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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	111-90-0
Chemical Name	2-(2-Ethoxyethoxy)ethanol
Substance ID	H30-A-006-METI, MOE
Classification year (FY)	FY2018
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
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 (Ver. 1.1))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)
Model SDS by MHLW (External link)
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 4	- Warning	H227	P370+P378 P403+P235 P210 P280 P501	It was classified in Category 4 based on a flash point of 90 deg C (closed cup) (GESTIS (Access Jan. 2019)).
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 190 deg C (GESTIS (Access Jan. 2019)).
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.

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)-(8), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: 10,502 mg/kg (SIAR (2005), DFG (2007), Patty (6th, 2012)). (2) LD50 for rats: 7,410 mg/kg (SCCS (2013), ECETOC TR 95 vol. II (2005)). (3) LD50 for rats: 5,400-5,500 mg/kg (SCCS (2013), ECETOC TR95 vol. II (2005)). (4) LD50 for rats: 6,000 mg/kg (SCCS (2013), ECETOC TR95 vol. II (2005)). (5) LD50 for rats: 6,310 mg/kg (SCCS (2013), ECETOC TR95 vol. II (2005)). (6) LD50 for rats: 8,690 mg/kg (SCCS (2013), Patty (6th, 2012)). (7) LD50 for rats: 5,540 mg/kg (SCCS (2013), Patty (6th, 2012)). (8) LD50 for rats: > 5,000 mg/kg (SCCS (2013)).
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1)-(4), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: 9,143 mg/kg (SIAR (2005), DFG (2007), Patty (6th, 2012)) (2) LD50 for rabbits: 8,300 mg/kg (SCCS (2013), ECETOC TR95 vol. II (2005)) (3) LD50 for rabbits: 4,200 mg/kg (SCCS (2013)) (4) LD50 for rats: 6,000 mg/kg (SCCS (2013), ECETOC TR95 vol. II (2005))
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	[Rationale for the Classification] Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, the test concentration is much higher than the saturated vapor concentration of 126 ppm (0.69 mg/L), and the reference as a mist was applied. [Evidence Data] (1) LC50 (4 hours) for rats: 5.24 mg/L (SCCS (2013), BG Chemie Toxicological Evaluations (1995))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Information indicating no irritation in (1)-(4) and information indicating slight irritation in (5)-(7) are obtained, and it was classified as "Not classified" (Category 3 in UN GHS classification) according to the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) There is a report that no irritation was observed when the preparation of this substance (20% petrolatum) was applied occlusively to 25 subjects for 48 hours (SIAR (2005), DFG (2007)). (2) There is a report that in a skin irritation test with rabbits (n=6), in which a 50% aqueous solution of this substance was applied occlusively for 24 hours, the mean scores of erythema and edema by 72 hours were both 0 (SCCS (2013)). (3) There is a report that this substance does not show primary skin irritation in humans (ECETOC TR95 vol. II (2005)). (4) There is a description that this substance is not irritating even when the application time to rabbit skin was extended or when exposure was repeated (Patty (6th, 2012)). (5) There is a report that only slight erythema (grade 1) was observed in one subject when this substance was applied occlusively to 10 human volunteers for 48 hours (SCCS (2013)). (6) There is a report that in a skin irritation test with rabbits (n=6), when the undiluted liquid of this substance was applied occlusively for 24 hours, score of erythema, crust or edema was 2, in one site of the intact sites, while the other scores were 0 and the mean score was 0.3 (SIDS Dossier (2005)). (7) There is a report that slight irritation was observed when it was applied occlusively to rabbit skin at up to 11,300 mg/kg, to guinea pigs skin at up to 1,000 mg/kg (SIDS Dossier (2005), DFG (2007)).
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	[Rationale for the Classification] Based on (1)-(5), this substance is slightly irritating to the eyes, and it was judged that subcategorization is possible from (1) and (2). Therefore, it was classified in Category 2B. Besides, although information (6) indicating Category 2 was also obtained, emphasis was placed on a plurality of highly reliable data (1) and (2) and their supporting data (3)-(5). [Evidence Data] (1) There is a report that in an eye irritation test (OECD TG405, GLP-compliant, n=3) with rabbits, in which the undiluted liquid of this substance was applied, after 24 hours, conjunctival edema (score 1) and conjunctival redness (score 1) were observed in 1/3 animals, and 3/3 animals, respectively, but these resolved in 48 hours (SCCS (2013)). (2) There is a report that in an eye irritation test (OECD TG405, GLP-compliant, n=3) with rabbits, in which a 30% aqueous solution of this substance was applied, after 1 hour, conjunctival redness (score 1) and edema (score 1) were observed in 2/3 animals, and 2/2 animals, respectively, but these resolved in 24 hours (SCCS (2013)). (3) There is a report that in an eye irritation test (Directive 79/831/EEC B.5 (equivalent to OECD TG405), GLP-compliant, n= 6) with rabbits, in which the undiluted liquid of this substance was used, the mean scores of conjunctival erythema, edema and corneal opacity were 1.37, 0.17, and 0.22, respectively (SIDS Dossier (2005)). (4) There is a report that in an eye irritation test with rabbits, in which the undiluted liquid of this substance was applied, slight irritation (degree of damage: level 2 on a scale of 1 to 10) was observed (SIDS Dossier (2005)). (5) There is a report that this substance was slightly irritating to rabbit eyes, and a slight pain response, conjunctival redness and thickening of the cornea were observed (ECETOC TR95 vol. II (2005)). [Reference Data, etc.] (6) There is a report that this substance was moderately irritating to rabbit eyes (Patty (6th, 2012)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Although data on humans were obtained, sufficient information to determine the presence or absence of sensitisation was not available. Therefore, it was classified as "Classification not possible" due to lack of data. [Reference Data, etc.] (1) There is a report that the occlusive application of this substance to the skin of the arm of 24 subjects was repeated 9 times for 3 weeks (induction phase) and it was applied to the dorsal skin (challenge phase) after 15 days of cessation of application, no sensitization was observed (SCCS (2013)). (2) There is a report that skin sensitization was negative in a maximization test in which a 20% preparation of this substance (in petrolatum) was applied to 25 subjects (SIAR (2005), DFG (2007)). (3) There is a report that this substance is not sensitizing to humans (ECETOC TR95 vol. II (2005)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Classification not possible" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) A negative result was obtained in an in vivo micronucleus test with mouse bone marrow (intraperitoneal administration, administered at 1,980 mg/kg for 2 consecutive days) (SCCS (2013), ECETOC TR 95 (2005), SIAR (2005), DFG (2007)). (2) A negative result was obtained in an in vivo unscheduled DNA synthesis test with primary hepatocytes of rats (oral administration, maximum of 2,000 mg/kg, single administration) (SCCS (2013)). (3) As for in vitro, it was negative (weakly positive in one test) in plural bacterial reverse mutation tests (ECETOC TR 95 vol. II (2005), SCCS (2013), SIAR (2005), NTP DB (Accessed Jan. 2019)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] As for carcinogenicity, there are no sufficient reports on humans. There are no classification results by domestic and international organizations. Therefore, classification was not possible due to lack of data. [Reference Data, etc.] (1) In a 2-year study with rats dosed by feeding (ca. 1,000 mg/kg/day) and in a 718-day study with rats dosed by drinking water (up to 950 mg/kg/day), no increase in the incidence of tumors was observed. However, none of these meet the requirements of the current carcinogenicity study and are not available for carcinogenicity assessment (SIAR (2005), ECETOC TR 95 vol. II (2005), DFG (2007), Patty (6th, 2012)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) and (2), this substance is not considered to show reproductive toxicity by the oral route. In addition, according to (3) and (4), the developmental effects in tests through the oral route were minimal in rats and not detected in mice, despite large doses at or above the limited dose, and no evidence for the classification was observed. As for other routes, from (5) and (6), there are no findings of concern with regard to developmental effects. However, in (3), a slight effect (delayed ossification) was observed at levels without maternal effects, and data on rabbits were not available. Therefore, it was classified as "Classification not possible" not as "Not classified." [Evidence Data] (1) In a two-generation test (continuous breeding test by NTP) with mice dosed by drinking water, decreased sperm motility in the cauda epididymis of the F1 paternal animals was observed at 25,000 ppm (4,400 mg/kg/day: SCCS (2013)), but no effect on fertility was observed in the F0 and F1 parental animals at up to 25,000 ppm of the highest dose (SIDS Dossier (2005), ECETOC TR95 vol. II (2005), DFG (2007), SCCS (2013), Patty (6th, 2012)). (2) In an one-generation reproductive toxicity study with rats (up to 2,000 mg/kg/day: OECD TG 415, GLP-compliant) using the product (Transcutol HP, purity: 99.9%) of this substance as the test material, when males were administered from 63 days before mating through the mating period to the day before necropsy, and females were administered from 14 days before mating through the mating period to Day 7 of pregnancy, decreased body weight gain and symptoms (salivation, sedation) were observed at or above 1,000 mg/kg/day in parental animals, but no reproductive and developmental effects were observed at up to the maximum dose of 2,000 mg/kg/day (SCCS (2013)). (3) In a prenatal development toxicity study (OECD TG 414, GLP-compliant) with rats using the product (Transcutol HP, purity: 99.98%) of this substance as the test material was administered by gavage during the organogenesis period (gestational Day 6-17) of pregnant rats. As a result, maternal toxicity (decreased body weight gain, decreased food consumption) was observed at a dose of 2,000 mg/kg/day, and delayed ossification was observed in fetuses at a lower dose of 1,000 mg/kg/day, but no other developmental effects were observed (SCCS (2013)). (4) In a study in which this substance was administered by gavage at 5,500 mg/kg/day during the organogenesis period (gestational Day 6-13) of pregnant mice, 14% (7/50 animals) of the maternal animals died, but no abnormal findings were observed in the fetuses obtained (SIDS Dossier (2005), DFG (2007), SCCS (2013)). (5) In a study in which pregnant rats were exposed by inhalation (7 hours/day) to this substance at 102 ppm during the organogenesis period (gestational Day 7-15), no abnormal findings were observed in either maternal animals or fetuses (SIDS Dossier (2005), Patty (6th, 2012), DFG (2007), SCCS (2013)). (6) In a study in which a total of 1.4 mL/rat/day (5,600 mg/kg/day: SCCS (2013)) of this substance was dermally applied during the organogenesis period (gestational Day 7-16) of pregnant rats 4 times/day, no abnormal findings were observed in either maternal animals or fetuses (SIDS Dossier (2005), DFG (2007), Patty (6th, 2012), SCCS (2013)). Besides, the SCCS points out that in this study, since the test substance was not occlusively applied, the loss due to evaporation from the application site could not be ignored, and no conclusion can be drawn (SCCS (2013)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) There is a report that an alcohol-dependent man who drank 300 mL of a liquid containing 47% of this substance developed severe central nervous system symptoms, respiratory disorder (dyspnea), thirst and acidosis, and albumin was contained in this urine (SCCS (2013), ECETOC TR 95 vol. II (2005), DFG (2007)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1), it was classified in Category 1 (respiratory organs). Besides, according to (2)-(4), through the oral and dermal routes, there are no findings that can identify the target organs within the dose range up to Category 2. [Evidence Data] (1) In a 28-day test (6 hours/day, 5 days/week: estimated to be the vapor) with rats exposed by inhalation, from 270 mg/m3 (converted guidance value: 0.06 mg/L, within the range of Category 1), slight irritation of the larynx and nasal turbinate, and necrosis (2/5-3/5 animals) of the small ventral cartilage of the larynx were observed (SIAR (2005), ECETOC TR 95 vol. II (2005), DFG (2007), Patty (6th, 2012), SCCS (2013)). Besides, the concentration range (0.02-0.24 mg/L: 3.6-10.9 ppm) of the test air was less than 90% of the saturated vapor concentration (126 ppm), and the reference as a vapor was applied. [Reference Data, etc.] (2) Although as for oral administration studies with rodent, there are reports of one test with rats dosed by gavage for 6 weeks, two tests with rats dosed by feeding for 90 days, and one test with mice dosed by feeding for 90 days, in general, this substance was shown to have low toxicity, with the minimum NOAEL of 250 mg/kg/day in the 90-day test with rats dosed by feeding. Besides, effects on the kidney are observed in all tests on exceeding doses above the range of Category 2 (SIAR (2005), ECETOC TR 95 vol. II (2005), DFG (2007), Patty (6th, 2012), SCCS (2013)). (3) In a test (OECD TG 408, GLP-compliant) in which the product (Transcutol HP, purity (as this substance): > 99.9%) of this substance was administered by gavage to dogs for 90 days, at the highest dose of 2,000 mg/kg/day, there were two deaths in males and one death in females, and severe degeneration of the renal tubules in the kidney was observed in dead animals. Although increased liver weight was observed at lower doses, this was considered an adaptive change, and the NOAEL is reported to be 1,000 mg/kg/day (SCCS (2013)). (4) In a test with rabbits dosed dermally for 12 weeks (5 days/week) and a test with rabbits dosed dermally for 90 days, effects on kidneys were observed at equivalent to 1,000 mg/kg/day or more, and NOEL is reported to be about 300 mg/kg/day (SIAR (2005), DFG (2007), SCCS (2013)).
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 (Acute)	Not classified	- -	-	-	It was classified as "Not classified" from 48-hour LC50 = 3340 mg/L for crustacea (Daphnia magna) (EPA AQUIRE: 2018, Thurston, R.V. et al. (1985)), and 96-hour LC50 = 6010 mg/L for fish (Ictalurus punctatus) (EPA AQUIRE: 2018, NLM HSDB:2018, Thurston, R.V. et al. (1985)).
11	Hazardous to the aquatic environment (Long-term)	Not classified	- -	-	-	It was classified as "Not classified" due to rapid degradability (readily biodegradable: judged by comparison with degradability of the related compounds (J-CHECK, 2012)), and 7-day NOEC (reproduction) = 7.38 mg/L for crustacea (Ceriodaphnia dubia) (OECD SIDS: 2005).
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

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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