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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
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EC number: - | CAS number: -
- 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
Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Remarks:
- 80% Polyethylene glycol 400 (PEG 400) in distilled water
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples for homogeneity analysis were also analyzed for verification of dose level concentration. Results of dose formulation were 94.8, 91.1 and 104.5% at each dose levels of 25, 75 and 250 mg/mL. They were acceptable as the mean concentration was within ± 20% of the nominal concentration.
- Duration of treatment / exposure:
- Dosing of the males will begin 14 days prior to mating and continue through the day prior to sacrifice (at least 28 days). Dosing of the females will begin 14 days prior to mating and continue through lactation day (LD) 13. Animals in recovery group will not be mated and will be assigned to 2 weeks of recovery period after the completion of administration.
- Frequency of treatment:
- once a day
- Dose / conc.:
- 0 mg/kg bw (total dose)
- Dose / conc.:
- 100 mg/kg bw (total dose)
- Dose / conc.:
- 300 mg/kg bw (total dose)
- Dose / conc.:
- 1 000 mg/kg bw (total dose)
- No. of animals per sex per dose:
- control: 18 animals
100, 300 mg/kg: 12 animals
1000 mg/kg: 18 animals - Control animals:
- yes
- Observations and examinations performed and frequency:
- 1. Mortalilty observation
Mortality and morbidity observations were conducted twice daily except for the acclimation period. In addition, it was conducted once on necropsy day.
2. Clinical signs
Clinical signs including general appearance and behavior changes were recorded with date/time of finding, and duration. During the gestation period, dams were especially monitored for signs of abortion or premature delivery. In addition, nursing dams were carefully observed during the lactation period. Detailed clinical observations were made in all animals individually for abnormalities. Signs noted were included (but are not limited to) evaluation of fur, skin, eyes, mucous membranes, occurrence of secretions and excretions, autonomic nervous system activity (lacrimation, piloerection, pupil size, and unusual respiratory pattern), changes in gait, posture, clonic and tonic movements, stereotypical and bizarre behavior, and difficult and prolonged parturition. General clinical signs including observation after dosing were not additionally recorded in the day of detailed clinical signs observation.
3. Functional observation
Sensory function tests (approach and touch response, tail pinch, acoustic startle response and pupillary reflex), grip strength and motor activity were conducted in first six animals per sex in main group (if possible) and in all animals of the recovery group shortly before scheduled sacrifice. - Sacrifice and pathology:
- 1. Hematology
Approximately 1.5 mL of blood sample was collected for hematology. For the hematological test about 0.5 ml of blood was put into tubes containing potassium salt of EDTA. About 1.0 mL of blood was put into tubes containing 3.2% sodium citrate and then centrifuged (approximate 3000
rpm, 10 min, at room temperature) to obtain plasma to determine the clotting potential test.
2. Clinical chemistry
Approximately 1.5 mL of blood samples was collected for clinical chemistry. Blood was put into tubes without anticoagulant for serum separation. The tubes were kept at room temperature for a minimum of 90 min and then centrifuged (approximate 3000 rpm, 10 min, at room temperature) to obtain serum. - Other examinations:
- 1. Macroscopic findings
Complete necropsy was performed under the direct supervision of a veterinary pathologist. After blood sampling, the animals were sacrificed by exsanguination from the vena cava and aorta. The animals were examined carefully for external abnormalities. The abdominal, thoracic and cranial cavities were examined for abnormalities and the organs were removed and examined. Special attention was paid to the organs of the reproductive system.
2. Organ weights
Organs were weighed for all animals at terminal and recovery sacrifice and organ/body weight ratios using the terminal body weight (TBW) obtained prior to necropsy was calculated. Paired organs were weighed together unless gross abnormalities are present. However, paired reproductive organs were weighed separately.
3. Microscopic findings
All tissues except reproductive organs collected from first six animals per sex in main group were further processed to slides, stained with hematoxylin and eosin, and examined microscopically. All reproductive organs collected from the main groups were further processed to slides, stained with H&E, and examined microscopically. - Statistics:
- Pristima system or SAS/STAS (Version 9.4 USA)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- In males at 100, 300 and 1000 mg/kg, salivation was observed in 11, 12, and 18 animals, respectively. In females at 100, 300 and 1000 mg/kg, salivation was observed in 9, 11, and 18 animals, respectively. It was considered test item-related but not toxicologically statistically significant since it was considered to be attributed to the palatability of the test item.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in body weight and body weight gain were observed in both sexes during the study.
Statistically significant changes in body weight gain during the study was not considered test item-related since it was transient. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in food consumption were observed in both sexes during the study.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Total red blood cell count (RBC) was significantly increased (1.07-fold over control, respectively) in males at 300 and 1000 mg/kg and mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were significantly increased (1.08 and 1.07-fold over control, respectively) in females at 1000 mg/kg. These changes were fully recovered after recovery period and considered not to represent meaningful toxicity as there were no histopathological
correlates. - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Inorganic phosphorus (IP) was significantly decreased (85% of control) in males at 1000 mg/kg.
These changes were fully recovered after recovery period and considered not to represent meaningful toxicity as there were no histopathological correlates. - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in functional behavior examination were observed in both sexes during the study.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes in organ weights were observed in both sexes during the study.
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw (total dose)
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- clinical signs
- haematology
- Key result
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 1 000 mg/kg bw (total dose)
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- System:
- other: hepatobiliary, urinary
- Organ:
- kidney
- liver
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
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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