The synergistic potential of azole fungicides does not directly correlate to the inhibition of cytochrome P450 activity in aquatic invertebrates

Michele Gottardi, Nina Cedergreen*

*Corresponding author for this work
10 Citations (Scopus)

Abstract

The ability of azole fungicides to inhibit cytochrome P450 dependent metabolism is proposed to be the main mechanism for their synergizing effect on pyrethroid insecticide toxicity in aquatic invertebrates. This study investigates the correlation between inhibition strength and synergistic potential of azole fungicides in the crustacean Daphnia magna and the insect larvae Chironomus riparius. Inhibition strength was measured in vivo toward the cytochrome P450 catalysed conversion of 7-ethoxycoumarin to 7-hydroxycoumarin (ECOD). Synergistic potentials were determined as the ratio between predicted and observed toxicity of mixtures based on the model of concentration addition (CA) and independent action (IA). Azoles (n = 9–11) enhanced the toxicity of α-cypermethrin in D. magna (Synergy ratios CA: 0.8 – 16; IA: 1.1 – 22) and inhibited cytochrome P450 activity by different degrees (IC50: 0.0023 – 36 μM for D. magna and 0.08 – 24 μM for C. riparius). Inhibition strengths were strongly correlated in the two organisms (r: 0.937 p: 0.019 for triazoles and r: 0.903 p: 0.097 for imidazoles). Lipophilicity governed the inhibition strength of triazoles in both species (r > 0.9, p < 0.05). No correlation was observed between inhibition strengths and synergistic potentials. Several reasons for the apparent lack of correlation were discussed.

Original languageEnglish
JournalAquatic Toxicology
Pages (from-to)187-196
Number of pages10
ISSN0166-445X
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • Azole fungicide
  • Enzymatic assay
  • In vivo model
  • Mixture toxicity
  • Pesticide synergy

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