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In vitro metabolism assessment of thiacloprid in rainbow trout and rat by LC-UV and high resolution-mass spectrometry
Citation:
Serrano, J., R. Kolanczyk, B. Blackwell, B. Sheedy, AND M. Tapper. In vitro metabolism assessment of thiacloprid in rainbow trout and rat by LC-UV and high resolution-mass spectrometry. XENOBIOTICA. Taylor & Francis, Inc., Philadelphia, PA, 51(5):536-548, (2021). https://doi.org/10.1080/00498254.2020.1840658
Impact/Purpose:
Metabolism mechanistic information obtained for the model chemicals THI, IMI and ACE will contribute to improve understanding of interspecies homology and comparative toxicity, advance methods for species extrapolation, and provide a platform for alternative in vitro/ex vivo methods to animal testing.
Description:
1. Thiacloprid (THI) is a neonicotinoid insecticide of interest to the USEPA due to its low absorption by crops, greater distribution into the surrounding areas, and potential for adverse effect to terrestrial and aquatic organisms. 2. Prior to this report, there was very limited information addressing the ex vivo metabolism of THI by fish species and the metabolic pathways regulating its potential adverse effects. 3. The in vitro and ex vivo biotransformation pathway of THI is defined by the formation of three primary metabolites (TM1, TM2 and TM3) via separate paths differentiated by reductive decyanation, reductive dechlorination with hydration and dealkylation processes, respectively. 4. Kinetic rates were calculated for the rat microsomal decyanation of THI into TM1 (Km=299.2 µM and Vmax=5.3 pmol/min/mg), and for the dealkylation of THI into TM3 (Km=368.9 µM µM and Vmax=3.95 pmol/min/mg). 5. Formation confirmation and identity inference of THI metabolites in absence of standards was achieved by LC-UV and High Resolution-MS strategies. 6. It was concluded that the in vitro and ex vivo metabolic products of THI are conserved both across species (rat and RBT) and levels of biological organization (microsomes and liver slices), as previously reported for the neonicotinoid insecticides Imidacloprid and Acetamiprid.
URLs/Downloads:
DOI: In vitro metabolism assessment of thiacloprid in rainbow trout and rat by LC-UV and high resolution-mass spectrometry