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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	108-20-3
Chemical Name	Isopropyl ether
Substance ID	R01-B-020
Classification year (FY)	FY2019
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	FY2018 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	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	Category 2	Danger	H225	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	It was classified in Category 2 based on a flash point of -28 deg C (closed cup) and a boiling point of 69 deg C (NFPA (2010)).
7	Flammable solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of 443 deg C (NFPA (2010)).
10	Pyrophoric solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	No data available.
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: 4,600-1,400 mg/kg (ACGIH (7th, 2001)) (2) LD50 for rats: 4,600 mg/kg, 8,470 mg/kg, 12,000 mg/kg (DFGOT vol.21 (2005)) (3) LD50 for rats: 6.4 mL/kg (4,645.12 mg/kg), 16.5 mL/kg (11,975.7 mg/kg) (PATTY (6th, 2012))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: 20 mL/kg (14,516 mg/kg) (ChemID (Access on August 2019)) [Reference Data, etc.] (2) As a result of 1-hour exposure of the skin of rabbits at 50,000 mg/kg, no visible signs of toxicity were observed (DFGOT vol.21 (2005)) (3) As a result of exposure of the skin of rabbits (concentration unknown), no adverse effects were observed (PATTY (6th, 2012)).
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Based on (1), the LC50 value was considered to be 16,000 ppm or above. However, because it was impossible to determine the category, it was classified as "Classification not possible." Besides, since the exposure concentration was lower than 90% of the saturated vapor pressure concentration (196,068 ppm), a reference value in units of ppm was applied as a vapor with little mist. The category was changed from the previous classification by the use of the new information sources. [Evidence Data] (1) Lethal vapor concentration (4 hours) for rats: 1.60% (16,000 ppm) (PATTY (6th, 2012)) [Reference Data, etc.] (2) LC50 (exposure time unknown) for rats: 162,000 mg/m3 (162 mg/L = 38,763.95 ppm) (ChemID (Access on August 2019)) (3) LC50 (15 minutes) for mice: 36,000 mL/m3 (36,000 ppm) (DFGOT vol.21 (2005))
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) In a ski irritation test in which 0.5 mL of this substance was applied semiocclusively to the skin of rabbits for 4 hours in accordance with OECD TG 404, the mean scores at 24/48/72 hours for erythema and edema were 1.77 and 0.87, respectively (REACH registration dossier (Access on July 2019)). [Reference Data, etc.] (2) This substance had a slight irritative effect on the skin and caused irritation to the eyes of rabbits (DFGOT vol.21 (2005)).
3	Serious eye damage/eye irritation	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, the category was changed by the use of the new information sources. [Evidence Data] (1) In an eye irritation test in which this substance was applied to the eyes of rabbits in accordance with OECD TG 405, the mean scores at 24/48/72 hours of corneal opacity, iris and conjunctival redness and chemosis were all 0 in 2 animals, and that for conjunctival redness was 0.33 in only 1 animal (REACH registration dossier (Access on July 2019)). [Reference Data, etc.] (2) In humans exposed at 800 ppm for 5 min, most subjects reported irritation of the eyes and nose (PATTY (6th, 2012)). (3) This substance had a slight irritative effect on the skin and caused irritation to the eyes of rabbits (DFGOT vol.21 (2005), PATTY (6th, 2012)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." Besides, the category was changed due to the new data obtained. [Evidence Data] (1) In a local lymph node assay (LLNA) with mice in accordance with OECD TG 429, Stimulation Indices of 0.75, 0.71 and 0.80 were determined with this substance at concentrations of 25, 50 and 100%, respectively. From these results, this substance was judged to be negative (REACH registration dossier (Access on July 2019)). (2) In a test to confirm reactivity with lysine-containing peptides, it was judged that this substance does not react with it (DFGOT vol.21 (2005)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] There were no in vivo data of this substance. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) As for in vitro, negative results in a bacterial reverse mutation test and a mammalian cell chromosomal aberration test are reported (DFGOT vol.21 (2005)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) In a carcinogenicity test with rats by oral gavage for 78 weeks, 4 days a week, at 250 or 1,000 mg/kg/day, an increased incidence of ear duct carcinomas in males and females, the onset of interstitial cell adenomas of the testis, and a slight increase in malignant sarcomas of the uterus and vagina were reported. However, a review of the data of this study indicated that the incidences of these tumors were in many cases consistent with those observed in historical control animals at the same facility, and the classification of ear duct carcinomas was inappropriate as a result of an independent review of slides from the same facility for another test. Therefore, these results were considered to be of limited usefulness for the purpose of identifying the potential carcinogenic effect of this substance (REACH registration dossier (Access on June 2019)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Based on (1), no reproductive effects were observed. Also, based on (2), no developmental effects were observed even at toxic doses for maternal animals. Since (1) was a screening test, it was classified as "Classification not possible" due to lack of data. Besides, the category was changed by the use of the new information sources. [Evidence Data] (1) In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422), no reproductive and developmental effects were observed even at toxic doses for parental animals (Safety Test (Ministry of Economy, Trade and Industry (METI), (2007))). (2) There is a report that in a developmental toxicity test with female rats exposed on gestational days 6-15 by inhalation, a skeletal variation (rudimentary or shortened 14th ribs) was observed, but no teratogenic effects were seen in the offspring at concentrations where reduced body weight gain and food consumption were observed in maternal animals (DFGOT vol.21 (2005)).
8	Specific target organ toxicity - Single exposure	Category 3 (narcotic effects, respiratory tract irritation)	Warning	H336 H335	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 3 (narcotic effects, respiratory tract irritation). In the previous classification, evidence of the classification was based on HSDB (2003) in which central nervous system depression and fatal respiratory paralysis in humans were described. However, this information was not adopted as the evidence of classification because it was described as an effect of ethyl ether in HSDB (Access on June 2019). Therefore, the classification was changed. [Evidence Data] (1) As for humans, there is a report that when exposed at 800 ppm of the vapour of this substance for 5 minutes, most subjects reported irritation of the nose (ACGIH (7th, 2001)). (2) There is a report that all animals (monkeys, rabbits and guinea pigs) survived a 1-hour exposure to the vapour of this substance at 30,000 ppm but showed signs of anesthesia (PATTY (6th, 2012), DFGOT vol.21 (2005)). (3) There is a description that this substance has an anesthetic action on experimental animals like diethyl ether (ACGIH (7th, 2001)).
9	Specific target organ toxicity - Repeated exposure	*	- -	-	-	[Rationale for the Classification] Based on (1), no effects that could be extrapolated to humans were observed within the range of the guidance values by the oral route. Based on (2), no effects were observed within the range of the guidance values either by the inhalation route. Therefore, it was classified as "Not classified" (oral and inhalation). Besides, there was no information of dermal exposure, and it was concluded that classification was not possible due to lack of data. [Evidence Data] (1) In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats by gavage at 100-1,000 mg/kg/day for 42 days in males and 41-55 days in females, eosinophilic bodies in the proximal tubule epithelium in males at or above 100 mg/kg/day (converted guidance value: male/female: 47/45 mg/kg/day, within the range for Category 2), increased liver and kidney weights, increases in total cholesterol, phospholipids and total protein, centrilobular hepatocyte hypertrophy, and necrosis of the proximal tubules (males), etc. at 300 or 1,000 mg/kg/day (converted guidance value: male: 140 or 467 mg/kg/day, female: 137 or 456 mg/kg/day, exceeding the range for Category 2) were observed. Among these results, the kidney lesions in males were considered to be a sign of alpha-2u globulin accumulation (Safety Test (Ministry of Economy, Trade and Industry (METI), 2007)). (2) In a 90-day inhalation test with rats exposed (6 hours a day, 5 days a week) at 480-7100 ppm, no effects were observed at 480 ppm (converted guidance value: 2.0 mg/L, exceeding the range for Category 2), and exposure to 3,300 ppm (converted guidance value: 13.8 mg/L, exceeding the range for Category 2) or above led to increased liver and kidney weights in males, and hypertrophic liver cells and an increased number of hyaline droplets in the proximal renal tubules were found in males at 7,100 ppm (converted guidance value: 29.7 mg/L, exceeding the range for Category 2) (DFGOT vol.21 (2005)).
10	Aspiration hazard	*	- -	-	-	[Rationale for the Classification] 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 Short term (Acute)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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