BackgroundLittle is known about the mechanisms involved in lung inflammation caused by the inhalation or instillation of nanoparticles. Current research focuses on identifying the particle parameter that can serve as a proper dose metric.ObjectivesThe purpose of this study was to review published dose–response data on acute lung inflammation in rats and mice after instillation of titanium dioxide particles or six types of carbon nanoparticles. I explored four types of dose metrics: the number of particles, the joint length—that is, the product of particle number and mean size—and the surface area defined in two different ways.FindingsWith the exception of the particle size–based surface area, all other parameters worked quite well as dose metrics, with the particle number tending to work best. The apparent mystery of three equally useful dose metrics could be explained. Linear dose–response relationships were identified at sufficiently low doses, with no evidence of a dose threshold below which nanoparticle instillation ceased to cause inflammation. In appropriately reduced form, the results for three different sets of response parameters agreed quite well, indicating internal consistency of the data. The reduced data revealed particle-specific differences in surface toxicity of the carbon nanoparticles, by up to a factor of four, with diesel soot being at the low end.ConclusionsThe analysis suggests that the physical characterization of nanoparticles and the methods to determine surface toxicity have to be improved significantly before the appropriate dose metric for lung inflammation can be identified safely. There is also a need for refinements in quantifying response to exposure.

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Human angiotensin II, chain B of bovine insulin, and porcine insulin were determined by time-of-flight secondary ion mass spectrometry under impact of approximately 25 keV Xe+ and SF5+ ion beams and approximately 100 MeV 252Cf fission fragments. Matrix-embedded samples, dissolved in a large surplus of alpha-cyano-4-hydroxycinnamic acid, were prepared by nebulizer spray deposition, neat samples by the droplet technique. It is shown that the status of the sample can be assessed by evaluating the matrix-specific features of the mass spectra. The beneficial effect of matrix isolation was small for angiotensin but large for the insulin samples, which did not show parent peaks from neat material. Negative ion yields under SF5+ impact were up to a factor of 50 higher than with Xe+. For positive secondary ions, the enhancement was much smaller. The mass spectra produced by slow ion beams or fast fission fragments were qualitatively similar. Quantitative differences include the following: with fast projectiles the yields were about 10-30 times higher than with slow ions, but similar for negative ion emission under SF5+ bombardment; the analyte-to-matrix yield ratios were higher with slow ions and up to 250 times higher than the molar analyte concentration; for analyte ions the peak-to-background ratios were higher using slow projectiles; the fraction of carbon-rich collisionally formed molecular ions was much higher with fast projectiles. Sample aging in vacuum for up to five weeks strongly reduced the yield of protonated analyte molecules ejected by slow ion impact, but not of deprotonated species. Hence protonation seems to correlate with sample "wetness" or the presence of volatile proton-donating additives.

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With very few exceptions, previous nanotoxicity studies implicitly involved the assumption that the techniques developed for risk assessment of hazardous chemical substances can be applied in unchanged form to explore cell response in NP laden media. This misleading approach has the consequence that the actual dose of exposure is ill defined or, more often, completely unknown. Here the effect of gravitational settling on the dose of exposure was explored for commercially available engineered nanostructured matter (nanopowder). Micrometer sized aggregates abundantly present in all nanopowders were fractured as much as possible by probe-type sonication in water or cell culture media. The morphology of cracked aggregates was studied by scanning electron microscopy. Size distributions were determined by dynamic light scattering (DLS). Possible pitfalls encountered in using DLS were documented. Absorbance measurements and optical microscopy served to monitor the rate of gravitational settling on time sales ranging from minutes up to several days. The sonicated particles settled rapidly in all liquid media. At the well bottom, they exhibited intense lateral (two-dimensional) Brownian-like motion, which allowed them to travel large distances. Taken together, the probability for particle-cell contact may be enhanced by a factor of more than 1000 compared to the commonly advocated picture. The very high levels of exposure can give rise to overload effects which are often misinterpreted as evidence of cytotoxicity. To identify the true toxic potential of NPs, future studies must account for these phenomena. It is also argued that stable dispersions of NPs are not required in nanotoxicity studies.