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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	106-88-7
Chemical Name	1,2-Epoxybutane (synonym: 1,2-Btylene oxide)
Substance ID	R03-B-002-METI
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)
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 (FY2019 revised edition (Ver. 2.0))
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 classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not classified (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	It was classified in Category 2 based on a flash point of -22 deg C (closed cup) and a boiling point of 63.3 deg C (ICSC(2017)). Besides, this substance (stabilized) is classified in Class 3, PG II in UNRTDG (UN 3022).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Type G	- -	-	-	There is a chemical group associated with self-reactive properties (epoxides) present in the molecule. But stabilized one is classified in Class 3 in UNRTDG (UN 3022) and it is considered to be not applicable to self-reactive substances and mixtures, hazards of the highest precedence, and it was classified in Type G.
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 370 deg C (ICSC(2017)).
10	Pyrophoric solids	Not classified (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 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).
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.
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 500 mg/kg (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011)) (2) LD50 for rats: 900 mg/kg (SIAR (2001), AICIS IMAP (2015))
1	Acute toxicity (Dermal)	Category 4	Warning	H312	P302+P352 P362+P364 P280 P312 P321 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 4. [Evidence Data] (1) LD50 for rabbits: 2.1 mL/kg (converted value at the density of 0.83 g/cm3: 1,743 mg/kg) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), DFG MAK (1990)) (2) LD50 for rabbits: 1,757 mg/kg (SIAR (2001)) (3) LD50 for rabbits (males): in the range from > 1,500 to 2,950 mg/kg (AICIS IMAP (2015)) (4) LD50 for rabbits: 1.77 mL/kg (converted value at the density of 0.83 g/cm3: 1,469 mg/kg) (AICIS IMAP (2015))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] The category with the highest degree as judged based on (1) and (2) was adopted and this substance was classified in Category 3. Besides, since the exposure concentration was lower than 90% (166,987 ppm) of the saturated vapor pressure concentration, it was judged to be in a vapor state and classified based on the reference value in units of ppmV. Also, based on the new findings, classification results were changed. [Evidence Data] (1) LC50 (4 hours) for rats: 6 to 20 mg/L (2,050 to 6,550 ppm, 2,050 ppm: No death occurred, 6,550 ppm: All rats died). (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), US AEGL (2009), SIAR (2001)) (2) LC50 (4 hours) for rats: > 6.3 mg/L (2,136 ppm) (AICIS IMAP (2015), SIAR (2001))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 1B	Danger	H314	P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1B. Also, based on the new findings, classification results were changed. [Evidence Data] (1) It was reported that, in a skin irritation test with rabbits (n=4) (occlusive, 1-hour application, 8-day observation), full-thickness necrosis of the skin was observed in 2 cases (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), SIAR (2001), AICIS IMAP (2015), REACH registration dossier (Accessed July 2021)). (2) This substance was corrosive under occlusive conditions but not irritating under semi-occlusive conditions. Under semi-occlusive conditions, this substance may have volatilized due to its high volatility (AICIS IMAP (2015)). (3) This substance has irritating effect on the skin and the intensity of the irritating effect depends on the application condition and the volatility (SIAR (2001)). [Reference Data, etc.] (4) It was reported that, in a skin irritation test with rabbits (n=2) (semi-occlusive, 4-hour application, 8-day observation), no erythema or edema was observed in the observation at 24 hours, 48 hours, and 8 days after application (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), SIAR (2001), AICIS IMAP (2015), REACH registration dossier (Accessed July 2021)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1. [Evidence Data] (1) It was classified in Category 1B for dermal corrosion/irritation. (2) It was reported that, in an eye irritation test with rabbits, moderate or severe eye irritation was observed (DFG MAK (1990)). (3) It was reported that, in an eye irritation test with rabbits, when 0.005 mL or 0.02 mL of this substance was instilled in the eyes, moderate corneal damage was seen in the group treated at 0.005 mL and marked eye damage was observed in the group treated at 0.02 mL (AICIS IMAP (2015), REACH registration dossier (Accessed July 2021)). [Reference Data, etc.] (4) It was reported that, in an eye irritation test with rabbits (n=2), slight reddening and edema were observed at 1 hour after application and corneal opacity was also observed at 24 hours after application, but all effects disappeared within 8 days (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), SIAR (2001), AICIS IMAP (2015), REACH registration dossier (Accessed July 2021)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a maximization test with guinea pigs (n=10), no skin sensitization was observed (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), SIAR (2001), AICIS IMAP (2015), REACH registration dossier (Accessed July 2021)).
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] In (1) to (3), no positive results were obtained in an in vivo test using mammals but from the structure-activity correlation, it was not confirmed that this substance had been transferred and distributed to the target tissues in sufficient concentrations, and in (4), the Ministry of Health, Labour and Welfare concluded that this substance was genotoxic. Based on the above information, it was classified in Category 2. With the additional new information sources, the classification was reviewed and the classification result was changed. [Evidence Data] (1) As for in vivo, negative results were obtained in a dominant lethal test using rats (inhalation exposure, up to 1,000 ppm) and negative results were obtained in a chromosomal aberration test using bone marrow cells of rats (inhalation exposure, single exposure (7 hours) or 5 consecutive days (7 hours/day), up to 1,000 ppm) (SIAR (2001), REACH registration dossier (Accessed July 2021), AICIS IMAP (2016), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)). (2) As for in vitro, in a bacterial reverse mutation assay, a mammalian cell gene mutation study (mouse lymphoma cells) and a chromosomal aberration study (CHO), all positive results were obtained (SIAR (2001), REACH registration dossier (Accessed July 2021), AICIS IMAP (2016), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), DFG MAK (1990), US AEGL (2009)). (3) Although this substance was clearly positive in vitro, no mutagenic effects were detected in the bone marrow or germ cells in the vivo test. Concerning this result, the SIDS indicated the possibility that the test substance did not reach the tissues of the cells in sufficient concentrations (SIAR (2001)). (4) Based on the NTP view (NTP TR329 (1988)) that the negative results in the dominant lethal test were induced by the lower concentration of this substance in the testes and the IARC indicating that this substance was an alkylating agent (IARC 71 (1999)), the Ministry of Health, Labour and Welfare concluded that this substance was genotoxic (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on the classification results by domestic and international organizations and the finding that it was positive in one animal species in (1) and (5), it was classified in Category 2. [Evidence Data] (1) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2B (IARC 71 (1999)) and the Japan Society For Occupational Health (JSOH) classified it in Group 2B (Recommendation of Occupational Exposure Limits (2020): Classification in 2001), the EU classified it in Carc. 2 (CLP classification result) and the DFG classified it in Category 2 (List of MAK and BAT values 2020). (2) In a 2-year carcinogenicity study by inhalation exposure with rats, an increased incidence of papillary adenomas of the nasal cavity, alveolar/bronchiolar adenocarcinomas and alveolar/bronchiolar adenomas or carcinomas (combined) in males and an increased incidence of papillary adenomas of the nasal cavity in females were observed in the group exposed at the high concentration (400 ppm) (NTP TR329 (1988), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), AICIS IMAP (2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), US AEGL (2009), Canada CMP Screening Assessment (2008), SIAR (2001), DFG MAK (1990), REACH registration dossier (Accessed July 2021)). (3) In a 2-year carcinogenicity study by inhalation exposure with mice, a squamous-cell papilloma was observed in the nasal cavity (incisive duct) in 1 of 50 males in the group exposed at the high concentration (100 ppm) but no other neoplastic lesions related to exposure were observed (NTP TR329 (1988), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), AICIS IMAP (2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), US AEGL (2009), Canada CMP Screening Assessment (2008), SIAR (2001), DFG MAK (1990), REACH registration dossier (Accessed July 2021)). (4) Based on the above animal study results, the NTP concluded that there was clear evidence of carcinogenicity for male rats and equivocal evidence for female rats and no evidence of carcinogenicity was presented in male and female mice (NTP TR329 (1988), SIAR (2001), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)). (5) The Ministry of Health, Labour and Welfare concluded that this substance was a suspected human carcinogen (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, in (2), no developmental toxicity effects were observed. But in (1), no general toxicity effects were observed in parental animals even at the highest dose, and since the dose was insufficient, the presence or absence of effects on fertility could not be judged. In the previous classification, general toxicity effects on parental animals observed in (2) were unknown. Therefore, based on a decrease in the number of pups and an increase in fetal resorption observed at 1,000 ppm, it was classified in Category 2, but at this dose, many death cases in parental animals were reported and the category was changed. [Evidence Data] (1) It was reported that, in a reproduction toxicity study by inhalation exposure with rats (for 3 weeks before mating and days 1 to 19 of gestation, 250 ppm and 1,000 ppm), lower body weight (nonsignificant) was observed in parental animals at 1,000 ppm, but there were no effects on weight and tissues of the main organs and parameters related to reproduction, fetal growth, viability and development were unaffected (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), AICIS IMAP (2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), SIAR (2001), US AEGL (2009)). (2) It was reported that, in a developmental toxicity study by inhalation exposure with rabbits (days 1 to 24 of gestation, 250 ppm and 1,000 ppm), marked general toxicity effects were observed in parental animals (12% died) but no developmental toxicity was observed at 250 ppm. 2 of 24 litters showed a decrease in the number of live fetuses and an increase in the frequency of resorptions, and marked general toxicity was observed in parental animals (58% died) at 1,000 ppm (SIAR (2001), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), AICIS IMAP (2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), US AEGL (2009)). (3) The Ministry of Health, Labour and Welfare reported that since there was little information about reproductive toxicity of this substance and no experimental results showing clear reproductive and developmental toxicity, the reproductive and developmental toxicity of this substance "could not be judged." (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)).
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) to (4), it was classified in Category 3 (respiratory tract irritation, narcotic effects). Besides, narcotic effects were adopted, since additional information was collected after the previous classification. [Evidence Data] (1) It was reported that, in an acute inhalation (vapor) exposure test with rats (4 hours), ocular discharge and dyspnea were observed at 2,050 ppm (6 mg/L, within the range for Category 1) and death was observed (in all animals) at 6,550 ppm (20 mg/L, within the range for Category 2) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), SIAR (2001), US AEGL (2009)). (2) It was reported that, in an acute inhalation (vapor) exposure test with mice (4 hours), dyspnea was observed at 2,050 ppm (6.05 mg/L, within the range for Category 1) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), US AEGL (2009), NTP TR (1988)). (3) It was reported that, in an animal test, this substance was irritating to the eyes, skin, and respiratory tract and might cause a reduction in consciousness at high concentration; inhalation exposure might cause confusion, cough, dizziness, headache, a feeling of suffocation, nausea, sore throat and loss of consciousness; and oral exposure might further cause stomachache (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011)). (4) It was reported that, in a high-concentration inhalation exposure study of an animal test, this substance had narcotic effects (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), DFG MAK (1990)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (respiratory organs)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on the effects on the nasal cavity in (1) to (3), it was classified in Category 2 (respiratory organs). Besides, renal tubular necrosis was observed but it was not adopted because it was observed in the range corresponding to "Not classified." In addition, the effects on the nervous system adopted in the previous classification were not observed in (1) to (6) and were not adopted. [Evidence Data] (1) In a 13-week inhalation toxicity study with rats (vapor, 6 hours/day, 5 days/week), effects on the nasal cavity (flattening and thickening of the olfactory and respiratory epithelium, an increased number of inflammatory cells in the nasal cavity), decreased hepatocellular size, decreased cell content in the cortex of the thymus gland and myeloid hyperplasia in vertebral bone marrow were observed at 600 ppm (1.17 mg/L, in the range corresponding to "Not classified"). It was reported that no effects were observed in the trachea and lungs (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), AICIS IMAP (2015), DFG MAK (1990), US AEGL (2009), SIAR (2001)). (2) It was reported that, in a 13-week inhalation toxicity study with rats (vapor, 6 hours/day, 5 days/week), decreased liver weight and inflammation of the nasal cavity were observed at 800 ppm (2.34 mg/L, in the range corresponding to "Not classified") (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), AICIS IMAP (2015), NTP TR (1988), US AEGL (2009), SIAR (2001)). (3) It was reported that, in a 103-week inhalation toxicity study with rats (vapor, 6 hours/day, 5 days/week), effects on the nasal cavity (inflammation, epithelial hyperplasia, squamous metaplasia, hyperostosis of the nasal turbinate bone, atrophy of the olfactory epithelium) were observed at 200 ppm (0.59 mg/L, within the range for Category 2) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), AICIS IMAP (2015), NTP TR (1988), DFG MAK (1990), US AEGL (2009), SIAR (2001)). [Reference Data, etc.] (4) In a 13-week inhalation toxicity study with mice (vapor, 6 hours/day, 5 days/week), flattening and thickening of the olfactory and respiratory epithelium, an increased number of inflammatory cells in the nasal cavity, decreased hepatocellular size and decreased cell content in the cortex of the thymus gland were observed at 600 ppm (1.17 mg/L, in the range corresponding to "Not classified"). Besides, it was reported that no effects were observed in the trachea and lungs (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), DFG MAK (1990), US AEGL (2009), SIAR (2001)). (5) It was reported that, in a 13-week inhalation toxicity study with mice (vapor, 6 hours/day, 5 days/week), inflammation of the nasal turbinates was observed at 100 ppm (0.295 mg/L, within the range for Category 1), decreased liver weight was observed at 400 ppm (1.18 mg/L, in the range corresponding to "Not classified"), and renal tubular necrosis and death (all cases) were observed at 800 ppm (2.34 mg/L, in the range corresponding to "Not classified") (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), AICIS IMAP (2015), NTP TR329 (1988), US AEGL (2009), SIAR (2001)). (6) It was reported that, in a 102-week inhalation toxicity study with mice (vapor, 6 hours/day, 5 days/week), effects on the nasal cavity (suppurative inflammation, epithelial hyperplasia, erosion, squamous metaplasia, lesions in the olfactory epithelium and nasolacrimal duct) were observed at 50 ppm (0.15 mg/ L, within the range for Category 1) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2011), AICIS IMAP (2015), NTP TR329 (1988), DFG MAK (1990), US AEGL (2009), SIAR (2001)).
10	Aspiration hazard	Classification not possible	- -	-	-	[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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