Residue Depletion Profile and Estimation of Withdrawal Period for Sulfadimethoxine and Ormetoprim in Edible Tissues of Nile Tilapia (Oreochromis sp.) on Medicated Feed.

Sulfadimethoxine (SDM) and ormetoprim (OMP) are antimicrobials used in combination to treat bacterial infections in fish farming. The use of this drug combination is not yet regulated in some countries, such as Brazil. Due to the lack of regulated drugs for aquaculture in Brazil, this study investigated the residue depletion profile of SDM and OMP in Nile tilapia (Oreochromis sp.) after oral administration. Fish were treated with medicated feed containing a 5:1 ratio of SDM:OMP at the dose of 50 mg kg BW-1 for five consecutive days with an average water temperature of 28 °C. The drugs were incorporated into the feed by using a gelatin coating process which promoted homogeneity in drug concentration and prevented the drug leaching into the water during medication. The SDM and OMP determination in fish fillets (muscle plus skin in natural proportions) was performed using the QuEChERS approach followed by LC-MS/MS quantification. The analytical method was validated according to Brazilian and selected international guidelines. A withdrawal period of 9 days (or 252 °C days) was estimated for the sum of SDM and OMP residues at concentration levels below the maximum residue level of 100 µg kg-1.

Exposure of tilapia (Oreochromis niloticus) to the antibiotic florfenicol in water: determination of the bioconcentration factor and the withdrawal period.

The demand for healthier foods with high nutritional value has resulted in intensive fish farming. In this production system, high-frequency infections occur, and antibiotics are administrated for control. Only two antibiotics are allowed for use in Brazilian aquaculture, one of which is florfenicol. In this work, a bioconcentration assay was performed to assess the accumulation of florfenicol in the muscle of Nile tilapia (Oreochromis niloticus). Tilapia was evaluated as it is the most produced fish species in Brazil. The fish were exposed to florfenicol at a nominal concentration of 10 mg/L, through the water. Muscle and water were collected at 0, 1.5, 3, 6, 24, and 48 h during the exposure phase and at 1.5, 3, 6, 24, 48, and 120 h during the depuration phase. Quantification was performed using an LC-MS/MS. The results showed rapid absorption and elimination of the antibiotic (half-life, t1/2 = 5 h), with low potential for accumulation of florfenicol in tilapia muscles. The study was performed to determine the bioconcentration factor (BCF) and withdrawal period of florfenicol, being 0.05 mL/µg and 1.8 h, respectively. The results contribute to set protocols for the safe use of florfenicol in tilapia transport, avoiding residues in fish that may pose risks to human health.

The effect of breed, sex, and drug concentration on the pharmacokinetic profile of ivermectin in cattle.

Ivermectin (IVM) is one of the most widely used antiparasitic drugs worldwide and has become the drug of choice for anthelmintic and tick treatment in beef cattle production. It is known that pharmacokinetic parameters are fundamental to the rational use of a drug and food safety and these parameters are influenced by different factors. The aim of this study was to evaluate the pharmacokinetic profile of IVM in Bos indicus, Bos taurus, and crossbreed cattle (B. indicus × B. taurus) kept under same field conditions and the possible impacts of sex and IVM formulation (1% and 3.15%). It was observed that IVM concentration was significantly affected by breed. The plasma concentrations of IVM, AUC, Cmax , and t1/2ß were significantly higher in B. indicus compared to B. taurus. Crossbreed animals showed an intermediate profile between European and Indian cattle. No alteration in pharmacokinetics parameters was detected when comparing different gender. Concerning the pharmacokinetic data of IVM formulation, it was verified that Tmax , AUC, and t1/2ß were higher in 3.15% IVM animals than those from 1% IVM formulation. The results clearly indicated that the IVM plasma concentrations in B. indicus were higher than that in B. taurus.

Pharmacokinetics and tissue disposition of enrofloxacin in rainbow trout after different routes of administration.

Plasma pharmacokinetics (PK) and tissue disposition of enrofloxacin (EFX) was studied in rainbow trout (Oncorhynchus mykiss) after a single oral administration of 10 mg/kg, and by immersion baths of 20 ppm during 2.5 h and 100 ppm during 0.5 h, at water temperature of 16.3 ± 0.3 °C.Concentrations of EFX in plasma and tissues (skin, muscle, liver, kidney and gut) were determined using high performance liquid chromatography (HPLC) with fluorescence detection.Pharmacokinetic parameters were analyzed with a non-compartmental model. After oral administration, t½ß, AUC and AUCtissues/AUCplasma ratio were 42.98 h, 21.80µg-h/ml and ≤ 18.63, respectively.After immersion baths of 20 ppm during 2.5 h and 100 ppm during 0.5 h, the t½ß, AUC and AUCtissues/AUCplasma were 42.77 and 44.67, 9.83 and 12.83 µg-h/ml and ≤ 9.81 and ≤ 7.13, respectively.Therefore, oral (10 mg/kg) and bath administration in rainbow trout can provide AUC/MIC of ≥125 and Cmax/MIC of ≥10 to treat diseases caused by susceptible bacteria with MIC ≤ 0.04 µg/ml. This information can be helpful for the right use of EFX in rainbow trout. Also, this is the first study that determines the antibiotic tissue disposition in rainbow trout by using different administration routes.

Food safety evaluation for the use of albendazole in fish: residual depletion profile and withdrawal period estimation.

Due to the lack of drugs regulated for aquaculture, we have evaluated the use of albendazole (ABZ) - a potential drug to be regulated for fish - under food safety perspectives assessing the depletion profile of ABZ and its main metabolites (albendazole sulphoxide - ABZSO, albendazole sulphone - ABZSO2 and albendazole amino sulphone - ABZ-2-NH2SO2) in fish fillets (muscle and skin) after single dose oral administration of 10 mg ABZ kg-1 body weight. For the drug administration, a suitable procedure for ABZ incorporation into fish feed was employed, obtaining good homogeneity of ABZ concentration among feed pellets (CV<4.1%) and low drug leaching when medicated feed remained in the water for up to 60 min (<2.7%). After medication, fish were euthanised at 8, 12, 24, 48, 72, 96 and 120 h and fillets collected. Depletion studies in various fish species (patinga and tilapia) were conducted simultaneously, under water temperature at 30.4 ± 0.3 °C and pH 6.8 ± 0.1. The highest concentrations for the sum of residues (ABZ, ABZSO, ABZSO2 and ABZ-2-NH2SO2) in fish fillet were 1210 ng g-1 in patinga and 637 ng g-1 in tilapia. Under the employed rearing conditions, the obtained results did not indicate a requirement for a minimum withdrawal period to be proposed for tilapia considering the maximum residue limit of 100 µg g-1, since the determined residual concentration was

Emamectin benzoate in tilapia: Alternative method for drug incorporation into feed and associated residual depletion study.

Due to the lack of regulated drugs for aquaculture, the present study considered specific issues relating to environmental and food safety aspects concerning the potential use of emamectin benzoate (EMA) in freshwater fishes such as tilapia (Oreochromis niloticus) - an important commercial fish species worldwide. The residual depletion of EMA (EMA-B1a) in fillet (muscle plus skin in natural proportions) of tilapia treated with a daily dose of 50 µg/kg BW during seven consecutive days was evaluated. To facilitate this, analytical methods for quantitation of EMA in fish feed and in fish fillet employing LC-MS/MS were developed and validated. To eliminate the risk of EMA leaching from feed into the aquatic environment during fish medication via oral administration, a promising procedure for drug incorporation into feed involving the coating of feed pellets with ethyl cellulose polymer containing EMA was evaluated. The medicated feed exhibited good homogeneity (CV < 2.1%) with negligible EMA release (< LOQ) when the medicated feed remained in the water for up to 20 min. Depletion study analysis revealed the highest EMA concentration obtained in fish fillet to be 13.3 ng/g. Therefore, under the employed rearing conditions of this study, the obtained results did not evidence requirement for a minimum withdrawal period to be proposed considering the maximum residue limit of 100 µg/g for fish muscle. In response to the well-recognized demands and need for new alternative veterinary drugs for use within aquaculture, this study offers impetus for consideration of EMA use in tilapia taking into account environmental contamination and food safety issues.

Tissue residue depletion of moxidectin in lambs (Ovis aries) following subcutaneous administration.

To date, a tissue depletion study of moxidectin (MOX) in lambs is not available. Thus, considering that lamb meat is of great commercial interest in the world, the aim of the present study was to determine the residue levels of MOX in lamb target-tissues (muscle, liver, kidney and fat) and subsequently calculate the MOX withdrawal period. For this purpose, the target-tissues were analysed by ultra-high-performance liquid chromatography-tandem mass spectrometry. Method validation was performed based on Commission Decision 2002/657/EC and VICH GL49. To quantify the analyte, matrix-matched analytical curves were constructed with spiked blank tissues. The limits of detection and quantitation were 1.5 and 5 ng g-1, respectively, for all matrices. The linearity, decision limit, detection capability accuracy and inter- and intra-day precision of the method are reported. The lambs were treated with a single subcutaneous dose of 0.2 mg MOX kg-1 body weight and were slaughtered in accordance with accepted animal care protocols. Samples of target-tissues were collected on 2, 4, 7, 14, 28 and 42 days after MOX administration. During the whole study, the highest drug residue level occurred in the fat. For the other target-tissues (muscle, liver and kidney), MOX concentrations were below the maximum residue limit (MRL). Considering the MRL value of 500 µg kg-1 for MOX residues in sheep fat, our results in lambs allowed the estimation of a MOX withdrawal period of 31 days. This indicates that the withdrawal period established for MOX in adult sheep (28 days) does not apply for lambs.

Growth performance and safety of meat from cattle feedlot finished with salinomycin in the diet / Desempenho produtivo e inocuidade da carne de bovinos terminados em confinamento com salinomicina na dieta

This study assessed production performance, carcass characteristics, serum parameters, residue depletion of meat, and economic performance during the finishing period of steers in feedlots using salinomycin in their diet. A total of 32 steers were finished in a feedlot on a diet comprising corn silage and concentrate (50:50), with or without added salinomycin (120 mg per animal day-¹). Study design was completely randomized, with eight repetitions. Results indicated that the use of salinomycin increased both weight gain (1.582 vs. 1.304 kg) and feed conversion (6.16 vs. 7.25 kg kg-¹). No significant alterations were observed in feed intake (9.52 vs. 9.25 kg animal day-¹), serum parameters, or apparent diet digestibility. The withdrawal period of 16 h prior to slaughter promoted a lower salinomycin concentration (0.25 μg kg-¹) in organs and edible tissues, which is below the levels allowed by legislation. Animals finished with salinomycin also exhibited greater warm carcass weight (287.76 vs. 275.81 kg) and better economic performance (profit margin increments of R$ 84.20 per animal). Salinomycin use in feedlot-finished steers promoted both production and economic performance improvements without added implications to either animal or consumer health since there were no significant residues found in any edible tissues.

Objetivou-se avaliar o desempenho produtivo, as características de carcaça, os parâmetros séricos, a depleção residual na carne e a economicidade da terminação de novilhos em confinamento com salinomicina na dieta. Foram confinados 32 animais com dieta constituída de silagem de milho e concentrado (50:50), adicionada ou não de salinomicina (120 mg por animal dia-¹). O delineamento foi inteiramente casualizado com 8 repetições. O uso de salinomicina melhorou o ganho de peso (1,582 vs 1,304 kg) e a conversão alimentar (6,16 vs 7,25 kg kg-¹). Não houve alterações significativas no consumo de alimento (9,52 vs 9,25 kg animal dia-¹), nos parâmetros séricos e na digestibilidade aparente da dieta. O período de carência de 16 h antes do abate promoveu concentrações de salinomicina inferiores a 0,25 μg kg-¹ nos órgãos e tecidos comestíveis, cujos valores estão abaixo dos permitidos na legislação. Animais terminados com salinomicina apresentaram maior peso de carcaça quente (287,76 vs 275,81 kg) e melhor resultado econômico, com incremento de R$ 84,20 por animal na margem de lucro. O uso de salinomicina para novilhos em confinamento promoveu melhorias no desempenho produtivo e econômico, sem prejudicar a saúde dos animais e dos consumidores, pois não houve resíduos significantes nos tecidos comestíveis.

Growth performance and safety of meat from cattle feedlot finished with salinomycin in the diet / Desempenho produtivo e inocuidade da carne de bovinos terminados em confinamento com salinomicina na dieta

This study assessed production performance, carcass characteristics, serum parameters, residue depletion of meat, and economic performance during the finishing period of steers in feedlots using salinomycin in their diet. A total of 32 steers were finished in a feedlot on a diet comprising corn silage and concentrate (50:50), with or without added salinomycin (120 mg per animal day-¹). Study design was completely randomized, with eight repetitions. Results indicated that the use of salinomycin increased both weight gain (1.582 vs. 1.304 kg) and feed conversion (6.16 vs. 7.25 kg kg-¹). No significant alterations were observed in feed intake (9.52 vs. 9.25 kg animal day-¹), serum parameters, or apparent diet digestibility. The withdrawal period of 16 h prior to slaughter promoted a lower salinomycin concentration (0.25 μg kg-¹) in organs and edible tissues, which is below the levels allowed by legislation. Animals finished with salinomycin also exhibited greater warm carcass weight (287.76 vs. 275.81 kg) and better economic performance (profit margin increments of R$ 84.20 per animal). Salinomycin use in feedlot-finished steers promoted both production and economic performance improvements without added implications to either animal or consumer health since there were no significant residues found in any edible tissues.(AU)

Objetivou-se avaliar o desempenho produtivo, as características de carcaça, os parâmetros séricos, a depleção residual na carne e a economicidade da terminação de novilhos em confinamento com salinomicina na dieta. Foram confinados 32 animais com dieta constituída de silagem de milho e concentrado (50:50), adicionada ou não de salinomicina (120 mg por animal dia-¹). O delineamento foi inteiramente casualizado com 8 repetições. O uso de salinomicina melhorou o ganho de peso (1,582 vs 1,304 kg) e a conversão alimentar (6,16 vs 7,25 kg kg-¹). Não houve alterações significativas no consumo de alimento (9,52 vs 9,25 kg animal dia-¹), nos parâmetros séricos e na digestibilidade aparente da dieta. O período de carência de 16 h antes do abate promoveu concentrações de salinomicina inferiores a 0,25 μg kg-¹ nos órgãos e tecidos comestíveis, cujos valores estão abaixo dos permitidos na legislação. Animais terminados com salinomicina apresentaram maior peso de carcaça quente (287,76 vs 275,81 kg) e melhor resultado econômico, com incremento de R$ 84,20 por animal na margem de lucro. O uso de salinomicina para novilhos em confinamento promoveu melhorias no desempenho produtivo e econômico, sem prejudicar a saúde dos animais e dos consumidores, pois não houve resíduos significantes nos tecidos comestíveis.(AU)