Co-Exposure with Fullerene May Strengthen Health Effects of Organic Industrial Chemicals

<div><p><i>In vitro</i> toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C<sub>60</sub> fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, <i>m</i>-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C<sub>60</sub> and organic chemicals represent different co-exposure scenarios in <i>in vitro</i> studies where acute cytotoxicity and immunotoxicity of C<sub>60</sub> and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C<sub>60</sub> that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of <i>m</i>-cresol and C<sub>60</sub> that is slightly less cytotoxic than <i>m</i>-cresol. Hydrophobicity of chemicals correlates with co-effects when secretion of pro-inflammatory cytokines IL-1β and TNF-α is considered. Complementary atomistic molecular dynamics simulations reveal that C<sub>60</sub> co-aggregates with all chemicals in aqueous environment. Stable aggregates have a fullerene-rich core and a chemical-rich surface layer, and while essentially all C<sub>60</sub> molecules aggregate together, a portion of organic molecules remains in water.</p></div>