NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	688046-61-9
Chemical Name	(5-Chloro-2-methoxy-4-methylpyridin-3-yl)(2,3,4-trimethoxy-6-methylphenyl)methanone; Pyriofenone
Substance ID	R02-A-085-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	- -	-	-	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 chlorine and oxygen (but not fluorine) 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). [Evidence Data] (1) LD50 for rats (females): > 2,000 mg/kg (OECD TG 423, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) LD50 for rats (males): > 2,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)) (2) LD50 for rats (females): > 2,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019))
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), (2). [Evidence Data] (1) LD50 for rats (males) (4 hours): > 5.18 mg/L (OECD TG 403, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)) (2) LD50 for rats (females) (4 hours): > 5.18 mg/L (OECD TG 403, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019))
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 skin irritation reactions 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, 2018), ECHA RAC Opinion (2019), CLH Report (2018), JMPR (2019), 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 = 3) (OECD TG 405, GLP, 72-hour observation), slight conjunctival redness was seen in 2 animals after 24 hours but disappeared after 48 hours (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 0.3/0/0.3, chemosis score: 0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), ECHA RAC Opinion (2019), CLH Report (2018), JMPR (2019), 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	Category 1B	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1B from (1). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 20) (GLP, intradermal administration: 1% suspension), the positive rate was 35% (7/20), 45% (9/20) after 24, 48 hours (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). [Reference Data, etc.] (2) It is reported that in a local lymph node assay (LLNA) with mice (n = 5/group) (OECD TG 429, GLP), the stimulation index (SI values) was 0.78 (5%), 1.04 (10%), 0.57 (25%) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), ECHA RAC Opinion (2019), CLH Report (2018), JMPR (2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) As for (2), it was pointed out in the ECHA RAC Opinion (2019) that setting 25% as a top application dose may not be considered to meet the requirement in OECD TG 429, mentioning that a 50% concentration was also used in a preliminary dose-range finding test (ECHA RAC Opinion (2019)).
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), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2018), RAC (Background Doc.) (2019)). (2) In an unscheduled DNA synthesis test using the liver of rats (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2018), RAC (Background Doc.) (2019)). (3) In a comet assay using the liver of rat (OECD TG 489, GLP), negative results were reported (CLH Report (2018), RAC (Background Doc.) (2019)). (4) In a comet assay using the liver of mice, negative results were reported (CLH Report (2018), RAC (Background Doc.) (2019)). (5) In a bacterial reverse mutation test (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (6) In a gene mutation test using the mouse lymphoma cells (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (7) In a chromosome aberration test using the cultured mammalian cells (CHL), positive (-S9) results were reported at the higher dose level (CLH Report (2018), RAC (Background Doc.) (2019)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), due to the negative results in male and female rats and female mice, and because it was determined that the liver tumors in male mice occurred spontaneously, 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): Classification in 2011). (2) In a two-year carcinogenicity study with rats dosed by feeding, there was no neoplastic lesion for which the incidence increased by the administration of the test substance, and no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) In a 78-week carcinogenicity study with mice dosed by feeding, a significant increase in the total incidence of hepatocellular adenoma and carcinoma was observed in males in the highest dose group of 5,400 ppm (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) The EPA classified the substance in NL because there was no evidence of carcinogenicity in the carcinogenicity studies with rats and mice (EPA Pesticide Fact Sheet (2012), Federal Register vol. 84, No. 104 (2019)). (5) In male mice, the incidence of hepatocellular adenoma was 13%, 11%, and 17% at 600, 1,800, and 5,400 ppm, respectively, while it was 6% in a control group, and there was no correlation with the dose. Furthermore, the incidence of carcinoma was 4%, 6%, and 6% respectively, while it was 2% in a control group, and there was no significant difference between the control group and the administrated groups. In the total incidence of hepatocellular adenoma and carcinoma, there was a statistically significant difference in a male group at the highest dose (5,400 ppm). However, it was within the range of the background data (9.8 to 36%) of the testing laboratory (CLH Report (2018), RAC (Background Doc.) (2019)).
7	Reproductive toxicity	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 a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG 416, GLP), at a dose at which general toxic effects (effects on the liver, kidney, thyroid, and blood, etc.) were observed in P and F1 parent animals, a reduction in body weight gain (F1) and a decrease in spleen weight (F2 female) were observed in offspring, but effects on fertility were not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2018)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage (OECD TG 414, GLP, days 6-19 of gestation), at a dose at which increases in liver and cecum weight were observed in parent animals, an increase in the number of fetuses with skeletal variations was observed in offspring, but teratogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2018)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage (OECD TG 414, GLP, days 6-27 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), CLH Report (2018)).
8	Specific target organ toxicity - Single exposure	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 an acute oral toxicity test with rats (OECD TG 423, GLP), no effect was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)). (2) It was reported that in an acute neurotoxicity study with rats (GLP), no neurotoxicity was observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (3) It was reported that in an acute dermal toxicity test with rats (OECD TG 402, GLP), at 2,000 mg/kg (within the range for Category 2), no effect was observed except for erythema, and scabbing (sites applied with the test substance) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)). (4) It was reported that in an acute inhalation (dust) toxicity test with rats (OECD TG 403, GLP, 4 hours), at 5.18 mg/L (in the range corresponding to "Not classified"), effects were not observed except for nasal discharge (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)).
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (7), it was classified as "Not classified" in the oral and dermal routes. An increase in ALP and hepatocyte hypertrophy which were the findings related to the liver, and chronic nephropathy which was the finding related to the kidney, were not adopted because those organs could not be considered to be the target organs based on those effects. 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 test with rats dosed by feeding (GLP), at or above 2,500 ppm (150 mg/kg/day (male), 171 mg/kg/day (female), in the range corresponding to "Not classified"), effects on the liver and kidney (increases in absolute and relative weight) (male), effects on the cecum (increases in absolute and relative weight) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)). (2) It was reported that in a two-year carcinogenicity study with rats dosed by feeding (GLP), at or above 1,000 ppm (36.4 mg/kg/day (male), 46.5 mg/kg/day (female), within the range for Category 2), chronic nephropathy (female) was observed; and at 5,000 ppm (197 mg/kg/day (male), 245 mg/kg/day (female), in the range corresponding to "Not classified"), effects on the kidney (increases in absolute and relative weight, chronic nephropathy (male)), effects on the cecum (increases in absolute and relative weight, distention), effects on the liver (centrilobular fatty change, hypertrophy, and necrosis of hepatocytes, increases in absolute and relative weight (female), focal congestion (female)), black contents in the large intestine (male), and sinus dilation of the mesenteric lymph node were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)). (3) It was reported that in a one-year oral toxicity test with rats dosed by feeding (GLP), at or above 1,000 ppm (42.9 mg/kg/day (male), 53.5 mg/kg/day (female), within the range for Category 2), an increase in GGT (female) was observed; and at 5,000 ppm (226 mg/kg/day (male), 275 mg/kg/day (female), in the range corresponding to "Not classified"), effects on the blood (decreases in Ht, Hb, and RBC, decreases in MCV, MCH, and MCHC (male), a decrease in reticulocyte count (female)), an increase in PLT, an extension of APTT, increases in TP, Alb, and Glob, effects on the cecum (distention, increases in absolute and relative weight), effects on the liver (increases in absolute and relative weight, centrilobular hypertrophy of hepatocytes (male)), effects on the kidney (increases in absolute and relative weight), effects on the epididymis (increases in absolute and relative weight) (male), increased hematopoiesis of the bone marrow (male), tubular basophilic change (male), soiled fur of the vulva (female), an increase in rearing (female), a decrease in A/G ratio (female), an increase in T.Chol (female), an increase in ketone bodies in urine (female), an increase in relative heart weight (female), and an increase in lipofuscin deposition on tubular epithelium (female) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)). (4) It was reported that in a 90-day oral toxicity test with dogs dosed by feeding (GLP), at or above 3,000 ppm (90.3 mg/kg/day (male), 89.8 mg/kg/day (female), within the range for Category 2), an increase in ALP (female) was observed; at 15,000 ppm (475 mg/kg/day (female), in the range corresponding to "Not classified"), an increase in PLT (female), and centrilobular hypertrophy of hepatocytes (female) were observed; and at 25,000 ppm (776 mg/kg/day (male), in the range corresponding to "Not classified"), effects on the liver (increases in absolute and relative weight, centrilobular hypertrophy of hepatocytes) (male) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)). (5) It was reported that in a one-year oral toxicity test with dogs dosed by feeding (GLP), at or above 3,000 ppm (83.5 mg/kg/day (male), 85.2 mg/kg/day (female), within the range for Category 2), an increase in ALP, and an increase in GGT (female) were observed; at 15,000 ppm (448 mg/kg/day (female), in the range corresponding to "Not classified"), an increase in relative liver weight was observed; and at 25,000 ppm (701 mg/kg/day (male), in the range corresponding to "Not classified"), effects on the liver (increases in absolute and relative weight) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)). (6) It was reported that in a 78-week carcinogenicity study with mice dosed by feeding (GLP), at or above 600 ppm (77.6 mg/kg/day (male), within the range for Category 2), centrilobular hepatocyte hypertrophy (male) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), CLH Report (2018), ECHA RAC Opinion (2019)). (7) It was reported that in a 28-day dermal toxicity test with rats (GLP), no effect was observed at 1,000 mg/kg/day (in the range corresponding to “Not classified”) (CLH Report (2018), ECHA RAC Opinion (2019)).
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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