Lead Toxicity

lead_poisonningLead has been the intense focus of environmental health research for many decades. Studies in humans were greatly assisted by the development of methods (such as graphite furnace atomic absorption spectroscopy) for the accurate and reliable measurement of lead in blood (measured in units of micrograms per deciliter [mg/dL]), a technique that is now widely available and used for surveillance and monitoring, as well as research. The general body of literature on lead toxicity indicates that, depending on the dose, lead exposure in children and adults can cause a wide spectrum of health problems, ranging from convulsions, coma, renal failure, and death at the high end to subtle effects on metabolism and intelligence at the low end of exposures. Children (and developing fetuses) appear to be particularly vulnerable to the neurotoxic effects of lead. A plethora of well-designed prospective epidemiologic studies has convincingly demonstrated that low-level lead exposure in children less than five years of age (with blood lead levels in the 5-25 mg/dL range) results in deficits in intellectual development as manifested by lost intelligence quotient points.6 As a result, in the U.S., the Centers for Disease Control (CD) lowered the allowable amount of lead in a child’s blood from 25 to 10 mg/dL and recommended universal blood lead screening of all children between the ages of six months and five years. (For more details, see http://www.cdc.gov/nceh/lead/lead.htm.) However, a number of issues still remain unresolved with respect to lead toxicity in children. Among the most important is the risk posed to the fetus posed by mobilization of longlived skeletal stores of lead in pregnant women. Recent research has clearly demonstrated that maternal bone lead stores are mobilized at an accelerated rate during pregnancy and lactation and are associated with decrements in birth weight, growth rate, and mental development. Since bone lead stores persist for decades it is possible that lead can remain a threat to fetal health many years after environmental exposure had actually been curtailed.

In contrast to children, adults are generally allowed by regulations to be exposed to higher amounts of lead. In the U.S., for example, the Occupational Safety and Health Administration requires that the blood lead levels of exposed workers be maintained below 40 mg/dL as a way of preventing toxic effects to nerves, the brain, kidney, reproductive organs, and heart. (For more information, see http://www.osha-slc.gov/OshStd_data/ 1910_1025_APP_C.html.) This standard is probably outdated, however. First, the standard does not protect the fetuses of women who become pregnant while on the job (or even if they leave the job for several years because of the issue of bone lead mobilization, as discussed above). Second, recent epidemiologic studies have linked blood lead levels in the range of 7-40 mg/dL with evidence of toxicity in adults, such as neurobehavioral decrements and renal impairments. Third, recent studies using a newly developed technique, K-x-ray fluorescence, to directly measure bone lead levels (as opposed to blood lead levels) have provided evidence demonstrating that cumulative lead exposure in individuals with blood lead levels well below 40 mg/dL is a major risk factor for the development of hypertension, cardiac conduction delays and cognitive impairments. Finally, even as research progresses to delineate the full toxicologic implications of lead exposure, investigations at the interface of genetics and environmental health are beginning to uncover subgroups of individuals who may be particularly susceptible to the toxicity of lead.