NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	272451-65-7
Chemical Name	N-[4-(1,1,1,2,3,3,3-Heptafluoropropan-2-yl)-2-methylphenyl]-3-iodo-N'-[2-methyl-1-(methylsulfonyl)propan-2-yl]phthalamide; Flubendiamide
Substance ID	R02-A-077-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	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 435 deg C (HSDB (Accessed Dec. 2020)).
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 fluorine and oxygen (but not chlorine), and the oxygen 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.
16	Corrosive to metals	Classification not possible	- -	-	-	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: > 2,000 mg/kg (OECD TG 401, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010))
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, 2019), JMPR (2010))
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] Classification is not possible due to lack of data because the category could not be determined from (1). [Evidence Data] (1) LC50 for rats (4 hours, dust): > 0.07 mg/L (OECD TG 403, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2010), HSDB (Accessed Dec. 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 irritation changes were seen in any animal (erythema/eschar score: 0/0/0, edema score: 0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), 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, 72-hour observation), slight conjunctival redness was observed after 24 hours in 3 animals in the unwashed eye group but disappeared after 48 hours (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), 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) (OECD TG 406, GLP, intradermal administration: 1% suspension), a positive rate was 0% (0/20) at both 24, 48 hours after the removal of patches (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), 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 (4), it was classified as "Not classified." [Evidence Data] (1) In two micronucleus tests using the bone marrow cells of mice (OECD TG 474, GLP, dosed once by gavage, 2-day intraperitoneal injection), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR Tox Monograph (2010)). (2) In a bacterial reverse mutation test (OECD TG 471, GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR Tox Monograph (2010)). (3) In an in vitro mammalian cell (Chinese hamster lung cells (V79) CHL) gene mutation test (OECD TG 476, GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR Tox Monograph (2010)). (4) In an in vitro mammalian cell (CHL) chromosome aberration test (OECD TG 473, GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR Tox Monograph (2010)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (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 2019 (Accessed Dec. 2020): Classification in 2008). (2) In a 2-year carcinogenicity study with rats (OECD TG 451, GLP, dosed by feeding), as for neoplastic lesions observed in the treated groups at up to 20,000 ppm, there was no finding of significant difference in the incidence between the control group and the treated group, and carcinogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR Tox Monograph (2010)). (3) In an 18-month carcinogenicity study with mice (OECD TG 451, GLP, dosed by feeding), as for neoplastic lesions observed in the treated groups at up to 10,000 ppm, there was no finding of significant difference in the incidence between the control group and the treated group, and carcinogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR Tox Monograph (2010)).
7	Reproductive toxicity	Category 1B, Additional category for effects on or via lactation	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1B, and effects on lactation were added. In (1), (2) and (3), at a dose at which general toxicity was observed in parent animals, growth inhibition and effects on the same organs as in parent animals such as the liver, thyroid, etc. were observed in offspring, and lesions of the eye were also observed. It was considered that in (4), effects in offspring were caused by transfer from the mother via milk after birth. [Evidence Data] (1) In a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG 416, GLP), at doses at which general toxic effects (effects on the thyroid, liver, kidney, and spleen, etc.) were observed in parent animals, similar effects were observed in offspring, and lesions of the eye (enlargement of the eyeball, adhesion of the iris, hemorrhage, hydropic degeneration of the basal cells of the corneal epithelium, vacuolization of the corneal epithelial cells, keratitis, iritis, and cataract (F1 and F2)), etc. were also observed. It was reported that no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2010)). (2) In a one-generation reproduction toxicity study with rats dosed by feeding (GLP), at doses at which general toxic effects (effects on the liver and thyroid, etc.) were observed in parent animals, decreases in weight of the thyroid, liver, and spleen, etc. were observed in offspring, and lesions of the eye (adhesion of the iris, hemorrhage, iritis, cataract, hydropic degeneration of the basal cells of the corneal epithelium, vacuolization of the corneal epithelial cells), an increase in anogenital distance, and a delay in preputial separation completion were also observed. It was reported that no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), JMPR (2010)). (3) It was reported that in a developmental neurotoxicity test with rats dosed by feeding (day 6 of gestation to day 21 of lactation), at 1,200 ppm, increases in absolute and relative liver weight, and centrilobular hepatocyte hypertrophy were observed in parent animals; and lesions of the eye (enlargement of the eyeball, corneal opacity, exophthalmos, anterior synechia of the iris), a reduction in body weight gain, and a delay in days of preputial separation were observed in offspring, but developmental neurotoxicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010)). (4) As a result of the study of the relationship between the effects of this substance on the blood coagulation system and the incidence of lesions of the eye, it was presumed that abnormalities of the eyeball in rat offspring did not occur by the treatment during the gestation period, but occurred by exposure via milk after birth, and that exposure to the sample via milk reduced the vitamin K-dependent blood coagulation ability, which continued and worsened internal hemorrhage of the eye chamber, caused a deposit of erythrocytes in the Fontana's space and iris corneal adhesion, impaired discharge of the aqueous humor, increased the eye pressure, and caused swelling of the eyeball (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)). [Reference Data, etc.] (5) In two-generation and one-generation reproduction tests and developmental neurotoxicity test with rats, as toxic effects that might occur by a single oral dose of this substance, abnormalities of the eye such as enlargement of the eyeball, adhesion of the iris, etc. were observed in offspring, and the symptoms were considered to be caused by exposure via milk after birth, therefore, the Food Safety Commission of Japan determined that setting an acute reference dose (ARfD) for lactating women was appropriate. Comprehensively assessing the above test results, it was determined that setting a nontoxic dose as 15.0 mg/kg body weight/day was appropriate, and based on this, 0.15 mg/kg body weight obtained by division by the safety factor of 100 was set as ARfD for lactating women (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified" in the oral and dermal routes. However, the information on toxicity in the inhalation route could not be used for classification because the dose setting was insufficient. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats (OECD TG 401, GLP), neither symptom nor death was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that in an acute neurotoxicity study with rats by single oral dose (OECD TG 424, GLP), no acute neurotoxicity was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that in an acute dermal toxicity test with rats (OECD TG 402, GLP), neither symptom nor death was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). [Reference Data, etc.] (4) It was reported that in an acute inhalation (dust) toxicity test with rats (OECD TG 403, GLP), neither symptom nor deaths was observed at 0.0685 mg/L (within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system, thyroid, liver)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (6), the target organs were considered to be the blood system, thyroid and liver, and effects were observed within the dosage range for Category 2, therefore, it was classified in Category 2 (blood system, thyroid, liver). [Evidence Data] (1) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by feeding (OECD TG 408, GLP), at 200 ppm (11.4 mg/kg/day (male), 13.1 mg/kg/day (female), within the range for Category 2), effects on the liver (increases in absolute and relative liver weight, perilobular fatty change of hepatocytes (female)) were observed; and at 2,000 ppm (116 mg/kg/day (male), 128 mg/kg/day (female), in the range corresponding to "Not classified"), an increase in PLT, decreases in Ht and Hb, increases in GGT and potassium (female), a decrease in TG (female), a reduction in ChE activity, increases in absolute and relative kidney weight, diffuse hepatocyte hypertrophy, and follicular cell hypertrophy of the thyroid (female) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that in a repeated dose 90-day oral toxicity study with dogs dosed by feeding (OECD TG 409, GLP), at 2,000 ppm (52.7 mg/kg/day (male), 59.7 mg/kg/day (female), within the range for Category 2), a shortening of APTT, increases in absolute and relative adrenal gland weight, adrenal cortex cell hypertrophy (female), and increases in ALP and TG (female) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that in a 1-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding (OECD TG 452, GLP), at 2,000 ppm (79.3 mg/kg/day (male), 97.5 mg/kg/day (female), within the range for Category 2), effects on the blood (an extension of PT, an increase in reticulocyte count, an extension of APTT (male), decreases in Ht, Hb, RBC, MCV, and MCH (female)), effects on the liver (an increase in relative liver weight, increases in GGT and Alb, perilobular fatty change of hepatocytes, diffuse hypertrophy of hepatocytes (female)), and effects on the thyroid (follicular cell hypertrophy) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) It was reported that in a 1-year chronic toxicity study with dogs dosed by feeding (GLP), at 1,500 ppm (35.2 mg/kg/day (male), 37.9 mg/kg/day (female), within the range for Category 2), effects on the blood (a shortening of APTT, an increase in PLT (female)), an increase in relative liver weight (male), and an increase in ALP (female) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (5) It was reported that in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding (OECD TG 451, GLP), at 1,000 ppm (33.9 mg/kg/day (male), 43.7 mg/kg/day (female), within the range for Category 2), effects on the liver (perilobular fatty change of hepatocytes (male), increases in absolute and relative liver weight, diffuse fatty change of hepatocytes, diffuse hypertrophy of hepatocytes (female)), effects on the kidney (chronic nephrosis, an increase in relative kidney weight (female)), and follicular cell hypertrophy of the thyroid (female) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (6) It was reported that in an 18-month combined chronic toxicity/carcinogenicity study with mice dosed by feeding (OECD TG 451, GLP), at 1,000 ppm (94 mg/kg/day (male), 93 mg/kg/day (female), within the range for Category 2), effects on the liver (centrilobular hypertrophy of hepatocytes, centrilobular fatty change of hepatocytes, diffuse fatty change of hepatocytes (small lipid droplets), increases in absolute and relative liver weight, diffuse fatty change of hepatocytes (large lipid droplets) (female)), and the thyroid (follicular cell hypertrophy with hydropic degeneration of the thyroid, an increase in large follicles (females)) were observe (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). [Reference Data, etc.] (7) It was reported that in a repeated dose 90-day oral toxicity study with mice dosed by feeding (OECD TG 408, GLP), at 1,000 ppm (123 mg/kg/day (male), 145 mg/kg/day (female), in the range corresponding to "Not classified"), effects on the liver (centrilobular hepatocyte hypertrophy, centrilobular fatty change of hepatocytes) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), JMPR (2010), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 48-hour EC50 = 0.0034 mg/L for crustacea (Daphnia magna) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 28-day NOEC = 0.020 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.

To GHS Information