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

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 nonlead

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 (for example: 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 significant markers

for 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 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 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.

Pediatrics (< or =15 years)

      Normal:  <10 ug/dL

      Toxic concentration:  > or = 20 ug/dL

Adults

      Normal:  <20 ug/dL

      Toxic concentration:  > 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 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 ug/dL.

The 95th percentile of the gaussian distribution of whole blood lead

concentrations in a population of unexposed adults is 20 ug/dL (Mayo

Clinic reference range data).

Normally, hair lead content is <5 ug/g.  Hair lead >25 ug/g indicates

hair lead exposure.

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. 

Gadolinium is known to interfere with most metals tests. If gadolinium-

containing contrast media has been administered a specimen can

not be collected for 48 hours.

Serum analysis for lead is of very limited utility, being abnormal

only for a short interval after exposure.(5)

1.   "OSHA Lead Standard - Requirements from the General Industry

      Standards Lead (1910.1025)," from 29 CFR 1910.1025,

      A.M. Best Safety and Security - 2000 Occupational Safety and

      Health Administration, cited March 2000.  Available from URL:

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

2.   Rosen JF:  Preventing Lead Posioning 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;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;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, June 3-6, 1985, pp 248-256