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EC number: 429-370-5 | CAS number: 220410-74-2
- 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
- Study period:
- 1999-02-16 to 1999-1999-05-06
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP compliant OECD Guideline study.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted July 27, 1995
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 429-370-5
- EC Name:
- -
- Cas Number:
- 220410-74-2
- Molecular formula:
- C34H67N3O13
- IUPAC Name:
- tris(1,4-dihydroxy-2,2,6,6-tetramethylpiperidin-1-ium) 2-hydroxypropane-1,2,3-tricarboxylate
- Test material form:
- other: Ivory-peach flakes
- Details on test material:
- - Identification: TKA 45021
- Appearance: Ivory-peach flakes
- Lot/batch No.: pax 2068 rd 100
- Test Item arrived at Test Facility: 1998-11-25
Documentation concerning chemical identification, purity, strength, stability and other required data are the responsibility of the Sponsor. Details of the chemical characterization of the test material are confidential information of the Sponsor.
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 Laboratories, Inc., Portage, Michigan, USA
- Age at study initiation: approximately seven weeks
- Weight at study initiation: ranging from 211 to 250 g for males and 151 to 193 g for females
- Fasting period before study: no
- Housing: 2 or 3 males or females per cage for six days following receipt to adjust to the automatic watering system. During remainder of acclimation and while on study: individually in suspended stainless steel cages
- Diet: PMI Certified Rodent Chow #5002 (Purina Mills, Inc.) ad libitum
- Water: municipal tap water ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature: 65 to 79°F (18.3 °C to 26.1 °C)
- Humidity: 30 to 70%
- Air changes: 10 to 15 air changes per hour
- Photoperiod: 12-hour light / 12-hour dark cycle
IN-LIFE DATES: From: 1999-03-04 To: 1999-04-01 or 1999-04-14 (recovery groups)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Prior to weighing, the test article was ground using a mortar and pestle, then weighed into a beaker. Reverse Osmosis Deionized (RODI) water was added to the beaker to achieve the desired concentration, and stirred for 15 minutes. Prepared fresh weekly, dispensed into daily aliquots and stored refrigerated. The physical state of the vehicle and each test article dosing mixture was recorded during each preparation. Daily aliquots of the dosing mixtures were removed from the refrigerator, stirred continuously and allowed to equilibrate to room temperature prior to dispensing.
VEHICLE
- Amount of vehicle: 10 mL / kg bw
The vehicle control material used in the preparation of dosing mixtures and for administration to control animals was Reverse Osmosis Deionized (RODI) water. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentration verification analysis was performed on the vehicle and each test article dosing mixture during weeks 1, 2, 3 and 4.
Prior to initiation of the 28-day study, homogeneity and stability analyses were performed on concentrations of the test article in the vehicle which bracketed the low- and high-doses administered in this study. Homogeneity analyses were performed on duplicate samples taken from the top, middle and bottom of the two mixtures. Stability of the test article in the vehicle was evaluated on duplicate samples at 0, 3 and 8 days following preparation and refrigerated storage.
The analytical results indicated that the doses were accurately formulated during the toxicity study. The results also confirmed that the formulations were homogeneous and stable from the time of preparation to completion of dosing. - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- Daily (7 days per week)
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 100, 500, 1000 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- five males and five females, in addition 5 males and 5 females per recovery group (vehicle and high dose)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: dosage levels were selected based on data from the range-finding study to produce graded responses to the test article.
- Post-exposure recovery period in satellite groups: 14 days
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: during weeks -1, 1, 2 and 3 (days - 1 , 7, 14 and 21, respectively) for each animal.
BODY WEIGHT: Yes
- Time schedule for examinations: -Day 2, 8, 15, 22 and 28 (during the treatment phase) and day 35 (during the recovery phase). In addition, a terminal body weight was recorded on the day of scheduled euthanasia (day 29 or 42) for calculation of relative organ weight data
FOOD CONSUMPTION: Yes
- Time schedule for examinations: -Day 2, 8, 15, 22 and 28 (during the treatment phase) and days 35 and 41 (during the recovery phase).
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: near the end of the treatment phase (day 26) and the recovery phase (day 37)
- Dose groups that were examined: all dose groups (surviving animals)
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the treatment phase (day 29) or the recovery phase (day 42)
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes
- How many animals: all surviving rats (incl. recovery groups)
- The following parameters were examined:
Erythrocyte count (RBC), hematocrit (Hct), hemoglobin concentration (Hgb), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), platelet count, total and differential leukocyte counts, reticulocyte count (reticulocyte slides were prepared, however, reticulocyte counts were not considered necessary by the Study Director)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the treatment phase (day 29) or the recovery phase (day 42)
- Animals fasted: Yes
- How many animals: all surviving rats (incl. recovery groups)
- The following parameters were examined:
Alanine aminotransferase (ALT), albumin, albumin/globulin ratio (calculated), alkaline phosphatase, aspartate aminotransferase (AST), calcium, cholesterol, blood creatinine, gamma glutamyl transpeptidase (GGT), globulin (calculated), glucose, electrolytes (sodium, potassium and chloride), phosphorus, total bilirubin, total serum protein, triglycerides, urea nitrogen
URINALYSIS: Yes
- Time schedule for collection of urine: at the end of the treatment phase (day 29) or the recovery phase (day 42), overnight, prior to scheduled euthanasia
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes (food withheld when in metabolic cage, water provided)
- The following parameters were examined:
Overnight volume, color and appearance, pH, specific gravity, protein, glucose, ketones, urobilinogen, nitrites, bilirubin, occult blood, leukocytes, microscopy of spun deposit
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: during weeks 4 and 6 (days 27/28 and 40/41, respectively).
- Dose groups that were examined: all dose groups
- Battery of functions tested: sensory activity / grip strength and motor activity - Sacrifice and pathology:
- - Euthanized by carbon dioxide Inhalation followed by exsanguination
GROSS PATHOLOGY: Yes, on all animals (incl. recovery groups)
- Parameters: external surfaces of the body and all viscera
- Fresh organ weights: liver, kidneys, adrenal glands, testes with epididymides, ovaries, spleen, thymus, thyroids, brain and heart of all animals. Paired organs were weighed together.
- Preserved from all animals: accessory genital organs (epididymides, seminal vesicles and prostate or uterus and vagina), adrenals, all gross lesions, aorta, brain (including sections of medulla/pons, cerebellar cortex and cerebral cortex), cecum, colon, duodenum, esophagus, exorbital lachrymal glands, eyes with optic nerve, femur (including articular surface) and bone marrow, heart, ileum, jejunum, kidneys, liver (3 sections collected), lungs (infused with formalin) with bronchi, mammary gland, mandibular lymph node, mediastinal lymph node, mesenteric lymph node, pancreas, peripheral nerve (sciatic) pituitary, rectum, skeletal muscle (thigh), skin, spinal cord (cervical, midthoracic and lumbar), spleen, sternum with bone marrow, stomach (glandular/nonglandular), submaxillary salivary gland, testes/ovaries, thymus, thyroid/parathyroid, tongue, trachea, urinary bladder
HISTOPATHOLOGY: Yes
Investigated: All tissues and organs collected at necropsy (days 29 and 42) from all animals in the control and high-dose groups - Statistics:
- - One-way analysis of variance (ANOVA): body weights, weight gain, food consumption, hematology, coagulation, biochemistry, organ weights and appropriate urinalysis parameters
- Tukey-Kramer Test (group comparisons when significance was observed)
- Kruskal-Wallis Test (rank and count data)
- Fisher's Exact Test (Descriptive (categorical) and quantal data)
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Mild, dose-dependent clinical abnormalities
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Mild, dose-dependent clinical abnormalities
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- A slight, dose-dependent decrease in mean body weights
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- A dose-dependent trend towards increased spleen weights was noted primarily in the 500 and 1000 mg/kg bw / day males at the end of the dosing phase of this study.
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Mild, dose-dependent clinical abnormalities were noted following test article administration in the 500 and 1000 mg / kg bw / day males and females (salivation and apparent blood around the facial area, neck and forelimbs). The clinical abnormalities resolved during recovery phase; no mortality occurred.
BODY WEIGHT AND WEIGHT GAIN
A slight, dose-dependent decrease in mean body weights (i.e., 3%, 4% and 6% for the 100, 500 and 1000 mg / kg bw / day groups, respectively) was noted in treated males by the end of the dosing phase. The biological impact of this change was considered marginal as the decrease in mean body weights for the 1000 mg / kg bw / day males (i.e., 6%) was well below 10%.
FOOD CONSUMPTION - no notable abnormalities
OPHTHALMOSCOPIC EXAMINATION - no notable abnormalities
HAEMATOLOGY and CLINICAL CHEMISTRY
Slight treatment-related effects: decreased RBC counts, hemoglobin concentration and hematocrit, increased serum bilirubin in the 500 and 1000 mg / kg bw / day groups.
URINALYSIS -no notable abnormalities
NEUROBEHAVIOUR - no notable abnormalities
ORGAN WEIGHTS
A dose-dependent trend towards increased spleen weights was noted primarily in the 500 and 1000 mg/kg bw / day males at the end of the dosing phase of this study.
HISTOPATHOLOGY:
A reversible minimal to mild increase in the congestion of the red pulp of the spleen was observed microscopically in several of the 1000 mg / kg bw / day males and females at the end of the dosing phase.
GROSS PATHOLOGY - no notable abnormalities
HISTORICAL CONTROL DATA: no notable abnormalities when compared to results of study
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Primarily induced by mildly and sporadically abnormal parameters regarding clinical signs, haematology, organ weight and histopathology at 500 and / or 1000 mg/kg bw/day.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
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.
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