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In vitro metabolism of imidacloprid and acetamiprid in rainbow trout and rat
Citation:
Kolanczyk, R., M. Tapper, B. Sheedy, AND J. Serrano. In vitro metabolism of imidacloprid and acetamiprid in rainbow trout and rat. XENOBIOTICA. Taylor & Francis, Inc., Philadelphia, PA, 50(7):805-814, (2020). https://doi.org/10.1080/00498254.2019.1694197
Impact/Purpose:
This study addresses the environmental and health problem of chemical metabolism by biological organisms also referred to as biotransformation. Biotransformation is the changes or modifications a chemical may undergo when it is taken up from the environment by an organism such as a plant, insect, fish or mammal. An organism can modify the original parent chemical into a different chemicals called metabolites. These metabolites may have less, more, or the same toxicity as the parent chemical. Limited availability of fish metabolic pathways for pesticides results in risk assessments with inherent uncertainties based upon the parent chemical only or the assumption that the rat metabolism map data will serve as an adequate surrogate. The current work compared the production of metabolites in rainbow trout microsomal and liver slice model systems exposed to two neonicotinoid insecticides, imidacloprid and acetamiprid, with those of the rat microsomal system. The study provides an assessment of similarities and differences in metabolic products across species in an effort to reduce ecological risk assessment uncertainties.
Description:
After replacing pyrethroids, organophosphates, and carbamates, the neonicotinoids are now the most widely used insecticides in the world. Chemically, they are highly water soluble and stable in soil and water which allows for run-off through surface waters and thus potentially impacting aquatic species and environments. While highly toxic to aquatic invertebrates and insects, neonicotinoids are considered not acutely toxic to fish. Modification of neonicotinoid nitro or cyano groups through biotransformation has resulted in metabolites with greater affinity for nAChR and higher toxicity in mammals. While the mammalian metabolism of neonicotinoids has been studied extensively, there is a lack of understanding of their metabolism in fish species including potential bioactivation to more toxic metabolites acting through the nAChR. The current study constitutes the first report of the metabolism of imidacloprid and acetamiprid in rainbow trout. Formation of respective metabolites 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid was validated by analytical methods and demonstrated to be conserved across orders of biological organization in both microsomal and liver slice assays. Michaelis-Menten kinetics were determined for the microsomal conversion of imidacloprid to 5-hydroxy-imidacloprid in rainbow trout (Km=79.2 µM; Vmax=0.75 pmole/min/mg) and rat (Km=158.7 µM; Vmax=38.4 pmole/min/mg). Kinetics for the microsomal demethylation of acetamiprid to N-desmethyl-acetamiprid were determined in the rat (Km=70.9 µM; 4.10 pmoles/min/mg). N-desmethyl-acetamiprid was found in detectable but below quatifiable levels across the range of test concentrations which precluded a calculation of kinetic rate constants in rainbow trout (RBT). Ultimately, the formation of the metabolites 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid was conserved across RBT and rat species. The RBT liver slice assay was shown to increase metabolite production proportionally with an increase in the number of slices per well up to four.
