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EC number: 202-951-9 | CAS number: 101-54-2
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP and guideline study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
- Reference Type:
- publication
- Title:
- Developmental toxicity studies in rats with 4-aminodiphenylamine (4-ADPA) and 4-nitrodiphenylamine (4-NDPA).
- Author:
- Bannister RM, Brewster DW, Rodwell DE, Schroeder RE, Barnett JW Jr
- Year:
- 1 992
- Bibliographic source:
- The Toxicologist 12: 103
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 1 989
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.4900 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- N-(4-aminophenyl)aniline
- EC Number:
- 202-951-9
- EC Name:
- N-(4-aminophenyl)aniline
- Cas Number:
- 101-54-2
- Molecular formula:
- C12H12N2
- IUPAC Name:
- N1-phenylbenzene-1,4-diamine
- Details on test material:
- IUCLID4 Test substance: other TS: purity 98.6 %
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Sprague-Dawley derived CD
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- yes
- Details on mating procedure:
- mating ratio 1:1
- Duration of treatment / exposure:
- day 6-15 of gestation
- Frequency of treatment:
- once daily
- Duration of test:
- termination on GD 20
- No. of animals per sex per dose:
- 24 dams
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Sex: female
Duration of test: day 20 of gestation
Results and discussion
Results: maternal animals
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
RS-Freetext:
MATERNAL TOXIC EFFECTS BY DOSE LEVEL:
- Mortality and day of death: none
- Number pregnant per dose level: 100 %, 91.7 %, 91.7 %,
100 % (0, 10, 50, 100 mg/kg bw/d)
- Number of resorptions: no effects
- Number of implantations: no effects
- Pre and post implantation loss: no effects
- Number of corpora lutea: no effects
- Duration of Pregnancy: no effects
- Body weight: 100 mg/kg: weight gain significantly lower
during early dosing (GD 6-11 and entire gestation period
GD 6-15); on GD 11-13 and 13-15 and pre- and
post-treatment weight gain comparable to controls;
corrected body weight on GD 20 (gravid uterine weight
subtracted) was comparable among all groups.
- Food consumption: significantly reduced at 100 mg/kg
during early dosing on GD 6-11, 26 % lower than control
value; for all other time intervals and doses comparable
to controls
- Description, severity, time of onset and duration of
clinical signs:
excessive salivation in all groups with dose relationship:
2/24, 8/24, 17/24, 24/24;
100 mg/kg: staining of the skin/fur in the anogenital
region and/or soft stool with increasing frequency during
dosing period
- Hematological findings incidence and severity: no data
- Clinical biochemistry findings incidence and severity: no
data
- Gross pathology incidence and severity: no effects
- Organ weight changes: 100 mg/kg: gravid uterine weight
significantly reduced
FETAL DATA:
- Litter size and weights: litter size no effect;
fetal weight: 100 mg/kg: significant reduction for both
sexes and all fetuses
- Number viable: 100 % at 0, 50 and 100 mg/kg; at 10 mg/kg:
14/15 in 1 litter, all other litters 100 %
- Sex ratio: no effects
- Grossly visible abnormalities:
- non significant increase of external variations in
fetuses resp. litters: 0 %, 0 %, 0.3 % resp. 4.3% (1/315 fetuses evaluated resp. 1/23 litters evaluated), 1.0 % resp. 4.5% (3/300 fetuses evaluated resp. 1/22 litters evaluated: glassy shiny
- appearance due to thin skin of these developmentally
retarded fetuses)
- non significant increase of external abnormalities in fetuses resp. litters:
0 % (0/334), 0 % (0/308), 0.3 % resp. 4.3% (1/315:
fetuses evaluated resp. 1/23 litters evaluated: edematous), 1.0 % resp. 13.6%
(3/300 fetuses evaluated resp. 3/22 litters evaluated: micrognathia, exencephaly, absence of eye bulge,
edema in cervical and thoracic region)
- Soft tissue abnormalities:
non significant increase of visceral malformations in fetuses resp. litters:
0 % (0/174), 0.6 % resp. 4.5% (1/160 fetuses evaluated resp. 1/22 litters evaluated); 0 % (0/165); 2.5 % resp. 13.6% (4/157 fetuses evaluated resp. 3/22 litters evaluated) (all dissimilar malformations);
visceral variations:
Fetal incidences (the groups differ significantly (p <= 0.05); the response is linearly related to the dose levels (p <= 0.05):
4.6 % (8/174), 1.3 % (2/160), 5.5 % (9/165),
9.6 % (15/157) (specific changes within historical
control range)
Litter incidence (no statistical differences among groups)
33.3% (8/24), 9.1% (2/22), 34.8% (8/23), 27.3% (6/22)
- Skeletal abnormalities:
skeletal malformations: significant increase at 100 mg/kg
both on a per litter and a per fetus basis: 0.6 % resp. 4.2% (1/159 fetuses evaluated resp. 1/24 litters evaluated, wavy rib), 0 % resp. 0% (0/147 fetuses evaluated resp. 0/22 litters evaluated), 0 % resp. 0% (0/150 fetuses evaluated resp. 0/23 litters), 27.6 % resp. 63.6% (40/145 fetuses evaluated resp. 14/22 litters evaluated);
types of defects: wavy rib (26 resp. 12), fused rib, vertebral defects
skeletal variations: significant decrease at 10 mg/kg,
significant increase at 100 mg/kg on per fetus basis; the statistical evaluation on per litter basis was not tested due to lack of variance : 87.4 % resp. 100 % (139/159 fetuses evaluated resp. 24/24 litters evaluated),
76.2 % resp. 100 % (112/147 fetuses evaluated resp. 22/22 litters evaluated), 84.7 % resp. 100 % (127/150 fetuses evaluated resp. 23/23 litters evaluated), 97.2 % resp. 100 % (141/145 fetuses evaluated resp. 22/22 litters evaluated);
at 100 mg/kg generally increased retardation of
ossification as a fetotoxic effect
STATISTICAL RESULTS:
maternal effects: 100 mg/kg: significant reduction of body
weight gain during GD 6-11 resulting from significant
reduction of food consumption; significant reduction of
gravid uterine weight.
fetal effects: 100 mg/kg: significant reduction of fetal
weight for both sexes and all fetuses; significant increase
of skeletal malformations and variations (most prevalent findings were wavy ribs, fused ribsm vertebral defects and ossification variations)
Applicant's summary and conclusion
- Conclusions:
- CL-Freetext:
Signs of maternal toxicity at 100 mg/kg bw were significantly depressed weight gain and food consumption during the early dosing period (GD 6-11) and a significant reduction of gravid uterine weight. A significant reduction of fetal weight and an increased incidence of skeletal malformations (e.g. wavy ribs, fused ribs, vertebral defects and ossification variations) were considered to be associated with maternal toxicity. Increased incidences of fetotoxic or developmental effects were not observed in the absence of maternal toxicity (at 10 or 50 mg/kg bw and day). - Executive summary:
In another developmental toxicity study by the same laboratory, groups of 24 pregnant CD® rats were exposed to 10, 50 or 100 mg/kg bw/d by gavage from gestational day 6 to 15. Reported clinical signs were excessive salivation in all groups with a dose relationship and in the highest dose group staining of the skin/fur in the anogenital region and soft stool with increasing frequency during the dosing period. At 100 mg/kg bw/d, the weight gain was significantly decreased and the food consumption of dams was 26% lower than that of the controls during early dosing on gestation day 6 to 11. The significant reduction in weight gain and the decrease in food consumption were considered clear signs of maternal toxicity. Mean number of viable foetuses, implantation sites and number of corpora lutea were comparable for the treatment and the control groups. A significant reduction in foetal weights in the high dose animals was indicative of a fetotoxic effect. An increased incidence of skeletal malformations and variations were restricted to the high dose group. The most prevalent findings were wavy ribs, fused ribs, vertebral defects and ossification variations. These findings were considered to be associated with maternal toxicity. At dose levels where no overt toxicity was seen, similar rib and vertebral defects were not seen. The NOAEL both for maternal and developmental effects was 50 mg/kg bw/d (Monsanto Co 1989).
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