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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	121552-61-2
Chemical Name	4-Cyclopropyl-6-methyl-N-phenylpyrimidin-2-amine; Cyprodinil
Substance ID	R02-A-086-METI
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)
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	- -	-	-	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)	- -	-	-	Organic compounds containing no oxygen, fluorine or chlorine.
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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (4). [Evidence Data] (1) LD50 for rats (males): about 2,970 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)) (2) LD50 for rats (females): about 2,500 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)) (3) LD50 for rats (males): > 2,000 mg/kg (OECD TG 401, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), EU EFSA (2005)) (4) LD50 for rats (females): > 2,000 mg/kg (OECD TG 401, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), EU EFSA (2005))
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 (males): > 2,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), EFSA (2005)) (2) LD50 for rats (females): > 2,000 mg/kg (OECD TG 402, GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), EFSA (2005))
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] The classification is not possible because effects are unknown at the upper limit for Category 4 in (1), (2). [Reference Data, etc.] (1) LC50 for rats (males) (4 hours): > 1.2 mg/L (OECD TG 403) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), EFSA (2005)) (2) LC50 for rats (females) (4 hours): > 1.2 mg/L (OECD TG 403) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), EFSA (2005))
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 = 3) (OECD TG 404, GLP, semi-occlusive, 4-hour application, 72-hour observation), no skin irritation changes were seen in any animal (erythema/eschar score: 0/0/0, edema score: 0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2003), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)).
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 = 3) (GLP, 72-hour observation), all the animals showed moderate erythema and slight edema after 1 hour, but erythema disappeared after 48 hours, and edema disappeared after 24 hours (corneal opacity score: 0/0/0, iritis score: 0/0/0, conjunctival redness score: 0/0/0.3, chemosis score: 0/0/0) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2003), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1B	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1B from (1), (2). [Evidence Data] (1) It is reported that in a maximization test with guinea pigs (n = 20) (GLP, intradermal administration: 0.5% suspension), the positive rate was 45% (9/20), 30% (6/20) at 24, 48 hours after the end of challenge exposure (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2003), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (2) This substance is a skin sensitizer (EFSA (2005)). [Reference Data, etc.] (3) It is reported that in a maximization test with guinea pigs (n = 20) (GLP, intradermal administration: 5% suspension), the positive rate was 15% (3/20), 5% (1/20) at 24, 48 hours after the end of challenge exposure (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)).
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 micronucleus test using the bone marrow cells of mice (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (2) In a bacterial reverse mutation test (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (3) In a gene mutation test using the cultured mammalian cells (Chinese hamster lung cells (V79)) (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (4) In a chromosomal aberration test using the cultured mammalian cells (CHO cells) (GLP), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (5) This substance was not considered to be genotoxic (JMPR Report (2003), EFSA (2005)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." An increase in mammary gland tumors was observed in rats in (2), but those tumors were only benign ones. [Evidence Data] (1) As for the classification results by domestic and international organizations, the EPA classified this substance in NL (Not Likely To Be Carcinogenic To Humans) (Annual Cancer Report (2019): Classification in 1998). (2) In a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, a significant increase in the incidence of benign tumors of the mammary gland (including adenoma, fibroadenoma, fibroma, and ductal papilloma) was observed in females in the maximum dose group of 2,000 ppm (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (3) In an 18-month carcinogenicity study with mice dosed by feeding, an increase in the incidence of administration-related tumors was not observed up to the maximum dose of 5,000 ppm, and no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (4) In carcinogenicity studies with rats and mice, no carcinogenicity was observed (JMPR Report (2003), EFSA (2005)). Therefore, the EPA classified it as NL (US Federal Register vol. 81, No. 75 (2016)).
7	Reproductive toxicity	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 two-generation reproduction toxicity study with rats dosed by feeding (GLP), no effect on fertility was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage (GLP, days 6-15 of gestation), at 1,000 mg/kg/day, reduced body weight gain in parent animals, and low body weight, and an increase in non-ossification and a delay in ossification of the limb ends in offspring were observed, but no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage (GLP, days 7-19 of gestation), no teratogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (4) It was reported that in a developmental toxicity study with pregnant rats and pregnant rabbits, low body weight and an increased incidence of delayed ossification in rat fetuses, and an increased incidence of litters with the 13th extra ribs in rabbits were observed. In a two-generation reproduction toxicity study with rats, low body weight was observed in F1 and F2 offspring (US Federal Register (2016)).
8	Specific target organ toxicity - Single exposure	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (6), it was classified as "Not classified." [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats (OECD TG 401, GLP), at 2,000 mg/kg (upper limit of Category 2), piloerection, hunchback/dyspnea, and a reduction in locomotor activity (males) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2003)). (2) It was reported that in an acute dermal toxicity test with rats (OECD TG 402, GLP), at 2,000 mg/kg (upper limit of Category 2), piloerection, hunchback, lying on side, and dyspnea were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2003)). (3) It was reported that in an acute oral toxicity test with rats, at LD50 value (2,970 mg/kg/day (male), 2,500 mg/kg/day (female)), but loose/watery stool, salivation, hunchback, dyspnea, a decrease in activity, red matter attached on the face, dark and yellow matters attached on the urogenital organ, yellow matters attached on the abdomen, lean figure, lacrimation, staggering gait, loss of righting/grasping reflex, mydriasis, prostration, transparent discharge on the nose, flaccid state, no-feces, dark matter attached on the anus, loss of fur of the urogenital organ/abdomen, and deaths (the sex and the number of animals were unknown, discharge on the mouth, nose, or around the anus) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2013)). (4) It was reported that in an acute inhalation (dust) toxicity test with rats (OECD TG 403, GLP, 4 hours), piloerection and dyspnea were observed at 1.2 mg/L (within the range for Category 2) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012), JMPR (2003)). (5) In an acute neurotoxicity test with rats (GLP), at 200 mg/kg (within the range for Category 1), subnormal temperature, and hunchback were observed; at 600 mg/kg (within the range for Category 2), lower rectal temperature, a reduction in locomotor activity, and a death (1 animal) were observed; and at 2,000 mg/kg (upper limit of Category 2), a reduction in locomotor activity and hypoactivity were observed. In a histopathological test, there were no effects related to the administration of the test substance observed, corresponding to the above symptoms. It was reported that no acute neurotoxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (6) In an acute neurotoxicity test with rats (GLP) that was carried out as a test for the confirmation of low-dose effects based on the fact that subnormal temperature, and hunchback were observed at 200 mg/kg (within the range for Category 1) in (5), no effect was observed at a dose of up to 200 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (liver)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2 (liver). [Evidence Data] (1) It was reported that in a 90-day subacute oral toxicity test with rats dosed by feeding (GLP), at or above 300 ppm (19 mg/kg/day (males), 19.3 mg/kg/day (females), within the range for Category 2), prolonged PT (males), an increase in ALT (males), effects on the liver (hypertrophy of periportal cells) (males), hypertrophy of adenohypophyseal cells (TSH positive cells) (males), and thyroid follicular cell hypertrophy (males) were observed; and at or above 2,000 ppm (134 mg/kg/day (males), 137 mg/kg/day (females), in the range corresponding to "Not classified"), increases in Chol/PL, increases in ALP and TP/Glob (males), increases in absolute/relative thyroid weight (males), effects on the liver (single cell necrosis (males), periportal hepatocyte hypertrophy (females), an increase in weight (females)), and effects on the kidney (chronic inflammation) (males) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (2) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding (GLP), at or above 1,000 ppm (35.6 mg/kg/day (males), 41.2 mg/kg/day (females), within the range for Category 2), prolonged PT (males), and effects on the liver (spongiform degeneration (cystic dilatation of sinusoids)) (males) were observed; and at 2,000 ppm (73.6 mg/kg/day (males), 87.1 mg/kg/day (females), within the range for Category 2), effects on the liver (increases in absolute/relative weight) (males), effects on the kidney (chronic progressive nephropathy) (males), and ovary cyst (females) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). [Reference Data, etc.] (3) It was reported that in a 90-day subacute oral toxicity test with mice dosed by feeding, at or above 2,000 ppm (257 mg/kg/day (males), 349 mg/kg/day (females), in the range corresponding to "Not classified"), effects on the liver (single cell necrosis (males), a reduction in hepatocyte glycogen (females)), and effects on the pancreas (increases in absolute/relative weight) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (4) It was reported that in a 90-day subacute oral toxicity test with dogs dosed by feeding (GLP), no effect was observed at a dose of up to 7,000 ppm (210 mg/kg/day (males), 232 mg/kg/day (females), in the range corresponding to "Not classified"), but at 20,000 ppm (560 mg/kg/day (males), 581 mg/kg/day (females), in the range corresponding to "Not classified"), reduced body weight gain, and a reduction in food consumption were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (5) It was reported that in a 90-day subacute neurotoxicity test with rats dosed by feeding (GLP), at 8,000 ppm (601 mg/kg/day (males), 631 mg/kg/day (females), in the range corresponding to "Not classified"), reduced body weight gain, a reduction in food consumption (transient), effects on the liver (increases in absolute/relative weight, centrilobular hepatocyte hypertrophy), effects on the kidney (increases in absolute/relative weight (females), chronic inflammation, an increase in renal tubular casts), and thyroid follicular cell hypertrophy were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (6) It was reported that in a two-year chronic toxicity study with dogs dosed by feeding (GLP), at 15,000 ppm (449 mg/kg/day (males), 446 mg/kg/day (females), in the range corresponding to "Not classified"), reduced body weight gain, a reduction in food consumption, and effects on the liver (pigment deposit in cells (lipofuscin)) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)). (7) It was reported that in an 18-month carcinogenicity study with mice dosed by feeding (GLP), at 5,000 ppm (630 mg/kg/day (males), 558 mg/kg/day (females), in the range corresponding to "Not classified"), reduced body weight gain, and an increase in hyperplasia of acinar cells of the pancreas (males) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2012)).
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)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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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