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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

LOEL was estimated to be 414.7308 mg/kg bw when Rattus norvegicus male and female rats were orally exposed with 4 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex.

As per United States Environmental Protection Agency (May 10, 2005), Absorption of aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is poor to nil via all routes of exposure, therefore no further dermal, oral, or inhalation exposure assessment is necessary. Hence, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is considered to be no safety concern. 

Link to relevant study records

Reference

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

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 QSAR Toolbox version 2.3

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3.

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): 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:

other: Rattus norvegicus

Sex:

male/female

Route of administration:

oral: unspecified

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

10 weeks

Frequency of treatment:

Daily

Details on study schedule:

not specified

Dose / conc.:

414.731 mg/kg bw/day (nominal)

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Positive control:

not specified

Parental animals: Observations and examinations:

not specified

Oestrous cyclicity (parental animals):

not specified

Sperm parameters (parental animals):

not specified

Litter observations:

not specified

Postmortem examinations (parental animals):

not specified

Postmortem examinations (offspring):

not specified

Statistics:

not specified

Reproductive indices:

not specified

Offspring viability indices:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

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

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Based on:

not specified

Sex:

not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

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

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

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

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

LOEL

Generation:

F2

Effect level:

414.731 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Effects observed on body weight and haematology

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: LOEL
Estimation method: Taking average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

(((((((((((("g" and ( not "h") ) and ("i" and ( not "j") ) ) and ("k" and ( not "l") ) ) and "m" ) and "n" ) and "o" ) and ("p" and ( not "q") ) ) and "r" ) and "s" ) and "t" ) and "u" ) and ("v" and "w" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Azo compounds AND MA: Nitrenium ion formation AND MA: Radical mechanism by ROS formation AND Mechanistic Domain: Radical AND Mechanistic Domain: SN1 by DNA binding by OASIS

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "c"

Similarity boundary:Target: c1(O)(.[Al]{3+})c(N=Nc2ccc(S(=O)(=O)O)cc2)c2c(cc(S(=O)(=O)O)cc2)cc1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Azo compounds AND MA: Nitrenium ion formation AND MA: Radical mechanism by ROS formation AND Mechanistic Domain: Radical AND Mechanistic Domain: SN1 by DNA binding by OASIS

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

Similarity boundary:Target: c1(O)(.[Al]{3+})c(N=Nc2ccc(S(=O)(=O)O)cc2)c2c(cc(S(=O)(=O)O)cc2)cc1
Threshold=50%,
Dice(Atom pairs)

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 1,1-Dihaloalkanes OR Aliphatic tertiary amines OR Allyl benzenes OR Arenes OR Aromatic nitro OR Furans OR MA: Carbenium Ion Formation OR MA: Iminium Ion Formation OR MA: Nitrenium Ion Formation OR MA: P450 Mediated Activation of Heterocyclic Ring Systems OR MA: P450 Mediated Activation to Acyl Halides OR MA: P450 Mediated Activation to Isocyanates or Isothiocyanates OR MA: P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Mechanistic Domain: Acyalation OR Mechanistic Domain: Michael addition OR Mechanistic Domain: SN1 OR Sulfonylureas OR Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acetates OR Allyl acetates and related chemicals OR MA: Direct Acylation Involving a Leaving group OR MA: SN2 reaction at a sp2 carbon atom OR MA: SN2 reaction at sp3 carbon atom OR Mechanistic Domain: Acylation OR Mechanistic Domain: SN2 OR Polarised alkenes with a halogen leaving group by Protein binding by OECD

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Protein Binding Potency

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Halogenated five membered heterocycles (SN2) OR Halogenated hydrocarbons (SN2) OR Non-reactive (GSH) by Protein Binding Potency

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as (N/A) by Oncologic Primary Classification

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Acrylate Reactive Functional Groups OR Aromatic Amine Type Compounds OR Carbamate Type Compounds OR Halogenated Aromatic Hydrocarbon Type Compounds OR Hydrazo Type Compounds by Oncologic Primary Classification

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Similarity boundary:Target: c1(O)(.[Al]{3+})c(N=Nc2ccc(S(=O)(=O)O)cc2)c2c(cc(S(=O)(=O)O)cc2)cc1
Threshold=30%,
Dice(Atom pairs)

Domain logical expression index: "t"

Similarity boundary:Target: c1(O)(.[Al]{3+})c(N=Nc2ccc(S(=O)(=O)O)cc2)c2c(cc(S(=O)(=O)O)cc2)cc1
Threshold=80%,
Dice(Atom pairs)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.8

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.59

Conclusions:

LOEL was estimated to be 414.7308 mg/kg bw when Rattus norvegicus male and female rats were orally exposed with 4 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex.

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 estimated for aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex. The LOEL was estimated to be 414.7308 mg/kg bw when Rattus norvegicus male and female rats were orally exposed with 4 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex.On the basis of this LOEL value it is indicated that aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex does not exhibit toxic effects to rat below the above mentioned dose.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

414.731 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity:

In different studies, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in mice and rats for aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex along with the study available on structurally similar read across substance Sunset Yellow (CAS no 2783-94-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex. The LOEL was estimated to be 414.7308 mg/kg bw when Rattus norvegicus male and female rats were orally exposed with 4 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex.

In another experimental study conducted by Mannellh et al (J. Pharm. Pharmacol. 10, 625, 1982) on structurally similar read across substance Sunset Yellow (CAS no 2783-94-0), male and female rats were treated with Sunset Yellow in the concentration of 0, 15, 150 and 750 mg/kg bw orally in feed Alphacel (a non-nutritive cellulose) for 64 weeks. No effect on survival of treated male and female rats were observed at 15, 150 and 750 mg/kg bw as compared to control. Decrease in mean body weight in females at 4, 32 and 16 weeks. Decreased in food consumption of females were observed with no correlation with the concentration given in diet. No significant difference in male or female food efficiency was observed as compared to control. The only significant difference observed was lowered white cell count for females at 750 mg/kg bw as compared to controls. No adverse effect on blood cells was observed. Similarly, Decrease in liver weight at 150 mg/kg bw and spleen weight at 750 mg/kg bw in female rat. These changes were not correlated with the level of food colour in the diet and are difficult to interpret. No effects on reproductive oragns were observed in treated male and female rats as compared to control. Respiratory tract infections accounted for 28 deaths. Two animals died of starvation, one of meningitis, one of a ruptured right auricle and three as the result of neoplasms. In addition, Middle ear and respiratory infections were observed, considered to be in older rats of the colony. Chronic otitis media was observed in nearly 50 per cent of the animals. The disease was evenly distributed in the various groups. Pathological changes in the adrenal cortex were observed in 22 animals. This particular pathology was acute in nature and was not considered to be an effect of the food colours since it was observed in two of the control animals and since there was no correlation between the incidence and the concentration of colour fed. 18 per cent tumour incidence was observed in treated rats. The differences in tumour incidence are not significant according to chi-square tests. The tracings of ECG were essentially normal. No significant deviation of electrical axis observed in treated rats. Therefore, NOAEL was considered to be 750 mg/kg bw when male and female rats were treated with Sunset Yellow orally in feed Alphacel (a non-nutritive cellulose) for 64 weeks.

Father supported by experimental study conducted by Tanaka et al (Toxicology and industrial health,Vol 12,No.1, 1996) on structurally similar read across substance Sunset Yellow (CAS no 2783-94-0), Crj: CD-1 male and female mice were treated with Sunset Yellow in the concentration of 0, 250, 500 and 1000 mg/kg bw orally in feed contained in basal diet (Nihon Clea, CE-2) for approx 17 weeks. No significant adverse effects were observed on body weight and food consumption of male and female mice during the preconception period, gestation or lactation periods. No significant adverse effect on movement activity of exploratory behavior in either sex at eight weeks of age. Abortion was observed in one dam and one dam killed all offspring in the third week of the lactation period and then died herself. That dam had a thymoma at 250 mg/kg bw. During the first week of the lactation period, two dams at 500 mg/kg bw showed underdeveloped mammary glands, which were observed as underdeveloped mammalae. No effects were observed in 1000 mg/kg bw treated female rats as compared to control in P generation. Similarly, Significant decrease in survival of pups were observed on PND 21 at 500 mg/kg bw as compared to control. The average body weight of offspring during the late lactation period was increased at 250 mg/kg bw in male and female and at 500 mg/kg bw in female as compared to control. In addition, Behavioral developmental parameters, swimming behavior of direction on PND 4 was significantly affected at 500 and 1000 mg/kg bw in male offspring and in all treatment groups in female offspring and those effects appeared significantly dose related (p < 0.01 in each sex). Swimming behavior of head angle on PND 4 was significantly affected at 500 and 1000 mg/kg bw in female offspring, and those effects appeared significantly dose-related (p < 0.05). Negative geotaxis on PND 4 and surface righting on PND 7 were affected significantly in male offspring at 500 mg/kg bw . Other parameters measured showed no adverse effects in either sex. Significant effects on multiple water T-maze performance in each sex were observed. No adverse effects on Movement activity of exploratory behavior were observed at eight weeks of age of F1 generation male and female rats. These results indicate that the dose levels of Sunset Yellow FCF produced some adverse effects on several behavioral developmental parameters during the early lactation period. Those dose levels, however, were approximately 662 times greater (at 500 mg/kg bw during the lactation period) than the human ADI of 2.5 mg/kg bw. Since the absorption of Sunset Yellow FCF was 3.6% in a study in rat, the active levels of Sunset Yellow FCF may be much lower than the actual dietary intake levels. The presumed actual daily intake of Sunset Yellow FCF in Japan is approximately 0.001 mg per person (0.02 pg/kg), which is much lower than the human ADI (Nakamura, 1995). It therefore seems that the level of actual dietary intake of Sunset Yellow FCF should have only a limited effect in humans. Therefore, NOAEL was considered to be 250 mg/kg bw for P and F1 generation when Crj: CD-1 male and female mice were treated with Sunset Yellow orally in feed contained in basal diet (Nihon Clea, CE-2) for approx 17 weeks.

Thus, based on the above studies and predictions on aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex and its read across substances, it can be concluded that LOEL value is 414.7308 mg/kg bw for target chemical and 250 mg/kg bw and above is for read across Sunset Yellow(CAS no 2783-94-0). But, as per United States Environmental Protection Agency (May 10, 2005), Absorption of aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is poor to nil via all routes of exposure, therefore no further dermal, oral, or inhalation exposure assessment is necessary. Hence, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is considered to be no safety concern. 

Effects on developmental toxicity

Description of key information

LOEL was estimated to be 274 mg/kg bw when New Zealand White rabbits were orally exposed with 4 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex.

As per United States Environmental Protection Agency (May 10, 2005), Absorption of aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is poor to nil via all routes of exposure, therefore no further dermal, oral, or inhalation exposure assessment is necessary. Hence, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is considered to be no safety concern. 

Link to relevant study records

Reference

Endpoint:

developmental toxicity

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 3.1 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Predicted data

Principles of method if other than guideline:

Data is predicted by QSAR toolbox version 3.1

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

- Name of test material (IUPAC name): 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:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Age-5-6.5 months

Route of administration:

oral: gavage

Vehicle:

other: methyl cellulose

Details on exposure:

Dose volume:2 ml/kg

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

GD 9-11

Frequency of treatment:

Daily

Duration of test:

29 days

Dose / conc.:

274 mg/kg bw/day (nominal)

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

Body weight range was 2.83-4.25 kg on GD8

Maternal examinations:

One female was found dead on GD 15 and the other on GD 17.

Ovaries and uterine content:

not specified

Fetal examinations:

There were no treatment-related necropsy observations.

Statistics:

not specified

Indices:

not specified

Historical control data:

not specified

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, treatment-related

Description (incidence):

Mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Increasce in body weight

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

Number of abortions:

not specified

Pre- and post-implantation loss:

not specified

Total litter losses by resorption:

not specified

Early or late resorptions:

not specified

Dead fetuses:

not specified

Changes in pregnancy duration:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified

Changes in number of pregnant:

not specified

Other effects:

not specified

Dose descriptor:

LOEL

Effect level:

274 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Abnormalities:

not specified

Localisation:

not specified

Description (incidence and severity):

not specified

Fetal body weight changes:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified

Reduction in number of live offspring:

not specified

Changes in sex ratio:

not specified

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

not specified

Skeletal malformations:

not specified

Visceral malformations:

not specified

Other effects:

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no data

Dose descriptor:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Abnormalities:

not specified

Localisation:

other: not specified

Description (incidence and severity):

not specified

Developmental effects observed:

not specified

Treatment related:

not specified

Relation to maternal toxicity:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

The prediction was based on dataset comprised from the following descriptors: LOEL,NOEL
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 ("h" and "i" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Azo AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Azo AND Fused carbocyclic aromatic AND Naphtalene AND Overlapping groups AND Phenol AND Sulfonic acid by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound AND Azo compound AND Cation AND Hydroxy compound AND Phenol AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.1

Domain logical expression index: "f"

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 >> Carbamates OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithioesters OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Diarylesters OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents 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 Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> Vinyl sulfonyl compounds OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone (di)imines OR Michael addition >> Quinone type compounds >> Quinone methides OR Nucleophilic addition OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Ketones OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond OR Nucleophilic addition >> Nucleophilic addition at polarized N-functional double bond >> C-Nitroso compounds OR Schiff base formation OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and pyrazolidinones derivatives >> Pyrazolones and pyrazolidinones OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-activated haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-haloalkanes OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes by Protein binding by OASIS v1.1

Domain logical expression index: "g"

Similarity boundary:Target: c1(O)(.[Al]{3+})c(N=Nc2ccc(S(=O)(=O)O)cc2)c2c(cc(S(=O)(=O)O)cc2)cc1
Threshold=20%,
Dice(Atom centered fragments)

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.75

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.42

Conclusions:

LOEL was estimated to be 274 mg/kg bw when New Zealand White rabbits were orally exposed with 4 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the developmental toxicity was estimated for aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex. The LOEL was estimated to be 274 mg/kg bw when New Zealand White rabbits were orally exposed with 4 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

274 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Developmental toxicity:

In different studies, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex has been investigated for developmental toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in mice and rats for aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex along with the study available on structurally similar read across substance Sunset Yellow (CAS no 2783-94-0). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the developmental toxicity was estimated for aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex. The LOEL was estimated to be 274 mg/kg bw when New Zealand White rabbits were orally exposed with 4 aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex.

In another experimental study given by European Food Safety Authority (EFSA)( EFSA Journal 2009; 7(11):1330) and Joint FAO/WHO Expert Committee on Food Additives (549. Sunset Yellow FCF (WHO Food Additives Series 17), 1964) on structurally similar read across substance Sunset Yellow (CAS no 2783-94-0), Charles River CD female rat were treated with Sunset Yellow at concentration 0, 100, 300 and 1000 mg/kg bw in methocel orally by gavage from day 6-15 of gestation. No effect on body weight was observed in treated female rats. Similarly no effect on reproductive parameters such as empty implantation sites, early- and late resorptions and dead fetuses were observed in treated female rats. In addition, No effect on live and dead offspring and sex ratio were observed. Mean body weight of the offspring of the exposed dams was decreased although with doubtful significance at 300, or 1000 mg/kg bw. No effect on external, internal, and skeletal abnormalities and fetuses with malformation were observed in treated rats. Therefore, NOAEL was considered to be 1000 mg/kg bw when Charles River CD female rat were treated with Sunset Yellow orally by gavage from day 6-15 of gestation.

Father supported by experimental study conducted by Tanaka et al (Toxicology and industrial health,Vol 12,No.1, 1996) on structurally similar read across substance Sunset Yellow (CAS no 2783-94-0), Crj: CD-1 male and female mice were treated with Sunset Yellow in the concentration of 0, 250, 500 and 1000 mg/kg bw orally in feed contained in basal diet (Nihon Clea, CE-2) for approx 17 weeks. No significant adverse effects were observed on body weight and food consumption of male and female mice during the preconception period, gestation or lactation periods. No significant adverse effect on movement activity of exploratory behavior in either sex at eight weeks of age. Abortion was observed in one dam and one dam killed all offspring in the third week of the lactation period and then died herself. That dam had a thymoma at 250 mg/kg bw. During the first week of the lactation period, two dams at 500 mg/kg bw showed underdeveloped mammary glands, which were observed as underdeveloped mammalae. No effects were observed in 1000 mg/kg bw treated female rats as compared to control in P generation. Similarly, Significant decrease in survival of pups were observed on PND 21 at 500 mg/kg bw as compared to control. The average body weight of offspring during the late lactation period was increased at 250 mg/kg bw in male and female and at 500 mg/kg bw in female as compared to control. In addition, Behavioral developmental parameters, swimming behavior of direction on PND 4 was significantly affected at 500 and 1000 mg/kg bw in male offspring and in all treatment groups in female offspring and those effects appeared significantly dose related (p < 0.01 in each sex). Swimming behavior of head angle on PND 4 was significantly affected at 500 and 1000 mg/kg bw in female offspring, and those effects appeared significantly dose-related (p < 0.05). Negative geotaxis on PND 4 and surface righting on PND 7 were affected significantly in male offspring at 500 mg/kg bw . Other parameters measured showed no adverse effects in either sex. Significant effects on multiple water T-maze performance in each sex were observed. No adverse effects on Movement activity of exploratory behavior were observed at eight weeks of age of F1 generation male and female rats. These results indicate that the dose levels of Sunset Yellow FCF produced some adverse effects on several behavioral developmental parameters during the early lactation period. Those dose levels, however, were approximately 662 times greater (at 500 mg/kg bw during the lactation period) than the human ADI of 2.5 mg/kg bw. Since the absorption of Sunset Yellow FCF was 3.6% in a study in rat, the active levels of Sunset Yellow FCF may be much lower than the actual dietary intake levels. The presumed actual daily intake of Sunset Yellow FCF in Japan is approximately 0.001 mg per person (0.02 pg/kg), which is much lower than the human ADI (Nakamura, 1995). It therefore seems that the level of actual dietary intake of Sunset Yellow FCF should have only a limited effect in humans. Therefore, NOAEL was considered to be 250 mg/kg bw for P and F1 generation when Crj: CD-1 male and female mice were treated with Sunset Yellow orally in feed contained in basal diet(Nihon Clea, CE-2) for approx 17 weeks.

Thus, based on the above studies and predictions on aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex and its read across substances, it can be concluded that LOEL value is 274 mg/kg bw for target chemical and 250 mg/kg bw and above is for read across Sunset Yellow (CAS no 2783-94-0). But, as per United States Environmental Protection Agency (May 10, 2005), Absorption of aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is poor to nil via all routes of exposure, therefore no further dermal, oral, or inhalation exposure assessment is necessary. Hence, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is considered to be no safety concern for developmental toxicity. 

Justification for classification or non-classification

Based on the above studies and predictions on aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex and its read across substances, it can be concluded that LOEL value is 274 mg/kg bw for target chemical and 250 mg/kg bw and above is for read across Sunset Yellow (CAS no 2783-94-0). But, as per United States Environmental Protection Agency (May 10, 2005), Absorption of aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is poor to nil via all routes of exposure, therefore no further dermal, oral, or inhalation exposure assessment is necessary. Hence, aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex is considered to be no safety concern for developmental toxicity.