Toxicology Brief: A case of zinc phosphide toxicosis


Toxicology Brief: A case of zinc phosphide toxicosis

A 3-year-old intact female Shetland sheepdog was observed chewing pellets of mole and gopher poison (zinc phosphide 2%). The dog's owner removed two pellets from the dog's mouth and contacted the ASPCA Animal Poison Control Center (APCC). The ASPCA APCC instructed the owner to administer two tablespoons of hydrogen peroxide orally to induce emesis. Emesis was induced, and, subsequently, the owner presented the animal to the University of Illinois Veterinary Teaching Hospital's emergency room.


On presentation, the animal was bright, alert, and responsive and had a normal rectal temperature (101.5 F [38.6 C]), pulse rate (88 beats/min), and respiratory rate (although the dog was panting). Therapy was initiated immediately and consisted of intravenous famotidine (0.5 mg/kg given every 12 hours), oral activated charcoal (ToxiBan—Vet-A-Mix; 20 ml/kg once), intravenous isotonic crystalloid fluid therapy (three times the physiologic maintenance rate for 48 hours), and intravenous N-acetylcysteine (150 mg/kg initially, then 50 mg/kg every four hours for six doses).

Initial diagnostic testing consisted of a complete blood count, serum chemistry profile, and venous blood gas analysis. The results of these tests were normal. Serial venous blood gases were obtained, and the results showed a trend toward metabolic acidosis. The results of venous blood gas analysis performed eight hours after presentation demonstrated a mild metabolic acidosis with respiratory compensation. This derangement corrected within six hours. The results of a complete blood count and serum chemistry profile performed eight hours before the patient was released from the hospital remained normal. The patient was released to the owner after 48 hours of therapy.


On follow-up two weeks later, the results of a complete blood count and serum chemistry profile were normal. No long-term deleterious effects from zinc phosphide ingestion have been noted in this patient to date.


Zinc phosphide is the active ingredient in a variety of pellets and tracking powders used as rodenticides.1 Trade names include Zinc Phosphide, Kilrat, Rumetan, Mous-Con, Phosvin, Zinc-Tox, Gopha-Rid, Ratol, and Ridall Zinc.2 Zinc phosphide has been used as a rodenticide since 1919.3 It is a dark-gray, tetragonal, crystalline powder often mixed with palatable bases, such as mash, bread, soaked wheat, cornmeal, or sugar, usually at concentrations of 2% to 5%. Its palatability makes it appetizing to wild and domestic species. Animals may ingest zinc phosphide directly or secondarily by consuming a poisoned carcass.2 Poisonings have occurred in nontarget wild and domestic species4 and people,5 including for suicidal purposes.6

Zinc phosphide is flammable and insoluble in water and has a rotten fish or acetylene odor. The metallophosphide is stable for long periods when kept dry but deteriorates rapidly when damp.2

Related chemical compounds include aluminum and magnesium phosphide; 23 products contain aluminum phosphide as the active ingredient, and four contain magnesium phosphide. The treatment is identical, as both aluminum and magnesium phosphide emit phosphine gas.7


Zinc phosphide's toxicity is primarily due to liberation of phosphine gas.5,8 Moist and acidic conditions favor the chemical reaction to produce phosphine gas [Zn3P2 + 6H2O = 3Zn(OH)2 + 2PH3]. Enhanced susceptibility to phosphine gas occurs when food is ingested with the toxin because of concomitant gastric acid secretion in the stomach leading to more rapid phosphine gas release.

Lethal dose. The lethal dose in dogs and cats has been reported to be 20 to 40 mg/kg. For example, if a 25-kg dog ingests a 5% zinc phosphide formulation, the toxic dose would be 10 to 20 g. However, any amount of ingested product should be treated as a potential toxicity. Dogs may survive ingesting large amounts (300 mg/kg) if the stomach is empty before ingestion.4

Precautions for caregivers of affected animals. Inhaling the liberated phosphine gas from vomitus or during postmortem examination is potentially dangerous to people. Therefore, take precautions. Warn pet owners and your veterinary staff to limit exposure to well-ventilated areas. Phosphine is considered an occupational hazard at 0.3 ppm, but the olfactory detection threshold in people is 1.5 to 3 ppm. Phosphine gas is known to cause serious illness and death in people at 7 ppm.9

Clinical signs

Clinical signs can occur in two phases—acute and subacute. The clinical signs associated with the acute phase occur within 15 minutes to four hours after ingestion and may include anorexia, lethargy, vomiting (often bloody), abdominal pain, and sudden death. Subacute clinical signs may include rapid and deep stertorous respiration, ataxia, weakness, hyperesthesia, extensor rigidity, and seizures.4,6 Animals may be bloated as a result of phosphine gas release in the stomach.3 Zinc phosphide is a direct irritant to the stomach. More important, phosphine gas causes loss of cell viability and cell membrane integrity, which accounts for many clinical signs, but especially the respiratory signs and abdominal pain.10 However, strychnine toxicosis can cause similar clinical signs. Seizures, if noted, are end-stage and in previous case reports preceded death.11 Death can occur at any time, usually within three to 48 hours of ingestion.12

Diagnostic testing

The results of a complete blood count are usually normal, although thrombocytopenia has been reported in people.13 Biochemical abnormalities usually begin 24 to 36 hours after ingestion and include metabolic acidosis, increased liver enzyme activities (especially alkaline phosphatase), azotemia (which may indicate acute renal failure), and hypoglycemia. Hypoglycemia may occur through several mechanisms. Impairment of glycogenolysis and gluconeogenesis in the liver is considered the main cause.14,15 The diagnosis is usually based on a history of ingestion, but in its absence, clinical signs, an acetylene or fishy odor to the patient’s breath, and concurrent biochemical abnormalities are suggestive.

In cases involving ingestion by people, testing vomitus, gastric fluid, or the patient’s breath with a silver nitrate-impregnated filter paper is suggested.10 Silver nitrate and phosphine react to form silver phosphide, which is a dark-gray substance. For veterinary practitioners, testing gastric fluid or vomitus is feasible, and direct-indicating detector tubes are commercially available. Analysis of airtight samples of vomitus or frozen stomach contents by liquid gas chromatography at an analytical laboratory can provide a definitive diagnosis.2,16


Phosphine exerts its toxic activity through oxidative injury. Mutagenic and cytologic effects result from an increase in reactive oxygen species, likely in the form of hydroxyl radicals.17 Phosphine targets cytochrome C oxidase, inhibiting cellular respiration.17-21 Phosphine increases production of hydrogen peroxide from mitochondria leading to a gradual accumulation of oxidant-derived cellular damage.21 Phosphine increases lipid peroxidation, superoxide dismutase, and reactive oxygen species. It decreases catalase, peroxidase, cytochrome C oxidase, glutathione peroxidase, glutathione, and glutathione disulfine.17,22 Organs with the greatest oxygen requirement (e.g. brain, liver, lungs, heart, kidneys) are the most sensitive to this oxidative damage, and long-term monitoring of their function is necessary.2,22


Treatment involves inducing emesis, reducing phosphine gas liberation, and providing supportive care and antioxidant therapy.

Administer an antiemetic. Induce emesis immediately in dogs and cats that have ingested zinc phosphide unless the animals are convulsing or comatose. To reduce exposure of phosphine gas to personnel and other patients, induce emesis in well-ventilated areas and, if possible, outdoors.

The emetic of choice is apomorphine (0.03 mg/kg intravenously or 0.25 mg/kg placed into the conjunctival sac) to minimize gastric acid secretion. However, 3% hydrogen peroxide (2 ml/kg orally, not to exceed 45 ml) is available over-the-counter and easy to administer promptly by pet owners before presentation to your clinic.

Reduce phosphine gas liberation in the stomach and protect the airway. Administer an intravenous H2-antagonist (famotidine 0.5 mg/kg b.i.d.) as soon as possible to minimize gastric acid production. Gastric lavage with 5% sodium bicarbonate solution or liquid antacids (e.g. aluminum or magnesium hydroxide) is useful after emesis has occurred. Nothing further should be allowed by mouth. Protecting the patient's airway and maintaining respiration are the priorities; mechanical ventilation may be necessary in some cases.

Provide supportive care. Provide supportive care, as necessary, to control electrolyte abnormalities, acid-base imbalances, and hypoglycemia. Treatment for seizures, if they occur, is indicated. As mentioned above, do not induce emesis in animals that are experiencing seizures.

Administer an antioxidant. Antioxidant therapy is indicated and should be initiated early. Antioxidants significantly attenuate in vitro phosphine-induced reactive oxygen species formation, lipid peroxidation, 8-OH-Fua formation (DNA oxidation), and, thus, cell death.17 Glutathione (a hydroxyl radical scavenger) is the most effective antioxidant against phosphine-induced oxidative damage in vitro.17 Endogenous glutathione modulates phosphine-induced oxidative damage in rats.23 Glutathione is a potent antioxidant that exists as glutathione disulfide (its reduced form). It reduces toxic substances before they can damage other molecules or important cellular components.

Two medications used in veterinary medicine that provide precursors for glutathione disulfide are S-adenosylmethionine (SAM-e) and N-acetylcysteine. SAM-e is administered orally, while N-acetylcysteine can be administered intravenously or orally. N-acetylcysteine stimulates glutathione disulfide synthesis, enhances glutathione-S-transferase activity, promotes detoxification, and acts directly on reactive oxygen species; it is capable of reducing hydroxyl radicals and hydrogen peroxide. Also, N-acetylcysteine increases intracellular glutathione disulfide concentrations in erythrocytes, hepatocytes, and lung cells and has been proved to replenish glutathione disulfide stores following experimental depletion.23 Therefore, N-acetylcysteine seems to be indicated to prevent the oxidative damage caused by phosphine.

Oral administration of drugs is not recommended in patients with zinc phosphide toxicosis because gastric acid secretion increases, so intravenous N-acetylcysteine administration of the oral preparation is required (140 mg/kg initially, followed by 70 mg/kg every four hours for three to five treatments).24 N- acetylcysteine, although labeled only for oral use in the United States, has been safely used intravenously in the clinical setting in people and animals.25 Infrequently, allergic reactions (generally confined to the skin) have occurred in people given N-acetylcysteine intravenously.25


Zinc phosphide rodenticides are toxic to a variety of species, including dogs. Induce emesis and administer intravenous H2-antagonists promptly. This initial treatment can be followed by gastric lavage with alkalizing solutions. These measures are important to reduce liberation of phosphine gas into the patient’s stomach. Institute antioxidant therapy with intravenous N-acetylcysteine as soon as possible. Early clinical signs can resemble strychnine toxicosis, and abnormal neurologic status often suggests a poor prognosis. Long-term effects may be seen involving the brain, liver, lungs, heart, and kidneys because of the oxidative injury caused by zinc phosphide toxicosis.

"Toxicology Brief" was contributed by Amanda G. Schnitker, DVM, Department of Emergency and Critical Care, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802, and Steven L. Marks, MS, MRCVS, DACVIM, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. Dr. Schnitker's current address is Bevlab South Suburban Animal Hospital, 2949 W. 127th St., Blue Island, IL 60406. The department editor is Petra Volmer, DVM, MS, DABVT, DABT.


1. Murphy MJ. Rodenticides. In: Howard JL, ed. Current veterinary therapy 3: food animal practice. Philadelphia, Pa.: WB Saunders Co, 1993;282-286.

2. Guale FG, Stair EL, Johnson BW, et al. Laboratory diagnosis of zinc phosphide poisoning. Vet Hum Toxicol 1994;36(6):517-519.

3. Shepard HH. The chemistry and action of insecticides. New York, N.Y.: McGraw-Hill, 1980;101.

4. Casteel SW, Bailey EM Jr. A review of zinc phosphide poisoning. Vet Hum Toxicol 1985;28(2):151-154.

5. Rodenberg HD, Chang CC, Watson WA. Zinc phosphide ingestion: a case report and review. Vet Hum Toxicol 1989;31(6):559-562.

6. Chugh SN, Aggarwal HK, Mahajan SK. Zinc phosphide intoxication symptoms: analysis of 20 cases. Int J Clin Pharmacol Ther 1998;36(7):406-407.

7. Environmental Protection Agency Reregistration Eligibility Database Facts; Aluminum and Magnesium Phosphide; Prevention, Pesticides, and Toxic Substances (7508C) EPA-738-F-98-015, December 1998.

8. Osweiler GD. Toxicology. Rodenticides. Philadelphia, Pa.: Williams and Wilkins, 1996;275-296.

9. Wilson R, Lovejoy FH, Jaeger RJ, et al. Acute phosphine poisoning aboard a grain freighter. Epidemiologic, clinical, and pathological findings. J Am Med Assoc 1980;244(2):148-150.

10. Balali-Mood M. Phosphine. International Programme on Chemical Safety Poisons Information Monograph 865. Available at:

11. Drolet R, Laverty S, Braselton WE, et al. Zinc phosphide poisoning in a horse. Equine Vet J 1996;28(2):161-162.

12. Buck WB, Van Gelder GA, Osweiler GD. Zinc phosphide. In: Clinical and diagnostic veterinary toxicology. Dubuque, Iowa: Kendall/Hunt Publishing Company, 1976;257-258

13. Stephenson JBP. Zinc phosphide poisoning. Arch Environ Health 1967;15(1):83-88.

14. Frangides CY, Pneumatikos IA. Persistent severe hypoglycemia in acute zinc phosphide poisoning. Intensive Care Med 2002;28(2):223.

15. Patial KR, Bansai SK, Kashyap S, Hypoglycemia following zinc phosphide poisoning. J Assoc Physicians India 1990:38(4)306-307.

16. U.S. EPA Office of Pesticide Programs. Manual of chemical methods for pesticides and devices. Zinc phosphide EPA-2. 2nd ed. Arlington, Va.: AOAC International 1992.

17. Hsu CH, Quistad GB, Casida JE. Phosphine-induced oxidative stress in Hepa 1c1c7 cells. Toxicol Sci 1998;46(1):204-210.

18. Chefurka W, Kashi KP, Bond EJ. The effect of phosphine on electron transport in mitochondria. Pestic Biochem Physiol 1976;6:65-84.

19. Price NR. The mode of action of fumigants. J Stored Prod Res 1985;21:157-164.

20. Nakakita H. The mode of action of phosphine. J Pestic Sci 1987;12:299-309.

21. Bolter CJ, Chefurka W. Extramitochondrial release of hydrogen peroxide from insect and mouse liver mitochondria using the respiratory inhibitors phosphine, myxothiazol, and antimycin and spectral analysis of inhibited cytochromes. Arch Biochem Biophys 1990;278(1):65-72.

22. Hsu C, Han B, Liu M, et al. Phosphine-induced oxidative damage in rats: attenuation by melatonin. Free Radic Biol Med 2000;28(4):636-642.

23. Hsu CH, Chi BC, Liu MY, et al. Phosphine-induced oxidative damage in rats: role of glutathione. Toxicology 2002;179(1-2):1-8.

24. Kelly, GS. Clinical applications of N-acetylcysteine. Altern Med Rev 1998;3(2):114-127.

25. Yip L, Dart RC, Hurlbut KM. Intravenous administration of oral N-acetylcysteine. Crit Care Med 1998;26(1):40-43.