Co-exposure with fullerene may strengthen health effects of organic industrial chemicals

PLoS One. 2014 Dec 4;9(12):e114490. doi: 10.1371/journal.pone.0114490. eCollection 2014.

Abstract

In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-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 C60 and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C60 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 C60 that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C60 that is slightly less cytotoxic than m-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 C60 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 C60 molecules aggregate together, a portion of organic molecules remains in water.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / chemistry
  • Acetophenones / toxicity
  • Air Pollutants, Occupational / chemistry
  • Air Pollutants, Occupational / toxicity*
  • Benzaldehydes / chemistry
  • Benzaldehydes / toxicity
  • Benzyl Alcohol / chemistry
  • Benzyl Alcohol / toxicity
  • Cell Line, Tumor
  • Cresols / chemistry
  • Cresols / toxicity
  • Drug Interactions
  • Fullerenes / chemistry
  • Fullerenes / toxicity*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Interleukin-1beta / metabolism
  • Macrophages / drug effects
  • Macrophages / physiology
  • Molecular Dynamics Simulation
  • Thermodynamics
  • Toluene / chemistry
  • Toluene / toxicity
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Acetophenones
  • Air Pollutants, Occupational
  • Benzaldehydes
  • Cresols
  • Fullerenes
  • IL1B protein, human
  • Interleukin-1beta
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • 4-cresol
  • Toluene
  • Benzyl Alcohol
  • fullerene C60
  • acetophenone
  • benzaldehyde

Grants and funding

OL received funding from the Finnish Work Environment Fund (Project 110358, www.tsr.fi), TK from the Finnish Academy of Science and Letters (Väisälän rahasto, www.acadsci.fi), OC from the Academy of Finland (www.aka.fi), and TR and IV from the European Research Council (Advanced Grant CROWDED-PRO-LIPIDS, erc.europa.eu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.