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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	4170-30-3
Chemical Name	2-Butenal (synonym: Isomer mixture of (E)-2-butenal and (Z)-2-butenal)
Substance ID	R03-B-039-METI, MOE
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2014 FY2008 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 13 deg C (closed cup) and a boiling point of 102 deg C (GESTIS (Accessed Nov 2021)). Besides, a stabilized one is classified in Division 6.1, Subsidiary Risk 3, PG I in UNRTDG (UN1143).
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 (ethylene group) present in the molecule, but it does not correspond to self-reactive substances and mixtures, hazards of the highest precedence, because a stabilized one is classified in Division 6.1, Subsidiary Risk 3, and PG I in UNRTDG (UN1143). Therefore, 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 155 deg C (GESTIS (Accessed Nov 2021)).
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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 3. [Evidence Data] (1) LD50 for rats: 300 mg/kg (DFG MAK (2012)) (2) LD50 for rats: 174 to 300 mg/kg (AICIS IMAP (2016)) (3) LD50 for rats: 200 to 300 mg/kg (CICAD 74 (2008))
1	Acute toxicity (Dermal)	Category 2	Danger	H310	P302+P352 P361+P364 P262 P264 P270 P280 P310 P321 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2 by adopting the category with the higher hazard. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) LD50 for rabbits: 380 mg/kg (DFG MAK (2012)) (2) LD50 for rabbits: 128 to 380 mg/kg (AICIS IMAP (2016)) (3) LD50 for rabbits: 128 to 324 mg/kg (CICAD 74 (2008)) (4) LD50 for rabbits: 324 mg/kg (CICAD 74 (2008))
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 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1. Besides, since the saturated vapor pressure concentration was 36,000 ppm, it was judged as a vapor and the criteria in ppmV were applied. Based on the new findings, the classification result was changed. [Evidence Data] (1) LC50 (4 hours) for rats: 200 to 290 mg/m3 (69.8 to 101.2 ppmV) (CICAD 74 (2008)) (2) LC50 (4 hours) for rats: 69～100 ppm（SCOEL (2013)） (3) The vapor pressure concentration of this substance was 30 mmHg (25 deg C) (HSDB in PubChem (Accessed Nov. 2021)). [Reference Data, etc.] (4) LC50 (0.5 hours) for rats: 4,000 mg/m3 (converted 4-hour equivalent value: 500 mg/m3= 493 ppmV) (DFG MAK (2012))
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) and (2), it was classified in Category 1B. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in a skin irritation test with rabbits (n=7) (open application, 15-minute application, observation for 2 months), severe erythema and edema occurred after 5 to 9 hours, and desquamation began and crusts and ulceration were seen after 2 to 3 days. These symptoms persisted for 12 to 15 days and were largely cured after 2 months (AICIS IMAP (2016), REACH registration dossier (Accessed Nov. 2021)). (2) It was reported that, in a skin irritation test with rabbits (n=6) (occlusive application to the abraded and non-abraded skin, 4-hour application, observation for 72 hours), the primary dermal irritation index (PDII) was 8 (AICIS IMAP (2016), REACH registration dossier (Accessed Nov. 2021)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1. [Evidence Data] (1) It was classified in Category 1B for skin corrosion/irritation. (2) It was reported that, in an eye irritation test with rabbits, it was highly irritating to the eyes, causing severe damages (SCOEL (2013)). [Reference Data, etc.] (3) In the EU CLP, it was classified in Eye Dam. 1.
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, the finding in (2) was not used for classification because details such as test conditions were unknown. The data were reviewed, and the classification result was changed. [Reference Data, etc.] (1) There was one case report of a worker in the textile industry showing sensitization (IARC 63 (1995)). (2) A study regarding the sensitizing properties of this substance was conducted by the US National Toxicology Program and the result showed that it was not sensitizing (SCOEL (2013)).
5	Germ cell mutagenicity	Category 1B	Danger	H340	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1B. [Evidence Data] (1) As for in vivo, a dominant lethal test with mice (5-day intraperitoneal injection, up to 27.2 mg/kg) yielded positive results (DFG MAK (2018), REACH registration dossier (Accessed Nov 2021)), a chromosomal aberration test using the bone marrow cells and spermatocytes of mice (single intraperitoneal injection, up to 27.2 mg/kg) yielded positive results (DFG MAK (2018), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), SCOEL (2013), REACH registration dossier (Accessed Nov 2021)), a micronucleus test using the bone marrow cells of mice (dosed by gavage) yielded negative results (CICAD 74 (2008), REACH registration dossier (Accessed June 2021)), and DNA adduct formation in the liver, lung, and kidney was observed in rats dosed by gavage (DFG MAK (2012), AICIS IMAP (2016), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), SCOEL (2013)). (2) As for in vitro, positive or negative results in a bacterial reverse mutation assay and positive results in a chromosomal aberration study with the cultured mammalian cells (CHO, human lymphocytes/lymphoblastoid cells) were reported (AICIS IMAP (2016), CICAD 74 (2008), DFG MAK (2012), SCOEL (2013), REACH registration dossier (Accessed Nov 2021)). In a gene mutation test with the cultured mammalian cells (V79, mouse lymphoma cells), positive results were reported (IARC, 2021). [Reference Data, etc.] (3) This substance was a target substance in the public announcement on guidelines in order to prevent the impairment of worker's health caused by the chemical substances (chemical substances with strong mutagenicity) decided by the Minister of Health, Labour and Welfare based on paragraph (3) of Article 28 of the Industrial Safety and Health Act. (4) In the EU CLP, it was classified in Muta. 2 (EU-CLP Classification Results (Accessed Nov 2021)). (5) In the MAK, it was classified in Category 3A for germ cell mutagenicity (DFG MAK, 2018).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Since this substance was designated as a substance subject to the Guidelines for Carcinogenicity by the Minister of Health, Labour and Welfare in (1) and the evidence of carcinogenicity in one species of animals was presented in (2) and (3), it was classified in Category 1B. Based on the new findings, the category result was changed. Besides, among the classifications by other organizations in (4), the classification of the IARC was the latest one, in which this substance was classified in Group 2B (equivalent to Category 2), but the category was determined based on the positive data obtained in the animal studies. [Evidence Data] (1) This substance is a target substance in the public announcement on revised 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 (guidelines in order to prevent the impairment of worker's health, announcement No. 23 on October 10, 2012). (2) In a 2-year study for this substance (trans-isomer: CAS RN 123-73-9) with male rats dosed by drinking water, increases in the incidence of hepatocellular neoplasms (neoplastic nodules, hepatocellular carcinomas) were observed (IRIS (1991), ACGIH (7th, 2001), AICIS IMAP (2016), CICAD 74 (2007), DFG MAK (2018), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). (3) In a carcinogenicity study with rats and mice exposed to crotonaldehyde (CAS RN 4170-30-3) by inhalation for two years, no increase in tumor incidence was observed in the study with mice, while in the study with rats, nasal cavity tumors, which rarely occur spontaneously, were observed in a small number (1 to 2 of 50 animals) of both males and females and it was considered to be an evidence for carcinogenicity of this substance (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2001), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). [Reference Data, etc.] (4) As for the classification results for crotonaldehyde (CAS RN 4170-30-3) by domestic and international evaluation organizations, the IARC classified it in Group 2B (IARC 128 (2021)), the EPA classified it in C (possible human carcinogen) (IRIS (1991)), the ACGIH classified it in A3 (ACGIH (7th, 2001)) and the DFG classified it in Category 3B (DFG MAK (2018)). (5) In an investigation among 220 workers employed in an aldehyde production factory in the former German Democratic Republic, 9 workers were diagnosed with malignant neoplasms (2 cases of squamous cell carcinoma of the oral cavity, 5 cases of squamous cell carcinomas of the lung, 1 case of adenocarcinoma of the stomach and 1 case of adenocarcinoma of the colon) and an excessive cancer risk among the workers was suspected. In an investigation of the workplace concentrations, this substance showed 1 to 7 mg/m3 and, at the same time, other chemical substances were also detected. The IARC judged that the data were too sparse to draw conclusions from this study (IARC 63 (1995), CICAD 74 (2008), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2018)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. In (1), no general toxicity effects were observed in parental animals, but there is a possibility that the dose setting was inappropriate, and it cannot be concluded that there were no reproductive effects. [Reference Data, etc.] (1) It was reported that, in a one-generation reproduction toxicity study with rats dosed by gavage (OECD TG 415, GLP, for 61 days prior to breeding (males), for 31 days prior to breeding (females)), no adverse effects were observed in either parental animals or pups up to the highest dose of 10 mg/kg/day (AICIS IMAP (2016), REACH registration dossier (Accessed Nov 2021)).
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1 (respiratory organs). [Evidence Data] (1) In human volunteers exposed to 2-butenal at 12 mg/m3 (4.1 ppm), lacrimation occurred in 30 seconds, and 15-minute exposures were highly irritating to the nose and upper respiratory tract (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2014), CICAD 74 (2008), ACGIH (7th, 2001)). (2) It was reported that, in an acute oral toxicity test (OECD TG 420) with rats, 7 of 10 animals died at 180 mg/kg (within the range for Category 1) and all the animals died at 300 and 500 mg/kg (within the range for Category 2). Observed sublethal effects for the surviving animals included lethargy, salivation, changes in motor activity, and lacrimation (AICIS IMAP (2016), REACH registration dossier (Accessed Nov 2021)). (3) Among the alpha, beta-unsaturated aldehyde compounds, this substance was strongly irritating to the murine respiratory tract, being slightly less irritating than acrolein and formaldehyde. The concentration that reduces the respiratory rate to 50% (RD50) was reported to be 10 mg/m3 in mice and 66.6 mg/m3 in rats (CICAD 74 (2008)). (4) This substance is a strong lung irritant, and effects after inhalation exposure include respiratory distress and peripheral convulsions after the excitatory stage. It was reported that the lethal concentration for rats in a 4-hour exposure was 100 ppm (10 mg/kg, within the range for Category 1) and changes in pulmonary performance resulted from a single exposure at 200 ppm (20 mg/kg, within the range for Category 1) for 10 minutes (ACGIH (7th, 2001), Patty (6th, 2012)). (5) In an acute inhalation exposure test with rats (males), the median lethal concentration (LC50) value for the 4-hour exposure was 69-120 ppm, 0.19-0.34 mg/L/4 hours. Therefore, this substance was classified as "Very toxic by inhalation" (T+; R26) in the Hazardous Substances Information System (HSIS) (Safe Work Australia) (AICS IMAP (2016), SCOEL, 2013, REACH registration dossier (Accessed Nov. 2021)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs, liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (5), the respiratory organs and liver were judged to be the target organs, and this substance was classified in Category 1 (respiratory organs, liver). The classification result was changed by adding and examining new information sources. [Evidence Data] (1) In a 13-week oral toxicity study with rats dosed by gavage, acute inflammation of the nasal cavity (females) was observed at or above 5 mg/kg/day; hyperplasia of the forestomach epithelia was observed at or above 10 mg/kg/day; acute inflammation of the nasal cavity (males), thickened forestomach, and nodules (males and females) were observed at or above 20 mg/kg/day; and forestomach hyperkeratosis, ulcers, moderate necrosis, and acute inflammation (males and females) were observed at 40 mg/kg/day (CICAD 74 (2008), AICIS IMAP (2016), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), REACH registration dossier (Accessed Nov 2021)). (2) In a drinking-water study performed for 113 weeks with male rats, altered liver cell foci were observed at or above 42 mg/L (corresponding to 2.0 to 7.6 mg/kg/day: Converted dose values differ by evaluation reports) and moderate to extensive liver damages (fatty metamorphoses, focal liver necroses, fibroses, cholestases, and mononuclear cell infiltration) were observed at 420 mg/L (corresponding to 15.75 to 53.9 mg/kg/day) (CICAD 74 (2008), AICIS IMAP (2016), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). (3) In a 13-week inhalation exposure study for vapor of this substance with rats and mice (6 hours/day, 5 days/week), squamous metaplasia in the nasal mucosa and inflammatory changes in the respiratory mucous membranes (inflammatory cell infiltration, edema of the dorsal wall of the nasal cavity) were observed in both rats and mice at or above 12 ppm (converted guidance value: 8.7 ppm: within the range for Category 1), and squamous metaplasia in the nasopharynx, larynx and tunica mucosa tracheae was observed at 24 ppm (converted guidance value: 17.3 ppm: within the range for Category 1) (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2001), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). (4) In a 104-week inhalation exposure study for vapor of this substance with rats (6 hours/day, 5 days/week), damages to the nasal cavity (inflammatory scars and hyperplasia of the respiratory epithelia, squamous metaplasia and squamous cell hyperplasia, atrophy of the olfactory epithelia and metaplasia in the respiratory epithelia, foreign body rhinitis, etc.) were observed at or above 3 ppm within the range for Category 1 (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2001), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). (5) In a 104-week inhalation exposure study for vapor of this substance with mice (6 hours/day, 5 days/week), damages to the nasal cavity (necrosis, atrophy and cuboidal and squamous metaplasia of the respiratory epithelia, atrophy of the olfactory epithelia and metaplasia of the respiratory epithelia, hyperplasia of the glands and metaplasia of the respiratory epithelia, emergence of exudate, edema of the lamina propria mucosae, etc.) were observed in both males and females at or above 6 ppm within the range for Category 1 (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 2001), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). [Reference Data, etc.] (6) In a 13-week oral toxicity study with mice dosed by gavage, hyperplasia of the epithelial lining of the stomach was observed at 40 mg/kg/day (CICAD 74 (2008), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), REACH registration dossier (Accessed Nov 2021)).
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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.072 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, 2002), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2006), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	It was classified in Category 2 because it was rapidly degradable (a degradation rate by BOD: 82% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1987)), and due to 21-day NOEC = 0.02 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2002), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2006), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)).
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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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