Test ID: LEADO    
Lead Profile Occupational Exposure, Blood

Detecting lead toxicity and monitoring treatment

Lead is a heavy metal commonly found in the man's environment that can be an acute and chronic toxin.

Lead is present in paints manufactured before 1970. It was banned from household paints in 1972 but is still found in paint produced for nondomestic use and in artistic pigments. Ceramic products available from noncommercial suppliers (such as local artists) often contain significant amounts of lead that can be leached from the ceramic by weak acids such as vinegar and fruit juices. Lead is found in dirt from areas adjacent to homes painted with lead-based paints and highways where lead accumulates from use of leaded gasoline. Use of leaded gasoline has diminished significantly since the introduction of unleaded gasoline, which has been required in personal automobiles since 1972. Lead is found in soil near abandoned industrial sites where lead may have been used. Water transported through lead or lead-soldered pipe will contain some lead with higher concentrations found in water that is weakly acidic. Some foods (eg, moonshine distilled in lead pipes) and some traditional home medicines contain lead.

Exposure to lead from any of these sources either by ingestion, inhalation, or dermal contact can cause significant toxicity.

Lead expresses its toxicity by several mechanisms. It avidly inhibits aminolevulinic acid dehydratase (ALA-D) and ferrochelatase, 2 of the enzymes that catalyze synthesis of heme. Inhibition of ALA-D and ferrochelatase causes accumulation of delta aminolevulinic acid in urine and protoporphyrin in erythrocytes, which are markers for significant lead exposure.

Lead also is an electrophile that avidly forms covalent bonds with the sulfhydryl group of cysteine in proteins. Thus, proteins in any tissues exposed to lead will have lead bound to them.

Keratin in hair contains a high fraction of cysteine relative to other amino acids. The cysteine residues are cross-linked through lead, thereby causing the tertiary structure of the protein to change; cells of the nervous system are particularly susceptible to this effect. Some lead-bound proteins change their tertiary configuration sufficiently that they become antigenic; renal tubular cells are particularly susceptible to this effect because they are exposed to relatively high lead concentrations during clearance.

A typical diet in the United States contributes approximately 300 mcg of lead per day, of which 1% to 10% is absorbed; children may absorb as much as 50% of the dietary intake, and the fraction of lead absorbed is enhanced by nutritional deficiency. The majority of the daily intake is excreted in the stool after direct passage through the gastrointestinal tract. While a significant fraction of the absorbed lead is rapidly incorporated into bone and erythrocytes, lead ultimately distributes among all tissues, with lipid-dense tissues such as the central nervous system being particularly sensitive to organic forms of lead. All lead absorbed is ultimately excreted in the bile or urine. Soft-tissue turnover of lead occurs within approximately 120 days.

Avoidance of exposure to lead is the treatment of choice. However, chelation therapy is available to treat severe disease. British anti-Lewisite (BAL) administered intravenously was the classical mode of chelation therapy. Oral dimercaprol has recently become available and is being used in the outpatient setting except in the most severe cases.

Measurement of urine excretion rates either before or after chelation therapy has been used as an indicator of lead exposure. However, blood lead analysis has the strongest correlation with toxicity.

Erythrocyte protoporphyrin (EP) is a biologic marker of lead toxicity and was previously used in conjunction with blood lead assays to screen for lead poisoning in children. However, because of poor sensitivity and specificity, EP is no longer recommended for lead screening in children. However, EP remains a useful tool for monitoring treatment of individuals with confirmed elevated lead levels.

Lead screening in children and protocols for assessment for treatment have been detailed by the Centers for Disease Control and Prevention (CDC).

LEAD

0-6 years: 0-4 mcg/dL

>or =7 years: 0-9 mcg/dL

Critical values

Pediatrics (< or =15 years): > or =20 mcg/dL

Adults (> or =16 years): > or =70 mcg/dL

ZINC PROTOPORPHYRIN

<100 mcg/dL

The Centers for Disease Control and Prevention (CDC) has identified the blood lead test as the preferred test for detecting lead exposure in children. Chronic whole blood lead levels <10 mcg/dL is often seen in children. For pediatric patients, there may be an association with blood lead values of 5 mcg/dL to 9 mcg/dL and adverse health effects. Follow up testing in 3 to 6 months may be warranted. Chelation therapy is indicated when whole blood lead concentration is >45 mcg/dL.

The Occupational Safety and Health Administration (OSHA) has published the following standards for employees working in industry:

-Employees with whole blood lead >60 mcg/dL must be removed from workplace exposure.

-Employees with whole blood lead >50 mcg/dL averaged over 3 blood samplings must be removed from workplace exposure.

-An employee may not return to work in a lead exposure environment until whole blood lead is <40 mcg/dL.

An elevated erythrocyte protoporphyrin (EP) indicates impairment of the heme biosynthetic pathway. Elevated EP levels in adults may indicate long-term lead exposure. Expected EP levels seen in heavy metal toxicity are in the range of >100 mcg/dL.

No significant cautionary statements

1. Occupational Safety and Health Administration: OSHA Lead Standard - Requirements from the General Industry Standards Lead (1910, 1025), from 29 CFR 1910, 1025, A.M. Best Safety and Security - 2000. Retrieved March 2000. Available from URL: ambest.com/safety/osha/chap10g.html

2. Centers for Disease Control and Prevention. Screening Young Children for Lead Poisoning. Guidance for State and Local Public Health officials. Atlanta, GA: US Dept of Health and Human Services. Public Health Service: November 1997 Available from URL: cdc.gov/nceh/lead/guide/guide97.htm

3. Belinger D, Leviton A, Waternaux C, et al: Longitudinal analyses of prenatal and postnatal lead exposure and early cognitive development. N Engl J Med 1987 Apr 23;316(17):1037-1043

4. Needleman HL, Schell A, Bellinger D, et al: The long-term effects of exposure to low doses of lead in childhood. An 11-year follow-up report. N Engl J Med 1990 Jan 11;322(2):83-88

5. Nixon DE, Moyer TP, Windebank AJ, et al: Lack of correlation of low levels of whole blood and serum lead in humans: an experimental evaluation in animals. In Trace Substances in Environmental Health XIX. Proceedings of the University of Missouri's 19th Annual Conference on Trace Substances in Environmental Health, Columbia, MO, 1985, pp 248-256

• Lead/Heavy Metals Reporting Form
• Metals Analysis-Collection and Transport