Registration Dossier

Administrative data

Description of key information

Acute Oral Toxicity: 

Acute oral toxicity dose was predicted based on OECD QSAR toolbox for target substance3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)was estimated to be 4566 mg/kg bw andfor differentstudies available on the closely related read across substance Niobium pentoxide (1313-96-8) was considered to be 4000 mg/kg bw for mouse and Dibismuth trisulphide (1345-07-9) was considered to be 5000 mg/kg bw for rats. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)can be classified as category V of acute oral toxicity.

Acute Inhalation Toxicity: 

3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt has very low vapor pressure (4.49E-018 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal Toxicity:

Acute dermal toxicity dose was predicted based on OECD QSAR toolbox for target substance substance3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)was estimated to be 14289.59 mg/kg bw for rabbits andfor differentstudies available on the structurally similar 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 (18472-87-2) was considered to be >2000 mg/kg bw for rats and for the closely related read across substance 2,2',6,6',-tetrabromo-4,4'-isopropylidenediphenol (79-94-7) was considered to be >2000 mg/kg bw for rabbits. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)can be classified as category V of acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
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:
equivalent or similar to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.3, 2017
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
yes
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:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
No data available
Route of administration:
oral: gavage
Vehicle:
vegetable oil
Details on oral exposure:
No data available
Doses:
4566mg/kg bw
No. of animals per sex per dose:
3
Control animals:
not specified
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
female
Dose descriptor:
LD50
Effect level:
4 566 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
50% mortality was observed
Clinical signs:
No data available
Body weight:
No data available
Gross pathology:
No data available
Other findings:
No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 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 ( not "o") )  )  and "p" )  and "q" )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and "aa" )  and ("ab" and ( not "ac") )  )  and ("ad" and ( not "ae") )  )  and ("af" and "ag" )  )

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) >> Conjugated Nitro Compounds 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 attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds 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 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 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 No alert found by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation 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 of Heterocyclic Ring Systems >> Thiophenes-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 >> 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 amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR 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 >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphonic esters by DNA binding by OECD

Domain logical expression index: "j"

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: "k"

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: "l"

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 by OASIS v1.3

Domain logical expression index: "m"

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 >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Radical reactions OR Radical reactions >> Free radical formation OR Radical reactions >> Free radical formation >> Hydroperoxides OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.3

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 3-Alken-2-ones (MA) OR Highly reactive (GSH) >> Furamates (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) by Protein binding potency

Domain logical expression index: "p"

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: "q"

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

Domain logical expression index: "r"

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: "s"

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

Domain logical expression index: "t"

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: "u"

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 log Kow > 9 AND Group All Melting Point > 200 C 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 Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Metals, oxidative stress (Nongenotox) OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "y"

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

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Amorphous silica silicates OR Cadmium (oxide) OR Chlorosilanes OR Nickel and nickel compounds OR Zinc metal and salts by OECD HPV Chemical Categories

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Moderate AND Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "ab"

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: "ac"

Referential boundary: The target chemical should be classified as Aliphatic Amines OR Inorganic Compound OR Not Related to an Existing ECOSAR Class OR Peroxy Acids by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "ad"

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

Domain logical expression index: "ae"

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

Domain logical expression index: "af"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.97

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.2

Interpretation of results:
other: Not Classified
Conclusions:
LD50 was estimated to be 4566mg/kg bw, when female wistar rats were exposed with 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)orally.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9).

The LD50 was estimated to be 4566mg/kg bw when femaleWistar rats were exposed with3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)orally.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 566 mg/kg bw
Quality of whole database:
Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.3,2017
GLP compliance:
not specified
Test type:
other: Estimated data
Limit test:
no
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
Sex:
male/female
Details on test animals and environmental conditions:
No data available
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
No data available
Duration of exposure:
24 hours
Doses:
14289.59 mg/kg bw
No. of animals per sex per dose:
No data available
Control animals:
not specified
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
14 289.59 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
No data available
Gross pathology:
No data available
Other findings:
No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 7 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 "l" )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and "u" )  )

Domain logical expression index: "a"

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: "b"

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: "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 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: "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 AN2 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 Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical 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 >> ROS formation after GSH depletion 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 metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines 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 P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation 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 to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Tertiary 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 AND Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

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: "k"

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: "l"

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: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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 log Kow > 9 AND Group All Melting Point > 200 C 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 Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

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: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Moderate AND Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.87

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.21

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LD50 value was estimated to be 14289.59 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively with 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) by dermal application for 24 hours.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9).TheLD50 was estimated to be 14289.59 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) by dermal application for 24 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
14 289.59 mg/kg bw
Quality of whole database:
Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Additional information

Acute Oral Toxicity: 

In different studies,3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)along with the study available on the closely related read across substance Niobium pentoxide (1313-96-8) and Dibismuth trisulphide (1345-07-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9). The LD50 was estimated to be 4566 mg/kg bw when female Wistar rats were exposed with 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9)orally.

The above study was further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the closely related read across substance Niobium pentoxide (1313-96-8). Acute oral toxicity study was done in mouse usingNiobium pentoxide(1313-96-8).No mortality was observed at dose 4000mg/kg bw. Clinical signs like Behavioral,muscle contraction or spasticity liver (hepatitis i.e. hepatocellular necrosis), in lungs, thorax, or respiration: acute pulmonary edema was observed in treated mouse. Hence, LD50was considered to be>4000mg/kgbody weight. When mouse was treated with Niobium pentoxide(1313-96-8)orally.

This is further supported by U.S. National Library of Medicine (Chemidplus Database,U.S. National Library of Medicine,2017) for the closely related read across substance Dibismuth trisulphide (1345-07-9). Acute oral toxicity study was done in rat using Dibismuth trisulphide (1345-07-9). 50% mortality was observed at dose 5000mg/kg bw. Hence, LD50was considered to be 5000 mg/kg body weight, when rats were treated with Dibismuth trisulphide (1345-07-9) orally.

Thus, based on the above studies on 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) and it’s closely related read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) can be classified as category V of acute oral toxicity.

Acute Inhalation Toxicity: 

3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt has very low vapor pressure (4.49E-018 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal Toxicity:

In different studies, 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) along with the study available on structurally similar 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 (18472-87-2) and the closely related read across substance 2,2',6,6',-tetrabromo-4,4'-isopropylidenediphenol (79-94-7).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9).TheLD50 was estimated to be 14289.59 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) by dermal application for 24 hours.

The above study was further supported by Sustainability Support Services (Europe) AB (study number:18810, 2016-10-19) for structurally similar 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 (18472-87-2). The study now reported was designed and conducted to determine the acute dermal toxicity profile of 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3- oxoxanthen-9-yl)benzoic acid in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals 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. It was concluded that the acute dermal median lethal dose (LD50) of 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabromo-6-hydroxy-3-oxoxanthen-9-yl)benzoic acid supplied by Sustainability Support Services (Europe) AB, when administered to male and female Sprague Dawley rats was found to be greater than 2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that 3,4,5,6-tetrachloro-2-(1,4,5,8-tetrabro mo-6-hyd roxy-3-oxoxanthen-9-yl)benzoic acid does not exhibits acute toxicity by the dermal route.

This is further supported by U.S. National Library of Medicine(HSDB (Hazardous Substances Data Bank); US national Library of Medicine,2017) and IFA GESTIS (Gestis Substance Database ,2017) for closely related read across substance 2,2',6,6',-tetrabromo-4,4'-isopropylidenediphenol (79-94-7). In acute dermal toxicity study,groups of 5 male and female rabbits were treated with2,2',6,6',-tetrabromo-4,4'-isopropylidenediphenol(79-94-7)in the concentration of 2000 mg/kg bw by dermal application.No mortality was observed in treated rabbits at dose 2000 mg/kg bw.Therefore, LD50 value was considered to be >2000 mg/kg bw,when rabbits were occlusively treated with 2,2',6,6',-tetrabromo-4,4'-isopropylidenediphenol (79-94-7) by dermal application for 24 hours following 14 days of observation period.        

Thus, based on the above studies on 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) and it’s structurally similar and closely related read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) and it’s closely related and structurally similar read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 3,4,5,6-tetrachloro-2-(2,4,5,7-tetrabromo-3,6-dihydroxyxanthen-9-yl)benzoic acid, aluminium salt (84473-86-9) can be classified as category V for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.