Occupational and Environmental Chemical Exposures Heavy Metals: Lead and Mercury

1. Occupational and Environmental Chemical Exposures Heavy Metals: Lead and Mercury Mary McDaniel, D.O., J.D., M.P.H. McDaniel Lambert Inc. mfmcdaniel@mclam.com UCLA February 21, 2006

2. Who’s at Risk? • Occupational Exposure • Household exposure • Ambient exposure • For many chemicals, fetuses, infants and/or children are at greatest risk due to susceptibility to toxic effects and/or increased exposure

3. Lead • Long history of human exposure (5000 yrs plus). • Thought to have been responsible for downfall of Greek and Roman civilizations. • Widespread environmental contaminant. • Childhood lead poisoning was first described in Australia 100 years ago

5. Sources of Lead Exposure – Ingestion and Inhalation • Occupational – lead mines, smelters and refiners, plumbers, auto repair, police officers, glass manufacturers, battery manufacturers. • Hobbies – glazed ceramics, target shooting, soldering (electronics, stained glass), painting, home repair activities. • Environmental – leaded gasoline and paints, water from corroded pipes, earthenware, contaminated soil and dust, imported canned foods/candy • Substance use – folk remedies, health foods

6. Nutrition and Lead • Ingestion of lead during a period of fasting results in greater absorption • Dietary intake of calcium has a very significant effect on lead uptake • Rats on a low-calcium diet had four times higher blood lead concentrations than rats on a normal diet • Intake of iron is also important with low levels increasing the uptake of lead

7. Lead Health Effects • Interferes with normal cell function and various physiological process: peripheral and central nervous systems, blood cell production, metabolism of vitamin D and calcium, kidneys, reproductive system • Probable human carcinogen (classified B2 by USEPA)

8. Lead Health Effects (cont.) • Children and pregnant women at highest risk • Children – higher exposures and postnatal susceptibility • For every 10 ug/dl increase in concentration there is a one to three-point drop in IQ • Pregnant women – lead crosses the placenta and damages nervous system • Lead in the fetus tends to equilibrate with maternal lead

9. Lead Health Effects (cont’d) • Symptoms of lead poisoning • Early symptoms are vague and nonspecific • Pallor, vomiting, abdominal pain, constipation, stupor, loss of appetite, irritability, and loss of muscular coordination • Classic signs include lead colic, lead “lines” on the gums and wrist drop

10. Lead Biological Fate • Inorganic lead not metabolized – directly absorbed, distributed and excreted • Inhaled lead completely absorbed; typically 10-15% of ingested lead absorbed from the GI tract • Lead half lives in adults • Blood – 25 days • Soft tissue – 40 days • Bone – 25+ years • Lead poisoning does not require major acute exposure - body accumulates over lifetime and releases slowly • Under stress, body may metabolize lead stores, thus increasing blood lead levels

11. Health Effects at Various Blood Lead Levels Health Effect (ug/dl)Blood Lead Level of concern for fetal effects <10 Blood enzyme changes 15-20 IQ deficiencies in children <25 Clinical anemia, children 40 Clinical anemia, adults 50 Reproductive effects in adults 50 Mental losses (writing/speech 50-60 problems, retardation) Irreversible brain damage 100

12. Lead Standards and Regulations Blood Levels CDC Advisory – level of concern for children 10 ug/dL OSHA – level of concern 40 ug/dL OSHA Regulation – medical removal from exposure 50 ug/dL Air Concentrations OSHA Action level 30 ug/m3 OSHA Regulation – PEL 50 ug/m3 US EPA – ambient air quality standard (3 month average) 1.5 ug/m3 Food EPA – drinking water action level 15 ug/L CalEPA – drinking water public health goal 2 ug/L CalEPA – drinking water maximum contaminant level 15 ug/L FDA – food advisory level 100 ug/day

13. Poverty and Lead Poisoning • Impact greatest among urban poor • Older housing more lead based paints and lead contaminated soils • Older schools • 4.5% of all 1 to 2 year-old children have blood lead levels >10 ug/dl • 21.6% of 1 to 2 year-old black children have blood lead levels >10 ug/dl

14. Blood Lead Levels for Various Groups of People Rural Children 7-11 Urban Children 9-33 Adults 15-22 Children near smelter 35-68

15. Diagnosis • Exposure Interviews • Occupation, housing, lifestyle/hobbies, school exposures, pica child • Signs and Symptoms: most persons with lead toxicity are not overly symptomatic • Continuum includes increasing severity of fatigue, irritability, lethargy, abdominal pain • School • Pica • Blood lead level is best screening and diagnostic test

16. Treatment • Depends on exposure level • Limit exposure • May be only therapy needed for asymptomatic patients with blood levels below 25 ug/dL • Dietary changes • Ca supplements • Chelation therapy (e.g. calcium disodium EDTA) • CDC recommends immediate chelation therapy for children with blood levels of 45 ug/dL and above

17. Mercury Hg0 • Long history of use • Metallic mercury used as a laxative • Mad Hatters disease from use in felt manufacture • Andrew Jackson thought to have died from mercuric chloride treatment • “Dancing Cat Disease” • Chemistry • Exists in 3 forms: elemental, inorganic salts and organic • Elemental (metallic) mercury (Hg0) can be converted to organic methylmercury (MeHg) in the environment by the action of bacteria

18. Sources of Mercury Exposure • Highest exposures have been from industrial or pesticide poisonings (Minamata, Japan – Chlor-alkali; Iraq – Wheat fungicide) • General population mostly exposed by eating contaminated fish (methylmercury) • Fish bioaccumulate methyl mercury with 99% of mercury in fish in the the methylated form • Older and larger carnivorous fish have the highest levels (swordfish, tuna, shark, king mackerel) • Can of tuna contains 0.20 ppm

20. Sources of Mercury Exposure (cont.) • Occupational (primarily elemental mercury vapor) – chlor-alkalai plants, laboratory personnel, miners and processors of cinnabar, gold, silver, copper, and zinc, metallurgists, ectroplaters, explosive manufacturers • Hobbies – fishing • Environmental – atmospheric deposition from coal-fired power plants, incineration of municipal and solid waste, latex paints, fish consumptions • Substance use – folk medicines, cosmetic; dental amalgams have not been proven to cause adverse effects.

21. Mercury Health Effects • Effects depend on duration, intensity, and route of exposure, and chemical form • Central nervous system and kidneys are key targets • Elemental mercury: nervous system • Mercury salts: respiratory or GI (acute exposure); kidneys (chronic exposure) • Organic mercury: nervous system; developmental effects • Elemental mercury not classified with respect to carcinogenicity (USEPA Class D)

22. Observed Effects of Methylmercury Toxicity • Iraq and Minamata (Japan) • Effects in utero quite different from childhood or adult exposures • Fetus is the most sensitive • Methylmercury exposed women have delivered infants with severe behavioral and sensory deficits, including deafness and blindness without maternal toxicity • Prenatal exposure results in a widespread pattern of adverse effects on brain development and organization • Alters the normal migration of neurons to cerebellar and cerebral cortices during brain development • Reduced brain size

23. Mercury Controversy • Two recent studies of predominately fish eating populations: • Faroese Islands • Dose dependent relationship seen (delayed language, reduced memory and attention spans) • Seychelle Islands • No health effects observed • Many experts strongly advise pregnant women and women of child bearing age to limit exposure • However, fish is a significant source of protein throughout the world, some argue that the benefits outweigh the potential risk from low-level exposure

24. Mercury Biological Fate • Chemical and physical form of mercury determine absorption, metabolism, distribution, and excretion pathways • Elemental mercury: nearly completely absorbed when inhaled; poorly absorbed when ingested or via dermal contact; readily crosses blood-brain barrier • Mercury salts: Mercuric Hg2+) salts are generally more soluble, and therefore more toxic than mercurous (Hg1+) salts; on average, less than 10% of ingested salts absorbed in GI tract; do not cross blood-brain barrier as readily • Organic mercury: readily absorbed by inhalation, dermal, contact, and ingestion; distributed uniformly to all tissues, although concentrated mostly in blood and brain.

25. Mercury Standards and Regulations Air Concentrations OSHA – organic mercury PEL 0.1 mg/m3 metallic mercury vapor PEL 0.05 mg/m3 Water (inorganic mercury) EPA – drinking water maximum contaminant level 2 ug/L CAlEPA – drinking water public health goal 1.2 ug/L CAlEPA – drinking water maximum contaminant level 2 ug/L Food FDA – Fish action level 1 ppm USEPA – fish action level 0.3 ppm Japan – fish action level 0.3 ppm Australia – fish action level 0.5 ppm

26. California Proposition 65 Fish Lawsuit • Filed by Attorney General/TI January 2003 • USFDA listed fish: swordfish, mackerel, tile fish, and shark • Safeway, Kroger, Albertsons, Trader Joe’s and Whole Foods • Dr. Katherine Mahaffey who wrote USEPA Mercury report to Congress and helped developed RfD says “ . . . other states are going to pick up the idea. Clearly it’s an important step.” • Red Lobster is next . . .

27. Diagnosis • Exposure Interviews • Occupation, housing (recent move), lifestyle/hobbies (fish consumption), school laboratory • Signs and Symptoms • Elemental mercury: pulmonary and CNS effects (cough, chest pain, colitis, pulmonary edema); chronic exposure may result in tremor and personality disorders • Mercury salts: affects GI tract and kidneys • Organic mercury: typically nonspecific and delayed (ataxia, malaise, blurred vision); chronic exposure may result in permanent CNS damage • Blood lead level typical test for acute exposure; urine test for chronic exposure

28. Signs and Symptoms at Various Urine Mercury Levels Sign and Symptoms Urine (ug/L) Decreased response on tests for nerve condition, brain wave activity and verbal skills; early indication of tremor 2-100 Irritability, depression, memory loss, minor tremor, other nervous system disturbances; disturbed kidney function 100-500 Kidney inflammation, swollen gums, significant tremor and nervous system disturbances 500-1000

29. Treatment • Depends on form of mercury exposure • Elemental mercury of mercury salts • Limit exposure • Chelation therapy • Organic mercury • No antidote; supportive care recommended • Chelating agent BAL contraindicated, as it has been shown to increase methylmercury concentrations in the brain

30. Toxicology