NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	107-02-8
Chemical Name	Acrylaldehyde
Substance ID	R03-B-004-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 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 -26 deg C (closed cup) and a boiling point of 52 deg C (GESTIS (Accessed July 2021)). Besides, a stabilized one is classified in Division 6.1, Subsidiary Risk 3, PG I in UNRTDG (UN 1092).
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 a stabilized one is classified in Division 6.1, Subsidiary Risk 3 in UNRTDG (UN 1092) 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 215 deg C (GESTIS (Accessed July 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 2	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) to (10), it was classified in Category 2. [Evidence Data] (1) LD50 for rats: between in the range from 42 to 46 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU RAR (2001), REACH registration dossier (Accessed July 2021)) (2) LD50 for mice: between in the range from 13.9 to 28 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU RAR (2001), REACH registration dossier (Accessed July 2021)) (3) LD50 for rats:11.2 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)) (4) LD50 for rats: 25 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CICAD 43 (2002)) (5) LD50 for rats: between in the range from 10.3 to 46 mg/kg (AICIS IMAP (2017)) (6) LD50 for rats: 46 mg/kg (ACGIH (7th, 2001)) (7) LD50 for rats (males): 10.3 mg/kg (CLH Report (2011), RAC (Background Doc) (2012)) (8) LD50 for rats (females): 11.8 mg/kg (CLH Report (2011), RAC (Background Doc) (2012)) (9) LD50 for rats: 11 mg/kg (EPA Pesticides (2005)) (10) LD50 for rats: 26 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 3. [Evidence Data] (1) LD50 for rabbits: 562 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), AICIS IMAP (2017), EU RAR (2001), REACH registration dossier (Accessed July 2021)) (2) LD50 for rabbits (males): 240 mg/kg (CLH Report (2011), RAC (Background Doc) (2012)) (3) LD50 for rabbits (females): 233 mg/kg (CLH Report (2011), RAC (Background Doc) (2012)) (4) LD50 for rabbits: 200 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004)) (5) LD50 for rabbits: 231 mg/kg (EPA Pesticides (2005), CLH Report (2011)) (6) LD50 for rabbits: 560 mg/kg (ACGIH (7th, 2001))
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) to (6), it was classified in Category 1. Since the test concentration was considerably lower than 90% (325,463.2 ppm: 746.3 mg/L) of the saturated vapor pressure concentration (361,626 ppm) of this substance, it was considered to be a vapor without a mist, and therefore, the reference value in units of ppmV was applied. [Evidence Data] (1) LC50 (4 hours) for rats: between 18 to 21 mg/m3 (between 7.9 to 9.2 ppm) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)) (2) LC50 (4 hours) for rats: 150 mg/m3 (65.4 ppm) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)) (3) LC50 (4 hours) for rats: between 16 to 150 mg/m3 (between 7.0 to 65.4 ppm) (AICIS IMAP (2017)) (4) LC50 (4 hours) for rats: 8.3 ppm (US AEGL (2010)) (5) LC50 (4 hours) for rats: 18 mg/m3 (7.9 ppm) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004)) (6) LC50 (4 hours) for rats: between 18 to 150 mg/m3 (7.9 to 65.4 ppm) (EU RAR (2001), REACH registration dossier (Accessed July 2021))
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 1	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 1. [Evidence Data] (1) In patch tests, in which 0.01 to 10% solutions of this substance were applied to the skin of volunteers, no positive reactions were observed in 8 subjects exposed to a 0.01% solution and 10 subjects exposed to a 0.1% solution. 12.5% (6/48 subjects) of 48 subjects exposed to a 1% solution showed positive reactions, out of which 4 subjects showed serious edema with bullae, and 2 subjects showed erythema and serious edema. It was reported that, with a 10% solution, bullae, necrosis, inflammatory cell infiltration, and papillary edema were observed in the skin of all the subjects (20/20 subjects) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ECHA RAC Opinion (2012), CLH Report (2011), EU RAR (2001), ATSDR (2007), AICIS IMAP (2017), CICAD (2002), CEPA PSAR (2000), REACH registration dossier (Accessed July 2021)). (2) It was reported that, in a skin irritation study with rabbits (n=6) (14-day observation), at 24 and 72 hours after exposure of 4 animals excluding 2 animals which died (cause not determined) during the test period, the average erythema score was 1, and the average edema score was 3, and the effects which were observed in 3 animals did not disappear within 14 days (ECHA RAC Opinion (2012), CLH Report (2011), AICIS IMAP (2017)). [Reference Data, etc.] (3) In the Ministry of Labour Notification No. 33 issued in 1996 (revised by the Minister of Health, Labour and Welfare Notification No. 316 in 2013), this substance is designated as "acrolein" in simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and diseases (skin disorders, disorders in the anterior part of the eye, respiratory tract and lung disorders) with specific symptoms or disorders caused by occupations exposed to this substance as main symptoms or disorders, are designated as occupational diseases.
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1. [Evidence Data] (1) It was classified in Category 1 for skin corrosion/irritation. (2) As a result of human exposure studies, minor eye irritation was caused at 0.1 to 0.3 ppm. A 5-minute exposure to 1 ppm (2.3 mg/m3) of vapor caused lacrimation, and marked eye, nose, and throat irritation. It was reported that, at 3 ppm (7 mg/m3) exposure concentration, this substance was a severe pulmonary irritant and powerful lachrymogen, affecting the conjunctiva and mucous membranes of the upper respiratory tract (ACGIH (7th, 2001), AICIS IMAP (2017), HSDB (Accessed July 2021)). (3) It was reported that, in an eye irritation test with rabbits, severe eye irritation was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). (4) It was reported that, in an eye irritation study with rabbits (n=9) (7-day observation), severe eye irritation was observed, and the effects were not reversible after 7-days (at 24, 48, and 72 hours after exposure, average score of corneal opacity: 4; average score of iris lesion: 2; average score of redness of conjunctiva: 4; and average score of chemosis of conjunctiva: 2) (RAC Background　Doc (2012), CLH Report (2011), AICIS IMAP (2017)). [Reference Data, etc.] (5) In the Ministry of Labour Notification No. 33 issued in 1996 (revised by the Minister of Health, Labour and Welfare Notification No. 316 in 2013), this substance is designated as "acrolein" in simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and diseases (skin disorders, disorders in the anterior part of the eye, respiratory tract and lung disorders) with specific symptoms or disorders caused by occupations exposed to this substance as main symptoms or disorders, are designated as occupational diseases.
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	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, in two dominant lethal studies with mice, negative results were reported, and in a chromosomal aberration test (intraperitoneal injection, inhalation exposure) with the bone marrow cells of rats, negative results were reported (CLH Report (2011), RAC (Background Doc) (2012), AICIS IMAP (2017), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), MOE (2004), CICAD (2002), CEPA PSAR (2000)). It was mentioned that especially a mammalian bone marrow chromosomal aberration test by intraperitoneal injection was well-conducted (OECD TG475, GLP), and lethal doses were administered, and that it was very likely that there would have been significant exposure of the bone marrow to an unchanged form of this substance as the ip route would eliminate first pass hepatic metabolism (CLH Report (2011), RAC (Background Doc) (2012)). (2) As for in vitro, in numerous bacterial reverse mutation tests, positive results were obtained mainly in the absence of a metabolic activation system (-S9) (partly positive also in +S9), but negative (partly positive) results were obtained in multiple gene mutation tests with cultured mammalian cells (CHO, etc.), and negative results were obtained in all chromosomal aberration tests with cultured mammalian cells (CHO, human lymphocytes) (CLH Report (2011), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004), CEPA PSAR (2000)). (3) It was possible that the positive findings in a bacterial reverse mutation test were related to the lack of an endogenous glutathione detoxification pathway (CLH Report (2011)).
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. As for the latest classification results by other organizations, the IARC changed the classification from Group 3 to Group 2A, and therefore, the classification was revised, and the classification result was changed. [Evidence Data] (1) As for the carcinogenicity classification results by domestic and international assessment organizations, the IARC recently changed the classification from the conventional Group 3 (IARC 63 (1995)) to Group 2A (IARC 128). In addition, the ACGIH classified it in A4 (ACGIH (7th, 2001)), the EPA classified it in I (Inadequate for an assessment of human carcinogenic potential) (IRIS (2003): Classification in 1999), and the DFG classified it in Category 3B (DFG MAK (2014): Classification in 1997). (2) In a carcinogenicity study by 2-year inhalation exposure of rats (vapor, 6 hours/day, 5 days/week), in a 2 ppm group, squamous cell carcinoma (rare tumor for which no incidence was observed in the background data in the testing laboratory) in the nasal cavity was observed in 1/50 males and 2/50 females, and an incidence of rhabdomyoma (rare tumor for which no incidence was observed in HCD) in the nasal cavity was observed in 4/50 females of the same group. The incidence of these tumors was considered to be the evidence of carcinogenicity in male and female rats (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare), 2016)). (3) In a carcinogenicity study by 93-week (males)/99-week (females) inhalation exposure of mice, there was no increase in the incidence of tumor in males at doses up to the highest concentration of 1.6 ppm, but in females, there was an increase in the incidence of adenoma in the nasal cavity in a 1.6 ppm group. This tumor was considered to be the evidence of carcinogenicity in female mice (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare), 2016)). (4) This substance was the target substance of the guidelines for prevention of health impairment (guidelines for carcinogenicity). [Reference Data, etc.] (5) In a carcinogenicity study by 2-year oral administration of up to 2.5 mg/kg/day to male and female rats dosed by gavage or by 18-month oral administration of up to 4.5 mg/kg/day to male and female mice dosed by gavage, there was no increase in the incidence of tumor related to the administration (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), AICIS IMAP (2017), CLH Report (2011), CICAD 43 (2002), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004), EU RAR (2001)). (6) As a result of 18-month inhalation exposure (1 hour/day, 5 days/week) of rats to 18.6 mg/m3 (8 ppm), there was no incidence of tumor related to the administration (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), AICIS IMAP (2017), CICAD 43 (2002), EU RAR (2001)). However, it was pointed out that this was an inappropriate test for assessing the carcinogenicity because the number of test animals (n=20) was not sufficient and the exposure time was also short (EU RAR (2001), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). (7) There was no information on human carcinogenicity (EU RAR (2001), CLH Report (2011)). In an epidemiological study of workers of a chemical plant, blood tumor was suspected, but it was concluded to be not related to the exposure to this substance (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CICAD 43 (2002), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2001)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in two two-generation reproduction toxicity studies (GLP) with rats by oral administration, no reproductive toxicity was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), RAC Background Doc (2012), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004), CICAD 43 (2002), EU RAR (2001), CEPA PSAR (2000)). (2) It was reported that, in a developmental toxicity study with rats or rabbits by oral administration, death and skeletal abnormalities were observed in pups at a dose at which death (14/40 animals) was observed in parent animals, but no developmental effects were observed in pups at a dose at which only decreased body weight was observed in parent animals (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007) , RAC Background Doc (2012), EU RAR (2001), CICAD 43 (2002), CEPA PSAR (2000)). [Reference Data, etc.] (3) It was reported that, in a one-generation reproduction toxicity study by inhalation exposure of rats (26 days, mated on day 4 of exposure), no reproductive toxicity was observed. Also, this test was considered to be insufficient for assessing reproductive and developmental toxicity because the test results were obtained only at one dose, the exposure period before mating was short, and the assessment items were limited (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU RAR (2001), CICAD 43 (2002), CEPA PSAR (2000)). (4) In a developmental toxicity study with mice dosed by gavage, at 10 mg/kg/day, slightly reduced body weight gain, lethargy, squinted eyes, dyspnea, and hunched posture were observed in parent animals; and increased resorption and an increase in the incidence of subcutaneous edema were observed in foetuses. In the test report, the information on whether subcutaneous edema was a slight focal effect or a severe systemic edema was not provided, however, since additional background data suggested that subcutaneous edema was a slight effect, the classification for developmental toxicity was considered to be not appropriate (RAC Opinion (2012)).
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] Based on (1) to (3), Category 1 (respiratory organs) was adopted, and based on (4) to (8), Category 3 (narcotic effects) was adopted. As for the digestive tract, eye, and skin, findings were considered to be local irritation effects and were not adopted as the rationale for the classification. With the additional new information sources, the classification was reviewed and the classification result was changed. Also, the central nervous system and the liver, which were the target organs for the previous classification, were excluded from the target organs based on (3) for the central nervous system and (8) for the liver. [Evidence Data] (1) Acrolein showed irritation to the eye and upper respiratory tract, and irritation to the eye was observed at 0.13 mg/m3; irritation to the nose was observed at 0.34 mg/m3; effects on the respiratory system such as cough, chest pain, suffocation, etc. were observed at 0.6 mg/m3; and a decrease in respiratory frequency was observed at 0.69 mg/m3. Adverse effects of oral ingestion or inhalation exposure focally occurred mainly in the stomach or respiratory tract, which were the exposure (contact) areas, and at massive ingestion or exposure, prostration, nausea, vomiting, diarrhea, panting, bronchitis, pulmonary edema, and loss of consciousness were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). (2) Effects of inhalation exposure to this substance were irritation to the nose, throat, and lung, pulmonary edema, hemorrhage in the lung, and death. The tissue of the nasal cavity was the most sensitive tissue to inhalation exposure, initially showed perceivable irritation within a few seconds at 0.3 ppm, and gradually showed severe irritation signs which extended into the entire respiratory tract at high concentrations of 2 to 5 ppm (ATSDR (2007)). (3) Animal studies indicated that the respiratory system was the major target organ for inhalation toxicity of this substance. Oral exposure might result in gastrointestinal discomfort, vomiting, and stomach ulceration and/or hemorrhage. The central nervous system inhibitory symptoms were observed in the animals after oral ingestion, but it was a finding only after the administration of a lethal dose. In other routes, there were no neurobehavioral changes nor histopathologically, and there was no finding of suspected neurotoxicity, and therefore, the central nervous system was considered to be not a major target organ of this substance (EPA Pesticides RED (2005), ATSDR (2007)). (4) It was reported that, in an acute oral toxicity test with rats, lethargy and hypothermia at or above 15 mg/kg (within the range for Category 1), and changes in respiration rate (no further information provided) at or above 25 mg/kg (within the range for Category 1) were observed (CLH Report (2011), RAC (Background Doc) (2012)). (5) It was reported that, in an acute oral toxicity test with mice, lethargy, squinted eyes, rough coat, hunched posture, and piloerection (females) were observed in all the animals of a group treated at 11.0 to 19.0 mg/kg (within the range for Category 1), and respiratory distress was observed at or above 15.8 mg/kg (within the range for Category 1) (CLH Report (2011), RAC (Background Doc) (2012)). (6) It was reported that, in an acute dermal toxicity test with rabbits, severe pain and hyperactive behavior were initially observed, followed by lethargy, respiratory distress, and cyanosis at 200 to 288 mg/kg (within the range for Category 1) (CLH Report (2011), RAC (Background Doc) (2012)). (7) As a result of examination of effects of inhalation exposure of cats to formaldehyde, acetaldehyde, and acrolein (this substance), it was found that this substance had the strongest effects. Exposure at approximately 10 ppm for 3.5 hours caused respiratory irritation, salivation, lacrimation, and mild narcosis (ACGIH (7th, 2001)). (8) It was reported that, in an acute oral toxicity test with rats (males), at 25 mg/kg (within the range for Category 1), increased mortality, and degenerative changes in the liver (eosinophilic degeneration with micro vesicular steatosis), forestomach, and glandular stomach (severe inflammation, hemorrhagic gastritis, multi-focal ulceration, fibrin deposition, focal hemorrhage, edema, and polymorphonuclear leukocyte infiltration) were observed (CICAD 43 (2002), CEPA PSAR (2000)). However, as for this report, the ATSDR described only the findings of the stomach (forestomach, glandular stomach) and did not adopt the findings of the liver (ATSDR (2007)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1 (respiratory organs). Based on (6) to (10), the stomach (forestomach, glandular stomach) was the target organ in the oral route, and based on (11), the skin was the target organ in the dermal route, however, since the findings were local effects of irritation, those organs were not adopted as the target organs. [Evidence Data] (1) It was reported that, in numerous 3-week to 90-days inhalation toxicity studies with rats, inflammatory changes in the respiratory organs (nasal cavity, trachea, lung, etc.) were observed at 0.51 to 0.9 mg/m3 (0.2 to 0.4 ppm, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). (2) It was reported that, in a 6-week inhalation toxicity study with dogs (8 hours/day, 5 days/week), chronic pulmonary inflammation and emphysema were observed at 1.6 mg/m3 (converted guidance value: 0.3 ppm, within the range for Category 1), and squamous metaplasia and basal cell hyperplasia of the trachea were observed at 8.5 mg/m3 (converted guidance value: 1.6 ppm, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CLH Report (2011) p. 36/66). (3) It was reported that, in a 90-day inhalation toxicity study with dogs (24 hours/day, 7 days/week), emphysema, lung congestion, some constriction of the bronchioles, vacuolization of the bronchiolar epithelial cells with increased secretory activity, and non-specific inflammatory reactions involving the liver, lung, kidney, and heart were observed at 0.5 mg/m3 (0.2 ppm, within the range for Category 1); lacrimation, nasal discharge, bronchopneumonia, bronchiolitis, and non-specific inflammatory reactions involving the liver, lung, and kidney were observed at 2.3 mg/m3 (1.0 ppm, within the range for Category 1); and lacrimation, salivation, bronchopneumonia, and non-specific inflammatory reactions involving the liver, lung, kidney, heart, and brain were observed at 4.1 mg/m3 (1.8 ppm, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CLH Report (2011) , Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004)). (4) It was reported that, in a 6-week inhalation toxicity study with monkeys (8 hours/day, 5 days/week), chronic pulmonary inflammation and emphysema were observed at 1.6 mg/m3 (converted guidance value: 0.7 ppm, within the range for Category 1), and eye irritation, salivation, dyspnea, inflammatory reactions involving the lung, liver, and kidney, squamous metaplasia and basal cell hyperplasia of the trachea, and necrosis and squamous metaplasia of the bronchus were observed at 8.5 mg/m3 (converted guidance value: 1.6 ppm, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CLH Report (2011)). (5) It was reported that, in a 90-day inhalation toxicity study with monkeys (24 hours/day, 7 days/week), non-specific inflammatory reactions involving the liver, lung, kidney, and heart were observed at or above 0.5 mg/m3 (0.2 ppm, within the range for Category 1); closed eyes were observed at or above 2.3 mg/m3 (1.0 ppm, within the range for Category 1); and lacrimation, salivation, squamous metaplasia and basal cell hyperplasia of the trachea, and non-specific inflammatory reactions involving the liver, lung, kidney, heart, and brain were observed at 4.1 mg/m3 (1.8 ppm, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CLH Report (2011), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004)). [Reference Data, etc.] (6) It was reported that, in a 13-week oral toxicity study with mice dosed by gavage (5 days/week), hemorrhage, necrosis, inflammations of the glandular stomach and forestomach, and squamous epithelial hyperplasia of the forestomach were observed at or above 1.25 mg/kg/day (0.893 mg/kg/day, within the range for Category 1), and increases in liver and kidney weight were observed at or above 2.5 mg/kg/day (1.79 mg/kg/day, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), IRIS (2003), AICIS IMAP (2017)). (7) It was reported that, in an 18-month oral toxicity study with mice dosed by gavage (OECD TG453, 7 days/week), reduced body weight gain and an increased incidence of death were observed in males at 45 mg/kg/day (within the range for Category 2) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CLH Report (2011), IRIS (2003), AICIS IMAP (2017), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004)). (8) It was reported that, in a 13-week oral toxicity study with rats dosed by gavage (5 days/week), hemorrhage, necrosis, inflammations of the glandular stomach and forestomach, and squamous epithelial hyperplasia of the forestomach were observed at or above 1.25 mg/kg/day (0.893 mg/kg/day, within the range for Category 1), and an increase in liver weight was observed at or above 2.5 mg/kg/day (1.79 mg/kg/day, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), IRIS (2003), AICIS IMAP (2017)). (9) It was reported that, in a 102-week oral toxicity study with rats dosed by gavage (OECD TG453, 7 days/week), reduced CPK activity (the toxicological significance was unclear) was observed at or above 0.05 mg/kg/day (within the range for Category 1), and increased mortality (the cause of death was unknown) was observed at or above 0.5 mg/kg/day (within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CLH Report (2011, IRIS (2003), AICIS IMAP (2017), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004)). (10) It was reported that, in a 53-week oral toxicity study with dogs dosed by gavage (GLP, 7 days/week), vomiting was observed at or above 0.5 mg/kg/day (within the range for Category 1), and lower serum total protein, calcium, and albumin were observed at or above 1.5 to 2 mg/kg/day (within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CLH Report (2011), AICIS IMAP (2017), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2004)). (11) In a 3-week dermal toxicity study with rabbits (8 hours/day, 5 days/week), local effects (erythema, edema, hyperkeratosis, acanthosis, and parakeratosis of the skin) as well as interstitial nephritis, and interstitial pneumonia were observed at 7 to 63 mg/kg/day (converted guidance value: 1.2 to 10.5 mg/kg/day: Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), AICIS IMAP (2017), CLH Report (2011)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) In a two-generation reproduction toxicity study with rats (administered by gavage), in the F0 and F1 male and female parental animals, increases in the incidences of mortalities and respiratory complications (e.g., rales, gasping) were observed in the highest dose group of 6 mg/kg/day. It was suggested that aspiration of the dosing solution resulted in these effects (HSDB (Accessed July 2021)). (2) In a developmental toxicity study with pregnant rabbits (administered by gavage), although deaths occurred in maternal animals, these were attributed to either misdosing or aspiration of acrolein (CLH Report (2011), EU CLP CLH (2012)).

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 because sufficient data on rapid degradability were not obtained and 72-hour ErC50 was 0.011 mg for algae (Skeletonema costatum) (EU CLP CLH, 2011).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 because it is not rapidly degradable (a 4-week degradation rate by BOD: 0% (Initial Risk Assessment (NITE, CERI, NEDO, 2007), Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1987)), and due to 72-hour NOErC = 0.0051 mg/L (EU CLP CLH, 2011).
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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