Metal toxicity (Arsenic, Lead, Mercury)

Metal toxicity ( Arsenic, Lead, Mercury)

1. METAL TOXICITY

2. INTRODUCTION A metal (from Greek μέταλλον métallon , "mine, quarry, metal") is a material that , when freshly prepared, polished, or fractured, shows a lustrous appearance, and conducts electricity and heat relatively well. Metals are typically malleable (they can be hammered into thin sheets) or ductile (can be drawn into wires ). A metal may be a chemical element such as iron; an alloy such as stainless steel; or a molecular compound such as polymeric sulfur nitride.

3. METALS Typical physical properties of metals High melting points. G ood conductors of electricity. G ood conductors of heat. High density. M alleable . D uctile .

4. Toxicity of metals Metal toxicity or metal poisoning is the toxic effect of certain metals in certain forms and doses on life. Some metals are toxic when they form poisonous soluble compounds. Certain metals have no biological role, i.e. are not essential minerals, or are toxic when in a certain form . 1 ) In the case of lead, any measurable amount may have negative health effects . 2 ) Often heavy metals are thought as synonymous, but lighter metals may also be toxic in certain circumstances, such as beryllium and lithium. Not all heavy metals are particularly toxic, and some are essential, such as iron. The definition may also include trace elements when in abnormally high doses may be toxic. An option for treatment of metal poisoning may be chelation therapy, which is a technique which involves the administration of chelation agents to remove metals from the body.

5. Toxicity of metals 3. Toxic metals sometimes imitate the action of an essential element in the body, interfering with the metabolic process resulting in illness. Many metals, particularly heavy metals are toxic, but some heavy metals are essential, and some, such as bismuth, have a low toxicity. Most often the definition of toxic metals includes at least thallium, cadmium, manganese, lead, mercury and the radioactive metals . 4. Metalloids (arsenic, polonium) may be included in the definition. Radioactive metals have both radiological toxicity and chemical toxicity. Metals in an oxidation state abnormal to the body may also become toxic: chromium(III) is an essential trace element, but chromium(VI) is a carcino gen.

6. Toxicity of metals 5. Toxicity is a function of solubility. Insoluble compounds as well as the metallic forms often exhibit negligible toxicity. The toxicity of any metal depends on its ligands. In some cases, organometallic forms, such as methyl mercury and tetraethyl lead, can be extremely toxic. In other cases, organometallic derivatives are less toxic such as the cobaltocenium cation. 6 . Decontamination for toxic metals is different from organic toxins: because toxic metals are elements, they cannot be destroyed. Toxic metals may be made insoluble or collected , possibly by the aid of chelating agents, or through bioremediation. Alternatively , they can be diluted into a sufficiently large reservoir, such as the sea, because immediate toxicity is a function of concentration rather than amount.

7. FACTORS INFLUENCING THE TOXICITY Of METALS The factors can be divided into 1.B iotic and 2.A biotic . 1.The biotic factors includes : Tolerance, size and life stages, species, and nutrition related to the test organisms

8. FACTORS INFLUENCING THE TOXICITY Of METALS 2.The abiotic factors includes : Organic substances, pH, Temperature , A lkalinity H ardness , I norganic ligands, I nteractions , S ediments and others

9. ARSENIC TOXICITY

10. Introduction The contamination of groundwater by arsenic in Bangladesh is the largest poisoning of a population in history, with millions of people exposed. In Bangladesh, arsenic contamination of water in tube-wells was confirmed in 1993 in the Nawabganj district . Since the 1970's, the people have been drinking and cooking with well water that exceeds the permissible arsenic limit.

11. What is Arsenic ? The word arsenic comes from the Persian word " zarnikh," meaning " yellow orpiment," which the Greeks adopted as " arsenikon, " according to the Los Alamos National Laboratory. The word is also related to the Greek word " arsenikos," meaning " masculine" or "potent." The Latin word for it became " arsenicum. “ Arsenic is typically considered a heavy metal . It is ubiquitous in the environment Arsenic is a natural component of the earth’s crust and is widely distributed throughout the environment in the air, water and land. It is highly toxic in its inorganic form. This component is extremely hard to convert to water-soluble or volatile products. Chemical Formula = As Atomic Number =33 Molecular Weight = 74.92 gram Color = lead gray, gray, white Nonmagnetic

12. C ontinued……. Arsenic is a metalloid element , meaning that it displays some properties of both a metal and a nonmetal. Poor conductor of heat & electricity Solubility Elemental arsenic is not soluble in water. In water, arsenic is mostly found in inorganic forms as oxyanions of trivalent arsenite (AsIII) or pentavalent arsenate (AsV). S ources Natural Activities : Soil, Air, Water, Food. Human Activities: Fruit sprays, Sheep-dips, Weed-killers, Rat poisons, Fly papers, Calico printing, Taxidermy preserving, timber against white ants, Cigarettes Smoking, Antifungal wood, Preservatives.

13. Continued…… Most likely to form compounds with oxygen, Chlorine, sulfur, carbon, hydrogen gold and iron. Types Arsenite There are two types of arsenic : 1.Inorganic 2.Organic Inorganic arsenic is formed when arsenic combines with metals and elements other than carbon . Inorganic arsenic is the type found in contaminated drinking water , and is the most harmful type of arsenic. (ex. Arsenite) This type of arsenic is also found in rice, cereal grains and other foods. Organic arsenic: usually with carbon or hydrogen . (ex. Di methyl arsonic acid)

14. Forms of arsenic It generally occurs in two forms (valences or oxidation states): pentavalent arsenic (also known as As (V), As(+5), or arsenate) and trivalent arsenic (also known as As (III), As(+3), or arsenite). In natural ground water, arsenic may exist as trivalent arsenic , pentavalent arsenic , or a combination of both. The most common As(+3) inorganic forms are arsenic trioxide,sodium arsenite and arsenic trichloride. The most common As(+5) inorganic forms are arsenic pentaoxide, lead arsenate, and calcium arsenate. Organic forms may be +3 or +5 As and may occur as methylated forms due to methylation by organisms in soil, fresh water and sea water. Arsenite the (trivalent form) has a slower excretion rate compared to arsenate the (pentavalent form) and organic arsenic, which may contribute to arsenite's increased toxicity . So, trivalent forms of As are the principal toxic . Pentavalent forms have little or no effect. However, +5 forms can be converted to +3 forms in vivo.

15. Concentration Mainly result of natural geological processes(ex. Natural mineral weathering). Arsenic is present in more than 200 mineral species, the most common of which is arsenopyrite. Natural Concentrations I gneous rocks : < 1 to 15 mg As/kg, with a mean value of 2 mg As/kg S andstone and limestone : < 1-20 mg As/kg Contaminated soil :upto 500 mg/kg Natural water: 1-2mg/kg Air: 0.2-1.5 ng/m3 for rural areas 0.5-3 ng/m3 for urban areas < 50 ng/m3 for industrial site Safe intake rates for humans Approximately 150µg/kg/day for an average, healthy person Some sensitive people can see side effects at 20µg/kg/day Arsenic intake limits EPA has a maximum concentration limit(MCL) of 20µg/L World Health Organization (WHO) has a limit of 10 µg/L

16. Statistical Results of Arsenic poisoning Total number of districts in Bangladesh 64 Total area of Bangladesh 147,570 km2 Total population of Bangladesh 153 million WHO standard for arsenic in drinking water 0.01 mg/L WHO-recommended maximum permissible limit for arsenic in drinking water 0.05 mg/L Bangladesh standard for arsenic in drinking water 0.05 mg/L Total number of tube-wells in Bangladesh 5 million Total number of affected tube-wells 3 million Number of districts surveyed for arsenic contamination of groundwater 64 Number of districts having arsenic above 0.05 mg/L : 61 Population at risk > 80 million Population potentially exposed > 30 million Number of patients suffering from arsenicosis > 38,000 Sources : Chakraboti et al.2010; Daily star 2008;Escobar et al.2006; Farque and Alam 2002; Fazal et al. 2001; ITNC 2008; Safiuddin and Karim 2003; Safiuddin et al. 2011

17. Toxicokinetics It can be inhaled and absorbed the skin or through GIT after ingestion. Once absorbed arsenic rapidly combines with the globins portion of haemoglobin and therefore localize in the blood, within 24 hours it redistribute to liver, kidney, spleen, lung and GI tract, with lesser accumulation in the muscle and nervous tissue. Excreted mainly through kidneys as methylated arsenic and some part by faces, sweat, and bile. Methylated forms have a longer half life . Dimethyl-As the principal detox product. It is excreted in stomach and intestine even when given by other routes (enterohepatic circulation). It becomes fixed in cancellous tissue or bones. Replaces phosphorous. Also concentrates in nails and hairs. Human milk contains some As and As can be transferred across the placenta. It is a known carcinogen: skin, liver, bladder.

18. Toxicokinetics

19. Cellular Targets Sulfhydryl containing proteins and enzymes systems are altered by exposure to As compounds . Affects mitochondrial enzymes. Mitochondria accumulate As. Succinic dehydrogenase activity is inhibited and oxidative phosphorylation is uncoupled . Interferes with cellular respiration: As chelates with alpha lipoic acid which is an essential cofactor for pyruvate dehydrogenase ,an enzyme required for energy production in the Krebs cycle .

20. Cellular targets It is a capillary poison: increased permeability causes tissue edema and hemorrhage . Hyperaemia and hemorrhage in the intestine . Interferes with glucose uptake, gluconeogenesis , fatty acid oxidation, Fatty degeneration of liver . Renal tubular necrosis. Peripheral nerves show axonal neuropathy: depression of nervous system . Some As forms, mimic the phosphate anion in cells . Arsenolysis is a major form of toxicity in which the arsenic anions can substitute for phosphate would disrupt a number of metabolic reactions that require phosphorylation.

21. Cellular targets

22. Medical Effects of Arsenic Arsenic poisoning is called Arsenicosis. Arsenicosis is caused by exposure over a period of time to arsenic in drinking water. It may also be due to intake of arsenic via food or air. Mode of testing people for arsenicosis Recent exposure: Urine Urine: Proteinuria, cast and albuminuria are there. Arsenic poisoning is usually diagnosed with the urine test for arsenic as arsenic ions are present very shortly after ingestion. A urinary excretion of arsenic >100mg/24 hours is regarded as indicative of exposure to a potentially toxic amount of arsenic. Monomethylarsine and dimethylarsine are present in the urine 24 hours after ingestion acute poisoning.

23. Medical Effects of Arsenic Instant exposure: Blood Blood: 0.9 µg/dl, monocytic hypochromic anaemia, leukocytosis and mild eosinophilia. Chronic exposure: Hair, nails and skin( usually caused by water contamination) Hair and nails samples containing >300 ppm or 100 mg of arsenic per 100 gm of specimen are diagnostic of arsenic poisoning. Liver function test: serum alkaline phosphatase and bilirubin is raised and there is excretion of urobilinogen in the urine.

24. Medical Effects of Arsenic Illness resulting from Aresenicosis Various Cancers: Skin,lung,bladder,kidney,liver Heart attacks and strokes Melanosis : Spotting of the skin, blemishes etc. Keratosis: Hardening of palms and soles,ulcers Hepatomegaly: liver enlargement Splenomegaly: Spleen enlargement Ascitis : Abdominal fluid Death Social problems Arsenicosis victims are rejected from society.

25. Figure : Arsenic effects on human

26. Non cancer Effects Acute effects : Large doses (70-180 mg)can be fatal . Sensory loss in Peripheral neuropathy (degeneration of axons) Anemia Renal and liver dysfunction Skin pigmentation EKG abnormalities Severe GI effects Chronic Toxicity: Humans Vascular • Poland –Vintners – cases of gangrene • Nervous system –Peripheral neuropathy – legs and arms • Cranial nerves –Loss of hearing in Japanese infants Liver injury is also characteristic of chronic exposure.

27. Cancer Effects Cancers Associated with Exposure to Arsenic in Drinking Water Cancer: Long-term Exposure (20-40 yrs) Skin cancer (Taiwan) Hyperkeratosis and Hyper pigmentation. Basal cell carcinoma and squamous cell carcinomas. Blackfoot Disease (Mainly Taiwan) Lung cancer (Taiwan, Japan, & Chile) Bladder cancer (Taiwan, Argentina) In a study conducted in the United States ,no reports of bladder cancer with average 40 µg of As/L . In a case control study in conducted in Western United States, it was found that smoking can elevate bladder cancer risk when drinking water has As levels near 200 µg/day.

28. Arsenicosis pictures

29. Acute T oxicity (upto 7 days) Patient experience a Metallic taste Garlicky odour in the breath Xerostomia Dysphagia. Increased salivation Excessive thirst. Severe nausea Vomiting. Colicky abdominal pain and Profuse diarrhea. The stool are dark colored and bloody and Later on Colorless, Odorless, and Watery resembling rice watery Due to vasodilatation with transudation of fluid into the bowel lumen in addition to mucosal vesicle formation and sloughing leading to increased peristalsis.

30. Acute Toxicity (upto 7 days) Vomiting is Projectile , Dark brown or yellow color and Contain stomach contents, Blood and mucus Purging, tenesmus , pain and irritation around anus. Severe headache, vertigo, periorbtal edema, skeletal muscles cramps. Renal damage manifested as Oligourea , Proteinurea , and Haematuria . Fatty infiltration of liver Delayed loss of hair, skin eruptions

31. Sub Acute Toxicity( 1 week to 1 month) Peripheral neuropathy Cardiac problems- dysrhythmias , hypotension GI symptoms- nausea , vomiting , abdominal pain and diarrhea. Pigmentation changes, keratosis Renal insufficiency Hemolysis, Anemia, Confusion Headache .

32. Chronic toxicity(1 month to years) 1.First stage : GIT disturbances Loss of weight Loss of appetite and salivation Colicky pain and constipation Vomiting and diarrhea 2.Second stage : Catarrhal stage Dryness and i tching of the skin Voice is harsh and husky Photophobia and conjunctivitis Liver is enlarged and cirrhotic Chronic nephritis

33. Chronic Toxicity(1 month to years) 3.Third stage: skin eruptions Erythematous flushing cauesd by cutaneous capillary dilation,generalised and localised. Rain drop type of pigmentation of the skin involving the covered part of the body such as flexors, nipples, lower abdomen, temples and eyelids. Epithelial hyperplasia Hyperkeratosis then occurs with desquamation of the palm and soles 4.Fourth stage :Nervous disturbance Peripheral neuritis with glove and stocking type of anesthesia resembling alcoholism. Encephalopathy may be seen in some cases. The predominant clinical feature of neuropathy are parasthesia,numbness,pain on particularly on the soles of the feet.

34. Treatment 1.Supportive care 2.GI decontamination Stomach wash should be done with milk and warm water. For Gastric Lavage 1% sodium thiosulphate in water is helpful . Nasogastric suction Whole bowel irrigation until radiopaque clears. Demulcent such as ghee and barley water are given. Purgatives like Castor oil and magnesium sulphate is administered to diminish intestinal absorption of arsenic

35. Treatment 3.Chelation BAL 3-5mg/kg every 4 hrs DMSA 10mg/kg PO for 5 days Oral Penicillamine 100mg/kg. Body wt. In 4 divide doses in 24 hours for 4-8 days after initial 12-48 hours of B.A.L therapy . 4. Morphine is given to relieve pain . 5.Saline is administered i.v for dehydration and enuresis . 6.To relieve cramps, massage employed body temperature to be maintained . 7. Hemodialysis institute of renal failure .

36. Control and prevention Control And prevention Emergency Pond –sand filter . Dug wells . Deep hand tube wells . Rainwater harvesting

37. Control and prevention Control And Prevention Long term Drinking water arsenic concentration below 10μg/L – Rain water collection. – Regular testing of water . – Installing arsenic removal system . • Occupational exposure to low level • Public awareness and education. • Monitor high risk population for early signs

38. Introduction Mercury is a heavy metals means a metal of relatively high density or of high relative atomic weight . Mercury toxicity( also known as hydrargyria or mercurialism ) is a type of metal poisoning caused by exposure to mercury or its compound mercury (Hg). Heavy metal occurring in several forms, all of which can produce toxic effects in high enough doses.

39. Forms of mercury Mercury exists in three chemical forms 1.Elemental mercury (Hg˚) 2.Mercurous inorganic mercury(Hg+) 3.Organic form (methyl mercury, ethyl mercury)

40. Elemental Mercury Most volatile Exist in liquid or vapour form . Inhalated and absorbed into lung (80%) and GIT(0.01%) and can cross the blood brain barrier or can cross the placenta . Most common form is amalgam restoration.

41. Elemental mercury Elemental mercury is used in T hermometers, Barometers,and P ressure-sensing devices . Fig: Elemental mercury

42. Inorganic mercury Mainly in liquid form . Normally minded as inorganic sulfide ore . Can also exist in other form than sulfide . Irritating in nature . Main route of entry is through lung(80%). Due to absence of fully formed blood brain barrier it has been found in neonatal brain .

43. Inorganic mercury Inorganic mercury form complexed with gluthione in the liver and secreted in the bile cysteine mercury or gluthione mercury complex . Sources /uses : In the past in laxatives ,skin-lightening creams and soaps ,and in latex paint

44. Organic mercury Mainly in the form of methyl mercury . Toxic in nature Main route of entry is absorption through GIT through food . Lipophilic in nature, distributed through body, readily cross BBB and placental barrier. Accumulate in brain and kidney. Sources /Uses: In fungicide and pesticide, fish poultry etc.

45. Methyl mercury

46. Sources of mercury toxicity Water Sea food Thermometer Batteries Dental amalgams Jewelry industry Neon lamps Paints Cosmetics such as skin-lightening products

47. Mercury exposure 1.Dietary exposure: Consumption of fish is the major route of exposure to methylmercury ,deposited in fat and cooking the fish does not lower the methyl mercury content . Inorganic mercury compounds are also found in food. The amount of ingested are far below known toxic levels .

48. Mercury exposure 2.Occupational exposure : Inhalation of mercury vapor can occur form the working environment ,as in the chloralkali industry, where mercury is used as a cathode in the electrolysis of brine . Occupational exposure may also occur during manufacture of a variety of scientific instruments and electrical control devices . Used in dentistry where mercury amalgams are used in tooth restoration

49. Mercury exposure 3.Medicinal exposure : Mercury was an important constituent of drugs like diuretics,antiseptics,skin ointments, and laxatives. These uses have largely been replaced by safer drugs . Thimerosal contains the ethyl mercury radical attached to the sulfur group of thiosalicylate (49.6%mercury by weight as ethyl mercury )and has been used as a preservative in many vaccines since 1930s . The use of mercury amalgam in dental restoration releases mercury vapor in the oral cavity and can results in increases mercury body burden.

50. Mercury exposure 4.Accidental exposure : Fatal mercury poisonings come mainly from accidental exposure . Elemental mercury spills can occur by broken of elemental mercury containers, Medicinal devices, barometers and from melting tooth amalgam fillings to cover silver. Inhalation of large amount of mercury vapor can be deadly .

51. Toxicokinetics Elemental mercury vapour is well absorbed by the lung. Inorganic mercury are absorbed by the gut (7-15%).These cause most cases of mercury poisoning .Systemic effects are possible from skin and lung exposure . Organic forms of mercury are extremely well absorbed across the gut though dermal absorption does not appear to be great . Organic mercury can cross BBB and placental barrier ; inorganic mercury cannot cross BBB or placental barrier and accumulate in kidney . Excretion occurs in the urine and faeces

52. Mechanism of mercury toxicity High –affinity binding of divalent mercury to sulfhydral groups of protein in the cells is an important mechanism of producing non-specific cell injury or even cell death . Other general mechanisms ,such as The interruption of microtubules formation . The inhibition of enzymes ,oxidative stress . Interruption of protein and DNA synthesis, and autoimmune responses . Mercury causes over expression of metallothionein and glutathione system –related gene in rat tissues .

53. Mechanism of mercury toxicity Fig: Mechanism of mercury toxicity

54. Mercury Poisoning, Diagnosis, and Treatment

55. Case Study 01 From 1932 to 1968, Methyl Mercury was released into the sea around the city of Minamata, Japan. The Toxic bioaccumulated in fish, which when eaten by the local population caused the largest case of mercury poisoning known. Minamata disease caused the deaths of over 1000 people and permanently disabled a great many more.

56. Case study 02 Another case of widespread mercury poisoning occurred in rural Iraq in 1971-1972, when grain treated with a methyl mercury-based fungicide was used by the rural population to make bread.

57. Case study 03 In December 1997, a chemistry professor, Karen Wetter Hahn, at Dartmouth College was contaminated with dimethylmercury when she spilled a drop on her latex glove. China's first emperor of unified China, Qin Shi Huang Di, was driven insane and killed by mercury pills intended to give him eternal life .

58. Acute poisoning Inhalation of mercury vapors causes Chemical pneumonia, Pulmonary oedema, Gingivostomatitis, Increased salivation CNS symptoms like Ataxia, Restriction of field of vision, Paresis, Delirium, Polyneuropathy.

59. Swallowing the Poison The signs and symptoms start immediately after swallowing the poison: Acrid metallic taste in mouth. Feeling of constriction or choking of throat. Hoarseness of voice, there is difficulty in breathing and mouth and tongue are corroded and swollen with grey white coating . Hot burning pain in mouth, stomach and abdomen. Stools are blood stained, urine is suppressed and scanty, contain blood and albumin is accompanied by necrosis of renal tubules and damage to the glomeruli. Pulse is quick small and irregular, there is circulatory failure.

60. Swallowing the Poison Thrombocytopenia and bone marrow depression . When injected intravenously, it produces dyspnea, cyanosis, hypotension and convulsions, death may be due to an anaphylactic shock or ventricular fibrillation. After 1-3 days- renal tubular necrosis l/t polyuria, albuminuria, uremia and acidosis and in GIT membranous colitis l/t dysentery may develop.

61. Diagnosis 1. F.D . 1-4 gm of mercuric chloride, 10-60 mg/kg of methyl mercury 10 mg/ m3 of Hg vapor. 2. F.P .: 3-5 days 3. Blood Hg level > 3.6 μg /dl 24 hr urine excretion >15 μg/dl. 4. Assessed by atomic absorption spectrophotometer .

62. Treatment Reduce exposure Albumin such as eggs, skimmed milk, vegetable glutens, to ppt Hg. Gastric lavage with 250 ml of sodium formaldehyde sulphoxylate. Sodium formaldehyde sulphoxylate is the chemical antidote that reduces the perchloride to metallic mercury. 5-10% sulphoxylate and 5% sodium bi carbonate is used for stomach wash of which 200ml should be left in stomach. This is beneficial if given in the first half an hour.

63. Treatment If colitis has developed, high colonic lavage as1:1000 solution is to be given with 1: 1000 solution of sulphoxylate BD B.A.L is to be given in the dose of: 3-5mg/kg 4 hourly for 2 days. 2.5 mg/kg 6 hourly for1 day. 2.5 mg/kg twice daily according to the severity. For diuresis , 5-10% glucose is used in normal saline.

64. Chronic Mercury Poisoning/ Hydragyrism Workers may get poisoned due to vapors or dust. When small doses are taken for prolonged time or used as ointment for long period. The signs and symptoms of chronic mercury start at a blood level 100 mg/ml. Patient is symptomatic at daily urinary excretion more than 300 mg/ml

65. Signs and symptoms Excessive salivation with swollen and painful salivary glands. Foul smelling breathing, inflamed and ulcerated gums with brownish blue line and loosening of teeth. Necrosis of jaw that should be differentiated from phosphorous poisoning. Mercura lentis: A brownish reflex from the anterior lens capsule of both the eyes is see when observed in slit lamp in person exposed to mercury vapors for some years. It is bilateral and has no effect on the visual acuity.

66. Signs and symptoms (Cont’d) ACRODYNIA (PINK DISEASE): There is generalized rashes over the body. This results from chronic exposure to mercury in any forms. Erythematous, eczematous (watery and weeping) popular type of skin lesion. Mostly in the hands and feet accompanied with thickening of skin are produced.

67. Signs and symptoms (Cont’d) Mercurial tremors (Hatter’s shake or glass blower’s shake): These are moderately coarse tremors starting from hands than to the lips and tongue and finally arms and legs occur (DANBURY TREMORS). These are detected early in the writing. These are excited by voluntary movements and are absent during sleep. These are interspersed with jerky movements, in coordination of movements, increased deep reflexes, paresis of limbs and peripheral neuritis. The tremors should be differentiated from thyrotoxicosis in which there is presence of fine tremors, exophthalmos , raised pulse and goiter.

68. Signs and symptoms (Cont’d) Mad hatter disease, mad hatter syndrome: Especially in the 19th century, inorganic mercury in the form of mercuric nitrate was commonly used in the production of felt for hats. During a process called carroting, in which furs from small animals such as rabbits, hares or beavers were separated from their skins and matted together, an orange-colored solution containing mercuric nitrate was used as a smoothing agent. The resulting felt was then repeatedly shaped into large cones, shrunk in boiling water and dried. In treated felts, a slow reaction released volatile free mercury. Hatters (or milliners) who came into contact with vapors from the impregnated felt often worked in confined areas.

69. Signs and symptoms (Cont’d) Mental symptoms: ERETHISM is seen in the person working in mirror manufacturing factory. Feature of insanity such as shyness, timidity, irritability , loss of confidence, mental depression, loss of memory, insomnia, hallucinations and delusion develop in the workers. Sometimes suicidal melancholia or manic-depressive psychosis (Mad hatter) develops.

70. Minamata Disease Chronic mercury intoxication d/t consumption of contaminated fish. Symptoms : Disturbance in hand co-ordination, Gait and speech, Chewing and swallowing difficulty, tremors, rigidity, Seizures and clouding of consciousness.

71. Minamata Disease Treatment Removal of the individual from the source of exposure. Plenty of milk should be given. Mouth wash by borax. Saline purgative to be given. Periodic medical checkup for workers.

72. Medico legal Aspects Mercuric chloride causes accidental poisoning when it is widely used as, disinfectant and antiseptic, contraceptive vaginal tablets, for anti-syphilitic treatment. Phenyl mercuric acetate jelly leads to poisoning when used as a contraceptive. Mercury is not a constituent of human body; hence its presence indicates that it must have been introduced into the system. 5-150 mg/ 100gm is normally presenting the tissues like kidney and liver.

73. Introduction The word “lead” is of an Anglo-Saxon heritage and stands for the element, initially known by the Latin word plumbum (Pb). The Latin word serves as the root of plumbism, which means “lead poisoning ”. Lead is a soft, blue-gray metal, usually found as lead compounds, combined with other elements. Much of its presence in the environment stems from. Its historic use in paint and gasoline in the United States, Recycling operations, Ongoing or historic mining/smelting, Commercial operations, and Lead contaminated consumer product

74. Forms of Lead 1)Elemental Lead 2)Organic Lead 3)Inorganic Lead

75. Properties of Lead 1) Lead is a- Very soft, Dense, and Ductile (moldable) metal . 2 ) Lead is very stable and resistant to corrosion, although acidic water may leach lead out of- Pipes, Fittings, and Solder (metal joints ). 3 ) Lead is a poor conductor of electricity and an effective shield against radiation.

76. General issues Lead is the most toxic metal . There is no biological need for lead . Lead is not biodegradable . The concern for ecotoxicity of lead are increasing day by day . Most susceptible populations are childrens , infants and neonatal.

77. Lead Exposures

78. Lead Exposures I ngestion Lead exposure in the general population (including children) occurs primarily through ingestion, making it the route that most commonly leads to elevated BLLs . Lead paint is the major source of higher lead level exposures in children in the US. As higher lead content paint- Deteriorates, Peels, Chips, Or crumbles due to friction Ingestion of contaminated Food, Water, or Alcohol may be significant for some populations . When fine particulate lead is inhaled, it can be absorbed directly through the lungs.

79. Lead Exposures Inhalation Inhalation is the second major pathway of exposure for the general population in the United States. The amount absorbed from the respiratory system depends on particle size, respiratory volume, amount of deposition, and the mucociliary clearance of the inhaled lead . Almost all inhaled lead is absorbed into the body. Since leaded gasoline additives were phased out beginning in the 1970s and control measures were implemented in industries. Leaded gasoline is still used in only a handful of countries, but the resulting emissions pose a major public health threat. Inhalation may be the primary route of exposure for some workers in industries that involve lead. Inhalation may be the primary route of exposure for adults involved in home renovation activities, and hobbies like lead glass making, stained glass making/soldering. Lead is a component of tobacco and tobacco smoke, and smokers have higher blood lead levels (BLLs) than do nonsmokers. Second hand smoke may contribute to increased BLLs in U.S. children.

80. Lead Exposures Dermal Dermal exposure plays a role for exposure to organic lead among workers, but is not considered a significant pathway for the general population . Organic lead may be absorbed directly through the skin . Organic lead (tetraethyl lead) is more likely to be absorbed through the skin than inorganic lead . Dermal exposure is most likely among people who work with lead or materials that contain lead.

81. Lead Exposures Endogenous Exposure Endogenous exposure to lead may contribute significantly to an individual's current BLL. Trans-placental exposure to the unborn child can happen if the mother is exposed to lead . Once absorbed into the body, lead may be stored for long periods in mineralizing tissue ( e.g. teeth and bone)

82. Symptoms The symptoms of lead poisoning depend on the degree and length of exposure but may include: • Anemia • Loss of appetite • Irritability • Fatigue • Abdominal pains • Nausea • Vomiting • Loss of physical coordination and balance (ataxia) • Muscular weakness • Seizures • Coma. • Reduced IQ • Slowed body growth • Hearing problems • Behavior or attention problems • Failure at school • Kidney damage • Irritability • Aggressive behavior • Low appetite and energy • Difficulty sleeping • Headaches • Reduced sensations • Loss of previous developmental skills

83. TOXICOKINETICS

84. ABSORPTION Lead absorption depends on a variety of factors, including particulate size, route of exposure, nutritional status, health, and age of the individual . Lead absorption can be impacted by route of exposure and is inversely proportional to the exposure particle size . Adults typically absorb up to 20% of ingested inorganic lead after a meal and up to 60-80% on an empty stomach [ATSDR 2010 ]. Children absorb about 50% of ingested lead after a meal [ATSDR 2010] and up to 100% on an empty stomach . Most inhaled lead in the lower respiratory tract is absorbed . Most of the lead that enters the body is excreted in urine or through biliary clearance (ultimately, in the feces).

85. DISTRIBUTION Lead is distributed to many tissues and organ systems of the body. It's important to remember that lead cannot be destroyed or changed to something else in the body. The amount of lead stored in the body has been described as the "body burden" of lead. Among adults over 95% of the total body stores of lead are found in bone. For children about 70% of lead is stored in bone. This lead is not simply stored away in bone forever, but moves in and out as the body functions normally. For example, as children grow their bones restructure to permit normal shapes as they develop. Half-life of lead in blood is 20 years. Lead crosses placenta to fetus to match levels in maternal blood.

86. ELIMINATION METABOLISM : Inorganic lead, the most common form of lead, is not metabolized in the liver. Nearly all organic lead that is ingested is absorbed. Organic lead compounds are metabolized in the liver . EXCRETION: Most of the lead that enters the body is excreted in urine or through biliary clearance. Renal excretion of lead is usually through glomerular filtrate with some renal tubular resorption. Fecal excretion via biliary tract accounts for one-third of total excretion of absorbed lead.

87. Toxicity of Lead 1)Health effects of lead Lead can cause several unwanted effects, such as : – Disruption of the biosynthesis of hemoglobin and anemia – A rise in blood pressure – Kidney damage – Miscarriages and subtle abortions – Disruption of nervous systems – Brain damage – Declined fertility of men through sperm damage – Diminished learning abilities of children – Behavioral disruptions of children, such as aggression, impulsive behavior and hyperactivity. Lead can enter a fetus through the placenta of the mother. Because of this it can cause serious damage to the nervous system and the brains of unborn children.

88. Toxicity of Lead 2)Environmental effects of lead poisoning Lead can end up in water and soils through corrosion of leaded pipelines in a water transporting system and through corrosion of leaded paints. It cannot be broken down; it can only convert to other forms . Lead accumulates in the bodies of water organisms and soil organisms. These will experience health effects from lead poisoning . Soil functions are disturbed by lead intervention, especially near highways and farmlands, where extreme concentrations may be present. Soil organisms than suffer from lead poisoning, too . Lead is a particularly dangerous chemical, as it can accumulate in individual organisms, but also in entire food chains.

89. Effects of lead on the human body Nervous system Lead disrupts the normal physiologic processes in the CNS due to the similarity of ionized lead to calcium, as both are divalent cations. However, lead can disrupt the physiologic effects of calcium at concentrations lower than those of calcium. Lead causes an inappropriate release of neurotransmitter at rest and competes with calcium to interfere with evoked neurotransmitter release. Chronic lead nephropathy or chronic tubulointerstitial nephritis (as seen on biopsy) occurs in the setting of long-term lead exposure and is often associated with hypertension and gout . Problems with thinking (cognition); Difficulties with organizing actions, decisions, and behaviors (executive functions); Abnormal social behavior (including aggression); and Difficulties in coordinating fine movements, such as picking up small objects

90. Effects of lead on the human body Cardiovascular system C ardiovascular disturbances linked to lead poisoning include the following: ECG disturbances, Heightened catecholamine sensitivity, Altered myocardial contractile responsiveness to inotropic stimulation, Hypertension, Hypercholesterolemia, Atherosclerosis, Increased vascular reactivity to alpha-adrenergic agonists, Ischemic coronary heart disease, Myocarditis, Cerebrovascular accidents, and Peripheral vascular disease.

91. Heme synthesis inhibition One of the mechanisms of lead induced anemia is, specifically, inhibition of heme synthesis. Lead inhibits three enzymes in the heme biosynthesis pathway-δ- aminolevulinic acid dehydratase (ALAD), coporphyrinogen oxidase, and ferrochelatase- but its effects on ALAD are the most profound.

92. Effects of lead on the human body Renal System In the kidneys, lead can give rise to Fanconi -like syndromes , chronic (lead) nephropathy, and gout due to lead-induced hyperuricemia. Lead impairs heme synthesis and therefore can give rise to anemia . Proximal tubular nephropathy, Glomerular sclerosis, and Interstitial fibrosis

93. Effects of lead on the human body Reproductive system Lead not only reduces the sperm count in males but also increases abnormal sperm frequencies as well. At present, its role in male or female infertility is controversial. There is an association between high lead exposure levels and adverse outcomes in pregnancy, but this association becomes equivocal women exposed to lower environmental levels of lead are evaluated. Reproductive effects examined in the literature include Sperm count, Fertility, and Pregnancy outcomes. Carcinogenesis Lead has been classified as group 2β carcinogen in animals, but data to support its role in human carcinogenesis are insufficient.

94. Treatment Chelation therapy is warranted in workmen with BLL>60µg/ dL . The oral chelating agent EDTA can be used. Oral Dimercaptosuccinic acid(DMCA) has advantages over EDTA and is effective in temporarily reducing BLL. However,DMSA does not improve long-term BLL in children, nor reduce brain lead levels beyond the cessation of lead exposures alone. The first step should be the removal from the exposure. Chelation therapy is being used for anyone showing severe symptoms, which is usually associated with BLL’s above 100 μg /dl. The therapy works by reducing lead in blood and soft tissues. The primary treatment for mild lead poisoning is to stop the exposure. Removal of the source of lead is critical to reducing blood lead levels. For Classes I through III, ceasing exposure to lead may be sufficient to reduce lead in your body. Children in this case may need to be retested a month after being removed from the source of the lead.

95. Prevention Following these suggestions can reduce lead exposure : • Clean the house regularly and ensure there is no build-up of dust. Wet dust floors, ledges, window sills and other flat surfaces . • Discourage your toddler from playing in or eating dirt and from putting dirty fingers or toys in their mouth. Wash toys and dummies frequently. Wash children’s hands and faces before they eat or nap . • Wash fruit and vegetables before eating . • Wash family pets frequently . • Ensure your child’s diet is adequate in calcium and iron and avoid high fat diets because they encourage lead absorption. Also, ensure young children have regular and frequent meals, as more lead is absorbed on an empty stomach . • Ensure that children do not have access to peeling paint or chewable surfaces painted with lead-based paint, such as old cots and window sills . • Old toys may contain lead-based paint. If you are unsure, take the safe option and do not give them to children to play with.

96. LIST OF MEMBERS OF GROUP 5 Rupa Akter (1116) Laila Akter Tania (1120) Fatema Tuz Zohora (1122) Azima Akter Pranty ( 1131) Pranto Chandra Malo ( 1146) Hridoy K Dey (1155 ) Mahmudul Hasan Anik (2399)