Based on our findings, which demonstrate that multiple metabolites significantly regulated following TCDD exposure can directly interact with the ERK1/2, in combination with previous literature demonstrating AHR and ERK1/2 codependency, we suggest that TCDD-induced changes in the metabolome contribute to systemic toxicity, renal pathology, inflammatory dysregulation, and atherosclerosis via activation of ERK1/2 [74]. Here, MAPK3 is linked to atherosclerosis.