Considerations for future quantitative structure-activity relationship (QSAR) modelling for heavy metals: A case study of mercury

With increasing annual chemical development and production, safety testing demands and requirements have also increased. In addition to traditional animal testing, quantitative structure-activity relationship (QSAR) modelling can be used to predict the biological effect of a chemical structure, based on the analysis of quantitative characteristics of structure features. Whilst suitable for e.g., pharmaceuticals, other compounds can be more challenging to model. The naturally occurring heavy metal mercury speciates in the environment, with some toxic species accumulating in aquatic organisms. Although this is well known, only little data is available from (eco)toxicological studies, none of which account for this speciation behaviour. The present work highlights the current toxicity data for mercury in aquatic animals and gaps in our understanding and data for future QSAR modelling. All publicly available ecotoxicology data was obtained from databases and literature. Only few studies could be determined that assessed mercury toxicity in aquatic species. Of these, likely speciation products were determined using PHREEQc. This highlighted that the mercury exposure species was not always the predominant species in the medium. Finally, the descriptors for the modelled species were obtained from ChemDes, highlighting the limited availability of such details. Additional testing is required, accounting for speciation and biological interactions, to successfully determine the toxicity profile of different mercury species in aquatic environments. In the present work, insufficient mercury-species specific data was obtained, to conduct QSAR modelling successfully. This highlights a significant lack of data, for a heavy metal with potentially fatal repercussions.