Part II Environmental Fate and Transformations of Veterinary Pharmaceuticals © 2008 by Taylor & Francis Group, LLC Fate and Transport of in Veterinary Medicines the Soil Environment Alistair B.A Boxall Contents 5.1 Introduction 123 5.2 Inputs of Livestock Medicines to the Environment 124 5.3 Fate of Veterinary Medicines in Soils 125 5.3.1 Sorption in Soil 125 5.3.2 Persistence in Soil 127 5.4 Transport of Veterinary Medicines in Soil Systems 128 5.4.1 Leaching to Groundwater 128 5.4.2 Runoff 129 5.4.3 Drain Flow 129 5.4.4 Uptake into Biota 129 5.5 Modeling Exposure in Soils 131 5.6 Occurrence in the Soil Environment 132 5.7 Conclusion 132 References 134 5.1 INTRODUCTION Veterinary medicines are widely used to treat disease and protect the health of animals Dietary enhancing feed additives (growth promoters) are also incorporated into the feed of animals reared for food in order to improve their growth rates Following administration to a treated animal, medicines are absorbed and in some instances may be metabolized Release of parent veterinary medicines and their metabolites to the environment can then occur both directly, for example, the use of medicines in fish farms, and indirectly, via the application of animal manure (containing excreted products) to land or via direct excretion of residues onto pasture.1–4 Over the past 10 years the scientific community has become increasingly interested in the impacts of veterinary medicines on the environment, and there have been significant developments in the regulatory requirements for the environmental assessment of veterinary products A number of groups of veterinary medicines including sheep dip chemicals, fish farm medicines, anthelmintics, and antibiotics have been well studied in recent years, and a large body of data is now available.5 This chapter 123 © 2008 by Taylor & Francis Group, LLC 124 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems reviews our understanding of the inputs of livestock medicines to the environment and synthesizes the available information on the fate and transport of veterinary pharmaceuticals in manure and soils Toward the end of this chapter, gaps in the current knowledge are highlighted and recommendations are made for future research 5.2 INPUTS OF LIVESTOCK MEDICINES TO THE ENVIRONMENT Large quantities of animal health products are used in agriculture to improve animal care and increase production Some drugs used in livestock production are poorly absorbed by the gut, and the parent compound or metabolites are known to be excreted in the feces or urine, irrespective of the method of application.6–11 The main routes of input to the soil environment and subsequent transport routes are illustrated in Figure 5.1 During livestock production, veterinary drugs enter the environment through removal and subsequent disposal of waste material (including manure/slurry and “dirty” waters), via excretion of feces and urine by grazing animals, through spillage during external application, via washoff from farmyard hard surfaces, or by direct exposure/discharge to the environment For hormones, antibiotics, and other pharmaceutical agents administered either orally or by injection to animals, the major route of entry of the product into the environment is probably via excretion following use and the subsequent disposal of contaminated manure onto land.12 Many intensively reared farm animals are housed indoors for long periods at a time Consequently, large quantities of farmyard manure, slurry, or litter are produced, which are then disposed of at high application rates onto land.13 Although each class of livestock production has different housing and manure production characteristics, the emission and distribution routes for veterinary medicines are essentially similar Manure or slurry will typically be stored before it is applied to land During this storage time it is possible that residues of veterinary medicines will be degraded A number of studies have therefore explored the Intensively Reared Dirty Water Pasture Manure Storage Soil Degradation Degradates Leaching Groundwater Runoff or Drainflow Surface Water Biota FIGURE 5.1 Input routes and fate and transport pathways for veterinary medicines in the soil environment © 2008 by Taylor & Francis Group, LLC Fate and Transport of Veterinary Medicines in the Soil Environment 125 persistence of a range of veterinary substances in different manure/slurry types.14–17 For example, macrolides and -lactam antibiotics have been shown to be rapidly degraded in a range of manure types, whereas avermectins and tetracyclines are likely to persist for months Available data indicate that the dissipation of veterinary medicines in manure or slurry can be very different from the dissipation behavior in soils.14 One possible explanation is that the mechanism of degradation in manure and slurry stores is anaerobic, whereas degradation in soils is most likely due to aerobic organisms Drugs administered to grazing animals may be deposited directly to land or surface water through dung or urine, exposing soil organisms to high local concentrations.6,13,18–20 Another significant route for environmental contamination is the release of substances used in topical applications Various substances are used externally on animals and poultry for the treatment of external or internal parasites and infection Sheep in particular suffer from a number of external insect parasites for which treatment and protection is sometimes obligatory The main methods of external treatment include plunge dipping, pour-on formulations, and the use of showers or jetters With all externally applied veterinary medicines, both diffuse and point source pollution can occur Sheep dipping activities provide several routes for environmental contamination In dipping practice, chemicals may enter watercourses through inappropriate disposal of used dip, leakage of used dip from dipping installations, and from excess dip draining from treated animals Current disposal practices rely heavily on spreading used dip onto land Wash-off of chemicals from the fleeces of recently treated animals to soil, water, and hard surfaces may occur on the farm, during transport, or at stock markets Medicines washed off, excreted, or spilt onto farmyard hardsurfaces (e.g., concrete) may be washed off to surface waters during periods of rainfall 5.3 FATE OF VETERINARY MEDICINES IN SOILS Once a veterinary medicine is released to the environment, its behavior will be determined by its underlying physical properties (including water solubility, lipophilicity, volatility, and sorption potential) In the following sections information on the fate and transport of veterinary medicines in the soil environment is reviewed 5.3.1 SORPTION IN SOIL Data are available on the sorption behavior of antibiotics, sheep dip chemicals, and avermectins in soils (Table 5.1) The degree to which veterinary medicines may adsorb to particulates varies widely Consequently, the mobility of different veterinary medicinal products also varies widely Chapter and Chapter in this book discuss sorption and mobility of selected veterinary pharmaceuticals in more detail Available data indicate that sulfonamide antibiotics and organophosphate parasiticides will be mobile in the environment, whereas tetracycline, macrolide, and fluoroquinolone antibiotics will exhibit low mobility The variation in partitioning for a given compound in different soils can be significant and cannot be explained by variations in soil organic carbon For instance, the maximum reported organic© 2008 by Taylor & Francis Group, LLC 126 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems TABLE 5.1 Measured Sorption Coefficients (Koc) for a Range of Veterinary Medicines Mean Avermectin Chlorfenvinphos Ciprofloxacin Enrofloxacin Cumaphos Deltamethrin Diazinon Fenbendazole Metronidazole Ofloxacin Olaquindox Oxytetracycline Sulfamethazine Tetracycline Tylosin Carbadox Sulfamethoxazole Sulfadiazine Sulfapyridine Sulfachloropyridazine Sulfadimethixine Minimum Maximum 17650 295 5300 — 30000 — 61000 392623 13449 8380000 889 815.5 47 44143 81 60554 60 40000 4270.5 8508.5 296.1 125 219 75.5 144 — 16506 5778 460000 229 631 38 — 46 27792 — — 553 184 62.2 — — 69 — — 768740 21120 16300000 1549 1000 56 — 116 93317 — — 7988 16833 530 — — 82 — (Data taken from review of Boxall et al.40 With permission.) carbon normalized sorption coefficient for carbadox is approximately two orders of magnitude greater than the lowest reported value These large differences in sorption behavior are explained by the fact that many veterinary medicines are ionizable with pKa values in the pH range of natural soils Medicines can therefore occur in the environment as negative, neutral, zwitterionic, and positively charged species.21,22 Depending on the species, interactions with soil can occur through electrostatic attraction, surface bridging, hydrogen bonding, or hydrophobic interactions.22 The sorption behavior is also influenced by the properties of the soil, including pH, organic carbon content, metal oxide content, ionic strength, and cation-cation exchange capacity.22–25 The complexity of the sorbate-sorbent interactions means that modelling approaches developed for predicting the sorption of other groups of chemicals (e.g., pesticides and neutral organics) are inappropriate for use on veterinary medicines (Figure 5.2) Manure and slurry may also alter the behavior and transport of medicines Recent studies have demonstrated that the addition of these matrices can affect the sorption behavior of veterinary medicines and that they may © 2008 by Taylor & Francis Group, LLC Fate and Transport of Veterinary Medicines in the Soil Environment 127 log Koc (experimental) 0 log Koc (predicted) FIGURE 5.2 Relationship between measured and predicted soil sorption coefficients for a range of veterinary medicine classes Koc predictions were obtained using the Syracuse Research Corporation PCKOC program affect persistence.26,27 These effects have been attributed to changes in pH or the nature of dissolved organic carbon in the soil/manure system 5.3.2 PERSISTENCE IN SOIL The main route for degradation of veterinary medicines in soils is via aerobic soil biodegradation Degradation rates in soil vary, with half-lives ranging from days to years Degradation of veterinary medicines is affected by environmental conditions such as temperature and pH and the presence of specific degrading bacteria that have developed to degrade groups of medicines.28,29 As well as varying significantly between chemical classes, degradation rates for veterinary medicines also vary within a chemical class For instance, of the quinolones, olaquindox can be considered to be only slightly persistent (half-life to days), while danofloxacin is very persistent (half-life 87 to 143 days) In addition, published data for some individual compounds show persistence varies according to soil type and conditions For example, diazinon was shown to be relatively impersistent (half-life 1.7 days) in a flooded soil that had been previously treated with the compound, but was reported to be very persistent in sandy soils (half-life 88 to 112 days).5 Of the available data, coumaphos and emamectin benzoate were the most persistent compounds in soil, with half-lives of 300 and 427 days, respectively, while tylosin and dichlorvos were the least persistent with half-lives of to and 2000 mg kg–1) Kumar et al.50 showed uptake of chlortetracycline from manure amended soils into corn (Zea mays L.), green onion (Allium cepa L.), and cabbage (Brassica oleracea L.) Tylosin was not taken up by the three crops Chapter of this book presents the results of a study investigating plant uptake of pharmaceuticals, while Chapter provides evidence of detoxification of antibiotics by plant-derived enzymes It is generally recognized that chemicals are taken up into plants via the soil pore water Data for pesticides and neutral organic substances show that root uptake of organic chemicals from soil water is typically related to the octanol-water partition coefficient of the compound.54,55 Uptake of chemicals by roots is greatest for more lipophilic compounds, whereas polar compounds are accumulated to a lesser extent.54 Studies of translocation of pesticides into shoots indicate that uptake into shoots (and, hence, aboveground plant material) is related to Log Kow by a Gaussian curve distribution.54,55 Maximum translocation is observed at a Log Kow around 1.8 More polar compounds are taken up less well by shoots, and uptake of highly lipophilic compounds (Log Kow>4.5) is low The available data indicate that these relationships may not hold true for veterinary medicines.51 This is perhaps not surprising as data for other environmental processes (e.g., sorption to soil) indicate that the behavior of veterinary medicines in the environment is poorly related to hydrophobicity but is determined by a range of factors, including H-bonding potential, cation © 2008 by Taylor & Francis Group, LLC Fate and Transport of Veterinary Medicines in the Soil Environment 131 exchange, cation bridging at clay surfaces, and complexation Through controlled experimental studies it may be possible in the future to begin to understand those factors and processes affecting the uptake of veterinary medicines into plants and to develop modelling approaches for predicting uptake 5.5 MODELING EXPOSURE IN SOILS From the information provided above it is clear that the behavior of veterinary medicines in the environment is complex and depends on a range of chemical properties and environmental processes In order to support the environmental risk assessment process for veterinary medicines, a number of approaches have therefore been developed for predicting concentrations of veterinary medicines in soil and the potential for a medicine to be transported to groundwaters and surface waters.13,56 These models incorporate many of the fate processes described above and will typically require data on sorption and persistence as input values Some of the approaches are described below In order to harmonize the environmental assessments of veterinary products, the European Federation for Animal Health (FEDESA now IFAH Europe) developed a uniform scheme for calculating predicted environmental concentrations of veterinary medicines in soil following spreading of manure from treated animals.56 The scheme provides a sequence of standard equations and a database containing information on three major agricultural species: cattle, pigs, and poultry The database also contains information on the agricultural practices and relevant regulations for various regions within the EU Inputs to the model are the dose and treatment regime If information is available on metabolism or degradation, this can be incorporated into the calculation The model calculated the concentration of the veterinary medicine in animal manure and then uses the nitrogen content of the manure and the maximum spreading rate of manure nitrogen onto land to calculate the maximum quantity of veterinary medicine applied per hectare The output from the model is a predicted soil concentration Since the introduction of this model there have been a number of minor modifications and amendments introduced, but the basic premise is that the predicted environmental concentration (PEC) depends on the nitrogen content of the manure and the maximum application rate to land The ETox models developed by Montforts13 predicts concentrations of veterinary medicines using scenarios that are specific to agricultural practices in the Netherlands The model is more complex than the uniform approach and can be used for medicines that are given internally (e.g., oral and injection treatments) or medicines applied externally (e.g., udder disinfection treatments) A range of input pathways are considered (i.e., direct excretion of dung and urine onto a field, spreading of manure and slurry, and direct spillage onto a field) The following groups of organisms are considered: cows (milk cows, suckling cows, beef cows), pigs (fattening pigs, sows), and poultry (hens, broilers, and turkeys) The outputs from the model include concentrations of the veterinary drug in soil, groundwater, surface waters, and biota VetCalc estimates PEC values for soil, groundwater, and surface water for 12 predefined scenarios that were chosen on the basis of the size and importance of their livestock production and its diversity, the range of agricultural practice covered © 2008 by Taylor & Francis Group, LLC 132 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems by the scenarios, and the desire to cover three different European climate zones (Mediterranean, Central, and Continental Scandinavian) Each of the scenarios has been ranked in terms of its importance as a scenario for each livestock species Background information on key drivers for exposure such as treatment regimes (both body weight and nonbody weight related), animal characteristics and husbandry practices, manure characteristics and management regimes, environmental characteristics (soil, hydrology, weather), agricultural practices, and chemical parameters are provided within the model databases 5.6 OCCURRENCE IN THE SOIL ENVIRONMENT In recent years a number of studies have begun to explore the occurrence of veterinary medicines in the soil environment resulting from normal agricultural practices.57–59 These studies have focused on antibacterial medicines and some parasiticides (Table 5.2) Selected studies have explored the distribution of medicines in the soil profile as well as the persistence over time While some groups of substances have not been detected in soils (e.g., the macrolides and fluoroquinolones), some classes have been detected at concentrations of tens to hundreds of µg kg–1 (Table 5.2) In some cases the compounds will persist in the soil for prolonged time periods These differences can usually be explained by the laboratory persistence data and usage and treatment scenarios for the different medicines The availability of real-world monitoring data allows us to evaluate the performance of the exposure models described previously Generally, these exposure models will overpredict concentrations of a veterinary medicine in the environment (Figure 5.4) by a number of orders of magnitude The reason for this is that the scenarios used in the models are highly conservative and that adequate data are not always available to describe the different dissipation processes that determine how much of a medicine will reach the soil 5.7 CONCLUSION This paper has reviewed the data available in the public domain on the pathways of veterinary medicines to the soil environment and their subsequent fate and transport There is clearly a large body of data available on veterinary medicines in the soil environment, and it is timely to begin to further synthesize this information in order to provide a general understanding of the fate and transport of medicines in the soil environment and to develop approaches for predicting how a substance will behave in the soil environment There are, however, still gaps in the data and in our understanding Those gaps are outlined in the following paragraphs Researchers are still focusing on only a small proportion of the medicines in use (including the avermectins, tetracyclines, sulfonamides, macrolides, and fluoroquinolones) There are many more classes of medicines in use, so it would be worthwhile to prioritize these and begin to develop an understanding of the fate (and effects) of some of the more important classes in the environment A large body of data is now available on the effects of the manure matrix on fate and transport, and there is evidence that these matrices can affect transport at the © 2008 by Taylor & Francis Group, LLC Fate and Transport of Veterinary Medicines in the Soil Environment 133 TABLE 5.2 Environmental Monitoring Data for Veterinary Medicines in Agricultural Soils Compound Therapeutic Use Chlortetracycline Antibiotic Ciprofloxacin Enrofloxacin Ivermectin Antibiotic Antibiotic Endectocide Lincomycin Antibiotic Monensin Oxytetracycline Coccidiostat Antibiotic Sulfadiazine Sulfadimidine Sulfamethazine Tetracycline Antibiotic Antibiotic Antibiotic Antibiotic Tilmicosin Trimethoprim Tylosin Antibiotic Antibiotic Antibiotic Concentration Detected (µg kg-1) LOD (µg kg-1) Country Reference 9.5 0.7 Germany 42 26.4 41.8 39 nd nd 46 98.5 1 — 1 10.2 Germany Germany Germany US UK UK US, UK — 1.26 — 0.7 — — — — 0.5 0.7 11 — US UK Canada Germany US Italy UK UK Germany Germany Germany Germany Germany Germany US US UK Germany US Italy 42 42 37 58 48 48 58 48 59 48 61 42 59 57 48 48 60 37 42 42 42 37 59 59 48 42 59 57 1.08 8.6 254 305 0.8 15 12.3 32.2 39.6 295