Can Treatment and Occurrence Research Keep up with the CCL Process? The case of DBPs (and PPCPs)

Transcription

1 Research ommittee Seminar on L3 VA Section AWWA an Treatment and ccurrence Research Keep up with the L Process? The case of DBPs (and PPPs) Dave Reckhow University of Massachusetts 20 ct 2008

2 utline Introduction DBPs: regulated vs emerging Deductive vs bservational approach Predictions from Structure Toxicity Models Biopolymers and DBP pathways New Analytical Methods onclusions

3 DBP Formation The THMs H The Precursors! H + natural organics (NM) Br H Br Br H xidized NM and inorganic chloride Aldehydes hlorinated rganics TX THMs HAAs Br Br H Br hloroform Bromodichloromethane hlorodibromomethane Bromoform 3

4 The Haloacetic Acids Br Br Br Br Br Br Trichloroacetic Bromodichloroacetic hlorodibromoacetic Tribromoacetic Acid Acid Acid Acid (TAA) H H Br Br H Br Dichloroacetic Bromochloroacetic Dibromoacetic Acid Acid Acid (DAA)

5 The DBP Iceberg DHAAs THMs, THAAs IR ompounds 50 MWDS DBPs Stuart Krasner ~700 Known DBPs Susan Richardson Halogenated ompounds Non-halogenated ompounds

6 DBPs on L3 Aldehydes Formaldehyde Acetaldehyde Nitrosamines Nitrosodimethylamine (NDMA) Nitrosodiethylamine (NDEA) Nitroso-di-n-propylamine (NDPA) Nitrosodiphenylamine Nitrosopyrrolidine (NPYR) Hydrazine

7 ther DBPs on PL hloropicrin Halophenols hlorophenol 2,4,5-trichlorophenol 2,4,6-trichlorophenol Benzoic acid, 3,6-dichloro-2-hydroxy Haloamines 1,2-benzenediamine, 4-chloro 2,4-Imidazolidinedione, 1,3-dibromo-5,5-dimethyl 1,2-propanediol, 3-chloro Many oxidation products

8 Epidemiology Bladder ancer DBPs linked to 9,300 US cases every year ther ancers Rectal, colon Reproductive & developmental effects Neural tube defects Miscarriages & Low birth weight eft palate ther Kidney & spleen disorders Immune system problems, neurotoxic effects 137,000 at risk in US?

9 TX: Known & Unknown Data from the Mills Plant (A) August 1997 (courtesy of Stuart Krasner) Haloketones hloropicrin Trihalomethanes 20% Regulated DBPs But, the Bad Stuff is somewhere here Unknown rganic Halogen 64% Haloacetonitriles 2% hloral Hydrate 1% Sum of 5 Haloacetic Acids 10% Bromochloroacetic Acid 3%

10 IR data 140 Are regulated DBPs good surrogates? TTHM (µg/l) Unknown TX (µg/l)

11 Species Model Simple competitive kinetic model From: MacNeill, 1993; owan & Singer, Probabilistic model THM Mole Fraction (THM4 only) H 3 HBr 2 HBr 2 HBr Dave Reckhow, UMass 11 THM Br/(+Br)

12 Bromo speciation 1.2 Full-scale data (small symbols) from Weinberg et al., 2002 (All 12 plants) THM Mole Fraction (THM4 only) Lab data (large symbols) from Hua & Reckhow, 2004 Lines are geometric model H3 HBr2 HBr2 HBr3 H3 Lab tests HBr2 Lab tests HBr2 Lab tests HBr3 Lab tests Dave Reckhow, UMass THM Br/(+Br) 12

13 Brominated 3 & 4-carbon acids Brominated 3-carbon and 4-carbon acids: like the HAAs, these are maximized with chlorine Examples from Weinberg et al., 2002: Propanoic acid (2,2-Br 2 ; Br) Butanoic acid (2-Br) Propenoic acid (3,3-2 ; 3,3-Br 2 ; cis-2,3-br 2 ; Br 3 ; BrI) Buten-2-oic acid (trans&cis-4-br; 2,3-Br 2 ; Br 2 ) Butenedoic acid (2-Br; trans-2,3-br 2 ) Dave Reckhow, UMass 13

14 Iodo speciation nly low THM I data available from field sites Suggestions of departure from probabilistic model at high THM I Higher iodoform than expected Possible decomposition of larger TI structures THM Mole Fraction (&I only) Full-scale data (small symbols) from Weinberg et al., 2002 Lab data (large symbols) from Hua & Reckhow, 2004 Lines are geometric model (All 12 plants) H3 HI2 HI2 HI3 H3 Lab tests HI2 Lab tests HI2 Lab tests HI3 Lab tests THM I/(+I) Dave Reckhow, UMass 14

15 Iodo-acids ompounds from chloramine system (Weinberg et al., 2002) Iodoacetic acid Bromoiodoacetic acid (E)-3,3-bromoiodopropenoic acid (Z)-3,3-bromoiodopropenoic acid (E)-2-iodo-3-methylbutenedioic acid Lab Data suggests Less TI formation than TBr formation at same molar halide levels Due to iodate formation Without iodate formation, TI forms as readily as TBr onclusion Iodoacids probably track Iodomethanes Dave Reckhow, UMass 15

16 MX Several isomers, congeners and related forms pen (ZMX, EMX) and closed (MX) xidized (ox-mx, ox- EMX) and reduced (red-mx) Brominated (BMX1-3, BEMX1-3) Dave Reckhow, UMass 16 Fig. 1. Ring and open forms of targeted halogenated furanones (MX-analogues); from nstad & Weinberg, 2005.

17 MX ompounds (cont.) MX ccurrence studies Kronberg and other early studies Generally < 60 ng/l Wright et al., 2002 [Env. Hlth. Pers.] Up to 80 ng/l Weinberg et al., 2002 Median = 20 ng/l; 75%ile = 60 ng/l; max = 310 ng/l ther forms BMX1 (170 ng/l) and BMX3 (200 ng/l) High Br plant using chlorine dioxide, chlorine and chloramines Dave Reckhow, UMass 17

18 MX Behavior Lab degradation studies Slow hydrolysis at neutral ph t ½ ~ 9 days Accelerated degradation in presence of sulfite t ½ ~ 9 hrs at 25 µm [S(IV)] Weinberg et al., 2002 zone destroys MX precursors, but 2 doesn t Apparent MX degradation in DS of Plant #2 Dave Reckhow, UMass 18

19 N-DBPs Nitrosamines NDMA etc. rganic chloramines N-haloamino acids, etc. Haloquinones Halonitriles DHANs and many others

20 H ytotoxicity Work of Michael Plewa DBP hemical ass IAA BAA TBAA hloroacetamide Trichloroacetonitrile 3-Iodo-3-bromopropenoic Acid DBAA MX DIAA DBAA BDAA BIAA BAA AA 2-Bromobutenedioic Acid 2,3-Dibromopropenoic Acid TAA DAA DBNM DBNM BNM TBNM BDNM 3,3-Dibromo-4-oxopentanoic Acid BNM 2-Iodo-3-bromopropenoic Acid 3,3-Dibromopropenoic Acid DNM NM TNM Tribromopropenoic Acid 2-Bromo-3-methylbutenedioic Acid hlorodibromomethane Bromoacetamide Dibromoacetamide Tribromopyrrole Bromate Dichloroacetamide Trichloroacetamide EMS +ontrol ther DBPs Iodoacetamide Haloacetamides Dibromoacetonitrile Bromoacetonitrile Iodoacetonitrile Bromochloroacetonitrile Haloacetonitriles Dichloroacetonitrile hloroacetonitrile Iodoform Halomethanes Halonitromethanes 3,3-Bromochloro-4-oxopentanoic Acid Bromoform hloroform Halo Acids Haloacetic Acids H ell ytotoxicity as %½ Values (~L 50 ) Log Molar oncentration (72 h Exposure) July

21 N-DBPs we know about: end products ertain to come from N-organics when using free chlorinen & NBr Major types: yanogen Halides Haloacetonitriles Halonitromethanes N hloropicrin 9 species (HP) 2 H Br Br N H N H N Br Dichloroacetonitrile Bromochloroacetonitrile Dibromoacetonitrile (DAN) (BAN) Special focus on these compounds because of large data set (DBAN) Trichloroacetonitrile (TAN) N

22 ccurrence DHANs are typically 10% of THM level Krasner et al., 2002 [WQT] 12 plant survey IR (mean for all) HAN4: 2.7 µg/l P: <0.5 µg/l N: 2.1 µg/l

23 Pathway to NDMA Role of Dichloramine and oxygen Based on recent work by Bill Mitch and colleagues Dichloramine H N N H 3 R H 3 Dimethyl(xx)amine PRDUTS R H N H N N Monochloro Unsymmetric Dimethylhydrazine (UDMH-) N H 3 H 3 N Nitrosodimethylamine (NDMA) xygen H 3 H 3

24 Reaction of UDMH Abbreviations DMD: dimethyldiazene TMT: tetramethyltetrazene FMMH: formaldehyde monomethylhydrazone FDMH: formaldehyde dimethylhydrazone DM: dimethylcyanamide DMF: dimethylformamide From: Mitch & Sedlak, 2002 [ES&T, 36:588]

25 The Unnatural Precursor? Ranitidine (Zantac) 63% conversion to NDMA Schmidt et al., 2006 [WQT] Introduced in 1981, largest selling prescription drug by 1988 Stomach ulcers and esophageal reflux Mean concentration of 3000 ng/l estimated for raw municipal WW (national average) Sedlak 2005 AWWARF report 450 ng/l formation in raw WW expected Unknowns: how much does this persist in treatment and in the environment? 25

26 Hunting for the bad DBPs bservational/empirical Multifaceted analysis of treated waters ompanion toxicity testing Deductive/theoretical Postulate DBPs from known NM substructures Exploit Structure-toxicity models Also allows us to probe NM contributions to regulated DBPs

27 g hemical Models to Prioritize DBP Research AWWARF funded study ( ) Richard Bull, Dave Reckhow Background Health risks associated with disinfection in epidemiology studies are poorly represented in the toxicology data of individual DBPs Effects specific to epidemiology, and/or Projected risks are much higher than sum of individual by-products studied in toxicology studies Toxicology data has identified the compounds in current regulations (e.g. THMs & HAAs) omplying with these MLs does not necessarily result in decreases in major health risks which are those identified in epidemiology studies

28 An Aquatic Humic Structure From Thurman, 1985 Hydroxy Acid H H H Phenolic- Aliphatic Dicarboxylic Acid Aromatic Dicarboxylic Acid H H 3 Aliphatic Acid Aromatic Acid

29 Aliphatics: Haloform Reaction RLS is deprotonation (k 1 ) under many conditions Many LFERs exist for estimating K a s E.g., Perrin et al., 1982 Then relate k 1 to K a H 3 H 3 H 3 H 2 H H 2 H + - H 3 H 2 H - H 3 H 2 H H 2 [ ] H 3 H 2 H H 3-3 H 3 H H 29 3

30 arbonaceous biopolymers ellulose Lignin Phenyl-propane units ross-linked Radical polymerization Ill defined structure Hemicellulose Terpeniods

31 H Lignin Monomers Aromatic structures from u degradation Syringyl Vanillyl innamyl 4-Hydroxybenzoic acid H Vanillin H 3 Vanillic acid H 3 H 3 H H 3 H 3 Syringaldehyde H 3 H 3 H 3 Syringic acid H 3 Acetovanilione H 3 H 3 H 3 H 3 4-Hydroxybenzaldehyde 4-Hydroxyacetophenone 4-Hydroxycinnamic acid Acetosyringone Ferulic acid

32 Demand TX Unkn TX 2.0 hlorine Demand (M/M-compound) TX Speciation hydroxy benzoic acid 4-hydroxy benzaldehyde 4-hydroxy acetophenone TX Formation (M-/M-compound) TTHM THAA DHAA DHAN Unkn TX 4-hydroxy benzenes Among the most reactive structures tested H H 3

33 Mining the literature to postulate new DBPs hlorination of p- hydroxybenzoic acid based on Larson and Rockwell (1979). A represents electrophilic aromatic substitution, B is oxidative decarboxylation H B H H A H H H H H H H H B H H H A 1 B 3 Haloquinones are likely intermediates 2 A A 4 5

34 horine + Aromatics hlorination of Resorcinol From Boyce & Hornig, 1983 All structures identified by G/MS except those in brackets Dave Reckhow, UMass 34

35 ther plant products Steroids Porphyrins Nucleic Acids Terpenoids Water Soluble Acids Mevalonic acid Acetate Amino Acids Misc. N & S compounds Unsaponifiable Liquids Flavonoids Saponifiable Liquids Pyruvate arbohydrates Shikimic Acid Aromatic ompounds Proteins Nitrogenous precursors Activated non-n precursors From: Robinson, 1991

36 Amino Acids: Estimated Abundance assification 50%ile 90%ile 99%ile DN Free AA ombined AA Nucleic acids Amino Sugars Humic-N From: Bull et al., 2007 Estimates in µg-n/l Amino Abun- Acid dance Glycine 11.7% Alanine 11.7% Valine 5.2% Isoleucine 4.4% Leucine 5.6% Serine 10.8% Threonine 7.0% Methionine 1.0% Aspartic Acid 10.2% Glutamic Acid 10.0% Lysine 1.6% rnithine 2.0% Arginine 7.4% Histidine 2.5% Asparagine 0.4% Glutamine 0.5% Tryptophan 2.5% Phenylalanine 3.4% Tryrosine 2.2% SUM 100.0% [1] Based on an average of: Isle Bay water (Yamashita & Tanoue, 2003), Lake Biwa (Wu et al., 2003), and water column values, summer, from Thomas,

37 R N-chloro-organics Reactions of chlorine with organic amines Primary amines H H NH 2 R NH R N 2 Secondary amines R 2 H NH R2 N Inorganic chloramines can transfer their active chlorine in a similar fashion

38 Degradation pathways R 1 H N R2 R 4 R 3 X + Nu R 1 X N R2 R 4 R 3 R 1 =H X + Nu X X N R2 R 4 R 3 R 2 =H or I II R 2 =H or HX ( 2 ) R 1 =H HX ( 2 ) General scheme for carbonyl and cyano formation from chlorination of amines and amino acids (adapted from Nweke and Scully, 1989, and Armesto et al., 1998). R 1 NH 2 R 1 R 4 N III R 3 R 4 R 3 V NH 2 X X + Nu X R 4 N IV R 4 =H N R 3 HX R 3 VI Monohalamine Pathway Dihalamine Pathway

39 assic Mechanism Isoleucine 2 Pathways Formation of nitriles with excess chlorine Formation of aldehydes with under-chlorination Froese, Kenneth L., Wolanski, Alina, and Hrudey, Steve E. Factors Governing dorous Aldehyde Formation as Disinfection By-Products in Drinking Water. Water Research 33[6], Aldehyde Nitrile

40 Phenylalanine Stable N-chloroaldimine Pathway favored at lower phs Half-life of onyers & Scully, 1993 [ES&T 27:261]

41 Aspartic Acid Early Recognition of DHAN pathway From Trehy, 1980 (MS Thesis)

42 H DAN N Asp (cont) k 2 k 1 k 4 H N H N H 2 fast DAN continues to degrade There is a direct pathway to DAA There is an important oxidation & deamination pathway too H 2 fast DAD H H k 1-1 H NH 2 NH 3 NH 2 fast fast NH (+II) S (+IV) H fast H H NH 2 H N pka = 3.7 k 1-2 N--DAD anion N--DAD NH H NH DAA

43 Polypeptide linkages # of AAs Amide nitrogen thought to react slowly About 5% under conditions used Based on Jensen et al., 1999 More reactive than expected 2 Demand (mg/mg-n) Demands calculated from component AAs both with and without amide reactivity Asp-Asp-Asp-Asp L-Aspartyl-L-Phenylalanine Albumin Measured al w/ amide al w/o amide Hemoglobin Lysozyme Insulin Demand (M/M-N) ompound

44 Larger Proteins omparison to free AAs Less dihalo; more trihalo Similar TX; maybe less UTX Hemoglobin Albumin DBP Formation (µg/mg-n) bserved Predicted DBP Formation (µg/mg-) DBP Formation (µg/mg-n) bserved Predicted DBP Formation (µg/mg-) 0 TTHM TAA DAA TX UnKn TX DBP 0 0 TTHM TAA DAA TX UnKn TX DBP 0

45 onclusions: from QSTR From: Bull et al., 2008, AwwaRF Report Research needs Group Example ccurrence Toxicology Haloquinones rganic N- haloamines Alkaloidal nitrosamines 2,6-dichloro-3-methyl-1,2- benzoquinone (DMBQ) Prioritize on range of stabilities and mutagenic activity N-nitrosonornicotine 1-Noxide yclopentenoic acids & MX-related 3,5-dichloro 1-hydroxy-4- ketocyclopent-2-enoic acid 1 2 MF 2 1 Halonitriles 2,3-Dichloropropenal (arc) 2,3-dibromopropionitrile (DT) 1 1

46 Higher MW DBPs NM research ESI with Ultra High- Resolution Fourier Transform Ion yclotron Resonance Mass Spectrometry Benefits Unambiguous molecular formulae

47 Raw Water - Winnipeg 4.00E E E+02 -ve ion + ve ion Intensity ESI-TF MS 2.50E E E E E+01 ESI-FTIR MS Abundance 0.00E m/z Same: comparison side-by-side 500 m/z

48 hlorinated Water + Br Winnipeg 7 6 Abundance m/z Abundance m/z

49 Ultra-high resolution MS Reemtsma et al., 2006 [ES&T: 40:19:5839] Zone of low solubility Area of predicted fulvic acid molecules in a - vs molecular mass diagram for the mass range m/z (marked by the lines) and fulvic acid molecules detected by SE-FTIRMS in the river isolate (dots (island no. 24) and triangles (island no. 25)). 49

50 Some examples hlorination of Winnipeg RW in presence of Iodide Possible structures H I 2 H Mass Mass H H I Mass

51 onclusions: DBPs The most toxicologically important DBPs have not yet been proposed for regulation Many biopolymers can produce important DBPs Amino acids and proteins produce substantial amounts of DBPs that may be of toxicological significance, especially N- DBPs Lignin and monomers probably produce haloquinones that are suspected to be carcinogenic DBPs for future Ls should be examined using deductive methods as well as the more conventional approaches

52 Acknowledgements Research Support American Waterworks Association Research Foundation Massachusetts Division of onservation and Recreation Many UMass students, post-docs and faculty Paula Rees, Klaus Nusslein, John Tobiason Darlene Bryan, Greg Devine, Junsung Kim, Gladys Makdissy, Teresa onneely, ynthia astellon, Alison Boutin Many Drinking Water Utilities

53 The End Suspect apprehended? 53