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EC number: 255-310-0 | CAS number: 41317-15-1
- 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
Skin Sensitization:
The skin sensitization potential of 4-methoxy-2-methyl-N-phenylaniline was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 4-methoxy-2-methyl-N-phenylaniline was predicted to be not sensitizing to the skin of female guinea pigs.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- in vivo
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- data is from OECD QSAR toolbox v3.3 and the QMRF report has been attached
- Qualifier:
- according to guideline
- Guideline:
- other: Estimated data
- Principles of method if other than guideline:
- Prediction was done using OECD QSAR toolbox v3.3
- GLP compliance:
- not specified
- Type of study:
- other: Estimated data
- Specific details on test material used for the study:
- - Name of test material: 4-methoxy-2-methyl-N-phenylaniline
- IUPAC name: 4-methoxy-2-methyl-N-phenylaniline
- Molecular formula: C14H15NO
- Molecular weight: 213.279 g/mol
- Smiles: c1(c(cc(cc1)OC)C)Nc1ccccc1
- InChl: 1S/C14H15NO/c1-11-10-13(16-2)8-9-14(11)15-12-6-4-3-5-7-12/h3-10,15H,1-2H3
- Substance type: Organic
- Physical state: Solid dry powder - Species:
- guinea pig
- Strain:
- not specified
- Sex:
- female
- Details on test animals and environmental conditions:
- no data available
- Route:
- intradermal and epicutaneous
- Vehicle:
- not specified
- Adequacy of induction:
- not specified
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- not specified
- Adequacy of challenge:
- not specified
- No. of animals per dose:
- 20 guinea pigs
- Details on study design:
- no data available
- Challenge controls:
- no data available
- Positive control substance(s):
- not specified
- Reading:
- 1st reading
- Group:
- test chemical
- Clinical observations:
- no signs of dermal sensitization observed
- Remarks on result:
- no indication of skin sensitisation
- Interpretation of results:
- other: not sensitizing
- Conclusions:
- 4-methoxy-2-methyl-N-phenylaniline was predicted to be not sensitizing to the skin of female guinea pigs.
- Executive summary:
The skin sensitization potential of 4-methoxy-2-methyl-N-phenylaniline was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 4-methoxy-2-methyl-N-phenylaniline was predicted to be not sensitizing to the skin of female guinea pigs.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode 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 ("n"
and (
not "o")
)
)
and ("p"
and (
not "q")
)
)
and "r" )
and "s" )
and "t" )
and "u" )
and "v" )
and "w" )
and "x" )
and "y" )
and "z" )
and ("aa"
and "ab" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Alkylarylether OR Amine OR
Aromatic compound OR Ether OR Secondary amine OR Secondary aromatic
amine by Organic functional groups, Norbert Haider (checkmol) ONLY
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] OR
Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic
Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Nitrogen,
two or tree olefinic attach [>N-] OR Olefinic carbon [=CH- or =C<] OR
Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)
ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Alkyl arenes OR Aromatic amine
OR Ether OR Overlapping groups OR Precursors quinoid compounds by
Organic Functional groups (nested) ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Alkyl arenes OR Aromatic amine
OR Aryl OR Ether OR Precursors quinoid compounds by Organic Functional
groups ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Nucleophilic
addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >>
Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >>
alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2
>> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR Michael
addition OR Michael addition >> Quinone type compounds OR Michael
addition >> Quinone type compounds >> Quinone methides OR Radical OR
Radical >> Radical mechanism via ROS formation (indirect) OR Radical >>
Radical mechanism via ROS formation (indirect) >> Single-Ring
Substituted Primary Aromatic Amines OR Radical >> ROS formation after
GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone
methides OR SN1 OR SN1 >> Alkylation after metabolically formed
carbenium ion species OR SN1 >> Alkylation after metabolically formed
carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR
SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR
SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >>
Single-Ring Substituted Primary Aromatic Amines OR SN2 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 P450-mediated
metabolic activation OR SN2 >> Alkylation, direct acting epoxides and
related after P450-mediated metabolic activation >> Polycyclic Aromatic
Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after
metabolic activation OR SN2 >> Direct acting epoxides formed after
metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an
activated carbon atom OR SN2 >> SN2 at an activated carbon atom >>
Quinoline Derivatives by DNA binding by OASIS v.1.3
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 Michael addition >> P450
Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic
(PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR
SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation
>> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary
aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic
amine by DNA binding by OECD
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Non binder, without OH or NH2
group by Estrogen Receptor Binding
Domain
logical expression index: "j"
Referential
boundary: The
target chemical should be classified as Non binder, impaired OH or NH2
group OR Non binder, MW>500 OR Non binder, non cyclic structure by
Estrogen Receptor Binding
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as No alert found by Protein
binding by OASIS v1.3
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 >> alpha,beta-Carbonyl compounds
with polarized double bonds OR Michael Addition >> Polarised Alkenes OR
Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl
pyridines, pyrazines, pyrimidines or triazines OR SN2 OR SN2 >>
Interchange reaction with sulphur containing compounds OR SN2 >>
Interchange reaction with sulphur containing compounds >> Thiols and
disulfide compounds by Protein binding by OASIS v1.3
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Bioavailable by Lipinski Rule
Oasis ONLY
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Group 14 - Carbon C AND Group 15
- Nitrogen N AND Group 16 - Oxygen O by Chemical elements
Domain
logical expression index: "o"
Referential
boundary: The
target chemical should be classified as Group 14 - Metalloids Si,Ge OR
Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements
Domain
logical expression index: "p"
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 CN Aqueous Solubility < 0.1 g/L by Skin
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "q"
Referential
boundary: The
target chemical should be classified as Group CN log Kow > 4.5 OR Group
CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion
rules by BfR
Domain
logical expression index: "r"
Similarity
boundary:Target:
Cc1cc(OC)ccc1Nc1ccccc1
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "s"
Referential
boundary: The
target chemical should be classified as Alkylarylether AND Amine AND
Aromatic compound AND Ether AND Secondary amine AND Secondary aromatic
amine by Organic functional groups, Norbert Haider (checkmol) ONLY
Domain
logical expression index: "t"
Referential
boundary: The
target chemical should be classified as Alkylarylether AND Amine AND
Aromatic compound AND Ether AND Secondary amine AND Secondary aromatic
amine by Organic functional groups, Norbert Haider (checkmol) ONLY
Domain
logical expression index: "u"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] AND
Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic
Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND
Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or
=C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups
(US EPA) ONLY
Domain
logical expression index: "v"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] AND
Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic
Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND
Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or
=C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups
(US EPA) ONLY
Domain
logical expression index: "w"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] AND
Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic
Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND
Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or
=C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups
(US EPA) ONLY
Domain
logical expression index: "x"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] AND
Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic
Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND
Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or
=C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups
(US EPA) ONLY
Domain
logical expression index: "y"
Referential
boundary: The
target chemical should be classified as Aliphatic Carbon [CH] AND
Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic
Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND
Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or
=C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups
(US EPA) ONLY
Domain
logical expression index: "z"
Referential
boundary: The
target chemical should be classified as Alkylarylether AND Amine AND
Aromatic compound AND Ether AND Secondary amine AND Secondary aromatic
amine by Organic functional groups, Norbert Haider (checkmol) ONLY
Domain
logical expression index: "aa"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 3.17
Domain
logical expression index: "ab"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 4.63
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Various studies have been investigated for assessing the dermal sensitization potential of 4-methoxy-2-methyl-N-phenylaniline to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs along with predicted data for target chemical and its structurally similar read across substances, Methyl 2-naphthyl ether[CAS: 93-04 -9] and Ethyl 2-naphthyl ether [CAS: 93-18-5].The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.
The skin sensitization potential of 4-methoxy-2-methyl-N-phenylaniline was estimated by SSS (2018) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. 4 -methoxy-2-methyl-N-phenylaniline was predicted to be not sensitizing to the skin of female guinea pigs.
This is supported by the results of an Open Epicutaneous Test (OET) performed (Curr. Probl. Derm., vol.14, pp.152-171 (Karger, Basel 1985)) on guinea pigs to assess the skin sensitization potential of structurally similar read across substance, Ethyl 2-naphthyl ether [CAS: 93-18-5]. On day 1 during induction, 0.1 ml of the Ethyl 2-naphthyl ether was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h. It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 2%.Thus the chemical, Ethyl 2-naphthyl ether (CAS No. 93-18-5) was considered to be not sensitizing on skin of guinea pigs at concentration of 2% in an Open Epicutaneous Test (OET).
The above results are supported by the experimental study summarized in Food and Cosmetics Toxicology,Vol. 13, Pg. 885, 1975 for the structurally similar read across substance, Methyl 2-naphthyl ether[CAS: 93-04-9]. Methyl 2-naphthyl ether 4% in petrolatum was applied to the skin of 26 human volunteers and observed for signs of dermal sensitization (duration not mentioned).
Methyl 2-naphthyl ether did not cause any adverse reactions to the skin of humans. Hence, methyl 2-naphthyl ether can be considered to be not sensitizing to skin.
Based on the available data for the target and read across substances and applying the weight of evidence approach, 4-methoxy-2-methyl-N-phenylaniline can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.”
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Available data for 4-methoxy-2-methyl-N-phenylaniline suggests that it is not likely to cause any dermal sensitization to skin.
4-methoxy-2-methyl-N-phenylaniline can be considered to be not sensitizer to skin and can be classified under the category “Not Classified” as per CLP regulation.
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