Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals?

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Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals? / Cedergreen, Nina; Dalhoff, Kristoffer; Li, Dan; Gottardi, Michele; Kretschmann, Andreas Christopher.

In: Environmental Science & Technology (Washington), Vol. 51, No. 24, 2017, p. 14379-14389.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Cedergreen, N, Dalhoff, K, Li, D, Gottardi, M & Kretschmann, AC 2017, 'Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals?', Environmental Science & Technology (Washington), vol. 51, no. 24, pp. 14379-14389. https://doi.org/10.1021/acs.est.7b02723

APA

Cedergreen, N., Dalhoff, K., Li, D., Gottardi, M., & Kretschmann, A. C. (2017). Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals? Environmental Science & Technology (Washington), 51(24), 14379-14389. https://doi.org/10.1021/acs.est.7b02723

Vancouver

Cedergreen N, Dalhoff K, Li D, Gottardi M, Kretschmann AC. Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals? Environmental Science & Technology (Washington). 2017;51(24):14379-14389. https://doi.org/10.1021/acs.est.7b02723

Author

Cedergreen, Nina ; Dalhoff, Kristoffer ; Li, Dan ; Gottardi, Michele ; Kretschmann, Andreas Christopher. / Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals?. In: Environmental Science & Technology (Washington). 2017 ; Vol. 51, No. 24. pp. 14379-14389.

Bibtex

@article{fae729226a214a67a61ccc4acee06d13,
title = "Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals?",
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.",
keywords = "Journal Article",
author = "Nina Cedergreen and Kristoffer Dalhoff and Dan Li and Michele Gottardi and Kretschmann, {Andreas Christopher}",
year = "2017",
doi = "10.1021/acs.est.7b02723",
language = "English",
volume = "51",
pages = "14379--14389",
journal = "Environmental Science & Technology (Washington)",
issn = "0013-936X",
publisher = "American Chemical Society",
number = "24",

}

RIS

TY - JOUR

T1 - Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals?

AU - Cedergreen, Nina

AU - Dalhoff, Kristoffer

AU - Li, Dan

AU - Gottardi, Michele

AU - Kretschmann, Andreas Christopher

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1021/acs.est.7b02723

DO - 10.1021/acs.est.7b02723

M3 - Journal article

C2 - 28901128

VL - 51

SP - 14379

EP - 14389

JO - Environmental Science & Technology (Washington)

JF - Environmental Science & Technology (Washington)

SN - 0013-936X

IS - 24

ER -

ID: 185403560