A diverse array of compound databases, often openly accessible, serve as primary sources of candidates for identification in NTS. These range from hundreds of thousands to just over a million entries (e.g., HMDB with 220,945 metabolites and CompTox 7 with 1,218,248 chemicals as of 20 Nov. 2024), through to hundreds of millions of entries (e.g., ChemSpider 8 , PubChem and the Chemical Abstract Services (CAS) Registry 10 , with 129, 119 and 219 million chemicals as of 20 Nov. 2024, respectively). Since the CAS Registry is licensed and ChemSpider introduced limitations to their application programming interface (API) in 2018, PubChem has become the de facto standard large chemical database for open sciencebased NTS methods. While PubChem, with >1000 sources, integrates the contents of many of the smaller openly available databases, PubChem also includes tens of millions of entries that are neither likely to be found in the environment, nor pertinent to the exposome. This hinders both the performance and efficiency of NTS. Additionally, many of the chemicals in other potential sources for NTS identification efforts, such as the Global Chemical Inventory (350,000 chemicals) and various lists from European regulators contributing to the NORMAN Suspect List Exchange (NORMAN-SLE) include large proportions of chemicals that have very little supporting evidence about their existence and relevance, which makes interpretation of potential hits in NTS very challenging.