TOXICOLOGY BRIEF

PEER-REVIEWED

Disulfoton: A deadly threat in pets Marcy E. Rosendale, DVM

1 isulfoton (O, O-diethyl-S-2-ethylthioethyl- those having an LD50 ≤ 50 mg/kg). Because of disulfo- phosphorodithioate), also called oxydisul- ton’s extremely toxic nature, dogs may ingest a suffi- Dfoton, is an organophosphorus insecticide cient amount to cause toxicosis while digging around and acaricide that is highly toxic in mammals. Trade treated plants. For example, a 55-lb (25-kg) dog would names include Di-Syston, Dimaz, Disultex, Ekanon, need to ingest only about a teaspoon of a pesticide

Frumin AL, Knave, Solvigran, and Solvirex. Disulfoton containing 1% disulfoton to reach the LD50. is considered a systemic insecticide because it is ab- sorbed by plant roots and distributed systemically to Clinical signs the rest of the plant. It is especially effective against Dogs usually present with signs typical of organo- sucking insects, such as aphids.1 Dogs are most com- phosphorus insecticide toxicosis. Muscarinic stimula- monly exposed to disulfoton by ingesting granular tion may cause miosis, salivation, lacrimation, dysp- rose care products applied to the soil at the base of nea, tachypnea, vomiting, diarrhea, and urination. the plant by pet owners. Dogs are attracted to the Frank blood may be seen in the vomitus and stool if disulfoton when it is formulated with or applied with vomiting and diarrhea are severe. Muscle tremors or fertilizers. Disulfoton may also be applied to potted fasciculations, muscle weakness (including diaphragm roses before purchase, so pet owners may be un- weakness), mydriasis, tachycardia, and ataxia are aware of any danger. signs of nicotinic stimulation. Central nervous system effects of organophosphorus insecticides include Mechanism of action seizures and coma. Organophosphorus insecticides such as disulfoton af- fect the nervous system by binding to the enzyme Physical examination findings acetylcholinesterase, allowing the neurotransmitter A patient’s mucous membranes may be tacky and acetylcholine to accumulate at autonomic and somatic pale or cyanotic. Bradycardia may be present as a re- nerve synapses. Excessive acetylcholine causes contin- sult of organophosphate-induced parasympathetic ued stimulation of parasympathetic muscarinic recep- stimulation. Conversely, tachycardia is possible from tors, preganglionic sympathetic receptors, and somatic overriding sympathetic tone.3 Evidence of bronchial nicotinic receptors. Sites affected include the brain, secretions may be heard on thoracic auscultation. Hy- heart, lungs, skeletal muscle, stomach, intestines, pan- perthermia may be seen with muscle tremors or fasci- creas, urinary bladder, adrenal medulla, salivary and culations, while hypothermia may be encountered lacrimal glands, and iris.2 after these signs resolve. Signs of pain may be elicited on abdominal palpation. Intussusceptions have been Toxicity reported in some dogs with disulfoton toxicosis

Disulfoton’s oral LD50 in rats is 2 mg/kg, placing it in (ASPCA Animal Poison Control Center [APCC] Data- the most toxic, Category I, group of pesticides (i.e. base: Unpublished data, 2003).

Clinicopathologic findings “Toxicology Brief” was contributed by Marcy E. Rosendale, DVM, The packed cell volume may be elevated from dehy- ASPCA Animal Poison Control Center, 1717 S. Philo Road, Suite 36, dration secondary to severe vomiting and diarrhea. Urbana, IL 61802; (888) 4ANI-HELP. Dr. Rosendale’s current Electrolyte imbalances are possible because of severe address is 2150 Centre Ave., Building B, Mail Stop 31011, Fort Collins, CO 80526-8117. The department editor is Petra A. fluid losses. Amylase and lipase activities may be Volmer, DVM, MS, DABVT, DABT, College of Veterinary Medicine, markedly elevated from autonomic stimulation of the University of Illinois, Urbana, IL 61802. pancreas or secondary to pancreatitis. Increases in as- partate transaminase and creatine kinase activities can

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Continued

result from excessive muscle activ- decontamination measures usually ity. Hyperglycemia and leukocyto- cannot be used in disulfoton toxi- sis have also been reported.4 cosis. Do not induce vomiting in patients exhibiting vomiting, diar- Making a definitive diagnosis rhea, and abdominal pain. Emetics A 50% or more decrease of acetyl- may exacerbate these signs and cholinesterase in whole blood, are unlikely to help the patient. serum, or plasma is suggestive of Gastric lavage may be useful once organophosphorus insecticide toxi- the patient is stabilized if large cosis.4 Analysis of whole blood is amounts of disulfoton have been preferred. Because a variety of ingested. Administering activated methods are used to determine charcoal is recommended in most acetylcholinesterase activity, the cases, but only after vomiting has test results should be interpreted been controlled and the patient is by a laboratory that has estab- stable. Cathartics may exacerbate lished normal values in dogs. Se- diarrhea and are not indicated. vere organophosphorus toxicosis Tailor treatment for disulfoton may lower acetylcholinesterase ac- toxicosis to the individual patient. tivities to less than 25% of normal.4 Clinical signs and their severity The results of acetylcholines- may differ, depending on the terase testing are usually not avail- quantity of disulfoton ingested and able in time to make treatment de- the length of time after exposure. cisions when an exposure history Prompt and aggressive supportive is uncertain. Observing the re- care must be provided for any life- sponse to a low (preanesthetic) threatening signs. Establish an air- dose of atropine sulfate (0.02 way, and administer oxygen if a mg/kg intravenously) may help patient is in respiratory distress. you establish a tentative diagnosis. Place an intravenous catheter for Since large doses of atropine are drug and fluid therapy administra- required to control the clinical tion. Atropine is usually recom- signs of organophosphorus toxico- mended early in the course of sis, a lack of response to a low organophosphorus insecticide toxi- dose is suggestive of exposure to cosis to counteract potential life- an acetylcholinesterase inhibitor. If, threatening pulmonary and cardiac after administering a low dose of effects. Atropine decreases the atropine, you observe an increased bronchial secretions, bronchocon- heart rate, dry mucous mem- striction, and bradycardia that may branes, and mydriasis, search for a compromise adequate oxygena- different diagnosis.4 tion. Depending on the severity of signs, the recommended dose of Treatment atropine in organophosphorus tox- Because clinical signs often begin icosis is 0.2 to 2 mg/kg. Give one- before treatment is sought, typical fourth to one-half intravenously

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and the rest intramuscularly or subcutaneously.5 Vomiting, diarrhea, and abdominal pain may be Overuse of atropine can cause central nervous system severe with disulfoton toxicosis (ASPCA APCC Data- excitation, tachycardia, hyperthermia, and intestinal base: Unpublished data, 2003). The severe pain may stasis. Since atropine should only be used to treat the lead to shock, so administer opioids when severe ab- life-threatening effects of acetylcholinesterase inhibi- dominal pain is suspected. Elevated pancreatic en- tion, discontinue its use when muscarinic signs are zyme activity and abdominal pain may indicate pan- under control to avoid potential adverse effects. Re- creatitis. Supportive care may include administering

peated doses of atropine may be needed if muscarinic sucralfate, H2 blockers, antibiotics, and bland diets as signs recur. needed for gastrointestinal signs and pancreatitis. When treating disulfoton-induced seizures, start Varying degrees of gastrointestinal upset often last for with diazepam because it is short-acting and has a two or three days and possibly longer in severe minimal effect on the cardiovascular system. Barbitu- cases. Monitor dogs for intussusception, and treat rates may be considered if diazepam is ineffective. In- them appropriately. halant anesthetics may be needed if seizures are refractory to other medications. A lack of response to a low dose Fluid therapy is indicated to im- prove blood pressure in patients of atropine suggests exposure to experiencing shock and hypoten- sion. Fluids are also often needed an acetylcholinesterase inhibitor. to replenish water and electrolytes lost through vomiting and diarrhea. Base the choice of Prognosis fluids on a patient’s needs, but a first choice would be A patient’s prognosis depends largely on the amount lactated Ringer’s solution when laboratory test results of disulfoton ingested and the treatment provided. A are not back yet. delay in treatment may considerably worsen the prog- Treat hyperthermia or hypothermia supportively. Hy- nosis. Animals with serious underlying health condi- perthermia is caused by excessive muscle activity, and tions may have a poorer prognosis than those in good body temperature may normalize or drop below normal health. A good to fair prognosis can be expected if the once these signs are controlled, so treat accordingly. amount of disulfoton ingested is small and prompt Pralidoxime chloride (2-PAM chloride) is an acetyl- medical care is provided. In cases of exposure to large cholinesterase reactivator used in moderate to severe amounts of disulfoton, such as access to the container, cases of organophosphorus toxicosis. Pralidoxime may a guarded to poor prognosis is more likely. help relieve the muscle weakness and tremors associ- ated with disulfoton toxicosis. It should be adminis- REFERENCES tered in stable patients at 20 mg/kg given intramuscu- 1. Thompson, W.T.: Insecticides. Agricultural Chemicals Book. Thompson Publications, Fresno, Calif., 1998; pp 216-217. larly or subcutaneously every 12 hours until severe 2. Hardman, J.G. et al.: Anticholinesterase agents. Goodman and weakness and tremors have resolved.5 Pralidoxime Gilman’s The Pharmacological Basis of Therapeutics, 9th Ed. ( J.G. may be administered as a slow intravenous bolus or Hardman et al., eds.). McGraw-Hill, New York, N.Y., 1996; pp 161- 176. intravenous infusion. Neuromuscular blockade may 3. Ford, M.D. et al.: Organophosphates and carbamates. Clinical Tox- occur with rapid administration.2 If the patient does icology. W.B. Saunders, Philadelphia, Pa., 2001; pp 819-828. not respond after three doses, discontinue the prali- 4. Fikes, J.D.: Organophosphorus and carbamate insecticides. Vet. Clin. North Am. (Small Anim. Pract.) 20 (2):353-367; 1990. doxime. Muscle weakness may be prolonged if prali- 5. Plumb, D.C.: Veterinary Drug Handbook, 3rd Ed. Iowa State Uni- doxime is not administered. versity Press, Ames, 1999; pp 64-67, 523-524. ■

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