TM-100, a feed premix containing the broad spectrum antibacterial agent 
oxytetracycline at a concentration of 220 g oxytetracycline/kg, is being 
developed for use to control columnaris in cool- and warmwater fish caused by 
Flavobacterium columnaris. The study objective was to determine the safety of 
TM-100F, administered in feed to walleye Stizostedion vitreum (WAE), hybrid 
striped bass Morone saxatilis x M. chrysops (HSB), and yellow perch Perca 
flavescens (YEP) at doses of 0 (control), 82.5, 248, or 413 mg/kg body weight 
(BW)/day (corresponding to 0, 1, 3, and 5X the recommended dose rate of 82.5 
mg/kg BW/day) for 10 (HSB and YEP) or 20 consecutive days (WAE; twice the 
recommended treatment duration of 10 days of dosing). The study design was a 
randomized-block with three tanks of 15 (WAE), 10 (HSB), or 13 (YEP) fish per 
tank assigned to each dose level. There was one tank of each dose level within 
each treatment block for a total of four tanks per block. The study was 
conducted at 20+2 °C (WAE and YEP) or 27+2?C (HSB). The parameters evaluated in 
this study included mortality, appetite, fish behavior, growth, gross pathology, 
and histopathology on selected tissues.
The oxytetracycline feed concentrations were between 91 and 99% of the target 
concentrations (99% at 1X, 94% at 3X, and 91% at 5X the target concentrations). 
The overall mean estimated doses offered to walleye were 100, 298, or 493 mg/kg 
BW/day and were between 111 to 132% of the nominal dose. The overall mean 
estimated doses offered to hybrid striped bass were 94, 269, or 433 mg/kg BW/day 
and were between 102 to 118% of the nominal dose. The overall mean estimated 
doses offered to yellow perch were 94, 269, or 433 mg/kg BW/day and were between 
102 to 117% of the nominal dose. 
The observed oxytetracycline-related changes were limited to the growth and 
histopathology data. Growth of hybrid striped bass offered a nominal dose of 413 
mg/kg BW/day were significantly smaller than untreated controls at the terminal 
sampling. Significant growth related effects associated with oxytetracycline 
therapy were not observed in other hybrid striped bass dosed at either 82.5 or 
248 mg/kg BW/day or in walleye or yellow perch at any dose level. Although not 
significant, walleye terminal fish weight appeared to inversely related to the 
TM-100F dose level.
Oxytetracycline-related histopathology findings were limited to walleye. A 
histomorphologically evident, statistically significant, increase in the 
incidence and severity of minimally decreased hematopoietic/lymphopoietic tissue 
was observed in the anterior kidneys of walleye. This finding was only 
statistically significant for walleye in the high dose group (413 mg/kg BW/day), 
although a non-significant dose-dependent trend existed in the data. There was 
no overt histopathological evidence of cell death, such as karyorrhexis, that 
would be expected if the reductions were due to cell death. Statistically 
significant, treatment-related histopathological findings observed in walleye 
also included diffuse gill filament epithelial hyperplasia and the decreased 
prevalence of eosinophilic droplets within the renal tubular epithelium. 
Although statistically significant, the actual biological significance of these 
changes associated with oxytetracycline therapy is unclear.
The only mortality recorded during the study was not attributed to 
oxytetracycline therapy and there were no signs of morbidity observed in any 
fish tested over the course of the study. No clinically observable changes were 
detected in fish behavior among the treated fish relative to the controls.