Groundwater can contain inorganic arsenic in the form of arsenite or arsenate, in which arsenic is bound to oxygen atoms. Trivalent arsenicals, or arsenites, are more soluble and therefore more toxic than the pentavalent, or arsenate, compounds. These include arsenic trioxide, arsenic pentoxide, sodium and potassium arsenate, sodium and potassium arsenite, and lead or calcium arsenate. The lethal oral dose of sodium arsenite in most species is 1–25 mg/kg. Cats may be more sensitive. In production animals, arsenates are 4–10 times less toxic than arsenites. Decreased use of these compounds as pesticides, ant baits, and wood preservatives has made poisonings less frequent. Arsenites were used to some extent as dips for tick control. Lead arsenate was sometimes used as a taeniacide in sheep. Many of these compounds are no longer used in the US but may still be available in other countries.
Toxicokinetics and Mechanism of Action of Inorganic Arsenicals
Absorption. Soluble forms of arsenic compounds are well absorbed orally.
Distribution. After absorption, most of the arsenic is bound to RBCs; it distributes to several tissues, with the highest levels found in liver, kidneys, heart, and lungs. In subchronic or chronic exposures, arsenic accumulates in skin, nails, hooves, sweat glands, and hair.
Metabolism. Arsenic undergoes hepatic metabolism.
Excretion. Arsenic undergoes renal excretion. Most of the absorbed arsenic is excreted in the urine as inorganic arsenic or in methylated form.
Mechanism of action. The mechanism of action of arsenic toxicosis varies with the type of arsenical compound. Generally, tissues rich in oxidative enzymes, such as the gastrointestinal tract, liver, kidneys, lungs, endothelium, and epidermis, are considered more vulnerable to arsenic damage. Trivalent inorganic and aliphatic organic arsenic compounds exert their toxicity by interacting with sulfhydryl enzymes, resulting in disruption of cellular metabolism. Arsenate can uncouple oxidative phosphorylation.
Clinical Findings of Inorganic Arsenical Toxicosis
Inorganic arsenical toxicosis is usually acute, with major effects on the gastrointestinal tract and cardiovascular system. Arsenic has a direct effect on the capillaries, causing damage to microvascular integrity, transudation of plasma, loss of blood, and hypovolemic shock. Profuse watery diarrhea, sometimes tinged with dark blood, is characteristic, as are severe colic, dehydration, weakness, depression, weak pulse, and cardiovascular collapse. Onset is rapid, and clinical signs are usually evident within a few hours (or up to 24 hours). The course may run from hours to several days, depending on the quantity ingested. In peracute poisoning, most animals may simply be found dead, and a few will be found dead without any lesions.
In peracute inorganic arsenical toxicosis, there are usually some lesions in the gastrointestinal tract. Inflammation and reddening of gastrointestinal mucosa (local or diffuse) may occur, followed by edema, rupture of blood vessels, and necrosis of epithelial and subepithelial tissue. In ruminants, characteristic hyperemic lesions (known as paintbrush lesions) may be evident on the serosal surface of the omasum, and the abomasal mucosa may be hyperemic or ulcerated. Necrosis may progress to perforation of the gastric or intestinal wall. Gastrointestinal contents are often fluid, foul smelling, and blood tinged; they may contain shreds of epithelial tissue. There is diffuse inflammation of the liver, kidneys, and other visceral organs. The liver may have fatty degeneration and necrosis, and the kidneys have tubular damage. In cases of cutaneous exposure, the skin may exhibit necrosis and be dry or leathery.
Diagnosis of Inorganic Arsenical Toxicosis
History of the area
Confirmatory diagnostic testing
Diagnosis of inorganic arsenical toxicosis is generally based on suspicion of arsenic poisoning, clinical signs, history of the area, and confirmatory diagnostic testing. Presence of inorganic arsenic can be confirmed at a diagnostic laboratory by testing of stomach contents, the suspect material, or soil (because large animals may lick the soil).
Chemical determination of arsenic concentration in tissues (liver or kidney) or stomach contents provides confirmation. Liver and kidneys of healthy animals rarely contain >0.1 ppm arsenic (wet weight); toxicity is associated with tissue concentrations >3 ppm (wet weight). The determination of arsenic concentration in stomach contents is usually of value if performed within the first 24–48 hours after ingestion. The concentration of arsenic in urine can be high for several days after ingestion. Drinking water containing >0.25 ppm arsenic is considered potentially toxic, especially for large animals.
Treatment of Inorganic Arsenical Toxicosis
IV fluid therapy and supportive care
Induction of emesis, followed by activated charcoal administration
Gastric lavage with warm water and kaolin-pectin
Blood transfusion in some severely affected patients
d-Penicillamine, as a chelator
Continual monitoring of liver and kidney functions
IV fluid therapy and supportive care
Thioctic acid, alone or in combination with dimercaprol
DMPS and DMSA (succimer)
d-Penicillamine, as a chelator
Continual monitoring of liver and kidney function
In animals with recent exposure to arsenic and no clinical signs of inorganic arsenical toxicosis, emesis should be induced (in capable species), followed by administration of activated charcoal with a cathartic (efficacy of charcoal in arsenic toxicosis remains to be determined) and then oral administration of demulcents (small animals, 1–2 hours after charcoal) such as kaolin-pectin, followed by fluid therapy as needed.
In animals already showing clinical signs, aggressive fluid therapy, blood transfusion (if needed), and administration of dimercaprol (British antilewisite, 4–7 mg/kg, IM, every 8 hours, for 2–3 days or until recovery) is recommended. In large animals, thioctic acid (lipoic acid or alpha-lipoic acid, as a 20% solution) may be used alone (50 mg/kg, IM, every 8 hours for the next 10 days or until recovery) or in combination with dimercaprol (3 mg/kg, IM, every 4 hours for the first 2 days, every 6 hours for the third day, and every 12 hours for the next 10 days or until recovery). In large animals, the efficacy of dimercaprol alone is questionable. Sodium thiosulfate has also been used, PO, at 20–30 g in 300 mL of water in horses and cattle, one-fourth this dose in sheep and goats, and 0.5–3 g in small animals or as a 20% solution, IV, at 30–40 mg/kg, every 6–8 hours for 3–4 days or until recovery. The water-soluble analogues of dimercaprol, 2,3-dimercaptopropane-1-sulfonate (DMPS) and dimercaptosuccinic acid (DMSA), are considered to be less toxic and more effective and could be given orally.
d-Penicillamine is reportedly an effective arsenic chelator in humans. It has a wide margin of safety and could be used in animals at 10–50 mg/kg, PO, every 6–8 hours for 3–4 days.
Supportive therapy may be of even greater value, particularly when cardiovascular collapse is imminent, and should involve IV fluid therapy to restore blood volume and correct dehydration. Kidney and liver function should be monitored during treatment.
Inorganic arsenical toxicoses still occur, in both companion and large animals.
Inorganic arsenical toxicosis should be considered when animals have intense abdominal pain and mucoid diarrhea, especially if fragments of intestinal epithelium slough in the stool.
Arsenic poisoning is usually acute and affects predominantly the cardiovascular system and gastrointestinal tract.
Liver and kidneys may be affected.
Treatment should include removal of the animal from the offending source, supportive care, and administration of specific chelators.
For More Information
More information on sample submission guidelines and the cost of testing may be obtained from a veterinary diagnostic laboratory.
Peterson M, Talcott P. Small Animal Toxicology. 3rd ed. St. Louis: Elsevier, 2013.
Osweiller GD. Toxicology. Philadelphia: Lippincott Williams & Wilkins, 1996.