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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	99-55-8
Chemical Name	2-Methyl-5-nitroaniline; 5-nitro-o-toluidine
Substance ID	R02-B-019-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	FY2008 FY2015
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	- -	-	-	There is a chemical group associated with explosive properties, a nitro group, present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN2660), and it does not correspond to explosives, hazards of the highest precedence, 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.
8	Self-reactive substances and mixtures	Type G	- -	-	-	There is a chemical group associated with explosive properties, a nitro group, present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN2660), and it is considered to be not applicable to self-reactive substances and mixtures, hazards of the highest precedence, it was classified in Type G.
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 classified in Division 6.1 in UNRTDG (UN2660), and it does not correspond to pyrophoric substances, hazards of the highest precedence.
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	Classification not possible	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine), which is chemically bonded to the element other than carbon or hydrogen (N). However, the classification is not possible due to no data.
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	- -	-	-	There is a chemical group associated with explosive properties, a nitro group, present in the molecule, but this substance was classified as "Not classified" for desensitized explosives because a pure substance does not correspond to any hazard class in explosives.

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). [Evidence Data] (1) LD50 for rats: 574 mg/kg (MAK (DFG) vol.21 (2005), AICIS IMAP (Access on April 2020), GESTIS (Access on April 2020), HSDB (Access on April 2020))
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 are descriptions in (1) - (4), but because there was no reliable information based on detailed evidence such as test results, it was classified as "Classification not possible." [Reference Data, etc.] (1) There are no studies on this substance, but consideration of the properties of related substances indicates that the substance penetrates the skin readily and that it probably has some irritant effects (MAK (DFG) vol.6 (1994)). (2) Limited information is available, but excessive exposure has been suggested to cause skin irritation (AICIS IMAP (Access on April 2020), NTP TR107 (1978)). (3) This substance may irritate the skin and cause dermatitis upon dermal contact (Patty (6th, 2012), HSDB (Access on April 2020)). (4) It is assumed that this substance can have a certain irritative effect on the eyes and skin (GESTIS (Access on April 2020)).
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] There are descriptions in (1), (2), but because there was no reliable information based on detailed evidence such as test results, it was classified as "Classification not possible." [Reference Data, etc.] (1) No data are available, but the structurally related substances were not eye irritants (AICIS IMAP (Access on April 2020)). (2) It is assumed that this substance can have a certain irritative effect on the eyes and skin (GESTIS (Access on April 2020)).
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.
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). The classification result was changed by examining the data carefully. [Evidence Data] (1) As for in vivo, it was reported to be negative in a micronucleus test in bone marrow cells of mice after oral administration (MAK (DFG) vol. 6 (1994)). (2) As for in vitro, it is reported that it was positive and negative in bacterial reverse mutation tests (IARC 48 (1990), ACGIH (7th, 2019), MAK (DFG) vol. 6 (1994)), positive in a chromosomal aberration test and a sister chromatid exchange test in cultured mammalian cells, and negative in a UDS test in cultured rat hepatocytes (MAK (DFG) vol. 6 (1994)). Furthermore, although the test method was not the standard one that could be used for classification, there are reports that it was positive and negative in transformation tests in mouse embryos (MAK (DFG) vol. 6 (1994)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] There is no information on carcinogenicity in humans. Among results in experimental animals in (2) and (3) and classification results by other organizations in (1), based on the most recent classification result by ACGIH, it was classified in Category 2. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in 3 by IARC (IARC 48 (1990)), A3 by ACGIH (ACGIH (7th, 2019)), Carc. 2 in EU CLP (EU CLP classification (Access on April 2020)), and 2 in MAK (DFG) (MAK (DFG) vol.21 (2005)). (2) As a result of 78-week diet administration of this substance to rats or mice followed by a 30-week (rats) or 20-week (mice) observation period and necropsy, in rats, only a trend toward an increase in hepatocellular carcinoma was seen in males at the high dose. However, in mice, there were dose-dependent increases in the incidences of hepatocellular carcinoma observed in both males and females (ACGIH (7th, 2019), NTP TR107 (1978), IARC 48 (1990)). (3) In a 24-week diet administration test with transgenic mice carrying the C-Ha-ras gene, dose-dependent malignant liver tumor induction was observed (ACGIH (7th, 2019)).
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	Category 1 (blood system, liver)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1 (blood system, liver). New information was added, and the classification result was changed from the previous classification. [Evidence Data] (1) There was a description that the major toxic effects of this substance in humans were methemoglobinemia with symptoms of bluish lips and fingernails, headache, nausea, and tiredness (NTP TR107 (1978)). (2) In death cases caused by liver failure (mainly fulminant) after oral ingestion of this substance as sweetener, high fever, nausea, vomiting, swollen liver, jaundice, and a tendency to bleeding were observed. Histopathological findings showed changes in the liver such as centrilobular necrosis and pseudo-bile duct formation. Thrombosis associated with endothelial cell injury was also found (AICIS IMAP (Access on April 2020)) (3) In animal studies, this substance caused acute toxicity, and methemoglobinemia, anemia, and central nervous system disorders (staggering, spasms, salivation, urinary incontinence) were observed (MAK (DFG) vol.6 (1993)). [Reference Data, etc.] (4) As a result of intraperitoneal administration of this substance at 100 to 500 mg/kg to cats, methemoglobin level became about 60% within 1 to 3 hours, resulting in death from hypoxia. Intraperitoneal administration at 1 mg/kg also resulted in methemoglobin level of 8% and damage to the erythrocytes (formation of Heinz bodies) (MAK (DFG) vol.6 (1993), GESTIS (Access on April 2020)). (5) As a result of intraperitoneal administration of this substance at 100 to 600 mg/kg to guinea pigs, distinct central nervous system disorders (spasm, salivation, urinary incontinence) were observed, and the animals died generally within 4 to 10 hours. Methemoglobin level was 14.5% (MAK (DFG) vol.6 (1993), GESTIS (Access on April 2020)). (6) There was a description that humans and cats were more sensitive to methemoglobin formation than rodents (AICIS IMAP (Access on April 2020)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1 (liver). [Evidence Data] (1) In the case of exposure in the working environment, 3 out of 15 workers were hospitalized with acute liver dysfunction, and 7 out of 15 workers showed liver dysfunction in blood tests. Histopathological findings from liver biopsies during the recovery period from treatment were similar to those of acute hepatitis (fatty changes, fibrosis, focal necrosis) (ACGIH (7th, 2019), HSDB (Access on April 2020)). (2) Liver dysfunction associated with occupational exposure (presumably via inhalation) to this substance was reported in several factory workers. The observed severity of the damage was dependent on the number and/or duration of exposures to this substance. It was reported that, in addition to liver damage, high fever, low back pain, fatigue, loss of appetite, dark urine, and upper abdominal discomfort were observed in the affected workers (AICIS IMAP (Access on April 2020)).
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	- -	-	-	Classification not possible due to lack of data. The classification result was changed from the previous classification by reviewing information.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	Classification not possible due to lack of data. The classification result was changed from the previous classification by reviewing information.
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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