Registration Dossier

Administrative data

Description of key information

Acute Oral Toxicity: 

In Acute oral toxicity ,LD50 value was predicted based on OECD QSAR toolbox for target substance 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)was estimated to be 6733.41 mg/kg bw,and for different studies available on the structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3734-67-6) was considered to be >2000 mg/kg bw and Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) was considered to be 5000 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)can be classified as category V of acute oral toxicity.

Acute inhalation Toxicity: 

4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid has very low  vapor pressure (2.61E-022 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value was predicted based on OECD QSAR toolbox for target substance 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)was estimated to be 3392.01 mg/kg bw,and for different studies available on structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3734-67-6) was considered to be >2000 mg/kg bw and Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) was considered to be >2000 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)can be classified as category V of acute dermal toxicity.

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 QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.3,2017
GLP compliance:
not specified
Test type:
other: estimated data
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (IUPAC name): 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid
- Molecular formula: C17H14N2O8S2
- Molecular weight: 438.4356 g/mol
- Smiles notation: c1cc(cc(c1)N)C(=O)Nc2ccc(c3c2c(cc(c3)S(=O)(=O)O)O)S(=O)(=O)O
-InChl:1S/C17H14N2O8S2/c18-10-3-1-2-9(6-10)17(21)19-13-4-5-15(29(25,26)27)12-7-11(28(22,23)24)8-14(20)16(12)13/h1-8,20H,18H2,(H,19,21)(H,22,23,24)(H,25,26,27)
- Substance type: Organic
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
No data available
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data available
Doses:
6733.41 mg/kg bw
No. of animals per sex per dose:
No data available
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:
6 733.41 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
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" or "e" or "f" or "g" or "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and "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 >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

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: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "j"

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 >> Acyl halide OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> 5-alkoxyindoles 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 amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Non binder, MW>500 OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.57

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LD50 was estimated to be 6733.41 mg/kg bw,when male and female wistar rats were orally exposed with 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9) via gavage.
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 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9).The LD50 was estimated to be 6733.41 mg/kg bw,when male and female wistar rats were orally exposed with 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)via gavage.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
6 733.41 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.3

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Quality of whole database:
Waiver

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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 QMRF report has been attached
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.3,2017
GLP compliance:
not specified
Test type:
other: estimated data
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (IUPAC name): 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid
- Molecular formula: C17H14N2O8S2
- Molecular weight: 438.4356 g/mol
- Smiles notation: c1cc(cc(c1)N)C(=O)Nc2ccc(c3c2c(cc(c3)S(=O)(=O)O)O)S(=O)(=O)O
-InChl:1S/C17H14N2O8S2/c18-10-3-1-2-9(6-10)17(21)19-13-4-5-15(29(25,26)27)12-7-11(28(22,23)24)8-14(20)16(12)13/h1-8,20H,18H2,(H,19,21)(H,22,23,24)(H,25,26,27)
- Substance type: Organic
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
No data available
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
No data available
Duration of exposure:
24 hours
Doses:
3392.01 mg/kg bw
No. of animals per sex per dose:
No data available
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:
3 392.01 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% Mortality was observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
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 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" or "e" or "f" or "g" or "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and "q" )  )

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 >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "e"

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: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides)  OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR No alert found OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  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 OR SNVinyl OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom >> Vinyl type compounds with electron withdrawing groups  by Protein binding by OASIS v1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Keratinocyte gene expression

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as High gene expression OR High gene expression >> N-Acylamides by Keratinocyte gene expression

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.77

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.28

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LD50 value was estimated to be 3392.01 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively with 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9) by dermal application for 24 hours.
Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid(70239-77-9).TheLD50 was estimated to be 3392.01 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9) by dermal application for 24 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 392.01 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR toolbox 3.3

Additional information

Acute Oral Toxicity: 

In different studies,4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)has been investigated for acute oral toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)along with the study available on the structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3734-67-6) and Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

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 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9).The LD50 was estimated to be 6733.41 mg/kg bw,when male and female wistar rats were orally exposed with 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)via gavage.

The above experimental study was further supported by Sustainability Support Services (Europe) AB, Sweden (study number: 8013-90-9/SSS/2018, 2014-02-22) for the structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3734-67-6). The acute oral toxicity profile of Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate in 12 female Sprague Dawley rats.The test material was dissloved in distilled water and given by oral gavage route.Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing.No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing. As no mortality were observed at 24 hours after the dosing, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality after the dosing.Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups.No moratlity was observed at dose concentration 2000mg/kg bw. Hence The LD50 value  was considered  to be >2000 mg/kg body weight,when Sprague Dawley rats were treated with Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate(3734 -67 -6) orally.

This is further supported by Sustainability Support Services (Europe) AB, Sweden (study number: 18819, 2016-10-25) the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6). The acute oral toxicity profile of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate was performed in 12 female Sprague Dawley rats. The test material was dissloved in distilled water and given by oral gavage route.Initially, three female animals were treated at the dose level of 300 mg/kg body weight of the test item (Step - I). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality at 24 hours after the dosing. As no mortality was observed at 24 hours after the dosing, three female animals were added to the study and treated with the same dose of 300 mg/kg of the test item (Step - II). Administration of the test item at 300 mg/kg did not result in any signs of toxicity and mortality after the dosing.No mortality was observed at 300 mg/kg dose group, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - I). Administration of the test item at 2000 mg/kg resulted in diarrhoea (reddish colour stools) in all animals with onset at 2 hours and no mortality after the dosing. As no mortality were observed at 24 hours after the dosing, hence additional three female animals were treated with the higher dose of 2000 mg/kg of the test item (Step - II). Administration of the test item at 2000 mg/kg resulted in diarrhoea (reddish colour stools) in all animals with onset at 2 hours and no mortality after the dosing. All animals from 300 mg/kg and 2000 mg/kg dose groups survived through the study period of 14 days. Staining of the stool is attributed to the reddish colour of the test item. Gross pathological examination did not reveal any abnormalities in animals from 300 mg/kg and 2000 mg/kg dose groups. Hence,The LD50 value was considered to be 5000 mg/kg body weight,when female Sprague Dawley rats were treated with Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) orally according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

Thus, based on the above studies on4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)and it’s structurally similar 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,4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)can be classified as category V of acute oral toxicity.

Acute inhalation Toxicity: 

4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid has very low  vapor pressure (2.61E-022 Pa), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal Toxicity:

In different studies,4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)has been investigated for acute dermal toxicity to a greater or lesser extent. Often the studies are based on in vivo experiments and estimated data in rodents, i.e. most commonly in rabbits for4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)along with the study available on structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3734-67-6) and Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS No. 3567-66-6).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid(70239-77-9).TheLD50 was estimated to be 3392.01 mg/kg bw,when male and female New Zealand White rabbits were exposed occlusively 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9) by dermal application for 24 hours.

The above study was further supported by Sustainability Support Services (Europe) AB, Sweden (study number: 18826, 2016-12-01) for the structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (3734-67-6). The acute dermal toxicity profile of Disodium 5-acetylamino-4-hydroxy-3-(phenyl azo)naphthalene-2,7-disulphonate(3734-67-6)in groups of 5 male and female Sprague Dawley rats according to OECD Guideline 402 (Acute Dermal Toxicity). The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. Hence,The LD50 value was considered to be >2000 mg/kg bw,whenmale and female Sprague Dawley rats were occlusively treated with Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate(3734-67-6) by dermal application according to OECD Guideline 402 (Acute Dermal Toxicity).

Also these results are further supported by Sustainability Support Services (Europe) AB, Sweden (study number: 18820, 2016-10-24) for the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS No. 3567-66-6). The acute dermal toxicity profile of Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate(3567-66-6) in Sprague Dawley rats. Distilled water was used as vehicle.The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days.Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. Hence,The LD50 value was considered to be >2000 mg/kg bw,when male and female Sprague Dawley rats were semiocclusively treated with Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate(3567-66-6)by dermal application according to OECD Guideline 402 (Acute Dermal Toxicity).

Thus, based on the above studies on4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)and it’s structurally similar 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,4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9)and it’s structurally similar 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,4-[(3-aminobenzoyl)amino]-5-hydroxynaphthalene-1,7-disulphonic acid (70239-77-9) can be classified as category V for acute oral and dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.