NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	615-05-4
Chemical Name	4-methoxy-m-phenylenediamine
Substance ID	R02-B-079-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	Revised
Classification result in other fiscal year	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. 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 (ICSC (2005)).
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	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) 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). 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)	- -	-	-	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."
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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] It was classified in Category 4 from (1) - (6). [Evidence Data] (1) LD50 for rats: 450-830 mg/kg (GESTIS (Access on May 2020)) (2) LD50 for rats: 460 mg/kg (GESTIS (Access on May 2020), HSDB (Access on May 2020)) (3) LD50 for rats: 460-831 mg/kg (AICIS (formerly, NICNAS) IMAP (2014)) (4) LD50 for rats: 515 mg/kg (MAK (DFG) vol.6 (1994)) (5) LD50 for rats: 831 mg/kg (MAK (DFG) vol.6 (1994))
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
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)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Classification not possible	- -	-	-	[Rationale for the Classification] There were descriptions of (1) and (2), but the classification was not possible due to lack of data. The classification result was changed because rationale data for the previous classification were considered to be data on a 2.5% aqueous solution of this substance or a 10% aqueous solution of its hydrochloride salt. [Reference Data, etc.] (1) A 10% aqueous solution of the sulfate of this substance (CAS RN 39156-41-7) caused mild irritation on the rabbit skin (MAK (DFG) vol.6 (1994), GESTIS (Access on May 2020)). (2) A 2.5% aqueous solution of this substance caused mild irritation (slight edema) on the rabbit skin (AICIS (formerly, NICNAS) IMAP (2014), GESTIS (Access on May 2020)).
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] There were descriptions of (1) and (2), but the classification was not possible due to lack of data. The classification result was changed because rationale data for the previous classification were considered to be data on a 2.5% aqueous solution of this substance or a 10% aqueous solution of its hydrochloride salt. [Reference Data, etc.] (1) A 10% aqueous solution of the sulfate of this substance (CAS RN 39156-41-7) caused no irritation in the rabbit eye (MAK (DFG) vol.6 (1994), GESTIS (Access on May 2020)). (2) A 2.5% aqueous solution of this substance caused no irritation in the rabbit eye (AICIS (formerly, NICNAS) IMAP (2014), GESTIS (Access on May 2020)).
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). Besides, the substance was classified based on knowledge in its sulfate. [Evidence Data] (1) In a skin sensitization test with guinea pigs on the sulfate of this substance (CAS RN 39156-41-7) (open epicutaneous test, application concentration 3%), no positive reactions were observed (MAK (DFG) vol.6 (1994)). (2) In a skin sensitization test with guinea pigs on the sulfate of this substance (maximization test, intradermal administration 5%), equivocal results in 2/10 animals after the first challenge and a positive reaction in 1/10 animals after the second challenge were found (AICIS (formerly, NICNAS) IMAP (2014), GESTIS (Access on May 2020), MAK (DFG) vol.6 (1994)). (3) Positive results were reported in patch tests in humans, but it was suggested that the findings could also result from cross-reactivity (GESTIS (Access on May 2020)).
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1), (2). [Evidence Data] (1) As for in vivo, DNA damage tests with hepatocytes after intraperitoneal administration to rats gave positive and negative results, and it was positive in a sister chromatid exchange test using bone marrow cells after intraperitoneal administration to mice, negative in micronucleus tests using bone marrow cells after oral administration to rats or intraperitoneal administration to mice, and negative in a dominant lethal test by intraperitoneal administration to rats (IARC 79 (2001), MAK (DFG) vol.6 (1994), AICIS (formerly, NICNAS) IMAP (2014)). (2) As for in vitro, there were positive and negative results in bacterial reverse mutation tests, and in test systems with cultured mammalian cells, there were positive and negative results in gene mutation tests and a negative result in a cell transformational test (IARC 79 (2001)). [Reference Data, etc.] (3) Muta.2 (EU CLP classification (Access on May 2020))
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Carcinogenicity test results for this substance were not obtained, but it was classified in Category 1B because in classification results by other organizations in (1), it was classified in 2 in MAK (DFG) from carcinogenicity test results on the sulfate of this substance, and it was also classified in Carc.1B in EU CLP classification, and because there was sufficient evidence of carcinogenicity in animal data: from carcinogenicity test results on the sulfate of this substance in (2) - (4), tumor formation was observed in both mice and rats, and in two independent carcinogenicity tests with rats, common evidence of carcinogenicity was shown. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in Group 2B by IARC (IARC 79 (2001)), Group 2B by the Japan Society for Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH)) (proposed in 1991)), 2 in MAK (DFG) (DFG List of MAK and BAT Values (2019)), and Carc.1B in EU CLP classification (EU CLP classification (Access on May 2020)). (2) In a carcinogenicity test by 78-week diet administration of the sulfate of this substance (CAS RN 39156-41-7) to male and female rats, increased incidences of malignant tumors were observed in the thyroid, skin, preputial gland, and Zymbal's gland in males and the thyroid and Zymbal's gland in females (IARC 79 (2001), MAK (DFG) vol.6 (1994)). (3) In a carcinogenicity test by diet administration of the sulfate of this substance (CAS RN 39156-41-7) to female rats for 82-86 weeks, increased incidences of malignant tumors in the thyroid and clitoral gland were found (IARC 79 (2001), MAK (DFG) vol.6 (1994)). (4) In a carcinogenicity test by 78-week diet administration of the sulfate of this substance (CAS RN 39156-41-7) to male and female mice, increased incidences of thyroid adenoma or carcinoma were seen in males and females (IARC 79 (2001), MAK (DFG) vol.6 (1994)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification was not possible due to lack of data.
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] In an animal test of (1), effects on the nervous system were suggested but details were unknown. Therefore, it was classified as "Classification not possible." [Reference Data, etc.] (1) In an oral administration of this substance to rats, signs of toxicity such as lethargy, piloerection, increased salivation, ataxia, and excessive production of urine (diuresis) were reported, but details were unknown (AICIS (previous NICNAS) IMAP (2014)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (thyroid)	Warning	H373	P260 P314 P501	[Rationale for the Classification] There was insufficient data on this substance, but in an animal test using the sulfate of this substance (CAS RN 39156-41-7), effects on the thyroid appeared at doses within the range for Category 2 as shown in (1) to (3). Therefore, it was classified in Category 2 (thyroid). [Evidence Data] (1) It was reported that, in an 8-week feeding test using the sulfate of this substance with rats, an increase in the serum concentration of thyroid-stimulating hormone (TSH) and a decrease in the serum concentration of triiodothyronine (T3) were observed at 0.25% (converted guidance value: 78 mg/kg/day, converted value equivalent to this substance: 46 mg/kg/day, within the range for Category 2) (IARC 79 (2001)). (2) It was reported that, in a 78-week feeding test using the sulfate of this substance with rats, hypertrophy and dark red or black discoloration of the thyroid and follicular cyst in the thyroid were observed at 0.5% (converted guidance value: 250 mg/kg/day, converted value equivalent to this substance: 146 mg/kg/day, exceeding Category 2) (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011)). (3) It was reported that, in a 78 to 96-week feeding test using the sulfate of this substance with mice, hyperplasia of thyroid follicular cells was observed in male at 0.24% (converted guidance value: 360 mg/kg/day, converted value equivalent to this substance: 211 mg/kg/day, exceeding Category 2) (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011)). [Reference Data, etc.] (4) It was reported that, in an animal test in which effects of this substance on the thyroid and pituitary morphology were studied, hypertrophy and pigmentation of the thyroid epithelium were observed in animals dosed with this substance for 6 weeks, but details were unknown (HSDB (Access on May 2020)). (5) It was reported that, in a dermal administration test using the sulfate of this substance with rats, no toxicity effects were observed (MAK (DFG) vol.6 (1994), IARC 79 (2001)). (6) It was reported that, in a 12-week oral administration test using the sulfate of this substance with rats dosed by gavage, slower growth, decreases in red and white blood cell count, slightly increased weight of the liver, kidney, and spleen, and a slight increase in red blood cell breakdown in various organs were observed only in females at 23 mg/kg/day (converted guidance value: 15 mg/kg/day, within the range for Category 2) (MAK (DFG) vol.6 (1994)).
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)	Classification not possible	- -	-	-	No data available.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.
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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