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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	946578-00-3
Chemical Name	[Methyl(oxo){1-[6-(trifluoromethyl)-3-pyridyl]ethyl}-lambda(6)-sulfanylidene]carbamonitrile; Sulfoxaflor
Substance ID	R02-A-001-MHLW, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/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)	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. It was classified as "Not classified."
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products. It was classified as "Not classified."
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
7	Flammable solids	Classification not possible	- -	-	-	No data available. Besides, there is information that it is combustible (GESTIS (Access on April 2020)).
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. It was classified as "Not classified."
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Not classified	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from information that it is stable at up to 167 deg C (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
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). It was classified as "Not classified."
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
14	Oxidizing solids	Classification not possible	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine), which is chemically bonded to the element other than carbon or hydrogen (S). 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. It was classified as "Not classified."
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. It was classified as "Not classified."

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) - (3). [Evidence Data] (1) LD50 for rats: males: 1,405 mg/kg, females: 1,000 mg/kg (ACGIH (7th, 2019), CLH Report (2012), RAC Background Document (2013), JMPR (2011)) (2) LD50 for rats: males: 1,410 mg/kg, females: 1,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)) (3) LD50 for rats: 1,000 mg/kg (EU CLP CLH (2013))
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 (ACGIH (7th, 2019), EU CLP CLH (2013), JMPR (2011), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014))
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). Besides, because an exposure concentration was higher than the saturated vapor pressure concentration (3.0E-007 mg/L), the reference value in the unit of mg/L was applied as dust. [Evidence Data] (1) LC50 for rats: > 2.09 mg/L (ACGIH (7th, 2019), CLH Report (2012), RAC Background Document (2013), JMPR (2011), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)) (2) In an inhalation exposure test (4 hours, nose exposure) in rats, the measured value of 2,090 mg/m3 (2.09 mg/L) was the highest possible concentration at which inhalable particles could be generated, and there were no dead animals at this concentration (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) Vapor pressure of this substance: 1.9E-008 mmHg (25 deg C) (HSDB (Access on April 2020)) (converted value for the saturated vapor pressure concentration: 3.0E-007 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) In a skin irritation test with rabbits according to OECD TG 404, the mean score at 24/48/72 hours was all < 2.3, and all signs disappeared after 72 hours (EU CLP CLH (2013), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) This substance was not irritating to the skin and eye of rabbits (JMPR (2011), HSDB (Access on April 2020)). (3) This substance caused only mild skin irritation in rabbits with minimal erythema and edema seen at 1 but not at 24 hours post-application (ACGIH (7th, 2019)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) This substance was not irritating to the skin and eye of rabbits (JMPR Report (2011), HSDB (Access on April 2020)). (2) Slight conjunctival redness, edema, and discharge were seen following instillation of this substance (50 mg) into the rabbit eye, and all changes were absent by 72 hours post-application (ACGIH (7th, 2019)). (3) In an eye irritation test with rabbits according to OECD TG 405, the mean score for cornea and iris at 24/48/72 hours after application was less than 2, the mean score for conjunctival redness and chemosis was less than 1, and all reactions disappeared after 72 hours (EU CLP CLH (2013), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
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) This substance was judged as negative in a local lymph node assay (LLNA) in mice (EU CLP CLH (2013), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo studies, in micronucleus tests (oral dose) using the mouse red blood cells and bone marrow cells, negative results were reported (ACGIH (7th, 2019), JMPR (2011), RAC Background Document (2013). Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) As for in vitro studies, in a bacterial reverse mutation test, a chromosome aberration test and a gene mutation test using the cultured mammalian cells, negative results were reported (same as above).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on the classification results by other organizations in (1) and the results of the studies with experimental animals in (2) and (3), it was classified in Category 2. [Evidence Data] (1) As for the classification results by domestic and international organizations, the ACGIH classified this substance in A3 (ACGIH (7th, 2019)) and EPA classified this substance in S (Suggestive Evidence of Carcinogenic Potential) (EPA Annual Cancer Report 2019 (Access on May 2020) Classification in 2012). (2) In a two-year combined chronic toxicity/carcinogenicity study with male and female rats dosed with this substance by feeding, a significant increase in the incidence of hepatocellular adenomas and testicular interstitial cell adenomas was observed in males (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), ACGIH (7th, 2019), JMPR (2011)). (3) In an 18-month carcinogenicity study with male and female mice dosed with this substance by feeding, a significant increase in the incidence of hepatocellular adenomas and hepatocellular carcinomas in males, and an increasing trend in the incidence of liver tumors in females were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2011)). [Reference Data, etc.] (4) It was suggested that the liver tumors were possibly developed by cell proliferation caused by involvement of drug-metabolizing enzyme induction and nuclear receptors (CAR and PXR). The increased incidence of testicular interstitial cell adenomas could be within the range of the historical incidence of spontaneous tumors specific to the strain of rats, but in a study of the mode of action, effects of a dopamine agonist were reported. Therefore, it could not be ruled out that the findings were related to the administration of the test substance (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)).
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (3), effects in rat fetuses and pups were observed. Based on (4), the fetal limb abnormalities among the observed effects in pups were likely to have been caused by species-specific mechanisms, while for the neonatal death, it could not be said that any species-specific mechanism was known. Therefore, considering that concerns about toxicity in humans could not be completely denied, it was classified as "Classification not possible." [Evidence Data] (1) In a two-generation reproduction toxicity test with rats dosed by feeding, increases in absolute and relative liver weight, centrilobular hepatocyte hypertrophy (with pigmentation) and multifocal hepatocellular necrosis were observed in male parental animals, and a decrease in the percentage of live born pups delivered and a reduction in postnatal survival rate were observed in pups (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2011)). (2) In a developmental toxicity study with female rats dosed by feeding on days 6-21 of gestation, at the dose at which maternal toxicity effects (reduced body weight gain and a decrease in food consumption, a decrease in gravid uterus weight) were observed, external abnormalities in fetuses (forelimb flexure and hindlimb rotation), etc. were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), JMPR (2011)). (3) In a developmental toxicity study with female rabbits dosed by feeding on days 7-28 of gestation, even at the dose at which maternal toxicity effects (a decrease in feces, reduced body weight gain, and a decrease in food consumption) were observed, no developmental toxicity was observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), EU CLP CLH (2013), JMPR (2011)). (4) With respect to the reproduction/developmental toxicity effects, the Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014) indicated "In a reproductive study, neonatal death in rats was observed, and in a developmental toxicity test, abnormalities of four limbs in rat fetuses were observed at the dose at which maternal toxicity was observed. As a result of a study of the mechanism, it was considered that because all these abnormalities were possibly attributed to nicotinic receptors that specifically expressed in the rat fetal period, there was a low possibility that these abnormalities might occur in humans. As for the neonatal death, the detailed mechanism was unknown, but it was considered to be relevant to pharmacological actions to nicotinic acetylcholine receptors (nAChRs) caused by the intrauterine exposure to this substance" (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)). In a test using Xenopus oocytes in which nAChRs from rat fetal or adult muscles, or human fetal or adult muscles were expressed, the reaction to the addition of sulfoxaflor was observed only in the cells derived from the rat fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)). [Reference Data, etc.] (5) The EU CLP CLH (2013) also indicated that the mode of action of reproductive toxicity observed in rats was not relevant to humans, and limb contractures and bent clavicles in rat fetuses and neonatal death were considered not to occur in humans, therefore, no classification for reproductive toxicity was necessary.
8	Specific target organ toxicity - Single exposure	Category 2 (nervous system)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	[Rationale for the Classification] There was no report on single exposure to this substance in humans. Based on the results of the animal tests in (1) to (3), it was classified in Category 2 (nervous system). [Evidence Data] (1) It was reported that in an acute oral neurotoxicity test with rats, a reduction in locomotor activity was observed at 75 mg/kg (within the range for Category 2) and muscle tremors, convulsions, vellications, splayed hindlimbs, etc. were observed at 750 mg/kg (within the range for Category 2) (ACGIH (7th, 2019), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) It was described that in acute oral toxicity tests with rats and mice, muscle tremors, hypoactivity, etc. were observed on the first day of the tests but the symptoms disappeared on the second day of the tests (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) In general pharmacological tests with rats and mice, a reduction in locomotor activity, a reduction in righting reflex, tremors, convulsions, etc. were observed in rats orally dosed at or above 500 mg/kg (within the range for Category 2) and in mice orally dosed at or above 250 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)). [Reference Data, etc.] (4) The Committee for Risk Assessment of the European Chemical Agency (ECHA RAC) concluded that the effects observed in the standard acute toxicity tests and acute neurotoxicity tests were essentially transient and general systemic toxicity effects caused by the exposure to high doses, and did not support classification for specific target organ toxicity by single exposure (RAC Background Document (2013)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2 (liver). [Evidence Data] (1) In 90-day repeated dose toxicity studies with rats and mice dosed by feeding, liver effects (such as an increase in weight, hepatocellular hypertrophy, and single cell necrosis of hepatocytes) were observed in male and female rats at or above 750 ppm (males/females: 47.6/51.6 mg/kg/day, within the range for Category 2) and in male mice at or above 750 ppm (98.0 mg/kg/day, within the range for Category 2) (ACGIH (7th, 2019), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)). (2) In a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, liver effects (such as an increase in weight, hepatocellular hypertrophy, and multifocal hepatocellular necrosis) were observed in males and females at 21.3 to 24.1 mg/kg/day and 39.0 to 43.0 mg/kg/day, respectively, (within the range for Category 2). In addition, it was described that the findings on the testes in males (such as seminiferous tubule atrophy and a decrease in sperm count in the duct of the epididymis with a decrease in epididymis weight) were observed, but they were secondary effects of the seminiferous tubule being pressed by increased interstitial cell adenomas and did not suggest any direct effect of the administration of the test substance on the testes (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014)). (3) In an 18-month carcinogenicity study with mice dosed by feeding, liver effects (such as an increase in weight, hepatocellular hypertrophy, and multifocal hepatocellular necrosis) were observed in males at 79.6 mg/kg/day (within the range for Category 2) (same as above).
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	It was classified in Category 1 from 48-hour EC50 = 0.643 mg/L for crustacea (Mysidopsis bahia) (EU CLP CLH, 2013).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	It was classified in Category 2 because it was not rapidly degradable (a 28-day degradation rate in a test according to OECD TG310: 3% (EU CLP CLH, 2013)) and due to 28-day NOEC = 0.114 mg/L for crustacea (Mysidopsis bahia) (EU CLP CLH, 2013).
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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