Can Toxicokinetic and Toxicodynamic Modeling Be Used to Understand and Predict Synergistic Interactions between Chemicals?

Nina Cedergreen, Kristoffer Dalhoff, Dan Li, Michele Gottardi, and Andreas C. Kretschmann (2017). “Can Toxicokinetic and Toxicodynamic Modeling Be Used to Understand and Predict Synergistic Interactions between Chemicals?” Environmental Science & Technology Article ASAP
DOI: 10.1021/acs.est.7b02723

Abstract: Some chemicals are known to enhance the effect of other chemicals beyond what can be predicted with standard mixture models, such as concentration addition and independent action. These chemicals are called synergists. Up until now, no models exist that can predict the joint effect of mixtures including synergists. The aim of the present study is to develop a mechanistic toxicokinetic (TK) and toxicodynamic (TD) model for the synergistic mixture of the azole fungicide, propiconazole (the synergist), and the insecticide, α-cypermethrin, on the mortality of the crustacean Daphnia magna. The study tests the hypothesis that the mechanism of synergy is the azole decreasing the biotransformation rate of α-cypermethrin and validates the predictive ability of the model on another azole with a different potency: prochloraz. The study showed that the synergistic potential of azoles could be explained by their effect on the biotransformation rate but that this effect could only partly be explained by the effect of the two azoles on cytochrome P450 activity, measured on D. magna in vivo. TKTD models of interacting mixtures seem to be a promising tool to test mechanisms of interactions between chemicals. Their predictive ability is, however, still uncertain.

Author: Laura B.

I'm the Illinois Sustainable Technology Center's Sustainability Information Curator, which is a fancy way of saying embedded librarian. I'm also Executive Director of the Great Lakes Regional Pollution Prevention Roundtable. When not writing for Environmental News Bits, I'm an avid reader. Visit Laura's Reads to see what I'm currently reading.

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