Roadmap for Interdisciplinary Research on Drinking Water - PowerPoint PPT Presentation

Roadmap for Interdisciplinary Research on Drinking Water Disinfection By-Products Susan D. Richardson U.S. Environmental Protection Agency, National Exposure Research Laboratory, Athens, GA U.S. Environmental Protection Agency Office of Research & Development

What I will cover… • Provide an overview • Summarize important issues with drinking water DBPs • Focus on emerging, unregulated DBPs C Identify gaps and where we need to go next to solve this important problem Richardson, Plewa, Wagner, Schoeny, and DeMarini. Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: A review and roadmap for research. Mutation Research 2007 , 636 , 178-242.

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

Drinking Water DBPs: How are they formed?

Tom Bellar DBPs discovered in 1974 Jon Rook

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

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

But, more than 50% still not known…. Unknown 69.9% HNMs 0.5% HACEs 0.5% HKs 0.9% HALDs 1.8% HANs 0.8% HAAs 11.8% THMs 13.5% Halofuranones 0.1% IodoTHMs 0.2% Nationwide Occurrence Study, Krasner et al., Environ. Sci. Technol . 2006 , 40 , 7175-7185. ~50% of TOX >1000 Da: Khiari, et al., Proc. 1996 AWWA Water Quality Technology Conference

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!

Only 11 DBPs Regulated in U.S. DBP MCL (µg/L) Total THMs 80 5 Haloacetic acids 60 Bromate 10 Chlorite 1000 And, you will hear some odd things next from David DeMarini, such as… - One regulated DBP never tested for cancer - Two unregulated DBPs are carcinogens - Many unregulated DBPs more genotoxic than regulated ones

Only 11 DBPs Regulated in U.S. DBP MCL (µg/L) Total THMs 80 5 Haloacetic acids 60 Bromate 10 Chlorite 1000 There are still many gaps to fill!!

Bladder cancer and drinking water: Pooled analysis 2 1,5 OR (95% CI) 0-1ug/L >1-5 ug/L 1 >5-25ug/L >25-50ug/L 0,5 >50ug/L 0 Men Women Both 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 , 357-367.

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

Route of exposure is important…. • Can get 2X exposure from 10 min shower compared to drinking 2L of tap water (inhalation) • Some DBPs dermally absorbed C Evidence of increased bladder cancer with swimming in indoor pools (inhalation, dermal): Villanueva et al., Am. J. Epidemiol . 2007, 165 , 148-156.

Route of exposure is important…. • Can get 2X exposure from 10 min shower compared to drinking 2L of tap water (inhalation) • Some DBPs dermally absorbed C Evidence of increased bladder cancer with swimming in indoor pools (inhalation, dermal): Villanueva et al., Am. J. Epidemiol . 2007, 165 , 148-156. Does this mean that bladder cancer is caused by volatile or dermally absorbed DBPs?? Does this mean we shouldn’t worry about high MW DBPs? Should we study rats taking showers?

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

But… On the new proposed U.S. EPA Contaminant Candidate List (CCL-3) for drinking water (104 chemicals) Only 10 of 104 chemicals are DBPs: 5 nitrosamines, formaldehyde, acetaldehyde, benzyl chloride, chlorate, bromochloromethane And, 4 of these chosen for other reasons (industrial contaminants, etc.) Many other DBPs far more prevalent than these, but they are not listed as priorities

Emerging DBPs Br • Halonitromethanes (up to 3 ppb; highly genotoxic); new in vivo effects; increased with preozonation Br C NO 2 Krasner, Weinberg, Richardson, et al., ES&T 2006, 40, H 7175-7185. I I O • Iodo-THMs and Iodo-Acids (iodo-THMs up to 15 ppb; iodo-acids H O Cl C H C C H up to 1.7 ppb; both classes highly cytotoxic or genotoxic); Cl H increased with chloramination Richardson et al., ES&T 2008, 42, 8330. Cl O Br C C NH 2 • Haloamides (up to 14 ppb; highly genotoxic) Cl H may be increased with chloramination Cl Cl • Halofuranones (up to 2.4 ppb for total MX analogues; O HO O genotoxic, carcinogenic); chloramination can also form MX Br • Haloacetonitriles (up to 41 ppb; ~10% of THM4; genotoxic, Br C C N cytotoxic); may be increased with chloramination H • Nitrosamines (up to 180 ppt; probable human carcinogens) H 3 C increased with chloramination N N O H 3 C

Emerging DBPs • EPA Method 521 for nitrosamines (GC/MS/MS); sub-ng/L detection • Also an LC/MS/MS method for 9 nitrosamines: Zhao, Boyd, Hrudey, Li, Environ. Sci. Technol . 2006, 40 (24): 7636- 7641. • NDMA on draft CCL-3 and UCMR-2

Nationwide DBP Occurrence Study • Prioritized >500 unregulated DBPs reported in literature (likely to cause cancer) • Measured these in waters across U.S. • Important findings: • New emerging DBPs identified (e.g., iodo-acids) • Alternative disinfectants increased formation of many priority DBPs • Many priority, unregulated DBPs found at significant levels Krasner, Weinberg, Richardson, et al., Environ. Sci. Technol . 2006, 40, 7175-7185.

Halonitromethane Genotoxicity Halonitromethane Genotoxicity Acute Cytotoxicity 100 % Viable Cells 70 50 30 90 20 Dibromonitromethane Average Median SCGE Tail Moment 80 Bromonitromethane Tribromonitromethane MX (EMX) 70 Bromoacetic Acid Dibromoacetic Acid 60 Tribromoacetic Acid Ethylmethanesulfonate 50 Chloroacetic Acid Dichloroacetic Acid 40 Trichloroacetic Acid Bromate 30 20 10 0 0.001 0.01 0.1 1 10 Water Disinfection By-Product (mM) Plewa et al., ES&T 2004, 38, 4713-4722. Halonitromethanes also genotoxic to Salmonella (DeMarini et al.)

Dibromonitromethane— —DNA Adducts DNA Adducts Dibromonitromethane 600 Control # 70 600 Control #10 Male Rat Liver DNA Female Rat Liver DNA 500 500 Butanol Extracted Butanol Extracted 9 9 (0.32 *10 ) (0.24 * 10 ) 400 400 DBNM produces DNA 300 300 1.49 1.37 1.16 1.26 1.26 1.49 200 200 adducts in the livers of P-32 Disintigrations per Minute (DPM) 100 100 rats after only 30 days 0 0 600 1200 High Dose Male # 58 DNBM High Dose Female # 119 DNBM of exposure Liver DNA Butanol Extracted Liver DNA Butanol Extracted 500 1000 9 9 (7.7 * 10 ) (3.7 * 10 ) 400 800 1.49 (in vivo, male and 1.37 1.26 300 600 0.88 1.16 1.16 0.88 200 400 female rats) 100 200 0 0 Tony also now seeing 600 1200 High Dose Female High Dose Male # 59 DNBM 1.26 # 120 DNBM Liver Liver DNA Butanol Extracted 500 1000 DNA Butanol effects in normal 9 (2.3 * 10 ) 9 Extracted (13.6 * 10 ) 400 800 1.26 9 1.4 human colon cells 0.95 1.12 300 0.88 600 7 1.3 1. 2 1 200 400 0. 5 8 9 0.8 100 200 0 0 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 Retention Time (min) Data courtesy of Tony DeAngelo & Leon King, U.S. EPA, NHEERL, RTP, NC

Iodo-THMs THM4 Iodinated THMs CHCl 2 I 12 CHCl 2 Br 10 8 THM ( μ g/L) CHClBr CHCl 3 6 2 4 CHClBrI CHClI 2 CHBr 2 I 2 CHBrI 2 0 Iodinated THMs 1 CHBr 3 3 Cl 2 2 Cl 3 THM4 4 1 Cl 5 0 Cl 6 Krasner, Weinberg, Richardson, et al., Environ. Sci. Technol . 2006, 40, 7175-7185.

New Iodo-Acids I I O O C C OH H Br C C OH H H Iodoacetic acid Bromoiodoacetic acid O O O O I C OH Br C OH HO C C OH C C C C C C I CH 3 Br H I H (Z) -3-Bromo-3-iodopropenoic acid (E) -3-Bromo-3-iodopropenoic acid (E) -2-Iodo-3-methylbutenedioic acid Initially discovered using GC/MS Highly genotoxic Increase in formation with NH 2 Cl vs. Cl 2 Occurrence Study now completed (23 cities in U.S. & Canada) Richardson et al., Environ. Sci. Technol. 2008, 42, 8330-8338.