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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	31218-83-4
Chemical Name	isopropyl 3-[[(ethylamino)methoxyphosphinothioyl]oxy]crotonate; Propetamphos
Substance ID	R02-B-088-MHLW, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/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. It was classified as "Not classified."
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products. It was classified as "Not classified."
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Classification not possible	- -	-	-	No data available. The classification result was changed because it was impossible to confirm flash point data used in the previous classification.
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
8	Self-reactive substances and mixtures	Type G	- -	-	-	There is a chemical group associated with self-reactive properties, an unsaturated bond, present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN3018), and it does not correspond to self-reactive substances and mixtures, hazards of the highest precedence, it was classified in Type G.
9	Pyrophoric liquids	Classification not possible	- -	-	-	No data available.
10	Pyrophoric solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to liquid 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 was classified as "Not classified" because it is estimated that it does not react vigorously with water from water solubility data of 110 mg/L (20 deg C) (EPA Pesticides RED (2006)).
13	Oxidizing liquids	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.
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified."
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] It was classified in Category 3 from (1) - (5). [Evidence Data] (1) LD50 for rats: females: 59.5 mg/kg, males: 119 mg/kg (EU EMEA (1999), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013), HSDB (Access on June 2020)) (2) LD50 for rats: females: 75.9 mg/kg, males: 98.8 mg/kg (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)) (3) LD50 for rats: females: 96.4 mg/kg, males: 116.1 mg/kg (EPA Pesticides RED (2006), Patty (6th, 2012)) (4) LD50 for rats: 62.4 mg/kg (GESTIS (Access on June 2020)) (5) LD50 for rats: 75 mg/kg (HSDB (Access on June 2020))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	[Rationale for the Classification] It was classified in Category 3 from (1) - (5). [Evidence Data] (1) LD50 for rabbits: 486 mg/kg (EU EMEA (1999), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)) (2) LD50 for rabbits: 486.4 mg/kg (EPA Pesticides RED (2006), Patty (6th, 2012)) (3) LD50 for rats: 564 mg/kg (GESTIS (Access on June 2020)) (4) LD50 for rats: females: 564 mg/kg, males: 1,282 mg/kg (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)) (5) LD50 for rats: females: > 2,260 mg/kg (EU EMEA (1999), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Category 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] From (1), (2), by prioritizing the value on the safe side, it was classified in Category 3. Besides, the classification result was changed from the previous classification by using new information sources. Because exposure concentrations were higher than the saturated vapor pressure concentration (2.2E-004 mg/L), a reference value in the unit of mg/L was applied as mist. [Evidence Data] (1) LC50 for rats (4 hours): females: 0.69 mg/L, males: 1.5 mg/L (EPA Pesticides RED (2006), Patty (6th, 2012)) (2) LC50 for rats (4 hours): females: 3.02 mg/L, males: 3.30 mg/L (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)) (3) Vapor pressure of this substance: 1.43E-005 mmHg (20 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 2.2E-004 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) This substance was not irritating to the skin in a skin irritation test with rabbits according to EPA OPPTS 870.2500 (EPA Pesticides RED (2006)). (2) This substance was not a skin irritant (EU EMEA (1999)). (3) In a skin irritation test with rabbits on this substance, only very slight erythema was found 24 hours after application, and it was assessed as not a skin irritant (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) This substance was not irritating in an eye irritation test with rabbits according to EPA OPPTS 870.2400 (EPA Pesticides RED (2006)). (2) This substance was not an eye irritant (EU EMEA (1999)). (3) In an eye irritation test with rabbits on this substance, no corneal tumorigenesis/opacity or conjunctival edema was observed, and conditions of the iris and conjunctiva were normal. Therefore, it was assessed as not an eye irritant (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)).
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) - (3). [Evidence Data] (1) This substance was not a skin sensitizer in a guinea pig skin sensitization test according to EPA OPPTS 870.2600 (EPA Pesticides RED (2006)). (2) This substance was not a skin sensitizer in a guinea pig skin sensitization test (Buehler test) (EU EMEA (1999), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (3) It is reported that in a guinea pig skin sensitization test on this substance (maximization test), it was sensitizing to the skin, and the positive rate was 20% (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) As for in vivo, it was reported to be negative in a chromosomal aberration test with rat bone marrow cells and a micronucleus test with mouse bone marrow cells (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (2) As for in vitro, it was reported to be negative in a bacterial reverse mutation test, a sister chromatid exchange test, and a mouse lymphoma test using cultured mammalian cells (same as the above).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Although sufficient test results to assess carcinogenicity were not obtained in rats, it was classified as "Not classified" based on (1) - (3). [Evidence Data] (1) As for classification results by domestic and international organizations, EPA classified it in NL (Not Likely to be Carcinogenic to Humans) (EPA Annual Cancer Report 2019 (Access on September 2020): classified in 1998). (2) In a combined chronic toxicity/carcinogenicity test by 93-week diet administration of this substance to male and female mice, no carcinogenicity was observed (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013), EU EMEA (1999)). (3) Taking into account the negative mutagenicity results and the lack of carcinogenicity in an adequately-conducted study in mice, EMEA concluded that this substance was not carcinogenic (EU EMEA (1999)). [Reference Data, etc.] (4) In a combined chronic toxicity/carcinogenicity test by 2-year diet administration of this substance to male and female rats, there was no apparent increase in the incidence of tumors, the test was inadequate for the assessment of carcinogenicity due to the poor survival (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013), EU EMEA (1999)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), effects on fertility were reported at a dose at which parental toxicity was observed. It was classified in Category 2 in accordance with the GHS Classification Guidance for the Japanese Government. A new information source was used and the classification results were changed from the previous classification. [Evidence Data] (1) In a two-generation reproductive study with rats dosed by feeding, evidence of infertility was observed in F1 males at a dose (75 mg/kg feed; converted guidance value: 3.75 mg/kg/day) at which parental toxicity (overt signs of toxicity, reduced body weight gain, reductions in plasma, erythrocyte and brain cholinesterase (ChE) activity) was observed. This dose was also toxic to offspring causing decreases in litter size, pup viability, and body weight gain, and significant reduction in plasma, erythrocyte, and brain ChE activity (EU EMEA (1999)). [Reference Data, etc.] (2) In a test (Seg I test) with rats dosed by gavage during pre-gestation and early gestation period, no effect was observed in male and female parent animals and fetuses up to the maximum dose of 2 mg/kg/day (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (3) In a test (Seg III test) with female rats dosed by gavage during perinatal and lactation period, no effect was observed in dams, fetuses, and offspring up to the maximum dose of 2 mg/kg/day (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (4) In a test (Seg II test) with female rats dosed by gavage during organogenesis period and on days 7 to 17 of gestation, no effect was observed in dams, fetuses, and offspring up to the maximum dose of 2 mg/kg/day (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (5) In a developmental toxicity study with female rats dosed by gavage on days 6 to 15 of gestation, overt signs of toxicity were observed in the dams given 3 and 6 mg/kg/day, and maternal body weight gain was significantly reduced at 6 mg/kg/day. There was no evidence of teratogenicity or fetotoxicity at any dose level (EU EMEA (1999)). (6) In a developmental toxicity study with female rabbits dosed by gavage on days 6 to 18 of gestation, maternal body weight was reduced at the maximum dose of 8 mg/kg/day, and no effect was observed in fetuses (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)).
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] Since effects on the nervous system were observed in a cases of human exposure in (1) and test animal studies in (2) to (4), it was classified in Category 1 (nervous system). A new information source was used and the classification results were changed from the previous classification. [Evidence Data] (1) It was described that 235 cases having difficulty breathing, chest tightness, shortness of breath, mental confusion, nausea, dizziness, headaches, vomiting, eye irritation, etc. were reported in humans exposed to this substance (Patty (6th, 2012)). (2) In an acute oral toxicity test and an acute dermal application test with rats (the dose levels were unknown in both cases), central nervous system inhibitory symptoms (such as a decrease in locomotor activity, ataxic gait, and gait disturbance), tremor, lacrimation, salivation, miosis, irregular breathing, etc. were observed (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (3) In a 4-hour acute inhalation exposure test with rats, quickening of respiration, slight clonic convulsion, salivation, lacrimation, loose stool excretion, and incontinence of urine were observed at 1,440 mg/m3 (within the range for Category 2) to 7,290 mg/m3 (exceeding Category 2) (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (4) It was reported that test animals such as dogs, rabbits, rats, and mice exhibited anticholinesterase and neurotoxic effects (EPA Pesticides RED (2006)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1 (nervous system). As a result of examination using the new information, the classification results were changed from the previous classification. [Evidence Data] (1) As a result of a 6-month test with dogs dosed by feeding, a decrease in cerebrum cholinesterase (ChE) activity in males was observed at or above 12/4 ppm (males/females: 0.089/0.083 mg/kg/day), and inhibition of erythrocyte ChE activity in males and females, a decrease in cerebrum ChE activity in males, higher leukocyte count and inorganic phosphorus, and a decrease in cerebrum ChE activity (65%) in females were observed at 24 ppm (males/females: 0.692/0.702 mg/kg/day) (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (2) As a result of a 52-week test with dogs dosed by feeding, at 20 ppm (0.5 mg/kg/day, within the range for Category 1), an increase in liver weight and a decrease in erythrocyte ChE activity were observed; and at 100 ppm (2.5 mg/kg/day, within the range for Category 1), diarrhea, a decrease in food consumption, and increases in liver enzymes and liver weight were observed, additionally, focal hepatic necrosis and decreases in erythrocyte and brain ChE activity were observed in 2 animals, and one male was euthanized due to a collapsed condition (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013), EU EMEA (1999)). (3) In a combined chronic toxicity/carcinogenicity study with mice, decreases in erythrocyte and brain ChE activity in males were observed at or above 1 mg/kg/day (within the range for Category 1); hyperplasia of the bone marrow was observed in males at 6 mg/kg/day; a decrease in food consumption in males, decreases in erythrocyte and brain ChE activity, and hyperplasia of the duodenal mucosa in females were observed at or above 6 mg/kg/day (within the range for Category 1); and hypoactivity in males and females, an increase in brain weight, and vacuolation degeneration of the nerve cells in males, and an increase in mortality, a decrease in food consumption, vacuolation degeneration of the nerve cells, and hyperplasia of the bone marrow in females were observed at 21 mg/kg/day (within the range for Category 2) (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (4) In a combined chronic toxicity/carcinogenicity study with rats, a decrease in erythrocyte ChE activity was observed at or above 12 ppm (0.6 mg/kg/day, within the range for Category 1), and a decrease in brain ChE activity was observed at 12 ppm (6 mg/kg/day). Since the mortality was high, surviving males were euthanized during week 91. Deaths, including those in a control group, were mostly due to chronic nephropathy (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2013)). (5) In a 3-week dermal toxicity test with rabbits, decreases in plasma and erythrocyte ChE activity were observed in males at or above 0.5 m/kg/day (converted guidance value: 0.08mg/kg/day, within the range for Category 1) (EU EMEA (1999)).
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 48-hour EC50 = 0.0033 mg/L for crustacea (Daphnia magna) (EPA OPP Pesticide Ecotoxicity Database, 2020).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 1 because it is not rapidly degradable (BIOWIN), and it was classified in Category 1 in acute toxicity.
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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