NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	494793-67-8
Chemical Name	5-Fluoro-1,3-dimethyl-N-[2-(4-methylpentan-2-yl)phenyl]-1H-pyrazole-4-carboxamide; Penflufen
Substance ID	R02-A-021-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.
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 decomposes at about 320 deg C or above (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
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	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. It was classified as "Not classified."
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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats: females: > 2,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EU CLP CLH (2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)) (2) LD50 for rats: > 5,000 mg/kg (EPA Pesticides FACTS (2012))
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 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EU CLP CLH (2018), EPA Pesticides FACTS (2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011))
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] It was classified as "Classification not possible" because the category could not be determined from (1). [Evidence Data] (1) LC50 for rats (nose exposure, 4 hours): > 2.02 mg/L (no dead animals) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), EU CLP CLH (2018), EU EFSA (2016), EPA Pesticides FACTS (2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) No irritation was observed in a skin irritation test with rabbits (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) In an eye irritation test with rabbits, transient and slight irritation was observed and disappeared after 72 hours, and the mean score at 24/48/72 hours application was less than 0.7 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
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" because the positive rate in the maximization test in (1) did not meet the criteria for Category 1B. [Evidence Data] (1) In a skin sensitization test with guinea pigs (maximization test, intradermal administration 2.5%), skin reactions were observed in 5/20 (positive rate 25%) after 24 hours and 5/20 (positive rate 25%) after 48 hours in the first challenge and 2/20 (positive rate 10%) after 24 hours in the second challenge (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
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, in a micronucleus test using the bone marrow cells after intraperitoneal injection to mice, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). (2) As for in vitro, in a bacterial reverse mutation test, a chromosome aberration test and a gene mutation test using cultured mammalian cells, negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011))
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] The Food Safety Commission's assessment reports in (3) and (4) indicated that no carcinogenicity was observed for this substance, but based on the classification results by domestic and international organizations in (1) and (2) as well as (5), it was classified in Category 2. [Evidence Data] (1) As for the classification results by domestic and international organizations, the EPA classified this substance in S (Suggestive Evidence Of Carcinogenic Potential) (EPA Annual Cancer Report 2019 (Access on October 2020): Classification in 2011) and EU CLP classified this substance in Carc.2 (Classification in EU CLP (Access on October 2020)). (2) The EPA reported that in a carcinogenicity study with rats, three tumor types (brain astrocytomas in males, ovarian tubulostromal neoplasms in females, histiocytic sarcomas in males) were observed, which were considered treatment-related, and there was no evidence of carcinogenicity in mice, and therefore, it was classified as S (EPA Pesticides FACTS (2012)). (3) In a two-year combined chronic toxicity/carcinogenicity study with male and female rats dosed by feeding, no treatment-related increase in the incidence of neoplastic lesions and no carcinogenicity was observed in females (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (4) In an 18-month carcinogenicity study with male and female mice dosed by feeding, no treatment-related increase in the incidence of neoplastic lesions and no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). The EU CLP CLH (2018) reported that an increased incidence of liver cancer was observed in males although it was not significant. (5) In the EU, with regard to (3) and (4) above, the increased incidence of hepatocellular adenoma in female rats was accompanied by an increase in eosinophilic foci of hepatocytes (pre-neoplastic changes), and was considered likely to be treatment-related. In addition, in a carcinogenicity study with mice, a slight increase in the incidence of hepatocellular carcinoma was observed in male mice. Hepatocellular carcinomas rarely occur spontaneously and the liver was the target organ of this substance, and therefore, the few hepatocellular carcinomas observed in males and females were considered to be treatment-related. However, the incidences of liver tumors in both rats and mice were mild and not due to genotoxicity, and the mechanism of action was not clear. Therefore, the EU judged the classification in Carc.2 as appropriate (CLH Report (2017), RAC Opinion (2018)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) In a two-generation reproduction study with rats dosed by feeding, at a dose at which parental toxicity effects (such as reduced body weight gain, increases in absolute and relative liver weight, centrilobular hypertrophy of the hepatocytes in males and females, and a decrease in absolute ovary weight in females) were observed, reduced body weight gain, decreases in absolute and relative spleen weight, a delay in vaginal opening, etc. were observed in pups, but no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (2) In a developmental toxicity study with female rats dosed by gavage on days 6 to 20 of gestation, even at doses at which maternal toxicity effects (reduced body weight gain, a decrease in food consumption, an increase in absolute liver weight, well-defined hepatic lobules) were observed, no effect was observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (3) In a developmental toxicity study with female rabbits dosed by gavage on days 6 to 28 of gestation, even at a dose at which maternal toxicity effects (reduced body weight gain) were observed, no effect was observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
8	Specific target organ toxicity - Single exposure	Category 3 (Narcotic effects)	Warning	H336	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] There was no report on acute exposure effects of this substance in humans. In experimental animals, based on (1) to (3), it was classified in Category 3 (narcotic effects). [Evidence Data] (1) In a four-hour inhalation exposure test with rats (nasal exposure), at 2.02 mg/L (within the range for Category 2), piloerection, reduced motility, bradypnea, labored breathing, red incrustations on the nose, limping, audible respiration, high-legged gait, staggering gait, and lower rectal temperature were observed, and the symptoms except for the red incrustations on the nose cleared on the next day (EU CLP CLH (2018), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). (2) The above findings on the respiratory organs were determined not to be due to respiratory tract irritation (EU CLP CLH (2018)). (3) In an acute neurotoxicity test with rats dosed by gavage, at or above 500 mg/kg (within the range for Category 2) in males and at or above 100 mg/kg (within the range for Category 1) in females, decreases in motion and locomotor activity were observed, and at or above 500 mg/kg (within the range for Category 2) in females, chromaturia, rigidity of the hindlimbs, ataxia, lower motility, lacrimation, and lower body temperature were observed, but no acute neurotoxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver)	Warning	H373	P260 P314 P501	[Rationale for the Classification] There was no report on hazard by repeated exposure to this substance in humans. In experimental animals, based on (1) and (2), at doses for Category 2, the effects on the liver were observed. Therefore, it was classified in Category 2 (liver). [Evidence Data] (1) It was reported that in a 90-day oral administration test with dogs dosed by feeding, diffuse panlobular hypertrophy of the hepatocytes was observed at or above 1,800 ppm (males/females: 55.7/63.1 mg/kg/day, both within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). (2) It was reported that in a two-year oral administration study with rats dosed by feeding, at or above 100 ppm (males/females: 4.0/5.6 mg/kg/day, both within the range for Category 1), centrilobular to panlobular hypertrophy of the hepatocytes was observed in males; and at or above 2,000 ppm (males/females: 79/113 mg/kg/day, within the range for Category 2/exceeding Category 2), giant vacuolation of the hepatocytes was observed; and furthermore in females, an increase in total protein, an increase in globulin, a lower A/G ratio, centrilobular to panlobular hypertrophy of the hepatocytes, brown pigmentation of the hepatocytes, acidophilic foci of altered hepatocytes, and thyroid colloid aggregation were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013)). [Reference Data, etc.] (3) In a 28-day oral administration test with rats dosed by feeding, at or above 2,000 ppm (males/females: 154/169 mg/kg/day, both exceeding Category 2), increases in total P450, BROD, and PROD activities were observed, and it was suggested that this substance had the mechanism of action similar to that of phenobarbital (CAS RN 50-06-6) which was known to induce these enzymes (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2013))
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 96-hour LC50 = 0.103 mg/L for fish (Cyprinus carpio) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011), EU CLP CLH, 2018).
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 35-day NOEC = 0.0234 mg/L for fish (Pimephales promelas) (EU CLP CLH, 2018).
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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