Arsenic, lead and mercury toxicity

toxicity metals

1. Arsenic toxicity in animals

2. INTRODUCTION Most common heavy metals toxicity: Lead ( P b ), Mercury (Hg), Arsenic (As) • mainly produced by industrial activities, and deposit slowly in the surrounding water and soil Toxicity may occur through ingestion, inhalation or dermal exposure Toxicity is either acute or chronic Metallic taste if ingested except arsenic which is tasteless Can cause both local & systemic effects Most metals cause diarrhea except lead which causes constipation The antidotes are called chelators

3. Arsenic Toxic principles Inorganic arsenicals Arsenic trioxide Arsenic penta -oxide Sodium and potassium arsenate Sodium and potassium arsenite Calcium and lead arsenate

4. SOURCES Pasture near smelters Paints Strong solutions of lead arsenate for animal dipping 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 Milk from arsenic poisoned animal Rodenticides Weedicides Baits and insecticides Use of lead arsenate as taenicide

5. animal Arsenic triioxide Sodium arsenite Horse 10-45 gm 1-3 gm cow 15-45 gm 1-4 gm Sheep and goat 3-10 gm 200-500 mg Swine 500-1000 mg 50-100 mg Dog 100-150 50-150 mg fowl 50-300 mg 10-100 mg Arsenic cumulative poison Stored in liver skin and hair Oral lethal dose of sodium arsenate 1-25 mg/kg in most animals Sodium arsenite is 10 times poisonous than arsenic trioxide

6. Factors influencing Toxicity: Species: Herbivores commonly poisoned Dog maliciously poisoned Cats are occasionally poisoned fowl, and swine rarely poisoned Oxidation state: Inorganic trivalent arsenic is more potent than inorganic pentavalent Organic arsenicals are less toxic than inorganic arsenicals Pentavalent arsenicals converted in-vivo to trivalent and becomes toxic Solubility/Form: Finely divided and soluble form -more toxic than coarse and poorly soluble Status of animals: Dehydrated, weak, Ill and poor body condition- more susceptible Tolerance: constant exposure increased toxicity

7. T oxicokinetics Distributed in almost all biological fluid of the body Higher concentration liver kidney spleen Does not stay in the body for longer time in domestic animals Rapidly excreted in urine feces, bile, milk and saliva Half life is 1.5 days in animals Does not cross BBB but readily cross placental barrier

8. Mechanism of Toxicity:

9. Clinical signs: Peracute Animals found dead showing no symptoms Severe colic, staggering, collapse, paralysis and death Acute: Severe colic, staggering, weakness trembling, salivationvomitting,thrist,projectile watery diarrhea, blood tinged feces, fast and weak pulse, hind limb paralysis , normal or subnormal temperature and death 1-3 days Subacute : Colic anorexia, blood mixed diarrhea, muscle threads in feces, polyuria followed by anuria, dehydration thrust, partial paralysis of hind limbs, trembling, stupor, cold extremities, subnormal temperature, hematuria, convulsion Chronic Wasting, poor condition, thirst, brick red coloration of mucus membrane,, normal body temperature, weak and irregular pulse

10. PM FINDINGS Cattle Reddened abomasal or duodenal mucosa Sub-mucosal edema Hemorrhage in the abomasum and duodenum Perforation of the gut wall Intestinal content foul smell Liver soft and yellow Lungs edematous and congested Swine Larynx and trachea edematous Fowl Proventriculus and gizzard inflamed Gelatinous exudates beneath the horny line of gizzard causes sloughing of the gizzard horny layer

11. Diagnosis Clinical signs PM findings Lab test Differential diagnosis Thallium poisoning Caustic Irritant plants Urea Chlorate Pesticides Enteric diseases

12. TREATMENT Non specific treatment Emetics, Gastric Lavage Specific antidote Dimercaprol / British Anti-Lewisite (BAL): Large animals-3 mg/kg i.v . until recovery Small animals- 2.5 mg/kg i.v . until recovery Sodium Thiosulphate : Horse & cattle: 20-30 mg; PO + 300 ml water twice daily till recovery Sheep goat 8-10 g orally Supportive therapy Good nursing care, animal should be kept in warm Should be treated symptomatically with Antibiotic and analgesic Rehydration Therapy High protein diet

13. Prognosis- grave If the treatment started late Extensive organ damage Analysis Stomach Intestine(feces or vomitus) Liver and kidneys Blood milk urine More than 3 ppm arsenic concentration in these organs confirms the arsenic poisoning in the animals

14. Thank you

15. Mercury Occurs in three forms elemental , inorganic salts, and organic compounds Contamination results from mining , smelting , and industrial discharges. Mercury in water can be converted by bacteria to organic mercury (more toxic) in fish. Can also be found in

16. Mercury thermometers, dental amalgams, fluorescent light bulbs, disc batteries, electrical switches, folk remedies, chemistry sets and vaccines. some medications, drinking water, and many other things. Young are more susceptible to getting mercury poisoning than adults. The vapor form of mercury is the most toxic.

17. Mercury - Exposure Elemental liquid at room temperature that volatizes readily rapid distribution in body by vapor, poor in GI tract Inorganic poorly absorbed in GI tract, but can be caustic dermal exposure has resulted in toxicity Organic lipid soluble and well absorbed via GI, lungs and skin can cross placenta and into breast milk

18. Elemental Mercury At high concentrations, vapor inhalation produces acute necrotizing bronchitis, pneumonitis, and death. Long term exposure affects CNS. Early: insomnia, forgetfulness, anorexia, mild tremor Late: progressive tremor and erythrism (red palms, emotional labiality, and memory impairment) Salivation, excessive sweating, renal toxicity (proteinuria, or nephrotic syndrome) Dental amalgams do not pose a health risk .

19. Inorganic Mercury Gastrointestinal ulceration or perforation and hemorrhage are rapidly produced, followed by circulatory collapse. Breakdown of mucosal barriers leads to increased absorption and distribution to kidneys (proximal tubular necrosis and anuria). Acrodynia (Pink disease) usually from dermal exposure maculopapular rash, swollen and painful extremities, peripheral neuropathy, hypertension, and renal tubular dysfunction.

20. Organic Mercury Toxicity occurs with long term exposure and effects the CNS. Signs progress from paresthesias to ataxia, followed by generalized weakness, visual and hearing impairment, tremor and muscle spasticity, and then coma and death. Teratogen with large chronic exposure Asymptomatic mothers with severely affected infants Infants appeared normal at birth, but psychomotor retardation, blindness, deafness, and seizures developed over time.

21. Diagnosis and Treatment Diagnosis made by history and physical and lab analysis. Inorganic mercury can be measured in 24 hour urine collection; organic mercury is measured in whole blood. The most important and effective treatment is to identify the source and end the exposure Chelating agents (DMSA) may enhance inorganic mercury elimination. Dimercaprol may increase mercury concentration in the brain .

22. Mercury - Prevention Elemental mercury spills: Roll onto a sheet of paper and place in airtight container Use of a vacuum cleaner should be avoided because it causes mercury to vaporize (unless it is a Hg Vac ) Consultation with environmental cleaning company is advised with large spills. avoid consumption of certain fish from specific bodies of water.

23. Absorption Most commonly by breathing contaminated air. Can also be absorbed by drinking water or eating contaminated food ( usually fish, especially those that eat other fish). There about 2 ppm of mercury in one billion parts of drinking water.

24. Distribution Mercury is distributed to the bloodstream from the lungs, then the blood carries it to the central nervous system. This is especially harmful to young, because their nervous systems are still developing.

25. Action There are no known mechanisms for mercury.

26. Metabolism Mercury is converted to HgCl2 where it remains in the body for years.

27. Excretion Mercury is excreted from the body through urine and feces. It can take the body several months to excrete it. Chelation therapy can also be used to help get rid of the toxin. This is where a substance that binds to the mercury is injected into the body, for easier removal.

28. Effects Of Mercury Exposure

29. Acute exposure Can lead to lung damage, vomiting, diarrhea, high blood pressure, eye and skin irritation. Mercury can cause damage to the body even before effects are noticed!! Some effects include: Tremors Shyness Irritability Insomnia Changes in hearing or vision Difficulty with memory

30. Chronic exposure A few drops can raise the surrounding air to those of high contamination!! When mercury is inhaled it can lead to Acute necrotizing bronchitis Chemical pneumontis Death due to respiratory failure Damage to the kidneys, lungs, brain. Symptoms can be passed from child to fetus through the placenta, resulting in birth defects; Mental retardation Blindness Seizures Problems with the nervous and digestive systems

31. References http://www.atsdr.cdc.gov/cabs/arsenic/ http://www.epa.gov/safewater/arsenic/ http://www.emedicine.com/neuro/topic20.htm http://physchem.ox.ac.uk/msds/AR/arsenic.html Chattopadhyay, S ; Bhaumik, S ; Purkayastha, M ; Basu, S ; Chaudhuri, AN ; Das Gupta, S . 2002. Apoptosis and necrosis in developing brain cells due to arsenic toxicity and protection with antioxidants. Toxicology Letters . v.136, no.1, p.65-76. Santra, A; Maiti, A; Das, S; Lahiri, S; Charkaborty, SK; Mazumder, DNG. 2000. Hepatic damage caused by chronic arsenic toxicity in experimental animals. Journal of Toxicology . v.38, no.4, p.395-405. http://www.atsdr.cdc.gov/tfacts46.html http://www.atsdr.cdc.gov/alerts/970626.html http://www.mercuryinschools.uwex.edu/ http://www.fda.gov/cder/fdama/mercury300.htm http://www.epa.gov/mercury/exposure.htm http://www.vaccinationnews.com/DailyNews/July2001/AutismUniqueMercPoison.htm http://www.tuberose.com/Mercury.html http://en.wikipedia.org/wiki/Mercury_poisoning http://enhs.unm.edu/5200/mercury/metabolism.html

32. 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 .

33. LEAD POISIONING

34. SOURCES Paint and paint cans Greases, linoleum, leaded gasoline, solid lead, solder, roofing materials and industrial effluents Grass near busy streets Licking of discarded batteries, paints, 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

35. Acute toxicity The acute single oral lethal dose in animal Calves 50-600 mg/kg ( leadd or lead salts) Cattle 50-100 gm ) 600-800 mg/kg lead salt Horse and goats 20-40 gm ( lead acetate) 600-800 mg/kg (lead salts) Swine 10-25 gm ( lead acetate) Dogs 1—25 gm ( lead acetate) Fowl 16-600 mg/kg (lead salts)

36. 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

37. Absorption and Fate: 

38. CNTD….

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

40. A. Neurotoxic mechanism:

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

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

43. CNTD… D. Immunotoxicity :  Decreased production of Antibodies E. Nephrotoxicity :  Inhibition of cellular respiration Generalized dysfunction of renal tubular & energy dependent function

44. CNTD.. F. Endocrine toxicity : Decreased release of GH & insulin growth factors G. Reproductive toxicity :  Gametotoxocity (both male and female)

45. Clinical Symptoms:  Acute or Chronic IN Acute:  common in cattle  Bellowing, rolling eyes and frothy mouth  Excitation followed by quiscient phase  Muscular spasm, tetany and death

46. CHRONIC  IN Chronic:  Anorexia, constipation, recumbency and death (cattle and sheep)  Paralysis of limbs, anorexia, jaundice, nasal discharge, Roaring due to laryngeal muscle paralysis (Horse)

47.  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

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

49. 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

50. DIFFERENTIAL DIAGNOSIS  Hypomagnesemic tetany  Tetanus  Vit.A deficiency  Listeriosis  Barley poisoning  Encephalitis  Acute pancreatitis  Hepatitis  Encephalits DOG  Rabies  Distemper

51. 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

52. MERCURY POISONING

53. MERCURY INGESTION CHAIN

54. MERCURY POISONING There are 3 different forms of mercury - ELEMENTAL - INORGANIC - ORGANIC EACH A DIFFERENT TOXICOLOGICAL PROFILE:

55. SOURCES OF MERCURY Elemental mercury : Sphygmomanometers, thermometers, barometers Liquid at room temp – volatilises easily Inorganic mercury: Traditional remedies ( ayurvedic , chinese ) Used in gold extraction, caustic soda manufacturing Rodenticides Organic mercury: Fungicides, seed dressings Methylmercury in fish

56. MERCURY ABSORPTION Inhalation : 60-80% Dermal : 3-15% GI Tract : Metallic <0.2% Inorganic 15% Organic 90 + %

57. Organic mercury poisoning: Rare … but severe Exposure: ingestion, topical or inhalation CNS Toxicity: poor concentration, fatigue, ataxia, tremor, constricted visual fields, coma & convulsions BM suppression Renal toxicity - dealkylation to inorganic form Poorer response to treatment

58. Inorganic mercury poisoning Gastrointestinal phase : Hg 2+ is a potent GI irritant gingivitis, stomatitis oesophageal, gastric, small and large bowel erosions haematemesis , bloody diarrhoea, CVS collapse Systemic toxicity : Hg 2+ inhibits sulphydryl enzymes hypotension, lactic acidosis Nephrotoxicity : Hg 2+ deposits in the tubules  ATN acute renal failure potentially leads to CRF in survivors

59. Elemental Mercury Inhaled Elemental Mercury (1) ACUTE Irritant respiratory effects: cough, dyspnoea pulmonary oedema, ARDS Metal fume fever: pyrexia, cough, malaise, flu-like symptoms CNS features: confusion, emotional lability , psychoses convulsions, CNS depression & coma Renal effects: rarely ARF (oxidation to Hg 2+ )

60. Inhaled Elemental Mercury (2) CHRONIC ‘ Erethism ’ TREMOR, dysarthria peripheral neuropathy, sweating personality change Stomatitis , gingivitis Chronic renal impairment

61. Diagnosis of Mercury poisoning Blood mercury: only really useful acutely normal <10µg/l symptoms with blood mercury >150-200µg/l Urine mercury probably the most reliable indicator normal <10µg/l symptoms with urine mercury >100-150µg/l U&E Radiology: for elemental ingestion/aspiration/injection

62. Treatment of Mercury poisoning Remove from source Supportive care particularly important with inhalation DMPS Chelation (2,3-Dimercapto-1-propanesulphonate) Chelation therapy of choice for mercury For both acute and chronic mercury poisoning For all forms of Hg (inorganic > metallic >> organic ) - Indications: symptomatic patients blood/urine mercury persistently > 100 - 150 m g/l