Identifying pathway-based bioactivity in the samples can inform the potential hazards of exposure to chemicals associated with the pyroplastics. The adverse outcome pathway framework aims to connect in vitro pathway-based bioactivity (e.g., AhR activation) with organismal-level responses and adverse outcomes (e.g., cardiotoxicity). Adverse outcome pathways have been defined on AOP-Wiki 86 for several of the activated end points, including PXR, AhR, ER, PPAR, and NRF2, while others (AP-1 and RXR) have yet to be established. The most developed adverse outcome pathways are for AhR and ER, whereby their activation has been connected to early mortality, several cancers, preeclampsia, cognitive decline, liver fibrosis and steatosis, and reproductive dysfunction. Activation of PPAR and PPAR have adverse outcome pathways resulting in vascular disruption, obesity, liver steatosis, cancers, and reproductive dysfunction. The adverse outcome pathways associated with PXR and NRF2 are more nascent than the others; their activation includes liver steatosis and vascular disruption. Having identified potential upstream molecular initiating events with the FACTORIAL bioassays, future work should focus on hypothesis-driven, in vivo measures of tangential and downstream key events within these pathways to further guide risk assessment of pyroplastics.