NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	822-06-0
Chemical Name	Hexamethylene diisocyanate (Hexane, 1,6-diisocyanato-)
Substance ID	m-nite-822-06-0_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	To Workplace Safety Site (MHLW)
Sample SDS by MHLW (External link)	To Workplace Safety Site (MHLW)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
6	Flammable liquids	Not classified	- -	-	-	It was classified as "Not classified" based on a flash point of 130 deg C (closed cup) (GESTIS (Access on September 2014)).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	Isocyanate is a cyanate compound in a broad sense. It easily polymerizes, but the classification is not possible due to no data.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 454 deg C (ICSC (1993)).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
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).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Organic substances containing no oxygen, fluorine or chlorine	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	There were 4 reports of LD50 values of 105-960 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), 710 mg/kg (OEL Documentations (Japan Society For Occupational Health (JSOH), 1995)), 746 mg/kg (SIDS (2004), Environmental Risk Assessment for Chemical Substances Vol.2, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2003)), and 959 mg/kg (SIDS (2004), OEL Documentations (Japan Society For Occupational Health (JSOH), 1995)) for rats. It was classified in Category 4 to which the largest number of values corresponded according to the GHS Classification Guidance for the Japanese Government.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	Based on reports of LD50 values of 570-599 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) and 599 mg/kg (SIDS (2004)) for rabbits, it was classified in Category 3.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
1	Acute toxicity (Inhalation: Vapours)	Category 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	Based on reports of LC50 values (4 hours) of 8.7 ppm (Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003)), 18.2-50.8 ppm (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), 18.2 ppm (SIDS (2004)), 22 ppm (SIDS (2004), OEL Documentations (Japan Society For Occupational Health (JSOH), 1995)), and 45 ppm (SIDS (2004), ATSDR (1998)) for rats, it was classified in Category 1. Besides, since LC50 values were lower than 90% of the saturated vapour concentration (69.1 ppm), the reference value in units of ppm was applied as a vapour without a mist.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
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	There is a report that in a skin irritation test (OECD TG 404) with rabbits, severe edema and erythema were observed, with necrosis 24 hours after application, and no recovery was observed 8 days after application (SIDS (2004)). In addition, it was also judged that it was corrosive in other skin irritation tests with rabbits and guinea pigs (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above results, it was classified in Category 1. Besides, this substance was classified in "Xi; R38" in the EU DSD classification and in "Skin Irrit. 2 H315" in the EU CLP classification.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	There is a report that in an eye irritation test (OECD TG 405) with rabbits, strong irritation in the cornea, iris and conjunctiva of both eyes 30 seconds after application, lack of response to light stimulation, bleeding, and damage of the iris 72 hours after application were observed, and no recovery was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). In addition, also in SIDS (2004), this substance was judged to be corrosive to the eye from the results of an eye irritation test (OECD TG 405) with rabbits. Moreover, this substance was classified in Category 1 for skin corrosion/irritation. From the above results, it was classified in Category 1. Besides, this substance was classified in "Xi; R36" in the EU DSD classification and in "Eye irrit. 2 H319" in the EU CLP classification.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
4	Respiratory sensitization	Category 1A	Danger	H334	P304+P340 P342+P311 P261 P284 P501	In humans, there were reports of the onset of asthma and hypersensitivity pneumonitis by exposure to this substance (OEL Documentations (Japan Society For Occupational Health (JSOH), 1995), ACGIH (7th, 2001)), and of moderate respiratory tract disorder (Environmental Risk Assessment for Chemical Substances Vol.2 (Ministry of the Environment, 2003)). In addition, this substance was classified as an occupational sensitizer to the airway Group 1 by Japan Society For Occupational Health (JSOH). From the above results, it was classified in Category 1A. Besides, this substance was classified in "R42" in the EU DSD classification and in "Resp. Sens. 1 H334" in the EU CLP classification. Based on facts that there were multiple reports of effects on the respiratory tract in humans and that it was classified as an occupational sensitizer to the airway Group 1 by Japan Society For Occupational Health (JSOH), it was subcategorized.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	In 3 reports of skin sensitization tests (OECD TG 406) with guinea pigs, since the positive rates were 20/20, 14/20 and 18/20, respectively, this substance was judged as sensitizing (SIDS (2004)). In addition, there are reports that dose-dependent ear swelling was observed in an ear swelling test with mice, and that a concentration-dependent increase in 3H-methylthymidine uptake was observed in a mouse Local Lymph Node Assay (LLNA) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above results, it was classified in Category 1. Besides, this substance was classified in "R43" in the EU DSD classification and in "Skin Sens. 1 H317" in the EU CLP classification.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
5	Germ cell mutagenicity	Classification not possible	- -	-	-	The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo, it was negative in a mouse bone marrow micronucleus test (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004), HSDB (Access on August 2014)). As for in vitro, it was negative in bacterial reverse mutation tests and a mammalian cell gene mutation test (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), IUCLID (2000), HSDB (Access on August 2014)).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
6	Carcinogenicity	Classification not possible	- -	-	-	There was no carcinogenicity classification by international organizations. There is a report that carcinogenicity was not confirmed in a 2-year inhalation carcinogenicity study with rats (SIDS (2004)). However, it was classified as "Classification not possible" since it was not possible to assign the carcinogenicity classification based on the data in rats only.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
7	Reproductive toxicity	Classification not possible	- -	-	-	In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats by the inhalation route, no effects on the fertility and development of the next generation were found even at doses where parental toxicities were observed. In addition, in a teratogenicity test (OECD TG 414) with rats by the inhalation route, no effects on the fetuses were observed even at doses where parental toxicities were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), SIDS (2004)). Although there were the above results, since they were screening tests, it was classified as "Classification not possible."	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	This substance was irritating to the respiratory tract (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ACGIH (7th, 2001), SIDS (2004)). In humans, although there were multiple cases, there were no data available for classification. As for experimental animals, there were reports of bradypnea, dyspnea, labored breathing, rales, cyanosis, prostration, reduced motility, hypothermia and piloerection by an inhalation exposure of rats to concentrations of 0.056 mg/L or above, and severe respiratory impairment, cyanosis, respiratory irritation, bronchopneumonia and bronchiectasis by an inhalation exposure of rats to 0.5 mg/L. These inhalation exposure data were found in the surviving animals. The effects on the respiratory organs observed by inhalation exposure were observed at concentrations within the guidance value range of Category 1. By the oral administration, pallor, cyanosis, slow breathing, deep breathing, and diarrhea were observed in rats (administration concentration not described) (ATSDR (1998), SIDS (2004), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). From the above, it was classified in Category 1 (respiratory organs).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	The lung function tests were conducted on a group of 41 male car painters exposed to this substance or paints containing this substance at an automobile maintenance shop and a control group. When having compared data between the both groups, an increase in closing volume (CV) was observed in the exposed group, suggestive of small airways disease. There is a description that in a follow-up investigation after six years, in the lung function test among the group of 36 exposed car painters and the non-exposed group, although there was no significant difference between the groups with non-smokers, in comparison between the groups of smokers (or former smokers), a significant decrease in lung function was observed in the exposed group, and the decrease in the lung function by exposure to this substance tended to increase due to smoking (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), IRIS (1994), ATSDR (1998)). In addition, in cases of occupational exposure to paints containing this substance or occupational exposure at manufacturing factories of this substance, there are many reports on onset of respiratory organ damage by repeated exposure to this substance (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ATSDR (1998)). As for experimental animals, in studies in which rats were exposed by inhalation to the vapor of this substance for 90 days or 1-2 years, although tissue damage in the nasal cavity (hyperkeratosis of the epithelium, squamous metaplasia, hyperplasia of mucus secretory cells, degeneration of the olfactory epithelium, etc.) and the lung (interstitial pneumonia, aggregation of alveolar macrophages, etc.) were observed within the dose range of Category 1 (0.000034-0.0017 mg/L/6 hours), no findings suggestive of target organs other than the respiratory system were observed (SIDS (2004), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ATSDR (1998)). From the above, it was classified in Category 1 (respiratory organs).	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))
10	Aspiration hazard	Classification not possible	- -	-	-	Classification not possible due to lack of data.	FY2014	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.0))

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Not classified	- -	-	-	It was classified into Not classified from 48 hours EC50>=89.1mg/L of the crustacea (Daphnia magna) (SIDS (2004) and others.).	FY2006	GHS Classification Manual （10 Feb, 2006）
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Since it was not water-insolubility (the water-solubility =117mg/L (PHYSPROP Database, 2005)), and acute toxicity was low, it was classified into Not classified.	FY2006	GHS Classification Manual （10 Feb, 2006）
12	Hazardous to the ozone layer	-	- -	-	-	-	-	-

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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