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Description of key information

The No Observed Adverse Effect Level (NOAEL) for the test compound 4-aminoazobenzene-3,4'-disulphonic acid is found to be 792.237976074 mg/Kg bw (actual dose ingested) using rats.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Reference:
Composition 1
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
No data
Frequency of treatment:
No data
Remarks:
Doses / Concentrations:No dataBasis:
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
No data
Positive control:
No data
Observations and examinations performed and frequency:
No data
Sacrifice and pathology:
No data
Other examinations:
No data
Statistics:
No data
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
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
No data
Dose descriptor:
NOAEL
Effect level:
792.238 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
clinical signs
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" or "e" or "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and "l" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Azo AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aniline AND Aryl AND Azo AND Overlapping groups AND Sulfonic acid by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, sulfur attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Suflur {v+4} or {v+6} AND Sulfinic acid [-S(=O)OH] AND Sulfonate, aromatic attach [-SO2-O] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Azo compound AND Primary amine AND Primary aromatic amine AND Sulfonic acid AND Sulfonic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Aromatic amines AND Sulfonic acids or their salts by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide 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) >> Diazenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 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 metabolic 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 >> Nitroaniline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.08

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.773

Conclusions:
The No Observed Adverse Effect Level (NOAEL) for the test compound 4-aminoazobenzene-3,4'-disulphonic acid is found to be 792.237976074 mg/Kg bw (actual dose ingested) using rats.
Executive summary:
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Repeated dose oral toxicity study was performed for the test compound 4-aminoazobenzene-3,4'-disulphonic acid using rats by the gavage route of exposure. The No Observed Adverse Effect Level (NOAEL) for the test compound 4-aminoazobenzene-3,4'-disulphonic acid is found to be 792.237976074 mg/Kg bw (actual dose ingested) using rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
792.238 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Prediction model based estimation

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

Mode of Action Analysis / Human Relevance Framework

Additional information

Repeated dose toxicity: Oral

Repeated dose oral toxicity study was performed for the test compound 4-aminoazobenzene-3,4'-disulphonic acid using rats by the gavage route of exposure. The No Observed Adverse Effect Level (NOAEL) for the test compound 4-aminoazobenzene-3,4'-disulphonic acid is found to be 792.237976074 mg/Kg bw (actual dose ingested) using rats.

Sub chronic repeated dose toxicity test was carried by Sondergaard et al (1977) for the test compound disodium 2-amino-5-[(4-sulphonatophenyl)azo]benzene sulphonate (RA CAS no 2706-28-7) with 2 male and 2 female SPF pigs of Danish Landrace. All pigs are dosed with 1000mg/kg and 1500mg/kg by gavage for total 77 days. Hematological examinations were performed at intervals and organ histopathology was performed at necropsy. No effects were detected and no Heinz bodies were found in the red blood cells. There is no significant toxic effect on the clinical & hematological parameters and on the examined liver and blood parameters. Therefore the NOAEL value is reported to be 1500mg/kg/day.

13 week subchronic toxicity study was conducted by Himri et al (2011) to evaluate the repeated dose toxic nature of the test compound tartrazine (RA CAS no 1934-21-0) on Wistar rats of both sexes. The animals were divided into 5 groups of 6 animals each, 3 of each sex, and fed a diet containing 5, 7.5, or 10 mg/kg b.w of Tartrazine. There were no treatment‐related adverse effects with regard to body weight, food and water consumption. Their blood samples were analyzed for hematological measurements, Glucose, Creatinine, Blood urea nitrogen, Cholesterol total, Triglecerid, alanine amino-transferase, aspartate amino-transferase. Tartrazine induced a morphological change from the discoid shape to an echinocytic form in rat RBCs. Relative weights of the liver were significantly increased in group treated with 10 mg/kg b.w, of Tartrazine. An increase in GLU, CREA, CHOL, TG, AST, and total Protein in serum of rats treated with Tartrazine and Sulfanilic acid compared to control rats was observed and these significant changes were more apparent in high doses than low ones. The histopathological changes of Liver and Kidney were in accordance with the biochemical findings. The Low Observed adverse effect level (LOAEL) for the test compound tartrazine is found to 7.5 mg/Kg bw.

The present study by Shinnawy et al (2013) was conducted to evaluate the possible influence of an azo dye (tartrazine, RA CAS no 1934-21-0) on some hematological and biochemical parameters of male albino rat Rattus norvegicus. Sixty adult male rats weighing 100-110g were divided into 3 groups; the first one served as a control, the second received 10mg/kg b.w. of tartrazine and the third group was treated with 25mg/kg b.w. of tartrazine. Rats were treated orally for 30 days followed a recovery for another 30 days. The data obtained reveal a marked decrease in the percentage of body weight gain, red blood cells (R.B.Cs) counts, hemoglobin (Hb) content, mean corpuscular hemoglobin concentration (MCHC), serum total lipids and serum total cholesterol of rats treated with the high dose of tartrazine. On the other hand, a noticeable increase in hematocrit (Hct) value, mean corpuscular volume (MCV), activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), glucose level, serum total protein and globulin were found in rats treated with the high dose of tartrazine. In general, there was appreciable improvement after the recovery period. The Low observed adverse effect level (LOAEL) for the test compound tartrazine is found to be 10 mg/Kg bw.

13 week subchronic toxicity study was conducted by Maekawa (1987) to evaluate the toxic nature of the test compound tartrazine (RA CAS no 1934-21-0). The test compound was administered in drinking water at a dose level of 0(control), 0.3, 0.6, 1.25, 2.5 or 5.0% (w/v) (0, 150, 300, 625, 1250 or 2500 mg/Kg bw). All rats were observed daily and clinical signs and deaths were recorded. Body weights were measured once a week. At the end of the study, all survivors were killed and organs and tissues were taken for gross and microscopical examination. The probable maximum tolerable dose of tartrazine in the drinking-water was found to be between 1.25 and 2.5%. Based on the results observed, the low observed adverse effect level (LOAEL) for the test compound tartrazine is found to be 2.5 % (1250 mg/Kg bw).

 

The weight of evidence data suggests that the test chemical 4-aminoazobenzene-3,4'-disulphonic acid (CAS no 101 -50 -8) is not toxic upon repeated dose exposure.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The No Observed Adverse Effect Level (NOAEL) for the test compound 4-aminoazobenzene-3,4'-disulphonic acid is found to be 792.237976074 mg/Kg bw (actual dose ingested) using rats.

Justification for classification or non-classification

Based on the data predicted for the target cas and data from read across suggests that the test chemical 4-aminoazobenzene-3,4'-disulphonic acid (CAS no 101 -50 -8) is not toxic upon repeated dose exposure by the oral route.