Dialuminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate]

Endpoint summary

Description of key information

The skin sensitization potential of Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8) was predicted to be not sensitizing to the skin of guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4 .

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

No data available.

Specific details on test material used for the study:

Name of test material (as cited in study report):Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate]
- Molecular formula :C20H8Br4O5.2/3Al
- Molecular weight :1991.5992 g/mol
- InChl :1S/3C20H8Br4O5.2Al/c3*21-11-5-9-17(13(23)15(11)25)28-18-10(6-12(22)16(26)14(18)24)20(9)8-4-2-1-3-7(8)19(27)29-20;;/h3*1-6,25-26H;;/q;;;2*+3/p-6
- Substance type: Organic
- Physical state: Solid

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available.

No. of animals per dose:

10

Details on study design:

No data available.

Challenge controls:

No data available.

Positive control substance(s):

not specified

Statistics:

No data available.

Positive control results:

No data available.

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization reaction was observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and "m" )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Aryl halide AND Carboxylic acid AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Phenol AND Xanthene by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "e"

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 and Trihydroxybenzenes OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom 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) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN2 OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4

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 >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation 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 esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR 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 AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithioesters  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 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  >> Carboxylic Acid Amides OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides 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 >> alpha,beta-Carbonyl compounds with polarized double bonds  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 OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds by Protein binding by OASIS v1.4

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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 SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

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 Tamoxifen (Hepatotoxicity) Alert OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.79

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.29

Interpretation of results:

other: Negative

Conclusions:

The skin sensitization potential of Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8) was predicted to be not sensitizing to the skin of guinea pig.

Executive summary:

The skin sensitization potential of Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8) was predicted to be not sensitizing to the skin of guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studies, Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction is based on in vivo experiments in guinea pig for target chemical disodium Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)and in vivo experiments in human and mouse for its structurally similar read across substances2',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 predicted data using the OECD QSAR toolbox have also been compared with the experimental data of read across.

The skin sensitization potential of Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8) was predicted to be not sensitizing to the skin of guinea pig.

Further supported by experimental data conducted by Guin JD. (Contact Dermatitis,2003) 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)in humans. The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. The sensitization potential of 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 determined by performing patch tests on humans. The test material was applied in Finn Chambers at the concentration of 2% in petrolatum and read first at 2 or (more commonly) 3 days and again at 4–7 days. 9 patients were tested with the test material.No sensitization reactions were reported in any 9 patients. Therefore 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) can be considered as a non- sensitizer in humans.

 It is further supported by experimental data conducted by Colipa (COLIPA n° C53 SCCNFP/0788/04, ,2004) 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)in mouse by LLNA mode .   The test material was tested in different concentrations (0.5, 1.5, 3.0, 7.0 % (w/v)) in DMSO (vehicle). On days 0, 1 and 2 the animal received 25 μl of the test item formulation, positive control or vehicle on the dorsal surface of each pinnae.   The mean stimulation index was 3.9 at the concentration of 1%.   The mean stimulation indices were 0.9, 1.3, 1.5 and 1.9 at the concentrations of 0.5 %, 1.5%, 3.0% and 7.0%, respectively. No sensitization effect was observed. Therefore 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)is not sensitizing to the skin of female CBA/J mouse by Mouse local lymph node assay (LLNA) .

 

Thus based on the above predictions on Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8) as well as its read across substances and applying weight of evidence, it can be concluded that Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)  is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)can be considered as not classified for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation, Di aluminium tris [2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)benzoate] (15876-39-8)can be considered as not classified for skin sensitization effects.