Matthew Scott Wagner

Silica nanoparticles administered at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do not

While the collection of genotoxicity data and insights into potential mechanisms of action for nano-sized particulate materials (NPs) are steadily increasing, there is great uncertainty whether current standard assays are suitable to appropriately characterize potential risks. We investigated the effects of NPs in an in vivo Comet/micronucleus (MN) combination assay and in an in vitro MN assay performed with human blood. We also incorporated additional endpoints into the in vivo study in an effort to delineate primary from secondary mechanisms. Amorphous silica NPs (15 and 55 nm) were chosen for their known reactivity, while gold nano/microparticles (2, 20, and 200 nm) were selected for their wide size range and lower reactivity. DNA damage in liver, lung and blood cells and micronuclei in circulating reticulocytes were measured after 3 consecutive intravenous injections to male Wistar rats at 48, 24 and 4h before sacrifice. Gold nano/microparticles were negative for MN induction in vitro and in vivo, and for the induction of DNA damage in all tissues. Silica particles, however, caused a small but reproducible increase in DNA damage and micronucleated reticulocytes when tested at their maximum tolerated dose (MTD). No genotoxic effects were observed at lower doses, and the in vitro MN assay was also negative. We hypothesize that silica NPs initiate secondary genotoxic effects through release of inflammatory cell-derived oxidants, similar to that described for crystalline silica (quartz). Such a mechanism is supported by the occurrence of increased neutrophilic infiltration, necrosis, and apoptotic cells in the liver, and induction of inflammatory markers TNF-α and IL-6 in plasma at the MTDs. These results were fairly consistent between silica NPs and the quartz control, thereby strengthening the argument that silica NPs may act in a similar, thresholded manner. The observed profile is supportive of a secondary genotoxicity mechanism that is driven by inflammation.

Analysis of Poly(amino acids) by Static Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS)

This study presents the static time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra of 15 poly(amino acids), solvent or spin cast onto either mica or silicon substrates. These poly(amino acid) spectra are useful for interpreting the complex static TOF-SIMS spectra obtained from adsorbed protein films and peptide-functionalized surfaces. Previous studies have reported poly(amino acid) spectra acquired with a quadrupole SIMS instrument. The spectra obtained with a TOF-SIMS instrument in this study have significantly higher sensitivity and mass resolution, which are essential for producing good, high-quality reference spectra.

Sodium Dodecyl Sulfate Adsorption onto Positively Charged Surfaces: Monolayer Formation With Opposing Headgroup Orientations

The adsorption and structure of sodium dodecyl sulfate (SDS) layers onto positively charged films have been monitored in situ with vibrational sum-frequency-generation (SFG) spectroscopy and surface plasmon resonance (SPR) sensing. Substrates with different charge densities and polarities used in these studies include CaF2 at different pH values as well as allylamine and heptylamine films deposited onto CaF2 and Au substrates by radio frequency glow discharge deposition. The SDS films were adsorbed from aqueous solutions ranging in concentration from 0.067 to 20 mM. In general the SFG spectra exhibited well resolved CH and OH peaks. However, at SDS concentrations between 1 and 8 mM the SFG CH and OH intensities decreased close to background levels. Combined data sets from molecular conformation, orientation, and order sensitive SFG with mass sensitive SPR suggest that the observed changes in SFG intensities above 0.2 mM are related to structural arrangements in the SDS layer. A model is proposed where the SFG intensity minimum between 1 and 8 mM is associated with a monolayer containing two headgroup orientations, one pointing toward the substrate and one pointing toward the solution phase. The SFG peaks observed at concentrations below 0.2 mM are dominated by the presence of adsorbed contaminants such as fatty alcohols (e.g., dodecanol), which are more surface active than SDS. As SDS solution concentration is increased above 1 mM SDS molecules are incorporated in the surface layer, with dodecanol continuing to be present in the surface layer for solution concentrations up to at least the critical micelle concentration.

The Procter and Gamble Company: Current State and Future Needs in Materials Modeling

New material development and commercial application is often quite complex due to the material properties and multiple transformations materials undergo in the supply chain, manufacturing process, and distribution of the finished product. In the fast-moving consumer goods industry of personal and household care products, these complexities are particularly acute due to the focus on and use of “commodity” materials that, at times, have significant variability in material properties. These materials are often formulated into complex liquids or assembled products, which undergo multiple transformations during making and can further undergo additional changes during distribution and use by the consumer (some desired, some not). At each stage of development, manufacturing, and distribution, materials models can be tremendously helpful in material and process selection and optimization. This chapter provides an overview of the current state-of-the-art in materials modeling as applied to the soft materials typically used in household and personal care products, with particular focus on modeling tools that span the length and time scales most relevant for modeling. We review the tools and methods in materials modeling and provide several examples where these tools have been used to guide the development of new materials. We conclude with commentary on additional advancements needed to drive practical application of these modeling tools more broadly for material development.