Cytotoxicity of binary mixtures of human pharmaceuticals in a fish cell line: Approaches for non-monotonic concentration–response relationships

Biphasic concentration–response relationships were observed for some compounds

Peter A. Bain; Anupama Kumar

2014

Scholarcy highlights

  • The in vitro cytotoxicity of ten pharmaceuticals was investigated using RTG-2 cells
  • Biphasic concentration–response relationships were observed for some compounds
  • Biphasic concentration–response relationships were observed in cells exposed to FL and PPN
  • Three equations describing non-monotonic concentration–response relationships were evaluated and one was found to consistently provide more accurate estimates of the median and 10% effect concentrations compared with a sigmoidal concentration–response model
  • The cytotoxicity of the all three binary combinations could be adequately predicted using concentration addition, suggesting that the toxic mode of action in RTG-2 cells is unrelated to the therapeutic mode of action of these compounds
  • The approach presented here is widely applicable to the study of mixture toxicity in cases where non-monotonic concentration–response relationships are observed

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