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EC number: 815-182-4 | CAS number: 12058-75-2
- 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:
- 25 October 2012 - 07 May 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
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:
- Revised 03 October 2008
- Qualifier:
- according to guideline
- Guideline:
- other: OPPTS 870.3050, Repeated Dose 28-Day Oral Toxicity Study in Rodents
- Version / remarks:
- July 2000
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Disodium hexatitanate
- EC Number:
- 815-182-4
- Cas Number:
- 12058-75-2
- Molecular formula:
- Na2Ti6O13
- IUPAC Name:
- Disodium hexatitanate
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- - Storage condition of test material:
Room temperature
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Crl:CD (SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 43 to 49 days old
- Weight at study initiation: males: 227 - 271g; females: 186 - 228g
- Fasting period before study: Not applicable
- Housing: Polycarbonate cages with a stainless steel mesh lid.
- Diet: Ad libitum (removed overnight before blood sampling)
- Water: Ad libitum
- Acclimation period: Two weeks before start of treatment
ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 23°C
- Humidity: 40-70%RH
- Air changes: Filtered fresh air which was passed to atmosphere and not recirculated.
- Photoperiod: 12 hours light: 12 hours dark
IN-LIFE DATES: From: 19 December 2012 (animal arrival) To: 30 January 2013 (Date of necropsy)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- methylcellulose
- Remarks:
- 1% aqueous
- Details on oral exposure:
- - PREPARATION OF DOSING SOLUTIONS:
Fresh formulations were prepared weekly
- VEHICLE
- Concentration in vehicle: 3, 30, 100 mg/mL
- Amount of vehicle: 10 mL/kg - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analytical procedure was successfully validated with respect to specificity, method accuracy and precision.
The specificity of the analysis was confirmed to be acceptable.
The homogeneity was confirmed for Terracess DSR in 1% w/v aqueous methylcellulose formulations at nominal concentrations of 3 mg/mL and 100 mg/mL during distribution between the bottles, during magnetic stirring for 2 hours, ambient temperature storage for 1 day and refrigerated storage for up to 15 days.
The mean concentrations of Terracess DSR in test formulations analysed for the study were within +10%/-15% of nominal concentrations, confirming accurate formulation.
Samples were analysed gravimetrically - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Vehicle control
- Dose / conc.:
- 30 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
- Rationale for animal assignment: Random
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly
BODY WEIGHT: Yes
- Time schedule for examinations: The weight of each animal was recorded one week before treatment commenced (Week -1), on the day that treatment commenced (Week 0), weekly throughout the study and before necropsy. The last scheduled bodyweight was recorded on Day 28 prior to overnight deprivation of food for clinical pathology investigations on Day 29.
FOOD CONSUMPTION AND COMPOUND INTAKE:
- 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: Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Fluid intake was assessed by daily visual observation. No effect was observed and consequently quantitative measurements were not performed.
OPHTHALMOSCOPIC EXAMINATION: Not specified
HAEMATOLOGY: Yes
- Time schedule for collection of blood: All animals were assessed on day 29
- Anaesthetic used for blood collection: Yes isoflurane
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 29
- Animals fasted: Yes
- How many animals: All animals
- Parameters checked in table 2 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (table 3)
HISTOPATHOLOGY: Yes (table 3)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no deaths and the general appearance and behaviour of the animals was unaffected by treatment.
Pale faeces were noted throughout the study in the cages housing animals receiving 1000 mg/kg/day. - Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Slightly low bodyweight gain was apparent during weeks 2 to 4 in males receiving 1000 mg/kg/day resulting in an overall reduction of 10%, when compared to the controls.
The majority of individual bodyweight gains for the high dose males were, however, within the concurrent control range of bodyweight gains seen during that period. Consequently, this finding was considered incidental and not related to treatment. - Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- Lower than control lymphocyte, monocyte and large unstained cell counts and consequentially low total white blood cell counts were observed in all treated groups of females on Day 28 but there was no dose relationship. The majority of individual values for the affected parameters were, however, still within the 90th percentile range of background data for these laboratories (see below). The lack of dose-relationship and slight reduction in differential white blood cell counts renders these findings of doubtful relationship to treatment. The white blood cell parameters for males were unaffected by treatment.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Aspartate amino-transferase activities were slightly low (maximum reduction of 0.78 X Control) for all treated groups of females. A review of the individual data revealed that 11/15 values were within the expected background control range for this parameter at these laboratories (90 percentile range: 56 to 98 U/L (n=301)). Those values that were just outside this range were distributed throughout the treated groups without any dose-relationship.
Consequently, this finding was considered to have a doubtful relationship to treatment. - Urinalysis findings:
- not specified
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Epididymis, testis and spleen weights were slightly high, when compared with the Controls, for males which received 1000 mg/kg/day but only the adjusted values attained statistical significance.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- The nature and incidence of all findings were consistent with the commonly seen background of macroscopic changes in Sprague-Dawley rats at these laboratories.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Description (incidence and severity):
- The nature and incidence of all findings were consistent with the commonly seen background of macroscopic changes in Sprague-Dawley rats at these laboratories.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- organ weights and organ / body weight ratios
- water consumption and compound intake
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- The oral administration of Terracess DSR to Sprague-Dawley (Crl:CD(SD)) rats for 4 weeks at dosages up to 1000 mg/kg/day was well tolerated with no adverse effect of treatment. Consequently, the No-Observed-Adverse-Effect-Level (NOAEL) was considered to be 1000 mg/kg/day.
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