The Next Generation of Drinking Water Disinfection By-Products: Occurrence, Formation, and Toxicity

Transcription

1 The Next Generation of Drinking Water Disinfection By-Products: Occurrence, Formation, and Toxicity Susan D. Richardson U.S. Environmental Protection Agency, National Exposure Research Laboratory, Athens, GA U.S. Environmental Protection Agency Office of Research & Development

2 Some perspectives on a lunch talk

3 Steps and episodes in scientists careers

4 Steps and episodes in scientists careers Position Research Conferences Graduate student Postdoc Primary producer Poster

5 Steps and episodes in scientists careers Position Research Conferences Graduate student Postdoc Primary producer Poster Assistant/junior scientist Primary producer Oral presentation

6 Steps and episodes in scientists careers Position Research Conferences Graduate student Postdoc Primary producer Poster Assistant/junior scientist Primary producer Oral presentation Senior scientist Group leader Secondary producer Consumer, herbivore Scientific committee

7 Steps and episodes in scientists careers Position Research Conferences Graduate student Postdoc Primary producer Poster Assistant/junior scientist Primary producer Oral presentation Senior scientist Group leader Department head Secondary producer Consumer, herbivore Tertiary producer Consumer, carnivore Scientific committee Plenary/keynote lecture

8 Steps and episodes in scientists careers Position Research Conferences Graduate student Postdoc Primary producer Poster Assistant/junior scientist Primary producer Oral presentation Senior scientist Group leader Department head Retiree Emeritus Secondary producer Consumer, herbivore Tertiary producer Consumer, carnivore Scientific committee Plenary/keynote lecture

9 Steps and episodes in scientists careers Position Research Conferences Graduate student Postdoc Primary producer Poster Assistant/junior scientist Primary producer Oral presentation Senior scientist Group leader Department head Retiree Emeritus Secondary producer Consumer, herbivore Tertiary producer Consumer, carnivore Consultant Historic reviewer Scientific committee Plenary/keynote lecture

10 Steps and episodes in scientists careers Position Research Conferences Graduate student Postdoc Primary producer Poster Assistant/junior scientist Primary producer Oral presentation Senior scientist Group leader Department head Retiree Emeritus Secondary producer Consumer, herbivore Tertiary producer Consumer, carnivore Consultant Historic reviewer Scientific committee Plenary/keynote lecture Lunch talk

11 Steps and episodes in scientists careers Position Research Conferences Graduate student Primary producer Poster Postdoc Assistant/junior scientist Primary producer Oral presentation Senior scientist Group leader Does this make me an honorary member of Secondary producer the OFC? Consumer, herbivore Scientific committee Department head Retiree Emeritus Tertiary producer Consumer, carnivore Consultant Historic reviewer Plenary/keynote lecture Lunch talk

12 Drinking Water DBPs What are the Issues? Concern over possible human health risk: Epidemiologic studies: risk of bladder cancer; some cause cancer in laboratory animals Recent concerns about possible reproductive & developmental effects (from epi studies) Goal: Comprehensively identify DBPs formed from different disinfectants, test for toxicity, understand their formation, minimize or eliminate in drinking water

13 Other new issues beyond cancer, miscarriage, birth defects Before Showering with chloraminated water After Showering with chlorinated water at the YMCA in another town

14 Drinking Water DBPs: How are they formed?

15

16 DBPs discovered in 1974 Jon Rook Tom Bellar

17 >600 DBPs Identified Halogenated DBPs Halomethanes Haloacids Haloaldehydes Haloketones Halonitriles Haloamides Halonitromethanes Halopyrroles Haloquinones Halofuranones (e.g., MX) Oxyhalides (e.g., bromate) Many others Non-halogenated DBPs Nitrosamines Aldehydes Ketones Carboxylic acids Others

18 >600 DBPs Identified Halogenated DBPs Halomethanes Haloacids Haloaldehydes Haloketones Halonitriles Haloamides Halonitromethanes Halopyrroles Haloquinones Halofuranones (e.g., MX) Oxyhalides (e.g., bromate) Many others Non-halogenated DBPs Nitrosamines Aldehydes Ketones Carboxylic acids Others N-DBPs

19 But, more than 50% still not known. Unknown 69.9% HAAs 11.8% HNMs 0.5% HACEs 0.5% HKs 0.9% HALDs 1.8% HANs 0.8% THMs 13.5% Halofuranones 0.1% IodoTHMs 0.2% Nationwide Occurrence Study, Krasner et al., Environ. Sci. Technol. 2006, 40, ~50% of TOX >1000 Da: Khiari, et al., Proc AWWA Water Quality Technology Conference

20 Only 11 DBPs Regulated in U.S. DBP MCL (µg/l) Total THMs 80 5 Haloacetic acids 60 Bromate 10 Chlorite 1000 Little known about occurrence, toxicity of unregulated DBPs Regulated DBPs do not cause bladder cancer in animals!

21 Only 11 DBPs Regulated in U.S. DBP MCL (µg/l) Total THMs 80 5 Haloacetic acids 60 Bromate 10 Chlorite 1000 By the way. - One regulated DBP never tested for cancer - A few unregulated DBPs are animal carcinogens (MX and nitrosamines) - Many unregulated DBPs more genotoxic than regulated ones

22 Bladder cancer and drinking water: Pooled analysis 2 OR (95% CI) 1,5 1 0,5 0 Men Women Both 0-1ug/L >1-5 ug/l >5-25ug/L >25-50ug/L >50ug/L OR adjusted by (sex), study, age, smoking status, ever worked in high-risk occupations, heavy coffee consumption and total fluid intake Villanueva et al., Epidemiology 2004, 15,

23 Inhalation (shower, swimming pool, etc.) Volatile DBP e.g. THMs Exposure routes Ingestion (water, coffee, tea, water-based food and beverages) All disinfection byproducts Dermal absorption (swimming pool, bath, etc.) Permeable DBPs e.g. THMs, haloketones, TOTAL INTERNAL DOSE Slide courtesy of Manolis Kogevinas, Centre for Research in Environmental Epidemiology/IMIM, Barcelona

24 Unlike other contaminants that may or may not be present in drinking water DBPs are ubiquitous

25 Emerging DBPs Halonitromethanes (up to 3 ppb; highly genotoxic); new in vivo effects; increased with preozonation Krasner, Weinberg, Richardson, et al., ES&T 2006, 40, Iodo-THMs and Iodo-Acids (iodo-thms up to 15 ppb; iodo-acids up to 1.7 ppb; both classes highly cytotoxic or genotoxic); increased with chloramination Richardson et al., ES&T 2008, 42, Cl O Br Br C NO 2 H I Cl C H Cl H I C H O C OH Haloamides (up to 14 ppb; highly genotoxic) may be increased with chloramination Br C H C NH 2 Cl Cl Cl Cl Halofuranones (up to 2.4 ppb for total MX analogues; genotoxic, carcinogenic); chloramination can also form Br HO O MX O Haloacetonitriles (up to 41 ppb; ~10% of THM4; genotoxic, cytotoxic) Br C H C N Cl Cl Cl Cl Nitrosamines (up to 630 ppt; probable human carcinogens) increased with chloramination EPA intends to regulate 5 nitrosamines H 3 C H 3 C N N O red-mx O Cl Br Cl Br

26 Stuart Krasner

27 Chlorine: Iodo-DBPs Maximized with Chloramines fast fast I - + HOCl HOI IO 2 - IO 3 - NOM Cl-DBPs NOM HOCl fast iodite iodo-dbps fast iodate Sink for iodide HOCl also competes for rxn with NOM, so much lower iodo-dbps with chlorine Chloramines: I - + NH 2 Cl HOI IO 2 - IO 3 - NOM fast Cl-DBPs NOM fast slow X iodo-dbps iodite HOCl HOI also has longer half-life in chloraminated waters iodate Adapted from Bichsel and von Gunten, 1999 and 2000

28 Dibromonitromethane DNA Adducts P-32 Disintigrations per Minute (DPM) Control #10 Male Rat Liver DNA Butanol Extracted (0.32 *10 9 ) High Dose Male # 58 DNBM Liver DNA Butanol Extracted (7.7 * 10 9 ) High Dose Male # 59 DNBM 1200 Liver DNA Butanol Extracted 1000 (2.3 * 10 9 ) Control # 70 Female Rat Liver DNA Butanol Extracted 9 (0.24 * 10 ) High Dose Female # 119 DNBM Liver DNA Butanol Extracted (3.7 * 10 9 ) High Dose Female # 120 DNBM Liver DNA Butanol Extracted (13.6 * 10 9 ) DBNM produces DNA adducts in the livers of rats after only 30 days of exposure (in vivo, male and female rats) Tony also now seeing effects in normal human colon cells Retention Time (min) Data courtesy of Tony DeAngelo & Leon King, U.S. EPA, NHEERL, RTP, NC

29 Genotoxicity: Comet Assay The tail moment is the integrated value of DNA density multiplied by the migration distance. The % tail DNA is the amount of DNA that has migrated into the gel from the nucleus.

30 Genotoxicity of Iodoacetic acid Plewa et al., Environ. Sci. Technol IA also caused developmental effects in mouse embryos (Hunter et al., 1995)

31 New Human Cell Results Average Median SCGE Tail Moment Iodoacetic Acid Bromoacetic Acid Chloroacetic Acid Haloacetic Acid µm CHO Cells Human Cells Plewa et al., ES&T. 2004, 38, (18), Attene-Ramos, Wagner, Plewa, ES&T, 2010, 44 (19), Nontransformed human small intestine epithelial cells Slide courtesy of Michael Plewa, Univ. IL

32 Genotoxicity of DBPs DBP Chemical Class Other DBPs Haloacetamides Haloacetonitriles Halonitromethanes Halo Acids Haloacetic Acids Bromo/iodo acetonitriles Bromonitromethanes IAA Haloamides IAA BAA Iodoacetamide Diiodoacetamide Tribromoacetamide Bromoacetamide DBNM Dibromoacetonitrile Iodoacetonitrile Bromoacetonitrile Dibromchlorooacetamide Bromoiodoacetamide BDCNM TBNM 3,3-Dibromo-4-oxopentanoic Acid TCNM BNM DBCNM BCNM MX Chloroiodoacetamide Tribromopyrrole Bromochloroacetonitrile 3,3-Bromochloro-4-oxopentanoic Acid DCNM CAA Bromochloroacetamide Chloroacetonitrile Dibromoacetamide Trichloroacetonitrile Chloroacetamide DBAA DIAA CNM TBAA Dichloroacetonitrile BIAA BCAA EMS +Control Trichloroacetamide Bromate 2-Bromobutenedioic Acid 2-Iodo-3-bromopropenoic Acid 2,3-Dibromopropenoic Acid CDBAA Single Cell Gel Electrophoresis Genotoxicity Potency Log Molar Concentration (4 h Exposure) Not Genotoxic: DCAA, TCAA, BDCAA, Dichloroacetamide, Chloroform Chlorodibromomethane, 3,3-Dibromopropenoic Acid, 3-Iodo-3-bromopropenoic Acid, 2,3,3,Tribromopropenoic Acid December 2006 Data courtesy of Michael Plewa, University of Illinois

33 But, all of this toxicity testing is for separate, individual DBPs DBPs are really present as MIXTURES >300 DBPs probably present in glass of water

34 Four Lab Study Integrated Disinfection By-products Mixtures Research: Toxicological and Chemical Evaluation of Alternative Disinfection Treatment Scenarios A collaborative effort between: NHEERL (National Health and Environmental Effects Research Laboratory), RTP NERL (National Exposure Research Laboratory), Athens NRMRL (National Risk Management Research Laboratory), Cincinnati NCEA (National Center for Environmental Assessment), Cincinnati Purpose: To address concerns related to potential health effects from exposure to DBPs that cannot be addressed directly from toxicological studies of individual DBPs or simple DBP mixtures 1 st phase: Published in J. Toxicol. Environ. Health 2008 (series of 7 papers) 2 nd phase: Published in Environ. Sci. Technol (Chemistry paper) Planning follow-up 4-Lab Chloramination Study

35 Four Lab Study: Linking DBPs measured to overall toxicity effects In vitro: Reproductive/developmental Mutagenicity Carcinogenicity Neurotoxicity Metabolism In vivo: Reproductive/developmental Mutagenicity/carcinogenicity Immunotoxicity Hepatic/renal toxicity Neurotoxicity/developmental neurotoxicity Kinetics/metabolism Chemistry: 70 Priority DBPs quantified and >100 DBPs comprehensively identified using GC/MS Jane Ellen Simmons

36 Full Study Concentration RAW SURFACE WATER BAG FILTER FLOW EQUALIZATION ION EXCHANGE COLUMNS ULTRAFILTRATION MEMBRANES PERMEATE 1 st Phase: Cl 2 & O 3 -Cl 2 ; treated water first Concentrated after ION EXCHANGE COLUMNS REVERSE OSMOSIS MEMBRAMES CONCENTRATE 2 nd Phase: Concentrated NOM first Treated with Cl 2 after Rats can t drink organic solvents!

37 DBPs can also form from pollutants Pesticides Pharmaceuticals Antibacterial agents Estrogens Textile dyes Bisphenol A Parabens Alkylphenol ethoxylate surfactants Algal toxins

38 Formation of NDMA from a fungicide H 3 C O 3 N N O H 3 C NDMA Tolylfluanide fungicide Schmidt and Brauch, ES&T 2008 Urs von Gunten also has new results indicating the catalytic effect of bromide on this reaction

39 Formation of iodo-dbps from X-ray contrast media + NOM HOCl NH 2 Cl Iodo-DBPs Iopamidol Duirk, Lindell, Cornelison, Kormos, Ternes, Attene-Ramos, Osiol, Wagner, Plewa, and Richardson, ES&T, ASAP, 2011

40 Iodo-DBP Occurrence Study Iodide (µg/l) Sum iodo-acids (µg/l) Sum iodo-thms (µg/l) Plant Plant 4 ND Plant Plant 15 ND Detection limit = 0.13 µg/l Richardson et al., Environ. Sci. Technol. 2008, 42,

41 ICM in U.S. Drinking Water Sources (ng/l) Iopamidol Iomeprol Iopromide Iohexol Diatrizoate Plant 1 11 ND ND ND ND Plant ND Plant ND 6 49 ND Plant 10 ND ND ND ND ND Plant ND ND 85 ND Plant ND ND 120 ND Plant 13 ND ND ND ND ND Plant ND 25 ND ND Plant 17 ND ND ND ND ND Plant 19 ND ND ND ND ND Courtesy of Thomas Ternes, Federal Institute of Hydrology, Germany ICM measured using LC/ESI-MS/MS; DLs = 5-20 ng/l

42 ICM in U.S. Drinking Water Sources (ng/l) Iopamidol Iomeprol Iopromide Iohexol Diatrizoate Plant 1 11 ND ND ND ND Plant ND Plant ND 6 49 ND Plant 10 ND ND ND ND ND Plant ND ND 85 ND Plant ND ND 120 ND Plant 13 ND ND ND ND ND Plant ND 25 ND ND Plant 17 ND ND ND ND ND Plant 19 ND ND ND ND ND Courtesy of Thomas Ternes, Federal Institute of Hydrology, Germany ICM measured using LC/ESI-MS/MS; DLs = 5-20 ng/l

43 ICM in U.S. Drinking Water Sources (ng/l) Iopamidol Iomeprol Iopromide Iohexol Diatrizoate Plant 1 11 ND ND ND ND Plant ND Plant ND 6 49 ND Plant 10 ND ND ND ND ND Plant ND ND 85 ND Plant ND ND 120 ND Plant 13 ND ND ND ND ND Plant ND 25 ND ND Plant 17 ND ND ND ND ND Plant 19 ND ND ND ND ND Courtesy of Thomas Ternes, Federal Institute of Hydrology, Germany ICM measured using LC/ESI-MS/MS; DLs = 5-20 ng/l

44 Controlled Laboratory Reactions Experiments React ICM with HOCl, NH 2 Cl (with and without NOM) 3 phs Follow formation of iodo-dbps Identify reaction products and intermediates Measure genotoxicity Methods Iodo-THMs: GC/EI-MS Iodo-Acids: GC/NCI-MS (with derivatization) Iopamidol (and other ICM): LC, LC/MS/MS Larger MW products and intermediates: LC/MS/MS Genotoxicity: Chinese hamster ovary cells, single cell gel electrophoresis Cristal and Steve

45 Results HOCl NH 2 Cl Iodo-DBPs trace Iopamidol HOCl + NOM Iodo-DBPs NH 2 Cl Iopamidol Iodo-THMs & Iodo-Acids

46 Genotoxicity of Chlorinated Waters Containing Iopamidol CHO Cells Genomic DNA Damage as the Average Mean SCGE %Tail DNA Value ACC + Iopamidol +HOCl 60 ACC +HOCl ACC + Iopamidol Organic Extracts from Water Samples (Concentration Fold)

47 Iodine-Based Disinfectants Smith, Plewa, Lindell, Richardson, Mitch, ES&T 2010, 44,

48 Iodine tincture Iodine-Based Disinfectants I 3- in 50:50 H 2 O/MeOH Smith, Plewa, Lindell, Richardson, Mitch, ES&T 2010, 44,

49 Iodine-Based Disinfectants Iodine tincture Iodine tablets I 3- in 50:50 H 2 O/MeOH Tetraglycine hydroperiodide Smith, Plewa, Lindell, Richardson, Mitch, ES&T 2010, 44,

50 Iodine-Based Disinfectants Iodine tincture Iodine tablets I 3- in 50:50 H 2 O/MeOH Lifestraw Tetraglycine hydroperiodide I 3- complexed to anion exchange resin with activated carbon post-treatment Smith, Plewa, Lindell, Richardson, Mitch, ES&T 2010, 44,

51 Iodo-THM Concentrations (nm) Lake Wintergreen CHCl 2 I CHBrClI CHBr 2 I CHClI 2 CHBrI 2 CHI 3 Total THM Toxicity* Iodine tincture ND 24 ND Iodine tablet ND ND ND 6.1 ND Lifestraw 1.6 ND ND ND ND ND 0 Cl ND ND ND ND ND 322 NH 2 Cl ND 99 ND * Total THM Toxicity = Σ (THM) x (%C 1/2 ) -1 x10 6 Smith, Plewa, Lindell, Richardson, Mitch, ES&T 2010, 44,

52 Iodo-THM Concentrations (nm) Lake Wintergreen CHCl 2 I CHBrClI CHBr 2 I CHClI 2 CHBrI 2 CHI 3 Total THM Toxicity* Iodine tincture ND 24 ND Iodine tablet ND ND ND 6.1 ND Lifestraw 1.6 ND ND ND ND ND 0 Cl ND ND ND ND ND 322 NH 2 Cl ND 99 ND * Total THM Toxicity = Σ (THM) x (%C 1/2 ) -1 x10 6 Smith, Plewa, Lindell, Richardson, Mitch, ES&T 2010, 44,

53 Iodo-acid Concentrations (nm) Lake Wintergreen IAA BrIAA DIAA Z E diacid Iodine tincture 18.9 ND 45.7 ND Iodine tablet ND ND ND ND ND ND Lifestraw ND ND ND ND ND ND Cl 2 ND ND ND ND ND ND NH 2 Cl ND ND ND ND ND ND Smith, Plewa, Lindell, Richardson, Mitch, ES&T 2010, 44,

54 Iodine tincture: 4-19 days exposure equivalent to 1 year of chlorine at 6x higher dose

55 In closing. Ever wonder what happens when you have to scale things up for toxicity testing???

56 The Land of Extraordinarily Large Lab Equipment Toxicity? 20 L 1 ml Chris Cristal Steve

57 Gordon Conference on DBPs August 5-10, 2012 Mount Holyoke College, South Hadley, MA