NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	106-92-3
Chemical Name	1-Allyloxy-2,3-epoxypropane (synonym: Allyl glycidyl ether)
Substance ID	R03-B-003-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	FY2009 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 (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 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 45 deg C (closed cup) (GESTIS (Accessed JnueJune 2021)). Besides, it is classified in class 3, PG III in UNRTDG (UN 2219).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Type G	- -	-	-	There are chemical groups associated with self-reactive properties (ethylene group, epoxides) present in the molecule. But it is classified in Class 3 in UNRTDG (UN 2219) and it is considered to be not applicable to self-reactive substances and mixtures, hazards of the highest precedence, and it was classified in Type G.
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 264 deg C (REACH registration dossier (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	Classification not possible	- -	-	-	No data available.
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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] The category with the highest degree as judged based on (1) to (4) was adopted and this substance was classified in Category 4. [Evidence Data] (1) LD50 for rats (males): 1,600 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), AICIS IMAP (2015), SIAP (2007), ACGIH (7th, 2001), DFG MAK (1992)) (2) LD50 for rats: in the range from 830 to 1,600 mg/kg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)) (3) LD50 for rats (males): 1,164 mg/kg (REACH registration dossier (Accessed July 2021)) (4) LD50 for rats (females): 830 mg/kg (REACH registration dossier (Accessed July 2021))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits (males): 2,550 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), AICIS IMAP (2015), SIAP (2007), ACGIH (7th, 2001), DFG MAK (1992))
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)	Category 2	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] The category with the highest degree as judged based on (1) and (2) was adopted and this substance was classified in Category 2. Besides, since the exposure concentration was lower than 90% (5,565 ppm) of the saturated vapor pressure concentration, it was judged to be in a vapor state and classified based on the reference value in units of ppmV. [Evidence Data] (1) LC50 (7 hours) for rats (males): 308 ppm (converted 4-hour equivalent value: 407 ppm) (AICIS IMAP (2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), REACH registration dossier (Accessed July 2021)) (2) LC50 (8 hours) for rats (males): in the range from 3.12 to 4.66 mg/L (converted 4-hour equivalent value: 948 to 1,414 ppm) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ACGIH (7th, 2001), REACH registration dossier (Accessed July 2021))
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2. Besides, from the findings of (4), the skin corrosion was suggested, but by reference to the original source, the findings were judged to support the skin irritation. [Evidence Data] (1) Dermatitis, consisting of itching, swelling, and blister formation, was reported by workers exposed to vapor or liquid of this substance (ACGIH (7th, 2001), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (2) It was reported that, in a skin irritation test (occlusive, 24-hour application, 72-hour observation) with rabbits (n=3), the mean erythema score after 24 hours and 72 hours was 1.33, and the mean edema score was 1.83, showing moderate irritation (AICIS IMAP (2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ACGIH (7th, 2001), REACH registration dossier (Accessed July 2021)). (3) It was reported that, in a skin irritation test with rabbits, based on tests with rabbits, this substance was a skin irritant (SIAP (2007)). [Reference Data, etc.] (4) This substance showed corrosion to the eye, skin, and respiratory tract, and its attachment to the skin caused drying, redness, pain, and bulla of the skin (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020)). (5) According to the ICSC (2018), which is an original source of (4), this substance was a skin irritant (ICSC 2018)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1. Besides, in view of the severity of the effects, the category was changed. [Evidence Data] (1) It was reported that this substance showed corrosion to the eye, skin, and respiratory tract, and that its attachment to the eye caused redness, pain, blurred vision, and severe burn (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020)). (2) It was reported that, in an eye irritation test with rabbits (n=3), the overall mean irritation score was 72 until 48 hours after the application, and although severe ocular injury occurred, there was no blindness, and reversible conjunctivitis, iritis, and corneal opacity occurred (AICIS IMAP (2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ACGIH (7th, 2001), REACH registration dossier (Accessed July 2021)). (3) It was reported that, in an eye irritation test with rabbits, this substance was a severe eye irritant (SIAP (2007)). (4) In an eye irritation test with rabbits, this substance caused severe but reversible corneal effects. It was also reported that high vapor concentration of this substance produced corneal opacities in rats (HSDB (Accessed July 2021)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1. [Evidence Data] (1) In a study conducted in patients exposed to epoxy resin compounds, patch testing with a 25% solution of this substance showed positive reactions in 12.9% of the tested patients. It was also reported that similar cases in the plastic and marble industry demonstrated skin sensitization from exposure to this substance (AICIS IMAP (2015)). (2) In patch testing of 20 workers who developed dermatitis after handling epoxy resin, 3 workers showed positive reactions to 0.25% of this substance (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (3) The DFG MAK classified it in Sh (skin sensitizing substance) (DFG MAK (2002)). (4) Several human case reports indicated that this substance had potential for skin sensitization (SIAP (2007)).
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. [Evidence Data] (1) As for in vitro, in multiple bacterial reverse mutation tests, and multiple chromosome aberration tests using cultured mammalian cells (CHO, CHL, rat liver cells), positive results were obtained (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), REACH registration dossier (Accessed July 2021), AICIS IMAP (2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), DFG MAK (1992), Mutagenicity Test Data of Existing Chemical Substances based on the toxicity investigation system of the Industrial Safety and Health Law (Accessed July 2021)). (2) It turned out that this substance showed genotoxicity in many in vitro and in vivo tests. It was also shown that this substance produced adducts of DNA after dermal application and intraperitoneal administration in mice (Government of Canada, Screening Assessment (2020), SIAP (2007)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), some evidence of carcinogenicity was observed in mice (males), and therefore, it was classified in Category 2. Also, based on the new findings, classification results were changed. [Evidence Data] (1) As for the classification results by domestic and international organizations, the ACGIH classified this substance in A4 (ACGIH (7th, 2001)) and the DFG classified it in Category 2 (DFG MAK (2002)). (2) In a carcinogenicity study by 103-week inhalation exposure (6 hours/day, 5 days/week) with rats, adenocarcinoma in the olfactory epithelium of the nasal passage, and papillary adenoma and squamous cell carcinoma in the respiratory epithelium were observed each in 1/50 males of a 10 ppm group. In females, papillary adenoma in the respiratory epithelium, and adenosquamous carcinoma in the lung were observed each in 1/50 animals of a 5 ppm group, but no tumor formation was observed in a 10 ppm group. As a result, it was concluded that there was equivocal evidence of carcinogenicity in males, and there was no evidence of carcinogenicity in females (NTP TR376 (1990), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), Government of Canada, Screening Assessment (2020), AICIS IMAP (2015), SIAP (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), DFG MAK (1992)). (3) In a carcinogenicity study by 102-week inhalation exposure (6 hours/day, 5 days/week) with mice, in a 10 ppm group, adenoma of the respiratory epithelium of the nasal passage was observed in 3/50 males and 1/50 females, and submucosal hemangiosarcoma was observed in 1/50 animals each in males and females. As a result, it was concluded that there was some evidence of carcinogenicity in males, and there was equivocal evidence of carcinogenicity in females (NTP TR376 (1990), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), Government of Canada, Screening Assessment (2020), AICIS IMAP (2015), SIAP (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), DFG MAK (1992)). [Reference Data, etc.] (4) In the EU, it was classified in Carc. 2 (EU CLP Classification Results (Accessed June 2021)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. In (1), a decrease in fertility and a decreased number of implantations, which were concentration-dependent, were observed at or above 30 ppm at which general toxic effects (reduced body weight gain) were observed in male rats. [Evidence Data] (1) In a reproduction toxicity study by inhalation exposure with rats (8 weeks, mating with unexposed males and females after exposure), in males exposed at or above 30 ppm, reduced body weight gain, and a decrease in fertility and a decreased number of implantations, which were concentration-dependent, by mating with unexposed females were observed. In females exposed at 200 ppm, decreased numbers of corpora lutea and implantations by mating with unexposed males were observed, but no effects on fertility were observed. Also, there was no increase in the incidence of malformations or variations of fetuses (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), AICIS IMAP (2015), SIAP (2007), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), DFG MAK (1992), REACH registration dossier (Accessed June 2021)). (2) It was reported that, in a reproduction toxicity study by inhalation exposure with mice (8 weeks, mating with unexposed males and females after exposure), there were no reproductive and developmental effects related to exposure both in males and females at the highest dose of 30 ppm (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), AICIS IMAP (2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), DFG MAK (1992), REACH registration dossier (Accessed June 2021)). [Reference Data, etc.] (3) In the EU, it was classified in Repr. 2 (EU CLP Classification Results (Accessed June 2021)).
8	Specific target organ toxicity - Single exposure	Category 1 (central nervous system, respiratory organs, liver)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (8), it was classified in Category 1 (central nervous system, respiratory organs, liver). [Evidence Data] (1) It was reported that, based on epidemiological studies and cases, this substance had strong irritation to the eye and respiratory organs, produced pulmonary edema by inhalation exposure, and had central nervous system depression actions (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (2) In an oral toxicity test with rats and mice, incoordination, ataxia, and reduced motor activity were observed, and then, labored breathing, and central nervous system depression were observed. Besides, in animals which died, piloerection, diarrhea, and coma were observed immediately before death. At necropsy of the surviving animals, irritation of the forestomach (hyperkeratosis, erosion, ulceration), and effects on the liver (necrosis) were observed. LD50 by this test was 830 to 1600 mg/kg in rats and 390 mg/kg in mice (PATTY (2012)). (3) It was reported that, in an acute inhalation (vapor) exposure test with rats (7 hours), slight nasal irritation and gasping were observed at 0.47 mg/L (converted 4-hour equivalent value: 0.622 mg/L, within the range for Category 1) (AICIS IMAP (2015), REACH registration dossier (Accessed July 2021)). (4) It was reported that, in an acute inhalation (vapor) exposure test with rats (8 hours), lacrimation, nasal and salivary discharge, dyspnea, gasping, and corneal opacity were observed at 1.4 mg/L (converted 4-hour equivalent value: 1.98 mg/L, within the range for Category 1) (REACH registration dossier (Accessed July 2021)). (5) It was reported that, in an acute inhalation (vapor) exposure test with rats (7 hours), dilatation of the stomach by air swallowing, congestion and edema of the nasal turbinate, nasal discharge, corneal opacity, and congestion in the liver and kidney were observed at 300 ppm (converted 4-hour equivalent value: 1.8 mg/L, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), PATTY (2012)). (6) It was reported that, in an acute inhalation (vapor) exposure test with mice (4 hours), central nervous system depression, and strong irritation to the eye and respiratory organs (lacrimation, salivation, dyspnea) were observed at 206 to 774 ppm (0.96 to 3.6 mg/L, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2005)). (7) It was reported that. in an acute inhalation (vapor) toxicity test with mice (4 hours), effects on the lung (inflammation, non-infectious pneumonitis), effects on the liver (discoloration, focal inflammatory cells and moderate congestion), and discoloration of the kidney were observed at 270 ppm (1.3 mg/L, within the range for Category 1) (PATTY (2012)). (8) It was reported that, based on the results of the animal studies, the main target organs of this substance were the liver and the kidney (PATTY (2012)).
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) to (4), since effects on the nasal cavity, trachea, bronchus, lung were observed, it was classified in Category 1 (respiratory organs). [Evidence Data] (1) It was reported that, in a 13-week inhalation toxicity study with rats (vapor, 6 hours/day, 5 days/week), effects on the nasal passage (epithelial hyperplasia, squamous metaplasia, inflammation) were observed at 4 ppm (converted guidance value 0.013 mg/L, within the range for Category 1); squamous metaplasia of the larynx (males) was observed at 10 ppm (converted guidance value 0.03 mg/L, within the range for Category 1); squamous metaplasia of the larynx (females) was observed at 30 ppm (converted guidance value 0.1 mg/L, within the range for Category 1); squamous metaplasia of the trachea was observed at 100 ppm (converted guidance value 0.3 mg/L, within the range for Category 2); and squamous metaplasia of the bronchi was observed at 200 ppm (converted guidance value 0.67 mg/L, within the range for Category 2) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), AICIS IMAP (2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ACGIH (7th, 2001), DFG MAK (1992), NTP TR376 (1990)). (2) It was reported that, in a 13-week inhalation toxicity study with mice (vapor, 6 hours/day, 5 days/week), squamous metaplasia of the respiratory epithelium and olfactory epithelium, and chronic inflammation were observed at 4 ppm (converted guidance value 0.013 mg/L, within the range for Category 1) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), AICIS IMAP (2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ACGIH (7th, 2001), DFG MAK (1992), NTP TR376 (1990)). (3) It was reported that, in a 103-week inhalation toxicity study with rats (vapor, 6 hours/day, 5 days/week), effects on the nasal passage, and effects on the lung (histiocytic cellular infiltration of the alveolus, an increased incidence of hyperplasia of the alveolar epithelium (females)) were observed at 5 ppm (0.023 mg/L, within the range for Category 1) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ACGIH (7th, 2001), DFG MAK (1992), NTP TR376 (1990)). (4) It was reported that, in a 102-week inhalation toxicity study with mice (vapor, 6 hours/day, 5 days/week), glandular proliferation of the nasal passage, suppurative inflammation of the mucosa of the nasal passage, degeneration, proliferation, and squamous metaplasia of the respiratory epithelium were observed at 5 ppm (0.023 mg/L, within the range for Category 1) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), Initial Risk Assessment Report (NITE, CERI, NEDO, 2005), ACGIH (7th, 2001), DFG MAK (1992), NTP TR376 (1990)).
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)	Category 3	- -	H402	P273 P501	It was classified in Category 3 from 96-hour LC50 = 30 mg/L for fish (Carassius auratus) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020), Initial Risk Assessment (NITE, CERI, NEDO, 2005)).
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" because it was not rapidly degradable (a 28-day degradation rate by BOD: 37% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law (Ministry of Economy, Trade and Industry (METI), 1994), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020))), and due to 72-hour NOEC = 20 mg/L for algae (Raphidocelis subcapitata) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (crustacea, fish), then it is classified in Category 3 because it was not rapidly degradable, and due to 96-hour LC50 = 30 mg/L for fish (Carassius auratus) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2020)). by drawing a comparison between the above results, it was classified in Category 3.
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.

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