The Society of Toxicology 55th Annual Meeting and ToxExpo will be held on March 13–17, 2016, in New Orleans, Louisiana.
You are welcome to visit us at booth #641 and at the poster board where Stuart Tugendreich will be presenting on “Functional and molecular responses to inhalation of MWCNT from the perspective of occupationally-relevant depositions”.
Functional and molecular responses to inhalation of MWCNT from the perspective of occupationally-relevant depositions
3485: Poster Board – P175
Thursday, March 17, 9:30 a.m. – 12:45 p.m.
Speaker: Stuart Tugendreich
In order to assess the toxicity response to occupationally-relevant depositions of multi-walled carbon nanotube (MWCNT), a dose- and time-dependent 4-week inhalation exposure to MWNCT (Mitsui-7) was initiated to represent a worker exposed to 76, 7.6 and 0.76 years at average inhalable workplace concentrations of 10.6 µg/m3. Mice were sacrificed at 0, 28, and 84 d post-exposure with lung, liver, and aorta collected for microarray-based gene expression profiling analyzed in conjunction with alterations in lavage proteins, alveolar macrophage function, histopathology, extrathoracic translocation, and systemic effects. Differentially expressed genes, upstream transcriptional regulators, and responses corresponding to inflammation/immune function and pathological changes (e.g. fibrosis) were persistent in the high dose but transient in the middle dose. The responses reflected the 58 lavage proteins measured and morphometric analysis of alveolar fibrosis which was increased in the high dose only. Similarly, isolated alveolar macrophages challenged with LPS (1 ug/ml) ex vivo enhanced cytokine production that was sustained in the high dose but transient in the middle dose. At all three doses, MWCNT translocated to the kidney and liver indicating a likely dependence on physicochemical properties. Analysis of systemic effects showed minimal to no changes in liver or aorta transcriptomics, 58 analyzed plasma proteins, or liver and renal histopathology. Plasma from only the high dose group increased adhesion molecule expression in primary endothelial cells. In summary, induced molecular mechanisms, histopathological changes, and systemic effects occur primarily at depositions (or dose rates) predicted to be significantly higher than expected in average workplace exposure scenarios.
More information about the SOT Annual Meeting and ToxExpo