GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 95-80-7 |
| Chemical Name | 2,4-Toluenediamine [2,4-diaminotoluene] |
| Substance ID | H27-B-058/C-094B_P |
| Classification year (FY) | FY2015 |
| 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 | FY2014 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 (FY2013 revised edition (Ver. 1.1)) |
| 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 applicable |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. |
| 2 | Flammable gases (including chemically unstable gases) | Not applicable |
- |
- | - | Solid (GHS definition). |
| 3 | Aerosols | Not applicable |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Not applicable |
- |
- | - | Solid (GHS definition). |
| 5 | Gases under pressure | Not applicable |
- |
- | - | Solid (GHS definition). |
| 6 | Flammable liquids | Not applicable |
- |
- | - | Solid (GHS definition). |
| 7 | Flammable solids | Classification not possible |
- |
- | - | It is described in ICSC (2014) that it is combustible, but the classification is not possible due to no data. |
| 8 | Self-reactive substances and mixtures | Not applicable |
- |
- | - | There are no chemical groups present in the molecule associated with explosive or self-reactive properties. |
| 9 | Pyrophoric liquids | Not applicable |
- |
- | - | Solid (GHS definition). |
| 10 | Pyrophoric solids | Not classified |
- |
- | - | It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 520 deg C (GESTIS (Access on August 2015)). |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | 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 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). |
| 13 | Oxidizing liquids | Not applicable |
- |
- | - | Solid (GHS definition). |
| 14 | Oxidizing solids | Not applicable |
- |
- | - | Organic compounds containing no oxygen, fluorine or chlorine. |
| 15 | Organic peroxides | Not applicable |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule. |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | Test methods applicable to solid substances are not available. |
| 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 |
Based on reports of LD50 values for rats of 73 mg/kg, 136 mg/kg (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)), 179-212 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)), 230 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), DFGOT Vol. 6 (1993)), 270 mg/kg (EU-RAR (2008), DFGOT Vol. 6 (1993), EHC (1987)), 300 mg/kg (EHC (1987)), and 73-300 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), this substance was classified in Category 3. |
| 1 | Acute toxicity (Dermal) | Category 4 |
 Warning |
H312 | P302+P352 P362+P364 P280 P312 P321 P501 |
There are reports of an LD50 value for rats of 1,200 mg/kg (EU-RAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), DFGOT Vol. 6 (1993), EHC (1987)) and an LD50 value for rabbits of > 5,750 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). This substance corresponds to Category 4 according to the rat data and to "Not classified" according to the rabbit data. As a result of comparison with the categories based on either the rat or rabbit data, this substance was classified in Category 4 which is the category with higher hazard. The category was revised since the LD50 value for rabbits was changed due to an update of the information sources. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Not classified |
- |
- | - | Although there is no data for this substance itself, there are two reports that LC50 values for rats for an isomeric mixture of 80% of this substance and 20% of 2,6-diaminotoluene were >5.57 mg/L (EU-RAR (2008)) and > 0.916 mg/L (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). While the category cannot be specified in one case, the other case corresponds to "Not classified." Therefore, this substance was classified as "Not classified." This classification was determined by considering that the toxicity data of the isomeric mixture could be used for the evaluation of this substance (EU-RAR (2008)). Besides, since there is a description that vapor-dust mixtures were used for the test, and the test substance was a solid, the reference value for dusts was applied. New information obtained in this survey was added, and the classification was revised. |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - | It was reported that in a skin irritation test with rabbits (OECD TG 404), no irritation was observed by the application of this substance (EU-RAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). In addition, it is described with no specific details that this substance is irritating to the skin (Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). From the above, this substance was classified as "Not classified" (Category 3 in the UN GHS classification) based on the information of the test following the Test Guideline. |
| 3 | Serious eye damage/eye irritation | Category 2 |
Warning |
H319 | P305+P351+P338 P337+P313 P264 P280 |
It was reported that severe irritation was observed within 24 hours after the application of 100 microg of this substance to rabbit eyes (EHC (1987)). In addition, there are reports that as a result of the application of 100 mg of this substance in a Draize test with rabbits, slight conjunctival redness was observed but this resolved within 7 days (EU-RAR (2008)), and that irritation was not observed by the application of this substance in an eye irritation test with rabbits (OECD TG 405) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Furthermore, it is described that mild conjunctivitis was observed in another eye irritation test with rabbits (DFGOT Vol.6 (1994)). From the above, this substance was classified in Category 2. |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | 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 |
There are reports that sensitization was observed in a maximization test with guinea pigs (OECD TG 406) (EU-RAR (2008), DFGOT Vol.6 (1994), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), and that sensitization was observed in 35% of the tested animals in the other sensitization test with guinea pigs (EHC (1987)). From the above, this substance was classified in Category 1. Besides, this substance is classified as "Skin sens. 1 H317" in EU CLP Classification (ECHA CL Inventory (Access on September 2015)). |
| 5 | Germ cell mutagenicity | Category 2 |
 Warning |
H341 | P308+P313 P201 P202 P280 P405 P501 |
As for in vivo, the following items are reported: negative in a dominant lethal test with mice; for micronucleus tests, positive in a test with rat bone marrow cells and multiple negative results in tests with rat and mouse bone marrow cells and with mouse peripheral blood erythrocytes; negative in a chromosome aberration test with mouse bone marrow cells; positive in gene mutation tests with the liver of transgenic animals (Big Blue mice); negative in a sister chromatid exchange test with mouse bone marrow cells; positive in unscheduled DNA synthesis tests with rat liver; for comet assays with rats and mice, positive in assays with comet assays with the stomach, kidney, brain, and colon of rats and with the liver, kidney, stomach, and lung of mice; and positive in DNA adduct formation tests with the liver, kidney, and mammary gland of rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), EHC (1987), EU-RAR (2008), DFGOT Vol. 6 (1993), NTP DB (Access on October 2015)). As for in vitro, this substance showed positive and negative results in bacterial reverse mutation tests, positive and negative results in gene mutation tests with mammalian cultured cells and mouse lymphoma tests, and positive results in chromosome aberration tests and sister chromatid exchange tests with mammalian cultured cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), EHC (1987), EU-RAR (2008), DFGOT Vol. 6 (1993), NTP DB (Access on October 2015)). From the above, since this substance showed positive results in in-vivo somatic cell mutagenicity tests with mammals and in in-vivo germ cell genotoxicity tests with mammals, it was classified in Category 2. |
| 6 | Carcinogenicity | Category 1B |
Danger |
H350 | P308+P313 P201 P202 P280 P405 P501 |
There are no reports of epidemiological studies available for of the correlation between exposure specifically limited to this substance and human carcinogenicity (NTP RoC (13th, 2014)). As for experimental animals, a carcinogenicity study was conducted in which rats or mice were dosed by the oral route (by feeding) for two years. In the administration groups of rats, the doses were reduced in the middle of the study due to marked decreases in body weight, and the test was continued. The control and low-dose groups were sacrificed and dissected after 103 weeks, and the high-dose groups were sacrificed and dissected after 79-84 weeks, respectively. However, dose-dependent incidences of liver tumors (hepatocellular carcinomas or neoplastic nodules in the liver) were observed in both sexes of rats and mice. In addition, in the rats, mammary-gland tumors (carcinomas or fibroadenomas) were seen in females; in the mice, tumors in the lung and hematopoietic system were found in males (EU-RAR (2008), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). As for the dermal route, in a test in which 0.05 ml of 6% solution of this substance was applied at a frequency of once a week to the skin of mice for two years or more, there was no difference in the incidence of tumors in the local site of the skin between in the treated groups and in the control groups, but significant increases in the incidences of pulmonary adenomas and adenocarcinomas were seen in both sexes of the treated groups (EU-RAR (2008)). It is described that in another test in which rats were dosed subcutaneously, a subcutaneous formation of sarcomas was observed in all of nine survivors after eight months (IARC 16 (1978)). As for the classification results for carcinogenicity by other organizations, this substance was classified in "Group 2B" by the IARC in 1987 (IARC 16 Suppl. 7 (1987)), "R" by the NTP in 1981 (NTP RoC (13th, 2014)), "2B" by the Japan Society For Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (2015)), and "Carc. 1B" by the EU (EU-RAR (2008)). This substance would correspond to Category 2 if it were to be classified on the basis of the classification results by the organizations other than the EU. However, the EU clearly stated the rationale for the classification of "Carc. 1B" (Category 2 according to the EU DSD Classification at the time of classification) as the following. The EU regarded that this substance to be a genotoxic carcinogen, also considered that in in experimental animals, increased cell proliferation following liver cell necrosis is related to the mechanism of liver tumor induction in experimental animals, and thought that this mechanism of carcinogenesis is not limited to experimental animals and may also occur in humans (EU-RAR (2008)). From the above, although there were no human epidemiological findings available for the classification, this substance was classified in Category 1B for this hazard class in support of the statement of the EU on the rationale for the classification. |
| 7 | Reproductive toxicity | Category 2 |
Warning |
H361 | P308+P313 P201 P202 P280 P405 P501 |
In multiple epidemiological studies for male workers who were employed in several plants manufacturing diaminotoluenes in the United States, there is a report that increased incidences of dysfunctional spermatogenesis and increased rates of spontaneous abortions among their wives were observed. Meanwhile, there is an other report concluding that there were no differences in semen analysis and in miscarriage rates between the exposed groups and the control groups. However, none of these reports were deemed suitable for the evaluation of the reproductive effects of this substance, for reasons such as combined exposures including the exposures to the isomers or other chemical substances other than this substance; cohorts of limited size; and the possibility included bias because the study subjects were volunteers (EU-RAR (2008)). There are no other available data on the reproductive effects of this substance in humans. As for experimental animals, male rats were mated with untreated females after being dosed with this substance in the diet for 9 weeks (1,000 ppm, approx. 50 mg/kg/day). All males in the treated group failed to impregnate females, suggesting male sterility (EU-RAR (2008)). Even in a follow-up study, male rats were mated with untreated females after being dosed with this substance in the diet for 10 weeks (at 100 or 300 ppm (approx. 5 or 15 mg/kg/day)). In the 300 ppm group, reduced body weight gain and reduced food consumption were observed during the administration period, 5 out of 10 males were mated, but none succeeded in impregnating a female (at the time of observation of implantation traces on day 14 after mating). Also, in this group, statistically significant reductions in both of the following indices: the mating index (the ratio of sperm-detected females to mated females) and the fertility index (the ratio of pregnant females to sperm-detected females). Histopathological investigation revealed a reduction of spermatocyte formation in seminiferous tubules of the testes and a decreased sperm count in the cauda epididymis (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). Together with other relevant findings, the EU concluded that in experimental animals, this substance causes a reduction in male fertility which impairs the ability to impregnate females through the testicular toxicity of this substance, and that the LOAEL and NOAEL for male sterility are 15 mg/kg/day and 5 mg/kg/day, respectively, and classified this substance in Category 3 (equivalent to "Repr. 2" in the CLP classification) (EU-RAR (2008)). There is no other information on developmental toxicity including teratogenicity, which is available for the classification of this substance. From the above, based on the findings of male sterility in experimental animals, this substance was classified in Category 2 for this hazard class. |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (central nervous system, liver, haemal 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 |
This substance is irritating to the respiratory tract (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), EHC (1987)). In humans, via inhalational exposure it causes coughs, sore throats, headaches, dizziness, nausea, vomiting, confusion, convulsions, loss of consciousness, and cyanosis; via ingestion abdominal pain also occurring in addition to these. This substance also affects the liver and blood and causes liver damage and methemoglobin production (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), EHC (1987)). In experimental animals, it is reported that marked central nervous system depression such as labored breathing, sedation, hypoactivity, loss of coordination, increase in respiration rate, piloerection, ptosis, and tremors, diarrhea, polyuria, bleeding and inflammation in the gastro-intestinal tract, ascites, pulmonary hyperemia, pulmonary edema, discoloration of the liver, jaundice, cyanosis, and methemoglobin production were observed when rats and mice were dosed orally (at the dose corresponding to Category 1). In rats and mice exposed by inhalation (at the dose corresponding to Category 1), there are reports of labored breathing and methemoglobin production (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008), EHC (1987), EU-RAR (2008), DFGOT Vol. 6 (1993)). From the above, since this substance is not only irritating to the respiratory tract but also affects the central nervous system, liver, and haemal system, it was classified in Category 1 (central nervous system, liver, haemal system), Category 3 (respiratory tract irritation). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (immune system, liver, testis) |
Danger |
H372 | P260 P264 P270 P314 P501 |
In humans, in a study involving 59 workers at a plant manufacturing this substance in Russia, each 2-4 of them complained of symptoms of headaches, coughs, stomach ache, and chest pains respectively, but no other anomalies were reported (Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). Including this information, there was no other information available for the identification of the target organs. In experimental animals, in multiple studies in which male rats were dosed by feeding for 3-10 weeks, as testicular toxicity, increased relative testes weights, decreased epididymal sperm count, Sertoli cell degeneration, reduced serum testosterone, and increased serum LH were observed (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). These symptoms were mostly observed in the dose range for Category 1 (converted guidance value: 3.8-11.5 mg/kg/day). In addition, in multiple studies in which rats were dosed by feeding for 7-103 weeks and a 14-day study with mice dosed by gavage, effects on the liver (degeneration, necrosis, and fibrosis of hepatocytes, cirrhosis, bile duct hyperplasia, and elevated activities of liver-derived enzymes in the serum) were observed in the dose range for Category 1 or Category 2 (converted guidance value: 5.8-45 mg/kg/day) (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). Furthermore, in the 14-day test with mice dosed with this substance by gavage, at 25 mg/kg/day (converted guidance value: 3.9 mg/kg/day) or above, effects on the immune system were observed, which suggested suppression of humoral immunity and enhancement of cellular immunity, such as decreased macrophage phagocytic ability in the spleen, decreased ability to produce antibodies against sheep erythrocytes, decreased host resistance to bacteria, decreased NK activity, increases in the number of leucocytes and the proportion of lymphocytes, and delayed hypersensitivity response (EU RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)). Therefore, the immune system was also considered as a target organ. Increased leukocytes and marked atrophy of the spleen, which were observed at a dose of approximately 28 mg/kg/day in a 15-month feeding study with rats (EU RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.6 (Ministry of the Environment, 2008)), were considered to be the findings corroborating the effects of this substance on the immune system. From the above, based on the findings of adverse effects in experimental animals, it was classified in Category 1 (immune system, liver, testis) for this hazard class. Besides, it was judged in the current classification that the haemal system and spleen, which were adopted separately in the previous classification, should be combined into the "immune system." In addition, the kidneys were not included in the target organs in the current classification because no findings as subacute effects, based on which the kidney was adopted as the target organ, were found, even though there were findings of pyelitis and chronic kidney damage from long term administration tests with rats for 15 months or longer. |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | 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 (Acute) | Category 1 |
 Warning |
H400 | P273 P391 P501 |
From 96-hour LC50 = 0.2-0.4 mg/L for fish (Pagrus major) (EU-RAR, 2008), it was classified in Category 1. |
| 11 | Hazardous to the aquatic environment (Long-term) | Category 1 |
Warning |
H410 | P273 P391 P501 |
If chronic toxicity data are used, then it is classified in Category 2 due to being not rapidly degradable (a degradation rate by 14-day BOD = 0%, non-biodegradable (Official Bulletin of Ministry of International Trade and Industry, 1977)), and 21-day NOEC (reproduction) = 0.52 mg/L for crustacea (Daphnia magna) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2001), Environmental Risk Assessment for Chemical Substances vol. 6 (Ministry of the Environment, 2008), Initial Risk Assessment (NITE, CERI, NEDO, 2008)). 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 due to being not rapidly degradable and 96-hour LC50= 0.2-0.4 mg/L for fish (Pagrus major) (EU-RAR, 2008). By drawing a comparison between the above results, it was classified in Category 1. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
| * A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted. * Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement. Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file. * Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users. * This is a provisional English translation of classification results and is subject to revision without notice. * The responsibility for any resulting GHS labelling and SDS referenced from this site is with users. * Codes assigned to each of the hazard statements and codes for each of the precautionary statement are based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations. |