Upper Midwest Environmental Sciences Center
Principal Investigator: Jeff Meinertz
The results from this study will provide the base for future human food safety studies that are required by the U.S. Food and Drug Administration to approve an immediate release fish sedative. These data will support the potential approval of an immediate release fish sedative that can be efficiently used by fishery managers throughout the U.S.
There is a critical need in U.S. public aquaculture and fishery management programs for the use of an immediate-release sedative, i.e. a compound that would safely and effectively sedate fish allowing for their release immediately after regaining normal swimming activity. An immediate-release sedative could be used during any field procedures involving the handling of fish (e.g. spawning and tagging). Such a sedative would have applications for nearly all freshwater fish species.
Currently, Finquel® (tricane methanesulphonate or MS-222) is the only fish sedative approved by the U.S. Food and Drug Administration (FDA). Use of this sedative is constrained by a 21-day withdrawal period meaning fish exposed to MS-222 cannot be made available for human consumption for at least 21 days. This restriction was established by the FDA because of a lack of mammalian toxicological information concerning MS-222 residues residing in the fillet tissue after an exposure. The 21-day withdrawal period was established to allow the MS-222 residues to deplete from the fish ensuring the fillet tissue could be safely consumed by humans. The data that would need to be developed to reduce the withdrawal time for MS-222 are cost prohibitive. Therefore, other sedatives are being pursued for FDA approval with the intent that one or more will be approved as an immediate-release sedative.
Aqui-S® 20E (active ingredient, eugenol; AQUI-S® New Zealand Ltd., Lower Hut, New Zealand) is being pursued for U.S. approval as an immediate-release sedative. As part of the approval process, a eugenol total residue depletion study is needed to characterize the depletion, distribution, and identity of eugenol residues in fillet tissue. Data from the total residue depletion study will be used to select a marker residue for eugenol. The marker will be the parent compound, metabolite, or combination of residues that persist in the skin-on fillet tissue for an appreciable period of time. After selecting the marker, depletion of the marker residue will be characterized allowing the FDA to establish a withdrawal time for eugenol ensuring all eugenol residues reach safe concentrations before fish become available for human consumption.
Because of the lack of information concerning eugenol depletion from freshwater fish, pivotal work will be conducted before this study to determine the exposure concentration and duration that will maximize eugenol residue concentrations in rainbow trout skin-on fillet tissue. Results from that work will be used to establish exposure parameters for this study. Additional pivotal work will be conducted before this study to determine the sample times that will adequately describe eugenol residue depletion. Results from that work will be used to establish sample times for this study.
The water temperature for the exposure and depuration phases of this study will be based on the results of Meinertz et al. (2006) where the fillet tissue concentrations of isoeugenol, a compound similar to eugenol, were determined in rainbow trout exposed to isoeugenol in 3 water temperatures, 7, 12, and 17°C. Although not significantly different than the isoeugenol concentrations in fillet tissue from fish exposed in water at 12°C, the greatest isoeugenol concentrations were found in the fillet tissue from fish exposed in water at 17°C. Therefore, the water temperature for the exposure and depuration phases of this study will be 17°C.
Characterize the residue profile and depletion of eugenol residues in the skin-on fillet tissue of rainbow trout after exposure to a formulation prepared with 14C-eugenol mimicking the commercially available AQUI-S® 20E.
Meinertz, J.R., S.L. Greseth, T.M. Schreier, J.A. Bernardy, and W.H. Gingerich. 2006. Isoeugenol concentrations in rainbow trout (Oncorhynchus mykiss) skin on fillet tissue after exposure to AQUI-S® at different temperatures, durations, and concentrations. Aquaculture 254: 347-354.