Quantifying cadmium and lead in whole blood.

In this issue of Clinical Chemistry, an electrochemical method is described for the simultaneous measurement of cadmium and lead in whole blood. Exposure to these toxic metals is an inevitable consequence of life in industrialized society. Blood Pb is currently measured, with little interlaboratory disagreement, by atomic absorption or electrochemical methods. In contrast, despite numerous attempts to establish reference values for Cd in blood-mainly by using electrothermal atomic absorption spectrometry-we cannot with certainty state the expected range of blood Cd in healthy individuals. Therefore, the development of a new method for Cd presents greater challenges than methods for Pb, but also potentially greater usefulness. The clinical indications for Pb and Cd measurements in blood also differ. The importance of the concentrations of blood Pb, particularly in infants and children, is well established. As concern grows about the concentration at which Pb can cause detectable cognitive impairment (1-3), it becomes increasingly important to monitor the concentrations in exposed children. At the concentrations of concern, 100-250 p.gfL, no great analytical challenge is presented. Direct analysis by Zeeman-corrected electrothermal atomic absorption methods, after dilution with a matrix modifier, is steadily replacing use of the Delves cup, although both approaches can be used reliably (4). Anodic stripping voltammetry (ASV) is an attractive alternative, especially at higher concentrations, and commercial instrumentation such as the ESA 3010A stripping analyzer (Environmental Science Associates, Burlington, MA) offers the advantage of low equipment costs and rapid analysis. Use of this instrumentation in the clinical laboratory is generally confined to the measurement of blood Pb, because many of the other elements that are in principle handled well by this technique are present in body fluids only at concentrations below its analytical range. The concentrations of Cd in the biosphere are increasing as a consequence of industrial activity and therefore represent an environmental problem of increasing proportions. Reports from the Cadmibel study, conducted in both rural and urban regions of Belgium, provide disturbing evidence for Cd body burdens that are associated with increased risk of renal tubular dysfunction in a substantial portion of the general population (5). Therefore, measurement of blood Cd will take on increasing clinical significance as reliable methods become available, but at present the expected values for Cd in blood demand control of analytical methods at concentrations at least an order of magnitude lower than for Pb. In the absence of renal damage, urinary Cd excretion, but not blood concentrations of Cd, correlate with the body burden of Cd (6, 7). However, there is some evidence that blood Cd is a useful indicator of exposure to the metal within recent months (6). Inhalation of tobacco smoke is a major cause of increases in blood Cd (8). There is still no clear consensus on the reference value for blood Cd in the healthy population. In perhaps the largest study to date, Pocock et al. (9) reported a median value of 1.4 jzg/L (range 0.1-1.7) in the blood of nearly 7000 British males. Higher values (2-4 jg/L) may occur in Japanese men (10), whereas values well below 1 p.gfL have been found throughout Europe and America (11). It is therefore clear that a laboratory procedure must be performing well below the 1 ,ug/L concentration to produce meaningful results for blood Cd. The Cd studies mentioned above have all used electrothermal atomic absorption spectrometry. In this issue, Ostapczuk (12) reports a method for the direct, simultaneous determination of Cd and Pb in whole blood by using commercial equipment for stripping volta.mmetry. The major achievement of this work is the improvement of sensitivity for direct analysis, which extends the approach beyond the measurement of increased Pb concentrations to a range useful for measuring Cd. The method may prove useful to those involved in determining reference values for Cd and other elements in blood. As a multielement technique, it also has the potential to reveal correlations related to simultaneous exposure or biological causes. An attractive property of volt.ammetric methods is their high sensitivity. In contrast to spectrophotometric methods, where the signal is exponentially related to the analyte concentration, the maximum current measured in volta.mmetry is directly proportional to the concentration of the electroactive species. The proportionality between current and concentration is given by the Faraday constant, F = 96500 C per mole. This large value implies a very good sensitivity, and detection limits comparable with those of electrothermal atomic absorption can be achieved. A further gain in sensitivity is realized by stripping methods. By depositing the analyte from the bulk solution onto a thin mercury film, reproducible concentration factors of iO to 106 can be achieved (13). For example, detection limits of 2 ng/L for Ni in seawater have been reported by this method (14), about two orders of magnitude better than can be achieved with atomic absorption. Determination of Pb at 1 pgIL under clean-room conditions has been cited (13); however, this performance has not been realized in biological specimens. The inherently low resolution of