Acellular oxidative potential assay for screening of amorphous silica nanoparticles.

Silica nanoparticles (SiNPs) are used in a wide range of consumer products, engineering and medical applications, with likelihood of human exposure and potential health concerns. It is essential to generate toxicity information on SiNP forms and associated physicochemical determinants to conduct risk assessment on these new materials. To address this knowledge gap, we screened a panel of custom synthesized, well-characterized amorphous SiNPs pristine and surface-modified (-C3-COOH, -C11-COOH, -NH2, -PEG) of 5 different sizes: (15, 30, 50, 75, 100 nm) for their oxidative potential using an acellular assay. The assay is based on oxidation of dithiothreitol (DTT) by reactive oxygen species and can serve as a surrogate test for oxidative stress. These materials were characterized for size distribution, aggregation, crystallinity, surface area, surface modification, surface charge and metal content. Tests for association between oxidative potential of SiNPs and their physicochemical properties were carried out using analysis of variance and correlation analyses. These test results suggest that the size of amorphous SiNPs influenced their oxidative potential irrespective of the surface modification, with 15 nm exhibiting relatively higher oxidative potential compared to the other sizes. Furthermore, SiNP surface area, surface modification and agglomeration in solution also appeared to affect oxidative potential of these SiNPs. These findings indicate that physicochemical properties are critical in influencing the oxidative behaviour of amorphous SiNPs, with potential to trigger cellular oxidative stress and thus toxicity, when exposed. This information advances our understanding of potential toxicities of these amorphous SiNPs and supports risk assessment efforts and the design of safer forms of silica nanomaterials.

Factors associated with plasma concentrations of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (p,p'-DDE) in the Canadian population.

This study describes blood plasma concentrations of PCBs and p,p'-DDE in the Canadian population aged 20-79 years. PCBs and p,p'-DDE were measured in 1668 participants in the Canadian Health Measures Survey, Cycle 1 (2007-2009). We investigated how concentrations vary by sociodemographic, anthropometric, and lifestyle variables, identified factors associated with exposures, and evaluated concentrations against health-based guidance values. Congeners of PCB most commonly detected were PCB-138, PCB-153, and PCB-180. p,p'-DDE was detectable in > 99% of the samples. Factors associated with ∑PCBs were age, region of birth, frequency of fish consumption, and liver intake (R2 = 58.1%). For p,p'-DDE, significant factors were sex, age, region of birth, household education, and ethnic origin (R2 = 47.0%). PCB concentrations in Canadians were similar to those in the United States, and lower than those reported in Europe. A small percentage equalled or exceeded the Human Biomonitoring value of 3.5 µg/L for PCBs. Few exceedances of the p,p'-DDE biomonitoring equivalent were observed.

Characterization of Commercial Metal Oxide Nanomaterials: Crystalline Phase, Particle Size and Specific Surface Area.

Physical chemical characterization of nanomaterials is critical to assessing quality control during production, evaluating the impact of material properties on human health and the environment, and developing regulatory frameworks for their use. We have investigated a set of 29 nanomaterials from four metal oxide families (aluminum, copper, titanium and zinc) with a focus on the measurands that are important for the basic characterization of dry nanomaterials and the determination of the dose metrics for nanotoxicology. These include crystalline phase and crystallite size, measured by powder X-ray diffraction, particle shape and size distributions from transmission electron microscopy, and specific surface area, measured by gas adsorption. The results are compared to the nominal data provided by the manufacturer, where available. While the crystalline phase data are generally reliable, data on minor components that may impact toxicity is often lacking. The crystal and particle size data highlight the issues in obtaining size measurements of materials with broad size distributions and significant levels of aggregation, and indicate that reliance on nominal values provided by the manufacturer is frequently inadequate for toxicological studies aimed at identifying differences between nanoforms. The data will be used for the development of models and strategies for grouping and read-across to support regulatory human health and environmental assessments of metal oxide nanomaterials.

Mapping acute systemic effects of inhaled particulate matter and ozone: multiorgan gene expression and glucocorticoid activity.

Recent epidemiological studies have demonstrated associations between air pollution and adverse effects that extend beyond respiratory and cardiovascular disease, including low birth weight, appendicitis, stroke, and neurological/neurobehavioural outcomes (e.g., neurodegenerative disease, cognitive decline, depression, and suicide). To gain insight into mechanisms underlying such effects, we mapped gene profiles in the lungs, heart, liver, kidney, spleen, cerebral hemisphere, and pituitary of male Fischer-344 rats immediately and 24h after a 4-h exposure by inhalation to particulate matter (0, 5, and 50mg/m(3) EHC-93 urban particles) and ozone (0, 0.4, and 0.8 ppm). Pollutant exposure provoked differential expression of genes involved in a number of pathways, including antioxidant response, xenobiotic metabolism, inflammatory signalling, and endothelial dysfunction. The mRNA profiles, while exhibiting some interorgan and pollutant-specific differences, were remarkably similar across organs for a set of genes, including increased expression of redox/glucocorticoid-sensitive genes and decreased expression of inflammatory genes, suggesting a possible hormonal effect. Pollutant exposure increased plasma levels of adrenocorticotropic hormone and the glucocorticoid corticosterone, confirming activation of the hypothalamic-pituitary-adrenal axis, and there was a corresponding increase in markers of glucocorticoid activity. Although effects were transient and presumably represent an adaptive response to acute exposure in these healthy animals, chronic activation and inappropriate regulation of the hypothalamic-pituitary-adrenal axis are associated with adverse neurobehavioral, metabolic, immune, developmental, and cardiovascular effects. The experimental data are consistent with epidemiological associations of air pollutants with extrapulmonary health outcomes and suggest a mechanism through which such health effects may be induced.