Dissolution of the metal sensitizers Ni, Be, Cr in artificial sweat to improve estimates of dermal bioaccessibility

Abstract

Dermal exposure to sensitizing metals is a serious occupational and public health problem. The usual approach to dermal exposure assessment is to process samples by chemical methods that use reactants to digest the metal particles and quantify the mass. In the case of dermal exposure assessment, these reactants are not representative of the skin surface film liquids and hence, may overestimate bioaccessibility. We hypothesize that the amount and form of sensitizer on a sample that leaches in a biological fluid, as can be estimated using artificial sweat, may be a more relevant metric for assessing health risks. Beryllium metal (Be), nickel metal (Ni), and chromium carbide (Cr3C2) particles were characterized and masses of sensitizing ions were measured using established reactant-assisted digestion procedures and extraction in artificial sweat under physiologically relevant conditions. Chromium ions released into artificial sweat were speciated to understand valence states. The ratios of the fraction of metal dissolved in artificial sweat relative to that dissolved by chemical-specific reactants were 1/2 (Be), 1/108 (Ni), and 1/2500 (Cr). The divalent Be and Ni cations were stable in artificial sweat over time (did not precipitate) whereas hexavalent chromium [Cr(VI)] ions decayed over time. Further analysis using speciated isotope dilution mass spectrometry revealed that the decay of Cr(VI) was accompanied by the formation of Cr(III) in the sweat model. Use of reactant-assisted analytical chemistry to quantify amounts of metal sensitizers on samples could overestimate biologically relevant exposure. In addition to mass, the valence state also influences penetration through the outer stratum corneum of the skin and is an important consideration when assessing exposure to complex sensitizers such as Cr which have multiple valence states with differing penetration efficiencies.

Fig. 1

A paradigm for measurement of skin exposure to metal sensitizers. Particles [denoted as ●] deposit on the outer stratum corneum (SC) at some mass loading (M_total). Depending upon the loading, all or just a fraction of these particles will contact the skin surface film liquids (SSFLs). This fraction of particles in contact with SSFLs represents the biorelevant fraction (f_biorelevant). i.e., the material available to react with skin liquids. A portion of f_biorelevant will undergo dissolution (oxidation or reduction) to form bioaccessible (f_{bioaccessible}) water soluble metal ions [denoted as ●⁺]. Depending upon the properties of the metal ions (formation of complexes. etc.) and the barrier properties of the SC some portion will penetrate through or around corneocyte cells and reach the underlying viable epidermis (VE) and interact with the immune system (f_bioavailable).

Fig. 2

Physicochemical properties of study powders. Note that the scale bar differs among images. ^a Geometric mean (geometric standard deviation).

Fig. 3

Plot of the mass fraction of the material remaining versus time for three sweat extraction temperatures (33, 36, and 45 °C) for (a) beryllium. (b) nickel. and (c) chromium. Dissolution of beryllium and chromi um was biphasic and consisted of an initial rapid phase followed by a slower long-term phase. Dissolution of nickel was linear over time.

Fig. 4

Plots of metal ion stability in artificial sweat (pH 5.3, 36 °C) with time.

Fig. 5

Reduction kinetics of Cr(vi) to Cr(iii) in artificial sweat using SIDMS analysis at low (a) 2 μg mL^–1 Cr(vi) and high (b) 10 μg mL^–1 Cr(vi) concentrations.