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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	118-96-7
Chemical Name	2,4,6-Trinitrotoluene
Substance ID	R02-B-018-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 FY2013
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	Division 1.1	Danger	H201	P370+P372+P380+P373 P210 P230 P234 P240 P250 P280 P401 P501	There is a chemical group associated with explosive properties, a nitro group, present in the molecule, but because it is classified in Division 1.1D in UNRTDG (UN0209), it was classified in Division 1.1.
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	- -	-	-	It was classified as explosives, and the prescribed test was not conducted. Therefore, the classification is not possible due to no data.
8	Self-reactive substances and mixtures	Not classified	- -	-	-	It was classified as "Not classified" because it was classified as explosives.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Classification not possible	- -	-	-	It was classified as explosives, and the prescribed test was not conducted. Therefore, the classification is not possible due to no data.
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	- -	-	-	It was classified as "Not classified" because it was classified as explosives. Besides, one wetted with not less than 30% water, by mass, is classified in Division 4.1, PG I in UNRTDG (UN1356) and corresponds to desensitized explosives (impossible to assign Category due to no data).

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: 607 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), GESTIS (Access on April 2020)) (2) LD50 for rats: females: 794 mg/kg (ACGIH (7th, 2019)) (3) LD50 for rats: females: 795 mg/kg (ATSDR (1995), HSDB (Access on April 2020)) (4) LD50 for rats: females: 820 mg/kg (ATSDR (1995)) (5) LD50 for rats: males: 1,010 mg/kg (ATSDR (1995), HSDB (Access on April 2020)) (6) LD50 for rats: males: 1,320 mg/kg (ACGIH (7th, 2019), ATSDR (1995))
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	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] It was classified in Category 2 from (1) - (3). [Evidence Data] (1) Exposure to this substance may cause skin irritation in humans (ACGIH (7th, 2019), IARC 65 (1996)). (2) Exposure to this substance is well known to irritate the skin or eye (Patty (6th, 2012), HSDB (Access on April 2020)). (3) It was moderately irritating in a skin irritation test in which this substance (500 mg) was applied to rabbits for 24 hours (GESTIS (Access on April 2020)). [Reference Data, etc.] (4) It is reported that it was not irritating in a skin irritation test with rabbits (equivalent to OECD TG 404) in which 50% paste of this substance was applied (REACH registration dossier (Access on May 2020)). (6) Skin disease, hematopoietic disorder such as hemolytic anemia and aplastic anemia, or liver disease due to work involving exposure to trinitrotoluene was designated as simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare or disease designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act (Notification No. 33).
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] It was classified in Category 2 from (1). [Evidence Data] (1) Exposure to this substance is well known to irritate the skin or eye (Patty (6th, 2012), HSDB (Access on April 2020)). [Reference Data, etc.] (2) It is reported that it was not irritating in an eye irritation test with rabbits (equivalent to OECD TG 405) in which 50% paste of this substance was applied (REACH registration dossier (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	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1 from (1) - (4). [Evidence Data] (1) In humans, there are reports on dermatitis due to exposure to this substance (ACGIH (7th, 2019), MAK (DFG) (2014)). (2) In humans, prolonged exposure to this substance may cause an allergic skin reaction (ATSDR (1995)). (3) This substance has a sensitizing potential to the skin (GESTIS (Access on April 2020)). (4) It is reported that there was moderate sensitization (positive rate 40%) in a skin sensitization test with guinea pigs (equivalent to OECD TG 406, maximization test) on this substance (REACH registration dossier (Access on May 2020)). [Reference Data, etc.] (5) Skin disease, hematopoietic disorder such as hemolytic anemia and aplastic anemia, or liver disease due to work involving exposure to trinitrotoluene was designated as simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare or disease designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act (Notification No. 33).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) As for in vivo, it is reported that it was negative in a micronucleus test in mouse bone marrow cells, a chromosomal aberration test in rat bone marrow cells, and an unscheduled DNA synthesis test in rat hepatocytes (IARC 65 (1996), ATSDR (1995), IRIS (1989)). (2) As for in vitro, it is reported that it was positive and negative in bacterial reverse mutation tests (IARC 65 (1996), ATSDR (1995), IRIS (1989), ACGIH (7th, 2019), MAK (DFG) vol.1 (1991)) and positive in a gene mutation test in cultured mammalian cells (IARC 65 (1996), ACGIH (7th, 2019)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] As for classification results by other organizations in (1), as described in (4), IARC did not include the reports of carcinogenicity tests in rats and mice, which were used in assessments in MAK (DFG) and EPA (IRIS), in IARC's assessment, in which carcinogenicity was considered to be underestimated. From (1) - (3), because it was classified in Category 2 in MAK (DFG), and there was an apparently increased incidence of urinary bladder carcinoma (tumors whose spontaneous development is rare) observed in rats, it was classified in Category 1B. The classification result was changed. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in 3 by IARC (IARC 65 (1996)), C (possible human carcinogen) in IRIS (IRIS (1989)), and Category 2 in MAK (DFG) (MAK (DFG) (2014), classified in 2007). (2) In a carcinogenicity test by 2-year diet administration of this substance to rats, there was a significantly increased incidence for combined transitional cell papilloma and carcinoma of the urinary bladder in females (IRIS (1989), MAK (DFG) (2014)). (3) In a carcinogenicity test by 2-year diet administration of this substance to mice, the incidence of leukemia /malignant lymphoma in the spleen of females increased with dose and was significant at the highest dose (MAK (DFG) (2014)). However, it is described in IRIS that when all types of malignant lymphomas and lymphocytic leukemia were counted in all organs, the incidence of tumors was not statistically significantly elevated nor was there a significant trend, and these neoplasms were, therefore, not considered to be treatment-related (IRIS (1989)). (4) As for classification results by other organizations, the rationale for Category 2 in MAK (DFG) was that carcinogenicity was observed in two species of rats and mice, and it was mutagenic (bacteria, cultured mammalian cells) (MAK (DFG) (2014)). The rationale for C by EPA (IRIS) was that papilloma and carcinoma in the urinary bladder were found in female rats, and it was mutagenic (bacterial reverse mutation test) (IRIS (1989)). On the other hand, the reports of carcinogenicity tests in rats/mice, which were used in the assessments in MAK (DFG) and EPA (IRIS), were not included in data for carcinogenicity assessment by IARC (IARC 65 (1996)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] There was no information on reproductive toxicity. Based on (1) to (3), effects on the testes were observed, but there was no information about effects on fertility that were considered to be related to toxicity on the male reproductive organs. Therefore, it was classified as "Classification not possible" due to lack of data. Toxicity on the male reproductive organs alone was not adopted as a rationale for the classification. Therefore, the classification result was changed from the previous classification. [Evidence Data] (1) In a 13-week repeated dose toxicity study with rats dosed by feeding, degeneration of the epithelium of the seminiferous tubules, atrophy, etc. of the testes were reported (IARC 65 (1996), Environmental Risk Assessment for Chemical Substances Vol. 5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), OEL Documentations (Japan Society For Occupational Health (JSOH), 1993), ATSDR (1995)). (2) In a 13-week repeated dose toxicity study with rats dosed by feeding, atrophy of the testes, hyperplasia of interstitial cells, etc. were reported (IARC 65 (1996), Environmental Risk Assessment for Chemical Substances Vol. 5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ATSDR (1995)). (3) It was reported that in a 6-week repeated dose toxicity study with rats dosed by gavage, a decrease in serum zinc level and a decrease in testis weight were observed (Environmental Risk Assessment for Chemical Substances Vol. 5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ATSDR (1995)). [Reference Data, etc.] (4) There was a statement about effects on the testes observed in rats that, in view of the presence of Leydig cell hyperplasia, a hormonal mechanism for the degeneration in the testes (secondary as a result of liver enzyme induction) was suggested by the authors, but oxygen deficiency resulting from anemia was also conceivable as a secondary mechanism (MAK (DFG) (2014)). (5) There was a statement that damage to the testes observed in animal experiments was probably a consequence of an anoxic effects (GESTIS (Access on April 2020)). (6) It was reported that in a case-control study with male workers, decreases in semen volume and motile spermatozoa, and a higher incidence of sperm malformation were observed. It was stated, however, that confounding variables (other than smoking and drinking) were not considered, and important variables included simultaneous exposures to other chemicals and heat in the workplace (ATSDR (1995)).
8	Specific target organ toxicity - Single exposure	Category 1 (blood system), Category 3 (respiratory tract irritation)	Danger Warning	H370 H335	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1 (blood system) and Category 3 (respiratory tract irritation). As for the liver, which was regarded as the target organ in the previous classification, since it was unclear whether the observed effect was caused by single exposure, the liver was excluded from the target organs and the classification was changed from the previous classification. [Evidence Data] (1) After exposing humans to this substance, dermatitis, cyanosis, gastritis, acute liver damage (yellow atrophy), and aplastic anemia were reported (ACGIH (7th, 2019)). (2) A young boy poisoned by respiratory and percutaneous exposure showed a methemoglobin concentration of 43% on the day following the exposure (HSDB (Access on April 2020)). (3) Thirty eight workers in a production and loading plant for this substance (Concentration: 0.1 to 1.2 mg/m3, up to 10 mg/m3) were examined. As a result, the workers presented more complaints about respiratory symptoms (sneezing, sore throat, cough) and gastrointestinal symptoms (stomachache, anorexia, constipation, flatulence, nausea, vomiting) than the control groups. Furthermore, the average blood hemoglobin level in the workers was 85% (96% in control groups) (IARC 65 (1996)). [Reference Data, etc.] (4) Skin disorders, hematopoietic disorders such as hemolytic anemia and aplastic anemia, or liver disorders caused by trinitrotoluene have been designated as simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare, and as diseases designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act (Ministry of Labour Notification No. 33).
9	Specific target organ toxicity - Repeated exposure	Category 1 (eye, nervous system, cardiovascular system, blood system, hematopoietic system, liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 1 (eye, nervous system, cardiovascular system, blood system, hematopoietic system, liver). As a result of a review based on the new information source, the target organs were partially changed from the previous classification. [Evidence Data] (1) After exposing humans to this substance, dermatitis, cyanosis, gastritis, acute liver damage (yellow atrophy), and aplastic anemia were reported (ACGIH (7th, 2019)). (2) There was a statement that clinical symptoms in workers were mainly tiredness, paleness, and cyanosis resulting from methemoglobinemia, aplastic anemia, and changes in the blood picture (reduced and damaged erythrocytes, leukopenia, leukocytosis, lymphocytosis, fragmented cells, etc.). Other toxic effects were irritation of the respiratory tract, digestive tract, and skin; systemic effects on the digestive tract, liver and gallbladder, cardiovascular system; and nervous system, and formation of cataracts (MAK (DFG) (2014)). (3) It was reported that in 6 out of 12 workers occupationally exposed to this substance at 0.14 to 0.58 mg/m3 for 6.8 years, and in 7 out of 9 workers occupationally exposed at 0.10 to 0.35 mg/m3 for an average of 14 years, formation of cataracts was observed (ACGIH (7th, 2019)). (4) As a result of examining 413 workers for cataracts and other abnormalities, cataracts occurred in approximately 35% of them, and there was a positive correlation with the duration of exposure to this substance and the nature for the work. The most severe cataracts were found in workers involved in mixing and filling this substance, suggesting that percutaneous exposure was important (ACGIH (7th, 2019)). (5) In a 2-year oral toxicity test with rats dosed by feeding, bone-marrow fibrosis on the sternum was observed at or above 2 mg/kg/day (within the range for Category 1), dose-related anemia, increased methemoglobin and platelets, increased kidney weight, hypertrophy and pigmentation of the renal tubules, chronic nephropathy, hepatomegaly, and hyperplasia of hepatocytes with purpura and cyst degeneration were observed at or above 10 mg/kg/day (within the range for Category 1), and degeneration such as hyperplasia of the mucosal epithelium of the bladder, increased spleen weight, pigmentation, congestion of the sinusoid, and extramedullary hematopoiesis in the spleen, etc. were observed at 50 mg/kg/day (within the range for Category 2) (Environmental Risk Assessment for Chemical Substances Vol. 5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ATSDR (1995)). (6) Skin disorders, hematopoietic disorders such as hemolytic anemia and aplastic anemia, or liver disorders caused by trinitrotoluene have been designated simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare, and as diseases designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act (Ministry of Labour Notification No. 33). [Reference Data, etc.] (7) In a 13-week repeated dose toxicity study with rats dosed by feeding, at or above 125 mg/kg/day (exceeding Category 2), degeneration of the epithelium of the seminiferous tubules and atrophy of the testes were reported (IARC 65 (1996), Environmental Risk Assessment for Chemical Substances Vol. 5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), OEL Documentations (Japan Society For Occupational Health (JSOH), 1993), ATSDR (1995)). (8) In a 13-week repeated dose toxicity study with rats dosed by feeding, at 125 mg/kg/day (exceeding Category 2), atrophy of the testes, hyperplasia of interstitial cells, etc. were reported (IARC 65 (1996), Environmental Risk Assessment for Chemical Substances Vol. 5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ATSDR (1995)). (9) It was reported that in a 6-week repeated dose toxicity study with rats dosed by gavage, at 200 mg/kg/day (exceeding Category 2), a decrease in serum zinc level and a decrease in testis weight were observed (Environmental Risk Assessment for Chemical Substances Vol. 5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ATSDR (1995)).
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 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 72-hour ErC50 = 0.64 mg/L for algae (Raphidocelis subcapitata) (REACH registration dossier, 2020).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 72-hour NOEC = 0.10 mg/L for algae (Raphidocelis subcapitata) (REACH registration dossier, 2020). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 because it is not rapidly degradable (BIOWIN) and due to 96-hour LC50 = 2.58 mg/L for fish (Pimephales promelas) (HSDB, 2020). By drawing a comparison between the above results, it was classified in Category 1.
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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