NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	25321-14-6
Chemical Name	Dinitrotoluene (Mixed isomers)
Substance ID	R02-B-017-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	- -	-	-	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 an autoignition temperature of 400 deg C (ICSC (2005)).
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	[Rationale for the Classification] It was classified in Category 3 from (1), (2). Besides, the classification result was changed from the previous classification by the use of new information sources. [Evidence Data] (1) LD50 for rats: 268-660 mg/kg (SIAR (2005)) (2) LD50 for rats: 1,000 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005))
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	Not classified	- -	-	-	[Rationale for the Classification] There are no data on this substance, but it was classified as "Not classified" from information on various dinitrotoluene (DNT) isomers, the constituents of this substance, in (1) - (3). [Evidence Data] (1) In a skin irritation test with rabbits (Draize test) on various DNT isomers, the constituents of this substance, there was moderate irritation for 2,5-DNT and slight irritation for 2,3-DNT and 3,4-DNT, and no irritation was seen for 2,4-DNT, 2,6-DNT, and 3,5-DNT (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009), MAK (DFG) vol.6 (1994), ACGIH (7th, 2001), GESTIS (Access on April 2020)). (2) Slight irritation was found in a skin irritation test in which 2,4-DNT or 2,6-DNT (dose: unknown) was applied to rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (3) 2,4-DNT and 2,6-DNT were slightly irritating to the rabbit skin (ATSDR (2016)). [Reference Data, etc.] (4) This substance was not irritating in a test by occlusive application to the interior side of the ear in rabbits (SIAR (2005), 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) and information on various dinitrotoluene (DNT) isomers, the constituents of this substance, in (2). [Evidence Data] (1) This substance was very slightly irritating in an eye irritation test with rabbits (non-TG test), and the effect was reversible within 7 days (SIAR (2005), AICIS IMAP (Access on April 2020)). (2) Any of six DNT isomers, the constituents of 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), AICIS IMAP (Access on April 2020), 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	Not classified	- -	-	-	[Rationale for the Classification] There are no data on this substance, but it was classified as "Not classified" from information on various dinitrotoluene (DNT) isomers, the constituents of this substance, in (1), (2). The classification result was changed due to new data obtained. [Evidence Data] (1) In a skin sensitization test with guinea pigs (10 animals, sex: unknown) (maximization test) on various DNT isomers, the constituents of this substance, 2/10 animals showed positive reactions for 2,6-DNT, but other isomers were all negative (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ATSDR (2016), MAK (DFG) vol.6 (1994), AICIS IMAP (Access on April 2020), GESTIS (Access on April 2020)). (2) Because 2,4-DNT, the primary constituent of this substance, was negative in a skin sensitization test with guinea pigs (maximization test), and 2,6-DNT, the secondary constituent, produced mild sensitization, the human sensitizing potential of this substance was considered to be low (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). 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 a dominant lethal test in mice (SIAR (2005)). And it is reported that it was negative a micronucleus test with mouse bone marrow cells, and a mouse spot test, weakly positive in a sister chromatid exchange test with rat lymphocytes, and positive in an unscheduled DNA synthesis test with rat liver (SIAR (2005)) (2) As for in vitro, it is reported that it was positive and negative in bacterial reverse mutation tests and negative in a gene mutation test with cultured mammalian cells (SIAR (2005)). (3) Both 2,4-DNT (CAS RN 121-14-2, about 80%) and 2,6-DNT (CAS RN 606-20-2, about 20%), the major constituents of this substance, were classified in Category 2 for this hazard class (GHS classification results in FY2020). [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] In humans, no information showed a clear relationship between exposure to dinitrotoluene and its carcinogenicity. It was classified in Category 1B from the classification result in EU CLP in (1) and the classification result for 2,6-DNT, the constituent of this substance, in (2) and (3). [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in A3 by ACGIH (ACGIH (7th, 2001)), 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) 2,4-DNT and 2,6-DNT, the major constituents of this substance, were classified in Category 2 and Category 1B, respectively, for this hazard class (GHS classification results in FY2020). (3) In a test by 52-week diet administration of 2,4-DNT (CAS RN 121-14-2), 2,6-DNT (CAS RN 606-20-2), or technical-grade dinitrotoluene (2,4-DNT 76%, 2,6-DNT 18%) to male rats, for 2,4-DNT, only hepatic neoplastic nodules were seen in 1/20, but as for 2,6-DNT, there were liver tumors metastasized to the lung and cholangiocarcinoma in addition to dose-dependent increases in incidences of hepatocellular carcinoma or hepatic neoplastic nodules (IARC 65 (1996), Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011)). On the other hand, as for technical-grade dinitrotoluene, hepatic neoplastic nodules, hepatocellular carcinoma, and cholangiocarcinoma were observed, but their incidences were lower than those for 2,6-DNT, and there was no metastasis to the lung. From these results, it was shown that 2,6-DNT is carcinogenic, and most of the carcinogenic effects of technical-grade dinitrotoluene can be accounted for by those of 2,6-DNT contained (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011), ACGIH (7th, 2001), ATSDR (2016)). [Reference Data, etc.] (4) In an initiation-promotion test in which gamma-GTP positive foci in the liver were used as a marker, and rats were administered each isomer of dinitrotoluene (2,3-DNT, 2,4-DNT, 2,5-DNT, 2,6-DNT, 3,4-DNT, 3,5-DNT), or technical-grade dinitrotoluene, a weak initiation activity was found in 2,6-DNT and technical-grade dinitrotoluene, but no initiation activity was seen in other isomers (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). And 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 diet administration of 2,4-DNT, 2,6-DNT, or technical-grade dinitrotoluene that 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 2,4-DNT (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) where toxicity on the male reproductive organs was observed, and based on (2) and (3), this substance, which was a mixture, was also classified in Category 2. [Evidence Data] (1) In a 104-week study with rats dosed by feeding with this substance (dinitrotoluene (DNT), mixture of isomers) (composition of isomers: 2,3-DNT 1.54%, 2,4-DNT 76.49%, 2,5-DNT 0.65%, 2,6-DNT 18.83%, 3,4-DNT 2.43%, 3,5-DNT 0.040%), effects on the blood and liver as well as effects on the male reproductive organs (testicular atrophy, a decrease in testicular weight, degeneration of the testes, reduced spermatogenesis) were observed (Environmental Risk Assessment for Chemical Substances for 2,4-DNT Vol. 5 (Ministry of the Environment, 2006)). (2) 2,4-DNT had effects on fertility which were considered to be related to toxicity on the male reproductive organs at doses at which toxicity effects were observed in parental animals. Therefore, the substance was classified in Category 2 in the classification in the current fiscal year (FY2020). (3) In 2,6-DNT and 3,5-DNT, toxicity on the male reproductive organs was observed, and in 2,4-DNT which was an isomer, effects on fertility, which were considered to be related to toxicity on the male reproductive organs, were observed. Based on these findings, these substances were classified in Category 2 in the classification in the current fiscal year (FY2020). [Reference Data, etc.] (4) In a developmental toxicity study with female rats dosed by gavage on days 7 to 20 of gestation, at a dose at which toxicity (mortality of 46%) was observed in dams, an increasing tendency in resorption was observed (Environmental Risk Assessment for Chemical Substances for 2,4-DNT Vol. 5 (Ministry of the Environment, 2006)). As for these studies, several assessment reports (such as SIAR (2005), Environmental Risk Assessment for Chemical Substances for 2,4-DNT Vol. 5 (Ministry of the Environment, 2006), and MAK (DFG) vol.6 (1994)) indicated that, although toxicity was observed in dams, there was no effect on embryos and fetuses. Also, this data was the basis for the previous classification, however, it was not adopted as the basis for classification because of the high mortality of 46% observed in dams. (5) For various DNT isomers (2,3-DNT, 2,4-DNT, 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, it was found that 2,4-DNT, 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 multinucleated giant cell formation in the testis). On the other hand, 2,3-DNT, 2,5-DNT, and 3,4-DNT had no effects on the male reproductive organs (such as testicular and epididymal weights and histopathological effects) (ATSDR (2016)). (6) 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) and (2), it was classified in Category 1 (blood system) and Category 3 (narcotic effects). [Evidence Data] (1) There was a statement about dinitrotoluene that acute intoxication in humans was caused by production of methemoglobin, which produced cyanosis, headache, irritability, dizziness, weakness, nausea, vomiting, dyspnea, drowsiness, unconsciousness, and possible death (ACGIH (7th, 2001)). (2) 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)). [Reference Data, etc.] (3) The general composition of dinitrotoluene is about 75% of 2,4-DNT and about 20% of 2,6-DNT (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, blood system, liver), Category 2 (reproductive organs (male))	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1 (nervous system, blood system, liver) and Category 2 (reproductive organs (males)). Of the basis for the previous classification, information on humans was considered to be a limited basis and it was not adopted. Also, in the previous classification, based on the information on rats in (3), the kidney and adrenal gland were identified as target organs. However, as for the effects on the kidneys, the possibility of age-related changes was considered, and as for the effects on the adrenal glands, dose-dependency was not identified. Therefore, these findings were considered to be insufficient as the basis for classification and the kidneys and adrenal glands were not adopted as target organs. Accordingly, the classification result was changed from the previous classification. [Evidence Data] (1) The general composition of dinitrotoluene is about 75% of 2,4-DNT and about 20% of 2,6-DNT (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (2) 2,4-DNT which was composed of about 75% of dinitrotoluene was classified in Category 1 (nervous system, blood system, liver) and Category 2 (reproductive organs (male)) (GHS Classification Results in FY2020). (3) In a 104-week study with rats dosed by feeding with this substance (2,4-DNT (76.5%), 2,6-DNT (18.8%), 3,4-DNT (2.4%), 2,3-DNT (1.5%), 2,5-DNT (0.7%), 3,5-DNT (0.7%)), at or above 3.5 mg/kg/day (within the range for Category 1), an increase in absolute liver weight was observed in males and females, and altered hepatocellular foci and hepatocellular basophilia, hypertrophy, vacuolation, and necrosis were observed in males; at or above 14 mg/kg/day (within the range for Category 2), degeneration of the adrenal gland (only at 14 mg/kg/day) was observed in males and females (ATSDR (2016) described that no histopathologic effects on the adrenal gland were observed); at 14 mg/kg/day (within the range for Category 2), increases in reticulocyte count and leukocyte count, and decreases in red blood cell count and hematocrit and hemoglobin levels were observed in males; and at 35 mg/kg/day (within the range for Category 2), exacerbation of chronic interstitial nephritis, an increase in interstitial pigments in the pancreas, extramedullary hematopoiesis, degeneration of the testes, and a reduction in spermatogenesis in males, and increases in reticulocyte count and leukocyte count, and decreases in red blood count and hematocrit and hemoglobin levels in females were observed (ATSDR (2016), SIAR (2005), ACGIH (7th, 2001)). [Reference Data, etc.] (4) 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)). (5) 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 96-hour ErC50 = 0.9 mg/L for algae (Chlorella pyrenoidosa) (SIAP, 2004, SIAR, 2005). The classification result was changed from the previous classification by using new information.
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 1 because it is not rapidly degradable (not readily degradable, a degradation rate by BOD: 0% (isomer ratio: 2,4-form 82.1%, 2,6-form 17.9%) (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1975)), and it was classified in Category 1 in acute toxicity. The classification result was changed from the previous classification by using new 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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