Biotic ligand models (BLMs) predict the toxicity of metals in aquatic environments by accounting for metal interactions with cell surface receptors (biotic ligands) in organisms, including water chemistry (metal speciation) and competing cations. Metal binding constants (log KMBL values), which indicate the affinity of metals for cell surface receptors, are fundamental to BLMs, but have only been reported for a few commonly investigated metals and freshwater species. This review evaluated literature toxicity and uptake data for seven key metals (cadmium (Cd), cobalt (Co), copper (Cu), nickel (Ni), lead (Pb), uranium (U), and zinc (Zn)) and four key competing cations (protons (H), calcium (Ca), magnesium (Mg), and sodium (Na)), to derive average metal binding constants for freshwater organisms/taxa. These constants will improve current BLMs for Cd, Cu, Ni, Pb, and Zn, and aid in developing new BLMs for Co and U. The derived metal binding constants accurately predicted metal toxicity for a wide range of freshwater organisms (75–88% of data were within a factor of two and 88–98% of data were within a factor of three of the ideal 1:1 agreement line), when considering metal speciation, competing cations and the fraction of cell receptors ((fC)M50%) occupied by the metal at the median (50%) effect concentration (EC50). For many organisms, toxicity occurs when 50% of cell surface receptors are occupied by the metal, though this threshold can vary. Some organisms exhibit toxicity with less than 50% receptor occupancy, while others with protective mechanisms show reduced toxicity, even with similar log KMBL values. For Cu, U, and Pb, the toxic effect of the metal hydroxide (as MOH+) must be considered in addition to the free metal ion (M2+), as these metals hydrolyse in circumneutral freshwaters (pH 5.5 to 8.5), contributing to toxicity.
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