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

Prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for the test compound Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate]. The study assumed the use of male and female Wistar. The females were treated for 49 days and males for 35 days. No significant alterations were noted at the mentioned dose level. The predicted No Observed Adverse Effect Level (NOAEL) for Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] is considered to be 620.0 mg/Kg bw/day.Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose 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 version 3.4and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4, 2017

GLP compliance:

not specified

Limit test:

no

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:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not specified.

Route of administration:

oral: unspecified

Details on route of administration:

Not specified.

Vehicle:

not specified

Details on oral exposure:

Not specified.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not specified.

Duration of treatment / exposure:

females were treated for 49 days and males for 35

Frequency of treatment:

Not specified.

Remarks:

Not specified.

No. of animals per sex per dose:

Not specified.

Control animals:

not specified

Details on study design:

Not specified.

Positive control:

Not specified.

Observations and examinations performed and frequency:

Not specified.

Sacrifice and pathology:

Not specified.

Other examinations:

Not specified.

Statistics:

Not specified.

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

620 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects were observed at the mentioned dose level.

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average 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" )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Phenolphthaleins by US-EPA New Chemical Categories

Domain logical expression index: "b"

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 ONLY

Domain logical expression index: "c"

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: "d"

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: "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 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters 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 >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives 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 >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide 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 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 nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted 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 substitution on diazonium ion OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 and Naphthalenediimide Derivatives OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives 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 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 No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as 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 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 >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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 ONLY

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Similarity boundary:Target: Oc1c(Br)cc2c(c1Br)Oc1c(cc(Br)c(O)c1Br)C21c2c(Cl)c(Cl)c(Cl)c(Cl)c2C(=O)O1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.24

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 13.6

Conclusions:

The predicted No Observed Adverse Effect Level (NOAEL) for Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] is considered to be 620.0 mg/Kg bw/day.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for the test compound Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate]. The study assumed the use of male and female Wistar. The females were treated for 49 days and males for 35 days. No significant alterations were noted at the mentioned dose level. The predicted No Observed Adverse Effect Level (NOAEL) for Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] is considered to be 620.0 mg/Kg bw/day.

Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

620 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from OECD QSAR toolbox version 3.4.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Prediction model based estimation and data from read across chemicals have been reviewed to determine the toxic nature of Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (15876-58-1 )upon repeated exposure by oral and dermal route of exposure. The studies are as mentioned below:

Repeated dose toxicity: Oral

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose toxicity was predicted for the test compound Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate]. The study assumed the use of male and female Wistar. The females were treated for 49 days and males for 35 days. No significant alterations were noted at the mentioned dose level. The predicted No Observed Adverse Effect Level (NOAEL) for Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] is considered to be 620.0 mg/Kg bw/day.Based on this value it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

 

Repeated dose oral toxicity study of structurally similar read across chemical D&C Red No. 28 ( RA CAS no 18472 -87 -2; IUPAC name: 2',4',5',7'-tetrabromo-4,5,6,7-tetrachloro-3',6'-dihydroxy-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one ) was performed in rats. Fischer-344 (F-344) male rats were treated with D&C Red No. 28 orally in diet in the concentration of 500 mg/kg/day. The animals were observed for changes in body weight and excretion of the dye in urine of treated animals. Increase in body weight gain was observed in treated rats over the 14 days observation period. 8-week-old rats weighed 168 g±6 g and by 10 weeks they weighed 225 g±10 g. As there is no control in the study the effect were not supposed to be treatment related. Daily intake was observed to be 500 mg/kg for 14 days. Therefore, the No Observed Adverse Effect Level (NOAEL) was considered to be 500 mg/kg/day when Fischer-344 (F-344) male rats were treated with D&C Red No. 28.

In another repeated dose oral toxicity study performed as part of the evaluation of teratogenicity for structurally similar read across chemical, the toxicity of Phloxine (RA CAS no 6441 -77 -6; IUPAC name: Food Dye Red No. 104) was studied using female Wistar rats. The female Wistar rats were orally exposed to Phloxine via their diet at a dosage of 0,280 ,920 and 2870 mg/kgbw/day .As seen by the results, an inhibition on maternal weight gain and a growth retardation in fetuses were observed in the highest dose level 2870 mg/kgbw/day of Phloxine. No evidence of increase in fetal death or no malformation to be related to dietary Phloxine administration was observed, and no teratogenicity except was is mentioned above. Therefore, NOAEL was considered to be 2870mg/kgbw/day in the F0 generation and 920mg/kgbw/day in the F1 generation when female Wistar rats were orally exposed to Phloxine (Food Red No. 104) during gestation.

 

Repeated dose toxicity: Inhalation

The melting point Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] is >300 C. This suggests that Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] decomposes between 333°C-335°C at 971.8hPa without melting and does not exhibit very high vapour pressure. Inhalation is therefore not the likely route of exposure and hence this end point is considered for waiver.

 

Repeated dose toxicity: Dermal

The results for acute toxicity by the dermal route indicate the LD50 value to be greater than 2000 mg/kg body weight. In addition, the skin sensitization also indicates negative skin sensitization potential by the chemical Di aluminiumtris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (15876-58-1). Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, given the above considerations, it is assumed that Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] shall not exhibit repeated dose toxicity by the dermal route.Hence this end point considered as waiver.

Based on the data available for the target chemical and its read across, 2' Di aluminium tris[2-(2,4,5,7-tetrabromo-6-oxido-3-oxoxanthen-9-yl)-3,4,5,6-tetrachlorobenzoate] (15876-58-1 ) does not exhibit toxicity upon repeated exposure by oral route of exposure and hence it is not likely to classify as toxic as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data presented and CLP criteria , the target chemical dialuminium tris[2-(2,4,5,7-tetrabromo-6-oxido- 3-oxoxanthen- 9-yl)benzoate] is not likely to be toxic upon repeated oral application.