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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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- repeated dose toxicity: dermal, other
- Remarks:
- 36 weeks, once per week (30 treatments)
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- not specified
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
Data source
Reference
- Reference Type:
- publication
- Title:
- Long-term exposure to commercially available sunscreens containing nanoparticles of TiO2 and ZnO revealed no biological impact in a hairless mouse model
- Author:
- Osmond-McLeod, M.J. et al.
- Year:
- 2 016
- Bibliographic source:
- Particle and Fibre Toxicology 13: 44.
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- A group of 10 female, albino, immune-competent, hairless SKH:QS mice were treated once per week for 36 weeks with a TiO2 containing sunscreen. The sunscreen was applied at 2 mg/cm² to the head, ears, back, sides and tail of each mouse and sunscreen were left to equlibrate for 20 min. Mice receiving no sunscreen application were sham treated. Mice were washed after 2 hrs. Once per month, the thickness of the dorsal skin on each mouse was measured 72 hrs after the last irradiation. After 36 weeks mice were sacrificed and skin neoplasms were counted and classified macroscopically. Major internal organs (brain, liver, spleen, kidneys, lung and heart) were histopathologically analyzed. Additionally, measurement of liver Ti by ICP-MS was conducted and liver tissue was chosen for an analysis of altered gene expression.
- GLP compliance:
- not specified
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:
- other: nanoparticles in suncream
- Details on test material:
- - Particle size distribution (TEM): 21.5 ± 0.6 nm
- Shape of particles (TEM): spheroidal
- Composition of test material, percentage of components: 40 mg/mL TiO2, 70 mg/mL octylmethoxycinnamate, 40 mg/mL butyl methoxydibenzoylmethane
This particular sunscreen was selected on the basis of its similarity to a sunscreen that had elsewhere been shown to contain nanoparticles with photocatalytic properties similar to Degussa P25, a commerciallyavailable product comprising both the anatase and rutile crystal phases of TiO2 nanoparticles (Barker & Branch, 2008)*; personal communication).
*Reference:
- Barker P, Branch A. The interaction of modern sunscreen formulations with surface coatings. Prog Org Coat. 2008;62: 313 – 20.
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: SKH:QS
- Remarks:
- hairless
- Details on species / strain selection:
- not specified
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: CSIRO Animal House
- Age at study initiation: 8 weeks
- Housing: housed in groups of 10 in open-topped polycarbonate cages (bedding material was removed and replaced by lining of paper towel during treatment)
- Diet (ad libitum): Gordon´s rat and mouse pellets
ENVIRONMENTAL CONDITIONS
- Temperature: ca. 21°C
- Relative humidity: 55 - 65 %
- Photoperiod (hrs dark / hrs light): 10/14
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- TEST SITE
- Area of exposure: head, ears, back, sides and tail
REMOVAL OF TEST SUBSTANCE
- Washing: pH balanced soapy water and soft cotton pads were used and mice were dried using fresh cotton pads
- Time after start of exposure: 2 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mg/cm²
The total volume of sunscreen applied vaired slightly per mouse according to its size, but on average approx. 110 µL.
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes, Elizabethan collars
Mice were not observed to groom each other or themselves during treatment periods. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 36 weeks
- Frequency of treatment:
- once per week (total: 30 treatments)
Doses / concentrations
- Dose / conc.:
- 2 other: mg/cm²
- No. of animals per sex per dose:
- 10 animals/group
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- not specified
- Positive control:
- not specified
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: no data
DETAILED CLINICAL OBSERVATIONS: no data
DERMAL IRRITATION: no data
BODY WEIGHT: Yes
- Time schedule for examinations: at study termination
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: no data
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 data
WATER CONSUMPTION: no data:
OPHTHALMOSCOPIC EXAMINATION: no data
HAEMATOLOGY: no data
CLINICAL CHEMISTRY: no data
URINALYSIS: no data
NEUROBEHAVIOURAL EXAMINATION: no data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
After 36 weeks (30 treatments), under anaesthesia mice were weighed and then euthanized, and skin neoplasms were counted and classified macroscopically. The dorsal skin was dissected, mounted, and stored on ice in 1 X Histochoice tissue fixative for histopathology. Major internal organs (brain, liver, spleen, kidneys, lung and heart) were retrieved, weighed and sectioned. Sections were either stored in 4 % neutral buffered formalin at room temperature for histopathology, or snap frozen in liquid nitrogen and stored at -80 °C for other analyses.
Abnormalities identified in organs were classified, typically on their degree of severity, and the incidence within a treatment group was then compared to the incidence across all groups. - Other examinations:
- MEASUREMENT OF LIVER Ti by ICP-MS
Total Ti concentrations in livers harvested from mice in control group and treatment group were determined in-house by ICP-MS. - Statistics:
- Histological findings in treatment group was assessed for statistical significance compared to control group using a two-sided Fisher´s exact test. Differences between groups for skin thickness and/or organ concentrations of Ti were assessed for statistical significance by unpaired t-tests with Welch’s Correction (if only two groups), with significance set at p < 0.05.
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Dermal irritation:
- not specified
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- mortality was observed in the TiO2 group (1 animal)
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- data not shown
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- data not shown
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- no macroscopic outcomes were observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Histological examination of the prematurely deceased mouse in the TiO2 treated group showed peritonitis.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Levels of liver Ti
TiO2 treated animals showed significantly elevated levels of Ti in liver tissue (0.31 mg/g) compared to untreated mice. However, untreated mice had a Ti basal level of 0.19 mg/g tissue weight. - Details on results:
- MORTALITY
- no treatment related mortality was observed. However, one animal of the TiO2-treated group died prematurely.
BODY WEIGHT AND WEIGHT CHANGES
- no changes in body weight could be observed (data not shown)
WATER CONSUMPTION
- water consumption remained unchanged (data not shown)
ORGAN WEIGHTS
- the test item had no effect on the organ weights of major internal organs (brain, liver, spleen, kidneys, lung and heart)
Macroscopic and histopathological outcomes
-TiO2 treated animals showed no tickening of the dorsal skin compared to the untreated animals.
Whole-genome analysis
-Whole genome gene-expression profiling showed no alterations in transcript levels of TiO2-treated animals.
Effect levels
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- This study evaluated the impact of sunscreen containing TiO2 as well as organic substances as active ingredients. Hairless mice were treated once per week for 36 weeks. Mice were sacrificed after 30 treatments and selected organs were histopathologically examined. No TiO2- treatment related effects could be observed.
Elevated TiO2 levels in liver tissue of treated animals was the only observed treatment related effect and could probably be explained by the fact that all mice per group were treated at the same time in one cage and oral application of TiO2 by grooming or after treatment in their home cages could not be excluded.
This study is not in accordance with any dermal toxicity testing guideline and due to major methodological restriction this study cannot be used for hazard assessment. However, this study demonstrates that the use of TiO2 containing sunscreen is not linked to any adverse effect in a hairless mice model.
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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