Sulfotep

Sulfotep (also known as tetraethyldithiopyrophosphate and TEDP[7]) is a pesticide commonly used in greenhouses as a fumigant. The substance is also known as Dithione, Dithiophos, and many other names. Sulfotep has the molecular formula C8H20O5P2S2 and belongs to the organophosphate class of chemicals. It has a cholinergic effect, involving depression of the cholinesterase activity of the peripheral and central nervous system of insects.[5] The transduction of signals is disturbed at the synapses that make use of acetylcholine. Sulfotep is a mobile oil that is pale yellow-colored and smells like garlic.[7][8] It is primarily used as an insecticide.

Sulfotep
Names
IUPAC name
Diethoxyphosphinothioyloxy-diethoxy-sulfanylidene-λ5-phosphane
Other names
Sulfotep, Dithiophos, Dithion, Bladafum, Dithiofos, Dithione, Dithiotep, Pirofos, TEDP[1][2]
Identifiers
3D model (JSmol)
ECHA InfoCard 100.020.905
EC Number
  • 222-995-2
RTECS number
  • XN4375000
UNII
UN number 1704
Properties
C8H20O5P2S2
Molar mass 322.31 g·mol−1
Appearance Pale yellow liquid[3]
Odor Garlic-like[3]
Density 1.196 g/cm3
Boiling point 136 to 139 °C (277 to 282 °F; 409 to 412 K) at 2 mm Hg
30 mg/L
Vapor pressure 0.0002 mmHg (20°C)[3]
Hazards[4][5]
NFPA 704 (fire diamond)
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilHealth code 4: Very short exposure could cause death or major residual injury. E.g. VX gasReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
4
0
Flash point −18 °C (0 °F; 255 K)
Lethal dose or concentration (LD, LC):
22 mg/kg (mouse, oral)
25 mg/kg (rabbit, oral)
5 mg/kg (dog, oral)
5 mg/kg (rat, oral)[6]
38 mg/m3 (rat, 4 hr)
40 mg/m3 (mouse, 4 hr)[6]
NIOSH (US health exposure limits):
PEL (Permissible)
 TWA 0.2 mg/m3 [skin][3]
IDLH (Immediate danger)
 10 mg/m3[3]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

History

Sulfotep was first commercially launched by Bayer in 1946. The first time that tetraethyl dithiopyrophosphate was registered to be used in the United States was in 1951. A Registration Standard for the chemical was issued by the Environmental Protection Agency in September 1988. Plans were made in 1999 by the Environmental Protection Agency to stop production of it by September 30, 2002 and to outlaw the use and distribution of products containing it by September 30, 2004.[9]

Chemistry

Synthesis

Sulfotep is synthesized by a reaction of tetraethyl pyrophosphate (TEPP) with sulfur. TEPP itself was first synthesized by Philipe de Clermont in 1854.[10] TEPP is made by a reaction of diethyl chlorophosphate with water to substitute the chloro group with a hydroxyl group. The product can react with another molecule of diethylchlorophosphate to form the ester, TEPP. In this reaction, pyridine is often used to neutralize the hydrochloric acid byproduct.[11]

Synthesis of sulfotep

An alternative route to TEPP can be a reaction of diethyl chlorothiophosphate an aqueous solution of sodium bicarbonate (Na2CO3).

Properties

When heated to a temperature that is high enough for sulfotep to decompose, it gives off fumes of phosphorus and sulfur oxides, which are highly toxic.[7][8] It can explode if containers of it are heated, and it can burn, although it does not do so easily. The chemical can also polymerize explosively.[12] The chemical also reacts to form toxic and flammable gases in the presence of hydrides and other reducing agents. It is able to corrode iron.[8] When it does this, it can release hydrogen gas.[12] The chemical has a specific gravity of 1.196 at 77 °F (25 °C) and its vapor density is 13.17 grams per liter at 25 °C (77 °F).[8][13] Its melting point is 88 °C (190 °F) and its boiling point is between 272 °F (133 °C) and 282 °F (139 °C) at 2 mmHg.[7][8] The chemical's sorption coefficient is 2.87 Log L/kg. Its Henry's Law constant is 0.000175 at 20 °C (68 °F). Its octanol-water partition coefficient is 3.9804 Log L/kg. Tetraethyl dithiopyrophosphate's diffusion coefficient in air is 0.015 cm2 per second and its diffusion coefficient in water is 0.0000055 cm2.[14]

Sulfotep's flash point is 178 °C (352 °F) and its enthalpy of vaporization is 59.4 kilojoules per mole. Its surface tension is 423 dynes per centimeter. The chemical has no Rule of 5 violations.[15] Its diffusivity in water is 0.63 × 10−5 cm2 per second. It is miscible with a large number of organic solvents, including methyl chloride and acetone[16] and its solubility in water is 30 milligrams per liter at 20 °C (68 °F).[13]

The alkaline and neutral hydrolysis of sulfotep results in the release of ethanol, phosphoric acid, and hydrogen sulfide.[17]

Applications

Sulfotep has applications as an insecticide, miticide, and acaricide.[8] However, because it does not leave behind a residue, it is less effective at these roles than DDT.[18] However, it is about as effective as the insecticide parathion.[19] Its use is restricted to greenhouses and ornamental plants. When the chemical is used as an insecticide, it is in the form of an impregnated smoke fumigant.[9] Sulfotep is used in greenhouses as a fumigant formulation to control aphids, spider mites, whiteflies and thrips. It is formulated as impregnated material in smoke generators containing 14 to 15% active ingredient. Smoke generators are placed in the greenhouses and then ignited using inserted sparklers to generate a thick white smoke for fumigation.

Sulfotep kills spider mites, mealybugs, whiteflies, and aphids. However, the chemical is not phytotoxic, unlike tetraethyl pyrophosphate.[20] However, it occasionally causes minor damage to plants, such as the slight puckering and cupping of leaves.[21] During several tests in the late 1940s, it was found to be the most toxic of several chemicals to whiteflies on vegetables, two-spotted spider mites on roses, and mealybugs on numerous plants.[20]

A mixture containing 5% sulfotep at the concentration of 0.5 grams of phosphate per 1000 cubic feet was found in tests in the late 1940s to kill 100% of nonresistant two-spotted spider mites and 68-97% of resistant two-spotted spider mites. Sulfotep aerosols killed 100% of the populations of a large number of insects, but only killed 98% of mealybugs in the same tests.[18] 88% of nonresistant spider mites can be killed be two minutes of exposure to a mixture containing 5% of the chemical, 98-99% can be killed after five to ten minutes, and all can be killed after 15 minutes.[21]

Mechanism of action

Sulfotep, just as all organophosphate pesticides, irreversibly inactivates acetylcholinesterase, which is essential to nerve function in insects, humans, and many other animals. Acetylcholinesterase normally hydrolyses acetylcholine after it was released in the synaps. When the acetylcholine is not degraded, it accumulates in the synaptic cleft. Thus, it keeps on stimulating the nerve.[22]

Metabolism
Metabolism of sulfotep

Uptake

Sulfotep is taken up well both orally, dermally as well as through inhalation. A few different organizations determined a maximum concentration sulfotep in the air. The maximum allowed concentration is 0.2 mg/m3.

Phase I

Sulfotep is desulfurated by either cytochrome P450 or the FAD-containing monooxygenases. In this reaction, the sulfur is replaced by oxygen, as seen in figure 2. The metabolites formed are monosulfotep and tetraethyl pyrophosphate (TEPP). To accomplish these reactions, a phospho-oxithirane ring is formed, which is highly reactive. This ring is thought to bind to acetylcholinesterase and cause toxicity.[23]

Phase II

The two Phase I metabolites are further transformed through a hydrolysis-reaction mediated by a type A-esterase. The products formed are O,O-diethyldithiophosphate and O,O-diethylphosphate.[23]

Excretion

An experiment in rats who were once given 0.4 mg radioactive phosphor-labelled sulfotep orally, has shown that sulfotep is excreted by both the kidneys (urine) and the liver (bile). The substance is completely metabolised. Two metabolites are found in the urine and faeces. The radioactivity showed that 85-91% was excreted in urine and 5-6% in the faeces.[22]

  • 88-96% metabolite 1: O,O-diethyldithiophosphate
  • 4-12% metabolite 2: O,O-diethylphosphate [2]

Toxicity

Acute toxic effects on animals

Sulfotep is toxic to some wildlife, including fish and aquatic invertebrates. It is also assumed by the Environmental Protection Agency to be toxic to birds.[9]

Exposure Toxic level
Inhalationmg/m3
Mouse 1 hr155 [2][24]
Mouse 4 hr40 [2][24]
Rat 1 hr160-330 [2][24]
Rat 4 hr38-59 [2][24]
Oral LD50mg/kg
Cat3 [2][24][25]
Dog5 [2][24][25]
Mouse21.5-29.4 [2][24][25]
Rabbit25 [2][24][25]
Rat5-13.8 [2][24][25]
Dermal LD50mg/kg
Rat 4 hr262 [2]
Rat 7 d65 [2]
Intravenous LD50μg/kg
Mouse300 [2][25]
Intramuscular LD50μg/kg
Mouse500 [2][25]
Rat55[2][25]
Intraperitoneal LD50μg/kg
Mouse940[2][25]
Rat6600[2][25]
Subcutaneous LD50mg/kg
Mouse8[2][25]

Surviving animals completely recovered in 1–4 days.

Chronic and sub-chronic toxicity

A long-term exposure to a low concentration showed no toxicity. This was tested in rats. They were exposed to different concentrations of sulfotep. Exposed to the highest concentration of 2.83 mg/m3 for six hours a day, five days a week for 12 weeks, there was no change in appearance, behavior or body weight. The plasma cholinesterase activity decreased and the weight of the lungs of female rats increased. The red blood cell acetylcholinesterase activity was not affected. At lower concentrations, there were no changes at all.

The rats were orally exposed to 0, 5, 10, 20 or 50 ppm sulfotep for three months. Only their plasma cholinesterase activity and RBC acetylcholinesterase activity were decreased. No further symptoms were observed. Dogs who were orally exposed to 0, 0.5, 3, 5, 15 or 75 ppm (equivalent to 0–3.07 mg/kg/day) for 13 weeks, ate less and lost weight. The plasma cholinesterase activity was already affected by a sulfotep concentration of 3 ppm (or higher). Red blood cell-acetylcholinesterase was decreased at 75 ppm. Diarrhea and vomiting occasionally occurred at 15 ppm, but were common at 75 ppm. The brain cholinesterase activity was unaffected.[24]

Poisoning symptoms and treatment

According to the Occupational Safety and Health Administration, the upper limit on exposure of sulfotep to human skin is 0.2 milligrams per cubic meter.[12]

Sulfotep causes an organophosphate poisoning. This means that it had an effect on the activity of cholinesterase. There are differences for the indications of a sulfotep poisoning between inhalation, ingestion, intake by the skin and intake by the eyes. However, examples of poisoned greenhouse workers teach us an overall route of symptoms for a sulfotepp poisoning. Within the first hour after a poisonous intake of sulfotep people often suffer from nausea or headaches. After some hours diarrhea and vomiting may occur. People who inhaled sulfotep are often disorientated and have difficulties to breath. A poisonous dose may lead to a coma or death after 24 hours. The point at 24 hours after the poisoning is very important. If the dose is not lethal, the symptoms will slowly disappear after the point of 24 hours.[26][27]

No embryotoxic or teratogenic effects occurred in tests. Neither were there any signs for carcinogenic effects. It was only mutagenic in one strain of S. typhimurium. In four other bacterial strains as well as in rats and mice it was not mutagenic at all.

There are two cases of acute toxicity known in man. The cholinesterase activity in these people was reduced. It took them 20 respectively 28 days to recover.[24] The most important poisoning symptoms are shown in the following table.[28]

Exposure Symptoms First aid treatment Other treatments
Inhalationblue skin, convulsions, dizziness, drowsiness, headache, sweating, labored breathing, nausea, unconsciousness, weaknessFresh air or artificial respiration. Rest is important to prevent a respiration-arrest
Ingestioncramps in intestines, diarrhea, vomiting, confusionVomiting may only be induced in conscious peopleActive charcoal to absorb compound. Atropine as an antidote
Eyesirritation, redness, constriction of the pupil, loss of focusRinsing with plenty of water will lead to recovery of sight within 24 hours
Skin (may be absorbed)redness, irritation, sweating, twitching of the areaFirst rinse with plenty of water. Then wash the skin with water and soap

References
  1. Eula Bingham, Barbara Cohrssen, and Charles H. Powell. Patty's toxicology. 7 (5th ed.). John Wiley and Sons.CS1 maint: multiple names: authors list (link)
  2. CID 19395 from PubChem
  3. NIOSH Pocket Guide to Chemical Hazards. "#0586". National Institute for Occupational Safety and Health (NIOSH).
  4. http://www.chemkoo.com/en/ProductDetail.aspx?ck=CK00174335
  5. Georg Kimmerle and Otto R. Klimmer, ‘’Acute and Subchronic Toxicity of Sulfotep’’, Arch. Toxicol. 33, 1-16 (1974)
  6. "TEDP". Immediately Dangerous to Life and Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH).
  7. Tetraethyl dithiopyrophosphate, retrieved July 30, 2013
  8. TETRAETHYL DITHIOPYROPHOSPHATE, retrieved July 29, 2013
  9. Sulfotepp (PDF), October 1999, retrieved July 31, 2013
  10. Toy, A. D. F. (1948). "The Preparation of Tetraethyl Pyrophosphate and Other Tetraalkyl Pyrophosphates". Journal of the American Chemical Society. 70 (11): 3882–3886. doi:10.1021/ja01191a104. PMID 18102975.
  11. Thomas A. Unger , Pesticide synthesis handbook – page 387
  12. OSHA/EPA Occupational Chemical Database, retrieved February 15, 2017
  13. John H. Montgomery (December 12, 2010), Groundwater Chemicals Desk Reference, Fourth Edition, ISBN 9781420009132
  14. Tetraethyl dithiopyrophosphate, retrieved July 30, 2013
  15. TETRAETHYL DITHIOPYROPHOSPHATE, retrieved July 31, 2013
  16. Keith, Lawrence H.; Walters, Douglas B. (1992), National Toxicology Program's Chemical Solubility Compendium, ISBN 9780873716536
  17. Donald Mackay, Robert S. Boethling (editors) (2000), Handbook of Property Estimation Methods for Chemicals: Environmental Health, ISBN 9781420026283CS1 maint: extra text: authors list (link)
  18. Floyd F. Smith, R.A. Fulton (June 1950), Tetraethyl dithiophosphate in Aerosols for the Control of Greenhouse Insects, Washington, D.C. : U.S. Department of Agriculture, Agricultural Research Administration, Bureau of Entomology and Plant Quarantine
  19. Haz-Map, April 2013, retrieved July 31, 2013
  20. Floyd F. Smith, R.A. Fulton (June 1950), Tetraethyl dithiophosphate in Aerosols for the Control of Greenhouse Insects, Washington, D.C. : U.S. Department of Agriculture, Agricultural Research Administration, Bureau of Entomology and Plant Quarantine
  21. Floyd F. Smith, R.A. Fulton (June 1950), Tetraethyl dithiophosphate in Aerosols for the Control of Greenhouse Insects, Washington, D.C. : U.S. Department of Agriculture, Agricultural Research Administration, Bureau of Entomology and Plant Quarantine
  22. Sulfotep, Bayer MAK 24, Lieferung 1997
  23. Timbrell John A., Principles of biochemical toxicology 4th edition 2009. Informa Healthcare New York. pp 91 & 99
  24. Eula Bingham, Barbara Cohrssen and Charles H. Powell. Patty’s toxicology (5th edition. Vol. 7. John Wiley and sons inc.)
  25. Richard J. Lewis, Sr. Sax’s Dangerous properties of industrial materials (10th edition. Vol. 3. John Wiley and sons inc.)
  26. https://www.cdc.gov/niosh/ipcsndut/ndut0985.html
  27. Chemwatch, Sulfotep sc-251093. Material Safety Data Sheet. https://datasheets.scbt.com/sc-251093.pdf
  28. International Chemical Safety Cards, ICSC: 0985, https://www.cdc.gov/niosh/ipcsndut/ndut0985.html
  • Sulfotep in the Pesticide Properties DataBase (PPDB)
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