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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	60-51-5
Chemical Name	O,O-Dimethyl S-(N-methylcarbamoyl)methyl phosphorodithioate (synonym: Dimethoate)
Substance ID	R03-B-027-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	FY2018 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 combustible (GESTIS (Accessed Aug. 2021)).
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 was classified as "Not classified" because it is classified in Division 6.1 in UNRTDG (UN 2783), and it does not correspond to pyrophoric substances, hazards of the highest precedence.
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 water solubility data of 25 g/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.
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 (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 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) to (6), it was classified in Category 3 by adopting the category with the higher hazard. [Evidence Data] (1) LD50 for rats: 245 mg/kg (EFSA (2006)) (2) LD50 for rats: about 310 mg/kg (JMPR (1996)) (3) LD50 for rats (females): 550 mg/kg (EPA OPP Human Health Risk Assessment (2015)) (4) LD50 for rats (males): 358 mg/kg (EPA Pesticides (2008)) (5) LD50 for rats (females): 414 mg/kg (EPA Pesticides (2008)) (6) LD50 for rats: between 314 to 600 mg/kg (JMPR (2003))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." Since the data adopted for the previous classification could not be obtained, the classification result was changed based on the new information source. [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (EFSA (2006)) (2) LD50 for rabbits: > 5,000 mg/kg (EPA OPP Human Health Risk Assessment (2015)) (3) LD50 for rabbits: > 2,000 mg/kg (EPA Pesticides (2008))
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), it was classified in Category 4. It was classified based on the new information source. [Evidence Data] (1) LC50 (4 hours) for rats: 1.68 mg/L (EFSA (2006, 2018))
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) It was reported that skin irritation was minimal and confined to slight, transient erythema (JMPR (1996)). (2) This substance is not irritating to the skin (EFSA (2006)).
3	Serious eye damage/eye irritation	Category 2A	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2A in accordance with the GHS Classification Guidance for the Japanese Government. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) The undiluted solution of this substance was irritating to the eye in rabbits (JMPR (1996)). (2) This substance was a moderate eye irritant (EPA OPP HHRA (2015)). (3) This substance was a mild eye irritant (EFSA (2006)). (4) This substance was irritating to the eye (EFSA (2018)). [Reference Data, etc.] (5) It was reported that, in an eye irritation test (10 mg) with rabbits, no eye irritation effects were observed (EHC 90 (1989), HSDB (Accessed August 2021)).
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), it was classified as "Not classified." [Evidence Data] (1) It was reported that, in a skin sensitization test with guinea pigs, negative results were obtained (EFSA (2018), EPA OPP HHRA (2015)). [Reference Data, etc.] (2) This substance was cited in four human cases of contact dermatitis, and sensitization reaction was observed in these individuals by patch testing (JMPR (1996)). (3) Undiluted solution of this substance was negative in a test with guinea pigs, but a formulation (32.7% emulsion) of this substance induced sensitization reaction in one of 10 guinea pigs (JMPR (1996)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (3), the classification was not possible. The in vivo tests in (1) showed that the results were all negative, and in vitro tests in (2), many positive results were reported. In (3), since the reliability of the in vivo test data was uncertain, it was judged that there was not sufficient in vivo data available for evaluation and it was classified as "Classification not possible." [Evidence Data] (1) As for in vivo, negative results were obtained in all of a chromosomal aberration test with the bone marrow cells of rats (intraperitoneal injection), a micronucleus assay using the bone marrow cells of mice (intraperitoneal injection), and a dominant lethal assay using mice (dosed by gavage, 5 days) (EPA OPP Human Health Risk Assessment (HHRA) (2015), Patty (6th, 2012)). (2) As for in vitro, negative or positive results in a bacterial reverse mutation test, equivocal or positive results in a gene mutation test using cultured mammalian cells (CHO, hprt gene loci), and positive results in a chromosomal aberration test using cultured mammalian cells were obtained (EPA OPP HHRA (2015), EFSA (2018), Patty (6th, 2012)). (3) With regard to the genotoxicity of this substance, the EFSA considered in the previous evaluation that it was positive in vitro but negative in vivo and the overall weight of evidence indicated no genotoxic potential (EFSA (2006)), but in the latest evaluation, it seemed that the EFSA questioned the negative results in vivo because some of the in vivo studies were not performed according to the current standards and appropriate follow-up testing in vivo was not conducted. The expert panel agreed that a genotoxic potential could not be excluded for this substance (EFSA (2018)).
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 2. It was classified based on the new information source. [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 2002). (2) In a 2-year combined chronic toxicity/carcinogenicity study with rats dosed by feeding (1 to 100 ppm: 0.05 to 5 mg/kg/day), male rats showed dose-related trends of increased incidences of spleen hemangiosarcoma, combined spleen hemangioma and hemangiosarcoma and combined spleen hemangioma, hemangiosarcoma, and skin hemangiosarcoma (EPA OPP Human Health Risk Assessment (HHRA) (2015), Patty (6th, 2012)). (3) In a 78-week carcinogenicity study with mice dosed by feeding (25 to 200 ppm: 3.75 to 30 mg/kg/day), hemolymphoreticular system tumors (combined leukemia, lymphoma and reticular sarcoma) in males and liver tumors in females were observed at 200 ppm (EPA OPP HHRA (2015), Patty (6th, 2012)). A pair-wise comparison result showed that there was a significant increase in hemolymphoreticular system tumors in males but there was no significant increase in liver tumors in females (Patty (6th, 2012)). (4) It has been described that the rationale for the classification in Group C by the EPA was based on equivocal evidence in male mice (hemolymphoreticular tumors), weak evidence in male rats (combined spleen (hemangioma, hemangiosarcoma), skin (hemangiosarcoma) and lymphoid organ (angioma and angiosarcoma) tumors), and positive mutagenic activity (EPA OPP HHRA (2015)). [Reference Data, etc.] (5) The EFSA evaluation showed that a potential carcinogenicity effect could not be excluded in rats, based on a small increased incidence over controls in brain granular cell tumors; however no carcinogenic effects were observed in mice (EFSA (2018)). Details of the evaluation and the reason for the difference from the EPA evaluation are unknown at present.
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1B. Also, in (1) to (3), at doses at which general toxicity effects were observed in parental animals, many serious reproductive toxicity effects such as reproductive effects (reduced numbers of pregnant females, testicular damages, decreased number of implantations) and lower survival rate in pups were reported. Based on these new findings, the classification was changed. [Evidence Data] (1) It was reported that, in a two-generation reproduction toxicity study with rats dosed by feeding, at 65 ppm, decreased plasma, erythrocyte, and brain cholinesterase (ChE) activity and reproductive effects (reduced numbers of pregnant females) in P and F1 male and female parental animals, and lower survival rate and body weights in pups were observed (EPA OPP Human Health Risk Assessment (HHRA) (2015), Patty (6th, 2012), JMPR (1996), EFSA (2006)). (2) It was reported that, in an oral toxicity test with male mice (20 days, mating with untreated females after dosed at 7 to 28 mg/kg/day), as general toxicity effects, cholinergic signs and decreased cholinesterase activity were observed at or above 15 mg/kg/day, as reproductive toxicity effects, reduced sperm count and decreased percentage of motile sperm at 15 mg/kg/day, and decreased number of implantations and live fetuses and increased number of dead and early resorptions in untreated females at 28 mg/kg/day were observed (Patty (6th, 2012)). (3) In a test with male rats dosed by feeding (90 days, 2 to 20 mg/kg/day), dose-related testicular damages (seminiferous tubule degeneration, partial arrest of spermatogenesis) were observed. In addition, in an oral toxicity test with male rats (65 days, 6.5 and 12.5 mg/kg/day), decreases in the weight of genital organs and sperm motility, an increase in the percentages of dead and morphologically abnormal spermatozoa, a decrease in plasma testosterone, degenerative changes of spermatogonial cells (moderate to severe), and partial arrest of spermatogenesis were observed (Patty (6th, 2012)). (4) Adverse effects on fertility indices (lower pregnancy rate, effects on male reproductive organs) and developmental effects in offspring (increased mortality rate) were observed in rats and mice, but these effects were observed at the level at which toxicity effects (inhibition of erythrocyte and brain ChE activity) appeared in parental animals (EFSA (2018)). (5) It was reported that, in a developmental toxicity study (days 6 to 15 of gestation (rats), days 6 to 20 of gestation (rabbits)) with rats and rabbits dosed by gavage, no developmental toxicity was observed (EPA OPP Human Health Risk Assessment (HHRA) (2015), Patty (6th, 2012), JMPR (1996), EFSA (2006)).
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) to (7), it was classified in Category 1 (nervous system). Also, the sources of (1) to (5), which indicated human data, were List 2, but since even in (6) and (7), which indicated animal experiment data, effects on the nervous system were observed within the range for Category 1, it was classified in Category 1. [Evidence Data] (1) It was reported that the signs of acute poisoning by this substance were headache, dizziness, weakness, anxiety, miosis, and blurred vision in mild cases, nausea, salivation, lacrimation, abdominal cramps, vomiting, sweating, bradycardia, and muscle tremor in moderate cases, and diarrhea, pinpoint and refractory pupils, dyspnea, pulmonary edema, cyanosis, loss of control over the sphincter, convulsions, coma, and death in severe cases (HSDB in PubChem (Accessed Aug. 2021)). (2) It was reported that, in a case of an 28-year-old man who was supposedly exposed to this substance by spraying it to olive trees during farm work, a severe feeling of lassitude and somnolence were observed, and on the following day, vomiting, chill, and severe prostration were observed, and then the boy was hospitalized, and furthermore, a decrease in pulse rate, marked miosis, massive vomiting, sweating, and marked inhibition of cholinesterase activity were observed (HSDB in PubChem (Accessed Aug. 2021)). (3) It was reported that, in a case of a female who was supposedly exposed to this substance by spraying it during farm work, she perceived unpleasant odor within 3 to 3.5 hours after spraying, followed by headache, dry coughing, dyspnea, nausea, and vomiting, and was hospitalized in a somnolent state with muscle fibrillation and asthma (HSDB in PubChem (Accessed Aug. 2021)). (4) It was reported that, in a case of a 52-year-old male who ingested approximately 20 g of this substance with a suicidal intent, he became comatose 2 hours later, and muscular fasciculation, extreme miosis, hypersalivation, and respiratory insufficiency were observed (PATTY (2012)). (5) It was reported that, in a case of 68-year-old male who ingested 3 ounces of a concentrated solution of this substance, he lost consciousness and developed cholinergic crisis (PATTY (2012)). (6) It was reported that, in an acute neurotoxicity test with rats dosed by gavage, absence of pupil response was observed at 20 mg/kg (within the range for Category 1) (JMPR (2003)). (7) It was reported that, in an acute neurotoxicity test with rats dosed by feeding, the inhibition rate of cholinesterase activity was 29% (males) in erythrocytes and 11% (females) in the brain cortex at 3 mg/kg (within the range for Category 1), both of which were statistically significant (JMPR (2003)).
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 (7), effects on the nervous system were adopted and it was classified in Category 1 (nervous system). Besides, the sources of (1) and (2), which indicated human data, were List 2, but since even in (3) to (7), which indicated animal experiment data, effects on the nervous system were observed within the range for Category1, it was classified in Category 1. Also, effects on the liver were observed in (7), but they could be uncertain findings and were not adopted for classification. [Evidence Data] (1) It was reported that, in a case in which this substance was orally administered to humans 5 days per week, inhibition of whole blood cholinesterase activity and erythrocyte cholinesterase activity was observed in a group dosed at or above 0.434 mg/kg/day (57 days). Besides, it was also reported that no localized gastrointestinal effects or any other signs of toxicity were noted (HSDB in PubChem (Accessed Aug. 2021)). (2) It was reported that, in a test in which 8 volunteers ingested this substance, in a group at or above 30 mg/day, reduced cholinesterase activity began to appear by day 20 and inhibition of cholinesterase activity persisted until the end day of the test (day 57). Besides, it was reported that no clinical symptoms were observed in any volunteer (HSDB in PubChem (Accessed Aug. 2021)). (3) It was reported that, in a 90-day oral toxicity study with rats dosed by feeding, inhibition of plasma, erythrocyte, and brain cholinesterase activity was observed at 50 ppm (2.5 mg/kg/day, within the range for Category 1), and decreased food consumption and increased kidney and liver weight ratios were observed at 400 ppm (20 mg/kg/day, within the range for Category 2) (EPA OPP Human Health Risk Assessment (2015), PATTY (2012)). (4) It was reported that, in a 2-year oral toxicity study with rats dosed by feeding, decreased brain and plasma cholinesterase activity was observed at 5 ppm (0.25 mg/kg/day, within the range for Category 1) and an increased leukocytes, and anemia (males) were observed at 100 ppm (5 mg/kg/day, within the range for Category 1) (EPA OPP Human Health Risk Assessment (2015), PATTY (2012)). (5) It was reported that, in a 90-day oral toxicity study with dogs dosed by feeding, inhibition of erythrocyte cholinesterase activities was observed at 10 ppm (0.25 mg/kg/day, within the range for Category 1), and tremor and decreased food consumption (females) were observed at 1,500 ppm (37.5 mg/kg/day, within the range for Category 2) (EPA OPP Human Health Risk Assessment (2015), PATTY (2012)). (6) It was reported that, in a one-year oral toxicity study with dogs dosed by feeding, decreased brain cholinesterase activity, findings of the liver (brown granular pigmentation and decreased liver weight (females)) were observed at 5 ppm (0.18 mg/kg/day, within the range for Category 1), decreased erythrocyte cholinesterase activity was observed at 20 ppm (0.7 mg/kg/day, within the range for Category 1), and decreased plasma ChE activity and decreased heart weight were observed at 125 ppm (4.18 mg/kg/day, within the range for Category 1) (EPA OPP Human Health Risk Assessment (2015), PATTY (2012)). (7) It was reported that, in a 52 to 78-week oral toxicity study with mice dosed by feeding, decreased plasma and erythrocyte cholinesterase activity (brain ChE was not measured), cholinesterase inhibition, and hepatocyte vacuolation (females) were observed at 25 ppm (3.75 mg/kg/day, within the range for Category 1) (EPA OPP Human Health Risk Assessment (2015), 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 2	- -	H401	P273 P501	It was classified in Category 2 from 48-hour EC50 = 2 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, 2013). The classification result was changed from the previous classification by using new information (a.i.: active ingredient).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 due to being not rapidly degradable (not readily degradable, a degradation rate by BOD: 0% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1983)) and 21-day NOAEC= 0.04 mg/L for crustacea (Daphnia magna) (EPA Pesticides RED, 2007, OPP Pesticide Ecotoxicity Database). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" due to being not rapidly degradable and 72-hour ErC50 = 280 mg/L for algae (Raphidocelis subcapitata) (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, 2013). 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.

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