Registration Dossier

Skin Irritation:

The dermal irritation potential of trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated to be not irritating to the skin of New Zealand White rabbits.

Eye Irritation:

The ocular irritation potential of trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

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 v3.3 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 v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: Cibacron Brilliant Yellow 3G-P
- IUPAC name: trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate
- Molecular formula: C25H18Cl3N9O10-S3.3Na
- Molecular weight: 872.974 g/mol
- Substance type: Organic
- Physical state: Solid
SMILES:CC1C(N=Nc2cc(Nc3nc(Nc4ccc(S(=O)(=O)O{-}.[Na]{+})cc4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C(=O)N(c2cc(Cl)c(S(=O)(=O)O{-}.[Na]{+})cc2Cl)N=1

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

500mg

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation 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 "j" ) and "k" ) and ("l" and ( not "m") ) ) and "n" ) and ("o" and "p" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Substituted Triazines (Acute toxicity) by US-EPA New Chemical Categories

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 Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones 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 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 OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND 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 by Chemical elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens F OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "i"

Similarity boundary:Target: CC1C(N=Nc2cc(Nc3nc(Nc4ccc(S(=O)(=O)O{-}.[Na]{+})cc4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C(=O)N(c2cc(Cl)c(S(=O)(=O)O{-}.[Na]{+})cc2Cl)N=1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Similarity boundary:Target: CC1C(N=Nc2cc(Nc3nc(Nc4ccc(S(=O)(=O)O{-}.[Na]{+})cc4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C(=O)N(c2cc(Cl)c(S(=O)(=O)O{-}.[Na]{+})cc2Cl)N=1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Similarity boundary:Target: CC1C(N=Nc2cc(Nc3nc(Nc4ccc(S(=O)(=O)O{-}.[Na]{+})cc4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C(=O)N(c2cc(Cl)c(S(=O)(=O)O{-}.[Na]{+})cc2Cl)N=1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNHal Aqueous Solubility < 0.001 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNHal Molecular Weight > 380 g/mol OR Group CNS log Kow < 0.5 OR Group CNS log Kow < -2 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: "n"

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

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.552

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.951

Interpretation of results:

other: not irritating

Conclusions:

Trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate 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 v3.3 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 v3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of the test material: Cibacron Brilliant Yellow 3G-P
- IUPAC name: trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate
- Molecular formula: C25H18Cl3N9O10-S3.3Na
- Molecular weight: 872.974 g/mol
- Substance type: Organic
- Physical state: Solid
SMILES:CC1C(N=Nc2cc(Nc3nc(Nc4ccc(S(=O)(=O)O{-}.[Na]{+})cc4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C(=O)N(c2cc(Cl)c(S(=O)(=O)O{-}.[Na]{+})cc2Cl)N=1

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:

0.1 ml

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1,24,48 and 72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1,24,48 and 72 hours

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation 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 "t" ) and "u" ) and ("v" and ( not "w") ) ) and ("x" and "y" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Substituted Triazines (Acute toxicity) by US-EPA New Chemical Categories

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 Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones 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 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 OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr AND 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 by Chemical elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens F OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Allyl esters (Hepatotoxicity) Rank A OR Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C OR Dantrolene (Hepatotoxicity) Alert OR Nitrophenols/ Halophenols (Energy metabolism dysfuntion) Rank B OR Oxyphenistain (Hepatotoxicity) Alert OR Perhexiline (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation at a carbonyl with a leaving group OR Acylation >> Direct acylation at a carbonyl with a leaving group >> Phenyl acetates OR Acylation >> Ring opening acylation at a carbonyl OR Acylation >> Ring opening acylation at a carbonyl >> Anhydrides OR Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Aminophenols OR Pro-Michael Addition >> Pro-quinone and related >> Phenylenediamines by Respiratory sensitisation

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "q"

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: "r"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 3-Alken-2-ones (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Chloroacetamides (SN2) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) OR Moderately reactive (GSH) >> Substituted 1-Alken-3-ones (MA) OR Slightly reactive (GSH) OR Slightly reactive (GSH) >> Substituted haloacetamides (SN2) by Protein binding potency

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Similarity boundary:Target: CC1C(N=Nc2cc(Nc3nc(Nc4ccc(S(=O)(=O)O{-}.[Na]{+})cc4)nc(Cl)n3)ccc2S(=O)(=O)O{-}.[Na]{+})C(=O)N(c2cc(Cl)c(S(=O)(=O)O{-}.[Na]{+})cc2Cl)N=1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alkylarylether OR Amine OR Azo compound OR Carbonyl compound OR Carboxylic acid OR Carboxylic acid amide OR Carboxylic acid ester OR Carboxylic acid prim. amide OR Carboxylic acid sec. amide OR Carboxylic acid tert. amide OR CO2 derivative (general) OR Dialkylether OR Diarylether OR Ether OR Hydroxy compound OR Hydroxylamine OR Ketone OR Lactam OR Lactone OR Nitro compound OR Oxohetarene OR Phenol OR Primary amine OR Primary aromatic amine OR Secondary aliphatic amine OR Secondary amine OR Secondary aromatic amine OR Sulfenic acid derivative OR Tertiary amine OR Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.853

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.99

Interpretation of results:

other: not irritating

Conclusions:

Trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate can be considered not irritating to 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, trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate has 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 chemical and its closely related read across substances, FD & C Red NO. 40 or Allura Red AC [CAS: 25956-17-6] and disodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5 -triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) [CAS: 4193-55-9]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the dermal irritation potential was estimated for trisodium 2,5-dichloro-4-(4-{[5-({4 -chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate. Trisodium 2,5-dichloro-4-(4-{[5-({4 -chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated to be not irritating to the skin of New Zealand White rabbits.

This result is supported by the experimental study performed by Fulton Jr, J. E (J. Soc. Cosmet. Chem. 40, 321-333, 1989)on rabbit ear, to indicate the comedogenicity and irritancy potential of the closely related read across substance, FD & C Red NO. 40 or Allura Red AC [CAS: 25956-17-6]. Ingredients are 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 is free from mites is used. Three rabbits, weighing two to three kilograms, are used for each assay. Animals are housed singly in suspended cages and fed Purina Rabbit Chow and water ad libitum. Animals are maintained on a 12-hour light and 12 -hour dark cycle. A dose of 1 ml of FD&C Red 40 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 a chemical or skin care product 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 and 5 = Epidermal necrosis and slough.

FD&C Red 40 falls under Grade 2 (diffuse scaling and no erythema). Hence it can be concluded that FD&C Red 40 was not irritating to rabbit ears.

These results are further supported by the experimental study summarized in U.S. Environmental Protection Agency, Hazard Characterization Document, 2010; for the closely related read across substance, disodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) [CAS: 4193-55-9]. Two New Zealand White rabbits were exposed to 500 mg of Disodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate, free acid as a dry powder applied to the inner surface the ears and covered with adhesive bandages for 24 hours. The ears were rinsed following exposure and the rabbits were observed for 7 days. No signs of skin irritation were observed.

Hence, disodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate can be considered not irritating to rabbit skin.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate can be 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, trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its closely related read across substances, FD & C Red NO. 40 or Allura Red AC [CAS: 25956-17-6] and phthalimide [CAS: 85-41-6].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for trisodium 2,5-dichloro-4-(4-{[5-({4 -chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate. Trisodium 2,5-dichloro-4-(4-{[5-({4 -chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

This result is supported by the experimental study summarized in SIDS Initial Assessment Report For SIAM 20, 19-22 April 2005; for the closely related read across substance, phthalimide [CAS: 85-41-6].50 mg of phthalimide was instilled into the conjunctival sac of 2 rabbits and signs of irritation were observed (duration not mentioned). No irritation was observed when phthalimide was instilled into the eyes of 2 rabbits.Hence, phthalimide can be considered as not irritating to eyes.

In an another study summarized in OTS10840346, received on October, 1984; for the closely related read across substance, phthalimide [CAS: 85-41-6], 100 mg of phthalimide was applied as finely ground powder into the eyes of 6 New Zealand White rabbits. This study was conducted as per F.H.S.A Guidelines. The rabbits were exposed to the test chemical for 24 hours. The effects were observed for 72 – 168 hours and scored. Immediate: Mild discomfort with eyes closed, 10 minutes: Slight erythema, moderate discharge 1 hr: Slight erythema, moderate discharge 24 hrs: Slight discharge, 48 hrs: All scores were zero. The average eye irritation index in rabbits after 72 hours was 0 on a scale of 8.

Hence, phthalimide was considered to be not irritating to rabbit eyes.

These results are further supported by the experimental study summarized in Scientific Committee on Cosmetology (seventh series), pg 23 -25, 1988; for the closely related read across substance, FD & C Red NO. 40 or Allura Red AC [CAS: 25956-17-6]. 0.1 ml of 1.0% aqueous solution of Allura Red AC was instilled into the rabbit eyes and the effects were observed (duration not specified).0.1 ml of 1.0% aqueous solution of Allura Red AC did not any changes in rabbit eyes. Hence Allura Red AC can be considered not irritating to rabbit eyes.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach, trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate can be 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 trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate suggests that it is not likely to cause any irritation to eyes and skin.

Trisodium 2,5-dichloro-4-(4-{[5-({4-chloro-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)-2-sulfonatophenyl]diazenyl}-3-methyl- 5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonate can be classified under the category “Not Classified” as per CLP regulation.