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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	52645-53-1
Chemical Name	3-Phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (synonym: Permethrin)
Substance ID	R03-B-023-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	- -	-	-	It is a solid with a melting point of 55 deg C or lower, but the classification is not possible due to no data.
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 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] Based on (1) to (9), it was classified in Category 4 by adopting the category with the higher hazard. [Evidence Data] (1) LD50 for rats (males) (the mixing ratio of cis- and trans-isomers was unknown): 539 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (2) LD50 for rats (females) (the mixing ratio of cis- and trans-isomers was unknown): 464 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (3) LD50 for rats (males) (the mixing ratio of cis- and trans-isomers was unknown): 430 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (4) LD50 for rats (females) (the mixing ratio of cis- and trans-isomers was unknown): 470 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (5) LD50 for rats (females) (the cis- and trans-isomers (20%: 80%)): 6,000 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (6) LD50 for rats (females) (the cis- and trans-isomers (30%: 70%)): 1,700 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (7) LD50 for rats (females) (the cis- and trans-isomers (40%: 60%)): 1,300 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (8) LD50 for rats (males) (the mixing ratio of cis- and trans-isomers was unknown): 3,580 mg/kg (EPA Pesticides RED (2007)) (9) LD50 for rats (females) (the mixing ratio of cis- and trans-isomers was unknown): 2,280 mg/kg (EPA Pesticides RED (2007)) [Reference Data, etc.] (10) LD50 for rats (the cis- and trans-isomers (80%: 20%)): 220 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (11) This substance with the cis-isomer to trans-isomer ratio of 80:20 is not used in Japan, but it has been reported that it is used as a drug for animals overseas (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)).
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, 2019)) (2) LD50 for rats: > 2,500 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)) (3) LD50 for rabbits: > 2,000 mg/kg (EPA Pesticides RED (2007))
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)	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1), classification was not possible since the category could not be judged. [Reference Data, etc.] (1) LC50 (3 hours, mist) for rats: > 0.685 mg/L (converted 4-hour equivalent value: 0.514 mg/L) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a skin irritation test with rabbits (n=5) (observation for 7 days), no irritating reaction was observed at all (erythema/eschar score: 0/0/0/0/0, edema score: 0/0/0/0/0) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (2) This substance was slightly skin irritating to skin (JMPR (1999)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in an eye irritation test with rabbits (n=3), no eye irritation was observed (cornea opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 0/0/0, chemosis score: 0/0/0) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (2) It was reported that, in an eye irritation test with rabbits, minimal pain, conjunctival redness, chemosis, and slight eye discharge were observed (EHC 94 (1990), JMPR (1979)). [Reference Data, etc.] (3) It was reported that this substance was mildly irritating to the eyes (JMPR (1999)).
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] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a skin sensitization test with guinea pigs (n=8) (intradermal injection: 5% or 1% solution), no sensitization reaction was observed in any animals (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (2) It was reported that, in a skin sensitization test (intradermal injection: 0.1% solution) with guinea pigs, negative results were obtained (EHC 94 (1990)). (3) In a Maximization test for this substance, no skin sensitization was observed (JMPR (1999)). (4) This substance was not a skin sensitizer (EPA Pesticides (2007)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, this substance was all negative in a micronucleus test using the bone marrow cells of mice (single oral dose), chromosomal aberration tests using the bone marrow cells of rats and mice (single or 5-day repeated intraperitoneal administration), and a dominant lethal test with mice (5-day repeated oral dose) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (2) As for in vitro, this substance was all negative in several bacterial reverse mutation tests and a chromosomal aberration test using the cultured mammalian cells (cells derived from Chinese hamster lung) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Classification Results] Based on (1) to (4), it was classified in Category 2. It has been pointed out that the benign tumors (pulmonary adenoma, hepatocellular adenoma) observed only in one species of experimental animal (mice) and one sex (female) can be caused through a nongenotoxic mechanism. Also, based on the new information source, the classification result was changed. [Evidence Data] (1) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 3 (IARC 53 (1991)) and the EPA classified it in S (Suggestive Evidence of Carcinogenic Potential) (EPA OPP Annual Cancer Report 2020 (Accessed July 2021)). Besides, the EPA reclassified it from the previous L (Likely to be Carcinogenic to Humans: corresponding to Category 1B) to S (corresponding to Category 2) in the quantitative reassessment of carcinogenicity in 2020 (Federal Register vol. 85, No. 145 (2020)). (2) In three 2-year combined chronic toxicity/carcinogenicity studies with rats dosed by feeding, no carcinogenicity was observed in any of the studies. In two out of the three studies, the results were obtained after this substance was administered at doses up to the highest dose (2,500 ppm (males/females: 107/121 mg/kg/day) and 250 mg/kg/day) until tremor was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (3) Among three carcinogenicity studies with mice dosed by feeding (98-week administration in one study and 2-year administration in 2 studies), in one study in which this substance was administered at doses up to 5,000 ppm (928 mg/kg/day), increased incidences of hepatocellular adenomas and pulmonary bronchiolar/alveolar epithelium adenomas were observed in females of the group treated at or above 2,500 ppm (462 mg/kg/day). In the other two studies, no carcinogenicity was observed. (In males treated at the highest dose (2,500 ppm) in the 98-week administration study, an increase in pulmonary adenomas was observed, but in another statistical test, there was no significant difference. Therefore, it was judged not to be the effect of administration of the test substance) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (4) The result of a study examining the mechanism of lung and liver tumor formation observed in one test with mice suggested that a long-term feeding of this substance caused enhanced proliferation of Clara cells in the lung and cell proliferation via activation of nuclear receptors (CAR, PPARα) in the liver. Since it was difficult to judge that the mechanism of tumor formation in mice was a genotoxic mechanism, it was concluded that it was possible to set a threshold (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). [Reference Data, etc.] (5) Since there was only one test result available each on rats and mice, respectively, at the time of the IARC evaluation, in which the result on rats was negative and the result on mice showed an increase in pulmonary adenoma in male (which was denied in the evaluation by the Food Safety Commission of Japan), the classification result was concluded obtained based on the fact that no data were was available as evidence for carcinogenicity in humans and that it was limited to only inadequate evidence even in experimental animals (IARC 53 (1991)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." Besides, although an increase in post-implantation embryo death rate in (1) was considered to be an effect of the administration of the test substance, it was considered to be an insignificant effect and also an effect observed at dose levels exceeding the limit. [Evidence Data] (1) It was reported that, in a developmental toxicity study with rabbits dosed by gavage (days 6 to 18 of gestation), at or above 600 mg/kg/day, reduced body weight gain and tremor (only at 1,800 mg/kg/day) in parental animals, and at or above 1,200 mg/kg/day, an increase in post-implantation embryo death rate (early and late) and lower body weight/delayed ossification of the limbs (only at 1,800 mg/kg/day) in pups were observed but no teratogenicity was observed. Also, it was considered that the increase in post-implantation embryo death rate and the lower body weight/delayed ossification of the limbs were not significant effects, but effects of the administration of the test substance (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019), Environmental Risk Assessment for Chemical Substances, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), EHC 94 (1990)). (2) It was reported that, in two 3-generation reproduction toxicity studies with rats dosed by feeding, no reproductive toxicity was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2009), EHC 94 (1990)). (3) It was reported that, in 3-generation reproduction toxicity study with mice dosed by feeding, no reproductive toxicity was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (4) In one of two reproduction toxicity studies with rats dosed by gavage, at a dose at which tremor and head shaking, reduced body weight gain, and decreased food consumption were observed in parental animals, slight developmental effects (lower body weight, increased incidences of extra ribs) were observed in pups, while in the other study, no effects were observed in either parental animals or pups. Also, it was reported that no teratogenicity was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (5) Based on the results of animal studies, the JMPR concluded that this substance (technical grade) had no reproductive or developmental toxicity (JMPR (1999)). The Food Safety Commission of Japan also concluded that this substance had no effects on fertility nor teratogenicity (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)).
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 (3), it was classified in Category 1 (nervous system). Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in two acute neurotoxicity tests with rats dosed by gavage, effects on the nervous system (tremor, convulsions, a decline in pupillary function, an increase in auditory response, decreased locomotor activity, abnormal gait, etc.) were observed at 200 mg/kg and 300 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (2) It was reported that, in multiple acute oral toxicity tests with rats and mice, effects on the nervous system (tremor, twitch and reduced locomotor activity, etc.) were observed within the dose range for Category 1 (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (3) It was reported that, in two acute inhalation exposure tests with rats and mice (3 hours, mist), excitation, salivation, lacrimation, urinary incontinence, and ataxia were observed at 0.685 mg/L (converted 4-hour equivalent value: 0.514 mg/L, within the range for Category 1) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). [Reference Data, etc.] (4) In examinations of 23 workers who had been exposed to multiple synthetic pyrethroids containing this substance and of the control group, 19 workers experienced an abnormal facial sensation 0.5 to 3 hours after exposure (which lasted for 0.5 to 8 hours) on one or more occasions, but there were no neurologically abnormal symptoms, and an electro-physiological test for the arms and legs also showed normal results (Environmental Risk Assessment for Chemical Substances, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009), EHC (1990)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (nervous system, liver, adrenal gland)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (8), it was classified in Category 2 (nervous system, liver, adrenal gland) since nervous system, liver, and adrenal gland effects were observed within the dose range for Category 2. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in a repeated dose 28-day oral toxicity study with rats dosed by feeding, tremor was observed at 1,000 ppm (100 mg/kg/day, converted guidance value: 31.1 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (2) It was reported that, in a 28-day subacute neurotoxicity test with rats dosed by feeding, tremor, splayed hindlimbs, staggering gait, and pigmentary rhinorrhea were observed at 1,500 ppm (75 mg/kg/day, converted guidance value: 23.3 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (3) It was reported that, in a 90-day subacute neurotoxicity test with rats dosed by feeding, staggering gait, splayed hindlimbs, tremor, and effects on the neurological function in an FOB test were observed at 1,500 ppm (91.5 mg/kg/day (males), 111 mg/kg/day (females), from the range for Category 2 to the range corresponding to "Not classified") (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019), Environmental Risk Assessment for Chemical Substances, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2009)). (4) It was reported that, in a 13-week subacute toxicity test with dogs dosed by gavage, tremor was observed at 2,000 mg/kg/day (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019)). (5) It was reported that, in a 6-month subacute toxicity test with rats dosed by feeding, hyperexcitability and tremors (both after day 1 of treatment), increased Chol, increased absolute and relative liver weight, slight enlargement of parenchymal cells of the liver, and reduced ChE (females) were observed at 3,000 ppm (185 mg/kg/day (males), 221 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019), EHC 94 (1990)). (6) In a one-year chronic toxicity study with dogs dosed by gavage, effects on the liver (increased weight, increased ALP, diffuse hepatocyte hypertrophy) and the adrenal gland (cell hypertrophy and vacuolation in the zona reticularis/zona fasciculata, focal degeneration/necrosis of the cortex (with inflammatory cell infiltration) (males)) were observed at 100 mg/kg/day (within the range for Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019), IRIS (1987), HSDB (Accessed July 2021)). (7) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, neurological symptoms (tremor, hyperexcitability) and liver effects (hypertrophy of centrilobular hepatocytes/hepatocyte vacuolation) were observed at 2,500 ppm (107 mg/kg/day (males), 121 mg/kg/day (females), in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2019), EHC 94 (1990)). (8) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, liver effects (hypertrophy of centrilobular hepatocytes, fatty hepatocyte vacuolation (males)) were observed at 50 mg/kg/day (within the range for Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 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 = 0.00002 mg/L for crustacea (Mysidopsis bahia) (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2010)).
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 30-day NOAEC = 0.000011 mg/L for crustacea (Mysidopsis bahia) (EPA Pesticides RED, 2009, 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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