Figure 3. Hypothetical cellular interaction of NSPs (adapted from Donaldson and Tran 2002). EGFR, epidermal growth factor receptor. Inflammation and oxidative stress can be mediated by several primary pathways: a) the particle surface causes oxidative stress resulting in increased intracellular calcium and gene activation; b) transition metals released from particles result in oxidative stress, increased intracellular calcium, and gene activation; c) cell surface receptors are activated by transition metals released from particles, resulting in subsequent gene activation; or d) intracellular distribution of NSPs to mitochondria generates oxidative stress.