Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 202-992-2 | CAS number: 101-96-2
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: according to OECD guideline, GLP
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted 1981-05-12
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- other: EC Guideline 84/449/EC, J. of Eur. Publ. L251, 1984-09-19
- Deviations:
- not specified
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- N,N'-di-sec-butyl-p-phenylenediamine
- EC Number:
- 202-992-2
- EC Name:
- N,N'-di-sec-butyl-p-phenylenediamine
- Cas Number:
- 101-96-2
- Molecular formula:
- C14H24N2
- IUPAC Name:
- N,N'-di-sec-butyl-p-phenylenediamine
- Details on test material:
- - Name of test material (as cited in study report): Kerobit BPD, N,N'-Di-sec.-butyl-p-phenylene diamine
- Physical state: reddish liquid
- Analytical purity: 98.8%
- Lot/batch No.: from continuous production of 1990-12-20, 13.30h
- Expiration date of the lot/batch: no limit when stored under nitrogen
- Storage condition of test material: room temperature, absence of light and under nitrogen
The test substance was administered as its hydrochloride salt. See section "preparation of dosing solutions".
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 6 weeks
- Weight at study initiation: average 186.75 g for males, average 140.7 for females
- Housing: suspended stainless steel cages fitted with wire mesh floor and front, in groups of 5, separated by sex
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: From: 1992-03-31 To: 1992-05-10
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: diluted aqueous HCl, adjusted to pH c. 3.8 using NaOH
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The top dose dilution was prepared by dissolving 0.6 g Kerobit BPD in 30 mL 0.2N HCl. Then 160 mL demineralized water was added and the pH was adjusted to 3.8 using 4N NaOH. Finally the dilution was made up to 200 mL with demineralized water. The top dose thus contained 0.6 g Kerobit BPD per 200 mL diluted HCl. The lower dose dilutions were prepared by diluting the top dose solution with demineralized water. If necessary, the pH was adjusted to the same pH value as the top dose dilution with either 4N NaOH or 2N HCl. The demineralized water and the 0.3N HCl solutions were saturated with argon prior to use to supersede oxygen. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Spectra of solutions of Kerobit BPD were run on a Varian Cary 219 UV spectrometer from 700 nm to 200 nm.
The actual concentrations of the Kerobit BPD solutions are close to the nominal concentrations. - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 3, 10 and 30 mg/kg
Basis:
other: nominal, dosed by gavage as a solution in diluted aqueous HCl.
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: dose levels were selected on the basis of a preceding oral (5-day) range-finding study with Kerobit BPD in rats (TNO-report v91.572, dated November, 1992 and amendment I to report v91.572, dated March, 1994)
data owner: BG Chemie (Berufsgenossenschaft Chemie)
data submitter has letter of access
Doses of 0, 10, 30 and 100 mg / kg body weight were administered daily for 5 consecutive days to groups of 5 male and 5 female rats. The test substances induced a number of changes in the top-dose group like a higher incidence of alopecia, growth retardation, in males associated with decreased food intake and food conversion efficiency and effects on red blood cell system, lymphocytes, clotting parameters and plasma clinical chemistry variables. Moreover in both sexes the relative liver weight was increased whereas the relative weight of the thymus was decreased in males. A number of these changes viz. effect on clotting parameters, clinical chemistry parameters and organ weights were also observed in the mid-dose group. Whether the intercurrent death of one female of the top-dose group has to be considered of toxicological significance is unclear since it can not be excluded that the cause of death is due to faulty dosing. Pathological examination of the animal (lungs) could not be performed anymore due to cannibalism.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least daily (2x on working days, 1x on weekend days)
CLINICAL OBSERVATIONS: All abnormalities, signs of ill health or reaction to treatment were recorded
BODY WEIGHT: Yes
- Time schedule for examinations: initially before the experiment and weekly thereafter
FOOD CONSUMPTION: Yes
- Food consumption for each cage was determined and mean daily diet consumption calculated as g food/rat/day
FOOD EFFICIENCY: Yes
- The efficiency of food utilization was calculated and expressed as gram weight gain per gram food consumed
WATER CONSUMPTION: Yes
- Time schedule for examinations: water bottles were weighted daily during day 1-7 (week 1) and during day 15-21 (week 3)
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 25
- Animals fasted: Yes
- How many animals: 27
- Examined parameters: haemoglobin concentration, percentage methaemoglobin, packed cell volume, red blood cell count, red blood cell distribution width, total white blood cell count, differential white blood cell count, prothrombin time, thrombocyte count, reticulocyte count, Heinz body count, mean platelet volume, platelet distribution width, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 25 and day 28
- Animals fasted: Yes
- How many animals: 27
- Examined parameters: alkaline phosphatase activity, aspartate aminotransferase activity, alanine aminotransferase acitivity, gamma glutamyl transferase activity, total protein, albumin, albumin/globulin ratio, urea, creatinine, bilirubin total, sodium (Na), potassium (K), calcium (Ca), chloride (Cl), inorganic phosphate, total cholesterol, triglycerides
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
All surviving rats were killed on day 28 in such a sequence that on the average the time of killing was about the same for each group. The animals were anaesthetized by ether, bled to death by cannulating the abdominal aorta and then examined grossly for pathological changes. Samples of the following tissues and organs of all animals were preserved in a neutral, aqueous, phosphate-buffered, 4% solution of formaldehyde: all gross lesions, adrenals, heart, kidneys, liver, ovaries, spleen, testes, thymus, thyroid (with parathyroids), urinary bladder, oesophagus and stomach.
The following organs of all surviving animals were weighed: adrenals, kidneys, liver, spleen, testes and thymus.
The tissues required for microscopic examination were embedded in paraffin wax, sectioned at 5 microm and stained with haematoxylin and eosin. Histological examination was performed on the liver, kidneys, spleen, adrenals and heart in all rats of the control group and the top-dose group.
Histopathological examination of the liver was extended to rats of mid- and low-dose groups because treatment-related microscopic changes were found in the top-dose group. - Statistics:
- Body weights were evaluated by one-way analysis of co-variance followed by Dunnett's multiple comparison tests. Haematological variables (except for those mentioned below), clinical chemistry values and organ weights were evaluated by one-way analysis of variance (ANOVA), followed by Dunnett's multiple comparison tests. Differential white blood cell count, methaemoglobin and Heinz body and reticulocyte counts were analysed by Kruskal-Wallis nonparametric ANOVA followed by the Mann-Whitney U-test (for percentages). Histopathological changes were evaluated by Fisher's exact probability test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- increased incidence of focal alopecic areas and sparsely haired regions
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- increased incidence of focal alopecic areas and sparsely haired regions
- Body weight and weight changes:
- no effects observed
- Food efficiency:
- no effects observed
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- increase in total white blood cell count, not dose-related and considered to be of no toxicological relevance
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- females of the mid and top-dose group: increased plasma concentrations of glucose and albumine
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- liver, kidney
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- liver
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY:
Female rats of the top-dose group: increased incidence of focal alopecic areas and sparsely haired regions
FOOD CONSUMPTION:
Not significantly changed.
FOOD EFFICIENCY:
Not significantly changed.
WATER CONSUMPTION:
Top-dose group (male and female): slight, but consistent increase in water consumption
HAEMATOLOGY:
Females of the low and top-dose group: increase in total white blood cell count, not dose-related and considered to be of no toxicological relevance
CLINICAL CHEMISTRY:
Females of the mid and top-dose group: increased plasma concentrations of glucose and albumine
Females of the top-dose group: CGT activity and the concentrations of the total protein, bilirubin, cholesterol and calcium were increased
Males of the low-dose group showed an isolated decrease in bilirubin concentration. This was considered to be fortuitous because it was not found in the top-dose group.
ORGAN WEIGHTS:
Liver: absolute and relative weight was increased in males and females of the top-dose group; kidney: relative weight increased in females in the top dose group
HISTOPATHOLOGY: NON-NEOPLASTIC:
Microscopic examination revealed clear histopathological changes in the liver of the mid- and top-dose rats. These changes consisted of too homogenous cytoplasm (ground-glass cytoplasm) in the periportal hepatocytes. The incidence and the degree of severity were dose-related and the difference with the controls were statistically significant in the top-dose group.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 3 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: The no-toxic effect level, as mentioned in the study report, is considered as the NOAEL.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Because no treatment-related changes were observed at the low-dose level, the no-toxic effect level of Kerobit BPD in this study was 3 mg/kg body weight/day.
- Executive summary:
1. The oral toxicity of Kerobit BPD was examined in a 28-day oral toxicity study. The test substance was dissolved in a HCl solution and further diluted in demineralized water. The Kerobit BPD solutions were administered daily by gavage to groups of 5 male and 5 female rats for 28 consecutive days at dose levels of 0 (control), 3, 10 and 30 mg/kg body weight.
2. One male of the mid-dose group died on day 24 of the study, probably due to a dosing error and/or regurgitation and aspiration of the dosing solution. The death of this animal was not ascribed to any toxicity of the test substance. An increased incidence of focal alopecic areas was observed in females of the top-dose group. Otherwise, there were no relevant differences in appearance or behaviour between the treated rats and the controls.
3. Body weights and food and water intake were not significantly affected by the treatment.
4. The total number of white blood cells was increased in females of the low and top-dose group, which was mainly due to an increase in lymphocytes. This effect was not dose-related.
5. Clinical chemistry showed increased glucose and albumine levels in the plasma of females in the mid- and top-dose groups. Plasma gamma-glutamyltransferase (GGT) activity and concentrations of the total protein, bilirubin, cholesterol and calcium were significantly increased in females of the top-dose group.
6. At the end of the treatment the absolute and relative weight of the liver were increased in the top-dose group of both sexes. In addition, the relative weight of the kidney was increased in females in the top dose group.
7. There were no treatment-related gross abnormalities. Upon microscopy, hepatocellular alterations in the periportal area of the liver (ground glass cytoplasm) was observed in the mid- and top-dose rats in both sexes. The incidence and severity of these alterations was treatment-related.
8. Because no treatment-related changes were observed at the low-dose level, the no-toxic effect level of Kerobit BPD in this study was 3 mg/kg body weight / day.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.