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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	66332-96-5
Chemical Name	alpha,alpha,alpha-Trifluoro-3'-isopropoxy-o-toluanilide (synonym: Flutolanil)
Substance ID	R03-B-028-METI, MOE
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2018 FY2006
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.
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 was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from information that it is stable at 150 deg C (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	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 fluorine and oxygen (but not chlorine) which are 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	- -	-	-	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] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats (males): > 10,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), JMPR (2002), EFSA (2008)) (2) LD50 for rats (females): > 10,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), JMPR (2002), EFSA (2008)) (3) LD50 for other rats (males): > 10,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (4) LD50 for other rats (females): > 10,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (5) LD50 for rats (females): > 2,000 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats (males): > 5,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), JMPR (2002), EFSA (2008)) (2) LD50 for rats (females): > 5,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), JMPR (2002), EFSA (2008)) (3) LD50 for rats (males): > 2,000 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (4) LD50 for rats (females): > 2,000 mg/kg (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016))
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] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) LC50 (4 hours) for rats (males): > 5.98 mg/L (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), EFSA (2008)) (2) LC50 (4 hours) for rats (females): > 5.98 mg/L (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), EFSA (2008)) (3) LC50 (4 hours) for rats (males): > 2.15 mg/L (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (4) LC50 (4 hours) for rats (females): > 2.15 mg/L (GLP) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (5) LC50 (4 hours) for rats: > 6 mg/L (JMPR (2002))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a skin irritation test with rabbits (GLP, semi-occlusive, 4-hour application, observation for 72 hours), no skin irritation was observed (erythema/eschar score: 0/0/0/0/0/0, edema score: 0/0/0/0/0/0) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), JMPR (2002), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) This substance was not an irritant to the skin (EFSA (2008)). [Reference Data, etc.] (3) It was reported that, in a skin irritation test with guinea pigs, very weak skin irritation was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in an eye irritation test with rabbits (n=6), conjunctival redness was observed in all animals 1 hour after the application, but disappeared completely within 72 hours (cornea opacity score: 0/0/0/0/0/0, iritis score: 0/0/0/0/0/0, conjunctival redness score: 0.7/0.7/0.7/0.7/0.3/0.3, chemosis score: 0/0/0/0/0/0) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), JMPR (2002), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) It was reported that, in an eye irritation test with rabbits (n=3), no eye irritation was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) This substance was not an irritant to the eye (EFSA (2008)).
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] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a Maximization test (GLP, intradermal administration: 2% solution) with guinea pigs (n=18), no sensitization reaction was observed in any of the animals at 24 hours and 48 hours after challenge (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), JMPR (2002), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) It was reported that, in a Maximization test with guinea pigs, this substance did not cause skin sensitization (EFSA (2008)).
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, negative results were obtained in all of a dominant lethal test with mice (mated with untreated females after 5-day oral dose) and two micronucleus tests using the bone marrow cells of mice (2-day oral dose, and single or 4-day oral dose) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) As for in vitro, negative results were obtained in all of a bacterial reverse mutation test, a gene mutation assay using the mouse lymphoma cells, and a chromosomal aberration tests using the Chinese hamster lung cells (CHL) and human lymphocytes (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
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, the EPA classified this substance in NL (Not likely to be Carcinogenic to Humans) (EPA OPP HHRA (2010)). (2) In a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, there was no neoplastic lesion for which the incidence increased by the administration of the test substance at doses up to 10,000 ppm (males/females: 461/536 mg/kg/day) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) In an 18-month carcinogenicity study with mice dosed by feeding, there was no neoplastic lesion for which the incidence increased by the administration of the test substance at doses up to 30,000 ppm (males/females: 3,330/3,680 mg/kg/day) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). [Reference Data, etc.] (4) The EPA classified this substance in NL based on the absence of significant tumor increases in two adequate rodent carcinogenicity studies (EPA OPP HHRA (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 (GLP) with rats dosed by feeding, at 2,000 ppm, increases in absolute/relative liver weight were observed in parent animals, but no effects were observed in offspring, and no effects on fertility were observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) It was reported that, in a two-generation reproduction toxicity study (GLP) with rats dosed by feeding, at 10,000 ppm, reduced body weight gain (males and females) and decreased food consumption (females) were observed in parent animals, but only slight developmental effects (reduced body weight gain, delayed ossification) were observed in offspring (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) It was reported that, in a developmental toxicity study with rats dosed by gavage (days 6 to 15 of gestation), no effects of the administration of the test substance were observed in any dose groups either in parent animals or offspring (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (4) It was reported that, in two developmental toxicity studies with rabbits dosed by gavage (days 6 to 27 of gestation or days 6 to 18 of gestation), no effects of the administration of the test substance were observed in any dose groups either in parent animals or offspring (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
8	Specific target organ toxicity - Single exposure	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in an acute oral toxicity test (GLP) with rats, no effects were observed at 2,000 mg/kg (upper limit of Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (2) It was reported that, in an acute neurotoxicity test (GLP) with rats dosed by gavage, at 2,000 mg/kg (upper limit of Category 2), no effects were observed, and no acute neurotoxicity was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (3) It was reported that, in an acute dermal toxicity test (GLP) with rats, no effects were observed at 2,000 mg/kg (upper limit of Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (4) It was reported that, in an acute inhalation exposure test (dust, 4 hours) with rats, no effects were observed at 5.98 mg/L (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), EFSA (2008), EPA OPP Human Health Risk Assessment (2010)). (5) It was reported that, in an acute inhalation exposure test (dust, GLP, 4 hours) with rats, no effects were observed at 2.151 mg/L (within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (6), no serious toxic effects were observed in the oral and dermal routes within the dose range for Category 2, and it was classified as "Not classified." However, classification was not possible due to lack of data since there was not sufficient information available for classification in the inhalation route. [Evidence Data] (1) It was reported that, in a 90-day oral toxicity study (GLP) with rats dosed by feeding, increases in absolute and relative weight of the thyroid/parathyroid gland (males), and increases in absolute and relative liver weight (females) were observed at 4,000 ppm (299 mg/kg/day (males), 339 mg/kg/day (females), in the range corresponding to "Not classified"), and an increase in relative liver weight (males), an increase in inorganic phosphates, and a decrease in Glu (females) were observed at 20,000 ppm (1,510 mg/kg/day (males), 1,740 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (2) It was reported that, in a subacute neurotoxicity test (GLP) with rats dosed by feeding, no effects were observed at 1,000 mg/kg/day (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (3) It was reported that, in a 90-day oral toxicity study (GLP) with mice dosed by feeding, increases in absolute and relative liver weight were observed at 50,000 ppm (7,510 mg/kg/day (males), 8,830 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (4) It was reported that, in a 90-day oral toxicity study (GLP) with dogs dosed by gavage, hepatocyte glycogen deposit (males) was observed at 400 mg/kg/day (in the range corresponding to "Not classified"), and an increase in ALP, and liver findings (increases in absolute and relative weight (males), increases in absolute weight and glycogen deposit (females)) were observed at 2,000 mg/kg/day (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (5) It was reported that, in a 2-year oral toxicity test with dogs dosed by gavage, vomiting, salivation, and loose stool were observed at 250 mg/kg/day (in the range corresponding to "Not classified"); and reduced body weight, decreased food consumption, hyperemia of the duodenum, jejunum, and ileum were observed at 1,250 mg/kg/day (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (6) It was reported that, in a subacute dermal neurotoxicity test (GLP) with rats, no effects were observed at 1,000 mg/kg/day (converted guidance value: 233 mg/kg/day, in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). [Reference Data, etc.] (7) It was reported that, in a combined 2-year chronic toxicity/carcinogenicity study with rats dosed by feeding, a decrease in spleen cell component (males), a decrease in MCH, and hyperplasia of the spleen reticulum cells (females) were observed at 2,000 ppm (86.9 mg/kg/day (males), 103 mg/kg/day (females), within the range for Category 2 (males), in the range corresponding to "Not classified" (females)); and an increase in relative liver weight (males), an increase in relative kidney weight (males), a decrease in T.Chol (females), vacuolar degeneration of the liver (females), and nephropathy (females) were observed at 10,000 ppm (461 mg/kg/day (males), 536 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (8) It was reported that, in an 18-month carcinogenicity study (GLP) with mice dosed by feeding, perilobular fatty vacuolation of the hepatocytes (males) was observed at 1,500 ppm (162 mg/kg/day (males), 168 mg/kg/day (females), in the range corresponding to "Not classified"), and an increase in relative liver weight (females) was observed at 30,000 ppm (3,330 mg/kg/day (males), 3,680 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)).
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 96-hour LC50 = 3.16 mg a.i./L for fish (Cyprinus carpio) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016), 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, 2009). The classification result was changed from the previous classification by using new information (a.i.: active ingredient).
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 due to being not rapidly degradable (BIOWIN) and 72-hour NOErC = 0.177 mg a.i./L for algae (Raphidocelis subcapitata) (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, 2009). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (crustacea, fish), then it is classified in Category 2 due to being not rapidly degradable and 96-hour LC50 = 3.16 mg a.i./L for fish (Cyprinodon variegatus) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016), 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, 2009). From the above results, it was classified in Category 2 (a.i.: active ingredient).
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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