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Alan M. Ducatman, MD, MSc West Virginia University School of Medicine: 

Alan M. Ducatman, MD, MSc West Virginia University School of Medicine

What is Lead?: 

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: 

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: 

Historic Production of Lead 3500 BC-1450 AD: Mostly mined as a byproduct of silver extraction, and mostly converted to… SMOKE. 1450-1750 AD: Byproduct of copper smelting. Industrial Revolution: Byproduct of coal and combustion. Taller stacks spread pollution. Peak emissions 1970-80 (400,000 tons/yr).

Historic Production of Lead: 

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: 

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 BLLS Geometric Mean >10 >15 >20 μg/dL 2.7 10.5 3.9 1.9 8.6 3.2 1.5 2.0 7.6 2.7 1.2 Approximate # of children tested= 1.2 million yearly From: MMWR 2000;49:1133-1137

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

Childhood Risk Factors for Elevated BLLs (>10μg/dl) Pre-1946 Housing Non-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 Young Children (Dec. 2000)

Lead- It’s Everywhere: 

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: 

Sources of Lead- Air Uncontaminated Contaminated 1-2 μg/m3 4-16 μg/m3 Near Smelter

SOURCES OF LEAD- Water: 

SOURCES OF LEAD- Water Uncontaminated Standards vary Internationally. In U.S. <15 μg/L 99% of water supplies

SOURCES OF LEAD- Food: 

SOURCES OF LEAD- Food Uncontaminated Mixed Diet 9.43 μg/kg/day Bottled Baby Food 3.5 μg/L Contaminated Older Canned Baby Food 202 μg/L Bone Meal 60-190 μg/g _______________________________________________ Compare this to a paint chip 100,000 μg/g or more Paint Chip 100,000 μg/g or more

Lead- It’s Everywhere: 

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: 

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: 

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: 

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?: 

How does lead enter the body? Respiratory Breathing 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?: 

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?: 

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? : 

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: 

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?: 

Where does lead go once in the body? Lead is absorbed into the bloodstream rapidly. It then travels to “soft tissue” such as kidneys, lungs, brain, spleen, muscles, and heart. 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: 

Lead Compartments BONE  BLOOD  SOFT TISSUE 10 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: 

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?: 

What Does Lead Do? Lead inhibits certain types of enzymes, Particularly enzymes dependant upon sulfhydryl groups. Organ systems affected include: Neurologic Endocrine (including BP) Reproductive Musculoskeletal Blood Renal GI

Microcytic Anemiawith Basophilic Stippling: 

Microcytic Anemia with Basophilic Stippling Larger area is a thick thick smear to demonstrate the frequency of basophilic stippling

Alternative tests to blood lead: 

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: 

CNS Symptoms in Adults

Peripheral Neuropathy in Lead Poisoning: 

Peripheral Neuropathy in Lead Poisoning Distal Symmetric Axonal Polyneuropathy: Wrist Drop Foot Pain Joint Pain Dexterity

Cognitive Performance Deficits* in Lead- Exposed Children: 

Cognitive Performance Deficits * in Lead- Exposed Children Deficits: Psychomotor performance Auditory and language processing Sustained attention & concentration Measured outcomes: Less likely to graduate High School More likely to be convicted of felonies *Deficits consistent across cultures and controlled for SES

Lead Poisoned Children as Young Adults: 

Lead Poisoned Children as Young Adults A 20-year follow up by ATSDR of 917 lead poisoned children (mean 50 ug/dl) measured lead bone storage by tibial KXRF. Diminished were: 1. Sural nerve sensory and peroneal motor evoked response amplitude. Vibro-tactile thresholds: Fingers and toes Standing coordination 2. Hand-eye coordination in several types of test performance (Trails B, Symbol Digit, Learning Error).

Lead Exposure in utero: 

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: 

Lead Outcomes in Children Exposed in Utero High Dose Lower Dose Spontaneous Abortion Low Birth Weight Stillbirth Neuropsychologic Problems Additional risk from breast milk

Lead and Adult Reproduction: 

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 & Bones

Lead & Hypertension: 

Lead & Hypertension

Lead and the KidneyAcute and Chronic Disease: 

Lead and the Kidney Acute and Chronic Disease Lead nephropathy (Fanconi syndrome) is characterized by aminoacidura, glucosuria, phosphaturia with hypophosphatemia, and deceased uric acid excretion. Chronic kidney disease may also arise, sometimes associated with gout.

Other Organ Systems Affected by Lead: 

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*: 

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: 

Key Presenting Symptoms

Physical Findings: 

Physical Findings Early Chronic Wrist Drop Transverse Nail Lines Distal Sensation Blue-Black Gum Lines Proprioception Vibration Sense

Detecting Lead Poisoning in Young Children: 

Detecting Lead Poisoning in Young Children

CDC“Preventing Lead Poisoning in Young Children” Oct- 1991: 

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: 

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: 

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: 

The Key to “Treatment” of Lead Poisoning Remove from exposure, or otherwise prevent exposure. Workplace Home Substitution Move Engineering Identify and Abate Personal Protection Work Practices Job Placement

Chelation Therapy: 

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: 

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 days In children Social Danger: Lowering blood level by oral chelation is not a substitute for workplace hygiene!!

Prevention of Lead Poisoning : 

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: 

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