NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	30560-19-1
Chemical Name	(RS)-O,S-Dimethyl acetylphosphoramidothioate (synonym: Acephate)
Substance ID	R03-B-021-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	FY2018 FY2008
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.
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
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	- -	-	-	It contains a metalloid (P), but it is estimated that it does not react vigorously with water from data obtained: water solubility of 650 g/L (GESTIS (Accessed Aug. 2021)).
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Classification not possible	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded to the element other than carbon or hydrogen (P). However, the classification is not possible due to no data.
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 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] Based on (1) to (10), it was classified in Category 4. [Evidence Data] (1) LD50 for rats: 1,040 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (2) LD50 for rats (males): 1,080 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (3) LD50 for rats (females): 1,010 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (4) LD50 for rats (males): 1,400 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), EPA Pesticides RED (2006)) (5) LD50 for rats (females): 1,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), EPA Pesticides RED (2006)) (6) LD50 for rats (males): 1,430 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (7) LD50 for rats (males): 1,230 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016) (8) LD50 for rats (males): 945 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (9) LD50 for rats (females): 866 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (10) LD50 for rats: between 1,000 to 1,400 mg/kg (JMPR (2005))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (5), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (2) LD50 for rats: > 5,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (3) LD50 for rabbits: > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (4) LD50 for rabbits (males): > 2,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)) (5) LD50 for rabbits (males): > 10,000 mg/kg (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), EPA Pesticides RED (2006), JMPR (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)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) LC50 (4 hours) for rats: > 6.26 mg/L (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)) (2) LC50 (4 hours) for rats: > 14.8 mg/L (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)) (3) LC50 (4 hours) for rats:> 15 mg/L (JMPR (2005))
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 (observation for 7 days) with rabbits (n=6), slight erythema was observed in 2 animals after 24 hours and 1 animal after 48 hours of application, but it disappeared completely within 72 hours (erythema and scab score: 0/1/0/0/0/0, edema score: 0/0/0/0/0/0) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) It was reported that, in a skin irritation test (GLP, 4-hour application, observation for 72 hours) with rabbits (n=6), slight erythema was observed in 1 animal 1 hour and 24 hours after application, but it disappeared completely within 48 hours (average score of erythema/scab: 0.2/0/0, and average score of edema: 0/0/0, in 6 animals after 24, 48, and 72 hours) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)).
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 (n=6), no eye irritation was observed (cornea opacity score: 0/0/0/0/0/0, iritis score: 0/0/0/0/0/0, conjunctival redness score: 0/0/0/0/0/0, chemosis score: 0/0/0/0/0/0) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) It was reported that, in an eye irritation test (GLP, observation for 72 hours) with rabbits (n=6), no eye irritation was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) This substance was not an eye irritant (JMPR (2005), EPA Pesticides (2006)).
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 (3), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a Maximization test (GLP, intradermal administration: 5% solution) with guinea pigs (n=20), negative results were obtained with the positive rate of 0% (0/20 animals) both after 24 and 48 hours (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) It was reported that, in a Maximization test (GLP, intradermal administration: 10% solution) with guinea pigs (n=20), the positive rate after the first challenge was 5% (1/20 animals), and the positive rate after re-challenge after 7 days was 0% (0/20 animals) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that, in a Buehler test (local administration: 35% solution) with guinea pigs (n=20), negative results were obtained with the positive rate of 0% (0/20 animals) both after 24 and 48 hours (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
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, two micronucleus tests (single oral dose) using the bone marrow cells of mice, a chromosomal aberration test and a sister chromatid exchange (SCE) test (single oral dose for both tests) using the bone marrow cells of mice, a chromosomal aberration/SCE test (single oral dose) using the peripheral blood lymphocytes obtained from monkeys after oral administration, and a dominant lethal test (dosed by feeding for 5 days) and a spot test (days 8 to 12 of gestation, dosed by feeding) with mice were carried out, and negative results were obtained in all of the tests (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) As for in vitro, negative (partly positive) results were obtained in numerous bacterial reverse mutation tests, positive results were obtained in multiple mammalian (mouse lymphoma cell) gene mutation test, and positive results were obtained both in a mammalian Chinese hamster lung cell (CHL) chromosomal aberration test and a mammalian Chinese hamster ovary cell (CHO) sister chromatid exchange test (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) The Food Safety Commission of Japan concluded that this substance was not genotoxic in vivo (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2. In mice, liver tumor was observed in females in both of the two tests, and in rats, nasal cavity tumor was observed in one of the two tests. With the additional new information sources, the classification result was changed. [Evidence Data] (1) 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 1985). (2) In a preceding test at doses of up to 700 ppm (report year: 1981), out of two carcinogenicity studies with rats dosed by feeding for two years, there was no increase in neoplastic lesions related to the administration of the test substance (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). On the other hand, in a carcinogenicity study at doses of up to 1,500 ppm (GLP, report year: 1999), which was carried out later, the incidence of nasal cavity tumors (adenoma, neuroepithelial tumor of the nasal cavity, squamous cell carcinoma, rhabdomyosarcoma, etc.) were observed in males and females at or above 500 ppm, and the possibility that the incidence of these neoplastic lesions was due to the administration of the test substance could not be ruled out (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) In a carcinogenicity study (GLP, report year: 1999) with mice dosed by feeding for 18 months, the incidence of tumors in the nasal cavity was observed in 1/50 animals each in males and females of a group at the highest dose of 500 ppm (males: nasal cavity adenoma; females: undifferentiated carcinoma). An increase in the incidence of liver tumors (hepatocellular adenoma, hepatocellular carcinoma) was also observed in females of a group at 500 ppm (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) In a carcinogenicity study (report year: 1982) with mice dosed by feeding for two years, an increase in the incidence of hyperplastic nodule considered to be preneoplastic changes and hepatocellular carcinoma in the liver, was observed in females of a group at the highest dose of 1,000 ppm (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1B. Also, in (1) and (2), although it was a dose at which general toxic effects were observed in parent animals, severe reproduction toxicity effects such as a decrease in the number of implantations, a decrease in the number of newborns, a decrease in the number of live pups, etc. were observed, and therefore, the classification result was changed. [Evidence Data] (1) It was reported that, in a two-generation reproduction toxicity study (GLP) with rats dosed by feeding, at 500 ppm, general toxic effects (reduced body weight gain, brain cholinesterase (ChE) activity inhibition (> 20%)), decreased sperm motor activity (F1 males), a decrease in the number of implantations (F1 females: 15.6 -> 12.0) were observed in P and F1 parent animals, and a decrease in the number of newborns (P: 13.7 -> 12.0)/(F1: 14.6 -> 11.3) and a decrease in the number of live pups (F1 13.3 -> 10.5/F2 14.0 -> 10.4), a decrease in the testis descent rate (F1 males), and decreased brain ChE activity (> 20%) (F2 males and females) were observed in offspring (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that, in a three-generation reproduction toxicity study (GLP) with rats dosed by feeding, at 500 ppm, reduced body weight gain (P males and females, F1 males and F2 males), and loose stool and watery stool (F1 males and F2 males) were observed in parent animals, and a decrease in the number of implantations (F2 females: 14.6 -> 11.8), and a decrease in the number of newborns (F1: 13.1 -> 9.7/F2: 13.2 -> 9.9/F3: 13.9 -> 9.7) were observed in offspring (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). [Reference Data, etc.] (3) It was reported that, in two developmental toxicity studies (GLP, days 6 to 15 of gestation) with rats dosed by gavage, at a dose at which reduced body weight gain, decreased food consumption, etc. were observed in parent animals, only lower body weight was observed in offspring, and no teratogenicity was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) It was reported that, in two developmental toxicity studies (GLP, days 7 to 19 of gestation or days 6 to 27 of gestation) with rabbits dosed by gavage, no teratogenicity was observed (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (5) In a developmental neurotoxicity study (GLP, day 6 of gestation to day 6 of lactation (P), postnatal days 7 to 21 (F1)) with rats dosed by gavage, in F1 offspring, ChE activity inhibition via milk was not observed on postnatal day 4, but on postnatal day 21, decreased brain ChE activity (> 20%) was observed in male offspring at the lowest dose of 0.5 mg/kg/day or higher, and decreased erythrocyte ChE activity (> 20%) was observed in male and female offspring at 10 mg/kg/day. There was no evidence of developmental neurotoxicity either at a dose at which these effects were directly observed by administration to F1 offspring (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016), JMPR (2005)).
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 nervous system effects were observed within the dose range for Category 1. [Evidence Data] (1) It was reported that, in an acute neurotoxicity test (GLP) with rats dosed by gavage, a decrease in crouching posture (hunched posture), a decrease in eye lids closure, subnormal temperature (FOB), a decrease in tail pinch reaction, slow righting reflex, and a decrease in locomotor activity were observed at or above 20 mg/kg (within the range for Category 1), and decreased auditory startle responses were observed at 80 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that, in another acute neurotoxicity test (GLP) with rats dosed by gavage, brain cholinesterase (ChE) activity inhibition (20% or above) and generalized tremor were observed at or above 10 mg/kg (within the range for Category 1), and erythrocyte ChE activity inhibition (20% or above), tremor of the limbs, spasm of the ear, awakening abnormality and reduced rearing behavior, tail pinch reaction and abnormality of righting reflex, subnormal temperature, decreases in ambulatory movement and locomotor activity, neurological symptoms such as salivation (males), lacrimation (females), etc. were observed at or above 100 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) It was reported that, in an acute oral toxicity test with mice, lethargy, salivation, tremor, spasm, lacrimation, dyspnea, reduced motor activity, ataxia, etc. were observed at or above 175 mg/kg (within the range for Category 1), and deaths were observed at or above 250 mg/kg (within the range for Category 1) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (4) It was reported that, in another acute oral toxicity test with mice, at 300 mg/kg (within the range for Category 1), tremor, lacrimation, salivation, and ptosis were observed, but there were no deaths (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). [Reference Data, etc.] (5) It was reported that, in multiple acute oral toxicity tests with rats and mice, neurological symptoms such as tremor, salivation, ataxia, etc. were observed within the dose range for Category 2 (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)). (6) It was reported that, in a safety test by single oral administration of this substance (pure substance, males: 0.35 to 1.25 mg/kg body weight, females: 1.0 mg/kg body weight) to 40 male adults and 10 female adults by capsules, some significant decreases in plasma and erythrocyte ChE activities from the time before the administration were also observed in all dose groups throughout the test period, but the degree extent of inhibition was up to 16.7% (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, blood system, respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (6), the symptoms of brain cholinesterase inhibition, effects on the blood (a decrease in RBC), and effects on the respiratory organs (nasal cavity olfactory epithelial degeneration, etc.) were observed within the dose range for Category 1, and therefore, it was classified in Category 1 (nervous system, blood system, respiratory organs). Besides, effects on the liver observed in (6) were not adopted for the classification because they were effects in the range corresponding to "Not classified." Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in a repeated dose 90-day oral toxicity study (GLP) with dogs dosed by feeding, at or above 50 ppm (2.1 mg/kg/day (males), 2.0 mg/kg/day (females), within the range for Category 1), a decrease in RBC and a decrease in Hb (females) were observed; and at or above 225 ppm (8.3 mg/kg/day (males), 9.8 mg/kg/day (females), within the range for Category 1), erythrocyte ChE activity inhibition (20% or above), spleen extramedullary hematopoiesis, and spleen hemosiderin deposit were observed, and increases in WBC and PLT, and decreases in Ht and MCHC were observed in females (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (2) It was reported that, in a 1-year chronic toxicity study (GLP) with dogs dosed by feeding, an increase in MCV, erythrocyte ChE activity inhibition (20% or above), centrilobular inflammation/pigmentation of the liver, a decrease in RBC (males), brain ChE activity inhibition (20% or above) (males), and a decrease in MCHC (females) were observed at or above 175 ppm (6.9 mg/kg/day (males), 7.4 mg/kg/day (females), within the range for Category 1); and increases in MCH and APTT, decreases in Hb and MCHC (males), a decrease in RBC (females), and brain ChE activity inhibition (20% or above) (females) were observed at 1,000 ppm (38.6 mg/kg/day (males), 36.1 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (3) It was reported that, in another 1-year chronic toxicity study (GLP) with dogs dosed by feeding, at or above 120 ppm (3.14 mg/kg/day (males), 3.08 mg/kg/day (females), within the range for Category 1), erythrocyte ChE activity inhibition (20% or above), brain ChE activity inhibition (20% or above), perivascular inflammatory cell infiltration in the liver (males), and hepatocellular hemosiderin deposit (males) were observed; and at 800 ppm (18.9 mg/kg/day (males), 21.4 mg/kg/day (females), within the range for Category 2), decreases in RBC, Hb, and Ht, prolonged APTT, and increasing tendencies in absolute and relative liver weight were observed in males, and increased absolute and relative liver weight, perivascular inflammatory cell infiltration in the liver, and hepatocellular hemosiderin deposit were observed in females (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (4) It was reported that, in an 18-month carcinogenicity study (GLP) with mice dosed by feeding, erythrocyte and brain ChE activity inhibitions (20% or above), alveolar macrophages with pigmentation, nasal cavity olfactory epithelial degeneration, and rhinitis were observed at or above 50 ppm (7.85 mg/kg/day (males), 9.67 mg/kg/day (females), within the range for Category 1); histiocyte pigmentation in the liver, and hepatocellular hypertrophy/karyomegaly were observed at or above 160 ppm (25.1 mg/kg/day (males), 30.6 mg/kg/day (females), within the range for Category 2); and dyspnea, nasal cavity epithelial hyperplasia, and atrophy of the respiratory epithelium were observed at 500 ppm (81.4 mg/kg/day (males), 90.1 mg/kg/day (females), within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (5) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study (GLP) with rats dosed by feeding, decreases in RBC, Hb, and Ht, nasal cavity olfactory epithelial degeneration/regeneration, nasal cavity/turbinate deformation/adhesion, and erythrocyte ChE activity inhibition (20% or above) (females) were observed at or above 500 ppm (23.5 mg/kg/day (males), 30.5 mg/kg/day (females), within the range for Category 2); and rhinitis, contracted seminal vesicle (males), nasal cavity adenomatous hyperplasia (males), a decrease in WBC (males), increases in MCH and MCHC (females), and nasal cavity squamous hyperplasia (females) were observed at 1,500 ppm (79.6 mg/kg/day (males), 96.8 mg/kg/day (females) within the range for Category 2) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2015)). (6) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding, erythrocyte ChE activity inhibition (20% or above), and brain ChE activity inhibition (20% or above) were observed at or above 50 ppm (2.4 mg/kg/day (males), 3.1 mg/kg/day (females), within the range for Category 1) (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). [Reference Data, etc.] (7) It was reported that, in a 2-year carcinogenicity study with mice dosed by feeding, at or above 250 ppm (36 mg/kg/day (males), 42 mg/kg/day (females), within the range for Category 1), centrilobular hepatocellular hypertrophy, hepatocellular intranuclear inclusion body, hepatocellular karyomegaly, alveolar hyaline degeneration, rhinitis, and mononuclear cell infiltrate in the liver (males) were observed; and at 1,000 ppm (146 mg/kg/day (males), 167 mg/kg/day (females), in the range corresponding to "Not classified"), hepatocellular vacuolation, alveolar macrophage aggregation, and eosinophilic foreign body in the lung were observed, and additionally, hepatocellular yellow-brown pigmentation, and focal mineralization in the renal cortex were observed in males, and increased relative liver weight, decreased absolute and relative ovary weight, cytoplasmic vacuolation in the liver, hyperplasia nodule in the liver, and mononuclear cell infiltrate in the liver were observed in females (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (8) It was reported that, in a safety test by oral administration of this substance (0.25 mg/kg/day) to 15 male adults by capsules for 28 days, there was no inhibition of plasma or erythrocyte ChE activity. It was also reported that, in a similar test for 11 male adults, as a result of oral administration of up to 0.75 mg/kg/day by capsules for 21 days, a 25% decrease in plasma ChE activity was observed in one subject of a 0.75 mg/kg/day dose group (there was no change in erythrocyte ChE), but in other subjects, there were no cases of plasma/erythrocyte ChE activity inhibition by 20% or more (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2016), JMPR (2005)).
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 3	- -	H402	P273 P501	It was classified in Category 3 from 48-hour EC50 = 55 mg a.i./L for crustacea (Daphnia magna) (Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2013). The classification result was changed from the previous classification by reviewing information (a.i.: active ingredient).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 3	- -	H412	P273 P501	If chronic toxicity data are used, then it is classified as "Not classified" due to being not rapidly degradable (BIOWIN) and 72-hour NOErC = 24 mg/L for algae (Raphidocelis subcapitata) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016), Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2013). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (crustacea, fish), then it is classified in Category 3 due to being not rapidly degradable and 48-hour EC50 = 56.7 mg/L for crustacea (Daphnia magna) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). By drawing a comparison between the above results, it was classified in Category 3. The classification result was changed from the previous classification by reviewing information.
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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