College of American Pathologists
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Lead Toxicity

Posted February 1, 2007

Julie Lemmon, MD
CAP Toxicology Resource Committee

Lead is a common metal whose long history is intertwined with societal developments and detriments. Because it is soft, malleable and resistant to corrosion, humans have found many and varied uses for the element.1 Ancient civilizations used lead as a component of cosmetics, a condiment and a wine preservative. It was a major component of kitchenware and coins. Roman civilization was supplied with water routed through a complex maze of pipes forged from lead. During the Middle Ages alchemists tried to produce gold from lead, but a more productive use of the metal was realized when the Gutenberg printing press used lead plates. The many uses of lead were not lost on those who settled the New World where many technological developments were based on its use. Modern societies have continued to use lead in a variety of ways, the most significant of which include the automotive industry’s introduction of tetraethyl lead fuel additive in the 1920s2 and the use of lead as a pigment and preservative in paint.3

This long history of lead use is not without consequences. Even in ancient times, the syndrome of acute lead poisoning was recognized and wary individuals took action to limit their exposure to lead. The less enlightened continued to drink their “leaded” wine with consequences that included psychiatric disturbances and decreased fertility. Workers in the United States involved in the development and production of tetraethyl fuel additive in the 1920s fell ill and some even died.2

Even though public health measures aimed at reducing lead exposure were enacted as early as the 1920s,2 lead remains the most common metal to cause poisoning.4 Governmental regulations designed to eliminate lead from gasoline and residential paint had remarkable success in decreasing the number of children with lead poisoning. Prior to the era of catalytic converters and unleaded gasoline, the bulk of lead toxicity was due to contact with leaded gasoline and its combustion byproducts. Now the major source of lead exposure is through absorption of deteriorating leaded paint.5

Lead toxicity can be due to acute or chronic exposure. Acute toxicity is frequently caused by pica syndrome; the symptoms can include abdominal pain, nausea and vomiting, hemolysis, renal failure, hepatotoxicity, seizures and coma. The symptoms of chronic lead poisoning are manifest in multiple organ systems, including the gastrointestinal tract, the hematopoietic process, the kidneys and the nervous system. The diverse clinical manifestations can be explained by the cellular mechanisms of lead toxicity that interfere with a variety of functions, including cell membrane integrity, neurotransmitter function, heme synthesis and mitochondrial oxidative phosphorylation. In the case of heme synthesis, for example, lead inhibits enzymes in the porphyrin pathway resulting in increases of substrates, which are subsequently eliminated and can be measured in urine. There is also inhibition of the ferrochelatase enzyme, resulting in failure to incorporate iron into the tetrapyrrole ring of heme.4

The preferred specimen for assessing lead toxicity is whole blood,4,6 although current research is exploring the viability of analyzing lead concentrations in plasma.7 When submitting a blood sample for lead testing, it is imperative to avoid contamination. The use of lead-free syringes and tubes should be used in conjunction with an immaculate venipuncture technique.6 Laboratory analysis should commence promptly, as lead in the specimen will adsorb onto the walls of glass tubes over time.4 Although up to 80% of lead can be lost during one week of storage, the addition of 1% nitric acid or 3% hydrogen peroxide will allow preservation for up to five days, and samples collected in EDTA and frozen at -20ºC are stable for several months.6

Measuring the amount of lead in a specimen is based on one of three different methods: spectrophotometry, atomic absorption spectrophotometry (AAS) or anodic stripping voltammetry (ASV). AAS, in one of its variations, and ASV are the most frequently used methods6 and have differing approaches. In AAS, the recommended method for analysis,8 the unknown sample is ashed (either with flame or furnace) to remove organic material and the resulting substance is reduced to its atomic state with spectrophotometric measurement of light absorbance at characteristic wavelengths. In ASV, ionic lead in a biological sample is reduced to elemental lead by the negative potential of a mercury electrode. The potential of the mercury electrode is then altered, and the anodic current that results from the reoxidation of the lead can be measured and is proportional to the concentration of lead in the specimen. While the ASV method is sometimes used because of its simplicity, it may lack sensitivity compared to AAS at the range of most critical concentrations (~10µg/dL).6

Lead test results inform clinicians about exposure and therapy may be started if the concentration is sufficiently elevated. While a blood lead concentration of 10µg/dL is the current benchmark used to diagnose lead poisoning, there is ongoing research and some evidence that intellectual deficits may occur with lead concentrations as low as 7.5 mg/dL.9 The American Academy of Pediatrics provides a thorough review of lead toxicity in its 2005 Policy Statement.5

Patients with lead toxicity may be treated with chelating agents as well as dietary supplements that include iron, calcium, magnesium, zinc, phosphate or vitamin D to help minimize intestinal absorption of lead. The effectiveness of treatment can be followed by measuring 24-hour urinary lead.8 The collection must be into a lead free container (for example a polyethylene bottle washed with hydrochloric acid4) and preserved with thymol.6

Cooperation among clinicians, laboratorians and patients will result in improved detection of lead toxicity in at-risk populations. The role of the clinical laboratory continues as further observation of treatment effectiveness in lead toxic patients is needed. This is an excellent opportunity for laboratory medicine to support public health with the detection and treatment of what the Centers for Disease Control and Prevention has designated as one of the leading environmental threats to children.


  1. Jefferson Lab Science Education Web site. Available at: Accessed January 18, 2007.
  2. United States Environmental Protection Agency History Web site. Lead Poisoning: A Historical Perspective. Available at: Accessed January 18, 2007.
  3. United States Department of Housing and Urban Development Energy Efficient Rehab Advisor Web site. Lead-based Paint as a Hazard During Remodeling. Available at: Accessed January 18, 2007.
  4. Yang JM, Lewandrowski KB. Trace elements, vitamins, and nutrition. In: McClatchey KD, Ed. Clinical Laboratory Medicine. 2nd ed. Philadelphia, Pa.: Lippincott Williams and Wilkins; 2002:456–460.
  5. American Academy of Pediatrics Committee on Environmental Health. Lead exposure in children: prevention, detection, and management. Pediatrics. 2005;116(4):1036–1046.
  6. Poklis A, Wong SHY, Pesce AJ. Toxicology. In: Kaplan LA, Pesce AJ, Kazmierczak SC, Eds. Clinical Chemistry: Theory, Analysis, and Correlation. 3rd ed. St. Louis, Mo.: Mosby;1996:1029–1031.
  7. Bergdahl IA, Gerhardsson L, Liljelind IE, et al. Plasma-lead concentration: investigations into its usefulness for biological monitoring of occupational lead exposure. Am J Ind Med. 2006;49(2):93–101.
  8. Alcock NW. Trace elements. In: Kaplan LA, Pesce AJ, Kazmierczak SC, Eds. Clinical Chemistry: Theory, Analysis, and Correlation. 4th ed. St. Louis, Mo.: Mosby; 2003:707–721.
  9. Lanphear BP, Hornung R, Khoury J, et al. Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ Health Perspect. 2005;113(7):894–899.

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