Part II
Environmental Fate
and Transformations of
Veterinary Pharmaceuticals
© 2008 by Taylor & Francis Group, LLC
123
5
Fate and Transport of
Veterinary Medicines in
theSoilEnvironment
Alistair B.A. Boxall
5.1 INTRODUCTION
Veterinary medicines are widely used to treat disease and protect the health of ani-
mals.Dietaryenhancingfeedadditives(growthpromoters)arealsoincorporated
intothefeedofanimalsrearedforfoodinordertoimprovetheirgrowthrates.Fol-
lowing administration to a treated animal, medicines are absorbed and in some
instancesmaybemetabolized.Releaseofparentveterinarymedicinesandtheir
metabolites to the environment can then occur both directly, for example, the use of
medicinesinshfarms,andindirectly,viatheapplicationofanimalmanure(con-
taining excreted products) to land or via direct excretion of residues onto pasture.
1–4
Over the past 10 years the scientic community has become increasingly interested
in the impacts of veterinary medicines on the environment, and there have been sig-
nicant developments in the regulatory requirements for the environmental assess-
ment of veterinary products. A number of groups of veterinary medicines including
sheep dip chemicals, sh farm medicines, anthelmintics, and antibiotics have been
wellstudiedinrecentyears,andalargebodyofdataisnowavailable.
5
This chapter
Contents
5.1 I

Figure 5.1. During l
ivestock production, veterinary drugs enter the
environment through removal and subsequent disposal of waste material (including
manure/slurryand“dirty”waters),viaexcretionoffecesandurinebygrazingani
-
ma
ls, through spillage during external application, via washoff from farmyard hard
surfaces,orbydirectexposure/dischargetotheenvironment.
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,orlitterareproduced,whicharethendisposedofathighapplication
rates onto land.
13
Although each class of livestock production has different housing
andmanureproductioncharacteristics,theemissionanddistributionroutesforvet-
er
inary 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 vet
-
er
inary medicines will be degraded. A number of studies have therefore explored the
Intensively
Reared
Pasture
Manure StorageDirty Water

andinfection.Sheepinparticularsufferfromanumberofexternalinsectparasites
for which treatment and protection is sometimes obligatory. The main methods of
externaltreatmentincludeplungedipping,pour-onformulations,andtheuseof
showersorjetters.Withallexternallyappliedveterinarymedicines,bothdiffuse
and point source pollution can occur. Sheep dipping activities provide several routes
for environmental contamination. In dipping practice, chemicals may enter water
-
co
urses 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 eeces of recently treated animals to soil, water, and hard surfaces may occur on
thefarm,duringtransport,oratstockmarkets.Medicineswashedoff,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
Onceaveterinarymedicineisreleasedtotheenvironment,itsbehaviorwillbedeter-
mined by its underlying physical properties (including water solubility, lipophilicity,
volatility, and sorption potential). In the following sections information on the fate
andtransportofveterinarymedicinesinthesoilenvironmentisreviewed.
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 d
egree to which veterinary medicines may
adsorb to particulates varies widely. Consequently, the mobility of different veteri-
na
rymedicinalproductsalsovarieswidely.Chapter6andChapter7inthisbookdis-
cu
ss sorption and mobility of selected veterinary pharmaceuticals in more detail.
Available data indicate that sulfonamide antibiotics and organophosphate para

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
TABLE 5.1
Measured Sorption Coefficients (Koc) for a Range
of Veterinary Medicines
Mean Minimum Maximum
Avermectin 17650 5300 30000
Chlorfenvinphos 295 — —
Ciprooxacin 61000 — —
Enrooxacin 392623 16506 768740
Cumaphos 13449 5778 21120
Deltamethrin 8380000 460000 16300000
Diazinon 889 229 1549
Fenbendazole 815.5 631 1000
Metronidazole 47 38 56
Ooxacin 44143 — —
Olaquindox 81 46 116
Oxytetracycline 60554 27792 93317
Sulfamethazine 60 — —
Tetracycline 40000 — —
Tylosin 4270.5 553 7988
Carbadox 8508.5 184 16833
Sulfamethoxazole 296.1 62.2 530
Sulfadiazine 125 — —
Sulfapyridine 219 — —
Sulfachloropyridazine 75.5 69 82
Sulfadimethixine 144 — —
(Data taken from review of Boxall et al.
40
With permission.)

theleastpersistentwithhalf-livesof3to8and<1day,respectively.
Forsomeveterinarymedicines,degradationratesinmanurecanbefasterthan
degradation in soil. For example, under methanogenic conditions the degradation
half-lifefortylosinAwaslessthan2daysandwasenhancedbyincreasingconcen
-
tr
ations of manure particles in the incubation medium under aerobic conditions.
15
Moreover,whenmanureiscombinedwithsoil,degradationmaybeenhancedfor
0
1
2
3
4
5
6
7
8
01234567
log Koc (predicted)
log Koc (experimental)
FIGURE 5.2 Relationship between measured and predicted soil sorption coefcients for
a range of veterinary medicine classes. Koc predictions were obtained using the Syracuse
Research Corporation PCKOC program.
© 2008 by Taylor & Francis Group, LLC
128 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
selected medicines. When manure or slurry is combined with soil, temperature has
beenshowntosignicantlyaffecttherateofdegradationofacompound.Forexam-
ple,ahalf-lifeof91to217dayswasrecordedforivermectininasoil/fecesmixture
during winter weather conditions.

recentlyanumberofstudieshaveexploredthefateandtransportofveterinarymedi-
ci
nes. Lysimeter, eld-plot, and full-scale eld studies have investigated the transport
of veterinary
medicinesfromthesoilsurfacetoelddrains,ditches,streams,rivers,
and groundwater.
33–41
A range of experimental designs and sampling methodologies
has been used. These investigations are described in more detail below.
5.4.1 LEACHING TO GROUNDWATER
Themovementofsulfonamideandtetracyclineantibioticsinsoilproleswasinves-
tigatedattheeldscaleusingsuctionprobes.
33,42
In these studies sulfonamides were
detectedinsoilporewateratdepthsofboth0.8and1.4m,buttetracyclineswerenot
(mostlikelyduetotheirhighpotentialforsorptiontosoil).CarlsonandMabury
43
reported that chlortetracycline applied to agricultural soil in manure was detected at
soildepthsof25and35cm,butmonensinremainedintheuppersoillayers.There
are only a few reports of veterinary medicines in groundwater.
42,44
In an extensive
monitoring study conducted in Germany,
44
noantibioticsweredetectedingroundwa-
terinmostofthemonitoringregionswithintensivelivestockproduction.However,
residues of sulfonamide antibiotics were detected at four sites. While contamination
at two of the sites was attributed to irrigation of agricultural land with domestic
sewage, the authors concluded that contamination of groundwater by the veterinary
antibiotic sulfamethazine at two of the sites was due to applications of manure.

45
5.4.3 DRAIN FLOW
The transport of a range of antibacterial substance (i.e., tetracyclines, macrolides,
sulfonamides, and trimethoprim) has been investigated using lysimeter and eld-
based studies in tile-drained clay soils.
38,46,48
Following application of pig slurry
spiked with antibiotics to an untilled eld, test compounds were detected in drain-
owatconcentrationsuptoamaximumof613µgl
–1
for oxytetracyline and 36 µg l
–1
for sulfachloropyridazine.
38
The spiking concentrations for the test compounds were
all similar, so differences in maximum concentrations were likely due to differences
insorptionbehavior.Inasubsequentinvestigationatthesamesite
38
in which the soil
was tilled, much lower concentrations were observed in the drainow (i.e., 6.1 µg l
–1
for sulfachloropyridazine and 0.8 µg l
–1
for oxytetracyline). While the pig slurry used
inthesestudieswasobtainedfromapigfarmwheretylosinwasusedasaprophy-
la
ctic treatment, this substance was not detected in any drainow samples—possibly
becauseitisnotpersistentinslurry.
15
5.4.4 UPTAKE INTO BIOTA

(Allium cepa L.), and cabbage (Brassica oleracea L.).Tylosinwasnottakenupby
the three crops. Chapter 8 of this book presents the results of a study investigating
plant uptake of pharmaceuticals, while Chapter 9 provides evidence of detoxication
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 parti-
ti
on coefcient 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,abovegroundplantmaterial)isrelatedtoLogK
ow
by a Gaussian
curve distribution.
54,55
Maximum translocation is observed at a Log K
ow
around 1.8.
More polar compounds are taken up less well by shoots, and uptake of highly lipo-
philic compounds (Log K
ow
>4.5) is low. The available data indicate that these rela-
tionshipsmaynotholdtrueforveterinarymedicines.
51
This is perhaps not surprising

tial 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
requiredataonsorptionandpersistenceasinputvalues.Someoftheapproachesare
described below.
In order to harmonize the environmental assessments of veterinary products, the
EuropeanFederationforAnimalHealth(FEDESAnowIFAHEurope)developeda
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 informa-
tionisavailableonmetabolismordegradation,thiscanbeincorporatedintothe
calculation. The model calculated the concentration of the veterinary medicine in
animalmanureandthenusesthenitrogencontentofthemanureandthemaximum
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 modications and amendments introduced, but the basic premise is that the
predicted environmental concentration (PEC) depends on the nitrogen content of the
manureandthemaximumapplicationratetoland.
The ETox models developed by Montforts
13
predicts concentrations of veterinary
medicinesusingscenariosthatarespecictoagriculturalpracticesintheNether-
lands.Themodelismorecomplexthantheuniformapproachandcanbeusedfor

tudies have explored the distribution of medicines
inthesoilproleaswellasthepersistenceovertime.Whilesomegroupsofsub-
stances have not been detected in soils (e.g., the macrolides and uoroquinolones),
some classes have been detected at concentrations of tens to hundreds of µg kg
–1
(Table 5.2). In s
ome cases the compounds will persist in the soil for prolonged time
periods. These differences can usually be explained by the laboratory persistence
dataandusageandtreatmentscenariosforthedifferentmedicines.Theavailability
of real-world monitoring data allows us to evaluate the performance of the exposure
models described previously. Generally, these exposure models will overpredict con
-
ce
ntrations 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
Thispaperhasr eviewed the data available in the public domain on the pathways of
veterinary medicines to the soil environment and their subsequent fate and transport.
Thereisclearlyalargebodyofdataavailableonveterinarymedicinesinthesoil
environment,anditistimelytobegintofurthersynthesizethisinformationinorder
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
inthesoilenvironment.Thereare,however,stillgapsinthedataandinourunder
-
st
anding.Thosegapsareoutlinedinthefollowingparagraphs.

LOD
(µg kg
-1
) Country Reference
Chlortetracycline Antibiotic 9.5 0.7 Germany 42
26.4 1 Germany 42
41.8
39
4
1
2
—
Germany
Germany
US
42
37
58
Ciprooxacin Antibiotic nd 1 UK 48
Enrooxacin Antibiotic nd 1 UK 48
Ivermectin Endectocide 2
46
10.2 US, UK 58
48
Lincomycin Antibiotic 98.5 —
1.26
US
UK
59
48

42
37
59
Tilmicosin Antibiotic <10 — US 59
Trimethoprim Antibiotic 0.5 — UK 48
Tylosin Antibiotic trace
<2
<10
0.2
—
10
Germany
US
Italy
42
59
57
© 2008 by Taylor & Francis Group, LLC
134 Fate of Pharmaceuticals in the Environment and in Water Treatment Systems
The uptake of veterinary medicines into plants is now being considered. It
appearsthatuptakecannotbemodelledusingexistingplantuptakemodelsforpes-
ti
cides and industrial chemicals. Further work to understand the mechanisms of
uptake of veterinary medicine into plants is therefore warranted.
From the information availableit appears that inputs from herd or ocktreatments
areprobablythemostsignicantintermsofenvironmentalexposure.However,the
relativesignicanceofnovelroutesofentry to the environment from livestock treat
-
m
e

10000.0
0.1 1.0 10.0 100.0 1000.0
Measured Concentration (+g/kg)
Predicted Concentration (+g/kg)
FIGURE 5.4 Comparison of predicted environmental concentrations obtained using expo-
suremodelslistedintheEUTechnicalGuidanceDocumentwithrangesofmeasuredcon-
centrationsinagriculturalsoils.
© 2008 by Taylor & Francis Group, LLC
Fate and Transport of Veterinary Medicines in the Soil Environment 135
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