Highlights
Human Biomonitoring (HBM) provides valuable insight into co-exposure to multiple chemicals.
HBM data can be interpreted in comparison to biomonitoring equivalents of health based guidance values.
Two generic physiologically based kinetic models were tested for deriving biomonitoring equivalents.
Uncertainties and limitations were identified and discussed.
The use of biomonitoring equivalents in assessing chemical mixtures was illustrated in a case study.
Introduction: The kidney is a major target for toxicity elicited by pharmaceuticals and environmental pollutants. Standard testing which often does not investigate underlying mechanisms has proven not to be an adequate hazard assessment approach. As such, there is an opportunity for the application of computational approaches that utilise multi-scale data based on the Adverse Outcome Pathway (AOP) paradigm, coupled with an understanding of the chemistry underpinning the molecular initiating event (MIE) to provide a deep understanding of how structural fragments of molecules relate to specific mechanisms of nephrotoxicity. The aim of this investigation was to review the current scientific landscape related to computational methods, including mechanistic data, AOPs, publicly available knowledge bases and current in silico models, for the assessment of pharmaceuticals and other chemicals with regard to their potential to elicit nephrotoxicity. A list of over 250 nephrotoxicants enriched with, where possible, mechanistic and AOP-derived understanding was compiled. Expert opinion: Whilst little mechanistic evidence has been translated into AOPs, this review identified a number of data sources of in vitro, in vivo and human data that may assist in the development of in silico models which in turn may shed light on the interrelationships between nephrotoxicity mechanisms.
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