Ecotoxicology and Environmental Safety 107 (2014) 30–35

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Chlorination and chloramination of tetracycline antibiotics: Disinfection by-products formation and influential factors Shiqing Zhou a, Yisheng Shao a,b,n, Naiyun Gao a, Shumin Zhu a, Yan Ma c, Jing Deng a a

State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Shanghai 200092, China China Academy of Urban Planning & Design, Beijing 100037, China c Shanghai Urban Water Resources Development and Utilization National Engineering Center Co. Ltd., Shanghai 200092, China b

art ic l e i nf o

a b s t r a c t

Article history: Received 26 December 2013 Received in revised form 8 May 2014 Accepted 12 May 2014

Formation of disinfection by-products (DBPs) from chlorination and chloramination of tetracycline antibiotics (TCs) was comprehensively investigated. It was demonstrated that a connection existed between the transformation of TCs and the formation of chloroform (CHCl3), carbon tetrachloride (CCl4), dichloroacetonitrile (DCAN) and dichloroacetone (DCAce). Factors evaluated included chlorine (Cl2) and chloramine(NH2Cl) dosage, reaction time, solution pH and disinfection modes. Increased Cl2/NH2Cl dosage and reaction time improved the formation of CHCl3 and DCAce. Formation of DCAN followed an increasing and then decreasing pattern with increasing Cl2 dosage and prolonged reaction time. pH affected DBPs formation differently, with CHCl3 and DCAN decreasing in chlorination, and having maximum concentrations at pH 7 in chloramination. The total concentrations of DBPs obeyed the following order: chlorination 4chloramination4pre-chlorination (0.5 h)4pre-chlorination (1 h)4 prechlorination (2 h). & 2014 Elsevier Inc. All rights reserved.

Keywords: Tetracycline antibiotics Chlorine dosage Reaction time pH Disinfection modes

1. Introduction Tetracycline antibiotics (TCs) are a family of broad-spectrum antibiotics. Since the first member, chlortetracycline (CTC), was developed in 1947 (Duggar, 1948), other natural TCs were soon isolated for clinical use, including tetracycline (TC) and oxytetracycline (OTC). Then some semisynthetic TCs were generated by modifying naturally occurring TCs and synthetizing novel compounds within the tetracycline family. Two of the more common semisynthetic TCs are doxycycline (DC) and minocycline (MC). The favorable antimicrobial properties of TCs led to their extensive use in human and veterinary medicine to treat bacterial infections and promote animal growth (De Liguoro et al., 2003; Kordick et al., 1997; Kumar et al., 2005; Sarmah et al., 2006). The usage of TCs was approximately 16.268 t in the UK in 2000 (Sarmah et al., 2006). The United States produced as high as 3000 t of TCs in 2003 for farm animals (Arikan et al., 2007; Bao et al., 2009). In China, TCs are also one of the most widely used antibiotics. The widespread and long-term usage of TCs resulted in the emergence of drug resistance in almost all bacteria genera (Adam, 2002; Boxall et al., 2003; Sarmah et al., 2006).

n Corresponding author at: State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Shanghai 200092, China. Fax: þ 86 21 65986313. E-mail address: [email protected] (Y. Shao).

http://dx.doi.org/10.1016/j.ecoenv.2014.05.008 0147-6513/& 2014 Elsevier Inc. All rights reserved.

In 1980s, Watts et al. (1983) first reported the presence of TC in river water samples. Since then, TCs have been frequently detected in surface water (Li et al., 2008; Lin and Tsai, 2009; Spongberg et al., 2011; Wei et al., 2011). As an antibiotic used against various bacterial infections, TC was measured in many US and Canadian sites with concentrations up to 300 ng/L (Kolpin et al., 2004; Miao et al., 2004). Kolpin et al. (2002) reported that maximum concentrations of CTC, OTC and TC in US surface waters were 690 ng/L, 340 ng/L and 110 ng/L, respectively. Even higher concentrations (i.e., 72.9 μg/L for OTC, and 10.3 μg/L for TC) were recorded by Wei et al. (2011) in Chinese surface waters. The frequent detection of TC residues and related microbial resistance in the environment poses threats to the human health and ecosystem. While many studies highlighted the occurrence of TCs in the environment, little attention has been paid to their behaviors in a drinking water treatment process. As conventional drinking treatment processes (i.e., coagulation, sedimentation and filtration) can poorly remove pharmaceuticals in water (Stackelberg et al., 2007), it is well-known that disinfection by chlorination or chloramination is a final step for drinking water treatment. Wang et al. (2011) reported that the oxidation kinetics of TCs by chlorine (Cl2) are rapid with large apparent second-order rate constants of 1.12
104–1.78
106 M  1 s  1 at pH 7. Wan et al. (2013) also observed the chloramination of TC exhibited pseudo-first-order kinetics with the rate constants (kobs) ranging from 0.0082 to 0.041 min  1 at pH of 6–8.

S. Zhou et al. / Ecotoxicology and Environmental Safety 107 (2014) 30–35

Disinfection by-products (DBPs) are concomitant problem of water disinfection, attracting considerable attention in the recent years (Hebert et al., 2010; Krasner et al., 2006; Sadiq and Rodriguez, 2004). They are generally formed by the reaction of disinfectants with natural organic matter (Hong et al., 2013; Lin and Wang, 2011), but it cannot be ignored that contaminants with activated benzene rings or other functional groups that can react with oxidants (i.e., Cl2 and NH2Cl) are potential DBPs precursors (Duirk et al., 2011; Richardson, 2009; Shen and Andrews, 2011b). Shen and Andrews (2011a) reported that controlled laboratory reactions of TC with chlorine and chloramine were able to form corresponding nitrosamines. And 25 nM TC showed 0.8–1.2 percent molar conversions in both Milli-Q and tap water, which decreased slightly with increasing initial tetracycline concentration. Although the trace level of TCs in surface water may not account for the majority of DBPs precursors during the disinfection process, the huge use of TCs makes it a potential risk to human health. The overall objectives of this research were (1) to demonstrate a connection between the transformation of TCs and the formation of DBPs during Cl2 and NH2Cl disinfection, (2) to evaluate the factors affecting DBPs formation, including Cl2 and NH2Cl dosage, reaction time, solution pH and disinfection modes.

31

for 0.5 h (Mode III), 1 h (Mode IV) and 2 h (Mode V) before NH4Cl addition were also investigated. Prior to DBPs analysis, the residual Cl2 was quenched by NH4Cl (20 mM) with a double normality of the initial added Cl2 normality to avoid the interaction with formed DBPs. 2.3. Analytical methods Cl2 and NH2Cl concentration were quantitatively determined by the N,N-dethyl-p-phenylenediamine (DPD) colorimetric method (APHA et al., 1998). pH was measured using a pH-meter (module PHS-3B, Shanghai LEICI Analysis Instrument Factory, China). The concentrations of DBPs including CHCl3, CCl4, DCAN and DCAce were measured based on USEPA method of 551.1 (U.S.EPA, 1995). Samples were extracted by MTBE, and then analyzed by a GC-ECD (GC-2010, Shimadzu, Japan). The column was a fused silica capillary (HP-5, 30 m
0.25 mm inner diameter with 0.25 μm film thickness, J&W, USA). All the tests were conducted at least in duplicate. The relative standard deviations (RSD) for different batches were normallyoten percent.

3. Results and discussion 3.1. Chlorination and chloramination of TCs

2. Materials and methods 2.1. Chemicals All chemicals were at least of analytical grade except as noted. TC (Z98.0 percent), OTC ( Z95.0 percent), and CTC (Z 97.0 percent) were obtained from Sigma-Aldrich (USA). DC (Z 98.0 percent) was purchased from Aladdin Chemistry Co., Ltd. (Shanghai, China). Chloroform (CHCl3), carbon tetrachloride (CCl4), dichloroacetonitrile (DCAN) and dichloroacetone (DCAce) were purchased from Sigma-Aldrich (USA). Sodium hypochlorite (NaOCl) solution (available chlorine 4.00–4.99 percent) was purchased from Sigma-Aldrich (USA). Analytical grade reagents including ammonium chloride (NH4Cl), ammonium acetate, NaH2PO4, Na2HPO4, NaOH, Na2CO3, NaHCO3, CH3COOH and HCl were purchased from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China) without further purification. All chemical solutions were prepared using ultrapure water produced from a Milli-Q water purification system (Millipore, USA). Methyl tert-butyl ether (MTBE) was obtained from J.T. Baker (USA).

Four kinds of TCs (Table 1), including TC, OTC, CTC and DC, were selected in this study to evaluate the impact of structural variation for the chlorination and chloramination. As shown in Table 1, TCs molecules contain connected ring systems with several electronrich moieties that are likely to be susceptible to attacks by oxidants like Cl2 and NH2Cl. CHCl3 was stable in the presence of Cl2 and was the final product during the chlorination of many compounds (Lopez et al., 2001). As shown in Fig. 1, CHCl3 was the major volatile degradation product during both chlorination and chloramination of all tested TCs. The maximum concentration of CHCl3 was 0.452 μM (molar yield as 1.81 percent) by chlorination of TCs, which was 1.6 times higher than that during chloramination (0.281 μM, molar yield as 1.12 percent). The concentrations of CCl4 were low and Table 1 Structures and properties of TCs investigated in this study. Compounds Formula

Molecular weight Molecular structure

TC

C22H24N2O8

480.90

OTC

C22H24N2O9

496.89

CTC

C22H23ClN2O8

515.34

DC

C22H24N2O8

480.90

2.2. Experimental procedures NH2Cl solutions were freshly generated by adding NaOCl solution gently into a stirred NH4Cl solution with the Cl:N molar ratio of at least 1:1.2 to prevent breakpoint chlorination due to local excess of OCl  , and pH was kept at around ten to avoid the disproportionation of NH2Cl to NHCl2 (Mitch and Sedlak, 2002). Chlorination experiments were carried out using sealed 45 mL amber glass bottles at controlled temperature (25 70.5 1C) in dark. The concentrations of TCs were 0.025 mM and appropriate Cl2 or NH2Cl was added to the TCs solutions at a desired molar ratio of 1, 5, 15, and 25. The pH range of the reactions was controlled from 5 to 9, which were buffered with 10 mM acetate (for pH 5), 10 mM phosphate (for pH 6–7) and 10 mM carbonate (for pH 8–9) solutions, and pH values were adjusted with small volumes of 0.01, 0.1, or 1 M HCl and/or NaOH. In all experiments, the initial and final pH difference was less than 0.1. For comparison, five chorination/chloramination disinfection modes, including chlorination (Mode I), chloramination (Mode II), and pre-chlorination

S. Zhou et al. / Ecotoxicology and Environmental Safety 107 (2014) 30–35

0.4

OTC CTC

0.3

DC

0.2

2.0 DCAN DCAN

0.15

1.5

DCAce DCAce CHCl3 CH3Cl CCl4 CCl4

0.10

1.0

0.05

0.5

0.1 0.00

0.0 1

0.0

DBPs concentration (μM)

TC

Chloramination

CTC DC

0.2

0.1

15

25

Cl2 : TC (mol/mol) 0.5

OTC

0.3

5

TC

DBPs concentration (μM)

DBPs concentration (μM)

Chlorination

DBPs concentration (μM)

0.20

0.5

CHCl3 concentration (μM)

32

CHCl3 CH3Cl

0.4

CCl4 CCl4 DCAN DCAN

0.3

DCAce DCAce 0.2 0.1

0.0 CH3Cl3

CCl44

DCAN

DCAce

Fig. 1. Formation of DBPs from 24-h chlorination and chloramination of TCs. (Cl2/NH2Cl:TCs molar ratio: 15, pH 7, 25 70.5 1C.)

ranged from 0.034 to 0.050 μM (molar yield as 0.14–0.20 percent). DCAce was almost below detection limit (lower than 0.02 μM, molar yield as 0.06 percent) after chlorination and chloramination of TC. Moreover, the amount of CCl4 and DCAce formed from chlorination was also both higher than chloramination. These results were well consistent with the findings of other literature (Cowman and Singer, 1995). While the reason for low DBPs production from chloramination of TCs was not entirely clear, Cowman and Singer (1995) proposed that chloramination might be a special case of chlorination with very low Cl2 generated from NH2Cl hydrolysis. Different from the DBPs mentioned before, DCAN formed at higher levels during chloramination than chlorination (Fig. 1). Chlorination of TCs led to the formation of 0.034–0.173 μM (molar yield as 0.14–0.69 percent) DCAN, while chloramination greatly increases DCAN formation. And the concentrations of DCAN were 0.328 μM, 0.109 μM, 0.123 μM and 0.187 μM (molar yield as 1.31 percent, 0. 43 percent, 0.49 percent, and 0.75 percent) during chloramination of TC, OTC, CTC, and DC, respectively. The result might be attributed to the capability of NH2Cl to provide more nitrogen source for the nitrile group in DCAN. The relationship between TCs and DBPs concentration was complicated. It might be caused by their molecular structures and functional groups, which shared different sensitivities to be attacked by Cl2 or NH2Cl. It was reported that hydrogen-bonding formed between C5–OH and dimethylamino group's N on OTC (Hussar et al., 1968). Such H-bond formation may lower the reactivity of dimethylamino group's N atom toward oxidation by Cl2; thus OTC formed the lowest concentration of DCAN among the four tested TCs. And the lower DBPs formation of CTC than TC (Fig. 1) was likely due to the electron-withdrawing effect of chlorine substituent that lowers reactivity for oxidation. 3.2. Effect of Cl2 and NH2Cl dosage Since TC produced the highest DBPs yield among the four kinds of TCs, it was selected to further investigate the influential factors on its DBPs formation during chlorination and chloramination.

0.0 1

5

15

25

NH2Cl : TC (mol/mol) Fig. 2. Effect of Cl2 and NH2Cl dosage on DBPs formation from 24-h chlorination and chloramination of TC. (pH 7, 25 7 0.5 1C.)

As known, the dosage of oxidant used in water disinfection is an important factor, which could significantly affect water treatment, as well as DBPs formation (Lu et al., 2009). Fig. 2 shows the effect of Cl2 and NH2Cl dosage on DBPs formation during chlorination and chloramination. A higher concentration of CHCl3 was evident in the presence of higher Cl2/NH2Cl dosage, indicating that more HOCl was generated from Cl2 or NH2Cl. The maximum of CHCl3 from chlorination and chloramination even reached up to 1.609 μM and 0.439 μM (molar yield as 6.44 percent and 1.75 percent), respectively. CCl4 concentration also increased with increasing Cl2/NH2Cl dosage, and reached a maximum when TC exhausted (Fig. 2). DCAN formation from chloramination of TC also followed the same increasing pattern. However, DCAN formation from chlorination exhibited a different trend. The concentration of DCAN was 0.173 μM (molar yield as 0.69 percent) at dosage of Cl2: TC¼15, while decreased to 0.132 μM (molar yield as 0.53 percent) when the ratio was up to 25. It was supposed that a higher rate of DCAN decomposition was achieved in the presence of a higher Cl2 dosage. And Reckhow et al. (2001) reported that the relationship between Cl2 concentration and the degradation rate of DCAN was a good observed first-order linear, with a slope of 0.13 M  1s  1. DCAce was below detection limit when Cl2:TC and NH2Cl:TC molar ratio were 1:1 and 5:1, while it was detected with the increasing Cl2/NH2Cl dosage. 3.3. Effect of reaction time Fig. 3 shows the time-dependent formation of DBPs during chlorination and chloramination of TC. The concentration of CHCl3 increased rapidly in the first 24 h chlorination and then the increases gradually slowed down. A similar trend was observed with increasing reaction time in chloramination, which was also consistent with the findings of Pourmoghaddas and Stevens (1995) and Lu et al. (2009). The reason for this phenomenon may be ascribed to the fact that active DBPs precursor sites of TC have been almost exhausted by Cl2 or NH2Cl in 24 h. At the end of

S. Zhou et al. / Ecotoxicology and Environmental Safety 107 (2014) 30–35

0.10

CH3Cl CHCl3

0.4

DCAce DCAce

0.3 0.2

0.05 0.1

CH3Cl CHCl3

6 24 Chloramination time (h)

30

CCl4 CCl4

0.3

DCAN DCAN DCAce DCAce

0.2

0.1

0.0 1

6

24

30

Reaction time (h) Fig. 3. Time-dependent formation of DBPs from chlorination and chloramination of TC. (Cl2/NH2Cl:TCs molar ratio: 15, pH 7, 25 7 0.5 1C.)

reaction time (30 h), the concentrations of CHCl3 reached up to 0.511 μM and 0.327 μM (molar yield as 2.04 percent and 1.31 percent) in chlorination and chloramination, respectively. As time was extended, the concentration of CCl4 increased, except a drop between 24 h and 30 h for chlorination, indicating that other factors may play a role in CCl4 formation. The yield of DACN followed an increasing and then decreasing pattern as reaction time went by, with maximum concentration of 0.173 μM and 0.328 μM (molar yield as 0.69 percent and 1.31 percent) at 24 h, respectively, which could be explained by the hydrolysis and oxidation of the formed DCAN by HOCl (Fang et al., 2010). In addition, the concentration of DCAce from chlorination and chloramination was under detection limit at the beginning of experiment (1 h and 6 h), then reached a maximum of 0.024 μM and 0.017 μM (molar yield as 0.10 percent and 0.07 percent), respectively. 3.4. Effect of pH It was well documented that solution pH exhibits significant influences on Cl2 dissociation (Duirk et al., 2005), NH2Cl autodecomposition (Acero et al., 2007) and the degree of hydrolysis reactions. Thus, it was expected that the formation of DBPs varied with pH during both chlorination and chloramination. Fig. 4 presents the DBPs formation after chlorination and chloramination of TC. In chlorination, the concentration of CHCl3 decreased with increasing pH with a maximum of 0.691 μM (molar yield as 2.76 percent) at pH 5, and a minimum of 0.342 μM (molar yield as 1.37 percent) at pH 9. As we all know, the proportion of HOCl and OCl  varies with pH (see Eq. (1)). HOCl is the major species when pH o7.5, while it almost turn to OCl  when pH 49.25. Thus, as the solution pH increased from 7 to 9, OCl  gradually became the dominate species. The decreasing CHCl3 was consistent with previous studies that OCl  was always negligible for most chemicals during chlorination (Deborde et al., 2004; Dodd and Huang, 2007; Rodríguez et al., 2007), due to its weaker electrophile than HOCl (Gerritsen and Margerum, 1990). Moreover, acid catalysis could attribute to the formation of H2OCl þ (see Eq. (2)), which was

0.8

Chlorination

CCl4 CCl4

0.20

DCAN DCAN DCAce DCAce

0.15

CH3Cl CHCl3

0.6

0.4 0.10 0.2

0.05

0.0

0.00

0.0 1

0.4

DBPs concentration (μM)

0.00 0.4

DBPs concentration (μM)

0.5

DCAN DCAN

0.25

CHCl3 concentration (μM)

0.15

0.6

Chlorination

DBPs concentration (μM)

CCl4 CCl4

CHCl3 concentration (μM)

DBPs concentration (μM)

0.20

33

1

6 24 Chloramination time (h)

30

0.3

CH3Cl CHCl3 CCl4 CCl4 DCAN DCAN DCAce DCAce

0.2

0.1

0.0

5

6

7

8

9

pH Fig. 4. Effect of pH on DBPs formation from 24-h chlorination and chloramination of TC. (Cl2/NH2Cl:TCs molar ratio: 15, 25 7 0.5 1C.)

a stronger electrophile than HOCl. Another possible way to explain the higher CHCl3 production at acidic condition was contribution from molecular chlorine, whose formation could be described by Eq. (3). It was clear that it will be favorable for molecular chlorine formation at lower pH and with the presence of Cl  . In this study, Cl  was not added into reaction solutions deliberately; however, small amounts of HCl were added when the solution was adjusted to pH 5. HOCl2OCl  þ H þ

(1)

HOCl þH þ 2 H2OCl þ

(2)

HOCl þH þ þCl  2 Cl2 þH2O

(3)

Furthermore, previous studies demonstrated that solution pH also affected the stability of unstable DBPs such as DCAN (Yang et al., 2007). As shown in Fig. 4, the concentrations of DCAN decreased continuously with a concentration of 0.234–0.173 μM (molar yield as 0.94–0.69 percent) when pH increased from 5 to 7, and then were nearly below the detection limits at pH 8–9. This trend was consistent with the finding that DCAN tended to hydrolyze at pH 7, which was accelerated in the presence of Cl2 (Peters et al., 1990). Reckhow et al. (2001) also found in their kinetic analysis experiments that the rate of DCAN degradation increased as the increasing pH. The yield of CCl4 followed a decreasing and then increasing pattern, with the minimum concentration of 0.038 μM (molar yield as 0.15 percent) at pH 7. Although HOCl is the main electrophilic species and more reactive than OCl  in water when pH o7.5, the CCl4 yield at pH 9 was greater than that at pH 7 (Fig. 4), which may be ascribed to the fact that haloform reaction requires the OH  and is favorable at basic pHs (Dore et al., 1982). DCAce was almost below detection limit at all the tested pH values, with a concentration of less than 0.01 μM. Different from chlorination, chloramination of TC underwent complex reactions due to the auto-decomposition of NH2Cl. Previous studies found that NHCl2 and NH2Cl usually coexisted in chloramines solution. NHCl2 can be formed by either NH2Cl hydrolysis (see Eqs. (4)–(6)) (Vikesland et al., 2001) or acid

34

S. Zhou et al. / Ecotoxicology and Environmental Safety 107 (2014) 30–35

0.4

CHCl3

CC4

DCAN

DCAce 0.6

Total DBPs 0.3

0.4 0.2 0.2

0.1

Total concentration (μM)

DBPs concentration (μM)

maximum concentration during chloramination. To sum up, the total concentrations of DBPs obeyed the following order: Mode I4Mode II4Mode III4 Mode IV4 Mode V. Therefore, the results indicated that evaluation and control of total DBPs are needed when different disinfection modes are being considered in practises.

0.8

0.5

4. Conclusion

0.0

0.0 Mode I

Mode II

Mode III

Mode IV

Mode V

Fig. 5. Effect of different disinfection modes on DBPs formation from 24-h chlorination and chloramination of TC. (Cl2/NH2Cl:TCs molar ratio: 15, pH 7, 257 0.5 1C.)

catalyzed NH2Cl disproportionation reaction (see Eqs. (7) and (8)) (Valentine and Jafvert, 1988): NH2Cl þH2O-HOCl þ NH3

(4)

HOCl þ NH2Cl-NHCl2 þ H2O

(5)

NH2Cl þ NH2Cl-NHCl2 þ NH3

(6)

þ

NH2Cl þ H 2 NH3Cl þ

þ

NH3Cl þ NH2Cl-NHCl2 þ NH3 þ H

(7) þ

(8)

In chloramination, all DBPs (CHCl3, CCl4, DCAN and DCAce) formation exhibited the similar trends, increased as pH increasing from 5 to 7, and then decreased from pH 7 to 9, with a maximum concentration of 0.281 μM, 0.034 μM, 0.328 μM and 0.012 μM (molar yield as 1.12 percent, 0.14 percent, 1.31 percent and 0.05 percent), respectively. These results were attributed to a series of auto-decomposition reactions of NH2Cl, which were a relatively complex process and highly related to the solution pH. It can be seen from Eqs. (4)–(6) that hydrolysis of NH2Cl could generate HOCl at neutral pH, which is the main electrophilic species and more reactive with TC than OCl  . Under acidic or alkaline conditions, the decrease of DBPs could be explained by the formation of NHCl2 from NH2Cl by means of disproportionation or hydrolysis reaction, which has low reactivity to TC. Considerable attention was paid to DCAN, because dual dependence of DCAN formation and degradation on its varying concentration was responsible. Except hydrolysis under acidic conditions and auto-decomposition under alkaline conditions mentioned before, Le Roux et al. (2011) found that total chlorine decay with NHCl2 was about 85 percent after 24 h, while it was only 25 percent with NH2Cl at pH 8. Thus, NHCl2 decomposition is more rapid than NH2Cl around pH 8, which could also explain why less DCAN was formed in the presence of NHCl2. 3.5. Effect of different disinfection modes As discussed above, chloramination of TC would form less DBPs than chlorination, except DCAN. Therefore, five chorination/chloramination disinfection modes, including chlorination (Mode I), chloramination (Mode II), and pre-chlorination for 0.5 h (Mode III), 1 h (Mode IV) and 2 h (Mode V) before NH4Cl addition, were comprehensively investigated. Fig. 5 exhibits the effect of five different disinfection modes on DBPs formation. As for the formation of CHCl3, pre-chlorination (Mode III, IV, and V) yielded significantly less CHCl3 than chlorination (Mode I). Moreover, the CHCl3 concentration decreased gradually as the prechlorination period prolonged. The formation of CCl4 was similar among the five disinfection modes. DCAN and DCAce achieved a

Four TCs (TC, OTC, CTC and DC) were chlorinated and chloraminated in this study. Factors including Cl2 and NH2Cl dosage, contact time, solution pH and disinfection modes were also investigated. The following conclusions can be drawn. (1) Different TCs yielded different DBPs concentrations due to the molecular structures and functional groups. Chloramination produced less DBPs than chlorination of TCs, except DCAN. (2) The concentration of CHCl3, CCl4 and DCAce increased with increasing Cl2 or NH2Cl dosage. DCAN formation from chloramination of TC also followed the same trend, while in chlorination it decreased to 0.132 μM with the ratio of Cl2: TC ¼25, lower than that of 15 (0.173 μM). (3) As the reaction time extended, the concentration of CHCl3 increased. However, the yield of DACN followed an increasing and then decreasing pattern as reaction time went by, reaching a peak at 24 h. (4) In chlorination, the concentrations of CHCl3 and DCAN decreased with increasing pH with a maximum of 0.691 μM and 0.234 μM at pH 5. While in chloramination, the concentrations of CHCl3 and DCAN increased as pH increasing from 5 to 7, and then decreased from pH 7 to 9, with a maximum concentration of 0.281 μM and 0.328 μM, respectively. (5) The total concentrations of DBPs obeyed the following order: chlorination4chloramination4pre-chlorination (0.5 h)4prechlorination (1 h)4pre-chlorination (2 h).

Acknowledgments This work was financially supported by the National Natural Science Foundation of China (Nos. 51178321 and 51108327), and the National Major Project of Science & Technology Ministry of China (No. 2012ZX07403-001). References Acero, J.L., Real, F.J., Benitez, F.J, Gonzalez, M., 2007. Kinetics of reactions between chlorine or bromine and the herbicides diuron and isoproturon. J. Chem. Technol. Biotechnol. 82, 214–222. Adam, D., 2002. Global antibiotic resistance in Streptococcus pneumoniae. J. Antimicrob. Chemother. 50, 1–5. APHA (American Public Health Association), American Water Works Association, Water Environment Federation, 1998. Standard Methods for the Examination of Water and Wastewater. 20th ed. Washington, DC: American Public Health Association. Arikan, O.A., Sikora, L.J., Mulbry, W., Khan, S.U., Foster, G.D., 2007. Composting rapidly reduces levels of extractable oxytetracycline in manure from therapeutically treated beef calves. Bioresour. Technol. 98, 169–176. Bao, Y.Y., Zhou, Q.X., Guan, L.Z., Wang, Y.Y., 2009. Depletion of chlortetracycline during composting of aged and spiked manures. Waste Manag. 29, 1416–1423. Boxall, A.B.A., Kolpin, D.W., Halling-Sørensen, B., Tolls, J., 2003. Are veterinary medicines causing environmental risks? Environ. Sci. Technol. 37, 286a–294a. Cowman, G.A., Singer, P.C., 1995. Effect of bromide ion on haloacetic acid speciation resulting from chlorination and chloramination of aquatic humic substances. Environ. Sci. Technol. 30, 16–24. De Liguoro, M., Cibin, V., Capolongo, F., Halling-Sørensen, B., Montesissa, C., 2003. Use of oxytetracycline and tylosin in intensive calf farming: evaluation of transfer to manure and soil. Chemosphere 52, 203–212.

S. Zhou et al. / Ecotoxicology and Environmental Safety 107 (2014) 30–35

Deborde, M., Rabouan, S., Gallard, H., Legube, B., 2004. Aqueous chlorination kinetics of some endocrine disruptors. Environ. Sci. Technol. 38, 5577–5583. Dodd, M.C., Huang, C.H., 2007. Aqueous chlorination of the antibacterial agent trimethoprim: reaction kinetics and pathways. Water Res. 41, 647–655. Dore, M., Merlet, N., De, Laat, Goichon, J., 1982. Reactivity of halogens with aqueous micropollutants: a mechanism for the formation of trihalomethanes. J. Am. Water Works Assoc. 74, 103–107. Duggar, B.M., 1948. Aureomycin: a product of the continuing search for new antibiotics. Ann. N.Y. Acad. Sci. 51, 177–181. Duirk, S.E., Gombert, B., Croué, J.P., Valentine, R.L., 2005. Modeling monochloramine loss in the presence of natural organic matter. Water Res. 39, 3418–3431. Duirk, S.E., Lindell, C., Cornelison, C.C., Kormos, J., Ternes, T.A., Attene-Ramos, M., Osiol, J., Wagner, E.D., Plewa, M.J., Richardson, A., 2011. Formation of toxic iodinated disinfection by-products from compounds used in medical imaging. Environ. Sci. Technol. 45, 6845–6854. Fang, J., Ma, J., Yang, X., Shang, C., 2010. Formation of carbonaceous and nitrogenous disinfection by-products from the chlorination of Microcystis aeruginosa. Water Res. 44, 1934–1940. Gerritsen, C.M., Margerum, D.W., 1990. Non-metal redox kinetics: hypochlorite and hypochlorous acid reactions with cyanide. Inorg. Chem. 29, 2757–2762. Hebert, A., Forestier, D., Lenes, D., Benanou, D., Jacob, S., Arfi, C., Lambolez, L., Levi, Y., 2010. Innovative method for prioritizing emerging disinfection by-products (DBPs) in drinking water on the basis of their potential impact on public health. Water Res. 44, 3147–3165. Hong, H.C., Huang, F.Q., Wang, F.Y., Ding, L.X., Lin, H.J., Liang, Y., 2013. Properties of sediment NOM collected from a drinking water reservoir in South China, and its association with THMs and HAAs formation. J. Hydrol. 476, 274–279. Hussar, D.A., Niebergall, P.J., Sugita, E.T., Doluisio, J., 1968. Aspects of the epimerization of certain tetracycline derivatives. J. Pharm. Pharmacol. 20, 539–546. Kolpin, D.W., Furlong, E.T., Meyer, M.T., Thurman, E.M., Zaugg, S.D., Barber, L.B., Buxton, H.T., 2002. Pharmaceuticals, hormones, and other organic wastewater contaminants in US streams, 1999–2000: a national reconnaissance. Environ. Sci. Technol. 36, 1202–1211. Kolpin, D.W., Skopec, M., Meyer, M.T., Furlong, E.T., Zaugg, S.D., 2004. Urban contribution of pharmaceuticals and other organic wastewater contaminants to streams during differing flow conditions. Sci. Total Environ. 328, 119–130. Kordick, D.L., Papich, M.G., Breitschwerdt, E.B., 1997. Efficacy of enrofloxacin or doxycycline for treatment of Bartonella henselae or Bartonella clarridgeiae infection in cats. Antimicrob. Agents Chemother. 41, 2448–2455. Krasner, S.W., Weinberg, H.S., Richardson, S.D., Pastor, S.J., Chinn, R., Sclimenti, M.J., Onstad, G.D., Thruston, A.D., 2006. Occurrence of a new generation of disinfection byproducts. Environ. Sci. Technol. 40, 7175–7185. Kumar, K., Gupta, S.C., Baidoo, S.K., Chander, Y., Rosen, C.J., 2005. Antibiotic uptake by plants from soil fertilized with animal manure. J. Environ. Qual. 34, 2082–2085. Le Roux, J., Gallard, H., Croué, J.P., 2011. Chloramination of nitrogenous contaminants (pharmaceuticals and pesticides): NDMA and halogenated DBPs formation. Water Res. 45, 3164–3174. Li, D., Yang, M., Hu, J.Y., Ren, L.R., Zhang, Y., Li, K.Z., 2008. Determination and fate of oxytetracycline and related compounds in oxytetracycline production wastewater and the receiving river. Environ. Toxicol. Chem. 27, 80–86. Lin, A.Y.C., Tsai, Y.T., 2009. Occurrence of pharmaceuticals in Taiwan's surface waters: impact of waste streams from hospitals and pharmaceutical production facilities. Sci. Total Environ. 407, 3793–3802. Lin, H.C., Wang, G.S., 2011. Effects of UV/H2O2 on NOM fractionation and corresponding DBPs formation. Desalination 270, 221–226. Lopez, A., Mascolo, G., Ciannarella, R., Tiravanti, G., 2001. Formation of volatile halogenated by-products during chlorination of isoproturon aqueous solutions. Chemosphere 45, 269–274. Lu, J.F., Zhang, T., Ma, J., Chen, Z.L., 2009. Evaluation of disinfection by-products formation during chlorination and chloramination of dissolved natural organic

35

matter fractions isolated from a filtered river water. J. Hazard. Mater. 162, 140–145. Miao, X.S., Bishay, F., Chen, M., Metcalfe, C.D., 2004. Occurrence of antimicrobials in the final effluents of wastewater treatment plants in Canada. Environ. Sci. Technol. 38, 3533–3541. Mitch, W.A., Sedlak, D.L., 2002. Formation of N-nitrosodimethylamine (NDMA) from dimethylamine during chlorination. Environ. Sci. Technol. 36, 588–595. Peters, R.J.B., De Leer, E.W.B., De Galan, L., 1990. Chlorination of cyanoethanoic acid in aqueous medium. Environ. Sci. Technol. 24, 81–86. Pourmoghaddas, H., Stevens, A.A., 1995. Relationship between trihalomethanes and haloacetic acids with total organic halogen during chlorination. Water Res. 29, 2059–2062. Reckhow, D.A., Platt, T.L., MacNeill, A.L., McClellan, J.N., 2001. Formation and degradation of DCAN in drinking waters. J. Water Supply Res. Technol.—Aqua 50, 1–13. Richardson, S.D., 2009. Water analysis: emerging contaminants and current issues. Anal. Chem. 81, 4645–4677. Rodríguez, E., Sordo, A., Metcalf, J.S., Acero, J.L., 2007. Kinetics of the oxidation of cylindrospermopsin and anatoxin-a with chlorine, monochloramine and permanganate. Water Res. 41, 2048–2056. Sadiq, R., Rodriguez, M.J., 2004. Disinfection by-products (DBPs) in drinking water and predictive models for their occurrence: a review. Sci. Total Environ. 321, 21–46. Sarmah, A.K., Meyer, M.T., Boxall, A.B.A., 2006. A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere 65, 725–759. Shen, R.Q., Andrews, S.A., 2011a. Demonstration of 20 pharmaceuticals and personal care products (PPCPs) as nitrosamine precursors during chloramine disinfection. Water Res. 45, 944–952. Shen, R.Q., Andrews, S.A., 2011b. NDMA formation kinetics from three pharmaceuticals in four water matrices. Water Res. 45, 5687–5694. Spongberg, A.L., Witter, J.D., Acuña, J., Vargas, J., Murillo, M., Umaña, G., Gómez, E., Perez, G., 2011. Reconnaissance of selected PPCP compounds in Costa Rican surface waters. Water Res. 45, 6709–6717. Stackelberg, P.E., Gibs, J., Furlong, E.T., Meyer, M.T., Zaugg, S.D., Lippincott, R.L., 2007. Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds. Sci. Total Environ. 377, 255–272. U.S.EPA Method 551.1, 1995. In: Much, J.W., Hautman, D.P. (Eds.), Determination of Chlorination Disinfection by Products, Chlorinated Solvents, and Halogenated Pesticides/Herbicides in Drinking Water by Liquid–Liquid Extraction and Gas Chromatography with Electron-Capture Detection (Revision 1.0). Office of Research and Development, Washington, DC. Valentine, R.L., Jafvert, C.T., 1988. General acid catalysis of monochloramine disproportionation. Environ. Sci. Technol. 22, 691–696. Vikesland, P.J., Ozekin, K., Valentine, R., 2001. Monochloramine decay in model and distribution system waters. Water Res. 35, 1766–1776. Wan, Y., Jia, A., Zhu, Z., Hu, J.Y., 2013. Transformation of tetracycline during chloramination: kinetics, products and pathways. Chemosphere 90, 1427–1434. Wang, P., He, Y.L., Huang, C.H., 2011. Reactions of tetracycline antibiotics with chlorine dioxide and free chlorine. Water Res. 45, 1838–1846. Watts, C.D., Craythorne, M., Fielding, M., Steel, C. P., 1983. In: Proceedings of the Third European Symposium on Organic Micropollutants. September 19–21. Oslo, Norway, . Wei, R.C., Ge, F., Huang, S.Y., Chen, M., Wang, R., 2011. Occurrence of veterinary antibiotics in animal wastewater and surface water around farms in Jiangsu Province, China. Chemosphere 82, 1408–1414. Yang, X., Shang, C., Westerhoff, P., 2007. Factors affecting formation of haloacetonitriles, haloketones, chloropicrin and cyanogen halides during chloramination. Water Res. 41, 1193–1200.