SEMINARSEMINAR

HEAVY METAL HEAVY METAL TOXICITYTOXICITY

PRESENTED BY PRESENTED BY

ANUJ M . PANDEYANUJ M . PANDEY

INTRODUCTIONINTRODUCTION• There are 35 metals that concern us because of occupational There are 35 metals that concern us because of occupational

or residential exposure; 23 of these are “or residential exposure; 23 of these are “Heavy MetalsHeavy Metals“.“.

• Small amounts of these elements are common in an Small amounts of these elements are common in an environment ,diet and are actually necessary for good health, environment ,diet and are actually necessary for good health, but large amounts of any of them may cause acute or chronic but large amounts of any of them may cause acute or chronic toxicity (poisoning). toxicity (poisoning).

• Heavy metal toxicity can result in damaged or reduced mental Heavy metal toxicity can result in damaged or reduced mental and central nervous function damage to blood composition, and central nervous function damage to blood composition, lungs, kidneys, liver, and other vital organs.lungs, kidneys, liver, and other vital organs.

• Allergies are not uncommon and repeated long-term contact Allergies are not uncommon and repeated long-term contact may even cause cancer .may even cause cancer .

DEFINITION:DEFINITION: ""Heavy metalsHeavy metals" are chemical elements with a " are chemical elements with a

specific gravity that is at least 5 times the specific gravity that is at least 5 times the specific gravity of water.specific gravity of water.

BENEFICIAL HEAVY METALSBENEFICIAL HEAVY METALS

In small quantities, certain heavy metals are nutritionally In small quantities, certain heavy metals are nutritionally essential for a healthy life. essential for a healthy life.

Some of these are commonly found naturally in Some of these are commonly found naturally in foodstuffs, in fruits and vegetables, and in commercially foodstuffs, in fruits and vegetables, and in commercially available multivitamin products.available multivitamin products.

Heavy metals are also common in industrial applications Heavy metals are also common in industrial applications such as in the manufacture of pesticides, batteries, such as in the manufacture of pesticides, batteries, alloys, electroplated metal parts, textile dyes, steel, and alloys, electroplated metal parts, textile dyes, steel, and so forth.so forth.

TOXIC HEAVY METALSTOXIC HEAVY METALS

Heavy metals become toxic when they are not metabolized by Heavy metals become toxic when they are not metabolized by the body and accumulate in the soft tissues.the body and accumulate in the soft tissues.

Heavy metals enter the human body through food, water, air, Heavy metals enter the human body through food, water, air, or absorption through the skin in agriculture and in or absorption through the skin in agriculture and in manufacturing, pharmaceutical, industrial, or residential manufacturing, pharmaceutical, industrial, or residential settings. settings.

Exposure to toxic heavy metals is generally classified as acute, Exposure to toxic heavy metals is generally classified as acute, 14 days or less; intermediate, 15-354 days; and chronic, more 14 days or less; intermediate, 15-354 days; and chronic, more than 365 days.than 365 days.

COMMONLY ENCOUNTERED COMMONLY ENCOUNTERED TOXIC HEAVY METALSTOXIC HEAVY METALS

ARSENICARSENIC

LEADLEAD

MERCURYMERCURY

CADMIUMCADMIUM

IRONIRON

ARSENICARSENIC

Most common cause of heavy metal poisoning in adults.Most common cause of heavy metal poisoning in adults.

Sources for arsenic are paints, red poisoning, smelting Sources for arsenic are paints, red poisoning, smelting process of copper, zinc and lead .process of copper, zinc and lead .

Symptoms of acute poisoning are sore throat , red skill , Symptoms of acute poisoning are sore throat , red skill , severe abdominal pain , vomiting and diarrhea.severe abdominal pain , vomiting and diarrhea.

Chronic exposure can lead to progressive peripheral and Chronic exposure can lead to progressive peripheral and central nervous changes.central nervous changes.

PHARMACOLOGICAL AND PHARMACOLOGICAL AND TOXICOLOGICAL EFFECT ON TARGET TOXICOLOGICAL EFFECT ON TARGET

ORGANSORGANS

Cardiovascular system :Cardiovascular system : Small doses of inorganic arsenic Small doses of inorganic arsenic induce mild vasodilatation. Larger doses evoke capillary induce mild vasodilatation. Larger doses evoke capillary dilation.dilation.

Gastrointestinal tract :Gastrointestinal tract : Small doses of inorganic arsenic Small doses of inorganic arsenic cause mild splanchnic hyperemia. Tissue damage and bulk cause mild splanchnic hyperemia. Tissue damage and bulk cathartic action leads to increase peristalsis and characteristic cathartic action leads to increase peristalsis and characteristic watery diarrhea.watery diarrhea.

Kidney :Kidney : Arsenic may cause severe renal damage Arsenic may cause severe renal damage

Skin :Skin : Effects on skin results in necrosis and sloughing. Effects on skin results in necrosis and sloughing.

Nervous systems :Nervous systems : Both short and long term exposures Both short and long term exposures cause encephalopathy , peripheral neuropathy.cause encephalopathy , peripheral neuropathy.

Blood :Blood : Affects the bone marrow .vascularity of the bone Affects the bone marrow .vascularity of the bone marrow is increased.marrow is increased.

Liver:Liver: Inorganic arsenic causes injury to hepatic Inorganic arsenic causes injury to hepatic parenchyma , produces fatty infiltration , central parenchyma , produces fatty infiltration , central necrosis and cirrhosisnecrosis and cirrhosis

LABORATORY TESTING AND DIAGNOSISLABORATORY TESTING AND DIAGNOSIS

History of potential exposure History of potential exposure

Laboratory test – Blood test , Liver function test , Renal function Laboratory test – Blood test , Liver function test , Renal function test , Urinalysis , Fecal test X-RAY”S and hair and finger nail test , Urinalysis , Fecal test X-RAY”S and hair and finger nail analysis.analysis.

TREATMENTTREATMENT

BAL , DMSA and D- penicillamine are the primary drug used .BAL , DMSA and D- penicillamine are the primary drug used .

Supportive care with abundant fluids to increase elimination of Supportive care with abundant fluids to increase elimination of arsenic . arsenic .

Decontamination of the gastro intestinal systems with gastric lavage Decontamination of the gastro intestinal systems with gastric lavage . .

Chelation therapy shortens the distribution of arsenic in the blood Chelation therapy shortens the distribution of arsenic in the blood

LEADLEAD

Lead accounts for most of the cases of pediatric heavy metal Lead accounts for most of the cases of pediatric heavy metal poisoning.poisoning.

Used in pipes, drains, shouldering materials, paint pigments, PVC Used in pipes, drains, shouldering materials, paint pigments, PVC plastics, X-ray shielding, crystal glass production, pencils & pesticides.plastics, X-ray shielding, crystal glass production, pencils & pesticides.

Symptoms include abdominal pain, convulsions, hypertension, renal Symptoms include abdominal pain, convulsions, hypertension, renal dysfunction, loss of appetite, fatigue, and sleeplessness, hallucination,dysfunction, loss of appetite, fatigue, and sleeplessness, hallucination,

headache, arthritis & vertigo.headache, arthritis & vertigo.

Chronic exposure results in birth defects, mental retardation, autism, Chronic exposure results in birth defects, mental retardation, autism, psychosis, allergies, dyslexia, hyperactivity, weight loss, shaky hands, psychosis, allergies, dyslexia, hyperactivity, weight loss, shaky hands, muscular weakness, and paralysis.muscular weakness, and paralysis.

PHARMACOLOGICAL AND PHARMACOLOGICAL AND TOXICOLOGICAL EFFECT ON TARGET TOXICOLOGICAL EFFECT ON TARGET

ORGANSORGANS

Gastrointestinal tract :Gastrointestinal tract : Affects smooth muscle of the gut, Affects smooth muscle of the gut, produces vague syndromes like anorexia, malaise, produces vague syndromes like anorexia, malaise, headache & constipation.headache & constipation.

Neuromuscular effects :Neuromuscular effects : Muscle weakness & easy fatigue Muscle weakness & easy fatigue occurs. muscle group involved are extensors of forearm, occurs. muscle group involved are extensors of forearm, wrist, fingers & extraocular muscles.wrist, fingers & extraocular muscles.

CNS effects :CNS effects : Lead encephalopathy is the most serious Lead encephalopathy is the most serious manifestation of lead poisoning.manifestation of lead poisoning.

Hematological effects :Hematological effects : Hypochromic microcytic Hypochromic microcytic anaemia is observed.anaemia is observed.

Renal effects :Renal effects : Renal toxicity occurs in two forms: Renal toxicity occurs in two forms: A reversible renal tabular disorder (usually seen after A reversible renal tabular disorder (usually seen after

acute exposure of children to lead) andacute exposure of children to lead) and An irreversible interstitial nephropathy (more commonly An irreversible interstitial nephropathy (more commonly

observed in long-term industrial lead exposure)observed in long-term industrial lead exposure)

Other effects:Other effects: Other signs and symptoms include an Other signs and symptoms include an ashen color of the face and pallor of the lips; retinal ashen color of the face and pallor of the lips; retinal stippling; appearance of “premature aging” with stooped stippling; appearance of “premature aging” with stooped posture, poor muscle tone, and emaciation; and a black, posture, poor muscle tone, and emaciation; and a black, grayish, or blue-black so-called lead line along the grayish, or blue-black so-called lead line along the gingival margin. gingival margin.

LABORATORY TESTING AND DIAGNOSISLABORATORY TESTING AND DIAGNOSISComplete blood count to check on abnormalities on red blood cells Complete blood count to check on abnormalities on red blood cells (basophylic stippling)(basophylic stippling)

Blood lead levels in children higher than 10 mcg/ dL are considered Blood lead levels in children higher than 10 mcg/ dL are considered

X-rays of long bones reveal “Lead Lines “ in children.X-rays of long bones reveal “Lead Lines “ in children.

TREATMENTTREATMENT

Chelation therapy with DMSA for children with blood lead levels of Chelation therapy with DMSA for children with blood lead levels of greater than 45 mcg/ dL.greater than 45 mcg/ dL.

Whole bowel irrigation is used if X-rays indicate the presence of Whole bowel irrigation is used if X-rays indicate the presence of lead .lead .

Follow up blood testing for stored lead in bones. Follow up blood testing for stored lead in bones.

MERCURYMERCURYMercury exists in three forms:Mercury exists in three forms:

Organic mercuryOrganic mercury Elemental mercury Elemental mercury Inorganic mercuryInorganic mercury

Used in thermometer, thermostats, dental amalgam & medicines Used in thermometer, thermostats, dental amalgam & medicines likelike

mercurochrome.mercurochrome.

Inhalation is the most frequent cause of exposure to mercury.Inhalation is the most frequent cause of exposure to mercury.

Symptoms of acute exposure are cough, sore throat, and shortness Symptoms of acute exposure are cough, sore throat, and shortness of breath;, abdominal pain, nausea, vomiting and diarrhea; of breath;, abdominal pain, nausea, vomiting and diarrhea; headaches, visual disturbances, tachycardia, and hypertension.headaches, visual disturbances, tachycardia, and hypertension.

Chronic exposure to mercury may result in permanent damage to Chronic exposure to mercury may result in permanent damage to the central nervous system and kidneys the central nervous system and kidneys

LABORATORY TESTING AND DIAGNOSISLABORATORY TESTING AND DIAGNOSIS24 hrs urine specimen24 hrs urine specimen

Chest X-ray, abdominal X-rayChest X-ray, abdominal X-ray

Liver and Kidney function test Liver and Kidney function test

TREATMENTTREATMENT

Chelation therapy using BAL, DMSA or D – PennicillamineChelation therapy using BAL, DMSA or D – Pennicillamine

Activated charcoal for gastrointestinal decontamination Activated charcoal for gastrointestinal decontamination

Supportive measures.Supportive measures.

CADMIUMCADMIUM

Cadmium is used in nickel – cadmium batteries, pvc Cadmium is used in nickel – cadmium batteries, pvc plastics and paint pigments.plastics and paint pigments.

Symptoms of cute exposure are nausea, vomiting , Symptoms of cute exposure are nausea, vomiting , abdominal pain , breathing difficulty abdominal pain , breathing difficulty

Chronic exposure results in chronic obstructive lung Chronic exposure results in chronic obstructive lung disease, renal disease fragile bones, arthritis , disease, renal disease fragile bones, arthritis , osteoporosis and cardiovascular diseases. osteoporosis and cardiovascular diseases.

PHARMACOLOGICAL AND PHARMACOLOGICAL AND TOXICOLOGICAL EFFECT ON TARGET TOXICOLOGICAL EFFECT ON TARGET

ORGANSORGANSkidney: damages the kidney cell resulting in proximal kidney: damages the kidney cell resulting in proximal tubular injury and proteinuria .tubular injury and proteinuria .

Lungs: excessive inhalation of cadmium fumes and dust Lungs: excessive inhalation of cadmium fumes and dust results in loss of ventilatory capacity.results in loss of ventilatory capacity.

Bones: body store of calcium have been found to be Bones: body store of calcium have been found to be decreased in subject exposed to cadmium.decreased in subject exposed to cadmium.

LABORATORY TESTING AND DIAGNOSISLABORATORY TESTING AND DIAGNOSIS

24- HOURS urine specimen .24- HOURS urine specimen .

CBC .CBC .

Hair and finger nail clippings.Hair and finger nail clippings.

TREATMENTTREATMENTNo known medical chelating method is effective.No known medical chelating method is effective.

Prevention or elimination of exposure is all that is Prevention or elimination of exposure is all that is required for cadmium toxicity .required for cadmium toxicity .

IRONIRON

ingesting dietary iron supplements may acutely poison ingesting dietary iron supplements may acutely poison young children .young children .

sources of iron are drinking water, iron pipes, and sources of iron are drinking water, iron pipes, and cookware .cookware .

Target organs are the liver, cardiovascular system and Target organs are the liver, cardiovascular system and kidneys.kidneys.

Symptoms of iron toxicity are pain in the stomach , Symptoms of iron toxicity are pain in the stomach , nausea , vomiting .nausea , vomiting .

Damages internal organs, particularly the brain and the Damages internal organs, particularly the brain and the liver, and metabolic acidosis develops. The body goes liver, and metabolic acidosis develops. The body goes into shock and death from liver failure can result.into shock and death from liver failure can result.

TREATMENTTREATMENT

Chelation with deferoxamine is commonly used with Chelation with deferoxamine is commonly used with blood serum levels greater than 500 mg/dL.blood serum levels greater than 500 mg/dL.

Supportive care with special attention to fluid balance Supportive care with special attention to fluid balance and cardiovascular stabilization are essential in iron and cardiovascular stabilization are essential in iron poisoning .poisoning .

BAL chelation is contraindicated for iron toxicity, because BAL chelation is contraindicated for iron toxicity, because BAL can combine with medicinal iron to become very BAL can combine with medicinal iron to become very

toxictoxic..

THERAPEUTIC OVERVIEWTHERAPEUTIC OVERVIEW

Therapies to remove heavy metals from human includes Therapies to remove heavy metals from human includes chelation and decontamination procedures as well as chelation and decontamination procedures as well as supportive measuressupportive measures

Chelation TherapyChelation Therapy : It is defined as the process by : It is defined as the process by which a molecule encircles and binds to the metal and which a molecule encircles and binds to the metal and removes it from tissue removes it from tissue

CHELATING AGENTSCHELATING AGENTSChelating AgentChelating Agent ToxinToxin RouteRoute DrugDrug

Dimercaprol (BAL) Dimercaprol (BAL) ArsenicArsenicLeadLeadMercury Mercury (inorganic) (inorganic)

i.m.i.m. DimercaptolDimercaptolInjection B.P.Injection B.P.BAL in Oil BAL in Oil

Dimercaptosiccinic acid Dimercaptosiccinic acid (DMSA)(DMSA)(Succimer)(Succimer)

ArsenicArsenicLeadLead

MercuryMercury p.o.p.o. Chemet Chemet

Dimercaptopropane- Dimercaptopropane- sulfonate (DMPS)sulfonate (DMPS)

Arsenic Arsenic p.o.p.o.i.m. i.m.

Bulk formBulk form(for compounding by (for compounding by

pharmacistspharmacists) )

D-pencillamineD-pencillamine ArsenicArsenicMercuryMercuryLead Lead

p.o. p.o. MetalcaptaseMetalcaptasePencillaminePencillamineCuprimineCuprimine

DepenDepen Ethylenediamintetra- Ethylenediamintetra- acetic acid (EDTA) acetic acid (EDTA) (Edetate disodium) (Edetate disodium)

LeadLead IV IV Chealamide VersenateChealamide Versenate

GASTROINTESTINAL GASTROINTESTINAL DECONTAMINATIONDECONTAMINATION

Gastric lavageGastric lavage

Whole bowel irrigationWhole bowel irrigation

CharcoalCharcoal

CatharticsCathartics

Supportive measuresSupportive measures

NATURAL THERAPIES TO PROMOTE NATURAL THERAPIES TO PROMOTE CHELATION DETOXIFICATION AND CHELATION DETOXIFICATION AND

PROTECTIONPROTECTION

There is no substitute for prompt professional medical There is no substitute for prompt professional medical attention in cases of heavy metal toxicity.attention in cases of heavy metal toxicity.

There are numbers of things of dietary nature that are There are numbers of things of dietary nature that are beneficial , protective and supportive of good health.beneficial , protective and supportive of good health.

Importance supplements are anti-oxidents , detoxifying Importance supplements are anti-oxidents , detoxifying agents and dietry fiber. agents and dietry fiber.

PREVENTING HEAVY METAL TOXICITYPREVENTING HEAVY METAL TOXICITY

No smoking, eating, or drinking in work areas.No smoking, eating, or drinking in work areas.

Provide appropriate protective clothing that will remain at Provide appropriate protective clothing that will remain at the facility. the facility.

Provide showering facilities as needed. Provide showering facilities as needed.

Work clothes and street clothes will not be kept in the Work clothes and street clothes will not be kept in the same area,same area,

CONCLUSIONCONCLUSION

For most people, acute heavy metal toxicity will rarely be a concern or pose a For most people, acute heavy metal toxicity will rarely be a concern or pose a problem. However, certain groups are at a higher risk:problem. However, certain groups are at a higher risk:

Those who live in homes that contain lead pipes and lead-based paint or in Those who live in homes that contain lead pipes and lead-based paint or in areas having high environmental levels of elemental mercury, iron, or areas having high environmental levels of elemental mercury, iron, or aluminum aluminum

Those who work in industries that manufacture batteries, pesticides, and Those who work in industries that manufacture batteries, pesticides, and fertilizers or who are members of their households fertilizers or who are members of their households

Those who work in industries that are involved in metal finishing Those who work in industries that are involved in metal finishing

Those who handle chemicals in scientific or laboratory settings Those who handle chemicals in scientific or laboratory settings

Unrecognized or untreated toxicity will likely result in illness and reduced quality Unrecognized or untreated toxicity will likely result in illness and reduced quality of life. Testing is essential if Heavy metal toxicity is suspected & initiation of of life. Testing is essential if Heavy metal toxicity is suspected & initiation of appropriate & natural medical procedure is required.appropriate & natural medical procedure is required.