Absorption, Distribution and Excretion
Qualitatively, the metabolism of dimethyl sulfide in mammals is largely the same as in insects. However, some quantitative differences exist. Generally, dimethyl sulfide degrades more rapidly in mammals and is excreted in urine. For example, after oral administration of dimethyl sulfide to cattle, 87-90% of the dose was detected in urine within 24 hours, primarily in the form of hydrolysis products. In rats, 60% of the dose was excreted in urine and exhaled gases within 24 hours after ingestion. Dimethyl sulfide rapidly penetrates the separated segments of the small intestine, colon, and rectum in mice, with the highest penetration rates in the colon and rectum. Age of the mice did not significantly affect the degree of penetration. (Initial dose not specified) After aerial spraying with 38% dimethyl sulfide, the concentration of dimethyl sulfide in animal tissues was higher than in soil, water, or plants. The tissue with the highest concentration was brain tissue, followed initially by lung tissue. ...
For more complete data on the absorption, distribution, and excretion of dimethyl sulfides (23 in total), please visit the HSDB record page.

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Metabolism/Metabolites
...Detoxification pathways...involving tissue or plasma carboxylesterases (sometimes called esterases) hydrolyzing the carboxyl ester or carboxamide bonds in certain pesticides. Malathion and dimethyl sulfide are examples.
Hepatic microsomes in rabbits and mice can convert dimethyl sulfide into oxygen analogs and de-N-methyl derivatives.
After administration of dimethyl sulfide to rats, the following compounds were detected in the urine: 1. dimethyl sulfide, 2. dimethoxyphosphine, 3. dimethyl sulfide carboxylic acid, 4. dimethyl dithiophosphate, 5. dimethyl thiophosphate, 6. dimethyl phosphate, 7. monomethyl phosphate, 8. thiophosphate, 9. formic acid, and 10. N-methyl-2-glucuronide acetamide. In rabbits and mice, the oxidative desulfurization of dimethyl sulfide rapidly generates oxygen analogs. Both dimethyl sulfide and its O-analytes undergo subsequent oxidative N-dealkylation to generate N-hydroxymethyl intermediates. For more complete metabolite/metabolite data on dimethyl sulfide (28 metabolites in total), please visit the HSDB record page. Known human metabolites of dimethyl sulfide include O-methyl sulfide. The metabolism of organophosphates primarily occurs through oxidation, esterase hydrolysis, and reactions with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphate pesticides can produce moderately toxic products. Generally, thiophosphates themselves are not directly toxic and require oxidative metabolism to be converted into proximal toxins. Products from glutathione transferase reactions are generally less toxic. Paraoxygenase (PON1) is a key enzyme in organophosphate metabolism. PON1 can inactivate some organophosphates through hydrolysis. PON1 can hydrolyze active metabolites in various organophosphate pesticides and nerve agents (such as soman, sarin, and VX). The existence of PON1 polymorphism leads to differences in the enzyme activity level and catalytic efficiency of this esterase, suggesting that different individuals may be more susceptible to the poisoning of organophosphate toxins.

Toxicity Summary
Dimethyl sulfide is a cholinesterase, or acetylcholinesterase (AChE) inhibitor. Cholinesterase inhibitors (or "anticholinesterases") inhibit the activity of acetylcholinesterase. Because acetylcholinesterase plays a vital physiological role, chemicals that interfere with its activity are potent neurotoxins; even low doses can cause excessive salivation and lacrimation, followed by muscle spasms and ultimately death. Substances used in nerve gases and many pesticides have been shown to exert their effects by binding to serine residues at the active site of acetylcholinesterase, thus completely inhibiting the enzyme's activity. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, which is released at the neuromuscular junction, causing muscle or organ relaxation. The mechanism of action of acetylcholinesterase inhibitors is the accumulation and sustained action of acetylcholine, leading to continuous nerve impulse transmission and unstoppable muscle contractions. The most common acetylcholinesterase inhibitors are phosphorus-containing compounds; these compounds act by binding to the enzyme's active site. The structural requirements are: one phosphorus atom connected to two lipophilic groups, one leaving group (e.g., a halide or thiocyanate), and one terminal oxygen atom.

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Toxicity Data
LC50 = 1,680 mg/m3
LD50: 60 to 387 mg/kg (oral, rat)
LD50: 60 mg/kg (oral, mouse)
LD50: 400 mg/kg (oral, dog)
LD50: 200 mg/kg (oral, hamster)
LD50: 300 mg/kg (oral, rabbit)
LD50: 350 mg/kg (oral, guinea pig)
LD50: 100 mg/kg (oral, cat)
LD50: 1000 mg/kg (skin, rabbit)
LD50: 353 mg/kg (skin, rat)
LC50: 1.2 mg/L (rat)

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Interactions
This study investigated the effects of various insecticides on the liver enzyme-catalyzed dimethylnitrosamine (DMN) in mice.
Effects of N-Demethylation. Organochlorine pesticides can increase the activity of dimethylnitrosamine demethylases I and II. Dimethyl sulfide (an organophosphorus compound) was the only pesticide tested that inhibited N-demethylation of dimethylnitrosamine, especially its effect on dimethylnitrosamine demethylase I. Organophosphorus pesticides are often present in the environment along with other pesticides and industrial pollutants, potentially leading to co-exposure to multiple substances with unknown interactions. In this study, female Wistar rats were administered 1/25 LD50 of dimethoate by gavage, concurrently with the same LD50 doses of propoxyurea and cypermethrin, or concurrently with arsenic (6.66 mg/kg). Administration occurred on days 5 to 15 of gestation, or days 5 to 15 of lactation, or days 5 to 15 of weaning and week 4 of lactation for male offspring, or week 8 of weaning for male offspring. Control rats were administered distilled water by gavage. Electrophysiological recordings were performed on male offspring at 12 weeks of age. Spontaneous activity and evoked potentials of the somatosensory, visual, and auditory cortices, as well as conduction velocity, absolute refractory period, and relative refractory period of the tail nerve, were measured. The overall trend was an increase in the frequency of spontaneous cortical activity and a prolonged latency of evoked potentials. The results suggest that combined exposure to multiple environmental toxins may be more harmful than exposure to a single substance…
Carbon disulfide pretreatment enhanced the anticholinesterase activity of phosphonium thiophosphate and EPN, but inhibited the anticholinesterase activity of dimethoate and diazinon. Carbon disulfide had no significant effect or only a slight inhibitory effect on other compounds. Some of these effects were compared with the recurring changes in toxicity following phenobarbital pretreatment.

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Non-human toxicity values
LD50 Female rats, oral administration: 240-336 mg/kg, active pharmaceutical ingredient / from table /
LD50 Mouse, subcutaneous injection: 60 mg/kg, active pharmaceutical ingredient / from table /
LD50 Male hamsters, subcutaneous injection: 60 mg/kg, active pharmaceutical ingredient / from table /
LD50 Rabbits, oral administration: 300 mg/kg, active pharmaceutical ingredient / from table /
For more complete non-human toxicity data for dimethyl sulfide (of 20), please visit the HSDB record page.

[1]. Toxic hazard from formulating the insecticide dimethoate in methyl 'Cellosolve'. Nature. 1961;189:507-508.

Dimethyl sulfide is a white crystalline solid with a camphor-like odor; the technical grade is a white to grayish-white crystal. It is a contact and systemic organophosphate insecticide effective against a variety of insects and mites, and suitable for a wide range of crops. Production of this substance has been discontinued in the United States since 1982 (EPA, 1998). Dimethyl sulfide is a monocarboxylic acid amide with the structure N-methylacetamide, where a hydrogen atom on the methyl group attached to the carbonyl group is replaced by a (dimethoxythiophosphate)thiodiacyl group. It is an EC 3.1.1.7 (acetylcholinesterase) inhibitor, agricultural chemical, acaricide, EC 3.1.1.8 (cholinesterase) inhibitor, insecticide, exogenous substance, and environmental pollutant. It is an organothiophosphate and monocarboxylic acid amide. Its function is similar to N-methyl-2-thioacetamide. Dimethyl sulfide is a synthetic organothiophosphate compound and an organophosphate acetylcholinesterase inhibitor used as an insecticide. It is a volatile white to gray crystalline solid with a camphor-like odor and can cause illness through inhalation, ingestion, or contact. Dimethyl sulfide is an organophosphate insecticide used for systemic control of mites and insects, and can also be used for contact control. It can be used to control a variety of insects, including aphids, thrips, planthoppers, and whiteflies on ornamental plants, alfalfa, apples, corn, cotton, grapefruit, grapes, lemons, melons, oranges, pears, pecans, safflower, sorghum, soybeans, oranges, tobacco, tomatoes, watermelons, wheat, and other vegetables. It can also be used as a residual spray on farmhouse walls to control houseflies. Dimethyl sulfide was once used on livestock to control horseflies. Dimethyl sulfide is moderately toxic; severe poisoning can affect the central nervous system. (L1188) An organothiophosphoric cholinesterase inhibitor used as a systemic and contact insecticide. Mechanism of Action: Organophosphate derivatives exert their effects by binding to and inactivating acetylcholinesterase (AChE). ...Cholinesterase inhibitors inactivate cholinesterase, leading to the accumulation of large amounts of acetylcholine, resulting in a wide range of effects, which can be divided into four categories: (1) Enhanced postganglionic parasympathetic activity. ... (2) Continuous depolarization of skeletal muscle ... (3) Initial stimulation after central nervous system cell inhibition ... (4) Varying degrees of ganglion excitation or blockage ... /Cholinesterase inhibitors / They mainly work by inhibiting acetylcholinesterase (AChE) at cholinergic synapses. /Organophosphates / Symptoms of organophosphate poisoning are caused by the accumulation of acetylcholine, leading to excessive excitation of the parasympathetic nervous system. They are usually divided into three categories: muscarinic, nicotinic, and central nervous system-related. Muscarinic symptoms ... include salivation, lacrimation, sweating, and nasal discharge. Miosis, dyspnea, vomiting, diarrhea, and urinary frequency ... Nicotinic effects include fasciculations, weakness, and paralysis. Central nervous system effects include tension, anxiety, ataxia, convulsions, and coma. The cause of death is respiratory failure, and sometimes cardiac arrest. Symptoms vary little among different organophosphate compounds, but the absorption pathways can affect different systems differently. /Organophosphate Compounds/
These toxins almost irreversibly phosphorylate varying amounts of acetylcholinesterase in tissues, leading to the accumulation of acetylcholine at cholinergic effector junctions (muscarinic effects), skeletal muscle neuromuscular junctions, and autonomic ganglia (nicotine-like effects). /Organophosphate Pesticides/
For more complete data on the mechanisms of action of dimethyl sulfide (6 types), please visit the HSDB record page.

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Therapeutic Use
Drug (Veterinary): It has also been experimentally applied in various animals via multiple routes (spraying, oral administration, subcutaneous injection, intramuscular injection, pouring, etc.), and has shown particular effectiveness in cattle and reindeer larvae (safety limits of 10 and 30 mg/kg, respectively) and in sheep during estrus (subcutaneous injection 25 mg/kg - avoid use in hot or fatigued animals). Older formulations may be more toxic to animals.

C5H12NO3PS2

229.24

228.999

60-51-5

Dimethoate-d6;1219794-81-6

3082

White crystalline solid
Colorless crystals (Tech., white solid pellets)

1.4±0.1 g/cm3

310.3±52.0 °C at 760 mmHg

52-52.5°C

141.4±30.7 °C

0.0±1.5 mmHg at 25°C

1.548

1.32

1

5

5

12

191

0

CNC(CSP(OC)(OC)=S)=O

MCWXGJITAZMZEV-UHFFFAOYSA-N

InChI=1S/C5H12NO3PS2/c1-6-5(7)4-12-10(11,8-2)9-3/h4H2,1-3H3,(H,6,7)

2-dimethoxyphosphinothioylsulfanyl-N-methylacetamide

L-395; Lurgo; Dimethoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~10.42 mg/mL (~45.45 mM)

Solubility in Formulation 1: 10 mg/mL (43.62 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)