NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	32809-16-8
Chemical Name	N-(3,5-Dichlorophenyl)-1,2-dimethyl-1,2-cyclopropanedicarboximide; Procymidon
Substance ID	R02-A-028-METI, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
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)
Model SDS by MHLW (External link)
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.
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with self-reactive properties (strained ring) 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	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data 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)	- -	-	-	It is an organic compound which does not contain fluorine but contains oxygen and chlorine, and the oxygen and chlorine are not chemically bonded to elements other than 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	- -	-	-	Classification is not possible because 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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) LD50 for rats (males): about 6,800 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)) (2) LD50 for rats (females): about 7,700 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)) (3) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) LD50 for rats: > 2,500 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007)) (2) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (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] Because effects are unknown at a dose near the upper limit for Category 4 from (1), the classification is not possible. [Reference Data, etc.] (1) LC50 for rats (4 hours): > 1.5 mg/L (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 5) (4-hour application, 7-day observation), very slight erythema was seen immediately after application but disappeared after about 1 hour, and irritation reactions such as edema and eschar were not observed (JMPR (2007), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 8) (5 animals in the group whose eyes were washed after 5 minutes, 3 animals in the group whose eyes were washed after 24 hours, 72-hour observation), no irritation changes in the cornea, iris, or conjunctiva were found after 1, 24, 48, and 72 hours (JMPR (2007), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)).
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] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 20) (GLP, intradermal administration: 1.0% solution), no topical reactions such as erythema and edema were observed at 24, 48 hours after the removal of patches (JMPR (2007), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). [Reference Data, etc.] (2) It is reported that in a skin sensitization test with guinea pigs (n = 8-10/group) (Landsteiner-Draize method, intradermal administration: injection of a 1% or 5% solution, 3 times per 1 week, 10 times in total), slight erythema and edema were locally seen after challenge but were similar to changes in the negative control group (JMPR (2007), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) In a chromosomal aberration test with mouse bone marrow cells (exposed once by intraperitoneal injection), negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (2) In a bacterial reverse mutation test, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (3) In a chromosomal aberration test with CHO cells, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (4) In a sister chromatid exchange test using the primary cultured cells of mouse fetuses, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (5) In an UDS test using the primary cultured hepatocytes of rats, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 2. In one of two studies using mice, it was reported that this substance induced liver tumors in males. In two studies using rats, an increased incidence of testicular interstitial cell tumors was reported, but the findings in (5) showed that the developmental mechanism of testicular interstitial cell tumors associated with this substance was the persistent stimulation of luteinizing hormone (LH) due to binding to androgen receptors (AR) and it could not be extrapolated to humans. EPA classified it in Group B in (6), which corresponded to Category 1B. However, the classification result was old, and therefore, it was classified based on the latest findings. [Evidence Data] (1) In a two-year combined chronic toxicity/carcinogenicity study with rats (Osborne-Mendel) dosed by feeding, an increased incidence of testicular interstitial cell tumors, which were treatment-related neoplastic lesions, was observed in the two high-dose groups of males (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (2) In a two-year carcinogenicity study with rats (SD) dosed by feeding, an increased incidence of testicular interstitial cell tumors, which were treatment-related neoplastic lesions, was observed in the highest-dose group of males (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (3) In a two-year combined chronic toxicity/carcinogenicity study with mice (B6C3F1) dosed by feeding, a tendency of an increased incidence of hepatoblastoma, which was neoplastic lesion, was observed in males in the 1,000 ppm dosed group. On the other hand, a tendency of an increased incidence of liver tumors was observed in females in the 1,000 ppm dosed group, but the incidence fell far below the upper limits of background values in the same strain of mice (hepatocellular carcinoma: 29% in males and 20% in females, hepatocellular adenoma: 60% in males and 50% in females, hepatocellular carcinoma + hepatocellular adenoma: 68% in males and 56% in females), and it was considered that the findings were not treatment-related (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). JMPR initially concluded that this substance produced hepatoblastoma in males and hepatocellular adenoma in females in the highest-dose group (JMPR (2007)). (4) In an 18-month carcinogenicity study with mice (ICR) dosed by feeding, no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (5) In a carcinogenicity study, an increased incidence of testicular interstitial cell tumors was observed in rats. As a result of studies about the developmental mechanism of tumors, it was found that this substance was capable of binding to androgen receptors (AR) and induced blood hormone unbalance (increased LH), and it was considered that testicular interstitial cell tumors were developed due to persistent stimulation of LH. A tendency of increased incidence of hepatoblastoma was also observed in male mice (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). [Reference Data, etc.] (6) As for the classification results by domestic and international organizations, EPA classified this substance in Group B (Probable Human Carcinogen) (EPA Annual Cancer Report 2018 (Accessed Spt. 2020): Classification in 1991).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1B. [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding, at 750 ppm, increases in absolute and relative testicular weight (males), a tendency of reduction of body weight gain, decreased food consumption, and reduced food efficiency (males and females) were observed in P and F1 parental animals; and abnormal penile shapes (hypospadias or trifoliate lump on the glans), decreased prostate size, prostatitis, vesiculitis, alterations in pituitary gland tissues (hypertrophy or hyperplasia of basophilic cells, formation of castration cells), shortened anogenital distance (AGD) (F1 and F2 males) and a reduction of fertility rate (F1 males) were observed in pups (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (2) It was reported that in a one-generation reproduction toxicity study with rats dosed by feeding, at 37.5 mg/kg/day, reduced body weight gain, decreased food consumption (females) and reduced food efficiency (males and females) were observed in parental animals; and reduced body weight gain, increases in absolute and relative testicular weight, decreases in the absolute and relative weight of accessory reproductive organs (prostate, seminal vesicle), and hypospadias at low frequency (males) were observed in F1 offspring (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (3) It was reported that in a developmental toxicity study with rats dosed by gavage (gestation days 6 to 19), shortened AGD was observed in pups at 12.5 mg/kg/day where no general toxicity was observed in parental animals; and reduced body weight gain, decreased food consumption, etc. in parental animals, lower body weight and skeletal variations (bifid thoracic vertebra) in fetuses, an increase in mortality on days 2 to 4 after birth, shortened AGD, lower body weight, genital abnormalities (such as undescended testes, focal or diffuse seminiferous tubule atrophy, hypospadias, preputial gland enlargement, inflammatory changes of the epididymis, seminal vesicle, prostate or coagulating gland) in F1 offspring (males), and abnormal penile shapes in F2 offspring were observed at 125 mg/kg/day (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (4) It was reported that in a developmental toxicity study with rabbits dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). [Reference Data, etc.] (5) The substance was orally administered to pregnant rabbits (gestation days 6 to 28) and pregnant monkeys (gestation days 22 to 99) in the critical period of external genitalia differentiation at the dose (125 mg/kg/day) where hypospadias of male fetuses was developed by dosing to pregnant rats. As a result, no abnormalities in AGD and external genitalia were observed in the rabbits and the monkeys. It was considered that the differentiating factor between the species was the difference of the blood concentration of major metabolites between rats and rabbits/monkeys (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)).
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] Based on (1) to (3), transient inhibition of the central nervous system was observed in the oral and inhalation routes. Therefore, it was classified in Category 3 (narcotic effects). [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats dosed by gavage, ataxia was observed at 100 mg/kg (within the range for Category 1), deep respiration, reduced spontaneous activity, and limb or generalized ataxia were observed from 30 hours to 3 days after the administration at 500 mg/kg (within the range for Category 2), and loose stool, piloerection, epistaxis, incontinence of urine, and death were observed until one week after the administration at 2,500 mg/kg (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (2) It was reported that in an acute oral toxicity test with rats dosed at 200 mg/kg (within the range for Category 1), reduced spontaneous activity was observed until one hour after the administration, reduced aerial righting reflex, lower body temperature, reduced grip strength of forelimbs/hindlimbs and higher landing foot splay width were observed until three hours after the administration, and staggering gait, decreased muscle tone, hyporeactivity, a decreased number of defecations, asynergy (males), bradypnea, decreased alertness (females) and staining of hair coat (vulva) were observed from 3 hours until one day after the administration (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (3) It was reported that in an acute (dust) inhalation toxicity test with rats (for 4 hours), nasal discharge, reduced spontaneous activity, and incontinence of urine (all females) were observed at 1.5 mg/L (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). [Reference Data, etc.] (4) It was reported that in several acute dermal toxicity tests with rats and mice, no effects were observed at 2,500 mg/kg to 5,000 mg/kg (in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver, reproductive organs)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on the liver effects in (1) to (6) and (8), the testis effects in (4) to (7) and (9) and the ovary effects in (4) and (5), it was classified in Category 2 (liver, reproductive organs). [Evidence Data] (1) It was reported that in a 6-month oral toxicity test with rats dosed by feeding, hepatocyte vacuolar (fatty) degeneration (males) was observed at 1,500 ppm (75.9 mg/kg/day (males), 87.3 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007)). (2) It was reported that in a 90-day oral toxicity test with mice dosed by feeding, liver effects (centrilobular hepatocyte hypertrophy, cellular necrosis) (males) were observed at or above 500 ppm (71 mg/kg/day, within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007)). (3) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with mice dosed by feeding, liver effects (increases in absolute and relative weight, centrilobular hepatocyte hypertrophy) (males) were observed at 300 ppm (45.8 mg/kg/day (males), 64.5 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007)). (4) It was reported that in a two-year oral toxicity test with rats dosed by feeding, liver effects (centrilobular hepatocyte hypertrophy, increases in absolute and relative weight), testis effects (increases in absolute and relative weight, hyperplasia of cells), alveolar histiocyte foci, ovary effects (increases in absolute and relative weight, stroma hyperplasia) and increased testosterone concentrations were observed at 1,000 to 2,000 ppm (47.6 to 96.9 mg/kg/day (males), 61 to 121 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007)). (5) It was reported that in a two-year carcinogenicity study with rats dosed by feeding, liver effects (cellular hypertrophy, necrosis, hyperplasia), testis effects (calcinosis), ovary effects (brown pigmentation), and kidney effects (interstitial lymphocytic infiltration) (females) were observed at 1,000 to 2,000 ppm (43.4 to 86.9 mg/kg/day (males), 55.4 to 118 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (6) It was reported that in an 18-month carcinogenicity study with mice dosed by feeding, liver effects (proliferation of oval cells, centrilobular hepatocyte hypertrophy, increases in absolute and relative weight (females)) and testis effects (atrophy, decreases in absolute and relative weight) were observed at 100 to 300 ppm (15 to 45 mg/kg/day, within the range for Category 2) and an increase in ALT (males) was observed at 1,000 ppm (150 mg/kg/day, in the range corresponding to "Not classified") (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)). (7) It was reported that in a 6-month oral toxicity test with mice dosed by feeding, testicular atrophy was observed at 500 ppm (25 mg/kg/day (males), 25 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), JMPR (2007)). (8) It was reported that the results of studies about the developmental mechanism of an increased incidence of testicular interstitial cell tumors in a carcinogenicity study with rats showed that this substance was capable of binding to androgen receptors (AR) and induced blood hormone unbalance (an increase in LH). It was also reported that in a reproduction study and a developmental toxicity study, abnormalities of the external genitalia, which were considered to be caused by antiandrogen action, were observed in male pups of rats (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (9) It was reported that based on various toxicity study results, the effects of this substance were observed manly in the liver (centrilobular hepatocyte hypertrophy, and so on) and the testis (hyperplasia of interstitial cells, and so on) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)).
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 2	- -	H401	P273 P501	It was classified in Category 2 from 72-hour ErC50 = 1.4 mg/L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 2	-	H411	P273 P391 P501	It was classified in Category 2 because it is not rapidly degradable (BIOWIN) and due to 72-hour NOErC = 0.87 mg/L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 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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