Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex

Endpoint summary

Description of key information

Prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) .The study assumed the use of male and female Sprague-Dawley rats in subacute study of 28days. No significant alterations were noted at the dose level of 585.3 mg/kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is considered to be 585.3 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:

Prediction is done using OECD QSAR Toolbox version 3.3 and 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 3.3, 2017

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material : aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex
- Molecular formula : C16H9AlN2O7S2
- Molecular weight : 432.368 g/mol
- Smiles notation : c12c(cc(S(=O)(=O)[O-])cc2)ccc(c1\N=N\c1ccc(S(=O)(=O)[O-])cc1)[O-].[Al+3]
- InChl : 1S/C16H12N2O7S2.Al/c19-15-8-1-10-9-13(27(23,24)25)6-7-14(10)16(15)18-17-11-2-4-12(5-3-11)26(20,21)22;/h1-9,19H,(H,20,21,22)(H,23,24,25);/q;+3/p-3/b18-17+;
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not specified.

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

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:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effect observed at this dose level.

Remarks on result:

other: No toxic effect were observed

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acid moiety OR Not classified OR Phenols by Aquatic toxicity classification by ECOSAR ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure OR Strong binder, OH group by Estrogen Receptor Binding ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Cation OR Mixture by Substance Type ONLY

Domain logical expression index: "d"

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: "e"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Diacylperoxides OR High reactive >> Organic disulfides OR High reactive >> Thiols OR Low reactive OR Low reactive >> Long-chain aliphatic aldehydes OR Moderate reactive OR Moderate reactive >> Glycidyl ether epoxides OR Moderate reactive >> Mono-methacrylic acid esters OR Moderate reactive >> Saturated aldehydes by DPRA Cysteine peptide depletion

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (Ka, pH 7)(Hydrowin) ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure AND Strong binder, OH group by Estrogen Receptor Binding ONLY

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Acrylamides (Neurotoxicity) Rank C OR Aliphatic amines (Mucous membrane irritation) Rank C OR Aliphatic nitriles (Hepatotoxicity) Rank B OR Aliphatic/Alicyclic hydrocarbons (Alpha 2u-globulin nephropathy) Rank C OR Allyl esters (Hepatotoxicity) Rank A OR Carboxylic acids (Hepatotoxicity) No rank OR Ethionine (Hepatotoxicity) Alert OR Ethyleneglycol alkylethers (Hemolytic anemia) Rank A OR Halogenated aliphatic compounds (Hepatotoxicity) Rank A OR Hydrazines (Hemolytic anemia with methemoglobinemia) Rank B OR Hydrazines (Hepatotoxicity) Rank C OR Methyldopa (Hepatotoxicity) Alert OR Oximes (Hemolytic anemia with methemoglobinemia) Rank B OR Oxyphenistain (Hepatotoxicity) Alert OR p-Alkylphenols (Hepatotoxicity) Rank A OR Perhexiline (Hepatotoxicity) Alert OR Phenols (Mucous membrane irritation) Rank C OR Tamoxifen (Hepatotoxicity) Alert OR Thioalcohols (Hepatotoxicity) No rank OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (Hydro)Peroxides OR Acyl halides OR Aliphatic acids and (Met)acrylic acids OR Aliphatic alpha-halogen-esters OR Esters including acrylic and methacrylic esters OR Esters of organic sulfonic or sulfuric esters OR Ethylenglycolethers OR Ketones OR Quaternary organic ammonium compounds OR Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62 mN/m AND Exclusion rules not met AND Group All Melting Point > 200 C AND Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group All log Kow < -3.1 OR Group C Melting Point > 55 C OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNS log Kow < 0.5 OR Group CNS log Kow < -2 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aliphatic halogens (Genotox) OR Alkyl carbamate and thiocarbamate (Genotox) OR Isocyanate and isothiocyanate groups (Genotox) OR Metals, oxidative stress (Nongenotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity OR Substituted n-alkylcarboxylic acids (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "q"

Similarity boundary:Target: [Al]{3+}_Oc1ccc2cc(S(O)(=O)=O)ccc2c1N=Nc1ccc(S(O)(=O)=O)cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log BCF max which is >= 0.961 log(L/kg wet)

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log BCF max which is <= 1.51 log(L/kg wet)

Conclusions:

The predicted No Observed Adverse Effect Level (NOAEL) for Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) is considered to be 585.3mg/Kg bw/day.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) .The study assumed the use of male and female Sprague-Dawley rats in subacute study of 28days. No significant alterations were noted at the dose level of 585.3 mg/kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is considered to be 585.3 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

585.3 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

K2 OECD QSAR 3.3

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose oral toxicity:

Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5)was assessed for its toxic potential. The target substance is prepared by laking the mother compound disodium 6-hydroxy-5-[(4-sulfonatophenyl)diazenyl]naphthalene-2-sulfonate Other name; Sunset Yellow (2783-94-0)with Aluminium hydroxide. The experimental study results for read-across substance (CAS: 2783-94-0) are used for toxicity studies . Since the read-across is a major component of the target Aluminium lake substance, the inference can be drawn using the information for the major component. Therefore, it is acceptable to derive information on toxicity from the mother compound. The prediction and experimental studies are as mentioned below for target and mother compound as read across substance.to determine the toxic nature of Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5)upon repeated exposure by oral, dermal and inhalation route of exposure. The studies are as mentioned below:

 

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, repeated dose oral toxicity was predicted for the test compound Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) .The study assumed the use of male and female Sprague-Dawley rats in subacute study of 28days. No significant alterations were noted at the dose level of 585.3 mg/kg bw/day. The predicted No Observed Adverse Effect Level (NOAEL) for Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is considered to be 585.3 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.

Another Repeated dose toxicity study was performed by I. F. GAUNTet al. (Food Cosmetic Toxicol.1974) to determine the oral toxic nature disodium 6-hydroxy-5-[(4-sulfonatophenyl)diazenyl]naphthalene-2-sulfonate(2783-94-0). In this study male and female mice were given diets containing 0, 250, 500, 1000 and 2000 mg/kg/day of Sunset Yellow FCF for 80 wk. The feeding of Sunset Yellow FCF did not adversely affect the death rate within the groups, the rate of body-weight gain, the organ weights or the haematological findings. The incidence and severity of the histopathological findings were similar in treated and control mice and there was no evidence of an increased incidence of tumours in the mice given Sunset Yellow FCF. It is concluded that in mice Sunset Yellow FCF fed at levels of up to 2000 mg/kg/day in the diet is not carcinogenic and does not exert any long-term toxic effects. Hence 2000 mg/kg/day is assessed to be the NOAEL (No observed adverse effect) value.

In another short-term repeated dose toxicity: oral study was performed by I. F. GAUNT-T et al.( Fd Cosmet. ToxicoL, 1967) for disodium 6-hydroxy-5-[(4-sulfonatophenyl)diazenyl]naphthalene-2-sulfonate(2783-94-0). Feeding of Sunset Yellow FCF to rats at dietary levels of 0.0 (control), 0.5, 1 .0, 2.0 or 3.0%.for 96 days evoked no adverse effect on growth or food consumption but there was slightdiarrhea throughout the study at 3% and during the first few weeks at 2%. There was nodeparture from normality in the haematological investigations or in the terminal liver an kidney function tests. At autopsy, the caecum was enlarged at the 2 and 3 % levels and the testes at the 3 % level. There were no histological changes attributable to Sunset Yellow FCF. A no-effect level (NOEL) of 1 % Sunset Yellow FCF was established in the diet for 96 days, a level equivalent to 500 mg/kg/day. A low-effect level (LOEL) of 2.0% Sunset Yellow FCF was established in the diet for 96 days, a level equivalent to 1000 mg/kg/day.

Based on the prediction and data available for substance Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) as well as applying weigh of evidence ,does not exhibit toxic nature upon repeated exposure by oral route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex / 15790-07-5, which is reported as 6.88E-018 Pa at 25 deg C. Also considering the particle size distribution of the substance the majority of the particles was found to be in the size of 150 micrometer which is much larger size range compared to the inhalable particulate matter. Thus, exposure to inhalable dust, mist and vapour of the chemical 1-hydroxybenzotriazole is highly unlikely. Therefore this study is considered for waiver.

 

Repeated dermal study

The acute toxicity value for Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) (as provided in section 7.2.3) is >2000 mg/kg body weight. 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, it is expected that Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available for the target chemical and its prediction, Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5)does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on theabove annotation for the target chemical . Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (15790-07-5) does not exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.