GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 1634-04-4
Chemical Name Methyl tert-butyl ether [MTBE]
Substance ID H29-B-045
Classification year (FY) FY2017
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 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)  
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
-
-
- - Liquid (GHS definition)
3 Aerosols Not applicable
-
-
- - Not aerosol products.
4 Oxidizing gases Not applicable
-
-
- - Liquid (GHS definition)
5 Gases under pressure Not applicable
-
-
- - Liquid (GHS definition)
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).
7 Flammable solids Not applicable
-
-
- - Liquid (GHS definition)
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 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)).
10 Pyrophoric solids Not applicable
-
-
- - Liquid (GHS definition)
11 Self-heating substances and mixtures Classification not possible
-
-
- - Test methods applicable to liquid substances are not available.
12 Substances and mixtures which, in contact with water, emit flammable gases 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).
13 Oxidizing liquids Not applicable
-
-
- - The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
14 Oxidizing solids Not applicable
-
-
- - Liquid (GHS definition)
15 Organic peroxides Not applicable
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule
16 Corrosive to metals Classification not possible
-
-
- - No data 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
-
-
- - 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.
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."
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Liquid (GHS definition)
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.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - Classification not possible due to lack of data.
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)).
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.
4 Respiratory sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
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."
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)).
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."
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.
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)).
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.
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 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."
11 Hazardous to the aquatic environment (Long-term) 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."
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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