NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	121-14-2
Chemical Name	2,4-Dinitrotoluene
Substance ID	R02-B-012-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 FY2014
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 (UN3454), 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. Besides, there is information that it is combustible (ICSC (2005)).
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 (UN3454), 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 estimated that it does not ignite at normal temperatures from information that an autoignition temperature was about 400 deg C for a mixture with 2,6-DNT (CAS RN 606-20-2) (Hommel (1991)).
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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Please also refer to dinitrotoluene (isomer mixture) (CAS RN 25321-14-6) when the classification result for this substance is "Classification not possible" for health hazards. Described information is considered to be useful, although effects of each isomer on health hazards could not be identified in dinitrotoluene (isomer mixture).] [Rationale for the Classification] It was classified in Category 3 from (1) - (8). Besides, the category was changed from the previous classification by the use of new information sources. [Evidence Data] (1) LD50 for rats: 268 mg/kg (MAK (DFG) vol.6 (1994), Environmental Risk Assessment for Chemical Substances vol. 5 (Ministry of the Environment, 2006), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)) (2) LD50 for rats: 268-790 mg/kg (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)) (3) LD50 for rats: 270 mg/kg (ATSDR (2016), EURAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)) (4) LD50 for rats: 400 mg/kg (EURAR (2008), SIAR (2001), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)) (5) LD50 for rats: 474 mg/kg (EURAR (2008)) (6) LD50 for rats: males: 568 mg/kg, females: 650 mg/kg (EURAR (2008), ATSDR (2016), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), MAK (DFG) vol.6 (1994), AICIS IMAP (Access on April 2020), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)) (7) LD50 for rats: 893 mg/kg (EURAR (2008)) (8) LD50 for rats: 1,000 mg/kg (MAK (DFG) vol.6 (1994))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats: > 2,500 mg/kg (EURAR (2008), SIAR (2001))
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	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). Besides, the classification result was changed because there is no Category 3 in the current GHS classification guidance for the Japanese government. [Evidence Data] (1) This substance was slightly irritating in a skin irritation test with rabbits (Draize test) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009), MAK (DFG) vol.6 (1994), ACGIH (7th, 2001)). (2) Slight irritation was seen in a skin irritation test in which this substance (dose: unknown) was applied to rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ATSDR (2016)). (3) This substance did not irritate the rabbit skin and eye (GESTIS (Access on April 2020)). [Reference Data, etc.] (4) This substance (50%) was not irritating in a skin irritation test with rabbits according to a modified Draize procedure (EURAR (2008), AICIS IMAP (Access on April 2020)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) Any of six isomers of dinitrotoluene, including this substance, was not irritating to the rabbit eye in an eye irritation test with rabbits (Draize test) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009), MAK (DFG) vol.6 (1994), ACGIH (7th, 2001)). (2) No irritation was seen in an eye irritation test in which 2,4- or 2,6-DNT (concentration: unknown) was applied to the rabbit eye (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (3) This substance did not irritate the rabbit skin and eye (GESTIS (Access on April 2020)). [Reference Data, etc.] (4) This substance irritates the eye and skin, contact with the skin may produce erythema, and contact with the eye causes erythema (Environmental Risk Assessment for Chemical Substances vol. 5 (Ministry of the Environment, 2006)). (5) This substance (concentration: unknown) was reported to be not irritating to the rabbit eye, while there is a report that this substance was slightly irritating (ATSDR (2016)). (6) This substance (50%) was not irritating in an eye irritation test with rabbits (EURAR (2008), AICIS IMAP (Access on April 2020)). (7) This substance is a mucous membrane irritant in rabbits (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	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). The classification result was changed due to new data obtained. [Evidence Data] (1) This substance was reported to be negative in a skin sensitization test with guinea pigs (10 animals, sex: unknown) (maximization test) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ATSDR (2016), EURAR (2008), MAK (DFG) vol.6 (1994), GESTIS (Access on April 2020), AICIS IMAP (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). [Evidence Data] (1) As for in vivo, it is reported that it was negative in dominant lethal tests in rats and mice, positive and negative in chromosomal aberration tests with hepatocytes or peripheral blood of rats, positive and negative in micronucleus tests with mouse bone marrow, positive and negative in unscheduled DNA synthesis tests with rat hepatocytes, and positive in DNA-binding tests with rat liver and others. And it is reported that it was negative in chromosomal aberration tests with bone marrow or kidney of dogs, and negative in a comet assay with rat liver (ATSDR (2016), EURAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), Environmental Risk Assessment for Chemical Substances vol. 5 (Ministry of the Environment, 2006), IARC65 (1996)). Furthermore, it is reported that no abnormal sperm morphology was observed in rodents (Environmental Risk Assessment for Chemical Substances vol. 5 (Ministry of the Environment, 2006)). (2) As for in vitro, it is reported that it induced DNA break in rat germ cells (ATSDR (2016), Environmental Risk Assessment for Chemical Substances vol. 5 (Ministry of the Environment, 2006)). And there are many reports that it was positive or negative in bacterial reverse mutation tests. Positive and negative results were reported in gene mutation tests and sister chromatid exchange tests with the cultured mammalian cells (ATSDR (2016), EURAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), Environmental Risk Assessment for Chemical Substances vol. 5 (Ministry of the Environment, 2006), IARC65 (1996)). (3) As for occupational exposure, induction of chromosomal aberrations was reported in lymphocytes of humans exposed to a mixture containing this substance (ATSDR (2016), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), EURAR (2008)). [Reference Data, etc.] (4) It was classified in Muta. 2 in EU CLP classification (EU CLP classification (Access on April 2020)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] As for classification results by domestic and international organizations in (1), it was classified in 2B by IARC and Group 2B by the Japan Society for Occupational Health (JSOH), while it was classified in 1B in EU CLP. Because there was evidence for carcinogenicity in experimental animals of two species in (2), (3), it was classified in Category 1B. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in 2B by IARC (IARC 65 (1996)) and Carc. 1B in EU CLP (EU CLP classification (Access on April 2020)), and the Japan Society for Occupational Health (JSOH) classified 2,4- (or 2,6-) dinitrotoluene (CAS RN 121-14-2) in Group 2B (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH)) (proposed in 1998)). And EPA classified a mixture of 2,4-/2,6-dinitrotoluene in B2 (probable human carcinogen) (IRIS (1990)). (2) In a test by 24-month diet administration of this substance to male and female mice, induction of adenoma or carcinoma in the kidney was observed in males (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)). (3) In a test by 24-month diet administration of this substance to male and female rats, there were increased incidences of hepatocellular carcinoma and mammary gland fibroadenoma in females and an increased incidence of skin fibroma in males (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009)). [Reference Data, etc.] (4) In humans, there is a report that an increased risk for cancer of the liver and gallbladder was found among workers exposed to a mixture of this substance and 2,6-DNT in a cohort study of workers in the United States, while there is a report that no such increase was detected. Due to inconsistent results, IARC concluded that there was inadequate evidence in humans for the carcinogenicity of dinitrotoluenes, including this substance (IARC 65 (1996)). (5) In a test to investigate the presence or absence of a promotion activity of dinitrotoluene in which male rats were given single intraperitoneal administration of N-nitrosodiethylamine followed by administration of this substance, 2,6-DNT, or an isomer mixture (2,3-DNT 1.5%, this substance 76.5%, 2,5-DNT 0.7%, 2,6-DNT 18.8%, 3,4-DNT 2.4%, 3,5-DNT 0.1%), which started 2 weeks after the initiation, and gamma-GTP positive foci in the liver were used as a marker, a promotion activity was found in all the substances, and the activity of 2,6-DNT was about 10 times higher than that of this substance (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009), Environmental Risk Assessment for Chemical Substances vol. 5 (Ministry of the Environment, 2006)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (6), effects on fertility, which were considered to be related to toxicity on the male reproductive organs, were observed at doses where toxicity effects were observed in parental animals. Therefore, it was classified in Category 2. [Evidence Data] (1) In a three-generation reproduction toxicity study with rats dosed by feeding, at a dose at which toxicity effects in parental animals (F0 and F1 parental animals: a decrease in body weight) were observed, a reduction in fertility index and reduced mean litter size in F1 parental animals and lower viability index in F1 neonates were observed (EURAR (2008), Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)). (2) In a breeding test with male rats after dosed by gavage and untreated female rats, at doses at which toxicity effects (cyanosis) in male parental animals were observed, a decrease in mating index and an increase in preimplantation embryo resorption were observed (EURAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (3) In a three-week oral toxicity test with male rats dosed by feeding, a decrease in sperm concentration, an increase in serum hormone levels (LH, FSH), morphological changes in the testes (such as degenerative changes in spermatocytes and spermatids and vacuolation of Sertoli cells) were observed (EURAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (4) In a 14-day oral toxicity test with male and female rats dosed by feeding, a decrease in the thickness of spermatogenic cell layers and a decrease in sperm count were observed in males and no effects on the female reproductive organs was observed (EURAR (2008)). (5) For various dinitrotoluene (DNT) isomers (2,3-DNT, this substance, 2,5-DNT, 2,6-DNT, 3,4-DNT, 3,5-DNT), 14-day repeated dose toxicity studies using male rats were conducted. As a result, this substance, 2,6-DNT, and 3,5-DNT had effects on the male reproductive organs (such as testicular atrophy, a decrease in testicular weight, degeneration of the seminiferous tubules, and formation of multinucleated giant cells in the testes). Similar effects were observed after administration of this substance at 142 mg/kg/day, 2,6-DNT at 68 mg/kg/day and 3,5-DNT at 19 mg/kg/day. On the other hand, 2,3-DNT, 2,5-DNT, and 3,4-DNT had no effect on the male reproductive organs (such as testicular and epididymal weight and histopathological effects) (ATSDR (2016)). (6) In 13-week oral toxicity tests with male rats, male mice and male dogs, a reduction in sperm production was observed in all the species, and testicular atrophy was further observed in rats (EURAR (2008)). [Reference Data, etc.] (7) In the EU CLP classification, it was classified as Repr.2 (Classification in EU CLP (Access on April 2020)).
8	Specific target organ toxicity - Single exposure	Category 1 (blood system), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] Based on (1) to (3), the data of dinitrotoluene (mixed isomers) was applied for the classification for this hazard class and this substance was classified in Category 1 (blood system) and Category 3 (narcotic effects). Based on the reference to the data of the mixed isomers, the classification result was changed from the previous classification. [Evidence Data] (1) The general composition of dinitrotoluene is about 75% of this substance and about 20% of 2,6-DNT (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (2) There was a statement about dinitrotoluene that acute intoxication in humans was caused by formation of methemoglobin, which produced cyanosis, headache, irritability, dizziness, weakness, nausea, vomiting, dyspnea, drowsiness, unconsciousness, and possible death (ACGIH (7th, 2001)). (3) There was a statement about dinitrotoluene that acute intoxication in experimental animals included central nervous system depression, respiratory depression, muscular incoordination, and cyanosis (ACGIH (7th, 2001)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, blood system, liver), Category 2 (kidney, reproductive organs (male))	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1 (nervous system, blood system, liver) and Category 2 (kidney, reproductive organs (males)). Classification was also conducted by adding new information and the classification result was changed from the previous classification. [Evidence Data] (1) In a study with rats dosed with this substance by feeding for 13 weeks, at 93 mg/kg/day (within the range for Category 2), demyelinization in the cerebellum and brain stem, abnormal gait, reticulocytosis, hemosiderosis, and a significant reduction in spermatogenesis were observed in males; at 108 mg/kg/day (exceeding Category 2), reticulocytosis and hemosiderosis were observed in females; at 145 mg/kg/day (exceeding Category 2), demyelinization in the cerebellum and brain stem, abnormal gait, and anemia were observed in females; and at 266 mg/kg/day (exceeding Category 2), anemia was observed in males (ATSDR (2016)). (2) In a study with rats dosed with this substance by feeding for 52 weeks, hepatocellular degeneration and vacuolation, and acidophilic and basophilic foci of altered hepatocytes were observed in males at 27 mg/kg/day (within the range for Category 2) (ATSDR (2016)). (3) In a study with mice dosed with this substance by feeding for 24 months, hepatocellular dysplasia, cystic dysplasia in the kidney, nephropathy, a decrease and degenerative changes in spermatogenesis, and testicular atrophy were observed in males at 14 mg/kg/day (within the range for Category 2) (ATSDR (2016)). (4) In a 9-month oral toxicity study with dogs, at 1.5 mg/kg/day (within the range for Category 1), an increase in methemoglobin levels was observed in females; and at 10 mg/kg/day (within the range for Category 1), increases in Heinz bodies and methemoglobin levels in males, and decreases in red blood cell count, hemoglobin, and hematocrit and increases in reticulocytes and Heinz bodies in females were observed (ATSDR (2016)). (5) In a 24-month oral toxicity study with dogs, loss of hindquarter control, convulsions and methemoglobinemia were observed at 1.5 mg/kg/day (within the range for Category 1), and biliary hyperplasia was observed at 10 mg/kg/day (within the range for Category 1) (ATSDR (2016)). [Reference Data, etc.] (6) The general composition of dinitrotoluene is about 75% of this substance and about 20% of 2,6-DNT (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (7) Results of occupational exposure studies and studies in laboratory animals identified the blood system (methemoglobinemia, anemia, and compensatory hematopoiesis) and nervous systems (clinical signs of neurotoxicity, ataxia, tremors, leg weakness, and convulsions) as the most sensitive targets of dinitrotoluene-induced toxicity. In animal studies, effects on the liver, respiratory tract, and reproductive organs at high doses were also found (ATSDR (2016)). (8) Available human data provided only limited evidence, as studies did not include appropriate control groups and exposure concentrations were not reported (ATSDR (2016)).
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 4-day IC50 = 0.49 mg/L for algae (Microcystis aeruginosa) (EURAR, 2008).
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 21-day NOEC = 0.04 mg/L for crustacea (Daphnia magna) (SIAR, 1996). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 4-day IC50 = 0.49 mg/L for algae (Microcystis aeruginosa) (EURAR, 2008). From 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.

To GHS Information