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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	112410-23-8
Chemical Name	N-tert-butyl-N'-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide; Tebufenozide
Substance ID	R01-B-076
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 (hydrazines) 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 is a hydrazine, 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 information that it is stable at up to 170 deg C (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)).
11	Self-heating substances and mixtures	*	- -	-	-	No data 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 oxygen (but not fluorine or chlorine) which is 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)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: >5,000 mg/kg (JMPR (2003), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016), Agricultural Chemicals Times supplement "Agricultural chemicals technology information," No.25 (Japan Crop Protection Association, 1998), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), HSDB (Access on August 2019))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: >5,000 mg/kg (JMPR (2003), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016), Agricultural Chemicals Times supplement "Agricultural chemicals technology information," No.25 (Japan Crop Protection Association, 1998), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014))
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)	*	- -	-	-	[Rationale for the Classification] It was impossible to exactly specify the category based on (1), however, since no animals died at the test concentration of 4.3 mg/L (male) and 4.5 mg/L (female) in both males and females, it is considered that the LD50 value is practically over 5.0 mg/L. Therefore, it was classified as "Not classified." [Evidence Data] (1) LC50 for rats (a dust, 4 hours) : male: >4.3 mg/L, female: >4.5 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016), Agricultural Chemicals Times supplement "Agricultural chemicals technology information," No.25 (Japan Crop Protection Association, 1998), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), HSDB (Access on August 2019))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a skin irritation test in which this substance (0.5 g) was applied to the skin of rabbits for 4 hours, no skin reactions were observed (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016)). (2) This substance is not irritating to the skin and is minimally irritating to the eyes in rabbits (JMPR (1996)).
3	Serious eye damage/eye irritation	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In an eye irritation test in which this substance (0.1 g) was applied to the eyes of rabbits, no irritation reactions were observed (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016)). (2) This substance is not irritating to the skin and is minimally irritating to the eyes in rabbits (JMPR (1996)).
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) and (2), it was classified as "Not classified." [Evidence Data] (1) In a skin sensitization test (maximization test and Buehler test) with guinea pigs, no skin sensitization was observed (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016))｡ (2) This substance showed no sensitization in a skin sensitization test with guinea pigs (JMPR (2003)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), since results in both in vivo and in vitro tests were negative, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, there is a report that it was negative in a chromosomal aberration test with rats (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016), HSDB (Access on August 2019)). (2) As for in vitro, there are reports that it was negative in a bacterial reverse mutation test, and a chromosomal aberration test, an unscheduled DNA synthesis test and a gene mutation test with cultured mammalian cells (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016)).
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 E (Evidence of Non-Carcinogenicity for Humans) by EPA (EPA Annual Cancer Report (2018): classified in 1994). [Reference Data, etc.] (2) In a combined chronic toxicity/carcinogenicity test in which this substance was administered by feeding to rats for 2 years, there were no neoplastic lesions the incidence of which incidence increased dose-dependently (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016)). (3) In a carcinogenicity test in which this substance was administered by feeding to mice for 18 months, there were no neoplastic lesions the incidence of which increased dose-dependently (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it is described in the summary of a Risk Assessment Report, Food Safety Commission that "in a two-generation reproductive study, an increase in the non-birth rate, decreases in the mean number of pups born and in the mean number of viable pups were observed." Since effects on fertility were observed at a dose where parental toxicity was observed, it was classified in Category 2. The classification result was changed from the previous classification by the use of new information sources. [Evidence Data] (1) In a two-generation reproductive test by feeding with rats, effects on fertility (a decrease in the mean number of implantations, an increase in the non-birth rate, decreases in the mean number of pups born and in the mean number of viable pups, etc.) were observed at dosages where reduced body weight gain, decreased feed consumption, tissue changes in the spleen, etc. were observed in parental animals (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016), JMPR (1996)). (2) In a two-generation reproduction test by feeding with rats, no effects on the reproductive ability and pups were observed at the highest dose where decreased body weight gain, tissue changes in the spleen and the vagina, etc. were observed in parental animals (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016)). Besides, in the JMPR (1996), it was reported that decreased body weight gain was observed on lactation Days 14-21 in lactating pups.
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] There is no report for single exposure to this substance in humans. Based on the information on experimental animals in (1), it was classified in Category 3 (narcotic effects). The classification result was changed from the previous classification by the use of the new information. [Evidence Data] (1) In a 4-hour single inhalation exposure test with rats, increased breathing rate, labored breath and lethargy were observed at 4.3 mg/L (corresponding to Category 2) of the aerosol of this substance. There are no dead animals, and no abnormal findings were observed at necropsy (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (blood system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1 (blood system). As a result of review by the use of new information sources, the classification result was changed from the previous classification. Besides, increased pigment deposition of Kupffer cells in the liver, used as the evidence of the classification for the liver in the previous classification, was considered to be a change reflecting the normal function of the live body due to hemolytic anemia. Therefore, the liver was not adopted as the target organ. [Evidence Data] (1) In a 1-year repeated dose toxicity study with dogs by feeding, increased incidence of Heinz bodies, pigment deposition of Kupffer cells in the liver, increased blood volume in the splenic sinus and sternal bone-marrow hyperplasia in males and females, increases in mean corpuscular volume and reticulocyte counts, decreases in erythrocyte counts, hemoglobin and hematocrit values, and increased hepatic weight in males, and increased splenic weight and femur bone-marrow hyperplasia in females were observed at or above 250 ppm (male/female: 8.7/8.9 mg/kg/day, within the range of Category 1). At 1500 ppm (male/female: 52.7/55.8 mg/kg/day, within the range of Category 2), increased mean corpuscular hemoglobin and methemoglobin levels, increased total bilirubin in males and females, increased splenic hematopoiesis and femur bone-marrow hyperplasia in males, and increased mean corpuscular volume, etc. in females were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016)). (2) In a 90-day repeated dose toxicity test with mice and dogs by feeding, a 2-year combined chronic toxicity/carcinogenicity test with rats by feeding and an 18-month carcinogenicity test with mice by feeding, the findings indicating hemolytic anemia were observed at doses within the range of Category 2 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2016)).
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	For crustacea (Mysidopsis bahia), 96-hour LC50 = 1.4 mg/L was obtained (U.S.EPA: OPP Pesticide Ecotoxicity Database, 2020), but because the expert judged that it might be actually around water solubility from reliable data on the water solubility of 0.83 mg/L (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2014)), it was classified in Category 1 in acute toxicity.
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 21-day NOEC = 0.032 mg/L for crustacea (Daphnia magna) (U.S.EPA: OPP Pesticide Ecotoxicity Database, 2020).
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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