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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	13463-67-7
Chemical Name	Titanium dioxide (excluding nanoparticle)
Substance ID	H28-B-020, C-028B
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

PHYSICAL HAZARDS

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.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	For this classification, classification was done using titanium oxide information excluding data specified as nanoparticles. Based on reports of LD50 values for rats of > 2,000 mg/kg, > 5,000 mg/kg (SIDS (2015)), > 10,000 mg/kg (HSDB (Access on May 2016), Environmental Risk Assessment for Chemical Substances Vol.8 (Ministry of the Environment, 2010)), > 12,000 mg/kg, > 20,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 8 (Ministry of the Environment, 2010)), it was classified as "Not classified."
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on reports of an LD50 value for hamsters of > 10,000 mg/kg (HSDB (Access on May 2016), Environmental Risk Assessment for Chemical Substances Vol. 8 (Ministry of the Environment, 2010)), it was classified as "Not classified."
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)	Not classified	- -	-	-	Based on a report of an LC50 value for rats of > 5.09 mg/L (SIDS (2015)), it was classified as "Not classified." There is also a report of > 3.43 mg/L (SIDS (2015)), however, because classification could not be judged, it was not adopted as data. New information was added and classification was changed.
2	Skin corrosion/irritation	Not classified	- -	-	-	From descriptions (SIDS (2015)) of slight or no irritation in skin irritation tests using rabbits, it was classified as "Not classified" (Category 3 in UN GHS classification).
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	There is a report that in an eye irritation test (OECD TG 405) using rabbits, mild conjunctival redness was observed in 2 out of 3 animals 24 hours after the application, but disappeared within 48 hours, and there is a report that slight irritation was observed 24 hours after the application, but no irritation was observed after 48 and 72 hours (SIDS (2015)). The irritation observed in these tests may be thought to be due to physical stimulation, however, since the particle shape could not be confirmed, it was classified as "Classification not possible."
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	Both a skin sensitization test using the guinea pigs (Buehler method, OECD TG 406) and a skin sensitization test using mice (LLNA method, OECD TG 429) were negative, and it was judged that this substance doesn't have skin sensitizing potential (SIDS (2015)). Therefore, it was classified as "Not classified."
5	Germ cell mutagenicity	Classification not possible	- -	-	-	As for in vivo, it was reported that micronucleus tests using peripheral erythrocytes or bone marrow cells of mice were negative, an hprt gene mutation assay using alveolar cells of rats was positive, a chromosomal aberration test using mouse bone marrow cells and a DNA damage test in rat lungs were negative (SIDS (2015), 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)). As for in vitro, negative results were reported in all of bacterial reverse mutation tests, micronucleus tests, chromosome aberration tests, and mouse lymphoma assays using cultured mammalian cells (SIDS (2015), OEL Documentations (Japan Society For Occupational Health (JSOH), 2013), 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)). In addition, it is evaluated in SIDS (2015) that it is not possible to conclude on the genotoxicity of this substance because positive in vivo findings are not by standard tests. From the above, it was classified as "Classification not possible."
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	In a large scale cohort study in Europe, a slightly increased risk of lung cancer in occupational exposure to this substance was indicated, however, dose?response relationship was not observed in the exposed group. In addition, in cohort studies and a case-control study in North America, an association between exposure of this substance and carcinogenesis was not shown, and it is concluded that the evidence in humans for the carcinogenicity is limited (IARC 93 (2010)). As for experimental animals, an increase in the incidences of lung adenomas and squamous cell carcinomas was seen in the high concentration group (250 mg/m3) in one study using rats exposed by inhalation for 2 years (IARC 93 (2010), SIDS (2015)). In addition, also in a study in which rats were exposed by inhalation to ultrafine particles (P25) of this substance for 2 years, an increase in incidence of lung tumors (benign squamous cell tumors, squamous cell carcinomas, adenomas, and adenocarcinomas) in exposed group (32/100 vs control group 1/217) was observed, but no increase in tumor incidence was observed in a mice study (IARC 93 (2010)). Other than this, an increase in incidence of benign and malignant lung tumors was observed in a test using rats in which titanium oxide was administered by intratracheal instillation. On the other hand, no increase in tumor was observed in any of the tests using rats or mice dosed orally, subcutaneously, or intraperitoneally (IARC 93 (2010)). From the above, IARC classified it in Group 2 based on the sufficient evidence of carcinogenicity in experimental animals (IARC 93 (2010)). In addition, the Japan Society For Occupational Health (JSOH) classified it in Group 2B as a provisional classification (Recommendation of Occupational Exposure (2015)). Therefore, the substance was classified in Category 2 for this hazard class.
7	Reproductive toxicity	Classification not possible	- -	-	-	In a reproduction/developmental toxicity screening test (OECD TG 421) using rats, no adverse effects on fertility of parental animals, survival and development up to 4 days after delivery of offspring were observed even up to at a dose of 1,000 mg/kg/day administered by gavage (SIDS (2015)). However, because this test is a screening test, it was not possible to classify this substance as "Not classified" only from this result, and there is no other data available for classification. Therefore, the classification was 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 a 2-year inhalation toxicity test using rats, increases in leukocyte and neutrophil counts, and increase in pneumonia, tracheitis, and rhinitis with squamous metaplasia in the anterior nasal cavity were observed at 10 mg/m3 which is in the range of Category 1, and in a 24-month inhalation toxicity study using rats, lung fibrosis, minor changes in cytologic pattern in bronchoalveolar lavage fluid (BALF), a slight increase in polymorphonuclear leukocyte count, increase in macrophage and hyperplasia of the lung-associated lymph nodes were observed at 5 mg/m3 (SIDS (2015)). Besides, as for oral route, no effects were observed even at doses corresponding to "Not classified" in 13-week or 103-week repeated dose toxicity tests using rats or mice dosed by feeding (Environmental Risk Assessment for Chemical Substances Vol. 8 (Ministry of the Environment, 2010)). Therefore, it was classified in Category 1 (respiratory organs).
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment (Acute)	Not classified	- -	-	-	From 72-hour EL50 (growth rate) > 100 mg/L for algae (Pseudokirchneriella subcapitata), 48-hour EL50 > 100 mg/L for crustacea (Daphnia magna), and 96-hour LL50 > 100 mg/L for fish (Oryzias latipes) (all SIDS, 2015), it was classified as "Not classified."
11	Hazardous to the aquatic environment (Long-term)	Category 4	- -	H413	P273 P501	Reliable chronic toxicity data were not obtained. It is poorly water-soluble (insoluble in water, ICSC, 2002), and classified as "Not classified" for acute toxicity, but due to the unknown environmental behavior of the inorganic compound, it was classified in Category 4.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

NOTE:

* 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.

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