Assessment of veterinary drugs in plants using pharmacokinetic approaches: The absorption, distribution and elimination of tetracycline and sulfamethoxazole in ephemeral vegetables.

The present study was carried out to demonstrate novel use of pharmacokinetic approaches to characterize drug behaviors/movements in the vegetables with implications to food safety. The absorption, distribution, metabolism and most importantly, the elimination of tetracycline (TC) and sulfamethoxazole (SMX) in edible plants Brassica rapa chinensis and Ipomoea aquatica grown hydroponically were demonstrated and studied using non-compartmental pharmacokinetic analysis. The results revealed drug-dependent and vegetable-dependent pharmacokinetic differences and indicated that ephemeral vegetables could have high capacity accumulating antibiotics (up to 160 µg g-1 for TC and 38 µg g-1 for SMX) within hours. TC concentration in the root (Cmax) could reach 11 times higher than that in the cultivation fluid and 3-28 times higher than the petioles/stems. Based on the volume of distribution (Vss), SMX was 3-6 times more extensively distributed than TC. Both antibiotics showed evident, albeit slow elimination phase with elimination half-lives ranging from 22 to 88 hours. For the first time drug elimination through the roots of a plant was demonstrated, and by viewing the root as a central compartment and continuous infusion without a loading dose as drug administration mode, it is possible to pharmacokinetically monitor the movement of antibiotics and their fate in the vegetables with more detailed information not previously available. Phyto-pharmacokinetic could be a new area worth developing new models for the assessment of veterinary drugs in edible plants.

Continuous fungal treatment of non-sterile veterinary hospital effluent: pharmaceuticals removal and microbial community assessment.

Source point treatment of effluents with a high load of pharmaceutical active compounds (PhACs), such as hospital wastewater, is a matter of discussion among the scientific community. Fungal treatments have been reported to be successful in degrading this type of pollutants and, therefore, the white-rot fungus Trametes versicolor was applied for the removal of PhACs from veterinary hospital wastewater. Sixty-six percent removal was achieved in a non-sterile batch bioreactor inoculated with T. versicolor pellets. On the other hand, the study of microbial communities by means of DGGE and phylogenetic analyses led us to identify some microbial interactions and helped us moving to a continuous process. PhAC removal efficiency achieved in the fungal treatment operated in non-sterile continuous mode was 44 % after adjusting the C/N ratio with respect to the previously calculated one for sterile treatments. Fungal and bacterial communities in the continuous bioreactors were monitored as well.

Estimation of residue depletion of cyadox and its marker residue in edible tissues of pigs using physiologically based pharmacokinetic modelling.

Physiologically based pharmacokinetic (PBPK) models are powerful tools to predict tissue distribution and depletion of veterinary drugs in food animals. However, most models only simulate the pharmacokinetics of the parent drug without considering their metabolites. In this study, a PBPK model was developed to simultaneously describe the depletion in pigs of the food animal antimicrobial agent cyadox (CYA), and its marker residue 1,4-bisdesoxycyadox (BDCYA). The CYA and BDCYA sub-models included blood, liver, kidney, gastrointestinal tract, muscle, fat and other organ compartments. Extent of plasma-protein binding, renal clearance and tissue-plasma partition coefficients of BDCYA were measured experimentally. The model was calibrated with the reported pharmacokinetic and residue depletion data from pigs dosed by oral gavage with CYA for five consecutive days, and then extrapolated to exposure in feed for two months. The model was validated with 14 consecutive day feed administration data. This PBPK model accurately simulated CYA and BDCYA in four edible tissues at 24-120 h after both oral exposure and 2-month feed administration. There was only slight overestimation of CYA in muscle and BDCYA in kidney at earlier time points (6-12 h) when dosed in feed. Monte Carlo analysis revealed excellent agreement between the estimated concentration distributions and observed data. The present model could be used for tissue residue monitoring of CYA and BDCYA in food animals, and provides a foundation for developing PBPK models to predict residue depletion of both parent drugs and their metabolites in food animals.

Probabilistic risk assessment of veterinary medicines applied to four major aquaculture species produced in Asia.

Aquaculture production constitutes one of the main sources of pollution with veterinary medicines into the environment. About 90% of the global aquaculture production is produced in Asia and the potential environmental risks associated with the use of veterinary medicines in Asian aquaculture have not yet been properly evaluated. In this study we performed a probabilistic risk assessment for eight different aquaculture production scenarios in Asia by combining up-to-date information on the use of veterinary medicines and aquaculture production characteristics. The ERA-AQUA model was used to perform mass balances of veterinary medicinal treatments applied to aquaculture ponds and to characterize risks for primary producers, invertebrates, and fish potentially exposed to chemical residues through aquaculture effluents. The mass balance calculations showed that, on average, about 25% of the applied drug mass to aquaculture ponds is released into the environment, although this percentage varies with the chemical's properties, the mode of application, the cultured species density, and the water exchange rates in the aquaculture pond scenario. In general, the highest potential environmental risks were calculated for parasitic treatments, followed by disinfection and antibiotic treatments. Pangasius catfish production in Vietnam, followed by shrimp production in China, constitute possible hot-spots for environmental pollution due to the intensity of the aquaculture production and considerable discharge of toxic chemical residues into surrounding aquatic ecosystems. A risk-based ranking of compounds is provided for each of the evaluated scenarios, which offers crucial information for conducting further chemical and biological field and laboratory monitoring research. In addition, we discuss general knowledge gaps and research priorities for performing refined risk assessments of aquaculture medicines in the near future.

Occurrence and ecological hazard assessment of selected veterinary medicines in livestock wastewater treatment plants.

The occurrence of some veterinary medicines in the livestock wastewater plants (WWTPs) was investigated. This investigation represented the occurrence of veterinary medicines to treat in the livestock WWTPs or be discharged into the water system in Korea since the sampling sites were widely distributed across the nation and samples were collected from the 11 livestock WWTPs. Nine antibiotics, two analgesics, and two disinfectants occurred in the livestock wastewater plants (WWTPs). From 11 livestock WWTP influents, chlortetracycline, oxytetracycline, acetylsalicylic acid, and disinfectants frequently occurred with the high concentrations. Meanwhile, sulfamethoxazole, erythromycin-H2O, and trimethoprim did not occur during sampling periods. The values for log Kow of each chemical showed a high correlation with the number of hydrogen bonding acceptors and were important parameters to estimate and understand the biodegradability and toxicity of a compound in the environment. The biodegradability of each compound was proportional to the hydrophilicity of each compound and the toxicity was proportional to the number of hydrogen bonding acceptors of each compound. The expected introductory concentration (EIC), predicted exposure concentration (PEC), and hazard quotient showed that the livestock WWTP effluents were hazardous to ecosystems.

Chemical safety of meat and meat products.

Since the Second World War the consumer behaviour in developed countries changed drastically. Primarily there existed the demand for sufficient food after a period of starvation, afterwards the desire for higher quality was arising, whereas today most people ask for safe and healthy food with high quality. Therefore a united approach comprising consistent standards, sound science and robust controls is required to ensure consumers' health and to maintain consumers' confidence and satisfaction. Chemical analysis along the whole food chain downstream (tracking) from primary production to the consumer and upstream (tracing) from the consumer to primary production is an important prerequisite to ensure food safety and quality. In this frame the focus of the following paper is the "chemical safety of meat and meat products" taking into account inorganic as well as organic residues and contaminants, the use of nitrite in meat products, the incidence of veterinary drugs, as well as a Failure Mode and Effect Analysis (FMEA) system assessing (prioritizing) vulnerable food chain steps to decrease or eliminate vulnerability.

Application of a luminescent bacterial biosensor for the detection of tetracyclines in routine analysis of poultry muscle samples.

Tetracyclines are extensively used in veterinary medicine. For the detection of tetracycline residues in animal products, a broad array of methods is available. Luminescent bacterial biosensors represent an attractive inexpensive, simple and fast method for screening large numbers of samples. A previously developed cell-biosensor method was subjected to an evaluation study using over 300 routine poultry samples and the results were compared with a microbial inhibition test. The cell-biosensor assay yielded many more suspect samples, 10.2% versus 2% with the inhibition test, which all could be confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Only one sample contained a concentration above the maximum residue limit (MRL) of 100 microg kg(-1), while residue levels in most of the suspect samples were very low (<10 microg kg(-1)). The method appeared to be specific and robust. Using an experimental set-up comprising the analysis of a series of three sample dilutions allowed an appropriate cut-off for confirmatory analysis, limiting the number of samples and requiring further analysis to a minimum.

A contribution to safety assessment of veterinary drug residues: in vitro/ex vivo studies on the intestinal toxicity and transport of covalently bound residues.

1. The gastrointestinal fate of protein-bound residues of the model compound furazolidone (FZD) was investigated in vitro and ex vivo. Protein-bound residues were generated in rat liver microsomes, isolated by solvent extraction and digested with 0.5% hydrochloric acid and Pronase E. 2. During digestion, 3-amino-2-oxazolidinone (AOZ), the side chain of furazolidone, was partly released from bound residues. 3. The absorption of free AOZ and digested protein-bound residues was tested in isolated perfused rat gut segments (IPGS) and in the intestinal cell line Caco-2. Free AOZ was transfered both in the IPGS model and in Caco-2 monolayer cultures, while no indications for passage of bound residues were obtained. 4. No acute toxicity of AOZ or digested food residues respectively was observed in gut segments and Caco-2 cells at concentrations that were substantially above maximum residue levels to be expected in food of animal origin after administration of therapeutic doses. 5. The results demonstrate that digestive processes can alter the chemical nature of drug residues and yield degradation products that may be bioavailable for the consumer. Thus, the covalent binding of xenobiotics to macromolecular tissue constituents cannot necessarily be regarded as an irreversible endpoint of residue bioavailability and toxicity.