Uncertainties in the Relationship between Tibia Lead and Cumulative Blood Lead Index
Environ Health Perspect. doi:10.1289/ehp.10778 available via http://dx.doi.org [Online 15 February 2008]
Referencing: Adult Lead Exposure: Time for Change
Uncertainties in the relationship between bone Pb and cumulative blood lead index (CBLI), including evidence of nonlinearity and differences between the sexes, should be appropriately recognized when setting workplace blood Pb limits to achieve target bone Pb concentrations.
Schwartz and Hu (2007) recommended a maximum occupational tibia Pb concentration of 15 µg/g. They stated that, based on the slope of the relationship between tibia Pb and CBLI calculated by Hu et al. (2007), a tibia Pb of 15 µg/g can be avoided by limiting the CBLI to < 200–400 µg-years/dL.
Hu et al. (2007) acknowledged the uncertainty in the slope of the relationship between tibia Pb and CBLI. However, over the range of cumulative Pb exposures that would produce a tibia Pb concentration of 15 µg/g, the slope of the relationship between tibia Pb and CBLI may be less than the slope of 0.05 [95% confidence interval (CI), 0.046–0.055] µg/g per µg-years/dL calculated by Hu et al. (2007).
Table 1 presents slopes and mean tibia Pb concentrations among subjects of eight published studies. Gerhardsson et al. (1993) reported a slope of 0.022 µg/g per µg-years/dL (no uncertainty reported) and Armstrong et al. (1992) reported a slope of 0.10 (± 0.02) µg/g per µg-years/dL. These represent a greater range of slopes than reported by Hu et al. (2007).
Table 1.
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These data also suggest that the tibia Pb versus CBLI slope may not be constant, with lower slopes evident for lower tibia Pb and CBLI levels. This trend has been noted previously (Chettle 2005; Fleming et al. 1997). For tibia Pb concentrations of approximately 15 µg/g, a slope of approximately 0.025 µg/g per µg-years/dL seems equally plausible as the slope calculated by Hu et al. (2007).
A slope of 0.025 µg/g per µg-years/dL yields an allowable CBLI of 600 µg-years/dL, or an average annual blood Pb concentration of 15 µg/dL for 40 working years. This compares to 5–10 µg/dL for 40 working years associated with Schwartz and Hu's (2007) recommended CBLI of 200-400 µg-years/dL.
These slopes are also based on studies of predominantly male subjects and may not account for differences in Pb toxicokinetics between the sexes (McNeill et al. 2000; Popovic et al. 2005).
D.R.C. has occasionally been retained by private and public sector interests as a consultant for his expertise on in vivo X-ray fluorescence (XRF) bone Pb measurement; a portion of his previous and current research efforts has been funded by industry. D.E.B.F. has twice been retained as a consultant by private and public sector interests for his expertise on lead exposure and XRF bone lead analysis; a portion of his research program has been partially funded by industry. The remaining authors declare they have no competing financial interests.
Norm Healey
Health Canada
Sidney, British Columbia, Canada
E-mail: norm_healey@hc-sc.gc.ca
David R. Chettle
Fiona E. McNeill
McMaster University
Hamilton, Ontario, Canada
David E. B. Fleming
Mount Allison University
Sackville, New Brunswick, Canada
References
Armstrong R, Chettle DR, Scott MC, Somervaille LJ, Pendlington M. 1992. Repeated measurements of tibia lead concentrations by in vivo X ray fluorescence in occupational exposure. Br J Ind Med 49 (1):14–16.
Cake KM. 1994. In Vivo X-Ray Fluorescence of Bone Lead in the Study of Human Lead Metabolism [Master's Thesis]. Hamilton, Ontario, Canada:McMaster University.
Chettle DR. 2005. Three decades of in vivo x-ray fluorescence of lead in bone. X-Ray Spectrometry 34(5): 446–450.
Erkkilä J, Armstrong R, Riihimaki V, Chettle DR, Paakkari A, Scott M, et al. 1992. In vivo measurements of lead in bone at four anatomical sites: long term occupational and consequent endogenous exposure. Br J Ind Med 49(9):631–644.
Fleming DEB, Boulay D, Richard NS, Robin JP, Gordon CL, Webber CE, et al. 1997. Accumulated body burden and endogenous release of lead in employees of a lead smelter. Environ Health Perspect 105:224–233.
Gerhardsson L, Attewell R, Chettle DR, Englyst V, Lundstrom NG, Nordberg GF, et al. 1993. In vivo measurements of lead in bone in long-term exposed lead smelter workers. Arch Environ Health 48(3):147–156.
Hu H, Pepper L, Goldman R. 1991. Effect of repeated occupational exposure to lead, cessation of exposure, and chelation on levels of lead in bone. Am J Ind Med 20(6): 723–735.
Hu H, Shih R, Rothenberg S, Schwartz BS. 2007. The epidemiology of lead toxicity in adults: measuring dose and consideration of other methodologic issues. Environ Health Perspect 115:455–462.
McNeill FE, Stokes L, Brito JA, Chettle DR, Kaye WE. 2000. 109Cd K X ray fluorescence measurements of tibial lead content in young adults exposed to lead in early childhood. Occup Environ Med 57(7):465–471.
Popovic M, McNeill FE, Chettle DR, Webber CE, Lee CV, Kaye WE. 2005. Impact of occupational exposure on lead levels in women. Environ Health Perspect 113: 478–484.
Schwartz BS, Hu H. 2007. Adult lead exposure: time for change. Environ Health Perspect 115: 451–454.
Somervaille LJ, Chettle DR, Scott MC, Tennant DR, McKiernan MJ, Skilbeck A, et al. 1988. In vivo tibia lead measurements as an index of cumulative exposure in occupationally exposed subjects. Br J Ind Med 45(3): 174–181.
Relationship between Tibia Lead and Cumulative Blood Lead Index: Schwartz et al. Respond
Environ Health Perspect. doi:10.1289/ehp.10778R available via http://dx.doi.org [Online 15 February 2008]
We thank Healey et al. for their thoughtful comments on our papers in the mini-monograph on adult lead exposure (Hu et al. 2007; Schwartz and Hu 2007). We agree with the points they raised concerning uncertainties in the relation of cumulative blood lead index (CBLI) with tibia lead, the need to address the possibility that the slope of the relation may not be constant across the range of tibia lead values, and uncertainty about how sex may influence the relation, as most data were derived from studies of men. Given the changing metabolism of bone across the life span, age must ultimately be factored in as well.
Healey et al. posit that the relation of CBLI with tibia lead may be nonlinear by presenting summary data from eight studies; they show that the estimated slope of the CBLI and tibia lead relation is relatively low in studies with lower mean tibia lead levels, whereas the estimated slope appears to be higher in studies with higher mean tibia lead levels. A problem with this argument is that it is prone to the ecologic fallacy of using summary data of CBLI and mean tibia lead from groupsacross studies to make inferences in individuals about the relation of CBLI with tibia lead. All of the literature evaluating relations of CBLI with tibia lead is based on measurements in only approximately 500 subjects. A rigorous assessment for possible nonlinearities in such a relation would require a pooled analysis of the original data, not an ecologic analysis of the summary results across studies (Lanphear et al. 1998). Several statistical techniques could then be used to evaluate possible departures from linearity in the CBLI versus tibia lead relation using the individual level data.
Concerning the range of slopes we reported, we wrote "Each study also reported sample size and the SE of the slope, which, across the studies, ranged from 0.028 to 0.067" (Hu et al. 2007). Healey et al. correctly report that the slopes ranged from 0.022 to 0.10 µg/g per µg-years/dL across the eight studies they included. This discrepancy is easily explained. Concerning the high end of their range, we chose not to use the Armstrong et al. slope estimates for 1983 or 1988 (both 0.10, based on 15 and 11 subjects, respectively), instead relying on their estimate (0.052) for the 11 subjects for both 1983 and 1988 (Armstrong et al. 1992). Concerning the low end of their range (0.022), Gerhardsson et al. (1993) did not present an SE of the slope, which is needed, along with the slope estimate, for use in a meta-analysis.
Given the ecologic fallacy issue discussed above, we respectfully disagree with the recommendation of Healey et al. that we should rely only on the two studies that reported the smallest slopes for the relation of CBLI with tibia lead (Gerhardsson 1993; Erkkilä 1992) simply because, as they note, these studies had average tibia lead levels closest to the 15 µg/g tibia lead limit we proposed (Schwartz and Hu 2007). In addition, we believe that relying on only two relatively small studies does not provide sufficient margin of safety for lead-exposed workers to accept Healey et al.'s recommendation at this time. Because our primary goal is preventing departures from health associated with cumulative lead dose in adults exposed to lead, we instead choose to rely on an estimate derived from a weighted mean across studies. At the present time, we believe we are justified in standing by our recommendation of a CBLI of 200–400 µg-years/dL.
The authors declare they have no competing financial interests.
Brian S. Schwartz
Johns Hopkins University
Baltimore, Maryland
E-mail: bschwart@jhsph.edu
Howard Hu
University of Michigan
Ann Arbor, Michigan
Stephen J. Rothenberg
Centro de Investigación y de Estudios Avanzados del I.P.N. Unidad de Mérida
Mérida, Yucatán, México
Andrew C. Todd
Mount Sinai School of Medicine
New York, New York
References
Armstrong R, Chettle DR, Scott MC, Somervaille LJ, Pendlington M. 1992. Repeated measurements of tibia lead concentrations by in vivo X ray fluorescence in occupational exposure. Br J Ind Med 49(1):14–16.
Erkkilä J, Armstrong R, Riihimaki V, Chettle DR, Paakkari A, Scott M, et al. 1992. In vivo measurements of lead in bone at four anatomical sites: long term occupational and consequent endogenous exposure. Br J Ind Med 49(9):631–644.
Gerhardsson L, Attewell R, Chettle DR, Englyst V, Lundstrom NG, Nordberg GF, et al. 1993. In vivo measurements of lead in bone in long-term exposed lead smelter workers. Arch Environ Health 48(3):147–156.
Hu H, Shih R, Rothenberg S, Schwartz BS. 2007. The epidemiology of lead toxicity in adults: measuring dose and consideration of other methodologic issues. Environ Health Perspect 115:455–462.
Lanphear BP, Matte TD, Rogers J, Clickner RP, Dietz B, Bornschein RL, et al. 1988. The contribution of lead-contaminated house dust and residential soil to children's blood lead levels. A pooled analysis of 12 epidemiologic studies. Environ Res 79(1):51–68.
Popovic M, McNeill FE, Chettle DR, Webber CE, Lee CV, Kaye WE. 2005. Impact of occupational exposure on lead levels in women. Environ Health Perspect 113: 478–484.
Schwartz BS, Hu H. 2007. Adult lead exposure: time for change. Environ Health Perspect 115: 451–454.
