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<p>Neonicotinoid insecticides (neonicotinoids) are widely used in agriculture, forestry and public health in the world. Environmental exposure to neonicotinoids has been increasing due to their continuous uses. Neonicotinoids act as agonists, antagonists, or modulators of acetylcholine receptors and have adverse effects on non-target species, such as invertebrates, amphibians, reptiles, birds, microbes and mammals. Although there is concern about their adverse effects on ecosystem services and their potential effects on human health, their xenobiotic kinetics and dynamics in humans are not understood well. In this study, we determined a xenobiotic kinetic parameter, plasma protein bindings (PPBs) of 7 neonicotinoids and 18 metabolites with human plasma using a Rapid Equilibrium Dialysis (RED) device and liquid chromatography-tandem mass spectrometry (LC–MS/MS), and compared their PPBs with their physicochemical properties. 6-chloronicotinic acid (6-CNA) exhibited the highest PPB (86.4%), followed by imidacloprid-olefin (86.3%) in human plasma. Their PPBs are much higher than that of the parent compound, imidacloprid (27.5%). The PPBs of neonicotinoids and metabolites are not related to their lipophilicity determined by reversed-phase LC. The results shed light on the behavior of environmentally exposed neonicotinoids and metabolites and warrant further research on their xenobiotic kinetics and dynamics in humans.</p>

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Human plasma protein bindings of neonicotinoid insecticides and metabolites

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月16日

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  • Kumiko Taira,
  • Yoshinori Ikenaka,
  • Jean-Marc Bonmatin,
  • Anton Safer

摘要

Neonicotinoid insecticides (neonicotinoids) are widely used in agriculture, forestry and public health in the world. Environmental exposure to neonicotinoids has been increasing due to their continuous uses. Neonicotinoids act as agonists, antagonists, or modulators of acetylcholine receptors and have adverse effects on non-target species, such as invertebrates, amphibians, reptiles, birds, microbes and mammals. Although there is concern about their adverse effects on ecosystem services and their potential effects on human health, their xenobiotic kinetics and dynamics in humans are not understood well. In this study, we determined a xenobiotic kinetic parameter, plasma protein bindings (PPBs) of 7 neonicotinoids and 18 metabolites with human plasma using a Rapid Equilibrium Dialysis (RED) device and liquid chromatography-tandem mass spectrometry (LC–MS/MS), and compared their PPBs with their physicochemical properties. 6-chloronicotinic acid (6-CNA) exhibited the highest PPB (86.4%), followed by imidacloprid-olefin (86.3%) in human plasma. Their PPBs are much higher than that of the parent compound, imidacloprid (27.5%). The PPBs of neonicotinoids and metabolites are not related to their lipophilicity determined by reversed-phase LC. The results shed light on the behavior of environmentally exposed neonicotinoids and metabolites and warrant further research on their xenobiotic kinetics and dynamics in humans.