| Florfenicol, also known as Fluprofen, was developed by the United States’Company of Schering-Plough in1988. It was an animal-specific bacteriostatic antibiotics with a range of activity similar to that of chloramphenicol and thiamphenicol, including many gram-negative and gram-positive organisms. Due to its characteristics of broad-spectrum antimicrobial activity, good absorption, wide distribution in the body, no residue or low residue, not carrying the risk of inducing human aplastic anemia, it had been widely used in the prevention and cure against bacterial diseases in aquatic products such as fish and livestock and poultry such as cattle, pigs, chickens and so on since it originally saled on the market of Japan in1990. In1999, Chinese government approved it to be a new national second-class veterinary drug used for the prevention and treatment of pigs, cattle, poultry and other animals against bacterial diseases. The currently and commonly used its formulations are premix agent, injection, soluble powder, drinking agent etc. As so far, there has been rarely reported literatures about toxicity of suspension emulsion injection of florfenicol, and little papers related to the residue of florfenicol and florfenicol amine in pigs has been reported at home and abroad. This paper aims to provide a theoretical basis for the clinical use of suspension emulsion injection of florfenicol, estimate its withdrawal time simultaneously in pigs.1Study on the toxicity of suspension emulsion injection of florfenicolThis experiment was designed to investigate acute toxicity, accumulative toxicity, sub-chronic toxicity, mutagenic toxicity and teratogenic toxicity of suspension emulsion injection of florfenicol. Using modified Karber method to detect its acute toxic effect, finally get the data of median lethal dose (LD50) and the dose-mortality curve. Dose escalation method was used for detecting its accumulative toxic effect in mice, and tolerance test would be done soon after the accumulative toxic experiment being completed. With the high, medium and low-dose groups being set, added with the control groups of organic solvent and physiological saline, the mice were injected with suspension emulsion injection of florfenicol consecutively for28days to evaluate the sub-chronic toxicity. The results revealed that:the oral LD50on the mice was greater than5000mg-kg-1. According to the toxicity grading standards of exogenous chemicals, this agent was actually non-toxic drug. Its LD50of intraperitoneal injection on the mice was3140mg·kg-1, the95%confidence interval was2930～3370mg-kg-1. No mouse was killed during the period of accumulative toxicity test, and the accumulation coefficient K was greater than5, which showed that florfenicol accumulation in the mice was mild. Tolerance test showed that the test group of mice had produced a certain tolerance to florfenicol. Sub-chronic toxicity test showed that:the high-dose group of mice exposed some mild symptoms of poisoning such as erecting tail, scratching their noses, mild excitement and startle and so on. And its weight gain was slow, which was different from the situation of other groups. No mouse died during the trial period. Blood routine detection and blood biochemical test results show that:suspension injection of florfenicol had a certain impact on mice’s blood count and their function of liver and kidney on this experimental condition. In addition, the pathological histology results showed that:mice of high-dose group exposed inflammatory response in liver and kidney, while the other groups had no significant pathological abnormalities. Mouse sperm deformity and bone marrow micronucleus tests’results were all negative, which indicated that suspension emulsion injection of florfenicol was non-mutagenic toxic to mice. The results of teratogenic experiment to SD rats showed that suspension emulsion injection of florfenicol had a certain teratogenic toxicity under the condition of this experiment. As reported above, suspension emulsion injection of florfenicol is low toxicity in clinical application with a wide range of safety.2Preliminary study on residue determination of florfenicol and florfenicol amine in PigsThe method of high performance liquid chromatography (HPLC) was established to detect the florfenicol and its main metabolism, florfenicol amine residues in pigs. Pigs were intramuscular injected with20%suspension injection of florfenicol with the single-dose of20mg·kg-1·bw-1on its position of quadriceps femoris muscle. Pigs were killed twice per different time point for sampling follow the scheduled time point of1,2,3,5,9,14,20,25 d after administration. Incise pigs’vena cava to bleeding out to death, then quickly collect their livers, kidneys, lungs, muscles, skin&fat and so on. Sample tissues followed the treatment procedure of homogenate, extraction, concentration, decontamination, organic membrane filtration, and finally detected by chromatography. The result revealed that:the method was proved to be linear in the range of10～1000μg·kg-1and linear regression coefficient was greater than0.99, the lowest detection limit was10μg·kg-1. Florfenicol and florfenicol amine were added to blank tissues respectively follow the dose levels of high, medium and low (500,100,20μg·kg-1), recoveries measured in muscle, liver, kidney, lung, skin&fat were greater than75%, RSD%of daytime and RSD%between different days(n=3) were all less than10%. Research findings of residue elimination showed that: florfenicol and florfenicol amine widely distributed in animal tissues. The liver was the highest in distribution, followed by kidney and lung, skin&fat content was also higher, muscle’s distribution is the lowest. Florfenicol and florfenicl amine rapidly eliminated in the first5days after single-dose intramuscular injection to pigs. In the next6-14days, elimination rates were significantly lower than before. Both florfenicol and florfenicol amine residue could not be detected at the25th day. The elimination residual curve showed that the florfenicol and florfenicol amine eliminated fast in pigs, with low residue. According to the European Union’s MRLS, Chinese MRLS and test results, it was proposed14days of off-drug period in pigs after pig intramuscular injection of20%of suspension injection of florfenicol. |
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