NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	68-12-2
Chemical Name	N,N-Dimethylformamide
Substance ID	m-nite-68-12-2_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecules.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
6	Flammable liquids	Category 3	Warning	H226	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	Its flash point is 58degC (closed cup) (ICSC (2000)), which falls under Category 3. It is rated as Class 3 with the packing group III by the UNRTDG (UN No. 2265).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
9	Pyrophoric liquids	Not classified	- -	-	-	It does not spontaneously ignite in contact with the air at room temperature (autoignition point: 445degC (ICSC, 2000).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
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).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	The substance contains oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Not classified	- -	-	-	Its rat LD50 values are 3000 mg/kg, 3920 mg/kg, 4000 mg/kg, 4320 mg/kg, 3200 mg/kg, and 7170 mg/kg (EHC 114 (1991)). Considering these reported values, the substance was classified into the "Not classified" category (Category 5 in the United Nations classification).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Its rat LD50 values are 3500 mg/kg (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 1 (2002)), 5000 mg/kg, 11140 mg/kg, and 11000 mg/kg (EHC 114 (1991)). Considering these reported values, the substance was classified into the "Not classified" category (Category 5 in the United Nations classification).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	It was classified into the "Not applicable" category since it is a liquid (GHS definition), and it is presumably not inhalable as a gas.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Vapours)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	Based on the 2-hour LC50 of 9400 mg/m3 for mice (4-hour conversion: 4.7 mg/L. since this value is below 90% of the saturated vapour pressure, we determined that the tests were conducted in a vaporous state) (HSDB, 2005), the substance was classified into Category 3.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] Because there are multiple pieces of evidence that this substance is irritating from (1)-(6), it was classified in Category 2. Besides, the previous category was revised by using new information sources. [Evidence Data] (1) There are multiple pieces of information that exposure to this substance causes symptoms of skin irritation and eruption in humans, and it is reported that it is slightly to moderately irritating to the skin (ACGIH (2018), CICAD (2001)). (2) A 52-year-old man who accidentally contacted this substance (about 20% of the body surface) washed himself, dressed, and drove home, and skin inflammation and hyperemia are reported as symptoms after 45 minutes (PATTY (6th, 2012), Ministry of Health, Labour and Welfare Hazard Assessment Report (CERI, NITE, 2017)). (3) It is reported that 21-year-old and 28-year-old men who exposed to this substance at work developed erythematous rash in their hands and forearms (Ministry of Health, Labour and Welfare Hazard Assessment Report (CERI, NITE, 2017)). (4) It is reported that after this substance was applied to the skin of mice at 500 mg/kg body weight, transient irritation was observed after 2-3 hours, and slight irritation was found at 2,500 and 5,000 mg/kg body weight (EHC (1991), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), Ministry of Health, Labour and Welfare Hazard Assessment Report (CERI, NITE, 2017)). (5) It is reported that when this substance was applied to the skin of rats at 94, 472, 944 mg/kg body weight, skin irritation was shown at 944 mg/kg body weight (PATTY (6th, 2012)). (6) It is reported that when this substance was applied to the skin of rabbits at 100, 200, 400 mg/kg body weight, it was irritating to the skin at 400 mg/kg body weight (PATTY (6th, 2012)). (7) In the notice regarding guidelines to prevent health problems, this substance was designated as a substance strongly irritating the skin, eye, and mucous membrane (the notice No. 0614001 issued by Director of Labour Standards Bureau, the Ministry of Health, Labour and Welfare, demolished by the notice No. 0331-26, March 31, 2016). [Reference Data, etc.] (8) In the announcement No. 33 of the Ministry of Labour (1996) (revised by the announcement No. 316 of the Ministry of Health, Labour and Welfare, 2013), this substance is designated as "dimethylformamide" in Simple chemical substances or compounds 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 a disease principally having specific symptoms and disorders (subjective symptoms such as headaches, dizziness, and vomiting, and skin disorders, anterior eye disorders, respiratory tract disorders, liver disorders, or gastrointestinal disorders) due to work involving exposure to this substance was designated as an occupational disease by the Minister of Health, Labour and Welfare. (9) In the notice No. 0811001 issued by Director of Labour Standards Bureau, the Ministry of Labour (2003), this substance is designated as "dimethylformamide" among hazardous substances for which installation of protective equipment to prevent eye disorders such as protective glasses is mandated in Article 593 in the Industrial Safety and Health Regulations.	FY2018	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	[Rationale for the Classification] This substance is thought to be irritating to from (1)-(5). By giving weight to evidence in a GLP-compliant test (1), it was classified in Category 2B. Besides, the category was revised from the previous classification by using information sources. [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (GLP-compliant, n = 6), after application of undiluted this substance, large blisters were observed on the inside of the upper and lower eyelids after 1 and 4 hours, but they decreased in size after 24 hours and resolved 48 hours (REACH registration dossier (Accessed Dec. 2018)). (2) It is reported that in an eye irritation test with rabbits (n = 3), after application of undiluted, 10%, 50% solution (0.9% NaCl) of this substance, chemosis and erythema were found after one hour but resolved after six days (REACH registration dossier (Accessed Dec. 2018)). (3) It is reported that in an eye irritation test in rabbits, effects were not observed after 0.1 mL of aqueous solution (25%) of this substance was applied to conjunctival sac, but slight irritation by a 50% aqueous solution and severe irritation by 75% aqueous solution and undiluted this substance were seen (EHC (1991), Ministry of Health, Labour and Welfare Hazard Assessment Report (CERI, NITE, 2017)). (4) It is reported that in an eye irritation test in rabbits, after 0.1 mL of this substance was applied, moderate corneal damage and conjunctival redness were found and pronounced after 2-3 days, and after 14 days, mild conjunctival redness and moderate corneal damage with severe injury, slight surface distortion, and subsurface vascularization were observed (EHC (1991), Ministry of Health, Labour and Welfare Hazard Assessment Report (CERI, NITE, 2017)). (5) In the notice regarding guidelines to prevent health problems, this substance was designated as a substance strongly irritating the skin, eye, and mucous membrane (the notice No. 0614001 issued by Director of Labour Standards Bureau, the Ministry of Health, Labour and Welfare, demolished by the notice No. 0331-26, March 31, 2016).	FY2018	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Although there are multiple pieces of evidence indicating that it is not sensitizing from (1)-(3), sufficient information to judge whether it is sensitizing was not obtained, therefore, it was classified as "Classification not possible." [Reference Data, etc.] (1) It is reported that in an LLNA test with mice (OECD TG406, n = 6), when a solution of this substance (acetone/olive oil (4:1 v/v)) was applied, clear signs of sensitization were not seen (SIAR (2001), ACGIH (2018), REACH registration dossier (Accessed Dec. 2018)). (2) It is reported that in an LLNA test with mice, after this substance was applied, no difference was observed between the control group and the treated group (CICAD (2001), ACGIH (2018)). (3) It is reported that in a maximization test with guinea pigs, when this substance was applied, it was not sensitizing (EHC (1991), SIAR (2001), REACH registration dossier (Accessed Dec. 2018)).	FY2018	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	According to the Hazard Assessment Report (CERI NITE, No. 8, 2005), a heritable mutagenicity test gave negative results, no in vivo germ cell mutagenicity test has been conducted, an in vivo mutagenicity tests using somatic cell gave positive results, and no in vivo germ cell genotoxicity test has been conducted.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	In carcinogenicity tests through inhalation, an increase in frequencies of hepatic adenomas and hepatic carcinomas were observed in rats of both sexes; similarly, an increase in frequencies of hepatic adenomas and hepatic carcinomas were observed at 200 ppm and above in mice of both sexes; furthermore, particularly malignant hepatoblastomas were noted in male mice, indicating clear carcinogenic effects of the substance on both sexes of rats and mice (Ministry of Health, Labour and Welfare (Results from Carcinogenicity Studies, 2000)). Thus, incidences of malignant liver neoplasm occur, regardless of animal species and sexes. In light of these results, the Ministry of Health, Labour and Welfare issued Guidelines for Preventing Health Impairment by N,N-Dimethylformamide (Ministry of Health, Labour and Welfare Guidelines, 2005). Based on this information, the substance was classified into Category 1B. As additional background information, the substance is rated as "Group 2B" by the Japan Society for Occupational Health (1991), "Group 3" by IARC 71 (1999), "A4" by ACGIH-TLV (2001); however, these classifications did not take into account test results mentioned above.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	According to the Hazard Assessment Report (CERI, NITE, No. 8, 2005), the substance was associated with malformations seen in the next generation (cleft palate, exencephaly, hydrocephaly, sphenoid bone defects, fused ribs, and tail defects) at concentrations that do not cause general toxicity to parental animals.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
8	Specific target organ toxicity - Single exposure	Category 1 (liver), Category 2 (respiratory organs)	Danger Warning	H370 H371	P308+P311 P260 P264 P270 P321 P405 P501	In humans, the substance is associated with eating disorders, vomiting, and pain in the abdominal, lumbar, and femoral regions; even after these symptoms disappear, fibrosis of the liver and accumulation of histiocytes were noted (Hazard Assessment Report (CERI, NITE, No. 8, 2005)). In animal studies, thickening of alveolar wall was detected (Hazard Assessment Report (CERI, NITE, No. 8, 2005)). Based on these results, we determine that the liver and respiratory system are the target organs. Effects of exposure seen in animal studies were observed at doses that fall under Category 2 guidance values. In conclusion, the substance was classified into Category 1 for the liver and Category 2 for the respiratory system.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver)	Danger	H372	P260 P264 P270 P314 P501	In humans, liver dysfunction, signs of alcohol intolerance (IRIS (1990)), increased hepatic disorder, increased AST or ALT, focal hepatocellular necrosis, and hepatocellular fatty change in microvesicles of smooth endoplasmic reticulum were observed as the effect of the substance exposure. In animal studies, the centrilobular hepatocellular hypertrophy (NTP TOX 22 (1992)), indicative of acute hepatocellular injury, increased SGPT and SGOT activities, histopathological changes in the liver of young animals (IRIS (1990)), increased ALP activity at 100 ppm or higher, increased ALT activity at 200 ppm or higher, and single cell necrosis in the liver at 200 ppm or higher (Hazard Assessment Report (CERI, NITE, No. 8, 2005)) were reported in association with the substance exposure. In animal studies, these effects were observed at Category 2 guidance doses. In conclusion, the substance was classified into Category 1 for the liver.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Not classified	- -	-	-	It was classified into Not classified from 96 hours LC50>100mg/L of the fish (Oryzias Latipest) (MOE eco-toxicity tests of chemicals (1995) and others.).	FY2006	GHS Classification Manual （10 Feb, 2006）
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Since it was not water-insolubility (the water-solubility =1.00*106mg/L (PHYSPROP Database, 2005)), and acute toxicity was low, it was classified into Not classified.	FY2006	GHS Classification Manual （10 Feb, 2006）
12	Hazardous to the ozone layer	-	- -	-	-	-	-	-

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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