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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	123-39-7
Chemical Name	N-methylformamide
Substance ID	H30-B-014-MHLW, MOE
Classification year (FY)	FY2018
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	FY2007
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	Not applicable	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases (including chemically unstable gases)	Not applicable	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Not classified	- -	-	-	A flash point is 98 deg C (closed cup) (ICSC (2012) (J)).
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 425 deg C (GESTIS (Accessed Aug. 2018)).
10	Pyrophoric solids	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 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 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 applicable	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified" (Category 5 in UN GHS classification). [Evidence Data] (1) LD50 for rats: 4,000 mg/kg (HSDB (Accessed Aug. 2018))
1	Acute toxicity (Dermal)	Category 4	Warning	H312	P302+P352 P362+P364 P280 P312 P321 P501	[Rationale for the Classification] Based on (1), it was classified in Category 4. [Evidence Data] (1) LD50 for rabbits: 1,289 mg/kg (REACH registration dossier (Accessed Aug. 2018))
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	[Rationale for the Classification] Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1), it corresponds to Category 4-"Not classified." However, it was classified as "Classification not possible" since it is not possible to identify the category with only this information. Besides, the saturated vapor concentration at 20 deg C of this substance is 332 ppm (0.8 mg/L), and since the test was conducted at a range exceeding the saturated vapor concentration, it was treated as an inhalation test with mist. [Evidence Data] (1) LC50 (4 hours) for rats: > 4.1 mg/L (at 4.1 mg/L, mortality was 0/10 animals in males and 0/10 animals in females) (REACH registration dossier (Accessed Aug. 2018))
2	Skin corrosion/irritation	Classification not possible	- -	-	-	[Rationale for the Classification] Although animal test data in (1) and (2) indicate that this substance shows no irritation, adequate evidence to judge it as "Not classified" was not obtained due to insufficient numbers of animals, so it was classified as "Classification not possible." [Evidence Data] (1) There is a report that in a skin irritation test (similar to OECD TG 404, n=2) with rabbits, in which this substance itself was applied openly for 1, 5 or 15 minutes (washed with Lutrol or 50% aqueous Lutrol), the edema score was 0, the erythema score was 1.67, and the animals recovered within 7 days (REACH registration dossier (Accessed Aug. 2018)). (2) There is a report that in a skin irritation test (similar to OECD TG 404, n=2) with rabbits, in which this substance itself was applied openly for 20 hours (unwashed), an erythema score of 1.67 was obtained, but the animals recovered within 6 days (REACH registration dossier (Accessed Aug. 2018)).
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. [Evidence Data] (1) There is a report that in an eye irritation test (n=6) with rabbits, in which this substance was applied, a conjunctival redness score at 24, 48, and 72 hours after application was 2.13, and the animals did not recover completely in 4 days (REACH registration dossier (Accessed Aug. 2018)). (2) There is a description that this substance was irritating to the eyes (HSDB (Accessed Aug. 2018)).
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] Information (1) indicating that this substance is not sensitizing to the skin is obtained. However, since adequate evidence to judge as "Not classified" is not obtained, it was classified as "Classification not possible." [Reference Data, etc.] (1) There is a report that in an LLNA test (OECD TG406, n=6) with mice, in which the preparation of this substance (in acetone: olive oil (4: 1 v/v)) was applied, no sensitization was shown (REACH registration dossier (Accessed Aug. 2018)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Classification not possible" in accordance with the GHS Classification Guidance for the Japanese Government. Besides, although the REACH registration dossier is not listed on the information source lists on GHS classification guidance for the Japanese government, classification was done using available data considering the reliability of the data. [Evidence Data] (1) As for in vivo, it was negative in a mouse dominant lethal test (REACH registration dossier (Accessed Aug. 2018)). (2) As for in vitro, it was negative in a bacterial reverse mutation test (REACH registration dossier (Accessed Aug. 2018)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] According to (1) and (2), in developmental toxicity tests with rats by the oral and inhalation routes, developmental effects including an increase in the incidence of malformations were observed at or below doses where the maternal toxicity was manifested. Therefore, it was classified in Category 1B. [Evidence Data] (1) In a developmental toxicity test with rats exposed by inhalation on gestational day 7-16, increased embryo resorptions, decreased litter size, decreased pup body weights, etc. were observed significantly at 150 ppm. In addition, increased malformations such as head cysts, microphthalmia, hydrocephaly are reported. A significantly decreased pup body weight was observed at 50 ppm (REACH registration dossier (Accessed Aug. 2018)). (2) In a developmental toxicity test with rats dosed by gavage on gestational day 6-15, no clear maternal toxicity was observed at up to 200 mg/kg/day of the highest dose. In fetuses, however, at 67 mg/kg/day of the middle dose, a decrease in fetal body weight and length, and increased variations (unknown details) and malformations (incidence: 51%, meningocele, malformations of ribs and vertebral column, etc.) were observed. At 200 mg/kg/day, 99.6% of implants were resorbed in the early stage, and in survival fetuses, malformations such as exencephaly and visceral ectopia were observed in one animal (REACH registration dossier (Accessed Aug. 2018)). [Reference Data, etc.] (3) In a test in which rats of gestational day 7-14 were dermally dosed, fetal deaths of 87% and malformations (hydronephrosis, hydrocephalus) in all surviving fetuses were observed. Also, in the oral route, similar results were obtained by the administration of 1 cc/kg/day (HSDB (Accessed Aug. 2018)).
8	Specific target organ toxicity - Single exposure	Category 1 (liver)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 1 (liver). Since the findings on the heart in (3) were judged as non-specific changes, it was not adopted as the target organ. Besides, since there are no reports of significant effects in the organs other than the liver, and nausea and vomiting were not adopted as findings of systemic toxicity, "systemic toxicity" in the previous classification was deleted from the target organ. [Evidence Data] (1) There is a report that the primary target organ in relation to acute toxicity of this substance in humans is the liver (HSDB (Accessed Aug. 2018)). (2) There is a report that in humans, in the case of a single oral exposure to up to the upper limit of 15 mg/kg, at not much higher doses, nausea, vomiting and liver dysfunction were observed (GESTIS (Accessed Aug. 2018)). (3) There is a report that in a single dermal administration test with rabbits, acute dilatation of the heart, hyperemia and greyish liver lobules were observed in the deceased animals at 400-2,000 mg/kg (REACH registration dossier (Accessed Aug. 2018)). [Reference Data, etc.] (4) There is a report that in a single dose test with mice by intraperitoneal administration, increases in sorbitol dehydrogenase (SDH) and in plasma concentrations of the indicators of hepatic toxicity were observed at 200-800 mg/kg (HSDB (Accessed Aug. 2018)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs, liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] This substance had been developed as an antitumor agent. It seems to be obvious that this substance exhibits liver toxicity in humans based on clinical reports in (1)-(4) and animal test data in (5). Also, according to (6), the respiratory organs were also considered as target organs in the inhalation route. Therefore, it was classified in Category 1 (respiratory organs, liver). Besides, according to (4), since toxicity was not observed in organs other than the liver, it was judged to be inappropriate to adopt "systemic toxicity" as a target organ, and this was deleted from the target organs. Besides, the target organ was changed from the previous classification by using the updated information sources. [Evidence Data] (1) In a case of multiple patients orally administered at doses of 100-4,000 mg/kg for 2-36 days, hepatic damage was observed in all patients (total doses: 80-870 mg). Necropsy of one patient revealed irregular destruction of lobular tissue, large-sized hepatocytes, and existence of an area of liver regeneration in the liver (HSDB (Accessed Aug. 2018)). (2) In 19 patients who were given initial intravenous or oral doses of 300 mg/m2/day for 5 days, and then a 5-day treatment every 2 weeks, escalated at up to 1,200 mg/m2/day and in 35 patients treated with a dose of 125 -3,125 mg/m2/week every 6 weeks, a reversible elevation of serum transaminases activity was observed in several patients (HSDB (Accessed Aug. 2018)). (3) In a study in which 200-1,200 mg/m2/day were administered orally or intravenously to humans 3 times a week for 4 weeks, increases in serum AST, ALT and alkaline phosphatase activity, hyperbilirubinaemia, and hepatomegaly were observed as reversible liver function changes (GESTIS (Accessed Aug. 2018)). (4) There is a description that in cases of oral or intravenous administration to humans, adverse effects were not detected in organs (kidneys, heart, blood, bone marrow) other than the liver (GESTIS (Accessed Aug. 2018)). (5) There is a report that in a test in which male rats were exposed by inhalation for 2 weeks (6 hours/day, 5 days/week), increased relative liver weight, and tissue changes (pale cytoplasm, an increase in mitotic indexes, lipid vacuolation, degenerative and regenerative changes in the cytoplasm) at or above 130 ppm (0.12 mg/L, converted guidance value: 0.036 mg/L, within the range of Category 1), and increases in AST and ALT activities at 400 ppm were observed (REACH registration dossier (Accessed Aug. 2018), GESTIS (Accessed Aug. 2018)). (6) There is a report that in a 2-week inhalation test with rats, wheezing and rales were observed at or above 50 ppm (0.12 mg/L, converted guidance value: 0.013 mg/L, within the range of Category 1) (GESTIS (Accessed Aug. 2018)).
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 (Acute)	Not classified	- -	-	-	It was classified as "Not classified" from 72-hour EC50 (growth rate) > 1000 mg/L for algae (Pseudokirchneriella subcapitata), 48-hour EC50 (immobile) > 1000 mg/L for crustacea (Daphnia magna), and 96-hour LC50 > 100 mg/L for fish (Oryzias latipes) (all Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2018)).
11	Hazardous to the aquatic environment (Long-term)	Not classified	- -	-	-	Although appropriate data on rapid degradability were not obtained, due to 72-hour NOEC (growth rate) = 1000 mg/L for algae (Pseudokirchneriella subcapitata), and 21-day NOEC (reproduction inhibition) > 100 mg/L for crustacea (Daphnia magna) (both Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2018)), it was classified as "Not classified."
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

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.

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