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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	120068-37-3
Chemical Name	5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-3-cyano-4-[(trifluoromethyl)sulfinyl]pyrazole; Fipronil
Substance ID	R01-B-079
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, and an S=O bond, a chemical group associated with self-reactive 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	*	- -	-	-	No data available.
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 fluorine, chlorine, and oxygen, and the oxygen is chemically bonded to an element (S) other than carbon or hydrogen. However, the classification is not possible due to no data.
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: male: 92 mg/kg, female: 103 mg/kg (JMPR (1997), Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016), HSDB (Access on September 2019)) (2) LD50 for rats: 100 mg/kg (HSDB (Access on September 2019)) (3) LD50 for rats: 97 mg/kg (HSDB (Access on September 2019))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	[Rationale for the Classification] Based on (1)-(3), it was classified in Category 3. The category was changed from the previous classification by using new information sources. [Evidence Data] (1) LD50 for rabbits: 354 mg/kg (JMPR (1997)) (2) LD50 for rabbits: male: 445 mg/kg, female: 354 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016), HSDB (Access on September 2019)) (3) LD50 for rats: >2,000 mg/kg (JMPR (1997), Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016), HSDB (Access on September 2019))
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 2	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2. The category was changed from the previous classification by using new information sources. [Evidence Data] (1) LC50 for rats (dusts, 4 hours): 0.682 mg/L (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), HSDB (Access on September 2019)) (2) LC50 for rats (dusts, 4 hours): male: 0.36 mg/L, female: 0.42 mg/L (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), HSDB (Access on September 2019)) [Reference Data, etc.] (3) LC50 for rats (exposure period is unknown): 0.36 mg/L (JMPR (1997))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) In a skin irritation test with rabbits in which this substance was moistened with water and applied, it was not irritating (JMPR (1997), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) Skin and eye irritation tests with rabbits were conducted, and no signs of skin irritation or eye irritation were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (3) In a skin irritation test with rabbits in which this substance was moistened with corn oil and applied for 4 hours, mild erythema (score of 1-2) and transient mild edema were observed, however, the edema disappeared within 7 days (JMPR (1997), HSDB (Access on September 2019)).
3	Serious eye damage/eye irritation	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) In an eye irritation test with rabbits, no change in the cornea or the iris was observed, while mild redness and edema in the conjunctiva were observed 1 hour after application, however, these subsided within 72 hours (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) Skin and eye irritation tests with rabbits were conducted, and no signs of skin irritation or eye irritation were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (3) It was slightly irritating in an eye irritation test with rabbits (JMPR (1997)).
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 skin sensitization tests (2 maximization tests and a Buehler test) with guinea pigs, positive response rates were 20% and 0% in the maximization method (intradermal induction concentrations were both 5% in both), and this substance was concluded as a mild sensitizer, but it was negative in the Buehler method (JMPR (1997), Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
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 that it was negative in a mouse micronucleus test (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (2) As for in vitro, there are reports that it was negative in a bacterial reverse mutation test, a mammalian cell gene mutation test, and a chromosomal aberration test with cultured human lymphocytes, and a report that it was positive (chromosomal aberrations were induced after 6-hour treatment only at concentrations at which the cytotoxicity was observed) in a mammalian cell chromosomal aberration test (same as the above).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on classification results by other organizations in (1), it was classified in Category 2 in accordance with the GHS Classification Guidance for the Japanese Government. The classification result was changed from the previous classification by adding classification results by other organizations [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified as C (Possible Human Carcinogen) by EPA (EPA Annual Cancer Report (2018): 1995 Classification). [Reference Data, etc.] (2) In a chronic toxicity/carcinogenicity combined study with rats administered this substance for 2 years by feeding, significant increases in thyroid follicular cell adenoma and carcinoma in males and thyroid follicular cell adenoma in females were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (3) In a carcinogenicity study with mice administered this substance for 78 weeks by feeding, no neoplastic lesions the incidence of which increased dose-dependently were found (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), since unambiguous effects on fertility and effects on pups (including effects on the nervous system) were observed at doses at which maternal toxicity was observed, it was classified in Category 2. [Evidence Data] (1) In a two-generation reproductive toxicity test with rats by feeding, at the highest dose, death (P male: 2/30 animals, P female: 5/30 animals, F1 male: 0/30 animals, F1 female: 2/30 animals), convulsions, decreased body weight gain, decreased food consumption, increased weights of the thyroid and liver, decreased pituitary weights, thyroid follicular epithelial hypertrophy, centriacinar fatty vacuolation in the liver, etc. were observed in parental animals, furthermore, decreased live birth index in parental animals and convulsions, decreased body weights, decreased litter size, reduced postnatal survival, reduced viability index on Day 4, etc. in the pups were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016), JMPR (1997)). (2) In a developmental neurotoxicity test with female rats fed from gestational Day 6 through lactation Day 10 (51 days), at a dose at which maternal toxicity was not observed, decreased body weight and delayed preputial separation were observed in the pups, and at a dose at which maternal toxicity (reduced body weight gain, decreased food consumption) was observed, reduced viability index on Day 4, delays in pinna unfolding, incisor eruption and vaginal opening, reduced acoustic startle response (reversible), and delayed swimming development, etc. were observed in the pups. No abnormalities however were observed by the neuro histopathological examination (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)).
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)-(4), it was classified in Category 1 (nervous system). [Evidence Data] (1) Multiple cases in which humans who ingested this substance accidentally or intentionally developed generalized tonic-clonic seizures were reported (HSDB (Access on September 2019)). (2) In a single oral dose toxicity test with rats, piloerection, diarrhea, hunched posture and abnormal gait at or above 50 mg/kg, lethargy, decreased respiratory rate, pallor in the extremities and ptosis at or above 80 mg/kg were observed. The doses at which these effects were observed corresponded to Category 1 (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (3) In a single dermal dose toxicity test with rabbits, convulsions, tremors, diarrhea, emaciation, increased locomotor activity and delayed convulsions were observed at or above 250 mg/kg (corresponding to Category 1) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (4) In a single 4-hour inhalation exposure test with rats, piloerection, hunched posture, vocalization on contact, salivation, hypothermia, tremors, convulsions and ataxia were observed at or above 0.259 mg/L (corresponding to Category 1) of the dust of this substance (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). [Reference Data, etc.] (5) There is a description that this substance is considered to exhibit an insecticidal action by inhibiting the chloride ion channel control by GABA, which is regarded as an inhibitory neurotransmitter, and inhibiting neuronal excitation in insects (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (central nervous system, thyroid, liver, kidney, blood system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1)-(4), effects on the central nervous system, thyroid, liver, kidney, and blood system were observed within the range of Category 1, by oral administration to experimental animals, and based on (5), effects on the central nervous system were observed within the range of Category 1, by dermal exposure to rabbits, therefore, it was classified in Category 1 (central nervous system, thyroid, liver, kidney, blood system). The review was done by using new information sources, and the classification result was changed from the previous classification. [Evidence Data] (1) In a 90-day repeated dose toxicity test with rats by feeding, decreased hematocrit and increased liver weight, etc. at or above 30 ppm (male/female: 1.93/2.28 mg/kg/day, within the range of Category 1), and increased thyroid weight, hypertrophy of the follicular epithelium of the thyroid, hyperplasia of the thyroid follicular cells, panacinar fatty vacuolation of hepatocytes, etc. at 300 ppm (male/female: 19.9/24.0 mg/kg/day, within the range of Category 2) were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (2) In a 90-day repeated dose toxicity test with dogs by feeding, sacrificed in extremis (1 male animal, 3 female animals), emaciation, tremors, convulsions, head nodding, sporadic generalized spasms, facial twitching, exaggerated blink, exaggerated gag responses, depressed tactile placing response, etc. were observed at 10 mg/kg/day (within the range of Category 1) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (3) In a 2-year chronic toxicity/carcinogenicity combined test with rats by feeding, convulsions, death after persistent convulsions, decreases in erythrocyte count, decreased hematocrit value, etc. at or above 1.5 ppm (male/female: 0.059/0.078 mg/kg/day, within the range of Category 1), decreased hemoglobin concentration, elevated urine volume and urine protein, increased incidence and severity of progressive nephropathy, increased kidney weight and thyroid weight, thyroid follicular cyst and growth abnormality, etc. at or above 30 ppm (male/female: 1.27/1.61 mg/kg/day, within the range of Category 1), and overactivity, increased weights of the adrenal gland, liver and spleen, accumulations of minerals in the aorta, parathyroid hyperplasia, increased uterus weight, etc. at 300 ppm (male/female: 12.7/16.8 mg/kg/day, within the range of Category 2) were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (4) In a 78-week carcinogenicity test with mice by feeding, microvesicular vacuolation of centrilobular hepatocytes, etc. at or above 10 ppm (male/female: 1.18/1.23 mg/kg/day, within the range of Category 1), increased liver weight, hepatocellular hyperplasia, chronic degenerative changes in the livers, etc. at 30 ppm (male/female: 3.43/3.62 mg/kg/day, within the range of Category 1) were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 2016)). (5) In a 21-day dermal exposure test with rabbits, locomotor hyperactivity was observed at 10 mg/kg/day (within the range of Category 1) in males and females (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission, 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	It was classified in Category 1 from 96-hour LC50 = 0.083 mg/L for fish (Lepomis macrochirus) (U.S.EPA: OPP Pesticide Ecotoxicity Database, 2020).
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 32-day NOEC = 0.00024 mg/L for fish (Cyprinodon variegatus) (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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