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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	950-37-8
Chemical Name	S-(2,3-Dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-yl)methyl O,O-dimethyl phosphorodithioate (synonym: Methidathion or DMTP)
Substance ID	R03-B-034-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	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.
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. Besides, there is information that it is a substance with a low melting point and a flash point of 100 deg C (ICSC (2006)).
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	Not classified	- -	-	-	It is consided that it does not ignite at normal temperatures because it is estimated that it does not decompose up to 150 deg C from the information that it decomposes from about 150 deg C (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, 2010).
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 240 mg/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	- -	-	-	It is a substance 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 (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 2	Danger	H300	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 2. [Evidence Data] (1) LD50 for rats: 12 mg/kg (EPA Pesticides RED (2006)) (2) LD50 for rats: 26 mg/kg (JMPR (1992)) (3) LD50 for other rats: 26 mg/kg (JMPR (1992)) (4) LD50 for rats: 43.8 mg/kg (JMPR (1992)) (5) LD50 for rats: between 25 mg/kg to 54 mg/kg (EHC 63 (1986))
1	Acute toxicity (Dermal)	Category 3	Danger	H311	P302+P352 P361+P364 P280 P312 P321 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 3. Based on the new findings, the classification result was changed. [Evidence Data] (1) LD50 for rats: 297 mg/kg (JMPR (1992))
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 4	Warning	H332	P304+P340 P261 P271 P312	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 4. Based on the new findings, the classification result was changed. [Evidence Data] (1) LC50 (4 hours) for rats: 3.6 mg/L (HSDB in PubChem (Accessed Aug. 2021)) (2) LC50 (1 hour) for rats: 19 mg/L (converted 4-hour equivalent value: 4.75 mg/L) (Patty (2012), HSDB in PubChem (Accessed Aug. 2021))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) This substance was not a skin irritant (EPA Pesticides RED (2006)). (2) This substance was not a skin irritant in rabbits (Patty (6th, 2012)).
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 2B in accordance with the GHS Classification Guidance for the Japanese Government. Also, based on the new findings, the category was changed. [Evidence Data] (1) It was reported that this substance was a mild eye irritant (EPA Pesticides RED (2006)). (2) It was reported that this substance was a mild eye irritant in rabbits (Patty (6th, 2012)).
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) and (2), it was classified as "Not classified" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) This substance was not a skin sensitizer (EPA Pesticides RED (2006)). (2) This substance did not cause skin sensitization in guinea pigs (Patty (6th, 2012)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) As for in vivo, negative results were reported in a dominant lethal test with mice and a sister chromatid exchange (SCE) test using the bone marrow cells of mice (JMPR (1992), Patty (6th, 2012)). (2) As for in vitro, a bacterial reverse mutation test was negative (JMPR (1992)), and a chromosomal aberration test and a DNA repair test with the cultured mammalian cells were negative (JMPR (1992)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on the classification results by other organizations in (1) and the evidence of carcinogenicity only in one species and one sex (male mouse) from the test results in (2) and (3), it was classified in Category 2. Also, based on the new information source, classification results were 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: corresponding to Category 2) (EPA OPP Annual Cancer Report 2020 (Accessed August 2021): Classification in 1988). (2) In a 23-month carcinogenicity study with mice dosed by feeding (3 to 100 ppm), an increase in the incidence of liver tumors (hepatocellular adenomas, hepatocellular carcinomas and adenomas and carcinomas combined), which was statistically significant and exceeded the historical control data range, was observed and considered evidence of carcinogenicity in males dosed at or above 50 ppm. However, in females, no increase in the incidence of tumors was observed in any organ (JMPR (1992), Patty (6th, 2012)). (3) In a 2-year carcinogenicity study with rats dosed by feeding (4 to 100 ppm), no evidence of carcinogenic potential was observed in either males or females (JMPR (1992), Patty (6th, 2012)).
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) and (2), it was classified in Category 2, and effects on lactation were added. Also, the information used for the previous classification (the application materials for registration of agricultural chemical (1987)), such as the lower mating rate, etc. at a dose at which effects in parental animals were observed, was not available due to expiration of the registration. Therefore, based on the new findings, classification results were changed. [Evidence Data] (1) It was reported that, in a three-generation reproduction toxicity study with rats dosed by feeding, at 32 ppm, a decrease in the number of live pups at weaning in F1 to F3 pups and a slight increase in liver weight at weaning in F3 pups were observed. However, general toxicity effects in parental animals were unknown (Lobdell & Johnston (1966), JMPR (1992), Patty (6th, 2012)). (2) In a two-generation reproduction toxicity study with rats dosed by feeding, tremors during lactation in parental animals (females) and clinical signs suggestive of poor maternal care (weakness/lethargy, coolness to the touch, starving appearance) in F1 and F2 pups were observed at or above 25 ppm, and additionally, decreased body weight in F0 and F1 parental animals and decreased survival rate in F1 pups were observed at 50 ppm (Salamon (1987), JMPR (1992), Patty (6th, 2012), HSDB in Pubchem (Accessed August 2021)). [Reference Data, etc.] (3) It was reported that, in a one-generation reproduction toxicity study with rats dosed by feeding, tremors and decreased food consumption in parental animals and decreased pup birth weight and pup weight during lactation were observed at 50 ppm (Patty (6th, 2012), HSDB in Pubchem (Accessed August 2021)). (4) It was reported that, in a developmental toxicity study with rats and rabbits dosed by gavage, no developmental toxicity was observed (JMPR (1992), Patty (6th, 2012), HSDB in Pubchem (Accessed August 2021)).
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) It was reported that, in an acute oral toxicity test with rats (acute neurotoxicity test), dose-dependent inhibition in plasma and erythrocyte cholinesterase was observed at 2.5 to 10 mg/kg (within the range for Category 1), cholinergic signs (miosis, hypoactivity, tremors, salivation, dyspnea, red-stained face and absence of pain reflex) were observed within 1 to 4 hours of treatment at 5 mg/kg (within the range for Category 1), and deaths occurred at or above 20 mg/kg (within the range for Category 1) (Patty (2012)). (2) It was reported that, in an acute oral toxicity test with rats (acute neurotoxicity test), decreased activity, tremors, bizarre behavior, abnormal gait, ataxia, a decrease in forelimb grip strength, and uncoordinated righting reflex were observed at 8 to 15 mg/kg (within the range for Category 1) (Patty (2012)). [Reference Data, etc.] (3) It was reported that a 25-year-old man who ingested a large amount of a formulation containing 40% of this substance became unconscious and semi-comatose approximately 2 hours after the ingestion and cholinesterase activity in the serum was found to be zero a few hours after admission to hospital (JMPR (1992)). (4) It was reported that a 50-year-old man who ingested 40 mL (approx. 6.2 g) of a formulation containing 15.5% of this substance suffered from mental confusion, muscle fasciculations, bradycardia, miosis, sweating, salivation, and lacrimation, and six hours after ingestion, the incidence of muscle fasciculations increased followed by bronchorrhea and coma. It was also reported that serum and RBC cholinesterase values, as measured over eight days, were less than 50% of normal values (JMPR (1992)). (5) It was reported that, in acute oral toxicity and dermal toxicity studies with rats, curved or ventral body position, dacryorrhea/chromodacryorrhea, diarrhea, dyspnea, exophthalmus, ruffled fur, sedation, tonic/clonic muscle spasms, and trismus were observed (JMPR (1992)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, liver)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Since effects on the nervous system were observed in (1) to (7) and effects on the liver were observed in (3) to (6), it was classified in Category 1 (nervous system, liver). Also, based on the new findings, classification results were changed. [Evidence Data] (1) It was reported that, in a 90-day subchronic neurotoxicity study with rats dosed by feeding, inhibition of serum, erythrocyte, and brain ChE activity was observed at 10 ppm (0.6 mg/kg/day (males), 0.7 mg/kg/day (females), within the range for Category 1); and cholinergic signs (decreased grip strength, tremors, compulsive sniffing, and hyperresponsive behavior) were observed at 100 ppm (6.3 mg/kg/day (males), 7.2 mg/kg/day (females), within the range for Category 1) (Patty (2012), EPA OPP Rev. report of Hazard Identification Assessment (1999)). (2) It was reported that, in a repeated dose 4-week oral toxicity study with rats dosed by gavage (5 days/week), a 6-month oral toxicity study with rats dosed by feeding, a 101-week oral toxicity study with rats, and a 23-month oral toxicity study with monkeys dosed by gavage (6 days/week), inhibition of erythrocyte, serum, plasma, and brain ChE activity was observed within the range for Category 1 (JMPR (1992)). (3) It was reported that, in a repeated dose 90-day oral toxicity study with dogs dosed by feeding, bile stasis, discoloration of the liver, and enhanced enzyme activity (ALP, SGOT, SGPT, GGT and sorbitol dehydrogenase activity) were observed at 45 ppm (1.96 mg/kg/day, within the range for Category 1); and inhibition of erythrocyte ChE activity (75-88%), inhibition of brain ChE activity (26.8%) (females), and decreased food consumption (males) were observed at 140 ppm (7 mg/kg/day, within the range for Category 1) (JMPR (1992)). (4) It was reported that, in a 12-month chronic toxicity study with dogs dosed by feeding, discoloration of the liver, bile stasis/chronic inflammation, elevated ALP, SGOT, SGPT, sorbitol dehydrogenase, and bilirubin levels, increased GGT (females) and decreased total protein and albumin values (females) were observed at 40 ppm (2 mg/kg/day, within the range for Category 1); and inhibition of erythrocyte ChE activity (76-87%), inhibition of brain ChE activity (16-27%), and decreased food consumption (males) were observed at 140 ppm (5.67 mg/kg/day, within the range for Category 1) (JMPR (1992), Patty (2012)). (5) It was reported that, in an 18-month chronic toxicity study with mice dosed by feeding, increased liver enzyme activity, discoloration of the urine (males), effects on the gall bladder (cholecystitis, hyperplasia) and effects on the liver (bile duct hyperplasia, bile stasis, cholangiofibrosis, chronic hepatitis, hypertrophy), and inhibition of erythrocyte ChE activity (females) were observed at 50 ppm (6.99. mg/kg/day, within the range for Category 1); and inhibition of brain ChE activity, slightly decreased survival rate (males), inhibition of erythrocyte ChE activity (males), increased extramedullary hematopoiesis associated with increased spleen weights (males), a significantly increased incidence of hepatocellular tumors (males), an increase in liver enzyme activity (females), and effects on the gall bladder and liver (females) were observed at 100 ppm (13.7 mg/kg/day, within the range for Category 1) (JMPR (1992), Patty (2012)). (6) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with dogs, a slight increase in serum GPT (ALT) (males) was observed at 4 ppm (0.171 mg/kg/day, within the range for Category 1); a marked increase in serum GPT, an increase in serum ALP, an increase in sulfobromophthalein retention and pigmentation in the liver, macrophages, and centrilobular hepatic cells were observed at 16 ppm (0.686 mg/kg/day, within the range for Category 1); and pigmentation in the kidneys was observed at 64 ppm (2.74 mg/kg/day, within the range for Category 1) (JMPR (1992)). (7) It was reported that, in a 2-year combined chronic toxicity/carcinogenicity study with rats, fasciculation, reduced body weight gain, decreased urinary volume, increased urinary specific gravity, inhibition of RBC (14-38%), serum (22-66%), and brain (42-74%) ChE activity, chromorhinorrhea, hyperactivity, tremors, skin lesions (ulceration, chronic purulent inflammation), alopecia, and hypersensitivity to the touch were observed at 40 ppm (1.72 mg/kg/day, within the range for Category 1), and decreased body weight, inverted neutrophil:lymphocyte ratios, reduced RBC parameters, increased platelet counts, and an increased incidence in focal accumulations of foamy macrophages in the alveoli were observed at 100 ppm (4.91 mg/kg/day, within the range for Category 1) (JMPR (1992), Patty (2012)).
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 = 0.0011 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, 2010) (a.i.: active ingredient).
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 due to being not rapidly degradable (BIOWIN) and 28-day NOAEC = 0.000022 mg a.i./L for crustacea (Mysidopsis bahia) (EPA Pesticides RED, 2006). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (algae, fish), then it is classified in Category 1 due to being not rapidly degradable and 96-hour LC50 = 0.0022 mg a.i./L for fish (Lepomis macrochirus) (EPA Pesticides RED, 2006). By drawing a comparison between the above results, it was classified in Category 1. (a.i.: active ingredient)
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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