Toenail speciation biomarkers in arsenic‐related disease: a feasibility study for investigating the association between arsenic exposure and chronic disease

Abstract

Long-term exposure to environmental arsenic has been associated with many chronic diseases, including several cancers, and diabetes. Urinary studies have implicated arsenic speciation as an important risk factor, however, such associations have not been replicated using toenail samples: a relatively new biosample for estimating long-term internal dose-exposure to arsenic. Despite having several advantages over conventional biosamples such as ease of collection and storage, standard methods for arsenic speciation analysis in toenails have not yet been established. The primary objectives of this study were to 1) establish an analytical method for arsenic speciation analysis in toenails, 2) describe preliminary arsenic speciation profiles of toenail samples from individuals with skin, lung, bladder, and kidney cancer, type II diabetes, and no known disease, and 3) determine if these speciation patterns differ between disease groups to inform the feasibility of subsequent research. A small cross-sectional feasibility study was carried out using 60 toenail samples and baseline questionnaire data from the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) study. Arsenic speciation profiles were determined using high performance liquid chromatography (HPLC) paired with inductively coupled plasma-mass spectrometry (ICP-MS). While no differences in total arsenic were found, arsenic speciation profiles were significantly different between certain cancer groups and the reference group with no known disease. Specifically, the percentage of monomethylarsonic acid (%MMA) was found to be significantly higher in the toenails of individuals with lung cancer and kidney cancer, compared to healthy individuals with similar total arsenic exposure. To the best of our knowledge, this is the first study to describe arsenic speciation patterns in individuals with several arsenic-related diseases using toenails: a convenient, non-invasive, biobankable sample capable of longer-term exposure estimation than conventional biosamples. These preliminary data provide evidence that toenail arsenic speciation patterns differ between groups with arsenic-related disease, and those with no known disease. Toenail arsenic speciation analysis is feasible and could potentially have important implications for research on arsenic-related diseases. Further investigation is warranted and would benefit from including detailed arsenic exposure data to explore the observed heterogeneity in arsenic speciation profiles.