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

Endpoint summary

Description of key information

LD50 was estimated to be 3359.94 mg/kg bw, when male and female wistar rat were exposed with 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) orally.

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 from OECD QSAR toolbox v3.4 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4, 2017

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of the test material: 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid
- IUPAC name: 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid
- Molecular formula: C10H9NO7S2
- Molecular weight: 319.3131 g/mol
- Substance type: Organic
- Smiles: c1c2cc(c(cc2c(cc1S(=O)(=O)O)O)N)S(=O)(=O)O

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

No data available

Doses:

3359.94 mg/kg bw

No. of animals per sex per dose:

Total : 6
male:3
female:3

Control animals:

not specified

Details on study design:

No data available

Statistics:

No data available

Preliminary study:

No data available

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 359.94 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

No data available

Clinical signs:

other: No data available

Gross pathology:

No data available

Other findings:

No data available

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

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 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: "c"

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

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 No alert found by DNA binding by OECD

Domain logical expression index: "f"

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 >> Alkyl phenols 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 Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones 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 >> 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: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 3-Alken-2-ones (MA) OR Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) by Protein binding potency

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Similarity boundary:Target: Nc1cc2c(cc1S(O)(=O)=O)cc(S(O)(=O)=O)cc2O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: Nc1cc2c(cc1S(O)(=O)=O)cc(S(O)(=O)=O)cc2O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: Nc1cc2c(cc1S(O)(=O)=O)cc(S(O)(=O)=O)cc2O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.46

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.454

Interpretation of results:

other: Not Classified

Conclusions:

LD50 was estimated to be 3359.94 mg/kg bw, when male and female wistar rat were exposed with 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) orally.

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 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4).LD50 was estimated to be 3359.94 mg/kg bw, when male and female wistar rats were exposed with3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) orally.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 359.94 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.4. (2017)

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, 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) 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 rats for 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4).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 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4).LD50 was estimated to be 3359.94 mg/kg bw, when male and female wistar rats were exposed with3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) orally.

 

 In another experimental study given by BG Chemie(BG Chemie "Toxikologische Bewertungen" 15. No. 227, Ergänzungslieferung, 06/2000) on structurally similar read across substance 6-amino-4-hydroxynaphthalene-2-sulphonic acid (gamma acid, In Acute oral toxicity test, Ten male Wistar-rats administered orally with the dose of 5000 mg/kg bw of 6-amino-4-hydroxynaphthalene-2-sulphonic acid (gamma acid), dry and ground, formulated in water).The observation period was 14 days, all animals were survived a single oral administration of >5000 mg/kg bw. Based on the study the lethal dose concentration (LD50) was considered to be >5000mg/kg bw.When rats were treated with 6-amino-4-hydroxynaphthalene-2-sulphonic acid (90 -51 -7) orally.   

Also it is supported by experimental study given Richard J. Lewis, Sr. (SAX's Dangerous properties of industrial material, 12th edition, 2012) on structurally similar read across substance 7-aminonaphthalene-1,3,6-trisulphonic acid (118 -03 -6), In Acute Oral toxicity test, 7-aminonaphthalene-1,3,6-trisulphonic acid (118 -03 -6) was administered orally to rodent rat, at dose concentration of 13000mg/kg, 50% mortality was observed. Hence LD50 was considered to be 13000mg/kg bw. When rats were treated with 7-aminonaphthalene-1,3,6-trisulphonic acid via oral route

.

Also it is further supported by experimental study given byU.S .National library of medicine (ChemID plusA TOXNET DATABASE.2017)on structurally similar read across substance 2-aminonaphthalene-1,5-disulfonic acid (117-62-4), In acute oral toxicity study, rat were treated with 2-aminonaphthalene-1,5-disulfonic acid orally. 50% mortality was observed in treated rat at 5430 mg/kg bw. Therefore, LD50 was considered to be 5430 mg/kg bw when rat were treated with 2-aminonaphthalene-1,5-disulfonic acid orally.    

Thus, based on the above studies and predictions on 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) and its read across substances, it can be concluded that LD50 value is 3359.94 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) can be “Not classified ” for acute oral toxicity.

 

 

 

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation 3-amino-5-hydroxynaphthalene-2,7-disulfonic acid (90-40-4) can be “Not classified ” for acute oral toxicity.