NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	75-21-8
Chemical Name	Ethylene oxide
Substance ID	23B5506
Classification year (FY)	FY2011
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)	Physical Hazards & Health Hazards: GHS Classification Guidance by the Japanese Government (July, 2010) Environmental Hazards: UN GHS Document (4th revised edition)
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	- -	-	-	Gas (GHS definition)
2	Flammable gases (including chemically unstable gases)	Category 1	Danger	H220	P210 P377 P381 P403	A lower explosive limit of 3 vol% (ICSC (2001)) corresponds to Category 1. Besides, it is classified in Division 2.3, Subsidiary Risk 2.1 in UNRTDG (UN1040).
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified	- -	-	-	It was classified as flammable gases. Besides, it is classified in Division 2.3, Subsidiary Risk 2.1 in UNRTDG (UN1040).
5	Gases under pressure	Low pressure liquefied gas	Warning	H280	P410+P403	A critical temperature is 196 deg C (Hommel (1996)), and it is a gas with a critical temperature above +65 deg C.
6	Flammable liquids	Not applicable	- -	-	-	Gas (GHS definition)
7	Flammable solids	Not applicable	- -	-	-	Gas (GHS definition)
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	Gas (GHS definition)
9	Pyrophoric liquids	Not applicable	- -	-	-	Gas (GHS definition)
10	Pyrophoric solids	Not applicable	- -	-	-	Gas (GHS definition)
11	Self-heating substances and mixtures	Not applicable	- -	-	-	Gas (GHS definition)
12	Substances and mixtures which, in contact with water, emit flammable gases	Not applicable	- -	-	-	Gas (GHS definition)
13	Oxidizing liquids	Not applicable	- -	-	-	Gas (GHS definition)
14	Oxidizing solids	Not applicable	- -	-	-	Gas (GHS definition)
15	Organic peroxides	Not applicable	- -	-	-	Gas (GHS definition)
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to gas substances are not available. Besides, there is information that steel, stainless steel, and Teflon are resistant as a container (Hommel (1996)).

HEALTH HAZARDS

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	LD50 values for rats of 72 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)) and 330 mg/kg (NTP TR 326 (1997)) correspond to Category 3 and Category 4, respectively. It was classified in Category 3 for higher hazard in accordance with the GHS classification guidance for the Japanese government.
1	Acute toxicity (Dermal)	Classification not possible	- -	-	-	No data available.
1	Acute toxicity (Inhalation: Gases)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	Among three LC50 values for rats [4,000 ppm/4 hours, 1,460 ppm/4 hours (the above, ACGIH (2001)), 800 ppm/4 hours (Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003))], two correspond to Category 3, and one corresponds to Category 4. It was classified in Category 3, to which most corresponded.
1	Acute toxicity (Inhalation: Vapours)	Not applicable	- -	-	-	Gas (GHS definition)
1	Acute toxicity (Inhalation: Dusts and mists)	Not applicable	- -	-	-	Gas (GHS definition)
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	It is reported that in an irritation test in which absorbent cotton was soaked in a 10% or 50% aqueous solution of this substance and applied to the rabbit skin for 1-60 minutes, inflammatory edema was formed (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)). In humans, the damage is characterized by edema and erythema, which occur 1-5 hours after exposure, followed by blister formation, and the severity of the damage depends on contact time and concentrations. Also, there is a report of skin irritation due to contact with ethylene oxide disinfectant attached to surgical gowns, etc. (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)). Based on the above knowledge, it was classified in Category 2. Besides, it was classified in Xi: R36/37/38 in EU classification (EC-JRC (ESIS) (Access on Sept. 2011)).
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	It is reported that in a test in which 0.1 to > 20% of this substance/saline solutions were repeatedly applied to the rabbit eye over 6 hours, congestion, swelling, iritis, and corneal opacity dose-dependently increased, indicating irritating effects on the corneal epithelium and mucous membranes (ACGIH (2001)). In humans, it is reported that severe corneal burns were observed in a worker accidentally exposed to the liquid of the substance, and the liquid of this substance was squirted into one eye, which was treated immediately by copious irrigation with water, but a mild irritation of the conjunctiva lasted only one day (ECETOC 5 (1984)). From the above, because irritation could not be judged as slight, it was classified in Category 2A. Besides, it was classified in Xi: R36/37/38 in EU classification (EC-JRC (ESIS) (Access on Sept. 2011)).
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available. Besides, there is a case report of occupational asthma attributed to exposure to ethylene oxide (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	This substance was classified in Category 1 because it is listed as a contact allergen in Contact Dermatitis (4th, 2006) (Contact Dermatitis (4th, 2006), corresponding to List 1), and the Japan Society For Occupational Health (JSOH) classified it as occupational skin sensitizers Group 2 (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2010)).
5	Germ cell mutagenicity	Category 1B	Danger	H340	P308+P313 P201 P202 P280 P405 P501	It was classified in Category 1B based on a positive result in a dominant lethal test by inhalation exposure of mice (in vivo heritable germ cell mutagenicity test) (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)). Furthermore, it was also reported to be positive in a chromosomal aberration test and a micronucleus test with rat bone marrow cells (in vivo somatic cell mutagenicity tests) (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)), and in humans, positive results were reported in a chromosomal aberration test, a micronucleus test, or a sister chromatid exchange test with peripheral blood lymphocytes of workers handling this substance (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)). Besides, as for in vitro tests, it was reported to be positive in all of an Ames test (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)), a micronucleus test with Chinese hamster V9 cells (IARC 60 (1994)), and a chromosomal aberration test with human lung fibroblast (IARC 60 (1994)) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	It was classified in Category 1A because it was classified in Group 1 by IARC (IARC 97 (2008)), K by NTP (NTP ROC 12th (2011)), and Group 1 by the Japan Society For Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits Vol. 52 (Japan Society For Occupational Health (JSOH), 2010)). Besides, in a 2-year inhalation exposure test with rats, subcutaneous fibroma, peritoneal mesothelioma, pancreatic adenoma, pituitary adenoma, brain neoplasm, and mononuclear cell leukemia were observed, mononuclear cell leukemia increased dose-dependently in males and females, and it was significant in females at high and mid doses. Males at the high and mid doses had increased incidences of peritoneal mesothelioma originating from the testis, and males at the high dose had an increased incidence of subcutaneous fibroma (ACGIH (2001)). In a 2-year inhalation test with mice, malignant neoplasms of the lung and benign neoplasms of the Harderian gland significantly increased. Also, in females, malignant neoplasms of the uterus, mammary gland, and malignant lymphoma of the hematopoietic system increased (NTP TR 326 (1987)). Furthermore, there are reports of significant increases in leukemia and gastric cancers in epidemiological surveys on workers handling this substance and increases in tumors of the hematopoietic or lymphatic system in many epidemiological studies on workers exposed occupationally (Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	In reproductive/developmental toxicity tests with rats or mice given inhalation exposure from before mating, adverse reproductive effects such as decreased litter size, decreased numbers of implantations, increased embryonic resorptions, and decreased numbers of live pups born were observed at the doses (100-150 ppm) where no general toxicity was seen in parent animals (NTP TR 326 (1987), Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)). Therefore, it was classified in Category 1B. Besides, after exposure of mice to 1,200 ppm after mating, congenital anomalies in live pups born, including omphalocele, eyeball defect (anophthalmia), thoracoschisis, acardia, and cleft palate, were reported (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)), but no teratogenicity was found after exposure of rats or rabbits during the organogenesis period (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)). Furthermore, in an epidemiological survey in humans, the pregnant women exposed to this substance had a higher incidence of miscarriages than those in the control group (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)).
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous 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	Nausea, vomiting, and headache occurred as acute effects on the nervous system in nearly all inhalation human cases, and less frequently reported effects included decreased consciousness (coma), excitement, sleeplessness, muscular weakness, diarrhea, and abdominal discomfort (EHC 55 (1985)). Also, in an inhalation exposure test with mice, dyspnea, lacrimation, incoordination, and semiconsciousness were observed at levels corresponding to the guidance values Category 1 and above LD50 (660 ppm) (NTP TR 326 (1987)). Therefore, it was classified in Category 1 (central nervous system). Furthermore, severe respiratory problems due to inflammatory reactions in the trachea and larynx were reported in 17 hospital patients who had received endotracheal intubation with tubes sterilized with this substance (EHC 55 (1985)). Therefore, it was classified in Category 3 (respiratory tract irritation).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system), Category 2 (blood, kidney, respiratory tract)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	Three out of four young persons who had been intermittently exposed for 2-8 weeks due to leakage from a sterilizer developed reversible peripheral neuropathy accompanied by headache, muscular weakness, decreased reflexes in the extremities, incoordination, etc., and one had acute reversible encephalopathy with an abnormal electroencephalogram (Environmental Risk Assessment for Chemical Substances vol. 2 (Ministry of the Environment, 2003)). Also, a worker who had been exposed to ethylene oxide adjacent to a sterilizer for ten years developed impaired memory, impaired concentration, and emotional disorder, and the poisoning case report indicates that the substance is toxic not only to the peripheral nerve but to the central nerve (OEL Documentations Vol. 32 (Japan Society For Occupational Health (JSOH), 1990)). In animal tests, neuromuscular effects were observed such as hindlimb ataxia, axonal degeneration of myelinated nerve fibers in the hindlimb after 13-week inhalation exposure of rats (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)), and reduced locomotion and righting reflex after inhalation exposure of mice for 10-11 weeks (ACGIH (2001)). From the above knowledge, it was classified in Category 1 (nervous system). Furthermore, there is a report on anemia after 26-week inhalation exposure of rats to 100-500 ppm and decreases in erythrocyte counts, hemoglobin, hematocrit, bone marrow cell density, and lymphocyte counts after inhalation exposure of mice to 255-600 ppm for 10-13 weeks (Initial Risk Assessment Report 36 (NITE, CERI, NEDO, 2005)), and it is reported that after 14-week inhalation exposure of mice, rhinitis, loss of polarity of olfactory and respiratory epithelial cells, necrosis of epithelium, and transmigration of inflammatory cells with accumulation of purulent exudate were most frequently found at or above 200 ppm in the nasal port of the respiratory tract in addition to renal tubular degeneration at 100-600 ppm and renal tubular necrosis at 600 ppm (NTP TR 326 (1987)). Because all the above effects were seen at doses corresponding to the guidance value range for Category 2, it was classified in Category 2 (blood, kidney, respiratory tract).
10	Aspiration hazard	Not applicable	- -	-	-	Gas (GHS definition)

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)	Category 3	- -	H402	P273 P501	It was classified in Category 3 from 96-hour LC50 = 84 mg/L for fish (Pimephales promelas) (EHC 55, 1985, etc.).
11	Hazardous to the aquatic environment (Long-term)	Not classified	- -	-	-	Reliable chronic toxicity data were not obtained. It was classified as "Not classified" due to being rapidly degradable (a 4-week degradation rate by BOD: 107% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1995)), and low bioaccumulation (BCF = < 0.36 to 0.88 (2 mg/L), < 3.7 to 6.0 (0.2 mg/L) (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1995)), although it was classified in toxicity Category 3 in acute toxicity.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

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.

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