A Common Adverse Outcome Pathway for Metal(loid)s Inducing Nephrotoxicity to Advance Next-Generation Risk Assessment of Chemical Mixtures
Schillemans, Tessa van den Brand, Annick D Åkesson, Agneta Mengelers, Marcel JB Luijten, Mirjam
Schillemans, Tessa
van den Brand, Annick D
Åkesson, Agneta
Mengelers, Marcel JB
Luijten, Mirjam
Series / Report no.
Open Access
Type
Journal Article
Review
Article
Review
Article
Language
en
Date
2025-07-16
Research Projects
Organizational Units
Journal Issue
Title
A Common Adverse Outcome Pathway for Metal(loid)s Inducing Nephrotoxicity to Advance Next-Generation Risk Assessment of Chemical Mixtures
Translated Title
Published in
Annu Rev Pharmacol Toxicol 2026; 66(1):305-323
Abstract
Chronic exposure to the metal(loid)s arsenic, cadmium, lead, and mercury via contaminated food or drinking water may induce kidney toxicity, but there is little consensus on the biological processes involved. Health risk assessment of these substances is further complicated by coexposures and the sometimes unclear causal interpretation of population studies. To address these issues, we developed a common adverse outcome pathway (AOP) describing how these metal(loid)s can induce kidney toxicity. Upon identification of renal dysfunction resulting from proximal tubular damage as a common adverse outcome, we developed the AOP by collecting evidence from relevant (experimental) studies. Evaluation of the weight of evidence revealed a moderate to high confidence in this AOP. It enhances our mechanistic understanding of metal(loid)-induced kidney toxicity and provides scientific evidence for a causal relationship between the adverse effect and effect biomarkers. As such, this is an example of how AOPs can facilitate next-generation risk assessment of combined exposure to different contaminants.