If two substances induce similar biomarker responses indicative of for instance genotoxicity, or endocrine disruption, they can be grouped. This approach can also help to identify common pathways of toxicity, adverse outcome pathways (AOPs), or mechanisms of toxicity. By grouping substances with similar toxic profiles as PMT/vPvM substances, effect biomarkers can aid in characterizing cumulative risks posed by mixtures and complex chemical substances. This proactive approach focuses on biological effects rather than relying solely on the structural and chemical properties of PMT/vPvM substances It is crucial to recognize that the effectiveness of strategies used for prioritizing substances largely depends on the availability of relevant data, including hazard and exposure data. To improve the availability and quality of such data, it is necessary to foster collective efforts such as high-quality data generation, community-level data collection, Open Science, FAIR data, and enhanced data sharing policies. When potential vPvM substances are identified by read-across and experimental evidence as substances that meet the PMT/vPvM criteria, then a hazard classification would be required. The data collected through these efforts can then be used to enhance the prioritization, identification, and regulation of PMT/vPvM substances. To manage PMT/vPvM substances effectively, manufacturers can be encouraged to submit a plan to remove these substances from wastewater. This approach can help improve the overall management of PMT/vPvM substances.