An Introduction To The Health Effects of Metals

1. An Introduction To The Health Effects of Metals A Small Dose of ™ Metal ENVIRONMENTAL AND OCCUPATIONAL TOXICOLOGY III (ENVH 516)

2. Complex relationship to metals – Nutritionally Important Toxicologically Important Medical Important Chelation Introduction

3. 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

4. Historical Awareness • 80 of 105 elements in the periodic table are labeled as metals • “Mad Hatter” – mercury exposure

5. 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

6. 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?)

7. 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

8. 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+

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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…

18. 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

19. 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

20. 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

21. 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

22. 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)

23. 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)

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. Summary We can not live without metals but some require our utmost respect.

35. A Small Dose of ™ Metal

36. 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.

37. 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