NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	123-91-1
Chemical Name	1,4-Dioxane
Substance ID	m-nite-123-91-1_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 molecules.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Flammable liquids	Category 2	Danger	H225	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	Classified into Category 2 since flash point is 12 degC (ICSC (2005)) and boiling point is 101 degC. The substance is classified into Class 3, PG II in UNRTDG (UN1165).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Pyrophoric liquids	Not classified	- -	-	-	Auto-ignition point is 180 degC (ICSC (2005)) exceeding 70 degC.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing oxygen which is chemically bonded only to carbon.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
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)	Not classified	- -	-	-	LD50 values are 4200 mg/kg (Initial Environmental Risk Assessment of Chemicals (Ministry of Environment) vol. 2 (2003)), 5170 mg/kg (Hazard Assessment Report (CERI, NITE) (2006)), 5170 mg/kg (DFGOT vol. 20 (2005)), 5200 mg/kg (IARC 11 (1976)), 5345 mg/kg (EU-RAR No. 21 (2002)), 5400 mg/kg (ACGIH (7th, 2001)), 6300 mg/kg (DFGOT vol. 20 (2005)), 6370 mg/kg (EU-RAR No. 21 (2002)), 6500 mg/kg (EU-RAR No. 21 (2002)), 7300 mg/kg (Hazard Assessment Report (CERI, NITE) (2006)) and 7339 mg/kg (EU-RAR No. 21 (2002)) for rats. Since nly one value, 4200 mg/kg (Initial Environmental Risk Assessment of Chemicals (Ministry of Environment) vol. 2 (2003)) corresponds to Category 5 and all of the other values correspond to "Not classified" in GHS classification, the substance was classified as "Not classified".	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on a LD50 value of 2100 mg/kg for rats (Hazard Assessment Report (CERI, NITE) (2006)), the substance was classified as "Not classified" (correspond to Category 5 in GHS classification).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Vapours)	Category 4	Warning	H332	P304+P340 P261 P271 P312	From LC50 values of 46 mg/L (2h) (Hazard Assessment Report (CERI, NITE) (2006), Initial Environmental Risk Assessment of Chemicals (Ministry of Environment) vol. 2 (2003)) and 51.3 mg/L (4h) (EU-RAR No. 21 (2004), ACGIH (7th, 2001)) in rat inhalation (vapour) exposure tests, the 4-hour equivalent LC50 values are calculated to be 9158 ppm and 14236 ppm, respectively. The saturated vapour pressure concentration at the saturated vapour pressure of 38.1 mmHg (25 degC) (5079 Pa (25 degC)) (HSDB (2005)) is 50132 ppm. Since the above LC50 values are lower than 90% of saturated vapour pressure concentration, classification criteria for ppm were adopted as vapour with almost no included mists. The substance was classified into Category 4. The alteration of classification is due to amendment of the guidance.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	Based on results of "moderately irritating" in a rabbit skin irritation test (open Draize test) (Hazard Assessment Report (CERI, NITE) (2006)) and "slightly irritating" in a rabbit, rat and mouse skin irritation tests (EU-RAR No. 21 (2002)), the substance was classified into Category 2.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	Although obvious positive reactions are reported for exposed humans, there is no report of corrosive (Hazard Assessment Report (CERI, NITE) (2006), EU-RAR No. 21 (2002)). In a rabbit eye irritation test, "severe chemosis, slight corneal opacity and conjunctival redness (conjunctival redness persisted to day 8 in one animal)" were observed (EU-RAR No. 21 (2002)). Based on the data, the substance was classified into Category 2A. As relevant information, in EU classification, the substance is classified into R36/37.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Skin sensitization	Classification not possible	- -	-	-	In a guinea pig skin sensitizing test (Directive 84/449/EEC, B.6) (GLP), a negative result is reported (EU-RAR No. 21 (2002), original literature BASF (1993)). On the other hand, positive results are reported in human patch tests (EU-RAR No. 21 (2002), NICNASPEC No. 7 (1998)). Classification was not possible.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Germ cell mutagenicity	Not classified	- -	-	-	Although there are positive and negative results in micronucleus test by oral gavage to mice (ATSDR (2007), Hazard Assessment Report (CERI, NITE) (2006), NICNAS No. 7 (1998)), the substance was classified as "Not classified" based on expert's decision for reliability of the test. There are reports of positive rat hepatic cell DNA damage test, DNA synthesis test and DNA repair test (Hazard Assessment Report (CERI, NITE) (2006), NICNAS No. 7 (1998), PATTY (5th, 2001)) and negative Ames test, mouse lymphoma test and chromosomal aberration test (Hazard Assessment Report (CERI, NITE) (2006)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] As for carcinogenicity, there is no sufficient report indicating carcinogenicity in humans. As for the oral route, in multiple tests conducted according to appropriate test guidelines and GLP standards, (1) and (2), increased incidences of tumors including malignant tumors were observed in multiple sites of two animal species. In rats, tumors similar to those in the oral route were also observed in the inhalation route as written in (3). On top of the above, on the basis that EPA classified it L on the similar rationale as described in (4), it was classified in Category 1B. Besides, the same test results as for the previous classification were used for the classification this time. However, the category was revised by putting importance on the fact that the substance was judged to be carcinogenic in animals in Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare), and that guidelines were issued by the ministry from concerns on carcinogenicity after discussions in the small committee of hazard evaluation. [Evidence Data] (1) In a carcinogenicity test in rats (2-year drinking water administration), increased incidences of malignant tumors (mainly squamous cell carcinoma) in the nasal cavity and hepatocellular adenoma and carcinoma were observed in male and female dosed groups, and an increased incidence of mesothelioma in the peritoneum was also observed in a male dosed group (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 1990)). (2) In a carcinogenicity test in mice (2-year drinking water administration), increases in hepatocellular carcinoma were observed in male and female dosed groups (Results from Carcinogenicity Studies (Ministry of Health, Labour and Welfare, 1990)). (3) In a test in which male F344 rats were exposed by inhalation of the vapour of this substance for 2 years, increased incidences of squamous cell carcinoma in the nasal cavity, hepatocellular adenoma, mesothelioma in the peritoneum were observed (OEL Documentations (Japan Society For Occupational Health, 2015), IRIS (2013); a test commissioned by Ministry of the Environment: Kasai et al. (2009)). (4) As for classification results by domestic and international organizations, it was classified in Group 2B by IARC (IARC 71 (1999)), in Carc. 2 in EU CLP, in R by NTP (NTP RoC (14th, 2016)), in L (Likely to be carcinogenic to humans) by EPA (IRIS (2013)), in A3 by ACGIH (ACGIH (7th, 2001)), in 2B by Japan Society for Occupational Health (JSOH) (OEL Documentations (Japan Society For Occupational Health, 2015)). [Reference Data, etc.] (5) In NTP's carcinogenicity tests in rats and mice (drinking water administration) that increased incidences of nasal cavity tumors hepatocellular adenoma in rats and hepatocellular carcinoma in mice are also reported (NTP TR80 (1979)). (6) Based on paragraph (3) of Article 28 of the Industrial Safety and Health Act, this substance is subject to guidelines in order to prevent the impairment of worker's health caused by the chemical substances decided by the Minister of Health, Labour and Welfare (Public announcement on guidelines in order to prevent the impairment of worker's health, No. 23, Oct 10, 2012).	FY2018	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Classification not possible	- -	-	-	In developmental toxicity tests in rats by oral administration (Hazard Assessment Report (CERI, NITE) (2006)) or inhalation exposure (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 2 (2003)) during the organogenesis period, no adverse effects on fetal development were seen while decreased fetal weight and delayed ossification were observed in some tests. However, classification was not possible due to lack of data for sexual function and fertility.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system), Category 3 (narcotic effects, respiratory tract irritation)	Danger Warning	H370 H336 H335	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	Based on findings of dizziness, sleepiness and unconsciousness in humans following inhalation exposure (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 2 (2003)), the substance was classified into Category 1 (central nervous system). Narcotic effects are reported in rats following inhalation at 155 mg/L (EU-RAR 21 (2002)) and rabbits following oral exposure at 6600 mg/kg (ATSDR (2007)). The substance was classified into Category 3 (narcotic effects). The substance is irritating to the nose and throat in humans (EU-RAR 21 (2002), ATSDR (2007)). In an inhalation test in rats, irritation of mucous membranes of the respiratory tract was observed (EU-RAR 21 (2002)). Based on these results, the substance was classified into Category 3 (respiratory tract irritation). Since the effects on the central nervous system (toxic symptoms) were transient and mild in degree, and were considered to correspond to narcotic effects, the data was not used as the basis of classification of central nervous system. As for liver and kidney, test data was not obtained. Other data was insufficient as evidence for classification.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 1 (kidney, liver, central nervous system), Category 2 (respiratory organs)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	In a case report of 5 workers who died following exposure to the substance, hemorrhage and necrosis in the kidney and necrosis in the liver are reported (Hazard Assessment Report (CERI, NITE) (2006)). There is a case report that a worker who had been exposed for one week in a closed, non ventilated room without respiratory equipment showed hypertonia, neurological symptoms, kidney failure, renal cortex necrosis, severe centrilobular necrosis in the liver and demyelination and partial loss of nerve fibre tissue in the brain (EU-RAR No. 21 (2002)). Based on the data, the substance was classified into Category 1 (kidney, liver, central nervous system). In a 2-year oral test in rats, degeneration of airway epithelium was observed at 16 mg/kg/day (corresponds to Category 2) (Initial Environmental Risk Assessment of Chemicals (Ministry of the Environment) vol. 2 (2003)). Based on this data, the substance was classified into Category 2 (respiratory system).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）

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	- -	-	-	Classified into Not classified from its 96h-LC50 >100 mg/L for fish (Oryzias latipes) (Test for the Ecological Effect of Chemical Substances (Ministry of the Environment), 1995, etc), 48h-EC50 >1000 mg/L for Crustacea (Daphnia magna) (Test for the Ecological Effect of Chemical Substances (Ministry of the Environment), 1995, etc) and 72h-ErC50 >1000 mg/L for algae (Pseudokirchneriella subcapitata) (Test for the Ecological Effect of Chemical Substances (Ministry of the Environment), 1995, etc).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Classified into Not classified since it is not non-water soluble (Water solubility = 1000000 mg/L (PHYSPROP Database, 2009) and its acute toxicity is low.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in Annexes to the Montreal Protocol.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）

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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