Residual Distribution And Metabolic Of Tilmicosin In Aquaculture Water And Crucian Carp Tissue

China is a big country of aquaculture production.In 2020,aquaculture production of our country reached 65.54 million tons,.In order to avoid the invasion of bacteria and other pathogenic microorganisms,fishery antibacterial drugs for aquaculture were used in various processes of aquaculture.However,the improper use of fishery antibacterial drugs caused safety incidents of aquatic products,which resulted in the influence for aquatic product trade of our country.Some researches have reported that tilmicosin and its derivatives were used in the treatment and prevention of aquatic animal diseases and growth promotion of aquatic animals.And some research results showed that tilmicosin was added as bactericidal and topical disinfectant in aquaculture medicine,among which the highest detection concentration was 1030 mg/L and the detection rate was 5.9%.Therefore,the comparative analysis of tilmicosin MRL standards between China and maj or trading countries,regions and organizations and the study for tilmicosin residual distribution and metabolism reduction rule in aquatic animals possess great significance for ensuring the aquatic products quality and safety of our country and improving their trade competitiveness.The objectives of this study were to further ascertain the control measures of fishery antibacterial drugs in China and major aquatic product trading countries,improved the maximum residue limit(MRL)standards system of fishery antibacterial drugs in Chinese aquatic products,enhanced the normative use of fishery antibacterial drugs,and improved the quality and safety of Chinese aquatic products and their international competitiveness.This paper performed the study for residual distribution and metabolism reduction rule of tilmicosin in aquaculture water and crucian carp tissues,and carried out the analysis for the pharmacokinetic parameters using DAS 2.0 pharmacokinetic software.Besides,this paper compared the current management status for MRL standards of fishery antibacterial drugs in aquatic products of China and maj or trading countries and organizations including Japan,USA,European Union(EU)and Codex Alimentarius Commission(CAC).Main research results are as follows:1.The residue concentration of tilmicosin in all aquaculture water samples reached the highest values on the 12th day,and then showed an overall downward trend.The tilmicosin was detected the highest residues in kidney of crucian carp,followed by gill and liver.It was not detected in muscle and blood of crucian carp.After exposure experiments,the tilmicosin residues all reached the highest values in gill,liver and kidney of crucian carp on the 8th day,indicating that tilmicosin was continuously absorbed and enriched in crucian carp tissues at the early stage of drug delivery.2.The pharmacokinetic characteristics of tilmicosin in crucian carp gill were consistent with the first-order absorption and one-compartment open model,while the tilmicosin pharmacokinetic characteristics in liver and kidney were consistent with the first-order absorption and two-compartment open model,along with short half-life and fast elimination rate.The kidney is the main organ for tilmicosin metabolism aimed at crucian carp,and the crucian carp liver presented the slowest metabolic rate for tilmicosin.The area under the curve(AUC)of drug concentration in gill,liver and kidney were 0.18,0.97,11.12(mg-d)/L and 1.91,6.85,58.44(mg-d)/L,respectively.The maximum drug concentrations(Cmax)were 0.09,0.54,6.78 mg/L and 0.50,1.57,19.61 mg/L,respectively.The elimination half-lives were 0.51,1.88,1.24 d and 1.25,1.33,0.99 d,respectively.3.Differences were existed in quantities,limit values and drug species for MRL standards of fishery antibacterial drugs in aquatic products between China and major trading countries including Japan,USA and EU.Japan developed the most MRL standards for fishery antibacterial drugs with 31 items,followed by EU(26 items)and China(22 items),while CAC and USA established the least MRLs for fishery antibacterial drugs with only 5 items.The residue limit system of fishery antibacterial drugs in China is most similar to that of EU,which set the residue limits for different species and different tissues of food animals.At present,only Japan has set the MRL aimed at tilmicosin as 0.05 mg/kg in skin muscle of natural proportion for aquatic products.