GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 13463-67-7 |
| Chemical Name | Titanium dioxide (nanoparticle) |
| Substance ID | H28-B-019, C-027B |
| Classification year (FY) | FY2016 |
| Ministry who conducted the classification | Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE) |
| New/Revised | Revised |
| Classification result in other fiscal year | FY2009 FY2006 |
| Download of Excel format | Excel file |
REFERENCE INFORMATION
| Item | Information |
|---|---|
| Guidance used for the classification (External link) | GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1)) |
| UN GHS document (External link) | UN GHS document |
| Definitions/Abbreviations (Excel file) | Definitions/Abbreviations |
| Model Label by MHLW (External link) | MHLW Website (in Japanese Only) |
| Model SDS by MHLW (External link) | MHLW Website (in Japanese Only) |
| OECD/eChemPortal (External link) | eChemPortal |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Explosives | Not applicable |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. |
| 2 | Flammable gases (including chemically unstable gases) | Not applicable |
- |
- | - | Solid (GHS definition). |
| 3 | Aerosols | Not applicable |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Not applicable |
- |
- | - | Solid (GHS definition). |
| 5 | Gases under pressure | Not applicable |
- |
- | - | Solid (GHS definition). |
| 6 | Flammable liquids | Not applicable |
- |
- | - | Solid (GHS definition). |
| 7 | Flammable solids | Not classified |
- |
- | - | It is not combustible (HSDB (Acess on May 2016)). |
| 8 | Self-reactive substances and mixtures | Not applicable |
- |
- | - | There are no chemical groups present in the molecule associated with explosive or self-reactive properties. |
| 9 | Pyrophoric liquids | Not applicable |
- |
- | - | Solid (GHS definition). |
| 10 | Pyrophoric solids | Not classified |
- |
- | - | It is not combustible (HSDB (Acess on May 2016)). |
| 11 | Self-heating substances and mixtures | Not classified |
- |
- | - | It is not combustible (HSDB (Acess on May 2016)). |
| 12 | Substances and mixtures which, in contact with water, emit flammable gases | Not classified |
- |
- | - | It is estimated that it does not react vigorously with water due to the observation result of being insoluble in water (ICSC (2002)). |
| 13 | Oxidizing liquids | Not applicable |
- |
- | - | Solid (GHS definition). |
| 14 | Oxidizing solids | Classification not possible |
- |
- | - | It is an inorganic compound containing oxygen, but the classification is not possible due to no data. |
| 15 | Organic peroxides | Not applicable |
- |
- | - | It is an inorganic compound. |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | Test methods applicable to solid substances are not available. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not classified |
- |
- | - |
This classification was conducted for titanium dioxide particles in the range of 1 to 100 nm. Based on the LD50 value of > 5,000 mg/kg (SIDS (2015)) for rats, it was classified as "Not classified." |
| 1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | Based on a report that no clear skin irritation was observed in the volunteer tests using an emulsion containing titanium dioxide nanoparticles and on a description that no skin irritation was observed in animals (OEL Documentations (Japan Society For Occupational Health (JSOH), 2013)), it was classified as "Not classified." |
| 3 | Serious eye damage/eye irritation | Not classified |
- |
- | - | Based on a description that no eye irritation was observed in animals (OEL Documentations (Japan Society For Occupational Health (JDOH), 2013)), it was classified as "Not classified." |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - |
As for in vivo, micronucleus tests in peripheral erythrocytes of mice using anatase (75%)/rutile (25%) was positive, DNA damage tests in peripheral erythrocytes and liver of mice using anatase (75%)/rutile (25%) were positive, a Comet assay using the lung of rats was negative (crystal type of used nanoparticles was unknown) (OEL Documentations (Japan Society For Occupational Health (JSOH), 2013)), Risk Assessment Documents (National Institute of Advanced Industrial Science and Technology, 2011), DFGOT (2014), Environmental Risk Assessment for Chemical Substances vol. 8 (Ministry of the Environment, 2010), IARC 93 (2010)). In addition, a gene mutation test (gpt/liver, Pig-a/red blood cell), a micronucleus test (reticulocyte) and the comet assay (liver) by intravenous administration to transgenic mice using anatase (75%)/rutile (25%) were reported recently, and all tests results were negative (Mutation Research (2016)). As for in vitro, it was reported that in tests using anatase (100%), anatase (80%)/rutile (20%), rutile (100%), and anatase (70-85%)/rutile (30-15%), bacterial reverse mutation tests were negative, gene mutation tests using cultured mammalian cells such as primary cultured embryonic fibroblasts derived from gpt delta transgenic mice, micronucleus test of mammalian cultured cells and chromosome aberration test were positive or negative (OEL Documentations (Japan Society For Occupational Health (JSOH), 2013)), Risk Assessment Documents (National Institute of Advanced Industrial Science and Technology, 2011), IARC 93 (2010), Environmental Risk Assessment for Chemical Substances vol. 8 (Ministry of the Environment, 2010), DFGOT (2014)). It is concluded in Initial Risk Assessment Report (Ministry of Health, Labour and Welfare, 2013) that it was considered to be genotoxic from positive results in multiple in vitro micronucleus tests, in vivo micronucleus tests, etc., however, in genotoxicity of poorly soluble particles such as this substance, indirect (secondary) genotoxicity caused by free radicals was involved rather than direct action on the nucleus. From the above, positive result in vivo could not be regarded as definite finding because there are contradictory findings to positive in vivo findings observed so far, and it is evaluated that indirect (secondary) genotoxicity caused by free radicals was involved rather than direct action by this substance. Therefore, it was classified as "Classification not possible." |
| 6 | Carcinogenicity | Category 2 |
 Warning |
H351 |
P308+P313
P201 P202 P280 P405 P501 |
In a study in which female rats were exposed by inhalation to titanium dioxide nanoparticles (P25 (80% anatase/20% rutile, average primary particle size: 25 nm) at an average weight concentration of 10 mg/m3 for 2 years (18 hours/day, 5 days/week), the number of animals which developed lung tumors increased as 19/100 in the exposed group versus 1/217 in the non-exposed group. The breakdown of lung tumors was 3/100 for squamous cell carcinomas, 4/100 for adenomas, and 17/100 for adenocarcinomas (OEL Documentations (Japan Society For Occupational Health (JSOH), 2013), IARC 93 (2010)). In a study in which male and female rats were exposed by inhalation to titanium dioxide (crystalline type unspecified), 99% of which had a primary particle size of 0.5 micrometer, at 15.95 mg/m3 for 12 weeks (6 hours/day, 5 days/week) and tumor incidences were checked after 140 weeks, mortality was high (male: 88%, female: 90%), but in surviving animals, adenoma and squamous cell papilloma of the respiratory tract were observed in each one male, and bronchiolar alveolar adenoma was observed in one female (OEL Documentations (Japan Society For Occupational Health (JSOH), 2013), IARC 93 (2010)). Moreover, in a test using rats given two types of titanium oxide fine particles of P25 or AL23 (anatase, average particle diameter: 200 nm or less) by intratracheal administration at three or six times, high incidence of lung tumors was observed (OEL Documentations (Japan Society For Occupational Health (JSOH), 2013)). As described above, there were the evidences that titanium oxide nanoparticles showed carcinogenicity in experimental animals, and part of them was the evidence data based on which IARC classified titanium oxide in Group 2B. Therefore, the substance was classified in Category 2 for this hazard class. |
| 7 | Reproductive toxicity | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 8 | Specific target organ toxicity - Single exposure | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (respiratory organs) |
Danger |
H372 |
P260
P264 P270 P314 P501 |
There is no information on humans. As for experimental animals, in studies in which rats, mice and hamsters were exposed by inhalation to titanium dioxide nanoparticles (particle size 21 nm, anatase 80%/rutile 20%) for 13 weeks (6 hours/day, 5 days/week) and pulmonary responses were measured at 4, 13, 26 and 52 weeks (49 weeks for hamsters) after the end of exposure, significant increases in total number of cells in bronchoalveolar lavage fluid (BALF), neutrophil count, macrophage count, and lymphocyte count as the fraction of BALF, LDH, protein concentration was observed at 10 mg/m3 (0.007 mg/L), which is equivalent to Category 1, and in rats and mice, pulmonary clearance was delayed, indicating that overload of titanium dioxide occurred (OEL Documentations (Japan Society For Occupational Health (JSOH), 2013), Environmental Risk Assessment for Chemical Substances vol. 8 (Ministry of the Environment, 2010), Risk Assessment Documents (National Institute of Advanced Industrial Science and Technology, 2011)). In addition, it was reported that in a 12-week (6 hours/day, 5 days/week) toxicity study using rats exposed by inhalation to 23 mg/m3 of titanium dioxide fine particles (particle diameter 250 nm, anatase type) or titanium dioxide nanoparticles (particle diameter 21 nm, anatase type), pulmonary inflammatory response appeared more strongly in the nanoparticle group, but after 64 weeks, it became almost the same as in the control group and exhibited reversibility at 23 mg/m3 (converted guidance value: 0.015mg/L), which is equivalent to Category 1 (Environmental Risk Assessment for Chemical Substances vol. 8 (Ministry of the Environment, 2010), Ferin, J. et al, Am J Respir Cell MoI Biol., 6, 535-542, (1992)). Therefore, it was classified in Category 1 (respiratory organ). |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Classification not possible |
- |
- | - | Because evaluation of the reliability of an ecological toxicity test using nanoparticles is not possible, it was classified as "Classification not possible." |
| 11 | Hazardous to the aquatic environment (Long-term) | Classification not possible |
- |
- | - | Because evaluation of the reliability of an ecological toxicity test using nanoparticles is not possible, it was classified as "Classification not possible." |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
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* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted. * Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement. Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file. * Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users. * This is a provisional English translation of classification results and is subject to revision without notice. * The responsibility for any resulting GHS labelling and SDS referenced from this site is with users. * Codes assigned to each of the hazard statements and codes for each of the precautionary statement are based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations. |