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

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GENERAL INFORMATION
 
Item Information
CAS RN 108-10-1
Chemical Name Methyl isobutyl ketone
Substance ID m-nite-108-10-1_v2
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. FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2 Flammable gases Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3 Aerosols Not classified (Not applicable)
-
-
- - Not aerosol products. FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4 Oxidizing gases Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5 Gases under pressure Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2015 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 14 deg C (closed cup), and a boiling point of 117-118 deg C (ICSC (1997)), it was classified in Category 2. Besides, it is classified in Class 3, PG II (UN 1245) in UNRTDG. FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7 Flammable solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2015 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. FY2015 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 460 deg C (ICSC (1997)). FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10 Pyrophoric solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2015 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. FY2015 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). FY2015 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. FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14 Oxidizing solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition) FY2015 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 FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16 Corrosive to metals Classification not possible
-
-
- - No data available. FY2015 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
-
-
- - Based on reports of LD50 values of 2,080 mg/kg (PATTY (6th, 2012), ACGIH (7th, 2010), Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008), EHC 117 (1990)), 2,780 mg/kg, 2,991 mg/kg (SIDS (2011)), 3,200 mg/kg (PATTY (6th, 2012), SIDS (2011)), 4,500 mg/kg, 4,570 mg/kg (PATTY (6th, 2012), SIDS (2011), ACGIH (7th, 2010), EHC 117 (1990)), 4,600 mg/kg (SIDS (2011), Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008), EHC 117 (1990)), 1,900-4600 mg/kg (SIDS (2011)), and 2,080-4,600 mg/kg (NTP TR 538 (2007), DFGOT Vol. 13 (1999)) for rats, this substance was classified as "Not classified" (Category 5 in UN GHS classification). FY2015 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 of > 3,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)) and 16,040 mg/kg (SIDS (2011)) for rabbits, this substance was classified as "Not classified." FY2015 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) FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1 Acute toxicity (Inhalation: Vapours) Category 3


Danger
H331 P304+P340
P403+P233
P261
P271
P311
P321
P405
P501
There are reports that LC50 values (4 hours) for rats were 8.2-16.4 g/m3 (1,968-3,936 ppm) (NTP TR 538 (2007), DFGOT Vol. 13 (1999), EHC 117 (1990)) and 3,000 ppm (SIDS (2011)). The former corresponds to Category 3 or 4 and the latter corresponds to Category 4. Since the source of these data was the same, this substance was classified in Category 3 with higher hazard. Since the LC50 values were lower than 90% of the saturated vapor pressure concentration (26,184 ppm), a reference value in the unit of ppm was applied as vapor without mist. FY2015 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. FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2 Skin corrosion/irritation Not classified
-
-
- - There is a report that in a skin irritation test with rabbits, as a result of an occlusive application with this substance for 10 hours, erythema was persistent until after 24 hours (SIDS (2011), EHC117 (1990), NTP TR 538 (2007)). In addition, there is a report that in a skin irritation test with guinea pigs, as a result of an application of this substance (5 or 10 mL), slight irritation was observed (DFGOT Vol. 13 (1999), PATTY (6th, 2012)). From the above, based on reports that recovery property was observed and slight irritation was observed, this substance was classified as "Not classified" (Category 3 in UN GHS classification). FY2015 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
There is a report that in an eye irritation test (OECD TG 405) with rabbits, as a result of application with a 0.1 mL undiluted solution of this substance, corneal opacity, conjunctival redness and conjunctivitis were observed, but they resolved within 7 days (ECETOC TR48 (1992)). In addition, there is a report that in another test with rabbits, as a result of application with a 0.1 mL undiluted solution of this substance, irritation was observed within 10 minutes after application, and symptoms resolved after 60 hours (SIDS (2011), NTP TR 538 (2007), EHC117 (1990)). From the above, this substance was classified in Category 2B. Besides, this substance was classified as "Eye Dam. 1 H318" in the EU CLP classification (ECHA CL Inventory (Access on September 2015)). FY2015 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. FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4 Skin sensitization Classification not possible
-
-
- - Classification not possible due to lack of data. Besides, there is a report that in a maximization test (OECD TG 406) with guinea pigs, no sensitization was observed (DFGOT Vol. 13 (1999)). However, information such as details of the test was not obtained. Therefore, it was judged that it was inadequate information to classify as "Not classified." FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5 Germ cell mutagenicity Classification not possible
-
-
- - Since it was no longer possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government, it was classified as "Classification not possible." As for in vivo, a micronucleus test with mouse bone marrow cells was negative (IARC 101 (2012), SIDS (2011), PATTY (6th, 2012), EHC 117 (1990), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), DFGOT Vol. 13 (1999)). As for in vitro, bacterial reverse mutation tests, a chromosome aberration test, a micronucleus test, and an unscheduled DNA synthesis assay with cultured mammalian cells were negative. There was an equivocal result in a mouse lymphoma test with cultured mammalian cells, but it was difficult to judge positive since there was no dose dependency (SIDS (2011), PATTY (6th, 2012), ACGIH (7th, 2010), EHC 117 (1990), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), DFGOT Vol. 13 (1999)). FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6 Carcinogenicity Category 1B


Danger
H350 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) and (2), an increase in the incidence of tumors including malign ones was observed in two animal species, and in animal studies, it was considered that there was sufficient evidence of carcinogenicity, and therefore, this substance was classified in Category 1B. Also, based on the new evaluation, the classification result was changed.

[Evidence Data]
(1) In a 2-year inhalation exposure test with rats (6 hours/day, 5 days/week), increased incidences of renal tubular adenomas and renal tubular adenomas or carcinomas combined were observed in males, and malignant renal mesenchymal tumors were observed in females (2/50 animals). It was judged that there was weak evidence for alpha 2mu-globulin-mediated mechanism by which kidney tumor developed in males and that there was a low probability of kidney tumor in females spontaneously occurring because it was a rare tumor in females (IARC 101 (2012)).
(2) In a 2-year inhalation exposure test with mice (6 hours/day, 5 days/week), increased incidences of hepatocellular adenomas and hepatocellular adenomas or carcinomas combined were observed in both males and females (IARC 101 (2012)).

[Reference Data, etc.]
(3) This substance is a target substance in the public announcement on guidelines in order to prevent the impairment of worker's health caused by the chemical substances decided by the Minister of Health, Labour and Welfare based on paragraph (3) of Article 28 of the Industrial Safety and Health Act. Besides, the fact that the IARC had added this substance in Group 2B was the rationale for the designation of this substance as a substance subject to the Guidelines for Carcinogenicity (guidelines in order to prevent the impairment of worker's health, announcement No. 27 on February 7, 2020).
(4) As for classification results by domestic and international organizations, based on (1) and (2), the induction of tumors in experimental animals was judged positive but there was no data available on human carcinogenicity, and therefore, the IARC classified it in Group 2B (IARC 101 (2012)), the ACGIH classified it in A3 (ACGIH (7th, 2010)), and the EU classified it in Carc. 2 (EU CLP Classification Results (Accessed Jan. 2022)).
FY2021 GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
7 Reproductive toxicity Classification not possible
-
-
- - There is no information on human reproductive effects. As for experimental animals, in a two-generation reproduction toxicity study with rats by the inhalation route, general toxic effects such as effects on the liver (increased weights, centrilobular hepatocellular hypertrophy), effects on the kidney (increased weights, nephropathy), effects on the central nervous system (reduced startle response) were observed mainly at or above 1,000 ppm in F0 and F1 parental animals, but no adverse effects on sexual function and fertility were observed in either of the sexes of each generation (SIDS (2011), ACGIH (7th, 2010), Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008)). Also in pups, transient low value of body weights were only observed at up to 1,000 ppm in F1 (SIDS (2011), ACGIH (7th, 2010), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). However, there is a description that at 2,000 ppm, after the resumption of exposure of postweaning F1 pups (postnatal 22 days of age), except that one male died, symptoms of central nervous system suppression were observed in 7 males and 14 females (Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). On the other hand, as for developmental toxicity studies, as a results of inhalation exposure of pregnant rats or pregnant mice on Gestational Day 6-15, at the dose (3,000 ppm) at which maternal toxicity were observed such as decreased body weight gain and an increase in kidney weights in rats, death (3/30 animals) and an increase in liver weights in mice, as effects of developmental toxicity, low value of fetal weight and delayed ossification were observed in fetuses in both species, in addition, increased resorption was observed in mice (SIDS (2011), IRIS Tox. Review (2003), ACGIH (7th, 2010), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)).
From the above, in animal test results by only the inhalation route, no adverse effects on sexual function and fertility were observed even at doses where general toxic effects on the liver and kidney were manifested in parental animals, and also in the developmental toxicity test, in a test with pregnant rats, minor effects (low value of fetal weight, delayed ossification) were observed at doses where maternal toxicity was manifested. Similarly, also in a test with pregnant mice, only minor effects similar to rats and increased resorption were observed at the doses where 10% of the maternal animals died. Therefore, it is possible to classify as "Not classified" in the inhalation route. However, since this substance is a central nervous system acting substance, there is a lack of information on adverse effects on neurodevelopment of the next generation, so it was classified as "Classification not possible" for this hazard class.
FY2015 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
This substance is irritating to the respiratory tract (Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008), OEL Documentations (Japan Society For Occupational Health (JSOH), 1984), ACGIH (7th, 2010), SIDS (2011), EHC 117 (1990), IRIS Tox. Review (2003), DFGOT Vol. 13 (1999), ECETOC JACC (1987), PATTY (6th, 2012)). In humans, in inhalation exposure, cough, headache, sore throat, dizziness, narcotic effects, central nervous system suppression, nausea, vomiting, diarrhea, weakness, anorexia, loss of consciousness were reported and, in oral ingestion, abdominal pain in addition to these symptoms were reported (Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), OEL Documentations (Japan Society For Occupational Health (JSOH), 1984), SIDS (2011), EHC 117 (1990), IRIS Tox. Review (2003), DFGOT Vol. 13 (1999), ECETOC JACC (1987), PATTY (6th, 2012), ACGIH (7th, 2010)).
As for experimental animals, narcotic effects in inhalation exposure (higher concentration) with mice and guinea pigs and central nervous system depression, incoordination, and collapse in other tests with rats were reported (ACGIH (7th, 2010), ECETOC JACC (1987), PATTY (6th, 2012)).
From the above, this substance has respiratory tract irritating potential and narcotic effects, and it was classified in Category 3 (respiratory tract irritation, narcotic effects).
FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9 Specific target organ toxicity - Repeated exposure Category 1 (central nervous system)


Danger
H372 P260
P264
P270
P314
P501
In epidemiological studies on 19 workers who were exposed to this substance for 20 to 30 minutes daily during the operation of a centrifuge at an Italian business place, the air concentration of this substance was 500 ppm near the centrifuge, and 80 ppm in other rooms. In addition to acute irritation symptoms in the eye, nose, and throat, more than half the workers out of 19 complained of headache, anorexia, weakness, stomach ache, nausea, and vomiting as subjective symptoms, and a few workers complained of insomnia, lethargy, and chest pain, but clinical chemistry results were within the normal range for all of the workers (ACGIH (7th, 2010)). It is described that even in a follow-up study conducted five years later (the air concentrations of this substance: 100-105 ppm near the centrifuge, 50 ppm elsewhere), a few workers out of the remaining 14 answered that the central nervous symptoms and gastrointestinal symptoms persisted (ACGIH (7th, 2010)).
As for experimental animals, in a 13-week test with rats dosed by gavage, an slight increase in liver and kidney weights was only observed at a dose above the range for Category 2 (250 mg/kg/day), and a NOAEL of 250 mg/kg/day was assigned (SIDS (2011)). In addition, it was reported that in a 14-week test with rats and mice dosed by inhalation (estimated as vapor), an increase in serum cholesterol and urine glucose (rats) and an increase in liver weight (mice) were observed at a dose above the range for Category 2 (250 ppm (1.02 mg/L/6 hr/day)), but there were no clear toxicological findings based on which target organs can be identified at up to 1,000 ppm, therefore, a NOAEL was reported to be 1,000 ppm (SIDS (2011), ACGIH (7th, 2010)). Moreover, in multiple tests in which neurotoxicity of this substance was researched, most of them could not detect neurotoxicity, but in a two-generation reproductive toxicity study with rats, reduced startle response was noted at or above 1,000 ppm in F0 and F1 animals, and it is considered as a finding suggesting central nervous system depression (SIDS (2011)).
As the above, it is difficult to identify target organs from the existing data from experimental animals, but it was considered reasonable to classify it in Category 1 (central nervous system) for this hazard class based on the results of epidemiological studies in humans.
FY2015 GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10 Aspiration hazard Classification not possible
-
-
- - There is a description that because of the low viscosity of this substance, it may also be aspirated into the lungs when swallowed, causing chemical pneumonitis (EHC 117 (1990)). There is a description that if this liquid is swallowed, aspiration into the lungs may result in chemical pneumonitis (Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008)), but these are not findings based on a report of the case of direct exposure to this substance. However, this substance belongs to ketones composed of carbon atoms of 3 or more and not more than 13, and its calculated kinematic viscosity is 0.691 mm2/sec (viscosity: 0.55 mPa*s (25 deg C) (CRC Handbook of Chemistry and Physics (85th, 2004)), density (specific gravity): 0.796 g/cm3 (25 deg C) (Thermophysical Properties of Chemicals and Hydrocarbons (2008))). As the above, it corresponds to Category 2 in the UN GHC classification, but it was classified as "Classification not possible" according to the current GHS classification guidance for the Japanese Government. FY2015 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 24-hour LC50 = 1250 mg/L for crustacea (Artemia salina) (SIDS, 2011), and 96-hour LC50 = 505 mg/L for fish (Pimephales promelas) (ECETOC TR91, 2003), it was classified as "Not classified." FY2015 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 rapidly degradable (a degradation rate by 14-day BOD = 84%, a degradation rate by TOC = 97.1%, a degradation rate by GC = 100% (Official Bulletin of Ministry of International Trade and Industry, 1975)), 21-day NOEC (reproduction) = 7.8-39 mg/L for crustacea (Daphnia magna) (SIDS, 2011), and 31-day NOEC (growth) = 57 mg/L for fish (Pimephales promelas) (Environmental Risk Assessment for Chemical Substances vol. 6 (Ministry of the Environment, 2008)).
For a trophic level for which chronic toxicity data are not obtained, acute toxicity data are not obtained either.
From the above results, it was classified as "Not classified."
FY2015 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. FY2015 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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