Pharmacokinetic differences, or other adaptive responses result in lower tissue chromium levels and fewer differentially expressed genes in rats. Additional studies are required to further elucidate differences in differential gene expressions relevant to species-specific outcomes. The following are the supplementary data related to this article. Cytoskeletal Signaling inhibitor Supplementary Fig. S1.   Automated dose–response modeling of (A) duodenal and (B) jejunal gene expression data at day 91. ToxResponse modeler identified

the best fit model and was used to calculate EC50 values. Significantly fewer probes met the filtering criteria and were included in the analysis at day 91 with majority (> 72%) of probes having EC50 values between 10 and 100 mg/L SDD. This work was funded by The Hexavalent Chromium Panel of the American Chemistry Council. The authors declare that there are no conflicts of interest. The authors would like to thank Drs. Michael Dourson, David Gaylor, Lucy Anderson and Rebecca Fry for a critical review of an earlier version of this manuscript. In addition, the authors also thank Courtney Goslowsky, Michelle Thomas, Marsha Grimes, Veronica Reardon, Lawanda Moon, and Sharell Lewis for their assistance with tissue collections.

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“Lead has historically been used in a wide variety of human activities, which has significantly increased its emission into the atmosphere (Patrick, 2006). Therefore, all humans have an associated lead burden due to Entinostat research buy exposure to exogenous sources (Levin and Goldberg, 2000). The adverse effects of lead on the heart and vessels have been previously demonstrated (Fiorim et al., 2011, Silveira et al., 2010 and Vassallo et al., 2008). Numerous studies have revealed that chronic or acute lead exposure increases oxidative stress (Silveira et al., 2010 and Vaziri et al., 1999a), lipid peroxidation (Ding et al., 1998 and Vaziri et al., 1999b), and affects antioxidant reserves (Farmand et al., 2005 and Vaziri et al., 2003). Vascular endothelium is highly sensitive to oxidative stress, and this stress is the main cause of the endothelial

dysfunction observed in cardiovascular diseases such as atherosclerosis, hypertension and stroke (Chatterje and Catravas, ADP ribosylation factor 2008 and Forstermann and Munzel, 2006). It is well established that lead exposure induces endothelial dysfunction, and therefore, it could be considered an important cardiovascular risk factor and a serious problem for public health (Patrick, 2006, Poreba et al., 2011, Silveira et al., 2010 and Vaziri et al., 1999a). Recently, we demonstrated that a 7-day treatment with a low concentration of lead acetate increases NO bioavailability and Na+/K+-ATPase activity in the rat aorta (Fiorim et al., 2011). NO, a short lived gas, is an important protective molecule in the vasculature, especially in conductance arteries.