Affiliation:
1. United States Environmental Protection Agency, Office of Research and Development, Center for Computational Toxicology and Exposure, Great Lakes Toxicology and Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, USA
2. National Research Council, 6201 Congdon Boulevard, Duluth, MN 55804, USA
Abstract
The in vitro biotransformation of phenol at 11 °C was studied using pre-spawn adult rainbow (Oncorhynchus mykiss) (RBT), brook (Salvelinus fontinalis) (BKT), and lake trout (Salvelinus namaycush) (LKT) hepatic microsomal preparations. The incubations were optimized for time, cofactor concentration, pH, and microsomal protein concentration. Formation of Phase I ring-hydroxylation and Phase II glucuronidation metabolites was quantified using HPLC with dual-channel electrochemical and UV detection. The biotransformation of phenol over a range of substrate concentrations (1 to 180 mM) was quantified, and the Michaelis–Menten kinetics constants, Km and Vmax, for the formation of hydroquinone (HQ), catechol (CAT), and phenylglucuronide (PG) were calculated. Species differences were noted in the Km values for Phase I enzyme production of HQ and CAT, with the following rank order of apparent enzyme affinity for substrate: RBT > BKT = LKT. However, no apparent differences in the Km for Phase II metabolism of phenol to PG were detected. Conversely, while there were no apparent differences in Vmax between species for HQ or CAT formation, the apparent maximum capacity for PG formation was significantly less in LKT than that observed for RBT and BKT. These experiments provide a means to quantify metabolic activation and deactivation of xenobiotics in fish, to compare activation and deactivation reactions across species, and to act as a guide for future predictions of new chemical biotransformation pathways and rates in fish. These experiments provided the necessary rate and capacity (Km and Vmax) inputs that are required to parameterize a fish physiologically based toxicokinetic (PB-TK) model for a reactive chemical that is readily biotransformed, such as phenol. In the future, an extensive database of these rate and capacity parameters on important fish species for selected chemical structures will be needed to allow the effective use of predictive models for reactive, biotransformation chemicals in aquatic toxicology and environmental risk assessment.
Reference56 articles.
1. Sijm, D., de Bruijn, J., de Voogt, P., and de Wolf, W. (May, January 28). Biotransformation in environmental risk assessment. Proceedings of the SETAC-Europe Workshop, Noordwijkerhout, The Netherlands.
2. A physiologically based toxicokinetic model for the uptake and disposition of waterborne organic chemicals in fish;Nichols;Toxicol. Appl. Pharmacol.,1990
3. Physiologically based toxicokinetic modeling of three chlorinated ethanes in rainbow trout (Oncorhynchus mykiss);Nichols;Toxicol. Appl. Pharmacol.,1991
4. A physiologically based toxicokinetic model for three waterborne chloroethanes in the channel catfish (Ictaturus punctatus);Nichols;Aquat. Toxicol.,1993
5. Modeling the accumulation of three waterborne chlorinated ethanes in fathead minnows (Pimephales promelas): A physiologically based approach;Lien;Environ. Toxicol. Chem.,1994
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献