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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	141-66-2
Chemical Name	(E)-3-(dimethylamino)-1-methyl-3-oxoprop-1-enyl dimethyl phosphate; Dicrotophos
Substance ID	R02-B-058-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 > 93 deg C (closed cup) (ICSC (1998)).
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 (P-O) present in the molecule, but because it is classified in Division 6.1 in UNRTDG (UN3018), 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	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 obtained information that it is miscible with water (HSDB (Access on May 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) - (4). [Evidence Data] (1) LD50 for rats: females: 8 mg/kg, males: 11 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007)) (2) LD50 for rats: 13 mg/kg (GESTIS (Access on May 2020)) (3) LD50 for rats: females: 16 mg/kg, males: 21 mg/kg (ACGIH (7th, 2002), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007), HSDB (Access on May 2020)) (4) LD50 for rats: 22 mg/kg (IPCS PIM G001 (2009))
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) - (4). [Evidence Data] (1) LD50 for rats: females: 42 mg/kg, males: 43 mg/kg (ACGIH (7th, 2002), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007), HSDB (Access on May 2020)) (2) LD50 for rats: 42-43 mg/kg (Patty (6th, 2012)) (3) LD50 for rabbits: 168 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007), GESTIS (Access on May 2020)) (4) LD50 for rabbits: 225 mg/kg (ACGIH (7th, 2002), HSDB (Access on May 2020), Patty (6th, 2012))
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). Besides, because an exposure concentration was higher than the saturated vapor pressure concentration (0.002 mg/L), a reference value in the unit of mg/L was applied as mist. [Evidence Data] (1) LC50 for rats (4 hours): 0.09 mg/L (ACGIH (7th, 2002), US AEGL (2009), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007), GESTIS (Access on May 2020), HSDB (Access on May 2020), Patty (6th, 2012)) (2) Vapor pressure of this substance: 0.00016 mmHg (25 deg C) (HSDB (Access on May 2020)) (converted value for the saturated vapor pressure concentration: 0.002 mg/L)
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). The classification result was changed due to new data obtained. [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 (2006), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007), HSDB (Access on May 2020), 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 from (1). The classification result was changed due to new data obtained. [Evidence Data] (1) In an eye irritation test with rabbits according to EPA OPPTS 870.2400, irritation was reversed by 14 days (EPA Pesticides (2006), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007), HSDB (Access on May 2020), Patty (6th, 2012)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1 from (1). The classification result was changed due to new data obtained. [Evidence Data] (1) This substance was reported to be a strong sensitizer in a skin sensitization test with guinea pigs according to EPA OPPTS 870.2600 (EPA Pesticides (2006), Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007), HSDB (Access on May 2020), Patty (6th, 2012)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Evidence Data] (1) As for in vitro, it was reported to be positive and negative in bacterial reverse mutation tests and positive in a sister chromatid exchange test with cultured mammalian cells (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007), ACGIH (7th 2002)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] There was no available report in humans. From (1), (2), it was classified A4 by ACGIH, but S by EPA, and carcinogenicity test results in mice were not obtained. Therefore, it was classified as "Classification not possible." [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified A4 by ACGIH (ACGIH (7th, 2002)) and S (Suggestive Evidence of Carcinogenicity, but not Sufficient to Assess Human Carcinogenic Potential) by EPA (EPA Annual Cancer Report 2019 (Access on July 2020): classified in 1999). (2) In a combined chronic toxicity/carcinogenicity test by 2-year diet administration of this substance to male and female rats, no associations were found between doses of this substance and incidences of neoplastic lesions (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), increased mortality in offspring was observed even at doses at which no parental toxicity was observed. Therefore, it was classified in Category 1B. A new information source was used and the classification results were changed from the previous classification. [Evidence Data] (1) In a three-generation reproductive study with rats, cholinergic toxicity findings (weakness, reduced body weight gain, effects on the central nervous system) and decreases in fertility rate and litter size were observed in parent animals, and cholinergic toxicity findings (weakness, reduced body weight gain, effects on the central nervous system) and higher mortality were also observed in offspring at the same dose level. In addition, increased mortality in offspring was observed even at doses at which no parental toxicity was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007)). [Reference Data, etc.] (2) In a developmental toxicity study with female rabbits dosed (the dose route was unknown) on days 6 to 18 of gestation, no effect was observed in fetuses even at a dose at which maternal toxicity (death (4/18 animals) and cholinergic toxicity findings (salivation and tremor)) was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007)). (3) In a developmental toxicity study with female mice dosed by intraperitoneal injection during the gestation period, mortality of mothers increased, and a decrease in fetal body weight was observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007)).
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system, respiratory organs)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1 (nervous system, respiratory organs). New information sources were used and the classification results were changed from the previous classification. [Evidence Data] (1) Signs and symptoms of acute intoxication in humans included muscarinic, nicotinic, and central nervous system manifestations (EHC 63 (1986), IPCS PIM G001 (2009)). (2) In a single ingestion by humans, respiratory and ocular symptoms were expected to appear first after exposure. Effects on the respiratory organs included bronchoconstriction, increased activity of the secretory glands, and pulmonary edema (IPCS PIM G001 (2009)). (3) An individual who inhaled a spray that contained this substance developed organophosphate poisoning. Upon hospital admission, he had abdominal cramps, nausea, vomiting, and diarrhea; the next day he exhibited lassitude, salivation, dyspnea, coarse tremor of both legs, and a feeling of weakness (Patty (6th, 2012)). (4) Symptoms which most often appeared were headaches, fatigue, giddiness, nausea, sweating, blurred vision, tightness in the chest, abdominal cramps, vomiting, and diarrhea. In more advanced poisoning, difficult breathing, tremors, convulsions, collapse, coma, pulmonary edema, and respiratory failure followed. The more advanced the poisoning, the more obvious were the typical signs of cholinesterase inhibition (HSDB (Access on May 2020)). (5) A woman who orally ingested this substance developed bulbar palsy, and proximal muscle and respiratory weakness in 3 days after the ingestion (HSDB (Access on May 2020)).
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), it was reported that effects on the nervous system were observed in humans. Based on (2), it was reported that effects on the nervous system at doses within the range for Category 1 were observed in experimental animals. Therefore, it was classified in Category 1 (nervous system). [Evidence Data] (1) There was a report of a case in which an individual developed organophosphate poisoning due to inhalation exposure after he inhaled for 2 to 3 weeks a spray that contained this substance used to control mosquitoes in his home. Upon hospital admission, the individual presented with abdominal cramps, nausea, vomiting, and diarrhea; the next day he exhibited sweating, salivation, dyspnea, coarse tremor of both legs, and generalized weakness. Plasma and RBC cholinesterase (ChE) activities were nonexistent. On day 6, respiratory paralysis which was a typical intermediate syndrome occurred, and he required artificial respirator support for 5 days, but he was discharged on day 22 (ACGIH (7th, 2002)). (2) It was reported that, in a 90-day oral toxicity test with rats, at or above 0.04 mg/kg (within the range for Category 1), plasma ChE activity and erythrocyte and brain acetylcholinesterase inhibitions were observed. It was also reported that in multiple 2-year tests with rats dosed by feeding, at or above 1.25 to 5 mg/kg (within the range for Category 1), cholinergic toxicity findings and tremors were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2007)).
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 = 0.0127 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	It was classified in Category 1 because it is not rapidly degradable (BIOWIN) and due to 21-day NOEC = 0.0017 mg/L for crustacea (Daphnia magna) (EPA OPP Pesticide Ecotoxicity Database, 2020).
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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