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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	183675-82-3
Chemical Name	1-Methyl-N-[2-(4-methylpentan-2-yl)-3-thienyl]-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide; Penthiopyrad
Substance ID	R02-A-080-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	- -	-	-	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	- -	-	-	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: > 2,000 mg/kg (OECD TG 423, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (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, 2019), CLH Report (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), (2). [Evidence Data] (1) LC50 for rats (4 hours): > 5.67 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, 2013)) (2) LC50 for rats (4 hours): > 5.59 mg/L (OECD TG 403, GLP) (CLH Report (2015))
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, occlusive, 4-hour application, 72-hour observation), no irritation changes 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, 2019), ECHA RAC Opinion (2015), CLH Report (2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)).
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, 72-hour observation), conjunctival redness and chemosis were observed at 1 hour after application in 3 animals in the unwashed eye group but completely disappeared within 48 hours (in 3 in the unwashed eye group: mean corneal opacity score: 0, mean iritis score: 0, mean conjunctival redness score: 0.2, mean chemosis score: 0.2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), ECHA RAC Opinion (2015), CLH Report (2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)).
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). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 20) (OECD TG 406, GLP, intradermal administration: 5% suspension), 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, 2019), ECHA RAC Opinion (2015), CLH Report (2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test using the bone marrow cells of mice (two oral doses), 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, 2013), CLH Report (2015)). (2) 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, 2019), CLH Report (2015). (3) In a bacterial reverse mutation test (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, 2013), CLH Report (2015)). (4) In a chromosomal aberration test using the Chinese hamster lung fibroblasts (GLP), positive (+S9) 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, 2013), CLH Report (2015)). (5) In a gene mutation test using the mouse lymphoma cell (OECD TG 475, GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2015)).
6	Carcinogenicity	Category 2	Warning	H351	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) As for the classification results by domestic and international organizations, EPA classified this substance in S (Suggestive Evidence of Carcinogenic Potential) (EPA Annual Cancer Report (2019): Classification in 2011). (2) In a two-year carcinogenicity study with rats dosed by feeding, a significant increase in the incidence of adenomas of thyroid follicular cells as a neoplastic lesion was observed in males of the terminally sacrificed animals in the group treated at 250 mg/kg/day. In all male animals in the same group, the incidence (18.4%) didn't show a statistically significant difference and no increase in precancerous lesions was observed. But the incidence exceeded the laboratory's historical data of male Wistar rats (adenomas of follicular cells: 0% to 14.3%, carcinomas of follicular cells: 0% to 6%). Therefore, the lesion was considered to be related to the administration of the test substance (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (3) In an 18-month carcinogenicity study with mice dosed by feeding, an increase in the incidence of hepatocellular adenomas as a neoplastic lesion was observed in males in the group treated at 200 mg/kg/day or more (same as above). (4) The EPA determined the increase in the incidence of liver tumors observed in male mice to be related to the administration of the test substance and classified this substance in "S." On the other hand, the thyroid adenomas observed in male rats were not considered to be related to the administration of the test substance (US Federal Register Vol. 84, No. 109 (2019)). [Reference Data, etc.] (5) It was considered that the adenomas of thyroid follicular cells observed in a two-year carcinogenicity study with rats were induced as a result of enhanced activities of the drug-metabolizing enzyme, UDPGT, in the liver, reduced serum levels of T4, and persistently enhanced secretion of TSH through negative feedback caused by the administration of this substance. It was indicated that the effects on thyroid hormones were reversible (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2015)). (6) In the EU, it was determined that the incidence of hepatocellular adenomas in male mice was within the latest historical control range, that thyroid neoplasms in rats were caused by the mode of action indicated in (5), that humans are less sensitive than rodents to perturbations of thyroid hormone homeostasis, and that the formation of tumors by this mode of action was not relevant to humans. Therefore, it was proposed that this substance should be classified as "Not classified" in the CLP classification, and RAC agreed to the proposal (CLH Report (2015), RAC opinion (2015)).
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. In (2), increases in the numbers of post-implantation losses, fetal mortalities, etc. were observed in pups at doses at which slight maternal toxicity effects were observed. [Evidence Data] (1) In a two-generation reproduction toxicity study with rats dosed by feeding (GLP), at doses at which general toxicity effects (effects on the liver, thyroid and kidney) were observed in parental animals, and pups showed lower body weight (F1 and F2) and a delay in preputial separation (F1 males). It was reported that no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013), CLH Report (2015)). (2) In a developmental toxicity study with rats dosed by gavage (GLP, days 6-19 of gestation), at doses at which general toxicity effects (reduced body weight gain, a reduction in food consumption, a reduction in gravid uterine weight) were observed in parental animals, and pups showed increases in the numbers of post-implantation losses and fetal mortalities and a decrease in the number of viable fetuses (females). It was reported that no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013), CLH Report (2015)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage (GLP, days 6-28 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013), CLH Report (2015)). (4) It was reported that in a developmental neurotoxicity study with rats dosed by gavage, at 250 mg/kg/day, a reduction in food consumption in parental animals, and perianal staining and reduced body weight gain/increased locomotor activity (males) in pups were observed, but no developmental neurotoxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2015)). The EPA reported that at doses at which no maternal toxicity was observed, offspring animals showed a decrease in body weight, an increase in locomotor activity, and tremors; and that in a preliminary study, a decrease in body weight, deterioration, and mortality were seen in offspring animals at doses at which no maternal toxicity was observed (US Federal Register (2019)). [Reference Data, etc.] (5) The RAC judged that no classification for this substance was necessary. The increases in post-implantation losses and fetal mortalities observed in pups in (2) were not considered to be a secondary consequence of maternal toxicity, and these increases were slight. Therefore, it was judged that no classification for developmental toxicity was necessary (RAC Opinion (2015)).
8	Specific target organ toxicity - Single exposure	Category 2 (nervous system)	Warning	H371	P308+P311 P260 P264 P270 P405 P501	[Rationale for the Classification] Based on the symptoms detected in the acute neurotoxicity test in (1), it was classified in Category 2 (nervous system). [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats by single oral dose, hunched posture, a decrease in body temperature, an increase in landing footsplay values, a reduction in locomotor activity, 'no response' in the approach and touch tests (males); and a reduction in trunk muscle tone, lower reactivity to handling, and abnormal gait (females) were observed at 500 mg/kg (within the range for Category 2); and reduced body weight gain, piloerection, a reduction in trunk muscle tone, lower reactivity to handling, abnormal gait, bradypnea, and a weak response in the tail pinch test (males); and tremor and chewing mouth movements, 'no response' in the approach and touch tests (females) were observed at 2,000 mg/kg (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019), CLH Report (2015)). [Reference Data, etc.] (2) In the U.S., the dose of 125 mg/kg at which no (neurological) symptom occurred in the acute neurotoxicity test of the above (1) was used as the Point of Departure (POD) to set the acute reference dose (acute RfD) (US Federal Register vol. 84, No. 109 (2019)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (2), it was classified in Category 2 (liver). [Evidence Data] (1) It was reported that in a 90-day oral toxicity study with rats dosed by feeding, liver effects (an increase in relative weight, hepatocellular hypertrophy) and a decrease in MCHC, a longer APTT, etc., in males were observed at 100 mg/kg/day (within the range for Category 2); and apparent hematological and liver effects were observed at high doses of 250 mg/kg/day or more (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)). (2) It was reported that in a two-year carcinogenicity study with rats dosed by feeding, periportal fatty degeneration of hepatocytes was observed in males at 83 mg/kg/day (within the range for Category 2); and effects on the liver, the kidney in males, and the adrenal gland in females were observed at 250 mg/kg/day (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)). [Reference Data, etc.] (3) In 90-day oral toxicity studies with mice and dogs dosed by feeding and one-year chronic toxicity studies with rats and dogs dosed by feeding, no toxicity effect was observed at doses within the range for Category 2 and effects on the liver, blood, thyroid, adrenal gland, etc., were observed at high doses in the range corresponding to "Not classified" (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2019)). (4) In a 28-day subacute dermal toxicity test with rats, there was no toxicity finding at doses up to 1,000 mg/kg/day (converted guidance value: 311 mg/kg/day, in the range corresponding to "Not classified") (CLH Report (2015)). (5) In short-term dose studies with rats, mice and dogs, critical effects were observed in the liver (an increase in weight and histopathological findings) and the gallbladder (edema in dogs). The dog was the most sensitive species among them. In long-term dose studies with rats and mice, critical effects were observed in the liver (an increase in liver weight in mice, periportal fatty degeneration of hepatocytes in rats) and in the thyroid (an increase in altered thyroid colloid in mice) (EFSA (2013)). (6) The liver and thyroid were identified as the target organs for toxicity of this substance. In short-term dose tests, liver alterations (such as a weight increase, enzyme changes, and hypertrophy) were observed in rats and mice at similar doses, and in dogs at higher doses. The liver findings (fatty change, hepatocellular degeneration, Kupffer cell proliferation) observed in rats, in particular, were more significant than the liver findings in the other species of test animals (US Federal Register vol. 84, No. 109 (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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.29 mg/L for fish (Pimephales promelas) (ECOTOX, 2021, OPP Pesticide Ecotoxicity Database).
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 33-day NOEC = 0.1 mg/L for fish (Pimephales promelas) (ECOTOX, 2021, OPP Pesticide Ecotoxicity Database).
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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