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Diss Factsheets
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EC number: 236-675-5 | CAS number: 13463-67-7
- 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
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Toxicity to reproduction: other studies
Administrative data
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Reliability:
- other: not rated acc. to Klimisch
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The publication is not relevant for human health risk assessment due to irrelevant route of test item application. In addition only one dose was tested and the frequency of treatment is not according a guideline. Test item insufficiently characterised, the given particle size of 2570nm (2.57µm) does not fall under the nano-definition and also does not correspond with the suface area of 2025m²/g (which is also unrealistic high for any commercially available titanium dioxide form).
Data source
Reference
- Reference Type:
- publication
- Title:
- Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse.
- Author:
- Shimizu, M. et al.
- Year:
- 2 009
- Bibliographic source:
- Part. Fibre Toxicol. 2009, 6: 20.
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The purpose of this study was to investigate the effects of maternal exposure to nano-sized anatase titanium dioxide (TiO2) on gene expression in the brain during the developmental period using cDNA microarray analysis combined with Gene Ontology (GO) and Medical Subject Headings (MeSH) terms information. A 100 μL volume of TiO2 suspended at 1 μg/μL was injected subcutaneously into pregnant mice on gestational days 6, 9, 12, and 15 for the exposure group, while 100 μL of vehicle alone was injected into pregnant mice as a control group. Brain tissue was obtained from male foetuses on embryonic day 16 and from male pups on postnatal days 2, 7, 14, and 21.
- GLP compliance:
- not specified
- Type of method:
- in vivo
Test material
- Reference substance name:
- Titanium dioxide
- EC Number:
- 236-675-5
- EC Name:
- Titanium dioxide
- Cas Number:
- 13463-67-7
- Molecular formula:
- O2Ti
- IUPAC Name:
- dioxotitanium
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): TiO2 nanopowder (purchased from Sigma-Aldrich Japan Inc. (Tokyo, Japan))
- Particle size: 2570 nm
- Surface area: 2025 m²/g
- Crystal form: anatase
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- ICR
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Japan SLC Inc. (Shizuoka, Japan)
- Diet (ad libitum): food
- Water (ad libitum):
ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 1°C
- Humidity: 55 ± 5%
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- subcutaneous
- Vehicle:
- other: saline with 0.05% (v/v) Tween 80
- Details on exposure:
- A 100 μL volume of TiO2 suspended at 1 μg/μL was injected subcutaneously into pregnant mice for the exposure group, while 100 μL of vehicle alone was injected into pregnant mice as a control group.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Duration of treatment / exposure:
- Gestational days 6, 9, 12, and 15
- Frequency of treatment:
- not stated
- Duration of test:
- Test ended on postnatal day 21
Doses / concentrations
- Remarks:
- Doses / Concentrations:
100 μL volume of TiO2 suspended at 1 μg/μL
Basis:
other: injected subcutaneously
- No. of animals per sex per dose:
- Treatment group: 15 mice
Control group: 14 mice - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Brain tissue was obtained from male foetuses on embryonic day (ED) 16 (n = 8/group) and from male pups on postnatal days 2 (n = 10/group), 7 (n = 10/group), 14 (n = 9/group), and 21 (n = 9/group).
Whole brain was frozen and tissue were homogenized. Total RNA was isolated from the brain tissue for complementary DNA microarray analysis and a functional analysis of microarray data with gene annotation. . - Statistics:
- Complementary DNA microarray analysis: statistical analysis was done with analysis of variance (ANOVA) and the level of statistical significance was set at P < 0.05.
Functional analysis of microarray data: statistical analysis was performed using Fisher's exact test with hypergeometric distribution and the level of statistical significance was set at P < 0.05.
Results and discussion
Effect levels
- Basis for effect level:
- other: Maternal exposure to test item caused changes in gene expression assoc. w/ brain developm., cell death, response to oxidative stress, & mitochondria in brain during perinatal period, & those associated with inflammation & neurotransmitter in later stage.
- Remarks on result:
- not measured/tested
- Remarks:
- Effect level not specified (migrated information)
Observed effects
In the maternal TiO2 exposure group, the expression levels of 462 genes were changed significantly in the brain of the foetus at ED 16 (upregulation 229 genes; downregulation 233 genes), and those of 864 (upregulation 234; downregulation 630), 417 (upregulation 351; downregulation 66), 738 (upregulation 450; downregulation 288), and 1887 (upregulation 613; downregulation 1274) were changed significantly in the brain of offspring 2, 7, 14, and 21 days old, respectively. The number of genes differentially expressed between groups was increased remarkably in the brain of 21 days old pups.
Functional categorization of microarray data:
Of the genes expressed differentially in the maternal TiO2 exposure group, 3, 2, 8, and 4 GO categories were enriched significantly in the brain at 2, 7, 14, and 21 days after birth, respectively, while 6, 2, 36, and 28 MeSH categories were enriched significantly at 2, 7, 14, and 21 days after birth. Eight MeSH categories were also enriched significantly in the foetal brain at ED 16. The largest group of GO categories enriched was those related to cell death 2 21 days after birth; 121 and 64 genes linked to apoptosis at 2 and 7 days after birth, respectively, and 92 and 173 genes linked to "cell death" were identified at 14 and 21 days after birth. "Brain development" was also a large category at 2 (34 genes) and 14 (43 genes) days after birth. GO categories related to oxidative stress, such as "superoxide dismutase activity", were also enriched significantly at 14 and 21 days after birth. The largest MeSH categories enriched were "Mitochondria" at ED 16 (31 genes) and 2 days (56 genes) after birth and "Apoptosis" at 14 (118 genes) and 21 (230 genes) days after birth. The "Mitochondria" category was persistently enriched at 14 (60 genes) and 21 (109 genes) days after birth. MeSH categories related to oxidative stress, such as "Glutathione", "Lipid Peroxidation", and "Reactive Oxygen Species", were also enriched significantly at ED 16 and 14 and 21 days after birth. MeSH categories related to inflammation and neurotransmitters including "Epinephrine", "Norepinephrine", "Serotonin", and "Glutamic Acid" were also highly enriched at 14 and 21 days after birth.
Applicant's summary and conclusion
- Conclusions:
- According to the authors, this study showed that maternal exposure to anatase TiO2 nanoparticle caused the changes in the expression of genes associated with brain development, cell death, response to oxidative stress, and mitochondria in the brain during the perinatal period, and those associated with inflammation and neurotransmitters in the later stage.
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