Sodium hydrogen 8-aminonaphthalene-1,6-disulphonate

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was estimated to be 2517 mg/kg bw when Wistar male and female rats were orally exposed with sodium hydrogen 8-aminonaphthalene-1,6-disulfonate.

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:

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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material: sodium hydrogen 8-aminonaphthalene-1,6-disulfonate
- Molecular formula: C10H8NNaO6S2
- Molecular weight: 325.2962 g/mol
- Smiles notation: c1cc2cc(cc(c2c(c1)S(=O)(=O)O)N)S(=O)(=O)[O-].[Na+]
- InChl: 1S/C10H9NO6S2.Na/c11-8-5-7(18(12,13)14)4-6-2-1-3-9(10(6)8)19(15,16)17;/h1-5H,11H2,(H,12,13,14)(H,15,16,17);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

not specified

Doses:

2517 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 517 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

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" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and "p" )  )

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 Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acid moiety AND Anilines (Unhindered) AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Cation 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: "h"

Referential boundary: The target chemical should be classified as 1,2-aminoalcohol OR 1,2-diol OR Acetal OR Alcohol OR Alkyl chloride OR Alkyl fluoride OR Alkyl halide OR Alkylarylether OR Aryl bromide OR Aryl chloride OR Aryl fluoride OR Aryl halide OR Aryl iodide OR Azo compound OR Carbamic acid ester (uretane) OR Carbamic acid halide OR Carbonic acid derivative OR Carbonic acid diester OR Carbonyl compound OR Carboxylic acid OR Carboxylic acid amide OR Carboxylic acid derivative OR Carboxylic acid ester OR Carboxylic acid hydrazine OR Carboxylic acid prim. amide OR Carboxylic acid sec. amide OR Carboxylic acid tert. amide OR CO2 derivative (general) OR Dialkylether OR Diarylether OR Enolether OR Ether OR Halogen derivative OR Heterocyclic compound OR Hydrazine derivative OR Hydrazone OR Hydroxy compound OR Imine OR Ketone OR Lactone OR Nitrile OR Nitro compound OR No functional group found OR Oxohetarene OR Phenol OR Phosphoric acid derivative OR Phosphoric acid ester OR Primary alcohol OR Primary aliphatic amine OR Secondary alcohol OR Secondary aliphatic amine OR Secondary amine OR Secondary aromatic amine OR Secondary mixed amine (aryl, alkyl) OR Sulfenic acid derivative OR Sulfonamide OR Sulfone OR Sulfonic acid ester OR Sulfuric acid derivative OR Sulfuric acid monoester OR Tertiary alcohol OR Tertiary aliphatic amine OR Tertiary amine OR Tertiary aromatic amine OR Tertiary mixed amine OR Thiocarbonic acid derivative OR Thiocyanate OR Thioether OR Thiophosphoric acid derivative OR Thiophosphoric acid ester by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "i"

Similarity boundary:Target: Nc1cc(S(O)(=O)=O)cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Similarity boundary:Target: Nc1cc(S(O)(=O)=O)cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Similarity boundary:Target: Nc1cc(S(O)(=O)=O)cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: Nc1cc(S(O)(=O)=O)cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

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: "n"

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

Domain logical expression index: "o"

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: "p"

Parametric boundary:The target chemical should have a value of log BCF max which is <= 0.963 log(L/kg wet)

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2517 mg/kg bw when Wistar male and female rats were orally exposed with sodium hydrogen 8-aminonaphthalene-1,6-disulfonate.

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 sodium hydrogen 8-aminonaphthalene-1,6-disulfonate. The LD50 was estimated to be 2517 mg/kg bw when Wistar male and female rats were orally exposed with sodium hydrogen 8-aminonaphthalene-1,6-disulfonate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 517 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, sodium hydrogen 8-aminonaphthalene-1,6-disulfonate has been investigated for acute oral 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 sodium hydrogen 8-aminonaphthalene-1,6-disulfonate along with the study available on structurally similar read across substance 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid (CAs no 40306-75-0) and1,5-Naphthalenedisulfonic acid, 4-amino- (CAS no 117-55-5). 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 acute oral toxicity was estimated for sodium hydrogen 8-aminonaphthalene-1,6-disulfonate. The LD50 was estimated to be 2517 mg/kg bw when Wistar male and female rats were orally exposed with sodium hydrogen 8-aminonaphthalene-1,6-disulfonate.

In another prediction done by SSS (2017) using the Danish QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for sodium hydrogen 8-aminonaphthalene-1,6-disulfonate. The LD50 was estimated to be 12000 mg/kg bw in rat and 10000 mg/kg bw in mice when orally exposed with sodium hydrogen 8-aminonaphthalene-1,6-disulfonate.

Further supported by experimental study conducted by Sustainability Support Services (Europe) AB (SSS sponsored lab, 2013) on structurally similar read across substance 3-acetamido-5-amino-4-hydroxybenzenesulphonic acid (CAs no 40306-75-0), Wistar female rat were treated with -acetamido-5-amino-4-hydroxybenzenesulphonic acid in the concentration of 2000 mg/kg bw in two steps. No effect on survival, clinical sing and body weight of treated female rat were observed. In addition, no gross pathological changes were observed in treated female rat at 2000 mg/kg bw. Therefore, LD50 was considered to be> 2000 mg/kg bw when Wistar female rat were treated with -acetamido-5-amino-4-hydroxybenzenesulphonic acid orally.

This is further supported by experimental study summarized by U.S. National Library of Medicine (ChemIDplus A TOXNET Database Lite Browse Advanced, 2017) on structurally similar read across substance 1,5-Naphthalenedisulfonic acid, 4-amino- (CAS no 117-55-5),rat were treated with1,5-Naphthalenedisulfonic acid, 4-amino- in the concentration of 56000 mg/kg bw orally. 50 % mortality was observed at56000 mg/kg bw in treated rat.Impaired Liver Function Tests and Kidney, Ureter, and Bladder: Renal Function Tests Depressed in treated rats at56000 mg/kg bw. Therefore, LD50 was considered to be 56000 mg/kg bw when rat was treated with1,5-Naphthalenedisulfonic acid, 4-amino- orally.

Thus, based on the above studies and predictions on sodium hydrogen 8-aminonaphthalene-1,6-disulfonate and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, sodium hydrogen 8-aminonaphthalene-1,6-disulfonate can be classified as category V of acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on sodium hydrogen 8-aminonaphthalene-1,6-disulfonate and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, sodium hydrogen 8-aminonaphthalene-1,6-disulfonate can be classified as category V of acute oral toxicity.