GHS Classification Results by the Japanese Government

Japanese



GENERAL INFORMATION
Item Information
CAS RN 75-12-7
Chemical Name Formamide
Substance ID R03-B-003-MHLW
Classification year (FY) FY2021
Ministry who conducted the classification Ministry of Health, Labour and Welfare (MHLW)
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 Not classified
-
-
- - A flash point is 120 deg C (closed cup) (ICSC (2018)).
7 Flammable solids Not classified (Not applicable)
-
-
- - Liquid (GHS definition)
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.
9 Pyrophoric liquids Not classified
-
-
- - It is estimated that it does not ignite at normal temperatures from an autoignition temperature of > 500 deg C (ICSC (2018)).
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 Category 1


Warning
H290 P234
P390
P406
It attacks aluminum, brass, copper, iron and lead (ICSC (2018)).
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) Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (3), it was classified as "Not classified."

[Evidence Data]
(1) LD50 for rats: 3,200 mg/kg (SIAR (2007))
(2) LD50 for rats: 5,325 mg/kg (SIAR (2007), Health Canada Screening Assessment (2009))
(3) LD50 for rats: 6,000 mg/kg (DFG MAK (2013), ACGIH (8th, 2020))
1 Acute toxicity (Dermal) Not classified
-
-
- - [Rationale for the Classification]
Based on (1) to (3), it was classified as "Not classified."

[Evidence Data]
(1) LD50 for rats: > 13,500 mg/kg (DFG MAK (2013), Health Canada Screening Assessment (2009))
(2) LD50 for rabbits: > 6,000 mg/kg (DFG MAK (2013), ACGIH (8th, 2020))
(3) LDLo for rabbits: 17,000 mg/kg (DFG MAK (2013), ACGIH (8th, 2020))
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.
1 Acute toxicity (Inhalation: Dusts and mists) Not classified
-
-
- - [Rationale for the Classification]
Based on (1) and (2), it was classified as "Not classified." Also, the exposure concentration was higher than the saturated vapor pressure concentration (0.15 mg/L) and it was judged as mist.

[Evidence Data]
(1) LC50 (4 hours) for rats: > 21 mg/L (SIAR (2007), Health Canada Screening Assessment (2009))
(2) LC50 (6 hours) for rats: > 3,900 ppm (converted 4-hour equivalent value: > 5,850 ppm (10.8 mg/L)) (ACGIH (8th, 2020))
2 Skin corrosion/irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1), it was classified as "Not classified" (Category 3 in UN GHS classification) in accordance with the GHS Classification Guidance for the Japanese Government.

[Evidence Data]
(1) It was reported that this substance was a slight skin and eye irritant (DFG MAK (2013)).

[Reference Data, etc.]
(2) In a skin irritation test with rabbits (n = 2) (occlusive, 20-hour application, observation for 5 days), marked erythema was observed in 1 animal at 24 hours after initiation of treatment, and slight erythema was observed in 1 animal at 24 and 48 hours after initiation of treatment. It was reported that erythema was absent on day 5, and scaling was seen at the treated sites (REACH registration dossier (Accessed Oct. 2021)).
3 Serious eye damage/eye irritation Not classified
-
-
- - [Rationale for the Classification]
Based on (1), it was classified as "Not classified." Also, based on the new findings, the classification result was changed.

[Evidence Data]
(1) It was reported that, in an acute eye irritation/corrosion test with rabbits (n = 6) (equivalent to OECD TG405, 0.1 mL undiluted solution, observation for 96 hours), the overall mean scores at 24, 48, and 72 hours were 1.91 for conjunctival redness, 0.44 for chemosis, and 0.17 for corneal opacity, and this substance was slightly irritating the rabbit eye (SIAR (2007), REACH registration dossier (Accessed Oct. 2021)).
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. Besides, the findings in (1) to (3) were not used for the classification because the details such as the test method were unknown.

[Reference Data, etc.]
(1) The contact dermatitis potential of this substance was slight when applied to the skin of guinea pigs (ACGIH (8th, 2020)).
(2) In a test with guinea pigs, a slight temporary skin irritation was observed, but it quickly disappeared, and no allergic skin sensitization was observed (ACGIH (8th, 2020)).
(3) In a test with guinea pigs, no allergic skin reactions occurred (DFG MAK (2013)).
5 Germ cell mutagenicity Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data. The findings in in vivo micronucleus tests in (1) were conflicting between negative results by repeated oral administration and positive results by single intraperitoneal injection, and micronucleus inducibility by oral administration in human exposure routes was unclear due to the limitations in each test, and therefore, the classification was not possible due to lack of data.

[Reference Data, etc.]
(1) As for in vivo, negative results were obtained in a dominant lethal test (intraperitoneal injection), negative results were obtained in a micronucleus test using the peripheral blood erythrocytes of mice (13-week oral administration), and positive results were obtained in a micronucleus test using the bone marrow cells of mice (single intraperitoneal injection) (SIAR (2007), Health Canada Screening Assessment (2009), DFG MAK (2013), AICIS IMAP (2013)).
(2) As for in vitro, negative results were reported in a bacterial reverse mutation test (SIAR (2007), Health Canada Screening Assessment (2009), DFG MAK (2013), AICIS IMAP (2013), ACGIH (8th, 2020)).
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
There was no information on human carcinogenicity. Based on the classification results by the ACGIH in (1), and the clear evidence of carcinogenicity (hemangiosarcoma of the liver) observed in males and the equivocal evidence (combined incidence of hepatocellular adenoma or hepatocellular carcinoma) observed in females in one animal species (mice) in (2) and (3), it was classified in Category 2. Also, based on the new information source, the classification result was changed.

[Evidence Data]
(1) As for the classification results by domestic and international organizations, the ACGIH classified this substance in A3 (ACGIH (8th, 2020)).
(2) In a 2-year carcinogenicity study (20 to 80 mg/kg/day) with rats dosed by gavage (5 days/week), no evidence of carcinogenic potential was observed in either males or females (NTP TR541 (2008), SIAR (2007), Health Canada Screening Assessment (2009), AICIS IMAP (2013), AICIS IMAP (2016), ACGIH (8th, 2020), REACH registration dossier (Accessed Sep. 2021)).
(3) In a carcinogenicity study (20 to 80 mg/kg/day) with mice dosed by gavage for two years (5 days/week), in males, a dose-dependent increase in hemangiosarcoma in the liver and a significant increase in the incidence at the mid-dose (40 mg/kg/day) or higher were observed, and they were considered to be clear evidence of carcinogenicity. In females, a significant increase was observed in the incidence of hepatocellular adenoma or hepatocellular carcinoma (combined) at the high dose (80 mg/kg/day), but since it was within the background data (incidence), it was considered to be equivocal evidence (NTP TR541 (2008), SIAR (2007), Health Canada Screening Assessment (2009), AICIS IMAP (2013), AICIS IMAP (2016), ACGIH (8th, 2020), REACH registration dossier (Accessed Oct. 2021)).
7 Reproductive toxicity Category 1B


Danger
H360 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1), adverse effects of this substance on fertility and sexual function were observed at a general toxicity dose in parent animals. Besides, based on (2) to (6), it was suggested that, in the oral and dermal routes, this substance caused severe developmental toxicity such as embryonic/fetal toxicity (lethal effects), teratogenicity (cleft palate, exencephaly) even at doses at which general toxicity effects on dams were equivocal, and therefore, it was classified in Category 1B.

[Evidence Data]
(1) In a Reproductive Assessment by Continuous Breeding (RACB) test with mice dosed by drinking water (100 to 750 ppm), in F0, a slight decrease in litter size/a decrease in live litter size, delayed first delivery, and a decrease in fertility rate in mating on day 5 were observed at the dose (high dose: 750 ppm) at which general toxicity effects such as lower body weight/reduced body weight gain, reduced water consumption appeared in F0 and F1 male and female parent animals. As a result of a test of crossover mating between dose groups and control groups, a marked decrease in fertility rate by mating between females of a 750 ppm dose group and males of a control group was observed. It was reported that, also in the mating performance of F1, a decrease in fertility rate, a decrease in live pups, delayed delivery, lengthened estrous cycles, a tendency of shortened estrus/a tendency of extended diestrus, etc. were observed (SIAR (2007), Health Canada Screening Assessment (2009), DFG MAK (2013) , ACGIH (8th, 2020)).
(2) In a developmental toxicity study with female mice dosed by gavage on days 6 to 15 of gestation, the highest dose (396 mg/kg/day) group showed significant maternal toxicity and the administration was discontinued midway, and at the lower dose (198 mg/kg/day), no serious effects were observed in dams, but an increase in post-implantation embryonic/fetal loss and an increase in malformations of live pups were observed. It was reported that major malformations were observed in the skull (exencephaly, presphenoidal aplasia, brachygnathia, cleft palate), the ribs (fused ribs), and the spinal cord (clefts and hypoplasia of vertebral bodies) (SIDS Dossier (2007), SIAR (2007), DFG MAK (2013)).
(3) It was reported that, in a test with pregnant mice dosed by gavage on any one day from day 6 to day 14 of gestation, the incidence of malformed fetuses in live fetuses were 58, 68, and 13% when high doses (991 mg/kg) with no apparent maternal toxicity were administered on days 8, 9, and 10 of gestation, respectively (SIDS Dossier (2007), SIAR (2007), Health Canada Screening Assessment (2009), DFG MAK (2013)).
(4) It was reported that, in numerous developmental toxicity studies with pregnant rats and rabbits by oral administration, developmental toxicity including malformations was observed in both animals at the dose at which maternal toxicity was marked (SIAR (2007), AICIS IMAP (2013)).
(5) In a test by dermal administration of 600 mg/kg of this substance to female rats on day 9, days 10 + 11, days 11 + 12, or days 12 + 13 of gestation, fetal toxicity was observed in 5 to 13% of fetuses, and abnormalities (subcutaneous hemorrhage) were observed in 4/60 fetuses from dams which were dosed on days 12 + 13 of gestation, and therefore, it was judged that this substance showed very weak fetal toxicity (SIDS Dossier (2007), SIAR (2007), Health Canada Screening Assessment (2009), DFG MAK (2013), ACGIH (8th, 2020)).
(6) In a test by a single or two-fold dermal administration of 113 mg (0.1 mL) of this substance to female mice on day 11 of gestation, after a single administration, embryonic/fetal mortality was 50%, and malformations (cleft palates) were observed in 50% of live fetuses. After a two-fold administration, embryonic/fetal mortality increased to 80%, and amelia was also observed in addition to malformations similar to those at a single administration (SIDS Dossier (2007), SIAR (2007), Health Canada Screening Assessment (2009), DFG MAK (2013), ACGIH (8th, 2020)).

[Reference Data, etc.]
(7) In the EU CLP, it was classified in Repr. 1B (EU-CLP Classification Results (Accessed Sep. 2021)).
8 Specific target organ toxicity - Single exposure Category 3 (Narcotic effects)


Warning
H336 P304+P340
P403+P233
P261
P271
P312
P405
P501
[Rationale for the Classification]
Based on (1), it was classified in Category 3 (narcotic effects). Also, based on the new findings, the classification result was changed.

[Evidence Data]
(1) In an acute inhalation exposure test with rats (mist, 4 hours), at 14 to 21 mg/L (in the range corresponding to "Not classified"), lethargy, hunched posture, clear or red ocular discharges, red nasal discharge, partial closed eyes, diarrhea, and brown-stained perineum were observed, and symptoms were almost absent by day 8 post exposure (SIAR (2007), Health Canada Screening Assessment (2009), AICIS IMAP (2013)).

[Reference Data, etc.]
(2) It was reported that, in an acute oral toxicity test (OECD TG 401) with rats, at 3.626 mg/kg (in the range corresponding to "Not classified"), poor general state, irregular respiration, apathy, and reduced food consumption were observed, and no abnormalities were observed at necropsy (SIAR (2007), Health Canada Screening Assessment (2009)).
(3) It was reported that, in an acute inhalation exposure test with rats (mist, 6 hours), no symptoms were observed at 3,900 ppm (converted 4-hour equivalent value: 5,515 ppm (14.4 mg/L, in the range corresponding to "Not classified") (ACGIH (8th, 2020)).
9 Specific target organ toxicity - Repeated exposure Category 2 (male reproductive organs)


Warning
H373 P260
P314
P501
[Rationale for the Classification]
Based on (1) to (5), it was classified in Category 2 (male reproductive organs) since effects on the testes were observed within the range for Category 2. Effects on the adrenal gland (necrotic areas in the adrenal cortex) observed in (1) were not adopted for the classification because no symptoms were observed in other long-term tests. Also, based on the new findings, the classification result was changed.

[Evidence Data]
(1) It was reported that, in a repeated dose 4-week oral toxicity study (5 days/week) with rats dosed by gavage, effects were observed on the blood system (increases in erythrocyte counts and hematocrit values, decreased number of thrombocytes, and increased coagulation times), adrenal gland (atrophy, reddish-brown coloration, necrotic areas in the cortex, dilation of blood vessels), kidney (atrophy, grayish-white radial stripes), and testes (atrophy, degeneration) at 113 and 340 mg/kg/day (converted guidance value: 25.1 and 76.5 mg/kg/day, within the range for Category 2) (SIAR (2007), DFG MAK (2013), AICIS IMAP (2013)).
(2) It was reported that, in a repeated dose 14-week oral toxicity study (5 days/week) with rats dosed by gavage, effects on the blood system (increased erythrocyte counts, an increase in MCV, increases in segmented neutrophil counts, etc.), and estrus cycle in females (extended estrus, shortened diestrus) were observed at 40 and 80 mg/kg/day (converted guidance value: 31 and 62 mg/kg/day, within the range for Category 2), and testicular toxicity (degeneration of the germinal epithelium of the seminiferous tubules) was observed at 160 mg/kg/day (converted guidance value: 114 mg/kg/day, in the range corresponding to "Not classified") (SIAR (2007), NTP TR541 (2008) , Health Canada Screening Assessment (2009), AICIS IMAP (2013), ACGIH (8th, 2020), REACH registration dossier (Accessed Sep. 2021)).
(3) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats and mice dosed by gavage, at 80 mg/kg/day (within the range for Category 2), bone marrow hyperplasia was observed in rats, and mineralization of the testicular arteries and testicular tunic, and hematopoietic cell proliferation of the spleen were observed in mice (NTP TR541 (2008), AICIS IMAP (2016), ACGIH (8th, 2020)).
(4) It was reported that, in two 90-day repeated dermal administration tests with rats, effects on the blood (increased erythrocyte counts and hemoglobin) were observed at 300 mg/kg/day (converted guidance value: 217 mg/kg/day, in the range corresponding to "Not classified") (SIAR (2007), Health Canada Screening Assessment (2009), DFG MAK (2013), AICIS IMAP (2013), ACGIH (8th, 2020), REACH registration dossier (Accessed Sep. 2021)).
(5) It was reported that, in a 2-week repeated inhalation exposure test (6 hours/day, 5 days/week) with rats (males), a decrease in platelet count was observed at or above 500 ppm (0.93 mg/L, converted guidance value: 0.10 mg/L, within the range for Category 2), and effects on the kidney (degeneration, necrosis), testicular degeneration, etc. were observed at 1,500 ppm (2.8 mg/L, converted guidance value: 0.31 mg/L, in the range corresponding to "Not classified") (SIAR (2007), Health Canada Screening Assessment (2009), DFG MAK (2013), AICIS IMAP (2013), ACGIH (8th, 2020), REACH registration dossier (Accessed Sep. 2021)).
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) -
-
-
- - -
11 Hazardous to the aquatic environment Long term (Chronic) -
-
-
- - -
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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