The synergistic potential of azole fungicides does not directly correlate to the inhibition of cytochrome P450 activity in aquatic invertebrates
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The synergistic potential of azole fungicides does not directly correlate to the inhibition of cytochrome P450 activity in aquatic invertebrates. / Gottardi, Michele; Cedergreen, Nina.
In: Aquatic Toxicology, 01.02.2019, p. 187-196.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The synergistic potential of azole fungicides does not directly correlate to the inhibition of cytochrome P450 activity in aquatic invertebrates
AU - Gottardi, Michele
AU - Cedergreen, Nina
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - Azole fungicide
KW - Enzymatic assay
KW - In vivo model
KW - Mixture toxicity
KW - Pesticide synergy
UR - http://www.scopus.com/inward/record.url?scp=85058621157&partnerID=8YFLogxK
U2 - 10.1016/j.aquatox.2018.12.010
DO - 10.1016/j.aquatox.2018.12.010
M3 - Journal article
C2 - 30579157
AN - SCOPUS:85058621157
SP - 187
EP - 196
JO - Aquatic Toxicology
JF - Aquatic Toxicology
SN - 0166-445X
ER -
ID: 213856939