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

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)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)was estimated to be not sensitizing to the skin of mouse . Based on the estimated result Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)failed to induce skin sanitization effects and hence is considered to be not sensitizing to mouse.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material(as cited in study report):Dialuminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate]
- Molecular formula:C20H4Br4Cl4O5 2/3Al
- Physical state:Solid
-Nature of chemical: Organic

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Vehicle:

dimethyl sulphoxide

Concentration:

No data available

No. of animals per dose:

No data available

Details on study design:

No data available

Parameter:

SI

Test group / Remarks:

No data available

Remarks on result:

no indication of skin sensitisation based on QSAR/QSPR prediction

Cellular proliferation data / Observations:

no skin sensitization reactions were observed.

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

(((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and ("k" and "l" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as High reactive AND High reactive >> Activated haloarenes by DPRA Cysteine peptide depletion

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Low reactive AND Low reactive >> Activated haloarenes by DPRA Lysine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates AND SNAr AND SNAr >> Nucleophilic aromatic substitution AND SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane 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 after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High reactive AND High reactive >> Activated haloarenes by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.1

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 21.2

Interpretation of results:

other: not sensitising

Conclusions:

The substance Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)was estimated to be not sensitizing to the skin of mouse.

Executive summary:

The skin sensitization potential of Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)was estimated to be not sensitizing to the skin of mouse . Based on the estimated result Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)failed to induce skin sanitization effects and hence is considered to be not sensitizing to mouse and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemicalDi aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemicalDi aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1) and its structurally similar read across substancesD&C Red 28 (CAS No: 18472-87-2) and Erythrosine (CAS No: 16423-68-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)was estimated using OECD QSAR toolbox version 3.3 with log Pow as the primary descriptor. The substance Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)was estimated to be not sensitizing to the skin of mouse . Based on the estimated result Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1)failed to induce skin sanitization effects and hence is considered to be not sensitizing to mouse.

 

The Guin JD. (2003) conducted patch test of structurally similar read across substance D&C Red 28 (CAS No: 18472-87-2) in humans to evaluate its skin sensitizing potential which supports the above result . During the patch test, the dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories 9 patients were tested with the dye. No reactions were reported by all the patients. Hence D&C Red 28(CAS No: 18472-87-2) can be considered as a non- sensitizer in humans.

 

 

The above results were further supported by the Sensitive mouse lymph node assay conductuded by Yoshiaki Ikarashi, Toshie Tsuchiya and Akitada Nakamura (1996) forstructurally similar read across substance Erythrosine (CAS No:16423-68-0) on female BALB/c strain mice. They were intradermally injected with 50 µl of test chemical –FCA emulsion into two sites of the abdominal skin at both sides of the ventral line. After 5 days 25 µl of test chemical in vehicle was applied to both sides of each ear for three consecutive days. Control mice were treated by intradermal injection of vehicle-FCA emulsion into the abdomen and then after 5 days they were exposed to vehicle alone on the ears for three consecutive days. The increases in LNC number and3HTdR incorporation relative to controls were derived for each experimental group and expressed as SI_nand SI_P, respectively; SI total as obtained from SI_n x SI_P, which indicates the total lymph node activation induced by the test chemical. A chemical was regarded as positive if it showed an SI_totalvalue of 3 or more. The SI_totalvalue of erythrosine was found to be 1.55 at 5% DMSO concentration. Hence, Erythrosine (CAS No: 16423-68-0), was considered to be not sensitizing to the skin of BALB/c strain mice in the sensitive mouse lymph node assay.

 

 

Thus on the basis of available data for thetarget chemicalDi aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1) and its structurally similar read across substancesD&C Red 28 (CAS No: 18472-87-2) and Erythrosine (CAS No:16423-68-0),it can be concluded thatchemical Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1) is unable to cause skin sensitization and considered as non skin sensitizer.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1) and its structurally similar read across substancesD&C Red 28 (CAS No: 18472-87-2) and Erythrosine (CAS No: 16423-68-0) were observed in various studies. From the results obtained from these studies it is concluded that the chemical Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (CAS No: 15876-58-1) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.