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Metabolism of diazinon in rainbow trout liver slices
Citation:
Tapper, M., J. Serrano, P. Schmieder, D. Hammermeister, AND Rick Kolanczyk. Metabolism of diazinon in rainbow trout liver slices. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, 4(1):13-23, (2018).
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. The current work evaluated the rainbow trout liver slice model system as a tool to study metabolism in an aquatic species, with the long-range goal of using this model to gain sufficient understanding of fish metabolic transformation reactions to be able to accurately predict fish metabolism. Previous biotransformation work has focused on subcellular in vitro studies which have the advantage of high throughput but may have limited metabolic capabilities, and whole organism in vivo studies which have full metabolic capacity but are low throughput. The liver slice model has the advantages of high throughput and robust metabolic capabilities. The chemical pesticide diazinon, which has been previously tested in a number of mammalian and aquatic species was used to evaluate the slice model. Like the results of previous in vitro and in vivo studies, the results from the slice model indicate the main diazinon metabolite was hydroxypyrimidine.Therefore, the rainbow trout liver slice model is a useful tool for the study of metabolism in aquatic species and can be used to produce a database of fish metabolic transformation reactions. Information generated by such a database would be of value to inform toxicological risk assessors where a metabolite may be equally toxic, or more toxic, than the parent chemical form.
Description:
Understanding biotransformation pathways in aquatic species is an integral part of ecological risk assessment with respect to the potential bioactivation of chemicals to more toxic metabolites. The long-range goal is to gain sufficient understanding of fish metabolic transformation reactions to be able to accurately predict fish xenobiotic metabolism. While some metabolism data exist, there are relatively few fish in vivo exposure studies where metabolites have been identified and the metabolic pathways proposed. Previous biotransformation work has focused on in vitro studies which have the advantage of high throughput but may have limited metabolic capabilities, and in vivo studies which have full metabolic capacity but are low throughput. Therefore, an aquatic model system in which a large number of chemicals could be tested would be a valuable tool. The current study evaluated the ex vivo rainbow trout liver slice model, which has the advantages of high throughput as found in vitro models and non-dedifferentiated cells and cell to cell communication found in in vivo systems. The pesticide diazinon, which has been previously tested both in vitro and in vivo in a number of mammalian and aquatic species including rainbow trout, was used to evaluate the ex vivo slice model as a tool to study biotransformation pathways. While somewhat limited by the analytical chemistry method employed, the results of slice model chiefly that hydroxypyrimidine was the major diazinon metabolite are in line with the results of previous rainbow trout in vivo studies. Therefore, the rainbow trout liver slice model is a useful tool for the study of metabolism in aquatic species.
