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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	88-72-2
Chemical Name	2-Nitrotoluene
Substance ID	R02-B-010-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 FY2011
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 (UN1664), 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)	- -	-	-	Liquid (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)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified	- -	-	-	It was classified as "Not classified" from a flash point of 95 deg C (closed cup) (ICSC (2016)).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
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 (UN1664), 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	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from an autoignition temperature of 420 deg C (ICSC (2016)).
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because 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). It was classified as "Not classified."
13	Oxidizing liquids	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.
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). 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	- -	-	-	No data 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) - (7). [Evidence Data] (1) LD50 for rats: 890 mg/kg (EURAR (2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)) (2) LD50 for rats: 890-2,546 mg/kg (MAK (DFG) vol.8 (1997), AICIS IMAP (Access on April 2020)) (3) LD50 for rats: 891 mg/kg (EURAR (2008), NTP TR504 (2002), Environmental Risk Assessment for Chemical Substances vol. 6 (Ministry of the Environment, 2008)) (4) LD50 for rats: 1,610 mg/kg (EURAR (2008)) (5) LD50 for rats: 2,100 mg/kg (EURAR (2008)) (6) LD50 for rats: 2,546 mg/kg (EURAR (2008))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) LD50 for rats: 5,000 mg/kg (AICIS IMAP (Access on April 2020)) (2) LD50 for rats: > 5,000 mg/kg (EURAR (2008), MAK (DFG) vol.8 (1997)) (3) LD50 for rabbits: > 20,000 mg/kg (EURAR (2008)) [Reference Data, etc.] (4) LD50 for rabbits (one dose test): > 200 mg/kg (EURAR (2008))
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)	Classification not possible	- -	-	-	[Rationale for the Classification] The classification is not possible because the category cannot be determined from (1), (2). Besides, because exposure concentrations were higher than the saturated vapor pressure concentration (1.11 mg/L), the reference value in the unit of mg/L was applied as mist. [Evidence Data] (1) LC50 for rats (4 hours): > 1.795 mg/L (EURAR (2008)) (2) LC50 for rats (4 hours): > 320 ppm (1.795 mg/L) (AICIS IMAP (Access on April 2020)) (3) Vapor pressure of this substance: 0.02 kPa (20 deg C) (ICSC (2016)) (converted value for the saturated vapor pressure concentration: 1.11 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (4). [Evidence Data] (1) This substance was not irritating to the rabbit skin (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)). (2) It was reported to be not irritating in a skin irritation test by 4-hour semi-occlusive application of this substance (purity 99.2%, 0.5 mL) to rabbits. Other than this, it was reported to be not irritating in three skin irritation tests by 24-hour application to the rabbit skin (EURAR (2008), AICIS IMAP (Access on April 2020)). (3) This substance is not irritating to the skin and eye (MAK (DFG) vol.8 (1997), SIAP (1994), GESTIS (Access on April 2020)). (4) There was no irritation in a skin irritation test with rabbits (24-hour occlusive application) similar to OECD TG 404 (REACH registration dossier (Access on May 2020)) [Reference Data, etc.] (5) This substance irritates the skin, eye, and respiratory tract (HSDB (Access on April 2020)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] There is a description that it causes erythema and pain when entering the rabbit eye in (1), but its details could not be confirmed. Therefore, it was classified as "Not classified" by prioritizing experimental data. [Evidence Data] (1) This substance causes erythema and pain when entering the rabbit eye (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009), Environmental Risk Assessment for Chemical Substances vol. 6 (Ministry of the Environment, 2008)). (2) It was reported to be not irritating in an eye irritation test in which this substance (purity 99%, 0.1 mL) was applied to the rabbit eye. Other than this, it was reported to be not irritating in an eye irritation test in which this substance (purity: unknown, 0.1 mL) was applied to the rabbit eye (EURAR (2008), AICIS IMAP (Access on April 2020)). (3) This substance is not irritating to the skin and eye (MAK (DFG) vol.8 (1997), SIAP (1994), GESTIS (Access on April 2020)). (4) There was no irritation in an eye irritation test with rabbits similar to OECD TG 405 (REACH registration dossier (Access on May 2020)). [Reference Data, etc.] (5) This substance irritates the skin, eye, and respiratory tract (HSDB (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] There are descriptions in (1), (2), but it was classified as "Classification not possible" due to lack of data. [Reference Data, etc.] (1) There are no data on this substance, and it was estimated to pose no risk of sensitization by read-across approach from data on 4-nitrotoluene (CAS RN 99-99-0) (REACH registration dossier (Access on May 2020)). (2) There has been no sensitizing potential for this substance from long-term occupational practice (GESTIS (Access on April 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) - (3). New information was added, and the classification result was changed from the previous classification. [Evidence Data] (1) As for in vivo, it was reported to be negative in n unscheduled DNA synthesis test in rat spermatocytes (IARC 101 (2013)). Other than this, it is reported that it was positive and negative in unscheduled DNA synthesis tests with rodent hepatocytes and DNA adduct formation tests with hepatocytes, and negative in micronucleus tests with bone marrow and peripheral blood of rodents (NTP TR504 (2002), SIAP (1994), IARC 101 (2013), EURAR (2008), NTP RoC (14th, 2016)). (2) As for in vitro, there are many reports on negative results in bacterial reverse mutation tests. And it is reported that it was negative in a chromosomal aberration test in cultured mammalian cells, positive in a micronucleus test, and positive in a sister chromatid exchange test (same as above). (3) There are reports on the formation of hemoglobin adducts of this substance, chromosomal aberrations in the circulating blood lymphocytes, and mutagenic urine due to occupational exposure to nitrotoluenes, including this substance (same as above).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] It was classified in Category 1B from classification results by other organizations in (1) and results in experimental animals in (2), (3). [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in 2A by IARC (IARC 101 (2013)), Group 2A by the Japan Society for Occupational Health (JSOH) (OEL Documentations (Japan Society For Occupational Health (JSOH), 2018)), R by NTP (NTP RoC (14th, 2016)), Carc.1B in EU CLP (EU CLP classification (Access on April 2020)), and 2 by MAK (DFG) (DFG List of MAK and BAT Values 2019). (2) In a carcinogenicity test by 2-year diet administration of this substance to rats, there were significant increases in incidences of malignant mesothelioma, subcutaneous skin neoplasms, mammary gland fibroadenoma, and liver neoplasms in males and significant increases in incidences of subcutaneous skin neoplasms and mammary gland fibroadenoma in females, and it was concluded that there was clear evidence of carcinogenicity in male and female rats (NTP TR504 (2002)). (3) In a carcinogenicity test by 2-year diet administration of this substance to mice, there were significant increases in incidences of hemangiosarcoma and carcinoma of the large intestine (cecum) in males and females and hepatocellular neoplasms (adenoma and carcinoma) in females, and it was concluded that there was clear evidence of carcinogenicity in male and female mice (NTP TR504 (2002)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification was not possible due to lack of data. [Reference Data, etc.] (1) In a reproduction toxicity study with rats dosed by gavage (reproduction toxicity screening test), toxicity in parent animals (deaths of dams (3/12 animals), reduced body weight gain, a reduction in food consumption, increases in liver and kidney weight, decreases in the weight of the epididymis, seminal vesicle, prostate, and testis) was observed, fetal death as a secondary effect of maternal toxicity was observed, and delayed growth was observed in offspring at doses at which no toxicity in parent animals was observed. It was reported that the delayed growth was of unknown severity, and it was not known whether it could be used for classification or it was only a minor developmental change (EURAR (2008)). Since the severity of the delayed growth was unknown, it was used as reference data. (2) In a reproduction toxicity study with rats dosed by gavage at one dose, toxicity in parent animals (effects on the blood, spleen, and kidney) was observed, however, there was no difference in fertility between treated rats and untreated rats (AICIS IMAP (Access on April 2020), EURAR (2008), Environmental Risk Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008)). (3) In a 13-week toxicity study with rats dosed by feeding, degeneration of the testis with reduced sperm count and sperm motility in males, and prolongation of the estrus cycle in females were observed (AICIS IMAP (Access on April 2020), EURAR (2008), Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008)). (4) In a 13-week toxicity study with mice dosed by feeding, reduced sperm motility was observed in males (AICIS IMAP (Access on April 2020), EURAR (2008), Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008)). (5) In the EU CLP classification, it was classified as Repr.2. (6) The SIAP (1994) stated that no reproductive effects were observed in a preliminary reproduction toxicity screening test.
8	Specific target organ toxicity - Single exposure	Category 1 (blood system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1 (blood system). Information from a new information source was added, and the classification result was changed from the previous classification. [Evidence Data] (1) Exposure to this substance at 200 ppm for 60 minutes caused serious toxic symptoms, and there was a possibility that similar symptoms might occur even at 40 ppm if the exposure time was longer (EURAR (2008), Initial Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)). (2) The oral LD50 of test animals were 890-2,546 mg/kg in rats, 970-2,462 mg/kg in mice, and 1,750 mg/kg in rabbits, and clinical findings were related to methemoglobin formation (EURAR (2008)). [Reference Data, etc.] (3) Aromatic compounds containing nitrogen had methemoglobin formation effects (ACGIH (7th, 2001))
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver, blood system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2 (liver, blood system). [Evidence Data] (1) In a 105-week test with rats dosed by feeding, as non-neoplastic lesions, hematopoietic cell proliferation of the spleen, and hyperplasia of the alveolar epithelium in males and females, eosinophilic focus in the liver in males, and basophilic focus and clear cell focus in the liver, and hyperplasia of the mammary gland in females were observed at or above 625 ppm (males/females: 25/30 mg/kg/day, within the range for Category 2); mixed cell focus and mixed cell infiltration in the liver in males, and eosinophilic focus in the liver, and hyperplasia of the bone marrow in females were observed at or above 1,250 ppm (males/females: 50/60 mg/kg/day, within the range for Category 2); and clear cell focus in the liver in males and mixed cell focus in the liver, and hyperplasia of the mandibular lymph node in females were observed at 2,000 ppm (males/females: 90/100 mg/kg/day, within the range for Category 2) (NTP TR504 (2002), EURAR (2008)) [Reference Data, etc.] (2) It was reported that in a 13-week test with rats dosed by feeding, an increase in liver weight was observed at or above 625 ppm (males/females: 45/44 mg/kg/day, within the range for Category 2); hyaline droplet nephropathy in males were observed at or above 1,250 ppm (males/females: 89/87 mg/kg/day, within the range for Category 2); and changes in hematological parameters indicating hepatotoxicity, infiltration/vacuolation of the cells in the liver, pigmentation and extramedullary hematopoiesis in the spleen, and degeneration of the testis with reduced sperm count and sperm motility in males, and prolongation of the estrus cycle, etc. in females were observed at doses exceeding Category 2 (NTP TR23 (1992), ACGIH (7th, 2001), EURAR (2008)). (3) It was reported that in a 30-day test by oral administration of 332 mg/kg/day to rats (the purity of the test substance was unknown), sulfhemoglobinemia, and prolonged blood clotting time were observed, but the test was a non-GLP test that did not comply with the test guideline, and the EURAR considered it to be inadequate to determine a NOAEL (EURAR (2008)).
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)	Category 2	- -	H401	P273 P501	It was classified in Category 2 from 48-hour LC50 = 5.4 mg/L for crustacea (Daphnia magna) (EURAR, 2008).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	It was classified in Category 2 because it is not rapidly degradable (BIOWIN) and due to 21-day NOEC = 0.5 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 6 (Ministry of the Environment, 2008), EURAR, 2008).
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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