UNASSIGNED: To determine the concentration, in comparison with the maximum residue limit (MRL), of anthelmintic marker residues in the target tissues (liver and fat) of sheep treated concurrently with two oral drenches, one containing monepantel and abamectin and the other oxfendazole and levamisole.
UNASSIGNED: On day 0 of the study, 12 sheep (six male and six female; 8-9-months old) were dosed according to individual body weight determined the day prior. Zolvix Plus (dual-active oral drench containing 25 g/L monepantel and 2 g/L abamectin) was administered to all animals prior to administration of Scanda (dual-active oral drench containing 80 g/L levamisole hydrochloride and 45.3 g/L oxfendazole). Six sheep (three male and three female) were slaughtered 21 and 28 days after treatment and renal fat and liver samples were collected.Using validated methods, analyses for monepantel sulfone, abamectin, levamisole and oxfendazole (expressed as total fenbendazole sulfone following conversion of the combined concentrations of oxfendazole, fenbendazole and fenbendazole sulfone) were performed on liver samples while renal fat specimens were analysed for monepantel sulfone and abamectin residues only. Detected concentrations were compared to the established MRL in sheep for each analyte determined by the Ministry for Primary Industries.
UNASSIGNED: All residues detected in samples of liver and fat collected 21 and 28 days after treatment were below the MRL for each analyte. All liver samples collected on day 21 had detectable monepantel sulfone (mean 232 (min 110, max 388) μg/kg) and oxfendazole (mean 98.7 (min 51.3, max 165) μg/kg) residues below the MRL (5,000 and 500 μg/kg, respectively). Monepantel sulfone (mean 644 (min 242, max 1,119) μg/kg; MRL 7,000 μg/kg) residues were detected in 6/6 renal fat samples. Levamisole residues were detected in 3/6 livers (mean 40.0 (min 14.3, max 78.3) μg/kg; MRL 100 μg/kg), and abamectin residues in 1/6 livers (0.795 μg/kg; MRL 25 μg/kg) and 2/6 fat samples, (mean 0.987 (min 0.514, max 1.46) μg/kg; MRL 50 μg/kg) 21 days after treatment.
UNASSIGNED: These results suggest that concurrent administration of Zolvix Plus and Scanda to sheep is unlikely to result in an extended residue profile for any of the active ingredients, with all analytes measured being under the approved New Zealand MRL 21 days after treatment. This work was not completed in line with guidance for establishing official residue profiles, nor is it sufficient to propose a new withholding period.

Semicarbazide (SEM), a marker residue used to monitor the use of prohibited drug nitrofurazone (NFZ), is commonly found in wild crustaceans, implying the natural origin. However, the difference between endogenous and exogenous SEM has rarely been investigated. So, tissue-bound SEM was determined in samples collected from giant river prawns cultured in an aquaculture farm and in samples from an experiment where giant river prawns were fed twice a day with NFZ at 30 mg/kg for 5 days. At day 10 of drug withdrawal, muscle SEM of the NFZ-fed prawn was 17.78 ng/g and depleted to 1.18 ng/g at day 90 (half-life 20.31 days) which was significantly higher than the control prawn (usually ≤ 0.1 ng/g). In contrast, the average SEM in the shell was independent of NFZ treatment. SEM was not found in the aquaculture farm samples, implying that the SEM in cultured prawn did not originate from SEM contamination.

Cobalt is an essential trace mineral required for ruminal vitamin B12 synthesis, but sources differ in ruminal microbial utilization, i.e., cobalt carbonate is poorly water soluble, whereas acetate and lactate forms are water soluble. Reports comparing organic cobalt lactate to other cobalt salts are lacking. The study objective was to determine if feeding cobalt lactate at two inclusion rates resulted in similar growth performance and tissue cobalt concentrations as the carbonate and acetate forms used in feeds. One hundred Angus cross bred steers weighing 385 ± 20 kg were randomly assigned to one of five treatments. Cattle were fed a basal diet plus: 1) cobalt carbonate to supply cobalt at 30 mg/steer/d, 2) cobalt acetate to supply cobalt at 30 mg/steer/d, 3) cobalt acetate to supply cobalt at 60 mg/steer/d, 4) cobalt lactate to supply cobalt at 30 mg/steer/d, and 5) cobalt lactate to supply cobalt at 60 mg/steer/d. Cattle were fed according to industry standards until body fat deposition was visually deemed to grade USDA Choice, which was 92 and 117 d for each of the 2 blocks, respectively. Steers were harvested and carcass measurements recorded along with sampling of adipose, heart, kidney, liver, and muscle for tissue cobalt concentrations. Three statistical contrasts consisted of: 1: inorganic (cobalt carbonate) vs. organic (cobalt acetate and lactate); 2: cobalt acetate vs. cobalt lactate; and 3: feeding rate of 30 vs. 60 mg/steer/d cobalt. Body weight gains, average daily gains, dry matter intake, and feed conversions were similar (P > 0.10) for steers fed all cobalt sources and feeding rates. Hot carcass weight, yield grade, back fat thickness, and ribeye area were similar (P > 0.10) among steers fed all cobalt sources and inclusion rates. Liver, kidney, muscle, and adipose cobalt concentrations were similar (P > 0.08) for steers fed inorganic vs. organic cobalt sources. Feeding cobalt lactate compared with cobalt acetate did not affect (P > 0.10) liver, kidney, heart, muscle, and adipose tissue cobalt concentrations. Feeding 60 mg/steer/d cobalt compared with 30 mg/steer/d increased (P < 0.01) liver, kidney, heart, and adipose tissue cobalt concentrations, while muscle was a tendency (P < 0.06). The study demonstrated that feeding soluble cobalt lactate, a new cobalt source, resulted in similar growth performance, carcass characteristics, and tissue cobalt concentrations when compared with cobalt acetate and carbonate.

Black-bone fowl are different from ordinary broilers in appearance and are considered to have rich nutritional properties. However, the metabolism of therapeutic drugs in black-bone fowl remains unclear. This study aimed to determine the tissue residue depletion kinetics of trimethoprim and sulfachloropyridazine in Yugan black-bone fowl, after daily oral administrations for 5 days at 4 mg/kg bw/day trimethoprim and 20 mg/kg bw/day sulfachloropyridazine, and to calculate the withdrawal times. After consecutive oral administrations, the tissues (liver, kidney, muscle and skin/fat) were collected at each of the following time points (0.16, 1, 3, 5, 7, 9, 20, 30 and 40 days). A newly-devised LC-MS/MS method was used to analyse the concentrations of trimethoprim and sulfachlorpyridazine in target tissues. The results showed that sulfachloropyridazine was rapidly metabolised in broilers, and there was no residue in all tissues 3 days post-administration. The concentration of trimethoprim in black-bone fowl skin/fat is the highest, and its metabolism rate is low. After 40 days, the concentration of trimethoprim in skin/fat is still as high as 140.1 ± 58.0 μg/kg, exceeding the maximum residue limit. In order to protect consumers\' health, it is suggested that the withdrawal time of TMP in Yugan black-bone fowl is 69 days.

The purpose of this study was to compare the pharmacokinetics, tissue residues, and withdrawal times of doxycycline after oral administration in rainbow trout reared at 10 and 17 °C. Fish received a 20 mg/kg oral dose of doxycycline after a single or 5-day administration. Six rainbow trout were used at each sampling time point for plasma and tissue samples, including liver, kidney, and muscle and skin. The doxycycline concentration in the samples was determined using high-performance liquid chromatography with ultraviolet detector. The pharmacokinetic data were evaluated by non-compartmental kinetic analysis. The WT 1.4 software program was used to estimate the withdrawal times. The increase of temperature from 10 to 17 °C shortened the elimination half-life from 41.72 to 28.87 h, increased the area under the concentration-time curve from 173.23 to 240.96 h * μg/mL, and increased the peak plasma concentration from 3.48 to 5.50 μg/mL. At 10 and 17 °C, the doxycycline concentration was obtained in liver > kidney > plasma > muscle and skin. According to the MRL values stated for muscle and skin in Europe and China (100 μg/kg) and in Japan (50 μg/kg), the withdrawal times of doxycycline at 10 and 17 °C were 35 and 31 days, respectively, for Europe and China and 43 and 35 days, respectively, for Japan. Since temperature significantly affected pharmacokinetic behavior and withdrawal times of doxycycline in rainbow trout, temperature-dependent dosing regimens and withdrawal times of doxycycline might be necessary.

Drug behavior in the bodies of fish is largely influenced by the water temperature. Antimicrobial drugs are needed for the control of bacterial outbreaks in farmed fish including Asian seabass (Lates calcarifer). However, little is known about the temperature effect on appropriate drug uses in this species. The purpose of this study was to investigate the differences in pharmacokinetics (PK), optimal dosages, tissue depletion, and withdrawal time (WDT) of florfenicol (FF) in Asian seabass reared at 25 and 30 °C. In the PK study, the fish were administered with a single oral dose of 10 mg/kg FF. The optimal dosing regimen was determined by the pharmacokinetic-pharmacodynamic (PK-PD) approach. In the tissue depletion and WDT study, FF was administered at the optimal dosages once daily for 5 days and the WDT was determined by linear regression analysis based on the sum of FF and its metabolite florfenicol amine (FFA) in the muscle/skin. When the temperature was increased from 25 to 30 °C, the elimination half-life of FF was significantly decreased from 11.0 to 7.2 h. While the other PK parameters were not changed significantly, the calculated optimal dosages for the target minimum inhibitory concentration (MIC) of 2 µg/mL were 10.9 and 22.0 mg/kg/day, respectively for 25 and 30 °C. The sum of FF + FFA is a preferable marker residue for WDT determination because differential FF metabolism was observed at different temperatures. The depletion half-life of the muscle/skin was shortened from 41.1 to 32.4 h by the 5 °C temperature increase. Despite different absolute amounts of FF given between the two temperature levels, the WDTs were very similar at 6-7 days. Thus, it appears that a single temperature-independent WDT can potentially be assigned when the drug was applied at the optimal dosage.

Asian seabass (Lates calcarifer) is an economically important fish in Asian and Australian markets, but few pharmacokinetic (PK) data of antimicrobial drugs in this species is available. The present study investigated the PK behaviour of florfenicol (FF) through medicated feed in Asian seabass cultured at 25°C. The serum and muscle/skin concentrations of FF and its metabolite florfenicol amine (FFA) were determined by the HPLC-FLD method and analysed by one-compartmental model. The optimal dosages were determined by pharmacokinetic-pharmacodynamic (PK-PD) approach and the linear regression analysis was used to determine the withdrawal time (WDT). The PK study following a single oral administration of 15 mg/kg FF via medicated feed revealed that the absorption half-life (t1/2Ka ), elimination half-life (t1/2K ), peak concentration (Cmax ), area under the concentration-time curve (AUC), volume of distribution (Vd/F) and clearance (CL/F) were 1.47 h, 8.07 h, 8.61 μg/ml, 146.41 h·μg/ml, 1.19 L/kg and 0.102 L/kg/h, respectively. The muscle/skin concentration-time profile was similar to that of the serum, suggesting well distribution but only a small fraction of FF was metabolized to FFA. The optimal dosage for a minimum inhibitory concentration of 2 μg/ml was calculated as 13.38 mg/kg/day. The appropriate WDT after multiple oral medications with 15 mg/kg FF once daily for 7 days was determined as 8 days. Information obtained from the current study can potentially be applied for the treatment of bacterial diseases in farming Asian seabass.

Lead has long been known as neurotoxic and immunotoxic heavy metal in human and animals including fish, whereas, 2, 3-dimethylsuccinic acid (DMSA) and fulvic acid (FA) are well-known biological chelators. The present investigation was carried out to assess the potential chelating and antioxidant effects of dietary supplementation with DMSA and FA against lead acetate (Pb)-induced oxidative stress in Nile tilapia, O. niloticus. One-hundred and eighty apparently healthy O. niloticus fish (30 ± 2.5 g) were allocated into six equal groups. The first group was fed on basal diet and served as control, while the second group was fed on DMSA-supplemented basal diets at levels of 30 mg/kg diet; the third group was fed on FA-supplemented basal diet at level of 0.3 mg/kg diet; the forth, fifths, and sixth groups were exposed to 14.4 mg Pb /L water (1/10 LC50) and feed on basal diet only, basal diet supplemented with DMSA (0.3 mg/kg diet), or basal diet supplemented with FA (0.3 mg/kg diet), respectively. Antioxidant and lipid peroxidative status, activity of glucose 6-phosphate dehydrogenase (G6PD), and lactate dehydrogenase (LDH) as well as the histopathologic findings were evaluated in brain tissues, while the Pb residues were evaluated in liver, muscles, and brain tissues. The results of the present study showed that DMSA and FA decreased malondialdehyde (MDA) and Pb residue in tissues of Pb-exposed fish and improved the histologic picture and brain contents of glutathione (GSH), glutathione-s-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), G6PD, LDH, and total antioxidant capacity (TAC). It could be concluded that DMSA and FA supplementation exhibited potential neuroprotective effect against Pb-induced oxidative brain damages in O. niloticus through improvement of antioxidant status of the brain tissue.

We aimed to identify patterns in the internal distribution of persistent organic pollutants (POPs) and assess contributing factors using sea turtles and their offspring as a case study of a long-lived wildlife species. We systematically synthesized 40 years of data and developed a lipid database to test whether lipid-normalized POP concentrations are equal among tissues as expected under steady state for lipophilic compounds. Results supported equal partitioning among tissues with high blood flow or perfusion including the heart, kidney, muscle, and lung. Observed differences in the brain, fat, and blood plasma, however, suggest the physiological influence of the blood-brain barrier, limited perfusion, and protein content, respectively. Polybrominated diphenyl ethers partitioned comparably to legacy POPs. Polycyclic aromatic hydrocarbons, meanwhile, partitioned more into the lung, colon, and muscle compared to the liver under chronic and acute field exposure. Partitioning ratios of individual POPs among tissues were significantly related to the lipophilicity of compounds (as estimated by Kow) in half of the observed cases, and significant differences between juveniles and adults underscore physiological differences across life stages. The comprehensive tissue partitioning patterns presented here provide a quantitative basis to support comparative assessments of POP pollution derived from biomonitoring among multiple tissues.

The aim of this study was to investigate the effect of different water temperatures (19, 25, and 30°C) on tissue residue depletion of tiamulin in Nile tilapia (Oreochromis niloticus) after five consecutive days of oral administration at the dose of 20 mg/kg body weight and to calculate the corresponding elimination half-life (T 1/2) and withdrawal times (WTs). After oral administration at scheduled 11 time points (1, 2, 3, 5, 7, 9, 12, 15, 20, 25, and 30 days), samples of plasma and tissues (muscle plus skin, liver, kidney, and gill) were collected. Tiamulin concentration in samples were determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). T 1/2 was calculated by the equation: T 1/2 = ln2/k. WT 1.4 software was used to calculate WT. The results showed that tiamulin was widely distributed in all tissue samples with the highest concentration in liver. At three different water temperatures, the T 1/2 were calculated as 2.76, 2.13, and 1.64 days in plasma, 2.71, 1.85, and 1.31 days in muscle plus skin, 2.27, 1.70, and 1.50 days in liver, 2.84, 2.32, and 1.94 day in kidney, and 3.16, 2.42, and 1.74 days in gill, respectively. At 19°C, the order of WT is kidney (11.88 days) > liver (10.41 days) > gill (10.77 days) > plasma (8.83 days) > muscle plus skin (7.14 days). The WT for tiamulin at 25°C was in the following order: kidney (8.40 days) > liver (8.21 days) > gill (8.07 days) > plasma (7.24 days) > muscle plus skin (4.05 days). At 30°C, the WT dropped and shown as follows: gill (6.99 days) > kidney (6.51 days) > liver (6.29 days) > plasma (3.27 days) > muscle plus skin (2.92 days). The present investigations indicated that increasing the temperature from 19 to 30°C shortened T 1/2 and WT of tiamulin in tilapia. To ensure the safety of fish consumption, the longest WT of tissues is suggested for tiamulin in Nile tilapia at the corresponding water temperature; i.e., WTs were 12 days at 19°C, 9 days at 25°C, and 7 days at 30°C, respectively. Overall, we intended to provide a theoretical basis for tissue residue depletion kinetics of tiamulin in fish and improve our understanding of the influence of the temperature on tissue residue depletion kinetics of tiamulin in fish.