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An International Pooled Analysis for Obtaining a Benchmark Dose for Environmental Lead Exposure in Children

Authors

  • Esben Budtz-Jørgensen,

    Corresponding author
    • Department of Biostatistics, University of Copenhagen, Denmark
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  • David Bellinger,

    1. Department of Environmental Health, Harvard School of Public Health, USA
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  • Bruce Lanphear,

    1. Faculty of Health Sciences, Simon Frasier University and British Columbia Children's Hospital, Vancouver, Canada
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  • Philippe Grandjean,

    1. Department of Environmental Health, Harvard School of Public Health, USA
    2. Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Denmark
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  • on behalf of the International Pooled Lead Study Investigators

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    • Bruce P. Lanphear, Richard Hornung, Jane Khoury, Kimberly Yolton, Peter Baghurst, David C. Bellinger, Richard L. Canfield, Kim N. Dietrich, Robert Bornschein, Tom Greene, Stephen J. Rothenberg, Herbert L. Needleman, Lourdes Schnaas, Gail Wasserman, Joseph Graziano, and Russell Roberts.


Address correspondence to E. Budtz-Jørgensen, Department of Biostatistics, University of Copenhagen, Øster Farimagsgade 5B, DK-1014 Copenhagen K, Denmark; tel:+4535327927; ebj@biostat.ku.dk.

Abstract

Lead is a recognized neurotoxicant, but estimating effects at the lowest measurable levels is difficult. An international pooled analysis of data from seven cohort studies reported an inverse and supra-linear relationship between blood lead concentrations and IQ scores in children. The lack of a clear threshold presents a challenge to the identification of an acceptable level of exposure. The benchmark dose (BMD) is defined as the dose that leads to a specific known loss. As an alternative to elusive thresholds, the BMD is being used increasingly by regulatory authorities. Using the pooled data, this article presents BMD results and applies different statistical techniques in the analysis of multistudy data. The calculations showed only a limited variation between studies in the steepness of the dose-response functions. BMD results were quite robust to modeling assumptions with the best fitting models yielding lower confidence limits (BMDLs) of about 0.1–1.0 μ g/dL for the dose leading to a loss of one IQ point. We conclude that current allowable blood lead concentrations need to be lowered and further prevention efforts are needed to protect children from lead toxicity.

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