Environ Sci Pollut Res (2017) 24:10786–10795

DOI 10.1007/s11356-017-8750-x

RESEARCH ARTICLE

Oxidation of indometacin by ferrate (VI): kinetics,

degradation pathways, and toxicity assessment
Junlei Huang 1 & Yahui Wang 1 & Guoguang Liu 1 & Ping Chen 1 & Fengliang Wang 1 &
Jingshuai Ma 1 & Fuhua Li 2 & Haijin Liu 3 & Wenying Lv 1

Received: 18 November 2016 / Accepted: 2 March 2017 / Published online: 13 March 2017
# Springer-Verlag Berlin Heidelberg 2017

Abstract The oxidation of indometacin (IDM) by ferrate(VI)
(Fe(VI)) was investigated to determine the reaction kinetics,
transformation products, and changes in toxicity. The reaction
between IDM and Fe(VI) followed first-order kinetics with
respect to each reactant. The apparent second-order rate con-
stants (kapp) decreased from 9.35 to 6.52 M−1 s−1, as the pH of
the solution increased from 7.0 to 10.0. The pH dependence of
kapp might be well explained by considering the species-specific
rate constants of the reactions of IDM with Fe(VI). Detailed
product studies using liquid chromatography-tandem mass
spectrometry (LC-MS/MS) indicated that the oxidation prod-
ucts were primarily derived from the hydrolysis of amide link-
ages, the addition of hydroxyl groups, and electrophilic oxida-
tion. The toxicity of the oxidation products was evaluated using
the Microtox test, which indicated that transformation products
exhibited less toxicity to the Vibrio fischeri bacteria.
Quantitative structure-activity relationship (QSAR) analysis
calculated by the ecological structure activity relationship
(ECOSAR) revealed that all of the identified products exhibited
lower acute and chronic toxicity than the parent pharmaceutical
for fish, daphnid, and green algae. Furthermore, Fe(VI) was
effective in the degradation IDM in water containing carbonate
ions or fulvic acid (FA), and in lake water samples; however,
higher Fe(VI) dosages would be required to completely remove
IDM in lake water in contrast to deionized water.
Keywords Indometacin . Ferrate (VI) . Kinetics . Oxidation
products . Toxicity

Responsible editor: Ester Heath

Highlights
• The reaction kinetics of indometacin oxidation by ferrate(VI) was
investigated.
• Five different degradation products were identified by means of LC-
MS/MS.
• Intermediates were observed to be less toxic than the parent
compound.
• Higher ferrate(VI) dosages would be required to completely remove
IDM in actual water.
* Guoguang Liu
liugg615@163.com
1
School of Environmental Science and Engineering, Guangdong
University of Technology, Guangzhou Higher Education Mega
Center, Panyu District, No. 100 Waihuan Xi Road,
Guangzhou 510006, People’s Republic of China
2
School of Environmental and Chemical, Foshan University,
Foshan 528000, People’s Republic of China
3
School of Environment, Henan Normal University,
Xinxiang 453007, People’s Republic of China
Introduction
Pharmaceuticals and personal care products (PPCPs) are like-
ly to be found in any body of water that is influenced by raw or
treated wastewater, including wastewater treatment plant
(WWTPs) effluents, surface water, seawater, and groundwa-
ter; many of which are employed as potable water sources
(Liu and Wong 2013; Borecka et al. 2015; Lapworth et al.
2012; Lin et al. 2016). Compared to other types of pollutants,
PPCPs have the feature of comparatively low concentrations
in water but continuous replenishment (FENT et al. 2006).
Studies have revealed that some pharmaceuticals are
suspected of direct imparting toxicity to certain aquatic organ-
isms (Ferrari et al. 2003; Grung et al. 2008; Quinn et al. 2008).
Additionally, their continual but undetectable effects might
accumulate slowly, and finally culminate in irreversible deg-
radative changes to ecosystems, wildlife, and humans
(Daughton and Ternes 1999; Pomati et al. 2006). Municipal
wastewater comprises a significant source of PPCPs in the
Environ Sci Pollut Res (2017) 24:10786–10795
environment as many of them are not completely removed via
conventional wastewater treatment plants (Yang et al. 2011a,
2011b; Radjenović et al. 2009; Rosal et al. 2010).
In recent years, due to the low efficiency of conventional
wastewater treatment processes, various technologies have
been shown to be inadequate for the elimination of PPCPs
from the aquatic environment, including adsorption (Salem
Attia et al. 2013), photocatalysis (Méndez Arriaga et al.
2008), and advanced oxidation processes (Esplugas et al.
2007; Xiang et al. 2015). The copious chemical oxidation
methods that have been scrutinized for the effective degrada-
tion of PPCPs include oxidation by permanganate (Hu et al.
2009) and chlorine dioxide (Wang et al. 2014), ozonation
(Ikehata et al. 2008), photodegradation (Kim and Tanaka
2009; Czech and Rubinowska 2013), Fenton and Fenton-
like processes (Méndez Arriaga et al. 2010; Ifelebuegu and
Ezenwa 2011), and Electrochemical advanced oxidation pro-
cesses (EAOPs) (Oturan and Brillas 2007; Sirés et al. 2007),
etc. However, heavy metal pollution may result from the per-
manganate oxidation processes. Moreover, the potent carcin-
ogen bromate, which is difficult to remove from water, may be
formed during the ozonation of bromide-bearing water
(Camel and Bermond 1998; Gunten 2003). The application
of photodegradation is restricted by the current inability to
prepare effective, economical, and long-lived catalysts.
Fenton and Fenton-like processes perform optimally only un-
der very harsh conditions, with the extra drawback of sludge
production. Finally, EAOPs can yield effective removal of
organic micro-pollutants, but it requires an additional energy.
Recently, iron-based materials have garnered particular at-
tention in view of their special attributes, such as their earth-
abundant and environmentally compatible nature. The use of
ferrate(VI) (Fe(VI)) as an oxidant/disinfectant, and the further
utilization of the ensuing Fe(III) oxides/hydroxide as coagu-
lants are other additional attributes of ferrate(VI) for water
treatment. Fe(VI) is a strong oxidizing agent with redox po-
tentials of +2.2 and +0.7 V in acidic and basic solutions, re-
spectively. Akin to ozone and chlorine dioxide, Fe(VI) is a
highly selective oxidant; however, it is also one of the few
oxidants that does not appear to form hazardous byproducts
(e.g., no brominated or chlorinated disinfection byproducts
(DBPs), bromated, or chlorite) (Sharma 2010). Fe(VI) reac-
tions with a number of organic micro-pollutants have been
investigated (Yang et al. 2012; Lee et al. 2009; Sharma et al.
2006; Li et al. 2008; Yang et al. 2011a, 2011b). These studies
have revealed that organic micro-pollutants containing phe-
nol, amine, olefin, or thioether-moieties, may be potentially
transformed during water treatment with Fe(VI). These reac-
tions may involve, (1) the generation of Fe(V) and Fe(IV)
through 1-e− and 2-e− transfer processes, (2) production of
radical species which can also generate Fe(V) and Fe(IV)
species, (3) further reactions of Fe(V) and Fe(IV) with con-
taminants, (4) self-decompositions of Fe(VI), Fe(V), and
10787
Fe(IV) species, and (5) reactions of ferrates with reactive ox-
ygen species, O 2 • − , and H 2 O 2 , produced from self-
decompositions (Sharma et al. 2015). Among the PPCPs, in-
domethacin (IDM) is a widely prescribed anti-inflammatory,
anti-pyretic, and analgesic non-steroidal drug (Lehmann et al.
1997) that has been frequently detected in treated wastewater
effluent and drinking water sources at concentrations of up to
micrograms per liter (Lishman et al. 2006; Joonwoo et al.
2009). The contamination of primary drinking water sources
with IDM would constitute a serious threat to public health. At
present, very little data is available regarding the reaction ki-
netics, transformation products, and variations in IDM solu-
tion toxicity during the Fe(VI) oxidizing process.
Thus, the primary objectives of this study were to (1) de-
termine the kinetics of Fe(VI) reactions of IDM as a function
of solution pH, (2) identify the oxidation products and propose
potential degradation pathways, (3) further evaluate the vari-
ations in the IDM solution toxicity during the oxidation pro-
cess, and (4) evaluate the potential of Fe(VI) to degrade IDM
in actual water samples.
Experimental
Reagents
IDM, 1-(p-chlorobenzyl)-5-methoxy-2-methylindole-3-acetic
(99% purity), was purchased from Aladdin (Shanghai, China).
Solid potassium ferrate (K2FeO4, 98%) was purchased from
Shanghai. Additional analytical grade reagents (Na2S2O3·
5H2O, NaOH, phosphate, etc.) were used without further pu-
rification. A stock solution of IDM was prepared in acetoni-
trile (chromatographic grade) at a concentration of 10.0 mM.
Fe(VI) stock solutions were prepared by adding solid K2FeO4
to a 5 mM Na2HPO4/1 mM Na2B4O7·10H2O buffer solution
(pH ≈ 9.0), where the aqueous Fe(VI) was known to be the
most stable (Anquandah et al. 2011); subsequent filtration
through 0.22 μm nylon syringe filters (ANPEL, Shanghai);
and the determination of the Fe(VI) concentration by measur-
ing the absorbance of the solution at 510 nm
(ε510 nm = 1150 M−1 cm−1) (Bielski 1980). For toxicity assess-
ments, freeze-dried Vibrio fischeri bacteria were obtained
from the Institute of Soil Science, Chinese Academy of
Sciences (Nanjing, China) and stored at 4 °C. All aqueous
solutions were prepared using ultrapure water from an
18 MΩ Milli-Q water purification system (TKA, Germany).
The pH of the solutions was adjusted prior to the addition of
Fe(VI) through the introduction of H3PO4 or NaOH, and test-
ed using a portable digital pH-meter (pHS-3B, Shanghai)
throughout experiment. For this study, the total organic carbon
(TOC) of samples filtrating through 0.22 μm filters was de-
termined by a TOC analyzer (Shimadzu TOC-VCPH, Japan).
10788
Reaction kinetics
In preliminary experiments, the reaction of Fe(VI) with IDM
followed first-order kinetics under condition with excess
Fe(VI) or excess IDM, indicating that the reaction followed
first-order kinetics with respect to Fe(VI) and IDM. The
pseudo-first-order rate constants for the decrease of IDM (k′)
were obtained by measuring the decrease of IDM concentra-
tion as a function of time in the presence of excess Fe(VI).
Then, k′ values were determined at various concentrations of
Fe(VI) at a setting pH value. Thus, the apparent second-order
reaction rate constants could be determined by k′ values.
Kinetic studies were performed in a 500 mL beaker on a
collector-type magnetic stirrer in a batch reactor within a pH
range of from 7.0 to 10.0. The reactions were initiated by
spiking an aliquot of the Fe(VI) stock solution into pre-
equilibrated solutions containing IDM. At preselected time
intervals, 3.00 mL of the reaction liquid was transferred from
the beaker to a tube using a pipette, which contained sufficient
preloaded Na2S2O3 to immediately terminate the reaction.
Samples were filtered through 0.22 μm nylon filters and main-
tained at 4 °C until analysis was conducted using a HPLC
(LC-20A, Shimadzu). The chromatographic conditions were
as follows: column: Zorbax Eclipse XDB-C18, 4.6 × 150 mm,
5 μm; temperature: 40 °C; mobile phase: acetonitrile/
ammonium acetate buffer solution (35:65 v/v, containing
0.2% ammonium acetate); flow rates: 1 mL·min−1; injection
volume: 20 μL; and detection wavelength: 228 nm. All ex-
periments were carried out in triplicate.
Reaction products
To identify reaction intermediates and products, a phosphate
buffered IDM solution (0.02 mM IDM; pH 7.0) was treated
with Fe(VI) (0.2 mM) for 3 h (tests have demonstrated that
reactions come to completion within this time), after which the
solution was concentrated to 1.2 mL in a rotary evaporator
(RE-5299, YU HUA INSTRUMENT, China). The resulting
solutions were then filtered (0.22 μm nylon filters) to remove
Fe(III) (hydr)oxide products, and filtrates were analyzed by
liquid chromatography-tandem mass spectrometry (LC-MS/
MS). The products were analyzed by an Agilent 1100 series
LC, which was coupled to a 6410 triple quadrupole mass
spectrometer (Agilent Technologies, USA). Separation was
accomplished using an Agilent SB-C18 column (5 μm,
4.6 × 150 mm). Elution was performed at a flow rate of
0.2 mL·min−1 with H2O containing 0.2% (v/v) ammonium
acetate, as eluent A, and acetonitrile as eluent B; employing
a linear gradient of from 5 to 95% B in 20 min. Mass spectral
analysis was conducted in negative mode using an
electrospray ionization (ESI) source. Instrument parameters
were as follows: capillary voltage 3.5 kV, fragmentor 125 V,
desolvation gas (nitrogen, P 99.99%) flow 10 L·min−1,
Environ Sci Pollut Res (2017) 24:10786–10795
temperature 350 °C, nebulizer pressure 40 psi, and nitrogen
(P 99.99%), which was used as the collision gas. The mass
analyzer was operated in full scan mode (m/z range 100–600)
in order to identify the products. Once a potential product was
identified, production scan MS/MS was performed for struc-
ture elucidation.
Toxicity analysis
To assay the acute toxicity, a 15-min Microtox bioassay using
the V. fischeri bacteria was carried out according to the
Chinese National Standard Test Method GB/T 15441-1995.
The toxicity of the resulting samples was examined using a
Microtox model DXY-2 toxicity analyzer (Nanjing, China),
which evaluates the ability of the translation products to in-
hibit the bioluminescence of the V. fischeri bacteria (Marco-
Urrea et al. 2010). The luminescence inhibition rate (I%) was
calculated based on Eq. (1), where Ix and I0 are the luminosity
of the sample solution and the blank solution, respectively.
The initial IDM concentration was 0.02 mM. To comprehen-
sively evaluate toxicity, QSAR analysis was also performed to
predict the ecotoxicity of the parent pharmaceutical and trans-
formation products by the Ecological Structure-Activity
Relationship Model (ECOSAR) program (Kuang et al. 2013).
I 0 ‐I x
T% ¼  100% ð1Þ
I0
Results and discussion
Kinetics study
The reactions of Fe(VI) and IDM are first order with respect to
each reactant and can be described as the following equation:
d½IDMtot
¼ ‐k app ½FeðVIÞtot ½IDMtot ð2Þ
dt
Where kapp represents the apparent second-order rate con-
stant for the reaction of Fe(VI) with IDM as a function of pH;
[Fe(VI)]tot and [IDM]tot represent the total concentration of
Fe(VI) and IDM, respectively.
The apparent second-order rate constants (kapp, M−1 s−1)
were determined in the pH range of from 7.0 to 10.0 by mea-
suring the IDM decrease in the presence of excess Fe(VI). A
plot of the values of kapp as a function of pH is presented in
Fig. 1. Apparently, the kapp of IDM oxidation by Fe(VI) was
heavily dependent on pH, and it decreased from 9.35 to
6.52 M−1 s−1 as the pH was increased from 7.0 to 10.0 at
25 ± 2.0 °C (square symbols, Fig. 1). A similar result of pH
dependence was also observed with the oxidation of bisphenol
A (Lee et al. 2005), diclofenac (Wang et al. 2015), and
Environ Sci Pollut Res (2017) 24:10786–10795 10789

Fig. 1 The observed second- -

IDM
order rate constants (kapp, 10 1.0
M−1 s−1) as a function of pH for Meas kapp
the reaction between Fe(VI) and
IDM (experimental conditions: 8 2-
0.8
[IDM]0 = 0.02 mM,
FeO4
Model kapp
[Fe(VI)]0 = 0.20 mM, and
T = 25 ± 2 °C) 6 0.6

Mole fraction
kapp(M s )
-1
k23

-1
2 3
4 0.4

k22 2 2
2 0.2

0 -
0.0
HFeO4

7.0 7.5 8.0 8.5 9.0 9.5 10.0

pH

carbamazepine (Hu et al. 2009) by Fe(VI). The observed pH-
dependent variations in kapp might be explained by consider-
ing species-specific reactions between Fe(VI) and IDM. The
acid-base equilibrium of IDM and Fe(VI) may be expressed in
Eqs. (3), (4), (5), and (6).
IDM↔Hþ þ IDM− pKa ¼ 4:5
Chemically, due to the pKa value of IDM and Fe(VI), the
protonated IDM is the major form in solution, whereas two major
species of Fe(VI) (i.e., HFeO4− and FeO42−) may be observed
under experimental pH conditions (7.0 ≤ pH ≤ 10.0). While there
were six possible reactions from the expression of Eq. (7), only
two of the following two reactions (8)–(9) might have contribut-
ð3Þ ed to the observed kinetics constants.

HFeO4 − þ IDM− →Products þ FeðOHÞ3 ð8Þ

(Gupta et al. 2007)
FeO4 2− þ IDM− →Products þ FeðOHÞ3 ð9Þ
H3 FeO4 þ ↔Hþ þ H2 FeO4 pKa ¼ 1:5 ð4Þ
As a result, the pH dependency of kapp for IDM can be
(Rush et al. 1996) modeled by Eq. (10).
H2 FeO4 ↔Hþ þ HFeO4 − pKa2 ¼ 3:5 ð5Þ k app ¼ k 22 α2 β2 þ k 23 α2 β3
(Sharma et al. 2001a, 2001b) k a ðk 22 k α1 ½Hþ  þ k 23 k α1 k α2 Þ
¼   ð10Þ
ð½Hþ  þ k α Þ ½Hþ  þ k α1 ½Hþ  þ k α1 k α2
2
‐ þ
HFeO4 ↔H þ FeO4 pKa3 ¼ 7:23
2−
ð6Þ

(Sharma et al. 2001a, 2001b).
Considering the studied pH range of the reaction between
Fe(VI) and IDM, the three species of Fe(VI) (i.e., H2FeO4,
HFeO4−, and FeO42−) with the two species of IDM (i.e., IDM
and IDM−) could possibly react with each other. The pH de-
pendence can therefore be modeled by the following equation:
k app ½FeðVIÞtot ½IDMtot
¼ Σi¼1;2; j¼1;2;3 k ij αi β j ½FeðVIÞtot ½IDMtot
where [Fe(VI)]tot = [H2FeO4] + [HFeO4−] + [FeO42−],
[IDM]tot = [IDM] + [IDM−]; kij is the species-specific sec-
ond-order rate constant between IDM and Fe(VI) species,
and αi and βj represent the equilibrium distribution coeffi-
cients of IDM and Fe(VI) species, respectively.
Figure 1 represents the experimental and modeled pH profiles
that were obtained from Eq. (10). The species-specific second-
order kinetics constants, k22 (11.01(±0.35) M−1 s−1) and k23
(6.82(±0.22) M−1 s−1), were calculated from least-squares non-
linear regressions of the experimental kapp data using SigmaPlot
10.0 software. A fairly good correlation (R2 = 0.967) between the
measured (square symbols, Fig. 1) and modeled kapp (solid line,
Fig. 1) was obtained. This indicated that HFeO4− was much more
ð7Þ reactive than FeO42−, in good agreement with a number of pre-
vious reports that described Fe(VI) reactivity (Anquandah et al.
2013; Jiang et al. 2014).
The contribution of the individual reactions to the kinetics
constant is also shown (dotted lines, Fig. 1). At pH 7.0 to 7.5,
the reaction (8) between HFeO4−and IDM− (k22α2β2) was the
key contributor to the rate constants, while the reaction (9)
10790 Environ Sci Pollut Res (2017) 24:10786–10795

between FeO42− with IDM− (k23α2β3) was the major reaction,
at from pH 7.5 to 10.0. In general, the kapp value decreased as
the solution pH was increased.
Degradation products and plausible pathways
A number of degradation products resulting from IDM oxida-
tion by Fe(VI) were identified by LC-MS/MS in ESI negative
mode (ESI−). Based on both the analysis of the total ion chro-
matogram (TIC) and their corresponding fragmentation pat-
tern, the best fit chemical structures of such degradation prod-
ucts were tentatively proposed by referring to prior knowledge
with considerations of the Fe(VI) oxidation mechanism (Jiang
et al. 2014) and the molecular pattern of target compounds
(Wu et al. 1997; Li et al. 2005). Five products and IDM peaks
were observed in the TIC, which were assigned to product P1,
P2, P3, P4, P5, and IDM, respectively. P1 with m/z 155 and
P2 m/z 218 with were proved to be the cleavage products of
amide linkage. P3 with m/z 390 was identified as the hydrox-
ylation product of IDM. P4 with m/z 372 and P5 with m/z 328
arose from electrophilic oxidation. Table 1 summarizes the
overall fragment ions of intermediates, retention time, and
the proposed corresponding molecular structures.
Based on the five identified degradation products, a possi-
ble pathway of IDM by Fe(VI) was proposed schematically in
Fig. 2. This shows that the total degradation of IDM followed
three primary degradation pathways: hydrolysis of the amide
linkage, hydroxyl group addition, and electrophilic oxidation.

Table 1 Degradation products detected by LC–MS/MS in ESI negative mode during IDM-Fe(VI) reaction

Peak Retention Fragment peaks Molecular Probable structure

time m(z) formula
(min)
O
O

N
IDM 356 C19H16
19.2 312 Cl
ClNO4
OH

P1 155
11.0 111, 73, 53 C7H5ClO2 OH

Cl

NH
P2 218 C12H13NO
13.5 203, 174, 159
3
OH

O
O

P3 390 374, 346, 330, C19H18 Cl

OH

14.6
OH

302 ClNO6 OH

O
O

P4 372 328, 155, 354, C19H16Cl

15.5
Cl OH
O

216 NO5
O

O
O

P5 328 C18H16Cl
NH

16.7 312, 284

NO3
Cl
O
Environ Sci Pollut Res (2017) 24:10786–10795
Fig. 2 A possible degradation
pathway of IDM by Fe(VI)
Pathway I is based on amide linkage hydrolysis, to give 4-
chlorobenzoate and 5-methoxy-2-methylindol-3-yl acetate.
The proposed amide linkage hydrolysis was observed by
Wu et al. 1997. Furthermore, similar C-N bond cleavage and
the subsequent formation of carbonyl or ammonia have been
observed for the Fe(VI) reaction with primary aliphatic amines
(Zimmermann et al. 2012; Karlesa et al. 2014). Therefore, the
proposed pathway (I) is reasonable.
Pathway II is electrophilic attack, by which the aromatic
ring initially formed a phenoxy radical (C6H5-O•) and then
abstracted hydrogen from HFeO4−. The hydroxylation of the
double bond by Fe(VI) occurred through addition mecha-
nisms, forming hydroxylated P3 degradation products.
Furthermore, P3 could continue to be oxidized by Fe(VI) via
the decarboxylation of the acetic chain, losing a H2O and
demethylation successively; eventually translating to small
molecule organic matter.
Pathway III involves initially formed oxygenated species
via an unstable indole-2, 3-epoxide intermediate, as shown in
Pathway III, Fig. 2. In this case, such an epoxide is unstable at
room temperature and the carboxyl would attack the 2-posi-
tion, which resulted in the opening of the epoxide ring and the
concomitant formation of P4 and lactone ring products (Route
10791
CO2
a, Fig. 2). Further, the decarboxylation of the epoxide was
accompanied by a simultaneous opening of the epoxide ring,
which in turn resulted in the cleavage of the C-N bond be-
tween the 1 and 2 positions, thereby yielding degradation
products P5 (Route b, Fig. 2).
Toxicity assessment
While the Fe(VI) treatment of IDM is effective for the degra-
dation of the parent pharmaceutical, another concern relates to
toxic variability. A variety of degradation products were ob-
served during the Fe(VI) treatment of IDM; hence, it was
critical to evaluate the toxicity of the treated solutions as an
important component of the data toward assessing the envi-
ronmental risk of organic micro-pollutants in engineered sys-
tems and ambient aquatic environments. As depicted in Fig. 3,
the initial V. fischeri bacteria inhibition rate of IDM was 65.3%
according to Eq. (1) above. As the reaction progressed, the
inhibition rate of the treated IDM solution was quickly de-
creased to 16.1%, and a ~98.8% transformation rate of IDM
was achieved following 60 min of treatment, while only
28.8% of the TOC removal rate was obtained. This indicated
that the majority of IDM was transformed to intermediate
10792 Environ Sci Pollut Res (2017) 24:10786–10795

In order to estimate the impact of the parent pharmaceutical

Fig. 3 Degradation rate, mineralization, toxicity variations by Microtox
test of IDM during the Fe(VI) degradation (experimental conditions:
[IDM]0 = 0.02 mM, [Fe(VI)]0 = 0.20 mM, pH = 7.0, and T = 25 ± 2 °C)
products, while the rest may be mineralized. And the com-
bined toxicity of the reaction solutions was lower than the
parent compound. This decreased toxicity can be attributed
to the loss of IDM and the lower toxicity of intermediate
products than their parent compound. Overall, it may be ver-
ified that Fe(VI) provides an important pathway for IDM re-
moval and toxicity reduction in engineered systems employed
for drinking water and wastewater treatment.
and transformation products on various species, QSAR anal-
ysis, calculated by the ECOSAR, was also employed to esti-
mate the acute and chronic toxicity for fish, daphnia, and
green algae. As shown in Table 2, the compounds revealed
different toxicity levels for different species. All transforma-
tion products imparted a lower impact on fish, daphnia, and
green algae, in terms of both of acute toxicity and chronic
toxicity analysis. As relates to acute toxicity, the LC50 or
EC50 values obtained for IDM for fish, daphnid, and green
algae were about 2.939, 2.05, and 3.573 mg/L, respectively,
while the LC50 or EC50 values obtained for P1–P5 for the
three species were about 31.458–439.828, 19.664–261.994,
and 21.798–237.917 mg/L, respectively. Apparently, the
LC50 or EC50 values for all products for the three species were
higher than that for IDM, suggesting that the products had
lower toxicity than IDM. In terms of chronic toxicity, the
ChV values obtained for IDM for the three species were about
0.366, 0.354, and 1.479 mg/L, respectively, while the ChV
values obtained for P1–P5 for the three species were about
3.444–45.491, 2.506–29.194, and 7.071–69.321 mg/L, re-
spectively. As with acute toxicity, all products exhibited lower
chronic toxicity than IDM for the three species.
Removal experiments
The effects of water quality on the removal of IDM were
examined using buffer solution and lake water. The lake

Table 2 Estimated acute and

chronic toxicity for fish, daphnid, (a) Acute toxicitya
and green algae of IDM and Acute toxicity Fish Daphnid Green algae
transformation products by Compound 96-h LC50b Compound 48-h LC50 Compound 96-h EC50
ECOSAR
1 IDM 2.939 IDM 2.050 IDM 3.573
2 P1 439.828 P1 261.994 P1 237.917
3 P2 140.990 P2 80.935 P2 63.076
4 P3 53.130 P3 32.694 P3 33.963
5 P4 40.989 P4 25.463 P4 27.509
6 P5 31.458 P5 19.664 P5 21.798
(b) Chronic toxicitya
Chronic toxicity Fish Daphnid Green algae
Compound ChVc Compound ChV Compound ChV
1 IDM 0.366 IDM 0.354 IDM 1.479
2 P1 45.491 P1 29.194 P1 69.321
3 P2 13.960 P2 8.137 P2 16.925
4 P3 5.710 P3 3.988 P3 10.639
5 P4 4.455 P4 3.189 P4 8.801
6 P5 3.444 P5 2.506 P5 7.071
a
Unit = mg L−1
b
LC50 represent half lethal concentration; EC50 represent half effective concentration
c
ChV, Chronic Value, represents chronic toxicity
Environ Sci Pollut Res (2017) 24:10786–10795
water samples all placed 24 h for precipitation, and then
filtered through 0.22 μm filters. At a dose of 20.0 mg·L−1,
Fe(VI), as FeO42−, successfully removed IDM in a buff-
ered solution at a pH of 7.0 at 25 ± 2 °C, with a removal
percentage of >99.0%. However, a Fe(VI) dose of
20.0 mg·L−1 was not sufficient to remove IDM complete-
ly in lake water at pH 7.0. The removal percentages were
82.2 and 86.3% in Haizhu Lake water and Baiyun Lake
water, respectively. Therefore, a Fe(VI) dose >20.0 mg·
L−1 would be required for the complete removal of IDM
in lake water. This suggests that the Fe(VI) reaction with
water matrix components may consume significant
amounts of Fe(VI) during water treatment, which might
act to decrease the treatment efficiency of micro-pollut-
ants. Matrix components may include carbonate ions and
dissolved organic matter (DOM) to increase the demand
for Fe(VI), since they typically have higher concentrations
in comparison to IDM. Results showed that the presence
of carbonate ions in the range of 0–1.0 mM did not
change the Fe(VI) dosage demand. The effect of DOM
was demonstrated by performing experiments in the pres-
ence of fulvic acid (FA) in a buffered solution (Fig. 4). A
small amount of FA (up to 1.5 mg·L−1) had no significant
effect on the removal efficiency. However, when the con-
centration of FA in solution was increased, the removal
efficiency of IDM decreased, which was 68.2% at a FA
concentration of 20 mg·L−1. The results clearly demon-
strated the potential of Fe(VI) to remove IDM in lake
water, where the required Fe(VI) dose would vary with
the nature and source, as well as the concentration of
NOM present in the contaminated water.
Fig. 4 Effect of fulvic acid on the removal of IDM by Fe(VI)
([IDM]0 = 2.0 mg L−1, [Fe(VI)]0 = 20.0 mg L−1, pH = 7.0, and
T = 25 ± 2 °C)
10793
Conclusion
The degradation of IDM by Fe(VI) has been systematically
investigated in this study and the primary conclusions drawn
are summarized as follows:
(1) The reaction between IDM and Fe(VI) followed second-
order kinetics and the dependence of the apparent
second-order rate constant on pH was successfully ex-
plained using the species-specific rate constants of the
reactions of IDM with Fe(VI).
(2) Five intermediate compounds were identified, which fa-
cilitates the proposal of possible pathways for the degra-
dation of IDM via Fe(VI) oxidation. IDM undergoes a
series of steps, including the hydrolysis of the amide
linkage, addition of hydroxyl groups, and electrophilic
oxidation, to achieve final mineralization.
(3) Toxicity tests conducted with the V. fischeri bacteria in-
dicated that the transformation products exhibited less
toxicity to V. fischeri bacteria, suggesting that the
Fe(VI) treatment might serve as an effective strategy to-
ward the reduction of toxicity in drinking water and
wastewater treatment. Further, QSAR analysis calculated
by ECOSAR revealed that all products exhibited lower
acute and chronic toxicity than did IDM for fish, daph-
nia, and green algae.
(4) Fe(VI) was effective for the degradation IDM in water
that contained carbonate ions or fulvic acid (FA), and in
lake water samples; however, higher Fe(VI) dosages
would be required to completely remove IDM in lake
water in contrast to deionized water.
Acknowledgments This work is supported by the National Natural
Science Foundation of China (Nos. 21377031 and 21677040) and the
Innovative Team Program of High Education of Guangdong Province
(2015KCXTD007). The authors would like to thank the anonymous re-
viewers and editors for their help in the improvement of this paper.
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