Correlation over time of toenail metals among participants in the VA normative aging study from 1992 to 2014



Scientists use biomarkers to evaluate metal exposures. One biomarker, toenails, is easily obtained and minimally invasive, but less commonly used as a biomarker of exposure. Their utility will depend on understanding characteristics of their variation in a population over time. The objective of our study is to describe the correlation of toenail metal levels many years apart among participants in the VA Normative Aging Study (NAS).


Toenail clippings from 825 participants of the NAS from year 1992 to 2014 were analyzed for lead (Pb), Arsenic (As), Cadmium (Cd), Manganese (Mn), and Mercury (Hg). We utilized linear mixed models to assess correlation between toenail metal concentrations in multiple toenail samples from the same subject collected years apart and identified the optimal covariance pattern by likelihood ratio tests and Akaike’s information criterion (AIC). Correlations among different metals were described using Spearman correlations.


The average number of times toenail samples were collected from each subject ranged from 1.63 (Hg) to 2.04 (As). The average number of years between toenails collected per subject ranged from 4.73 (SD = 2.44) (Mn) to 5.35 (SD = 2.69) (Hg). Metal concentrations had slightly different correlation patterns over time, although for all metals correlations decreased with increasing time between samples. Estimated correlations over a 3-year span were highest for toenail Pb (0.68) and Hg (0.67), while As, Cd, and Mn had lower correlations of 0.49, 0.44, and 0.47, respectively. Even across a 6-year span, the lowest correlation was 0.35 (Cd).


Our results suggest that Pb, As, Cd, Mn, and Hg levels from toenail clippings can reasonably reflect exposures over several years in elderly men in the NAS. Even across 6 years, toenail metal levels were generally well correlated among NAS participants. As such, they may be useful as biomarkers of exposure in epidemiological studies of similar populations.

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We thank all the participants and dedicated staff of the VA Normative Aging Study. The VA Normative Aging Study is supported by the Cooperative Studies Program/ERIC, Department of Veterans Affairs, and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). We also thank Anna Kosheleva at the Harvard T.H. Chan School of Public Health for her help as the data manager.

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Correspondence to Marc G. Weisskopf.

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U.S. Centers for Disease Control and Prevention, National Institute of Occupational Health and Safety, Education and Research Center training grant T42 OH008416 (Alexander Wu), National Institutes of Health, National Institute of Environmental Health Sciences grant ES05257 and P30 00002 (Marc Weisskopf), and National Institutes of Health R01 ES015172 (Chitra Amarasiriwardena, Joel Schwartz) and R01 ES027747 (Joel Schwartz).

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The authors declare that they have no conflict of interest.

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Wu, A.C., Allen, J.G., Coull, B. et al. Correlation over time of toenail metals among participants in the VA normative aging study from 1992 to 2014. J Expo Sci Environ Epidemiol 29, 663–673 (2019).

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