NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	123572-88-3
Chemical Name	5-Chloro-1,3-dimethyl-N-(1,1,3-trimethyl-1,3-dihydroisobenzofuran-4-yl)-1H-pyrazole-4-carboxamide; Furametpyr
Substance ID	R02-A-048-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	- -	-	-	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 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	- -	-	-	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), (2). [Evidence Data] (1) LD50 for rats (males): 640 mg/kg (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)) (2) LD50 for rats (females): 590 mg/kg (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019))
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 (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 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). [Evidence Data] (1) LC50 for rats (4 hours): > 5.44 mg/L (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008))
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) (GLP, occlusive, 4-hour application, 72-hour observation), no skin irritation reactions 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, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)).
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), very slight irritation reactions in the conjunctiva were observed after 1 hour, but all local reactions disappeared after 72 hours (corneal opacity score: 0/0/0/0/0/0, iritis score: 0/0/0/0/0/0, conjunctival redness score: 0.3/0.7/0.3/0.3/0.7/0.3, chemosis score: 0/0.3/0/0/0.3/0.3) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 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] It was classified as "Not classified" because a positive rate was less than 30% in a maximization test in (1), and a positive rate was less than 15% in a Buehler test in (2). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 10) (GLP, intradermal administration: 1% sample), a positive rate was 0% (0/20) at both 24, 48 hours when challenged with 5% sample, and a positive rate was 20% (2/10) at both 24, 48 hours when challenged with 25% sample (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (2) It is reported that in a Buehler test with guinea pigs (n = 10) (GLP, topical administration: 100% sample), a positive rate was 0% (0/10) at both 24, 48 hours (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (8), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test with the bone marrow cells of mice (single oral dose, GLP), it was positive in males (group at a high dose), and negative in females (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (2) In a micronucleus test with the bone marrow cells of mice (repeated dose by feeding, maximum 13 weeks), the substance was negative (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (3) In an unscheduled DNA synthesis (UDS) test using hepacytes from rats (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (4) In a bacterial reverse mutation test (GLP), the substance was negative (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (5) In an in vitro chromosomal aberration test, chromosomal aberration induction was observed. In an in vivo micronucleus test with mice, the incidence frequency of large micronuclei (1/4 or above of the diameter of a red blood cell) increased in the male group at a high dose. However, since no micronuclei was induced in a feeding administration test, it was considered that furametpyr had no genotoxicity that might become a problem for a living body (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)). (6) In an in vitro chromosomal aberration test (GLP), chromosomal aberration induction was observed. (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (7) As a result of a chromosomal aberration test/ a micronucleus test with the bone marrow cells of mice, it was negative for chromosomal aberrations and positive for micronuclei. Based on this result and the result of (5), it was considered to be based on the cell division inhibition effect, and it was concluded that chromosomal aberrations were not induced and there was no chromosomal break effect (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (8) In a mechanism examination test for micronucleus induction using a CREST antibody, the rate of induction was similar to that of micronuclei and centromere-positive micronuclei by vincristine, an inhibitor of spindle fiber formation, which was a positive control substance, and based on this result and (7), the data was considered to support that the micronucleus induction by the active ingredient of this substance was not genotoxicity that directly damaged DNA (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] There was no classification result by domestic and international organizations. However, based on the test results of (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a 2-year combined chronic toxicity/carcinogenicity study with rats (dosed by feeding), as a result of the substance administration to the level where clear general toxicity occurred in both males and females, no increase in the incidence of neoplastic lesions was observed in association with the administration. The carcinogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (2) Also in a 78-week carcinogenicity study with mice (dosed by feeding), the substance was administered to the level where liver effects occurred in both males and females, but no increase in the incidence of neoplastic lesions was observed in association with the administration. The carcinogenicity was not observed. (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2. [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding (GLP), at 1,000 ppm, general toxic effects (a decrease in weight of the pituitary, inhibition of body weight gain, a decrease in food consumption, etc.), and a decrease in the number of implantations (P female) as effects on reproductive ability were observed in parent animals, and inhibition of body weight gain was observed in F1 and F2 offspring (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (2) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding (GLP), which was carried out as an additional test of (1), no effect on reproductive ability was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (3) It was reported that in a developmental toxicity study with rats dosed by gavage (GLP, days 6-15 of gestation), at or above 60 mg/kg/day, inhibition of body weight gain and a decrease in food consumption were observed in parent animals, and low body weight, delayed ossification, and visceral variations (an increase in the incidence frequency of thymic remnant in the neck and supernumerary coronary ostium) were observed in offspring, but teratogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (4) In a developmental toxicity study with rabbits dosed by gavage (GLP, days 7-19 of gestation), at 100 mg/kg/day, inhibition of body weight gain and a decrease in food consumption were observed in parent animals, and a high value of the incidence frequency of visceral malformations (left azygos vein venous return of the posterior vena cava) was observed in offspring. However, there was no significant difference from the control group in the total incidence frequency of the left azygos vein venous return and the right azygos vein venous return, which was considered to be the same abnormal type as the left azygos vein venous return of the posterior vena cava, it was considered not to be the effect of the sample administration, and teratogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)).
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1), effects on the nervous system were observed within the dose range for Category 1, and ataxic gait, and a decrease in locomotor activity in (2) and (3) were also considered to be the findings for supporting the effects on the nervous system, therefore, it was classified in Category 1 (nervous system). [Evidence Data] (1) It was reported that in a general pharmacological test (general condition observation) with mice by a single oral administration, at or above 300 mg/kg (within the range for Category 1), a decrease in locomotor activity, decreases in alertness and pinna reflex, sedation, ataxic gait, a decrease in respiration, passivity, abnormal position of the limbs, decreases in position vision, grip strength, and abdominal muscle tone (male), incontinence of urine (male), and a decrease in pain sensation (female) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (2) It was reported that in an acute oral toxicity test with rats (GLP), at or above 300 mg/kg (within the range for Category 1), low body temperature, lying on belly, lying on side, ataxic gait, irregular respiration, piloerection, lacrimation, a decrease in locomotor activity, and incontinence of urine (female) were observed; and at or above 550mg/kg (within the range for Category 2), chromaturia (female) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (3) It was reported that in an acute oral toxicity test with mice (GLP), at or above 500 mg/kg (within the range for Category 2), a decrease in locomotor activity, low body temperature, lying on belly, lying on side, ataxic gait, irregular respiration, piloerection, lacrimation, incontinence of urine, and blackening and loss of the tail end were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (3), the target organ was considered to be the liver, and based on (2), effects were observed within the dosage range for Category 1, therefore, it was classified in Category 1 (liver). [Evidence Data] (1) It was reported that in a repeated dose 90-day oral toxicity study with dogs dosed by gavage (GLP), at 50 mg/kg/day (within the range for Category 2), effects on the liver (an increase in relative weight, an increase in ALP, an increase in BSP retention rate, chronic hypertrophy of the hepatocytes, an increase in absolute weight (male)), etc. were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (2) It was reported that in a 1-year chronic toxicity study with dogs dosed by gavage (GLP), at or above 5 mg/kg/day (within the range for Category 1), effects on the liver (focal necrosis of the hepatocytes, ballooning hepatocytes, an increase in ALP (male), hypertrophy of the hepatocytes, hepatic fibrosis, hydropic degeneration of the hepatocytes (female)) were observed; and at 50 mg/kg/day (within the range for Category 2), effects on the liver (increases in absolute and relative weight, an increase in BSP retention rate, an increase in GGT, an increase in ALT, hypertrophy of the hepatocytes, hepatic fibrosis, hydropic degeneration of the hepatocytes (male), an increase in ALP (female)), and effects on the blood (an increase in platelet count, an extension of APTT) were observed. (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (3) It was reported that in combined chronic toxicity/carcinogenicity studies with rats dosed by feeding (GLP), at or above 1,000 ppm (45.9 mg/kg/day (female), within the range for Category 2), increases in PL and T.Chol, an increase in relative weight of the liver, centrilobular hypertrophy of the hepatocytes, pelvic calcification, and foam cell infiltration in the pulmonary alveoli (female) were observed; and at or above 2,000 ppm (73.0 mg/kg/day (male), 93.5 mg/kg/day (female), within the range for Category 2), an increase in GGT, an increase in T.Chol, an increase in relative weight of the liver, and centrilobular hypertrophy of the hepatocytes (male) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). [Reference Data, etc.] (4) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by feeding (GLP), at or above 3,000 ppm (184 mg/kg/day (male), 195 mg/kg/day (female), in the range corresponding to "Not classified"), effects on the liver, kidney, blood system, etc. (inhibition of body weight gain, a decrease in food consumption, increases in alpha 2-Glob, PL, and T.Chol, increases in absolute and relative weight of the liver, centrilobular hypertrophy of the hepatocytes, an increase in the reticulocytes, increases in TP and beta-Glob (male), a decrease in A/G ratio (female)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (5) It was reported that in a repeated dose 90-day oral toxicity study with mice dosed by feeding (GLP), at or above 1,000 ppm (123 mg/kg/day (male), in the range corresponding to "Not classified"), an increase in TG, an increase in absolute weight of the liver, and hypertrophy of the hepatocytes (male) were observed; and at or above 2,000 ppm (243 mg/kg/day (male), 311 mg/kg/day (female), in the range corresponding to "Not classified"), an increase in relative weight of the liver, decreases in RBC, Hb, and Ht, and hypertrophy of the hepatocytes (female) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). (6) It was reported that in 78-week combined chronic toxicity/carcinogenicity studies with mice dosed by feeding (GLP), at or above 1,500 ppm (159 mg/kg/day (male), 185 mg/kg/day (female), in the range corresponding to "Not classified"), an increase in absolute weight of the liver, centrilobular hypertrophy of the hepatocytes (male), and an increase in relative weight of the liver (female) were observed; and at 3,000 ppm (309 mg/kg/day (male), 355 mg/kg/day (female), in the range corresponding to "Not classified"), an increase in relative weight of the liver (male), centrilobular hypertrophy of the hepatocytes, and altered hepatocellular foci (female) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)).
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 = 1.56 mg/L for fish (Cyprinus carpio) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)).
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 as "Not classified" because it is not rapidly degradable (BIOWIN) and due to 72-hour NOErC = 10 mg/L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 because it is not rapidly degradable (BIOWIN) and due to 96-hour LC50 = 1.56 mg/L for fish (Cyprinus carpio) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2008)). By drawing a comparison between the above results, it was classified in Category 2.
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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