NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	13194-48-4
Chemical Name	O-ethyl-S,S-dipropyl phosphorodithioate; ethoprophos
Substance ID	R02-B-090-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	Not classified	- -	-	-	It was classified as "Not classified" from a flash point of 140 deg C (GESTIS (Access on June 2020)).
7	Flammable solids	Not classified (Not applicable)	- -	-	-	Liquid (GHS definition). It was classified as "Not classified."
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. It was classified as "Not classified."
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 750 mg/L (20-25 deg C) (HSDB (Access on June 2020)).
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 2	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1) - (6). [Evidence Data] (1) LD50 for rats: females: 32.8 mg/kg, males: 61.0 mg/kg (EPA Pesticides RED (2006)) (2) LD50 for rats: females: 33 mg/kg, males: 62 mg/kg (JMPR (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)) (3) LD50 for rats: females: 56 mg/kg (JMPR (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)) (4) LD50 for rats: females: 30.2 mg/kg, males: 56.2 mg/kg (Patty (6th, 2012)) (5) LD50 for rats: females: 33 mg/kg, males: 61 mg/kg (HSDB (Access on June 2020)) (6) LD50 for rats: 34 mg/kg (GESTIS (Access on June 2020))
1	Acute toxicity (Dermal)	Category 1	Danger	H310	P302+P352 P361+P364 P262 P264 P270 P280 P310 P321 P405 P501	[Rationale for the Classification] It was classified in Category 1 from (1) - (3). [Evidence Data] (1) LD50 for rabbits: 8.5 mg/kg (JMPR (1999), EPA Pesticides RED (2006), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010), Patty (6th, 2012), HSDB (Access on June 2020)) (2) LD50 for rabbits: 26 mg/kg (JMPR (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)) (3) LD50 for rats: 26 mg/kg (IPCS PIM G001 (1998)) [Reference Data, etc.] (4) LD50 for rats: 226 mg/kg (JMPR (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)) (5) LD50 for rats: females: 424 mg/kg, males: 1,280 mg/kg (JMPR (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010), Patty (6th, 2012), HSDB (Access on June 2020))
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 2	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1), (2). Besides, because exposure concentrations were higher than the saturated vapor pressure concentration (0.005 mg/L), a reference value in the unit of mg/L was applied as mist. [Evidence Data] (1) LC50 for rats (4 hours): 0.123 mg/L (EPA Pesticides RED (2006), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010), Patty (6th, 2012)) (2) LC50 for rats (4 hours): 0.250 mg/L (JMPR (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)) (3) Vapor pressure of this substance: 3.8E-004 mmHg (20-25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 0.005 mg/L)
2	Skin corrosion/irritation	Classification not possible	- -	-	-	[Rationale for the Classification] Although there were descriptions of (1) - (4), it was classified as "Classification not possible" due to lack of data. It was judged as appropriate to classify it as "Classification not possible" because rationale data for the previous classification could not be confirmed, and it was considered impossible to assess a skin irritation test according to guidelines due to the death of animals. Therefore, the classification result was changed. Besides, data in (4) were also referred to EPA's data, and it was impossible to find the rationale for a severe skin irritant. [Reference Data, etc.] (1) In a skin irritation test with rabbits on the undiluted liquid of this substance, all the animals died within 8 hours after application (JMPR Report (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (2) In a test with rabbits (0.03, 0.1, 1 mg/kg/day, 3 weeks), slight irritation was observed (JMPR Report (1999)). (3) In a skin irritation test with rabbits according to EPA OPP 81-5, 6/6 animals applied with this substance (0.5 mL) died (EPA Pesticides RED (2006)). (4) This substance was a severe skin and eye irritant after application of 0.5 mL and 0.1 mL, respectively, causing death in animals (Patty (6th, 2012)).
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] It was classified in Category 2A because it was estimated to cause moderate or higher irritation from (1) - (3). [Evidence Data] (1) Undiluted this substance caused not only irritation in the rabbit eye (moderate erythema and blistering in the nictitating membrane and sclera) also severe toxicity, causing the death of animals within 1 hour after application (JMPR Report (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (2) In an eye irritation test with rabbits according to EPA OPP 81-4, 3/3 animals applied with this substance (0.1 mL) died (EPA Pesticides RED (2006)). (3) This substance was a severe skin and eye irritant after application of 0.5 mL and 0.1 mL, respectively, causing death in animals (Patty (6th, 2012)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Reference Data, etc.] (1) It was classified in Skin Sens. 1 (H317) in EU-CLP classification (EU CLP classification (Access on June 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1) - (3). [Evidence Data] (1) As for in vivo, it was reported to be negative in a dominant lethal test with rats and a micronucleus test with rat bone marrow cells (JMPR (1999), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (2) As for in vitro, it was reported to be negative in a bacterial reverse mutation test and a gene mutation test with cultured mammalian cells. On the other hand, it was reported to be positive in a chromosomal aberration test and a sister chromatid exchange test in cultured mammalian cells in the presence of metabolic activation (same as the above). (3) It is reported that it was considered that this substance did not have genotoxicity that could pose a problem in vivo (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] There was no available report in humans. It was classified in Category 1B because it was considered that there was sufficient evidence for carcinogenicity in animal tests: increased incidences of malignant tumors were observed in multiple tests, independently conducted in (2), although no carcinogenicity was found in a test in mice (3), and based on EPA's classification result in (1). An investigation was performed by using new information sources, and the classification result was changed. [Evidence Data] (1) As for classification results by domestic and international organizations, EPA classified it in L (Likely to be Carcinogenic to Humans) (EPA Annual Cancer Report 2019 (Access on September 2020): classified in 1998). (2) In three combined chronic toxicity/carcinogenicity tests by 2-year diet administration of this substance to male and female rats, increased incidences of C cell adenoma and carcinoma in the thyroid and malignant pheochromocytoma in the adrenal gland in males and endometrial polyps in females were found (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (3) In a carcinogenicity test by 2-year diet administration of this substance to male and female mice, no carcinogenicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)).
7	Reproductive toxicity	Category 2, Additional category for effects on or via lactation	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), at doses at which parental toxicity was observed, an increase in the mortality of offspring, a decrease in the survival rate on postnatal day 14, etc. were observed, and no other effects on fertility were observed, and therefore, it was classified in Category 2, and since the decrease in the survival rate on postnatal day 14 could be an effect via breast milk, it was classified in "additional category: effects on or via lactation". A new information sources 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, at a dose at which parental toxicity (inhibition of brain ChE activity at or above 30 ppm, reduced body weight gain at or above 150 ppm, loose stool, tremor, etc. at 300 ppm) was observed, no effect on fertility was observed, but effects in offspring (a decrease in the survival rate of F2 offspring on postnatal day 14, and a decrease in the lactation index at or above 150 ppm, an increase in the mortality of F1 offspring, and reduced body weight gain at 300 ppm) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). [Reference Data, etc.] (2) In a developmental toxicity study with female rats dosed by gavage on days 6 to 15 of gestation, no effect in fetuses was observed even at doses at which maternal toxicity (loose stool, reduced body weight gain, etc.) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (3) In a developmental toxicity study with female rabbits dosed by gavage on days 6 to 18 of gestation, no effect in fetuses was observed even at doses at which maternal toxicity (reduced body weight gain) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)).
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] There was no report on acute exposure to this substance in humans. In experimental animals, based on (1) to (7), it was classified in Category 1 (nervous system). [Evidence Data] (1) In an acute oral toxicity test with female rats (the minimum dose at which effects were observed was not described, and it was assumed that effects were observed at least around the LD50 values (56 mg/kg, within the range for Category 1)), wasting, ataxic gait, salivation, hypoactivity, hunchback position, and tremor were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010), JMPR (1999)). (2) In an acute dermal application test with rats (the minimum dose where effects were observed was not described, and it was assumed that effects were observed at least around the LD50 values (226 mg/kg, within the range for Category 1)), tremor, spasm, hypoactivity, and dyspnea were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010), JMPR (1999)). (3) In an acute dermal application test with rats (the minimum dose where effects were observed was not described, and it was assumed that effects were observed at least around the LD50 values (males: 1,280 mg/kg; females: 424 mg/kg, within the range for Category 2)), chromaturia, tremor, salivation, hypoactivity, ataxia, loose stool, diarrhea, labored breathing, lacrimation, and exophthalmos were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010), JMPR (1999)). (4) In an acute dermal application test with rabbits (the minimum dose where effects were observed was not described, and it was assumed that effects were observed at least around the LD50 values (8.5 mg/kg, within the range for Category 1)), piloerection, labored breathing, salivation, a decrease in locomotor activity, tremor, ataxia, loose stool, diarrhea, lacrimation, and a decrease in body weight (in dead animals) were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010), JMPR (1999)). (5) In a 4-hour acute inhalation exposure test with rats (the minimum dose where effects were observed was not described, and it was assumed that effects were observed at least around the LD50 values (0.25 mg/kg, within the range for Category 1)), apathy, labored breathing, and salivation were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010), JMPR (1999)). (6) In an acute neurotoxicity test by an oral administration to rats (males: 0, 30, 60 mg/kg; females: 0, 20, 40 mg/kg), tremor and salivation were observed in males at 60 mg/kg and in females at 40 mg/kg; and hunchback position, labored breathing, unkempt fur, coloring of fur, paleness of the body, discharge of the eye, hypoactivity, and cold sensation on contact were observed in males of the same group. In 2 hours after the administration, cholinesterase (ChE) activity of erythrocytes and each region of the brain was inhibited by 43 to 93% in relation to the dose in all treated groups. In 15 days after the administration, cerebellum ChE activity in males and females and erythrocyte ChE activity in females returned to normal, but inhibition of ChE by about 20% or more was observed in the erythrocyte and brain frontal cortex in males and females of all administrated groups, and in the hippocampus in males and females of a high dose group (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (7) In an acute neurotoxicity test by an oral administration to rats (males: 0, 5, 50, 75 mg/kg; females: 0, 5, 25, 50 mg/kg), lying on belly, lethargy, a change in manageability, lacrimation, gasping, staggering gait, loss of corneal reflex, delayed reflex to heat, subnormal temperature, and a decrease in grip strength of the forelimbs were observed in males at 75 mg/kg. At or above 50 mg/kg, hunchback position, tremor, labored breathing, exophthalmos, hypoactivity, incoordination, salivation, cold sensation on contact, slight subnormal temperature, a decrease in locomotor activity, and inhibition of erythrocyte ChE activity (20% or above) were observed in males, and hunchback position, tremor, exophthalmos, incoordination, hypoactivity, cold sensation on contact, lying on belly, lethargy, a change in manageability, lacrimation, labored breathing, gasping, staggering gait, loss of corneal reflex, delayed reflex to heat, subnormal temperature, a decrease in grip strength of the forelimbs, and a decrease in locomotor activity were observed in females. At or above 25 mg/kg, salivation, lip smacking, ataxia, loss of pupillary reflex, tremor, and inhibition of erythrocyte ChE activity (20% or above) were observed in females (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, blood system, liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 1 (nervous system, blood system, liver). 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 90-day test with rats dosed by feeding, inhibition of erythrocyte and brain cholinesterase (ChE) activity was observed in males and females at or above 0.3 ppm (0.015 mg/kg/day, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (2) As a result of a 90-day test with dogs dosed by feeding, vomiting, decreases in erythrocyte count and hematocrit values, and inhibition of erythrocyte ChE activity were observed at 100 ppm (2.5 mg/kg/day, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (3) As a result of a 21-day dermal toxicity test with rabbits, inhibition of erythrocyte and brain ChE activity was observed in males and females at or above 1 mg/kg/day (converted guidance value: 0.23 mg/kg/day, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (4) There were 3 reports on the results of combined chronic toxicity/carcinogenicity studies with rats dosed by feeding, all of which reported effects on the nervous system (inhibition of brain ChE activity, etc.) and blood system within the range for Category 1 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (5) As a result of a 2-year carcinogenicity study with mice dosed by feeding, inhibition of erythrocyte, and brain ChE activity was observed at 30 ppm (males/females: 4.0/4.9 mg/kg/day, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)). (6) As a result of a 1-year chronic toxicity study by an oral administration to dogs, at or above 1.0 mg/kg/day (within the range for Category 1), hepatocyte vacuolation, etc. in males and females, and inhibition of erythrocyte ChE activity in females were observed; and at or above 10 mg/kg/day (within the range for Category 1), inhibition of brain ChE activity, focal hepatic necrosis, hepatic fibrosis, and bile duct proliferation in males and females, decreases in erythrocyte count, hemoglobin, and hematocrit levels, and inhibition of erythrocyte ChE activity in males, and a tendency of reduced body weight gain and food intake in females were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2010)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment Short term (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.0063 mg/L for fish (Lagodon rhomboides) (ECOTOX, 2020, EPA OPP Pesticide Ecotoxicity Database, 2020).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 28-day NOEC = 0.00036 mg/L for crustacea (Americamysis bahia) (EPA OPP Pesticide Ecotoxicity Database, 2020). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 2 because it is not rapidly degradable (BIOWIN) and due to 96-hour EC50 = 8.4 mg/L for algae (Skeletonema costatum) (ECOTOX, 2020, EPA OPP Pesticide Ecotoxicity Database, 2020). By drawing a comparison between the above results, it was classified in Category 1.
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.

To GHS Information