10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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In Vivo Toxicity of Soot Can Be Predicted from Both Surface Area Dose and in Vitro Assays
OTMAR SCHMID, Tobias Stoeger, Helmholtz Zentrum Munchen, Comprehensive Pneumology Center
Abstract Number: 1692 Working Group: Aerosol Toxicology
Abstract Inhalation of insoluble particles is believed to cause an oxidative cellular stress response, which may lead to pulmonary or even systemic inflammation. In addition to concern about urban dust and particularly soot particles, an increasing number of engineered nanoparticles is expected to be emitted into the atmosphere due to the economic success of nanotechnology. In the interest of consumer and workers’ safety fast, reliable and affordable screening techniques for (nano-)particle toxicity are required. In addition, animal protection demands the development of straightforward in vitro tests, which are verified against in vivo results. Responding to these demands we combined data on acute pulmonary inflammation in mice (in vivo) with a cell-free oxidative potency (in vitro) for six types of soot particles.
For soot particle, inflammatory responses are likely to be induced by serval pathways including oxidative potency of the soot core and detoxification of organic compounds (e.g. PAHs) (Stoeger et al., 2009). Following this hypothesis we correlated our data on acute pulmonary inflammation in BALB/cJ mice (influx of polymorphonuclear neutrophils (PMNs) into the lungs) 24h after intratracheal instillation of various doses of six types of soot particles with corresponding (in vitro) data from a cell-free oxidative potency assay (consumption of ascorbate (antioxidant) and expression of the cytochrome (CYP) P450 gene (Cyp1a1) gene in a murine epithelial cell line (LA4) as marker of the detoxification pathway.
With this approach more than 90% of the observed variation in in vivo inflammatory efficacy of soot could be explained by an additive linear model involving oxidative potency and Cyp1a1 expression. This is particularly remarkable, since the six types of soot used here represent a wide dynamic range of some of the most relevant physico-chemical properties, namely (primary) particle diameter (10-50nm), organic mass content (OC; 1-20%) and BET surface area (43-800m2/g) (Stoeger et al., 2009; Matuschek et al., 2007). Consistent with our pathway hypothesis, oxidative potency contributed most significantly to low OC soot the toxicity of high O soot was dominated by the detoxification pathway (Cyp1a1 induction).
May be even more remarkably, BET surface area dose explained more than 90% of the observed variability of the in vivo inflammatory response. Moreover, the six types of soot particles investigated here show similar toxicity as many engineered nanomaterials such as TiO2, amorphous silica or even many types of multi-walled carbon nanotubes (graphene sheets), if – and only if – the inflammatory dose-response is expressed in terms of surface area as dose metric (not in terms of mass, volume or number).
In summary, while the assessment of soot-induced acute inflammation in mice is well correlated to lung-deposited surface area dose, more detailed information on the involved pathways of toxicity and their relative contributions to in vivo toxicity can be deciphered by the employment of suitable in vitro assays. The soot particles investigated here do not show enhanced toxicity as compared other low-solubility, low toxicity materials. However, a wider array of soot particles should be investigated to further assess this issue.
Stoeger et al. (2009). Environ. Health Persp., 117, 54-60. Matuschek et al. (2007). Environ. Sci. Technol. 41, 8406-8411.