NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	473278-76-1
Chemical Name	2-{2-Chloro-4-(methylsulfonyl)-3-[(oxolan-2-ylmethoxy)methyl]benzoyl}cyclohexane-1,3-dione; Tefuryltrione
Substance ID	R02-A-042-METI, MOE
Classification year (FY)	FY2020
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 (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)
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 classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	- -	-	-	No data available.
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 (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) 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)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Classification not possible	- -	-	-	The substance is an organic compound containing chlorine and oxygen (but not fluorine), and the oxygen is chemically bonded to an element (S) other than carbon or hydrogen. However, the classification is not possible due to no data.
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	- -	-	-	Classification is not possible because test methods applicable to solid substances are not 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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats (females): > 2,500 mg/kg (OECD TG 423, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (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.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] The classification is not possible because effects are unknown at a dose near the upper limit for Category 4 in (1). [Evidence Data] (1) LC50 for rats (4 hours): > 1.34 mg/L (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 3) (OECD TG 404, GLP, semi-occlusive, 4-hour application, 72-hour observation), no skin irritation was seen (erythema/eschar score: 0/0/0, edema score: 0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 3) (OECD TG 405, GLP, 72-hour observation), slight conjunctival redness was observed after 24 hours but disappeared after 48 hours (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 0/0.3/0.3, chemosis score: 0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
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] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 10) (OECD TG 406, GLP, intradermal administration: 1% solution), a positive rate was 0% (0/10) at both 24, 48 hours after a challenge (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test using the bone marrow cells of mice (equivalent to OECD TG474, GLP, intraperitoneal injection), the substance was negative (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020)). (2) In a bacterial reverse mutation test (OECD TG471, GLP), negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020)). (3) In a mammalian chromosomal aberration test (OECD TG473, GLP), negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020)). (4) In an in vitro mammalian cell gene mutation tests (OECD TG476, GLP), negative results were obtained (REACH registration dossier (Accessed Sep. 2020)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a 2-year combined chronic toxicity/carcinogenicity study with rats (OECD G453, dosed by feeding), carcinogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). (2) In an 18-month carcinogenicity study with mice (dosed by feeding), carcinogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2. [Evidence Data] (1) In a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG 416, GLP), at 20 ppm, general toxic effects (eye lesions, effects on the liver/thyroid, etc.) in parent animals, and weight gain inhibition (F1) and ocular keratitis (F1 and F2 female) in offspring were observed; and at 200 ppm, general toxic effects (eye lesions, effects on the liver/thyroid/kidney, weight gain inhibition, etc.) in parent animals, and weight gain inhibition (F1 and F2), opacity of the eyeballs, coarsened corneal surface (F1 and F2), and ocular keratitis (F1 and F2 male/female) in offspring were observed. It was reported that no effect on reproductive ability was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage (GLP, days 6 to 19 of gestation), at 30 mg/kg/day, weight gain inhibition in parent animals, and low body weight and an increase in the frequency of skeletal variations (supernumerary rib) in offspring were observed, but teratogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage (GLP, days 6 to 27 of gestation), at 10 mg/kg/day, low body weight (male) and an increase in the frequency of skeletal variations were observed in offspring, but teratogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
8	Specific target organ toxicity - Single exposure	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), in all the oral, dermal, and/or inhalation routes, it was classified as "Not classified." Based on (3), symptoms were observed within the range for Category 2, but since they were considered to be nonspecific symptoms that were normally observed in exposure to dust, they were not regarded as target organ toxicity. [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats (OECD TG 423, GLP), at 2,000 mg/kg (within the range for Category 2), neither death nor appearance of symptoms was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (2) It was reported that in an acute dermal toxicity test with rats (OECD TG 402, GLP), at 2,000 mg/kg (within the range for Category 2), neither death nor appearance of symptoms was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (3) In an acute inhalation (dust) exposure test with rats (GLP, 4 hours), at 1.34 mg/L (within the range for Category 2), wet fur, an increase in respiratory rate, and hunchback position appeared, and then disappeared within 5 days at the most after the exposure. It was reported that there was no death, and no abnormality was observed in the necropsy (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (visual organs), Category 2 (blood system)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (5), the visual organs and the blood system (anemia findings) were considered to be the target organs. In (2) to (4), effects on the visual organs were observed within the range for Category 1, and in (2) and (3), effects on the blood system were observed within the range for Category 2, therefore, it was classified in Category 1 (visual organs) and Category 2 (blood system). Although hypertrophy of the hepatocytes, etc. were observed in the liver, they were considered to be adaptive changes, and although effects on the thyroid were also observed, they were considered to be secondary effects of drug-metabolizing enzyme induction in the liver, therefore, those organs were excluded from the target organs. Chronic nephropathy was observed in (4), but since it was a lesion specific to rodents, and the findings of the kidney in (5) were observed only in male mice and lacked consistency, the kidney was excluded from the target organs. [Evidence Data] (1) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by feeding (OECD TG408), at or above 600 ppm (39 mg/kg/day (male), 45.6 mg/kg/day (female), within the range for Category 2), ocular lesion (partial whitening, corneal opacity/neovascularization) and effects on the liver (increases in absolute and relative weight, centrilobular hypertrophy of the hepatocytes (male)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (2) It was reported that in a 90-day oral toxicity test with dogs dosed by feeding, at or above 20 ppm (0.564 mg/kg/day (male), 0.591 mg/kg/day (female), within the range for Category 1), eye lesions (ocular corneal epithelial cell degeneration, female: ocular corneal cloudiness) were observed; and at or above 2,000 ppm (58.6 mg/kg/day (male), 62.1 mg/kg/day (female), within the range for Category 2), effects on the hematology (increased hematopoiesis of the bone marrow, decreases in MCV/MCH, female: increases in platelet count/neutrophil count), and ocular cloudiness in males were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (3) It was reported that in a 1-year oral toxicity test with dogs dosed by feeding, at or above 20 ppm (0.515 mg/kg/day (male), 0.514 mg/kg/day (female), within the range for Category 1), eye lesions (ocular corneal cloudiness, ocular corneal epithelial degeneration) in males were observed; and at or above 2,000 ppm (53.5 mg/kg/day (male), 53.6 mg/kg/day (female), within the range for Category 2), effects on the hematology (decreases in Ht/Hb/MCV/MCH, increases in red blood cell count/platelet count), and ocular corneal epithelial degeneration in females were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). (4) It was reported that in a 2-year oral toxicity test with rats dosed by feeding (OECD TG453), at or above 50 ppm (2.33 mg/kg/day (male), 3.21 mg/kg/day (female), within the range for Category 1), eye lesions (ocular cloudiness/corneal opacity/keratitis/neovascularization/"snow flake"-like cloudiness, hydrops (male)), and effects on the thyroid (follicular epithelial cell hypertrophy/colloid degeneration/follicular epithelial pigmentation), the kidney (increases in absolute and relative weight/rough surface of the kidney/chronic nephropathy (male)), and the pancreas in females (acinar atrophy/fibrosis) were observed; and at or above 1,500 ppm (72 mg/kg/day (male), 99.6 mg/kg/day (female), within the range for Category 2), effects on the pancreas in males (acinar atrophy/fibrosis) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009), REACH registration dossier (Accessed Sep. 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). (5) It was reported that in an 18-month carcinogenicity study with mice dosed by feeding, at or above 150 ppm (21 mg/kg/day (male), 27.1 mg/kg/day (female), within the range for Category 2), as non-neoplastic lesions, effects on the liver (increases in absolute and relative weight (male), centrilobular hypertrophy of the hepatocytes), the gallbladder (gall stone, acidophilic degeneration of bile duct epithelial cytoplasm (female)), and the kidney (hyperplasia of collecting tubules/hyperplasia of pelvic epithelial cells/papilla necrosis (male)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)). [Reference Data, etc.] (6) It was known that triketone compounds, which had a structure similar to this substance, inhibited 4-HPPDase of the liver and raised the blood tyrosine concentration, and accordingly, the tyrosine concentration of the aqueous humor of the anterior chamber increased, and tyrosine crystals were taken into the lysosome of corneal epithelial cells, causing degeneration/necrosis and inflammations of the corneal epithelial cells. It was also known that this tyrosine metabolic capacity differed depending on animal species. It was reported that, also in this substance, 4-HPPDase was inhibited in a test using the hepatic enzyme solution of rats, and in rats and dogs for which eye lesions were observed, the plasma tyrosine concentration showed the value exceeding 1,000 microΜ, whereas in mice and rabbits, an increase exceeding 1,000 microΜ was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2009)).
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 2	- -	H401	P273 P501	It was classified in Category 2 from 72-hour ErC50 = 5.3 mg/L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 2 because it is not rapidly degradable (BIOWIN) and due to 72-hour NOErC = 1 mg/L for algae (Raphidocelis subcapitata) (REACH registration dossier, 2021). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" because it is not rapidly degradable (BIOWIN) and due to 48-hour EC50 > 100 mg/L for crustacea (Daphnia magna) and 96-hour LC50 > 100 mg/L for fish (Cyprinus carpio) (both, A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2009)). By drawing a comparison between the above results, it was classified in Category 2.
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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