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EC number: 228-406-5 | CAS number: 6259-53-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Acute oral toxicity:
Acute oral toxicity dose (LD50) of 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) was predicted based on OECD QSAR toolbox 4603 mg/kg bw; Danish (Q)SAR Database 3700 mg/kg bw and different studies available on structurally similar read across substances 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) >2000 mg/kg bw and Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) >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, 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid cannot be classified for acute oral toxicity.
Acute Inhalation toxicity:
4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) has very low vapour pressure (6.99E-009 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 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) was predicted based on OECD QSAR toolbox 4419 mg/kg bwand differentstudies available for the structurally similar read across substances 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) >2000 mg/kg bw and Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) >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, 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid cannot be classified for acute dermal toxicity.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- 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: 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid
InChI: 1S/C11H11NO4S/c1-12-8-3-2-7-4-9(17(14,15)16)6-11(13)10(7)5-8/h2-6,12-13H,1H3,(H,14,15,16)
Smiles: CNc1ccc2cc(cc(c2c1)O)S(=O)(=O)O
- Molecular formula (if other than submission substance):C11H11NO4S
- Molecular weight (if other than submission substance):253.2769 g/mol
- Substance type:Organic - 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:
- 4603 mg/kg
- No. of animals per sex per dose:
- not specified
- Control animals:
- not specified
- Details on study design:
- not specified
- Statistics:
- not specified
- Preliminary study:
- not specified
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 4 603 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
- Interpretation of results:
- other: Not classified
- Conclusions:
- LD50 was estimated to be 4603 mg/kg bw, when female Wistar rats were treated with 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) 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 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6). The LD50 was estimated to be 4603 mg/kg bw, when female Wistar rats were treated with 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid via oral gavage route.
Reference
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 ("j"
and (
not "k")
)
)
and ("l"
and (
not "m")
)
)
and ("n"
and (
not "o")
)
)
and ("p"
and (
not "q")
)
)
and "r" )
and ("s"
and (
not "t")
)
)
and ("u"
and (
not "v")
)
)
and ("w"
and (
not "x")
)
)
and ("y"
and "z" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine
by DNA binding by OECD
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 >> N-Substituted Aromatic Amines 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 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 AN2 OR AN2 >> Michael-type
addition, quinoid structures OR AN2 >> Michael-type addition, quinoid
structures >> Quinoneimines OR AN2 >> Michael-type addition, quinoid
structures >> Quinones and Trihydroxybenzenes OR AN2 >> Michael-type
addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >>
Michael-type addition on alpha, beta-unsaturated carbonyl compounds >>
Four- and Five-Membered Lactones OR AN2 >> Nucleophilic addition
reaction with cycloisomerization OR AN2 >> Nucleophilic addition
reaction with cycloisomerization >> Hydrazine Derivatives OR AN2 >>
Schiff base formation OR AN2 >> Schiff base formation >> Polarized
Haloalkene Derivatives OR AN2 >> Shiff base formation after aldehyde
release OR AN2 >> Shiff base formation after aldehyde release >>
Specific Acetate Esters OR AN2 >> Thioacylation via nucleophilic
addition after cysteine-mediated thioketene formation OR AN2 >>
Thioacylation via nucleophilic addition after cysteine-mediated
thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR
AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated
thioketene formation >> Polarized Haloalkene Derivatives OR Non-covalent
interaction OR Non-covalent interaction >> DNA intercalation OR
Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR
Non-covalent interaction >> DNA intercalation >> DNA Intercalators with
Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction
>> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR
Non-covalent interaction >> DNA intercalation >> Quinones and
Trihydroxybenzenes OR Radical OR Radical >> Radical mechanism via ROS
formation (indirect) OR Radical >> Radical mechanism via ROS formation
(indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via
ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR
Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine
Derivatives OR Radical >> Radical mechanism via ROS formation (indirect)
>> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation
(indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism
via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and
Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation
(indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical
mechanism via ROS formation (indirect) >> Single-Ring Substituted
Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion
(indirect) OR Radical >> ROS formation after GSH depletion (indirect) >>
Quinoneimines OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion
formation OR SN1 >> Nucleophilic attack after carbenium ion formation >>
Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic
nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic
nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic
attack after metabolic nitrenium ion formation >> Fused-Ring Primary
Aromatic Amines OR SN1 >> Nucleophilic attack after nitrenium ion
formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >>
Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic
attack after reduction and nitrenium ion formation OR SN1 >>
Nucleophilic attack after reduction and nitrenium ion formation >> Nitro
Azoarenes OR SN1 >> Nucleophilic attack after reduction and nitrenium
ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack
after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl
Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >>
Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting
epoxides and related after P450-mediated metabolic activation OR SN2 >>
Alkylation, direct acting epoxides and related after P450-mediated
metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR
SN2 >> Alkylation, direct acting epoxides and related after
P450-mediated metabolic activation >> Polarized Haloalkene Derivatives
OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation,
ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >>
Direct acting epoxides formed after metabolic activation OR SN2 >>
Direct acting epoxides formed after metabolic activation >> Quinoline
Derivatives OR SN2 >> Direct nucleophilic attack on diazonium cation OR
SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine
Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR
SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate
Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an
activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3 and
activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon
atom >> Polarized Haloalkene Derivatives by DNA binding by OASIS v.1.4
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Strong binder, OH group by
Estrogen Receptor Binding
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Moderate binder, OH grooup OR
Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non
binder, non cyclic structure OR Non binder, without OH or NH2 group OR
Weak binder, OH group by Estrogen Receptor Binding
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as No superfragment by
Superfragments ONLY
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding by OECD
Domain
logical expression index: "k"
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 >> Polarised Alkenes OR Michael addition >> Polarised Alkenes
>> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >>
Polarised alkene - ketones by Protein binding by OECD
Domain
logical expression index: "l"
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: "m"
Referential
boundary: The
target chemical should be classified as Highly reactive (GSH) OR Highly
reactive (GSH) >> 3-Alken-2-ones (MA) by Protein binding potency
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Aromatic Amine Type Compounds
AND Phenol Type Compounds by Oncologic Primary Classification
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Halogenated Aromatic Hydrocarbon
Type Compounds OR Not classified by Oncologic Primary Classification
Domain
logical expression index: "p"
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: "q"
Referential
boundary: The
target chemical should be classified as alpha,beta-unsaturated carbonyls
OR Aromatic diazo OR Aromatic mono-and dialkylamine OR Hydrazine OR
Nitro-aromatic by in vitro mutagenicity (Ames test) alerts by ISS
Domain
logical expression index: "r"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "s"
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: "t"
Referential
boundary: The
target chemical should be classified as 3-Methylcholantrene
(Hepatotoxicity) Alert OR Methyldopa (Hepatotoxicity) Alert by Repeated
dose (HESS)
Domain
logical expression index: "u"
Referential
boundary: The
target chemical should be classified as Amine AND Aromatic compound AND
Hydroxy compound AND Phenol AND Secondary amine AND Secondary mixed
amine (aryl, alkyl) AND Sulfonic acid AND Sulfonic acid derivative by
Organic functional groups, Norbert Haider (checkmol)
Domain
logical expression index: "v"
Referential
boundary: The
target chemical should be classified as Carboxylic acid by Organic
functional groups, Norbert Haider (checkmol)
Domain
logical expression index: "w"
Referential
boundary: The
target chemical should be classified as Aromatic amine AND Fused
carbocyclic aromatic AND Naphtalene AND Overlapping groups AND Phenol
AND Sulfonic acid by Organic Functional groups (nested)
Domain
logical expression index: "x"
Referential
boundary: The
target chemical should be classified as Sulfonate ester by Organic
Functional groups (nested)
Domain
logical expression index: "y"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -1.18
Domain
logical expression index: "z"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 3.52
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 4 603 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
- Endpoint:
- acute toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
Reference
Endpoint conclusion
- Quality of whole database:
- Waiver
Acute toxicity: via dermal route
Link to relevant study records
- 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
- 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: 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid
InChI: 1S/C11H11NO4S/c1-12-8-3-2-7-4-9(17(14,15)16)6-11(13)10(7)5-8/h2-6,12-13H,1H3,(H,14,15,16)
Smiles: CNc1ccc2cc(cc(c2c1)O)S(=O)(=O)O
- Molecular formula (if other than submission substance):C11H11NO4S
- Molecular weight (if other than submission substance):253.2769 g/mol
- Substance type:Organic - Species:
- rabbit
- Strain:
- other: Albino
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- not specified
- Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- not specified
- Duration of exposure:
- 18-22 hours
- Doses:
- 4419 mg/kg
- No. of animals per sex per dose:
- 5
- Control animals:
- not specified
- Details on study design:
- not specified
- Statistics:
- not specified
- Preliminary study:
- not specified
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 4 419 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
- Interpretation of results:
- other: Not classified
- Conclusions:
- LD50 was estimated to be 4419 mg/kg bw, when 5 male albino rabbits were treated with 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS no: 6259-53-6) for 18-22 hours by dermal application semiocclusively.
- 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-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (CAS no: 6259-53-6). The LD50 was estimated to be 4419 mg/kg bw, when 5 male albino rabbits were treated with 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid for 18-22 hours by dermal application semiocclusively.
Reference
The
prediction was based on dataset comprised from the following
descriptors: LD50
Estimation method: Takes average value from the 7 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" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion
formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine
by DNA binding by OECD
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 >> N-Substituted Aromatic Amines 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 by
Aquatic toxicity classification by ECOSAR
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding by OECD
Domain
logical expression index: "f"
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 by Protein binding by OECD
Domain
logical expression index: "g"
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: "h"
Referential
boundary: The
target chemical should be classified as 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 Toluene and small alkyl toluene derivatives (8a)
by DART scheme v.1.0
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62
mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND
Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by
Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Group CN Molecular Weight > 290
g/mol by Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62
mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND
Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by
Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Group CHal Molecular Weight >
280 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow >
4.5 by Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CNS Surface Tension > 62
mN/m AND Group All Melting Point > 200 C AND Group CNS log Kow < 0.5 AND
Group CNS Melting Point > 120 C AND Group CNS Melting Point > 50 C by
Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Group C Molecular Weight > 350
g/mol by Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -1.5
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 6.97
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 4 419 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, 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) 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 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid along with the study available on structurally similar read across substances 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) and Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5). 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-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6). The LD50 was estimated to be 4603 mg/kg bw, when female Wistar rats were treated with 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid via oral gavage route.
In another study based on the QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for the 4-hydroxy-6-(methylamino)naphthalene-2-sulfonic acid (6259-53-6). The LD50 was estimated to be 3700 mg/kg bw with Reliability Index 0.59 (0.5-0.75 = moderate prediction quality), when rats were treated with 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid orally.
The above study is supported by Sustainability Support Services (Europe) AB (study no.19166, 2017) was designed and conducted for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) 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, 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. The acute oral LD50 of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) was >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5), 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.201303, 2013) was designed and conducted for the structurally similar read across substance Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) in female wistar albino rats. The study was conducted under the OECD Guideline-423 for testing of chemicals. The healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization to standard laboratory condition and divided into test compound and vehicle control group each having three animals. Initially, the test compound was mixed with distilled water and administered orally at the dose level of 2000 mg/kg body weight (dose volume 10ml/kg) to three female rats. However; vehicle control group treated with distilled water at the dose level of 10 ml/kg bw. The treated animals were closely observed for clinical signs of intoxication during first 4 hours of test compound administration. Thereafter, all the animals were observed periodically at 1 hour interval for 24 hrs and twice daily for a period of 14 days. The necropsy was performed on all animals at the termination of the study. The test compound did not produce any mortality at the dose level of 2000 mg/kg body weight during the entire observation period. Animals did not produce any clinical signs of toxicity during the entire observation period. Animals showed normal gain in body weight on day 7th and 14th as compared to control group. No significant gross pathological changes related to compound toxicity were observed. Skin and hair coat was observed wet. It was concluded that the test compound Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No. 15790-07-5) is non-toxic at the tested dose level 2000 mg/kg body weight. According to CLP criteria, it comes under the “Category Unclassified”.
Thus, based on the above studies on 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) 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, 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid cannot be classified for acute oral toxicity.
Acute Inhalation toxicity:
4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) has very low vapour pressure (6.99E-009 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, 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) 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 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid along with the study available on the structurally similar read across substances 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) and Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5). 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-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6). The LD50 was estimated to be 4419 mg/kg bw, when 5 male albino rabbits were treated with 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid for 18-22 hours by dermal application semiocclusively.
This study is supported by Sustainability Support Services (Europe) AB (study no.19167, 2017) was designed and conducted for the structurally similar read across substance 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5)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 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5), 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 6-aminonaphthalene-2-sulphonic acid (CAS No. 93-00-5) 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.201303, 2013) was designed and conducted for the structurally similar read across substance Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No: 15790-07-5) in wistar albino rats. The study was conducted under the OECD Guideline-402 for testing of chemicals. In limit test, healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization. Approximate 10% back skin of total body surface area was prepared 24 hrs prior to application of test compound. Test drug was applied dermally at the dose of 2000 mg/kg bw for each animal. The treated animals were observed for clinical signs of intoxication. The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment). The Necropsy was performed on all at the termination of the study. After 72 hrs, a confirmatory test was conducted in same species of animals to confirm the limit test of the test compound. Rats were observed for mortality at 30 minutes time interval for first 6 hours on the day of test compound and thereafter twice a day for 14 days. All the rats were observed at least twice daily with the purpose of recording any symptoms of ill-health or behavioural changes. The organ which showed gross pathological change during necropsy subjected for histopathological study. No mortality was observed at 2000 mg/kg bw. Animals did not produce any clinical signs of intoxication throughout the period of observation. Animals showed normal gain in body weight on day 7th and 14th as compared to control group.No significant gross pathological changes related to compound toxicity were observed. Skin and hair coat was observed wet. Therefore, it was concluded that the test compound Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex (CAS No. 15790-07-5) is non-toxic at the tested dose level 2000 mg/kg body weight. According to CLP criteria, it comes under the “Category Unclassified”.
Thus, based on the above studies on 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) 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, 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid cannot be classified for acute dermal toxicity.
Justification for classification or non-classification
Based on the above studies and prediction on 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid (CAS no: 6259-53-6) 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, 4-hydroxy-6-(methylamino) naphthalene-2-sulfonic acid cannot be classified for acute oral and dermal toxicity. For Acute Inhalation toxicity wavier was added so, not possible to classify.
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