NITE - Chemical Management Field

GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	109-86-4
Chemical Name	Ethylene glycol monomethyl ether
Substance ID	H26-B-022, -
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 39 deg C (closed cup) (ICSC (2003)). Besides, it is classified in Class 3, PGIII (UN1188) 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 285 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, steel and stainless steel are durable as a container. There is information that it is corrosive to copper and aluminum (Hommel (1991)).

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	Based on 10 reports of LD50 values within the range of 2,370-5,490 mg/kg for rats (PATTY (6th, 2012), CICAD 67 (2010), OEL Documentations (Japan Society For Occupational Health (JSOH), 2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ACGIH (7th, 2006), Environmental Risk Assessment for Chemical Substances Vol. 4 (Ministry of the Environment, 2005), ECETOC TR95 (2005), DFGOT vol. 6 (1994), EHC 115 (1990)), it was classified as "Not classified."
1	Acute toxicity (Dermal)	Category 4	Warning	H312	P302+P352 P280 P312 P321 P362 P364 P501	There are 11 reports of LD50 values within the range of 1,280-3,920 mg/kg for rabbits. According to the revised GHS classification guidance for the Japanese government, it was classified in Category 4 to which most of the data sets (7data) (1,280 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 4 (Ministry of the Environment, 2005)), 1,290 mg/kg (PATTY (6th, 2012)), 1,300 mg/kg (ECETOC TR95 (2005), EHC 115 (1990)), 1,300 mg/kg (EHC 115 (1990)), 2,000 mg/kg (Environmental Risk Assessment for Chemical Substances Vol. 4 (Ministry of the Environment, 2005)), 2,000 mg/kg (PATTY (6th, 2012)), 2,000 mg/kg (DFGOT vol. 6 (1994))) corresponded. Besides, 1 set corresponded to Category 5, and 3 were aggregated sets of multiple data. Therefore they were excluded from the number for the classification.
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 a report of an LC50 value (4 hours) of 16,000 mg/m3 (=5,136 ppm) (CICAD 67 (2010)) for rats, it was classified in Category 4. Besides, since the LC50 value was lower than 90% of the saturated vapor concentration (8,193 ppm), the reference value in units of ppm was applied as a vapour without a mist. Instead of the 7-hour data of the previous classification, the classification was reviewed by giving priority to the 4-hour test data as a new information source (CICAD 67 (2010)).
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 were multiple primary skin irritation tests with rabbits, among which there is a report that no irritation was observed in a test by 4-hour application of 0.5 mL of the undiluted liquid of this substance (according to EEC guideline) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ECETOC TR95 (2005), BUA 198 (1996)), and a report that mild irritation was observed in a test by 24-hour application of 483 mg of this substance (IUCLID (2000)). From the above results, it was classified as "Not classified" (Category 3 in UN GHS classification).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	There is a report that, in an eye irritation test with rabbits (OECD TG 405), after applying 0.1 mL of the undiluted liquid of this substance, the average irritation scores of 24 to 72 hours after application stood at 1.3-1.1 for conjunctival redness, 0.5-0.2 for conjunctival edema and 0.2-0.0 for corneal opacity, and it was not irritating (BUA 198 (1996)). In addition, there is a report that, in another eye irritation test with rabbits, no irritation was observed after applying 0.5 mL of the undiluted liquid of this substance (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ECETOC TR95 (2005)). From the above results, it was classified as "Not classified."
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, there is a report that, in a maximization test with guinea pigs, no sensitization was observed (CICAD 67 (2010)). However, because details including test conditions and test results were unknown, it was classified as "Classification not possible."
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 showed mostly negative results with some weakly positive results in dominant lethal tests and chromosomal aberration tests with rats and mice, a micronucleus test with mice and sister chromatid exchange tests with humans peripheral blood and mice bone marrow cells (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), OEL Documentations (Japan Society For Occupational Health (JSOH), 2009), CEPA (2002), ECETOC TR95 (2005), CICAD 67 (2010), DFGOT vol. 6 (1994), PATTY (6th, 2012)). As for in vitro, it was negative in a bacterial reverse mutation test and a gene mutation test with cultured mammalian cells, and except for one positive result in a chromosomal aberration test, it was all negative in a chromosomal aberration test and a sister chromatid exchange test with humans lymphocytes, and an unscheduled DNA synthesis test with humans fibroblasts (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), Environmental Risk Assessment for Chemical Substances Vol. 4 (Ministry of the Environment, 2005), OEL Documentations (Japan Society For Occupational Health (JSOH), 2009), CEPA (2002), ECETOC TR95 (2005), CICAD 67 (2010), DFGOT vol. 6 (1994), PATTY (6th, 2012)).
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 multi-generation reproductive toxicity test with rats and mice by the oral route (drinking water), a decrease in the number of surviving fetuses, reduced conception rate and a decrease in the number of pregnancies were observed at doses equivalent to ca. 20-200 mg/kg bw/day (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). In teratogenicity tests by the oral route, in mice, at doses (60-300 mg/kg/day) where no maternal toxicity was observed, or decreased body weight gain was observed, increased incidence of fetal death, malformations of the fore/hind limbs (syndactyly, brachydactyly, oligodactyly and polydactyly), skeletal malformations (bifurcation or split of cervical vertebral arches), external malformation (exencephaly) were observed. In rats, cardiovascular malformations were observed at a dose (equivalent to 31 mg/kg/day) where no maternal toxicities were observed. In Macaca fascicularis, there is a report on embryonic death at or above 12 mg/kg/day, all embryonic deaths and a missing digit on each forelimb in one dead embryo at 36 mg/kg/day. In teratogenicity tests by the inhalation route, in mice, testicular hypoplasia and skeletal variations were observed in the fetus at a concentration (50 ppm) where decreased body weight gain was observed in maternal animals. In rats, skeletal variations were reported. In rabbits, increased fetal resorptions, decreased fetal weight, external malformations (arthrogryposis, clubfoot, no nails, brachydactyly, oligodactyly and umbilical hernia, etc.), skeletal malformations (phalanx defect), visceral malformations (ventricular septum defect, subclavian arterial hypoplasia, renal agenesis, renal malformation, renal pelvis dilatation, diaphragmatic hernia, ovarian defects and bladder hypoplasia, etc.) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)) were reported. In teratogenicity tests by the dermal route, in rats, external malformations (bent forelimbs) and visceral anomalies (swelling of the kidney pelvis, dilatation of the ureter) were reported at a dose (500 mg/kg) where decreased body weight gain was observed in maternal animals (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). From the above, reproductive effects were observed clearly in experimental animals. Additionally, it was listed as reproductive toxicants Group 1 (known to exhibit reproductive toxicity in humans) in Recommendation of Occupational Exposure Limits (2013) (provisional proposed in 2013). In the OEL Documentations (Japan Society For Occupational Health (JSOH), 2009), regarding reproductive effects on humans, it was described that "A follow-up survey was conducted on 28 female workers who were exposed to EGME for an average of 4.6 years between 1970 and 1977 at a manufacturing facility of radio and television capacitors. 41 children were born from 28 females. Children who were not exposed during the pregnancy period served as a control group. As the result, although the frequency of congenital anomaly and chromosomal aberrations seemed significantly higher in the exposed group, it was necessary to decipher cautiously because exposure levels in the past and at the survey time were unknown, and the genotoxicity of this substance was negative, and the observed increase in the frequency of chromosomal structural abnormalities was considered due to possible effects from combined exposure with other substances." From the above, although clear reproductive effects on experimental animals were observed, the effects on humans were ambiguous. Therefore, it was classified in Category 1B.
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, haemal system, kidney), Category 3 (respiratory tract irritation, narcotic effects)	Danger Warning	H370 H335 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	It was mildly irritating to the respiratory tract in humans. By the inhalation route, it caused cough, sore throat, dizziness, headache, nausea, vomiting and confusion, and there were some cases of loss of consciousness at high concentrations. By the oral route, as in the case reports, there were reports of acute effects such as death, nausea, cyanosis, tachypnea, tachycardia, metabolic acidosis, central nervous symptoms such as confusion and frenzy, acute hemorrhagic gastritis, acute pancreatitis, blackened kidneys and renal tubular degeneration, congestive edema in the brain and meninges (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)), fatty changes in the liver, blackened kidneys and renal tubule degeneration, congestion and edema in the brain and meninges, metabolic acidosis and lung disorders (Environmental Risk Assessment for Chemical Substances Vol. 4 (Ministry of the Environment, 2005), CICAD 67 (2010)). Moreover, it is described in the CICAD 67 (2010) that human epidemiological data are indicative of a clear association between exposure and effects on the hemal system as well as those on the nervous system. In experimental animals, there were reports of hematological effects by the oral, inhalation and dermal routes in rats, etc. (CICAD 67 (2010)), lung and kidney disorder by inhalation in mice (OEL Documentations (Japan Society For Occupational Health (JSOH), 2009), ACGIH (7th, 2006)), lung edema, slight liver injury, marked kidney injury and hemoglobinuria by the oral route in mice (PATTY (6th, 2012)), neurological toxicity such as inhibition of conditioned avoidance response, increased barbiturate induced sleeping time and partial hindlimb paralysis at and above 395 mg/m3 by inhalation of rats and mice (CICAD 67 (2010)). These findings were observed within the guidance value range of Category 1. Besides, findings of the liver and lungs were considered as secondary effects of this substance. From the above, it was classified in Category 1 (central nervous system, hemal system, kidney), Category 3 (respiratory tract irritation, narcotic effects).
9	Specific target organ toxicity - Repeated exposure	Category 1 (haemal system, testis)	Danger	H372	P260 P264 P270 P314 P501	In epidemiological studies from human occupational exposure, red blood cell count, hemoglobin concentration and hematocrit value were significantly reduced in the group of male workers exposed to this substance, compared to the non-exposed control group, and the frequency of anemia increased to 26.1% in the exposed group compared to 3.2% in the control group. At the time when clear hematotoxicities were observed in the exposed group, and 2.5 months and 6 months after the time when the workplace environments were improved, follow-up measurement of the air concentrations of this substance at the workplace and the urinary metabolites (methoxyacetic acid: MAA) in the exposed group were conducted. As a result, both showed a high correlation, and it was considered that the exposure to this substance and the onset of hematotoxicity were related (CICAD 67 (2010)). In addition, among epidemiological survey reports, there is a report that inhibited spermatogenesis was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ECETOC TR95 (2005), CICAD 67 (2010)). In experimental animals, atrophy of the thymus and testis was observed at a dose (70 mg/kg/day) equivalent to Category 2 in a test in which rats were dosed by drinking water for 13 weeks, and decreased weight and tissue changes in the testis were observed at high doses exceeding the range of Category 2 in a test in which mice were dosed by drinking water for 13 weeks (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), CICAD 67 (2010)). Additionally, decreased leukocyte counts, hemoglobin concentration and hematocrit value, and testis atrophy were observed at concentrations (0.31-0.93 mg/L) equivalent to Category 2 also in tests in which rats or rabbits were exposed to the vapour of this substance by inhalation for 13 weeks (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ECETOC TR95 (2005), CICAD 67 (2010)). From the above, based on the findings in humans and experimental animals, it was classified in Category 1 (hemal system, testis). Besides, it was confirmed that multiple findings, adopted in the previous classification, to humans related to the effects on the central nervous system (such as nervous symptom, encephalopathy) were all due to effects of acute or repeated exposure by combined exposure with other substance (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), ECETOC TR95 (2005), CICAD 67 (2010)). Therefore, it was deleted from the target organs in the current classification.
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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