Aquaflor, a feed premix containing the broad spectrum antibacterial agent florfenicol (50% w/w), is being developed for use to control enteric septicemia (ESC) in channel catfish Ictalurus punctatus caused by the gram-negative enterobacterium Edwardsiella ictaluri. The recommended dose of Aquaflor to control ESC is 10 mg/kg body weight (BW)/day for 10 days. The study objective was to determine the safety of Aquaflor administered in feed to channel catfish at doses of 0 (control), 10, 30, and 50 mg/kg BW/day for 20 consecutive days. Parameters evaluated included daily mortality, behavioral (appetite, distribution, flight/fright response), and water chemistry observations, initial and terminal weight measurements, and gross and microscopic pathology. Medicated feed consumption was 67—86% of target with group mean doses of 8.5 mg/kg BW/day, 24.6 mg/kg BW/day, and 34.9 mg/kg BW/day. There were no mortalities or clinically observable changes noted at any of the dose levels tested. Aquaflor-related changes were limited to the food consumption and histopathology data. Although Aquaflor-related decreased feed consumption was noted in the 30 and 50 mg/kg BW/day groups, there were no differences in fish growth among the treatment groups. Aquaflor-related histopathology findings were limited to a histomorphologically evident dose-dependent decrease in hematopoietic/lymphopoietic tissue in the anterior kidneys, posterior kidneys, and spleens of channel catfish.
Abou-Kahil S. , Abou-Kahil WH, Whitney PL, Yunis AA (1987). Importance of the mitochondrial amino acid pool in the sensitivity of erythroid cells to chloramphenicol: role of glycine and serine. Pharmacology35: 308—316.
2.
AOAC (Association of Official Analytical Chemists) (1998). In: Official Methods of Analysis of AOAC International . 16th edn, 5th revision, Cunniff P (ed). Author, Gaithersburg, Maryland.
3.
APHA (American Public Health Association, American Water Works Association, and Water Environment Federation) (1995). Standard Methods for the Examination of Water and Wastewater. 19th edn. APHA, Washington, DC.
4.
Baxa DV, Hedrick RP (1989). Two more species are susceptible to experimental infections with Edwardsiella ictaluri. Fish Health Section/American Fisheries SocietyNewsletter. 17: 4.
5.
Burns KF, Timmons EH, Poiley SM (1971). Serum chemistry and hematological values for axenic (germfree) and environmentally associated inbred rats. Lab Anim Sci24: 415—419.
6.
Cannon M., Harford S., Davies J. (1990). A comparative study on the inhibitory actions of chloramphenicol, thiamphenicol and some fluorinated derivatives. J Antimicrob Chemother26: 307—317.
7.
Close B. (Chair), Banister K. , Baumans V., Bernoth E., Bromage N., Bunyan J., Erhardt W., Flecknell P., Gregory N., Hackbarth H., Morton D., Warwick C. (1996). Recommendations for euthanasia of experimental animals: part 1. Lab Anim30: 293—316.
8.
Close B. (Chair), Banister K. , Baumans V., Bernoth E., Bromage N., Bunyan J., Erhardt W., Flecknell P., Gregory N., Hackbarth H., Morton D., Warwick C. (1997). Recommendations for euthanasia of experimental animals: part 2. Lab Anim31: 1—32.
9.
Ferrari V., Pajola E. (1981). Types of haemopoeitic inhibition by chloramphenicol and thiamphenicol. In: Safety Problems Related to Chloramphenicol and Thiamphenicol Therapy, Najean Y, Tognoni G, Yunis AA (eds). Raven Press, New York, pp 43—59.
10.
Fukui H., Fujihara Y., Kano T. ( 1987). In vitro and in vivo antibacterial activities of florfenicol, a new fluorinated analog of thiamphenicol, against fish pathogens. Fish Pathol22(4): 201—207.
11.
Grizzle JM, Rogers WA (1976). Anatomy and histology of the channel catfish. Auburn University Agricultural Experiment Station, Auburn, AL, USA, pp 29—30.
12.
Grondel JL, Nouws JFM, van Muiswinkel WW (1987a). The influence of antibiotics on the immune system: immuno-pharmokinetic investigations on the primary anti-SRBC response in carp, Cyprinus carpio L., after oxytetracycline injection. J Fish Dis10: 35—43.
13.
Grondel JL, Nouws JFM, De Jong M., Schutte AR, Driessens F. (1987b). Pharmacokinetics and tissue distribution of oxytetracycline in carp, Cyprinus carpio L., following different routes of administration . J Fish Dis10: 153—163.
14.
Hashimoto M. , Hashimoto N. (1968). Histological study of bone marrow in breeding rats. In: Advances in Germfree Research and Gnotobiology, Miyakawa M, Luckey TD (eds). CRC Press, Cleveland , pp 149—161.
15.
Horsberg TB , Martinsen B., Varma KJ (1994). The disposition of 14C-florfenicol in Atlantic salmon (Salmo salar). Aquaculture122: 97— 106.
16.
Iijima S., Yamane T. (1968). The spleen of animals germfree. In: Advances in Germfree Research and Gnotobiology, Miyakawa M, Luckey TD (eds). CRC Press, Cleveland, pp 139—148.
17.
Inglis V., Richards RH, Varma KJ, Sutherland IH, Brokken ES (1991). Florfenicol in Atlantic salmon, Salmo salar L, parr: tolerance and assessment of efficacy against furunculosis. J Fish Dis14: 343—351.
18.
Keiser G., Buchegger U. (1973). Hematological side effects of chloramphenicol and thiamphenicol. Helvetica Medica Acta37: 365—278.
19.
Klausen B., Hougen HP (1987). Quantitative studies of lymphoid organs, blood and lymph in inbred athymic and euthymic LEW rats under germfree and specific-pathogen-free conditions. Lab Anim21: 342—347.
20.
Lunden T., Bylund G. (2000). The influence of in vitro and in vivo exposure to antibiotics on mitogen-induced proliferation of lymphoid cells in rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immunol10: 395—404.
21.
Lunden T., Miettinen S., Lönnström L-G., Lilius E-M., Bylund G. (1998). Influence of oxytetracycline and oxolinic acid on the immune response of rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immunol8: 217—230.
22.
Lunden T., Miettinen S., Lönnström L-G., Lilius E-M., Bylund G. (1999). Effect of florfenicol on the immune response of rainbow trout (Oncorhynchus mykiss). Vet Immunol Immunopathol8: 217—230.
23.
Nagabhushan T., Miller GH, Varma KJ (1992). Chloramphenicol and Analogues. In: Offprints from Kirk-Othmer: Encyclopedia of Chemical Technology, 4th edn, vol 2. John Wiley and Sons, Inc, New York, pp 961— 978.
24.
Penny RHC , Watson ADJ , Moyle GG (1973). Observations of the effects of chloramphenicol and starvation on the haemopoietic system of the dog. Clin Toxicol6: 229—246.
25.
Plumb JA, Sanchez DJ (1983). Susceptibility of five species of fish to Edwardsiella ictaluri. J Fish Dis6: 261—266.
26.
Rijkers GT, Teunissen AG, Van Oosterom R., van Muiswinkel WB (1980). The immune system of cyprinid fish. The immunosuppressive effect of the antibiotic oxytetracycline in carp (Cyprinus carpio L.). Aquaculture19: 177—189.
27.
SAS Institute Inc (1997). SAS/STAT Software: Changes and enhancements through release 6.12. SAS Institute Inc, Cary, NC.
28.
Shapiro SS, Wilk MB ( 1965). An analysis of variance test for normality (complete samples). Biometrika52: 591—611.
Schering-Plough Research Institute (SPRI) ( 2001). Method transfer report—florfenicol in fish feed; procedure 025298-123A-007-01. Lafayette, NJ.
31.
Sieroslawska AM, Studnicka AK, Siwicki A., Bownik A., Rymuszka A., Slonka J. (1998). Antibiotics and cell-mediated immunity in fish—in vitro study. Acta Vet Brno67: 329—334.
32.
Tucker CS, Robinson EH (1990). Channel catfish farming handbook. Van Nostrand Reinhold, New York.
33.
Uno Y., Sumi Y., Sakura K. (1968). Studies on the thymus of germfree rats. In: Advances in Germfree Research and Gnotobiology, Miyakawa M, Luckey TD (eds). CRC Press, Cleveland , pp 129—137.
34.
US Food and Drug Administration. (1991). Good Laboratory Practices for Nonclinical Laboratory Studies. Food and Drug Administration, 21 Code of Federal Registration Part 58, USFDA, Washington, DC.
