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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 262-679-1 | CAS number: 61260-55-7
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 19 Oct 2005 - 24 May 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP - Guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted September 21, 1998
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Freie und Hansestadt Hamburg, Behörde für Soziales, Familie, Gesundheit und Verbraucherschutz, Hamburg, Germany
- Limit test:
- no
Test material
- Reference substance name:
- N,N'-bis(2,2,6,6-tetramethylpiperidin-4-yl)hexane-1,6-diamine
- EC Number:
- 262-679-1
- EC Name:
- N,N'-bis(2,2,6,6-tetramethylpiperidin-4-yl)hexane-1,6-diamine
- Cas Number:
- 61260-55-7
- Molecular formula:
- C24H50N4
- IUPAC Name:
- N1,N6-bis(2,2,6,6-tetramethylpiperidin-4-yl)hexane-1,6-diamine
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld, Germany
- Age at study initiation: males: 26 days, females: 27 days
- Weight at study initiation: males: 68 - 81.3 g, females: 68.4 - 81.8 g
- Housing: individually in MAKROLON cages type III
- Diet (ad libitum): commercial Ssniff R/M-H V1530-1534
- Water (ad libitum): tap water
- Acclimation period: 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- The test item-vehicle mixture was freshly prepared every day. The test item was dissolved in the vehicle to the appropriate concentrations and was administered orally by gavage at a constant volume daily for 90 days. The control animals received the vehicle for 90 days in the same manner. The amount of the test item was adjusted to each animal´s current body weight daily.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Test substance-vehicle mixture analysis was conducted at study initiation and at study termination. The samples were analysed according to a gas chromatographic method.
- Duration of treatment / exposure:
- 90 test days plus 6 additional test weeks for the animals scheduled for the recovery period.
- Frequency of treatment:
- once daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
44, 110, 275 mg/kg bw/day
Basis:
other: nominal conc.
- No. of animals per sex per dose:
- 10 in main group
5 in recovery group - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Dose levels were selected based on the 28-day dose-range-finding study in rats (LPT study no. 19518/05). In this dose-range-finding study dose levels of 40, 120 and 360 mg test substance/kg bw/d were tested. 40 mg/kg bw/d was regarded to be the NOAEL, starting at 120 mg/kg bw/d clinical signs of toxicity were noted in form of pilo-erection. At 360 mg/kg bw/d further signs of toxicity were noted in form of a reduced body weight in males and hematological and biochemical changes in both sexes.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once daily
- Cage side observations: signs of behavioral changes, reaction to treatment or illness, skin/fur, eyes, mucous membranes, respiratory and circulatory systems, somatomotor activity and behavior patterns
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: before the first exposure and once a week thereafter (1, 2, 4, 8 and 24 hour after administration)
Signs noted included changes in skin, fur, eyes, mucous membranes, occurence of secretions and excretions and autonomic activity (e.g. lacrimation, piloerection, pupil size, unusual respiratory pattern). Changes in gait, posture and response to handling as well as the presence of clonic or tonic movements, stereotypies (e.g. excessive grooming, repetitive circling) or bizarre behavior (e.g. self-mutilation, walking backwards) were also recorded.
BODY WEIGHT: Yes
- Time schedule for examinations: The weight of each rat was recorded at the time of group allocation, on the day of commencement of treatment and once a week thereafter, always on the same day of the week throughout the experimental period.
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
WATER CONSUMPTION: Yes
- Time schedule for examinations: Drinking water consumption was monitored by daily visual appraisal throughout the study.
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Examination of all animals prior to the start of administration, at main study termination and at the end of the recovery period.
- Parameters checked: adnexa oculi, conjunctiva, cornea, anterior chamber, iris (pupil dilated), lens, vitreous body, fundus
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at main study termination and at the end of the recovery period
blood samples were taken from the retrobulbar venous plexus under light ether anesthesia from animals fasted overnight
- How many animals: main study: all animals; recovery: all animals
- Parameters checked: HGB, RBC, WBC, differential blood count (absolute and relative), Reti, PCT, HCT, TPT, aPTT, MCV, MCH, MCHC
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at main study termination and at the end of recovery
Blood samples were taken from the retrobulbar venous plexus under light ether anesthesia from animals fasted overnight.
- How many animals: all main study animals and all animals scheduled for the recovery period.
- Parameters checked: albumin, bilirubin (total), cholesterol (total), creatinine, glucose, protein (total), blood urea nitrogen, calcium, chloride, potassium, sodium, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase
URINALYSIS: Yes
- Time schedule for collection of urine: at main study termination and at the end of the recovery period
Urine samples were collected from animals fasted overnight. The urine was collected for 16 hours in an URIMAX funnel cage.
- Parameters checked: pH, specific gravity, volume, protein, glucose, bilirubin, urobilinogen, ketones, hemoglobin, nitrite, epithelial cells, leucocytes, erythrocytes, organisms, further constituents, crystalluria
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: In test week 12/13 approx. 1-2 hours after dosing and before any blood sampling for laboratory examinations, screening of sensory reactivity to stimuli of different types, as well as the assessment of grip strength and motor activity assessment were conducted in all main study animals.
- Battery of functions tested: righting reflex, body temperature, salivation, startle response, respiration, mouth breathing, urination, convulsions, pilo-erection, diarrhoea, pupil size, pupil response, lacrimation, impaired gait, stereotypy, toe pinch, tail pinch, wire maneuver, hind leg splay, positional passivity, tremors, positive geotropism, limb rotation, auditory function, grip strength, locomotor activity,
OTHER:
Oestrus cycle: At the end of the main study and at the end of the recovery period, vaginal lavages were taken daily from all female animals for periods 2 weeks each. The stage of estrus cycle observed in each vaginal lavage was recorded.
Sperm count and spermatogenic staging:
Staging of spermatogenesis was conducted by histological examination of one testicle and epididymis of all male animals of groups 1-4. From the other testicle and epididymis a sperm count was carried out during necropsy. The sperm viability was determined and the sperm morphology was examined for the control and for the treated animals. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes: all superficial tissues were examined visually and by palpation. The abdominal viscera were examined before and after removal, the urinary bladder was examined externally and by palpation. The gastro-intestinal tract was examined as a whole and the stomach and caecum were incised and examined.
HISTOPATHOLOGY: Yes: adrenal gland, aorta abdominalis, bone marrow, brain, epididymis, eye with optic nerve, gross lesions, heart, intestine, kidney and ureter, liver, lungs, lymph nodes, mammary gland, nerve, oesophagus, ovary, pancreas, pituitary, prostate, salivary glands, skin, spinal cord, spleen, stomach, testicle, thymus, thyroid, tissue masses or tumors, trachea, urinary bladder, uterus, vagina - Statistics:
- The test substance groups were compared to the control group. The following statistical methods were used: Student's t-test for analysis of data on all numerical functional tests, urinalysis, haematology (recovery), clinical biochemistry (recovery), oestrus cycle and sperm parameter (differences considered statistically significant if p ≤ 0.01); multiple t-test based on Dunnett for analysis of data on body weight, food consumption, haematology, clinical biochemistry, absolute and relative organ weights (differences considered statistically significant if p ≤ 0.01), Exact test of Fisher for analysis of data on histology and sperm parameter (differences considered statistically significant if p ≤ 0.05).
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY
44 mg/kg bw/d: no effects
110 mg/kg bw/d: 1 male and 1 female revealed a laboured breathing on one or two test days in test week 10, 11 or 8, respectively. Further, pilo-erection was noted for the same female animal on the same test day of test week 8.
275 mg/kg bw/d: reduced motility for male and female animals, laboured breathing and pilo-erection were noted in nearly all animals on several test days,salivation for two animals (male and female), the same animal revealed an abdominal position on four test days.
recovery: all changes noted for animals (275 mg/kg/bw/d) had subsided immediately at the beginning of the recovery period.
275 mg/kg bw/d: 3 of 15 male animals died prematurely during the day on test days 21, 26, 52. additionally, 3 of 15 females died on test days 16 or 22. Four of these animals revealed a laboured breathing starting one or two days before their premature deaths. All other animals survived.
BODY WEIGHT AND WEIGHT GAIN
44 and 110 mg/kg bw/d: no effects (male and female)
275 mg/kg/bw/d: reduced body weight in males from test week 1 onwards up to 13% compared to the control. Body weight gain was reduced accordingly.
FOOD CONSUMPTION
44 mg/kg bw/d: no effects (male and female)
110 or 275 mg/kg/bw/d: reduced food consumption in females from test week 1 onwards by up to 16 or 20% in test week 10 or in test weeks 2, 5, 6, 7, 8 and 11, respectively.
recovery: changes observed for the females had subsided by the end of the 6-week recovery period.
HAEMATOLOGY
44 and 110 mg/kg bw/d: no effects (male and female)
275 mg/kg: leucocytes (WBC) +69%, neutrophilic granulocytes (abs.) +106%, lymphocytes (abs.) +90%, large unstained cells (LUC) (abs.) +103% in females
recovery: no test substance-related changes noted for the previously high dosed animals (male and female)
CLINICAL CHEMISTRY
44 and 110 mg/kg bw/d: no effects (male and female)
275 mg/kg bw/d: slightly increased activity of alkaline phosphatase in the male animals (+31%) on test day 91 compared to control
recovery: changes noted for the male animals with 275 mg/kg bw/d had subsided at the end of the recovery period
GROSS PATHOLOGY
Oral treatment with 44, 110, 275 mg/kg bw/d caused ulcerous lesions in the stomach in several animals. The effect appeared to be dose-related but only in male animals. Further, an increased lobular pattern was noted in the liver of one male and one female treated with 110 mg/kg bw/d and in three animals treated with 275 mg/kg bw/d.
HISTOPATHOLOGY: NON-NEOPLASTIC (male and female)
Histomorphological examination revealed an ulcerative gastritis in the fore-stomach and purulent tracheitis in male and female rats treated with 110 or 275 mg/kg bw/d and a purulent laryngitis in the animals treated with 275 mg/kg bw/d. These local changes are considered due to the corrosive properties of the test item. No systemic histopathological changes were noted.
At the end of the 6-week recovery the forestomach showed a mild recovery and the trachea and the larynx a complete reversibility of the lesions observed. Spermatogenic examination (staging) did not reveal any test substance-related influence.
Evaluation of the estrus cycle and sperm count/viability/morphology: No test substance-related influence was noted.
No effects occurred for neurobehavior, urinalysis, water consumption, ophthalmoscopic examination.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- > 275 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: systemic toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 44 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: local effects
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Results of the analysis showed that the test substance-vehicle mixtures were correctly prepared and the concentration, stability and homogeneity found were in good agreement to those expected. The results of 92.2% to 107.5% of the nominal value were well within the admissible limits.
Applicant's summary and conclusion
- Conclusions:
- All changes observed were considered to be due to the local corrosive changes noted, causing behavioural, biochemical and haematological changes and in some cases mortality. The changes observed were not considered to be due to systemic toxicity of the test substance given by gavage but due to its corrosive properties. Under consideration of all changes noted and the corrosive properties of the test substance, the NOAEL for systemic changes was above 275 mg/kg bw/day; the NOAEL for local changes was 44 mg/kg bw/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.