Lead Toxicity

Julie Lemmon, MD
CAP Toxicology Resource Committee
Lead is a common metal whose long history is intertwined with societal developments and
detriments !ecause it is so"t, mallea#le and resistant to corrosion, humans have "ound many
and varied uses "or the element
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Ancient civili%ations used lead as a component o" cosmetics, a
condiment and a wine preservative &t was a ma'or component o" (itchenware and coins Roman
civili%ation was supplied with water routed through a complex ma%e o" pipes "orged "rom lead
During the Middle Ages alchemists tried to produce gold "rom lead, #ut a more productive use o"
the metal was reali%ed when the )uten#erg printing press used lead plates The many uses o"
lead were not lost on those who settled the *ew +orld where many technological developments
were #ased on its use Modern societies have continued to use lead in a variety o" ways, the
most signi"icant o" which include the automotive industry,s introduction o" tetraethyl lead "uel
additive in the $-./s
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and the use o" lead as a pigment and preservative in paint
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This long history o" lead use is not without conse1uences 2ven in ancient times, the syndrome o"
acute lead poisoning was recogni%ed and wary individuals too( action to limit their exposure to
lead The less enlightened continued to drin( their 3leaded4 wine with conse1uences that included
psychiatric distur#ances and decreased "ertility +or(ers in the 5nited 6tates involved in the
development and production o" tetraethyl "uel additive in the $-./s "ell ill and some even died
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2ven though pu#lic health measures aimed at reducing lead exposure were enacted as early as
the $-./s,
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lead remains the most common metal to cause poisoning
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)overnmental regulations
designed to eliminate lead "rom gasoline and residential paint had remar(a#le success in
decreasing the num#er o" children with lead poisoning Prior to the era o" catalytic converters and
unleaded gasoline, the #ul( o" lead toxicity was due to contact with leaded gasoline and its
com#ustion #yproducts *ow the ma'or source o" lead exposure is through a#sorption o"
deteriorating leaded paint
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Lead toxicity can #e due to acute or chronic exposure Acute toxicity is "re1uently caused #y pica
syndrome9 the symptoms can include a#dominal pain, nausea and vomiting, hemolysis, renal
"ailure, hepatotoxicity, sei%ures and coma The symptoms o" chronic lead poisoning are mani"est
in multiple organ systems, including the gastrointestinal tract, the hematopoietic process, the
(idneys and the nervous system The diverse clinical mani"estations can #e explained #y the
cellular mechanisms o" lead toxicity that inter"ere with a variety o" "unctions, including cell
mem#rane integrity, neurotransmitter "unction, heme synthesis and mitochondrial oxidative
phosphorylation &n the case o" heme synthesis, "or example, lead inhi#its en%ymes in the
porphyrin pathway resulting in increases o" su#strates, which are su#se1uently eliminated and
can #e measured in urine There is also inhi#ition o" the "errochelatase en%yme, resulting in
"ailure to incorporate iron into the tetrapyrrole ring o" heme
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The pre"erred specimen "or assessing lead toxicity is whole #lood,
7,:
although current research is
exploring the via#ility o" analy%ing lead concentrations in plasma
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+hen su#mitting a #lood
sample "or lead testing, it is imperative to avoid contamination The use o" lead<"ree syringes and
tu#es should #e used in con'unction with an immaculate venipuncture techni1ue
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La#oratory
analysis should commence promptly, as lead in the specimen will adsor# onto the walls o" glass
tu#es over time
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Although up to =/> o" lead can #e lost during one wee( o" storage, the addition
o" $> nitric acid or 0> hydrogen peroxide will allow preservation "or up to "ive days, and samples
collected in 2DTA and "ro%en at <./?C are sta#le "or several months
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Measuring the amount o" lead in a specimen is #ased on one o" three di""erent methods@
spectrophotometry, atomic a#sorption spectrophotometry AAA6B or anodic stripping voltammetry
AA6CB AA6, in one o" its variations, and A6C are the most "re1uently used methods
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and have
di""ering approaches &n AA6, the recommended method "or analysis,
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the un(nown sample is
ashed Aeither with "lame or "urnaceB to remove organic material and the resulting su#stance is
reduced to its atomic state with spectrophotometric measurement o" light a#sor#ance at
characteristic wavelengths &n A6C, ionic lead in a #iological sample is reduced to elemental lead
#y the negative potential o" a mercury electrode The potential o" the mercury electrode is then
altered, and the anodic current that results "rom the reoxidation o" the lead can #e measured and
is proportional to the concentration o" lead in the specimen +hile the A6C method is sometimes
used #ecause o" its simplicity, it may lac( sensitivity compared to AA6 at the range o" most critical
concentrations AD$/EgFdLB
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Lead test results in"orm clinicians a#out exposure and therapy may #e started i" the concentration
is su""iciently elevated +hile a #lood lead concentration o" $/EgFdL is the current #enchmar(
used to diagnose lead poisoning, there is ongoing research and some evidence that intellectual
de"icits may occur with lead concentrations as low as ;8 gFdL
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The American Academy o"
Pediatrics provides a thorough review o" lead toxicity in its .//8 Policy 6tatement
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Patients with lead toxicity may #e treated with chelating agents as well as dietary supplements
that include iron, calcium, magnesium, %inc, phosphate or vitamin D to help minimi%e intestinal
a#sorption o" lead The e""ectiveness o" treatment can #e "ollowed #y measuring .7<hour urinary
lead
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The collection must #e into a lead "ree container A"or example a polyethylene #ottle washed
with hydrochloric acid
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B and preserved with thymol
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Cooperation among clinicians, la#oratorians and patients will result in improved detection o" lead
toxicity in at<ris( populations The role o" the clinical la#oratory continues as "urther o#servation o"
treatment e""ectiveness in lead toxic patients is needed This is an excellent opportunity "or
la#oratory medicine to support pu#lic health with the detection and treatment o" what the Centers
"or Disease Control and Prevention has designated as one o" the leading environmental threats to
children
Re"erences@
$ Je""erson La# 6cience 2ducation +e# site Availa#le at@
http@FFeducation'la#orgFitselementalFele/=.html Accessed January $=, .//;
. 5nited 6tates 2nvironmental Protection Agency Gistory +e# site Lead Poisoning@ A Gistorical
Perspective Availa#le at@ http@FFwwwepagovFhistoryFtopicsFperspectFleadhtm Accessed January
$=, .//;
0 5nited 6tates Department o" Gousing and 5r#an Development 2nergy 2""icient Reha# Advisor
+e# site Lead<#ased Paint as a Ga%ard During Remodeling Availa#le at@
http@FFreha#advisorpathnetorgFspaspHidI$/7./ Accessed January $=, .//;
7 Jang JM, Lewandrows(i K! Trace elements, vitamins, and nutrition &n@ McClatchey KD, 2d
Clinical Laboratory Medicine .nd ed Philadelphia, Pa@ Lippincott +illiams and +il(ins9
.//.@78:L7:/
8 American Academy o" Pediatrics Committee on 2nvironmental Gealth Lead exposure in
children@ prevention, detection, and management Pediatrics .//89$$:A7B@$/0:L$/7:
: Po(lis A, +ong 6GJ, Pesce AJ Toxicology &n@ Kaplan LA, Pesce AJ, Ka%mierc%a( 6C, 2ds
Clinical Chemistry: Theory, Analysis, and Correlation 0rd ed 6t Louis, Mo@ Mos#y9$--:@$/.-L
$/0$
; !ergdahl &A, )erhardsson L, Lil'elind &2, et al Plasma<lead concentration@ investigations into
its use"ulness "or #iological monitoring o" occupational lead exposure Am J Ind Med.
.//:97-A.B@-0L$/$
= Alcoc( *+ Trace elements &n@ Kaplan LA, Pesce AJ, Ka%mierc%a( 6C, 2ds Clinical
Chemistry: Theory, Analysis, and Correlation 7th ed 6t Louis, Mo@ Mos#y9 .//0@;/;L;.$
- Lanphear !P, Gornung R, Khoury J, et al Low<level environmental lead exposure and
childrenMs intellectual "unction@ an international pooled analysis Environ Health Perspect.
.//89$$0A;B@=-7L=--