Fish Physiology and Biochemistry 21: 173–178, 1999. © 1999 Kluwer Academic Publishers. Printed in the Netherlands. 173 Effect of ethanol, clofibric acid and temperature on the uptake and elimination of 2-methylisoborneol in channel catfish (Ictalurus punctatus) D. Schlenk, E. J. Perkins and W. B. Hawkins Department of Pharmacology, University of Mississippi, University, MS 38677; USA; Vanderbilt University Medical Center Center for Clinical Toxicology Nashville, TN 37232-4632, USA; (Phone: 601-232-5150; Fax: 601-232-5148; E-mail: dschlenk@olemiss.edu) Accepted: February 2, 1999 Key words: catfish, clofibric acid, cytochrome P450, ethanol, MIB, off-flavor, organoleptic Abstract Off-flavor, due to organoleptic compounds such as 2-methylisoborneol (MIB), is the single largest detriment to the harvest, production and profit from the channel catfish aquaculture industry of the Southeastern United States. Methods to increase the metabolism and/or elimination of compounds like MIB would provide a means towards improving catfish rearing practices. Previous studies indicated one or more forms of cytochrome P450 monooxy- genase (CYP) may be involved in the biotransformation and elimination of specific organoleptic compounds, such as 2-methylisoborneol (MIB). In order to determine the role of CYP in the elimination of MIB, various compounds that have been shown to modulate cytochrome P450 expression in catfish were administered before and after exposure to 14 C-MIB. Uptake and elimination was monitored in fish over 24 and 48 h, respectively. Pretreatment with clofibric acid (100 mg kg −1 -gavage) which induces a CYP2K-like isoform, and ethanol (1.0% v/v-aqueous) a CYP2 represser, alone and with enhanced temperature (added 10 ◦ C) failed to affect uptake of MIB. Pretreatment with these compounds and conditions also failed to enhance elimination of MIB from channel catfish. However, when fish were treated with 1.0% ethanol after MIB exposure (i.e., during depuration), beta elimination halflives were changed from 144 ± 35 to 71 ± 13 h. in sexually mature animals but unchanged (191 ± 113) in juveniles. The failure of CYP-modulating agents to alter MIB elimination in catfish suggests MIB may not readily undergo Phase I oxidation via CYP. The enhanced elimination of MIB in adults by ethanol warrants further study as to its potential use in aquaculture in purging MIB and related compounds prior to fish processing. Introduction 2-Methylisoborneol (MIB) is one of several causative agents responsible for the occurrence of ‘off-flavor’ in various cultured fish species (Martin et al. 1988). Off-flavored channel catfish have been shown to an- nually account for hundreds of millions of dollars in lost revenue in the Southeastern United States (Kin- nucan et al. 1988). Compounds such as MIB are produced by numerous microorganisms that co-inhabit culture ponds (Lorio et al. 1992; Lovell et al. 1986). Since attempts to control microbial MIB production have been largely unsuccessful, several groups have suggested the possibility of placing tainted catfish in holding facilities with clean water prior to processing in an attempt to purge organoleptic compounds from the fish (Johnsen and Dionigi 1994). However, elim- ination half-lives (β ) for MIB have been estimated to vary between 3 and 147 hours for individual catfish (Martin et al. 1990; Johnsen and Lloyd 1992; Johnsen and Dionigi 1994; Johnsen et al. 1996; Perkins and Schlenk 1997). Although some correlations have been observed with fat content and temperature, factors that influence elimination of MIB and other naturally pro- duced organic chemicals in fish are largely unknown (Johnsen and Lloyd 1992; Johnsen et al. 1996). Biotransformation has been shown to significantly influence elimination of many organic compounds (Parkinson 1996). Although it is unknown whether MIB is metabolized in fish, earlier studies in chan-