NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	337458-27-2
Chemical Name	1-Acetyl-6-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-3-[(pyridin-3-ylmethyl)amino]-3,4-dihydroquinazolin-2(1H)-one; Pyrifluquinazon
Substance ID	R02-A-039-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	Classification not possible	- -	-	-	No data available.
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).
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	- -	-	-	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.

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). [Evidence Data] (1) LD50 for rats (females): between 300-2,000 mg/kg (OECD TG 423, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020))
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, 2020))
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)	Category 4	Warning	H332	P304+P340 P261 P271 P312	[Rationale for the Classification] It was classified in Category 4 from (1). [Evidence Data] (1) LC50 for rats (4 hours): between 1.2-1.4 mg/L (OECD TG 403, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 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) (GLP, semi-occlusive, 4-hour application, 72-hour observation), no skin irritation was seen (erythema/eschar score: 0/0/0, edema score: 0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), 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) (GLP, 72-hour observation), no changes in the cornea and iris were observed in 3 animals in the unwashed eye group or 3 in the washed eye group, and conjunctival redness was seen in both the groups after 4 hours but disappeared after 48 hours, and conjunctival discharge was found only in the unwashed eye group (in 3 in the unwashed eye group: corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 0.3/0.3/0, chemosis score: 0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), 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] A positive rate was less than 30% from (1), and it was classified as "Not classified." [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 20) (GLP, intradermal administration: 5% suspension), a positive rate was 20%, 10% at 24, 48 hours after challenge (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), 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 (6), it was classified as "Not classified." [Evidence Data] (1) In a UDS test using the hepatocyes of rats (oral administration), the substance was negative (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) In a micronucleus test using the bone marrow cells of mice (GLP, oral administration), the substance was negative (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) In a bacterial reverse mutation test (GLP), negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) In a mouse lymphoma assay, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (5) In a chromosomal aberration test (GLP, short-time processing, -S9) with cultured mammalian cells, positive (numerically abnormal) results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (6) As an opinion of the Food Safety Commission of Japan, it was comprehensively considered that there was no genotoxicity that might become a problem in a living body (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
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 carcinogenicity classification results by domestic and international organizations, EPA evaluated the substance as NL in 2012 and it was judged that the substance was "Not Likely to be Carcinogenic to Humans: At Levels That Do Not Alter Rodent Hormone Homeostasis" (Annual Cancer Report (2018): Classification in 2012). In addition, USEPA concluded that the substance is not likely to be carcinogenic to humans at levels that are below the chronic reference dosage (0.06 mg/kg/day) (US Federal Register Vo. 83, No. 227 (2018)). (2) In a carcinogenicity study with rats, as a neoplastic lesion, an increase of testicular interstitial cell tumors (350 ppm: 49/50 animals, 1,300 ppm: 47/49 animals) was observed in the male group dosed at or above 350 ppm (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (3) In a carcinogenicity study with mice, as a neoplastic lesion, an increase of testicular interstitial cell tumors (12/52 animals) was observed in the male group dosed at 1,000 ppm. An increased incidence of testicular interstitial cell tumors was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (4) In the test with mice in (2) and the test with rats in (3), an increase of testicular interstitial cell tumors was observed, but the possibility of extrapolation to humans was considered to be low (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (3), it was classified in Category 1B. [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding, at 750 ppm, general toxicity effects (death (maximum 2/24 (8.3%)), weight gain inhibition, effects on the liver, kidney and thyroid, etc.), a decrease in the percentage of normally shaped sperms, an increase in relative testis weight (P and F1 male), prolonged pregnancy period (P and F1 female), preputial separation delay (F1 male) were observed in P and F1 parental animals; and weight gain inhibition (F2 female), weight gain inhibition, a decrease in the number of births, decreases in the absolute weight of the brain and the thymus (F1 and F2 male/female), nipple remnant, shortening of the anogenital distance (AGD) (F1 and F2 male), hypospadias, a decrease in the absolute weight of the spleen (F1 male), and pyelectasia (F2 male/female) were observed in offspring (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage, at 10 mg/kg/day at which general toxicity was not observed in parental animals, shortening of the AGD (male) and a high incidence of skeletal variations (supernumerary rib) were observed in offspring; and at 50 mg/kg/day, low body weight, weight gain inhibition, a decrease in food intake, and a low value of pregnant uterus weight were observed in parental animals; and low values of fetal body weight and placental weight, and a high value of lumbosacral transitional vertebrae were observed in offspring (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
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] Based on (1) to (4), it was classified in Category 3 (narcotic effects). [Evidence Data] (1) It was reported that in an acute oral neurotoxicity test (GLP) with rats, at or above 300 mg/kg, abnormal posture, ataxia, gait abnormality, abnormal breathing, a decrease in locomotor activity, and decreases in body weight and food intake were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that in an acute oral toxicity test (general pharmacology, FOB observation) with rats, at 50 mg/kg (within the range for Category 1), piloerection, a decrease in mobility and a decrease in the degree of muscle tone were observed; and at 500 mg/kg (within the range for Category 2), abnormal posture, abnormal breathing, eyelid ptosis, lacrimation, salivation, subnormal temperature, ataxic gait, walking on tiptoe or inability to walk, decreased alertness, a decrease or loss of reflex/responsiveness, decreased grip strength, mydriasis, incontinence of urine, and poor skin color were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that in an acute oral toxicity test (OECD TG 423, GLP) with rats (female), at or above 300 mg/kg, moribundity, prone position, lying on side, crouching position, a decrease in locomotor activity, loss of locomotor activity, gait abnormality, a decrease in respiratory rate, subnormal temperature, piloerection, lacrimation, incontinence of urine, and soiled fur were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) It was reported that in an acute inhalation (dust) exposure test (OECD TG 403, GLP, 4 hours) with rats, at or above 1.2 mg/L (within the range for Category 2), prone position, lying on belly/side, hunchback position, subnormal temperature, piloerection, hematoid lacrimation, red stain around the eye, eyelid ptosis, dark eye, effort respiration, bradypnea, wasting, lethargy, paleness, incoordination, clonic convulsion, and brown or yellow soiled fur were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system, liver, reproductive organs)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (7), the target organs were considered to be the blood system, liver, adrenal gland, and reproductive organs, but since the toxicity finding of the adrenal gland was considered to be the change in the antistress adaptivity, the adrenal gland was excluded from the target organs. In addition, since effects on these target organs were considered to be within the dosage range for Category 2, it was classified in Category 2 (blood system, liver, reproductive organs). [Evidence Data] (1) It was reported that in a 90-day oral toxicity test with rats, at 500 ppm (29.3 mg/kg/day (male), 33.0 mg/kg/day (female), within the range for Category 2), increases in the absolute/relative weight of the liver, reticulocytosis (male), and an increase in the relative weight of the kidney (male) were observed; and at 2,500 ppm (155 mg/kg/day (male), 159 mg/kg/day (female), in the range corresponding to “Not classified”), effects were observed on the blood, thyroid, liver, kidney, adrenal gland, spleen, and male/female reproductive organs, etc. (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (2) It was reported that in a 90-day oral toxicity test with dogs dosed by capsules, at or above 5 mg/kg/day (within the range for Category 1), an increase in ALP (male), and hypertrophy of thyroid follicular epithelium (female) were observed; and at 30 mg/kg/day (within the range for Category 2), effects on the liver (increases in the absolute/relative weight of the liver, chronic hypertrophy of hepatocytes, an increase in ALT), and effects on the thyroid (hypertrophy of follicular epithelium (male), absolute/relative weight increases (female)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (3) It was reported that in a 1-year chronic toxicity study with dogs dosed by capsules, at or above 1.5 mg/kg/day (within the range for Category 1), mononuclear cell infiltrate of the nasal cavity olfactory region was observed; and at 15 mg/kg/day (within the range for Category 2), effects on the liver (centrilobular hypertrophy of hepatocytes/an increase in ALP, an increase in the specific weight of the liver (male)), and an increase in the relative weight of the thyroid (male) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (4) It was reported that in a 1-year chronic toxicity study with rats dosed by feeding, at or above 350 ppm (14.4 mg/kg/day (male), 18.0 mg/kg/day (female), within the range for Category 2), histopathological changes were observed in the eye (retinal atrophy (female)), the blood system (reticulocytosis, hemoglobin/hematocrit decrease (male)), the thyroid (hypertrophy of follicular epithelium), the liver (centrilobular hepatocytes, perilobular fatty changes of hepatocytes (female), single cell necrosis of hepatocytes (female), biliary duct hyperplasia (female)), the adrenal gland (hypertrophy of fasciculata cells (female)), and the testis (seminiferous tubule atrophy, hyperplasia of interstitial cells, increased degenerated cells in the epididymal duct) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (5) It was reported that in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, at or above 350 ppm (12.5 mg/kg/day (male), 16.4 mg/kg/day (female), within the range for Category 2), effects on the eye (opacity/white turbidity of eyeball, retinal atrophy, cataract), effects on the thyroid (an increase of small follicles, and hypertrophy of follicular epithelium), effects on the liver (centrilobular hypertrophy of hepatocytes, diffuse fatty metamorphosis of hepatocytes/biliary duct hyperplasia (female)), effects on the kidney (chronic nephropathy, basophilic renal tubules (female)), effects on the adrenal gland (hypertrophy of adrenal zona fasciculata and reticularis cells), effects on the male genetic organs (atrophy of the testis, epididymis, coagulating gland, and prostate), and effects on the female genetic organs (atrophy of the ovary and mammary gland, endometrial gland hyperplasia) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (6) It was reported that in a 18-month chronic toxicity/carcinogenicity study with mice dosed by feeding, at or above 250 ppm (27.1 mg/kg/day (male), 25.0 mg/kg/day (female), within the range for Category 2), effects on the adrenal gland (hyperplasia of subcapsular cells (male)), and effects on the uterus (horn lining membrane hyperplasia) were observed; and at 1,500 ppm (206 mg/kg/day (male), 202 mg/kg/day (female), in the range corresponding to "Not classified"), effects were observed in the nasal cavity, the thyroid, the liver, the testis (hyperplasia of interstitial cells, atrophy of seminiferous tubules), and the mammary gland (glandular epithelium hyperplasia) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (7) As for the finding of the thyroid in oral toxicity tests for 90 days or more with rats, the results of the examination test for UDP glucuronosyl transferase (UDPGT) of the thyroid axis and the liver of rats suggest that effects of this substance on the thyroid of rats were the secondary mechanism related to the thyroid stimulating via the hypermetabolism of the thyroid hormone in the liver (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). [Reference Data, etc.] (8) It was reported that in a 90-day oral toxicity test with mice dosed by feeding, at 750 ppm (102 mg/kg/day (male), 119 mg/kg/day (female), in the range corresponding to "Not classified"), effects were observed in the blood, thyroid, liver, spleen, adrenal gland, and testis (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)). (9) Based on the results of the in vivo tests (Hershberger test, uterotrophic assay, measurements of AR protein/AR mRNA in tissue, etc.) and in vitro tests (receptor binding test, reporter gene assay, 5 alpha-inhibiting action, etc.), the knowledge was obtained that this substance has an antiandrogen action and an antiestrogen action, and effects on the male/female genetic organs may be the actions via these mechanisms (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2020)).
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 = 0.0027 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	If chronic toxicity data are used, then it is classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 21-day NOEC < 0.0014 mg/L for crustacea (Daphnia magna) (EPA OPP Pesticide Ecotoxicity Database, 2021). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 3 because it is not rapidly degradable (BIOWIN) and due to 72-hour ErC50 = 11.8 mg/L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). By drawing a comparison between the above results, it was classified in Category 1.
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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