Alan M. Ducatman, MD, MSc West Virginia University

School of Medicine

What is Lead?

Lead is a blush gray metallic element which occurs naturally (in small amounts) in the earth’s crust.

It is dense, hence its use as a ballast, ammunition, or radiation shield.

Lead is insoluble in water, but some salts are soluble.

Significant Health Characteristics of Lead

Lead has a low melting point and can easily be aerosolized by heating.

Lead can be formed into organic compounds by some organisms, and some organic compounds (such as “leaded gasoline”) have industrial uses.

Historic Production of Lead

1. 3500 BC-1450 AD: Mostly mined as a byproduct of silver extraction, and mostly converted to… SMOKE.

2. 1450-1750 AD: Byproduct of copper smelting.

3. Industrial Revolution: Byproduct of coal and combustion. Taller stacks spread pollution. Peak emissions 1970-80 (400,000 tons/yr).

Historic Production of Lead

Lead in paints (never permitted in some alert countries). Banned 1978 in the U.S.

Automobile (1923 - depends on country)

Emission byproduct of leaded gasoline.

Improved Lead Levels in the US

Blood lead levels in children <6 years old showed an approximately 80% decline from the 1970’s to 1994, and a continuing drop from 1994-1998.

% with elevated BLLSGeometric Mean >10 >15 >20 μg/dL

1994 2.7 10.5 3.9 1.91996 8.6 3.2 1.51998 2.0 7.6 2.7 1.2

Approximate # of children tested= 1.2 million yearlyFrom: MMWR 2000;49:1133-1137

Childhood Risk Factors for Elevated BLLs (>10μg/dl)

Pre-1946 HousingNon-Hispanic Black 21.9%Mexican American 13.0%White 5.6%

Low Income 16.4%High Income 0.9%

NHANES III, and CDC Recommendations for BL Screening of YoungChildren (Dec. 2000)

Lead- It’s Everywhere

USES OF Pb

Storage batteries Automobile radiators

Cable Brass and bronze Production

Radiation shielding Construction

Galvanizing Ammunition

Annealing Printing

Plating

Paint Plastics

Soldering Television electronics

Glass Petroleum

Insecticides

Sources of Lead- Air

Uncontaminated Contaminated

1-2 μg/m3 4-16 μg/m3

Near Smelter

SOURCES OF LEAD- Water

Uncontaminated

Standards vary Internationally.

In U.S. <15 μg/L 99% of water supplies

SOURCES OF LEAD- Food

Uncontaminated

Mixed Diet 9.43 μg/kg/day

Bottled Baby Food 3.5 μg/LContaminated

Older Canned Baby Food 202 μg/L

Bone Meal 60-190 μg/g_______________________________________________

Compare this to a paint chip 100,000 μg/g or morePaint Chip 100,000 μg/g or more

Lead- It’s Everywhere

Unusual oral sources of lead:Ceramic glazes, art pottery, primitive equipment for making maple syrup, crystal glass used to contain alcohol products, certain cosmetics applied to hands or face, some candle wicks, folk medicines, used lead radiators, moonshine liquor.

Lead- It’s Everywhere

What is Lead Paint?Lead paint uses LEAD as a pigment.It was advantageous to do this because it “sticks” (coats or penetrates) well.

There are 2 types-White lead (basic lead carbonate)Red lead (a form of lead oxide)

SOURCES OF LEAD- Soil

Uncontaminated

Remote area 2-200 µg/g

Contaminated

Urban residential mean 585 µg/g

City parks 194 - 3,357 µg/g

Near smelter mean 7,600 µg/g

SOURCES OF LEAD-House Dust

Uncontaminated- New inner-city home

Floor Surface- 2-24 µg/sq ft

Contaminated- Old inner-city home

Floor Surface- 33-486 µg/sq ft

How does lead enter the body?

1. RespiratoryBreathing in dust that contain lead. Lead is absorbed and distributed to other parts of the body via the bloodstream.

How Does Lead Enter the Body?

2. Ingestion

Adults absorb about 6% of ingested lead. Fasting adults absorb more.

Children absorb much more lead

(30-50% if well fed, and more, if fasting or malnourished).

How Does Lead Enter the Body?

3. Skin

Skin is relatively impervious to lead, lead oxides , or lead salts. Some may get through scrapes or wounds, but organic leads (such as in leaded gasoline), will go through skin into the bloodstream quite well.

Does the Route of Entry Matter?

• Lead, lead salts, lead oxide, all have same toxicity (whether inhaled or ingested), but more is absorbed when inhaled.

• Organic lead has greater affinity for CNS – therefore skin absorption may be SERIOUS

Lead Metabolism and Nutrition

Low dietary intake of vitamin D, vitamin C, and iron enhance absorption and retention of lead in the body.

It is believed that vitamin D modifies lead-bone metabolism, while vitamin C and iron may also modify excretion.

Cheny L, et al AJ Epi 1998:147:1162-1174

Where does lead go once in the body?

1. Lead is absorbed into the bloodstream rapidly.

2. It then travels to “soft tissue” such as kidneys, lungs, brain, spleen, muscles, and heart.

3. After several weeks, most lead moves into bones and teeth (and some into hair).

• About 94% of adults total lead burden is in bones and teeth

• Only about 73% for children

4. Lead in bones and teeth equilibrates over time and

circumstance with other “compartments”.

Lead Compartments BONE BLOOD SOFT TISSUE10 Days 27 Days 30-40 Days TEETH URINE BILE, HAIR, SWEAT, NAIL

Figure 2.5 A simple three-compartment model for absorption, retention, and elimination of lead in humans. Quantitative estimates apply to adult males . Source: derived from Rabinowitz et al. (1975)

How Does Lead Get Out of the Body

• Kidneys- urine

• Bowels- stool

• Glands- sweat

• Breast- breast milk

• Hair, nails, teeth (very slow turnover)

• It takes >10 years to turn over one half the body’s stored lead. Bone source slowly leaches into the blood.

What Does Lead Do?

Lead inhibits certain types of enzymes,Particularly enzymes dependant uponsulfhydryl groups.

Organ systems affected include:Neurologic Endocrine (including BP)Reproductive MusculoskeletalBlood RenalGI

Microcytic Anemiawith Basophilic Stippling

Larger area is a thick thick smear to demonstrate the frequency of basophilic stippling

Alternative tests to blood lead

• Erythrocyte protoporphyrin and zinc protoporphyrin tend to become elevated as

lead-induced hemoglobin salvage increases.

• These tests are neither sensitive nor specific for detecting lead exposure. They have limited usefulness in the diagnosis, surveillance, or treatment of lead exposure and lead poisoning.

CNS Symptoms in Adults

Early Later Chronic

Irritability Ataxia Hearing Loss

Impaired Judgment

Hallucinations Diminished Judgment

Depression Seizure ↓ Memory

↓ Dexterity Death ↓Cognition

Peripheral Neuropathy in Lead Poisoning

Distal Symmetric Axonal Polyneuropathy:

Wrist Drop

Foot Pain

Joint Pain

Dexterity

Cognitive Performance Deficits* in Lead- Exposed Children

Deficits:Psychomotor performanceAuditory and language processingSustained attention & concentrationMeasured outcomes: Less likely to graduate High SchoolMore likely to be convicted of felonies

*Deficits consistent across cultures and controlled for SES

Lead Poisoned Children as Young Adults

A 20-year follow up by ATSDR of 917 leadpoisoned children (mean 50 ug/dl) measuredlead bone storage by tibial KXRF.Diminished were:1. Sural nerve sensory and peroneal motor evoked response

amplitude.Vibro-tactile thresholds: Fingers and toesStanding coordination

2. Hand-eye coordination in several types of test performance (Trails B, Symbol Digit, Learning Error).

Lead Exposure in utero

• Lead crosses the placenta in plasma.• Pregnancy (and lactation) causes lead release from

bone stores into plasma• Plasma lead is about 1% of circulating blood lead.• Epidemiologic effects on CNS have been

documented.• Peak transfer is at 12-14 weeks gestation

Lead Outcomes in ChildrenExposed in Utero

High Dose Lower Dose

Spontaneous Abortion Low Birth WeightStillbirth Neuropsychologic

ProblemsAdditional risk from breast milk

Lead and Adult Reproduction

Reproductive

Females- Miscarriage, still birth- Inability to conceive

Males- Decreased libido- Decreased fecundity- Sperm abnormalities: counts, abnormal forms Dose response relationship

Lead & Bones

Lead & Hypertension

Lead and the KidneyAcute and Chronic Disease

1. Lead nephropathy (Fanconi syndrome) is characterized by aminoacidura, glucosuria, phosphaturia with hypophosphatemia, and deceased uric acid excretion.

2. Chronic kidney disease may also arise, sometimes associated with gout.

Other Organ Systems Affected by Lead

Hearing (8th nerve damage)

Gout

GI- Anorexia, colic

Endocrine- Vitamin D Metabolism

Genotoxicity

Key Aspects of the Clinical History*

Home environment (or environment where a child visits)

Home remodeling (occupational histories: all family members)

Hobbies, making glazed ceramics, fishing sinkers

Unusual medications, cosmetics

For children, the vast majority of sources will be paint.

For adults, it will be occupation.

For adults and children, home remodeling is an issue

Occupational Histories All family members

*The exposure history provides the key to successful Rx!

Key Presenting Symptoms

Mild Moderate Severe

Fatigue Paresthesia Paralysis

Irritability Myalgia Colic

Arthralgia

Headache

Tremor

GI Distress

Physical Findings

Early Chronic

Wrist Drop Transverse Nail Lines

Distal Sensation Blue-Black Gum Lines

Proprioception

Vibration Sense

Detecting Lead Poisoning in Young Children

CDC“Preventing Lead Poisoning in Young Children”

Oct- 1991

Initial Test (12 months)

Surveillance Strategy

<10 µg/dl 10-14 µg/dl

Repeat at 24 months Retest in 1-3 months

>15 µg/dl Individual Case Management

Medical Surveillance for Adult Workers

When: Exposure above “action level”

>30 days/yr

What: Triggers periodic exams and biologic monitoring (including blood level)

Removal threshold: 50 µg/dl (repeated) or 60 µg/dl once.

Repeat testing: Monthly, depending on lead level

Adult Return to Work

• Lead poisoned workers can return to the workplace when blood lead is <40 µg/dl.

• Symptomatic workers can remain out of the workplace at lower levels.

• Workers whose blood lead is near 40 µg/dl are most likely to be able to remain in the workplace if they can perform modified duty without lead exposure.

The Key to “Treatment”of Lead Poisoning

Remove from exposure, or otherwise preventexposure.

Workplace Home Substitution MoveEngineering Identify and AbatePersonal ProtectionWork PracticesJob Placement

Chelation Therapy

• For symptoms, or physical findings.• May prevent dread acute consequences- seizure• No longer believed to protect CNS in

asymptomatic children• Must be considered in light of possible

complications- kidney damage and arrhythmia.• Will cause increased lead absorption if exposure

persists.

Choice of Chelation Agents

Outpatient: Succimer 1050 mg/m²x 7 days 700 mg/m²x14-19 days

Inpatient: CaNa² -EDTA 1000 –1500 mg/m²/dx 5 days

Encephalopathy Add: BAL 300-450 mg/m²/d x 3 daysIn childrenSocial Danger:Lowering blood level by oral chelation is not a substitute forworkplace hygiene!!

Prevention of Lead Poisoning

Prevention of lead poisoning is a superior public health measure; medical treatment alone is disappointing.

The key to treatment is cessation of exposure, and the public health need is to consider and find other possible victims.

Helpful Web Sites

• ATSDR http://www.atsdr.cdc.gov/HEC/CSEM/lead/index.html

•  ATSDR Toxicological Profiles http://www.atsdr.cdc.gov/toxpro2.html• ATSDR ToxFAQs ™  http://www.atsdr.cdc.gov/toxfaq.html• CDC-NCEH  http://www.cdc.gov/nceh/lead/lead.htm• NIOSH  http://www.cdc.gov/niosh/leadpg.html