Chloramination of iodide-containing waters: Formation of iodinated disinfection byproducts and toxicity correlation with total organic halides of treated waters

Science of the Total Environment 697 (2019) 134142

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Chloramination of iodide-containing waters: Formation of iodinated disinfection byproducts and toxicity correlation with total organic halides of treated waters Mahmut S. Ersan a, Chao Liu a, Gary Amy a, Michael J. Plewa b, Elizabeth D. Wagner b, Tanju Karanfil a,⇑ a b

Department of Environmental Engineering and Earth Sciences, Clemson University, Anderson, SC 29625, USA Department of Crop Sciences, Safe Global Water Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

h i g h l i g h t s

g r a p h i c a l a b s t r a c t


DOC and Iodide concentration have

shown to alter I-THM formation.
Increasing DOC gradually increased

measured cyto and genotoxicity.
Calculated CTI values do not

represent the measured CTI values.
Unknown TOX showed high

correlation with measured cytotoxicity.

a r t i c l e

i n f o

Article history: Received 23 June 2019 Received in revised form 25 August 2019 Accepted 26 August 2019 Available online 27 August 2019 Editor: Paola Verlicchi Keywords: I-THMs TOX Cytotoxicity Genotoxicity

⇑ Corresponding author. E-mail address: [email protected] (T. Karanfil). https://doi.org/10.1016/j.scitotenv.2019.134142 0048-9697/Ó 2019 Elsevier B.V. All rights reserved.

a b s t r a c t The formation of iodinated disinfection byproducts (I-DBPs) in drinking waters is of a concern due to their higher cyto- and genotoxicity than their chlorinated and brominated analogues. This study investigated the formation of I-DBPs under chloramination conditions using preformed chloramine and associated cyto- and geno-toxicities obtained with Chinese Hamster Ovary (CHO) cell assay. Cyto- and genotoxicity of the samples were also calculated using DBP toxicity index values and correlated with total organic halide (TOX) formation. In low iodide (I-) (0.32 lM, 40 lg L1) water, increasing dissolved organic carbon (DOC) concentration of selected waters from 0.1 to 0.25 mg L1 increased the formation of iodinated trihalomethanes (I-THMs), while further increases from 0.25 to 4 mg L1 produced an opposite trend. In high iodide water (3.2 lM, 400 lg L1), increasing DOC from 0.5 to 4 mg L1 gradually increased the I-THM formation, while a decrease was observed at 5.4 mg L1 DOC. Iodoform was the most influenced species from the changes in DOC concentration. While increasing the initial iodide concentration from 0 to 5 lM increased the formation of iodoform, it did not make any considerable impact on the formation of other I-THMs. The measured cytotoxicity of samples was significantly correlated with increasing DOC concentration. Unknown TOCl and TOI showed a high correlation with measured cytotoxicity, while calculated total organic chlorine (TOCl) and total organic iodine (TOI) did not correlate. The comparison of measured and calculated cytotoxicity values showed that the calculated values do not always represent the overall cytotoxicity, since the formation of unknown DBPs are not taken into consideration during the toxicity calculations. Ó 2019 Elsevier B.V. All rights reserved.

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1. Introduction Two oxidants, chlorine and chloramine, are commonly used for disinfection in water treatment. Although chlorine is stronger oxidant and disinfectant, it leads to the formation of regulated disinfection by products (DBPs) such as trihalomethanes (THMs) and haloacetic acids (HAAs) due to its reactions with dissolved organic matter (DOM) (Liu and Croue, 2016). Four THMs and five HAAs are currently regulated under the stage 2 DBP/R by USEPA at concentrations of 80 lg L1 and 60 lg L1, respectively (USEPA, 2001). Chloramine (mostly in the form of NH2Cl) (Seidel et al., 2005) has been considered as an alternative disinfectant, which has slower reaction kinetics and yields with DOM (Hancock et al., 2017; Zhu and Zhang, 2016), to reduce the formation of regulated THMs and HAAs (Hong et al., 2007; Liu et al., 2017). One unintended consequence, however, has been the formation of unregulated DBPs such as iodinated DBPs, including iodinated trihalomethanes (I-THMs), haloacetic acids (I-HAAs), and haloacetamides (I-HAcAms), in the presence of iodide (I-) in source waters (Allard et al., 2015; Cancho et al., 2000; Chu et al., 2012; Criquet et al., 2012; Ding and Zhang, 2009; Jones et al., 2012a; Karanfil et al., 2011; Krasner, 2006; Krasner et al., 2006; Liu et al., 2019; Liu et al., 2017). During water treatment, I is rapidly oxidized to hypoiodous acid (HOI) during chlorination or chloramination (Bichsel and Von Gunten, 1999; Nagy et al., 1988). While chlorine further rapidly oxidize HOI to IO 3 (Allard et al., 2015; Bichsel and Von Gunten, 1999, 2000; Ding and Zhang, 2009; Hua et al., 2006), chloramine cannot, resulting in the reactions between HOI and DOM, and thus the formation of iodinated DBPs (I-DBPs). Formation and occurrence of unregulated iodinated DBPs have been drawing attention because of their higher cyto- and geno-toxicity than their regulated brominated and chlorinated analogues (Plewa et al., 2004; Richardson et al., 2008). Iodide levels in fresh waters has been reported in the range of 0.1 to ~600 lg L1(Gong and Zhang, 2015; Liu et al., 2014; Moran et al., 2002; Richardson et al., 2008). Under extreme circumstances, such as groundwater adjacent to halide rocks, source waters affected by hydraulic fracturing brines, the iodide concentration can be >100 lg L1(Harkness et al., 2015). A DBP occurrence study conducted for 23 water treatment plants across the US and Canada reported I concentrations ranging from 0.4 to 104 lg L1 (Richardson et al., 2008). A survey conducted in Western Australian source waters found iodide concentrations ranging from <5 to 593 lg L1(Gruchlik et al., 2014). Another survey carried out in Alaskan, Canadian, European, and U.S rivers reported iodide concentrations in the rivers from 0.5 to 212 lg L1(Moran et al., 2002). It is possible to detect higher I concentrations in surface waters impacted by saline wastewaters, which results from seawater use for toilet flushing (e.g., in Hong Kong) as well as in groundwater sources under the influence of seawater intrusion (Gong and Zhang, 2015). The formation of I-DBPs during chloramination is controlled by multiple factors. Higher formation of iodinated THMs (I-THMs) was observed in low SUVA (low aromaticity) than high SUVA (high aromaticity) waters (Allard et al., 2015; Jones et al., 2011, 2012a; Karanfil et al., 2011). While it has been also shown that the formation of iodoform was higher at high pH conditions, which may be due to enhanced hydrolysis step in iodoform formation, the formation of mixed species (Cl/Br/I-THMs) decreased as the pH increased, which may be due to higher stability of monochloramine at high pH (Hua and Reckhow, 2008; Vikesland et al., 2001). Jones et al. investigated the formation of I-THMs under constant Br/I mass ratios (i.e., 100/10, 200/20, and 800/80), at two DOC concentrations (i.e., 6.0 mg L1 vs 1.7 mg L1), and different pH conditions (i.e., 6, 7.5, and 9). The results showed decreasing

I-THM formation with decreasing DOC concentration at pH 6, while the opposite trend was observed at higher pH conditions at the 800/80 (Br/I) ratio (Jones et al., 2012a). While characteristics and concentration of DOM and pH affected the formation of I-THMs, other factors such as the presence of bromide did not alter the formation of I-THMs during chloramination (Jones et al., 2011; Trofe et al., 1980). In fact, some researchers reported Cl/Br/I-THMs (i.e. BCIM, DBIM, BDIM) in the presence of bromide, whereas others observed Cl/I-THMs (i.e. DCIM, CDIM, TIM) (Allard et al., 2015; Criquet et al., 2012). Iodinated DBPs are more cyto- and geno-toxic than their brominated and chlorinated analogues (Wagner and Plewa, 2017). In some previous studies, using the reported individual cyto- toxicity values of DBP species (~LC50: concentration of the compound that reduces the cell density of Chinese Hamster Ovary (CHO) cells by 50% as compared to negative control), theoretical toxicities were calculated in chloraminated waters using the concentration of known DBP species (Chuang and Mitch, 2017; Smith et al., 2010). However, calculations do not represent the overall toxicity of treated waters considering the formation of several unknown and/or unidentified DBPs (unknown total organic halides (UTOX) is a surrogate parameter). Previous studies have reported that calculated cytotoxicity showed good correlation with total organic halides (TOX) (Echigo et al., 2004; Han and Zhang, 2018; Jiang et al., 2017; Liu et al., 2017; Pan et al., 2014). However, a systematic study which investigates the roles of both DOC and iodide concentrations on I-THM formation and speciation and their relationship with measured and/or calculated cyto- and genotoxicity, and UTOX/TOX is still needed. To our best of knowledge, this study reports, for the first time, the correlation of UTOX and TOX with experimental and calculated cyto- and genotoxicities of unknown and known DBPs (i.e. Cl/I-THMs, Cl/Br-HAAs) under chloramination. While these findings will provide broader understanding on the formation of unregulated/regulated DBPs (i.e. Cl/Br/I-DBPs) and their toxic impacts on Chinese Hamster Ovary cells, the results will guide scientists and practitioners to develop mitigation strategies. The objective of this study is to examine the effect of (i) concentration and type of DOM, (ii) initial concentration of bromide and iodide, and (iii) oxidant dose on the formation, and speciation of I-THMs under chloramination conditions along with the cytoand geno-toxicity evaluations at the selected conditions. Pearson product moment correlation analysis was performed to understand the association between unknown/measured TOX data and calculated cyto- and genotoxicities.

2. Material and method 2.1. Chemicals and reagents Six I-THM standards, dichloroiodomethane (DCIM), bromochloroiodomethane (BCIM), dibromoiodomethane (DBIM), chlorodiiodomethane (CDIM), bromodiiodomethane (BDIM), and triiodomethane (TIM) were obtained from CanSyn Chemical Corp (Toronto, ON, Canada). Four THM standards, trichloromethane (TCM), dichlorobromo methane (DCBM), dibromochloro methane (DBCM) and tribromomethane (TBM); Nine HAA standards, monochloroacetic acid (CAA), monobromoacetic acid (BAA), dichloroacetic acid (DCAA), bromochloroacetic acid (BCAA), dibromoacetic acid (DBAA), bromodichloroacetic acid (BDCAA), and tribromoacetic acid (TBAA) were obtained from Sigma-Aldrich (Milwaukee, WI). All other chemicals used in this study were purchased at the highest purities available from VWR (Marietta, GA). The preformed chloramine stock solution (500 mg L1 as Cl2) was

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M.S. Ersan et al. / Science of the Total Environment 697 (2019) 134142 Table 1 Selected characteristics of studied waters. Sampling locations Myrtle Beach Myrtle Beacha a

Type

Sample Code

UV254 (cm1)

DOC (mg L1)

DON (mg L1)

SUVA254 (Lmg1.m1)

Br (lg L1)

pH

Treated Raw

MB-T MB-R

0.124 1.273

5.4 25.0

0.32 0.85

2.1 5.1

49 50

6.5 6.9

Sample was diluted prior to UV absorbance measurements.

prepared by titrating ammonium sulfate stock solution (1000 mg L1) with sodium hypochlorite solution (5% available free chlorine) (1000 mg L1) at a Cl2:N mass ratio of 3.5:1 at pH 7.8. 2.2. Water samples Treated (MB-T) and raw water (MB-R) samples were collected from a drinking water treatment plant located in South Carolina (SC), USA. The SUVA254 (specific ultraviolet absorbance at 254 nm) values, which are used as surrogate parameters for hydrophobicity and aromaticity of DOM, were 2.1 vs 5.1 L mg 1 m1 in the treated and raw waters, respectively. Treated samples were collected after conventional clarification and sand-filtration (before any oxidant addition). Upon arrival at the laboratory, samples were filtered through 0.2 lm pore size WhatmanÒ Polycap 150 TC filters, and kept in the dark at 4 °C until use. Water characteristics, including ultraviolet absorbance at 254 nm (UV254), dissolved organic carbon (DOC), dissolved organic nitrigen (DON), SUVA, bromide (Br), and pH were shown in Table 1. Iodide concentration in the water samples was below the minimum reporting limit. 2.3. Experimental design Prior to the experiments, samples were diluted to target DOC levels (i.e., 0.1, 0.25, 0.5, 1, 2, 4 mg L1), with distilled deionized water (DDW), and divided into 250 mL of amber glass bottles. The pH of the samples was adjusted with 20 mM phosphate buffer to pH 7.5 (Ersan et al., 2019; Jones et al., 2011; Liu et al., 2018, 2019). For Br and I effect experiments, bottles were spiked with appropriate amounts of Br and I solutions to evaluate the impact of Br (5 lM, 400 lg L1) and I (0.32, 0.8, 1.6, 3.2 lM; corresponding to 40, 100, 200, 400 lg L1) concentrations on I-DBP formation. DOM concentration experiments were conducted under ambient Br- (0.01, 0.025, 0.05, 0.11, 0.22, 0.45, 0.61 lM; corresponding to 0.1, 0.25, 0.5, 1, 2, 4, 5.4 mg L1 DOC, and at two different I concentrations (0.32 and 3.2 lM). Chloramine stock solution (500 mg L1 as Cl2, Cl/N mass ratio: 3.5:1) was spiked into the samples with a target initial concentration of 2.3 mg Cl2/L (32 lM as Cl2) to obtain a residual of 2.0 ± 0.2 mg L1 after 24 h of contact time (Jones et al., 2011, 2012a). Two chloramine doses (2.3 mg L1 and 20 mg L1 as Cl2) were selected to investigate the impact of chloramine dose on the formation of Cl/Br/I-THM. During chloramine dose effect experiments, a stock solution of chloramine at 2500 mg L1 as Cl2 was used to target 20 mg Cl2/L (281 lM as Cl2) chloramine dose. Following oxidation, samples were kept in head space free amber glass bottles to prevent volatilization of volatile DBPs and reacted at 20 °C in the dark for 24 h. Later, samples were withdrawn and analyzed for residual oxidants according to DPD colorimetric method (SM 4500-Cl G) (APHA et al., 2005). Residual chloramine was quenched with a stoichiometric amount of ascorbic acid. Afterwards, samples were analyzed for THMs, ITHMs, HAAs, and TOX (TOCl-TOBr-TOI). Analyses of THMs, I-THMs, and HAAs were performed following U.S. EPA Method 551.1, and 552.2, respectively, with minor modifications (USEPA, 1995). The analysis of total organic halides was

conducted according to a method described elsewhere (Hua and Reckhow, 2006). A sample calculation for measured, calculated and unknown TOX is given as below (Eqs. (1)–(3)).

½TOXmeasured ¼ ½TOClmeasured þ ½TOBrmeasuredþ ½TOImeasured

ð1Þ

½TOXcalculated ¼ ½TOClcalculated þ ½TOBrcalculated þ ½TOIcalculated ¼ ½Cl=Br=I-THMs þ ½Cl=Br-HAAs ½TOXunknown ¼ ½TOXmeasured —½TOXcalculated

ð2Þ ð3Þ

Detailed analytical procedures for DBPs, TOX and all the other parameters are described in the supporting information section (S1) and summarized in Table S1. The description of the analytical methods can be also found in our previous publications (BeitaSandí et al., 2016; Ersan et al., 2015, 2016, 2019). 2.4. Chinese Hamster Ovary Cell (CHO) toxicity assays To be used in the toxicity assays, chloraminated samples were extracted using a procedure explained in the SI section according to previously published study (Plewa et al., 2012). Later, CHO cells, line AS52 clone 11–4-8, were exposed to extracted samples for the mammalian cell cytotoxicity analyses. Clone 11–4-8 expresses a stable chromosome complement and was calibrated for cytotoxicity and genotoxicity with a series of different toxic agents (Wagner et al., 1998a, 1998b). The CHO cells were maintained in Ham’s F12 + 5% fetal bovine serum (FBS) medium at 37 °C in a humidified atmosphere of 5% CO2. 2.4.1. CHO cell chronic cytotoxicity assay The CHO cell microplate chronic cytotoxicity assay measures the reduction in cell density as a function of the concentration of the test agent during a 72 h exposure period (Plewa et al., 2002; Plewa and Wagner, 2009). Regression analysis was applied to each water sample concentration-response curve, which was used to calculate the LC50. The LC50 is the calculated concentration of the test agent that induced a cell density that was 50% of the negative control. More detailed step by step procedure can be found in the SI section. 2.4.2. CHO single cell acute genomic DNA damage analyses Single cell gel electrophoresis (SCGE) is a molecular genetic assay that can quantitatively measure the level of genomic DNA damage induced in individual nuclei of cells (Fairbairn et al., 1995; Rundell et al., 2003; Tice et al., 2000; Wagner and Plewa, 2009). A flow diagram of the SCGE procedure is presented in Fig. S2 (SI). For each experiment, two microgels were prepared per treatment group. Twenty-five randomly chosen nuclei were analyzed in each microgel using a charged coupled device camera. A computerized image analysis system (Comet IV, Perspective Instruments, Ltd., Suffolk, UK) was employed to determine the % Tail DNA (the amount of DNA that migrated from the nucleus into the microgel) of the nuclei as the measure of DNA damage (Kumaravel and Jha, 2006). The digitalized data (Fig. S3, SI) were automatically transferred to a computer-based spreadsheet for

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subsequent statistical analysis. In general, the experiments were repeated 2–3 times for each water sample concentrate. 3. Results and discussion 3.1. Effect of DOM concentration and type Fig. 1-a shows the effect of DOM concentration (0.1–4.0 mg C L1) on the formation and speciation of Cl/I-THMs at initial I concentration of 0.32 lM. Overall, the main I-THMs formed were TIM, CDIM, and DCIM, and brominated I-THMs were not detected. When the I/DOC ratio decreased from 400 to 160 (lg/mg) (or DOC increased from 0.1 to 0.5 mg L1), there was an increase in the total I-THM formation, reaching the maximum at the 0.5 mg L1 DOC concentration. In this case, TIM was the main species, which was responsible for I-THMs increase. However, further increases in DOC concentration (or decrease in I/DOC ratio) decreased the total I-THM formation (i.e. DCIM, CDIM, and TIM). The decomposition of chloramine to chlorine is in equilibrium with the reaction between chlorine and ammonia. Increasing the DOM concentration enhanced the reaction between chlorine and DOM, facilitating the decomposition of chloramine (Fig. S4-a, SI) (Duirk et al., 2005). This likely resulted in the production of free chlorine (HOCl) that may further oxidize HOI to IO 3 and/or outcompeted HOI for reactive/ non-reactive sites of DOM, thus decreasing the formation of I-THMs (Allard et al., 2015; Hua and Reckhow, 2007; Jones et al., 2012b). On the other side, gradual increase in the formation of

Cl-THM (i.e., TCM) was also observed as the DOM concentration increased from 0.5 to 4.0 mg L1. Another set of experiments were conducted by increasing the initial I concentration by 10-fold (3.2 lM, 400 lg L1) (e.g., higher I/DOC ratios) (Fig. 1-b). The results showed that TIM was the dominant species at all DOM concentrations. In addition, the formation of I-THMs increased as the DOM concentration increased, and the inflection point of maximum I-THM formation was shifted to 4.0 mg DOC L1. With increasing DOC concentrations, autodecomposition of chloramine may still occur, which may led the formation of trace amount of free chlorine (HOCl) (Fig. S4-b, SI). However, because of the higher iodide concentration in the background, higher HOI levels can outcompete with HOCl and continue forming I-THMs with increasing DOC concentrations (reaching a maximum at the 4 mg L1 DOC concentration). A further increase in DOM concentration from 4 to 5.4 mg L1 decreased the formation of I-THMs. On the other hand, while the concentration of ITHMs increased up to their maximum (at 4 mg L1) and then decreased in response to changes in DOM concentrations (5.4 mg L1), there was no considerable impact on TCM. This may suggest that the high HOI / HOCl ratio in the system favored the formation of TIM rather than mixed Cl/I- THM species (Hua et al., 2006). Concentrations of HAAs were also measured at selected DOM concentrations (i.e. 0.5–4.0 mg C L1) under both studied I concentrations (0.32 lM and 3.2 lM). Results showed that only two HAA species, i.e., CAA and DCAA, were detected (Fig. S5-a&b, SI). The increase in DOC concentration mainly resulted in the formation of DCAA while other chlorinated and brominated HAAs were not detectable. This may be due to low concentration of Br in MB-T and/or faster reaction kinetics between trace amount of HOCl (from NH2Cl decomposition) and DOM. Hong et al. (2007) also showed that DCAA was the only species formed under chloramination of low bromide surface waters (Hong et al., 2007). On the other hand, the formation of HAAs (mainly DCAA) was suppressed when background I concentration was higher, which may be a result of reaction between trace amount of HOCl and I in the system (Fig. S5-b, SI). The impact of DOM type on the formation and speciation of Cl/ITHMs were also studied by comparing low vs. high SUVA DOM samples (Fig. 2). The formation of I-THMs was higher in low SUVA (i.e., 2.1 L mg 1 m1) Myrtle Beach treated (MB-T) water than high SUVA (i.e., 5.1 L mg 1 m1) Myrtle Beach raw (MB-R) water at all DOC concentrations (0.5 to 4.0 mg L1). These results indicate that not only concentration of DOM but also the characteristics of DOM can alter the formation of I-THMs. This was attributed to higher reactivity of iodine than chlorine with low SUVA components, which are known to contain more hydrophilic organic and lower molecular weight components than high SUVA waters at the same DOC levels. On the other hand, in contrast to I-THMs, higher formation of TCM was found at MB-R water with higher SUVA. This suggested that free chlorine resulting from the hydrolysis of monochloramine may preferentially reacts with highly reactive aromatic sites. The effect of DOM type on the formation of HAAs was also examined at 0.5 and 4 mg C L1 DOM concentrations (Fig. S6-a&b, SI). The formation of CAA and DCAA was slightly higher in the high SUVA MB-R water as compared to low SUVA MB-T water in both examined DOC concentrations. This indicated that HAA formation was less influenced by the characteristics of DOM as compared to THM formation (Hua et al., 2006). 3.2. Effect of Br and I concentration

Fig. 1. Effect of DOC concentration on the formation and speciation of THMs: (a) [I] 0 = 0.32 lM, and (b) [I] 0 = 3.2 lM. Experimental conditions: MB-T; pH = 7.5, [NH2Cl]0 = 2.3 mg L1, [Br] 0 = 0.05, 0.11, 0.22, 0.45 lM (corresponding to DOC: 0.5, 1, 2, 4 mg L1, respectively), T = 21 ± 1 °C, Contact time (t) = 24 h.

The effect of initial bromide concentration on the formation and speciation of I-THM was studied under ambient and 5 lM Br, and 0.32 lM background I concentrations at two different chloramine

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Fig. 2. Effect of DOM type on the formation and speciation of Cl/I-THMs. Experimental conditions: MB-T; [SUVA] 254 = 2.1 L mg 1 m1, MB-R; [SUVA] 254 = 5.1 L mg 1 m1, pH = 7.5, [NH2Cl] 0 = 2.3 mg L1, [DOC] 0 = (a) 0.5 mg L1, (b) 1 mg L1, (c) 2 mg L1, (d) 4 mg L1, [I] 0 = 0.32 lM, [Br]0 = 0.05, 0.11, 0.22, 0.45 lM (DOC: 0.5, 1, 2, 4 mg L1, respectively), T = 21 ± 1 °C, Contact time (t) = 24 h.

concentrations in MB-T water background (Fig. 3 and S7, SI). Brominated and/or chloro-bromo I-THMs were not detected regardless of the bromide concentrations (i.e., ambient and 5 lM)

under both chloramine doses (i.e., 2.3 and 20 mg L1) (Allard et al., 2015; Criquet et al., 2012). Chloramination of bromide containing waters results in the formation of less reactive bromamines

Fig. 3. Effect of initial Br concentration on the formation and speciation of Cl/I-THMs in the presence of various concentrations of NOM. Experimental conditions: MB-T; pH = 7.5, [DOC] 0 = (a) 0.5 mg L1, (b) 1 mg L1, (c) 2 mg L1, (d) 4 mg L1), [NH2Cl] 0 = 2.3 mg L1, Ambient [Br]0 concentrations = 0.05, 0.11, 0.22, 0.45 lM (DOC: 0.5, 1, 2, 4 mg L1, respectively), Fortified [Br]0 concentration = 5 lM, [I] 0 = 0.32 lM, T = 21 ± 1 °C, Contact time (t) = 24 h.*The detected Br/I-THMs were below MRL.

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(i.e. mostly bromochloramine) rather than bromine (Gazda et al., 1993). The former is less reactive than HOBr towards DOM to produce brominated DBPs, and thus the formation of brominated IDBPs was below method detection limits. On the other hand, increasing bromide concentration from 0.05 lM ([DOC]0: 0.5) and 0.11 lM ([DOC]0: 1) to 5 lM slightly decreased the formation of Cl-HAAs (only DCAA detected) (Fig. S8-a&b, SI). The effect of initial I concentrations (i.e., 0.32, 0.8, 1.6, 3.2 lM) on the formation and speciation of I-THMs was investigated in MBT and MB-R waters at 0.5 mg C L1 DOM concentration (Fig. 4). For both waters, increasing the initial iodide concentration increased the formation of TIM due to the increasing ratio of iodide/DOC. In contrast, there was no considerable change for TCM, DCIM, and CDIM concentrations in MB-T and MB-R waters. The trend of I-THMs (i.e. TIM) in terms of increasing iodide concentrations from MB-T water differs from that of MB-R water. At low iodide concentration (0.32 lM), MB-R produced less I-THM than MB-T. However, at high iodide concentrations (at 1.6 and 3.2 lM), MB-R water yielded more I-THMs. This can be ascribed to the competition between chlorine and iodine. At low initial iodide concentration, in addition to the formed HOI, chlorine can be formed from the autodecomposition of chloramine, which can be enhanced by the presence of DOM with higher reactivity (i.e., MB-R) (Vikesland et al., 2001). While chlorine can compete with iodine with highly reactive sites of DOM and convert some of the HOI into IO 3 , excess amount of HOI in the system can still lead to the formation of iodinated DBPs. However, for the lower SUVA

water (i.e., MB-T), HOI preferentially reacts with DOM with lower reactivity, and thus outcompetes with the free chlorine formed from the decomposition of chloramine. When initial iodide concentration is 3.2 lM (i.e., 400 lg L1), the HOI is the dominant oxidant, and free chlorine from the hydrolysis of chlorine is minor. Higher SUVA water with more reactive sites produces more ITHMs than lower SUVA water does. 3.3. Effect of initial NH2Cl concentration Fig. 5 shows the effect of initial NH2Cl concentration on the formation and speciation of Cl/I-THMs. At 0.5 and 1 mg C L1 DOM concentration, increasing the initial NH2Cl concentration from 2.3 to 20 mg L1 decreased the formation of all I-THM species. The observed lower formation of I-THMs, at 20 mg L1 chloramine dose, can be either attributed to higher concentration of HOCl resulted from autodecomposition of chloramine in the system, which can outcompete with HOI for the limited reactive sites, or formation of inorganic byproducts resulting from reactions between chloramine and iodide (Table S2; Eq. 7–8) (i.e., NHCll). This was further evidenced by the fact that increasing the initial NH2Cl concentration increased the formation of TCM. When the concentration of DOM increased from 2.0 to 4.0 mg C L1, the total formation of I-THMs at 20 mg L1 chloramine dose was similar to that at 2.3 mg L1 chloramine dose. While more sites were available at 4.0 mg C L1, higher autodecomposition of chloramine occurs (Duirk et al., 2005); therefore, formed HOCl may outcompete HOI to produce chlorinated DBPs (e.g., TCM) and reduce the formation of I-THMs. Furthermore, at 20 mg L1 chloramine dose, since the enhanced autodecomposition of chloramine at higher DOM concentrations occurred, which led to the formation of HOCl; and therefore, resulted in formation of Cl/I-THMs, such as TCM and DCIM. The impact of initial NH2Cl concentration on the formation of HAA9 at two DOM concentrations (0.5 and 4 mg C L1) was also investigated (Fig. S8-a&b, SI). While only DCAA were detected at 0.5 mg C L1 DOM concentrations, CAA and DCAA were observed at 4 mg C L1 DOM concentration. The total formation of HAAs increased as the DOM concentration increased from 0.5 to 4 mg L1. Furthermore, at 0.5 mg C L1 DOM concentration, increasing NH2Cl concentration increased the formation of DCAA (Fig. S9-a, SI). This was ascribed to the reaction of trace amount of HOCl with reactive sites of DOM, therefore, increasing the formation of DCAA in the system. On the other hand, at 4 mg C L1 DOM concentration, the elevated formation of CAA and DCAA were controlled by both NH2Cl and DOC concentration, where higher NH2Cl likely resulted in higher concentration of decomposition by products (i.e. HOCl and NH3), which were reacted with increased available reactive sites (4 mg C L1 DOM) to form ClHAA (Fig. S9-b, SI). Overall, the formation of HAAs indicated a similar trend with that for THMs. A lower initial chloramine concentration (e.g., 2.3 mg Cl2 L1), which is typically employed at water treatment plants, favored the formation of I-DBPs with decreasing DOC concentrations. 3.4. CHO cell chronic cytotoxicity evaluations

Fig. 4. Effect of initial I concentration on the formation and speciation of Cl/I-THMs. Experimental conditions: (a) MB-T; [SUVA] 254 = 2.1, (b) MB-R; [SUVA] 254 = 5.1, pH = 7.5, [NH2Cl] 0 = 2.3 mg L1, [I] 0 = 0.32, 0.8, 1.6, 3.2 lM, [Br] 0 = 0.05 (in both background waters), [DOC]0: 0.5 mg L1, T = 21 ± 1 °C, Contact time (t) = 24 h.

Since increasing the DOM concentration from 0.5 to 5.4 mg C L1 significantly impacted the I-THM concentration, the effect of DOM concentration on the CHO cell chronic cytotoxicity was evaluated. The concentration-response curves for the CHO cell cytotoxicity of water samples are shown in Fig. S10. The data demonstrated that each sample induced mammalian cell cytotoxicity and generated a significant difference from their concurrent negative control (Table S2) (Box et al., 1978). However, to determine if there was a significant difference among the

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Fig. 5. Effect of NH2Cl concentration on the formation and speciation of Cl/I-THMs in the presence of various concentrations of NOM ([DOC] 0 = (a) 0.5 mg L1, (b) 1 mg L1, (c) 2 mg L1, (d) 4 mg L1). Experimental conditions: MB-T; [SUVA] 254 = 2.1, pH = 7.5, [I] 0 = 0.32 lM, [Br]0 = 0.05, 0.11, 0.22, 0.45 lM (DOC: 0.5, 1, 2, 4 mg L1, respectively), T = 21 ± 1 °C, Contact time (t) = 24 h.

samples, a series of LC50 values were generated using Bootstrap statistics and converted these value into cytotoxicity index (CTI) 3 values (LC1 50 ) (10 ) (Singh and Xie, 2008; Varian, 2005). This generates a metric in which the larger the number the greater the cytotoxic potency of the sample. The cytotoxicity index values are presented in Fig. 6. The CTI values (±SE) were also analyzed for significant differences using an ANOVA test statistic with pairwise comparison (Table S3). The data demonstrated that the CTI values for DOC: 0.5 mg L1  DOC: 2 mg L1 < DOC: 4 mg L1 < DOC: 5.4 mg L1.

For the same experimental conditions, cytotoxicity of the waters was also calculated by using cytotoxicity index values obtained from literature assuming the cyto-toxicity of each DBP is additive, and this approach has been used in our previous studies to assess the toxicity of treated waters (Ersan et al., 2019; Liu et al., 2018; Plewa et al., 2017). The results are shown in Fig. S11 (SI). The calculated cytotoxicity followed the same trend as TIM formation, which increased up to 4 mg L1 DOC, but decreased at 5.4 mg L1 DOC. The comparison of calculated and measured cytotoxicity values shows that the calculated values do not always represent the measured overall cytotoxicity, since the formation of unknown DBPs was not taken into consideration during the toxicity calculations.

3.5. CHO cell acute genomic DNA damage analyses

Fig. 6. CHO cell chronic cytotoxicity values. Experimental conditions: MB-T; [NH2Cl] 0 = 2.3 mg L1, [I] 0 = 3.2 lM, [Br] 0 = 0.05, 0.22, 0.45, 0.6 lM (DOC: 0.5, 2, 4, 5.4 mg L1, respectively), pH = 7.5, T = 21 ± 1 °C, Contact time (t) = 24 h.

The impact of DOM concentration on the CHO cell genomic DNA damage was also evaluated. The concentration-response curves for the CHO cell genotoxicity of water samples are shown in Fig. S12. The results showed that at low DOC concentration (0.5 mg L1), the concentration factor did not alter the genotoxicity (as compared to negative control), however, genotoxicity of samples at 2, 4, and 5.4 mg L1 showed an induced genotoxicity with increasing concentration factor, which may be due to increased formation of unknown disinfection by products with increasing DOC concentration (Table S4). To compare the genotoxicity of samples, LC50 values were generated using the Bootstrap statistics and the values were converted into geno3 toxicity index (GTI) values (LC1 50 ) (10 ). The results demonstrated an ascending order of the increased genotoxicity index (GTI) values for DOC values 0.5 < < 2 < 4  5.4 mg L1 (Fig. 7). This indicated that increasing DOC concentration increased the genotoxicity of treated waters.

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M.S. Ersan et al. / Science of the Total Environment 697 (2019) 134142

measured TOCl and TOI did not alter the CTI. These unknown DBPs may be associated with non-volatile disinfection by products (Han and Zhang, 2018). Therefore, when the toxicity of waters is of concern, unknown DBPs (TOX unknown) should be carefully investigated. As for GTI of the studied waters, although GTI showed positive correlation with DOC (r2 = 0.91), it was not statistically significant (p-value = 0.09). Also, GTI values did not significantly correlated with other parameters. Thus, other non-halogenated DBPs should be carefully investigated to elucidate the impact of chloramination on GTI values of waters. 4. Conclusions

Fig. 7. CHO cell acute genotoxicity values. Experimental conditions: MB-T; [NH2Cl]0 = 2.3 mg L1, [I] 0 = 3.2 lM, [Br]0 = 0.05, 0.22, 0.45, 0.6 lM (DOC: 0.5, 2, 4, 5.4 mg L1, respectively), pH = 7.5, T = 21 ± 1 °C, Contact time (t) = 24 h.

3.6. Pearson product moment correlation Total organic halide concentration of MB-T water was measured under varying DOC concentration (0.5, 1, 2, 4, 5.4 mg L1) and the data are shown in Fig. S13. The results suggest that increasing DOC concentration from 0.5 to 5.4 mg L1 gradually increased the total formation of TOX. In addition, UTOX/TOX ratio was also increased with increasing DOC concentrations, which may suggest the favored formation of unknown DBPs at higher DOC values. To understand the correlation among measured cyto- and genotoxicity values and measured and unknown TOX data, a Pearson product moment correlation test was conducted. The result demonstrated that measured CTI and GTI are not statistically correlated (r2 = 0.86, p-value = 0.14) (Table 2). This indicates that the cytotoxicity and genotoxicity are measuring different adverse biological effects induced by the chloraminated samples. On the other hand, for the cytotoxicity, CTI, there were high and significant positive correlations between CTI and DOC (r2 = 0.97, p-value = 0.03), CTI and unknown TOCl and TOI (r2 = 0.99, p-value = 0.01). These results have shown that CTI of the samples increased with increasing DOC concentration, which may be due to increased formation of unknown Cl/Br/I-DBPs. In addition, while unknown TOCl and TOl was significantly contributing to the CTI of the waters,

In this study, the impact of DOM concentration and type, initial bromide and iodide, and oxidant dose on the formation and speciation of I-THMs were investigated under chloramination conditions using preformed chloramine. In addition, Pearson product moment correlation tests were performed to understand the relationship between measured/calculated cyto- and geno-toxicity values and calculated/unknown TOX at the selected conditions. The results showed that increasing DOC concentration increased the total formation of I-THMs at a certain point (0.5 mg L1 DOC) after which the concentrations decreased. The type of the DOM was also shown to impact the formation of DBPs, which low SUVA water had higher formation of I-THMs while high SUVA water had low formation. At studied initial background Br levels, none of the Br and/or Cl/Br-I-THMs were formed regardless of the bromide concentrations (i.e., ambient and 400 lg L1). Increasing the chloramine dose from 2.3 to 20 mg L1 decreased the formation of I-THMs while increased the formation of regulated THMs (i.e., chloroform). The toxicity results revealed that DOM concentration play a key role on the measured CTI values of the water studied, where CTI were increasing with increasing DOC concentration. Futhermore, unknown TOCl and TOI showed high and significant correlation with CTI values (r2 = 1.00, p-value = 0.00). This highlights the importance of unknown/unregulated DBPs when evaluating the cytotoxicity of the waters. GTI values have also shown to correlate well with DOC, unknown TOCl and total unknown TOX concentrations. Overall, the results from this study suggests that unknown/unknown DBPs (unknown TOX) carries a higher importance from health effect stand-point (characterized as cytoand geno-toxicity in this study) than regulated DBPs. Therefore, more research is warranted to have a better understanding on the formation, control, and toxicity of unknown disinfection by products.

Table 2 Pearson product moment correlation test. n

GTImeasured

DOC

TOClcalculated

TOIcalculated

TOClunknown

TOIunknown

Total TOXcalculated

Total TOXunknown

CTImeasured

4

GTImeasured

4

0.86 0.14 1.00

DOC

5

0.97 0.03 0.91 0.09 1.00

TOClcalculated

5

0.11 0.89 0.56 0.44 0.18 0.77 1.00

TOIcalculated

5

0.43 0.57 0.81 0.19 0.52 0.37 0.93 0.02 1.00

TOClunknown

5

0.99 0.01 0.93 0.07 0.99 0.00 0.22 0.72 0.54 0.35 1.00

TOIunknown

5

0.99 0.01 0.78 0.22 0.90 0.04 0.05 0.94 0.33 0.59 0.94 0.02 1.00

Total TOXcalculated

5

0.39 0.62 0.78 0.22 0.47 0.42 0.95 0.01 1.00 0.00 0.50 0.40 0.29 0.63 1.00

Total TOXunknown

5

1.00 0.00 0.89 0.11 0.97 0.01 0.17 0.79 0.48 0.42 0.99 0.00 0.97 0.01 0.44 0.46 1.00

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements This work was funded by the National Science Foundation, USA (CBET 1511051). The authors would like to thank South Carolina water utilities for their assistance in sample collections.

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