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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
Key value for chemical safety assessment
Effects on fertility
Description of key information
Toxicity to reproduction
The reproductive toxicity of 4-methoxy-2-methyl-N-phenylaniline (41317-15-1)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and NOAEL was estimated to be 952.77mg/kg bw.When male and female Sprague-Dawleyratswere exposed with 4-methoxy-2-methyl-N-phenylaniline (41317-15-1) orally. Thus, based on the above predictions and experimental study of4-methoxy-2-methyl-N-phenylaniline (41317-15-1)) and its structurally similar read across substance, No Observed Adverse Effect Level (NOAEL) was considered to be 952.77mg/kg bw Thus, comparing this value with the criteria of CLP regulation4-methoxy-2-methyl-N-phenylaniline (41317-15-1)cannot be classified as reproductive toxicant.
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- 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:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- Prediction was done using OECD QSAR toolbox v3.3, 2018
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
- 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 - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- No data available
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- other: NOT_SPECIFIED
- Vehicle:
- not specified
- Details on exposure:
- No data available
- Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 10 weeks
- Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
- Dose / conc.:
- 952.77 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- No data available
- Control animals:
- not specified
- Details on study design:
- No data available
- Positive control:
- No data available
- Parental animals: Observations and examinations:
- No data available
- Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- No data available
- Postmortem examinations (parental animals):
- No data available
- Postmortem examinations (offspring):
- No data available
- Statistics:
- No data available
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 952.77 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- reproductive performance
- Remarks on result:
- other: overall no effects on reproductive parameters
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 952.77 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- viability
- body weight and weight gain
- Remarks on result:
- other: overall no developmental toxic effects observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- In reproductive toxicity study, NOAEL was estimated to be 952.77mg/kg bw. When male and female Sprague-Dawley rats were exposed with 4-methoxy-2-methyl-N-phenylaniline (41317-15-1) orally.
- Executive summary:
The reproductive toxicity of 4-methoxy-2-methyl-N-phenylaniline (41317-15-1)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and NOAEL was estimated to be 952.77mg/kg bw.When male and female Sprague-Dawleyratswere exposed with 4-methoxy-2-methyl-N-phenylaniline (41317-15-1) orally.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
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 ("o"
and "p" )
)
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
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 >> Polycyclic
(PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR
Michael addition >> Polarised Alkenes-Michael addition OR Michael
addition >> Polarised Alkenes-Michael addition >> Alpha, beta-
unsaturated ketones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >>
Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs)
aromatic hydrocarbons-SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >>
Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as No alert found by DNA binding by
OASIS v.1.3
Domain
logical expression index: "h"
Referential
boundary: The
target chemical should be classified as SN1 OR SN1 >> Alkylation after
metabolically formed carbenium ion species OR SN1 >> Alkylation after
metabolically formed carbenium ion species >> Polycyclic Aromatic
Hydrocarbon Derivatives OR SN2 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 by
DNA binding by OASIS v.1.3
Domain
logical expression index: "i"
Referential
boundary: The
target chemical should be classified as Basesurface narcotics by Acute
aquatic toxicity MOA by OASIS ONLY
Domain
logical expression index: "j"
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 Eye
irritation/corrosion Exclusion rules by BfR
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as Group All Aqueous Solubility <
0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All
log Kow > 9 OR Group C Aqueous Solubility < 0.0001 g/L OR Group C
Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group
C Molecular Weight > 380 g/mol by Eye irritation/corrosion Exclusion
rules by BfR
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as Known precedent reproductive and
developmental toxic potential AND Toluene and small alkyl toluene
derivatives (8a) by DART scheme v.1.0
Domain
logical expression index: "m"
Referential
boundary: The
target chemical should be classified as Di-substituted hydrocarbons
(24b) by DART scheme v.1.0
Domain
logical expression index: "n"
Referential
boundary: The
target chemical should be classified as Alkyl arenes AND Aromatic amine
AND Aryl AND Ether AND Precursors quinoid compounds by Organic
Functional groups ONLY
Domain
logical expression index: "o"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 2.62
Domain
logical expression index: "p"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 4.55
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 952.77 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2018)
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity
In different studies4-methoxy-2-methyl-N-phenylaniline (41317-15-1)has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for4-methoxy-2-methyl-N-phenylaniline (41317-15-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies performed on structurally similar read across substance.
The reproductive toxicity of 4-methoxy-2-methyl-N-phenylaniline (41317-15-1)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and NOAEL was estimated to be 952.77mg/kg bw. When male and female Sprague-Dawley rats were exposed with 4-methoxy-2-methyl-N-phenylaniline (41317-15-1)orally.
Further supported by experimental study conducted byGESTIS(IFA, Institute for Occupational Safety and Health of the German Social Accident Insurance) on structurally similar read across substance Diphenyl ether(101-84-8) .Reproductive and development toxicity study of Diphenyl ether(101-84-8) was performed on mated female Sprague Dawley rats according to OECD Test Guideline 414. The test material73.5%Diphenyl ether & 26.5% biphenyl mixed in corn oil at volume of 5 ml/kg were administered in dose concentration 0,50, 200, 500 mg/kg/day on gestation days 6-15by oral gavage route. .96 rats were divided as 24 rats /dose group. Animals was checked daily for clinical signs. Food consumption and body weight were recorded; the dams were sacrificed and subjected to a macroscopic examination. Approximately 1/2 of the fetuses in each litter were processed for soft-tissue evaluations while the other half for skeletal evaluations. Statistical evaluation of equality of means was made by the appropriate one-way analysis of variance technique (ANOVA) for parametric procedures and Kruskal-Wallis test for nonparametric procedures were used after applying Bartlett's test for determination of equal variance. Statistical tests for trend, using either standard regression techniques (parametric cases) or Jonckheere's test in nonparametric cases. Levels of statistical significance used were either p<0.05 or p<0.01. Two deaths occurred at 500 mg/kg. Statistically reduced maternal weight gain and food consumption were observed at 200 and 500 mg/kg/d. Excessive alopecia, salivation and/or anogenital staining was observed but no pattern of treatment relationship could be determined. No effects observed on fetal resorptions, fetal viability, postimplantation loss or total implantations. Mean litter weights in treated and control groups were similar. No significant increases were observed in incidence of malformations or variations at any treatment level. Therefore No Observed Adverse Effect Level (NOAEL) for maternal toxicity was considered to be 50 mg/kg/day, and No indications of any influence on reproductive parameters or damage to reproductive organs were found and No developmental toxic effects were seen up to the highest dose of 500 mg/kg bw. Hence the dose-level of 500 mg/kg/day was considered to be the NOAEL for embryo-foetal toxicity and reproductive toxicity .When female Sprague Dawley rats were treated with Diphenyl ether(101-84-8)orally.
Thus, based on the above predictions and experimental study of4-methoxy-2-methyl-N-phenylaniline (41317-15-1)) and its structurally similar read across substance, No Observed Adverse Effect Level (NOAEL) was considered to be 952.77mg/kg bw Thus, comparing this value with the criteria of CLP regulation4-methoxy-2-methyl-N-phenylaniline (41317-15-1)cannot be classified as reproductive toxicant
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Thus, comparing this value with the criteria of CLP regulation4-methoxy-2-methyl-N-phenylaniline (41317-15-1)cannot be classified as reproductive toxicant.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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