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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	123-73-9
Chemical Name	Crotonaldehyde (synonym: (E)-2-butenal)
Substance ID	R03-B-038-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
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 8 deg C (closed cup) and a boiling point of 102 deg C (GESTIS (Accessed June 2021)). Besides, it is classified in Division 6.1, Subsidiary Risk 3, and PG I in UNRTDG (UN1143), including a stabilized one.
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 it is classified in Division 6.1, Subsidiary Risk 3, and PG I in UNRTDG (UN1143), including a stabilized one. 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 230 deg C (GESTIS (Accessed June 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)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) This substance is a trans-isomer of 2-butenal (CAS RN: 4170-30-3) which is a mixture of cis- and trans-isomers, but there is no available data of the trans-isomer. 2-butenal (CAS RN: 4170-30-3) which is a mixture of cis- and trans- isomers was classified in "Category 3" for this hazard class in the GHS classification (GHS Classification Results in FY2021). (2) LD50 of 2-butenal (CAS RN: 4170-30-3) used as the test substance for rats: 300 mg/kg (DFG MAK (2012)) (3) LD50 of 2-butenal (CAS RN: 4170-30-3) used as the test substance for rats: 174 to 300 mg/kg (AICIS IMAP (2016)) (4) LD50 of 2-butenal (CAS RN: 4170-30-3) used as the test substance for rats: 200 to 300 mg/kg (CICAD 74 (2008))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) This substance is a trans-isomer of 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, but there is no available data of the trans-isomer. 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, was classified in "Category 2" for this hazard class in the GHS classification (GHS Classification Results in FY2021). (2) LD50 of 2-butenal (CAS RN: 4170-30-3) used as the test substance for rabbits: 380 mg/kg (DFG MAK (2012)) (3) LD50 of 2-butenal (CAS RN: 4170-30-3) used as the test substance for rabbits: 128 to 380 mg/kg (AICIS IMAP (2016)) (4) LD50 of 2-butenal (CAS RN: 4170-30-3) used as the test substance for rabbits: 128 to 324 mg/kg (CICAD 74 (2008)) (5) LD50 of 2-butenal (CAS RN: 4170-30-3) used as the test substance 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)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) This substance is a trans-isomer of 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, but there is no available data of the trans-isomer. 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, was classified in "Category 1" for this hazard class in the GHS classification (GHS Classification Results in FY2021). (2) LC50 (4 hours) of 2-butenal (CAS RN: 4170-30-3) used as the test substance for rats: 200 to 290 mg/m3 (69.8 to 101.2 ppmV) (CICAD 74 (2008)) (3) LC50 (4 hours) of 2-butenal (CAS RN: 4170-30-3) used as the test substance for rats: 69 to 120 ppm (AICIS IMAP (2016))
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	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) This substance is a trans-isomer of 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, but there is no available data of the trans-isomer. 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, was classified in "Category 1B" for this hazard class in the GHS classification (GHS Classification Results in FY2021). (2) In the EU CLP, it was classified in Skin irrit. 2.
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) This substance is a trans-isomer of 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, but there is no available data of the trans-isomer. 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, was classified in "Category 1" for this hazard class in the GHS classification (GHS Classification Results in FY2021). (2) 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.
5	Germ cell mutagenicity	Category 1B	Danger	H340	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] This substance is a trans-isomer of 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, but there is no data available. Based on the data of 2-butenal in (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 June 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), REACH registration dossier (Accessed June 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)). However, the report of the positive results in the dominant lethal test provided no data on the slaughter timing, early/late post-implantation embryonal mortality, and resorption rate of pregnant females, and because of problems in the test method, the assessment was not conducted using the appropriate parameters. Therefore, it was not possible to judge whether this substance was genetoxic or not. In addition, the positive results in the chromosomal aberration test with mice were obtained only at a dose at which a decrease in cell division index was observed, and it was pointed out that it was also suggested that they might be cytotoxic effects (DFG MAK (2018)). (2) As for in vitro, positive or negative results in a bacterial reverse mutation assay and positive results in a chromosomal aberration assay with the cultured mammalian cells (CHO, human lymphocytes/lymphoblastoid cells) were reported (AICIS IMAP (2016), CICAD 74 (2008), DFG MAK (2012), REACH registration dossier (Accessed June 2021)). In a gene mutation test with 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 (guidelines in order to prevent the impairment of worker's health, announcement No. 23 on October 10, 2012). (4) 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, was classified in "Category 1B" for this hazard class in the GHS classification (GHS Classification Results in FY2021). (5) In the EU CLP, it was classified in Muta. 2 (EU-CLP Classification Results (Accessed June 2021)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1B. Also, based on the new information source, the category was changed. [Evidence Data] (1) 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)). (2) 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)). (3) 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). (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 3 (IARC 63 (1995)), 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)). [Reference Data, etc.] (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)). (6) 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers was classified in "Category 1B" for this hazard class in the GHS classification (GHS Classification Results in FY2021).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. In (1), no effects on fertility were observed, but there was no data available on developmental toxicity. [Evidence Data] (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 June 2021)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) This substance is a trans-isomer of 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, but there is no available data of the trans-isomer. 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, was classified in "Category 1 (respiratory organs)" for this hazard class in the GHS classification (GHS Classification Results in FY2021). (2) In human volunteers exposed to 2-butenal (CAS RN: 4170-30-3) at 12 mg/m3 (4.1 ppm), lacrimation was caused in 30 seconds, and 15-minute exposures were highly irritating to the nose and upper respiratory trace (CICAD 74 (2008), ACGIH (7th, 2001)). (3) In humans, irritation of the respiratory tract mucosa is induced after inhalation exposure to crotonaldehyde (CAS RN: 4170-30-3) (DFG MAK (2012)). (4) It was reported that, in an acute oral toxicity test with rats (OECD TG 420) using 2-butenal (CAS RN: 4170-30-3) as a test substance 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)). (5) Crotonaldehyde (CAS RN: 4170-30-3) is a deep lung irritant, and effects after inhalation exposure include respiratory distress, an excitatory stage, and terminal convulsions. It was reported that the lethal concentration for rats in a 4-hour exposure was 100 ppm and changes in pulmonary performance resulted from single exposure at 200 ppm for 10 minutes (ACGIH (2001), Patty (2012)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) This substance is a trans-isomer of 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, but there is no available data of the trans-isomer. 2-butenal (CAS RN: 4170-30-3), which is a mixture of cis- and trans-isomers, was classified in "Category 1 (respiratory organs, liver)" for this hazard class in the GHS classification (GHS Classification Results in FY2021). (2) It was reported that, in a repeated dose 13-week oral toxicity study using 2-butenal (CAS RN: 4170-30-3) as a test substance with rats dosed by gavage, acute inflammation of the nasal cavity (females) was observed at or above 5 mg/kg/day (within the range for Category 1), hyperplasia of the forestomach epithelia was observed at or above 10 mg/kg/day (within the range for Category 1), acute inflammation of the nasal cavity (males), thickened forestomach and nodules were observed at or above 20 mg/kg/day (within the range for Category 2), and forestomach hyperkeratosis, ulcers, moderate necrosis, and acute inflammation were observed at 40 mg/kg/day (within the range for Category 2) (CICAD 74 (2008), AICIS IMAP (2016), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015), REACH registration dossier (Accessed Aug. 2021)). (3) It was reported that, in a repeated dose 113-week oral toxicity study using 2-butenal (CAS RN: 4170-30-3) as a test substance with rats (males) dosed by drinking water, altered liver cell foci were observed at or above 42 mg/L (equivalent to 2.0 to 7.6 mg/kg/day, within the range for Category 1) and moderate to severe liver lesions (fatty metamorphosis, focal necrosis, fibrosis, cholestasis, and mononuclear cell infiltration) were observed at 420 mg/L (equivalent to 15.75 to 53.9 mg/kg/day, within the range for Category 2) (CICAD 74 (2008), AICIS IMAP (2016), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2015)). (4) It was reported that, in a 13-week inhalation (vapor) exposure study using 2-butenal (CAS RN: 4170-30-3) as a test 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 at or above 6 ppm (converted guidance value: 4.3 ppm, within the range for Category 1) in mice (males) and at or above 12 ppm (converted guidance value: 8.7 ppm, within the range for Category 1) in rats and mice (females); and squamous metaplasia in the nasopharynx, larynx, and tunica mucosa tracheae were 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)). (5) It was reported that, in a 104-week inhalation (vapor) exposure study using 2-butenal (CAS RN: 4170-30-3) as a test substance with rats (6 hours/day, 5 days/week), damages to the nasal cavity (inflammatory scars and hyperplasia of the respiratory epithelium, squamous metaplasia and squamous cell hyperplasia, atrophy of the olfactory epithelium and metaplasia of the respiratory epithelium, 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)). (6) It was reported that, in a 104-week inhalation (vapor) exposure study using 2-butenal (CAS RN: 4170-30-3) as a test substance with mice (6 hours/day, 5 days/week), damages to the nasal cavity (necrosis, atrophy and cuboidal and squamous metaplasia of the respiratory epithelium, atrophy of the olfactory epithelia and metaplasia of the respiratory epithelium, hyperplasia of the glands and metaplasia of the respiratory epithelium, emergence of exudate, edema of the lamina propria mucosae, etc.) were observed 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)).
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 2	- -	H401	P273 P501	It was classified in Category 2 from 96-hour LC50 = 1.3 mg/L for fish (Menidia beryllina) (HSDB, 2021). The classification result was changed from the previous classification by using new information.
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Reliable chronic toxicity data were not obtained. It was classified as "Not classified" because it was rapidly degradable (a 28-day degradation rate by BOD: Average 82% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1987)) and due to a low bioaccumulation estimate ((logKow =0.6(KOWWIN v1.68)). The classification result was revised from the previous classification by changing how to classify it in chronic toxicity and using new information.
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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