SummaryLead accumulates in bone over many years or decades. Accordingly, the study of lead in bone is important in determining the fate of ingested lead, the potential for remobilization, and for the application of bone lead measurements as a biomarker of lead exposure. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to measure the spatial distribution of lead in bone on the micrometer scale. In general, LA-ICP-MS studies are somewhat limited by the lack of matrix-matched standards and/or reference materials for calibration and validation purposes. Here we describe the application of pressed pellets prepared from New York State Department of Health candidate Reference Materials for Lead in Bone (levels 1 through 4), to provide a linear calibration for 208 Pb/ 43 Ca in the concentration range <1 to 30 μg g −1 . The limit of detection was estimated as 0.2 μg g −1 . The measured lead values for pelletized NIST SRM 1486 Bone Meal and SRM 1400 Bone Ash were in good agreement with certified reference values. Using this approach, we quantitatively measured the spatial distribution of lead in a cross-section of goat metacarpal from a lead-dosed animal. The lead content was spatially variable in the range of 2 to 30 μg g −1 with a complex distribution. In some sections, lead appeared to be enriched in the center of the bone relative to peripheral areas, indicating preferential accumulation in trabecular (spongy) rather than cortical bone. In addition, there were discrete areas of lead enrichment, or hot spots, of 100 to 200 μm in width.

Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 μg g −1 . Linear regression of whole tooth lead (μg g −1 ) on the cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r 2 = 0.647 (p<0.0001).Laser ablation inductively coupled plasma mass spectrometry was employed to determine lead content at micrometer scale spatial resolution in the teeth of seven goats representing the dosing range. Highly localized concentrations of lead, ranging from about 10 to 2000 μg g −1 , were found in circumpulpal dentine. Linear regression of circumpulpal lead (μg g −1 ) on cumulative lead dose (g) yielded a slope of 23 with r 2 = 0.961 (p = 0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats.

Bone lead measurements assess chronic exposure and can be obtained via a noninvasive analytical technique based on K‐she ll x‐ray fluorescence (KXRF) spectrometry. While KXRF has been practiced by a number of laboratories around the world, this technique has not, until now, undergone an assessment of interlaboratory agreement. The study described here provides such an assessment via circulation of nine bare tibiae selected from a repository of bones that were derived from lead‐dosed goats. Fifteen KXRF systems were used by ten participating laboratories, to make five measurements on each of the nine caprine tibiae. Reported bone lead concentrations ranged from the KXRF detection limit to 63 µg g−1 bone mineral. None of the data from the ten participant laboratories was found to be a statistical outlier. However for each of the nine tibiae, differences between the 15 reported bone lead concentrations were statistically significant. The standard deviations of the five replicate KXRF‐measured concentrations ranged, across all laboratories and all tibiae, from 0.5 to 6.5 µg g−1, bone mineral. Copyright © 2007 John Wiley & Sons, Ltd.

Four candidate ground bone reference materials (NYS RMs 05-01 through 04), were produced from lead-dosed bovine and caprine sources, and characterized by interlaboratory study. The consensus value ( X ) and expanded standard uncertainty (U(X) ) were determined from the robust average and standard deviation of the participants' data for each NYS RM 05-01 through 04. The values were 1.08 ±0.04, 15.3 ±0.5, 12.4 ±0.5, and 29.9 ±1.1 μg g(-1) Pb, respectively. Youden plots of z-scores showed a statistically significant correlation between the results for pairs of NYS RM 05-02 through 04, indicating common sources of between-laboratory variation affecting reproducibility. NYS RM 05-01 exhibited more random variability affecting repeatability at low concentration. Some participants using electrothermal atomic absorption spectrometry (ETAAS) exhibited a negative bias compared to the all-method consensus value. Other methods used included inductively coupled plasma mass spectrometry (ICP-MS), isotope dilution (ID-) ICP-MS, and ICP atomic (optical) emission spectroscopy (-OES). The NYS RMs 05-01 through 04 were subsequently re-analyzed in house using double ID-ICP-MS to assign certified reference values (C ) and expanded uncertainty (U(C) ) of 1.09 ± 0.03, 16.1 ± 0.3, 13.2 ± 0.3 and 31.5 ± 0.7, respectively, indicating a low bias in the interlaboratory data. SRM 1486 Bone Meal was analyzed for measurement quality assessment obtaining results in agreement with the certified values within the stated uncertainty. Analysis using a primary reference method based on ID-ICP-MS with full quantification of uncertainty calculated according to ISO guidelines provided traceability to SI units.

The production of modest quantities of candidate bone lead (Pb) reference materials is described, and an optimized production procedure is presented. The reference materials were developed to enable an assessment of the interlaboratory agreement of laboratories measuring Pb in bone; method validation; and for calibration of solid sampling techniques such as laser ablation ICP-MS. Long bones obtained from Pb-dosed and undosed animals were selected to produce four different pools of a candidate powdered bone reference material. The Pb concentrations of these pools reflect both environmental and occupational exposure levels in humans. The animal bones were harvested post mortem, cleaned, defatted, and broken into pieces using the brittle fracture technique at liquid nitrogen temperature. The bone pieces were then ground in a knife mill to produce fragments of 2-mm size. These were further ground in an ultra-centrifugal mill, resulting in finely powdered bone material that was homogenized and then sampled-scooped into vials. Testing for contamination and homogeneity was performed via instrumental methods of analysis.