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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	52315-07-8
Chemical Name	alpha-Cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (synonym: Cypermethrin) *Including alpha-Cypermethrin and zeta-Cypermethrin
Substance ID	R03-B-022-METI, MOE
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/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 (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)	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	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. Besides, there is information that it is combustible (GESTIS (Accessed Aug. 2021)).
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There are chemical group associated with self-reactive properties (ethylene group) and strained rings present in the molecule, but the classification is not possible due to no data.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Not classified	- -	-	-	It is estimated that it does not correspond to pyrophoric substances, hazards of the highest precedence, because it is classified in Division 6.1 in UNRTDG (UN3352). Therefore, it was classified as "Not classified."
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 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	- -	-	-	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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) to (7), it was classified in Category 3 by adopting the category with the higher hazard. [Evidence Data] (1) LD50 for rats (males): 221 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)) (2) LD50 for rats (females): 195 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)) (3) LD50 for rats: 334 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)) (4) LD50 for rats (females): 500 mg/kg (OECD TG 423, GLP) (CLH Report (2018)) (5) LD50 for rats: 1,945 mg/kg (1,723 mg/kg (males), 2,150 mg/kg (females)) (CLH Report (2018)) (6) LD50 for rats (males): 247 mg/kg (EPA Pesticides RED (2006)) (7) LD50 for rats (females): 309 mg/kg (EPA Pesticides RED (2006))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)) (2) LD50 for rabbits (females): > 2,400 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)) (3) LD50 for rabbits: > 2,460 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018), EPA Pesticides RED (2006))
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)	Category 4	Warning	H332	P304+P340 P261 P271 P312	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 4. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) LC50 (4 hours, aerosol, OECD TG 403) for rats: 3.894 mg/L (3.281 mg/L (males), 5.038 mg/L (females)) (CLH Report (2018)) (2) LC50 (4 hours) for rats: 1.26 mg/L (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018), JMPR (2006), EFSA (2008)) [Reference Data, etc.] (3) LC50 (4 hours) for rats: > 0.254 mg/L (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)) (4) LC50 (4 hours, mist) for rats: > 3.56 mg/L (CLH Report (2018))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified" (Category 3 in UN GHS classification). [Evidence Data] (1) It was reported that, in a skin irritation test with rabbits and rats, slight irritation was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (2) This substance was slight skin irritant substance (JMPR (2006)). (3) In a skin irritation test with rabbits, slight to mild erythema was observed but resolved within 48 hours. The primary irritation index (PII) was reported to be 0.71 (EPA Pesticides (2006)). (4) This substance was not a skin irritant substance (EFSA (2018)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in an eye irritation test with rabbits, very slight irritative effects (slight conjunctivitis, conjunctival redness and chemosis) were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (2) It was reported that, in an eye irritation test with rabbits, slight eye irritation was observed (JMPR (2006)). (3) It was reported that, in an eye irritation test with rabbits, slight redness of conjunctivae and chemosis were observed and persisted to day 7 (EPA Pesticides (2006)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1) and (2), since positive findings were obtained in the Maximization test, it was classified in Category 1 in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) This substance was a skin sensitizer in a Maximization test with guinea pigs, but negative in a Buehler method (JMPR (2006)). (2) This substance was negative in a Buehler assay but induced moderate sensitization in a Maximization method (EPA Pesticides (2006)). [Reference Data, etc.] (3) In a skin sensitization test (Buehler method and Maximization method) with guinea pigs, negative results were obtained (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, this substance was negative in chromosomal aberration tests using the bone marrow cells of hamsters (dosed by gavage for 2 days), a UDS test using liver cells of rats (single dose by gavage), a dominant lethal test with mice, and a DNA damage test with rats; positive in a micronucleus test using the bone marrow cells of mice (by oral (by feeding) and dermal administrations); negative in an intraperitoneal application test; and positive in a sister chromatid exchange study using the bone marrow cells of mice by subcutaneous administration (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018), EHC 82 (1989)). (2) As for in vitro, this substance was all negative in several bacterial reverse mutation tests and chromosomal aberration tests using the cultured mammalian cells (cells derived from Chinese hamster lung, cells derived from rat liver) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (3) This substance gave negative results in an adequate battery of studies of genotoxicity in vitro and in vivo (JMPR (2006)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." The US EPA judged pulmonary tumors (adenomas) observed in the study with mice in (2) as the effect of administration of the test substance, while the Food Safety Commission of Japan concluded that it was a finding within the historical control data range and not an effect of administration of the test substance. [Evidence Data] (1) In two 2-year carcinogenicity studies with rats dosed by feeding (up to 1,000 ppm (47.1 to 60.3 mg/kg/day), up to 1,000/1,500 ppm (75 mg/kg/day)), no carcinogenicity was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (2) In two carcinogenicity studies with mice dosed by feeding for 97 to 101 weeks and 18 months (up to 1,600 ppm (128 to 139 m/kg/day), up to 300 ppm (35.2 to 37.7 mg/kg/day)), a significant increase in pulmonary adenomas was observed in females of a group treated at 1,600 ppm in the former but the incidence (21.7%) was within the historical control data range (3% to 31%), and it was not considered to be the effect of the administration of the test substance. In other words, no carcinogenicity was observed in either test (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (3) It was concluded that this substance was not carcinogenic (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018), EHC (1989), JMPR (2006)). [Reference Data, etc.] (4) As for the classification results by domestic and international organizations, the EPA classified this substance in Group C (Possible Human Carcinogen) (EPA OPP Annual Cancer Report 2020 (Accessed July 2021): Classification in 1988). (5) The US EPA classified it as a Group C (Possible human carcinogen), based on the increased incidence of lung adenomas and adenomas plus carcinomas combined in females of a high-dose group in a mouse carcinogenicity study as the evidence for carcinogenicity and the presence of only benign tumors (lung adenomas), in one species (mice) and one sex (female) (EPA OPP Human Health Risk Assessment (2012)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." Also, it was taken into account that, although in (1), decreased number of live birth and decreased number of viable pup were observed in pups, in (2) in which this substance was administered at a higher dose, no reproductive toxicity effects were observed. [Evidence Data] (1) It was reported that, in a three-generation study of reproductive toxicity with rats dosed by feeding, at the highest dose (1,000/750 ppm), clinical signs (high-legged gait, ataxia, increased sensitivity to sound and touch, increased/decreased activity, unsteady gait, tremor, etc.) were observed in P male and female parental animals; reduced body weight gain and decreased food consumption were observed in P to F2 male and female parental animals (except F1 males); and reduced body weight gain after birth was only observed in F1 to F3 pups (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018), JMPR (2006)). (2) It was reported that, in a developmental toxicity study (days 5 to 14 of gestation) with rats dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (3) It was reported that, in three developmental toxicity studies with rabbits dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). [Reference Data, etc.] (4) It was reported that, in a three-generation study of reproductive toxicity with rats dosed by feeding, at 500 ppm, reduced body weight gain and decreased food consumption were observed in parental animals; and lower body weight, a decreased number of live birth and a decreased number of viable pup were observed in F1 pups, but these effects were not observed in F2 and F3 pups, and no effects on fertility were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
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) to (4), it was classified in Category 1 (nervous system) since effects on the nervous system (neurological symptoms and tissue changes in the peripheral nerves) were observed within the dose range for Category 1. [Evidence Data] (1) It was reported that, in an acute oral toxicity test with rats, sedation, ataxic gait, salivation, piloerection, startle response, abnormal phonation, and jumping/circling were observed at or above 175 mg/kg and 296 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018), CLH Report (2018)). (2) It was reported that, in an acute oral toxicity test with mice, jumping/circling, sedation, and tremors were observed at 118 mg/kg and 154 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018), CLH Report (2018)). (3) It was reported that, in an acute inhalation toxicity study (mist) with rats (4 hours, exposure to the nose), lethargy, salivation, eye discharge, nasal discharge, and tremors were observed at 3.56 mg/L (within the range for Category 2) (CLH Report (2018)). (4) It was reported that, in four acute neurotoxicity tests with rats, neurotoxic symptoms (ataxia, abnormal gait, tremor, convulsion, reduced locomotor activity, salivation, lacrimation, etc.) and damage to nerve tissues (sciatic/peroneal nerve degeneration, myelin sheath edema, axonotmesis of the sciatic nerve) were observed at 20 to 200 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (nervous system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 2 (nervous system) since nervous system effects were observed within the dose range for Category 2. Besides, although the blood system effects in the 13-week study with rats in (1) were observed within the dose range for Category 2, the symptoms appeared only in females and were not observed in the 2-year study conducted at the same level of dose. Therefore, the blood system was not adopted as target organ. [Evidence Data] (1) It was reported that, in a repeated dose 13-week oral toxicity study with rats dosed by feeding, at 1,600 ppm (80 mg/kg/day, within the range for Category 2), hypersensitive reaction, ataxia, increased plasma urea, axonotmesis and vacuolation of the sciatic nerve were observed, and increased plasma K and decreased APTT in males and increased ALP and TP and decreased Hb, Ht and RBC in females were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (2) It was reported that, in a 90-day subacute neurotoxicity test with rats dosed by feeding, increased landing foot splay width (males) and ataxia/splayed hindlimbs/gait disorder (females) were observed at 1,300 ppm (77 mg/kg/day (males), 95 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (3) It was reported that, in a 90-day subacute neurotoxicity test with rats dosed by feeding, abnormal gait, hypersensitive reaction to sound, tremor, clonic convulsion, hunched posture, splayed hindlimbs, straub tail, motility disorder, abnormal gait, etc. were observed at 1,500 ppm (100 mg/kg/day (males), 111 mg/kg/day (females), the upper limit of Category 2 to in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (4) It was reported that, in a one-year chronic toxicity study with dogs dosed by feeding, abnormal gait and tremor (males) were observed at 600 ppm (20.4 mg/kg/day (males), 18.1 mg/kg/day (females), within the range for Category 2); and sacrifice in extremis (2/4 dogs), weakness, incoordinate gait, reduced activity, and clonic convulsion in males and tremor, abnormal gait, etc. in females were observed at 1,100 ppm (33.9 mg/kg/day (males), 38.1 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (5) It was reported that, in a 52-week chronic toxicity study with dogs dosed by gavage, tremor, abnormal gait, incoordinate gait, disorientation, and hypersensitive reaction to sound were observed at 15 mg/kg/day (within the range for Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (6) It was reported that, in a 2-year chronic toxicity study with dogs dosed by feeding, rigorous steppage gait, tremor, and incoordinate gait were observed at 1,000/750/600 ppm (weeks 1 to 3 of treatment: 1,000 ppm, weeks 4 to 5 of treatment: 750 ppm, week 9 and subsequent weeks following the cessation of treatment: 600 ppm, 21.0 mg/kg/day (males), 21.2 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). [Reference Data, etc.] (7) It was reported that, in a repeated dose 90-day oral toxicity study with rats dosed by feeding, at 1,500 ppm (116 mg/kg/day (males), 132 mg/kg/day (females), in the range corresponding to "Not classified"), staggering gait, splayed hindlimbs, tremor, shivering, loss of muscle coordination, hypersensitive reaction, hypoplasia of hair coat, yellow staining of the abdomen, and decreased RBC and Ht were observed, and increased MCH, MCV, and GGT in males, and clonic convulsion, decreased Hb, increased ALT, decreased Alb, increased BUN and K in females were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)). (8) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, at 1,000/1,500 ppm (75 mg/kg/day, within the range for Category 2), face rubbing, incoordination of the hindlimbs, hypersensitive reaction to sound, decreased T.Chol and TG were observed, and prolonged PT, decreased urine protein etc. were observed in males (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
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 = 0.00283 mg/L for fish (Oncorhynchus mykiss) (EU CLP CLH, 2018).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 due to being not rapidly degradable (BIOWIN) and 21-day NOEC = 0.00004 mg/L for crustacea (Daphnia magna) (EU CLP CLH, 2018).
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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