title: How Biotransformation Influences Toxicokinetics of Azole Fungicides in the Aquatic Invertebrate Gammarus pulex.
abstract: Biotransformation is a key process that can greatly influence the bioaccumulation potential and toxicity of organic compounds. In this study, biotransformation of seven frequently used azole fungicides (triazoles: cyproconazole, epoxiconazole, fluconazole, propiconazole, tebuconazole and imidazoles: ketoconazole, prochloraz) was investigated in the aquatic invertebrate Gammarus pulex in a 24 h exposure experiment. Additionally, temporal trends of the whole body internal concentrations of epoxiconazole, prochloraz, and their respective biotransformation products (BTPs) were studied to gain insight into toxicokinetic processes such as uptake, elimination and biotransformation. By the use of high resolution tandem mass spectrometry in total 37 BTPs were identified. Between one (ketoconazole) and six (epoxiconazole) BTPs were identified per parent compound except for prochloraz, which showed extensive biotransformation reactions with 18 BTPs detected that were mainly formed through ring cleavage or ring loss. In general, most BTPs were formed by oxidation and conjugation reactions. Ring loss or ring cleavage was only observed for the imidazoles as expected from the general mechanism of oxidative ring openings of imidazoles, likely affecting the bioactivity of these BTPs. Overall, internal concentrations of BTPs were up to 3 orders of magnitude lower than that of the corresponding parent compound. Thus, biotransformation did not dominate toxicokinetics and only played a minor role in elimination of the respective parent compound, with the exception of prochloraz.
authors.affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology , 8600 Dübendorf, Switzerland.|Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , 8092 Zürich, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rösch
authors.affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology , 8600 Dübendorf, Switzerland.|Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , 8092 Zürich, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Anliker
authors.affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology , 8600 Dübendorf, Switzerland.|Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , 8092 Zürich, Switzerland.
authors.forename: Juliane
authors.initials: J
authors.lastname: Hollender
mesh_terms: D033304:Amphipoda; D000818:Animals; D001393:Azoles; D001711:Biotransformation; D005659:Fungicides, Industrial / Q000633:toxicity*; D066007:Toxicokinetics
chemical_list: D001393:Azoles; D005659:Fungicides, Industrial