Disodium 8-hydroxynaphthalene-1,6-disulphonate

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) was predicted based on OECD QSAR toolbox 4064 mg/kg bw and different studies available on structurally similar read across substances Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS No. 3567-66-6) >2000 mg/kg bw and Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6) >2000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Disodium 8-hydroxynaphthalene-1,6-disulfonate cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) has very low vapour pressure (1.22E-16 Pa at 25°C), 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: 

Acute Dermal toxicity dose (LD50) for Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) was predicted based on OECD QSAR toolbox 4668 mg/kg bwand differentstudies available for the structurally similar read across substances Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3567-66-6) >2000 mg/kg bw and Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6) >2000 mg/kg bw. All these studies concluded that the LD50 value is>2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Disodium 8-hydroxynaphthalene-1,6-disulfonate cannot be classified for 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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

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: Disodium 8-hydroxynaphthalene-1,6-disulphonate
SMILES:Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
InChI:1S/C10H8O7S2.2Na/c11-8-5-7(18(12,13)14)4-6-2-1-3-9(10(6)8)19(15,16)17;;/h1-5,11H,(H,12,13,14)(H,15,16,17);;/q;2*+1/p-2
Mol. formula: C10H6Na2O7S2
Molecular Weight: 348.2624 g/mole

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

4064 mg/kg

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

4 064 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was 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 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and "p" )  and "q" )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and ("v" and ( not "w") )  )  and ("x" and ( not "y") )  )  and ("z" and ( not "aa") )  )  and ("ab" and ( not "ac") )  )  and ("ad" and "ae" )  )

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 Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "c"

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 Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols AND Salt by Aquatic toxicity classification by ECOSAR

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 >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation 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 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 SN1 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 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 OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Michael addition OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-diimine OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> Phosphonates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Halo-pyrimidines OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Arylethanamine-like derivatives (11a) OR Dihalogen-, dinitro-phenol and their ester derivatives (8e) OR Inorganic chemical OR Known precedent reproductive and developmental toxic potential OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> 4-alkylphenol-like derivatives (2b-3) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> Other non-steroidal estrogen receptor (ER) binding compounds (2b-2) OR Not covered by current version of the decision tree OR Piperazine-, dioxane-, morpholine-, tetrahydrothiopyran-like derivatives and cyclohexanamine (17c) OR Polyhalogenated benzene derivatives (8c) OR Steroid derivatives OR Steroid nucleus derived ER and AR binders OR Steroid nucleus derived ER and AR binders >> Androgens, anti-androgens (2a-4) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as 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 >> Conjugated systems with electron withdrawing groups  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones 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 by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkaline Earth OR Halogens by Groups of elements

Domain logical expression index: "o"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Chlorphentermine (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Benzene/ Naphthalene sulfonic acids (Less susceptible) Rank C by Repeated dose (HESS)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Oxyphenistain (Hepatotoxicity) Alert OR Phenols (Mucous membrane irritation) Rank C OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Organic sulphonic salts by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group All log Kow < -3.1 AND Group All Melting Point > 200 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Group All Aqueous Solubility < 0.000005 g/L by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Aromatic alcohol  [-OH] AND Aromatic-H AND Sulfonic acid / salt -> aromatic attach by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as -CH2-  [cyclic] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as ECHA PR AND EINECS AND METI Japan AND REACH ECB by Inventory Affiliation

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Canada DSL by Inventory Affiliation

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is >= -4.14

Domain logical expression index: "ae"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.29

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 4064 mg/kg bw, when 10 female Wistar rats were treated with Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) via oral gavage route.

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 Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3). The LD50 was estimated to be 4064 mg/kg bw, when 10 female Wistar rats were treated with Disodium 8-hydroxynaphthalene-1,6-disulfonate via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 064 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4.

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 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

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: Disodium 8-hydroxynaphthalene-1,6-disulphonate
SMILES:Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
InChI:1S/C10H8O7S2.2Na/c11-8-5-7(18(12,13)14)4-6-2-1-3-9(10(6)8)19(15,16)17;;/h1-5,11H,(H,12,13,14)(H,15,16,17);;/q;2*+1/p-2
Mol. formula: C10H6Na2O7S2
Molecular Weight: 348.2624 g/mole

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

4668 mg/kg

No. of animals per sex per dose:

Total = 6 (3 animals/sex/group)

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 668 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was 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" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "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 Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "c"

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 Phenols by Protein binding by OASIS v1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acid moiety AND Phenols AND Salt by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

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 and Aminoalkylamine Side Chain OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom by DNA binding by OASIS v.1.4

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 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 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 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 Phenols 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) ester group OR Acylation >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters 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 by Protein binding by OASIS v1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol AND Sulfonic acid by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkyl arenes by Organic Functional groups

Domain logical expression index: "o"

Similarity boundary:Target: Oc1cc(S(=O)(=O)O{-}.[Na]{+})cc2cccc(S(=O)(=O)O{-}.[Na]{+})c12
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 160 Da

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 394 Da

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 4668 mg/kg bw, when 6 (3 animals/sex/group) New Zealand White male and female rabbit was treated with Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) for 24 hours by dermal application occlusively.

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 Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3). The LD50 was estimated to be 4668 mg/kg bw, when 6 (3 animals/sex/group) New Zealand White male and female rabbit was treated with Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 668 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.4.

Additional information

Acute oral toxicity:

In different studies, Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for Disodium 8-hydroxynaphthalene-1,6-disulfonate along with the study available on structurally similar read across substances Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS No. 3567-66-6) and Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6). 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 Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3). The LD50 was estimated to be 4064 mg/kg bw, when 10 female Wistar rats were treated with Disodium 8-hydroxynaphthalene-1,6-disulfonate via oral gavage route.

The above study is supported by Sustainability Support Services (Europe) AB (study no.18819, 2016) was designed and conducted for the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS No. 3567-66-6) in Sprague Dawley rats. 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. The acute oral LD50 of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate (CAS No. 3567-66-6) was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate, when administered via oral route in Sprague Dawley rats falls into the “Category Unclassified” criteria of CLP.

This study is further supported by Sustainability Support Services (Europe) AB (study no.18825, 2014) was designed and conducted for the structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6) in Sprague Dawley rats. 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. It was concluded that the acute oral median lethal dose (LD50) of Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate supplied by Sustainability Support Services (Europe) AB, Sweden, when administered to Sprague Dawley rats was found to be >2000 mg/kg body weight and falls into the “Category Unclassified” criteria of CLP.

Thus, based on the above studies on Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Disodium 8-hydroxynaphthalene-1,6-disulfonate cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) has very low vapour pressure (1.22E-16 Pa at 25°C), 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, Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits and rats for Disodium 8-hydroxynaphthalene-1,6-disulfonate along with the study available on the structurally similar read across substances Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3567-66-6) and Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6). 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 Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3). The LD50 was estimated to be 4668 mg/kg bw, when 6 (3 animals/sex/group) New Zealand White male and female rabbit was treated with Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) for 24 hours by dermal application occlusively.

This study is supported by Sustainability Support Services (Europe) AB (study no.18820, 2016) was designed and conducted for the structurally similar read across substance Disodium 5-amino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3567-66-6) in Sprague Dawley rats. 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. It was concluded that the acute dermal median lethal dose (LD50) of Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disul phonate, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that Disodium 5-amino-4-hydroxy-3-(phenylazo) naphthalene-2, 7-disulphonate does not classify as an acute dermal toxicant. CLP Classification: “Unclassified”.

The above study is further supported by Sustainability Support Services (Europe) AB (study no.18826, 2016) was designed and conducted for the structurally similar read across substance Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate (CAS no: 3734-67-6) in Sprague Dawley rats. 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. It was concluded that the acute dermal median lethal dose (LD50) of Disodium 5-acetylamino-4-hydroxy-3-(phenylazo)naphthalene-2,7-disulphonate supplied by Sustainability Support Services (Europe) AB, Sweden, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight.

Thus, based on the above studies on Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, Disodium 8-hydroxynaphthalene-1,6-disulfonate cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on Disodium 8-hydroxynaphthalene-1,6-disulfonate (CAS no: 83732-80-3) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, Disodium 8-hydroxynaphthalene-1,6-disulfonate cannot be classified for acute oral and dermal toxicity. For Acute Inhalation toxicity wavier was added so, not possible to classify.