Etiology

• Commercially arsenic may be found in products in organic and inorganic forms of either trivalent or pentavalent states:
  • Organic arsenicals could be either aliphatic or aromatic.
  • Toxicity due to inorganic or aliphatic organic arsenicals results in a similar clinical picture.
  • Of the inorganic (trivalent or pentavalent) and aliphatic organic arsenicals, the trivalent inorganic forms are the most toxic forms of arsenic.
  • Phenylarsenicals (ie aromatic organic pentavalent arsenicals) may be used typically in pig and poultry production as feed additive growth promoters and can result in arsenic toxicosis in pigs with dosing errors for example, but are the least toxic form. However, such organic pentavalent phenylorganic arsenical pig and poultry supplements have now been banned in the European Union and North America.
• Most cattle poisoning cases are acute and are due to the ingestion of inorganic or aliphatic organic arsenicals.
• Possible sources of oral arsenic exposure in cattle include:
  • Old arsenical product containers discarded onto cattle pasture.
  • Accidental access to old arsenical product containers.
  • Access to arsenic contaminated land and/or water.
  • Access to land that was used historically for the insecticidal dipping of livestock.
  • Ash from burnt wood treated with arsenical containing wood preservatives.
• Dermal and percutaneous absorption of arsenicals can occur and may result in systemic toxicity:
  • Through non-intact or inflamed skin.
  • From exposure to insecticidal dips.

Predisposing factors

• Weak, elderly, dehydrated or debilitated animals are more susceptible to toxicity, possibly due to decreased renal excretion.
• Subclinical arsenical toxicity can occur in cattle in regions where there is environmental contamination (either natural or anthropogenic) and the animals are chronically exposed to arsenic contaminated water and/or vegetation.

Pathophysiology

• The concentration of arsenic, its chemical form and its solubility determine its toxicity.
• Soluble arsenic salts are more toxic. Soluble arsenicals are quickly absorbed from the gastrointestinal tract (GIT).
• Arsenicals cause vascular changes that can result in increased permeability. Fluid will leak from the capillaries into the intestinal mucosa and GI lumen, causing fluid loss and hypovolemia, hypotension and eventual circulatory collapse. Thrombosis may also occur.
• Trivalent, inorganic arsenicals and aliphatic organic arsenicals disrupt cellular energy metabolism by reacting with sulfhydryl groups in cells and inhibiting sulfhydryl enzyme systems required for oxidative phosphorylation and the production of adenosine triphosphate (ATP):
  • Actively dividing cells and tissues with high oxidative systems and energy requirements such as the mucosa of the gastrointestinal tract, liver, kidney, spleen and lung, are the organs most vulnerable.
  • Inorganic arsenical and aliphatic arsenicals toxicity causes a typical enteric clinical picture (eg gastroenteritis, diarrhea, dehydration).    
• The pentavalent form of arsenic is substituted for phosphate resulting in uncoupling of oxidative phosphorylation. This leads to axonal degeneration and demyelination and neurological effects.
• Nervous system signs seen with organic arsenicals such as the pentavalent phenylorganic arsenicals are due to the inhibition of dehydrogenase enzymes resulting in peripheral nerve degeneration and demyelination:
  • Aromatic organic pentavalent arsenicals typically used as pig and poultry growth promoters (eg phenylarsonicals) are reportedly less toxic, but quickly absorbed following ingestion.
• Arsenicals can be excreted in various ways, via the urine or feces: 
  • Arsenic is generally quickly excreted in livestock.
  • With phenylarsenicals and pentavalent forms of arsenicals, renal excretion typically occurs in many species with approx. 40-70% of the absorbed quantity being excreted quickly, within a couple of days. 
  • The excretion rate for trivalent, inorganic arsenicals is slower and they are largely excreted via the bile into the feces.   
• Chronic exposure may result in the build-up of arsenic in the skin, hair and hooves.
• If the skin is exposed to high levels of arsenic or the skin circulation is reduced, local dermal necrosis may occur in the absence of systemic effects. However, dermal absorption can be rapid when there is good skin circulation resulting in systemic effects in the absence of damage to the skin.
• Lesions occur due to capillary damage:
  • Gastrointestinal tract:
    • Marked inflammation, submucosal edema, congestion and vesicle development. There may be GIT mucosal and submucosal necrosis and associated sloughing. Necrosis may result in perforation.
  • Kidneys:
    • Capillaries within the glomeruli dilate, swell and undergo degeneration. Tubular necrosis and renal fibrosis may develop. Hypotension and dehydration occur which leads to proteinuria and oliguria.
  • Skin:
    • Dermal exposure to arsenicals leads to hyperemia, blistering and edema.

Timecourse

• Inorganic arsenicals and aliphatic organic arsenicals:
  • Peracute cases:
    • Depression and sudden death is typical. 
    • Death may occur within 3-4 hours. 
  • Acute cases:
    • Most common form in cattle.
    • Associated with a high morbidity and high mortality which can occur over 1-3 days. 
    • Clinical effects may occur from 12-50 hours following oral exposure, the timing of which is also influenced by the amount of ingesta present in the forestomachs.
    • Death can occur within 24-48 hours of onset of clinical effects.
  • Subacute cases:
    • Clinical signs are like those seen in acute cases, but the clinical course is more prolonged; affected cattle could survive for several days (eg 2-7 days). 
    • Deaths may be seen several days following the removal of cattle from the source of arsenic exposure.
  • Chronic cases:
    • Can occur in cattle, but are uncommon as arsenic is quickly excreted.
    • These cases may be sub-clinically affected and so harder to diagnose.
    • Chronic cases are seen with those animals in which exposure is continuous or regularly repeated. An example would be in some regions of India, where there are high levels of arsenic in water, soil and vegetation.
• Clinical signs associated with organic pentavalent phenylarsenical feed supplement toxicity are generally neurological and may occur 2-4 days after a large dose, or following chronic exposure.