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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	431-03-8
Chemical Name	Diacetyl
Substance ID	R01-B-003
Classification year (FY)	FY2019
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2015
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)	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	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	Category 2	Danger	H225	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	It was classified in Category 2 based on a flash point of 6 deg C (closed cup) and a boiling point of 88 deg C (ICSC (2009)). Besides, it is classified in Class 3, PG II in UNRTDG (UN 2346).
7	Flammable solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of 365 deg C (ICSC (2009)).
10	Pyrophoric solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	No data available.
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	*	- -	-	-	[Rationale for the Classification] (1) corresponds to Category 4 in the GHS classification guidance for the Japanese government, and (2) and (3) correspond to "Not classified" (Category 5 in UN GHS classification). Therefore, it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: 1,580 mg/kg (PATTY (6th, 2012), JECFA FAS42 (1999)) (2) LD50 for rats (male): 3,400 mg/kg (PATTY (6th, 2012), JECFA FAS42 (1999), NTP TR593 (2018)) (3) LD50 for rats (female): 3,000 mg/kg (PATTY (6th, 2012), JECFA FAS42 (1999), NTP TR593 (2018))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: > 5,000 mg/kg (PATTY (6th, 2012))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] The LC50 value was estimated to be between 2,250 ppm and 5,200 ppm in (1), and respiratory tract damage was observed in workers who were exposed by inhalation to this substance in (2). Therefore, it was classified in Category 3. Besides, since the exposure concentrations were lower than 90% of the saturated vapor pressure concentration (74,742.7 ppm), a reference value in unit of ppm was applied as a vapour with little mist. The category was changed due to the revised information. [Evidence Data] (1) In a test by 4-hour inhalation exposure to the vapour of this substance at 2,250, 5,200, and 23,900 ppm, all the animals died in groups at or above 5,200 ppm, and the LC50 value was estimated to be between 2,250 ppm and 5,200 ppm (EU SCOEL SUM 149 (2014)). (2) Since workers exposed by inhalation to this substance were found to develop damage to the airways, it was registered as a hazardous substance with a non-negligible toxic potential (GESTIS (Access on May 2019)). [Reference Data, etc.] (3) Rats were exposed to 99.3 ppm for 6 hours (converted 4-hour equivalent value: 122 ppm) and found to be unaffected (PATTY (6th, 2012)).
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] Based on the case in humans in (1), it was classified in Category 2. [Evidence Data] (1) There is a description that eye, skin and nasal irritation were observed in workers exposed to butter flavoring vapours composed mainly of this substance in popcorn manufacturing facilities (EU SCOEL SUM 149 (2014)). [Reference Data, etc.] (2) There is a description that in a test in which this substance was applied to the skin of rabbits, moderate to severe irritation was observed (PATTY (6th, 2012)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1), (2), it was classified in Category 1. [Evidence Data] (1) There is a description that in a test in which this substance was applied to the eyes of rabbits, irritation was observed and was not resolved within 21 days (PATTY (6th, 2012)). (2) In a study in which 0.1 mL of the undiluted liquid of this substance was applied to the eyes of rabbits, this substance was severely irritating to the mucous membranes and the cornea, and it was judged to be a corrosive substance (GESTIS (Access on May 2019)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] The EC3 values used for sub-categorization were reported in (1). However, since mice of the strain recommended for use by OECD TG 429 were not used in the former, and the latter is a report before OECD TG 429 approval, sub-categorization was not conducted. Therefore, it was classified in Category 1. [Evidence Data] (1) It was reported that it was positive in mouse local lymph node assays (LLNA), and that EC3 values were 1.9% (Anderson et al., Toxicol. Sci., 97, 355, 2007) or 11.3% (Roberts et al., Contact Dermat., 41, 14, 1999) (PATTY (6th, 2012)). [Reference Data, etc.] (2) In a human maximization test in which a plaster containing 2% of this substance in vaseline was applied 5 times for 2 days each time, and the same formulation was applied in a challenge 10-14 days later, all the subjects had negative reactions. And, in patch tests on subjects not exposed to this substance, 2 out of 102 patients with contact dermatitis showed a positive reaction (GESTIS (Access on May 2019)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), the positive result of the in vivo unscheduled DNA synthesis test with rats is a finding at doses where inflammation of the glandular stomach mucosa developed, and it cannot be clearly judged to be positive. Therefore, it was classified as "Classification not possible." [Evidence Data] (1) As for in vivo, there was one positive report in an unscheduled DNA synthesis test with rat stomach (PATTY (6th, 2012)). However, according to EU SCOEL SUM 149 (2014), this was a finding at doses where inflammation of the glandular stomach mucosa developed. In addition, there were four negative results in micronucleus tests, including a micronucleus test with mouse bone marrow by intraperitoneal administration and micronucleus tests with peripheral blood in mice and rats by inhalation exposure (NTP TR593 (2018), PATTY (6th, 2012)). (2)As for in vitro, it was positive and negative in bacterial reverse mutation tests and positive in a mouse lymphoma test and a sister chromatid exchange test with mammalian cells (NTP TR593 (2018), ACGIH (7th, 2012), JECFA FAS42 (1999), PATTY (6th, 2012)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), tumors in the nasal cavity of the target organ were observed in experimental animals in two species, although this was at a low incidence. Therefore, it was classified in Category 2. Besides, the category was changed from the previous classification by use of the new information sources. [Evidence Data] (1)In a 2-year carcinogenicity test with rats exposed by inhalation (12.5, 25, 50 ppm), squamous cell carcinoma (3/50) and squamous cell papilloma (1/50) of the nasal cavity in males and squamous cell carcinoma (3/50) of the nasal cavity in females were observed at 50 ppm. Based on these, it was concluded that there was some evidence of carcinogenicity with this substance in both male and female rats (NTP TR593 (2018)). (2) In a 2-year carcinogenicity test with mice exposed by inhalation (12.5, 25, 50 ppm), no tumors were observed in males and nasal adenocarcinoma (2/50) was observed in females at 50 ppm. Based on these, it was concluded that there was no evidence of carcinogenicity in male mice and equivocal evidence of carcinogenicity in female mice (NTP TR593 (2018)). [Reference Data, etc.] (3) As for classification results by domestic and international organizations, it was classified in A4 by ACGIH (ACGIH (7th, 2012)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Based on (1), no teratogenicity was observed. However, there was no information on sexual function and fertility. Therefore, it was classified as "Classification not possible" due to lack of data. [Evidence Data] (1) In teratogenicity tests in which a 90% solution of this substance was administered by gavage to female rats on gestational Day 6-15, female mice on gestational Day 6-15, and female hamsters on gestational Day 6-10, no maternal toxicity or fetal malformation was observed in any species (PATTY (6th, 2012), JECFA FAS42 (1999), HSDB (Access on May 2019)).
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), it was classified in Category 1 (respiratory organs). There was a report indicating effects on the respiratory organs in a case report of human exposure in (2), but this was only one case, and it was exposure to a mixture with an unknown amount of this substance. Therefore, it was not adopted as evidence of the classification. [Evidence Data] (1) In a test with rats by single 6-hour inhalation exposure, there were reports of minimal nasal necrosuppurative rhinitis at 99 ppm (0.35 mg/L, converted 4-hour equivalent value: 0.43 mg/L), mild nasal necrosuppurative rhinitis with neutrophilic inflammation at 198 ppm (0.70 mg/L, converted 4-hour equivalent value: 0.86 mg/L), and significant necrosis of nasal epithelium and tracheal epithelium with neutrophilic inflammation, including statistically significant minimal and mild necrosuppurative bronchitis and rhinitis at the 295 ppm (1.04 mg/L, converted 4-hour equivalent value:1.27 mg/L) (PATTY (6th, 2012), EU SCOEL SUM 149 (2014)). The concentrations where these effects were observed correspond to Category 1. [Reference Data, etc.] (2) A 36-year-old man who had been handling a hot mixture containing this substance for several hours for flavoring product production developed sore and reddened eyes and conjunctival secretion. Also nine months later, he showed a decrease in forced expiratory flow suggesting an airway disease (EU SCOEL SUM 149 (2014)).
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), effects on the respiratory organs were observed in humans. Based on (2)-(4), effects on the respiratory organs were observed within the range of Category 1 in experimental animals. Therefore, it was classified in Category 1 (respiratory organs). [Evidence Data] (1) A bronchiolitis obliterans-like illness was reported in workers cooking of microwave popcorn using this substance as a flavoring agent, and similar cases were reported in workers mixing in a popcorn manufacturing plant. In addition, there was a report that asthma was observed in food production workers exposed to butter flavored oils used in popcorn manufacture (ACGIH (7th, 2012), PATTY (6th, 2012)). (2) In a test in which rats were exposed by inhalation at 6.25-100 ppm for 14 weeks (6 hours/day, 5 days/week), squamous metaplasia of the respiratory epithelium and degeneration of the olfactory epithelium in the nose were observed at or above 25 ppm (converted guidance value: 0.07 mg/L, within the range of Category 1), suppurative inflammation, hyperplasia of the respiratory epithelium, respiratory metaplasia of the olfactory epithelium, hyperplasia of the lymphoid tissue, etc. in the nose and squamous metaplasia of the respiratory epithelium in the larynx were observed at or above 50 ppm (converted guidance value: 0.14 mg/L, within the range of Category 1), and increased neutrophil counts, necrosis of the respiratory epithelium, necrosis of the olfactory epithelium, etc. in the nose, hyperplasia of the squamous epithelium, etc. in the larynx, necrosis of the epithelium, etc. in the trachea, bronchial epithelial hyperplasia, etc. in the lung were observed at 100 ppm (converted guidance value: 0.27 mg/L, within the range of Category 2) (NTP TR593 (2018)). (3) In a test in which mice were exposed by inhalation at 6.25-100 ppm for 14 weeks (6 hours/day, 5 days/week), nonneoplastic lesions of the respiratory tract were found in each dose group at or above 25 ppm (converted guidance value: 0.07 mg/L, within the range of Category 1), similar to those in the test with rats in (2) described above. In addition, increased neutrophil counts were observed at 50 ppm (converted guidance value: 0.14 mg/L, within the range of Category 1) (NTP TR593 (2018)). (4) When mice were exposed by inhalation at 25-100 ppm for 12 weeks (6 hours/day, 5 days/week), peribronchial lymphocytic inflammation, atrophy and metaplasia of the nasal and olfactory epithelium were observed at or above 25 ppm (converted guidance value: 0.06 mg/L, within the range of Category 1), increased LDH activity was observed at or above 50 ppm (converted guidance value: 0.12 mg/L, within the range of Category 1), and body weight loss, decreases in respiratory rates and minute volume decreases, moderate suppurative rhinitis, chronic active inflammation, epithelial ulceration, necrosis, atrophy, and metaplasia of the nasal and olfactory epithelium, bronchi atrophy, denudation, and regeneration that extended into the smaller airways and bronchioles, and peribronchial lymphocytic inflammation were observed at 100 ppm (converted guidance value: 0.23 mg/L, within the range of Category 2) (ACGIH (7th, 2012), PATTY (6th, 2012)).
10	Aspiration hazard	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment Short term (Acute)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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