NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	112-07-2
Chemical Name	Ethylene glycol monobutyl ether acetate [2-butyoxyethyl acetate or EGBEA]
Substance ID	m-nite-112-07-2_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 present in the molecule associated with explosive properties.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Flammable gases	Not classified (Not applicable)	- -	-	-	"Liquids" according to GHS definition.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not an aerosol product.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	"Liquids" according to GHS definition.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	"Liquids" according to GHS definition.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Flammable liquids	Category 4	- Warning	H227	P370+P378 P210 P280 P403 P501	Based on a flash point of 71 degrees C (closed cup) (HSDB (Access on June 2015)), it was classified in Category 4.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Flammable solids	Not classified (Not applicable)	- -	-	-	"Liquids" according to GHS definition.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an ignition point of 340 degrees C (HSDB (Access on June 2015)).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	"Liquids" according to GHS definition.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No established test method suitable for liquid substances.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (Not applicable)	- -	-	-	Not containing metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	It is an organic compound which does not contain fluorine or chlorine but contains oxygen, and the oxygen is not chemically bonded to the elements other than carbon or hydrogen.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	"Liquids" according to GHS definition.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	It is an organic compound that does not contain bivalent -O-O- structure in the molecule.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
16	Corrosive to metals	Classification not possible	- -	-	-	Due to no data, the classification is not possible.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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	- -	-	-	From reported LD50 values of 2,350 mg/kg (EU-RAR (2006)), 3,000 mg/kg (males), 2,400 mg/kg (females) (EU-RAR (2006), SIDS (2006), ACGIH (7th, 2003), ATSDR (1998), ECETOC TR 64 (1995), DFGOT vol. 6 (1994)), and 7,000 mg/kg (EU-RAR (2006), ACGIH (7th, 2003)) for rats, it was classified as "Not classified" (Category 5 in UN GHS classification).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Dermal)	Category 4	Warning	H312	P302+P352 P362+P364 P280 P312 P321 P501	From reported LD50 values of 1,485 mg/kg (EU-RAR (2006), ACGIH (7th, 2003)) and 1,500 mg/kg (EU-RAR (2006), SIDS (2006), ACGIH (7th, 2003), ATSDR (1998), ECETOC TR 64 (1995), DFGOT vol. 6 (1994)) for rabbits, it was classified in Category 4.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	"Liquids" according to GHS definition.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	The classification is not possible due to lack of data. The category could not be determined only by the information that toxicity effects were not reported after 4-hour inhalation to the saturated vapour pressure concentration (about 400 ppm) of this substance in rats (EU-RAR (2006), SIDS (2006), ACGIH (7th, 2003)). Besides, a reference value in the unit of ppm was applied from the information that the saturated vapour was used in the test.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	Due to lack of data, the classification is not possible.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
2	Skin corrosion/irritation	Not classified	- -	-	-	It is reported that in a Draize test using rabbits, 4 out of 6 animals showed minimal irritation after application of this substance (unknown application time), and a primary dermal irritation index was 0.17 (SIDS (2006), EU-RAR (2006), ATSDR (1998), ECETOC TR 64 (1995)). Besides this, in skin irritation tests using rabbits, there are multiple reports of no irritation or slight irritation (EU-RAR (2006)). On the other hand, it is reported that the moderate redness was observed after 4-hour occlusive application of 0.5 mL undiluted this substance to rabbits (EU-RAR (2006), ECETOC TR 64 (1995)). Moreover, in a test in which 83 uL of undiluted this substance was applied to eight volunteers for 48 hours and cutaneous blood flow value (CBFV) was measured, this substance was reported to be slightly irritating (EU-RAR (2006)). From the above results, it was judged to be "Not classified" (Category 3 in UN GHS classification).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
3	Serious eye damage/eye irritation	Not classified	- -	-	-	In an eye irritation test using rabbits, an irritation score was 0.67, and slight conjunctival redness and discharge were observed but resolved within 48 hours (SIDS (2006), ATSDR (1998), DFGOT vol. 6 (1994), ECETOC TR 64 (1995)). It is reported that in another test using rabbits, after application of undiluted this substance, slight redness and edema were found but resolved within 1 hour (EU-RAR (2006)). From the above results, the substance was judged to be "Not classified."	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Respiratory sensitization	Classification not possible	- -	-	-	Due to lack of data, the classification is not possible.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
4	Skin sensitization	Not classified	- -	-	-	It is reported that in a Buehler test using guinea pigs (in accordance with European technical guideline B6, GLP compliance), skin reaction was not observed after induction and challenge of this substance (99.1 %) (EU-RAR (2006), ATSDR (1998)). Moreover, it is reported on ethylene glycol monobutyl ether, a metabolite of this substance that sensitization was not found in a maximization test using guinea pigs (SIDS (2006)). From the above results, the substance was judged to be "Not classified."	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
5	Germ cell mutagenicity	Classification not possible	- -	-	-	The classification is not possible due to lack of data. There are no data on this substance, but there exist data on ethylene glycol monobutyl ether, an analog substance of this substance.As for in vivo, a micronucleus test using bone marrow cells of rats and mice and a DNA damage test using brain, liver, kidney, spleen, and testis of rats and mice were all negative (EU-RAR (2006), SIDS (2006)). As for in vitro, a positive result was observed only at a high dose in a gene mutation test and a sister chromatid exchange test. However, other tests, namely, a bacterial reverse mutation test, and a gene mutation test, a chromosomal aberration test, and a sister chromatid exchange test in cultured mammalian cells were all negative (SIDS (2006)). Besides, it is written in EU-RAR (2006) that mutagenicity data of ethylene glycol monobutyl ether are applicable as data for this substance for which data do not exist.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
6	Carcinogenicity	Classification not possible	- -	-	-	There is no carcinogenicity test report on this substance itself, but this substance is decomposed by esterases in vivo and metabolized to ethylene glycol butyl ether (EGBE) (SIDS (2006), EU-RAR (2006)). For EGBE, a 2-year inhalation exposure test using rats and mice was conducted, and increased incidences of liver hemangiosarcoma (male mice) and papilloma or carcinoma in squamous epithelium of the forestomach (female mice) were regarded as known information (SIDS (2006), EU-RAR (2006)). Based on this knowledge, ACGIH classified this substance in A3 in carcinogenicity (ACGIH (7th, 2003)). However, either liver hemangiosarcoma or forestomach tumor was not observed in male and female rats (SIDS (2006), EU-RAR (2006)). Because as a result of detailed investigation of the mechanism of tumors in mice, IARC and EU considered that liver hemangiosarcoma possibly resulted from pigmentation in the liver by hemolytic action of this substance, and this mechanism is unlikely to happen in humans who are highly resistant to hemolysis of red blood cells, and forestomach tumor is not applicable to humans (EU-RAR (2006), IARC vol. 88 (2006)), IARC classified EGBE in Group 3 in carcinogenicity (IARC vol. 88 (2006)). EU concluded that EGBE does not correspond to a carcinogenic substance in the re-evaluation of EGBE in 2000 because there is no serious risk of human carcinogenicity, judging from the mechanism, and described how this conclusion was confirmed again in the carcinogenicity evaluation in 2004 (SIDS (2006)). As above, there is little evidence to classify EGBE, a metabolite of this substance as a carcinogenic substance, and this substance is considered to be the same. However, due to no epidemiological knowledge in humans, and IARC's Group3 classification result for EGBE, the substance was classified as "the classification is not possible" in this hazard class. Besides, due to the revised classification criteria in the revised classification Guidance, the classification result was different from the previous one ("Not classified" in 2009).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
7	Reproductive toxicity	Classification not possible	- -	-	-	There is no reproductive toxicity information on this substance. As for ethylene glycol butyl ether (EGBE), an in vivo metabolite, it is written that in a continuous breeding test using mice in drinking water administration, reproductive toxicity effects such as decreased numbers of pregnant females and live litter, and lower body weight in offspring were observed at the dose (above the limit dose, corresponding to 1,340 mg/kg/day) higher than the dose where general toxicity effects (increased relative weight of liver/kidney) occurred in parent animals (SIDS (2006), ACGIH (7th, 2003)). Moreover, in each test in pregnant rats or rabbits in inhalation exposure to EGBE during an organogenetic period, in rats, there is no abnormality except an increased incidence of skeletal variations in fetuses even at the dose where anemia and weight gain reduction were found in maternal animals. Also in rabbits, only a decreased number of implanted embryos was observed at the dose where weight gain reduction and deaths (a part of animals) were observed in maternal animals (SIDS (2006), ACGIH (7th, 2003)). However, due to not direct test results on this substance, it was classified as "the classification is not possible" in this hazard class.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, blood system, kidney)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	There is no human information on this substance. In an incident where 18-year-old male swallowed 360-480 mL of a glass cleaner containing 22% ethylene glycol monobutyl ether, a metabolite of this substance, severe central nervous depression, metabolic acidosis, and hematuria were observed. In an incident where 50-year-old female swallowed 30-60 mL of a cleaning solution (ingested about 30-60 mL of EGBE) containing 9-13% ethylene glycol monobutyl ether as a glass cleaner, dyspnea, coma, mydriasis, hematuria, decreased hemoglobin, metabolic acidosis, and hypokalemia were found. Other than these, in multiple cases in humans of accidental ingestion containing ethylene glycol monobutyl ether, central nervous depression, hematuria, metabolic acidosis, decreased red blood cell count, and decreased hemoglobin were observed (SIDS (2006), ATSDR (1998)). As for experimental animals, there are multiple pieces of information on this substance. Hypoactivity, labored breathing, weakness, tremors, hemoglobinuria, hematuria, and visual changes in the kidney were observed in oral administration (rats (LD50=3,089 mg/kg), mice (LD50=1,774 mg/kg), corresponding to Category 2) in rats and mice. Hemoglobinuria and anemia were found in oral administration (188 mg/kg, corresponding to Category 1) in rabbits, but resolved after three weeks. Shallow breathing and incoordination in inhalation exposure (LC50 > 0.56 mg/L, corresponding to Category 1) in rats and transient hemoglobinuria, hematuria, and hemolysis in inhalation exposure (2.66 mg/L, corresponding to Category 1) in rabbits were observed, but these signs resolved within 48 hours. In rabbits, weakness, hypothermia, and hemoglobinuria were observed after dermal exposure (435-1,500 mg/kg, corresponding to Category 1), and animals showed hemoglobinuria, hematuria, decreased red blood cell count, and hemolytic action after dermal exposure (610-2,200 mg/kg, corresponding to Category 1) and died. However, the surviving animals recovered 8-14 days after exposure and did not show pathologic damage in necropsy (above SIDS (2006), ATSDR (1998), ACGIH (7th, 2003), EU-RAR (2006), DFGOT vol. 6 (1994)). It is written that because after in vivo absorption of alkoxyethanol acetate, it hydrolyzes easily to form alkoxyethanol and acetic acid, toxicity and metabolism of ethylene glycol monobutyl ether (including biological monitoring) are also applicable to this substance (Provisional Acceptable Concentration of the Japan Society for Occupational Health (2008)). Therefore, human data on ethylene glycol monobutyl ether were also adopted. From the above, for ethylene glycol monobutyl ether, a metabolite of this substance, central nervous depression, metabolic acidosis, hematuria, decreased red blood cell count, and decreased hemoglobin were observed in humans, and central nervous depression and effects on blood system and kidney were found in experimental animals. Therefore, the substance was classified in Category 1 (central nervous system, blood system, kidney).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system, kidney)	Warning	H373	P260 P314 P501	There is no human information. As for experimental animals, effects on blood system and kidney were observed. As effects on blood system, in a 1-month inhalation toxicity test using rats and rabbits, hemoglobinuria in rats and hemoglobinuria, hematuria, and decreased RBC/hematocrit in rabbits were found at 400 ppm (converted to a Guidance value equivalent: 0.39 mg/L) (EU-RAR (2006), ACGIH (2003), DFGOT vol. 6 (1994)). Moreover, in a 4-week inhalation toxicity test using rats and rabbits, hemoglobinuria and hemolytic anemia were observed at 340 ppm (converted to a Guidance value equivalent: 0.49 mg/L) (EU-RAR (2006), ATSDR (1998), ACGIH (2003), DFGOT vol. 6 (1994)). The following was found as effects on kidney (EU-RAR (2006), ATSDR (1998)): tubular nephrosis, cloudy swelling, and hemorrhagic necrosis in a 1-month inhalation toxicity test using rats at 400 ppm (converted to a Guidance value equivalent: 0.39 mg/L); tubular nephritis with cortical tubular enlargement or atrophy, inflammatory fibrosis, dilatation of distal convoluted tubule and Henle's loop, and tubular enlargement with hyaline casts in a 10-month inhalation toxicity test using rats at 100 ppm/6h (converted to a Guidance value equivalent: 0.44 mg/L); and hypertrophic kidney, kidney swollen with blood, pooling of blood in the bladder, necrotic tubular nephritis, atrophic tubular dilatation, and luminal granular deposits in a 1-month inhalation toxicity test using rabbits at 400 ppm (converted to a Guidance value equivalent: 0.39 mg/L). Besides, because all these used a single dose, clear LOAEL and NOAEL could not be determined. Besides, there is the comment in SIDS (2006) that there are no reliable data. However, all effects were observed at least within a range of Category 2. Therefore, the substance was classified in Category 2 (blood system, kidney).	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
10	Aspiration hazard	Classification not possible	- -	-	-	Due to lack of data, the classification is not possible.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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)	Category 3	- -	H402	P273 P501	From 96-hour LC50 = 20 to 40 mg/L for fish (Oncorhynchus mykiss) (EU-RAR, 2006), it was classified in Category 3.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
11	Hazardous to the aquatic environment Long term (Chronic)	Category 3	- -	H412	P273 P501	If chronic toxicity data are used, then it is classified as "Not classified," due to 72-hour NOEC = 300 mg/L for algae (Pseudokirchneriella subcapitata) (SIDS, 2006) although appropriate data on rapid degradability were not obtained. If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 3 due to appropriate data not obtained on rapid degradability, and 96-hour LC50 = 20 to 40 mg/L for fish (Oncorhynchus mykiss) (EU-RAR, 2006). It was classified in Category 3 by drawing a comparison between the above results.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data.	FY2015	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))

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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