NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	111-77-3
Chemical Name	2-(2-Methoxyethoxy)ethanol (synonym: Diethylene glycol monomethyl ether)
Substance ID	R03-B-009-METI, MOE
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2008 FY2007
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
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 classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Category 4	- Warning	H227	P370+P378 P210 P280 P403 P501	It was classified in Category 4 based on a flash point of 87 deg C (closed cup) (GESTIS (Accessed July 2021)).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
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.
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 215 deg C (GESTIS (Accessed July 2021)).
10	Pyrophoric solids	Not classified (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 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).
13	Oxidizing liquids	Not classified (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 classified (Not applicable)	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Not classified	- -	-	-	It was classified as "Not classified" from information that steel and aluminum are resistant as containers (Hommel (1996)).
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: 6,900 mg/kg (EU RAR (2000)) (2) LD50 for rats: > 5,500 mg/kg (EU RAR (2000), AICIS IMAP (2013)) (3) LD50 for rats: 9,210 mg/kg (EU RAR (2000), ECETOC TR (2005))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: between 6,540 to 20,400 mg/kg (EU RAR (2000), AICIS IMAP (2013)) (2) LD50 for rabbits: 9,284 mg/kg (EU RAR (2000)) (3) LD50 for rabbits: 9,404 mg/kg (Government of Canada, Hazardous Substance Assessment (2020))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Also, since there was a description in the literature that an experiment was conducted at the saturated vapor pressure concentration, this substance was judged as vapor. [Reference Data, etc.] (1) LC50 (6 hours) for rats: > Saturated vapor pressure concentration (EU RAR (2000)) (2) LC50 (4 hours) for rats: > Saturated vapor pressure concentration (value described in the literature: 1.47 mg/L) (Government of Canada, Hazardous Substance Assessment (2020))
1	Acute toxicity (Inhalation: Dusts and mists)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Also, the exposure concentration was higher than the saturated vapor pressure concentration (1.31 mg/L) and it was judged to be in a mist state. [Evidence Data] (1) LC50 (1 hour) for rats: > 200 mg/L (converted 4-hour equivalent value: 50 mg/L) (EU RAR (2000))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in an acute dermal irritation/corrosion test (equivalent to OECD TG 404, occlusive, 4-hour application, 72-hour observation) with rabbits (n=6), no skin irritation was observed (erythema and scab score: 0/0/0/0/0/0, edema score: 0/0/0/0/0/0) (EU RAR (2000), AICIS IMAP (2013), REACH registration dossier (Accessed July 2021), Government of Canada, Hazardous Substance Assessment (2020)). (2) It was reported that, in a Draize study with rabbits and guinea pigs, slight skin irritation was observed (Government of Canada, Hazardous Substance Assessment (2020)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in an acute eye irritation/corrosion test with rabbits (n=6) (equivalent to OECD TG 405, observation for 72 hours), the mean chemosis score at 24/48/72 hours after application was 0.1, the mean conjunctival redness score was 0.1, the mean cornea opacity score was 0, and the mean iris score was 0 (EU RAR (2000), AICIS IMAP (2013), REACH registration dossier (Accessed July 2021), Government of Canada, Hazardous Substance Assessment (2020)). (2) It was reported that, in an eye irritation test with rabbits, very slight irritation with no corneal effects was observed (Government of Canada, Hazardous Substance Assessment (2020)). (3) It was reported that a repeated application of undiluted test material into rabbit eyes for 5 days/week in 2 weeks (a total of 10 times) failed to cause more than a mild irritation (Government of Canada, Hazardous Substance Assessment (2020)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a Maximization test with 25 volunteers using a 20% solution of this substance, no skin sensitization was observed (EU RAR (2000), AICIS IMAP (2013), Government of Canada, Hozadous Substance Assessment (2020)). (2) It was reported that, in a Maximization test with guinea pigs (n=10) (OECD TG 406, GLP, intradermal administration: 5% solution), no sensitization reaction was observed in any of the cases (EU RAR (2000), REACH registration dossier (Accessed July 2021), Government of Canada, Hazardous Substance Assessment (2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] No in vivo data was available, however, the negative results obtained in two standard in vitro tests in (1) and the information about analogous compounds in (2) were taken into account and it was classified as "Not classified." [Evidence Data] (1) As for in vitro, in a bacterial reverse mutation test, and a chromosome aberration test with the cultured mammalian cells (Chinese hamster V79 cells), negative results were obtained (EU RAR (2000), ECETOC TR 95 vol. 2 (2005), AICIS IMAP (2013), Government of Canada, Hazardous Substance Assessment (2020)). In a chromosome aberration test with the cultured mammalian cells (CHO cells), negative results were obtained (Government of Canada, Hazardous Substance Assessment (2020)). (2) Based on the above findings, etc., the EU, Canada, Australia, and the ECETOC concluded that this substance was not mutagenic (EU RAR (2000), ECETOC TR 95 vol. 2 (2005), AICIS IMAP (2013), Government of Canada, Hazardous Substance Assessment (2020)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 1B. It was reported that, at a dose at which no general toxicity effects were observed in parental animals in many animal tests, a lower viability index, skeletal variations, malformations, etc. were observed in pups. [Evidence Data] (1) It was reported that, in a developmental toxicity study by oral administration to rats (days 7 to 16 of gestation), at a dose at which no general toxicity effects were observed in parental animals, increased skeletal variations (rudimentary cervical ribs, wavy/fused ribs) and malformations (cardiovascular malformations), etc. were observed (CLH Report (2019)). (2) It was reported that, in a developmental toxicity study by oral administration to rats (days 7 to 16 of gestation), at a dose at which no general toxicity effects were observed in parental animals, skeletal variations (an increase in the combined rib variations) and malformations of the heart (1 case) were observed in foetuses (CLH Report (2019), EU RAR (2000), ECETOC TR 95 vol. II (2005)). (3) It was reported that, in a developmental toxicity study by oral administration to rats (days 7 to 17 of gestation), at 1,800 mg/kg/day, reduced body weight gain, a decrease in food consumption, and a decrease in thymus weight were observed in parental animals, and visceral malformations (mainly malformations of the cardiovascular system: 28%), external malformations (mainly anasarca, anury: 18%), dilated renal pelvis (53%) were observed in foetuses (CLH Report (2019), EU RAR (2000), ECETOC TR 95 vol. II (2005), Government of Canada, Hazardous Substance Assessment (2020)). (4) It was reported that, in a developmental toxicity study by dermal administration to rabbits (days 6 to 18 of gestation), at 750 mg/kg/day, reduced body weight gain, decreases in red blood count and hematocrit, a marked decrease in the ratio of embryonic resorptions/fetuses were observed in dams, and mild forelimb flexure, dilation of the renal pelvis, retrocaval ureter and delayed ossification of the skull were observed in foetuses (CLH Report (2019), EU RAR (2000), ECETOC TR 95 vol. II (2005) , Government of Canada, Hazardous Substance Assessment (2020)). (5) It was reported that, in a developmental toxicity study by oral administration to rats (days 7 to 17 of gestation), a dose-dependent decrease in the number of live fetuses was observed at or above 125 mg/kg/day at which no general toxicity effects were observed in parental animals (CLH Report (2019)). (6) It was reported that, in a developmental toxicity study by oral administration to rats (days 7 to 17 of gestation), a lower viability index of fetuses was observed at 600 mg/kg/day at which no general toxicity effects were observed in parental animals, and a prolonged duration of gestation and a decrease in the number of live pups were observed in parental animals at 1,800 mg/kg/day (CLH Report (2019), EU RAR (2000)). [Reference Data, etc.] (7) In a developmental toxicity study by oral administration to mice (days 7 to 15 of gestation), at 4,000 mg/kg/day at which 10% of parental animals (5/50 cases) died, a decrease in the percentage of viable litters (number of litters having one or more live pups/number of live pregnant females), reduced litter size, and a lower viability index on days 1 to 3 postpartum were observed. Also, it should be noted that this was a test result at only a single dose (CLH Report (2019), EU RAR (2000), Government of Canada, Hazardous Substance Assessment (2020)). (8) Under the EU CLP, 2-methoxy acetic acid (2-MAA: CAS RN 625-45-6), which is a metabolite of this substance, is classified in Repr. 1B as a teratogen. 2-MAA has a 3.1 to 6.8 fold longer half-life in humans (77.1 ± 9.1 hours) compared to rats (12.8 to 21.8 hours) and effects may occur in humans at lower dose levels compared to rats (CLH Report (2019)). (9) Based on (1) to (4), even at a dose exceeding the limit dose at which no maternal toxicity was observed, serious developmental effects including malformations were observed in fetuses, and based on (8), a metabolite of this substance induced teratogenicity and has been designated as SVHC, and there are concerns that, since the time when it remains in the body in humans is longer than that in rat, effects may appear at lower concentrations in humans than in rats. Therefore, Repr. 1B was proposed (CLH Report (2019)) and the RAC agreed to this proposal (RAC Opinion (2020)). (10) One available case report described that anomalies in the cardiovascular system and skeletal system and retrocaval ureter were observed in a child born from a mother who worked in the textile industry and may have been exposed to this substance. As the report did not include blood concentration or work environment concentration measurements, no conclusions could be drawn about a possible correlation between the observed anomalies and the exposure to this substance (CLH Report (2019), RAC Opinion (2020)). (11) In the EU CLP, it was currently classified in Repr. 2 (EU-CLP Classification Results (Accessed June 2021)).
8	Specific target organ toxicity - Single exposure	Category 3 (Narcotic effects)	Warning	H336	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 3 (narcotic effects). [Evidence Data] (1) It was reported that, in an acute oral toxicity test with rats, giddiness, loss of balance, and apathy as well as liver and kidney damage were observed (EU RAR (2000)). (2) It was reported that, in an acute oral toxicity test with mice, effects on the autonomic nervous system, somnolence, and cyanosis were observed (EU RAR (2000)). (3) It was reported that, in an acute dermal toxicity test with rabbits, sluggishness, unsteady gait and prostration were observed (EU RAR (2000)). (4) It was reported that, in an acute oral toxicity test with mice, labored breathing, rapid respiration, anorexia, slight to moderate weakness, tremors, and prostration were observed at 7,128 mg/kg (fasted animals) and at 8,188 mg/kg (fed animals) (in the range corresponding to "Not classified") (REACH registration dossier (Accessed July 2021)). (5) It was reported that, in an acute dermal toxicity test with rabbits, anorexia, slight depression, cyanosis, ataxia, and soft feces were observed at lower doses, and salivation, nasal discharge, iritis, significant depression, labored breathing, and prostration were observed at higher doses (REACH registration dossier (Accessed July 2021)). [Reference Data, etc.] (6) It was reported that, in an acute inhalation toxicity test with rats (OECD TG403, 6 hours), no effect was observed at the saturated vapor concentration (estimated value: 1.2 mg/L, converted 4-hour equivalent value: 1.47 mg/L, within the range for Category 2) (REACH registration dossier (Accessed July 2021)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1), it was considered to have effects on the liver in the dermal route, but based on (2), the liver was not adopted as a target organ. Based on (3), no category could be identified in the inhalation route. In addition, based on (4) and (5), effects on the testes were observed in the oral route but it was classified as "Not classified." Based on the above, classification not possible due to lack of data. [Evidence Data] (1) It was reported that, in a 13-week dermal administration test with guinea pigs (6 hours/day, 5 days/week), no change in tissues was observed in the kidney but fatty changes of periportal hepatocytes and elevated urinary Ca levels were observed at 40 mg/kg/day (28.6 mg/kg/day, within the range for Category 2), and an increase in serum LDH was observed at 200 mg/kg/day (143 mg/kg/day, within the range for Category 2) (EU RAR (2000), ECETOC TR (2005), AICIS IMAP (2013), Government of Canada, Hazardous Substance Assessment (2020)). (2) As for the effects on the liver observed in the dermal administration test, they were evaluated as minute changes in the SIAR, and there was a description in the EU RAR that associations between the effects on the liver and this substance were unknown (SIAR (1999), EU RAR (2000)). (3) It was reported that, in a 90-day inhalation toxicity study with rats (GLP, vapor, 6 hours/day, 5 days/week), no effect was observed at 1.06 mg/L (0.757 mg/L, within the range for Category 2) (EU RAR (2000), ECETOC TR (2005), AICIS IMAP (2013), Government of Canada, Hazardous Substance Assessment (2020)). [Reference Data, etc.] (4) It was reported that, in a 20-day oral administration test with rats dosed by gavage, a dose-dependent decrease in thymus weight was observed at 500 mg/kg/day (converted guidance value: 111 mg/kg/day, in the range corresponding to "Not classified"), and decreased body weight, decreased liver and testes weight, and lymphocyte depletion in the thymus cortex were observed at 2,000 mg/kg/day (converted guidance value: 444 mg/kg/day, in the range corresponding to "Not classified") (EU RAR (2000), ECETOC TR (2005), Government of Canada, Hazardous Substance Assessment (2020)). (5) It was reported that, in a 6-week oral administration test with rats dosed by gavage, reduced body weight gain and decreased food consumption were observed at 1,800 mg/kg/day (converted guidance value: 840 mg/kg/day, in the range corresponding to "Not classified"), and increased relative liver, heart, and kidney weight, decreased absolute and relative testis weight, degenerated spermatozoa in the epididymis, and oligospermia were observed at 3,600 mg/kg/day (converted guidance value: 1,680 mg/kg/day, in the range corresponding to "Not classified") (EU RAR (2000), AICIS IMAP (2013), Government of Canada, Hazardous Substance Assessment (2020)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] 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 Short term (Acute)	Not classified	- -	-	-	It was classified as "Not classified" from 96-hour EC50 > 1000 mg/L (EU RAR, 2000) for algae (Raphidocelis subcapitata), 48-hour EC50 > 500 mg/L for crustacea (Daphnia magna) (EU RAR, 2000), and 96-hour LC50 = 5700 mg/L for fish (Pimephales promelas) (EU RAR, 2000).
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Reliable chronic toxicity data were not obtained. It was classified as "Not classified" because it is not water-insoluble (water solubility = 1,000,000 mg/L, PHYSPROP Database 2021) and it was classified as "Not classified" 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.
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.

To GHS Information