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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 952-967-1 | 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
In this study, the subacute and subchronic oral toxicity of agglomerated/aggregated TiO2 P25 (approximately 180 nm) were investigated in rats according to the standard procedure (OECD Guidelines, No. 407 and 408) for testing chemicals.
No systemic toxicological effects were related with the agglomerated/aggregated TiO2 P25 in the repeated-dose 28-day and 90-day oral toxicity and 28-day recovery studies in SD rats under the experimental conditions used. Therefore, the NOAEL of the agglomerated/aggregated TiO2 P25 was identified as 1000 mg/ kg//d, and this test substance was not detected in the target organs.
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
- Justification for type of information:
- Sodium titanates are effectively the sodium salts of the unstable titanic acid (titanium hydroxide). Titanium hydroxide is hard to isolate without rapid hydrolysis to titanium dioxide and sodium chloride. It is therefore proposed to base environmental and health assessment on these two hydrolysis products. There has been extensive research on similar substances in the ‘titanate’ grouping and these all exhibit similar behaviour in that under acid biological conditions (eg if ingested) or if dispersed in water, there is dissociation of the ions and subsequent hydrolysis / oxidation. Read-across justification for the use of TiO2 data is available in section 13.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- In this study, the NOAEL (no observed adverse effect level) of the agglomerated/aggregated TiO2 P25 (approximately 180 nm) administered at repeated doses to Sprague-Dawley (SD) rats for 28 and 90 days was observed. Ten of the 15 animals were necropsied for toxicity evaluation after the repeated-dose 90-day study, and the remaining five animals were allowed to recover for 28 days.
- GLP compliance:
- yes
- Remarks:
- approved by the Institutional Animal Care and Use Committee (IACUC) of Korea Conformity Laboratories
- Limit test:
- no
- Specific details on test material used for the study:
- TiO2 nanoparticles (AEROXIDEⓇ TiO2 P25, KRISS CRM 301–03-001, anatase/rutile (80/20), 99.9%; average primary particle size range 14–21 nm) were purchased from Evonik Industries AG (Essen, Germany). Agglomerated/aggregated TiO2 P25 (approximately 180 nm)
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Pathogen-free SD rats [Crl:CD(Sprague-Dawley)] were purchased from Orient Bio Inc. (Seongnam, Korea). Healthy young adult animals (males and non-pregnant females) were acclimated and closely monitored for 6 days after arrival in the SPF animal facility area, and were randomly assigned to the control and treatment groups. Only animals with the best appearance were selected for subsequent testing. The body weights of the male and female rats were 210–232 g and 157–185 g, respectively, at the time of the first administration in the repeated-dose 28-day experiment. The body weights of the male and female rats were 185–207 g and 149–183 g, respectively, at the time of the first administration in the repeated-dose 90-day experiment. Rats were housed two per cage in an environmentally controlled room at 22.9 ± 0.5 °C and relative humidity of 54.3 ± 4.2%. The room air was replaced 10–15× per hour. Lighting was set to a 12-h light/dark cycle (on at 08 h00 and off at 20 h00).
- Route of administration:
- oral: gavage
- Vehicle:
- other: 5 mM sodium phosphate buffer (pH 8.0)
- Details on oral exposure:
- One hundred and forty healthy adult SD rats were used in this study. For the repeated-dose 28-day experiment, the animals were randomly divided into four groups, each consisting of five animals per sex. For the repeated-dose 90-day experiment, the animals were randomly assigned to four groups. Each group consisted of 10–15 animals per sex. One group was administered 5 mM sodium phosphate buffer by gavage and served as the vehicle control group (G1). The three remaining groups received one of three agglomerated/aggregated TiO2 P25 dosages by gavage (250 mg kg− 1 d− 1 (G2), 500 mg kg− 1 d− 1 (G3), and 1000 mg kg− 1 d− 1 (G4)). The dosing volume was 10 mL kg− 1 body weight. The agglomerated/aggregated TiO2 P25 were administered every morning for either 28 days or 90 days.
- Frequency of treatment:
- The dosing volume was 10 mL kg− 1 body weight. The agglomerated/aggregated TiO2 P25 were administered every morning for either 28 days or 90 days.
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Group 1 (vehicle control)
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Remarks:
- Group 2
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Remarks:
- Group 3
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- Group 4
- No. of animals per sex per dose:
- For the repeated-dose 28-day experiment, the animals were randomly divided into four groups, each consisting of five animals per sex.
For the repeated-dose 90-day experiment, the animals were randomly assigned to four groups. Each group consisted of 10–15 animals per sex. - Control animals:
- yes, concurrent vehicle
- Observations and examinations performed and frequency:
- Detailed clinical observations were made once on all surviving animals before the onset of administration. Functional observations were conducted during the last week of treatment for the 90-day treated study and during the last week of observation for the recovery study. Functional observations were performed within 6 h after administration. Individual animal weights were recorded at acquisition and grouping, before administration, once weekly during the study, and before necropsy. Food consumption was measured immediately before the first administration and once weekly during the study.
- Sacrifice and pathology:
- After administration, necropsies were conducted on all surviving animals, and complete post-mortem examinations were performed on all organs. All organs were harvested, and some organs were weighed immediately after extraction (Table S9). Excised organs were fixed in 10% neutral phosphate-buffered formalin. Testes and epididymis were fixed in Bouin’s solution, and eyes were fixed in Davidson’s solution. Bilateral organs were fixed and organs with macroscopically abnormal lesions were preserved. Thin sections were made from all the preserved organs and tissues of the vehicle control and high-dose groups, mounted on histology slides, and examined histopathologically by hematoxylin and eosin (H&E) staining.
- Statistics:
- Statistical differences among the vehicle control and dosing groups were analyzed by parametric or nonparametric multiple comparison methods. Differences were considered statistically significant at P < 0.05. The incidence rate was represented as a percentage.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- In the test on SD rats for 90 days. At 24 h after the last treatment, a recovery study (5 animals in each group) with a non-dose period of 28 days was performed to confirm the persistence of toxicity without treatment. No mortality or abnormal clinical signs were detected in any of the treatment groups during the exposure and recovery periods
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- effects observed, non-treatment-related
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- dermal irritation
- food consumption and compound intake
- food efficiency
- gross pathology
- haematology
- histopathology: neoplastic
- histopathology: non-neoplastic
- immunology
- mortality
- neuropathology
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
- water consumption and compound intake
- Key result
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Conclusions:
- In this study, the subacute and subchronic oral toxicity of agglomerated/aggregated TiO2 P25 (approximately 180 nm) were investigated in rats according to the standard procedure (OECD Guidelines, No. 407 and 408) for testing chemicals.
No systemic toxicological effects were related with the agglomerated/aggregated TiO2 P25 in the repeated-dose 28-day and 90-day oral toxicity and 28-day recovery studies in SD rats under the experimental conditions used. Therefore, the NOAEL of the agglomerated/aggregated TiO2 P25 was identified as 1000 mg kg− 1 d− 1, and this test substance was not detected in the target organs.
Reference
The NOAEL of the agglomerated/aggregated TiO2 P25 was 1000 mg/kg/d. Although there were significant differences in some results, they were unrelated to the test substance.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Additional information
Sodium titanates are effectively the sodium salts of the unstable titanic acid (titanium hydroxide). Titanium hydroxide is hard to isolate without rapid hydrolysis to titanium dioxide and sodium chloride. It is therefore proposed to base environmental and health assessment on these two hydrolysis products. There has been extensive research on similar substances in the ‘titanate’ grouping and these all exhibit similar behaviour in that under acid biological conditions (eg if ingested) or if dispersed in water, there is dissociation of the ions and subsequent hydrolysis / oxidation. Read-across justification for the use of TiO2 data is available in section 13.
The focus has been placed on the titanium element of the hydrolysis expected from this substance. Sodium ions are naturally present in cells in the human body and can be tolerated by ingestion of NaCl through inclusion in normal food and as a food additive up to a daily recommended intake of 6g. It is unlikely that the substance under registration would result in an excess of NaCl being ingested or as a result of absorption through lung fluid following inhalation. The amount to achieve this would be in excess of ~50g. Therefore, there is no reason to evaluate the potential toxicology of the sodium element of the hydrolysis further.
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.
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.