NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	111-15-9
Chemical Name	Ethylene glycol monoethyl ether acetate (Cellosolve acetate)
Substance ID	H26-B-020, -
Classification year (FY)	FY2014
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	FY2012 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)
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	Category 3	Warning	H226	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	It was classified in Category 3 based on a flash point of 51.1 deg C (closed cup) (ICSC (2003)). Besides, it is classified in Class 3, PG III (UN1172) in UNRTDG.
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 379 deg C (ICSC (2003)).
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. Besides, there is information that steel, stainless steel, and aluminum are durable as a container (Hommel (1991)), or that aluminum is unsuitable as a container (GESTIS (Access on Aug 2014)).

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	There are 6 reports of LD50 values of 2,700 mg/kg, 2,900 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)), 3,900 plus or minus 100 mg/kg (male), 2,900 plus or minus 100 mg/kg (female) (DFGOT vol. 6 (1994), PATTY (6th, 2012)), 5,100 mg/kg (EHC 115 (1990), PATTY (6th, 2012)), 2,900-7,500 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ECETOC TR95 (2005)) for rats. According to the revised GHS classification guidance for the Japanese government, it was classified as "Not classified" (Category 5 in UN GHS classification) to which the larger number of values corresponds.
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on LD50 values of 10,227 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)), 10,300 mg/kg (ACGIH (7th, 2001), PATTY (6th, 2012)), 10,333 mg/kg (EHC 115 (1990)), 10,500 mg/kg (DFGOT vol. 6 (1994), PATTY (6th, 2012)), 10,300-10,500 mg/kg (ECETOC TR95 (2005), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) for rabbits, it was classified as "Not classified."
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Category 4	Warning	H332	P304+P340 P261 P271 P312	Based on an LC50 value (2 hours) of >1,500 ppm for rats (converted 4-hour equivalent value: >1,061 ppm) (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)), and on LC50 values (8 hours) of 2,239 ppm (converted 4-hour equivalent value: 3,166 ppm) (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)) and 1,499-2,239 ppm (converted 4-hour equivalent value: 2,119-3,166 ppm) for rats, it was classified in Category 4. Besides, because LC50 values were lower than 90% of the saturated vapor concentration (3,079 ppm), the reference value in units of ppm was applied as a vapour without a mist.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Classification not possible due to lack of data.
2	Skin corrosion/irritation	Not classified	- -	-	-	There is a report that in a Draize test with rabbits, slight irritation was observed after application of this substance for 24 hours (ECETOC TR95 (2005), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). In addition, there are multiple reports that in a skin primary irritating test (EEC test method), no irritation was observed after occlusive application for 4 hours (ECETOC TR95 (2005), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), and that it was slightly irritating (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), PATTY (6th, 2012)). From the above, it was classified as "Not classified" (Category 3 in UN GHS classification).
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	Based on a report that in a primary irritation test with four rabbits (OECD TG 405, GLP), although corneal opacity of a score 2 in 1 animal, conjunctival redness of a score 1 or 2 in 4 animals, conjunctival edema of a score 1 or 2 in 3 animals were observed after application of 0.1 mL of the undiluted test substance, all of these almost disappeared 7 days after application, and the maximum average score, MMAS (corresponding to AOI) was 15.0 (ECETOC TR 48 (1988)), it was classified in Category 2. Besides, there were multiple reports of other skin irritation tests with rabbits, and there were reports of no irritation results or mild irritation results (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ECETOC TR95 (2005), PATTY (6th, 2012)).
4	Respiratory sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	Classification not possible due to lack of data. Besides, although there is a report that in a Magnusson-Kligman test with guinea pigs, no sensitization was observed after induction with 10% of this substance (ECETOC TR95 (2005)), these data were judged as insufficient for use in the classification since the details of the test conditions, etc. were unknown. The category was changed due to addition of information.
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), Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)). As for in vitro, both negative and positive results were obtained in bacterial reverse mutation tests, and gene mutation tests, chromosomal aberration tests and sister chromatid exchange tests with cultured mammalian cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013), NTP DB (Access on July 2014)).
6	Carcinogenicity	Classification not possible	- -	-	-	Classification not possible due to lack of data.
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	In a teratogenicity test with rats by the inhalation route, visceral malformations (cardiovascular malformations) and skeletal malformations were observed at a dose where maternal toxicity was not observed (2,140 mg/m3) (ECETOC TR95 (2005), DFGOT vol. 6 (1994)). In addition, in a teratogenicity test with rabbits by the inhalation route, increases in external, skeletal and visceral malformations and in complete resorptions were observed at a dose where maternal toxicity appeared (550 mg/m3) (ECETOC TR95 (2005), DFGOT vol. 11 (1998)). Additionally, in a teratogenicity test with rats by the dermal route, decreased body weights in the fetuses, a decreased number of offspring/litter, an increase in prenatal mortality, visceral malformations (cardiovascular malformations) and skeletal malformations were observed at an extremely high dose where maternal toxicity appeared (5,923 mg/kg bw/day) (ECETOC TR95 (2005), DFGOT vol. 11 (1998)). From the above, there is a report that in a teratogenicity test with rats by the inhalation route, visceral malformations and skeletal malformations were observed at a dose where maternal toxicity did not appear. Therefore, it was classified in Category 1B.
8	Specific target organ toxicity - Single exposure	Category 1 (haemal system), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	When rats were exposed by inhalation to 2,000 ppm of this substance for 4 hours, hematuria was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). There was a report on hematuria and hypertrophic kidneys dilated with blood by an oral dose of 2,900 mg/kg to rats (PATTY (6th, 2012)). In addition, there was a report of gastrointestinal tract irritation and mild liver injury (PATTY (6th, 2012)). Moreover, there were descriptions of dizziness, lethargy, headache, loss of consciousness by an inhalation exposure, and of vomiting added to the above symptoms by an oral dose (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)). Additionally, although no description of the subjects, it is described that this substance affected blood, and caused blood cell disorder, anemia, and kidney injury, effects on the central nervous system and loss of consciousness at high concentrations (Environmental Risk Assessment for Chemical Substances Vol.11 (Ministry of the Environment, 2013)), and caused injury of the central nervous system, hemal system, lung and kidney at high concentrations (HSDB (Access on June 2014)). Among all the above information, not all the pieces of information are ones by which clear categorization is possible. However, hematuria data by inhalation exposure was observed within the guidance value range of Category 1, and the symptoms by an oral dose were observed within the guidance value range for Category 2. The findings for the liver and kidney by oral dose to rats occurred at doses exceeding the guidance value of Category 2, and the category from the lung findings was unknown. Moreover, since the category from the symptoms such as dizziness by inhalation exposure was unknown, narcotic effects were judged as appropriate based on the type of symptoms. From the above, it was classified in Category 1 (hemal system), Category 3 (narcotic effects).
9	Specific target organ toxicity - Repeated exposure	Category 1 (haemal system, testis)	Danger	H372	P260 P264 P270 P314 P501	This substance is rapidly hydrolyzed via esterase in various tissues in the body to produce ethylene glycol monoethyl ether (EGEE; CAS RN: 110-80-5) (CICAD 67 (2010), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). EGEE is oxidized by alcohol dehydrogenase, via ethoxy acetaldehyde to ethoxy acetic acid (EAA) and excreted in the urine as EAA or its glycine conjugate (CICAD 67 (2010), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). This EAA is a common active metabolite to this substance, the acetate ester of EGEE and EGEE. Since this substance is also hydrolyzed after being absorbed and metabolized to the active metabolite, EAA, the substance is thought to cause similar toxicities to EGEE. In CICAD 67 (2010), both substances were treated in the same group and evaluated together. In fact, as for both this substance and EGEE, there is a report that effects on the hemal system and genetic organs were observed in humans and experimental animals (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), CICAD 67 (2010)). In humans, the ability to metabolize to EAA was higher than that in rats, and EAA clearance tended to be delayed than in rats. Therefore, the EAA residence time in the body of humans is longer than in the experimental animals, so it was pointed out that toxic effects might appear from at lower dose (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), CICAD 67 (2010)). From the above, since the classification of this substance was considered the same as that of EGEE, it was classified in Category 1 (hemal system, testis). Besides, because information sources that were not used in the previous classification were used, the classification result was different.
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)	-	- -	-	-	-
11	Hazardous to the aquatic environment (Long-term)	-	- -	-	-	-
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.

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