Registration Dossier

Administrative data

Description of key information

Skin Irritation:

The dermal irritation potential of 3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated to be not irritating to the skin of New Zealand White rabbits.

Eye Irritation:

 The ocular irritation potential of 3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated to be not irritating to the eyes of New Zealand White rabbits.

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 v3.3 and the QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt
- Molecular formula: C20H4Br4Cl4O5.xAl
- Molecular weight: 2387.0295 g/mol
- Smiles notation : c1c2c(c(c(c1Br)O)Br)Oc3c(cc(c(c3Br)O)Br)C2c4c(c(c(c(c4Cl)Cl)Cl)Cl)C(=O)[O-].c1c2c(c(c(c1Br)O)Br)Oc3c(cc(c(c3Br)O)Br)C2c4c(c(c(c(c4Cl)Cl)Cl)Cl)C(=O)[O-].c1c2c(c(c(c1Br)O)Br)Oc3c(cc(c(c3Br)O)Br)C2c4c(c(c(c(c4Cl)Cl)Cl)Cl)C(=O)[O-].[Al+3]
- InChl: 1S/3C20H6Br4Cl4O5.Al/c3*21-5-1-3-7(8-9(20(31)32)13(26)15(28)14(27)12(8)25)4-2-6(22)17(30)11(24)19(4)33-18(3)10(23)16(5)29;/h3*1-2,7,29-30H,(H,31,32);/q;;;+3/p-3
- Substance type: Organic
- Physical state: Solid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
no data available
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
Not specified
Duration of treatment / exposure:
24hours
Observation period:
Not specified
Number of animals:
Not specified
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: Not specified
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No irritation estimated

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

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aluminum Compounds AND Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aromatic perhalogencarbons OR Aryl OR Aryl halide OR Carboxylic acid OR Fused carbocyclic aromatic OR Fused saturated heterocycles OR No functional group found OR Phenol OR Xanthene by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic perhalogencarbons OR Aryl halide OR Carboxylic acid OR No functional group found OR Overlapping groups OR Phenol OR Xanthene by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] OR Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic Carbon, two phenyl attach [-C-]  OR Aliphatic Oxygen, two aromatic attach [-O-] OR Aluminium [Al] OR Aromatic Carbon [C] OR Bromine, aromatic attach [-Br] OR Bromine, olefinic attach [-Br] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Chlorine, aromatic attach [-Cl] OR Chlorine, olefinic attach [-Cl] OR Hydroxy, aromatic attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Oxygen, two olefinic attach [-O-] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound OR Aryl bromide OR Aryl chloride OR Aryl halide OR Carbonic acid derivative OR Carboxylic acid OR Carboxylic acid derivative OR Diarylether OR Ether OR Halogen derivative OR Heterocyclic compound OR Hydroxy compound OR No functional group found OR Phenol by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR Radical >> ROS formation after GSH depletion >> Quinone methides 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 carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR 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 OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha, beta - Unsaturated Carbonyls and Related Compounds 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 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael-type addition to quinoid structures OR AN2 >> Michael-type addition to quinoid structures >> Phenols OR AN2 >> Shiff base formation with carbonyl compounds OR AN2 >> Shiff base formation with carbonyl compounds >> Pyrazolone and Pyrazolidine Derivatives by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic perhalogencarbons AND Aryl AND Aryl halide AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND No functional group found AND Phenol AND Xanthene by Organic Functional groups ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aromatic compound AND Aryl bromide AND Aryl chloride AND Aryl halide AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Diarylether AND Ether AND Halogen derivative AND Heterocyclic compound AND Hydroxy compound AND No functional group found AND Phenol by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B OR Carboxylic acids (Hepatotoxicity) No rank OR Ethionine (Hepatotoxicity) Alert OR Perhexiline (Hepatotoxicity) Alert OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Butanedioic acid OR C14+Aliphatics hydrocarbon solvents (less than 2 percent aromatics) OR C7-9 Aliphatics hydrocarbon solvents OR C9-13 Aliphatics hydrocarbon solvents (less than 2 percent aromatics) by OECD HPV Chemical Categories

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Phtalate (or buthyl) diesters and monoesters (Nongenotox) OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Halogenated Aromatic Hydrocarbon Type Compounds AND Not classified AND Phenol Type Compounds by Oncologic Primary Classification

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Halogenated Cycloalkane Type Compounds OR Organophosphorus Type Compounds OR Peroxide Type Compounds by Oncologic Primary Classification

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Group 13 - Metals Al,Ga,In,Tl AND Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens Br AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Group 14 - Metals Sn,Pb OR Group 15 - Nitrogen N OR Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.266

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.13

Interpretation of results:
other: not irritating
Conclusions:
3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated to be not irritating to the skin of rabbits.
Executive summary:

The dermal irritation potential of 3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated to be not irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt 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 v3.3 and the QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt
- Molecular formula: C20H4Br4Cl4O5.xAl
- Molecular weight: 2387.0295 g/mol
- Smiles notation : c1c2c(c(c(c1Br)O)Br)Oc3c(cc(c(c3Br)O)Br)C2c4c(c(c(c(c4Cl)Cl)Cl)Cl)C(=O)[O-].c1c2c(c(c(c1Br)O)Br)Oc3c(cc(c(c3Br)O)Br)C2c4c(c(c(c(c4Cl)Cl)Cl)Cl)C(=O)[O-].c1c2c(c(c(c1Br)O)Br)Oc3c(cc(c(c3Br)O)Br)C2c4c(c(c(c(c4Cl)Cl)Cl)Cl)C(=O)[O-].[Al+3]
- InChl: 1S/3C20H6Br4Cl4O5.Al/c3*21-5-1-3-7(8-9(20(31)32)13(26)15(28)14(27)12(8)25)4-2-6(22)17(30)11(24)19(4)33-18(3)10(23)16(5)29;/h3*1-2,7,29-30H,(H,31,32);/q;;;+3/p-3
- 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:
100 mg
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
24,48,72 hours till 7 days
Duration of post- treatment incubation (in vitro):
no data available
Number of animals or in vitro replicates:
6
Details on study design:
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 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" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and "aa" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aluminum Compounds AND Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aromatic perhalogencarbons OR Aryl OR Aryl halide OR Carboxylic acid OR Fused carbocyclic aromatic OR Fused saturated heterocycles OR No functional group found OR Phenol OR Xanthene by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic perhalogencarbons OR Aryl halide OR Carboxylic acid OR No functional group found OR Overlapping groups OR Phenol OR Xanthene by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid, aromatic attach [-COOH] OR Alcohol, olefinic attach [-OH] OR Aliphatic Carbon [CH] OR Aliphatic Carbon, two phenyl attach [-C-]  OR Aliphatic Oxygen, two aromatic attach [-O-] OR Aluminium [Al] OR Aromatic Carbon [C] OR Bromine, aromatic attach [-Br] OR Bromine, olefinic attach [-Br] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Chlorine, aromatic attach [-Cl] OR Chlorine, olefinic attach [-Cl] OR Hydroxy, aromatic attach [-OH] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Oxygen, two olefinic attach [-O-] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound OR Aryl bromide OR Aryl chloride OR Aryl halide OR Carbonic acid derivative OR Carboxylic acid OR Carboxylic acid derivative OR Diarylether OR Ether OR Halogen derivative OR Heterocyclic compound OR Hydroxy compound OR No functional group found OR Phenol by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated aldehydes 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 Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Aziridines OR SN2 >> Direct Acting Epoxides and related >> Epoxides by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR 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 OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 4 (Compounds and groups of compounds acting by a specific mechanism) AND Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found AND SNAr AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds AND SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "l"

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 >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Acylation >> Direct acylation involving a leaving group >> Diacyl peroxides, anhydrides (sulphur analogues of diacyl peroxides)   OR Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aromatic perhalogencarbons AND Aryl AND Aryl halide AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND No functional group found AND Phenol AND Xanthene by Organic Functional groups ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aliphatic acids and (Met)acrylic acids by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group 13 - Metals Al,Ga,In,Tl AND Group 14 - Carbon C AND Group 16 - Oxygen O AND Group 17 - Halogens Br AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Group 14 - Metals Sn,Pb OR Group 15 - Metals Bi OR Group 15 - Nitrogen N OR Group 15 - Phosphorus P OR Group 16 - Sulfur S OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Carboxylic acids (Hepatotoxicity) No rank OR Perhexiline (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Exclusion rules not met AND Group All Aqueous Solubility < 0.000005 g/L AND Group All Aqueous Solubility < 0.00002 g/L AND Group All log Kow > 9 AND Group All Melting Point > 200 C AND Group All Molecular Weight > 650 g/mol AND Group CHal log Kow > 4.5 AND Group CHal Melting Point > 65 C AND Group CHal Molecular Weight > 280 g/mol AND Group CHal Molecular Weight > 370 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Group C Aqueous Solubility < 0.0001 g/L OR 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: "x"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols, Poly AND SHOULD NOT BE PROFILED by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Inorganic Compound OR Neutral Organics OR Peroxy Acids by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.839

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.79

Interpretation of results:
other: not irritating
Conclusions:
3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated to be not irritating to the eyes of New Zealand White rabbits.
Executive summary:

 The ocular irritation potential of 3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt was estimated to be not irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt 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:

In different studies,4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt 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, 2',4',5',7'-tetrabromo-4,5,6,7-tetrachloro-3',6'-dihydroxy-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (D&C RED 27) [CAS: 13473-26-2], Disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate (Erythrosine) [CAS: 16423-68-0] and Dodecanedioic acid [CAS: 693-23-2]. 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 skin irritation potential was estimated for 4, 5, 6-tetrachloro-2-(2,4,5,7 -tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt.4, 5, 6-tetrachloro-2 -(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium saltwas estimated to be not irritating to 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) to indicate the Comedogenicity and irritancy of the closely related read across substance, 2',4',5',7'-tetrabromo-4,5,6,7-tetrachloro-3',6'-dihydroxy-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (D&C RED 27) [CAS: 13473-26-2] in rabbit ear. D&C Red 27 was mixed in propylene glycol at a 9 to 1 dilution for testing unless otherwise indicated (10% concentration). A colony of New Zealand White 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 27 falls under Grade 0 (no irritation observed).

Hence it can be concluded that D&C Red 27 was not irritating to rabbit ears.

These results are also supported by the experimental study conducted inan OECD GLP laboratory (Sustainability Support Services (Europe) AB has the letter of access) forthe closely related read across substance, Disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate (Erythrosine) [CAS: 16423-68-0]. 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 femaleSprague 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 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate was not-Irritating to the skin of rats under the experimental conditions tested .Thus it can be concluded that the substance Disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate can be classified under the category "Not Classified" as per CLP regulation.

The above results are further supported by the experimental study summarized in International Journal of Toxicology, Vol 31, Issue 4_suppl, pp. 5S - 76S, 2012; for the closely related read across substance, Dodecanedioic acid [CAS: 693-23-2]. The study was performed according to FHSA Guidelines.0.5 g of dodecanedioic acid was applied to the rabbit skin and observed for signs of irritation (duration not mentioned). Application of 0.5 g of dodecanedioic acid to rabbit skin was not irritating to skin.

Hence, dodecanedioic acid can be considered as not irritating to skin.            

Based on the available data for the target and read across substances and applying the weight of evidence approach, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye Irritation:

In different studies,4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt 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, Disodium 2-(2,4,5,7 -tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate (Erythrosine) [CAS: 16423-68-0] and 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol [CAS: 79-94-7]. 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 4, 5, 6-tetrachloro-2-(2,4,5,7 -tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt.4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium saltwas estimated to be not irritating to eyes of New Zealand White rabbits.

This result is supported by the experimental study summarized in Scientific Committee on Consumer Safety (SCCS),SCCS/1314/10, last updated 2010; for theclosely related read across substance, Disodium 2-(2,4,5,7-tetraiodo-6-oxido-3-oxoxanthen-9-yl)benzoate (Erythrosine) [CAS: 16423-68-0].0.2mL of 10% aqueous solution was applied in the conjuctival sac of one eye of a group of at least 6 albino rabbits. The application was repeated twice daily, 5 days per week for 4 weeks. One hour after each application the eyes were examined for evidence of staining and irritation was scored according to Draize. Three days after the last application, two animals of each group (erythrosine colour and erythrosine lake) were killed; upper lids were taken for microscopic examination. Eyeballs and posterior parts were examined grossly for evidence of staining or other abnormalities. Erythrosine colour caused intense colouring of the iris and moderate conjunctival irritation. Staining lasted from 2 to 7 days. Erythrosine lake did not cause severe eye irritation but resulted in spotty staining in some animals and very slight but uniform staining in other animals.

Erythrosine colour caused intense colouring of the iris and moderate conjunctival irritation. Thus, erythrosine can be regarded as non-irritating to the rabbit eyes.

The above results are also supported by the experimental study summarized in Hazardous Substance Databank (HSDB), U.S National Library for Medicine, last updated 2013;for theclosely related read across substance, 2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol [CAS: 79-94-7]. 3 mg of finely ground powder of Tetrabromobisphenol A was applied to the conjunctival sac of albino rabbits (number and sex not specified) and observed for signs of irritation. The treated eyes were observed and examined at5 minutes, 1, and 4 hours after the application and daily thereafter for 7 days.

Application of 3 mg of Tetrabromobisphenol A to rabbit eyes did not cause any adverse effects to cornea, iris or conjunctivae at any time point.

Hence, Tetrabromobisphenol A can be considered as not irritating to eyes.

Based on the available data for the target and read across substances and applying the weight of evidence approach, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt can be considered to be not irritating to eyes. 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

Based on the available information, 3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium saltis not likely to cause any irritation to eyes and skin. Hence,3, 4, 5, 6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt can be classified under the category “Not Classified” as per CLP regulation.