NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	210880-92-5
Chemical Name	(E)-1-(2-Chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine; Clothianidin
Substance ID	R02-A-027-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	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (nitro group) present in the molecule, and the oxygen balance is -90, higher than the criteria: -200, but the classification is not possible due to no data.
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. Besides, there is information that it is combustible (GESTIS (accessed Aug. 2020)).
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (nitro group) present in the molecule, but the classification is not possible due to no data.
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	- -	-	-	No data 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 (N) 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	- -	-	-	No data available.
17	Desensitized explosives	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (nitro group) present in the molecule, but the classification is not possible due to no data.

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 higher hazard was adopted from (1) - (4), and it was classified in Category 4. [Evidence Data] (1) LD50 for rats (males): between > 1,216-2,000 mg/kg (JMPR (2010)) (2) LD50 for rats (females): between > 523-1,216 mg/kg (JMPR (2010)) (3) LD50 for rats: 2,000 mg/kg (HSDB (Accessed Aug. 2020)) (4) LD50 for rats: > 5,000 mg/kg (OECD TG 401) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010), HSDB (Accessed Aug. 2020), REACH registration dossier (Accessed Aug. 2020))
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) (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)) [Reference Data, etc.] (2) LD50 for rabbits: > 652 mg/kg (OECD TG 402, purity: 32.6% (medium: xylene)) (ECHA RAC Opinion (2018))
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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) LC50 for rats (4.5 hours): > 6.23 mg/L (OECD TG 403) (JMPR (2010)) (2) LC50 for rats (dust, 4 hours): > 6.14 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 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) (OECD TG 404, GLP, 4-hour application, 72-hour observation), no skin irritation was seen (erythema/eschar score: 0/0/0/0/0/0, edema score: 0/0/0/0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
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) (OECD TG 405, GLP, 3-day observation), slight conjunctival redness, edema, and discharge were found, but irritation reactions disappeared within 24 hours (corneal opacity score: 0/0/0/0/0/0, iritis score: 0/0/0/0/0/0, conjunctival redness score: 0/0/0/0/0/0, chemosis score: 0/0/0/0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
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 = 20) (equivalent to OECD TG 406, GLP, intradermal administration: 1.0% solution), a positive rate was 0% (0/20) 24, 48 hours after challenge (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (6), it was classified as "Not classified." [Evidence Data] (1) In two micronucleus tests using mouse bone marrow (oral and intraperitoneal administrations), negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)). (2) In vivo/in vitro unscheduled DNA synthesis tests using rat primary cultured hepatocytes (oral administration), negative results were reported (JMPR (2010)). (3) In several bacterial reverse mutation tests, negative results (in some cases, weakly positive results (+S9)) were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (4) In an in vitro mammalian cell gene mutation test, negative results were obtained in V79 cells and positive results were obtained in mouse lymphoma cells (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (5) In an in vitro mammalian cell chromosome aberration test, positive results were obtained both in CHL cells and V79 cells (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (6) Based on a comprehensive judgement, it was considered that this substance was not genotoxic in vivo (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on the classification results by other organizations of (1) and the test results of (2) and (3), it was classified as "Not classified." [Evidence Data] (1) As for the classification results by domestic and international organizations, EPA classified this substance in NL (Not Likely to be Carcinogenic to Humans) (EPA Annual Cancer Report (2018): Classification in 2003). (2) In a two-year combined chronic toxicity/carcinogenicity study with rats (OECD TG453), there were increased findings of thyroid C-cell adenomas in females at or above 1,500 ppm, but no dose relationship was observed. Also, precancerous lesions (C-cell hyperplasia) were not dose-related. Therefore, these signs were not considered to be treatment-related (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (3) In an 18-month carcinogenicity study with mice, no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding, at 500 ppm, reduced body weight gain (females) was observed in parental animals, reduced body weight gain and a delay in preputial separation were observed in F1 offspring, and no effects on reproduction were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (3) It was reported that a developmental toxicity study with rabbits dosed by gavage, at 75 mg/kg/day, scant feces and increased chromaturia were observed in parental animals, incidences of absent intermediate lung lobe and delayed ossification in pups increased within the range of background data, and no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (4) In a developmental neurotoxicity test with rats dosed by feeding, at 500 ppm where no general toxicity was observed in parental animals, reduced body weight gain was only observed in pups. It was reported that at 1,750 ppm, reduced body weight gain was observed in parental animals, and reduced body weight gain, a slight increase in the thickness of the dentate gyrus of the hippocampus and cerebellum and and a decrease in stratum granulosum cerebelli thickness (day 12 after birth) and a slight increase in the thickness of the dentate gyrus of the hippocampus and caudate putamen (day 63 after birth) were observed in pups. However, the changes were slight and discontinuous, and no relevant histopathological changes were observed. Therefore, the changes were not considered to be toxicologically significant (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)).
8	Specific target organ toxicity - Single exposure	Category 2 (central nervous system), 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] In (1) and (4), narcotic effects were observed in the oral and inhalation routes. In (2) and (3), effects on the central nervous system were observed within the dose range for Category 2 in the oral route. Therefore, it was classified in Category 2 (central nervous system) and Category 3 (narcotic effects). [Evidence Data] (1) It was reported that in an acute oral toxicity test with mice dosed by gavage (OECD TG401), palpebral closure, reduced spontaneous activity, ataxia, tremors, lethargy and respiratory impairment were observed at 304 to 742 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (2) It was reported that in an acute oral toxicity test with rats dosed by gavage, tremors, locomotor incoordination, hypoactivity, oral red-brown stain and lacrimation were observed at 500 to 1,000 mg/kg (within the range for Category 2) (JMPR (2010)). (3) It was reported that in an acute neurotoxicity test with rats dosed by gavage, reduced spontaneous activity, hypothermia, tremors, decreased activity, ataxia and pinpoint constriction of the pupils were observed at 100 to 400 mg/kg (within the range for Category 2). It was also reported that a retest was conducted with reduced doses and no nervous system effects were observed at 20 to 60 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)). (4) It was reported that in an acute (dust) inhalation toxicity test with rats, a decrease in body weight, ataxia, semi-closed eyes, hunched posture and lethargy were observed and LC50 was >6.14 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)). [Reference Data, etc.] (5) This substance is a neonicotinoid insecticide and acts as an agonist at the nicotinic acetylcholine receptors localized in the insect central nervous system (CNS). It was reported that the neurobehavioral changes observed after oral administration of this substance corresponded to nicotinic CNS stimulating and inhibitory actions (ECHA BPC (Biocidal Products Committee) Opinion (2014)). (6) It was reported that in an acute dermal toxicity test with rats, presuming from LD50 (> 2,000mg/kg, in the range corresponding to "Not classified"), no effects were observed at doses exceeding the range for Category 2 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2 (blood system). [Evidence Data] (1) It was reported that in a 90-day repeated oral dose toxicity test with dogs dosed by feeding, hematological effects such as decreases in white blood cells and lymphocyte percentage and decreases in hematocrit and segmented neutrophils (males) were observed at 2,250 ppm (58.2 mg/kg/day (males), 61.8 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). (2) It was reported that in a one-year chronic toxicity study with dogs dosed by feeding, hematological effects such as decreases in white blood cells and hematocrit, decreases in lymphocytes and segmented neutrophils (males) and decreases in red blood cells, hemoglobin and neutrophils (females) were observed at 2,000 ppm (46.4 mg/kg/day (males), 52.9 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2010)). [Reference Data, etc.] (3) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, hyperplasia of the ovarian interstitial gland (females) was observed at 500 ppm (27.4 mg/kg/day (males), 32.5 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014). JMPR (2010)). (4) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by feeding, an increase in hepatic drug-metabolizing enzyme activities and spleen pigmentation (males) were observed at 3,000 ppm (202 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, 2014), JMPR (2010)).
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 1	Warning	H400	P273 P391 P501	This substance is a neonicotinoid pesticide known to have a specific efficacy profile. By the expert judgment, it was classified in Category 1 from 48-hour EC50 = 0.028 mg/L for crustacea (larvae of Chironomus riparius) (Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2016).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	This substance is a neonicotinoid pesticide known to have a specific efficacy profile. It is not rapidly degradable (BIOWIN), and by the expert judgment, it was classified in Category 1 from 39-day NOEC = 0.0051 mg/L for crustacea (Mysidopsis bahia) (EPA OPP Pesticide Ecotoxicity Database, 2021).
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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