title: An application of the biotic ligand model to predict the toxic effects of metal mixtures.
abstract: The rapidly developing biotic ligand model (BLM) allows us to predict the toxicity of heavy metals in water of various chemistries; however, the current BLM predicts the toxicity of a single metal and not the toxic effects of metal mixtures. The toxic mechanisms of heavy metals are not yet completely understood, but hypocalcemia is suggested to be the most likely toxic mechanism for some metals. The BLM, which predicts the toxicity of metals by the amount of metals binding to ligand, is modified to predict the toxicity by the proportion of nonmetal binding ligand that is available for calcium uptake under the assumption that the organisms die because of hypocalcemia when so few ligands are available for calcium uptake. Because the proportion can be computed when multiple metals are present, the toxic effects of metal mixtures can be predicted. Zinc, copper, and cadmium toxicity to rainbow trout (Oncorhynchus mykiss) are considered. All data are collected from the literature, and a meta-analysis using the modified version of the BLM is conducted. The present study found that the proportion of nonmetal binding ligand is a constant value for any test condition. The proportion is not influenced by water chemistry or by metal species. Using the nature of constant proportion, toxicities of metals are well estimated. In addition, the toxic effects of metal mixtures are the simple sum of the toxicities of each metal (additive effect) corresponding to the bioavailable form of the metals. In terms of total concentration of metals in water, however, nonadditive effects, such as antagonism and synergism, are possible.
authors.affiliation: Advanced Industrial Science and Technology Research Center for Chemical Risk Management, Onogawa 16-1, Tsukuba, Ibaraki 305-8569, Japan. masashi-kamo@aist.go.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Kamo
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagai
mesh_terms: D000818:Animals; D001682:Biological Availability; D002118:Calcium / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007928:Lethal Dose 50; D008024:Ligands; D019216:Metals, Heavy / Q000032:analysis / Q000633:toxicity*; D008954:Models, Biological; D017686:Oncorhynchus mykiss; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D015996:Survival Rate; D013696:Temperature; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*
chemical_list: D008024:Ligands; D019216:Metals, Heavy; D014874:Water Pollutants, Chemical; D002118:Calcium