Post marketing surveillance of selected veterinary medicines in Tanzania mainland.

BACKGROUND: Veterinary medicines have been widely used for the prevention and treatment of animal diseases. Globally, the veterinary medicine industry is growing. However, there is a significant increase of concern on the quality of veterinary medicines in various developing countries' legal markets. Poor-quality medicines are associated with treatment failure, development of drug resistance, increased healthcare cost, and death. These reasons warrant a need for monitoring the quality of the medicines circulating in the Tanzania Mainland. METHODS: This was a survey study and veterinary medicines samples were collected from 9 out of 26 regions of Tanzania mainland between 2014 and 2017. Veterinary medicines were sampled from wholesale pharmacies, retail pharmacies, veterinary clinics and Veterinary Accredited Drug Dispensing Outlets (ADDO-vet). All sampled medicines were subjected to product information review and full quality control testing at the Tanzania Medicines and Medical Devices Authority-World Health Organization prequalified laboratory. RESULTS: A total of 238 samples of veterinary medicines were collected. Out of these, 97.1% (231/238) were subjected to full quality control testing and product information review. All sampled veterinary medicines conformed to visual appearance, clarity, pH, solubility and sterility tests. Also, of the sampled veterinary medicines 97.8% (226/231) and 89.2% (206/231) passed identification and assay tests, respectively. As well as, the majority of the collected samples 92% (219/238) failed to comply with product information requirements. The most observed deficiencies on product information were inadequate information on the package insert 94.1% (224/238), inappropriate storage conditions 55.5% (132/238) and lack of Tanzania registration number 27% (64/238). CONCLUSION: Veterinary medicines with poor quality were found circulating in the legal markets of Tanzania. This can potentiate treatment failure and the development of drug resistance in animals and humans. Post marketing surveillance program will continue to be implemented to ensure that only good quality, safe and efficacious medicines are circulating in the Tanzania Mainland market.

Ecotoxicological effects of fipronil, neem cake and neem extract in edaphic organisms from tropical soil.

Veterinary medicines are widely applied for the treatment and prevention of animal diseases. Consequently, animal manure contains significant amounts of environmental pollutants that are potential sources of environmental pollution when inappropriately applied in soils. This work aimed to evaluate ecotoxicological effects of doses of commercial fipronil, neem cake and neem extract in the survival and reproduction of earthworms (Eisenia andrei), enchytraeidae (Enchytraeus crypticus) and springtails (Folsomia candida) in Oxisol and tropical artificial soil (TAS). Applications of fipronil, neem cake and extract in soil were carried out according to standardized ISO methodologies by using a random experimental design with five replicates. Toxic effects of fipronil for springtails in Oxisol and TAS were observed with LC50 of 0.26 mg kg-1 (0.18-0.35 mg kg-1) and 0.29 mg kg-1 (0.22-0.37 mg kg-1), respectively. It was not observed significant toxic effects of fipronil for earthworms and enchytraeidae in both soils. However, significant amounts of juvenile earthworm and adult enchytraeidae decreased in fipronil doses higher than 10 mg kg-1. Neem cake and extract were not toxic for earthworms and enchytraeidae but, significant amounts of juvenile springtails decreased in neem cake doses from 500 to 1000 mg kg-1. It can be concluded that the use of veterinary medicines containing synthetic compounds for preventing diseases in animals needs to be controlled to avoid environmental pollution after applying manure in soil. Veterinary medicines containing natural compounds as neem cake and extract are eco-friendly and could be efficiently applied in soil in a sustainable way.

Network on veterinary medicines initiated by the European Federation For Pharmaceutical Sciences.

The European Federation for Pharmaceutical Sciences (EUFEPS) was founded 25 years ago by more than 20 national pharmaceutical societies and faculty members. As a pan-European organization, it brings together pharmaceutical societies as well as academic, industrial and regulatory scientists engaged in drug research and development, drug regulation and education of professionals working in these fields. EUFEPS represents pharmaceutical sciences in Europe and is recognized as such by both the European Commission and the European Medicines Agency. EUFEPS cooperates with the European Federation of Pharmaceutical Industries and other European organizations and maintains global connections with agencies such as the US Food and Drug Administration and the American Association of Pharmaceutical Scientists. EUFEPS has established specified networks forming the basis of its activities. The creation of a Network on Veterinary Medicines is prompted by the manifold problems resulting from the use of veterinary drugs and its inherent interconnections with human medicine, environmental and public health. A long-term goal of this initiative was to expand the spectrum of available therapeutics for use in animals, including the development of innovative delivery systems.

Assessment of environmental risks to groundwater ecosystems related to use of veterinary medicinal products.

The current EU guidelines for the environmental risk assessment of veterinary pharmaceutical products (VMPs) in groundwater (GW) suggest an approach based on the comparison between the calculated concentration in GW (PECgw) and a threshold concentration of 0.1 µg/L. The latter is the upper limit of the concentration for pesticides in groundwater in the EU. If the calculated PECgw does not exceed the threshold, then the risk is considered acceptable. It is assumed that the concentration of 0.1 µg/L is by default safe for both humans and exposed GW organisms. On this basis, it is not clear whether the GW is recognized as an ecosystem or as a source of drinking water. Largely unrecognized biodiversity in GW is worthy of protection through the adoption of a more scientifically sound risk analysis, which should be based on the consideration of ecological criteria. Based on the evidence of their vulnerability, we propose that risk assessments of GW ecosystems should be a compulsory part of the overall risk assessment of VMPs (as well as pesticides, biocides and feed additives). Furthermore, we suggest the use of a risk quotient approach based on the PEC/PNEC ratio in which the PNEC is calculated including an additional safety factor of 10 to the calculated PNEC for surface water.

[Research strategies for feed additives and veterinary medicines from side products of Chinese medicine resources industrialization].

The global antimicrobial resistance has been a big challenge to the human health for years. It has to make balance between the safety of animal products and the use of antimicrobials in animal husbandry. Any methods that can minimize or even phase out the use of antimicrobials in animal husbandry should be encouraged. We herein describe the research strategies for feed additives and veterinary medicines from the side products of Chinese medicine resources industrialization. Killing two birds with one stone-besides the major purposes, the rational utilization of non-medicinal parts and wastes of industrialization of Chinese herbal medicines is also achieved under the proposed strategies.

Biodegradation strategies of veterinary medicines in the environment: Enzymatic degradation.

One Health closely integrates healthy farming, human medicine, and environmental ecology. Due to the ecotoxicity and risk of transmission of drug resistance, veterinary medicines (VMs) are regarded as emerging environmental pollutants. To reduce or mitigate the environmental risk of VMs, developing friendly, safe, and effective removal technologies is an important means of environmental remediation for VMs. Many previous studies have proved that biodegradation has significant advantages in removing VMs, and biodegradation based on enzyme catalysis presents higher operability and specificity. This review focused on biodegradation strategies of environmental pollutants and reviewed the enzymatic degradation of VMs including antimicrobial drugs, insecticides, and disinfectants. We reviewed the sources and catalytic mechanisms of peroxidase, laccase, and organophosphorus hydrolases, and summarized the latest research status of immobilization methods and bioengineering techniques in improving the performance of degrading enzymes. The mechanism of enzymatic degradation for VMs was elucidated in the current research. Suggestions and prospects for researching and developing enzymatic degradation of VMs were also put forward. This review will offer new ideas for the biodegradation of VMs and have a guide significance for the risk mitigation and detoxification of VMs in the environment.

Exploring the Confluence of Animal Medicine and its Implications for Human Health: A Systematic Literature Review.

INTRODUCTION: The abuse of veterinary drugs has emerged as a concerning trend, with global fatalities on the rise. Our understanding of this phenomenon remains limited. This study aims to identify the veterinary drugs being misused, the reasons behind their misuse, and how they are obtained. METHODS: Utilising PubMed, Scopus, and Web of Science databases, along with related grey literature, we applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) framework for data collection. Screening and cross-referencing yielded 66 relevant articles, encompassing case reports, surveys, reports, and systemic literature reviews. The analysis identified 28 distinct veterinary drugs being misused in humans, primarily falling into categories, e.g., α-2- and ß-2-adrenergic receptor agonists, GABAergic receptor modulators, opioid receptor agonists, nonsteroidal anti-inflammatory drugs (NSAIDs), and N-methyl-D-aspartate (NMDA) receptor antagonists. These drugs were used for various purposes, including recreational use, weight loss, bodybuilding, pain relief, and self-medication for stress-related symptoms. RESULTS: Routes of administration predominantly included parenteral, oral, and inhalation methods. Veterinary workers/assistants and individuals connected to animals were identified as contributors to the misuse of these medications. Motivations for their utilisation ranged from affordability and accessibility to the ease of obtaining multiple prescriptions from various veterinary sources, often in conjunction with other illicit substances. Dependence and addiction were common outcomes of the misuse of veterinary medicines by humans. CONCLUSION: Overall, this systematic review underscores the increasing popularity of veterinary prescription drug misuse despite being under-reported with limited available data. Healthcare professionals are urged to remain vigilant to potential overdose events involving these medications.

Application of hollow-fiber-assisted liquid-phase microextraction to identify avermectins in stream water using MS/MS.

In this study, a hollow-fiber-assisted liquid-phase microextraction (HF-LPME) technique coupled with LC-MS/MS is described to detect avermectins (abamectin, ivermectin, moxidectin, and doramectin) in stream water. An Accurel polypropylene membrane was used as the hollow fiber, and dihexyl ether was used as the extraction solvent. The optimal extraction conditions for HF-LPME were 4 cm fiber length, 45 min extraction time, 200 rpm, and 1 min desorption time with methanol as the desorption solvent. The linear range was 0.15-100 ng/mL (r(2) = 0.994-0.998), and the LOD and LOQ were 0.15 and 0.5 ng/mL, respectively. Recovery rates were determined at 1, 5, and 10 ng/mL, and the results were in the range of 80.1 to 93.7%. The intraday and interday repeatability ranged from 2.8 to 8.0% and from 6.1 to 13.3%, respectively. The HF-LPME method developed was applied to detect avermectins in stream water samples collected from 14 different sites near livestock farms located in Honam area, Republic of Korea; however, none of the samples contained avermectin residues. HF-LPME combined with a LC-MS/MS method was successfully applied for an environmentally friendly identification of avermectins in water samples. HF-LPME represents an attractive approach for conventional liquid-liquid extraction.

Expiry of veterinary medicines in supply outlets in Central Uganda: prevalence, management and associated factors.

BACKGROUND: Animal diseases are a danger to livestock, businesses, and public health. This is why the public and private sectors in Africa have invested immensely in the manufacture and distribution of veterinary drugs. However, veterinary drug supply chain actors still suffer losses as a result of expiration. Besides, the way expired products are managed might pose risks to human, animal, and environmental health. This study investigated the prevalence, management of, and factors associated with the expiry of veterinary medicines in supply outlets in Central Uganda. METHODS: A cross-sectional study was conducted among owners and caretakers of veterinary drug supply outlets. Data were collected using self-administered, semi-structured questionnaires. The level of expiry was computed as "acceptable" (for levels reported as ≤ 5%) and "unacceptable" (for levels reported as ˃5%). Logistic regression was used to assess associations between the level of drug expiry and predictor variables. RESULTS: A total of 168 owners/caretakers of veterinary drug supply outlets were included in this study. The majority (148/168, 88.1%) of respondents reported having experienced expiries in their outlets. Unacceptable levels of expiry were reported in 38/168 (22.6%) of the outlets. Retail outlets accounted for the majority (34/38, 89.5%) of the unacceptable levels. Powdered drugs accounted for most expiries (106/148, 71.6%). Most expiries were for drugs supplied to outlets on credit (58/124, 46.8%) and those used to treat rare diseases (26/124, 21%). Major reasons for expiry included irrational prescription, inaccurate forecasts, overstocking, dry seasons, and stocking without considering stock-at-hand. Methods of disposal of expired drugs included throwing at pits (74/168, 44.1%); returning drugs to suppliers (51/168, 30.4%); and incineration (33/168, 19.6%). Factors associated with acceptable levels of expiry included the caretaker being female [adjusted OR = 2.9, 95% CI = 1.22-5.08]; having a procurement policy [adjusted OR = 3.9, 95% CI = 1.29-4.81] and practicing first expiry, first out [adjusted OR = 6.07, 95% CI = 4.71-8.70]. CONCLUSIONS: Veterinary drug expiries are common in Uganda, and environmentally unfriendly methods of disposal are widely used. Acquisition and use of inventory tracking technologies that support First-Expiry-First-Out principles as well as proper disposal of expired medicines are recommended.

The effect of anaerobic pig slurry redox potentials on the degradation of veterinary medicines.

Veterinary medicines are frequently used within intensive livestock husbandry and there has been a growing interest regarding their fate in the environment. However, research has seldom assessed the influence of pig slurry properties on the fate of veterinary medicines even though such an understanding is essential for a more robust environmental risk assessment. Changes within manure degradation rates have the potential to alter the concentration of antibiotics applied to land, and the outcome of the risk assessment. The aim of this work was to investigate whether commonly reported redox potentials affect the degradation rates of acetyl-salicylic acid, ceftiofur, florfenicol, oxytetracycline, sulfamethoxazole, and tylosin. The employed redox potentials were -100 mV (reduced), -250 mV (anaerobic) and -400 mV (very anaerobic). A compound specific relationship was observed where the degradation of ceftiofur, florfenicol, oxytetracycline and sulfamethoxazole was inhibited under reduced conditions over that of very anaerobic; the respective DT50 values were 0.7-1.84 h, 1.35-3.61 h, 22.2-49.8 h, 131-211 h and 35.4-94 h. In contrast, tylosin was found to degrade faster at reduced conditions over very anaerobic (DT50 6.88-19.4 h). The presented research demonstrates the importance of redox potential on degradation rates and suggests we need stringent and harmonized redox control to improve the environmental risk assessment of veterinary medicines. Environmental relevance and significance: Given the significant effect of anaerobic redox potentials on veterinary medicine fate tighter regulation is required in manure degradation trials.

The new Veterinary Medicines Regulation: rising to the challenge.

This article focuses on the new Veterinary Medicines Regulation, which is applicable across all Member States of the European Union, including Ireland, from 28 January 2022. From this date, prophylactic use of antimicrobials (AMs) in groups of animals is banned, metaphylactic use in groups of animals is restricted, and certain AMs are reserved for humans only. In the Irish dairy industry, as elsewhere, successful implementation of the Regulation will require a high level of mastitis control across all herds, and measures to support high standards in antibiotic stewardship. National actions will be critical, to support optimal mastitis control throughout the national herd. For private veterinary practitioners (PVPs), the Regulation will lead to specific prescribing changes, including the requirement to shift from blanket to selective dry cow therapy. Further, prescribing choices will need to be guided by the categorisation for AMs developed by the European Medicines Agency (EMA). More broadly, the Regulation requires a fundamental shift in thinking both in terms of AM usage and of the role of the PVP. Given the close association between mastitis control and intramammary AM stewardship, it is imperative that prescribing and mastitis control decisions are made concurrently. A herd health approach will be critical, within a Client-Patient-Practice Relationship as outlined by the Veterinary Council of Ireland. On those farms with sub-optimal mastitis control, mastitis issues need to be sustainably resolved. A detailed farm investigation by the PVP, in partnership with the farmer and other milk quality professionals, is essential, to understand the epidemiology and on-farm drivers of mastitis, to develop farm-specific action plans, and to facilitate ongoing monitoring of progress. It is vital that PVPs provide leadership, with the provision of a holistic, herd health approach to inform both prescribing and mastitis control decisions in herds under their care.

Validated Screening Method for 81 Multiclass Veterinary Drug Residues in Food via Online-Coupling High-Throughput Planar Solid-Phase Extraction to High-Performance Liquid Chromatography-Orbitrap Tandem Mass Spectrometry.

Current screening capabilities for veterinary drugs (VDs) in foods are limited, requiring time-consuming and expensive trace-level analyses. For the first time, a high-throughput planar solid-phase extraction (HTpSPE) cleanup, controlled by UV/vis/FLD imaging, was developed for screening 81 VDs from 6 different groups (glucocorticoids, anthelmintics, antiparasitics, coccidiostats, nonsteroidal anti-inflammatory drugs, and antibiotics) in 4 different matrices (honey, pig muscle, cow milk, and chicken eggs). It consumed 13 times less solvent and was more eco-friendly and 5 times faster than routine methods. The VDs were automatically eluted using the autoTLC-LC-MS interface, separated online on a high-performance liquid chromatography column via a 10-min gradient, and detected by Orbitrap high-resolution tandem mass spectrometry. The screening method was validated according to the latest European Commission Implementing Regulation 2021/808. Most VDs except penicillins and cephalosporins were detected at the 5-µg/kg level in pig muscle, cow milk, and chicken eggs and 25-µg/kg level in honey.

Assessing the mobility of veterinary drugs with column experiments using different soils and under controlled flow conditions.

Veterinary pharmaceuticals are pollutants that received much attention during the last 20 years. Macrocyclic lactones are a class of drugs globally used in animal and human health, as well as crops protection. Some of its members are key substances for global food security. In this research, the mobility of eprinomectin (EPM) in soil columns (25 cm soil height; 10 cm diameter) was assessed for the first time. Soil density in the columns was 1.1-1.2 g/cm3. Porosity was 0.54-0.60. Three different soil types were used (agricultural, pastoral, wetland). In the experiment, chloride was used as a non-reactive tracer to determine the hydrodynamic conditions in the columns. Therefore, water velocity (v) was 0.146-0.151 cm/h, dispersion coefficient (D) 0.011-0.017 cm2/h and dispersivity (D/v) was 0.072-0.121. Our results showed that the drug remained in the top layers of the columns, after applying an extreme irrigation scenario. The retardation factor for EPM was 43.4-54.5 while for chloride was 0.99-1. EPM fraction (% of applied mass) in 0-1 cm was 13.8-18.0% and in 1-5 cm was 53.3-73.0%. An amount 13-29% was irreversibly bound or degraded during this experiment. From a soil management perspective, the continuous application of EPM contaminated manure, could result in high concentrations in the top 10 cm of the soil profile. Soil column experiments, where hydrodynamic conditions are well defined, are useful for the environmental impact assessment of veterinary pharmaceuticals.

Evaluation of Bacterial Nanocellulose Membranes Loaded or Not with Nisin as a Complementary Treatment in Surgical Dehorning Wounds in Bovines.

Treatments of postsurgical dehorning in cattle usually includes topical application of healing agents in wounds. The Bacterial Nanocellulose (BNC) may come to a complementary treatment for these wounds. Two new complementary treatments with BNC and BNC loaded with nisin were evaluated for wound healing in surgical dehorning in bovine. Hence, two groups of experiments were run, and 12 animals were used in each group. All animals, in right and left horns, received antisepsis treatment. For the first group, the left horn was the control, and on the right one the BNC was applied. For the second group, BNC was applied on the left horn (control) and on the right ones BNC+nisin was applied. In both experiments, wounds were evaluated macroscopically by photographic images and microscopically by histology. For macroscopic evaluations, a significant difference was observed over time, but only in the comparison within the same groups. Microscopic analyzes did not showed significant differences in any type of comparison. In conclusion, there was a clinical improvement in the wound healing response with the application of BNC. However, there was no significant difference between BNC compared to the nisin loaded in BNC. For the first time it was applied a BNC in surgical dehorning wounds in bovines and evaluated the efficacy of treatment in a real animal handling situation.

Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines.

The current concept in searching for new bioactive products, including mainly original active substances with potential application in pharmacy and medicine, is based on compounds with a previously determined structure, well-known properties, and biological activity profile. Nowadays, many commonly used drugs originated from natural sources. Moreover, some natural materials have become the source of leading structures for processing further chemical modifications. Many organic compounds with great therapeutic significance have the nitro group in their structure. Very often, nitro compounds are active substances in many well-known preparations belonging to different groups of medicines that are classified according to their pharmacological potencies. Moreover, the nitro group is part of the chemical structure of veterinary drugs. In this review, we describe many bioactive substances with the nitro group, divided into ten categories, including substances with exciting activity and that are currently undergoing clinical trials.

Sorption and desorption of 17α-trenbolone and trendione on five soils.

The metabolites 17α-trenbolone and 17α-estradiol are principal metabolites in cattle excreta following the administration of Synovex® ONE, which contains trenbolone acetate and estradiol benzoate. As part of the environmental assessment of the use of Synovex ONE, data were generated to characterize the fate of 17α-trenbolone, and its metabolite trendione in the environment. Predictions of the fate and environmental concentrations of these hormones after land application require accurate estimates of the sorption of these compounds in soils. The sorption and desorption of 17α-trenbolone and trendione were measured at 5 nominal concentrations in 5 soils from different geologic settings using a batch equilibrium technique following guideline 106 of the Organisation for Economic Co-operation and Development. Both the sorption and desorption of 17α-trenbolone and trendione to soils were adequately described by the Freundlich sorption model and by linear partition coefficients. The mean sorption coefficients were 9.04 mL/g and 32.2 mL/g for 17α-trenbolone and trendione, respectively. The corresponding mean Freundlich sorption exponents were 0.88 and 0.98, respectively. Sorption of 17α-trenbolone and trendione was correlated principally with soil organic carbon. Average sorption coefficients normalized to soil organic carbon content (KOC ) were 460 mL/g and 1804 mL/g for 17α-trenbolone and trendione, respectively. The mean desorption coefficients were 22.1 mL/g and 43.8 mL/g for 17α-trenbolone and trendione, respectively. Calculated hysteresis coefficients based on the difference in the area between sorption and desorption isotherms indicated that sorption equilibrium was not fully reversible and hysteresis of desorption isotherms occurred for both 17α-trenbolone and trendione. Environ Toxicol Chem 2017;36:613-620. © 2016 SETAC.

Multiresidue determination of veterinary medicines in lyophilized egg albumen with subsequent consumer exposure evaluation.

The process of lyophilization causes that the veterinary drugs residues present in egg albumen do not decompose, as it takes place during the process of high-temperature drying. Thus, lyophilized albumen may be a potential source of their residues for consumers. As a consequence, reliable methods for the determination of veterinary medicinal products from egg albumen are needed. The method for the determination of 85 analytes in lyophilized egg albumen was developed and successfully validated. The recoveries were between 84 and 110%, within laboratory repeatability and reproducibility - in the range of 3.29-16.8% and -5.93 to 19.3%. The presence of enrofloxacin and doxycycline was confirmed in real egg albumen samples. The concentrations ranged from 5.65-596µg/kg for doxycycline to 0.89-134µg/kg for enrofloxacin. Nevertheless, the evaluated daily intake and % of the ADI (Acceptable Daily Intake) received by the consumers' were at a toxicologically accepted level.

Occurrence and transformation of veterinary pharmaceuticals and biocides in manure: a literature review.

The spread of veterinary medicinal products (VMPs) and biocides via manure onto agriculturally used areas represents a very important emission into the environment for these product groups. Within this literature study, publicly available transformation studies with liquid manure are summarized. Transformation studies were evaluated regarding the transformation fate of tested substances, the origin and characteristics of used manure, the experimental setup, and the measured parameters. As main topics within the 42 evaluated transformation studies, the high dependency of transformation on temperature, redox potential, dry matter content, and other parameters is reported. Test duration throughout the studies ranged from 2 to 374 days and study temperature ranged from 5 to 55 °C. Only seven publications gave information on the redox potential of the manure. Further, the characterization of the matrix in many cases was inadequate due to missing parameters such as dry matter content or pH. Only three publications studied transformation of biocides. To allow for a consistent assessment of studies within the registration process, a harmonized internationally accepted and validated test method is needed. Additionally, monitoring data of VMPs in manure were collected from literature and evaluated regarding the origin and characteristics of the manure, the minimum/maximum found concentrations, and the percentage of identified compounds. Within the 27 evaluated publications, 1568 manure samples were analyzed and 39 different active substances for VMPs and 11 metabolites and transformation products of VMPs could be found in manure. Most often, the samples were analyzed for sulfonamides, tetracyclines, and fluoroquinolones. Not one study searched for biocides or worked with a non-target approach. For sulfadiazine and chlortetracycline, concentrations exceeding the predicted environmental concentrations were found.

National monitoring study in Denmark finds increased and critical levels of copper and zinc in arable soils fertilized with pig slurry.

The increasing consumption of copper and zinc in modern farming is linked to their documented benefit as growth promoting agents and usefulness for controlling diarrhoea. Copper and zinc are inert and non-degradable in the slurry and the environment and thereby introducing new challenges and concern. Therefore, a follow-up to pervious national soil monitoring programs on heavy metals was initiated in 2014 with special focus on the historical trends in soil concentrations of copper and zinc in Danish arable soils. Hereby it is possible to analyse trends for a 28 year period. Data shows that: 1) Amendment of soils with pig slurry has led to a significant increase in soil concentrations of copper and zinc, especially in the latest monitoring period from 1998 to 2014; 2) Predicted no-effect concentrations for soil dwelling species published by the European Union is exceeded for zinc in 45% of all soil samples, with the highest proportion on sandy soils; 3) The current use of zinc and copper in pig production may lead to leaching of metals, especially zinc, from fields fertilized with pig slurry in concentrations that may pose a risk to aquatic species.

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.