NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	108-78-1
Chemical Name	Melamine
Substance ID	R02-A-004-MHLW, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
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. It was classified as "Not classified."
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products. It was classified as "Not classified."
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
7	Flammable solids	Classification not possible	- -	-	-	No data available. Besides, there is information that it is combustible under specific conditions (ICSC (2006)).
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. It was classified as "Not classified."
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Not classified	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of > 500 deg C (ICSC (2006)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data 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). It was classified as "Not classified."
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine. It was classified as "Not classified."
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified."
16	Corrosive to metals	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) LD50 for rats: 3,161 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011)) (2) LD50 for rats: males: 3,200 mg/kg, females: 3,800 mg/kg (IARC 73 (1999), HSDB (Access on April 2020)) (3) LD50 for rats: males: 3,160 mg/kg, females: 3,850 mg/kg (HSDB (Access on April 2020)), 3,160 mg/kg (GESTIS (Access on April 2020)), 3,160-3,850 mg/kg (Patty (6th, 2012))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. There are data in (1), but because the category could not be determined from the data alone, it was classified as "Classification not possible." [Reference Data, etc.] (1) LD50 for rabbits: > 1,000 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011), GESTIS (Access on April 2020), HSDB (Access on April 2020))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (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] It was classified as "Not classified" from (1). [Evidence Data] LC50 for rats (aerosol, 4 hours): > 5.19 mg/L (REACH registration dossier (Access on June 2020))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) No skin reactions were observed in a skin irritation test with rabbits according to OECD TG 404 (REACH registration dossier (Access on June 2020)). (2) In a patch test in humans, no skin irritation or sensitization was found. And dermatitis was reported from the manufacture of melamine-formaldehyde resins or intermediate reaction products of formaldehyde and this substance, but not this substance itself (Environmental Risk Assessment for Chemical Substances vol. 8, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2010)). (3) This substance produced little or no irritation or sensitization when its 1% aqueous solution was applied to the guinea pig skin under occlusion. There was a similar result also in rabbits (Patty (6th, 2012), GESTIS (Access on April 2020)).
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] There is a description of (1), but it was classified as "Classification not possible" due to lack of data. [Reference Data, etc.] (1) When powder of this substance was tested on the rabbit eye, mild transient irritation occurred, but a 10% aqueous suspension had no effect (Patty (6th, 2012)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) It was reported to be negative in a skin sensitization test (maximization test) with guinea pigs according to OECD TG 406 (REACH registration dossier (Access on June 2020)). (2) In a patch test in humans, no skin irritation or sensitization was found. And dermatitis was reported from the manufacture of melamine-formaldehyde resins or intermediate reaction products of formaldehyde and this substance, but not this substance itself (Environmental Risk Assessment for Chemical Substances vol. 8, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2010)). (3) This substance produced little or no irritation or sensitization when its 1% aqueous solution was applied to the guinea pig skin under occlusion. There was a similar result also in rabbits (Patty (6th, 2012), GESTIS (Access on April 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, in a micronucleus test using the bone marrow cells of mice (intraperitoneal injection), negative results were reported (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011), CEBS (Access on April 2020), IARC 73 (1999)), and in a chromosomal aberration test using the bone marrow cells of mice (intraperitoneal injection), equivocal results were reported (IARC 119 (2019)). In a sister chromatid exchange test using the bone marrow cells of mice (intraperitoneal injection), positive results were reported (IARC 119 (2019)). In a comet assay using the urothelial cells of the urinary bladder and the hepatocytes of rats (oral dose), negative results were reported (IARC 119 (2019)). In a peripheral blood pig-a mutation test with rats (oral dose), negative results were reported (IARC 119 (2019)). (2) As for in vitro, in a bacterial reverse mutation test, a mammalian cell chromosome aberration test, and a mammalian cell gene mutation test, negative results were reported; and in a sister chromatid exchange analysis with the cultured mammalian cells, negative results or equivocal results were reported (IARC 119 (2019), CEBS (Access on April 2020), (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011)). In a mammalian cell micronucleus test, negative results were reported (IARC 119 (2019)). [Reference Data, etc.] (3) As a result of the concentration measurement of the oxidative DNA damage marker (8-OHdG) in human urine, an increase in 8-OHdG concentration was not observed (IARC 119 (2019)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2. [Evidence Data] (1) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2B (IARC 119 (2019), the JSOH classified this substance in Group 2B (Japan Society For Occupational Health (JSOH), 2019)), and the EPA classified this substance in Group D (Not Classifiable as to Human Carcinogenicity) (EPA Cancer Annual Report 2019 (Access on July 2020): classification in 1993). (2) In two-year carcinogenicity studies with male and female rats and mice dosed by feeding, a significant increase in the incidence of transitional epithelial carcinoma of the urinary bladder was observed in male rats, and urinary bladder stones were observed in 7/8 animals in which transitional epithelial carcinoma was observed. In female rats and male and female mice, no tumors showed a significant increase in incidence (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011), NTP TR245 (1983), IARC 119 (2019)). (3) In a 22-week test with male and female mice dosed by feeding, a significant increase in the incidence of dysplasia or carcinoma in situ of the urinary bladder and ureter was observed (IARC 119 (2019)). [Reference Data, etc.] (4) In a large cohort study in the United States which targeted the workers exposed to formaldehyde, the workers exposed to other chemicals including this substance were also identified, and there was a positive correlation between mortality attributable to lung cancer, leukemia, and nasopharynx cancer and duration of exposure to this substance. However, the amount of exposure to this substance was not measured, and there was no analysis on tobacco smoking or exposure to other chemicals (IARC 119 (2019)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Although there were data of (1), effects on sexual function and fertility were unknown, and classification was not possible due to lack of data. [Evidence Data] (1) In a developmental toxicity study with female rats dosed by feeding on days 6 to 16 of gestation, no effect was observed in fetuses even at a dose at which maternal toxicity effects (reduced body weight gain, a decrease in food consumption, hematuria) were observed (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011), HSDB (Access on April 2020)). [Reference Data, etc.] (2) In a test in which a single dose (70 mg/kg/day) was administered by intraperitoneal injection to female rats during the gestation period (days 4 and 5 of gestation, days 7 and 8 of gestation, or days 11 and 12 of gestation), no effect was observed in either maternal animals or fetuses (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011), HSDB (Access on April 2020)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] The information on humans in (1) was not detailed enough, and the effects on test animals in (2) to (4) were all observed at high doses exceeding Category 2, and therefore, they were not adopted as evidence of the classification. Therefore, it was determined that classification was not possible. [Reference Data, etc.] (1) It was reported that there were moderate effects on the exposed tissues in oral dose to humans, but the details were unknown (HSDB (Access on April 2020)). (2) As a result of an oral dose of 2,400 mg/kg (within the range exceeding Category 2) to rats and dogs, diuresis and crystalluria were observed (HSDB (Access on April 2020), Patty (6th, 2012)). (3) In an oral toxicity test with rats, white crystals in the stomach were observed in males at or above 2,150 mg/kg (within the range exceeding Category 2) and in females at or above 3,160 mg/kg (within the range exceeding Category 2) (REACH registration dossier (Access on June 2020)). (4) In an inhalation exposure test with rats, a decrease in respiratory rate, blepharospasm, and petechiae, gray discoloration, and white spots in the lung were observed at 5.19 mg/L (aerosol, 4 hours, within the range exceeding Category 2) (REACH registration dossier (Access on June 2020)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (urinary organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) and (2), as it was reported that effects on the urinary organs were observed in humans, it was classified in Category 1 (urinary organs). [Evidence Data] (1) In the case of contamination of infant formula with this substance in China, such damages as kidney stones in infants, which were thought to have been caused by the infant formula contaminated with this substance, were reported. The amount of exposure to this substance was estimated to be up to 8.6-23.4 mg/kg/day, and since the amount of the detected cyanuric acid, etc., which was a compound similar to this substance in formula contaminated with this substance, was about 0.1% of this substance, the expert meeting of the WHO concluded that this substance alone could cause stone formation if ingested in large amounts (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011)). (2) The Food Safety Commission of Japan stated that clinical findings in the case of contamination of infant formula with this substance in China were crying while urinating, hematuria, percussion pain in the lumbar, discharge of stones and dysuria, acute obstructive renal failure accompanied by oliguria or anuria, and subsequent high-blood pressure and edema (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011)). [Reference Data, etc.] (3) It was reported that in 13-week tests with rats and mice dosed by feeding, effects on the urinary organs were also observed at a dose exceeding Category 2 (NTP TR245 (1983)).
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)	Not classified	- -	-	-	It was classified as "Not classified" from 72-hour EbC50 = 196 mg/L for algae (Raphidocelis subcapitata) (REACH registration dossier, 2020) and 48-hour EC50 = 200 mg/L for crustacea (Daphnia magna) (REACH registration dossier, 2020).
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	It was classified as "Not classified" because it was not rapidly degradable (BIOWIN) and due to 72-hour NOEC (area method) = 31 mg/L for algae (Raphidocelis subcapitata), 21-day NOEC >= 11 mg/L for crustacea (Daphnia magna), and 36-day NOEC >= 5.1 mg/L for fish (Pimephales promelas) (all, REACH registration dossier, 2020).
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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