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EC number: 229-792-8 | CAS number: 6737-68-4
- 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 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4) was predicted based on OECD QSAR toolbox 2953 mg/kg bw and different studies available on structurally similar read across substances sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate (CAS No: 4430-18-6) >2000 mg/kg bw and 1,4-Bis(p-tolylamino)anthraquinone (CAS no: 128-80-3) 3660 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, 1,4-bis[(2-methylphenyl)amino]anthraquinone cannot be classified for acute oral toxicity.
Acute Inhalation toxicity:
1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4) has very low vapour pressure (3.02E-11 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 1,4-bis[(2-methylphenyl)amino] anthraquinone (CAS no: 6737-68-4) was predicted based on OECD QSAR toolbox 5857 mg/kg bw and different studies available for the structurally similar read across substance sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate (CAS No: 4430-18-6) >2000 mg/kg bw and 1-(2-hydroxyethylamino)-4-(methylamino) anthracene-9,10-dione (CAS no: 2475-46-9) >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, 1,4-bis[(2-methylphenyl)amino] anthraquinone 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: 1,4-bis[(2-methylphenyl)amino]anthraquinone
1S/C28H22N2O2/c1-17-9-3-7-13-21(17)29-23-15-16-24(30-22-14-8-4-10-18(22)2)26-25(23)27(31)19-11-5-6-12-20(19)28(26)32/h3-16,29-30H,1-2H3
SMILES:Cc1ccccc1Nc1ccc(Nc2ccccc2C)c2c1C(=O)c1ccccc1C2=O
Molecular Weight: 418.494 g/mole
Molecular Formula: C28H22N2O2 - Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/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:
- 2953 mg/kg bw
- 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:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 2 953 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 2953 mg/kg bw, when 10 male and female Fischer 344 rats were treated with 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4) 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 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4). The LD50 was estimated to be 2953 mg/kg bw, when 10 male and female Fischer 344 rats were treated with 1,4-bis[(2-methylphenyl)amino]anthraquinone via oral gavage route.
Reference
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" )
and ("c"
and (
not "d")
)
)
and ("e"
and (
not "f")
)
)
and ("g"
and (
not "h")
)
)
and ("i"
and (
not "j")
)
)
and "k" )
and ("l"
and "m" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as AN2 AND AN2 >> Michael-type
addition, quinoid structures AND AN2 >> Michael-type addition, quinoid
structures >> Quinones and Trihydroxybenzenes AND Non-covalent
interaction AND Non-covalent interaction >> DNA intercalation AND
Non-covalent interaction >> DNA intercalation >> Quinones and
Trihydroxybenzenes AND Radical AND Radical >> Radical mechanism via ROS
formation (indirect) AND Radical >> Radical mechanism via ROS formation
(indirect) >> Quinones and Trihydroxybenzenes by DNA binding by OASIS
v.1.4
Domain
logical expression index: "b"
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 by Protein binding
by OASIS v1.4
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as AN2 AND AN2 >> Michael-type
addition, quinoid structures AND AN2 >> Michael-type addition, quinoid
structures >> Quinones and Trihydroxybenzenes AND Non-covalent
interaction AND Non-covalent interaction >> DNA intercalation AND
Non-covalent interaction >> DNA intercalation >> Quinones and
Trihydroxybenzenes AND Radical AND Radical >> Radical mechanism via ROS
formation (indirect) AND Radical >> Radical mechanism via ROS formation
(indirect) >> Quinones and Trihydroxybenzenes by DNA binding by OASIS
v.1.4
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as AN2 >> Michael-type addition,
quinoid structures >> Flavonoids OR AN2 >> Michael-type addition,
quinoid structures >> Quinoneimines OR AN2 >> Carbamoylation after
isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation
>> N-Hydroxylamines 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 >> Schiff base formation by aldehyde formed after
metabolic activation OR AN2 >> Schiff base formation by aldehyde formed
after metabolic activation >> Geminal Polyhaloalkane 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 No alert found OR Non-covalent interaction >>
DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine
Derivatives 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
Nitroaromatics OR Non-specific OR Non-specific >> Incorporation into
DNA/RNA, due to structural analogy with nucleoside bases OR
Non-specific >> Incorporation into DNA/RNA, due to structural analogy
with nucleoside bases >> Specific Imine and Thione Derivatives OR
Radical >> Generation of ROS by glutathione depletion (indirect) OR
Radical >> Generation of ROS by glutathione depletion (indirect) >>
Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via
ROS formation (indirect) >> Acridone, Thioxanthone, Xanthone and
Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation
(indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via
ROS formation (indirect) >> C-Nitroso Compounds OR Radical >> Radical
mechanism via ROS formation (indirect) >> Flavonoids OR Radical >>
Radical mechanism via ROS formation (indirect) >> Fused-Ring
Nitroaromatics OR Radical >> Radical mechanism via ROS formation
(indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical
mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR
Radical >> Radical mechanism via ROS formation (indirect) >>
N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation
(indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism
via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR
Radical >> Radical mechanism via ROS formation (indirect) >>
Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >>
Radical mechanism via ROS formation (indirect) >> Polynitroarenes OR
Radical >> Radical mechanism via ROS formation (indirect) >> Specific
Imine and Thione Derivatives OR Radical >> ROS formation after GSH
depletion (indirect) OR Radical >> ROS formation after GSH depletion
(indirect) >> Haloalcohols OR Radical >> ROS formation after GSH
depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Carbenium ion
formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1
>> Nucleophilic attack after carbenium ion formation OR SN1 >>
Nucleophilic attack after carbenium ion formation >> Acyclic Triazenes
OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific
Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or
carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or
carbenium ion formation >> Nitroarenes with Other Active Groups 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 nitrenium ion
formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >>
N-Hydroxylamines OR SN1 >> Nucleophilic attack after reduction and
nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction
and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >>
Nucleophilic attack after reduction and nitrenium ion formation >>
Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction
and nitrenium ion formation >> Nitroarenes with Other Active Groups OR
SN1 >> Nucleophilic attack after reduction and nitrenium ion formation
>> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >>
Nucleophilic attack after reduction and nitrenium ion formation >>
Polynitroarenes OR SN1 >> Nucleophilic substitution after
glutathione-induced nitrenium ion formation OR SN1 >> Nucleophilic
substitution after glutathione-induced nitrenium ion formation >>
C-Nitroso Compounds OR SN1 >> Nucleophilic substitution on diazonium ion
OR SN1 >> Nucleophilic substitution on diazonium ion >> Specific Imine
and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >>
N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters OR SN2
>> Acylation involving a leaving group after metabolic activation OR SN2
>> Acylation involving a leaving group after metabolic activation >>
Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation by epoxide
metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide
metabolically formed after E2 reaction >> Haloalcohols OR SN2 >>
Alkylation, direct acting epoxides and related OR SN2 >> Alkylation,
direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >>
Alkylation, direct acting epoxides and related after cyclization OR SN2
>> Alkylation, direct acting epoxides and related after cyclization >>
Nitrogen and Sulfur Mustards 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, nucleophilic substitution at sp3-carbon atom OR
SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >>
Haloalkanes Containing Heteroatom 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 >> Haloalkanes Containing Heteroatom OR
SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate
Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after
thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at
sp3 carbon atom after thiol (glutathione) conjugation >> Geminal
Polyhaloalkane Derivatives 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 OR SN2 >>
SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >>
Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2
OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes
with Other Active Groups by DNA binding by OASIS v.1.4
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OECD
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as 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 >> P450
Mediated Activation to Quinones and Quinone-type Chemicals >>
Methylenedioxyphenyl 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 ketones OR Michael
addition >> Quinones and Quinone-type Chemicals OR Michael addition >>
Quinones and Quinone-type Chemicals >> Quinones 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 nitro OR SN1 >> Nitrenium Ion formation >>
Secondary aromatic amine by DNA binding by OECD
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as Non binder, impaired OH or NH2
group OR Non binder, MW>500 OR Strong binder, OH group by Estrogen
Receptor Binding
Domain
logical expression index: "i"
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: "j"
Referential
boundary: The
target chemical should be classified as Extremely reactive (GSH) OR
Extremely reactive (GSH) >> Benzoquinones (MA) by Protein binding potency
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Not bioavailable by Lipinski
Rule Oasis ONLY
Domain
logical expression index: "l"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 5.73
Domain
logical expression index: "m"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 10.9
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 953 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 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: 1,4-bis[(2-methylphenyl)amino]anthraquinone
1S/C28H22N2O2/c1-17-9-3-7-13-21(17)29-23-15-16-24(30-22-14-8-4-10-18(22)2)26-25(23)27(31)19-11-5-6-12-20(19)28(26)32/h3-16,29-30H,1-2H3
SMILES:Cc1ccccc1Nc1ccc(Nc2ccccc2C)c2c1C(=O)c1ccccc1C2=O
Molecular Weight: 418.494 g/mole
Molecular Formula: C28H22N2O2 - 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:
- 5857 mg/kg bw
- 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:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 5 857 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 5857 mg/kg bw, when male and female New Zealand White rabbits were treated with 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4) 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 1,4-bis[(2-methylphenyl)amino] anthraquinone (CAS no: 6737-68-4). The LD50 was estimated to be 5857 mg/kg bw, when male and female New Zealand White rabbits were treated with 1,4-bis[(2-methylphenyl)amino] anthraquinone for 24 hours by dermal application occlusively.
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" )
and ("c"
and (
not "d")
)
)
and ("e"
and (
not "f")
)
)
and ("g"
and "h" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as AN2 AND AN2 >> Michael-type
addition, quinoid structures AND AN2 >> Michael-type addition, quinoid
structures >> Quinones and Trihydroxybenzenes AND Non-covalent
interaction AND Non-covalent interaction >> DNA intercalation AND
Non-covalent interaction >> DNA intercalation >> Quinones and
Trihydroxybenzenes AND Radical AND Radical >> Radical mechanism via ROS
formation (indirect) AND Radical >> Radical mechanism via ROS formation
(indirect) >> Quinones and Trihydroxybenzenes by DNA binding by OASIS
v.1.4
Domain
logical expression index: "b"
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 by Protein binding
by OASIS v1.4
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Weak binder, OH group by
Estrogen Receptor Binding
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group All Lipid
Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4
g/kg AND Group All Melting Point > 200 C AND Group CN Aqueous Solubility
< 0.0001 g/L AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN log
Kow > 4.5 AND Group CN log Kow > 5.5 AND Group CN Melting Point > 180 C
AND Group CN Molecular Weight > 290 g/mol AND Group CN Vapour Pressure <
0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as (!Undefined)Group C Surface
Tension > 62 mN/m by Skin irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "g"
Parametric
boundary:The
target chemical should have a value of Molecular weight which is >= 219
Da
Domain
logical expression index: "h"
Parametric
boundary:The
target chemical should have a value of Molecular weight which is <= 596
Da
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 857 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, 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4) 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 1,4-bis[(2-methylphenyl)amino]anthraquinone along with the study available on structurally similar read across substances sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino] toluene-3-sulphonate (CAS No: 4430-18-6) and 1,4-Bis(p-tolylamino)anthraquinone (CAS no: 128-80-3). 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 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4). The LD50 was estimated to be 2953 mg/kg bw, when 10 male and female Fischer 344 rats were treated with 1,4-bis[(2-methylphenyl)amino]anthraquinone via oral gavage route.
The above study is supported by Sustainability Support Services (Europe) AB (study no.18811, 2016) was designed and conducted for the structurally similar read across substance Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate (CAS No: 4430-18-6) 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 Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate supplied by Sustainability Support Services (Europe) AB, when administered to Sprague Dawley rats was found to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate falls into the Category "Not classified”.
This study is further supported by Richard J. Lewis (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set, 2012) and U.S. National Library of
Medicine (ChemIDplus, 2017), for the structurally similar read across substance 1,4-Bis(p-tolylamino)anthraquinone (CAS no: 128-80-3). Acute oral toxicity study was conducted in rats at the concentration of 3660 mg/kg bw. 50% mortality was observed in treated rats at 3660 mg/kg bw. Therefore, LD50 was considered to be 3660 mg/kg bw, when rats were treated with1,4-Bis(p-tolylamino)anthraquinone (CAS no: 128-80-3) via oral route.
Thus, based on the above studies on 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4) 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, 1,4-bis[(2-methylphenyl)amino]anthraquinone cannot be classified for acute oral toxicity.
Acute Inhalation toxicity:
1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4) has very low vapour pressure (3.02E-11 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, 1,4-bis[(2-methylphenyl)amino] anthraquinone (CAS no: 6737-68-4) 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 1,4-bis[(2-methylphenyl)amino] anthraquinone along with the study available on the structurally similar read across substance sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate (CAS No: 4430-18-6) and 1-(2-hydroxyethylamino)-4-(methylamino) anthracene-9,10-dione (CAS no: 2475-46-9). 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 1,4-bis[(2-methylphenyl)amino] anthraquinone (CAS no: 6737-68-4). The LD50 was estimated to be 5857 mg/kg bw, when male and female New Zealand White rabbits were treated with 1,4-bis[(2-methylphenyl)amino] anthraquinone for 24 hours by dermal application occlusively.
This study is supported by Sustainability Support Services (Europe) AB (study no.18812, 2016) was designed and conducted for the structurally similar read across substanceSodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl)amino]toluene-3-sulphonate (CAS No: 4430-18-6) 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 Sodium 4-[(9,10-dihydro-4-hydroxy-9,10-dioxo-1-anthryl) amino]toluene-3- sulphonate supplied by Sustainability Support Services (Europe) AB, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that Sodium 4-[(9,10-dihydro-4- hydroxy-9,10-dioxo- 1-anthryl)amino]toluene-3-sulphonate does not exhibits acute toxicity by the dermal route. Classification - Not classified.
The above study is further supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the functionally similar read across substance 1-(2-hydroxyethylamino)-4-(methylamino) anthracene-9,10-dione (CAS no: 2475-46-9). Acute Dermal toxicity study was conducted in rabbits at the concentration of 2000 mg/kg bw. No mortality was observed in treated rabbits at 2000 mg/kg bw. Therefore, LD50 was considered to be >2000 mg/kg bw, when rabbits were treated with1-(2-hydroxyethylamino)-4-(methylamino) anthracene-9,10-dione by dermal application to the skin.
Thus, based on the above studies on 1,4-bis[(2-methylphenyl)amino]anthraquinone (CAS no: 6737-68-4) 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, 1,4-bis[(2-methylphenyl)amino]anthraquinone cannot be classified for acute dermal toxicity.
Justification for classification or non-classification
Based on the above studies and prediction on 1,4-bis[(2-methylphenyl)amino] anthraquinone (CAS no: 6737-68-4) 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, 1,4-bis[(2-methylphenyl)amino]anthraquinone 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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