GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 584-84-9 |
| Chemical Name | 2,4-Tolylene diisocyanate [2,4-Toluene diisocyanate] |
| Substance ID | H29-B-049 |
| Classification year (FY) | FY2017 |
| 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 (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) | |
| 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 classified |
- |
- | - | It is a solid according to GHS definition, but melting point is around 21 deg C, and a flash point is 127 deg C (closed cup) (GESTIS (Access on June 2017)). |
| 7 | Flammable solids | Classification not possible |
- |
- | - | No data available. |
| 8 | Self-reactive substances and mixtures | Type G |
- |
- | - | There is a chemical group associated with self-reactive properties (oxidized cyanides) in the molecule, but because it is classified in Division 6.1, PGII in UNRTDG (UN 2078), it is estimated that it does not correspond to self-reactive substances and mixtures, hazard class with the highest precedence. |
| 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 620 deg C (GESTIS (Access on June 2017)). |
| 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 |
- |
- | - | The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. |
| 15 | Organic peroxides | Not applicable |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | It is a substance with a melting point of 55 deg C or lower, but the classification is not possible due to no data. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not classified |
- |
- | - |
Based on the report that an LD50 value was 5,800 mg/kg (ACGIH (7th, 2004), PATTY (6th, 2012), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) for rats, this substance was classified as "Not classified." Besides, commercial-grade m-tolylene diisocyanate (TDI) is a mixture of this substance and the isomer 2,6-tolylene diisocyanate (2,6-TDI, CAS RN: 91-08-7) (generally, the mixing ratio of this substance and the 2,6-isomer is 80:20), and there is a description that no significant toxicological difference is observed between the 2,4-isomer and the 2,6-isomer (ACGIH (7th, 2004)). |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | Based on LD50 values of 10,000 mg/kg and > 16,000 mg/kg for rabbits (both Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), DFGOT vol. 20 (2003)), this substance was classified as "Not classified." |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | This substance is solid in the GHS definition. Since the melting point is 20.5 deg C (HSDB (Access on June 2017)), it is considered to be liquid at temperature higher than that. |
| 1 | Acute toxicity (Inhalation: Vapours) | Category 1 |
 Danger |
H330 |
P304+P340
P403+P233 P260 P271 P284 P310 P320 P405 P501 |
It is solid in the GHS definition, however, the melting point is 20.5 deg C (HSDB (Access on June 2017)), so it is considered to be liquid at temperature higher than that. There is no information on an LC50 value of this substance alone, however, for the commercial-grade TDI which is a mixture of this substance and 2,6-TDI (hereinafter refer to as TDI. Generally, the mixing ratio of 2,4-TDI and 2,6-TDI is 80:20), it is reported that LC50 values in a 4-hour inhalation test are 13.9-49.8 ppm (0.1-0.36 mg/L) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) for rats. Because there is a description that no significant toxicological difference is observed between 2,4-isomer and 2,6-isomer (ACGIH (7th, 2004)), it is considered possible to use the information of TDI for classification of this substance. When a reference value in the unit of ppm is applied as vapour with little mist since the minimum value of 13.9 ppm is lower than 90% of the saturated vapor pressure level (26.4 ppm) of TDI, this substance corresponds to Category 1. Therefore, it was classified in Category 1. |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Category 2 |
Danger |
H330 |
P304+P340
P403+P233 P260 P271 P284 P310 P320 P405 P501 |
It is solid in the GHS definition, however, the melting point is 20.5 deg C (HSDB (Access on June 2017)), so it is considered to be liquid at temperature higher than that. There is no information on an LC50 value of this substance alone, however, LC50 values of the commercial-grade TDI which is a mixture of this substance and 2,6-TDI (hereinafter refer to as TDI. Generally, the mixing ratio of 2,4-TDI and 2,6-TDI is 80:20) is reported as 13.9-49.8 ppm (0.1-0.36 mg/L) in a 4-hour inhalation test with rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Because there is a description that no significant toxicological difference is observed between the 2,4-isomer and 2,6-isomer (ACGIH (7th, 2004)), it is considered possible to use the information of TDI for classification of this substance. When a reference value in the unit of mg/L is applied since the maximum value of 49.8 ppm (0.36 mg/L) is higher than the saturated vapor pressure concentration (26.4 ppm) of TDI, this substance corresponds to Category 2. Therefore, it was classified in Category 2. Besides, the report of the LC50 value of 600 ppm (converted 4-hour equivalent value: 734.8 ppm, 5.23 mg/L) in a 6-hour inhalation test with rats (PATTY (6th, 2012)) used in the previous classification is from the RTECS, which is an information source listed in List 3, and the detail is unknown, so it was not adopted. Thus, the classification result changed from the previous classification. |
| 2 | Skin corrosion/irritation | Category 2 |
 Warning |
H315 |
P302+P352
P332+P313 P362+P364 P264 P280 P321 |
Based on the reports that it is a strong skin irritant in humans (HSDB (Access on June 2017)) and that this substance was irritating to the skin in the skin irritation tests with rabbits and guinea pigs (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), this substance was classified as Category 2. In the EU CLP classification, this substance is classified as Skin Irrit. 2 (ECHA CL Inventory (Access on June 2017)). In addition, there is no distinction between isomers, but in the "Simple chemical substances or compounds designated by the Minister of Health, Labour and Welfare or disease designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act.," tolylene diisocyanate (synonym: TDI) is listed as a substance causing skin disorder. |
| 3 | Serious eye damage/eye irritation | Category 2 |
Warning |
H319 |
P305+P351+P338
P337+P313 P264 P280 |
Since it is reported that this substance caused stinging pain in the eyes in the human eye irritation test (DFGOT vol. 20 (2003)), and that this substance caused moderate irritation of the eyelid conjunctiva and mild damage to the corneal epithelium in the eye irritation test with rabbits (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), it is classified in Category 2. Besides, in the EU CLP classification, this substance is classified as Eye Irrit. 2 (ECHA CL Inventory (Access on June 2017)). In addition, there is no distinction between isomers, but in the "Simple chemical substances or compounds designated by the Minister of Health, Labour and Welfare or disease designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act.," tolylene diisocyanate (synonym: TDI) is listed as a substance causing anterior ocular disorder. |
| 4 | Respiratory sensitization | Category 1 |
 Danger |
H334 |
P304+P340
P342+P311 P261 P284 P501 |
As for humans, it is described that commercial-grade TDI which is a mixture of this substance (2,4-TDI) and the isomer (2,6-TDI, CAS RN 91-08-7) (the mixing ratio of 2,4-TDI and 2,6-TDI is generally 80:20), causes asthma, showing respiratory irritation and respiratory sensitization, resulting in chronic bronchitis, focal respiratory disease, etc. (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Japan Society of Occupational Health (JSOH) classified toluene diisocyanates as occupational sensitizers to the airway Group 1 (Recommendation of Occupational Exposure Limits (2016)), and this substance is included in toluene diisocyanates. Therefore, it was classified in Category 1. Besides, in the EU CLP classification, this substance is classified as Resp. Sens. 1 (ECHA CL Inventory (Access on June 2017)). |
| 4 | Skin sensitization | Category 1 |
Warning |
H317 |
P302+P352
P333+P313 P362+P364 P261 P272 P280 P321 P501 |
The Japan Society of Occupational Health classified toluene diisocyanates as occupational skin sensitizers Group 2 (Recommendation of Occupational Exposure Limits (2016)), and this substance is included in toluene diisocyanates. Therefore, it was classified in Category 1. Besides, in the EU CLP classification, this substance is classified as Skin Sens. 1 (ECHA CL Inventory (Access on June 2017)). |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | As for in vivo tests with commercial-grade TDI (80% of this substance and 20% of the 2,6-isomer), a micronucleus assay with rat and mouse bone marrow cells was negative, and an unscheduled DNA synthesis with rat hepatocytes was negative (IARC 71 (1999), DFGOT vol. 20 (2003)). As for in vitro tests, this substance was positive in a bacterial reverse mutation test, positive in a mouse lymphoma test with mammalian cultured cells, negative in a chromosomal aberration test and equivocal in a sister chromatid exchange test (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016), DFGOT vol. 20 (2003), ATSDR (2015)). From the above, this substance was classified as "classification not possible" according to the revised GHS classification guidance for the Japanese government. |
| 6 | Carcinogenicity | Category 2 |
Warning |
H351 |
P308+P313
P201 P202 P280 P405 P501 |
In a carcinogenicity study in which rats or mice were dosed by gavage with the commercial-grade TDI (about 86% of this substance and 14% of 2,6-isomer) for 2 years, in rats, an increase in total frequency of benign and malignant tumors (fibroma and fibrosarcoma) of the subcutaneous tissue in both of males and females, an increase in frequency of pancreatic benign tumor (acinar-cell adenoma) in males, an increase in frequency of mammary fibroadenoma and pancreatic benign tumor (islet cell adenomas) in females were observed (IARC 39 (1986), NTP RoC (14th, 2016)). In mice, no increase was observed in tumor incidence in males, but, in females, an increase in total frequency of benign and malignant tumors of the blood vessels (hemangioma and hemangiosarcoma) and an increase of frequency of liver tumor (hepatocellular adenoma) were observed (IARC 39 (1986), NTP RoC (14th, 2016)). IARC classified it in Group 2B because there was sufficient evidence of carcinogenicity in laboratory animals (IARC 71 (1999)). Other than this, it is classified in A3 by ACGIH (ACGIH (7th, 2016)), in R by NTP (NTP RoC (14th, 2016)), in Carc. 2 by EU (ECHA CL Inventory (Access on June 2016)), and Japan Society of Occupational Health classified toluene diisocyanates (CAS RN 26471-62-5) in Group 2B (Recommendation of Occupational Exposure Limit (2016): proposed in 1991). Based on the classification results by other organizations, this substance was classified in Category 2. |
| 7 | Reproductive toxicity | Classification not possible |
- |
- | - |
In a two-generation test in which rats were exposed by inhalation to the commercial-grade TDI (TDI mixture of 80% of this substance and 20% of 2,6-isomer), in both males and females of both F0 and F1 parental animals, inflammation of the nasal cavity at or above 0.02 ppm, decreased weight gain and changes in general condition (crust formation around the nose, etc.) at or above 0.08 ppm were observed, but there was no adverse effect on fertility, and the only slight effects on pups were noted (lower values in body weight in F2 at or above 0.08 ppm) (Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Moreover, in the study in which pregnant rats were exposed by inhalation to TDI (80:20) during the organogenesis period (gestation days 6-15), only slight effects (delayed ossification of the fifth cervical vertebra) on fetuses were observed at 0.5 ppm where maternal toxicity (decrease weight gain, a decrease in food consumption, etc.) was noted (Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above, as for inhalation route, there is a possibility that it is classified as "not classified," but there was no toxicity information on other routes, so this substance was classified as "Classification not possible" due to lack of data. |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (respiratory organs) |
Danger |
H370 |
P308+P311
P260 P264 P270 P321 P405 P501 |
As for humans, it is reported that in the inhalation test of this substance with volunteers, prickling in the nose was seen by inhalation at 0.08 ppm for 30 minutes (DFGOT vol. 20 (2003)). In addition, exposure effects of commercial-grade TDI which was a mixture of this substance and the isomer 2,6-TDI (CAS RN 91-08-7) (hereinafter refer to as TDI. The mixing ratio of 2,4-TDI and 2,6-TDI is generally 80:20) were reported. Multiple cases were reported in which acute respiratory insufficiency occurred due to exposure of large quantity of TDI in an accident (DFGOT vol. 20 (2003)). Furthermore, it is described that acute exposure can produce irritant effects on the mucosa and respiratory tract and exposure to high concentrations may lead to chemical bronchitis with severe bronchospasm, pneumonia, pulmonary edema (ACGIH (7th, 2004)). As for experimental animals, it is reported that in a 4-hour single inhalation exposure test of TDI with mice, rats, guinea pigs and rabbits, focal coagulation necrosis and crust formation of the trachea and bronchial epithelium were seen at 2 ppm, and coagulation and necrosis of the trachea and bronchial epithelium and aggregation of acute inflammatory cells around the site of onset were observed at 5 ppm, followed by severe bronchiolar injury and complete obstruction by fibrous tissue observed 4 weeks after exposure (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). The doses in experimental animals correspond to Category 1. Since it is reported that no significant toxicological difference is observed between the 2,4-isomer and the 2,6-isomer (ACGIH (7th, 2004)), it is thought to be appropriate to use the toxicity information of the mixture TDI as evidence for the classification. Therefore, this substance was classified in Category 1 (respiratory organs). Besides, there is no distinction between isomers, but in the "Simple chemical substances or compounds designated by the Minister of Health, Labour and Welfare or disease designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act.," tolylene diisocyanate (synonym: TDI) is listed as a chemical causing airway/lung disorder. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (respiratory organs) |
Danger |
H372 |
P260
P264 P270 P314 P501 |
As for humans, there is the information of m-tolylene diisocyanate (TDI) which is a mixture of this substance (2,4-TDI) and the isomer (2,6-TDI) (the mixture ratio of 2,4-TDI and 2,6-TDI is generally 80:20), and it is described that "TDI causes asthma, shows respiratory irritation and respiratory sensitization, and causes chronic bronchitis, focal respiratory disease, etc. in humans" (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). As for experimental animals, it is reported that in a 21-day inhalation toxicity study (6 hours/day, 5 days/week) with rats, laboured breathing, reparative hyperplasia, squamous metaplasia in the larynx, rhinitis, slight effect in the lung (histiocytosis) at or above 0.24 ppm (1.74 mg/m3) (converted guidance value: 0.00041mg/L) within a guidance value range for Category 1, and reparative hyperplasia of the trachea, necrotizing bronchitis/bronchiolitis, hyperplasia and metaplasia, edema and alveolitis in the lung at 0.67 ppm (4.85 mg/m3) (converted guidance value: 0.0011 mg/L), and increased mortality (25%), decreased body weight, decreased volume and protein content of urine, increase blood urea nitrogen, increased hemoglobin/hematocrit and erythrocytes, decreased thrombocytes and leucocytes at 2.83 ppm (20.49 mg/m3) (converted guidance value: 0.0048 mg/L) were observed (DFGOT vol. 20 (2003)). It is reported that in a 79-day inhalation toxicity study (6 hours/day) with rats, bronchitis was noticed at 1.5 ppm (10.8 mg/m3) (converted guidance value 0.0094 mg/L) within a guidance value for Category 1, and that in a 30-day inhalation toxicity test (6 hours/day) tracheitis and bronchitis were observed at or above 1 pm (7.2 mg/m3) (converted guidance value: 0.0024 mg/L) which is within the guidance value of Category 1 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Among the above, the effects on the hematological system were not adopted as evidence of the classification because erythrocyte parameters increased and the decreased thrombocytes and leukocyte were the findings at the concentration where 25% of animals died. Therefore, this substance was classified in Category 1 (respiratory organs). Besides, there is no distinction between isomers, but in the "Simple chemical substances or compounds designated by the Minister of Health, Labour and Welfare or disease designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act.," tolylene diisocyanate (synonym: TDI) is listed as a chemical causing airway/lung disorder. |
| 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 3 |
- |
H402 |
P273
P501 |
From 96-hour LC50 <508.3 mg/L for crustacea (Palaemonetes pugio) (Environmental Risk Assessment for Chemical Substances vol. 14 (Ministry of the Environment, 2016)), it was classified in Category 3. |
| 11 | Hazardous to the aquatic environment (Long-term) | Category 3 |
- |
H412 |
P273
P501 |
Due to being rapidly degradable (non-biodegradable, although average degradation rate by BOD is 0%, it is judged that it degrades 100% due to a degradation rate by GC of 100% (J-CHECK, 2003)), no bioaccumulation (LogKow: 3.74 (PHYSPROP Database: 2017)), and 21-day NOEC (reproduction inhibition) = 1.1 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances vol. 14 (Ministry of the Environment, 2016)), it was classified in Category 3. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
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* 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. |