Arsenic and Lead Poisoning in Animals

This is an assignment of Toxicology subject, 6th Semester

1. Welcome - Yuvraj Panth 6 th Semester, B.V.Sc . & A.H., IAAS, Nepal Arsenic and Lead Poisoning in animals

2. Arsenic Poisoning

3. Sources : Indiscriminate use of drug as a drug for control of ectoparasites , blood parasites and skin tonics Water, herbage contamination Animals licking wood preserved in arsenical preparations Overdose of arsenical feed additives

4. Factors Affecting Toxicity: Species: Herbivores> Dog,cats > fowl,swine Oxidation state: organic arsenicals< Arsenate< Arsenite <Arsine Solubility/Form: Finely divided & soluble-more toxic Status of animals: Dehydrated,weak,ill and poor body condition- more susceptible Tolerance: constant exposure- increased tolerance

5. Toxicokinetics : Absorption- Readily absorbed from all body surfaces Distribution- Throughout the body High concentration in liver,kidney,heart & lungs High concentration in nails & hair because of high sulphydryl contents Cross placental barrier Partly methylated in liver Excreted in urine, feces, bile,milk,saliva & sweat Lethal oral dose of sodium arsenite in most species 1–25 mg/kg. Cats more sensitive. In livestock, arsenates are 5–10 times less toxic than arsenites .

6. Mechanism of Toxicity: A. Trivalent Arsenic Trivalent As Binds with two sulphydryl groups of Lipoic acid Stable six-membered ring ( As- Lipoic acid complex) Inhibition of Glycolysis and TCA cycle Lipoic acid is a sulphydryl containing cofactor for the enzymatic decarboxylation of ketoacids -pyruvate, ketoglutarate

7. Mechanism of Toxicity: B. Pentavalent Inorganic Arsenic: Blocks Mitochondrial Oxidative Phosphorylation No ATP Production

8. C . Pentavalent Organic Arenicals : MOA-not clearly understood Pentavalent Organic Arenicals : Interference with Vit.B Demyelination and Axonal Degeneration

9. D. Arsine gas: MOA-not clearly understood Arsine + Hb React with O2 Hemolysis Pulmonary Edema

10. Clinical signs: Acute , subacute or chronic Acute: High morbidity & mortality GI pain,colic Diarrhoea,vomiting , Ruminal atony,etc . Subacute : Watery bloody diarrhoea Depression,dehydration Anuria

11. Chronic: Poor condition Excessive thirst Weak regular pulse Nervous derrangement like ataxia, incoordination and blindness

12. PM findings: GIT inflammation Rupture of blood vessel Liver- diffuse inflammation Kidneys-pale swollen

13. Diagnosis: Clinical signs PM findings Urinalysis

14. Treatment: A. Dimercaprol / British Anti-Lewisite (BAL): Large animals-3 mg/kg i.v. until recovery Small animals- 2.5 mg/kg i.v. until recovery B. Thiocitric acid 50 mg/kg b.w i/m tid (cattle) C. Sodium Thiosulphate : Horse & cattle: 20-30 mg; PO + 300 ml water 8-10 g i.v in 10% solution Emetics, Gastric Lavage Rehydration Therapy High protein diet

15. Sources: Grass near busy streets Licking of discarded batteries, paints, etc. Milk secreted from lead-poisoned animals Agricultural use of fertilizers, fungicides, herbicides Drinking water from old lead pipes Lead parasiticide sprays particularly those containing lead arsenate

16. Factors influencing Toxicity: Age: Young animals more susceptible Species: Goats, swine, chicken are more resistant Reproductive state: Pregnant ewe more susceptible than nonpregnant Rate of ingestion: large amount within short time is more toxic Undernutrition and presence of other debilitating factors Presence of food or ingesta in stomach or intestine delays absorption and thereby reduces toxicity

17. Absorption and Fate: Almost lead enters through ingestion Absorption from gut (only 1 or 2 %) 85-90% binds to Hb in erythrocyte Remainder bind to serum albumin Less than 1% actually free

18. Distribution of unbound fraction to various parts of body Mainly sink in bone (90-98%) Via portal circulation reaches to liver and then to duodenum via bile Excretion via milk, urine and feces. Can cross Blood Brain Barrier and Placental Barrier Concentrations of lead in the blood at 0.35 ppm, liver at 10 ppm, or kidney cortex at 10 ppm in most species lead concentrations in blood >0.05–0.10 ppm to be a notifiable disease in food-producing animals

19. Mechanism Of Toxicty : Toxicity mainly by inhibiting sulfhydryl groups of essential enzymes of cellular metabolism

20. A. Neurotoxic mechanism: lead Enter into brain cells Disturbs the function of cellular calcium Damage to capillary endothelium Inactivates BBB Cerebral edema & hemorrhages

21. B. Gastro-Intestinal toxicity: Specific mechanism-not understood Could be secondary to neurological mechanisms Lead Contraction of smooth m/s of intestinal wall -gastroenteritis -anorexia - Vomition -Colic

22. C. Haematopoietic toxicity: Inhibition of Heme synthesis by inhibiting key enzymes involved in synthesis eg . ∂-ALAS,∂-ALAD, HS Inhibits Na+/K+ ATPase pump Attach to RBC membrane Lysis of RBC

23. D. Immunotoxicity : Decreased production of Antibodies E. Nephrotoxicity: Inhibition of cellular respiration Generalized dysfunction of renal tubular & energy dependent function F. Endocrine toxicity: Decreased release of GH & insulin growth factors G. Reproductive toxicity: Gametotoxocity (both male and female)

24. Clinical Symptoms: Acute or Chronic Acute: common in cattle Bellowing, rolling eyes and frothy mouth Excitation followed by quiscient phase Muscular spasm, tetany and death Chronic: Anorexia, constipation, recumbency and death (cattle and sheep) Paralysis of limbs, anorexia, jaundice, nasal discharge, Roaring due to laryngeal muscle paralysis (Horse)

25. Pigs- considerably resistant Dog- i ) Gastrointestinal symptoms (anorexia, vomiting, colic, diarrhoea ) ii) Nervous symptoms (anxiety, hysterical barking, salivation, convulsions) Cats- not very common Birds- anorexia, ataxia, excitement, loss of condition;decrease in fertility, hatchability and egg production; High mortality

26. Post-Mortem Lesions: No observable gross lesions Stomach and intestine may present ingested lead Brain edema, gastritis, hyperemia and petechiae on various organs

27. Diagnosis: History, Clinical signs, PM lesions, lead content in body inclusions Measurement of ALA dehyratase in blood Urine ALA is increased Level of lead >4 ppm in liver , 0.2 ppm in whole blood indicates lead poisoning

28. Differential Diagnosis: Hypomagnesemic tetany Tetanus Vit.A deficiency Listeriosis Barley poisoning Encephalitis Acute pancreatitis Hepatitis Encephalits Dog Rabies Distemper

29. Treatment: Calcium Ethylenediamine tetra acetate (EDTA) as an antidote Cattle and horses:110 mg/kg i /v or s/c two doses @ 6hrs. Interval every other day for three treatments Dogs: 110 mg/kg s/c as 1% solution diluted with 0.9%saline divided into four doses every other day for three treatments BAL increases lead excretion in urine Intestinal lavage or a cathartic to eliminate the unabsorbed lead Vit.D and Ca-borogluconate give additional support MagSulf will prevent further absorption of lead by reducing lead solubilty Cerebral oedema can be controlled using dexamethasone and mannitol Broad spectrum antibiotics to control secondary bacterial infection

30. THANK YOU