There has been a conceptual shift in toxicological studies from describing what happens to explaining how the adverse outcome occurs, thereby enabling a deeper and improved understanding of how biomolecular and mechanistic profiling can inform hazard identification and improve risk assessment. Compared to traditional toxicology methods, which have a heavy reliance on animals, new approaches to generate toxicological data are becoming available for the safety assessment of chemicals, including high-throughput and high-content screening (HTS, HCS). With the emergence of nanotechnology, the exponential increase in the total number of engineered nanomaterials (ENMs) in research, development, and commercialization requires a robust scientific approach to screen ENM safety in humans and the environment rapidly and efficiently. Spurred by the developments in chemical testing, a promising new toxicological paradigm for ENMs is to use alternative test strategies (ATS), which reduce reliance on animal testing through the use of in vitro and in silico methods such as HTS, HCS, and computational modeling. Furthermore, this allows for the comparative analysis of large numbers of ENMs simultaneously and for hazard assessment at various stages of the product development process and overall life cycle. Using carbon nanotubes as a case study, a workshop bringing together national and international leaders from government, industry, and academia was convened at the University of California, Los Angeles to discuss the utility of ATS for decision-making analyses of ENMs. After lively discussions, a short list of generally shared viewpoints on this topic was generated, including a general view that ATS approaches for ENMs can significantly benefit chemical safety analysis.

The potential adverse health effects of PM2.5 and vapor samples from three communities that neighbor railyards, Commerce (CM), Long Beach (LB), and San Bernardino (SB), were assessed by determination of chemical reactivities attributed to the induction of oxidative stress by air pollutants. The assays used were dithiothreitol (DTT) and dihydrobenzoic acid (DHBA) based procedures for prooxidant content and a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) assay for electrophiles. Prooxidants and electrophiles have been proposed as the reactive chemical species responsible for the induction of oxidative stress by air pollution mixtures. The PM2.5 samples from CM and LB sites showed seasonal differences in reactivities with higher levels in the winter whereas the SB sample differences were reversed. The reactivities in the vapor samples were all very similar, except for the summer SB samples, which contained higher levels of both prooxidants and electrophiles. The results suggest the observed reactivities reflect general geographical differences rather than direct effects of the railyards. Distributional differences in reactivities were also observed with PM2.5 fractions containing most of the prooxidants (74–81%) and the vapor phase most of the electrophiles (82–96%). The high levels of the vapor phase electrophiles and their potential for adverse biological effects point out the importance of the vapor phase in assessing the potential health effects of ambient air.

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