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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	2104-64-5
Chemical Name	O-Ethyl O-4-nitrophenyl phenyl phosphonothioate; EPN
Substance ID	R02-B-007-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 FY2017
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	- -	-	-	There is a chemical group associated with explosive properties, a nitro group, present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN2783), it does not correspond to explosives, hazards of the highest precedence, and was classified as "Not classified."
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (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)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
7	Flammable solids	Classification not possible	- -	-	-	No data available. Besides, there is information that it is combustible (ICSC (2008)).
8	Self-reactive substances and mixtures	Type G	- -	-	-	There is a chemical group associated with explosive properties, a nitro group, present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN2783), and it is considered to be not applicable to self-reactive substances and mixtures, hazards of the highest precedence, it was classified in Type G.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because 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 was classified as "Not classified" because it is estimated that it does not react vigorously with water from water solubility data of 3.11 mg/L (20-25 deg C) (HSDB (Access on April 2020)).
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
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. It was classified as "Not classified."
16	Corrosive to metals	Classification not possible	- -	-	-	It is a solid with a melting point of 55 deg C or lower, but the classification is not possible due to no data.
17	Desensitized explosives	Not classified	- -	-	-	It was classified as "Not classified" because it is not desensitized by wetting, dilution, etc.

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: 7 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 4 Tentative Hazard Assessment Sheet (Ministry of the Environment, 2005), GESTIS (Access on April 2020), HSDB (Access on April 2020)) (2) LD50 for rats: males: 36 mg/kg, females: 7.7 mg/kg (ACGIH (7th, 2019)) (3) LD50 for rats: 8 mg/kg (HSDB (Access on April 2020)) (4) LD50 for rats: 14 mg/kg (IPCS PIM G001 (1985)) (5) LD50 for rats: males: 36 mg/kg, females: 24 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)) (6) LD50 for rats: 36 mg/kg (HSDB (Access on April 2020))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	[Rationale for the Classification] By giving weight to (1), which is the result of a GLP test, and its solvent was water, it was classified in Category 3. [Evidence Data] (1) LD50 for rats (slovent: water): males: 2,850 mg/kg, females: 538 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017), HSDB (Access on April 2020)) (2) LD50 for rats (slovent: acetone): males: 230 mg/kg, females: 25 mg/kg (ACGIH (7th, 2019), HSDB (Access on April 2020))
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)	Category 1	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] It was classified in Category 1 from (1) - (3). Besides, because exposure concentrations were higher than the saturated vapor pressure concentration (1.7E-005 mg/L), the reference value in the unit of mg/L was applied as dust. The category was changed from the previous classification by the use of new information sources. [Evidence Data] (1) LC50 for rats (1 hour): 106 mg/m3 (0.106 mg/L) (converted 4-hour equivalent value: 0.0265 mg/L) (ACGIH (7th, 2019), Environmental Risk Assessment for Chemical Substances vol. 4 Tentative Hazard Assessment Sheet (Ministry of the Environment, 2005)) (2) LC50 for rats (1 hour): 160 mg/m3 (0.16 mg/L) (converted 4-hour equivalent value: 0.04 mg/L) (HSDB (Access on April 2020)) (3) Vapor pressure of this substance: 0.00000095 mmHg (25 deg C) (converted value for the saturated vapor pressure concentration: 1.7E-005 mg/L) (HSDB (Access on April 2020))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) In a skin irritation test with rabbits on this substance, slight irritation was observed, and the mean score at 24/48/72 hours after application was 0.3/0.1/0.1 (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (2) Overexposure to this substance is irritating to the skin and eye (HSDB (Access on April 2020)).
3	Serious eye damage/eye irritation	Classification not possible	- -	-	-	[Rationale for the Classification] There are descriptions of (1) and (2), but it was classified as "Classification not possible" due to lack of data. Data that was used as the rationale in the previous classification was those on preparations, and because animals died in a test on the undiluted substance, sufficient information for categorization could not be obtained. Therefore, the category was changed. [Reference Data, etc.] (1) In an eye irritation test with rabbits, it was irritating to the conjunctiva, which was judged to recover immediately. However, as for the rabbits used in the test, 5 out of 6 animals died within 18 hours after application, and the remaining one died within 48 hours (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (2) Overexposure to this substance is irritating to the skin and eye (HSDB (Access on April 2020)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) No skin sensitization was observed in a skin sensitization test with guinea pigs (Buehler test) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] From (1), (2), it was negative in an in-vivo test and positive in part of in vitro tests, but it was classified as "Not classified" based on the expert judgment. [Evidence Data] (1) As for in vivo, it was reported to be negative in a micronucleus test with mouse bone marrow cells (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (2) As for in vitro, it is reported that it was negative in a bacterial reverse mutation test and a chromosomal aberration test in cultured mammalian cells, and positive in a mouse lymphoma test in cultured mammalian cells and a chromosomal aberration test in human lymphocytes (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from classification results by other organizations in (1) and the results of carcinogenicity tests in experimental animals in (2), (3). [Evidence Data] (1) As for classification results by domestic and international organizations, ACGIH classified it in A4 (ACGIH (7th, 2019)). (2) In carcinogenicity tests by diet administration of this substance for 2 years to male and female rats and 18 months to mice, no treatment-related increased incidences of neoplastic lesions were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (3) There was no evidence of carcinogenicity observed in a test by 2-year diet administration of this substance to male and female rats (ACGIH (7th, 2019)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), at a dose at which toxicity effects were observed in parental animals, a lower survival rate in pups was observed. Therefore, it was classified in Category 2 in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) In a two-generation reproduction study with rats dosed by feeding, at a dose at which toxicity effects (reduced body weight gain) were observed in parental animals, a lower survival rate in pups was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). [Reference Data, etc.] (2) In a developmental toxicity study with female rats dosed by gavage on days 6 to 15 of gestation, even at a dose at which maternal toxicity effects (tremor, prostration, hunched posture, nasal discharge, lacrimation) were observed, no effect was observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (3) In developmental toxicity studies with female rabbits dosed by gavage on days 7 to 19 of gestation, at doses at which maternal toxicity effects (death (2/15 cases), a decrease in food consumption) were observed, low body weight was observed in fetuses (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (4) In a developmental neurotoxicity test with female rats dosed by gavage on days 6 of gestation to days 10 of lactation, at a dose at which maternal toxicity effects (tremor, reduced body weight gain) were observed, reduced body weight gain was observed in fetuses but no developmental neurotoxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)).
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) and (2), it was classified in Category 1 (nervous system). [Evidence Data] (1) This substance was an organophosphorus pesticide and exhibited an inhibitory action on cholinesterase (ACGIH (7th, 2019), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (2) It was reported that symptoms of intoxication by this substance in humans include salivation, lacrimation, incontinence of urine and feces, tightness in the chest, easy fatigability, weakness, weight loss, atrophied muscles, and optical media discoloration appeared.These symptoms were caused by a nervous system disorder and were observed over multiple years after acute or chronic exposure (ACGIH (7th, 2019), Environmental Risk Assessment for Chemical Substances, Vol. 4, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2005)). [Reference Data, etc.] (3) In an acute oral toxicity test with rats, a decrease in locomotor activity, lacrimation, salivation, an increase in urine volume, a decrease in blood pressure, bradypnea, lower sensory reception, and apparent hypoactivity were observed at or above 5 mg/kg; and in addition to these symptoms, incoordination, hunched posture, tremor and lethargy were observed at or above the lethal dose of 20 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (4) In the "Designation of simple chemical substances or compounds (including alloys) designated by the Minister of Labour or disease designated by the Minister of Labour based on the provision of the Ordinance for Enforcement of the Labor Standards Act" (Ministry of Labour Notification No. 33 in 1996), it was stated that with regard to o-ethyl=o-p-nitrophenyl phenyl phosphonothioate (EPN), which was another name of this substance, the diseases designated by the Minister of Labour (current Minister of Health, Labour and Welfare) include subjective symptoms such as headache, dizziness and emesis, consciousness disorders such as clouding of consciousness, neuropathy such as dysphasia, mental disorders such as confusion, motor nerve disorders such as muscle fasciculation and convulsion, or autonomic disorders such as miosis, salivation and hidrosis (Appended table for Article 35 of the Ordinance for Enforcement of the Labor Standards Act (1996)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, blood system)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) and (2), effects on the nervous system were observed in humans, and based on (3) to (5), effects on the nervous system and blood system were observed in experimental animals at doses within the range for Category 1. Therefore, it was classified in Category 1 (nervous system, blood system). [Evidence Data] (1) As symptoms of intoxication by this substance, salivation, lacrimation, incontinence of urine and feces, tightness in the chest, easy fatigability, weakness, weight loss, atrophied muscles, and optical media discoloration appeared. These symptoms were caused by a nervous system disorder and were observed over multiple years after short-term and long-term exposure (Environmental Risk Assessment for Chemical Substances, Vol. 4, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2005)). (2) In five volunteers dosed by capsules with this substance at 9 mg/day (about 0.13 mg/kg/day) for 56 days, decreases in plasma and red blood cell cholinesterase activities were observed (ACGIH (7th, 2019)). (3) In a 90-day repeated oral dose toxicity test with rats dosed by feeding, red blood cell cholinesterase activity inhibition (20% of more) was observed at or above 25 ppm (males: 1.48 mg/kg/day, females: 1.89 mg/kg/day, within the range for Category 1), and decreases in red blood cell count, hemoglobin, hematocrit, and blood sugar, brain cholinesterase activity inhibition, and hemosiderosis in the spleen were observed at 125 ppm (males: 7.34 mg/kg/day, females: 11.6 mg/kg/day, within the range or near the upper limit for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (4) In a 90-day inhalation toxicity test with rats (6 hours/day, 5 days/week), red blood cell cholinesterase activity inhibition was observed in females at or above 0.0008 mg/L (converted guidance value: 0.00058 mg/L, within the range for Category 1) and in males at 0.008 mg/L (converted guidance value: 0.0058 mg/L, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)). (5) In a 21-day dermal exposure test with rats, red blood cell cholinesterase activity inhibition was observed at or above 1.5 mg/kg/day (converted guidance value: 0.35 mg/kg/day, within the range for Category 1); brain cholinesterase activity inhibition was observed at or above 5.0 mg/kg/day (converted guidance value: 1.2 mg/kg/day, within the range for Category 1); and tremor, hunched posture, emaciation, reduced body weight gain, multifocal hepatocyte degeneration/necrosis, etc. were observed at 15.0 mg/kg/day (converted guidance value: 3.5 mg/kg/day, within the range for Category 1) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2017)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment Short term (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 26-hour LC50 = 0.00006 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 2 (Ministry of the Environment, 2003)).
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 was not rapidly degradable (a 4-week degradation rate by BOD: 3% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1983)) and due to 31-34-day NOEC = 0.0111 mg/L for fish (Pimephales promelas) (Environmental Risk Assessment for Chemical Substances Vol. 2 (Ministry of the Environment, 2003)). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 1 because it was not rapidly degradable (a 4-week degradation rate by BOD: 3% (Environmental Risk Assessment for Chemical Substances Vol. 2 (Ministry of the Environment, 2003), Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1983)) and due to 26-hour LC50 = 0.00006 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 2 (Ministry of the Environment, 2003)). From 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.

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