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Reliability of low mass toenail samples as biomarkers of chronic metal exposure

Journal of Exposure Science & Environmental Epidemiology volume 33, pages 945–953 (2023)Cite this article

Abstract

Background

Toenails are a promising matrix for chronic metal exposure assessment, but there are currently no standard methods for collection and analysis. Questions remain about sample mass requirements and the extent to which metals measured in this matrix are representative of chronic body burden.

Objective

This study proposes a method to maximize sample conservation for toenail metals analysis using inductively coupled plasma mass spectrometry (ICP-MS). We demonstrate the reliability of an ~25 mg toenail sample (typically 1–2 clippings) for metals analysis and evaluate the intra-individual variability of multiple metals in this matrix over time in men from the Gulf Long-term Follow-up (GuLF) Study.

Methods

Toenail samples from 123 GuLF Study participants were collected at two visits 3 years apart and analyzed for 18 elements using ICP-MS. Participants with samples exceeding 200 mg at the first visit (n = 29) were selected for triplicate sub-sample analysis. Kendall’s coefficient of concordance (W) was used to assess sub-sample reliability and Spearman’s correlation coefficients (ρ) were used to evaluate fluctuations in elemental concentrations over time.

Results

Results were not reported for Cd, Co, Mo, Sb, and V (detected in <60% of the samples). There was strong agreement among triplicate samples (Kendall’s W: 0.72 (Cu)–0.90 (Cu)) across all elements evaluated, moderate correlations of elemental concentrations (Spearman’s ρ: 0.21–0.42) over 3 years for As, Ca, Cr, Fe, Pb, Mn, and Zn, and strong correlations (>0.50) for Se, Cu, and Hg.

Impact Statement

This toenail reliability study found that a low-mass (~25 mg) toenail sample (1-2 clippings) is suitable for the determination of most elements using ICP-MS and helps to increase the analytical capacity of limited toenail biospecimens collected in cohort studies. The results highlight differences in the suitability of toenails for chronic metal exposure assessment by element and underscore the need to consider intra-person variability, especially when comparing results across studies. We also provide recommendations for analytical standardization and the partitioning of the total collected toenail sample into multiple analytic sub-samples for future studies using toenail biospecimen for multiple assays.

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Fig. 1: Flowchart of participant selection for toenail metal analysis.
Fig. 2: Correlation between sub-sample metal concentrations (log10 (µg/g)) for Cu (W = 0.90 | ICC = 0.88) and Cr (W = 0.72 | ICC = 0.64).

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Data availability

The data and code can be requested by email to the corresponding author.

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Acknowledgements

We thank all GuLF study participants, the field visit examiners who assisted with data collection, and Kate Christenbury for data management on this project.

Funding

This research was supported in part by a grant from the U.S. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health to the Johns Hopkins Education and Research Center for Occupational Safety and Health (award number T42 OH0008428), by the Office of The Director of the National Institutes of Health under Award Number S10OD030355, the NIH Common Fund, the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZO1 ES 102945), and the 21st Century Cities Initiative at Johns Hopkins University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Joyce J. Y. Lin, Mina W. Tehrani, Rui Chen, Seok Gyu Han, Gurumurthy Ramachandran & Ana M. Rule

  2. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Lily J. Koffman

  3. Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA

    Dale P. Sandler, Kaitlyn G. Lawrence & Lawrence S. Engel

  4. Social & Scientific Systems, Inc., Durham, NC, USA

    W. Braxton Jackson II

  5. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Aisha S. Dickerson

  6. Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA

    Lawrence S. Engel

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Contributions

JJYL: conceptualization, methodology, formal analysis, writing—original draft. LJK: formal analysis. MWT: review and editing, data curation. RC: data curation. SGH: data curation. DPS: data management, review and editing. KGL: data management, review and editing. WBJ II: data management. ASD: review and editing. GR: supervision. LSE: supervision, data management. AMR: project administration, supervision.

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Correspondence to Joyce J. Y. Lin.

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Lin, J.J.Y., Koffman, L.J., Tehrani, M.W. et al. Reliability of low mass toenail samples as biomarkers of chronic metal exposure. J Expo Sci Environ Epidemiol 33, 945–953 (2023). https://doi.org/10.1038/s41370-023-00560-y

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