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EC number: 201-990-9 | CAS number: 90-41-5
- 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
Carcinogenicity
Administrative data
Description of key information
The Low Observed Adverse Effect Level (LOAEL) in male/female F344/N rats is found to be 10000 ppm (500 mg/Kg bw/day) while the NOAEL was reported to be 150 mg/kg bw/day.
Administration of 2-biphenylamine resulted in the formation of erythroid hyperplasia and transitional cell hyperplasia in male and female rats. Hyperplasia is defined as the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells, often as an initial stage in the development of cancer. Thus, the chemical is likely to be a suspected human carcinogen which is in line with the Harmonized classification of Carcinogen Category 2 within the CLP regulation.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer reviewed journal
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- 13 week chronic study was conducted to evaluate the carcinogenic effects of 2-Biphenylamine on Mice.
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Source: Frederick Cancer Research Center (Frederick, MD)
- Age at study initiation: 5 weeks old
- Weight at study initiation: No data available
- Housing: Five per cage in polycarbonate cages and covered with nonwoven polyester filter sheets containing Aspen Bed and Beta chips
- Diet: ad libitum Wayne Lab Blox® meal, Allied Mills, Inc. (Chicago, IL). ad libitum
- Water: ad libitum - Tap water via Edstrom Automatic Watering System, Edstrom Industries (Waterford, WI)
- Acclimation period:1 week
ENVIRONMENTAL CONDITIONS
Temperature: 17.2°-32.2°C.
- Humidity (%): Humidity uncontrolled.
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): Fluorescent lighting provided 12 hours per day. - Route of administration:
- oral: feed
- Vehicle:
- other: Diet
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): Single preparation was made
- Mixing appropriate amounts with (Type of food): Wayne Lab Blox® feed
- Storage temperature of food: at 4°C
VEHICLE
- Justification for use and choice of vehicle (if other than water): Wayne Lab Blox® feed - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis was performed by vapor-phase chromatographic method
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- Daily
- Remarks:
- Doses / Concentrations:
0, 300, 1,000, 3,000, 10,000 and 30,000 ppm (0, 50, 166.7, 500, 1666.7 and 5000 mg/kg/day)
Basis:
nominal in diet - No. of animals per sex per dose:
- Total: 120
0 ppm: 10 male, 10 female
300 ppm: 10 male, 10 female
1000 ppm: 10 male, 10 female
3000 ppm: 10 male, 10 female
10000 ppm: 10 male, 10 female
30000 ppm: 10 male, 10 female - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Rationale for animal assignment (if not random): Animal were assigned to test groups so that average cage weights approximately equal for all animals of same sex and species.
- Positive control:
- No data available
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations checked in table [No.?] were included. Mortality and morbidity
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly
BODY WEIGHT: Yes
Time schedule for examinations: Weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, Weekly
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the completion of 1, 4, and 13 weeks of chemical administration
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: All animals
- Parameters checked in table [No.?] were examined. White cell count, hemoglobin, red blood cell count, hematocrit, neutrophils and differential leucocyte
counts - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
All tissues were fixed for a minimum of 48 hours in 10% neutral buffered formalin, embedded in parablast, sectioned, and stained with hematoxylin and eosin. Selected kidneys were cut in 4 µ sections and stained with VonKossa, Mallory trichrome, MacManus-PAS, or Prussian blue solutions.
Tissues examined included: skin, mandibular lymph node, mammary gland, salivary gland, thigh muscle, sciatic nerve,
sternebrae including marrow, costochondral junction (rib), thymus, larynx, trachea, lungs and bronchi, heart, thyroids, parathyroid, lymph nodes, esophagus, stomach, duodenum,
jejunum, ileum, colon, cecum, rectum, mesenteric lymph node, liver, pancreas, spleen, kidneys, adrenal, urinary bladder, seminal vesicles, prostate, testes, ovaries, uterus, brain, pituitary, spinal cord, and eyes. - Other examinations:
- Tissues examined included: skin, mandibular lymph node, mammary gland, salivary gland, thigh muscle, sciatic nerve,
sternebrae including marrow, costochondral junction (rib), thymus, larynx, trachea, lungs and bronchi, heart, thyroids, parathyroid, lymph nodes, esophagus, stomach, duodenum,
jejunum, ileum, colon, cecum, rectum, mesenteric lymph node, liver, pancreas, spleen, kidneys, adrenal, urinary bladder, seminal vesicles, prostate, testes, ovaries, uterus, brain, pituitary, spinal cord, and eyes. - Statistics:
- For the hematology data, Jonckeere's test was employed to assess the significance of dose response trend-so When a significant trend was detected, pairwise comparisons between dosed and control animals were made by the Mann-Whitney U-test.
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- 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:
- effects observed, treatment-related
- Description (incidence and severity):
- HAEMATOLOGY Significant (P < 0.001) dose-related decreases in hemoglobin concentration and red blood cells were observed in both male and female rats examined at weeks 1,4, and 13.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Splenic enlargement was noted in male and female mice fed 30000 ppm
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Splenomegaly was observed in all rats fed 30,000 ppm and in 8/10 males and 2/ 10 females fed 10,000 ppm.
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Erythroid hyperplasia in bone marrow was seen in 10/ 10 females and 9/10 males receiving 30,000 ppm and in 9/10 females and 7/10 males receiving 10,000 ppm.
- Details on results:
- MORTALITY: One male rat from the group receiving 300 ppm and five female rats receiving 30,000 ppm died on day 26. All five females were from the same cage and were found dead on the same day, suggesting that the deaths were not chemical-related.
BODY WEIGHT AND WEIGHT GAIN- compound-related depression in the mean body weight gains was observed. The maximum depression in body weight gain relative to controls
was observed at 30,000 ppm, amounting to 47.6% for males and 38.9% for females - Dose descriptor:
- LOAEL
- Effect level:
- 500 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Test material provided through oral feed resulting in the formation of hyperplasia
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effects observed at this dose
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
- Conclusions:
- The Low Observed Adverse Effect Level (LOAEL) in male/female F344/N rats is found to be 10000 ppm (500 mg/Kg bw/day) while the NOAEL was reported to be 150 mg/kg bw/day
- Executive summary:
The chronic carcinogenicity study was conducted with 2-biphenylamine by feeding diets containing 00, 300, 1,000, 3,000, 10,000 and 30,000 ppm (0, 15, 50, 150, 500 and 1500 mg/kg/day) test compound to groups of 10/10 male/female F344/N rats for 13 weeks. Groups of 10 rats of each sex served as controls.
Administration of 2-biphenylamine resulted in the formation of erythroid hyperplasia and transitional cell hyperplasia in male and female rats.
The Low Observed Adverse Effect Level (LOAEL) in male/female F344/N rats is found to be 10000 ppm (500 mg/Kg bw/day) while the NOAEL was reported to be 150 mg/kg bw/day
Reference
HAEMATOLOGY
Significant (P < 0.001) dose-related decreases in hemoglobin concentration and red blood cells were observed in both male and female rats examined at weeks 1,4, and 13. Leucocyte count was markedly (P < 0.001) increased in both
male and female rats at weeks 1 and 4, but this trend had diminished by week 13. This diminishing trend in leucocyte count with time may be due to activation of a hemeostatic mechanism in these animals. Hematocrit levels showed no consistent effect, although there was some evidence of a dose-related decrease in female rats at week 1 (P < 0.05) and week 13 (P<0.001).
HISTOPATHOLOGY: NON-NEOPLASTIC
Splenomegaly was observed in all rats fed 30,000 ppm and in 8/10 males and 2/ 10 females fed 10,000 ppm. Hemosiderosis, congestion, and extramedullary hematopoiesis were found in the spleens of 9/10 or 10110 of each group of rats receiving 3,000 ppm or more and in females receiving 1,000 ppm or more of 2-biphenylamine.
Renal effects in rats receiving 30,000 ppm technical-grade 2-biphenylamine included cystic tubular degeneration and papillary necrosis (9/10 or 10/ 10 rats of each sex), interstitial fibrosis (all males and 4/10 females), and chronic nephritis (all males and 4110 females).
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 150 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Data is from peer reviewed journal.
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Additional information
Studies for carcinogenicity from reliable sources having Klimisch rating 2 were reviewed for the target and read across chemical
The summary of the results are presented below:
Sr. No |
End point |
Value |
Species |
Route |
Effects |
Remarks |
1 |
NOAEL |
166.7 mg/kg bw/d |
Mouse |
Oral |
No adverse effects due to the test chemical |
Experimental data for target CAS 90-41-5 |
2 |
LOAEL |
500mg/kg bw/d |
Mouse |
Oral |
Test material provided through oral feed resulting in the formation of hyperplasia |
Experimental data for target CAS 90-41-5 |
3 |
NOAEL |
150 mg/kg bw/d |
Rat |
Oral |
No adverse effects due to the test chemical |
Experimental data for target CAS 90-41-5 |
4 |
LOAEL |
500 mg/kg bw/d |
Rat |
Oral |
Test material provided through oral feed resulting in the formation of hyperplasia |
Experimental data for target CAS 90-41-5 |
5 |
LOAEL |
50 mg/ kg bw/ d |
Mouse |
Oral: feed |
Neoplastic in females and ambiguous results in males. |
Experimental data for RA CAS: 2185-92-4 |
6 |
NOEL
|
150 mg/ kg bw/ d |
Rat |
Oral: feed |
Clinical signs, body weight, mortality and carcinogenic effects if any observed in control and dosed rats |
Experimental data for RA CAS: 2185-92-4 |
Based on the studies summarized in the above table it can be observed that the read across substance is found to be carcinogenic in female mice whereas it is non-carcinogenic in rats and male mice.
Justification for selection of carcinogenicity via oral route endpoint:
The Low Observed Adverse Effect Level (LOAEL) in male/female F344/N rats is found to be 10000 ppm (500 mg/Kg bw/day) while the NOAEL was reported to be 150 mg/kg bw/day.
Administration of 2-biphenylamine resulted in the formation of erythroid hyperplasia and transitional cell hyperplasia in male and female rats.
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