Experimental methods are not this review's focus. Briefly, nail trace elements can be assessed by the most sensitive Instrumental Neutron Activation Analysis (INAA)⁵⁰ and / or Inductively-Coupled-Plasma Mass Spectroscopy (ICP-MS)⁵¹ methodologies. INAA, at a high-flux steady-state research reactor, is a very sensitive trace element analysis technique. Neutron irradiations can be done using a pneumatic-tube system (for short irradiations) or in light-water / graphite moderated irradiation positions in close proximity to the reactor core (for long irradiations). Fundamentally, INAA protocols have five sequential sub-protocols: sample preparation, neutron irradiation, planned decay of induced radioactivity, measurement of residual radioactivity, and data reduction. With few exceptions, INAA protocols measure decay gamma rays (γ_d), which can be detected with excellent energy resolution and high sensitivity using state-of-the-art high-resolution gamma-ray spectroscopy (HRGRS). In addition, ICP-MS is a very powerful tool for trace (ppb-ppm) and ultra-trace (ppq-ppb) elemental analysis. In ICP-MS, a plasma or gas consisting of ions, electrons and neutral particles is formed from Argon gas. The plasma is used to atomize and ionize the elements in a sample. The resulting ions are then passed through a series of apertures (cones) into the high vacuum mass analyzer. Of note, in epidemiological studies, the nail samples are likely limited in mass. Consequently, a serial approach, using the same sample passed through each individual analysis protocol, can be used. The INAA and ICP-MS methodologies are ideally suited to this approach.

Accumulative literature supports that nail particularly toenail concentrations of most trace elements are useful biomarkers of exposure in which a single sample is assumed to represent long-term exposure. Previous studies indicate the ability of trace elements measured in toenails predicting chronic diseases including cancer and CVD in clinical studies. As compared to other potential biomarkers of trace elements, toenail measurement provides the most time-integrated measure and is less likely to be contaminated. The chemicals introduced by nail polishing can be largely washed out in the laboratory, and the element contents in nails are less likely to be affected. Nail trace element concentrations can be accurately quantified by INAA and ICP-MS.