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EC number: 202-823-2 | CAS number: 100-15-2
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 13.02.2008 - 22.02.2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study (OECD ) and in compliance with GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- N-methyl-4-nitroaniline
- EC Number:
- 202-823-2
- EC Name:
- N-methyl-4-nitroaniline
- Cas Number:
- 100-15-2
- Molecular formula:
- C7H8N2O2
- IUPAC Name:
- N-methyl-4-nitroaniline
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): N-Methyl-4-nitroaniline
- Physical state: yellow to orange crystalline substance or powder
- Analytical purity: 99.3%
- Purity test date: 06 February 2008 date of CoA
- Lot/batch No.: 304269
- Expiration date of the lot/batch: 30 November 2008
- Storage condition of test material: At room temperature in the dark (ambient humidity)
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- 100, 300, 1000, 3000 and 5000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used:DMSO
Controls
- Untreated negative controls:
- yes
- Remarks:
- Dimethylsulfoxide (DMSO)
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- mitomycin C
- other: 2-Aminoanthracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: soft agar
DURATION
- Exposure duration: 2 days (TA 102: 3 days)
NUMBER OF REPLICATIONS: 3 - Evaluation criteria:
- A reproducible, concentration-dependent increase in the number of revertants of at least one
tester strain over the vehicle control value and/or outside the historical control range is
indicative of genotoxic activity. Since the results were unequivocal, no detailed statistical
evaluation was performed.
Assay acceptance criteria
All tester strains of S. typhimurium exhibited a characteristic number of spontaneous
revertants per plate. The historical control ranges are based on ca 100 experiments conducted
in our laboratory (not filed in the raw data). In the absence of a distinct difference between
non-activation and activation, the mean control values were combined and given as ranges:
TA 1535: 5-22
TA 1537: 3-39
TA 98: 16-68
TA 100: 49-164
TA 102: 249-531
Results and discussion
Test results
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥3000 μg/plate
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
SOLUBILITY AND TOXICITY
N-Methyl-4-nitroaniline precipitated and was bacteriotoxic primarily at concentrations ≥3000 μg/plate.
MUTAGENICITY
The OD600 of the individual overnight bacterial cultures varied between 2.04 and 2.84 (raw
data). These values correspond to a bacterial titer of ca 100 millions/0.1 mL.
N-Methyl-4-nitroaniline induced a concentration-dependent increase in the number of mean
revertants in S. typhimurium TA 98 starting at 300 μg/plate with and without S9 mix. The
increase was 4-5-fold at 1000 μg/plate. In addition, there was a 4-fold increase in the number
of revertants in strain TA 1537 at 1000 μg/plate in absence of S9 mix. No mutagenic
response was seen in the strains TA 1535, TA 100 and TA 102. In view of the clear
mutagenic response in TA 98 and TA 1537, no repeat experiment was performed. However,
the Ames test is known to be oversensitive for aromatic nitro compounds and therefore,
further investigations are needed to evaluate the biological relevance of this in vitro result.
The validity of this study is given since the vehicle control plates showed spontaneous
revertants in different tester strains of S. typhimurium at frequencies similar to those
described in the literature and within the historical control range experienced in our
laboratory. The diagnostic mutagens NaN3, 9-AA, 2-NF, MMC and 2-AA showed the
expected strain specific responses in the absence and presence of a metabolic activation
system.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
positive
N-Methyl-4-nitroaniline, an intermediate in the synthesis of BIBF 1120 ES, induced a
concentration-dependent increase in the number of revertants in S. typhimurium strain TA 98
starting at 300 μg/plate with and without metabolic activation. There was also a clear increase
at 1000 μg/plate in strain TA 1537 without metabolic activation. Therefore, it was concluded
that N-Methyl-4-nitroaniline induces frameshift mutations in the Ames test when tested up to
insoluble and bacteriotoxic concentrations and has to be classified as "Ames positive" under
the conditions of this study. Nevertheless, in view of the oversensitivity of the Ames test for
aromatic nitro compounds, the biological relevance still needs to be determined in an in vivo
experiment
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