Detecting lead toxicity

Lead is a heavy metal commonly found in man's environment that

can be an acute and chronic toxin.

Lead is present in paints manufactured before 1970. Lead was

banned from household paints in 1972 but is still found in paint

produced for non-domestic use and in artistic pigments. Ceramic

products available from non-commercial 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 non-lead gasolines that have

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,

two 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 all tissues

exposed to lead will have 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 ug

of lead per day, of which 1-10% 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 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.

<10 ug/dL

Critical values

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

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

The Centers for Disease Control and Prevention have identified

the blood lead test as the preferred test for detecting lead exposure

in children. Chronic whole blood lead <10 ug/dL is normal in children.

Chelation therapy is indicated when whole blood lead concentration

is >45 ug/dL.

The Occupational Safety and Health Administration has published

the following standards for employees working in industry: Employees

with whole blood lead >60 ug/dL must be removed from workplace

exposure. Employees with whole blood lead >50 ug/dL averaged

over three 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 ug/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. Cited March 2000. Available from URL:

      http://www.ambest.com/safety/osha/chap10g.html

2.   Rosen JF:  Preventing Lead Poisoning in Young Children. US

      Public Health Service, Centers for Disease Control, Atlanta, GA,

      1991

3.   Bellinger 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 level sof whole blood and serum lead in humans: an

      experimental evaluation in animals. In Trace Substances in

      Envrionmental Health XIX. Proceedings of the University of

      Missouri's 19th Annual Conference on Trace Substances in

      Environmental Health, Columbia, MO, June 3-6, 1985, pp248-256