Proposal Antibiotics 1206

download Proposal Antibiotics 1206

of 15

Transcript of Proposal Antibiotics 1206

  • 8/2/2019 Proposal Antibiotics 1206

    1/15

    1

    M.S. THESIS PROPOSAL

    OFARIN KKDOAN

    MODELLING ANTIBIOTIC TRANSPORT

    AND MAPPING THE ENVIRONMENTAL

    RISK IN THE MARMARA REGION BY

    USING GEOGRAPHICAL INFORMATION

    SYSTEMS (GIS)

    Boazii University

    Bebek-stanbul

  • 8/2/2019 Proposal Antibiotics 1206

    2/15

    2

    1. INTRODUCTION

    As human population increases, livestock farming has become more intensive for some

    decades (Venglovsky et al., 2009). Veterinary antibiotics (VAs), one type of the drugs

    approved for agriculture, are among the most widely preferred for animal health and

    management (Sarmah et al., 2006). A considerable quantity of VAs originates from increased

    number of large-scale animal feeding operations for swine, poultry, and cattle (Zhao et al.,

    2010). Antibiotics regarded as micropollutants affect both water quality and human health by

    transportation to surface waters via runoff. Thus, there has been an increased concern about

    the adverse effects of released antibiotics causing chemical pollution in the environment.

    The primary objective of this proposed study is to investigate the transport of tetracycline,

    sulphonamide andfluoroquinolone antibiotic groups, which were analyzed in the soil samples

    collected from the Marmara region by using Geographic Information Systems (GIS) and

    modelling techniques. Moreover, the environmental risk of agricultural antibiotic runoff in the

    Marmara region will be mapped.

    2. LITERATURE REVIEW

    Antibiotics have been used for treating infectious diseases in animals since 1900s. In addition

    to therapeutic purposes, they are used for promotion of food animal growth, control and

    prevention of diseases. The antibiotic dosages vary from 3 to 220 g/Mg of feed according to

    animal type, size and growth stage. As can be seen from Table 1., animals utilize certain

    proportion of these dosages and rest of them enter the terrestrial environment as urine, faeces

    or manure excreted by them because they are poorly absorbed in the animal gut (Kumar et al.,

    2005).

    Table 1. Pro ortion of Antibiotics Fed Excreted in Urine and Feces Kumar et al. 2005

  • 8/2/2019 Proposal Antibiotics 1206

    3/15

    3

    The treatment of animals on pasture is direct release of veterinary antibiotics to environment.

    The most important indirect reason for contamination of water bodies such as rivers and lakes

    is surface runoff of manure applied to lands as soil fertilizer since many of antibiotics cannot

    be degraded in the manure (Lertpaitoonpan et al., 2009). Furthermore, manure is stored in the

    tanks systems for a period of time before dispersing on fields which may cause leaching

    through soil (Kim et al., 2010). Fresh manure production varies according to animal type and

    data on livestock manure production can be presented as Table-2.

    Table 2. Fresh manure production per 1000 lb live animal mass per day

    (ASAE Standards, 2003)

    Animal Type

    Parameter Units *

    Da

    iry

    Be

    ef

    Ve

    al

    Sw

    ine

    Sh

    eep

    Goat

    Ho

    rse

    Layer

    Br

    oiler

    Tu

    rkey

    Total Manure lb Mean 86 58 62 84 40 41 51 64 85 47

    Differences within species according to usage exist, but sufficient fresh manure data to list these differences was

    not found. Typical live animal masses for which manure values represent are: dairy, 1400 lb; beef, 800 lb; veal, 200

    lb; swine, 135 lb; sheep, 60 lb; goat, 140 lb; horse, 1000 lb; layer, 4 lb; broiler, 2 lb; turkey, 15 lb; and duck, 3 lb.

    * All values wet basis

    Feces and urine as voided.

    Parameter means within each animal species are comprised of varying populations of data. Maximum numbers of

    data points for each species are: dairy, 85; beef, 50; veal, 5; swine, 58; sheep, 39; goat, 3; horse, 31; layer, 74;

    broiler, 14; turkey, 18; and duck, 6.

    If application of manure to agricultural lands exceeds recommended values, antibiotics bring

    about significant environmental problems such as toxicity to soil flora and fauna also

    antibiotic resistance in aquatic and terrestrial environment (Sarmah et al., 2006). Liu et al.

    (2009) carried out seed germination test on filter paper and plant growth test in soil, soil

    respiration and phosphatase activity tests to evaluate phytotoxic efects of different types of

    antibiotics on plant growth and soil quality. The authors realized that these effects change

    depending on the antibiotic type and plant sensitivity. Venglovsky et al. (2009) observed that

    antibiotics which are strongly bound to soil and have low half-life value can remain in the soil

    longer than others. Thus, they have a chance to be degraded easily so contamination of

    surface water can be prevented. However, they insisted on that there was a concern for plants

    which could take up them. Another important drawback of antibiotics is occurrence of

    antibiotic resistance bacteria in terrestrial and aquatic media leading to untreatable human and

    animal diseases due to subsequent antibiotic ineffectiveness (Kim et al., 2010). Jorgensen and

    Halling-Sorensen (2000) have suggested that antibiotic resistant bacteria originate from

    excessive production and consumption of antibiotics and low concentrations are responsible

  • 8/2/2019 Proposal Antibiotics 1206

    4/15

    4

    for this problem. More harmful bacteria come into existence so gene pool of microorganisms

    changes. Such kind of bacteria are irreversible also cannot be eliminated (Kumar et al., 2005).

    In order to protect the environment, the marketing of veterinary medicinal products is actively

    regulated in the European Union (EU) by Directive 2004/28/EC (Montforts, 2006). Moreover

    the antibiotics used for growth-promoting purposes were banned in Europe in 2006 (Kemper,

    2008).

    Several factors can affect the transportation of VAs in the environment. In addition to

    antibiotic and soil properties; weather and surface water flow conditions affect transport

    behaviour in terrestrial environments (Kumar et al., 2005). Kay et al. (2005) carried out some

    pilot studies to evaluate the transport of veterinary antibiotics in overland flow following the

    application of pig slurry to arable land by irrigating soil pilots. Some antibiotic types are

    detected in runoff samples greater than the others because they have lower organic carbon-

    water partitioning coefficient value.

    Davis et al. (2006) conducted some rainfall simulation experiments for various types of

    antibiotics. After spraying soil surface with a solution containing antibiotics, runoff samples

    are collected and analyzed for aqueous and sediment antibiotic concentrations. They realized

    significant differences in two phases of antibiotic concentrations due to different pseudo-

    partitioning coefficients (P-PC; ratio of sediment concentration to runoff concentration) of

    them. They stated that erosion control practices could be used to decrease agricultural runoff

    of antibiotics with high P-PC. Similarly, Kim et al. (2010) carried out rainfall simulated

    studies to evaluate the impact of different physicochemical properties of antibiotics on

    transport of them. They found that sorption and persistence characteristics of various

    antibiotics play role on runoff behaviour of aqueous and sediment phases of them.

    Boxall et al. (2002) investigated the sorption behaviour of sulphonamide,

    sulfachloropyridazine by performing field and laboratory studies to assess the risk of surface

    water contamination. They found that sulfachloropyridazine is highly mobile in clay sites

    thereby it would easily be transported to surface waters due to its low sorption potential. In

    addition to sulphonamides, Blackwell et al. (2007) investigated surface run-off of

    tetracyclines and macrolides antibiotic groups originating from pig slurry in sandy loam soil

    under field conditions. They realize that manure management practices, the nature of the landand climate conditions play role in mass loss in runoff.

  • 8/2/2019 Proposal Antibiotics 1206

    5/15

    5

    Fate and transport processes of pollutants are important to evaluate environmental effects on

    the subsurface and surface waters since they facilitate the understanding of mobility and

    degradation processes of pollutants to control environmental pollution and develop water

    management practices (Joyce et al., 2010). Thanks to modelling, contamination pathways and

    sources of pollutant contamination in the landscape are identified thereby pollutant

    concentrations are estimated at any point to assess the pollutant mitigation strategies to protect

    water resources from contamination (Blenkinsop et al., 2008).

    There are many models different from one another in terms of representing hydrological

    processes and objectives. They can simulate surface runoff pollution or leaching of pollutants

    through subsurface (Branger et al., 2009). Basically, models can be categorized into two

    classes: analytical and numerical models. In analytical modelling, there is few input data since

    more assumptions are done to simply the initial and boundary conditions, flow conditions,

    porous media, as well as physical and (bio)chemical processes of the simulated pollutants.

    Therefore analytical models are easy to use and compute. On the other hand, numerical

    models can overcome more complex contaminant transport issues (Chu and Marino, 2007).

    However, they require more input data and limited availability of input data sometimes hinder

    mathematical models (Schriever and Liess, 2007).

    The models studied in the literature for evaluating pesticide transport in surface runoff are

    plentiful. On the other hand, modeling studies for antibiotics are scarce. Kay et al. (2005) state

    the fact that a number of models such as PRZM, PELMO and GLEAMS recommended by

    FOCUS (FOrum for the Co-ordination of pesticide fate models and their USe) could be used

    for veterinary medicines since their physicochemical properties is similar to that of pesticides.

    Huber et al. (1998) developed a transport model for pesticide runoff from agricultural areas to

    surface waters in Germany. They used various spatial data related to climate, soil, and land

    use in addition to pesticide application rates to estimate runoff losses of pesticides from fields.

    As a result, they constituted runoff-susceptibility maps to determine the risk of runoff-losses

    of pesticides. However, inadequate reliable information regarding pesticide transport

    behaviour under site specific conditions caused limitation in the study.

    Branger et al. (2009) developed a transport model namely PESTDRAIN to simulate pesticide

    transport in a subsurface tile-drained field. This model as a promising tool for agricultural

  • 8/2/2019 Proposal Antibiotics 1206

    6/15

  • 8/2/2019 Proposal Antibiotics 1206

    7/15

    7

    3. METHODOLOGY

    An antibiotic transport model will be developed for the Marmara Region by using

    Geographical Information Systems (GIS). GIS based maps and data system including land

    use, land cover and antibiotic concentration obtained from previously analyzed in 30 soil and

    8 manure samples will be used for creation of a conceptual model. In order to set up equations

    used in hydrologic (rainfall-runoff) and hydrodynamic (pollutant transport) models, the

    transport processes taking place in the model will be identified. ModelBuilder function

    embedded in ArcGIS will be worked to turn conceptual model into GIS-based simulation

    transport model. Thanks to establishment of spatially explicit calculation based on antibiotic

    use, precipitation, topography, land use and cover, the environmental risk of antibiotics in the

    Marmara region will be mapped.

    3.1. Site Description

    Marmara region is located in the northwest part of Turkey having approximately an area of

    67,000 square kilometres and a total of more than 23 million people because of relatively high

    immigration (Doan et al., 2007). In the region; industry, commerce, tourism and agriculture

    have developed. Among the seven geographical regions, the region has lowest elevation.

    Whereas the planted area accounts for 30 % of the region, the forests cover around 11.5 % of

    the entire region. Forests are found in particularly Trakya region at high elevations. Wheat

    forms more or less half of the cultivated areas and rest of these areas consists of mainly sugar

    beets, corn and sunflower. Poultry raising and silk culture are widespread. Throughout the

    region, there is a dense stream network despite its small scale. The main rivers are Sakarya,

    Ergene, Susurluk, Meri and Biga. There are also many large and small natural and artificial

    lakes such as Bykekmece, Kkekmece, Durusu, znik, Sapanca, Uluabat and Manyas.

    The effects of black sea, terrestrial and mediterranean climates prevail in the region. The

    annual precipitation is between 500 and 1000 mm. Since terrestrial climate increases towards

    upcountry, the cold effect takes place rather than coastal zone

    (http://tr.wikipedia.org/wiki/Marmara_B%C3%B6lgesi). In Fig. 1, the study area, sampling

    locations and precipitation stations are showed by means of ArcGIS.

    http://tr.wikipedia.org/wiki/Biga_%C3%87ay%C4%B1http://tr.wikipedia.org/wiki/Marmara_B%C3%B6lgesihttp://tr.wikipedia.org/wiki/Marmara_B%C3%B6lgesihttp://tr.wikipedia.org/wiki/Biga_%C3%87ay%C4%B1
  • 8/2/2019 Proposal Antibiotics 1206

    8/15

    8

    Fig.

    1.

    Mapofthestudyarea,

    samplinglocationsandprecipitationstations

  • 8/2/2019 Proposal Antibiotics 1206

    9/15

    9

    3.2. Modelling Antibiotic Transport

    3.2.1. GIS as a tool

    In order to modelling the antibiotic transport in Marmara region, a GIS-based model will be

    formulated. Geo-statistics methods will be used to build the relationship between the data

    available and the data be obtained from GIS-based maps. In the first part of modelling study;

    as can be summarized by Fig. 2, the aim of this study is to develop a conceptual model

    including physical and logical components. The processes taking place in this conceptual

    model will be brought into functional mode by using ModelBuilder component available in

    the GIS software and the model will be worked.

    Fig. 2: Antibiotic Application

    The use of Model Builder enables following operations:

    The results of model are monitored through ArcMap or ArcCatalog, Model simulates for variable parameters by changing parameter values, Desired number of data are added, Undesired process and data are removed.

    3.2.2. Data Requirements

    One of the most effective factors in the case of hydrological characterization of catchments is

    to determine flow direction. Catchments are identified on the base of cells by means of

    ArcGIS program scan pattern. Elevation and slope data are used with Flow Direction

    function available in ArcGIS. As a result, cellular based flow direction data will be obtained

    for all catchment.

  • 8/2/2019 Proposal Antibiotics 1206

    10/15

    10

    Since precipitation quantity is used as input data in the study, first step is to convert

    precipitation into over-flow that calls as Rainfall-Runoff Modelling. In accordance with this

    purpose, Spatial Analyst component of ArcGIS software will be used. In addition to annual

    precipitation data, flow coefficients obtained from field and land use data belonging to

    subcatchments will be used to compute over-flow quantities originating from precipitation.

    Spatial analyst component will be used also for pollutant transport process which depends

    upon over-flow. This process will be identified as following equation:

    Runoff = Subcatchment Area x Annual Precipitation Quantity x Runoff Coefficient

    All these steps create the conceptual model which can be illustrated as Fig. 3.

    Fig. 3: Conceptual Model

    For the pollutant transport process depending upon surface flow planned to be modelled,

    Spatial Analyst and/or Particle Tracking tool taking place in Spatial Analyst will be used.

    Model will use flow quantity found in previous stage and the concentrations determined for

    each pollutant parameter. By doing this, the model will calculate pollutant load through

    empirical methods for any catchment. Following equation will be used for this purpose:

    Pollutant Load = Run-off x Estimated Mean Concentration (EMC)

    Urine and faeces originating from animal excretion is responsible of antibiotic concentration

    in soil. Due to antibiotics are poorly absorbed in the animal gut, residues can leach from dunginto soil. Highest concentration in soil is calculated as following equation (Montforts, 1999):

    (2)

    (1)

  • 8/2/2019 Proposal Antibiotics 1206

    11/15

    11

    InputQproduct: dosage product used [kg.kg bw

    -1.d

    -1] S

    Cc: concentration a.i. in product [mgc.kg-1

    ] S

    manimal: (averaged) body weight [kgbw.animal-1

    ] P

    Ttreatment: duration of treatment [d] D

    Fexcreted urine: fraction excreted in urine [-] S/D

    Nanimalfield: stocking density animals [animal.ha-1

    ] P

    RHOsoil: dry bulk density of soil [kg.m-3

    ] Dc

    DEPTHfield: mixing depth with soil [m] Dc

    CONVareafield: conversion factor for the area of the field [m2.ha

    -1] D

    c

    RHOsoliddung: density of dung solids [kg.m-3] DcRHOwater: density of water [kg.m

    -3] D

    c

    Fwaterdung: fraction water in dung [m3.m

    -3] P

    Fsoliddung: fraction solids in dung [m3.m

    -3] P

    Focdung: weight fraction of fraction organic carbon in dung [kg.kg-1

    ] Dc

    Koc: partition coefficient organic carbon - water [dm3.kg

    -1] S/O

    Intermediate Results

    Qexcreted urine: quantity a.i. excreted with urine [mgc.animal-1

    ] O

    Qleached dung: quantity a.i. leached with dung [mgc.animal-1

    ] O

    Fexcreted dung: fraction excreted in dung [-] O/SFleached dung: fraction leached from dung [-] O

    Kdung-water: partition coefficient solids and water in dung [m3.m

    -3] O

    Kpdung: partition coefficient solids and water in dung [dm3.kg

    -1] O

    Output

    PIECsoil: highest concentration in the soil [mgc.kgsoil-1

    ] O

    3.3. Mapping the environmental Risk: A GIS-based Approach

    In the scope of this study, it is intended to build a semi-distributed model. In the case of fully-

    distributed or semi-distributed models, spatial parameters show different distributions from

    region to region. Thus, the effects of pollutants will vary depending on the geographical

    region in which they exist. With the aim of clarifying these differences, an Environmental

    Risk Map based on pollutant transport in Marmara region will be constituted.

    (3)

  • 8/2/2019 Proposal Antibiotics 1206

    12/15

    12

    For each compartment evaluated, after identifying catchment on cellular basis, a separate Risk

    Characterization Ratio (RCR) is calculated for every single cell, based on the PEC/PNEC

    concept (Montforts, 1999):

    Input

    PECcom predicted environmental concentration in compartment [mgc.kg-1

    ] or [mgc.l-1

    ] O

    PNECcomp predicted no effect concentration for compartment [mgc.kg-1

    ] or [mgc.l-1

    ] O

    Output

    RCRcomp risk characterisation ratio for compartment [-] O

    Risk factors for every single cell will be illustrated by means of GIS based maps. Main

    parameters taken into consideration in the process of constituting these maps are cellular

    space, arable field area, distance from water resources, population/residential density, and

    slope, etc.

    Through the amount of arable fied area in a given grid cell (x,y), gLOAD per grid cell is

    calculated and the rule of proportion is applied as shown in Eq. (5) (OECD, 1998):

    Astream i,j is the amount of arable land in the near upstream environment of a stream site

    located in grid cell (x,y),

    Acell i,jis the amount of arable land in cell (x,y),

    Estream i,j is the theoretical size of the near-stream environment of the stream site located in

    grid cell (x,y),

    Ecellis the size of the grid cell (x,y).

    Runoff Potential (RP) can be transformed into the estimated median effect value of a grid cell.

    Data about catchment areas i.e. the frequency of stream sites gives the potential effect

    frequency per grid cell. The median effect value multiplied by the effect frequency forms an

    estimate of the environmental risk in a grid cell. Predicted environmental risk for study region

    is calculated as following equation by taking into account the grid cells where stream sites

    exist. (Schriever and Liess, 2007).

    (5)

    (4)

  • 8/2/2019 Proposal Antibiotics 1206

    13/15

    13

    index irefers to one of the environmental risk classes Very low to Very high,

    mRiskcell(x,y) is the median (lower; upper) estimate of environmental risk for streams in gridcells that belong to risk class i,

    n is the number of investigated sites that are located in grid cells of risk class i.

    4. PROBABLE OUTCOMES

    Once it is built, the model will be run under different scenarios to account for the changes in

    the catchment area. Scenarios will be developed based on the application of 3 different types

    of antibiotics in various dosages, in different seasons on different types of soil. If the study is

    completed successfully:

    For Marmara region, a GIS based data set including analyzed antibiotics collected fromvarious points, soil type, and land use data will be formed,

    Hydrological model exhibiting rainfall-runoff relationship in the catchment alsothermodynamic and hydrodynamic models determining antibiotic transport will be built,

    The effects of land use on rainfall-runoff and antibiotic transport will be evaluated, The variables and parameters that affect antibiotic transport will be determined and

    significance levels will be researched,

    Besides determining the variables and parameters creating model, the correlations witheach other will be clarified,

    Environmental Risk Map for Marmara region depending on antibiotic transport will beillustrated.

    (6)

  • 8/2/2019 Proposal Antibiotics 1206

    14/15

    14

    REFERENCES

    Blackwell, P.A., Kay, P., Boxall, A.B.A, 2007. The dissipation and transport of veterinary

    antibiotics in a sandy loam soil, Chemosphere, 67, 292-299.

    Blenkinsop, S., Fowler, H.J., Dubusi, I.G., Nolan, B.T., Hollis, J.M., 2008. Developing

    climatic scenarios for pesticide fate modelling in Europe. Environmental Pollution, 154, 219-

    231.

    Boxall, A.B.A., Blackwell, P., Cavallo, R., Kay, P., Tolls, J., 2002. The sorption and transport

    of a sulphonamide antibiotic in soil systems. Toxicology Letters, 131, 1928.

    Branger, F., Tournebize, J., Carluer, N., Kao, C., Braud, I., Vauclin, M., 2009. A simplified

    modelling approach for pesticide transport in a tile-drained field: The PESTDRAIN model.

    Agricultural Water Management 96, 415-428.

    Chu, X., Marino, M.A., 2007. IPTM-CS: A windows-based integrated pesticide transport

    model for a canopyesoil system. Environmental Modelling & Software, 22 1316-1327.

    Davis, J. G., Truman, C. C., Kim, S. C., Ascough II, J. C., Carlson, K., 2006. Antibiotic

    Transport via Runoff and Soil Loss. Journal of Environmental Quality, 35, 22502260.

    Doan, K., Celepolu, A., Aknclar, ., 2007. Trkiye 2007, Basn-Yayn ve Enformasyon

    Genel Mdrl, THA Trk Haberler Ajans.

    Fedra, K., 1999. Urban environmental management: monitoring, GIS, and modelling.

    Computers, Environment and Urban Systems, 23, 443-457.

    Halling-Sorensen, B., Nors Nielsen, S., Lanzky, P. F., Ingerslev, F., Holten Liitzhofl, H.C.,

    Jorgensen, S.E., 1998. Occurrence, Fate and Effects of Pharmaceutical Substances in the

    Environment- A Review. Chemosphere, 36, 357-393.

    Huber, A., Bach, M., Frede H.G., 1998. Modelling pesticide losses with surface runoff in

    Germany, The Science of the Total Environment, 223, 177-191.

    Joyce, B.A., Wallender, W.W., Mailapalli, D.R., 2010. Application of pesticide transport

    model for simulating diazinon runoff in Californias central valley. Journal of Hydrology,

    395, 7990.

    Kay, P., Blackwell, P.A., Boxall, A.B.A., 2005. Transport of veterinary antibiotics in overland

    flow following the application of slurry to arable land. Chemosphere, 59, 951959.

    Kemper K., 2008. Veterinary antibiotics in the aquatic and terrestrial environment, Ecological

    Indicators, 8, 113.

  • 8/2/2019 Proposal Antibiotics 1206

    15/15

    15

    Kim, S-C., Davis, J.G., Truman, C.C., Ascough, J.C., Carlson, K., 2010. Simulated rainfall

    study for transport of veterinary antibiotics mass balance analysis. Journal of Hazardous

    Materials, 175, 836843.

    Kumar, K., Gupta, S.C., Chander, Y., Singh, A.K., 2005. Antibiotic use in agriculture and its

    impact on the terrestrial environment. Advances in Agronomy, 87, 1-53.

    Lertpaitoonpan, W., Ong, S.K., Moorman, T.B., 2009. Effect of organic carbon and pH on

    soil sorption of sulfamethazine. Chemosphere, 76, 558564.

    Liu, F., Ying, G.G., Tao, R., Zhao, J.L., Yang, J.F., Zhao, L.F., 2009. Effects of six selected

    antibiotics on plant growth and soil microbial and enzymatic activities. Environmental

    Pollution, 157, 16361642.

    Matjck, L., Engst, P., Jaour, Z., 2006. A GIS-based approach to spatio-temporal analysis

    of environmental pollution in urban areas: A case study of Pragues environment extended by

    LIDAR data, Ecological Modelling, 199, 261-277.

    Montforts, M.H.M.M., 1999. Environmental risk assessment for veterinary medicinal

    products, Part 1. Other than GMO-containing and immunological products, National Institu of

    Public Health and the Environment, Centre for Substances and Risk Assessment, Bilthoven,

    The Netherlands.

    Montforts, M.H.M.M., 2006. Validation of the exposure assessment for veterinary medicinal

    products. Science of the Total Environment, 358, 121136.

    OECD. Report of Phase 1 of the Aquatic Risk Indicators Project. Paris, France, Organisation

    For Economic Cooperation And Development; 1998. p. 2832.

    Sarmah, A.K., Meyer, M.T., Boxall, A.B.A, 2006. A global perspective on the use, sales,

    exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the

    environment. Chemosphere, 65, 725759.

    Schriever, C.A., Liess, M., 2007. Mapping ecological risk of agricultural pesticide runoff.

    Science of the Total Environment, 384, 264279.

    Venglovsky, J., Sasakova, N., Placha, I., 2009. Pathogens and antibiotic residues in animal

    manures and hygienic and ecological risks related to subsequent land application. Bioresource

    Technology, 100, 53865391.

    Zhao, L., Dong, Y.H., Wang, H., 2010. Residues of veterinary antibiotics in manures from

    feedlot livestock in eight provinces of China. Science of the Total Environment, 408, 1069

    1075.

    http://tr.wikipedia.org/wiki/Marmara_B%C3%B6lgesi