Arsenic

Arsenic poisoning in animals is caused by several different types of inorganic and organic arsenical compounds. Toxicity varies with factors such as oxidation state of the arsenic, solubility, species of animal involved, and duration of exposure.

Sources:  Pesticides, herbicides, defoliants, insecticides, rodenticides, slug/snails’ baits

• Na and K arsenite and thioarsenite. They are frequently used as insecticides, wood preservatives, and weedicide.
• Contaminated herbage due to the use of lead (Pb) arsenite and calcium arsenite.
• Household paint containing lead arsenite or arsenic trioxide.
• Arsenic contaminated drinking water.
• Arsenic compounds used as poultry feed additives.
• Industrial contaminated pasture land.
• Ingestion of arsenic rat-bait.
• Over dose of arsenic medicinal compounds. (Acetarsol, Arsphenamide etc.)

Organic arsenicals :  (Monosodium methane arsonate: MSMA, pesticide & Disodium methyl arsonate: DSMA, herbicide)

Toxic dose:-

Cattle:- 1-4gm Na-arsenite and

• 15-45gm arsenic trioxide is lethal.

 Horse:-

• 1-5gm Na arsenite and 10-45gm arsenic trioxide is lethal.

Sheep and goat:-

• 5gm Na-arsenite and 1-3 gm arsenic trioxide is lethal.

Poultry:-

• 01-0.1gm Na-arsenite and 0.05-0.3gm arsenic trioxide is lethal.

Toxcokinetics:

 Absorption : Soluble forms of arsenic compounds are well absorbed orally. Following absorption, most of the arsenic is bound to RBC.

Trivalent arsenicals, also known as arsenites, are more soluble and therefore more toxic than the pentavalents or arsenate compounds.

Distribution : 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.

Mrtabloism and excretion : The majority of the absorbed arsenic is excreted in the urine as inorganic arsenic or in methylated form.

Mechanism of action : Arsenites form a stable complex with the thiol(–SH) group of lipolic acid and lipolic acid is unavailable to serve as coenzyme . Arsenic inhibit the enzyme that require lipolic acid as coenzyme. Pyruvate dehydrogenase and Alpha – ketoglutarate dehydrogenase.

As(III) Inhibit cellular glucose uptake, gluconogenesis,   

                                                                                           fatty acid oxidation           

 

Binds to the sulfhydryl group inhibit other enzyme



Inhibit pyruvate dehydrogenase



Disrupts oxidative phosphorylation



Decrease cellular ATP level



Increase production of H2O2



Reactive oxygen species(ROS) formation



Oxidative stress

The mechanism of action may be summarized by the following 3 ways:-

• Arsenic gives the irritation to the gastro-intestinal mucous lining.
• Arsenic increases the capillary permeability and simultaneously causes the dilatation of blood vessels, which brings the lower blood pressures. As a result, in per acute cases, animal may die suddenly without showing any clinical sign.
• Arsenic binds the pyruvic oxidase enzymes and its co-factor as a result TCA cycle and oxidative phosphorylation process is disrupted.

Presentations/Clinical Signs :

• Acute (30 min to hours) :

 Sudden death , Severe colic ,Weakness, trembling, ataxia , Salivation , Diarrhoea- hemorrhagic with mucosal shreds , (In case of dogs: vomit repeatedly and recover, cats often die despite vomiting) , Rapid Heart Rate ,Collapse & death

• Subacute :

 Depression, anorexia , Watery diarrhea , Polyuria/Polydipsia to anuria , Paraparesis, Stupor, death

• Chronic toxicity rare in animals.

Post mortem lesion:-

• Intense rose-red inflamed stomach or intestinal tract.
• Extravasations of blood in the alimentary canal.
• Soft and yellowish discoloration of liver.
• Edematous, swollen and congested lungs.

Hemorrhagic lesions in heart and spleen

Diagnosis :

• History of exposure
• Clinical Signs (rapid bloody diarrhea) No other heavy metal has this rapid GI signs (severe)
• Postmortem lesions
• Lab: Feed, GI, liver, kidney, urine levels > 10 ppm
• Blood values: Azotemia (Increase BUN & creatinine), Anemia

Treatment:

• Remove Source
• Prevent further absorption: Induce vomiting, Gastric lavage, Activated charcoal (Mix 1g/5ml water, give 10ml of slurry/kg or 1-4g/kg bw granules) PO, Cathartic (Mineral oil and saline purgatives) PO
• Na thiosulphate PO (20-30 g/300 ml of water), safer but less effective than BAL
• Antidote: BAL (British Anti-Lewisite, Dimercaprol) IM 3 mg/kg/4hrs, chelates As, hastens elimination
• Succimer (DMSA, 2,3Dimercaptosuccinic acid) – chelating agent, expensive
• Symptomatic: Correct acidosis, hypocalcemia, hypokalemia, blood transfusions .

Prognosis • Poor to guarded

 DDX

• Thallium
• Lead
• Caustic.