NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	1634-04-4
Chemical Name	Methyl tert-butyl ether [MTBE]
Substance ID	m-nite-1634-04-4_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Category 2	Danger	H225	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	Based on a flash point of -33.0 deg C (closed cup), and a boiling point of 55 deg C (HSDB (Access on June 2017)), it was classified in Category 2. Besides, it is classified in Class 3, PGII in UNRTDG (UN 2398).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 374 deg C (HSDB (Access on June 2017)).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (Not applicable)	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Not classified	- -	-	-	There are five reports of LD50 values for rats: 2,963 mg/kg (IARC 73 (1999), ACGIH (7th, 2002)), 3,800 mg/kg (EHC 206 (1998), EU-RAR (2002), DFGOT Vol. 17 (2002)), 3,866 mg/kg (ATSDR (1996), EHC 206 (1998), EU-RAR (2002), PATTY (6th, 2012)), 4,000 mg/kg (EU-RAR (2002), DFGOT Vol. 17 (2002)), and > 2,000 mg/kg (EU-RAR (2002)). Four cases correspond to "Not classified" (Category 5 in UN GHS classification), and one case corresponds to "Not classified" (Category 5 in UN GHS classification) or "Not classified." By adopting the category with a larger number of cases, it was classified as "Not classified" (Category 5 in UN GHS classification). The category was changed from the previous classification in accordance with the GHS classification guidance for the Japanese government.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on reports of LD50 values for rabbits of 10,000 mg/kg (EHC 206 (1998), DFGOT Vol. 17 (2002)), > 7,400 mg/kg (IARC 73 (1999)), > 10,000 mg/kg (ATSDR (1996), EHC 206 (1998)), and > 10,200 mg/kg (EHC 206 (1998), DFGOT Vol. 17 (2002), EU-RAR (2002)) and LD50 values for rats of > 2,000 mg/kg (EU-RAR (2002)), and > 6,800 mg/kg (DFGOT Vol. 17 (2002)), it was classified as "Not classified."	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Not classified	- -	-	-	Based on reports of LC50 values of 23,576 ppm (ACGIH (7th, 2002)), 85 mg/L (23,800 ppm) (EU-RAR (2002)), 86 mg/L (24,080 ppm) (IARC 73 (1999)), 33,370 ppm (ATSDR (1996), EU-RAR (2002), PATTY (6th, 2012)), 39,395 ppm (PATTY (6th, 2012), EU-RAR (2002)), and 85-142 mg/L (23,800-39,760 ppm) (DFGOT Vol. 17 (2002)) in 4-hour inhalation exposure tests with rats, it was classified as "Not classified." Besides, since the LC50 values were lower than 90% of the saturated vapour pressure concentration (267,327 ppm), the reference values in the unit of ppm were applied as vapour with little mist.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	Based on a report that in a skin irritation test (OECD TG 404 compliant) with rabbits, moderate to severe edema and moderate erythema were observed by an application of this substance for 4 hours (EU-RAR (2002)), it was classified in Category 2. Besides, this substance is classified as "Skin Irrit. 2" in the EU CLP classification (ECHA CL Inventory (Access on June 2017)).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	Based on a report that in an eye irritation test (OECD TG 405 compliant) with rabbits, symptoms of eye irritation such as erythema, thickening, chemosis, and hypersecretion were observed by applying this substance, but these resolved within 7 days (DFGOT Vol. 17 (2002)), it was classified in Category 2B.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Skin sensitization	Not classified	- -	-	-	Based on a report that in skin sensitization tests with guinea pigs, this substance was negative in multiple tests (EHC 206 (1998), DFGOT Vol. 17 (2002), EU-RAR (2002), ATSDR (1996)), it was classified as "Not classified."	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Germ cell mutagenicity	Classification not possible	- -	-	-	The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo, it was negative in all the micronucleus tests with mouse peripheral blood, chromosomal aberration tests with bone marrow cells of rats and mice, a gene mutation test with mouse spleen lymphocytes, and an unscheduled DNA synthesis test with mouse hepatocytes, and positive in a comet assay with rat lymphocytes (EU-RAR (2002), IARC 73 (1999), Environmental Risk Assessment for Chemical Substances Vol.4 (Ministry of the Environment, 2005), ACGIH (7th, 2002), ATSDR (1996), EHC 206 (1998), DFGOT Vol. 17 (2002), ECETOC TR72 (1997)). As for in vitro, bacterial reverse mutation tests were negative, a gene mutation test, a micronucleus test and a chromosomal aberration test with mammalian cultured cells were negative, and a mouse lymphoma test was positive, and a sister chromatid exchange test showed an equivocal result (EU-RAR (2002), IARC 73 (1999), Environmental Risk Assessment for Chemical Substances Vol.4 (Ministry of the Environment, 2005), ACGIH (7th, 2002), DFGOT Vol. 17 (2002), EHC 206 (1998), PATTY (6th, 2012), ECETOC TR72 (1997)).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Carcinogenicity	Classification not possible	- -	-	-	In carcinogenicity studies in which rats were exposed by inhalation for 2 years and mice for 18 months, a significant increase in renal tumors (total incidences of renal tubular adenomas and carcinomas) and testicular interstitial adenomas was seen at 3,000 ppm in male rats, and in the test with mice, increased hepatocellular adenomas at 8,000 ppm group in females were observed (ACGIH (7th, 2002), IARC 73 (1999), EU-RAR (2002)). In addition, in a carcinogenicity study with rats dosed by gavage for 2 years, an increase in testicular interstitial cell tumors in males and lymphoma and leukemia in females were observed at 1,000 mg/kg/day (ACGIH (7th, 2002), IARC 73 (1999), EU-RAR (2002)). Among these tumors, renal tumors were specific findings for male rats related to an increase in alpha 2u-globulin (EU-RAR (2002)), and tumors of testicular interstitial cells had a large contribution from aging (ACGIH (7th, 2002)), etc., and it was concluded that none of the findings was applicable to humans (EU-RAR (2002)). As for the classification by other organizations, IARC classified it in Group 3 because there was limited evidence in experimental animals for carcinogenicity (IARC 73 (1999)), and on the other hand, ACGIH judged that the renal tumors in male rats from alpha 2u-globulin and the liver tumors in female mice were findings showing carcinogenicity in experimental animals, and classified it in A3 (ACGIH (7th, 2002)). Meanwhile, in the EU risk assessment, it was concluded that liver tumors in mice and cancers of the lymphatic blood system of rats also created uncertainties in considering extrapolation to humans, and the classification of this substance for carcinogenicity corresponded to a borderline case between non-classification and Category 3 (in the former DSD classification, but was corresponding to Category 2 of the current CLP classification) (EU-RAR (2002)), and this substance was not classified for carcinogenicity by EU (ECHA CL Inventory (Access on June 2017)). From the above, based on the conclusion by IARC and the opinion of the EU, it is considered that there is insufficient evidence to classify it in Category 2, therefore, it was classified as "Classification not possible."	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Classification not possible	- -	-	-	In a one-generation study with rats exposed by inhalation, in the parental animals, a decreasing tendency of the pregnancy rate (no significant difference) in the second pregnancy at or above 250 ppm, and in the pups, a decrease in the survival rate at birth and on postnatal day 4 at or above 1,000 ppm were seen, but there was no decrease in the survival rate of the second litter pups (EU-RAR (2002)). In addition, in a 2-generation test with rats exposed by inhalation, in the parent animals, hypoactivity and blepharospasm at or above 3,000 ppm, and decreased body weight gain at or above 8,000 ppm in F0, and decreased body weight gain at or above 3,000 ppm in F1 were found, and in the pups, only an increase in the number of dead pups at 8,000 ppm in F1 was observed (since it was an increase in dead pups due to the death of all 16 pups in the one litter, there was no change in the overall survival rate, and it was not considered to be an effect by administration of this substance), and effects on fertility were not indicated (EU-RAR (2002), ACGIH (7th, 2002)). On the other hand, in developmental toxicity studies with pregnant rats or pregnant mice exposed by inhalation during the organogenesis period, in both rats and mice, a decrease in food consumption was observed in maternal animals from 250 ppm, but in fetuses, there was no effect at up to 2,500 ppm in rats, and fused sternebrae were observed at 2,500 ppm in mice (EU-RAR (2002), ACGIH (7th, 2002)). However, it was not considered to be an effect of administration because no abnormality in the ribs and vertebrae was observed (EU-RAR (2002)). In addition, also in developmental toxicity tests with pregnant mice and pregnant rabbits at higher concentrations (up to 8,000 ppm), no developmental effects were observed in the test with rabbits, and increased incidences of cleft palate were seen in the fetuses at 8,000 ppm in the test with mice (EU-RAR (2002), ACGIH (7th, 2002)), but they were considered to be a secondary effect due to the significant maternal toxicity (symptoms such as ataxia, weakness, labored breathing at or above 4,000 ppm, and decreased body weight gain and the embryo loss after implantation etc. at 8,000 ppm) (EU-RAR (2002)). On the other hand, there is a description in ACGIH that in a developmental toxicity test with pregnant mice, both the increased incidence of skeletal variations which was observed at or above 4,000 ppm and the cleft palate at 8,000 ppm were judged to be effects of administration of this substance, and the NOEL both for maternal toxicity and for developmental toxicity was 1,000 ppm (ACGIH (7th, 2002)). From the above, there was no evidence of reproductive and developmental toxicity in the 1-generation and 2-generation studies and the multiple developmental toxicity tests with rats by an inhalation route. However, it was difficult to judge whether the increased incidences of cleft palate, which were seen at the highest dose in the developmental toxicity test with pregnant mice, were a secondary effect due to maternal toxicity, therefore, it was classified as "Classification not possible" for this hazard class in accordance with the GHS classification guidance for the Japanese government.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	Category 3 (respiratory tract irritation, narcotic effects)	Warning	H335 H336	P304+P340 P403+P233 P261 P271 P312 P405 P501	It was reported that in a single inhalation exposure test with mice, at or above 300 mg/m3, a decrease in the respiratory rate was seen immediately after the start of the exposure, and it showed respiratory tract irritation (EHC 206 (1998), ACGIH (7th, 2002), EU-RAR (2002)). In addition, there is a report that in a 4-hour single inhalation exposure test with rats, ataxia, abnormal gait, and tremors were observed at or above 20 mg/L exceeding Category 2 (EHC 206 (1998), ACGIH (7th, 2002), EU-RAR (2002), DFGOT Vol. 17 (2002), IARC 73 (1999)). Furthermore, there is a report that in a single oral administration test with rats, a decrease in locomotor activity, muscle weakness, hyperpnea, ataxia, tremors, and loss of righting reflex were seen at or above 2,000 mg/kg exceeding Category 2 (EHC 206 (1998), EU-RAR (2002)). These symptoms were considered by reporters to indicate a transient suppression of the central nervous system (EHC 206 (1998), EU-RAR (2002), DFGOT Vol. 17 (2002)). From the above, it was classified in Category 3 (respiratory tract irritation, narcotic effects). Besides, as for humans, there is a report that in an inhalation exposure test with volunteers, by inhalation exposure at 75 ppm for 3 hours, some of the subjects complained of very slight heavy-headedness as a result of interviews (EU-RAR (2002), EHC 206 (1998), DFGOT Vol. 17 (2002)).	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	As for humans, it is reported that among the workers exposed to gasoline containing this substance, in those persons who had high concentrations in the blood, the odds ratio of the persons who complained of one or more symptoms associated with exposure (headache, eye irritation, burning sensation of the nose and throat) was 8.9 (95% confidence interval 1.2-75.6) and this was significantly high (Environmental Risk Assessment for Chemical Substances Vol.4 (Ministry of the Environment, 2005), ACGIH (7th, 2002)). As for experimental animals, multiple oral or inhalation toxicity studies with rats or mice were conducted, and no effects which are available for evidence of the classification were found within the guidance value range for Category 2. Besides, at the doses exceeding the guidance value range for Category 2, effects on the nervous system were mainly observed, and renal disorders specific to male rats were observed (Environmental Risk Assessment for Chemical Substances Vol.4 (Ministry of the Environment, 2005), ACGIH (7th, 2002), EHC 206 (1998), DFGOT Vol. 17 (2002), EU-RAR (2002)). From the above, although no findings available for evidence of the classification were found, headache was seen other than irritation in humans, and even in experimental animals, the effects on the nervous system were seen at high doses, therefore, it was not classified as "Not classified," but was classified as "Classification not possible." The classification result was different from the previous classification due to the consideration of human findings.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Not classified	- -	-	-	From 72-hour EC50 (rate method) >110 mg/L for algae (Pseudokirchneriella subcapitata) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)), it was classified as "Not classified."	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	If chronic toxicity data are used, then it is classified as "Not classified" due to being not rapidly degradable (non-biodegradable, average degradation rate by BOD: 0% (J-CHECK, 2002)), 21-day NOEC (reproduction inhibition) = 11 mg/L for crustacea (Daphnia magna), and 72-hour NOEC (rate method) >110 mg/L for algae (Pseudokirchneriella subcapitata) (both Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" due to being not rapidly degradable (non-biodegradable, average degradation rate by BOD: 0% (J-CHECK, 2002)), and 96-hour LC50 >120 mg/L for fish (Oryzias latipes) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2017)). From the above results, it was classified as "Not classified."	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.	FY2017	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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