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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	55861-78-4
Chemical Name	1-(5-tert-Butyl-3-isoxazolyl)-3,3-dimethylurea; Isouron
Substance ID	R02-A-036-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	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.
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)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] It was classified in Category 4 from (1), (2). [Evidence Data] (1) LD50 for rats (males): 630 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)) (2) LD50 for rats (females): 760 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015))
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 category could not be determined from (1), and the classification is not possible. [Evidence Data] (1) LC50 for rats (8 hours): > 415 mg/m3 (converted 4-hour equivalent value: 0.83 mg/L) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015))
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 = 6) (24-hour application of 0.5 g of the neat substance, 24-hour application, 5-day observation), no skin irritation signs were observed (Japanese Journal of Pesticide Science Vol. 11 No. 1 (Pesticide Science Society of Japan, 1986)).
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 = 6), slight corneal damage was found in 2 animals after 1 hour but disappeared within 48 hours (Japanese Journal of Pesticide Science Vol. 11 No. 1 (Pesticide Science Society of Japan, 1986)).
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] There was no knowledge corresponding to Category 1 from (1), and it was classified as "Not classified" in accordance with the GHS classification guidance for the Japanese government. [Evidence Data] (1) It is reported that in a maximization test with guinea pigs, there was a negative result (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)).
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 (oral administration, single-dose or four-day) with the bone marrow cells of mice, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (2) In a bacterial reverse mutation test, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (3) In a mammalian cell chromosome aberration test, positive (S9+) and negative (S9-) results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (4) It was considered that this substance was not genotoxic in vivo (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] There were no classification results by domestic and international organizations. However, based on the test results of (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, mononuclear cell leukemia significantly increased in females of a group treated at 5,000 ppm, but it is the most frequently occurring lesion in Fischer rats. Therefore, it was not considered to be treatment-related. No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). It was also reported that the increased incidence of mononuclear cell leukemia was almost on the same level as the rate of natural occurrence (Japan Crop Protection Association (1986)). (2) In a two-year combined chronic toxicity/carcinogenicity study with mice dosed by feeding, no treatment-related increase in the incidence of neoplastic lesions was observed at doses of up to 5,000 ppm. No carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), Japan Crop Protection Association (1986)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), developmental abnormality of the eyes was observed. Therefore, it was classified in Category 1B. [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding, at 1,800 ppm, reduced body weight gain, decreased food consumption (P and F1 males and females), increases in absolute and relative liver weight (P males and females), and a decreased number of implantations (P females) were observed in parental animals; and reduced body weight gain (F1 and F2) and increases in absolute and relative liver weight (F2 females) were observed in pups (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), Japan Crop Protection Association (1986)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage, at 200 mg/kg/day, decreased food consumption and reduced body weight gain were observed in parental animals; and an increase in mortality rate and decreases in the weight of live fetuses and microphthalmia (5 cases) were observed in pups (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), Japan Crop Protection Association (1986)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015), Japan Crop Protection Association (1986)).
8	Specific target organ toxicity - Single exposure	Category 2 (visual organs), Category 3 (narcotic effects)	Warning	H371 H336	P308+P311 P260 P264 P270 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] The symptoms of inactivity, sedation, and reduced spontaneous activity observed in (1), (2) and (6) were considered to be caused by the temporary central nervous system inhibitory actions observed in (3) to (5), and it was classified in Category 3 (narcotic effects). Based on (2), effects on the eyes were observed in the dose range for Category 2, and it was classified in Category 2 (visual organs). [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats, inactivity or sedation, piloerection, lacrimation, and salivation were observed at 435 mg/kg (males) (within the range for Category 2) and at 500 mg/kg (females) (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (2) It was reported that in an acute oral toxicity test with mice, inactivity or sedation, rotational behavior, and jumping behavior were observed at 380 mg/kg (within the range for Category 2), and corneal opacity and mydriasis (females) were observed at 437 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (3) It was reported that in an acute oral toxicity test with mice (general pharmacological test, FOB), central nervous system symptoms (reduced righting reflex, ataxia) were observed at 150 mg/kg (within the range for Category 1), and reduced pain response, increased passivity and flaccid limbs were observed at 500 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (4) It was reported that in an acute oral toxicity test with rabbits (general pharmacological test, FOB), central nervous system symptoms (reduced spontaneous activity) were observed at 50 mg/kg (within the range for Category 1), and reduced righting reflex, ataxia, hypothermia and mydriasis were observed at 500 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (5) It was reported that in an acute oral toxicity test with rabbits (general pharmacological test, electroencephalography), an increase in resting brain wave activities and reducd deep sleep were observed at 150 mg/kg (within the range for Category 1), and a reduction of the brain wave activities during awakening and increased deep sleep were observed at 500 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (6) It was reported that in an acute (dust) inhalation toxicity test with rats (for 8 hours), reduced spontaneous activity and slower response to sound were observed at 415 mg/m3 (converted 4-hour guidance value: 0.83 mg/L, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (visual organs, nervous system, blood system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (4), the target organs were the blood system, visual organ, and nervous system, and clear effects were observed in the dose range for Category 2. Therefore, it was classified in Category 2 (visual organs, nervous system, blood system). [Evidence Data] (1) It was reported that in a one-year chronic toxicity study with dogs dosed by capsules, hematological effects, increases in absolute and relative liver weight, and retinal degeneration (males) were observed at or above 20 mg/kg/day (within the range for Category 2); and mydriasis, slow or incomplete light reflex of the pupil, changes in pupil size and light reflex, and autonomic nervous system effects (tremors, tachycardia, vasodilation, relaxed nictitating membrane) were observed at 50 mg/kg/day (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (2) It was reported that in a one-year chronic toxicity study with monkeys by nasal administration and intragastric administration, sedation (males), recumbency (males), vomiting (males), and reduced body weight gain (females) were observed at or above 20 mg/kg/day (within the range for Category 2); and a decrease in body weight, decreased food consumption, decreased response to external stimulation, decreases in RBC, Hb and Ht (males), vomiting (females), recumbency and prone position (females), and sedation (females) were observed at 50 mg/kg/day (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (3) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, hyperplasia of the bile duct and interstitium in the liver and an increase in Ret (females) were observed at or above 200 ppm (7.26 mg/kg/day (males), 8.77 mg/kg/day (females), within the range for Category 1); and hematological effects (a decrease in Ht, decreases in RBC and Hb (males), increases in PLT and Ret (males)), liver effects (increases in absolute and relative liver weight), kidney effects (chronic progressive nephropathy and brown pigmentation of the proximal tubular epithelium (males)), and increases in absolute and relative testis weight were observed at or above 1,000 ppm (37.5 mg/kg/day (males), 45.0 mg/kg/day (females), within the range for Category 2); and clear histopathological changes in the brain, pituitary gland, nerve tissues, retina, cataract, adrenal gland, etc. were observed at 5,000 ppm (224 mg/kg/day (males), 254 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (4) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with mice dosed by feeding, decreases in RBC, Hb, and Ht and centrilobular hepatocyte hypertrophy (males) were observed at or above 200 ppm (17.5 mg/kg/day (males), 16.6 mg/kg/day (females), within the range for Category 2); and clear histopathological changes in the medulla, spinal cord, nerve tissues, aortic smooth muscle, adrenal gland, testis, and ovary were observed at 5,000 ppm (482 mg/kg/day (males), 540 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). [Reference Data, etc.] (5) It was reported that in a 90-day oral toxicity test with rats dosed by feeding, increases in absolute and relative liver weight (males) were observed at or above 1,000 ppm (60.8 mg/kg/day (males), 64.8 mg/kg/day (females), within the range for Category 2); and hematological effects (decreases in red blood cells (RBC), hemoglobin (Hb), and hematocrit (Ht)), liver effects (centrilobular cloudy swelling and fatty changes of hepatocytes), and kidney effects (increases in absolute and relative weight, hyaline droplet degeneration of the proximal tubular epithelium and localized atrophy, renal tubular epithelial degeneration and renal collecting tubule epithelial degeneration, interstitial edema, and protein casts (males)) were observed at 5,000 ppm (318 mg/kg/day (males), 326 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)). (6) It was reported that in a 90-day oral toxicity test with mice dosed by feeding, liver effects (increases in absolute and relative liver weight, centrilobular hepatocyte cloudy swelling), and hematological effects (decreases in Hb and Ht (females)) were observed at 5,000 ppm (617 mg/kg/day (males), 657 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2015)).
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)	Classification not possible	- -	-	-	No data available.
11	Hazardous to the aquatic environment Long term (Chronic)	Classification not possible	- -	-	-	No data available.
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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