4Introduction Risk Assessment in the Safe Drinking Water Act (SDWA) Establishing public health protection goalsMaximum Contaminant Level Goal (MSLG)Estimating and comparing the benefits of risk reduction for regulatory optionsMaximum Contaminant Levels (MCLs)Treatment Technique (TT)Two aspects of SDWA regulations involve health risk assessments.
7What is Safe? Free from harm or risk Secure from threat of danger, harm, or lossZero riskAdapted from:
8What is Risk? Possibility of loss or injury, peril The chance of loss; the degree of probability of such lossAdapted from:
9Introduction What is risk? The probability of injury, disease, or death from exposure to a chemical agent or a mixture of chemicalsEPA definition from IRIS (Integrated Risk Information System)
10Developing NPDWR’s (National Primary Drinking Water Regulations) Risk Assessment 101Developing NPDWR’s (National Primary Drinking Water Regulations)
11National Primary Drinking Water Regulations (NPDWRs) Microorganisms7 standards addressing microorganisms3 bacteria, viruses, 4 indicators (i.e. turbidity)Disinfection Byproducts4 standardsDisinfectants3 standardsInorganic Chemicals16 standardsOrganic Chemicals53 standardsRadionuclidesCurrently there are 87 legally enforceable standards
12Key Steps for Developing NPDWRs Setting the MCLGHealth effects informationExposure informationRelevant information and procedures developed by EPA for risk assessment and characterizationAssess whether an MCL or TT is more appropriateIdentify and evaluate costs and effectiveness of treatment alternativesSpecify Best Available Technology (BAT)
13Key Steps for Developing NPDWRs Evaluate contaminant occurrenceNumber or systems affectedTo what degree are they affectedEvaluate contaminant exposureNumber of people affectedCharacterize compliance choices for regulatory alternatives
14Key Steps for Developing NPDWRs Develop multiple MCL (or TT) alternativesCompare benefits and costs; address uncertaintyDocument the underlying data and analyses to support the proposed or final ruleEconomic AnalysisHealth Criteria DocumentOccurrence and Exposure DocumentCost and Technology Document
16Maximum Contaminant Level Is enforceableSet as close to the MCLG as feasible“Feasible” is the level that may be achieved:Best available technology (BAT), treatment techniqueExamination for efficiency under field conditions and not solely under laboratory conditionsTaking cost into considerationRequires a determination as to whether the benefits justify the costs
17Treatment TechniqueAlternative to an MCL when it is not economically and technologically feasible to ascertain the level of the contaminantCommon for microbiological contaminantsA TT is also an enforceable standard involving a measurable procedure or level of technological performance (e.g. “Action Level”)Surface Water Treatment RuleLead and Copper Rule
19Components of Risk Assessment in Rulemaking Health Effects EvaluationDose-Response AssessmentRisk CharacterizationRisk Management: Regulatory Alternatives DevelopmentHazard Identification• This slide provides a graphical overview of EPA’s risk-based rulemaking process.• Hazard Identification -Determine if a contaminant is causally linked to particular health effects (e.g., cancer or birth defects), usually using data from other animals or test organisms.• Dose-Response Assessment -Characterize the relationship between the dose of a contaminant and incidence of an adverse health effect. There can be many different relationships depending on varying responses (cancer, acute illness).• Exposure Assessment -Determine the size and nature of the population exposed to the contaminant, and the length of time and concentration of the contaminant (need to consider age and health of the exposed population, and other factors).• Risk Characterization – Integrate the first three components, resulting in an estimate of the magnitude of the public health problem.• Regulatory Alternative Development – Formulate options to achieve compliance by evaluating multiple MCLs or TTs, comparing costs and benefits, and developing the regulatory structure.Exposure Assessment
20Types of Contaminants Microbiological Biological toxins Chemicals Waterborne pathogensBiological toxinsChemicalsNaturally occurringMan-madeUsed in commerce, pesticidesDisinfection products and byproducts
21Identifying Adverse Health Effects MagnitudeFrequencyRouteDuration of exposureTwo broad categories of health effects:CancerNon-cancer
22Exposure Assessment Acute Exposure – Short term exposure Chronic Exposure – Long term exposureCritical Periods – Period when an organ/system is most vulnerableRoute of exposure – inhalation, ingestion, dermalCarcinogenicity CategoriesCarcinogenic to HumansLikely to be Carcinogenic to HumansSuggestive Evidence of Carcinogenic PotentialInadequate Information to Assess Carcinogenic PotentialNot Likely to be Carcinogenic to Humans
23Sensitive Populations Infants and childrenPound for pound, drink more, eat more, breathe more than adultsDeveloping (i.e. lead)Immature organs may not be able to metabolize/ neutralize contaminantsHabits (i.e. putting objects in mouth, pica)Pregnant women & fetusesDeveloping organsCritical period
24Sensitive Populations Elderly peopleBiological changes associated with agingEx. ↓ blood flow ↓ metabolic rates ↓ kidney function ↓ ability to eliminate substances from bodyImmunocompromised individualsWeakened immune systemDrugs, cancer, transplant patients, HIV/AIDSParticularly sensitive to pathogens, may experience longer or more severe symptomsHighly exposed individualsHigher intake rates (i.e. athlete drinking more water than the average person)Occupational exposures
27MCLGs: Maximum Contaminant Level Goals Maximum level of a contaminant in drinking water at which no known or anticipated adverse health effect would occur, and which allows an adequate margin of safety.Do not consider cost and technology.Considerations in setting an MCLG:End-Point – cancer or non-cancerAcute or chronic exposure concernsSensitive populationsData obtained from epidemiological and toxicological studies
28Toxicological Studies Toxicology – the study of poisons and their actionsToxicological experiments oftenInvolve non-human experimentsInvolve small numbers of animalsHigh exposure dosesUse mathematical models to determine the concentration of the chemical that would cause disease in peopleEPA uses the studies with the greatest margin of safety (overestimation of risk)
29Toxicological Study Methods Some animals subjected to high doses of chemicalsNecessary to observe statistically significant rates of diseaseOther animals exposed to lower doses of chemicalsNecessary to provide data inputs for a dose-response curveLong-term carcinogenicity studiesUse these studies together to develop a dose-response curve
30Strengths and Limitations of Toxicology Studies Environmental Factors, i.e. exposure to contaminants can be controlledContaminant under studyOther exposuresFacilitates interpretation of resultsUncertainty associated with extrapolatingFrom high doses tested to environmentally relevant dosesFrom effects on animals to effects on humans
31Epidemiological Studies Epidemiology – the study of how, when, and where diseases occur in populations of humans, and the application of study results to control a public health problemStudies based on human exposureEpidemiologists seek to identify:Risk factors associated with the occurrence of diseaseProtective factors that reduce the risk of disease
32Linking Risk Factors and Disease Associations notCause & Effect
33Strengths and Limitations of Epidemiological Studies Especially useful where high rates of rare diseases occur in small populationsProvide data on the actual incidence of diseaseDose-responses and exposure estimates are not neededLess effective in determining the causes of common diseases in large populationsDifficulties in correlating data across geographic areasCannot definitively prove cause and effectOften involve occupational exposures or case studies
34Dose-Response Relationships CV = Comparison Value, i.e. RfDNOAEL = No Observed Adverse Effect LevelLOAEL = Lowest Observed Adverse Effect LevelExposure DoseUncertainty Factor(3 – 1000 X)Response• Once the data has been collected from the toxicological and epidemiological studies, a dose-response curve can be drawn. A dose-response curve is a quantitative or semi-quantitative relationship describing the dose (exposure) and response (adverse effect incidence).• Dose-response curves are derived by plotting the incremental risk of cancer (or illness) on the y-axis and the lifetime daily dose on the x-axis.• Mathematical curves are fitted to the observed data (curve fitting).• For genotoxic carcinogens, the curve goes through the 0,0 origin (that is, no threshold).• The slope of the dose-response curve is called the slope factor or potency factor (PF). This can be thought of as the risk corresponding to a chronic daily intake of 1 mg/kg-day of the contaminant involved.• Incremental lifetime cancer risk = chronic daily intake x slope factor.• The relationship between dose and response may be linear (proportional) or non-linear (disproportional). Using the curve, the corresponding responses can be estimated for specific doses.Assess the relevance of the critical studyReview other dose-response dataCVNOAELLOAELDose
35RfD = 𝑁𝑂𝐴𝐸𝐿 𝑈𝐹 ×𝑀𝐹 or 𝐿𝑂𝐴𝐸𝐿 𝑈𝐹 ×𝑀𝐹 Reference Dose (RfD)RfD = 𝑁𝑂𝐴𝐸𝐿 𝑈𝐹 ×𝑀𝐹 or 𝐿𝑂𝐴𝐸𝐿 𝑈𝐹 ×𝑀𝐹UF = Uncertainty Factorex. interspeciesMF = Modifying Factorex. Completeness of overall dataThe daily exposure level which, during an entire lifetime of a human, appears to be without appreciable risk – mg/kg/day
36Estimated Exposure Dose EXP = Exposure Dose Cwater = Concentration IR = Ingestion Rate FI = Fraction of intake from source ABSf = Bioavalability absorption factor EF = Exposure frequency ED = Exposure Duration BW = Body Weight AT = Averaging Time
37MCLG MCLG = 𝐷𝑊𝐸𝐿 ×𝑅𝑆𝐶 RfD (mg/kg-day) Determined from toxicological or epidemiological dataThe Drinking Water Equivalent Level (DWEL) (mg/L)computed from the RfD assuming 2 L/day consumption and 70 kg body weightRSC is applied to DWEL to get MCLG• A key assumption for noncarcinogens is there is usually an exposure-effect threshold; that is, a level below which exposures would be expected to show no increase in adverse health effects.• In evaluating threshold noncarcinogens, EPA assumes a drinking water intake of two liters per day and a body weight of 70 kilograms 154 pounds).• Exposure from other sources is also considered. The drinking water program commonly uses a “percentage” method in deriving MCLGs. That is, the percentage of total exposure accounted for by drinking water, referred to as the RSC, is applied to the RfD to determine the maximum amount of the RfD “allocated” to drinking water. A ceiling level of 80 percent of the RfD and a floor level of 20 percent of the RfD are used as defaults. In other words, the MCLG cannot account for more than 80 percent of the RfD, nor less than 20 percent of the RfD.MCLG = 𝐷𝑊𝐸𝐿 ×𝑅𝑆𝐶MCL = Maximum Contaminant LevelDWEL = Drinking Water Equivalent LevelRSC = Relative Source Contribution
38Carcinogens The MCLG is traditionally set at zero for all carcinogens Assumed to be genotoxic (affects the cell’s genetic material)No thresholdNon-zero MCLGs are possible, reflecting non-genotoxic mode of action considerations• For genotoxic carcinogens, exposure to any amount is assumed to involve a risk of producing cancer; that is, there is no threshold.• Genotoxic refers to carcinogens that interact directly with DNA.• Non-genotoxic refers to carcinogens that produce genotoxic effects by any of a variety of other processes, such as interfering with normal growth control mechanisms, or affecting enzymes involved in DNA synthesis, recombination, or repair.
39Cancer Risk Assessment EPA applies a model to the available dataset to calculate the “cancer slope factor”Experimental exposures are highCancer happens after low-dose exposuresCancer Risk is calculated using exposure calculations and the cancer slope factor𝑅𝑖𝑠𝑘=𝐶× 𝐼𝑅×𝐸𝐹×𝐸𝐷 𝐵𝑊×𝐴𝑇 ×𝑆𝐹×𝐴𝐷𝐴𝐹C = ConcentrationED =Exposure durationIR = Intake rateAT =Averaging timeBW = Body weightSF = Cancer slope factorEf = Exposure frequencyADAF = Age-dependent adjustment factor
40Cancer Risk Example of cancer risk 2.4 X 10-05 This means that the risk calculation estimates that there will be 2.4 extra cases of cancer per 100,000 people over a lifetime of exposure.10-05 = 1/100,000
41Health Advisories & Other Sources of Health Effects Information Risk Assessment 101Health Advisories & Other Sources of Health Effects Information
42EPA’s Health Advisories Serve as a technical guidance for federal, state, and local officialsHealth effectsAnalytical methodologiesTreatment technologiesTypesLifetime Health AdvisoryTen-day Health AdvisoryOne-day Health Advisory
43Drinking Water Standards and Health Advisories Prepared semi-annuallyContainHAsMCLGsMCLsOther information
44Other Sources of Health Effects Information Scientific LiteratureCCR – Consumer Confidence ReportsRequired by public water suppliers to be provided to customersSummarizes information regarding sources used, any detected contaminants, compliance, and educational informationIRIS – Integrated Risk In formation SystemMaintained by EPA:IRIS database is web accessible and contains human health information on more than 550 chemical substances
45Other Sources of Health Effects Information CDC – Centers for Disease Control and PreventionMaintains information on diseases, etiologies, and treatmentsMorbidity and Mortality Weekly ReportSurveillance Summaries for Waterborne Disease Outbreaks – USATSDR – Agency for Toxic Substances and Disease RegistryToxicological profiles,The World Health OrganizationGuidelines for Drinking Water Quality
48Key Terminology NPDWR – National Primary Drinking Water Regulation Legally enforceable standardLimits levels of specific contaminants that can adversely affect public healthMaximum Contaminant Level or Treatment TechniqueNSDWR – National Secondary Drinking Water RegulationNon-enforceable guidelineCovers contaminants that may cause cosmetic or aesthetic effectsMCLG – Maximum Contaminant Level Goal§ 1412(b)(4)(A): “…level at which no known or anticipated adverse effects… occur and which allows for an adequate margin of safety”Not enforceableMCL – Maximum Contaminant Level§ 1412(b)(4)(B):“…level… which is as close to the maximum contaminant level goal as is feasible”EnforceableMCLGs do not take cost and technologies into consideration. They are sometimes set at a level that water systems cannot meet. For most carcinogens (contaminants that cause cancer) and microbiological contaminants, MCLGs are set at zero because a safe level often cannot be determined.SDWA defines “feasible” as the level that may be achieved with the use of the best available technology (BAT), treatment technique, or other means specified by EPA, after examination for efficacy under field conditions (that is, not solely under laboratory conditions) and taking cost into consideration.
49Key Terminology TT – Treatment Technique § 1412(b)(7): “… in lieu of establishing a maximum contaminant level, if…it is not economically or technologically feasible to ascertain the level of the contaminant.”EnforceableMRDL – Maximum Residual Disinfectant LevelAnalogous to an MCLSets enforceable limits on residual disinfectants in the distribution systemMRDLG – Maximum Residual Disinfectant Level GoalAnalogous to an MCLG• For some contaminants, especially microbiological contaminants, there is no reliable method that is economically and technically feasible to measure a contaminant at particularly low concentrations. In these cases, EPA establishes treatment techniques.• A treatment technique is an enforceable procedure or level of technological performance that public water systems must follow to ensure control of a contaminant. Examples of rules with treatment techniques are the surface water treatment rule and the lead and copper rule.
50Key TerminologyDose – A measure of intake of a substance, usually expressed in units of mg/kg-day (mg of contaminant per kg body weight per day)RfD – Reference Dose: The daily exposure level which, during an entire lifetime of a human, appears to be without appreciable riskRSC - Relative source contribution: The percentage of the RfD remaining after considering other exposure routesNOAEL – No Observed Adverse Effect Level: A dose based on experimental data that appears to result in no adverse effects.LOAEL – Lowest Observed Adverse Effect Level: The lowest dose used in a study that results in an observed adverse effect.