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Howard Hu,^1,2,3 Regina Shih,⁴ Stephen Rothenberg,^5,6 and Brian S. Schwartz^7,8

¹Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; ²Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; ³Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA; ⁴Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA; ⁵Departamento de Ecología Humana, Centro de Investigación y de Estudios Avanzados del I.P.N., Unidad de Mérida, Mérida, Yucatán, México; ⁶Centro de Investigación de Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México; ⁷Departments of Environmental Health Sciences and Epidemiology, Bloomberg School of Public Health, and ⁸ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

Abstract
We review several issues of broad relevance to the interpretation of epidemiologic evidence concerning the toxicity of lead in adults, particularly regarding cognitive function and the cardiovascular system, which are the subjects of two systematic reviews that are also part of this mini-monograph. Chief among the recent developments in methodologic advances has been the refinement of concepts and methods for measuring individual lead dose in terms of appreciating distinctions between recent versus cumulative doses and the use of biological markers to measure these parameters in epidemiologic studies of chronic disease. Attention is focused particularly on bone lead levels measured by K-shell X-ray fluorescence as a relatively new biological marker of cumulative dose that has been used in many recent epidemiologic studies to generate insights into lead's impact on cognition and risk of hypertension, as well as the alternative method of estimating cumulative dose using available repeated measures of blood lead to calculate an individual's cumulative blood lead index. We review the relevance and interpretation of these lead biomarkers in the context of the toxicokinetics of lead. In addition, we also discuss methodologic challenges that arise in studies of occupationally and environmentally exposed subjects and those concerning race/ethnicity and socioeconomic status and other important covariates. Key words: adults, biomarkers, epidemiologic methods, epidemiology, lead, toxicity. Environ Health Perspect 115:455–462 (2007) . doi:10.1289/ehp.9783 available via http://dx.doi.org/ [Online 22 December 2006]

This article is part of the mini-monograph "Lead Exposure and Health Effects in Adults: Evidence, Management, and Implications for Policy.

Address correspondence to H. Hu, Rm. 1518 Vaughan Bldg. (SPH-I) , Department of Environmental Health Sciences, University of Michigan School of Public Health, 109 S. Observatory St., Ann Arbor, MI 48109-2029 USA. Telephone: (734) 764-3188. Fax: (734) 936-7283. E-mail: howardhu@umich.edu

We thank M. Weisskopf and H. Nie for comments and helpful suggestions in the preparation of this manuscript.

This work was supported in part by National Institute of Environmental Health Sciences (NIEHS) grants R01-ES05257, R01-ES10798, R01-ES07821, R01-AG19604, R01-AG10785, P42-ES05947, and NIEHS Center grant P30-ES00002. R.S. was supported in part by NICHD intramural funds.

The authors declare they have no competing financial interests.

Received 3 October 2006 ; accepted 20 December 2006.