Registration Dossier

Skin irritation:

The dermal irritation potential of Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)is estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)cannot be considered as skin irritant and can be classified under the category “Not Classified” as per CLP regulation

Eye irritation:

The ocular irritation potential of Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)is estimated to be not irritating to the eye of New Zealand White rabbits. Based on the estimated result Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)can be considered to be not irritating to eye 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 v3.3 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 test material: Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate
- Molecular formula: C40H42K2N12O10S2
- Molecular weight: 993.174 g/mol
- Smiles notation: [K+].[K+].C(=C\c1c(cc(cc1)Nc1nc(nc(n1)N(CCO)CCO)Nc1ccccc1)S(=O)(=O)[O-])\c1c(cc(cc1)Nc1nc(nc(n1)N(CCO)CCO)Nc1ccccc1)S(=O)(=O)[O-]
- InChl: 1S/C40H44N12O10S2.2K/c53-21-17-51(18-22-54)39-47-35(41-29-7-3-1-4-8-29)45-37(49-39)43-31-15-13-27(33(25-31)63(57,58)59)11-12-28-14-16-32(26-34(28)64(60,61)62)44-38-46-36(42-30-9-5-2-6-10-30)48-40(50-38)52(19-23-55)20-24-56;;/h1-16,25-26,53-56H,17-24H2,(H,57,58,59)(H,60,61,62)(H2,41,43,45,47,49)(H2,42,44,46,48,50);;/q;2*+1/p-2/b12-11+;;
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5ml

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

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:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no signs of irritation observed

Estimation method: Takes mode value from the 9 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 "n" ) and "o" ) and ("p" and "q" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as C.I. Fluorescent Brightener 28 113 by OECD HPV Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety OR Salt OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines 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 OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

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 4,4'-Diethylaminoethoxyhexestrol (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "m"

Similarity boundary:Target: OCCN(CCO)c1nc(Nc2ccccc2)nc(Nc2ccc(C=Cc3ccc(Nc4nc(Nc5ccccc5)nc(N(CCO)CCO)n4)cc3S(=O)(=O)O{-}.K{+})c(S(=O)(=O)O{-}.K{+})c2)n1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Similarity boundary:Target: OCCN(CCO)c1nc(Nc2ccccc2)nc(Nc2ccc(C=Cc3ccc(Nc4nc(Nc5ccccc5)nc(N(CCO)CCO)n4)cc3S(=O)(=O)O{-}.K{+})c(S(=O)(=O)O{-}.K{+})c2)n1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Similarity boundary:Target: OCCN(CCO)c1nc(Nc2ccccc2)nc(Nc2ccc(C=Cc3ccc(Nc4nc(Nc5ccccc5)nc(N(CCO)CCO)n4)cc3S(=O)(=O)O{-}.K{+})c(S(=O)(=O)O{-}.K{+})c2)n1
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.35

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.37

Interpretation of results:

other: not irritating

Conclusions:

Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate was estimated to be not irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate can be considered to be 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 test material: Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate
- Molecular formula: C40H42K2N12O10S2
- Molecular weight: 993.174 g/mol
- Smiles notation: [K+].[K+].C(=C\c1c(cc(cc1)Nc1nc(nc(n1)N(CCO)CCO)Nc1ccccc1)S(=O)(=O)[O-])\c1c(cc(cc1)Nc1nc(nc(n1)N(CCO)CCO)Nc1ccccc1)S(=O)(=O)[O-]
- InChl: 1S/C40H44N12O10S2.2K/c53-21-17-51(18-22-54)39-47-35(41-29-7-3-1-4-8-29)45-37(49-39)43-31-15-13-27(33(25-31)63(57,58)59)11-12-28-14-16-32(26-34(28)64(60,61)62)44-38-46-36(42-30-9-5-2-6-10-30)48-40(50-38)52(19-23-55)20-24-56;;/h1-16,25-26,53-56H,17-24H2,(H,57,58,59)(H,60,61,62)(H2,41,43,45,47,49)(H2,42,44,46,48,50);;/q;2*+1/p-2/b12-11+;;
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1g

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

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:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no signs of irritation observed

Estimation method: Takes mode value from the 9 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 "p" ) and "q" ) and ("r" and "s" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as C.I. Fluorescent Brightener 28 113 by OECD HPV Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety OR Salt OR Triazines, Aromatic by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR SN1 OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines 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 OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards by DNA binding by OASIS v.1.3

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, non cyclic structure OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "j"

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 Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isocyanates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Toluene and small alkyl toluene derivatives (8a) OR Triarylmethane dyes (12c) by DART scheme v.1.0

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Similarity boundary:Target: OCCN(CCO)c1nc(Nc2ccccc2)nc(Nc2ccc(C=Cc3ccc(Nc4nc(Nc5ccccc5)nc(N(CCO)CCO)n4)cc3S(=O)(=O)O{-}.K{+})c(S(=O)(=O)O{-}.K{+})c2)n1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: OCCN(CCO)c1nc(Nc2ccccc2)nc(Nc2ccc(C=Cc3ccc(Nc4nc(Nc5ccccc5)nc(N(CCO)CCO)n4)cc3S(=O)(=O)O{-}.K{+})c(S(=O)(=O)O{-}.K{+})c2)n1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Similarity boundary:Target: OCCN(CCO)c1nc(Nc2ccccc2)nc(Nc2ccc(C=Cc3ccc(Nc4nc(Nc5ccccc5)nc(N(CCO)CCO)n4)cc3S(=O)(=O)O{-}.K{+})c(S(=O)(=O)O{-}.K{+})c2)n1
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.35

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.37

Interpretation of results:

other: not irritating

Conclusions:

Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, Dipotassium 4,4'-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate can be considered to be 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:

Various studieshas been investigated for the test chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)and its structurally similar read across substancesdisodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) (CAS No: 4193-55-9)and C.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6).The chemical Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)is estimated to be not irritating to skin of New Zealand White rabbits.

SIDS INITIAL ASSESSMENT PROFILE (2010) performed a dermal irritation study to assess the irritation potential ofstructurally similar read across substancedisodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) (CAS No: 4193-55-9) in rabbits which supports the above result. In this study, 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 (CAS No: 4193-55-9)can be considered not irritating to rabbit skin.

Above results were further supported by experimental study conducted by OECD SIDS (2005) forstructurally similar read across substanceC.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7) in rabbits. C.I. Fluorescent Brightener 28/113 was applied as dry powder at the inner surface of 2 New Zealand White rabbit ears under semi-occlusive conditions for 24 hours. The ears were rinsed after the exposure and rabbits were observed for a period of 7 days. The treated skin areas were inspected for lesions after 24 h, day 2, 3, 6 and 7. The treated sites showed no signs of irritation. Hence, C.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7) can be considered not irritating to rabbit skin.

Thus on the basis of available data for thetarget chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)and its structurally similar read across substancesdisodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) (CAS No: 4193-55-9)and C.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7) ,it can be concluded thatchemical Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)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 chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)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 chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)and its structurally similar read across substancesdisodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) (CAS No: 4193-55-9)and C.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7).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 ocular irritation potential was estimated for test chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6).The chemical Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)is estimated to be not irritating to eye of New Zealand White rabbits.

The OECD SIDS (2005)and Bayer AG (1979) performed a ocular irritation study to assess the irritation potential ofstructurally similar read across substancedisodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) (CAS No: 4193-55-9) rabbits which supports the above result. In this study, New Zealand White rabbits (3/sex) were administered C.I. Fluorescent Brightener 28, disodium salt by the instillation of 100 mg into one eye. The eyelids were held closed for 1 second. The eyes were examined 24, 48 and 72 hours and 7 days following application. Examination at 24 hours was aided with fluorescein dye. No eye reactions as well no clinical signs were observed throughout the study. The Irritation Score was 0. Based on the scores and observations, disodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (CAS No: 4193-55-9) can be considered not irritating to eyes.

Above results were further supported by experimental study conducted by OECD SIDS (2005) forstructurally similar read across substanceC.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7) in rabbits. About 50 mg C.I. Fluorescent Brightener 28/113 was instilled into the conjunctival sac of 2 New Zealand White rabbits. The rabbits were observed for a period of 7 days. The treated eyes were inspected for lesions after 24 h, day 2, 3, 6 and 7. The treated eyes showed no signs of irritation. Hence, C.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7) can be considered not irritating to New Zealand White rabbit eyes.

Thus on the basis of available data for thetarget chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)and its structurally similar read across substancesdisodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) (CAS No: 4193-55-9)and C.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7) ,it can be concluded thatchemical Dipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)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”.

The skin and eye irritation potential of test chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)and its structurally similar read across substancesdisodium 4,4'-bis[6-anilino-[4-[bis(2-hydroxyethyl)amino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate (Blankophor BA) (CAS No: 4193-55-9)and C.I. Fluorescent Brightener 28/113 (CAS No: 70942-01-7)were observed in various studies. The results obtained from these studies indicates that the chemicalDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonateis unlikely to cause skin and eye irritation. HenceDipotassium 4,4’-bis[6-anilino-4-[bis(2-hydroxyethyl)amino-1,3,5-triazin-2-yl]amino]stilbene-2,2’-disulphonate (CAS No: 71230-67-6)can be classified under the category “Not Classified” for skin and eye as per CLP.