyl compounds (AN2) >> Pyrazolone and Pyrazolidine Derivatives OR Schiff base formation OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base on pyrazolones and pyrazolidinones >> Pyrazolones and Pyrazolidinones by Protein binding by OASIS v1.4 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) OR Moderately reactive (GSH) >> Vinyl bromides (SN2) by Protein binding potency

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Aqueous Solubility < 0.000005 g/L AND (!Undefined)Group All Aqueous Solubility < 0.00002 g/L AND (!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 Molecular Weight > 650 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

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: "m"

Referential boundary: The target chemical should be classified as Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

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: "o"

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

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 598 Da

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 934 Da

Interpretation of results:

other: not irritating

Conclusions:

Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor.

Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated result; Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium can be considered not irritating to the eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin Irritation:

In different studies,Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodiumhas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemicaland its structurally similar read across chemicals, disodium 5-acetamido-4-hydroxy-3-(phenyldiazenyl)naphthalene-2,7-disulfonate [CAS: 3734-67 -6] and disodium 4-[(E)-2-(4-methyl-2-sulfophenyl)diazen-1-yl]-3-oxidonaphthalene-2-carboxylate(D&C Red 6)[CAS: 5858-81-1].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2018) using the OECD QSAR toolbox v3.4 with log kow as the primary descriptor, the skin irritation potential was estimated forChromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium.Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodiumwas estimated to be not irritating to New Zealand White rabbit skin.

This result supported by the experimental study conducted in an OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access,2016) for the structurally similar read across chemical, Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate[CAS: 3734-67-6]The study was performed as per OECD Guidelines 402 and complying to the GLP procedures.

The test item was applied to shorn skin of 5 male and 5 female Sprague Dawley rats at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.

Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment.

The overall irritation score of the substance was determined to be 0 and no erythema and edema (skin irritation) were observed at the end of 14 days after patch removal. Hence, it was concluded that Disodium 8-acetamido-1-hydroxy-2-phenylazo-naphtalene-3,6-disulphonate was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance, Disodium 8-acetamido-1-hydroxy-2-phenylazo-naphtalene-3,6-disulphonate can be classified under the category "Not Classified" as per CLP regulation.

These results are further supported by the experimental study summarized in J. Soc. Cosmet. Chem., 40, 321-333 (November/December 1989), for the structurally similar read across chemical, disodium 4-[(E)-2-(4-methyl-2-sulfophenyl)diazen-1-yl]-3-oxidonaphthalene-2-carboxylate(D&C Red 6)[CAS: 5858-81-1]. D&C Red 6 was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand albino rabbits that have genetically good ears and free from mites were used. Three rabbits, weighing two to three kilograms, were used for each assay. Animals were housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals were maintained on a 12-hour light and 12-hour dark cycle. A dose of 1 ml of the test material was applied and spread once daily to the entire inner surface of once for five days per week for two weeks. The opposite untreated ear of each animal served as an untreated control.

The irritancy produced by repeated application of the chemical on the surface epidermis in the rabbit ear is evaluated on a scale of 0 to 5. The grades are summarized as follows:

0 = No irritation; 1 = few scales, no Erythema; 2 = diffuse scaling, no Erythema; 3 = Generalized scaling with Erythema; 4 = Scaling, Erythema and Edema; 5 = Epidermal necrosis and slough. D&C Red 6 falls under Grade 0 (no irritation observed).

Hence it can be concluded that D&C Red 6 was not irritating to rabbit ears.

Based on the available data for the target and applying the weight of evidence approach, C Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was considered not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Eye Irritation:

In different studies,Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5 -methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodiumhas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemicaland its structurally similar read across chemicals,trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate(Tartrazine)[CAS: 1934-21-0]and disodium 4-[(E)-2-(4-methyl-2-sulfophenyl)diazen-1-yl]-3-oxidonaphthalene-2-carboxylate(D&C Red 6)[CAS: 5858-81-1].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2018) using the OECD QSAR toolbox v3.4 with log kow as the primary descriptor, the eye irritation potential was estimated forChromate(2-), [4-[4-[(5-chloro-2 -hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium.Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodiumwas estimated to be not irritating to New Zealand White rabbit eyes.

This is supported by the experimental study performed by S D Gettings et.al (Food & Chemical Toxicology, Vol. 30, No. 12, pp. 1051-1055, 1992) to evaluate the staining, embedment and ocular irritation potential of the structurally similar read across substance, Tartrazine (FD & C Yellow No. 5)[CAS: 1934-21-0 in rabbits. The study was performed according to a modification of the Draize test (Draize, 1959).

Tartrazine (FD & C Yellow No. 5) was prepared daily as a 3% (w/v) suspension in aqueous vehicle containing 0.5% (w/v) hydroxypropyl methylcellulose and 0.25% (w/v) laureth -10 acetate. Tartrazine (FD & C Yellow No. 5) 3% w/v in aqueous vehicle was administered once daily, for a total of 21 days, to the conjunctival sac of the right eye of New Zealand White Rabbits (6 of each sex/ group) at a dose volume of 30µl. Control animals (6 of each sex) received 30/µl of the vehicle daily. Ocular irritation was determined according to a modification of the Draize test (Draize, 1959). Interpretation of observations and assignment of scores were consistent with those described by the Consumer Product Safety Commission (1972).All eyes were scored for ocular irritation pretest (8 days, 24 hr and immediately prior to the initial dose) and approximately 24 hr after each treatment, prior to the next instillation of test material; on days 1, 3, 7, 14 and 21, the eyes were also evaluated for irritation 1 hr after treatment. In addition, all readily observable ocular structures were evaluated for eye stain and particle embedment 24 hr after each treatment.

No lethality or significant clinical signs, and no substance-related weight change were observed. Except slight conjunctival redness or discharge, that were seen sporadically in the eyes of the animals, all animals were free of significant signs of ocular irritation. No significant signs of eye staining or particle depositions were observed. At ophthalmoscopic examinations, no ocular abnormities were noticed.

Hence, FD&C Yellow No.5 (tartrazine) was not expected to cause any irritant effects following repeated exposure to rabbit eyes.

The above results are further supported by the experimental study summarized in GESTIS SUBSTANCE Database (information system in hazardous substance of the Berufsgenossenscheftn), 2017; for the structurally similar read across chemical,disodium 4-[(E)-2-(4-methyl-2-sulfophenyl)diazen-1-yl]-3-oxidonaphthalene-2-carboxylate(D&C Red 6)[CAS: 5858-81-1]. Rabbits received(number not specified) 2 installation of 0.2 ml of a 10% D & C Red No. 6 aqueous suspension into the conjunctival sac of rabbits 5 times per week for 4 weeks.

The chemical produced only minimal irritative effects after 2 hours which could not confirm the irritation potential. Hence, on the basis of findings D & C Red No. 6 (CAS no: 5858-81-1)can be considered as not irritating to the rabbits’ eye.

Based on the available data for the target and applying the weight of evidence approach, C Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium was considered not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Available data for Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium indicates that it is not likely to cause severe irritation or corrosion to eyes and skin.

Hence, Chromate(2-), [4-[4-[(5-chloro-2-hydroxyphenyl)azo]-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl]benzenesulfonato(3-)][4-[(5-chloro-2-hydroxyphenyl)azo]-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-onato(2-)]-, sodium can be classified under the category “Not Classified” for skin and eye irritation as per CLP regulation.