NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	129558-76-5
Chemical Name	N-[4-(p-Tolyloxy)benzyl]-1-methyl-3-ethyl-4-chloro-1H-pyrazole-5-carboxamide; Tolfenpyrad
Substance ID	R01-B-082
Classification year (FY)	FY2019
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2006
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)	MHLW Website (in Japanese Only)
Model SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	eChemPortal

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	*	- -	-	-	There is a chemical group associated with explosive properties (neighboring nitrogen atoms) present in the molecule, but the classification is not possible due to no data.
2	Flammable gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7	Flammable solids	*	- -	-	-	No data available.
8	Self-reactive substances and mixtures	*	- -	-	-	There are neighboring nitrogen atoms, a chemical group associated with explosive properties, present in the molecule, but the classification is not possible due to no data.
9	Pyrophoric liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10	Pyrophoric solids	*	- -	-	-	It was classified as "Not classified" because it is estimated that it does not ignite at normal temperatures from data: it is stable to heat at or below 250 deg C (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
11	Self-heating substances and mixtures	*	- -	-	-	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	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	The substance is an organic compound containing chlorine and oxygen (but not fluorine) which are chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	*	- -	-	-	It was classified as "Not classified" because it is not desensitized by wetting, dilution, etc.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 3. [Evidence Data] (1) LD50 for rats (CMC-Na solution): male: 260-386 mg/kg, female: 113-150 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)) (2) LD50 for rats (olive oil): male: 86 mg/kg, female: 75 mg/kg (JMPR (2013), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)) (3) LD50 for rats (CMC-Na solution): >=113 mg/kg (JMPR (2013))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: male: >2,000 mg/kg, female: >3,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)) (2) LD50 for rats: >2,000 mg/kg (JMPR (2013))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[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] Based on (1), it was classified in Category 4. [Evidence Data] (1) LC50 for rats (dust, 4 hours): male: 2.21 mg/L, female: 1.50 mg/L (JMPR (2013), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." The category was changed due to new data obtained. [Evidence Data] (1) This substance was not irritating to the skin (JMPR (2013)). (2) In a test in which rabbits were exposed to this substance (0.5 g) under semi-occlusion for 4 hours, the total scores of erythema and edema at 24/48/72 hours were 0.3, 0.2 and 0 (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). [Reference Data, etc.] (3) In a skin irritation test with rabbits, slight irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)).
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2A. [Evidence Data] (1) This substance was slightly irritating to the eyes (JMPR (2013)). (2) In an eye irritation test with rabbits, transient irritation was observed, and the total scores (maximum 110) at 1/24/48/72 hours were 7.5, 5.7, 3.7, 1.7. All reactions cleared by Day 14 (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). [Reference Data, etc.] (3) In an eye irritation test with rabbits, slight irritation was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) In a dermal sensitization test (maximization test) with guinea pigs, no skin reactions were observed, and it was judged to be negative for sensitization (JMPR (2013), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, there is a report of a negative result in a micronucleus test with mice (Risk Assessment Report (Pesticides) (Food Agricultural Materials Inspection Center, 2011)). (2) As for in vitro, there are reports of negative results in a bacterial reverse mutation test and a gene mutation test with cultured mammalian cells and a positive result (S9-) in a chromosomal aberration test with cultured mammalian cells (Same as above).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Based on the classification results by other organizations in (1), it was classified as "Not classified" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) In the classification results by domestic and international organizations, it was classified as NL (Not Likely to be Carcinogenic to Humans) by EPA (EPA Annual Cancer Report (2018): 2010 classification) [Reference Data, etc.] (2) In a combined chronic toxicity/carcinogenicity study in which this substance was administered by feeding to rats for 2 years, no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). (3) In a carcinogenicity test in which this substance was administered by feeding to mice for 18 months, no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), since reproductive and developmental effects were clearly observed at doses where parental toxicity was observed, it was classified in Category 2. [Evidence Data] (1) In a two-generation reproduction toxicity study in which rats were dosed by feeding, a prolonged gestation period, abnormal delivery, a low birth index, developmental effects of pups (reduced body weight gain, delayed pinna unfolding, delayed eye-opening, delayed surface righting reflex), decreased number of live pups, lower thymus weights, etc. were observed at doses where parental toxicity (death (death due to dystocia 2/30 animals, killed in a moribund state 1/30 animals), decreased body weight gain, etc.) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). (2) In a developmental toxicity test in which female rabbits were dosed by gavage on gestational Days 6-18, a decrease in feed consumption, premature birth (1 animal) and total litter death (1 animal) were observed in maternal animals (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). [Reference Data, etc.] (3) In a developmental toxicity test in which female rats were dosed by gavage on gestational Days 6-15, lower fetal weight and an increased incidence of lumbar ribs in fetuses were observed in fetuses at the dose at which maternal toxicity (decreased body weight gain, decrease in feed consumption) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)).
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] There is no report of single exposure to this substance in humans. As for experimental animals, as described in (1), since abnormal breath sounds, lethargy and coma were observed, it was classified in Category 1 (respiratory organs), Category 3 (narcotic effects). The classification result was changed from the previous classification by using new information sources. [Evidence Data] (1) In a 4-hour single inhalation exposure test with rats, increased or decreased number of breath, labored breath, abnormal breath sounds, ataxia and hunched posture were observed in both males and females by exposure to the dust of this substance at 0.95-2.07 mg/L (corresponding to from the vicinity of the upper limit of Category 1 to Category 2). In addition, there is a description that coma, cyanosis, discolored extremities, hypothermia, lethargy, gasping, toe gait and ptosis were occasionally observed. At necropsy of dead animals, reddening, red spots, bleeding and dark red colored foci were observed in the lungs (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)). [Reference Data, etc.] (2) In a single oral dose test with rats, abdominal position, lateral position, hunched position, hypolocomotion, ataxic gait, irregular respiration and dyspnea were observed in both males and females. Though there is no description of a minimum dosage where effects were observed, if the effects were observed near the LD50 value (male: 86 mg/kg, female: 75 mg/kg), it corresponds to Category 1 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (liver, kidney, hematopoietic system), Category 2 (reproductive organs (male))	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) and (2), by oral administration to rats, the effects on the liver, kidney and hematopoietic system were observed within the range of Category 1. Based on (3), by oral administration to dogs, the effects on the liver and reproductive organs (men) were observed within the range of Category 2. Therefore, it was classified in Category 1 (liver, kidney, hematopoietic system), Category 2 (reproductive organs (men)). Though effects on the pancreas, ovary and uterus were also observed within the range of Category 1 in (1), findings of such were not observed in (2) which is the more prolonged test. Therefore, these were not adopted as target organs. As a result of reviewing the data by adding information from new sources, the classification result was changed from the previous classification. [Evidence Data] (1) In a 90-day repeated oral dose toxicity test by feeding with rats, decreased leukocyte counts and platelets, increased MCV, MCH and reticulocyte counts, increased ALP, gamma-GT and BUN, increased weights of the liver and kidney, diffuse hypertrophy of hepatocytes, hypertrophy of the proximal renal tubule epithelium, hyaline droplets in the proximal renal tubule epithelium, diffuse hypertrophy of the pancreas acinar cells, decreased hematopoietic cells in the femur and sternal bone marrow, atrophy of the ovary and uterus, etc. were observed at doses up to 160 ppm (male/female: 9.33/9.32 mg/kg/day, within the range of Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). (2) In a combined chronic toxicity/carcinogenicity study in which this substance was administered by feeding to rats for 2 years, decreased leukocyte counts, increased weights of the liver and kidney, hypertrophy of the proximal renal tubule epithelium, hyaline droplets in the proximal renal tubule epithelium, increased basophilic foci of hepatocytes, etc. were observed at doses up to 80 ppm (male/female: 3.07/3.79 mg/kg/day, within the range of Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)). (3) In a 90-day repeated dose toxicity test by gavage with dogs, increases or a trend toward increases in ALT and BUN, decreased weight of the testis, atrophy of the seminiferous tubules, eosinophilia in the liver cytoplasm, centrilobular hepatocellular vacuolation, etc. were observed at doses up to 30 mg/kg/day (within the range of Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2011)).
10	Aspiration hazard	*	- -	-	-	[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 = 0.001 mg/L for crustacea (Daphnia magna) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2011)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 1 because sufficient data on rapid degradability were not obtained, and it was classified in Category 1 in acute toxicity.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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