The aim of this study is to compare the azole synergy across an insect, Chironomus riparius, and a crustacean species, Daphnia magna. We use a combination of in vivo measurements of cytochrome P450 monooxygenase (CYP) biotransformation potential and toxicokinetic (TK) and toxicodynamic (TD) modeling to understand the mechanism behind the synergy of two azole fungicides: the imidazole prochloraz and the triazole propiconazole on the pyrethroid insecticide α-cypermethrin. For both species, the synergistic effect of prochloraz was well-described by its effect on in vivo CYP activity, which corresponded to the biotransformation rate of the TK model parameterized on the survival data of the mixture experiment. For propiconazole, however, there were 100-fold and 50-fold differences between the 50% effect concentration of in vivo CYP activity and the modeled biotransformation rate for C. riparius and D. magna, respectively. Propiconazole, therefore, seems to induce synergy through a mechanism that cannot be quantified solely by the CYP activity assay used in this study in either of the two species. We discuss the differences between prochloraz and propiconazole as synergists across the two species in the light of the type and time dynamics of affected biotransformation processes.

中文翻译：

---

使用 TKTD 模型与体内酶抑制分析相结合，研究两种物种协同相互作用背后的机制

本研究的目的是比较一种昆虫、河岸摇蚊和甲壳类动物Daphnia magna的唑类协同作用。我们结合使用细胞色素 P450 单加氧酶 (CYP) 生物转化潜力和毒代动力学 (TK) 和毒物动力学 (TD) 模型的体内测量来了解两种唑类杀菌剂协同作用背后的机制：咪唑丙氯灵和三唑丙环唑对拟除虫菊酯的作用杀虫剂α-氯氰菊酯。对于这两个物种，丙氯灵的协同作用通过其在体内的影响得到了很好的描述。CYP 活性，对应于以混合物实验的存活数据为参数的 TK 模型的生物转化率。然而，对于丙环唑，体内CYP 活性的 50% 效应浓度与C. riparius和D. magna的模拟生物转化率之间分别存在 100 倍和 50 倍的差异。因此，丙环唑似乎通过一种机制诱导协同作用，这种机制不能仅通过本研究中使用的两种物种中任何一种的 CYP 活性测定进行量化。我们根据受影响的生物转化过程的类型和时间动态，讨论了丙氯灵和丙环唑作为这两个物种的增效剂之间的差异。