GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 91-08-7
Chemical Name 2,6-Tolylene diisocyanate [2,6-Toluene diisocyanate]
Substance ID H29-B-050
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) 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 applicable
-
-
- - There are no chemical groups associated with explosive properties present in the molecule.
2 Flammable gases (including chemically unstable gases) Not applicable
-
-
- - Liquid (GHS definition)
3 Aerosols Not applicable
-
-
- - Not aerosol products.
4 Oxidizing gases Not applicable
-
-
- - Liquid (GHS definition)
5 Gases under pressure Not applicable
-
-
- - Liquid (GHS definition)
6 Flammable liquids Not classified
-
-
- - A flash point is 127 deg C (closed cup) (GESTIS (Access on June 2017)).
7 Flammable solids Not applicable
-
-
- - Liquid (GHS definition)
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 classified
-
-
- - It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 620 deg C (ICSC (J) (1998)).
10 Pyrophoric solids Not applicable
-
-
- - Liquid (GHS definition)
11 Self-heating substances and mixtures Classification not possible
-
-
- - Test methods applicable to liquid 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
-
-
- - The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
14 Oxidizing solids Not applicable
-
-
- - Liquid (GHS definition)
15 Organic peroxides Not applicable
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule
16 Corrosive to metals Classification not possible
-
-
- - No data available.

HEALTH HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
1 Acute toxicity (Oral) Classification not possible
-
-
- - Classification not possible due to lack of data.
1 Acute toxicity (Dermal) Classification not possible
-
-
- - Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Liquid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Category 1


Danger
H330 P304+P340
P403+P233
P260
P271
P284
P310
P320
P405
P501
There is no information on an LC50 value of this substance alone, however, for commercial-grade TDI, a mixture of isomers, 2,4-tolylene diisocyanate (2,4-TDI, CAS RN: 584-84-9) and this substance (hereinafter referred to as TDI. Generally, the mixing ratio of 2,4-TDI and 2,6-TDI is 80:20), an LC50 value was reported to be 13.9-49.8 ppm (0.1-0.36 mg/L) in a 4-hour inhalation study with rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). The content of this substance is as low as about 20%, but there is a description that no significant toxicological difference between the 2,4-isomer and 2,6-isomer is recognized (ACGIH (7th, 2004)), so 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 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 as Category 1.
1 Acute toxicity (Inhalation: Dusts and mists) Category 2


Danger
H330 P304+P340
P403+P233
P260
P271
P284
P310
P320
P405
P501
There is no information on the LC50 value of this substance alone, however, for commercial-grade TDI, a mixture of 2,4-TDI and this substance (hereinafter referred to as TDI. Generally, the mixing ratio of 2,4-TDI and 2,6-TDI is 80:20), an LC50 value was reported to be 13.9-49.8 ppm (0.1-0.36 mg/L) in a 4-hour inhalation study with rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). The content of this substance is as low as about 20%, but there is a description that no significant toxicological difference between the 2,4-isomer and 2,6-isomer is recognized (ACGIH (7th, 2004)), so 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 as mist 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, it corresponds to Category 2. Therefore, it was classified in Category 2.
2 Skin corrosion/irritation Category 1


Danger
H314 P301+P330+P331
P303+P361+P353
P305+P351+P338
P304+P340
P260
P264
P280
P310
P321
P363
P405
P501
In the skin irritation test with rabbits, it was reported that the commercial-grade TDI (containing 20% of this substance and 80% of 2,4-TDI) is caustic, and the skin lesions were not reversible in observation at 8 and 28 days (DFGOT vol. 20 (2003)). Though the content of this substance is as low as about 20%, as there is a description that no significant toxicological difference between the 2,4-isomer and 2,6-isomer is recognized (ACGIH (7th, 2004)), by adopting this information, this substance was classified in Category 1. 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. The category was revised based on the information obtained in this survey.
3 Serious eye damage/eye irritation Category 1


Danger
H318 P305+P351+P338
P280
P310
This substance was classified in Category 1 because it was classified in Category 1 for skin corrosion/irritation. Besides, it is reported that the commercial-grade TDI (contained 20% of this substance and 80% of 2,4-TDI) often caused strong irritation which did not resolve within 30 days in the eye irritation test with rabbits (DFGOT vol. 20 (2003)), and there is a description that no significant toxicological difference between 2,4-isomer and 2,6-isomer (this substance) is recognized (ACGIH (7th, 2004)). 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. The category was changed according to the GHS classification guidance for the Japanese government.
4 Respiratory sensitization Category 1


Danger
H334 P304+P340
P342+P311
P261
P284
P501
As for humans, it is stated that the commercial-grade TDI, a mixture of this substance (2,6-TDI) and its isomer (2,4-TDI, CAS RN: 584-84-9) (the mixture ratio of 2,6-TDI and 2,4-TDI is generally 20:80), causes asthma, showing respiratory irritation and respiratory sensitization, resulting in chronic bronchitis, focal respiratory disease, etc. (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). The content of this substance is about 20%, but there is a description that no significant toxicological difference between 2,4-isomer and 2,6-isomer (this substance) was recognized (ACGIH (7th, 2004)), thus, information of the commercial-grade TDI was used for the classification. In the Japan Society of Occupational Health, toluene diisocyanates are classified 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
In the Japan Society of Occupational Health, toluene diisocyanates are classified 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 Resp. Sens. 1 (ECHA CL Inventory (Access on June 2017)).
5 Germ cell mutagenicity Classification not possible
-
-
- - As for in vivo tests with the commercial-grade TDI (20% of this substance and 80% of 2,4-isomer) a micronucleus assay with rat and mouse bone marrow cells was negative (IARC 71 (1999)), and as for in vitro tests, this substance was positive in all of a bacterial reverse mutation test, a mouse lymphoma test, a chromosomal aberration test and a sister chromatid exchange test with mammalian cultured cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol. 14 (Ministry of the Environment, 2016), ATSDR (2015), DFGOT Vol. 20 (2003)). From the above, this substance was classified as "Classification not possible" according to the GHS classification guidance for the Japanese government. Because of reviewing the information sources and adding the findings of in vivo tests, the category of the previous classification was revised.
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 commercial-grade TDI (about 14% of this substance and 86% of 2,4-isomer) for 2 years, in rats, an increase in total frequency of benign and malignant tumors (fibroma and fibrosarcoma) of 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 this substance 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 classifies toluene diisocyanates (CAS RN 26471-62-5) in Group 2B (Recommendation of Occupational Exposure Limits (2016): proposed in 1991). Based on the existing classification results of other organizations, this substance was classified in Category 2.
7 Reproductive toxicity Classification not possible
-
-
- - Classification not possible due to lack of data. Besides, for commercial-grade TDI (TDI mixture of 20% of this substance and 80% of 2,4-isomer), it is reported that in the two-generation test in which rats were exposed by inhalation, 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 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, it is reported that 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 (decreased 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)).
8 Specific target organ toxicity - Single exposure Category 1 (respiratory organs)


Danger
H370 P308+P311
P260
P264
P270
P321
P405
P501
As for humans, there is a report that in an inhalation test of this substance with volunteers, prickling in the nose was noted by inhalation at 0.08 ppm for 30 minutes, and the irritative effect was severer than that of isomer 2,4-TDI (CAS RN 584-84-9) (DFGOT vol. 20 (2003)). As for experimental animals, it is reported that in a 30-minute inhalation test in which mice inhaled 0.37-7.6 mg/m3 (0.051-1.05 ppm) of vapor of this substance (purity 99.1%), a decrease in breathing rate and respiratory irritation were observed. And the RD50 value is described as 1.85 mg/m3 (0.255 ppm) (EHC 75 (1987), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). In addition, for commercial-grade TDI, a mixture of 2,4-TDI and this substance (hereinafter referred to as TDI, the mixing ratio of 2,4-TDI and 2,6-TDI is generally 80:20), multiple cases were reported in which acute respiratory insufficiency occurred due to accidental massive exposure in humans (DFGOT vol. 20 (2003)). Furthermore, it is described that acute exposure of TDI 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)).

The content of this substance is as low as about 20%, but there is a description that no significant toxicological difference between 2,4-isomer and 2,6-isomer is recognized (ACGIH (7th, 2004)), so it is considered to be appropriate to use the information of TDI for classification of this substance. Therefore, it was classified in Category 1 (respiratory organs). The category was revised from of the previous classification by use of a new information source.
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 substance causing damages of airway/lung.
9 Specific target organ toxicity - Repeated exposure Category 1 (respiratory organs)


Danger
H372 P260
P264
P270
P314
P501
As for humans, there is information of m-tolylene diisocyanate (TDI), a mixture of isomer (2,4-TDI) and this substance (2,6-TDI) (the mixture ratio of 2,4-TDI and 2,6-TDI is generally 80:20), and it is stated 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, there is no report on this substance (2,6-TDI) alone, but there is a report on the commercial-grade TDI (2,4-TDI:2,6-TDI=80:20). In a 106-week repeated dose toxicity study with rats dosed by gavage, the effect on the respiratory organs (acute bronchial pneumonia), decreased weight gain and increased mortality were observed at the lowest dose of 30 mg/kg/day in males and 60 mg/kg/day or higher in female (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). In addition, in a 104-week inhalation toxicity test with mice, there is a report that atrophic rhinitis, metaplasia of the mucosa or squamous epithelium, necrotic rhinitis with necrotic foci at or above 0.00036 mg/L within a guidance value range for Category 1, and decreased weight gain, interstitial pneumonia, catarrhal bronchitis, keratitis at 0.00108 mg/L were observed (Initial Risk Assessment Report (NITE, CERI, NEDO) (2008)).
In addition, there is a description that no significant toxicological difference between the 2,4-isomer and 2,6-isomer is recognized (ACGIH (7th, 2004)).
From the above, 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 substance causing damages of airway/lung.
10 Aspiration hazard Classification not possible
-
-
- - 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 (Acute) Classification not possible
-
-
- - Reliable acute toxicity data were not obtained.
11 Hazardous to the aquatic environment (Long-term) Classification not possible
-
-
- - No data available.
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.

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