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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

UCLAFebruary 21, 2006

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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

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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

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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

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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 uptakeRats 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

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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)

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Lead Health Effects (cont.)

Children and pregnant women at highest riskChildren – higher exposures and

postnatal susceptibilityFor 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

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Lead Health Effects (cont’d)

Symptoms of lead poisoningEarly symptoms are vague and

nonspecificPallor, 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

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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

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Health Effects at Various Blood Lead Levels

Health Effect (ug/dl) Blood Lead

Level of concern for fetal effects <10Blood enzyme changes 15-20IQ deficiencies in children <25Clinical anemia, children 40Clinical anemia, adults 50Reproductive effects in adults 50Mental losses (writing/speech 50-60problems, retardation)Irreversible brain damage 100

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Lead Standards and Regulations

Blood LevelsCDC Advisory – level of concern for children 10 ug/dLOSHA – level of concern 40 ug/dLOSHA Regulation – medical removal from exposure 50 ug/dL

Air ConcentrationsOSHA Action level 30 ug/m3

OSHA Regulation – PEL 50 ug/m3

US EPA – ambient air quality standard (3 month average) 1.5 ug/m3

FoodEPA – drinking water action level 15 ug/LCalEPA – drinking water public health goal 2 ug/LCalEPA – drinking water maximum contaminant level 15 ug/LFDA – food advisory level 100

ug/day

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Poverty and Lead Poisoning

Impact greatest among urban poorOlder housing more lead based paints and lead

contaminated soilsOlder 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

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Blood Lead Levels for Various Groups of People

Rural Children 7-11Urban Children 9-33Adults 15-22Children near smelter 35-68

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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

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Treatment

Depends on exposure levelLimit exposure

May be only therapy needed for asymptomatic patients with blood levels below 25 ug/dL

Dietary changesCa supplements

Chelation therapy (e.g. calcium disodium EDTA)CDC recommends immediate chelation therapy for

children with blood levels of 45 ug/dL and above

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Mercury

Long history of useMetallic mercury used as a laxativeMad Hatters disease from use in felt manufactureAndrew Jackson thought to have died from

mercuric chloride treatment“Dancing Cat Disease”

ChemistryExists in 3 forms: elemental, inorganic salts and

organicElemental (metallic) mercury (Hg0) can be

converted to organic methylmercury (MeHg) in the environment by the action of bacteria

Hg0

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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 formOlder and larger carnivorous fish have the

highest levels (swordfish, tuna, shark, king mackerel)

Can of tuna contains 0.20 ppm

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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.

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Mercury Health Effects

Effects depend on duration, intensity, and route of exposure, and chemical form

Central nervous system and kidneys are key targetsElemental mercury: nervous systemMercury salts: respiratory or GI (acute

exposure); kidneys (chronic exposure)Organic mercury: nervous system;

developmental effectsElemental mercury not classified with

respect to carcinogenicity (USEPA Class D)

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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 organizationAlters the normal migration of neurons to cerebellar

and cerebral cortices during brain developmentReduced brain size

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Mercury Controversy

Two recent studies of predominately fish eating populations:Faroese Islands

Dose dependent relationship seen (delayed language, reduced memory and attention spans)

Seychelle IslandsNo 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

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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.

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Mercury Standards and Regulations

Air ConcentrationsOSHA – 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/LCAlEPA – drinking water public health goal 1.2 ug/LCAlEPA – drinking water maximum contaminant level 2

ug/L

FoodFDA – Fish action level 1 ppmUSEPA – fish action level 0.3 ppmJapan – fish action level 0.3 ppmAustralia – fish action level 0.5 ppm

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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 . . .

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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

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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 tremor2-100

Irritability, depression, memory loss, minor tremor, other nervous system disturbances; disturbed kidney function100-500

Kidney inflammation, swollen gums, significant tremor and nervous system disturbances500-1000

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Treatment

Depends on form of mercury exposureElemental 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

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Toxicology