1. A Small Dose of Metals – 04/13/11 An Introduction To The Health Effects of Metals A Small Dose of ™ Metal ENVIRONMENTAL AND OCCUPATIONAL TOXICOLOGY III (ENVH 516)

2. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology Introduction Complex relationship to metals – Nutritionally Important Toxicologically Important Medical Important Chelation

3. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology  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 Ancient Awareness

4. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology  80 of 105 elements in the periodic table are labeled as metals  “Mad Hatter” – mercury exposure Historical Awareness

5. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology  Chromium (Cr)  Copper (Cu)  Iron (Fe)  Magnesium (Mg)  Manganese (Mn)  Selenium (Se)  Zinc (Zn) Nutritionally Important Some metals have very important physiological functions Cr Cu Fe Mg Mn Se Zn

8. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 – Cr 3+, Cr 6+ Chromium (Cr)

9. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Copper (Cu)

10. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Iron (Fe)

11. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Magnesium (Mg)

12. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Manganese (Mn)

13. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Selenium (Se)

14. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Zinc (Zn)

15. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology  Aluminum (Al)  Arsenic (As)  Cadmium (Cd)  Cobalt (Co)  Lead (Pb)  Mercury – Inorganic (Hg)  Mercury – Organic (Hg-CH 3 )  Nickel (Ni)  Tin (Sn) Toxic Metals Pb Co Al As Cd Hg Hg-CH 3 Ni Sn

16. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Aluminum (Al)

17. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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… Arsenic (As)

18. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Beryllium (Be)

19. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Cadmium (Cd)

20. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Cobalt (Co)

21. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Lead (Pb)

22. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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) Inorganic Mercury (Hg)

23. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology Use – limited laboratory use - most common is methyl mercury (Hg-CH 3 ) 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) Organic Mercury (Hg-CH 3 )

24. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Nickel (Ni)

25. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Tin (Sn)

26. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology  Bismuth (Bi)  Fluoride (F)  Gallium (Ga)  Gold (Au)  Lithium (Li)  Platinum (Pt) Medically Important A small group of metals are used to treat disease F Li Pt Ga Au Bi

27. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Bismuth (Bi)

28. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Fluoride (F)

29. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Gallium (Ga)

30. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology Use – treat rheumatoid arthritis, range of industrial uses Source – mining, medical injection Absorption – poor Toxicity – kidney, skin and mouth lesions Facts – long half-life Gold (Au)

31. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Lithium (Li)

32. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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 Platinum (Pt)

33. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology  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 Chelation

34. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology We can not live without metals but some require our utmost respect. Summary

35. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology A Small Dose of ™ Metal

36. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology 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. A Small Dose of Metals – 04/13/11 A Small Dose of Toxicology Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail: sgilbert@innd.org Web: www.asmalldoseof.org This presentation is supplement to “A Small Dose of Toxicology”