Environ. Sci. Technol. 2006, 40, 6007-6014
Nitrosamine Formation Pathway Revisited: The Importance of Chloramine Speciation and Dissolved Oxygen I. MARIE SCHREIBER AND WILLIAM A. MITCH* Department of Chemical Engineering, Yale University, Mason Lab 313b, 9 Hillhouse Avenue, New Haven, Connecticut 06520
Nitrosamine formation during chloramination previously has been linked to a reaction between monochloramine and organic nitrogen precursors via unsymmetrical dialkylhydrazine intermediates. Our results demonstrate the critical importance of dichloramine and dissolved oxygen. We propose a new nitrosamine formation pathway in which dichloramine reacts with secondary amine precursors to form chlorinated unsymmetrical dialkylhydrazine intermediates. Oxidation of these intermediates by dissolved oxygen to form nitrosamines competes with their oxidation by chloramines. Even when preformed monochloramine was applied, our model explained nearly all N-nitrosodimethylamine formation from the traces of dichloramine formed via monochloramine disproportionation. We suggest that, in contrast to unsymmetrical dialkylhydrazines, the weak, nonpolar nature of the N-Cl linkage in chlorinated unsymmetrical dialkylhydrazine intermediates enables incorporation of dissolved oxygen to form nitrosamines. With the improved understanding of the nitrosamine formation pathway, strategies are suggested that could significantly reduce nitrosamine formation during chloramination.
Introduction The formation of nitrosamines, particularly N-nitrosodimethylamine (NDMA), during chloramine disinfection of waters containing appropriate organic nitrogen precursors has caused significant concern among drinking water utilities because these are potent carcinogens. NDMA formation is particularly problematic for utilities practicing chlorine disinfection of non-nitrified secondary municipal wastewater effluents in indirect potable reuse operations or chloramination of wastewater-impacted surface waters (1). In several cases, expensive ultraviolet treatment units have been installed downstream of disinfection operations at advanced wastewater treatment plants to remove NDMA (2). NDMA is considered a priority pollutant, but currently no federal maximum contaminant level (MCL) for drinking water has been established. Previous studies (3, 4) modeled NDMA formation from the model precursor, dimethylamine (DMA), as a two-step mechanism. The first step involved a nucleophilic substitution reaction between monochloramine (NH2Cl) and the unprotonated form of DMA to form an unsymmetrical dimethylhydrazine (UDMH) intermediate: * Corresponding author phone (203)432-4386; fax (203)432-4387; e-mail:
[email protected]. 10.1021/es060978h CCC: $33.50 Published on Web 08/24/2006
2006 American Chemical Society
In the second step, NH2Cl oxidized the UDMH intermediate to form NDMA at 1 (13). Even at molar ratios < 1, NHCl2 formation occurs due to the pH-dependent reaction shown in eq 1 (16). NH2Cl predominates above pH 8.5, while NHCl2 predominates below pH 5. For the experiments depicted in Figure SI-1 (Supporting Information), ∼5% of the chloramines were attributable to NHCl2 after 3 h. To quantify the extent to which partial NHCl2 formation could explain NDMA formation, preformed NH2Cl or NHCl2 were applied to DMA in deionized water to assess NDMA formation kinetics. In all experiments, chloramines were in excess compared to DMA, as anticipated for chloramines compared to organic nitrogen-based NDMA precursors under typical disinfection conditions. In accordance with a previous hypothesis that the reaction of NH2Cl with DMA was ratelimiting (3), NDMA formation was fit to eqs 2a or 2b.
d[NDMA] ) kmono[NH2Cl]xmono[DMA]ymono dt
(2a)
d[NDMA] ) kdi[NHCl2]xdi[DMA]ydi dt
(2b)
Over the time scale of the experiments, both chloramines and DMA concentrations were constant and NDMA formation was linear. NDMA formation rates were at least an order of magnitude faster for NHCl2 than for NH2Cl, corresponding to previous research (10) suggesting that NHCl2 is the more potent NDMA-forming oxidant. Plots of log[NDMA formation rate] vs log [DMA] yielded a rate order with respect to DMA of ∼1 (Figure 1A) for both NH2Cl (i.e., ymono ) 0.99 ( 0.15 standard deviation) and NHCl2 (i.e., ydi ) 0.87 ( 0.09 standard deviation). However, similar plots for varying inorganic chloramine concentrations (Figure 1B) indicated fractional rate orders for both NH2Cl (i.e., xmono ) 0.52 ( 0.09 standard deviation) and NHCl2 (i.e., xdi ) 0.40 ( 0.05 standard deviation). Two potential explanations for the observed fractional rate orders are chain reactions involving radical intermediates and branching reaction pathways. Previous research indicated that oxidation of hydrazines in aqueous solution occurs via one-electron transfer processes that are catalyzed by glass surfaces, phosphate buffers, and Cu(II) (17). Such reactions may proceed via chain reactions involving hydroxyl radical (OH*) and hydrogen peroxide (H2O2). To examine whether such chain reactions could explain the observed fractional rate orders, NDMA concentrations (Figure SI-2A, Supporting Information) were monitored after application of NHCl2 (0.3 mM) to DMA (5
FIGURE 1. Rate order with respect to DMA (A) or inorganic chloramines (B). NDMA formation kinetics following addition of (A) 0.32 mM NHCl2 (0) or 1.45 mM NH2Cl (O) to various concentrations of DMA over 2 h and (B) various concentrations of NHCl2 (0) to 5 µM DMA over 6 h or NH2Cl (O) to 10 µM DMA over 8 h, in deionized water buffered at pH 6.9 with 5 mM PO4. µM) in either glass or fluorinated polyethylene containers at pH 6.9 (5 mM phosphate or carbonate buffer) and pH 7.5 (20 mM phosphate or borate buffer). No significant differences in NDMA formation were observed for different buffers or surfaces. NDMA concentrations (Figure SI-2B, Supporting Information) also were monitored after application of 0.35 mM NHCl2 to 5 µM DMA or UDMH and various potential catalysts (i.e., phosphate, Cu(II), and H2O2) or inhibitors (i.e., tertbutyl alcohol as a OH* scavenger) at pH 6.9. For most additives, no significant differences in NDMA formation were observed. Elevated phosphate concentrations significantly decreased NDMA formation, although for DMA, the decrease was only ∼50% for an order of magnitude increase in phosphate concentration. For the low phosphate buffer concentrations employed in this study (i.e., 5 mM), no significant differences in NDMA formation were observed for different buffers (Figure SI-2A). Only Cu(II) increased NDMA formation; however, observed increases were only 80% and 30% for DMA and UDMH, respectively, despite the extremely high Cu(II) (50 µM) concentration employed. These results suggest that chain reactions associated with one-
FIGURE 2. Effect of dissolved oxygen concentration on NDMA formation over 3.5 h. Dissolved oxygen concentration was varied between 0 and 1.32 mM in deionized water buffered at pH 6.9 with 5 mM PO4. NDMA formation from (A) 0.73 mM NH2Cl and 10 µM DMA, (B) 0.32 mM NHCl2 and 5 µM DMA, and (C) 0.32 mM NHCl2 and 5 µM UDMH. Error bars represent one standard deviation (n g 2). Yields were calculated based upon the initial DMA concentration. Solid curves were calculated using the kinetic model developed in this manuscript. electron transfer processes may not explain the observed fractional rate orders. Previously proposed pathways (3, 4) did not explain the incorporation of oxygen during the hypothesized NH2Cl oxidation of UDMH to form NDMA. Oxygen could derive either from dissolved oxygen or from water. Since dissolved oxygen (0.28 mM) and NH2Cl (0.1-0.4 mM) concentrations are the same order of magnitude for our previous experiments, we examined whether competitive reactions involving these two oxidants could explain the observed fractional rate orders. NDMA concentrations were monitored 3.5 h after application of NH2Cl (0.73 mM) to DMA (10 µM) in solutions with 0-1.32 mM dissolved oxygen at pH 6.9 (Figure 2A). NDMA formation increased with dissolved oxygen concentrations up to 0.3 mM; above this concentration, no significant differences in NDMA formation were observed. VOL. 40, NO. 19, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
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To represent the observed dependence of NDMA formation on dissolved oxygen, we modified the previously proposed model to include competing reactions for the oxidation of the UDMH intermediate by either NH2Cl to form unspecified products or by dissolved oxygen to form NDMA. kmono1
NH2Cl + DMA 98 UDMH + H+ + Clkmono2
UDMH + NH2Cl 98 products kmono3
UDMH + O2(aq) 98 NDMA + H2O
(step 1)
(step 2a) (step 2b)
Assuming steady-state conditions for UDMH, NDMA formation can be fit to eq 3:
d[NDMA] kmono1[NH2Cl]kmono3[O2(aq)][DMA] ) (3) dt kmono2[NH2Cl] + kmono3[O2(aq)] Optimization of the three rate constants with Kintecus using the NDMA reaction system model (Table SI-3, Supporting Information, reactions 1-20) yielded kmono1 ) 2.3 ( 0.2 M-1 s-1, kmono2 ) 0.9 ( 0.1 M-1 s-1, and kmono3 ) 0.3 ( 0.1 M-1 s-1. Interestingly, the values determined for kmono1 and kmono3 are comparable to the rate constants Choi and Valentine derived for UDMH formation and oxidation of UDMH to NDMA by NH2Cl (6.4 M-1 s-1 and 0.3 M-1 s-1, respectively), even though these researchers assumed that NH2Cl, not dissolved oxygen, oxidized UDMH to NDMA. However, as previously noted for the Choi and Valentine model, our rate constant (kmono1) for UDMH formation from NH2Cl and DMA is 2 orders of magnitude higher than the reported rate constant of 0.081 M-1 s-1 (7). Therefore, we assumed kmono1 ) 0.081 M-1 s-1 (i.e., the Yagil and Anbar model) and optimized the reaction system for kmono2 and kmono3. Even assuming a diffusion-controlled rate for kmono3, NDMA formation was always underpredicted by ∼2 orders of magnitude (Figure 2A). We monitored NDMA concentrations 3.5 h after application of NHCl2 (0.32 mM) to DMA (5 µM) in solutions with 0-1.32 mM dissolved oxygen at pH 6.9 (Figure 2B). Similar to NH2Cl, NDMA formation increased up to 0.3 mM dissolved oxygen. Applying a similar reaction scheme for NHCl2 as that discussed above for NH2Cl, we derived eq 4.
d[NDMA] kdi1[NHCl2]kdi3[O2(aq)][DMA] ) dt kdi2[NHCl2] + kdi3[O2(aq)]
(4)
In this case, an initial nucleophilic substitution reaction between NHCl2 and DMA would form chlorinated UDMH (UDMH-Cl), rather than UDMH.
Optimization of the three rate constants, in combination with the NDMA reaction system model (Table SI-3, Supporting Information, reactions 1-20) and UDMH formation rates from DMA or chlorinated DMA (Table SI-3, reactions 21-22), yielded kdi1 ) 51.5 ( 8.9 M-1 s-1, kdi2 ) 0.75 ( 0.04 M-1 s-1, and kdi3 ) 1.4 ( 0.2 M-1 s-1. Because the computed rate constants for kdi2 and kdi3 describing oxidation of UDMHCl are comparable and the concentrations of NHCl2 (0.040.32 mM) and dissolved oxygen (0.28 mM) were similar in the experiments depicted in Figure 1B, the rate order for NDMA formation with respect to NHCl2 would appear fractional (eq 4). 6010
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To quantify the extent to which partial NHCl2 formation during chloramination could explain NDMA formation, we determined whether the small concentrations of NHCl2 formed as a result of the acid-catalyzed disproportionation of NH2Cl (eq 1) could alone explain NDMA formation observed during application of preformed 0.73 mM NH2Cl to 10 µM DMA (Figure 2A). Applying eq 4, we obtained optimized values for the three rate constants of kdi1 ) 64.2 ( 1.8 M-1 s-1, kdi2 ) 0.7 ( 0.2 M-1 s-1, and kdi3 ) 1.5 ( 0.2 M-1 s-1. These rate constants are with 25% of those obtained from fitting NDMA formation data from applications of preformed NHCl2, indicating that our proposed NHCl2 reaction pathway can explain nearly all of the NDMA formation observed. The predominance of NH2Cl over NHCl2 under typical chloramination conditions should foster UDMH formation. NDMA formation from the reaction of UDMH with NH2Cl (Figure SI-1) or dissolved oxygen (data not shown) was insignificant. However, to assess the importance of NDMA formation from the oxidation of UDMH with NHCl2, we monitored NDMA concentrations 3.5 h after application of NHCl2 (0.32 mM) to UDMH (5 µM) in solutions with 0-1.32 mM dissolved oxygen at pH 6.9 (Figure 2C). Observed NDMA formation trends were similar to those observed for the same experiment using DMA (Figure 2B); however, NDMA formation was approximately 3 times smaller. Previously (18), the oxidation of UMDH by free chlorine was shown to proceed predominately through a dimethyldiazene intermediate to form a variety of oxidation byproducts, rather than by Cl[+1] transfer to form UDMH-Cl. Since DMA has been identified as one of the many oxidation byproducts from UDMH (19), we have updated our proposed pathway to include the oxidation of UDMH by NHCl2 to form DMA. kdi4
UDMH + NHCl2 98 DMA + products Optimization for kdi4, in conjunction with the NDMA reaction system model (Table SI-3, Supporting Information, reactions 1-22) and our three rate constants (i.e., kdi1, kdi2, and kdi3) for NDMA formation, yielded 4.5 ( 0.2 M-1 s-1. To demonstrate the robustness of our reaction scheme, we evaluated its ability to predict NDMA formation with experiments involving a range of concentrations of NHCl2 (0.04-0.3 mM), NH2Cl (0.01-0.60 mM), dissolved oxygen (0.28 mM and 1.06 mM), and DMA (1-100 µM) at pH 6.9 (Table SI-4). Our model predicted NDMA formation within a factor of 3 for all experimental data. While predictions from the Choi and Valentine model also were within a factor of 3 for experiments involving NH2Cl application (Table SI-4 D and E), the Yagil and Anbar model consistently underpredicted NDMA formation by at least 2 orders of magnitude. However, the reaction system is particularly sensitive to pH as a result of variations in chloramine and DMA speciation. When NDMA concentrations (Figure 3A and B) were monitored 2 h after application of preformed NHCl2 (0.2 mM) or NH2Cl (0.4 mM) to DMA (5 or 10 µM, respectively) at pH 6-11, NDMA formation was maximized at pH 8-10 during application of either NH2Cl or NHCl2. Our model predicted NDMA formation within a factor of 5 of experimental data, even at pH greater than 10, when only trace concentrations of NHCl2 occur. The Choi and Valentine model overpredicted NDMA formation by 2 orders of magnitude at pH > 8, while the Yagil and Anbar model underpredicted NDMA formation by 2 orders of magnitude at pH < 9 (Figure 3B). Other secondary amines should react with chloramines to form their corresponding nitrosamines (i.e., NMOR formation from morpholine (MOR)) by a similar pathway. To investigate whether our proposed pathway could explain
FIGURE 3. Effect of pH on NDMA formation over 2 h in deionized water with 5 mM buffer (PO4 for pH 6-8, BO3 for pH 9, CO3 for pH 10, and NaOH for pH 11). (A) NDMA formation from 0.2 mM NHCl2 and 5 µM DMA. (B) NDMA formation from 0.4 mM NH2Cl and 10 µM DMA. Error bars represent one standard deviation (n g 2). Yields were calculated based upon the initial DMA concentration. Solid curves were calculated using the kinetic model developed in this manuscript. other nitrosamine formation (Figure 4A), nitrosamine concentrations were monitored from the application of preformed NH2Cl or NHCl2 to 5 additional secondary amines in deionized water containing 0 mM or 0.3 mM dissolved oxygen. In all cases, nitrosamine formation was at least an order of magnitude higher for NHCl2 than for NH2Cl and ∼1 order of magnitude higher in the presence of 0.3 mM dissolved oxygen. Since the pKa of MOR (8.5 (20)) is significantly lower than those of DMA (10.7 (3)) and the other amines investigated, NMOR and NDMA formation (Figure 4B) were compared after the application of 0.4 mM NH2Cl to 10 µM amine or 0.2 mM NHCl2 to 5 µM amine at pH 6-11 to assess the impact of amine speciation. Maximum NMOR formation from NHCl2 occurred at a lower pH than NDMA formation, reflecting the enhanced fraction of unprotonated amines due to the lower pKa value. To assess the ability of our reaction scheme to explain NDMA formation during chloramination of municipal wastewater effluents, we monitored NDMA formation 3 h after application of 0.8 mequiv/L NH2Cl or NHCl2 to effluents collected from two municipal wastewater treatment plants (Figure 4C). In municipal wastewater effluents, the most probable NDMA-forming precursors include DMA and tertiary amines with DMA functional groups (5). Similar to experiments involving DMA as a model precursor, we observed a nearly linear increase in NDMA formation for dissolved oxygen concentrations up to 0.3 mM; above this concentration, nitrosamine formation leveled off. NDMA concentrations from samples treated with NH2Cl never exceeded 0.14 nM.
FIGURE 4. Effect of dissolved oxygen (A and C) and pH (B) on nitrosamine formation from other amines. (A) Nitrosamine formation from 10 µM amine and 0.73 mM NH2Cl or 5 µM amine and 0.32 mM NHCl2 over 3.5 h in deionized water buffered at pH 6.9 with 5 mM PO4. Dissolved oxygen concentrations were 0 mM (black bar) or 0.28 mM (white bar). Note break in y-axis and scale change. (B) Nitrosamine formation from 10 µM amine and 0.4 mM NH2Cl or 5 µM amine and 0.2 mM NHCl2 over 2 h in deionized water with 5 mM buffer (PO4 for pH 6-8, BO3 for pH 9, CO3 for pH 10, and NaOH for pH 11). Yields were calculated based upon the initial amine concentration. (C) NDMA formation 3 h after application of 0.2 mM NHCl2 to secondary municipal wastewater effluents buffered with 5 mM PO4 (pH 6.9). Dissolved oxygen concentrations were 0, 0.28, and 1.32 mM. Error bars represent one standard deviation (n g 2) except for Wallingford August 2005 (n ) 1). VOL. 40, NO. 19, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
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Discussion
SCHEME 1
While the ability of our model to predict NDMA formation over a range of conditions indicates the importance of NHCl2 and dissolved O2 for NDMA formation, two additional pathways involving NHCl2 and O2 should be considered. First, our hypothesized UDMH-Cl intermediate could undergo a nucleophilic substitution reaction with hydroxide to form hydroxylated UDMH. This intermediate could then be oxidized by oxygen species (i.e., dissolved O2 or superoxide) to form NDMA and hydrogen peroxide (Scheme 1). In this pathway, the oxygen in NDMA would derive from water and not dissolved oxygen. However, when 0.4 mM NHCl2 was applied to 5 µM DMA in the presence and absence of 12 300 units/L of superoxide dismutase, no significant difference in NDMA formation was observed over 3 h at pH 8.5. Furthermore, when 0.4 mM NHCl2 was applied to 1 mM DMA in 18O-labeled water, no incorporation of 18O into NDMA was observed over 24 h. Second, an electrophilic attack of nitroxyl (HNO) on unprotonated amines could nitrosate secondary amines by forming a hydroxylamine intermediate which could be oxidized by dissolved oxygen as described in Scheme 1 (21). HNO was proposed as an intermediate in the decay of NHCl2 during breakpoint chlorination (22). Although not explicitly included in the Jafvert and Valentine chloramine model (9), we considered whether HNO could be the unspecified intermediate (I) formed during the base-catalyzed decomposition of NHCl2 (Table SI-3, reaction 7). However, in accordance with our earlier experiments, this pathway requires that the oxygen in HNO be derived from dissolved oxygen. Therefore, we corrected the rate constant for the formation of I to account for dissolved oxygen in addition to hydroxide. NDMA formation was assumed to result from a reaction between DMA, HNO, and O2. k
DMA + HNO + O2 98 NDMA + products Optimization of this rate constant for observed NDMA formation at pH 6.9 yielded 8.0 ((2.9) × 1010 M-2 s-1. However, this model predicted linear NDMA formation with increases in O2 concentration and overpredicted NDMA formation with NH2Cl by 2 orders of magnitude at pH > 8 (Figure 3B).
SCHEME 2
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Our results demonstrate the critical importance of NHCl2 and dissolved oxygen for nitrosamine formation during chloramination. We propose that nitrosamine formation can be explained through the reaction pathway described in Scheme 2 for NDMA formation from DMA. The initial step in this pathway involves a nucleophilic substitution reaction between secondary amines and NHCl2 to form chlorinated unsymmetrical dialkylhydrazine intermediates (e.g., UDMHCl for DMA), rather than unsymmetrical dialkylhydrazines (e.g., UDMH), for the previously proposed NH2Cl reaction. This intermediate can then be oxidized by either dissolved O2 to form NDMA or by chloramines to form other unidentified products. Similar to chloramine oxidation of UDMH (23), step 2a of our pathway may incorporate reactions for the formation of several products. Regardless, our model predicted NDMA concentrations within a factor of 3 of experimental data at pH 6.9 (Figure 2, Table SI-4) and within a factor of 5 for other pH conditions (Figure 3), while predictions of other models were off by several orders of magnitude under certain conditions. Although NH2Cl is the predominant chloramine species under typical chloramination conditions, our model adequately predicted NDMA concentrations based solely on the low concentrations of NHCl2 that formed via disproportionation of applied, preformed NH2Cl. We propose that two factors explain the importance of NHCl2 for NDMA formation. First, the rate constant for UDMH-Cl formation (step 1 of Scheme 2) is 3 orders of magnitude faster than the rate constant for the formation of UDMH from the reaction of NH2Cl and DMA. Nonetheless, the predominance of NH2Cl under typical chloramination conditions might foster UDMH formation. Our results indicate that NDMA can be formed through a reaction of UDMH with NHCl2 (Figure 2C); however, this reaction likely proceeds via a dimethyldiazene intermediate, rather than via Cl[+1] transfer to form UDMH-Cl. Dimethyldiazene can be further oxidized to various products including DMA, tetramethyltetrazene, formaldehyde monomethylhydrazone, and formaldehyde dimethylhydrazone (18). DMA could then react via Scheme 2 to form NDMA. Although attempts were unsuccessful to isolate UDMH-Cl and UDMH using a LCMS (typical detection limit of 1 µM), their steady-state concentrations were predicted to be < 10 nM and < 1 nM, respectively, for most experimental conditions (pH 6.9) in this work. Second, we propose that, unlike UDMH, the structure of UDMH-Cl enables incorporation of dissolved oxygen. While oxidation of UDMH proceeds predominantly via dimethyldiazene (18), oxidation of UDMH with dissolved oxygen to form NDMA required the presence of metals catalyzing oneelectron transfers (e.g., Cu(II) (19)). To further examine UDMH-Cl, we preformed structural calculations using Guassian 03W in the gas phase for UDMH-Cl, UDMH, and
nonpolar N-Cl linkage in UDMH-Cl is different from the more typical, polar N-Cl bond in NH2Cl. Verification of the proposed pathway for oxygen incorporation would require a more detailed examination of the potential energy surfaces. Our results suggest that nitrosamine formation during chloramination could be reduced by minimizing concentrations of NHCl2 and dissolved oxygen. Previously, we demonstrated that application of chloramines preformed under conditions favoring NH2Cl (i.e., pH > 8.5 and Cl:N molar ratios , 1) minimizes NDMA formation by reducing partial NHCl2 formation (10, 11). Because NHCl2 formation from disproportionation is slow (i.e., reaction 5, Table SI-3), NHCl2 formation after application of preformed NH2Cl should be minimal over extended contact times. For wastewater treatment plants using activated sludge processes, minimization of dissolved O2 concentrations could be achieved by creating a nonaerated zone in the downstream section of the activated sludge tank. Microbial respiration in this section would deplete dissolved oxygen concentrations upstream of the secondary clarifier and disinfection. Our results indicated that NDMA formation is proportional to dissolved oxygen concentrations up to 0.3 mM (
