2-amino-5-hydroxynaphthalene-1,7-disulphonic acid

Endpoint summary

Description of key information

The LD50 was estimated to be 3199 mg/kg bw for rats. 

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 3.3 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: 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid
- Molecular formula: C10H9NO7S2
- Molecular weight: 319.3131 g/mol
- Smiles notation: c1cc(c(c2c1c(cc(c2)S(=O)(=O)O)O)S(=O)(=O)O)N
- InChl: 1S/C10H9NO7S2/c11-8-2-1-6-7(10(8)20(16,17)18)3-5(4-9(6)12)19(13,14)15/h1-4,12H,11H2,(H,13,14,15)(H,16,17,18)
- Physical state: Solid
- Substance type: Organic

Species:

rat

Strain:

Sprague-Dawley

Sex:

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:

3199 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

3 199 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: 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 6 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 ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and ("r" and ( not "s") )  )  and "t" )  and "u" )  and ("v" and "w" )  )

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 Strong binder, NH2 group AND Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "e"

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: "f"

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

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 Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Alkyl carbamyl halides OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group OR Acylation >> Acylation involving an activated (glucuronidated) sulfonamide group >> Arenesulfonamides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 >> Michael-type addition to quinoid structures  >> Carboxylic Acid Amides OR AN2 >> Michael-type addition to quinoid structures  >> N-Substituted Aromatic Amines OR AN2 >> Nucleophilic addition at polarized N-functional double bond OR AN2 >> Nucleophilic addition at polarized N-functional double bond >> Arenesulfonamides OR No alert found OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aromatic carbonyl compounds 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 v1.4

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes by Protein binding by OECD

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aromatic diazo OR Primary aromatic amine,hydroxyl amine and its derived esters by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Hydroxy compound AND Phenol 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: "s"

Referential boundary: The target chemical should be classified as Thioether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "t"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Similarity boundary:Target: Nc1ccc2c(O)cc(S(O)(=O)=O)cc2c1S(O)(=O)=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.55

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= -1.42

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 3199 mg/kg bw for rats.

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 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid. The LD50 was estimated to be 3199 mg/kg bw for rats. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 199 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, isopropyl 4-hydroxybenzoate 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 isopropyl 4-hydroxybenzoate along with the study available on structurally similar read across substance Butylparaben (CAS no 94-26-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In another prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid. The LD50 was estimated to be 3199 mg/kg bw for rats. 

In another experimental study given by U.S. National Library of Medicine (ChemIDplusA TOXNET Database, 2017) on structurally similar read across substance 2-aminonaphthalene-1,5-disulfonic acid (CAS no 117-62-4), rat were treated with 2-aminonaphthalene-1,5-disulfonic acid orally. 50% mortality was observedin treated rat at 5430 mg/kg bw. Therefore, LD50 was considered to be 5430 mg/kg bw when rat were treated with2-aminonaphthalene-1,5-disulfonic acid orally.    

Further experimental study given by Lewis et al (SAX's Dangerous properties of industrial material, 12th edition, 2012) on structurally similar read across substance 7-aminonaphthalene-1,3,6-trisulphonic acid (CAs no 118-03-6), rat were treated with 7-aminonaphthalene-1,3,6-trisulphonic acid was administered orally to rodent rat, at dose concentration of 13000mg/kg, 50% mortality was observed in treated rats. Therefore, LD50 was considered to be 13000 mg/kg bw when rat were treated with 7-aminonaphthalene-1,3,6-trisulphonic acid orally.

This is supported by experimental study given by RTECS database (Registry of Toxic Effects of Chemical Substances, 1986 Pg. 1329, 1986.) on structurally similar read across substance 6-aminonaphthalene-1,3-disulphonic acid (CAS No. 118-33-2). rat were treated with 6-aminonaphthalene-1,3-disulphonic acid in the concentration of 2000 mg/kg bw orally. 50% mortality was observed at 2000 mg/kg bw in treated rats. Therefore, the acute oral median lethal dose (LD50) of 6-aminonaphthalene -1,3-disulphonic acid in rat was observed to be 2000 mg/kg bw.

Thus, based on the above studies and predictions on 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid 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, 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid can be “Not classified” as acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid 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, 2-amino-5-hydroxynaphthalene-1,7-disulfonic acid can be “Not classified” as acute oral toxicity.