1. Above and Beyond Drinking Water Guidelines: Health Canada’s challenges and progress Richard Carrier Head, Chemical Assessment Section Water Quality Science Division Water, Air and Climate Change Bureau Health Canada

2. 2 Background  Guidelines for Canadian Drinking Water Quality have been established for over 80 chemicals  Numerical value → Maximum Acceptable Concentrations (MACs)  MACs derived using epidemiological or toxicological studies looking at cancer & non- cancer effects  MACs established to protect from possible health effects from lifetime exposure to contaminant at the MAC

3. 3 Drinking water quality in Canada: Shared responsibilities  Guidelines developed in collaboration with the FPT Committee on Drinking Water and published by Health Canada  Health Canada provides science-based assessments  Provinces/territories generally use Guidelines when setting their own enforceable standards and objectives

4. 4 Addressing exceedances  MACs serve as benchmark by which drinking water quality can be verified through monitoring  Uncertainty of health effects if concentration of a specific chemical > MAC ?  Potential issues: Magnitude of “exceedance” over the MAC Magnitude of “exceedance” over the MAC Frequency of “exceedance” over the MAC Frequency of “exceedance” over the MAC Nature of potential health effects Nature of potential health effects

5. 5 Current approach in Guideline Technical Documents  Addressed this issue “qualitatively” with some wording: THMs (2006): “Because of the limitations in current scientific methodology, it is not possible to quantify the increased risk to human health when a drinking water supply exceeds the guideline value…Although individual measurements may exceed the guideline value, this would be of concern only if they caused the running average of quarterly samples to exceed the guideline value.” THMs (2006): “Because of the limitations in current scientific methodology, it is not possible to quantify the increased risk to human health when a drinking water supply exceeds the guideline value…Although individual measurements may exceed the guideline value, this would be of concern only if they caused the running average of quarterly samples to exceed the guideline value.” Chlorite/chlorate (2009): “ Short-term exceedances above the guideline value are unlikely to have an effect on health. However, in the event that monitoring data show elevated levels on a yearly basis, it is suggested that a plan be developed and implemented to address these situations. Chlorite/chlorate (2009): “ Short-term exceedances above the guideline value are unlikely to have an effect on health. However, in the event that monitoring data show elevated levels on a yearly basis, it is suggested that a plan be developed and implemented to address these situations.

6. 6 How to better address the issue?  Qualitative wording difficult for jurisdictions to interpret/implement  What we know: MAC protective for lifetime exposure to contaminant at MAC level  What we don’t know: Whether we can establish a “numerical value” that would be protective for a time-limited exposure to a specific drinking water contaminant  Request from F/P/T CDW to develop a protocol to address short-term exceedances over MAC (based on practical needs/time-frame)

7. 7 Protocol that was considered to address short-term exceedances  Approach used: Timeframe of exceedance: 5-7 years of exposure above MAC Timeframe of exceedance: 5-7 years of exposure above MAC Several case-studies were developed, including: Several case-studies were developed, including: THMsTHMs ArsenicArsenic  Different approaches are needed for contaminants causing different effects: Non-cancer Non-cancer Cancer Cancer

8. 8 Non-cancer endpoints: Similar approach to MAC derivation  Threshold endpoints Dose below which no effects are observed Dose below which no effects are observed Use NOAEL/LOAEL to derive Tolerable Daily Intake (TDI) Use NOAEL/LOAEL to derive Tolerable Daily Intake (TDI) TDI = NOAEL/LOAEL UFs UFs  Short-term considerations: Use a sub-chronic study to select appropriate NOAEL/LOAEL (different key study used to derive MAC) Use a sub-chronic study to select appropriate NOAEL/LOAEL (different key study used to derive MAC) Choose appropriate uncertainty factors based on study and database limitations Choose appropriate uncertainty factors based on study and database limitations

9. 9 Non-cancer endpoints: Limitations from use of sub-chronic studies  Sub-chronic studies are often “range-finding” for chronic studies (number of doses, dose spacing…)  Not all possible endpoints are examined following exposure  Some routes of exposure not relevant (I.V., I.P.)  Extrapolation of risk from sub-chronic studies to longer term exposure (5 years)

10. 10 Non-cancer endpoints: Limitations to approach (cont’d)  Approach cannot be used for some contaminants: Contaminants for which there are little or no sub-chronic data available Contaminants for which there are little or no sub-chronic data available Contaminants with reproductive or developmental effects, where a single exposure at a critical time could cause adverse health effects (e.g., TCE) Contaminants with reproductive or developmental effects, where a single exposure at a critical time could cause adverse health effects (e.g., TCE)  Approach cannot predict additional risk

11. 11 Cancer endpoints: Approach  Cancer is treated as a non-threshold endpoint, using the following assumptions: Theoretically, very small exposures can lead to increased risk Theoretically, very small exposures can lead to increased risk Non-constant dosing can be re-amortized to be constant over the standard lifetime – mathematical model Non-constant dosing can be re-amortized to be constant over the standard lifetime – mathematical model Amortized lifetime dose used in risk calculation Amortized lifetime dose used in risk calculation

12. 12 Cancer - Example Schematic Cancer - Example Schematic Concentration in drinking water (µg/L) Exposure duration (years) MAC 2 X MAC 70 0 0 Lifetime dose

13. 13 Concentration in drinking water (µg/L) Exposure duration (years) 70 0 0 5 Years MAC Lifetime dose Cancer - Example Schematic Cancer - Example Schematic 2 X MAC

14. 14 Concentration in drinking water (µg/L) Exposure duration (years) 70 0 0 Amortized Lifetime Dose MAC Lifetime dose Cancer - Example Schematic Cancer - Example Schematic 2 X MAC

15. 15 Cancer endpoints: Approach (cont’d)  Must still consider “acceptability” of risk level  Increased risk would be established using the same key study and methodology as used to derive the MAC  Amortized lifetime exposure used to estimate long-term effects of exceedance

16. 16 Cancer endpoints: Assumptions  Individual exposure throughout lifetime does not exceed the MAC except for the period that the exceedance occurs  Time and duration of exceedance exposure do not affect risk other than the amount they contribute to the cumulative lifetime dose  Vulnerability to the contaminant is the same for all periods of life (children, adults equally vulnerable)  A person maintains a constant drinking rate (1.5 L/day) and body weight (70 kg) from birth to age 70

17. 17 Comparison of approaches: Non-cancer vs cancer Non-Cancer  Based on different study than MAC subchronic subchronic  Uses TDI approach Determine NOAEL/LOAEL Determine NOAEL/LOAEL Estimate uncertainty factors Estimate uncertainty factors  Cannot easily calculate increased risk at a given dose (no model used to fit data) Cancer  Based on same study as MAC chronic  Based on acceptable risk Uses models to extrapolate lifetime risk for a given dose and duration of exposure  Can use models to calculate increased risk at a given dose

18. 18 Trihalomethanes  MAC of 0.1 mg/L, risk managed from health- based value (HBV) of 0.08 mg/L  HBV based on non-cancer endpoint of chloroform: treatment related liver changes (fatty cysts) in 7.5 year study in dogs  Short-term limit can be developed using sub- chronic study (3 weeks in mice corresponding to 2 years in humans) showing liver histopathological changes in females

19. 19 Trihalomethanes  Total THMs: short-term limit for 5-7 year exceedance NOEL = 7 mg/kg bw/day NOEL = 7 mg/kg bw/day UF = 10  10  3 UF = 10  10  3 (x 3: extrapolation from 2 to 5-7 years in humans) (x 3: extrapolation from 2 to 5-7 years in humans) Allocation to water 80% Allocation to water 80% Consumption 4.11 Leq/day (multi-route exp.) Consumption 4.11 Leq/day (multi-route exp.)  Potential short-term limit = 0.3 mg/L = 300 µg/L

20. 20 Arsenic  MAC of 0.010 mg/L, risk managed from health- based value (HBV) of 0.0003 mg/L corresponding to 10 -5 risk  HBV based on internal cancers (liver, lung, bladder, kidney) in human studies  No short-term limit can be developed at an acceptable level of risk

21. 21 Arsenic (cont’d) Arsenic (cont’d) Duration of exceedance (months) Level of exposure (µg/L) Total amortized lifetime cancer risk (per 100,000) 840 10 (MAC) 3.0 – 39 1220 3.10 – 39.1 1250 3.24 – 40.7 6020 3.28 – 41.3 6050 3.93 – 49.5 6050

22. 22 Arsenic (cont’d) Arsenic (cont’d) Total Dose = MAC x duration + exceedance dose x duration = 10 µg/L x 780 months + 50 µg/L x 60 months = 10800 µg-months/L Amortized lifetime dose= total dose ÷ lifetime (70 years = 840 months) = 10800 ÷ 840 months = 12.86 µg/L New lower risk = lower unit risk x amortized lifetime dose = 3.06 x 10 -6 x 12.86 µg/L = 3.93 x 10 -5 New upper risk= upper unit risk x amortized lifetime dose = 3.85 x 10 -5 x 12.86 µg/L = 49.5 x 10 -5

23. 23 Lessons learned from Health Canada’s preliminary work  The approach considered has several limitations and challenges: Limited applicability of studies Limited applicability of studies need to quantify increased risks for both cancer and non-cancer need to quantify increased risks for both cancer and non-cancer  It also creates risk communication challenges Interpretation/application of “Big MAC” Interpretation/application of “Big MAC”  Need to identify and consider feasibility of other options

24. 24 Moving forward  Expert Workshop on risk assessment held in Ottawa, Ontario, Feb. 2010.  Objectives of workshop: To share and compare scientific information on approaches/methodology used in risk assessment (U.S. EPA and Health Canada) To share and compare scientific information on approaches/methodology used in risk assessment (U.S. EPA and Health Canada) To seek recommendations from experts on how to deal with short-term exceedances of drinking water guidelines To seek recommendations from experts on how to deal with short-term exceedances of drinking water guidelines

25. 25 Expert workshop  List of Experts: Dr. John Lipscomb, National Center for Environmental Assessment- Cincinnati Division, US EPA; Dr. John Lipscomb, National Center for Environmental Assessment- Cincinnati Division, US EPA; Dr. Kannan Krishnan, Environmental and Occupational Department, Université de Montréal; Dr. Kannan Krishnan, Environmental and Occupational Department, Université de Montréal; Dr. Rita Schoeny, Office of Water, US EPA, Washington Dr. Rita Schoeny, Office of Water, US EPA, Washington Dr. Michael Dourson, TERA, Cincinnati Dr. Michael Dourson, TERA, Cincinnati Dr. Bette Meek, University of Ottawa (Health Canada) Dr. Bette Meek, University of Ottawa (Health Canada)

26. 26 U.S. EPA approach  Derives health advisories for drinking water, which are not legally enforceable: One-day health advisory One-day health advisory Ten-day health advisory Ten-day health advisory  While this approach has its advantages, it does not address the need of the provinces and territories for an acceptable level for a 5-7 years time frame

27. 27 Framework proposed by experts  Developed based on discussions that took place throughout the workshop  A tiered approach was proposed Progressively more data-intensive and complex Progressively more data-intensive and complex Flexible – approach can vary depending on nature of question Flexible – approach can vary depending on nature of question  Takes advantage of existing risk assessment methodologies No need to design a novel approach No need to design a novel approach  However, it is based on regulatory requirements which are not relevant in Canada

28. 28 Proposed framework for assessing risk above the guideline Tier 1 Perform a Screening Evaluation Tier 2 Revise Risk Values Tier 3 Assess Risk C O M M U N I C AT I O N If required DATA&TIMEDATA&TIME

29. 29  Data requirements: Knowledge of how existing guideline was developed Knowledge of how existing guideline was developed  Assessment options: Review literature for more recent risk value Review literature for more recent risk value Determine whether exceedance falls within an acceptable “cushion” Determine whether exceedance falls within an acceptable “cushion”  If exposure exceeds newer risk values & the acceptable cushion, proceed to Tier 2 Tier 1 Perform a Screening Evaluation

30. 30 Proposed acceptable “cushions” Adverse effect upon which MAC is based Cancer Developmental effects (critical window of exposure) Other systemic effects Acceptable Ideal Tier 2 or 3 10 -5 10 -6 Ideal Tier 2 or 3 MAC Acceptable Ideal Tier 2 or 3 MAC POD MAC

31. 31  Data requirements: Knowledge of exposure of target population Knowledge of exposure of target population  Assessment options: Adjust source allocation factors or exposure parameters, based on other sources of exposure Adjust source allocation factors or exposure parameters, based on other sources of exposure If target population does not contain sensitive subpopulation, derive less conservative value If target population does not contain sensitive subpopulation, derive less conservative value  If exposure exceeds new risk value, proceed to Tier 3 Tier 2 Revise Risk Values

32. 32  Data requirements: Rich toxicological database for chemical Rich toxicological database for chemical  Assessment options: Employ sophisticated risk assessment tools to quantify the level of risk associated with the exposure (probabilistic methods, categorical regression) Employ sophisticated risk assessment tools to quantify the level of risk associated with the exposure (probabilistic methods, categorical regression) Calculate new risk values Calculate new risk values Scenario-specific – value for shorter durationScenario-specific – value for shorter duration More precise values – incorporate mode-of-action assessments, CSAFs, PBPK modelsMore precise values – incorporate mode-of-action assessments, CSAFs, PBPK models Tier 3 Assess Risk

33. 33 Next steps  Receive comments/approvals on draft framework from panelists  Publish proceedings from workshop  Determine the feasibility/relevance of the use of the approach by members of the Federal-Provincial-Territorial Committee on Drinking Water.