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OSE 13.degradation of Aqueous Pharmaceuticals by Ozonation and Advanced Oxidation Processes: A Review
OSE 13.degradation of Aqueous Pharmaceuticals by Ozonation and Advanced Oxidation Processes: A Review
To cite this article: Keisuke Ikehata, Naeimeh Jodeiri Naghashkar & Mohamed Gamal El-Din (2006): Degradation of Aqueous
Pharmaceuticals by Ozonation and Advanced Oxidation Processes: A Review, Ozone: Science & Engineering: The Journal of the
International Ozone Association, 28:6, 353-414
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Ozone: Science and Engineering, 28: 353–414
Copyright # 2006 International Ozone Association
ISSN: 0191-9512 print / 1547–6545 online
DOI: 10.1080/01919510600985937
A vast number of pharmaceuticals have been detected in in the urine and feces, and subsequently enter into sewage
surface water and drinking water around the world, which treatment plants where these compounds are treated,
indicates their ineffective removal from water and waste-
water using conventional treatment technologies. Concerns along with other organic and inorganic constituents in
have been raised over the potential adverse effects of phar- wastewater. However, it has been shown that some of
maceuticals on public health and aquatic environment. these pharmaceutical compounds are not completely
Among the different treatment options, ozonation and removed in sewage treatment plants (Halling-Sørensen
advanced oxidation processes are likely promising for effi- et al., 1998; Ternes, 1998; Ternes et al., 1999; Heberer,
cient degradation of pharmaceuticals in water and waste-
water. Recent progress of advanced oxidation of aqueous 2002; Boyd et al., 2003). As a result, they have been found
pharmaceuticals is reviewed in this paper. The pharmaceu- in some sewage treatment plant effluents as well as in
ticals and non-therapeutic medical agent of interest include surface water and groundwater in many countries
antibiotics, anticonvulsants, antipyretics, beta-blockers, (Ternes, 1998; Sacher et al., 2001; Soulet et al., 2002;
cytostatic drugs, H2 antagonists, estrogenic hormone and Miao et al., 2004). In addition, non-therapeutic medical
contraceptives, blood lipid regulators, and X-ray contrast
media. agents such as X-ray contrast agents (also known as
radiocontrasts) and some veterinary drugs have been
Keywords Ozone, Advanced Oxidation Processes, Antibiotic, also found in the aquatic environment (Ternes and
Antipyretic, Anticonvulsants, Blood Lipid Regula- Hirsch, 2000; Drewes et al., 2001; Kümmerer, 2001).
tor, Beta-blocker, Cytostatic Drug, X-Ray Contrast Although some of these pharmaceuticals and their meta-
Media, Estrogens bolites can be partially removed through sorption and
biotic or abiotic degradation in the environment, they
can eventually reach drinking water sources. Several
INTRODUCTION recent studies have revealed that conventional water
treatment processes cannot remove some prescription
A large amount of numerous prescription and non- and non-prescription drugs completely from source
prescription drugs of different classes are consumed waters (Ternes et al., 2002; Stackelberg et al., 2004;
annually throughout the world. These pharmaceutical Jones et al., 2005a).
compounds include antipyretics, analgesics, blood lipid The frequent occurrence of pharmaceuticals in the
regulators, antibiotics, antidepressants, chemotherapy aquatic environment as well as in finished drinking
agents, and contraceptive drugs. After the administration, water has raised a concern about their potential impact
these compounds are partially metabolized and excreted on environmental and public health. Some of the adverse
effects caused by pharmaceutical pollution include aqua-
tic toxicity, resistant development in pathogenic bacteria,
genotoxicity, and endocrine disruption (Arcand-Hoy
Received 03/28/2006; Accepted 06/05/2006 et al., 1998; Halling-Sørensen et al., 1998; Sumpter,
Address correspondence to Mohamed Gamal El-Din, Dept. of 1998; Kümmerer, 2004). The presence of trace pharma-
Civil and Environmental Engineering, 3-093 Markin/CNRL
Natural Resources Engineering Facility, University of Alberta, ceutical and other xenobiotic compounds in finished
Edmonton, Alberta T6G 2W2, Canada. E-mail: mgamalel-din@ drinking water is another public health concern, since
ualberta.ca little is known about potential chronic health effects
2005), and activated carbon adsorption (Hartig et al., pitals and clinics. After the administration, drug
2001; Ternes et al., 2002). molecules are absorbed, distributed, metabolized, and
The latter two processes are highly energy and material finally excreted from the body. To be used safely most
intensive (Larsen et al., 2004) and only suitable for the of the modern pharmaceuticals are designed in a way to
treatment of relatively clean surface water and ground- undergo metabolism in organs such as liver and kidney
water with less background contamination such as natural after they have achieved desired pharmacological effects.
organic matter (NOM). These physical treatment processes Metabolisms detoxify excess drug molecules, as well as
also require the disposal of wastes such as membrane other toxic xenobiotics, via a series of enzymatic biotrans-
retentate and spent activated carbon generated during formations and convert them to be more polar and
the treatment. In addition, activated carbon adsorption hydrophilic (Silverman, 1992). The drug metabolism
has a limited ability to remove polar organic compounds begins with various biochemical reactions including
due to its removal mechanism (i.e., hydrophobic inter- hydroxylation, epoxidation, reduction, and hydrolysis,
actions), especially in the presence of competitive NOM in which functional groups are introduced or unmasked
(Snyder et al., 2003), and many pharmaceutical com- (phase I transformation). Afterwards, highly polar endo-
pounds and metabolites are indeed polar substances. On genous molecules such as glucuronic acid, sulfate, and
the other hand, chemical oxidation such as ozonation and amino acids are attached to drugs or metabolites of
advanced oxidation processes (AOPs) may be a more phase I transformation to generate conjugates (phase II
appropriate treatment option for pharmaceutical com- transformation) that are water-soluble and can be readily
pounds in wastewater as well as in surface water and excreted in the urine or bile. There are certain drugs, non-
groundwater. therapeutic medical agents, and xenobiotics that are non-
In this review, recent literature concerning ozonation metabolizable because they are poor substrates for meta-
and advanced oxidation treatment of a number of phar- bolizing enzymes such as cytochrome P-450. These com-
maceutical compounds in aqueous medium are reviewed pounds may be eliminated slowly from the body without
and discussed in terms of the degree of reaction (i.e., biotransformation.
degradation), reaction kinetics, identity and characteris-
tics of oxidation by-products, and possible degradation Occurrence and Fate of Pharmaceuticals in the
pathways. Nine major classes of pharmaceuticals listed in Environment
Table 1 are covered, including antibiotics, anticonvul- Until recently pharmaceutical compounds in the envir-
sants and antidepressants, antipyretics and non-steroidal onment have drawn very little attention. Although their
anti-inflammatory drugs, beta-blockers, cytostatic drugs, presence in sewage treatment plant effluents was reported
histamin H2-receptor antagonists, hormones and oral (Richardson and Bowron, 1985), it had been anticipated
contraceptives, lipid regulators, and X-ray contrast that these compounds were easily biodegradable in
media. A brief review of pharmaceuticals and its metabo- environment as most of them could be metabolized and
lism, their occurrence and fate in the environment, and transformed to some extent in humans, as discussed
their potential impact on environmental and public health before (Kümmerer, 2001; Debska et al., 2004). However,
is provided in the following section as well. Please also a large number of recent studies have demonstrated
refer to the comprehensive surveys published elsewhere persistence of these pharmaceuticals in the aquatic
environment. The occurrence of several pharmaceutical clinics. These drugs are partially metabolized and
compounds have been reported in sewage treatment plant excreted in the urine and feces and go into a wastewater
effluents as well as in surface waters in Germany (Ternes, collection system (Heberer, 2002; Jones et al., 2005b).
1998; Hirsch et al., 1999; Putschew et al., 2000), the Some unused, surplus, or expired drugs may be disposed
Netherlands (Belfroid et al., 1999), Switzerland (Soulet into toilets, although this kind of practice is not recom-
et al., 2002), Canada (Ternes et al., 1999; Miao et al., mended nowadays. Wastewater from the hospitals may
2004), Brazil (Ternes et al., 1999), Italy (Castiglioni et al., be treated separately or combined with municipal waste-
2004), Spain (Rodrı́guez et al., 2003), and the United water and then treated at sewage treatment plants.
States (Drewes et al., 2001; Kolpin et al., 2002). The Some of the pharmaceuticals and (human) metabolites
detected compounds included antibiotics, anticonvul- in wastewater are degraded completely or partially, giving
sants, painkillers, cytostatic drugs, hormones, lipid regu- rise to a mixture of parent compounds and a variety of
lators, beta-blockers, antihistamines, and X-ray contrast microbial metabolites (Ternes, 1998; Drewes et al., 2001;
media. The concentrations of these pharmaceuticals were Miao et al., 2002; Soulet et al., 2002; Jones et al., 2005b).
in the range of ng/L to mg/L in sewage treatment plant Some pharmaceuticals such as ibuprofen and bezafibrate
effluents and surface water. In addition, a number of are relatively biodegradable, while others such as carba-
polar pharmaceutical compounds and metabolites, such mazepine and diazepam are practically non-biodegradable
as diclofenac, carbamazepine, sulfamethoxazole, and (Larsen et al., 2004). It is also known that some drug
amidotrizoic acid, have been detected in groundwater conjugates such as glucoronides can be cleaved by micro-
samples at concentrations up to 1 mg/L (Sacher et al., bial degradation resulting in a release of parent com-
2001; Cahill et al., 2004; Clara et al., 2004). pounds (Heberer, 2002; Jones et al., 2005b). Effluent
There are several possible sources and routes for the from sewage treatment plants may be released to surface
occurrence of pharmaceutical compounds in the aquatic water or be subjected to groundwater recharges, so that
environment (Figure 1). For human pharmaceuticals, the mixture of compounds enters the aquatic environment.
non-prescription drugs and some prescription drugs are In some cases, biologically treated municipal wastewater
consumed in households, and other prescription drugs are may be treated further to produce various reclaimed
consumed in healthcare facilities such as hospitals and waters for different purposes including portable re-use.
Sorption can also occur during the sewage treatment application of livestock manure is often practiced and
processes and some of the pollutants can be transferred to may cause contamination problems in surface water and
sewage sludge (Larsen et al., 2004). Sewage sludge may be groundwater similar to the case of municipal sewage
subjected to anaerobic or aerobic digestion, conditioning sludge disposals described above. Additional sources of
and dewatering, and is subsequently landfilled, inciner- pharmaceuticals in the aquatic environment include was-
ated, or applied to lands as a biosolid. Pharmaceutical tewater from pharmaceutical production/formulation
compounds in the sludge can be degraded further during plants and waste disposal of unused drugs as a solid
the digestion, although some of them may remain intact. waste.
These compounds can be seeped into groundwater aqui-
fers or be flushed by surface water runoff after the land ENVIRONMENTAL AND PUBLIC HEALTH IMPACTS
application and can cause additional contamination pro- OF PHARMACEUTICALS IN THE ENVIRONMENT
blems in the aquatic environment. Therefore, the sorption
of pharmaceuticals during sewage treatment processes After publication of the earlier occurrence data, the
cannot be counted as a removal process unless the sludge risks associated with pharmaceutical contamination of
was incinerated (Larsen et al., 2004). the aquatic environment have become a major issue of
In addition to the drugs and medical agents for human concern for environmental scientists and engineers, as
use, a large amount of pharmaceutical compounds, espe- well as among the public. Drugs are the chemicals that
cially antibiotics, are used for various agricultural pur- are designed to give a certain therapeutic (= biological)
poses, such as veterinary therapeutics, growth promotion effect; therefore, certain environmental and public health
of livestock, and feed additives in fish farms (Halling- risks can be anticipated from the exposure to the envir-
Sørensen et al., 1998). As shown in Figure 1, these phar- onmental pharmaceuticals. Besides, there are a few
maceuticals can enter into the aquatic environment classes of pharmaceuticals that pose unambiguous
directly (feed additives for fish) or indirectly through live- impacts on the aquatic organisms, including microorgan-
stock manure (growth promoters and therapeutics). Land isms, phytoplankton, plants, crustaceans, fish, and
FIGURE 2. Possible points to apply ozonation and AOPs for the degradation of pharmaceuticals.
water sources, which is increasingly common in semi-arid compounds toward ozonation and AOPs and can be use-
areas, complete removal or destruction of pharmaceuti- ful to model the treatment process (Beltrán, 2003;
cals may be desired. As shown in Figure 2, ozonation and Oppenländer, 2003). Typically, the reaction kinetics can
AOPs can be applied to water treatment as a part of pre- be described by a second order rate law:
oxidation and/or disinfection steps. Wastewater from
pharmaceutical production/formulation plants and hos- rðMÞ ¼ d½Mt =dt ¼ koxidant;M ½M½oxidant
pital wastewater can be treated in a similar manner to where r(M) represents the rate of diminution of the
domestic wastewater, with appropriate pretreatment such concentration of M (organic substrate = pharmaceuti-
as pH adjustment. cals), and koxidant,M is the second order rate constant for
During the treatment by ozonation or advanced oxida- the reaction of oxidant (O3 or OH) and M. In addition to
tion, organic pollutants such as pharmaceutical com- molecular ozone and hydroxyl radical reactions, direct
pounds undergo a series of oxidation and spontaneous photolysis also contribute to the degradation of pharma-
transformations. In other words, primary degradation ceutical compounds during the AOPs in which UV-Vis
products are often degradated further in prolonged treat- irradiation is involved. In such a case, the quantum yield
ment. In some cases, disappearance of parent pharmaceu- (F), defined by the amount of reactant consumed per
tical compounds does not indicate successful treatment amount of photon absorbed, of the direct photolysis
because the degraded products may be as biologically may be determined. These three types of reactions can
active as the parent compounds. Likewise, some conven- occur simultaneously and competitively, depending on
tional water quality parameters can be used to evaluate the AOP combination used, the presence of other water
the effectiveness of the process, such as total organic and wastewater constituents, and pH.
carbon (TOC), chemical oxygen demand (COD), dis- A tabulated summary is presented in the Appendix
solved organic carbon (DOC), absorbable organic halo- with major reaction conditions such as initial pH and
gene (AOX), and aromaticity; however, they do not temperature. It should be noted that in most of the ozo-
provide direct information about the identity of degrada- nation studies, only the amount of applied ozone has
tion products and the safety of treated water. been given, and there was not enough information
Consequently, the analysis of pharmaceutical compounds about the actual amount of ozone utilized during the
and their degradation products (by-products) using gas treatment.
chromatography (GC) or liquid chromatography (LC)
coupled with mass spectrometry (MS) has been increas-
ingly common and becoming an asset in recent studies Antibiotics
(Ternes, 2001; Debska et al., 2004). Antibiotics are a group of pharmaceuticals used for the
In some cases, the rate constants for the reaction treatment of both human and animals with bacterial and
between a pharmaceutical compound and oxidant (i.e., fungal infections. Many of the antibiotics are derived
molecular ozone and hydroxyl radicals) has been deter- from wholly or partially from certain microorganisms,
mined. These rate constants indicate the reactivity of the but some are synthetic (e.g., sulfonamides). A wide
H H
O N S
N
H H
N S O N
N O
O N S N O OH
H2N S O O
N
O OH N OH penicillin G (334.39)
ceftriaxone (554.57)
O
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O O
O N H
O
O N
H H O S O
N S H2N
O N S O
H H
O N
O
O sultamicillin (594.65)
O
penicillin VK (388.47) K+
N N
HS N S N
S S
5-methyl-1,3,4-thiadiazole-2-thiol 5-methyl-1,3,4-thiadiazole-2-methylthiol
(MMTD; 132.20) (MMTD-Me; 146.24)
at pH 12 with an applied ozone dose of 1.8 g/L in 1 h. was improved from 0.25 to 0.45, while acute toxicity
Overall second-order rate constants for the COD removal (assessed by Daphnia magna mortality) was reduced mark-
from the penicillin formulation by ozonation was deter- edly after the 30 min of photo-Fenton-like treatment men-
mined as 0.042 and 0.67 M1s1 at pH 3 and 7, respec- tioned previously (Arslan-Alaton and Gurses, 2004).
tively (Arslan-Alaton and Caglayan, 2005). Andreozzi et al. (2005) investigated the kinetics and
Arslan-Alaton and Gurses (2004) investigated the pathway of amoxicillin degradation by ozonation. Rate
photo-Fenton-like process for the treatment of penicillin of reaction between amoxicillin and molecular ozone was
G-procaine formulation using a 125-W black light emitting found to be strongly pH dependent: from 4 · 103 M1s1
UV-A in the range of 300 to 370 nm with an incident light at pH 2.5 to 6 · 106 M1s1 at pH 7. The second-order
flux of 1.7 · 103 Einsteinmin1. Under optimum reaction rate constant for hydroxyl radical reaction with amoxi-
conditions ([Fe3+]0 = 1.5 mM, [H2O2]0 = 25 mM, pH 3), cillin was also calculated as 3.93 · 109 M1s1 at pH 5.5
56% and 42% of initial COD and TOC, respectively, were using H2O2/UV AOP to generate hydroxyl radicals
removed after 30 min of photo-Fenton-like treatment. It (Andreozzi et al., 2005). Whereas hydroxylation of the
was also demonstrated that Fenton-like treatment without phenol ring was confirmed, no evidence was found for
UV-A irradiation was slightly less effective in COD S-oxidation of amoxicillin molecules by molecular ozone.
removal from the penicillin formulation and that No further degradation was noticed, probably due to the
neither UV-A alone, ferric ion with UV-A, nor H2O2/ short reaction time (up to 4 min) and the absence of
UV-A was effective (Arslan-Alaton and Gurses, 2004). hydroxyl radicals in the system as 2-methyl-2-propanol
Biodegradability of the penicillin G-procaine formulation was used as a scavenger.
O O O
O O
O N
N
HO
HO
O HO OH
N O S OH
O
N O
H O
HO OH O
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OH O OH
O
lincomycin (406.54)
O
roxithromycin (837.05)
O O
O N H N H
H H2N S N
H2N S N H2N S N
N O N O
O N O
O O O N
O S H H
H H2N S N H2N S N
H2N S N
N
O N N O O
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O S O
H H
H2N S N H2N S N
O N O O N
Macrolide Antibiotics
Among the antibiotics shown in Figure 4, azithro-
mycin, clarithromycin, erythromycin, and roxithromy-
N
cin are macrolide antibiotics, and lincomycin is a
HO
lincosamide antibiotic, which has an antibacterial spec- O OH
HO
trum similar to macrolides. Although not shown in OH
O
Figure 4, there is another lincosamide antibiotic called O
O
clindamycin, which is a derivative of lincomycin and O
more commonly prescribed nowadays because of its O
O
OH
improved absorption property after oral administration
(Merck & Co., 1999). These antibiotics are character- O
ized by a property to inhibit bacterial protein synthesis.
FIGURE 10. Chemical structure of dehydroerythromycin, an
These antibiotics are mostly excreted in the bile (Merck environmental metabolite of erythromycin (Huber et al., 2005).
& Co., 1999).
reactions is considered to be negligible. Besides the pyr- cular structure, and subsequent decontamination and
rolidine nitrogen, a sulfur atom of methylthio group is regeneration of zeolite by ozonation (Ötker and
suggested as a prime target of ozone attack (see Figure 11). Akmehmet-Balcioglu, 2005). They demonstrated the suc-
Based on their kinetic model, the absolute second-order cessful decontamination of enrofloxacin-loaded zeolite
rate constants for lincomycin ozonation were calculated (equilibrated with 200 mg/L enrofloxacin for 24 h) by
as 3.26 · 105 and 2.43 · 106 M1s1 for protonated and 30 min of ozonation (consumed ozone = 100 mg), sug-
neutral forms, respectively (Qiang et al., 2004). gesting that the zeolite adsorption-ozonation system
In addition to ozonation, Addamo et al. (2005) might be a good method to control antibiotic pollution
reported photo-catalytic degradation of lincomycin due to animal manure land application.
using two types of TiO2 catalysts. Addition of TiO2 pow- Ofloxacin. Andreozzi et al. (2004) investigated the
der (0.4 g/L Degussa P25 or 1 g/L Merck TiO2) strongly ozonation, H2O2/UV, and TiO2 photo-catalysis for the
enhanced the degradation of lincomycin from UV irradia- decontamination of an aqueous pharmaceutical mixture
tion alone with a 125 W medium pressure Hg lamp with a containing ofloxacin, as well as five other drugs, namely
photo flux of 8.5 mWm2. Complete conversion of 50 carbamazepine, propranolol, clofibric acid, diclofenac,
mg/L lincomycin was achieved in 2 h by the TiO2/hn and sulfamethoxazole. It was shown that 2 min of ozona-
treatment at pH 6 and 20 C, and about 60% of initial tion (13.9 mg/L absorbed O3) as well as H2O2/UV treat-
TOC was removed from the solution. Although S-oxida- ment ([H2O2]0 = 5–10 mM, a low-pressure Hg lamp, at
tion of methylthio group and oxidation of pyrrolidine 254 nm, 2.51 · 106 Einsteins1) was sufficient for the
ring followed by a cleavage of amide bond were suggested complete conversion of 560 mg/L ofloxacin at pH 7.4 and
as possible routes of lincomycin degradation by TiO2 25 C, whereas TiO2/hn process was less effective. Algal
process (Addamo et al., 2005), the actual degradation (Synechococcus leopoliensis) and protozoan (Brachionus
intermediates and by-products were not determined, calyciflorus) toxicities of the drug mixture were eliminated
with the exception of sulfate ion. completely by the ozone treatment in 2 min. The H2O2/
UV treatment was also effective for algal toxicity reduc-
Quinolone Antibiotics tion; however, it was less effective for protozoan toxicity
Two types of quinolone antibiotics, including enro- reduction. Finally, the TiO2/hn treatment was ineffective
floxacin and ofloxacin, have been studied for their in either case (Andreozzi et al., 2004), probably because
degradation by ozonation and AOPs. More specifi- of insufficient drug conversion. Degradation by-products
cally, both are fluoroquinolones. While enrofloxacin is of ofloxacin were not determined.
used as a veterinary antibiotic, ofloxacin is intended
for human consumption. These compounds have a
property to inhibit the activity of bacterial DNA gyr- Sulfonamide Antibiotics
ase (Merck & Co., 1999). The chemical structure and Sulfonamides are synthetic antibiotics also called sulfa
molecular weight of these quinolone antibiotics are drugs that inhibit multiplication of bacteria by acting as
shown in Figure 5. Please note that ofloxacin is a competitive inhibitors of p-aminobenzoic acid in the folic
racemic mixture of chiral molecules, and the biologi- acid metabolism cycle (Merck & Co., 1999). A variety of
cally active S-enantiomer, which is also called levoflox- sulfonamides have been produced, consumed, and subse-
acin, is shown in the figure. It is known that the quently detected in the environment, and some of them
for nine other sulfonamide antibiotics, has been reported the formation of stable organic by-products bearing nitro-
(Boreen et al., 2004; 2005) as shown in Table 2. Fenton gen atom(s), although these by-products were not deter-
process was employed to generate hydroxyl radicals, and a mined. During the TiO2/hn treatment, formation of
competition kinetics method was used to estimate the rate hydroxylated intermediate of sulfadiazine was suggested
constants using acetophenone as a reference compound. (Figure 13), which quickly disappeared as the degradation
Unlike direct photolysis, which is strongly affected by the proceeded (Calza et al., 2004a). As aniline is not particu-
types of heteroaromatic ring attached to sulfonamide nitro- larly persistent toward advanced oxidation (Sauleda and
gen, the rate constants for hydroxyl radical reactions are Brillas, 2001; Li et al., 2003), the N-bearing intermediates
nearly equal and close to diffusion-controlled limit of 1010 suggested by Calza et al. are likely derived from 2-amino-
M1s1. It has been also shown that the reactivity of these pyrimidine (R-NH2 in Figure 13) released by the cleavage
sulfonamides toward direct photolysis is dependent on the of S-N bond of sulfadiazine.
protonation state of the concerned compound (Figure 12, Sulfadimethoxine, Sulfamerazine and Sulfathiazole.
Table 2; Boreen et al., 2004; 2005), although the effect of Similar to the cases of other sulfonamide antibiotics,
pH on hydroxyl radical reactions has not been studied. No rapid conversion of sulfadimethoxine, sulfamerazine,
degradation by-product/intermediate was identified for sul- and sulfathiazole by ozonation in river water was
fachlorpyridazine ozonation or AOP. reported (Adams et al., 2002; Huber et al., 2005), and
TABLE 2. pKa, Second-Order Rate Constant for Hydroxyl Radical Reaction (kOH), and Quantum Yield (F) of Sulfonamide Antibiotics (Boreen
et al., 2004; Boreen et al., 2005)
FP (mMEins1)
SH2+ SH S-
FIGURE 12. Protonation states of the sulfonamide antibiotics (Boreen et al., 2004). SHþ
2 ; SH, and S represent cationic, neutral, and anionic
forms, respectively.
O O O
H •OH H
H2N S N R H2N S N R O N O N
H H
O O H2N S N N H2N S N
OH
hydroxylated sulfonamide
O O N
parent sulfonamide OH O OH
•OH •OH hydroxylated sulfamerazine
hydroxylated sulfadimethoxine
O O (aniline side)
H2N S OH + R-NH2 R-NH2 + H2N S OH
O O O
OH
O N
H N
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•OH •OH
•OH
•OH H2N S N N H2N
O N
SO42- SO42- HO O
Further degradation, release of NH 4+ 4-methyl-2-aminopyrimidine
hydroxylated sulfadimethoxine
FIGURE 13. Degradation of sulfonamides by advanced oxidation (pyrimidine side)
process (Calza et al., 2004a).
O S
H
O H2N S N
N O N
comparable second-order rate constants for the hydroxyl H2N N OH
radical reactions of these sulfonamide antibiotics were hydroxylated sulfathiazole
determined (see Table 2; Boreen et al., 2005). Calza O
ozone reactions. It has been demonstrated in the studies with 200 mg/L TiO2 and a 1500-W xenon lamp with a 340
reviewed here that the complete conversion of antibiotics nm cut-off filter (1.35 · 105 Einsteinmin1) at 50 C,
is readily achievable by either ozonation or AOP; how- and a number of degradation intermediates were identi-
ever, their mineralization is not always confirmed. fied by LC-MS-MS as shown in Figure 17. It was sug-
Similarly, the identity and quantity of degradation by- gested that hydroxylation of pyrimidine ring and
products arising from ozonation and advanced oxidation azaspirone decane dione substructure occurred simulta-
treatment are largely unknown for most antibiotics. neously followed by cleavage and eventual loss of pyri-
Sulfonamides are the only class of antibiotics whose midine ring. The formation of another intermediate, 1-
degradation pathway has been proposed (Figure 13), pyrimidinyl-piperazine, was also confirmed (Figure 17).
although it applies only to AOPs and their degradation These intermediates subsequently disappeared within 30
mechanisms by molecular ozone alone is still elusive. On min of the TiO2/hn treatment (Calza et al., 2004b).
the other hand, kinetic information for ozonation and Carbamazepine. Carbamazepine is a carboxamide-
advanced oxidation is available for many antibiotics. type anticonvulsant widely used to control generalized
The kinetic data consistently indicate the high reactivity tonic-chronic seizures (Merck & Co., 1999). This pharma-
of antibiotics toward molecular ozone (kO3 >105 ceutical has been found ubiquitously in the aquatic envir-
M1s1) and hydroxyl radical (kOH >109 M1s1). onment often at 1 to 2 mg/L levels (Ternes, 1998; Sacher
The effect of ozonation and AOPs on the toxicity and et al., 2001; Stackelberg et al., 2004) and is probably one of
biodegradability has been studied only for some b-lactam the most persistent pharmaceuticals in the environment.
antibiotics, two quinolones, and one sulfonamide. More Carbamazepine is highly resistant to biodegradation
studies will be needed to ensure not only the complete (Clara et al., 2004). It has been also suggested that
transformation of antibiotics but also the diminution of
toxicity toward environmental microbes and other aqua-
tic organisms, because once released these compounds
N
can directly interact with natural bacterial population. N N O
Although the concentrations of antibiotics in the environ- N N
ment are generally low (less than one microgram per N
O NH2
liter), the bacterial population and aquatic life may be O
disturbed and resistance against particular types of anti- buspirone (385.51) carbamazepine (236.27)
N N
N N O N N O
N HO N
N N
hydroxy-bispirone hydroxy-bispirone
OH
O O
•OH •OH
•OH HN
•OH N N O
H2N
N N
N N O
HO N
O
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N •OH
dihydroxy-buspirone despyrimidinyl
OH buspirone-amidine
N O
N N O
HN N O
N •OH
N
N
oxo-buspirone O despyrimidinyl
O
buspirone O
HN
N N O
H2N
N
despyrimidinyl-hydroxy-buspirone-amidine OH
O
FIGURE 17. Oxidative transformation of buspirone by TiO2/hn treatment (Calza et al., 2004b).
carbamazepine-glucuronide conjugate can be cleaved in is apparent from the molecular structure of carbamaze-
sewage treatment plant, which may contribute to the pine. A number of degradation intermediates were iden-
increase of environmental concentration of this drug tified in two separate studies (Andreozzi et al., 2002;
(Ternes, 1998). McDowell et al., 2005) as shown in Figure 18. It was
High reactivity of carbamazepine toward ozonation suggested that an ozone molecule first attacked the
was reported by several groups of researchers non-aromatic carbon-carbon double bond of carbamaze-
(Andreozzi et al., 2002; Ternes et al., 2002; Huber et al., pine, leading to ring opening through the Criegee
2003). For example, an applied ozone dose of 0.5 mg/L mechanism, followed by ring closure to form the quinazo-
was sufficient to convert 1 mg/L carbamazepine spiked in line moiety of 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quina-
surface water after flocculation ([DOC] = 1.3 mg/L) at zoline-2-one (BQM) shown in the figure [see McDowell et
pH 7.8 (Ternes et al., 2002). Andreozzi et al. (2002) also al. (2005) for the detail of proposed reaction mechanism].
reported a complete conversion of 118 mg/L carbamaze- Quinazoline derivatives were also detected in the surface
pine and 30% mineralization monitored as CO2 evolution water treated by ozone in a full scale water treatment
in one hour of ozonation treatment at a utilized ozone plant (McDowell et al., 2005). McDowell et al. (2005)
dose of 1.0 mg/L at pH 5.5. Algal toxicity of carbamaze- also presented a kinetic model that accounted for the
pine was diminished after the ozone treatment (Andreozzi formation and subsequent degradation of these
et al., 2002). intermediates.
Two considerably large second-order rate constants Vogna et al. (2004b) reported a different pathway of
for the molecular ozone reaction of carbamazepine at 25 carbamazepine degradation by H2O2/UV AOP (Figure 19),
C were reported: 7.81 · 104 M1s1 (Andreozzi et al., which involves epoxidation of the carbon-carbon double
2002) and 3 · 105 M1s1 (Huber et al., 2003). The rate bond followed by the formation of a heteroaromatic inter-
constant was pH-independent (Huber et al., 2003), which mediate, acridine. Carbamazepine could be converted
(further degradation)
rapidly by H2O2/UV treatment; about 4.7 mg/L carbama- Frimmel, 2005a). Doll and Frimmel (2005c) identified a
zepine was completely converted within 4 min of treatment number of carbamazepine degradation products during
with 170 mg/L H2O2 and UV irradiation at 254 nm using a the TiO2/hn treatment, and a degradation pathway simi-
17 W low-pressure Hg lamp (2.7 · 106 Einsteins1) at pH lar to the one proposed for H2O2/UV AOP (see Figure 19)
5.0 (Vogna et al., 2004b). About 35% of initial TOC was was indicated. They also suggested the possible environ-
also removed during the 4-min H2O2/UV treatment, which mental impact of acridine and its derivatives generated
is apparently more efficient than ozonation (Andreozzi during the carbamazepine degradation as these com-
et al., 2002). A negative effect of humic substances on the pounds are polycyclic heteroaromatics known to be
aqueous carbamazepine degradation was observed (Vogna toxic to aquatic organisms, especially via photosensitiza-
et al., 2004b). Two different second-order rate constants tion (Wiegman et al., 2002).
for the hydroxyl radical reaction of carbamazepine were Diazepam. Diazepam is a benzodiazepine-type anti-
reported: 2.05 · 109 M1s1 (Vogna et al., 2004b) and 8.8 · anxiety agent that is also used to treat many other
109 M1s1 (Huber et al., 2003). The difference might be neurological and psychiatric disorders such as sleep dis-
originated from the difference in the methods of rate con- order, movement disorders, and motion sickness (Merck
stant determination: the former group used a direct model & Co., 1999). After administration, diazepam is meta-
fitting with the experimental data, whereas the latter group bolized and excreted mainly in the urine. Huber et al.
employed a competition kinetics method using p-chloro- (2003) reported very slow degradation of diazepam by
benzoic acid as a reference compound. molecular ozone with a second-order rate constant of
Recently, the carbamazepine degradation by TiO2 0.75 M1s1 at 20 C. Ozonation of 142 mg/L diazepam
photocatalysis was investigated in a series of study (Doll in natural water samples resulted in 24% to 65% con-
and Frimmel, 2004, 2005a, 2005b, 2005c). Doll and version of this pharmaceutical (applied ozone dose = 2
Frimmel (2004) showed that as compared with other mg/L, 10 min, pH 8, 10 C). Their kinetic analysis
persistent pharmaceuticals including clofibric acid, iome- revealed that the diazepam was mostly degraded
prol, iopromide, carbamazepine could be rapidly through hydroxyl radical reactions (kOH = 7.2 · 109
degraded by TiO2/hn process. More than 90% of initial M1s1) (Huber et al., 2003). Deactivation of aromatic
carbamazepine (4.2 mg/L) was converted in nine minutes rings by the imine group (C=N-) and chlorine atom
by treatment using 100 mg/L TiO2 (P25) and a 1000-W (Beltrán, 2003) may be the reason for the low reactivity
xenon short-arc lamp as a source of simulated solar UV of diazepam toward ozonation. No degradation inter-
rays (1.35 · 104 Einsteinm2s1, l <400 nm) at pH 6.5 mediate/by-product was determined.
(Doll and Frimmel, 2005a). A successful pilot-scale inves- Primidone. Primidone is an anticonvulsant of the pyr-
tigation of the continuous treatment of carbamazepine by imidinedione class, which used to treat disorders of move-
the TiO2/hn process was reported using a cross-flow ment such as tremor (Merck & Co., 1999). This drug is
microfiltration to retain catalyst (Doll and Frimmel, metabolized in the liver to phenobarbital, which is also an
2005b). The degradation of carbamazepine was strongly anticonvulsant (Bergey, 2004), and excreted in the urine.
inhibited in the presence of NOM in a lake water sample Ternes et al. (2002) reported moderate reactivity of primi-
by competing for hydroxyl radicals, as well as by deacti- done toward ozonation. About 87% of 1 mg/L primidone
vating TiO2 catalyst surface by adsorption (Doll and spiked in a flocculated surface water sample was converted
•OH/HO2•
N
N N
O NH2
O NH2 O NH2
carbamazepine
R R
N N
O NH2 •OH
R = -COOH
organic acids
•OH N
•OH
acridine
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O O
OH
OH OH
NH2 OH OH
N OH
2-aminobenzoic acid salicylic acid catechol hydroxyacridine
FIGURE 19. Degradation of carbamazepine by H2O2/UV treatment (Vogna et al., 2004b). Compounds in square brackets were not
identified.
by ozonation at an applied ozone dose of 3 mg/L, pH 7.8 other three drugs, as well as on those anticonvulsants/antide-
and 23 C. No further study has been reported on the pressants currently marketed and prescribed frequently, such
degradation of this anticonvulsant by ozonation or AOP. as paroxetine (Kwon and Armbrust, 2004).
(Ternes, 1998), groundwater (Sacher et al., 2001), and (Vogna et al., 2004a). Andreozzi et al. (2004) reported the
wastewater effluent (Ternes, 1998; Soulet et al., 2002; effective detoxification of a mixture of pharmaceuticals
Ternes et al., 2003), with concentration levels up to 1.3 containing 2.8 mg/L diclofenac and five other drugs by
mg/L (Ternes et al., 2003). A number of studies indicated ozonation and H2O2/UV treatment (see Ofloxacin, qui-
a high reactivity of diclofenac toward ozonation (Zwiener nolone antibiotic for the details).
and Frimmel, 2000; Ternes et al., 2002, 2003; Huber et al., The Fenton-type process has an apparent disadvan-
2005). For example, as low as 1 mg/L applied ozone was tage on the degradation of acidic drugs such as diclofenac
enough to convert 1 mg/L diclofenac spiked in a floccu- (pKa = 4.15) because the drug precipitates in an acidic
lated surface water sample at pH 7.8 and 23 C (Ternes medium, which is required maintaining iron in solution.
et al., 2002). Huber et al. (2003) reported a large second Packer et al. (2003) observed no conversion of diclofenac
order rate constant (1 · 106 M1s1) for the reaction of by Fenton treatment at pH 3.5 and 22 C. While increas-
ozone with this pharmaceutical in the dissociated form at ing pH can help the dissolution of the drug, precipitation
pH 5–10 and 20 C. Another kinetic study indicated of iron hydroxides occurs at high pH. To overcome this
smaller rate constants ranging from 1.76 · 104 to 1.84 · difficulty, it was suggested that the addition or generation
104 M1s1 at pH 5–6 and 25 C (Vogna et al., 2004a). of organic ligands or photo-reduction of colloidal iron to
The inconsistency may be due to the difference in meth- soluble ferrous ion by UV irradiation might improve the
ods used by these two groups of investigators: the com- performance of Fenton-type oxidation of diclofenac
petition kinetics method employed by the former (Pérez-Estrada et al., 2005b). Ravina et al. (2002) investi-
researchers and the direct measurement of residual drug gated photo-Fenton oxidation of diclofenac using a con-
using HPLC by the latter. Various degradation intermedi- centric photo-reactor with a 400 W low-pressure Hg lamp
ates have been identified during the ozonation treatment (l = 254 nm). Majority of initial TOC (> 90%) could be
of 1 mM (296 mg/L) diclofenac at pH 7.0 (Vogna et al., removed from 10 to 80 mg/L diclofenac solution within 1
2004a). Hydroxylation of the aromatic rings and cleavage h by photo-Fenton treatment with 14 mg/L Fe2+ and 340
at the diphenyl amine nitrogen likely occur simulta- mg/L H2O2 at pH 2.8 and 50 C. No remark was given on
neously during the treatment (Figure 21), followed by the solubility of diclofenac in this study, although it may
the ring opening and further mineralization. About 95% be possible that the drug solubility increased at the ele-
of chlorine from diclofenac molecules was released as vated temperature. It was noted that dark Fenton and
chloride and more than 30% of initial TOC was removed H2O2 alone with UV irradiation (H2O2/UV) were much
after 1.5 h of ozonation treatment (Vogna et al., 2004a). less effective than the photo-Fenton treatment (Ravina
Several AOPs have been also evaluated for the degra- et al., 2002).
dation of diclofenac. Zwiener and Frimmel (2000) noted a Perez-Estrada et al. (2005b) reported that neutral and
positive effect of hydrogen peroxide addition on the acidic photo-Fenton treatment in buffered media was not
diclofenac conversion by ozone. A second-order rate con- very effective for diclofenac degradation because of the
stant for the reaction of hydroxyl radical and diclofenac precipitation of either drug or iron hydroxides. The
was determined as 7.2 · 109 M1s1 (Huber et al., 2003). photo-Fenton treatment was performed in a pilot scale
Vogna et al. (2004a) investigated H2O2/UV treatment of solar photo reactor at 35 C ([diclofenac]0 = 50 mg/L,
this pharmaceutical and compared the results with concentration of H2O2 was maintained around 200 to
OH
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Cl Cl
HO HO OH
NH2 O
O O
H2N
HO HO Cl
Cl OH
OH OH
ring opening
FIGURE 21. Degradation of diclofenac by ozonation and H2O2/UV AOP (Vogna et al., 2004a).
400 mg/L by continuous addition). A non-buffered sys- above (Pérez-Estrada et al., 2005b). Complete conversion
tem with an initial pH of 7.0 was superior to the buffered of 43 mg/L diclofenac was achieve with 0.2 g/L TiO2 in 200
systems; however, some precipitation and subsequent min, which was twice longer than the case of photo-Fenton
re-dissolution of diclofenac was observed during the treat- treatment. Chloride and ammonium ions were detected
ment. This was likely due to the pH drop (around pH 4.0) during the TiO2/hn treatment (Pérez-Estrada et al., 2005b).
as a result of the generation of organic acids intermediates. Ibuprofen. Ibuprofen is a NSAID widely used for the
Consequently, Perez-Estrada et al. (2005b) recommended a relief of headache, rheumatoid arthritis, fever, and
pH control around 4.5 to 5 for the photo-Fenton treat- general pain, and is an active ingredient of a number of
ment of diclofenac. A number of degradation intermedi- over-the-counter pain-relief drugs. Ibuprofen has been
ates were detected during the photo-Fenton treatment frequently detected in the aquatic environment (Halling-
(Ravina et al., 2002; Pérez-Estrada et al., 2005a). Sørensen et al., 1998; Ternes, 1998; Heberer, 2002; Kolpin
Hydroxylation and subsequent quinoneimine formation et al., 2002; Boyd et al., 2003). Moderate reactivity of this
depicted in Figure 22 was considered as the major degra- NSAID toward ozonation was reported (Zwiener and
dation pathway of diclofenac in the photo-Fenton process Frimmel, 2000; Ternes et al., 2003; Huber et al., 2005).
(Pérez-Estrada et al., 2005a). These quinoneimine inter- A second-order rate constant for the molecular ozone
mediates are likely decomposed into hydroquinone deriva- reaction of ibuprofen was reported as 9.6 M1s1
tives and aniline derivatives that have been detected in (Huber et al., 2003), which is much lower than that of
ozonation and H2O2/UV treatment (Figure 21). Near- diclofenac. This is primarily due to the absence of reactive
quantitative recovery of chlorine and nitrogen as chloride functional group or moiety such as amine and non-aro-
and ammonium, respectively, was also confirmed during matic carbon-carbon double bonds in the ibuprofen
the treatment (Pérez-Estrada et al., 2005a). molecule, besides the aromatic ring that is weakly acti-
Titanium dioxide photocatalysis was also evaluated for vated by the isobutyl group (see Figure 20).
the degradation of diclofenac in the same solar photo Zwiener and Frimmel (2000) reported that ozonation
reactor employed in the photo-Fenton process discussed (1 mg/L applied ozone) alone was not sufficient to
Cl Cl Cl
O O O
NH NH N
OH OH OH
Cl Cl Cl
diclofenac
Cl-
O O
O O
Cl OH
Cl Cl
O
O
N OH N
N HO N
OH
OH
Cl Cl
Cl Cl
FIGURE 22. The major degradation pathways of diclofenac (via quinoneimine formation) by photo-Fenton process (Pérez-Estrada et al., 2005).
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convert 2 mg/L ibuprofen in distilled water, resulting in reaction of naproxen has been reported as 9.6 · 109
only 12% conversion in 10 min. However, increasing the M1s1 at pH 3.5 and 22 C using Fenton reaction to
ozone dose and adding hydrogen peroxide (O3/H2O2 generate hydroxyl radicals (Packer et al., 2003). No
AOP) greatly improved the ibuprofen conversion. They further study has been found on the ozonation or
also investigated the effect of water matrix on the degra- advanced oxidation treatment of these NSAIDs.
dation of ibuprofen using a river water sample. The pre- Salicylic Acid. Salicylic acid is a decomposition pro-
sence of hydroxyl radical scavenger, bicarbonate ion and duct of acetylsalicylic acid (aspirin), which is a common
natural DOC, in the river water significantly reduced the over-the-counter NSAID. Salicylic acid itself, which is
extent of ibuprofen conversion by O3/H2O2 AOP, imply- derived naturally from willow tree bark, has been also
ing the importance of hydroxyl radical reactions. In the used as an antipyretic since ancient times, and still been
river water, they noted that the treatment with 5.0 mg/L used as an additive of some skin-care products (Merck &
applied ozone and 1.8 mg/L hydrogen peroxide was suffi- Co., 1999). Only one study on salicylic acid removal by
cient to convert 2 mg/L ibuprofen in 10 min at pH 7.5 and ozonation has been reported. Khan et al. (2004) demon-
10 C (Zwiener and Frimmel, 2000). Two comparable strated partial degradation of salicylic acid by ozonation
second-order rate constants for the hydroxyl radical reac- in the advanced water recycling demonstration plant in
tion of this pharmaceutical were reported: 6.5 · 109 Australia. The demonstration plant consists of lime clar-
M1s1 at pH 3.5 and 22 C by Fenton (Packer et al., ification, dissolved air flotation, dual media filtration,
2003) and 7.4 · 109 M1s1 at pH 7 and 25 C by H2O2/ ozonation, biological activated carbon filtration, micro-
UV (Huber et al., 2003). No further study was found on filtration, combined reverse osmosis/nanofiltration, and
the mineralization of ibuprofen by ozonation or AOP, or UV disinfection. About 60% of 0.65 mg/L salicylic acid
the degradation pathway of this NSAID. found in the influent of ozonation unit was degraded by
Indomethacin and Naproxen. Indomethacin and ozonation at an ozone dose of 17.5 mg/L for 15 min
naproxen are NSAIDs having methylated indole and (Khan et al., 2004). No further study has been reported
naphthalene rings, respectively. Like other acidic on the degradation of salicylic acid or acetylsalicylic acid
NSAIDs, the occurrence of these compounds in the by ozonation or AOP.
aquatic environment have been reported (Halling- Paracetamol. Paracetamol, also known as acetami-
Sørensen et al., 1998; Ternes, 1998), although their nophen, is a non-NSAID antipyretic agent used for the
environmental concentrations are generally less than relief of fever, headaches, and other minor aches and
those of diclofenac and ibuprofen. Ternes et al. (2003) pains. This drug is metabolized in the liver to mostly
reported the effective abatement of 0.1 mg/L indometha- sulfate- and glucuronide-conjugates and excreted in the
cin and 0.1 mg/L naproxen present in a biologically urine (Johnson and Plumb, 2005). Andreozzi et al.
treated wastewater sample by ozonation at pH 7.2 with (2003a) showed that ozonation at pH 2 and 7 could
an applied ozone dose of 5 mg/L. Similar result was effectively degrade 0.8 g/L paracetamol in 30 min with
reported by Huber et al. (2005) as well, although the an ozone flow rate of about 72 g/h (reactor
concentrations of these drugs were not specified. A volume = 1.09 L). After two hours of ozonation, about
second-order rate constant for the hydroxyl radical 20% and 30% of initial TOC was removed from the
NH
O HO OH
•OH HO NH
OH
O 1,4-hydroquinone
HO NH - H•
O
paracetamol HO NH
- H• •OH OH O
O
O NH NH2
O O
- H•
O
O N 1,4-benzoquinone
O
NH2
FIGURE 24. Formation of 1,4-hydroquinone and 1,4-benzoquinone from paracetamol by H2O2/UV AOP (Vogna et al., 2002).
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section include atenolol, celiprolol, metoprolol, propra- required to completely convert 0.36 mg/L atenolol and
nolol, and sotalol. While propranolol and sotalol are non- 1.7 mg/L metoprolol (Ternes et al., 2003). No further
selective b-blockers, the others are b1 antagonists (selec- study has been published on the degradation of these
tive b-blockers). Chemical structure and molecular weight b-blockers, except for propranolol (see below), by ozona-
of these pharmaceuticals are shown in Figure 25. tion or AOP.
Atenolol, Celiprolol, Metoprolol, and Sotalol. Ternes Propranolol. In addition to the study conducted by
et al. (2003) demonstrated that ozonation at pH 7.2 was Ternes et al. (2003) above, the high reactivity of propra-
effective for the degradation of five b-blockers, namely nolol toward ozonation was also reported elsewhere
atenolol, celiprolol, metoprolol, propranolol, and sotalol, (Andreozzi et al., 2004). Complete conversion of 325.5
present in an effluent from municipal sewage treatment mg/L propranolol was achieved by ozonation in 2 min at
plant. Celiprolol, propranolol, and sotalol were appar- an absorbed ozone dose of as low as 4.75 mg/L, pH 7.4
ently more reactive than atenolol and metoprolol: 5 mg/L and 25 C in a mixture of six pharmaceuticals, including
of applied ozone was sufficient to convert 0.28 mg/L ofloxacin, sulfamethoxazole, carbamazepine, clofibric
celiprolol, 0.18 mg/L propranolol, and 1.32 mg/L sotalol, acid, diclofenac, and propranolol. Besides ozonation,
whereas higher ozone dose (i.e., 10 to 15 mg/L) was H2O2/UV treatment ([H2O2]0 = 5–10 mM, a low-pressure
Hg lamp, l = 254 nm, 2.51 · 106 Einsteins1) was also
effective for the complete conversion of propranolol at
NH2 O
H pH 7.4 and 25 C, whereas TiO2 photocatalysis was less
O N N
N O effective (Andreozzi et al., 2004). Algal (Synechococcus
H
OH N O
O leopoliensis) and protozoan (Brachionus calyciflorus) toxi-
H
atenolol (266.34) OH cities of the drug mixture were eliminated completely by
celiprolol (379.50) the ozone treatment. It was also shown that the H2O2/UV
O treatment was also effective in algal toxicity reduction;
O N
however, it was less effective in protozoan toxicity reduc-
N O H
H
OH OH tion. Finally, no toxicity reduction was achieved by the
TiO2/hn treatment (Andreozzi et al., 2004). Degradation
metoprolol (267.37)
intermediates or by-products of propranolol were not
propranolol (259.35)
OH
determined.
O O
S HN
N
H
Summary of b-Blockers
Despite their prevalence in the aquatic environment
sotalol (272.36) (Ternes, 1998; Sacher et al., 2001; Bendz et al., 2005),
there have been very few reports on the degradation of
FIGURE 25. Beta-blockers.
aqueous b-blockers by ozonation and AOPs. Neither
Cytostatic Drugs
Cytostatic drugs, also known as antineoplastic agents, difference in the reaction rates at two pHs, indicating the
are the pharmaceuticals used to treat various forms of major contribution of molecular ozone reactions over
cancers. Some cytostatic drugs are also used to treat hydroxyl radicals, and that the presence of multiple
autoimmune diseases and to suppress transplant rejec- reactive sites, which is apparent from their molecular
tions. There are a number of classes of cytostatic drugs, structures (see Figure 26b). Mutagenicity of these anti-
such alkylating agents, anti-metabolites, alkaloids, and metabolites, with or without metabolic activation, were
anti-tumor antibiotics. The majority of these drugs inter- diminished after the ozone treatment (Rey et al., 1999).
fere with mitosis (cell division) to selectively kill fast- Degradation by-products were not identified in this
growing tumor cells through a number of mechanisms study.
such as inhibition of DNA synthesis. Cytostatic drugs Alkylating Agents (Cyclophosphamide, Ifosfamid,
are cytotoxic by nature, as well as potentially carcino- and Melphalan). As the name suggests, alkylating
genic and genotoxic (Merck & Co., 1999). The cytostatic agents are cytostatic drugs capable to covalently modify
drugs reviewed here include six anthracyclines anti-tumor electronegative groups of DNA (i.e., DNA alkylation),
antibiotics (aclarubicin, daunorubicin, doxorubicin, epir- and thus interfere DNA replication in tumor cells. Similar
ubicin, idarubicin, and pirarubicin; Figure 26a), four anti- to the cases of anthracyclines above, Fenton oxidation, as
metabolites (5-fluorouracil, azathioprine, cytarabine, and well as chlorination, of three alkylating agents, including
methotrexate; Figure 26b), and three nitrogen mustard cyclophosphamide, ifosfamid, and melphalan, were inves-
alkylating agents (cyclophosphamide, ifosfamide, and tigated as an effective treatment of hospital wastes con-
melphalan; Figure 26b, inset). taminated with these cytotoxic pharmaceuticals (Hansel
Anthracyclines (Aclarubicin, Daunorubicin, Doxo- et al., 1997). It was demonstrated that complete conver-
rubicin, Epirubicin, Idarubicin, and Pirarubicin). sion of these alkylating agents could be achieved by the
Anthracyclines are chemotherapeutic antibiotics that treatment with Fenton reagent (10.3 g/L Fe2+, 150 g/L
inhibit DNA and RNA synthesis by intercalating between H2O2, pH unknown) within one hour. However, the for-
base-pairs of the DNA or RNA strands. They have a mation of unidentified direct mutagens was noticed by
common structure: 7,8,9,10-tetrahydro-5,12-naphthace- the Ames test in the treated cyclophosphamide formula-
nedione moiety with a sugar chain (see Figure 26a). tion that had also contained 5% dextrose (Hansel et al.,
Castegnaro et al. (1997) evaluated Fenton reagent as 1997). As no residual mutagenicity was found in the same
well as sodium hypochlorite and hydrogen peroxide to formulation without dextrose, this additive was complet-
effectively decompose six anthracyclines, including aclar- ing for the oxidant (hydroxyl radicals) with cyclopho-
ubicin, daunorubicin, doxorubicin, epirubicin, idarubicin, sphamide, resulting in incomplete destruction of
and pirarubicin, that may be found in hospital wastes at mutagenic degradation by-products.
high concentrations. All anthracyclines (0.4 to 5 g/L; see
Appendix for the concentrations of individual drugs) Summary of Cytostatic Drugs
were completely degraded after 1 h of treatment with A large number of cytostatic drugs have been exam-
either 2.6% sodium hypochlorite or Fenton reagent ined for their degradation by ozonation or Fenton pro-
(10.3 g/L Fe2+, 150 g/L H2O2, pH unknown), and there cess in a very limited number of studies. The
was no residual mutagenicity, assayed by the Ames test concentrations of the drugs treated therein were very
H2N N N
O
F N N
HN N OH
H
NH2 N
O N O
H
O
5-fluorouracil (130.08) methotrexate (454.44)
O OH
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O
Cl Cl
Cl
Cl OH
N Cl NH2
NH N
O P NH
O P N
O
O
Cl
FIGURE 26b. Cytostatic agents, anti-metabolites and nitrogen mustard alkylating agents (inset).
HO HO
HO
17β-estradiol (272.38) estrone (270.37) 17α-ethinylestradiol (296.41)
OH
HO
diethylstilbestrol (268.35)
manufactured and used in oral contraceptives and hor- scavenger (Figure 31). It is apparent that ozone molecules
mone replacement therapy in large quantities. 17b- attack and cleave hydroxylated aromatic ring of this estro-
Estradiol is metabolized in the body to a number of gen to produce these intermediates. Huber et al. (2004)
metabolites, including estrone, hydroxylated estrones, 2- suggested that the destruction of aromatic ring virtually
methoxyestrone, estriol, and their conjugates, and subse- diminished estrogenicity of estrogens including 17b-
quently excreted in the urine (Arcand-Hoy et al., 1998). estradiol.
Deconjugation of sulfate and glucuronide derivatives of It was also documented the effectiveness of several
estradiol in sewage treatment plant is also suggested AOPs including O3/H2O2 (Shishida et al., 2000; Onda
(Arcand-Hoy et al., 1998; Belfroid et al., 1999). 17b- et al., 2002) H2O2/UV (Rosenfeldt and Linden, 2004)
Estradiol has been frequently detected in the aquatic and TiO2/hn processes (Ohko et al., 2002) on the degra-
environment (Ternes, 1998; Kolpin et al., 2002; Snyder dation of 17b-estradiol and the removal of associated
et al., 2003), and is considered as a major contributor of estrogenicity. Shishida et al. (2000) showed that in addi-
estrogenic activity found in municipal sewage treatment tion to estrogenicity, cytotoxicity, mutagenicity, and gen-
plant effluent (Onda et al., 2002). otoxicity initially present in a secondary effluent from
Several groups of investigators reported the effective domestic wastewater treatment plant containing 17b-
decomposition of 17b-estradiol by ozonation (Onda estradiol (concentration not shown) was reduced by the
et al., 2002; Alum et al., 2004; Kim et al., 2004; Huber O3/H2O2 treatment with 30 mg/L ozone and 2 mg/L
et al., 2005). For example, ozonation at 2 mg/L applied H2O2. A second-order rate constant for the reaction of
ozone dose was sufficient to convert 0.5 mg/L 17b-estradiol 17b-estradiol and hydroxyl radical was determined as
spiked in biologically treated municipal wastewater at pH 1.41 · 1010 M1s1 using a competitive kinetics method
7 and 16 C (Huber et al., 2005). Some studies also with isopropyl alcohol as a reference compound
addressed the effects of ozone treatment on estrogenic (Rosenfeldt and Linden, 2004). Ohko et al. (2002) demon-
activity, which is assayed by a number of methods such strated complete mineralization of 0.272 mg/L 17b-
as recombinant yeast assay (Onda et al., 2002), estrogen estradiol by TiO2 photocatalysis with 1.0 g/L TiO2 and
competition binding assay (Kim et al., 2004), E-screen a 200-W Hg-Xe lamp (with a 365 nm band-pass filter) in 3
assay (Alum et al., 2004), MCF-7 cell proliferation assay h. They also identified several degradation intermediates
(Liu et al., 2005), and ER-binding assay combined with detected during the TiO2 photocatalytic treatment of 17b-
ultrafiltration (Liu et al., 2005). Generally, all of these estradiol, including 10-17b-dihydroxy-1,4-estradien-3-
studies indicated that estrogenic activity of 17b-estradiol one, androsta-4,16-dien-3-one, and testosterone (Figure 32),
solution decreased upon the ozone treatment. A slight although it is unlikely to occur the introduction of methyl
increase of estrogenicity assayed by E-screen was noted group on the C10 position by the TiO2/hn treatment. Ohko et
in the first five minutes of ozone treatment (Alum et al., al. (2002) suggested that hydroxyl radical attacked the hydro-
2004), indicating the formation of more potent estrogenic xylated aromatic ring of 17b-estradiol to initiate its degrada-
intermediates, although the estrogenicity decreased during tion. In addition to the three AOPs discussed here, the
the subsequent 5 min of treatment. Huber et al. (2004) degradability of 17b-estradiol by photo-Fenton-like process
identified four degradation intermediates of 17b-estradiol was briefly compared with that of three estrogens, including
by ozonation in the presence of a hydroxyl radical diethylstilbestrol, 17a-ethinylestradiol, and estrone (Feng
HO
O
HO HO
HO O
17β-estradiol estrone
OH OH
OH
O
O O HO
HO
HO O
FIGURE 31. Proposed degradation pathways for 17b-estradiol and estrone by ozonation (Huber et al., 2004).
Downloaded by [Dalhousie University] at 15:51 13 September 2012
O
HO O
HO
O
HO O
O
O
O
HO O
O
HO OH O OH
O
O O
HO HO HO
O O O
HO O HO O HO O
O
HO OH
O OH
O
O O O
O O
HO HO
HO HO
HO
HO
FIGURE 33. Some ozonation by-products of 17a-ethinylestradiol. The compounds in brackets were not detected, but likely formed during
ozonation, based on the results of model compound degradation [see Huber et al. (2004) for the details of the degradation mechanisms].
O O
O OH O
O O
HN OH
Cl O
Cl Cl
O
O O
O HO O OH
O Cl O Cl
O
O O gemfibrozil (250.34)
fenofibrate (360.84) fenofibric acid (318.75)
(2004) also investigated the detoxification of a drug mix- fenofibric acid, a metabolite of lipid regulator fenofibrate,
ture that contained clofibric acid by ozonation, H2O2/ in a sewage treatment plant effluent was achieved by
UV, TiO2 photocatalysis (see Propranolol, b-blocker for ozonation with an applied ozone dose of 10 or 15 mg/L
the results). at pH 7.2 (Ternes et al., 2003). No further study was
A series of studies was published on the clofibric acid found on the degradation of fenofibric acid or its parent
degradation by TiO2 photocatalysis (Doll and Frimmel, compound fenofibrate by ozonation or AOP.
2004, 2005a, 2005b, 2005c). More than 90% of 0.53 mg/L Gemfibrozil. Huber et al. (2005) mentioned the pre-
clofibric acid was converted in five minutes with 80 mg/L sence of another fibrate lipid regulator, gemfibrozil, in a
TiO2 (P25) and a 1000-W xenon short-arc lamp as a municipal wastewater effluent that was subsequently trea-
source of simulated solar UV rays (1.35 · 104 ted by ozonation; however, no description was given on
Einsteinm2s1, l <400 nm) at pH 6.5 (Doll and the removal efficiency of this pharmaceutical. It can be
Frimmel, 2004). The degradation of clofibric acid was anticipated that gemfibrozil is probably more reactive
dependent on the initial concentration of substrate; toward ozonation than clofibric acid because of the
degradation efficiency was higher as the initial clofibric absence of chlorine on the aromatic ring, although aro-
acid concentration decreased, indicating that the capacity matic hydroxylation is somehow hindered by the two
of catalyst is a limiting factor (Doll and Frimmel, 2004). methyl groups (see Figure 34).
O O
HO
O OH OH
OH
O
OH O +
Cl
Cl OH
clofibric acid 4-chlorophenol
HO
OH
O
OH
O
OH Cl OH
HO
HO 4-chlorocatachol
hydroquinone
2-(4-hydroxyphenoxy)-isobutyric acid ring opening
and
mineralization
FIGURE 35. Degradation of clofibric acid by TiO2 photocatalysis (Doll and Frimmel, 2004).
HO OH
diatrizoate (613.91)
iomeprol (777.09) iopamidol (777.09)
O O
HO HN I HO HN I
O
HO I N OH HO I NH
O I O O I O O
NH N
Downloaded by [Dalhousie University] at 15:51 13 September 2012
HO OH HO OH
iopentol (835.17)
iopromide (791.12)
Because of the high UV absorbance of iodine in the by-products or intermediates were not identified in any of
aqueous solution, iopentol mineralization was inhibited, these studies.
although it was found that air stripping could solve this
problem (Sprehe et al., 2001). They also suggested that
the iodine recovery from the exhaust air by the use of
solvent or sublimation might be feasible as about 85% of Summary of X-ray Contrast Media
elemental iodine could be recovered this way. It is evident that triiodinated X-ray contrast media are
Iopromide. Iopromide is another non-ionic triiodi- the most refractory class of pharmaceutical/medical
nated X-ray contrast medium resistant to oxidative degra- agents reviewed in this review. Anionic diatrizoate is
dation. However, as compared with other triiodinated particularly resistant to ozone-based treatment, whereas
contrast media, this compound was apparently more reac- non-ionic contrast media (iomeprol, iopamidol, iopentol,
tive, but very slightly, toward ozonation (Ternes et al., and iopromide) are somewhat degradable, especially by
2003; Huber et al., 2005). As the second-order rate con- AOPs such as H2O2/UV and TiO2/hn. It has been shown
stant for the reaction between iopromide and molecular that deiodination of these contrast media occurs chiefly
ozone is very small: less than 0.8 M1s1 at pH 5 to 10 by direct UV photolysis in the H2O2/UV treatment. Other
and 20 C, the degradation of this compound mostly occur than that, degradation mechanisms of these contrast
by hydroxyl radicals, although the rate constant for the media by ozonation and AOPs are still largely unknown;
hydroxyl radical reaction is also fairly small: 3.3 · 109 kinetic data are very scarce and no degradation by-
M1s1 at pH 7 and 25 C (Huber et al., 2003). product was identified. It is probably desirable to discern
Like the case of iopentol, effective AOX removal and the identity and property of degradation by-products of
mineralization of iopromide by H2O2/UV AOP was triiodinated X-ray contrast media because even though
demonstrated (Sprehe et al., 2001). Major contribution the parent compounds are non-toxic (Steger-Hartmann
of direct UV photolysis to the deiodination was con- et al., 1999), their degradation products may have some
firmed in a separate photolysis experiment without potential ecological and public health impacts. Finally,
hydrogen peroxide addition. In addition to ozone-based there are two ionic triiodinated X-ray contrast media,
and H2O2/UV AOPs, TiO2/hn process was evaluated for iothalamic acid and ioxithalamic acid, that have not
the iopromide degradation. It was shown that the degra- been studied for their degradation by ozonation or AOP
dation rate of this contrast medium was comparable to but been detected in the aquatic environment (Ternes and
that of iomeprol (Doll and Frimmel, 2004). Degradation Hirsch, 2000).
ural and synthetic hormones, which can indeed affect this goal has been confirmed only for some antibiotics
populations of aquatic organisms. Besides, the chronic through limited types of treatment process (see
health effects of a mixture of biologically active sub- Appendix). Likewise, toxicity reduction by ozonation or
stances are still largely unknown. Therefore, the removal AOPs has been evaluated in just a handful of cases, exclud-
of these substances before entering the aquatic environ- ing the estrogenicity of natural and synthetic hormones. In
ment and drinking water is probably desirable based on water treatment, considering the very small amounts of
the precautionary principle. Chemical oxidation by ozone pharmaceuticals in finished drinking water, the destruction
and AOPs has been thought to be one of the promising of key molecular structures for biological activity may be
treatment methods to deal with this problem. sufficient to protect public health, if the degradation by-
The studies reviewed here have indeed showed satisfac- products do not exert similar or other unprecedented and
tory efficiencies of ozonation and AOPs for the degradation undesirable effects. Thus, identification and characteriza-
of a wide range of pharmaceutical compounds in aqueous tion of degradation by-products and intermediates is
solution. Some pharmaceuticals are extremely reactive highly important task, although this has not been done
toward molecular ozone, including some antibiotics, an yet for all the substances discussed here. In addition,
anticonvulsant carbamazepine, a NSAID diclofenac, and kinetic data are still scarce for many pharmaceuticals
an estrogen 17b-estradiol. These pharmaceuticals can be reviewed here. Further validation may be as well required
characterized by one or more functional groups and moi- for those substances already studied for their degradation
eties in the molecules such as non-aromatic carbon-carbon kinetics by ozone or hydroxyl radicals, because of some
double bonds, amines, thioether sulfurs, and activated aro- discrepancies, high experimental errors, or limited pH and
matic rings. There are also some pharmaceuticals relatively temperature coverage.
resistant to ozonation, including a lipid regulator metabo- In order to minimize the load of pharmaceuticals in the
lite clofibric acid, an anti-anxiety agent diazepam, and a aquatic environment, a number of actions should be
NSAID ibuprofen. Triiodinated X-ray contrast media, taken simultaneously, besides the end-of-pipe treatment
which are biologically stable, non-therapeutic medical approach discussed in this review. It has been recognized
agents, are particularly refractory to ozonation. Ozone- that source separation is one of the key for a successful
based AOPs, Fenton-type processes and photochemical waste management practice in general (Jonsson et al.,
AOPs are generally more effective than ozonation alone 1997; Tanskanen et al., 1998), and this approach should
primarily due to enhanced generation of hydroxyl radicals be applicable to wastewater pollutants such as pharma-
and photon-initiated cleavage of carbon-halogen bonds, ceuticals. As many pharmaceuticals are excreted mostly
thus are recommended for the treatment of these recalci- in the urine, its separation from the solids portion (feces)
trant substances. There are a number of pharmaceuticals of wastewater and the provision for separate treatment
that have not been studied for their degradation by ozona- system may be of an ultimate solution particularly for
tion or AOP but been found in the aquatic environment highly contaminated hospital wastewater (Larsen et al.,
(Table 3). These pharmaceuticals may warrant further 2004). Ozonation and advanced oxidation are likely sui-
study. table for the treatment of the pharmaceutical-laden urine,
The degree of degradation of water and wastewater as suggested by Larsen et al. (2004); thus this strategy
pollutants, including pharmaceutical compounds, achieved should be investigated in the future.
drug
Belomycin Cytostatic drug Up to 19, 17, and 13 ng/L in effluents from WWTP,
surface water, and potable water, respectively
(Halling-Sørensen et al., 1998)
Equilin Steroid hormone, estrogen Up to 0.147 mg/L in surface water (Kolpin et al., 2002)
Testosterone Steroid hormone, androgen Up to 0.214 mg/L in surface water (Kolpin et al., 2002)
Iothalamic acid Triiodinated X-ray contrast media Up to 0.049 mg/L in groundwater (Ternes and Hirsch, 2000)
Ioxithalamic acid Triiodinated X-ray contrast media Up to 0.010 mg/L in groundwater (Ternes and Hirsch, 2000)
Heterocyclic Groups: Identification of an SO2 Extrusion (NOM) and Other Organic Water Constituents’’, Water Res.,
Photoproduct’’, Environ. Sci. Technol., 39(10):3630–3638 (2005). 39(2–3):403–411 (2005a).
24. Boyd, G.R., H. Reemtsma, D.A. Grimm, and S. Mitra, 41. Doll, T.E. and F.H. Frimmel, ‘‘Cross-Flow Microfiltration with
‘‘Pharmaceuticals and Personal Care Products (PPCPs) in Surface Periodical Back-Washing for Photocatalytic Degradation of
and Treated Waters of Louisiana, USA and Ontario, Canada’’, Sci. Pharmaceutical and Diagnostic Residues—Evaluation of the Long-
Total Environ., 311(1–3):135–149 (2003). Term Stability of the Photocatalytic Activity of TiO2’’, Water Res.,
25. Bozzi, A., A. Lopez, G. Mascolo, and G. Tiravanti, 39(5):847–854 (2005b).
‘‘Pharmaceuticals Degradation by UV and UV/H2O2 Treatments’’, 42. Doll, T.E. and F.H. Frimmel, ‘‘Removal of Selected Persistent
Water Sci. Technol. Water Suppl., 2(2):19–26 (2002). Organic Pollutants by Heterogeneous Photocatalysis in Water’’,
26. Brillas, E., I. Sirés, C. Arias, P.L. Cabot, F. Centellas, R.M. Catal. Today, 101(3–4):195–202 (2005c).
Rodrı́guez, and J.A. Garrido, ‘‘Mineralization of Paracetamol in 43. Drewes, J.E., P. Fox and M. Jekel, ‘‘Occurrence of Iodinated X-ray
Aqueous Medium by Anodic Oxidation with a Boron-Doped Contrast Media in Domestic Effluents and Their Fate During
Diamond Electrode’’, Chemosphere, 58(4):399–406 (2005). Indirect Potable Reuse’’, J. Environ. Sci. Health Part A-Toxic/
27. Buser, H.R., M.D. Müller, and N. Theobald, ‘‘Occurrence of the Hazard. Subst. Environ. Eng., 36(9):1633–1645 (2001).
Pharmaceutical Drug Clofibric Acid and the Herbicide Mecoprop in 44. Fan, S.H., Y. Shen, L.P. Chen, X.L. Gu, Y.G. Li and Z.B. Shi,
Various Swiss Lakes and in the North Sea’’, Environ. Sci. Technol., ‘‘Photocatalytic Degradation of Cefradine in Water over
32(1):188–192 (1998). Immobilized TiO2 Catalyst in Continuous-Flow Reactor’’, Chin. J.
28. Cahill, J.D., E.T. Furlong, M.R. Burkhardt, D. Kolpin, and L.G. Catal., 23(2):109–112 (2002).
Anderson, ‘‘Determination of Pharmaceutical Compounds in 45. Feng, X.H., S.M. Ding, J.F. Tu, F. Wu and N.S. Deng,
Surface- and Ground-Water Samples by Solid-Phase Extraction and ‘‘Degradation of Estrone in Aqueous Solution by Photo-Fenton
High-Performance Liquid Chromatography-Electrospray Ionization System’’, Sci. Total Environ., 345(1–3):229–237 (2005).
Mass Spectrometry’’, J. Chromatogr. A, 1041(1–2):171–180 (2004). 46. Gartiser, S., L. Brinker, T. Erbe, K. Kümmerer and R. Willmund,
29. Calza, P., C. Medana, M. Pazzi, C. Baiocchi, and E. Pelizzetti, ‘‘Contamination of Hospital Wastewater with Hazardous
‘‘Photocatalytic Transformations of Sulphonamides on Titanium Compounds as Defined by 7a WHG’’, Acta Hydrochim.
Dioxide’’, Appl. Catal. B-Environ., 53(1):63–69 (2004a). Hydrobiol., 24(2):90–97 (1996).
30. Calza, P., M. Pazzi, C. Medana, C. Baiocchi, and E. Pelizzetti, ‘‘The 47. Halling-Sørensen, B., S.N. Nielsen, P.F. Lanzky, F. Ingerslev,
Photocatalytic Process as a Tool to Identify Metabolitic Products H.C.H. Lützhøft, and S.E. Jørgensen, ‘‘Occurrence, Fate and
Formed from Dopant Substances: The Case of Buspirone’’, J. Effects of Pharmaceutical Substances in the Environment—A
Pharm. Biomed. Anal., 35(1):9–19 (2004b). Review’’ Chemosphere, 36(2):357–394 (1998).
31. Castegnaro, M., M. De Méo, M. Laget, J. Michelon, L. Garren, M.H. 48. Hansel, S., M. Castegnaro, M.H. Sportouch, M. De Méo, J.C.
Sportouch, and S. Hansel, ‘‘Chemical Degradation of Wastes of Milhavet, M. Laget, and G. Duménil, ‘‘Chemical Degradation of
Antineoplastic Agents. 2. Six Anthracyclines: Idarubicin, Doxorubicin, Wastes of Antineoplastic Agents: Cyclophosphamide, Ifosfamide
Epirubicin, Pirarubicin, Aclarubicin, and Daunorubicin’’, Int. Arch. and Melphalan’’, Int. Arch. Occup. Environ. Health, 69(2):109–114
Occup. Environ. Health, 70(6):378–384 (1997). (1997).
32. Castiglioni, S., R. Fanelli, D. Calamari, R. Bagnati, and E. Zuccato, 49. Hartig, C., M. Ernst, and M. Jekel, ‘‘Membrane Filtration of Two
‘‘Methodological Approaches for Studying Pharmaceuticals in the Sulphonamides in Tertiary Effluents and Subsequent Adsorption on
Environment by Comparing Predicted and Measured Concentrations Activated Carbon’’, Water Res., 35(16):3998–4003 (2001).
in River Po, Italy’’, Regul. Toxicol. Pharmacol., 39(1):25–32 (2004). 50. Heberer, T., ‘‘Occurrence, Fate, and Removal of Pharmaceutical
33. Christian, T., R.J. Schneider, H.A. Färber, D. Skutlarek, M.T. Residues in the Aquatic Environment: A Review of Recent
Meyer, and H.E. Goldbach, ‘‘Determination of Antibiotic Research Data’’, Toxicol. Lett., 131(1–2):5–17 (2002).
Residues in Manure, Soil, and Surface Waters’’, Acta Hydrochim. 51. Heberer, T., D. Feldmann, K. Reddersen, H.J. Altmann, and T.
Hydrobiol., 31(1):36–44 (2003). Zimmermann, ‘‘Production of Drinking Water from Highly
34. Clara, M., B. Strenn, and N. Kreuzinger, ‘‘Carbamazepine as a Contaminated Surface Waters: Removal of Organic, Inorganic and
Possible Anthropogenic Marker in the Aquatic Environment: Microbial Contaminants Applying Mobile Membrane Filtration
Investigations on the Behaviour of Carbamazepine in Wastewater Units’’, Acta Hydrochim. Hydrobiol., 30(1):24–33 (2002).
Concentric Photo-Reactor’’, Water Res., 36(14):3553–3560 (2002). Trends Anal. Chem., 20(8):419–434 (2001).
99. Rey, R.P., A.S. Padrón, L.G. León, M.M. Pozo, and C. Baluja, 118. Ternes, T.A. and R. Hirsch, ‘‘Occurrence and Behavior of X-ray
‘‘Ozonation of Cytostatics in Water Medium. Nitrogen Bases’’, Contrast Media in Sewage Facilities and the Aquatic
Ozone Sci. Eng., 21(1):69–77 (1999). Environment’’, Environ. Sci. Technol., 34(13):2741–2748 (2000).
100. Reynolds, G., N. Graham, R. Perry, and R.G. Rice, ‘‘Aqueous 119. Ternes, T.A., M. Stumpf, J. Mueller, K. Haberer, R.D. Wilken,
Ozonation of Pesticides — A Review’’, Ozone Sci. Eng., 11(4):339– and M. Servos, ‘‘Behavior and Occurrence of Estrogens in
382 (1989). Municipal Sewage Treatment Plants—I. Investigations in
101. Richardson, M.L. and J.M. Bowron, ‘‘The Fate of Pharmaceutical Germany, Canada and Brazil’’, Sci. Total Environ., 225(1–2):81–
Chemicals in the Aquatic Environment’’, J. Pharm. Pharmacol., 90 (1999).
37(1):1–12 (1985). 120. Ternes, T.A., J. Stüber, N. Herrmann, D. McDowell, A. Ried, M.
102. Rodrı́guez, I., J.B. Quintana, J. Carpinteiro, A.M. Carro, R.A. Kampmann, and B. Teiser, ‘‘Ozonation: A Tool for Removal of
Lorenzo, and R. Cela, ‘‘Determination of Acidic Drugs in Sewage Pharmaceuticals, Contrast Media and Musk Fragrances from
Water by Gas Chromatography-Mass Spectrometry as Tert- Wastewater?’’, Water Res., 37(8):1976–1982 (2003).
Butyldimethylsilyl Derivatives’’, J. Chromatogr. A, 985(1–2):265– 121. Ternes, T.A., M. Meisenheimer, D. McDowell, F. Sacher, H.J.
274 (2003). Brauch, B.H. Gulde, G. Preuss, U. Wilme, and N.Z. Seibert,
103. Rosenfeldt, E.J. and K.G. Linden, ‘‘Degradation of Endocrine ‘‘Removal of Pharmaceuticals During Drinking Water
Disrupting Chemicals Bisphenol A, Ethinylestradiol, and Treatment’’, Environ. Sci. Technol., 36(17):3855–3863 (2002).
Estradiol During UV Photolysis and Advanced Oxidation 122. Vogna, D., R. Marotta, A. Napolitano, and M. d’Ischia,
Processes’’, Environ. Sci. Technol., 38(20):5476–5483 (2004). ‘‘Advanced Oxidation Chemistry of Paracetamol. UV/H2O2-
104. Sacher, F., F.T. Lange, H.J. Brauch, and I. Blankenhorn, Induced Hydroxylation/Degradation Pathways and 15N-aided
‘‘Pharmaceuticals in Groundwaters—Analytical Methods and Inventory of Nitrogenous Breakdown Products’’, J. Org. Chem.,
Results of a Monitoring Program in Baden-Wurttemberg, 67(17):6143–6151 (2002).
Germany’’, J. Chromatogr. A, 938(1–2):199–210 (2001). 123. Vogna, D., R. Marotta, A. Napolitano, R. Andreozzi, and M.
105. Sauleda, R. and E. Brillas, ‘‘Mineralization of Aniline and d’Ischia, ‘‘Advanced Oxidation of the Pharmaceutical Drug
4-Chlorophenol in Acidic Solution by Ozonation Catalyzed with Diclofenac with UV/H2O2 and Ozone’’, Water Res., 38(2):414–
Fe2+ and UVA Light’’, Appl. Catal. B-Environ., 29(2):135–145 (2001). 422 (2004a).
106. Shishida, K., S. Echigo, K. Kosaka, M. Tabasaki, T. Matsuda, H. 124. Vogna, D., R. Marotta, R. Andreozzi, A. Napolitano, and M.
Takigami, H. Yamada, Y. Shimizu, and S. Matsui, ‘‘Evaluation of d’Ischia, ‘‘Kinetic and Chemical Assessment of the UV/H2O2
Advanced Sewage Treatment Processes for Reuse of Wastewater Treatment of Antiepileptic Drug Carbamazepine’’, Chemosphere,
Using Bioassays’’, Environ. Technol., 21(5):553–560 (2000). 54(4):497–505 (2004b).
107. Silverman, R.B., The Organic Chemistry of Drug Design and Drug 125. Wiegman, S., J.A.G. Termeer, T. Verheul, M.H.S. Kraak, P. De
Action (San Diego, CA: Academic Press, 1992), pp. 277–351. Voogt, R. Laane, and W. Admiraal, ‘‘UV Absorbance
108. Snyder, S.A., P. Westerhoff, Y. Yoon, and D.L. Sedlak, Dependent Toxicity of Acridine to the Marine Diatom
‘‘Pharmaceuticals, Personal Care Products, and Endocrine Phaeodactylum tricornutum’’, Environ. Sci. Technol.,
Disruptors in Water: Implications for the Water Industry’’, 36(5):908–913 (2002).
Environ. Eng. Sci., 20(5):449–469 (2003). 126. Zbaida, S., R. Kariv, P. Fischer, J. Silmangreenspan, and Z.
109. Soejima, K., J. Uozumi, T. Kanou, C. Fujiyama, and Z. Masaki, Tashma, ‘‘Reaction of Cimetidine with Fenton Reagent — A
‘‘Nonionic Contrast Media are Less Nephrotoxic Than Ionic Biomimetic Model for the Mixed-Function Oxidase Drug-
Contrast Media to Rat Renal Cortical Slices’’, Toxicol. Lett., Metabolism’’, Eur. J. Biochem., 154(3):603–605 (1986).
143(1):17–25 (2003). 127. Zhou, H. and D.W. Smith, ‘‘Advanced Technologies in Water and
110. Soulet, B., A. Tauxe, and J. Tarradellas, ‘‘Analysis of Acidic Drugs Wastewater Treatment’’, Can. J. Civ. Eng., 28:S49–S66 (2001).
in Swiss Wastewaters’’, Int. J. Environ. Anal. Chem., 82(10):659– 128. Zwiener, C. and F.H. Frimmel, ‘‘Oxidative Treatment of
667 (2002). Pharmaceuticals in Water’’, Water Res., 34(6):1881–1885 (2000).
December 2006
(=1,395 mg/L) and M1s1 at pH 5.5 zero to 10 mg/L
6% of initial TOC (Andreozzi (Arslan-Alaton and
(=920 mg/L) removed et al., 2005) Dogruel, 2004)
at pH 7
([H2O2]0 = 1.02 g/L)
(Arslan-Alaton and
Dogruel, 2004)
(Continued)
393
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APPENDIX. (Continued)
394
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
K. Ikehata et al.
Fenton-like 46% of initial TOC Fenton) and 21 mg/L
(=920 mg/L) removed (photo-Fenton-like)
by photo-Fenton, 66% (Arslan-Alaton and
COD and 42% TOC Dogruel, 2004)
removed by photo-
Fenton-like, both at
pH 3, 1 mM Fe2+ or
December 2006
Fe3+, 20 mM H2O2
(Arslan-Alaton and
Dogruel, 2004)
Photolysis No COD/TOC FP = 0.571 N/D No BOD5 increase
reduction (Arslan- molEinstein1 at pH (Arslan-Alaton and
Alaton and Dogruel, 5.5 (Andreozzi et al., Dogruel, 2004)
2004) 2005)
Penicillin VK Antibiotic, Ozonation 70% of initial COD N/D N/D BOD5/COD increased
(132-98-9) b-lactam (=450 mg/L) and from 0 to 0.25
40% of initial TOC (Akmehmet Balcio glu
(=162 mg/L) removed and Ötker, 2003)
at pH 7-11
(Akmehmet Balcioglu
and Ötker, 2003)
Downloaded by [Dalhousie University] at 15:51 13 September 2012
December 2006
Cefradine Antibiotic, TiO2/hv Complete conversion of N/D N/D N/D
(38821-53-3) b-lactam 70 mg/L cefradine,
(cephalosporin) addition of H2O2
accelerate
decomposition (Fan
et al., 2002)
(Continued)
395
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APPENDIX. (Continued)
396
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
Ceftriaxone Antibiotic, Ozonation 53%, 74% and 82% of N/D N/D BOD5/COD increased
(73384-59-5) b-lactam initial COD (=450 from zero to 0.10
(cephalosporin) mg/L) removed at pH (Akmehmet Balcio glu
3, 7, and 11 and Ötker, 2003)
(Akmehmet Balcioglu
and Ötker, 2003)
O3/H2O2 About 90% of initial N/D N/D N/D
COD (=450 mg/L)
removed at pH 7
(Akmehmet Balcioglu
and Ötker, 2003)
MMTD Intermediate of H2O2/UV Complete conversion of kOH = 1.6 · 1010 Degradation N/D
(29490-19-5) cefazolin 1 mg/L MMTD in 20 M1s1 at 25 C pathway
(cephalosporin min, 60% TOC (Lopez proposed (Lopez
antibiotic) removed in 4 h (Lopez et al., 2003) et al., 2002)
et al., 2002)
Photolysis About 90% conversion FP = 12 One by-product N/D
K. Ikehata et al.
of 1 mg/L MMTD in mmolEinstein1 identified (Lopez
60 min, no (Lopez et al., 2002) et al., 2002)
mineralization (Lopez
et al., 2002)
MMTD-Me Intermediate of H2O2/UV Complete conversion kOH = 8.3 · 108 S-Oxidation N/D
(1925-78-6) cefazolin of 1 mg/L MMTD-Me M1s1 precedes
(cephalosporin in 20 min, 80% TOC at 25 C (Lopez mineralization
December 2006
antibiotic) removed in 4 h (Bozzi et al., 2003) (Bozzi et al.,
et al., 2002) 2002)
photolysis Complete conversion FP = 14.1 Two by-products N/D
of 1 mg/L MMTD-Me mmolEinstein1 identified (Bozzi
in 60 min, no (Lopez et al., 2003) et al., 2002)
mineralization (Bozzi
et al., 2002)
Azithromycin Antibiotic, Ozonation Complete conversion of N/D N/D N/D
(83905-01-5) macrolide azithromycin
(concentration
unknown) at pH 7
(Huber et al., 2005)
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December 2006
7 (Akmehmet
Balcioglu and Ötker,
2003), successfully
decontaminated
enrofloxacin-loaded
zeolite (Ötker and
Akmehmet-Balcioglu,
2005)
(Continued)
397
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APPENDIX. (Continued)
398
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
Ofloxacin Antibiotic, Ozonation Complete conversion of N/D N/D Algal and protozoan
(levofloxacin; quinolone 560 mg/L ofloxacin in toxicity eliminated (as
637328-10-0) a mixture of six a mixture) (Andreozzi
pharmaceuticals at pH et al., 2004)
7.4 (Andreozzi et al.,
2004)
H2O2/UV Complete conversion of N/D N/D Algal toxicity
560 mg/L ofloxacin in eliminated, protozoan
a mixture of six toxicity reduced (as a
pharmaceuticals at pH mixture) (Andreozzi
7.4 (Andreozzi et al., et al., 2004)
2004)
TiO2/hn Incomplete conversion N/D N/D No toxicity reduction
of 560 mg/L ofloxacin (as a mixture)
in a mixture of six (Andreozzi et al.,
pharmaceuticals 2004)
(Andreozzi et al.,
K. Ikehata et al.
2004)
Sulfachlorpyridazine Antibiotic, Ozonation Complete conversion of N/D N/D N/D
(80-32-0) sulfonamide 50 mg/L
sulfachlorpyridazine at
pH 7.5 in 1.5 min
(Adams et al., 2002)
Fenton N/D (See Table 2) N/D N/D
December 2006
Sulfadiazine Antibiotic, Ozonation Complete conversion of N/D N/D N/D
(68-35-9) sulfonamide 2 mg/L sulfadiazine at
pH 7 (Huber et al.,
2005)
Fenton N/D (See Table 2) N/D N/D
þ
TiO2/hn 80% conversion of 15 N/D SO2
4 ; NH 4; N/D
mg/L sulfadiazine in NO3 ; hydroxy-
30 min, 80% and 15% lated sulfadiazine
recovery of sulfur and (Calza et al.,
nitrogen, respectively 2004b)
(Calza et al., 2004b)
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December 2006
N4-acetylation lower
the reactivity toward
ozonation (Huber
et al., 2005)
Fenton N/D (See Table 2) N/D N/D
(Continued)
399
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APPENDIX. (Continued)
400
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
Sulfamethoxazole Antibiotic, Ozonation Complete conversion of kO3 = 2.5 · 106 M1s1 N/D Algal and protozoan
(723-46-6) sulfonamide 0.62-2 mg/L at 20 C (Huber et al., toxicity eliminated (as
sulfamethoxazole at 2003) a mixture) (Andreozzi
pH 7-7.2 (Ternes et al., et al., 2004)
2003; Huber et al.,
2005), Complete
conversion of 2.24 mg/
L sulfamethoxazole in
a mixture of six
pharmaceuticals at pH
7.4 (Andreozzi et al.,
2004), N4-acetylation
reduces reactivity
(Huber et al., 2005)
H2O2/UV Complete conversion of kOH = 5.5 · 109 N/D Algal toxicity
2.24 mg/L M1s1 at pH 7 and eliminated, protozoan
sulfamethoxazole in a 25 C (Huber et al., toxicity reduced (as a
K. Ikehata et al.
mixture of six 2003), see also Table 2 mixture) (Andreozzi
pharmaceuticals at pH et al., 2004)
7.4 (Andreozzi et al.,
2004)
TiO2/hn Incomplete conversion N/D N/D No toxicity reduction
of 2.24 mg/L (as a mixture)
sulfamethoxazole in a (Andreozzi et al.,
December 2006
mixture of six 2004)
pharmaceuticals
(Andreozzi et al.,
2004)
Sulfamethizole Antibiotic, Fenton N/D (See Table 2) N/D N/D
(144-82-1) sulfonamide
Sulfamoxole Antibiotic, Fenton Unstable in weakly (See Table 2) N/D N/D
(729-99-7) sulfonamide acidic solution (Boreen
et al., 2004)
Sulfapyridine Antibiotic, Ozonation Complete conversion of N/D N/D N/D
(144-83-2) sulfonamide 2 mg/L sulfapyridine at
pH 7 (Huber et al.,
2005)
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December 2006
Addamo et al., 2005)
Trimethoprim Antibiotic, chemotherapeutic Complete N/D
(738-70-5) conversion of
0.34-50 mg/L
trimethoprim at
pH 7-7.5 (Adams
et al., 2002;
Ternes et al.,
2003)
401
(Continued)
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APPENDIX. (Continued)
402
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
N/D N/D
Buspirone Anti-anxiety TiO2/hn Complete conversion of N/D Degradation N/D
(36505-84-7) agent 15 mg/L buspirone in pathway
30 min (Calza et al., proposed (Calza
2004a) et al., 2004a)
Carbamazepine Anticonvulsant Ozonation Complete conversion of kO3 = 7.81 · 104 Degradation Algal toxicity
(298-46-4) 0.5-118 mg/L M1s1 (Andreozzi pathway diminished (Andreozzi
carbamazepine et al., 2002), 3 · 105 proposed et al., 2002)
(Andreozzi et al., M1s1 (Huber et al., (Andreozzi et al.,
2002; Ternes et al., 2003) 2002; McDowell
2002; Huber et al., et al., 2005)
2003), 30%
mineralization as CO2
(Andreozzi et al.,
2002)
H2O2/UV Complete conversion of kOH = 2.05 · 109 Degradation N/D
4.7 mg/L M1s1 (Vogna et al., pathway
K. Ikehata et al.
carbamazepine and 2004a), 8.8 · 109 proposed (Vogna
35% TOC removal in M1s1 (Huber et al., et al., 2004a)
4 min at pH 5.0 2003)
(Vogna et al., 2004a)
TiO2/hn >90% conversion of 4.2 Pseudo-1st-order Degradation N/D
mg/L carbamazepine kinetics (Doll and pathway
in 9 min (Doll and Frimmel, 2004) proposed (Doll
December 2006
Frimmel, 2005c), pilot and Frimmel,
scale treatment (Doll 2005b)
and Frimmel, 2005a)
Diazepam Anti-anxiety Ozonation 24%-65% conversion of kO3 = 0.75 M1s1 at N/D N/D
(439-14-5) agent/ 142 mg/L diazepam at 20 C (Huber et al.,
anticonvulsant pH 9 and 10 C 2003)
(Huber et al., 2003)
H2O2/UV, g- N/D kOH = 7.2 · 109 N/D N/D
radiolysis M1s1 at pH 7 and
25 C (Huber et al.,
2003)
Primidone Anticonvulsant Ozonation Up to 87% conversion N/D N/D N/D
(125-33-7) of 1 mg/L primidone at
pH 7.8 and 23 C
(Ternes et al., 2002)
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Diclofenac Non-steroidal Ozonation Complete conversion of kO3 = 1 · 106 M1s1 Degradation Algal and protozoan
(15307-86-5) anti- 1 mg/L – 296 mg/L at 20 C (Huber et al., pathway toxicity eliminated (as
inflammatory diclofenac (Zwiener 2003), 1.84 · 104 proposed (Vogna a mixture) (Andreozzi
drug (NSAID) and Frimmel, 2000; M1s1 at 25 C et al., 2004b) et al., 2004)
Ternes et al., 2002; (Vogna et al., 2004b)
Ternes et al., 2003;
Vogna et al., 2004b;
Huber et al., 2005),
>30% TOC removal,
95% dechlorination
(Vogna et al., 2004b)
O3/H2O2 Complete conversion of N/D N/D N/D
2 mg/L diclofenac in 10
min (Zwiener and
Frimmel, 2000)
H2O2/UV Complete conversion of N/D Degradation Algal toxicity
296 mg/L diclofenac, pathway eliminated, protozoan
40% TOC removal, proposed (Vogna toxicity reduced (as a
50% dechlorination et al., 2004b) mixture) (Andreozzi
(Vogna et al., 2004b) et al., 2004)
g-radiolysis N/D kOH = 7.2 · 109 N/D N/D
M1s1 at pH 7 and
25 C (Huber et al.,
2003)
Fenton No conversion at pH 3.5 N/D N/D N/D
and 22 C (Packer
December 2006
buffered acidic and
neutral media (Pérez-
Estrada et al., 2005a)
TiO2/hn Complete conversion of N/D N/D No toxicity reduction
50 mg/L diclofenac, (as a mixture)
55% DOC removal (Andreozzi et al.,
(Pérez-Estrada et al., 2004)
2005a)
(Continued)
403
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APPENDIX. (Continued)
404
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
Ibuprofen Non-steroidal Ozonation Less reactive than other kO3 = 9.6 M1s1 at 20 N/D N/D
(15687-27-1) anti- NSAIDs (Zwiener and C (Huber et al., 2003)
inflammatory Frimmel, 2000; Ternes
drug (NSAID) et al., 2003; Huber
et al., 2005)
O3/H2O2 Complete conversion of N/D N/D N/D
2 mg/L diclofenac at
pH 7.5 and 10 C
(Zwiener and
Frimmel, 2000)
H2O2/UV N/D kOH = 7.4 · 109 N/D N/D
M1s1 at pH 7 and
25 C (Huber et al.,
2003)
Fenton N/D kOH = 6.5 · 109 N/D N/D
M1s1 at pH 3.5 and
22 C (Packer et al.,
K. Ikehata et al.
2003)
Indomethacin Non-steroidal Ozonation Complete conversion of N/D N/D N/D
(53-86-1) anti- 0.1 mg/L indomethacin
inflammatory at pH 7.2 (Ternes
drug (NSAID) et al., 2003)
Naproxen Non-steroidal Ozonation Complete conversion of N/D N/D N/D
(22204-53-1) anti- 0.1 mg/L naproxen at
December 2006
inflammatory pH 7.2 (Ternes et al.,
drug (NSAID) 2003)
Fenton N/D kOH = 9.6 · 109 N/D N/D
M1s1 at pH 3.5 and
22 C (Packer et al.,
2003)
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Salicylic acid A decomposition Ozonation 60% conversion of 0.65 N/D N/D N/D
(69-72-7) product of mg/L salicylic acid
acetylsalicylic (Khan et al., 2004)
acid
Paracetamol Antipyretic/ Ozonation Complete conversion of kO3 = 1.41 · 103 Degradation N/D
(103-90-2) analgesic 0.8 g/L paracetamol at M1s1 (neutral), 9.91 pathway
pH 2 and 7 in 20 min, · 108 M1s1 proposed
20% and 30% TOC (dissociated) (Andreozzi et al.,
removal at pH 2 and (Andreozzi et al., 2003a)
7, respectively, in 2 h 2003a)
(Andreozzi et al.,
2003a)
H2O2/UV >90% conversion of kOH = 2.2 · 109 Degradation N/D
1.51 mg/L M1s1 (Andreozzi pathway
paracetamol at pH 5.5 et al., 2003a) proposed (Vogna
in 1 min, 40% TOC et al., 2002;
removal in 4 min Andreozzi et al.,
(Andreozzi et al., 2003a)
2003a)
Anodic Complete conversion N/D Oxalic acid, oxamic N/D
oxidation and 70%-98% TOC acid (Brillas
using a removal of 78-948 mg/ et al., 2005)
boron-doped L paracetamol (Brillas
diamond et al., 2005)
anode
Atenolol b-blocker Ozonation Complete conversion of N/D N/D N/D
December 2006
Metoprolol b-blocker Ozonation Complete conversion of N/D N/D N/D
(37350-58-6) 1.7 mg/L metoprolol at
pH 7.2 (Ternes et al.,
2003)
Propranolol b-blocker Ozonation Complete conversion of N/D N/D Algal and protozoan
(525-66-6) 0.18-325.5 mg/L toxicity eliminated (as
propranolol at pH 7.2- a mixture) (Andreozzi
7.4 (Ternes et al., 2003; et al., 2004)
Andreozzi et al., 2004)
(Continued)
405
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APPENDIX. (Continued)
406
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
H2O2/UV Complete conversion of N/D N/D Algal toxicity
325.5 mg/L eliminated, protozoan
propranolol at pH 7.4 toxicity reduced (as a
(Andreozzi et al., mixture) (Andreozzi
2004) et al., 2004)
TiO2/hn Incomplete conversion N/D N/D No toxicity reduction
of 325.5 mg/L (as a mixture)
propranolol (Andreozzi et al.,
(Andreozzi et al., 2004)
2004)
Sotalol (3930-20-9) b-blocker Ozonation Complete conversion of N/D N/D N/D
1.32 mg/L sotalol at
pH 7.2 (Ternes et al.,
2003)
Aclarubicin Cytostatic drug, Fenton Complete conversion of N/D Absence of No residual
(57576-44-0) anthracycline 0.5 g/L aclarubicin fluorescent by- mutagenicity
(Castegnaro et al., products (Castegnaro et al.,
K. Ikehata et al.
1997), H2O2 alone was (Castegnaro 1997)
less effective et al., 1997)
(Castegnaro et al.,
1997)
Daunorubicin Cytostatic drug, Fenton Complete conversion of N/D Absence of No residual
(20830-81-3) anthracycline 5 g/L daunorubicin fluorescent by- mutagenicity
(Castegnaro et al., products (Castegnaro et al.,
December 2006
1997), H2O2 alone was (Castegnaro 1997)
less effective et al., 1997)
(Castegnaro et al.,
1997)
Doxorubicin Cytostatic drug, Fenton Complete conversion of N/D Absence of No residual
(23214-92-8) anthracycline 0.4 g/L doxorubicin fluorescent by- mutagenicity
(Castegnaro et al., products (Castegnaro et al.,
1997), H2O2 alone was (Castegnaro 1997)
less effective et al., 1997)
(Castegnaro et al.,
1997)
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December 2006
et al., 1999)
Methotrexate Cytostatic drug, Ozonation Complete conversion of N/D N/D No residual
(59-05-2) anti-metabolite 491 mg/L mutagenicity (Rey
methotrexate at pH 3 et al., 1999)
and 7 in 60-75 min
(Rey et al., 1999)
(Continued)
407
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APPENDIX. (Continued)
408
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
Cyclophosphamide Cytostatic drug, Fenton Complete conversion of N/D N/D Mutagenic by-products
(50-18-0) alkylating 4 g/L formed in the presence
agent cyclophosphamide of 5% dextrose
(Hansel et al., 1997) (Hansel et al., 1997)
Ifosfamid Cytostatic drug, Fenton Complete conversion of N/D N/D No residual
(3778-73-2) alkylating 27 g/L ifosfamid mutagenicity (Hansel
agent (Hansel et al., 1997) et al., 1997)
Melphalan Cytostatic drug, Fenton Complete conversion of N/D N/D No residual
(148-82-3) alkylating 2 g/L melphalan mutagenicity (Hansel
agent (Hansel et al., 1997) et al., 1997)
Cimetidine Histamine H2- Fenton N/D kOH = 6.5 · 109 Four degradation N/D
(51481-61-9) receptor M1s1 (Latch et al., products
antagonist 2003) identified
(Zbaida et al.,
1986)
Ranitidine Histamine H2- Fenton N/D kOH = 1.5 · 1010 N/D N/D
(66357-35-5) receptor M1s1 (Latch et al.,
K. Ikehata et al.
antagonist 2003)
TiO2/hn Complete conversion of Kinetic model presented N/D N/D
50 mg/L ranitidine in (Addamo et al., 2005)
1 h, 60% TOC
removal in 5 h
(Addamo et al., 2005)
17b-Estradiol Hormone, Ozonation Complete conversion of N/D Degradation Estrogenicity removed
December 2006
(50-28-2) natural 0.02 mg/L–1.4 mg/L of pathway (Onda et al., 2002;
estrogen 17b-estradiol (Onda proposed (Huber Alum et al., 2004; Kim
et al., 2002; Alum et al., 2004) et al., 2004; Liu et al.,
et al., 2004; Kim et al., 2005)
2004; Huber et al.,
2005)
O3/H2O2 Complete conversion of N/D N/D Estrogenicity removed
7-36 ng/L (Shishida et al., 2000;
17b-estradiol (Onda Onda et al., 2002)
et al., 2002)
H2O2/UV Complete conversion of kOH = 1.41 · 1010 N/D N/D
17b-estradiol M1s1, a kinetic
(unknown model presented
concentration) (Rosenfeldt and
(Rosenfeldt and Linden, 2004)
Linden, 2004)
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December 2006
17a-ethinylestradiol M1s1 (Rosenfeldt
(unknown and Linden, 2004), 9.8
concentration) · 109 M1s1 (Huber
(Rosenfeldt and et al., 2003), a kinetic
Linden, 2004) model presented
(Rosenfeldt and
Linden, 2004)
(Continued)
409
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APPENDIX. (Continued)
410
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
Photo-Fenton- >85% conversion of N/D N/D N/D
like 5 mg/L 17a-
ethinylestradiol at pH
3.0, intermediate
reactivity among four
estrogens (Feng et al.,
2005)
Diethylstilbestrol Synthetic Photo-Fenton- Complete conversion of N/D N/D N/D
(56-53-1) estrogen, like 5 mg/L
contraceptive diethylstilbestrol at pH
3.0, highest reactivity
among four estrogens
(Feng et al., 2005)
Bezafibrate Lipid regulator Ozonation Complete conversion of kO3 = 590 M1s1 at N/D N/D
(41859-67-0) up to 181 mg/L pH 5-10, 20 C (Huber
bezafibrate at pH 8 et al., 2003)
and 10 C (Huber
K. Ikehata et al.
et al., 2003),
incomplete conversion
at lower ozone doses
(Ternes et al., 2002)
H2O2/UV N/D kOH = 7.4 · 109 N/D N/D
M1s1 at pH 7, 25 C
(Huber et al., 2003)
December 2006
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Clofibric acid Lipid regulator Ozonation Complete conversion of kO3 > 20 M1s1 N/D Algal and protozoan
(882-09-7) metabolite 0.12 mg/L – 322 mg/L (Huber et al., 2005), toxicity eliminated (as
clofibric acid apparent rate a mixture) (Andreozzi
(Andreozzi et al., constants = 29.8 et al., 2004)
2003b; Ternes et al., M1s1 at pH 2 –
2003), 49% TOC 2550 M1s1 at pH
removal in 1 h at pH 6.5 (Andreozzi et al.,
5.0 (Andreozzi et al., 2003b), a kinetic
2003b), incomplete model presented
conversion at lower (Andreozzi et al.,
ozone doses (Zwiener 2003b)
and Frimmel, 2000;
Ternes et al., 2002;
Ternes et al., 2003),
quantitative
dechlorination
(Andreozzi et al.,
2003b)
O3/H2O2 98% conversion of 2 mg/ N/D N/D N/D
L clofibric acid at pH
7 and 10 C in 10 min
(Zwiener and
Frimmel, 2000)
H2O2/UV >90% conversion of FP = 1.08 · 10–2 N/D Algal toxicity
322 mg/L clofibric molEinstein1 at pH eliminated, protozoan
acid at pH 5.0 and 25 5.5 and 254 nm, toxicity reduced (as a
December 2006
et al., 2003)
TiO2/hn Complete conversion of Pseudo-1st-order Degradation No toxicity reduction
0.5 mg/L clofibric acid kinetics (Doll and pathway (as a mixture)
at pH 6.5 in 4 min Frimmel, 2004) proposed (Doll (Andreozzi et al.,
(Doll and Frimmel, and Frimmel, 2004)
2004), pilot scale 2004)
experiments
performed (Doll and
Frimmel, 2005a)
411
(Continued)
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APPENDIX. (Continued)
412
Pharmaceutical Applied Intermediates/ Biodegradability and
(CAS #) Class process Degree of degradation Kinetic parameters by-products toxicity
Fenofibric acid Lipid regulator Ozonation Complete conversion of N/D N/D N/D
(42017-89-0) metabolite 0.13 mg/L fenofibric
acid at pH 7.2 (Ternes
et al., 2003)
Gemfibrozil Lipid regulator Ozonation Presence of unknown N/D N/D N/D
(25812-30-0) amount of gemfibrozil
was reported in a
sewage treatment
plant effluent that was
treated by ozonation
(Huber et al., 2005)
Diatrizoate Triiodinated Ozonation 0% to 14% conversion N/D N/D N/D
(737-31-5; X-ray contrast of 5.7 mg/L diatrizoate
sodium salt) medium at pH 7.2 (Ternes
et al., 2003), no
conversion of 5.0 mg/L
diatrizoate at pH 7
K. Ikehata et al.
(Huber et al., 2005)
O3/H2O2 25% conversion of 5.7 N/D N/D N/D
mg/L diatrizoate at pH
7.2 (Ternes et al.,
2003)
O3/UV 36% conversion of 5.7 N/D N/D N/D
mg/L diatrizoate at pH
December 2006
7.2 (Ternes et al.,
2003)
Iomeprol Triiodinated Ozonation 34% to 90% conversion N/D N/D N/D
(78649-41-9) X-ray contrast of 2.3-5 mg/L iomeprol
medium at neutral pH (Ternes
et al., 2003; Huber
et al., 2005)
O3/H2O2 85% conversion of 2.3 N/D N/D N/D
mg/L iomeprol at pH
7.2 (Ternes et al.,
2003)
O3/UV 88% conversion of 2.3 N/D N/D N/D
mg/L iomeprol at pH
7.2 (Ternes et al.,
2003)
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December 2006
medium iopromide at neutral (Huber et al., 2003)
pH (Ternes et al.,
2003; Huber et al.,
2005)
O3/H2O2 89% conversion of 5.2 kOH = 3.3 · 109 N/D N/D
mg/L iopromide at pH M1s1 at pH 7 and
7.2 (Ternes et al., 25 C (Huber et al.,
2003) 2003)
(Continued)
413
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414
APPENDIX. (Continued)
K. Ikehata et al.
removal of 769 mg/L
iopromide at pH 6.6
(Sprehe et al., 2001)
TiO2/hn Similar degradability to N/D N/D N/D
iomeprol (Doll and
Frimmel, 2004)
December 2006
Note: N/D = not determined, TOC = total organic carbon, BOD5 = 5-day biochemical oxygen demand, COD = chemical oxygen demand,
DOC = dissolved organic matter, AOX = absorbable organic halogens, kO3 = second-order rate constant for molecular ozone reaction, kOH = second-order
rate constant for hydroxyl radical reaction, FP = quantum yield of direct photolysis.