GHS Classification Results by the Japanese Government
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 606-20-2 |
| Chemical Name | 2,6-Dinitrotoluene |
| Substance ID | R02-B-014-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 FY2016 |
| 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 |
| 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 2,4-DNT (CAS RN 121-14-2) (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. |
| 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. Information on dinitrotoluene 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) - (5). [Evidence Data] (1) LD50 for rats: 177 mg/kg (MAK (DFG) vol.6 (1994), Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011), GESTIS (Access on April 2020), HSDB (Access on April 2020)) (2) LD50 for rats: 180 mg/kg (ATSDR (2016)) (3) LD50 for rats: males: 180 mg/kg, females: 795 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)) (4) LD50 for rats: 180-795 mg/kg (AICIS IMAP (Access on April 2020)) (5) LD50 for rats: males: 535 mg/kg, females: 795 mg/kg (ATSDR (2016), MAK (DFG) vol.6 (1994)) |
| 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) | Category 2 |
Danger |
H330 | P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501 |
[Rationale for the Classification] It was classified in Category 2 from (1) - (5). Because exposure concentrations were higher than the saturated vapor pressure concentration (0.0056 mg/L), a reference value in the unit of mg/L was applied as dust. Wrong data were described in the rationale for the previous classification, and the classification result was changed from the previous classification. [Evidence Data] (1) LC50 for rats (4 hours): 360 mg/m3 (0.36 mg/L) (Chemical Substance Hazard Data 98-15 (2) (CERI, 1998)) (2) LC50 for rats (6 hours): males: 240 mg/m3 (converted 4-hour equivalent value: 0.36 mg/L), females: 660 mg/m3 (converted 4-hour equivalent value: 0.99 mg/L) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)) (3) LC50 for rats (6 hours): 240 mg/m3 (converted 4-hour equivalent value: 0.36 mg/L) (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011)) (4) LC50 for rats (6 hours): 430 mg/m3 (converted 4-hour equivalent value: 0.645 mg/L) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)) (5) Vapor pressure for this substance: 0.000567 mmHg (25 deg C) (HSDB (Access on April 2020)) (converted value for the saturated vapor pressure concentration: 0.0056 mg/L) |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | [Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) This substance was not 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) This substance (dose: unknown) was slightly irritating in a skin irritation test in which it was applied to rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ATSDR (2016)). (3) This substance is a skin irritant (HSDB (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-DNT or this substance (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)). |
| 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" because a positive rate was less than 30% in (1). The classification result was changed due to new data obtained. [Evidence Data] (1) A positive rate was reported to be 20% in a skin sensitization test with guinea pigs (10 animals, sex: unknown) (maximization test) on this substance (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), 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), (2). [Evidence Data] (1) As for in vivo, there are multiple reports that it was positive in unscheduled DNA synthesis tests with rat hepatocytes, DNA-binding tests with rats and mice (multiple organs), and comet assays with the hepatocytes or peripheral blood of rats (ATSDR (2016), IARC 9 (1975), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). And it was reported to be negative in chromosomal aberration tests and micronucleus tests with the peripheral blood or bone marrow cells of rats (ATSDR (2016)). (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 the cultured mammalian cells (same as above). And it was reported to be positive in a comet assay with rat Sertoli cells (ATSDR (2016)). [Reference Data, etc.] (3) 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 other 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. The results in experimental animals in (2), (3) suggested that this substance is a very potent carcinogen for the liver. It would be classified in Category 2 from the old classification result by IARC, but it was classified in Category 1B based on the results in experimental animals and the classification result in EU CLP. [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-) DNT (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 52-week diet administration of 2,4-DNT (CAS RN 121-14-2), this substance, or technical-grade dinitrotoluene (2,4-DNT 76%, this substance 18%) to male rats, for 2,4-DNT, only hepatic neoplastic nodules were seen in 1/20, but as for this substance, 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 this substance, and there was no metastasis to the lung. From these results, it was shown that this substance is carcinogenic, and most of the carcinogenic effects of technical-grade dinitrotoluene can be accounted for by those of this substance contained (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011), ACGIH (7th, 2001), ATSDR (2016)). (3) 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, this substance, 3,4-DNT, 3,5-DNT) or technical-grade dinitrotoluene, a weak initiation activity was found in this substance 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, this substance, or technical-grade dinitrotoluene (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%) 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 (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)), and the activity of this substance was about 10 times higher than that of 2,4-DNT. From these results, this substance was considered to be a complete hepatocarcinogen (Environmental Risk Assessment for Chemical Substances vol. 9 (Ministry of the Environment, 2011)). [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 2,4-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)). |
| 7 | Reproductive toxicity | Category 2 |
Warning |
H361 | P308+P313 P201 P202 P280 P405 P501 |
[Rationale for the Classification] There was no standard data on reproductive and developmental toxicity studies. However, based on (1) and (2), toxicity on the male reproductive organs was observed in rats, mice, or dogs, and based on (3), 2,4-dinitrotoluene (2,4-DNT, CAS RN 121-14-2), which was an isomer of this substance, had effects on fertility, which were considered to be related to toxicity on the male reproductive organs, and it was classified in Category 2. Therefore, this substance was also classified in Category 2. [Evidence Data] (1) In 13-week repeated dose toxicity studies with rats, mice, and dogs dosed by gavage, degeneration of the testes, lower spermatogenic ability, etc. were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011)). (2) For various DNT isomers (2,3-DNT, 2,4-DNT, 2,5-DNT, this substance, 3,4-DNT, 3,5-DNT), 14-day repeated dose toxicity studies using male rats were conducted. As a result, 2,4-DNT, this substance, 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 the administration of 2,4-DNT at 142 mg/kg/day, this substance 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 effects on the male reproductive organs (such as testicular and epididymal weight and histopathological effects) (ATSDR (2016)). (3) 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 year (FY2020). [Reference Data, etc.] (4) 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 2 (blood system), Category 3 (narcotic effects) |
 Warning |
H371 H336 |
P308+P311 P260 P264 P270 P405 P501 P304+P340 P403+P233 P261 P271 P312 |
[Rationale for the Classification] With respect to effects on humans of dinitrotoluenes, which are mixed isomers, this substance was considered to have partial effects and there was no report on humans available for this hazard class. Based on (1) and (2), it was classified in Category 2 (blood system) and Category 3 (narcotic effects). The information in the information sources was reviewed and the classification result was changed from the previous classification. [Evidence Data] (1) In an inhalation toxicity study with rats exposed to aerosol of this substance for 6 hours, at or above 0.196 mg/L (converted 4-hour equivalent value: 0.294 mg/L, within the range for Category 1), respiratory distress, ataxia, lethargy, and death were observed, and lung congestion and an increase in relative lung weight were observed in rats that died (ATSDR (2016), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)) (2) There was a statement that, in experimental animals, acute toxicity of this substance was higher than the toxicity of 2,4-DNT, and in tests with cats, formation of methemoglobin was less pronounced than in 2,4-DNT, whereas symptoms of a depressive effect to the central nervous system including the respiratory center were evident (GESTIS (Access on May 2020)). [Reference Data, etc.] (3) The general composition of dinitrotoluene is about 75% of 2,4-DNT and about 20% of this substance (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (4) 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)). (5) 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)). (6) It was reported that in an intraperitoneal administration test of this substance to rats, death and extensive centrilobular hemorrhagic necrosis in the liver were observed at or above 55 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (7) It was reported that in an intraperitoneal administration test of this substance to cats, neuropathy such as emesis, extension convulsions, rigidity of the hindlimbs, mydriasis, incontinence of feces/urine, and increases in methemoglobin levels and Heinz bodies formation were observed at or above 60 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (blood system, liver), Category 2 (nervous system, kidney, reproductive organs (male)) |
Danger Warning |
H372 H373 |
P260 P264 P270 P314 P501 |
[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1 (blood system, liver) and Category 2 (nervous system, kidney, reproductive organs (males)). [Evidence Data] (1) In a study with mice dosed with this substance by feeding for 13 weeks, a decrease in food consumption, reduced body weight gain, death, an increase in extramedullary hematopoiesis in the spleen, testicular atrophy, lower spermatogenic ability, and hyperplasia of the biliary epithelium were observed at or above 51 to 55 mg/kg/day (within the range for Category 2) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ATSDR (2016)). (2) In a study with rats dosed with this substance by feeding for 13 weeks, a decrease in food consumption, reduced body weight gain, an increase in ALT, methemoglobinemia, an increase in platelets, an increase in extramedullary hematopoiesis in the spleen, and testicular atrophy were observed at or above 35 to 37 mg/kg/day (within the range for Category 2) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ATSDR (2016)). (3) In a study with rats dosed with this substance by feeding for one year, reduced body weight gain and increases in liver weight and ALT were observed at or above 7 mg/kg/day (within the range for Category 1); an increase in gamma GT was observed at 14 mg/kg/day (within the range for Category 2); and hyperplasia of the biliary epithelium and hepatocellular degeneration and vacuolation were observed in almost all groups dosed at or above 7 mg/kg/day (within the range for Category 1) (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2011)). (4) In a study with dogs dosed with this substance by gavage for 13 weeks, an increase in extramedullary hematopoiesis in the spleen was observed at or above 4 mg/kg/day (within the range for Category 1); and anorexia, a decrease in body weight, rigidity, convulsions, paralysis, anemia, methemoglobinemia, an increase in platelets, a decrease in lymphocytes, an increase in ALP, increases in ALT and urea nitrogen, hyperplasia of the biliary epithelium, degeneration/inflammation of the liver, degeneration/inflammation of the kidney, and testicular atrophy were observed at or above 20 mg/kg/day (within the range for Category 2) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ATSDR (2016)) [Reference Data, etc.] (5) The general composition of dinitrotoluene is about 75% of 2,4-DNT and about 20% of this substance (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (6) 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)). (7) 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. |
| 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 96-hour LC50 = 5 mg/L for crustacea (Americamysis bahia) (Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2010)). |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Category 1 |
 Warning |
H410 | P273 P391 P501 |
It was classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 21-day NOEC = 0.06 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006), Environmental Risk Assessment for Chemical Substances Vol. 9 (Ministry of the Environment, 2010)). |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | This substance is not listed in the Annexes to the Montreal Protocol. |
NOTE:
|