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An Introduction To The Health Effects of Metals. A Small Dose of ™ Metal. ENVIRONMENTAL AND OCCUPATIONAL TOXICOLOGY III (ENVH 516). Complex relationship to metals – Nutritionally Important Toxicologically Important Medical Important Chelation. Introduction. Ancient Awareness.
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An Introduction To The Health Effects of Metals A Small Dose of ™ Metal ENVIRONMENTAL AND OCCUPATIONAL TOXICOLOGY III (ENVH 516)
Complex relationship to metals – Nutritionally Important Toxicologically Important Medical Important Chelation Introduction
Ancient Awareness • Lead - usage began 4000 years ago • Hippocreates – 370 BC noted abdominal colic in miner • Arsenic – therapeutic and a poison (400 BC) • “Lead makes the mind give way”. The Greek Dioscerides 2nd century BC
Historical Awareness • 80 of 105 elements in the periodic table are labeled as metals • “Mad Hatter” – mercury exposure
Thoughts on Metals • Redistribution • Naturally occurring – break down of rock • Human – mining, purify, recombine, use • E.g. lead – rise in Greenland ice • Changed form • E.g. inorganic to organic mercury • Occupational exposure • Home exposure
Susceptibility to Metals • Age – young or old? • Nutrition (competion with essential metals) • Allergic response (immune system) • Form of metal (organic or inorganic) • Lifestyle – smoking or alcohol • Occupation • Home environment (lead paint?)
Nutritionally Important Some metals have very important physiological functions • Chromium (Cr) • Copper (Cu) • Iron (Fe) • Magnesium (Mg) • Manganese (Mn) • Selenium (Se) • Zinc (Zn) Cr Cu Fe Mg Mn Se Zn
Chromium (Cr) • Use – essential element, associated with insulin, stainless steel, tanning leather • Source –food supply, inhalation • Recommended daily – 50-200 µg • Absorption – intestine • Toxicity – acute exposure cause kidney damage, lung cancer • Facts – comes in different oxidized forms – Cr3+, Cr6+
Copper (Cu) • Use – essential element, widely used • Source – readily available in food • Recommended daily – 1.5-3.0 mg • Absorption – intestine • Toxicity – deficiency – anemia • - excess rare, Wilson’s disease • Facts – excess treated with penicillamine • - can be toxic grazing animals
Iron (Fe) • Use – oxygen carrying hemoglobin • Source – food • Recommended daily – 10-15 mg • Absorption – intestine • Toxicity – excess causes bloody fesses, bloody vomit, liver damage • Facts - 3-5 grams in the body • 67% associated with hemoglobin
Magnesium (Mg) • Use – essential nutrient, associated with many enzymes, antacids • Recommended daily – 280-350 mg • Source – food supply, nuts, cereals, seafood, meats, drinking water • Absorption – small intestine • Toxicity – deficiency – convulsions • - excess – nervous system • Facts – 20 grams in body
Manganese (Mn) • Use – trace element, associated with many enzymes • Source – food supply, grains, nuts • Recommended daily – 2 to 5 mg • Absorption – intestine poor (5%) • Toxicity – inhalation – respiratory disease, nervous system, Parkinson’s -like syndrome, psychiatric disorders • Facts – half-live 37 days
Selenium (Se) • Use – essential element, present in most tissue, anticancer, reduces toxicity of metal mercury and cadmium • Source – food supply, shrimp, meat • Recommended daily – 55-70 µg/day, not to exceed 200 µg/day • Absorption – intestine • Toxicity – deficiency – heart disorders • - excess – “blind staggers”, neurological effects
Zinc (Zn) • Use – essential element, cofactor with several enzymes, and proteins • Source – food supply, drinking water • Recommended daily – 12-25 mg • Absorption – intestine • Toxicity – deficiency – impaired growth, neurological disorders, - inhalation can cause metal fume fever
Toxic Metals • Aluminum (Al) • Arsenic (As) • Cadmium (Cd) • Cobalt (Co) • Lead (Pb) • Mercury – Inorganic (Hg) • Mercury – Organic (Hg-CH3) • Nickel (Ni) • Tin (Sn) Al As Cd Co Pb Hg Hg-CH3 Ni Sn
Aluminum (Al) • Use – wide range of consumer products, airplanes to cans • Source – food, drinking water • Absorption – poor • Toxicity – Dialysis dementia, possibly neurotoxic • Facts – non-essential, intake 1-10 mg/day
Arsenic (As) • Use – pesticide and herbicide • Source – food, drinking water • Absorption – intestine • Toxicity – cancer, heart, liver, neurological • Facts – exists in different states – trivalent (most common), pentavalent, arsenic trioxide, organic and inorganic ...etc…
Beryllium (Be) • Use – metal alloy, nuclear power plants • Source – workplace, coal combustion • Absorption – lung, skin • Toxicity – lung, can be delayed and is progressive, contact dermatitis probable carcinogen • Facts – discovered in 1828, more that 1250 tons from oil and coal combustion
Cadmium (Cd) • Use – alloy in metal, paint • Source – shellfish, cigarette smoke, workplace – welding, paints • Absorption – intestine, lungs • Toxicity – lung, emphysema, kidney, calcium metabolism, possible lung carcinogen • Facts – “Itai-Itai” is Japanese for “ouch-ouch” – refers to bone pain related to calcium loss
Cobalt (Co) • Use – component of vitamin B12, • Source – alloy in metals, magnets • Recommended daily – none • Absorption – intestine • Toxicity – excessive heart failure, inhalation – “hard metal” lung disease • Facts – once used a foaming agent in beer
Lead (Pb) • Use – not essential, batteries, old paint and previously gasoline, hobbies • Source – home, paint, dust, kids-hands to mouth, workplace • Absorption – intestine (50% kids, 10% adults) • Toxicity – developmental and nervous system • Facts – developing nervous system very sensitive to low levels of exposure
Inorganic Mercury (Hg) • Use – consumer products, industry, dental amalgams, switches, thermometers • Source – mining, environment • Absorption – inhalation, intestine poor • Toxicity – nervous system toxicant, “Mad Hatters” disease • Facts – liquid silver evaporates at room temperature, bacteria convert to organic methyl mercury (see next slide)
Organic Mercury (Hg-CH3) • Use – limited laboratory use - most common is methyl mercury (Hg-CH3) • Source – contaminates some fish (e.g. tuna, shark, pike) • Absorption – intestine very good (90%) • Toxicity – nervous system toxicant, and developmental toxicant • Facts – bacteria convert inorganic mercury to methyl mercury then in to food supply (bioaccumulation)
Nickel (Ni) • Use – not essential, metal alloy, stainless steel • Source – food supply, jewelry, workplace • Absorption – intestine, skin • Toxicity – carcinogen (lung), contact dermatitis • Facts – discovered in 1751, 200,000 metric tons used yearly
Tin (Sn) • Use – inorganic – consumer products • - organic – fungicide, bactericides • Source – food packaging • Absorption – intestine (low inorganic, high organic) • Toxicity – inorganic - little • - organic – central nervous system • Facts – triethyltin and trimethyltin most toxic
Medically Important A small group of metals are used to treat disease Bi • Bismuth (Bi) • Fluoride (F) • Gallium (Ga) • Gold (Au) • Lithium (Li) • Platinum (Pt) F Ga Au Li Pt
Bismuth (Bi) • Use – antacids, diarrhea • Source – mining, consumer products • Absorption – intestine • Toxicity – kidney, chronic use results in range of effects • Facts – discovered in 1753, used to treat syphilis and malaria
Fluoride (F) • Use – tooth protection • Source – drinking water, food supply • Absorption – intestine • Toxicity – excess causes mottled teeth enamel (fluorosis) • Facts – common water level 0.5 to 1.5 ppm, 3 ppm effects teeth
Gallium (Ga) • Use – visualization tool for soft tissues in x-rays • Source – mining, medical injection • Absorption – very poor • Toxicity – kidney • Facts – liquid at room temperature, half-life 4 to 5 days
Gold (Au) • Use – treat rheumatoid arthritis, range of industrial uses • Source – mining, medical injection • Absorption – poor • Toxicity – kidney, skin and mouth lesions • Facts – long half-life
Lithium (Li) • Use – treat psychiatric disorders • Source – food supply, plants & meat • Absorption – intestine • Toxicity – wide range, e.g. tremor, seizures, slurred speech, cardiovascular, nausea, vomiting • Facts – daily intake about 2 mg
Platinum (Pt) • Use – anti-cancer agent (cisplatin), catalytic converters, metal alloy • Source – mining, road dust • Absorption – poor, as a drug intravenous administration • Toxicity – neuromuscular, kidney • Facts – inhibits cell division, treat ovarian & testicular cancer
Chelation • Properties • Metal chelators accelerate the excretion of metal from the body • Non-specific – can remove essential metals and elements • Chelate is from the Geek word for claw • Examples • BAL – one of the first, broad action but potentially toxic • Calcium EDTA – lead • Penicillamine – copper • Desferrioxamine – iron • DMPS – lead, mercury • Number of others
Summary We can not live without metals but some require our utmost respect.
Additional Information • Web Sites • Health Canada - Nutrition. http://www.hc-sc.gc.ca/english/lifestyles/food_nutr.html • U.S. Agency for Toxic Substance Disease Registry (ATSDR). http://www.atsdr.cdc.gov/ • Dartmouth Toxic Metals Research Program. http://www.dartmouth.edu/~toxmetal/HM.shtml The site has general information on toxic metals.
Authorship Information This presentation is supplement to “A Small Dose of Toxicology” For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail:sgilbert@innd.org Web: www.asmalldoseof.org