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Veterinary Drugs in the Environment: Current Knowledge and Challenges for the Future Gerd Hamscher* and Ghada Bachour Institute of Food Chemistry and Food Biotechnology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 17, D-35392 Gießen, Germany In this context, the anaerobic fermentation process was demonstrated for an efficient elimination of various veterinary drugs, including chlortetracycline, colistin, and various βlactames. However, the frequently used term “elimination” may not reflect quantitative molecular aspects in an environmental matrix and cannot be equated with “degradation”. The latter requires the identification of degradation products and the preparation of a mass balance. “Elimination” may include degradation or transformation as well as sorption. Many compounds, including fluoroquinolones, sulfonamides, and tetracyclines, are well-known to be difficult to extract from environmental samples as a result of strong sorption to organic or inorganic matrix compounds. In addition, biotic or abiotic transformation to structurally closely related compounds may result in similar or even more toxic effects when compared to the parent drug. Therefore, comprehensive laboratory and field studies must be accompanied by sophisticated analytical methods, including the structural elucidation and, subsequently, uman and veterinary drugs have been demonstrated as the quantitative detection of metabolites and/or transformation ubiquitously occurring persistent contaminants in the products.2 environment. Substance classes with an established environAnother important point for the study design may be mental impact include antibiotics, antiparasitic agents, and illustrated by very recent work.3 Field and lysimeter studies hormones. Specific health issues arise from the heavy use of demonstrated that, although sulfamethazine was not applied for antibiotics in human as well as veterinary medicine. In this several years to agricultural soils, very low concentrations (ng/ context, the development and spread of antimicrobial resistance L) of the compound were transferred over years to groundwere recognized by the G7 Partners in 2015 as a challenging water. Thus, veterinary drugs, similar to various pesticides, may global health problem [see also Berlin Declaration on be present in the environment even years after their application. Antimicrobial Resistance: A Global Union for Antibiotics Research Considering recent work establishing threshold values for the and Development (GUARD)]. Following the one health induction of antibiotic resistance, even these amounts far below approach, besides human and animal health, also agricultural microbial inhibition concentrations may have an impact on the and environmental effects have to be considered. formation of antimicrobial resistance in the environment.4 For hundreds of years, liquid manure and other animal What are the main implications for future measures in wastes from livestock farming have been applied to agricultural veterinary medicine and research in agricultural and environfields as a sustainable principle of nutrient recycling. As a result mental chemistry? of a poor metabolism in farm animals, more than 50% of the It is far obvious that there is an urgent need for a reduction of the overuse of antibiotics in livestock farming. Thus, to applied drugs finally reach via manure application the soil minimize the entry of veterinary drugs into the environment, a compartment. Here, highly complex reactions take place, number of efforts in various fields must be taken into account. including sorption, transport, and degradation processes. All First, the use of veterinary drugs in livestock farming should together, this makes predictions regarding the environmental be strictly reduced to therapeutic use only. To reach this goal, behavior of a drug extremely difficult. Furthermore, the transfer preconditions, such as the use of healthy feed and the of veterinary drugs into groundwater and in plants has already prevention of infection, are elementary. Strict regulatory rules been described for many compounds. In addition, the cofor the use of veterinary drugs worldwide are essential, to occurrence of antibiotics and resistant bacterial strains in the support a sustainable livestock production in the future. stable dust of pig confinement buildings can lead to the Second, pretreatment of liquid manure, e.g., with passive inhalation of a dangerous “bio-cocktail” by animals and last but 1 storage and/or fermentation procedures before field fertilizanot least farmers. In the current research, there were various biotechnological procedures regarding a reduction of the environmental loads of Received: November 28, 2017 veterinary antibiotics in the environment under consideration.
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© XXXX American Chemical Society
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DOI: 10.1021/acs.jafc.7b05601 J. Agric. Food Chem. XXXX, XXX, XXX−XXX
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Journal of Agricultural and Food Chemistry tion, does not lead to a complete degradation of all drugs applied. However, a stronger sorption of veterinary drugs to fermentation residues may at least lead to a reduced bioavailability after applying these fertilizers to the soil. There are big knowledge gaps, e.g., which microbiological strains, additives, and/or enzyme preparations might be helpful to enforce this process. Third, the development of new drug formulations can lead to lower emissions into the stable dust and a lower exposition of farm animals, farmers, and veterinarians can be obtained.5 Further research in this area is highly recommended, because new formulations may additionally lead to lower amounts of drugs in the pharmaceutical product as a result of better bioavailability. Fourth, as a result of the very large number of registered pharmaceuticals and their corresponding metabolites, there will be an evident need to address efforts toward additional and more developed analytical methods for the detection and qualification of these compounds. Furthermore, in all future monitoring, field, and laboratories studies, metabolites and/or transformation products must be considered to reveal a complete picture about the biotechnological or environmental fate of a veterinary drug. Whenever possible, microbiological and toxicological assays should be employed to characterize biological (rest) activities of all compounds under investigation. Furthermore, the common quantitative monitoring of antibiotic resistance genes will help to demonstrate that a reduced entry of antibiotic residues will also restrict the spread of antibiotic resistance.
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AUTHOR INFORMATION
Corresponding Author
*Telephone: +49-641-99-34950. Fax: +49-641-99-34909. Email:
[email protected]. ORCID
Gerd Hamscher: 0000-0002-5137-5510 Funding
The authors thank the Alexander von Humboldt Foundation and the German Federal Environmental Foundation (Deutsche Bundesstiftung Umwelt, Grant 32732/01-31) for funding. Notes
The authors declare no competing financial interest.
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REFERENCES
(1) Schulz, J.; Ruddat, I.; Hartung, J.; Hamscher, G.; Kemper, N.; Ewers, C. Antimicrobial-resistant Escherichia coli survived in dust samples more than 20 years. Front. Microbiol. 2015, 7, 866. (2) Wohde, M.; Berkner, S.; Junker, T.; Konradi, S.; Schwarz, L.; Dü r ing, R. A. Occurrence and transformation of veterinary pharmaceuticals and biocides in manure: A literature review. Environ. Sci. Eur. 2016, 28, 23. (3) Spielmeyer, A.; Höper, H.; Hamscher, G. Long-term monitoring of sulfonamide leaching from manure amended soil into groundwater. Chemosphere 2017, 177, 232−238. (4) Gullberg, E.; Cao, S.; Berg, O. G.; Ilback, C.; Sandegren, L.; Hughes, D.; Andersson, D. I. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 2011, 7, e1002158. (5) Stahl, J.; Zessel, K.; Schulz, J.; Finke, J. H.; Müller-Goymann, C. C.; Kietzmann, M. The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings. BMC Vet. Res. 2016, 12, 68.
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DOI: 10.1021/acs.jafc.7b05601 J. Agric. Food Chem. XXXX, XXX, XXX−XXX
