EVALUATIVE ASSESSMENT OF THE FATE AND

TRANSPORT OF OXYTETRACYCLINE
FERNANDEZ, JEFFREY JOSEPH P.
School of Chemical Engineering and Chemistry, Mapua Institute of Technology
Intramuros, Manila
Philippines
jjpfchem@yahoo.com

ABSTRACT
The use and abuse of oxytetracycline (OTC) both in human medicine, veterinary medicine,
and livestock promotion are potential human and environmental exposure routes for low
concentrations of this antibiotic. While the mechanisms of such exposure scenarios are
unknown, continuous emission of OTC to the environment may facilitate the development or
proliferation of antibiotic resistance. Due to the health and economic impacts of antibiotic
resistance, it is imperative to improve our understanding of the fate of OTC in the
environment. This paper provides an example of an evaluation procedure to predict the fate
of OTC in the environment that can also be applied to other antibiotics by using the
EQuilibrium Criterion (EQC) model. Three emission scenarios were investigated: 100%
emission to soil, 100% emission to water, and 50% emission to soil with 50% emission to
water. It has been found that when OTC is released 100% to water, more than 99% will
remain in the water compartment until it is degraded and advected. When 100% released to
soil, only 12.4% leaves the soil compartment and the residence time of OTC in the
environment increases by a magnitude of 15. In the mixed emission scenario, about 75% of
the OTC remains in the soil compartment due to low reaction and advection rates in soil. The
results of the study also suggest that the future risk assessments should focus on the soil
compartment and the terrestrial ecosystems.
Keywords: oxytetracycline, chemical fate, EQC model, antibiotic resistance
INTRODUCTION
Antibiotics are invaluable to humans in the fight against infectious diseases. However,
the emergence of antibiotic-resistant strains has challenged the effectiveness of antibiotics
and has already become a major threat to global public health. Oxytetracycline (OTC) is one
of the most widely used pharmaceuticals today not only to humans but also in veterinary
medicine [1]. It is also commonly used in livestock animals, including cattle, swine, poultry,
and fish for therapeutic treatment and as a growth promoter due to its broad spectrum and low
cost [2]. In the US, Streptomycin and OTC are the only antibiotics allowed for plant
agriculture while OTC is the only antibiotic that can be used internally in plants [3].
OTC, together with other antibiotics, is widely found in the environmental
compartments [4][5][6][7][8][9]. This is due to the fact that 75% of the administered OTC
dose is eliminated in the urine and feces of animals, still in its biologically active form [10].
This is one of the dominating pathways by which OTC can enter the environment [11]. Also,
studies show that elimination in municipal wastewater treatment plants is often incomplete
[12] and although the concentration is low, the presence of OTC in the environment could
facilitate the exchange of antibiotic-resistant genes among microorganisms [13][14][15].
Antibiotic resistance is a major threat to global public health and jeopardizes even advanced
medical treatments [16]. It has been noted that antibiotic-resistant infections double the
duration of hospital stay, mortality, and probably morbidity and the costs as compared with

drug-susceptible infections [17]. Along with the adverse effects of antibiotic resistance, other
negative effects of OTC and other antibiotics in the environment may include, but are not
limited to allergic reactions, nephrotoxicity (kidney toxicity), negative interaction with the
gut, sensitivity to light, and teeth damage among children [18].
Most of the studies regarding the occurrence of OTC in the environmental
compartments are conducted in the USA and Europe. The data on environmental levels of
OTC are also insufficient and needs to be expanded geographically, particularly in
developing countries. Lack of data can be attributed to the high cost of modern equipment
and techniques being used to detect trace amounts of antibiotics in the environmental
compartments that developing countries cannot afford. Moreover, the behaviour of OTC in
the environment is different from that of the human body [19]. In this respect, very little is
known about the fate and risks of OTC found in environments like wastewater, sludge,
surface water, and soil as compared to its medical use and effectiveness [20]. Without
fundamental data on the fate and risks associated with OTC entering the environment, a full
environmental risk assessment cannot be performed.
The main objective of this study is to provide an example of an evaluation procedure
on the fate of OTC which can also be applied to other antibiotics. The study also aims to
determine the possible distribution and residence time of OTC in the environment and to
identify the major processes that govern the fate of OTC by using the EQC multimedia
fugacity model.
Minimizing exposure to antibiotics is still the best way to combat antibiotic resistance
as development of new antibiotics takes time and money. If data are available regarding the
fate and transport of antibiotics, environmental hotspots can be identified and a better
course of action can be planned. In that way, exposure to antibiotics is minimized and the
antibiotic becomes effective for a longer period of time. For example, regulations in
developing countries mostly emphasize on limiting the biological oxygen demand (BOD) and
chemical oxygen demand (COD) but not the concentration of antibiotics present in
wastewater effluents. In addition, antibiotics as growth promoters for animals are often not
regulated. The results of this study can be directly used to perform a hazard assessment and
may guide assessors in performing an environmental risk assessment. It can also help
decision-makers whether or not additional treatments or new policies are needed.
The focus of this paper is limited to the parent molecule, OTC. Metabolites of OTC
may merit further investigation regarding their fate and transport in the environmental
compartments. Furthermore, hydrolysis, photolysis, and biodegradation are the only reactive
processes covered in this study. The EQC model is an evaluative fate and transport model for
predicting and quantifying migration and partitioning within a standard environment [21].
Therefore, the environmental parameters (i.e., air volume, water depth) are fixed.
Nevertheless, even if the model used in this study is evaluative, as opposed to a real model,
the EQC model is sufficient in meeting the objectives of this study.
MATERIALS AND METHODS
The main objective of this study is to provide an example of an evaluation procedure
of OTC fate that can be applied to other antibiotics and establish the general features of OTC
behaviour namely, percentage distribution and residence times. This process also aims to
identify the dominating processes that govern OTC fate. Figure 1 shows the process of how
the evaluation procedure of OTC fate will take place. The data gathering involves an
extensive literature research to look for the experimental values of the physico-chemical
properties needed as model input. When data from the literature are not sufficient, the EPI
SuiteTM will be used to estimate the missing data. The input data will then be processed in the
EQC model program and the results obtained.

Figure 1: Conceptual Framework

Data gathering. Data gathering is the first step in developing an evaluation procedure of
OTC fate using the EQC model. The data to be gathered consist of physico-chemical and
environmental properties needed as model inputs. Under the literature review, the available
data for OTC is summarized in Table 1.
Table 1: Properties of OTC
Property
Molecular weight

Value
460.4 g/mol

Reference
*calculated from molecular formula

Melting point

184.5 C

Lewis (1997)

Water solubility

313 mg/L (25C)

Yalkowsky and Dannenfelser (1992)

log Octanol-water partition

coefficient
Hydrolysis reaction half-life

-1.12

Loke et al. (2002)

14.04 d (25C)

Doi and Stoskopf (2000)

12.4 d (27C)

Choo (1994)

Photodecomposition half-life
in water

Using the EPI SuiteTM. In case of insufficient experimental data, the EPI SuiteTM uses the
molecular structure of the substance in predicting physico-chemical and environmental
properties. There are three ways by which the molecular structure can be interpreted by the
software. Any one of the CAS number, the SMILES string, or the chemical name of the
substance can be used as input. After processing the input, one may click on one of the many
tabs above the results window according to the property being sought.
EQC Model Simulation. Once the input data is complete, they will be encoded in the EQC
computer program. However, some properties are temperature dependent so one must make
sure that the reference temperature is the same for all the properties being encoded. The

following equations will help the assessor in bringing the parameter values to the same
reference temperature
To estimate a chemical property at a different temperature using the enthalpy of phase
change, H, use Eq. (1).
[

(1)

)]

To estimate a reaction half-life at a different temperature using the activation energy,

Ea (always positive), use Eq. (2).
[

(2)

)]

Reaction half-lives are more common in the literature than the overall environmental halflives in each of the compartments. For first order kinetics, use Eq. (3) to determine the overall
half-life in each compartment,
(3)

where n is the number of degradation reactions considered. In the context of this study,
hydrolysis, photolysis, and biodegradation all occur in the water phase however, only the
effects of biodegradation were considered in the soil and sediment compartment. Note that all
the reactions follow first order kinetics.
In the simulations, only Level III calculations will be performed as it is the most
realistic of the three levels and is the most useful. Three emission scenarios will be
considered as outlined in Table 3.
Table 3: Emission Scenarios for EQC Simulation

Air
Water
Soil
Sediment

Scenario 1
0
1000 kg/h
0
0

Scenario 2
0
0
1000 kg/h
0

Scenario 3
0
500 kg/h
500 kg/h
0

The percentage distribution and the residence time will be directly obtained from the output
diagram. The dominating processes will be determined by comparing the process flow rates
in each process.
RESULTS AND DISCUSSION
Scenario 1. When OTC is emitted 100% to water, as depicted in Figure 5, most of the OTC
will be present there. The major disappearance phenomena is reaction at 830 kg/h. This only
means that when OTC is initially released to the water compartment, most of it (about
99.80%) will remain in the waters and only 0.20% will move out to the other compartments.
Then, in the water, the OTC will stay until 83% of it is lost by degradation reactions
primarily photolysis and hydrolysis and some (17%) is advected or transported into other
systems.

Figure 5: Output Diagram for Scenario 1

In the illustrative example, when 1000kg/h of OTC is released continuously to the
water compartment, it will stay there and 830 kg/h will disappear by degradation reactions
(photolysis, hydrolysis, and biodegradation) and 170 kg/h is lost by advection.
The inability of OTC to move out of the waters is expected from the very low value of
the Soil-Water (1.49E-003) and Sediment-Water (2.99E-003) partition. The partition
coefficients reflect chemical partitioning at equilibrium. Therefore, OTC is really expected to
partition to water rather than soil and sediment.
The residence time of OTC in the environment due to degradation reactions alone is
8.5d while that of advection alone is 42d. This gives an overall residence time in the
environment of 7.08d. Even if OTC resides almost entirely in water, the overall residence
time is low. This is due to the fact that hydrolysis and photolysis reactions which are major
contributors in OTC disappearance both occur in the water compartment where it mostly
resides in this scenario.

Figure 6: Output Diagram for Scenario 2

Scenario 2. In this scenario, when 100% of the OTC is initially applied to soil (e.g.
application of animal manure), 87.6% of this will partition in the soil compartment and
12.4% will move out from the soil into the water compartment. The major process that
contributes to OTC disappearance is reaction from water at 639 kg/h. The residence times are
as follows: 337d by advection alone, 50.8d by reaction alone, with an overall residence time
of 44 d.
In the illustrative example, when 1000 kg/h is emitted continuously to the soil, 230
kg/h will be lost by degradation in soil. The remaining 770 kg/h will be transported to the
water compartment (through surface runoff and/or leaching) until 639 kg/h is degraded (by
photolysis, hydrolysis, and biodegradation) and 131 kg/h is advected. This is the fate of OTC
in Scenario 2.
It is interesting to note that most of the OTC stays in the soil compartment, however
the main disappearance phenomenon is in water. Thus, a major portion of the OTC actually
has to wait to be transported from the soil to the water compartment before it finally
disappears. This explains why the residence time in Scenario 2 is about 7 times longer than in
Scenario 1. This behavior is expected from the larger half-life in soil compared to water and
the moderate OTC water solubility. This phenomenon also clearly illustrates the importance
of intermedia mass transfer, particularly, transfer from the soil compartment to the water
compartment (surface runoff and leaching). Thus, if more rainfall occurs than usual, it is
expected that more OTC will partition to water and the overall residence time will decrease
due to a faster half-life in water. This is also an indication that OTC tends to persist in soil
rather than in water. Appreciable ecosystem exposure, hence development of antibiotic
resistance, will be primarily in the terrestrial ecosystem suggesting that the focus of any risk
assessment should be in this media.
Scenario 3. In the third and more realistic scenario (Figure 7), the OTC is emitted 50% to
soil and 50% to water. Of all the OTC released, 75.5% is found in the soil and 24.5% is in the
water compartment. The major loss process is still reaction from water. The residence times
are 170 d by advection alone and 30 d by reaction alone, giving an overall residence time of
25.6 d.

Figure 7: Output Diagram for Scenario 3

In the illustrative example in Scenario 3, of the 500 kg/h of OTC that is released to
soil, 115 kg/h will be lost by biodegradation in soil and 385 kg/h will be transported to the
water compartment (either by surface runoff/leaching). The latter will join the 500 kg/h
emission to water totalling 885 kg/h where 150 kg/h is advected and the remaining 735 kg/h
disappears by reaction (photolysis, hydrolysis, and biodegradation).
It is important to note that the results of Scenario 3 are in fact, a weighted mean of the
results from Scenarios 1 and 2. In all of the scenarios, there is practically negligible presence
of OTC in the soil and sediment.
CONCLUSION
EQC model is an invaluable tool in predicting the fate of chemicals in the
environment. The application of an evaluative approach for predicting OTC fate provides a
clear example of how the model can be used beneficially to other antibiotics. It has been
found that OTC tends to remain to the media where it is emitted. For the most realistic
scenario, where 50% of the OTC is released to the soil and 50% is released to the water, the
distribution in soil and water is 75.4% and 24.5%, respectively. The residence time in the
environment is found to be 26d and is 7 times longer when OTC is released solely to soil than
when released solely to water. Results suggest that future risk assessment should focus on the
soil compartment. Based on the three scenarios, emission to soil may serve as the major
contributor to the development of OTC resistance. Thus, anthropogenic activities that release
OTC to soil (e.g., as livestock growth promoters, plant agriculture) should be regulated. It has
also been shown that the model can identify the relative importance of the different processes
that affect OTC fate. The dominating process that affect OTC fate is reaction in water
(photolysis, hydrolysis, and biodegradation). The significance of intermedia transfer has also
been illustrated. Surface runoff and/or leaching is the intermedia transfer that affects OTC
fate the most. The output diagrams of the three scenarios provide a convenient visualization
of how partitioning and transformation properties interact to determine OTC fate. The EQC
model is easy-to-use and act as a reliable tool for conducting an evaluative fate assessment of
chemicals. This model can be applied to other antibiotics which are present in the
environment.
ACKNOWLEDGEMENT

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