Science of the Total Environment 636 (2018) 477–486

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Science of the Total Environment

journal homepage: www.elsevier.com/locate/scitotenv

Review

Uptake of pharmaceuticals by plants grown under hydroponic conditions

and natural occurring plant species: A review
Lawrence Mzukisi Madikizela a,⁎, Somandla Ncube b, Luke Chimuka b
a
Department of Chemistry, Durban University of Technology, P. O. Box 1334, Durban 4000, South Africa
b
Molecular Sciences Institute, University of Witwatersrand, Private Bag X3, Johannesburg 2050, South Africa

H I G H L I G H T S G R A P H I C A L A B S T R A C T

• We evaluated the plant uptake of phar-

maceuticals from water and soil.
• The negative effects of plant uptake of
pharmaceuticals are discussed.
• Most studies use concentrations higher
than those expected in the environ-
ment.
• Plant uptake studies focused more on
antibiotics than other pharmaceutical
classes.
• Pharmaceutical uptake is through plant
roots and translocated into aerial
tissues.

a r t i c l e i n f o a b s t r a c t

Article history: Sizeable amount of research has been conducted on the possible uptake of pharmaceuticals by plants from con-
Received 17 February 2018 taminated soil and water used for irrigation of crops. In most cases, pharmaceuticals are taken by roots and
Received in revised form 22 April 2018 translocated into various tissues by transpiration and diffusion. Due to the plant uptake, the occurrence of phar-
Accepted 22 April 2018
maceuticals in food sources such as vegetables is a public concern. Few review papers focusing on the uptake of
Available online 27 April 2018
pharmaceuticals, in particular antibiotics, and their translocation in plant tissues have been published. In the cur-
Editor: Jay Gan rent review paper, the work conducted on the uptake of pharmaceuticals belonging to different therapeutic
groups such as antibiotics, non-steroidal anti-inflammatory drugs, β-blockers and antiepileptics is reviewed.
Keywords: Such work includes the occurrence of pharmaceuticals in plants, translocation once taken by plants, toxicity stud-
Pharmaceuticals ies as well as implications and future studies. Furthermore, the advantages and drawbacks associated with the
Plant uptake detection and uptake of these pharmaceuticals by plants are discussed. In addition, the physico-chemical prop-
Toxicity erties that could influence the plant uptake of pharmaceuticals are deliberated.
Translocation © 2018 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478
2. Sources of pharmaceuticals in the environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478
3. Physicochemical properties of pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478

⁎ Corresponding author.
E-mail address: lawrencem2@dut.ac.za. (L.M. Madikizela).

https://doi.org/10.1016/j.scitotenv.2018.04.297
0048-9697/© 2018 Elsevier B.V. All rights reserved.
478 L.M. Madikizela et al. / Science of the Total Environment 636 (2018) 477–486

4. Uptake of pharmaceuticals by plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479

4.1. Uptake of pharmaceuticals by plants grown under hydroponic conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479
4.2. Uptake of pharmaceuticals by plants in the environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479
4.3. Phytoremediation of pharmaceuticals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
5. Occurrence of pharmaceuticals in vegetables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
6. Translocation of pharmaceuticals in plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
7. Toxicity of pharmaceuticals in plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
8. Implications and future studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
9. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484

1. Introduction presented on the plant uptake of pharmaceutical groups that include

In recent years, pharmaceuticals have been found in aquatic systems
which include drinking water (Odendaal et al., 2015), wastewater
(Yang et al., 2017), ground water (Balakrishna et al., 2017) and surface
water (Balakrishna et al., 2017). The scarcity of rainfall in winter seasons
of certain countries increases the demand of using wastewater for irri-
gation of crops. Globally, it is generally known that wastewater treat-
ment plants (WWTPs) are unable to completely remove organics from
wastewater effluents which include pharmaceuticals during the decon-
tamination process. Therefore, studies have shown that the re-use of
wastewater effluent with pharmaceutical constituents for irrigation of
crops could result in the uptake of pharmaceuticals by plant roots
(Christou et al., 2017). This could result in the occurrence of pharmaceu-
ticals in food sources such as vegetables which may cause threats to the
health of the consumer. On the other hand, the uptake of pharmaceuti-
cals by plants can be an advantage because it could assist in the
reduction of the pollutant load in surface water (Cui et al., 2015). Con-
structed wetlands have been investigated for their ability to remove
pharmaceuticals from water through the usage of certain plants (Dan
et al., 2013).
Although pharmaceuticals are ingested by humans and animals for
the purpose of disease treatment and prevention, as well as growth pro-
motion (Chuang et al., 2015), extreme consumption can result in sick-
ness. The example of this was documented elsewhere where the
ingestion of 24–36 g fenoprofen led to coma, hypotension, metabolic ac-
idosis, and respiratory depression within 4 h (Kolodzik et al., 1990). Ac-
cumulation of pharmaceuticals in plants as documented in literature
lead to growth suppression and reduction in photosynthetic pigments
among other side effects (Carter et al., 2015; Migliore et al., 1996). The
effects of extended daily consumption of pharmaceuticals through the
contaminated food sources and water are not yet fully understood.
Recently, few review papers on the uptake of pharmaceuticals by
plants have been documented in literature (Bártíková et al., 2016; Pan
and Chu, 2017; Tasho and Cho, 2016; Wu et al., 2015; Zhang et al.,
2017). The main focus of these review papers is on the plant uptake of
antibiotics. For example, Pan and Chu (2017) presented a review
paper on fate of antibiotics in soil and their uptake by edible crops
(Pan and Chu, 2017). The review paper published by Tasho and Cho
(2016) is based on veterinary antibiotics in animal waste, their distribu-
tion in soil and uptake by plants (Tasho and Cho, 2016). The review
paper presented by Bártíková et al. (2016) focused on the veterinary
drugs in the environment and their toxicity to plants (Bártíková et al.,
2016). The overview of pharmaceuticals and personal care products in
the soil–plant systems, including analytical methods for their determi-
nation in plant tissues, their fate in agricultural soils receiving treated
wastewater irrigation or biosolids amendment, and their plant uptake
under laboratory and field conditions has been reported (Wu et al.,
2015). Most recently, uptake and translocation of organic pollutants in
plants have been reviewed with more focus on antibiotics together
with organics such as herbicides (Zhang et al., 2017). Therefore, the
aim of the present review paper is to give an overview of the work
non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, antibacte-
rial agent, β-blockers, calcium channel blocker, antiepileptics, steroid
hormones, antidepressant, antidiabetic, antihistamine, antineoplastic
agent, anti-itch, x-ray contrast agent, lipid-lowering agents, benzodiaz-
epines and tranquilizers from soil and contaminated water. The scope of
the present work includes the plant uptake of pharmaceuticals from the
surrounding environment which could be sediments or water, and their
translocation within the plant tissues. Further to this, the effects of the
plant uptake such as toxicity to humans and plants are discussed.
2. Sources of pharmaceuticals in the environment
Pharmaceuticals enter the environment through various sources as
elaborated in Fig. 1 (Kostopoulou and Nikolaou, 2008). These sources
include direct disposal of pharmaceuticals into water resources, excre-
tion into sewers that lead to the transportation of high loads of pharma-
ceuticals into WWTPs. Some pharmaceuticals tend to partition in sludge
during wastewater treatment, which lead to their introduction into ag-
ricultural fields. Different classes of pharmaceuticals found present in
sewage sludge include NSAIDs, antibiotics, antiplatelets, psychiatric
drugs, antidiabetics and β-blockers (Fijalkowski et al., 2017; Subedi
et al., 2014, 2013). The growth of plants or vegetables in contaminated
soil or soil fertilized with sludge could result in the uptake of pharma-
ceuticals by plants. Recently, composted biosolids and treated wastewa-
ter have been reported as the sources of pharmaceuticals and personal
care products for plant uptake (Ben Mordechay et al., 2017). In a
study conducted in China, high levels of antibiotics were found in soils
from vegetable greenhouses, where manure and animal feces fertiliza-
tion were identified as their primary source (Li et al., 2015). The mean
concentrations of antibiotic classes reported in their work decreased
in the following order: tetracyclines (102 μg/kg) N quinolones (86
μg/kg) N sulfonamides (1.1 μg/kg) N macrolides (0.62 μg/kg). In a differ-
ent study, Boxall et al. (2006) discovered that selected pharmaceuticals
used in veterinary medicines may occur in soils for at least 5 months fol-
lowing the application of manure containing them (Boxall et al., 2006).
3. Physicochemical properties of pharmaceuticals
There is a wide variability in the physicochemical properties of phar-
maceuticals. Such properties are summarized in Table 1. In most cases,
pharmaceuticals enter the environment through excretion and end-up
in water bodies. As shown in Table 1, some pharmaceuticals such as
tylosin, and dilantin are relatively water insoluble and have high log
KOW, which could easily result in their adsorption into sediments and
sludge. These become readily available for uptake by plants. Furthermore,
uptake of organic compounds into plant roots partly depends on the
properties of the compounds (Trapp, 2000). For example, it is docu-
mented in literature that properties such as molecular weight and hydro-
phobicity with the parameters KOW (partition coefficient between octanol
and water) and KOA (partition coefficient between octanol and air) have a
direct influence on plant uptake of pharmaceuticals (Calderón-Preciado
 L.M. Madikizela et al. / Science of the Total Environment 636 (2018) 477–486
Fig. 1. Sources of pharmaceuticals in water. Adapted from Ref: (Kostopoulou and Nikolaou, 2008) with permission from Elsevier.
et al., 2012; Zhang et al., 2017). Furthermore it is elaborated that com-
pounds of molecular mass below 1000 and with high KOW values are eas-
ily absorbed by plant roots (Zhang et al., 2017). Therefore, due to the
spread in physicochemical properties of pharmaceuticals, it is important
to study the plant uptake for a large number of the compounds in order
to assess the possibility of phytoremediation.
Another essential property that could affect the behavior of a com-
pound in the environment is its pKa value (Goldstein et al., 2014;
Herklotz et al., 2010). A pKa value is an estimation of a pH value in
which a weak acid would ionize. Pharmaceuticals with lower pKa values
are relatively stronger and ionize easily under normal environmental
conditions. This becomes important in the understanding of absorption
and translocation of pharmaceuticals from the soil into the plant
system.
4. Uptake of pharmaceuticals by plants
4.1. Uptake of pharmaceuticals by plants grown under hydroponic
conditions
Hydroponic experiments have been conducted to demonstrate the
uptake of several pharmaceuticals by plants (Table 2). In such experi-
ments, plant species are subjected to known concentrations of pharma-
ceuticals for a known period of time. Thereafter, plants are harvested,
and the pharmaceuticals absorbed are determined in the plant tissues.
Several plant species that are capable of taking pharmaceuticals from
both water and soil are given in Table 2. Interestingly, there is evidence
of antibiotics uptake from irrigation water by carrot (Daucus corota L.)
and lettuce (Lactuca sativa L.), the plants that can be eaten raw (Azanu
et al., 2016). Wu et al. (2010) have demonstrated the uptake of carba-
mazepine, diphenhydramine, and fluoxetine from biosolids and waste-
water irrigation by soybean (Glycine max (L.) Merr.) (Wu et al., 2010). In
the case of uptake from contaminated solids, it is documented that the
uptake of the pharmaceuticals could be depended on the soil type
(Karnjanapiboonwong et al., 2011; Zhang et al., 2016). For example,
the extent of uptake and accumulation of 17α-ethynylestradiol in
pinto bean (Phaseolus vulgaris) grown in sand is known to be higher
479
than in plants grown in other soil types (Karnjanapiboonwong et al.,
2011). This was explained to be due to 17α-ethynylestradiol being less
bioavailable for plant uptake from soil compared to sand. Furthermore,
the organic carbon (OC) content of the soil (1.3%) was higher than OC
content of the sand (0%). Therefore, sorption of 17α-ethynylestradiol
was greater in soil, resulting in less availability of the analyte in pore
water available for plant uptake. In addition, the physicochemical prop-
erties of soil such as its OC content are capable of influencing the plant
uptake of pharmaceuticals (Carter et al., 2018).
Investigations on the differential uptake of pharmaceuticals by plant
species for the purpose of remediation of water resources have also
been performed (Bartha et al., 2014; Zhang et al., 2013). This is elabo-
rated in Section 4.3; however, it is worth mentioning at this stage that
under hydroponic conditions, certain plants have shown the ability to
uptake pharmaceuticals. In this case, Bartha et al. (2014) detected
diclofenac in roots and shoots of Typha latifolia in as early as 1 day of
exposure (Bartha et al., 2014). The same authors also reported the de-
cline in the concentration of diclofenac in roots which could have
translocated to other plant tissues. The fate of pharmaceuticals in wet-
lands have also been investigated under laboratory settings (Zhang
et al., 2013). In this context, it was reported that in 21 days of Scirpus
validus exposure to pharmaceuticals, 74 and N98% of carbamazepine
and naproxen, respectively had been eliminated from the nutrient solu-
tion (Zhang et al., 2013).
4.2. Uptake of pharmaceuticals by plants in the environment
The plant uptake of pharmaceuticals from water result in
phytoremediation. Topal (2015) investigated the uptake of tetracycline
and its degradation products by Phragmites australis grown in stream car-
rying municipal WWTP effluents, where various compounds were found
present in different plant tissues (Topal, 2015). The highest concentra-
tions found for tetracycline, 4-epitetracycline, 4-epianhydrotetracycline
and anhydrotetracycline in roots of Phragmites australis were 31.5, 46.1,
27.0 and 16.5 ng/g, respectively. In the same study, maximum concentra-
tions of tetracycline, 4-epitetracycline, 4-epianhydrotetracycline and
anhydrotetracycline detected in stems of Phragmites australis were 8.3,
480 L.M. Madikizela et al. / Science of the Total Environment 636 (2018) 477–486

Table 1
Physicochemical properties of pharmaceuticals that have been detected in plant tissues.

Therapeutic group Pharmaceuticals Molecular weight (g/mol) Water solubility (mg/L) Log KOW Log KOC (L/kg) pKa

NSAIDs Ibuprofen 206 58 3.97 2.60 5.20

Naproxen 230 44 3.18 2.54 4.15
Diclofenac 296 2.37 4.51 2.92 4.15
Ketoprofen 254 51 3.00 2.46 4.45
Acetaminophen 151 14,000 0.46 – 9.38
Antibiotics Sulfamethazine 277 1500 0.28 – 7.59
Sulfamethoxazole 253 610 0.89 2.40 5.70
Sulphadimethoxine 310 343 – – 6.91, 1.95
Sulfadiazine 250 77 −0.09 – 6.36
Penicillin G 334 210 1.83 – –
Trimethoprim 290 400 0.91 – 7.12
Oxytetracycline 460 313 −0.90 – 9.50
Norfloxacin 319 1,78E05 0.46 – 6.34, 8.75
Ciprofloxacin 331 3E04 0.28 – 6.09, 8.74
Minocycline 457 5.2E04 0.05 – 2.80, 5.00,7.80, 9.30
Tetracycline 444 231 −1.37 – 3.30
Chlortetracycline 479 288 – – –
Lincomycin 407 927 0.2 – 7.60
Tylosin 916 5 3.27 – 7.73
Antibacterial Carbadox 262 1755 −1.22 – –
β-Blockers Propanolol 259 62 3.5 – 9.67
Atenolol 266 9.54 × 105 0.16 1.80 9.6
Calcium channel blocker Verapamil 454 4.47 – – 8.92
Antiepileptics Carbamazepine 236 18 2.50 3.59 13.90
Dilantin 252 32 2.47 3.10 8.33
Primidone 218 500 0.91 – 6.20
Steroid hormones 17α-Ethinylestradiol 296 11.3 3.67 – 1.70
Antidepressant Fluoxetine 309 50,000 4.10 – 9.80
Antidiabetic Metformin 129 1380 −4.3 – –
Gliclazide 323 – 2.12 – 4.07, 1.38
Glyburide 494 4 – – 4.32
Antihistamine Diphenhydramine 255 363 3.44 3.90 8.98
Antineoplastic agent Cyclophosphamide 260 1–5E04 0.97 – 0.57
Anti-itch Crotamiton 203 – 2.73 – –
X-ray contrast agent Iopromide 791 – – – –
Lipid-lowering agents Atorvastatin 6.36 0.00112 6.36 – 4.30
Gemfibrozil 250 11 4.77 2.60 4.50
Benzodiazepines Diazepam 285 50 2.82 2.40 3.40
Tranquilizers Meprobamate 218 4700 0.70 15.17 1.80E-10

The information contained herein the table was compiled from the literature cited in this document and drugbank website (https://www.drugbank.ca/) assessed in the period between
March and April 2018.

9.99, 6.6 and 4.69 ng/g, respectively. The same compounds, tetracycline,
4-epitetracycline, 4-epianhydrotetracycline and anhydrotetracycline in
leaves were 4.74, 5.58, 2.96 and 3.71 ng/g, respectively (Topal, 2015).
In a separate study, salicylic acid was the main pharmaceutical detected
in root tissues in the concentration range of 123–2560 ng/g (Hijosa-
Valsero et al., 2016). Also, a high number of pharmaceuticals belonging
to different therapeutic groups were detected in plants found in surface
treatment wetland (Nuel et al., 2018). Elsewhere, the detection of 17
micropollutants which included pharmaceuticals (propranolol,
ketamine, venlafaxine, mirtazapine, carbamazepine, diltiazem,
methadone, tramadol, 3,4-methylenedioxymethamphetamine and
desvenlafaxine) and their metabolites (norketamine, carbamazepine
10,11 epoxide, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
and N-desmethyltramadol) in P. australis from a constructed wet-
land treating secondary municipal (trickling filter) effluent in the
UK was reported (Petrie et al., 2017). In a most recent study, carba-
mazepine and its metabolites were detected at significantly higher
concentrations in plants grown in soils irrigated with treated waste-
water as compared to plants grown in the same soils amended with
biosolids (Ben Mordechay et al., 2017). This implies that the contri-
bution of contaminated water to uptake of pharmaceuticals is stron-
ger compared to that of biosolids.

Table 2
Uptake of several pharmaceuticals from water and soil.

Pharmaceuticals Therapeutic group Plant species Common name Source of pharmaceuticals Reference

Tetracycline and amoxicillin Antibiotics Daucus corota L. and Carrot and lettuce Irrigation water (Azanu et al., 2016)
Lactuca sativa L.
sulfadiazine, sulfamethazine and Antibiotics Brassica chinensis Pakchoi cabbage Contaminated soil (X. Li et al., 2013)
sulfamethoxazole
Diclofenac NSAID Typha latifolia L. Cattail Nutrient solution (Bartha et al., 2014)
Carbamazepine and naproxen Antiepileptic and NSAID Scirpus validus Bulrushes Nutrient solution (Zhang et al., 2013)
Carbamazepine, sulfamethoxazole, Antiepileptic, antibiotics Brassica campestris Cabbage Fortified and biosolids-amended soils (Holling et al., 2012)
trimethoprim and salbutamol and asthma treatment agent
Carbamazepine and propanolol Antiepileptic and β-blocker Lolium perenne Ryegrass Contaminated soil (Williams et al., 2015)
Carbamazepine Antiepileptic Triticum aestivum Wheat Soils irrigated with reclaimed wastewater (Paz et al., 2016)
 L.M. Madikizela et al. / Science of the Total Environment 636 (2018) 477–486
4.3. Phytoremediation of pharmaceuticals
Plants have the potential to remove pharmaceuticals from the envi-
ronment. Several studies have been done to find potential plants that
can be used in phytoremediation of pharmaceuticals. The plants re-
ported in literature are given in Table 3. As can be seen in Table 3, the
removal efficiency for pharmaceuticals could be depended on the
plant type, and the physicochemical properties of pharmaceutical con-
taminants. For example, the elimination efficiency observed for codeine
after 48 h of treatment with I. pseudacorus was 87% (Mackul'ak et al.,
2015). In the same conditions, the elimination efficiency for codeine
after treatment with C. caroliniana, L. sessiliflora and E. najas did not ex-
ceed 33% (Mackul'ak et al., 2015). In a separate study, the evidence of re-
moval of tetracycline and degradation products by Phragmites australis
in WWTP effluent was presented (Topal, 2015). The results in Table 3
are in total agreement with Malchi et al. (2014) who have observed
that the extent of pharmaceutical uptake is influenced by the physico-
chemical properties of the compound, the physiological properties of
the crop, and the soil properties (Malchi et al., 2014).
In addition, a considerable amount of work has been documented for
the removal of pharmaceuticals using constructed wetland systems
where plants are used to clean-up contaminated water (Dan et al.,
2013; Li et al., 2014; Petrie et al., 2017; Rühmland et al., 2015). A review
that summarizes the removal performance of pharmaceuticals in differ-
ent aquatic plant-based systems together with various removal mecha-
nisms has been published (Zhang et al., 2014). Based on the presented
information, it is no doubt that plants are capable of removing pharma-
ceuticals from water, thereby cleaning water resources. Interestingly,
diclofenac an extensively used NSAID which is not easily removed by
current wastewater treatment technologies (Madikizela and Chimuka,
2017), is reported to be efficiently taken up by plants such as Hordeum
vulgare (barley) and Armoracia rusticana (horse radish) (Huber et al.,
2012).
5. Occurrence of pharmaceuticals in vegetables
The uptake of pharmaceuticals which include antibiotics, NSAIDs
and antiepileptic drugs by vegetables has been investigated (Hu et al.,
2010; Hurtado et al., 2017, 2016; Rajapaksha et al., 2014; Wu et al.,
2014, 2012). The main source of pharmaceuticals in vegetables is re-
ported to be through the usage of contaminated water for irrigation
(Wu et al., 2014). Due to the shortage of fresh water in certain countries,
re-use of treated wastewater for irrigation purposes is becoming an
ideal solution more especially in arid and semi-arid areas (Wu et al.,
2013). However, the uptake of water contaminants by food sources is a
health risk. In this aspect, antibiotics such as oxytetracycline, tetracycline,
chlortetracycline, sulfamethoxazole, sulfadoxine, sulfachloropyridazine,
chloramphenicol, ofloxacin, pefloxacin and lincomycin have been de-
tected in vegetables from Northern China at the concentration range of
0.1–532 μg/kg (Hu et al., 2010). In the same geographical area (Northern
china), the concentration of norfloxacin, ciprofloxacin and enrofloxacin
ranging from 18.2 to 658.3 μg/kg were found in vegetables such as to-
mato, cucumber, pepper, spinach, eggplant and crown daisy (X.W. Li
et al., 2013). In a different study, the analysis of vegetables which
Table 3
Removal efficiency of pharmaceutical drugs from aquatic environment by plants.
Plant
Typha latifolia
Typha spp.
I. pseudacorus
Typha latifolia
Ceratophyllum demersum, Lemna minor, Salvinia molesta, and Elodea Canadensis
a, b, c and d are Ceratophyllum demersum, Salvinia molesta, Lemna minor and Elodea Canadensis, respectively.
481
included roots of carrot, leaves of lettuce, cabbage, and spinach, stem of
celery, and fruits of cucumber, bell pepper, and tomato showed detection
frequency of 64% of pharmaceuticals and personal care products (19
compounds were investigated) with their source being the treated
wastewater used for irrigation (Wu et al., 2014). However, the results
presented elsewhere indicate that the potential for drug uptake into veg-
etables grown under normal farming conditions is very low when there
is a one year offset between biosolid application and crop harvest
(Sabourin et al., 2012). Another potential source of pharmaceuticals in
vegetables could be the application of sewage sludge as a fertilizer. How-
ever, Cortés et al. (2013) reported no detectable concentration of NSAIDs
in soybean and wheat grown using sludge as the fertilizer (Cortés et al.,
2013).
The respective health care professionals based on the nature of the
illnesses usually recommend the quantity of pharmaceuticals to be con-
sumed by humans on a daily basis. As of now, the presence of most of
the pharmaceutical products and by-products in food and surface
water sources is not regulated. Therefore, the occurrence of pharmaceu-
ticals in food sources such as vegetables could imply that humans are
continually consuming pharmaceuticals at levels that exceed the thera-
peutic limits recommended by their health care professionals. This sug-
gest that the pharmaceutical drug resistance on humans could arise.
Lately, there is a rise in the number of studies focusing on the occur-
rence of pharmaceuticals in water resources that include the drinking
water. However, it has been indicated that the introduction of pharma-
ceuticals through the food chain pathway is within the same magnitude
or even higher than via drinking water (Shenker et al., 2011). Therefore,
further studies on the occurrence of pharmaceuticals in both food
sources and products should be conducted.
6. Translocation of pharmaceuticals in plants
Plants take up pharmaceuticals through roots and transport them to
aerial tissues (Bartrons and Peñuelas, 2017). As shown in Table 4, once
taken up by plants, pharmaceuticals get translocated to different parts
of the plants which result in their detection in stem, leaves and edible
parts such as fruits (Fig. 2). In this case, recent work has been presented
on translocation of paracetamol within the maize plant to edible plant
parts (Hammad et al., 2018). Transportation of pharmaceuticals into
and within the plants is known to be driven by transpiration and diffu-
sion (Dodgen et al., 2015; Sauvêtre et al., 2018; Winker et al., 2010). The
absorption of water and dissolved organic compounds from soil water
to the plant is believed to be a passive process controlled by the transpi-
ration stream via the xylem vessels and tracheids (Briggs et al., 1982;
Collins et al., 2006; Miller et al., 2016). A constant transpiration stream
is itself maintained by continuous evaporation of water from the sto-
mata found on the surface of the leaves. Initially, water is absorbed
from the soil by roots through osmosis. Transportation to the leaves is
through a transpiration-cohesion-adhesion mechanism. This involves
creation of a suction force due to loss of water from the leaf surface,
and a capillary action due to the cohesive interaction of water molecules
and the adhesion of the water molecules onto the walls of the xylem
vessels. The concentration of dissolved organics in the xylem sap is rel-
atively low compared to phloem vessels. The phloem vessels are the
Pharmaceutical Exposure period (days) Removal efficiency (%) Reference
Metformin 28 81 (Cui and Schröder, 2016)
Carbamazepine 21 82 (Dordio et al., 2011)
Codeine 48 h 87 (Mackul'ak et al., 2015)
Iopromide 28 87 (Cui et al., 2017)
Diclofenac 38 99a,b,c,d (Matamoros et al., 2012)
Naproxen 38 53a,d, 43b, 40c
Ibuprofen 38 52a, 48b, 44c, 77d
482 L.M. Madikizela et al. / Science of the Total Environment 636 (2018) 477–486

Table 4
Concentrations of pharmaceuticals detected in various parts of the plants.

Pharmaceutical Plant Spiked concentration Study duration (days) Mean concentration detected in plant (μg/g) Reference

Roots Stem Leaves

Diclofenac Typha latifolia 1 mg/L 1 0.2 Not reported 0.013 (Bartha et al., 2014)
Fluoxetine hydrochloride Brassicaceae 280 ng/mL 12 weeks Not detected 0.49 0.26 (Redshaw et al., 2008)
Carbamazepine Cucumber 4.14 μg/L 3 months 4.5a 1.9a 39.1a (Shenker et al., 2011)
Scirpus validus 0.5–2.0 mg/L 21 3.3–19.0 Not reported 0.3–0.7 (Zhang et al., 2013)
Naproxen Scirpus validus 0.5–2.0 mg/L 21 0.2–2.4 Not reported 0.3–0.7 (Zhang et al., 2013)
Diclofenac Medicago sativa L. 10 μg/L 50 162.8a Not reported Not detected (Christou et al., 2016)
Sulfamethoxazole Medicago sativa L. 10 μg/L 50 52.5a Not reported 3.5a (Christou et al., 2016)
Trimethoprim Medicago sativa L. 10 μg/L 50 311.9a Not reported 23.5a (Christou et al., 2016)
17α-Ethinylestradiol Medicago sativa L. 10 μg/L 50 28.9a Not reported 28.3a (Christou et al., 2016)
a
Concentrations are given in μg/kg.

main pathway for the downward transportation of end products of pho-
tosynthesis from the leaves towards roots.
The extent of translocation has been found to be dependent on var-
ious factors that include physicochemical properties of the pharmaceu-
tical, the soil properties, the plant physiology and environmental
conditions. In a study conducted for the uptake of pharmaceuticals by
lettuce, carrot and tomato, Dodgen et al. (2015) reported that carba-
mazepine, meprobamate and dilantin were the most translocated
when compared to atorvastatin, ibuprofen, and sulfamethoxazole
(Dodgen et al., 2015). This was explained in terms of differences in hy-
drophobicity and charge of the pharmaceutical. Generally, pharmaceu-
ticals with log Kow between 1 and 3.5 are likely to accumulate in the
leaves. The neutral and cationic pharmaceuticals are also likely to accu-
mulate in leaves while the anionic ones remain in roots. This is an indi-
cation that the pKa value of a compound also determines its fate during
absorption and translocation studies. This has also been observed by
Goldstein et al. (2014) in which nonionic pharmaceuticals were found
to accumulate in leaves (Goldstein et al., 2014). The accumulation of
cationic and neutral organics in leaves are an indication that the trans-
location of these compounds is predominantly in the direction of the
transpiration stream. This also implies that their transportation could
be affected by the transpiration rate.
Goldstein et al. (2014) have also observed that uptake of ionic phar-
maceuticals is affected by soil properties, plant physiology and water
quality. In their study, the weakly acidic pharmaceuticals were observed
to exhibit a lower uptake. The presence of soil organic matter tends to
reduce the bioavailability of anionic pharmaceuticals. In addition,
these acidic pharmaceuticals are repelled by the negatively charged
cell walls and cytosol. Several other studies have conferred with these
observations. Eggen et al. (2011) observed that the root concentration
factors were higher than the corresponding leaf concentration factors
for three pharmaceuticals (metformin, ciprofloxacin and narasin) in
carrot (Daucus carota ssp. sativus cvs. Napoli) and barley (Hordeum
vulgare) (Eggen et al., 2011). This was also the case in the translocation
of sulfamethazine, where the highest average amount of target pharma-
ceutical (8.58 μg/kg) was detected in the root zone, followed by the top
portion (1.89 μg/kg), middle one-third (1.30 μg/kg), and sap (0.38
μg/kg) samples (Kurwadkar et al., 2017). Also, leaf and stems of the
cabbage (Brassica rapa var. pekinensis) were found to contain lower
concentrations of trimethoprim, salbutamol, carbamazepine, and
sulfamethoxazole when compared to roots (Herklotz et al., 2010).
The same authors further observed highest accumulation of sulfa-
methoxazole than other pharmaceuticals which was explained by
its low pKa value compared to other studied compounds. As a result,
sulfamethoxazole was easily deprotonated in the nutrient solution
from the inception of the experiment (Herklotz et al., 2010).
Root uptake of antibiotics from soil within 6 days with no transloca-
tion observed within the rice (Oryza sativa L.) plant was reported by
Hawker et al. (2013) (Hawker et al., 2013). Similar observations were
reported for the uptake of antibiotics (oxytetracycline and norfloxacin)

Fig. 2. Uptake of pharmaceuticals by plant roots and their translocation into stem and leaves. The given concentration levels are based on studies reported for uptake of tetracyclines by
Brassica campestri a(Topal, 2015) and uptake of carbamazepine by Phragmites australis b(Holling et al. (2012).
 L.M. Madikizela et al. / Science of the Total Environment 636 (2018) 477–486
by soybeans (Glycine max (L.) Merr.) as well as rice (Oryza sativa L.) up-
take of tetracycline antibiotics in study periods of 35 and 15 days, re-
spectively (Boonsaner and Hawker, 2012, 2010). These observations
provide further evidence that the translocation mechanism depends
on the physicochemical properties of the pharmaceutical, the physiolog-
ical characteristics of plant material and the exposure time (Kurwadkar
et al., 2017). This has further been confirmed, where most tested phar-
maceuticals, in E. horemanii were found to accumulate more in leaves,
whereas, similar compounds in E. crassipes were observed to allocate
more in roots (Pi et al., 2017). Furthermore, highly hydrophilic pharma-
ceuticals such as trimethoprim and sulfonamides are known for their
ability to accumulate in roots (Tanoue et al., 2012). Also, ionization as
well as the properties of sorption and water solubility may affect how
plants uptake pharmaceuticals (Herklotz et al., 2010).
7. Toxicity of pharmaceuticals in plants
Negative effects of some pharmaceuticals on plants have been docu-
mented in literature (Amy-Sagers et al., 2017; Carter et al., 2015; Kong
et al., 2007; Lin and Li, 2016; Marsoni et al., 2014). Greater details on
the toxicity of veterinary antibiotics have already been discussed else-
where (Bártíková et al., 2016). Therefore, herein the focus is expanded
to other pharmaceuticals in extension of veterinary antibiotics as
shown in Table 5. The specific effects on each plant species depend on
the class of the pharmaceutical drug, drug concentration, and plant spe-
cies exposed to the drug (Bartrons and Peñuelas, 2017). As an example,
an anti-depressant, fluoxetine, has been reported to decrease L. minor
root growth and asexual reproduction when the plant is exposed to
323 nmol/L of the pharmaceutical for 21 days (Amy-Sagers et al.,
2017). The presence of carbamazepine in soil at concentrations exceed-
ing 4 mg/kg has resulted in mature leaves of Cucurbita pepo suffering
from burnt edges, white spots and reduction in photosynthetic pig-
ments (Carter et al., 2015). Elsewhere, oxytetracycline was found to in-
hibit alfalfa (Medicago sativa L.) shoot and root growth by up to 61% and
85%, respectively (Kong et al., 2007). Further to this, the leaves of alfalfa
plant turned to light green or even yellow with increasing oxytetracy-
cline dosage (Kong et al., 2007). A decrease in root length was observed
in Z. mays seedlings with no effect on germination in the plants irrigated
with water spiked with a mixture of salbutamol, atenolol, lincomycin,
cyclophosphamide, carbamazepine, bezafibrate, ofloxacin and raniti-
dine (Marsoni et al., 2014). Furthermore, a detailed study on the effects
of ten antibiotics on seed germination and root elongation in three plant
species, namely; lettuce (Lactuca sativa), alfalfa (Medicago sativa), and
carrot (Daucus carota) was presented where effects such as decreased
root length and plant growth, were observed (Hillis et al., 2011).
Mixture⁎ - contained 8 pharmaceuticals which were salbutamol
(bronchodilator), atenolol (anti-Arrhythmia), lincomycin (antibacterial),
cyclophosphamide (antineoplastic), carbamazepine (antiepileptic),
Table 5
The negative effects of pharmaceuticals in plants.
Therapeutic group Pharmaceuticals Plant species
Antidepressant Fluoxetine Lemna minor
Antiepileptic Carbamazepine Cucurbita pepo
Antipyretic Acetaminophen Brassica juncea L. Czern
Antidiabetic Metformin Daucus carota cvs. Napoli and
Amagar
Antimicrobial Sulphadimethoxine Mixture⁎ Hordeum distichum L.
Zea mays
Antibiotics Chlortetracycline and oxytetracycline D. carota and M. sativa
Antibiotic Oxytetracycline Medicago sativa L.
Antibiotic Sulfadiazine Salix fragilis L. and Zea mays L.
483
bezafibrate (antilipemic), floxacin (antibacterial) and ranitidine (hista-
mine H2 antagonists).
8. Implications and future studies
The occurrence of pharmaceuticals in vegetables could imply a po-
tential risk to humans through the food consumption. Future studies
should be directed to the effects of long-term consumption of low con-
centrations of pharmaceuticals through the food sources. In a study re-
ported by Dodgen et al. (2013) the concentrations of selected
pharmaceutical drugs in plant tissues ranged from 0.22 to 927 ng/g,
which suggest that an average individual would consume the equiva-
lent of much less than one dose of target drugs in a year due to con-
sumption of the analyzed leafy vegetables (Dodgen et al., 2013). Some
studies have indicated that the majority of individual pharmaceuticals
found in the edible tissue of plants or fruits harvested from plants due
to biosolids or manure amendment or wastewater irrigation represent
a de minimis risk to human health (Christou et al., 2017; Prosser et al.,
2014; Prosser and Sibley, 2015). Ahmed et al. (2015) reported similar
observations where they found high levels of tetracyclines and sulfon-
amides in the nonedible parts such as roots and leaves of cucumber
and tomato, with fruit parts accumulating them at concentrations
lower than acceptable daily intake (Ahmed et al., 2015). In a study con-
ducted by Chitescu et al. (2013) on the uptake of oxytetracycline, sulfa-
methoxazole and ketoconazole from fertilized soils by plants (grass and
watercress), it was reported that plant contamination does not cause an
acute risk for humans (Chitescu et al., 2013). However, it is projected
that due to the growing demand for alternative irrigation resources
and the potential increase in the application of sewage sludge on farm-
land, pharmaceutical residues will increase in soil, which means the
threats posed by uptake of pharmaceuticals by vegetables should be of
more concern in future than at present (Carter et al., 2014).
Most of the work have focused on the plant uptake of pharmaceuti-
cals that belong to the antibiotics, antiepileptic and NSAIDs. However,
recent work show the spread of antiretroviral drugs in water especially
in African countries (Mashiane, 2015; Ngumba et al., 2016; Wood et al.,
2015). Other pharmaceutical compounds that are known to be present
in water bodies belong to antimalarials and steroid hormonal groups
(Madikizela et al., 2017). Therefore, it is anticipated that more studies
on plant uptake of antiretroviral drugs, antimalarials and steroid hor-
mones will emerge in the near future.
The detection of metabolites of pharmaceuticals in water and plants
have been reported in few studies (Ben Mordechay et al., 2017; Dordio
et al., 2011; Koba et al., 2018; Paz et al., 2016; Reichl et al., 2018). Metab-
olites such as 4′-hydroxy-flurbiprofen which originates from flurbiprofen
is more toxic that the parent pharmaceutical (Ma et al., 2017). Therefore,
in future more focus should be directed on the occurrence and plant up-
take of metabolites, as these could have a potential to cause more health
Effect on plants Reference
Decreased root growth (Amy-Sagers et al., 2017)
The mature leaves suffered from burnt edges, white (Carter et al., 2015)
spots and reduction in photosynthetic pigments
Oxidative stress as well as increasing amounts of bleaching (Bartha et al., 2010)
and dot-like lesions occurred on adaxial side of the leaf, and
necroses.
Reduced growth and biomass production (Eggen and Lillo, 2012)
Growth suppression (Migliore et al., 1996)
Decreased in root length (Marsoni et al., 2014)
Decreased in root length (Hillis et al., 2011)
Leaves colour changed. Also, leaves and roots biomass (Kong et al., 2007)
decreased
Stress developed in Salix fragilis L. (e.g., reduced C/N ratio (Michelini et al., 2012)
and total chlorophyll content) and death of Zea mays L.
484 L.M. Madikizela et al. / Science of the Total Environment 636 (2018) 477–486
risks to the consumers of plants. On the other hand, some studies cited in
this work conducted their research using water and soil spiked with
pharmaceuticals at concentrations higher than those expected in real
world such as WWTP effluent and surface water as well as soil. This
was mostly done to accommodate the detection ability of analytical in-
strumentation. For example, Amy-Sagers et al. (2017) have spiked fluox-
etine at 323 nmol/L whereas its maximum concentration reported in
surface water was 32 nmol/L (Amy-Sagers et al., 2017). In addition, a
number of pharmaceuticals at concentrations higher than those expected
in the environment have been reported to have negative impact on the
plant growth (Lin and Li, 2016; Mikes and Trapp, 2010). Therefore,
there is an opportunity to conduct future work using more realistic levels
of pharmaceuticals in order to fully understand the plant uptake pro-
cesses and toxicity of pharmaceuticals on plants under normal conditions.
9. Conclusion
In this review, the work conducted on the uptake of pharmaceuticals
by plants from soil and water is discussed. Thus far, most of the work
has been conducted for plant uptake of pharmaceuticals hydroponically
with little focus on real situations. For example, there is little work con-
ducted on the occurrence of pharmaceuticals in vegetables purchased
from supermarkets and in natural occurring plants sampled from rivers.
The work done on pharmaceutical uptake by plants points out the
possibility of utilizing constructed wetlands and certain plants for
phytoremediation. The efficiencies given in literature for removal of
pharmaceuticals from water by plants are somewhat similar to those
reported for certain WWTPs. More investigation should be conducted
in order to find the point where the plants can reach saturation (a
stage where they cannot absorb pharmaceuticals anymore). The trans-
location of pharmaceuticals within the plant tissues towards the edible
crops remains a serious concern. Therefore, investigations on the effects
of extended daily consumption of pharmaceuticals through the con-
taminated food sources and water needs to be conducted in future.
Acknowledgements
This work is based on the research supported wholly by the National
Research Foundation of South Africa (Grant Numbers: 114415).
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