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 from 1–25 mg/kg. Cats may be more sensitive. In livestock, arsenates are 5–10 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 USA, but may still be available in other countries.
Toxicokinetics and Mechanism of Action
Soluble forms of arsenic compounds are well absorbed orally. Following absorption, most of the arsenic is bound to RBC; 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. The majority of the absorbed arsenic is excreted in the urine as inorganic arsenic or in methylated form.
The mechanism of action of arsenic toxicosis varies with the type of arsenical compound. Generally, tissues rich in oxidative enzymes, such as the GI 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.
Poisoning is usually acute with major effects on the GI 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. The onset is rapid, and signs are usually seen within a few hours (or up to 24 hr). 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 toxicosis, there are usually some lesions in the GI tract. Inflammation and reddening of GI mucosa (local or diffuse) may be seen, followed by edema, rupture of blood vessels, and necrosis of epithelial and subepithelial tissue. In ruminants, hyperemic “paintbrush” lesions may be seen on the serosal surface of the omasum, and the abomasal mucosa may be hyperemic. Necrosis may progress to perforation of the gastric or intestinal wall. GI 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.
Chemical determination of arsenic in tissues (liver or kidney) or stomach contents provides confirmation. Liver and kidneys of normal animals rarely contain >0.1 ppm arsenic (wet wt); toxicity is associated with tissue concentrations >3 ppm. The determination of arsenic in stomach contents is of value usually within the first 24–48 hr 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.
In animals with recent exposure and no clinical signs, emesis should be induced (in capable species), followed by activated charcoal with a cathartic (efficacy of charcoal in arsenic toxicosis remains to be determined) and then oral administration of GI protectants (small animals, 1–2 hr after charcoal) such as kaolin-pectin, and 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, tid for 2–3 days or until recovery). In large animals, thioctic acid (lipoic acid or α-lipoic acid) may be used alone (50 mg/kg, IM, tid, as a 20% solution) or in combination with dimercaprol (3 mg/kg, IM, every 4 hr for the first 2 days, qid for the third day, and bid 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, bid-tid for 3–4 days or until recovery. The water-soluble analogs 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 has been reported to be 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, tid-qid for 3–4 days. Supportive therapy may be of even greater value, particularly when cardiovascular collapse is imminent, and should involve IV fluids to restore blood volume and correct dehydration. Kidney and liver function should be monitored during treatment.
Last full review/revision March 2012 by Tam Garland, DVM, PhD, DABVT