H.R.Sarreshtahdar, MD Occupational Medicine Specialist Heavy Metal Toxicity H.R.Sarreshtahdar, MD Occupational Medicine Specialist Arsenic Lead Mercury

HEAVY METALS The term heavy metal refers to any metallic chemical element that has a relatively high density and is toxic or poisonous at low concentrations.

HEAVY METALS Are natural components of the Earth's crust To a small extent they enter our bodies via food, drinking water and air As trace elements, some heavy metals (e.g. copper, selenium, zinc) are essential to maintain the metabolism of the human body however, at higher concentrations they can lead to poisoning Heavy metal poisoning could result, for instance, from drinking-water contamination (e.g. lead pipes), high ambient air concentrations near emission sources, or intake via the food chain

Mercury - Hg Mercury is the only common metal which is liquid at ordinary temperatures. It rarely occurs free in nature and is found mainly in cinnabar ore (HgS) in Spain and Italy. It alloys easily with many metals, such as gold, silver, and tin - these alloys are called amalgams. Its ease in amalgamating with gold is used in the recovery of gold from its ores.

Health effects of mercury Disruption of the nervous system Damage to brain functions DNA damage and chromosomal damage Allergic reactions, resulting in skin rashes, Tiredness and headaches Negative reproductive effects, such as sperm damage, birth defects and miscarriages

Environmental effects of mercury Fish are organisms that absorb great amounts of methyl mercury from surface waters every day (mercury can accumulate in fish and in the food chains) The effects that mercury has on animals are: kidneys damage, stomach disruption, damage to intestines, reproductive failure and DNA alteration

What is Cadmium? A metal most often encountered in earth’s crust combined with chlorine (cadmium chloride), oxygen (cadmium oxide), or sulfur (cadmium sulfide) Exists as small particles in air, result of smelting, soldering or other high temp. industrial processes By-product of smelting of zinc, lead, copper ores Used mainly in metal plating, producing pigments, batteries, plastics and as a neutron absorbent in nuclear reactors Cadmium is used in batteries

Cadmium and Smelters/Mine Sites Cadmium is a by-product of smelters Has been a concern at the Summitville mine site in Colorado Photo of Smelter

Exposure Sources - Tobacco Tobacco smoke (a one pack a day smoker absorbs roughly 5 to 10 times the amount absorbed from the average daily diet) Tobacco smoke is an important source of cadmium exposure

Exposure Sources – By Mouth Foods (only a small amount is absorbed) Itai Itai disease (cadmium contamination + diet low in calcium & vitamin D)

Cadmium – Cd HEALTH EFFECTS Human uptake of cadmium takes place mainly through food Foodstuffs that are rich in cadmium can greatly increase the cadmium concentration in human bodies (liver, mushrooms, shellfish, mussels, cocoa powder and dried seaweed)

Why Is Cadmium a Health Hazard? Affects lungs & kidneys 2o effects on skeletal system Binds to sulfhydryl groups, displacing other metals from metalloenzymes, disrupting those enzymes Competes with calcium for binding sites on regulatory proteins

Respiratory Effects Acute inhalation may mimic metal fume fever Fever, chills & decreases in FVC and FEV1 Initial symptoms: flu-like symptoms Later: chest pain, cough, dyspnea Bronchospasm and hemoptysis may occur Chronic inhalation MAY result in impairment of pulmonary function with reduction in ventilatory capacity

Renal Effects May cause tubular and glomerular damage with resultant proteinuria May follow chronic inhalation or ingestion Latency period of ~10 yrs Nephropathy is progressive & irreversible

Renal Effects Chronic exposure – progressive renal tubular dysfunction Toxic effects are dose related Critical renal concentration Decreased GFR Chronic renal failure Kidney stones more common

Skeletal Effects Bone lesions occur late in severe chronic poisoning Pseudofractures Other effects of osteomalacia and osteoporosis Appear to be secondary to increased urinary calcium and phosphorus losses

Signs and Symptoms - Acute Food poisoning (ingestion) Bronchitis (inhalation) Interstitial pneumonitis (inhalation) Pulmonary edema (inhalation) A condition that mimics metal fume fever Children who eat dirt (pica behavior) are at risk

Signs & Symptoms - Chronic Chronic exposure may result in renal dysfunction and bone disease Mild anemia, anosmia & yellow discoloration of the teeth may occur Chronic exposure may effect the sense of smell

HEALTH EFFECTS Diarrhoea, stomach pains and severe vomiting Bone fracture Reproductive failure and possibly even infertility Damage to the central nervous system Damage to the immune system Psychological disorders Possibly DNA damage or cancer development

Chromium - Cr Chromium(III) is an essential nutrient for humans and shortages may cause heart conditions, disruptions of metabolisms and diabetes But the uptake of too much chromium(III) can cause health effects as well, for instance skin rashes

Chromium - Cr Chromium(VI) is a danger to human health, mainly for people who work in the steel and textile industry People who smoke tobacco also have a higher chance of exposure to chromium Hexavalent Chromium – Chromium (VI) is a species of chromium that is forbidden to use in electrical & electronic industry.

HEALTH EFFECTS When it is a compound in leather products, it can cause allergic reactions, such as skin rash After breathing it in, chromium(VI) can cause nose irritations and nosebleeds Upset stomachs and ulcers Respiratory problems Weakened immune system Kidney and liver damage Alteration of genetic material Lung cancer Death

Environmental effects of chromium Chromium(III) is an essential element for organisms that can disrupt the sugar metabolism and cause heart conditions, when the daily dose is too low Chromium(VI) is mainly toxic to organisms - it can alter genetic materials and cause cancer

Lead - Pb Foods such as fruit, vegetables, meats, grains, seafood, soft drinks and wine may contain significant amounts of lead Cigarette smoke also contains small amounts of lead

Lead sources application of lead in gasoline fuel combustion industrial processes solid waste combustion

Lead Paint The use of lead in residential paint was banned in 1977 Lead-containing pigments still are used for outdoor paint products because of their bright colors and weather resistant properties Tetraethyl and tetramethyl lead are still used as additives in gasoline in several countries

ToxicoKinetics and ToxicoDynamics Absorption: Lungs: depends on size particle GI: Adults: 20-30% Children: as much as 50% of dietary lead Inadequate intake of iron, calcium, and total calories are associated with higher lead levels Skin: Inorganic lead is not absorbed Organic lead is well absorbed Lead is carried bound to the RBC

PharmacoKinetics and PharmacoDynamics Distributed extensively throughout tissues: bone, teeth, liver, lung, kidney, brain, and spleen Body lead storage: bones- can constitute a source of remobilization and continued toxicity after the exposure has ceased Lead crosses the BBB and concentrates in the gray matter Lead crosses the placenta Excretion: Kidneys. The excretion increases with increasing body stores (30g-200 g/day) Feces

Signs and Symptoms of Lead Toxicity Fatigue Irritability Lethargy Paresthesis Myalgias Abdominal pain Tremor Headache Vomiting Weight loss Constipation Loss of libido Motor neuropathy Encephalopathy Cerebral edema Seizures Coma Severe abdominal cramping Epiphyseal lead lines in children (growth arrest) Renal failure

Range of Lead-induced Health Effects in Adults and Children Blood lead levels Adults Children 10 g/dL Hypertension may occur Crosses placenta Impairment IQ, growth Partial inhibition of heme synthesis 20 g/dL Inhibition of heme synthesis Increased erythrocyte protoporphyrin Beginning impairment of nerve conduction velocity 30 g/dL Systolic hypertension Impaired hearing() Impaired vitamin D metabolism 40 g/dL Infertility in males Renal effects Neuropathy Fatigue, headache, abd pain Hemoglobin synthesis inhibition 50 g/dL Anemia, GI sx, headache, tremor Colicky abd pain, neuropathy 100 g/dL Lethargy, seizures, encephalopathy Encephalopathy, anemia, nephropathy, seizures

Health effects of lead Disruption of the biosynthesis of haemoglobin and anemia A rise in blood pressure Kidney damage Miscarriages Disruption of nervous systems Brain damage Declined fertility of men through sperm damage Diminished learning abilities of children Behavioural disruptions of children, such as aggression, impulsive behaviour and hyperactivity

Health effects of lead Lead can enter a foetus through the placenta of the mother Because of this it can cause serious damage to the nervous system and the brains of unborn children That is why women in pregnancy can not work with lead.

The average lead level of American children is 2 g/dl 8.9% of American children have lead poisoning Lead intoxication is more prevalent in minority groups and among those living in the northeast

Diagnosis Evaluation of clinical symptoms and signs CBC Serum iron levels, TIBC, ferritin Abdominal radiographs (for recent ingestion of lead-containing material) Whole blood lead level X-ray fluorescence (XRF)- to asses body burden

Arsenic

Introduction Commercial products Wood preservatives Pesticides Herbicides Fungicides Food Seafood and fish Others Antiparasitic drugs

Toxicokinetics T1/2 of inorganic arsenic in the blood is 10 hrs and of organic arsenic is around 30 hours 2-4 weeks after the exposure ceases, most of the remaining arsenic in the body is found in keratin-rich tissues (nails, hair, skin)

Toxicokinetics Inorganic arsenic is converted to organic arsenic (biomethylation to monomethyl arsonic- MMA or DMA) in the liver. This may represent a process of detoxification Renally excreted (30-50% of inorganic arsenic is excreted in about 3 days). Both forms are excreted depend on the acuteness of the exposure and dose

Manifestations of acute arsenic poisoning Bodily system affected Symptoms or signs Time of onset Systemic Thirst Hypovolemia, Hypotension Minutes Minutes to hours Gastrointestinal Garlic or metallic taste Burning mucosa Nausea and vomiting Diarrhea Abdominal pain Hematemesis Hematochezia, melena Rice-water stools Immediate Hours Hematopoietic system Hemolysis Hematuria Lymphopenia Pancytopenia Several weeks Pulmonary (primarily in inhalational exposures) Cough Dyspnea Chest Pain Pulmonary edema Liver Jaundice Fatty degeneration Central necrosis Days Kidneys Proteinuria Acute renal failure Hours to days

PALMAR KERATOSIS

Biological Monitoring Urinary arsenic measurement Spot sample (mcg/L) Timed urine collection (mcg/24 hours) Normal values Spot urine= ~10 mcg/L (10-150 mcg/L) 24 hours urine collection=<25 mcg/24 hours Whole blood= <1mcg/L (usually is elevated in acute intoxication)

Chromium Common oxidation states Cr+3 & Cr+6, in aerobic conditions Cr exists primarily as the chromate ion –highly soluble, toxic, can dimerize to dichromate Anerobic (reducing) conditions Cr exists the +3 ion; not very toxic or soluble under basic neutral or even acidic conditions Env. Chemistry, Baird & Cann

Cr Contamination of Water Used for electroplating, corrosion resistance & tanning Second most abundant inorganic contaminant of groundwater under hazardous waste sites MCL in US 100 ppb Removal –most heavy metals increase the pH but Cr+6 soluble at any pH but Cr+3 low solubility so Cr+6 usually reduced to +3 Env. Chemistry, Baird & Cann