Figure 1: Schematic overview of the possible PN disruptions through toxicant-mediated oxidative adduction, free radical damage, and non-radical modifications.

Briefly, toxicants can impact the PN via direct mechanisms, like redox cycling and direct oxidation of critical proteins involved in proteasomal degradation, autophagy, and heat shock protein chaperones. Additionally, the PN can be negatively impacted by toxicant exposure via toxicant-mediated mitochondrial dysfunction, which can impair ATP production and exacerbate ROS production.