Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate

Endpoint summary

Description of key information

The acute oral LD50 value of substance FD&C Red No. 4 is considered to be >2000 mg/kg in rat.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from QSAR Toolbox version 3.3

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.3

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: Predicted data

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

4952.15 mg/kg

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not specified

Details on study design:

no data

Statistics:

no data

Preliminary study:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 952.152 mg/kg bw

Based on:

test mat.

Mortality:

no data

Clinical signs:

other: no data

Gross pathology:

no data

Other findings:

no data

The prediction was based on dataset comprised from the following descriptors: LD50
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" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Naphthalene sulfonic acids, condensates by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl arenes AND 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 Alkyl arenes AND Aryl AND 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 Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Aromatic Carbon [C] AND Azo [-N=N-] AND Hydroxy, aromatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Suflur {v+4} or {v+6} 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 Anion AND Aromatic compound AND Azo compound AND Cation AND Hydroxy compound AND Phenol 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 No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes 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 reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.18

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.12

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal dose (LD50) value of Disodium 3-((2,4-dimethyl-5-sulphonatophenyl)azo)-4-hydroxynaphthalene-1-sulphonate in rat is estimated to be 4952.15 mg/kg bw. This value indicates that the substance is not expected to exhibit acute toxicity by oral route as per the CLP criteria.

Executive summary:

The acute median lethal dose (LD50) value of Disodium 3-((2,4-dimethyl-5-sulphonatophenyl)azo)-4-hydroxynaphthalene-1-sulphonate in rat is estimated to be 4952.15 mg/kg bw. This value indicates that the substance is not expected to exhibit acute toxicity by oral route as per the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 952.15 mg/kg bw

Additional information

Acute oral toxicity:

Various studies and prediction model based data was used to determine the acute oral toxic nature of the test compound Ponceau SX (CAS no 4548 -53 -2). The studies are summarized as below:

The acute median lethal dose (LD50) value of Disodium 3-((2,4-dimethyl-5-sulphonatophenyl)azo)-4-hydroxynaphthalene-1-sulphonate in rat is estimated to be 4952.15 mg/kg bw by SSS QSAR, 2016. This value indicates that the substance is not expected to exhibit acute toxicity by oral route as per the CLP criteria.

Acute oral toxicity study was conducted on rats to evaluate the toxic nature of the test compound Ponceau Sx. The acute oral LD50 value of substance FD&C Red No. 4 is considered to be >2000 mg/kg in rat (Maryadele, 2006).

Acute oral toxicity test was conducted by Gaunt et al, 1967 on Carworth Farm E strain 5 male and 5 female rat exposed by chemicalCarmoisine orally by stomach tube.Aqueous solutions of Carmoisine (RA CAS no 3567 -69 -9) were administered in single doses by stomach tube at dosage volumes of 10 ml/kg.Observations of toxic signs and deaths were made for 7 days after dosage,In both sexes of rats oral doses of up to and 10,000 mg/kg in rats were tolerated without lethal effect. Hence, LD50 value was observed to be >10,000 mg/kg in acute oral toxicity test of chemical Carmoisine exposed to rat orally by stomach tube.

Similar study on mice revelaed LD50 value to be >8000 mg/kg when the chemical Carmoisine (RA CAS no 3567 -69 -9) wasexposed toICI Alderley Park strain of 5 male and 5 femalemice orally by stomach tube.

Acute oral toxicity test by Lamia et al, 2016 has been performed to study the lethal dose of chemical carmoisine (RA CAS no 3567 -69 -9). 72-male Sprague- Dawley white mice were exposed to chemical carmoisine with dose concentration of 1250 mg/kg, 2500 mg/kg, 3750 mg/kg, 5000 mg/kg, 6250 mg/kg to 6 animals per dose by oral route. Control animals received distilled water only. The mice were observed for 3 days for the signs and symptoms of toxicity as well as the death rate of each group were recorded. In the animals that received different doses of the carmoisine dye ranging from (1250 to 6250 mg/Kg) administered orally in a single dose by stomach tube, the signs of loss of appetite drowsiness, tachycardia, decrease in locomotion & anorexia was distinctive signs observed on the mice before dead. The LD50 value was found to be 4166.66 mg/kg bw.

Acute oral toxicity study was performed to evaluate the oral toxic nature of the test compound C.I. Direct Blue 8 (RA CAS no 2429 -71 -2). The test compound 3, 3'-[(3, 3' -Dimethoxy-4,4'-biphenylene )-bis- (azo )7bis[4-hydroxy-1-naphthalenesulfonic acid disodium salt has an acute oral median lethal dose (LD50) of >3200 mg/Kg bw. In another study, The test compound 3, 3'-[(3, 3' -Dimethoxy-4,4'-biphenylene )-bis- (azo )7bis[4-hydroxy-1-naphthalenesulfonic acid disodium salt had an acute oral median lethal dose (LD50) of >3200 mg/Kg bw in mice.

 

Based on the weight of evidence data and as per the CLP classification, the test material does not classify as an acute oral toxicant.

Justification for selection of acute toxicity – oral endpoint
The acute median lethal dose (LD50) value of Disodium 3-((2,4-dimethyl-5-sulphonatophenyl)azo)-4-hydroxynaphthalene-1-sulphonate in rat is estimated to be 4952.15 mg/kg bw. This value indicates that the substance is not expected to exhibit acute toxicity by oral route as per the CLP criteria.

Justification for classification or non-classification

Acute oral toxicity:

Based on the weight of evidence considered and the other available data, the test material FD and C red no 4 does not classify as an acute oral toxicant.