NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	101463-69-8
Chemical Name	N-({4-[2-Chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl}carbamoyl)-2,6-difluorobenzamide; Flufenoxuron
Substance ID	R02-A-081-METI
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)
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	- -	-	-	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	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing fluorine, chlorine, and oxygen, 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] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (OECD TG 401, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) (2) LD50 for rats: > 3,000 mg/kg (OECD TG 401, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 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: > 2,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LC50 for rats (4 hours): > 5.1 mg/L (OECD TG 403, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) [Reference Data, etc.] (2) LC50 for rats (exposure time: unknown): > 3.3 mg/L (EFSA (2011))
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, semi-occlusive, 4-hour application, 7-day observation), no irritation changes were seen in any animal (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), ECHA RAC Opinion (2011), CLH Report (2009), 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, 7-day observation), all the animals showed conjunctival redness but recovered by day 2 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), ECHA RAC Opinion (2011), CLH Report (2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)).
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), (2). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 20) (GLP, intradermal administration: 1% solution), the 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, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It is reported that in a maximization test with guinea pigs (n = 10) (intradermal administration: 5% solution), the sensitization rate was 0% (0/10) (ECHA RAC Opinion (2011), CLH Report (2009)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (7), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test using the bone marrow cells of mice (GLP, intraperitoneal injection, 2 days), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2009)). (2) In a chromosomal aberration test using the bone marrow cells of rats (GLP, single oral dose), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2009)). (3) In an unscheduled DNA synthesis test with the hepatocytes of rats as an in vivo/in vitro test system, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2009)). (4) In bacterial reverse mutation tests, two positive results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2009)). (5) In an in vitro mammalian gene mutation test, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2009)). (6) In one of four chromosomal aberration tests using the mammalian cultured cells or human lymphocytes, a positive result was obtained, while in the other tests, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2009)). (7) This substance was not considered to be genotoxic in vivo (JMPR (2014)). [Reference Data, etc.] (8) The RAC of ECHA considered that no classification was necessary because this substance did not show mutagenic activities (RAC Opinion (2011)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), 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 Annual Cancer Report (2019): Classification in 2006) (2) In a carcinogenicity study with rats (dosed by feeding for two years), no evidence of carcinogenicity was observed up to the highest dose of 50,000 ppm (males/females: 2,290/2,900 mg/kg/day) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2014), JMPR Report (2014)). (3) In a carcinogenicity study with mice (dosed by feeding for two years), no evidence of carcinogenicity was observed up to the highest dose of 10,000 ppm (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), JMPR Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) In another carcinogenicity study with mice (dosed by feeding for two years), which was different from the study of (3), an increase in the incidence of spleen hemangiosarcomas was observed in females in the 50,000 ppm dose group. However, as this finding was not accompanied by an increase in angiomas (benign tumors), it was not considered to be related to the administration of the test substance. An increase in the incidence of hepatocellular carcinomas in administrated male mice was observed. However, this finding was not considered to be related to the administration of the test substance because the incidence of hepatic tumors in the control group happened to be low (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), JMPR Report (2014)).
7	Reproductive toxicity	Category 2, Additional category for effects on or via lactation	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 2, and effects on lactation were added. In (1), a lower survival rate of pups was observed at doses where slight maternal toxicity was observed. Based on (2) and (3), it was considered that there was a possibility that this substance was excreted in the milk of lactating female rats, inducing the increased mortality, etc. of pups exposed via the milk. [Evidence Data] (1) In a two-generation reproduction toxicity study with rats dosed by feeding (GLP), at doses where no effect was observed in dams (an increase in kidney weight (P) and reduced body weight gain (F1) were observed in male animals), a decrease in body weight of weanlings and an increase in relative liver weight were observed in pups. At the highest dose where only alopecia was observed in dams, a lower survival rate of weanlings (F1 and F2), delayed acoustic startle reaction (F1), a decrease in body weight (F2), etc. were observed. It was reported that no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2009)). (2) It was reported that in an oral toxicity test with rats (for about 10 weeks from 2 weeks before mating until parturition), after exposure of 20,000 ppm, this substance was excreted in milk in lactating rats at levels of 450 ± 377 ppm (day 1 post-partum) and 9.4 ± 6.1 ppm (day 14 post-partum) (CLH Report (2009)). It was shown that this substance was excreted in milk of lactating rats and it accumulated in body fat (JMPR (2014)). (3) In the two-generation reproduction toxicity study of (1), there were increased mortality of pups and increased total litter losses in the four generations (F1a, F1b, F2a, F2b) at or above the dose of 710 ppm. In the opinion of the RAC, lactational exposure of the pups was essential for the induction of the effects, and based on (2), this substance was detected in the milk of exposed dams after parturition. The plausible explanation for the cause of the increased mortality of pups was that as a consequence of exposure to this substance, triglyceride (TG) levels in the dams were reduced, resulting in a decreased fat quantity in the milk, which was therefore poorer in quality, and the RAC supported the additional proposal on "effects on or via lactation" (RAC Opinion (2011)). [Reference Data, etc.] (4) In the EU CLP classification, it was classified as Lact. (effects on or via lactation) (Accessed Oct. 2020).
8	Specific target organ toxicity - Single exposure	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (7), it was classified as "Not classified." [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats (OECD TG 401, GLP), no deaths or symptoms were observed at 5,000 mg/kg (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that in an acute oral toxicity test with rats (OECD TG 401, GLP), there was a death of one female and lethargy, lacrimation, bloody lacrimation, etc. were observed at 3,000 mg/kg (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that in an acute oral toxicity test with mice (GLP), there was no death case and piloerection was observed at 5,000 mg/kg (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) It was reported that in an acute oral toxicity test with mice (GLP), no deaths or symptoms were observed at 3,000 mg/kg (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (5) It was reported that in an acute dermal toxicity test with rats (OECD TG 402, GLP), no deaths or symptoms were observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (6) It was reported that in an acute dermal toxicity test with mice (GLP), no deaths or symptoms were observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (7) It was reported that in an acute inhalation (dust) toxicity test with rats (OECD TG 403, GLP, 4 hours), no deaths or symptoms were observed at 5.1 mg/L (in the range corresponding to “Not classified”) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2 (blood system) [Evidence Data] (1) It was reported that in a 90-day oral toxicity test with rats dosed by feeding, at or above 500 ppm (32.9 mg/kg/day (males), 39.3 mg/kg/day (females), within the range for Category 2), an increase in the mean corpuscular diameter and a decrease in hemoglobin (Hb) were observed in females, and hematological effects (such as anemia) were observed in males and females at high doses in the range corresponding to "Not classified" (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2009), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that in a 90-day oral toxicity test with dogs dosed by feeding, at or above 500 ppm (18.9 mg/kg/day (males), 21.1 mg/kg/day (females), within the range for Category 2), increases in sulfhemoglobin and methemoglobin, an increase in femur bone marrow hyperplasia in males and females, a decrease in Hb levels, decreases in red blood cell count (RBC), hematocrit (Ht) and MCHC in males, a decrease in lymphocyte ratio, an increase in Kupffer cell pigmentation, etc. in the liver in females were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2009), JMPR (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that in a one-year oral toxicity test with dogs dosed by feeding, at or above 500 ppm (19 mg/kg/day (males), 19 mg/kg/day (females), within the range for Category 2), an increase in sulfhemoglobin in males and females, increases in MCV, methemoglobin, and platelet count (PLT), decreases in RBC and MCHC in males, an increase in white blood cell count (WBC), etc. in females were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), CLH Report (2009), JMPR (2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) The hematological toxicity was considered to be hemolytic anemia (JMPR Report (2014)). [Reference Data, etc.] (5) It was reported that the medical surveillance of the personnel at manufacturing plants of this substance revealed no abnormal health effects, except for one case of skin allergy in a worker potentially exposed to this substance (JMPR Report (2014)). (6) In a 90-day subacute oral toxicity test and a two-year carcinogenicity study with mice, and a two-year carcinogenicity study with rats, there were no toxicity findings at doses within the range for Category 2 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2014), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2009)).
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)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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