GUIDANCE FOR THE CALCULATION OFCANCER AND NON-CANCER RISK FROMINHALATION EXPOSURES:AN UPDATEMichael Sivak, EPA Region 2EPA Risk Assessors AnnualConferenceMay 3, 2006TopicszPurpose of the documentzProject historyzWorkgroup memberszComparison of previous and updated inhalationmethodologieszExample issues discussed by workgroupzNext StepsPurpose of DocumentzTo update existing Superfund guidance on calculatingcancer risk and non-cancer hazard from contaminantexposures through the inhalation route (e.g., RAGS, PartA) to be consistent with current science concerninginhalation dosimetry.zDocument will endorse the use of the ReferenceConcentration (RfC) and Inhalation Unit Risk (IUR)approach to inhalation risk assessment instead of the useof Inhalation Reference Doses (RfDis) and inhalationCancer Slope Factors (CSFis).zDocument will provide recommendations concerning keyissues in inhalation risk assessment (e.g., route-to-routeextrapolation).Project HistoryzOctober 1994 –EPA publishes “Methods forDerivation of InhalationReference Concentrationsand Application of Inhalation Dosimetry.”zJuly 1996 & December 2002– EPA publishes Soil Screening Guidancedocuments implementing the RfC/IURapproach in developing risk-basedSoil Screening Levels(SSLs) for volatile contaminants.zSeptember 2003- EPA Workshop, “Inhalation Risk Assessment: ASuperfund Focus.” Strawman document presented.zFall 2004- Industrial Economics (IEc)updates Strawman based oncomments and discussion from workshop. Outline of draft guidancedocument prepared.zSpring 2005– Inhalation risk workgroup established. Draft guidancedocument prepared by IEc fordistribution to EPA workgroup.zSummer 2005– Draft guidance document distributed to EPA workgroupmembers. Bi-weekly conferencecalls begin to discuss key issues.zSpring 2006– Bi-weekly workgroup meetingsconclude. IEc begins toincorporate consensus decisions made by the groupinto the document.Workgroup MemberszDave Crawford (OSWER/OSRTI)*zMichael Sivak (Region 2)*zBrenda Foos (OCHP)zGary Foureman (ORD/NCEA)zAnn Johnson (OA/OPEI)zDeirdre Murphy (OAR/OAQPS)zHenry Schuver (OSWER/OSW)zJohn Stanek (ORD/NCEA)zNeil Stiber (ORD/OSP)zTimothy Taylor (OSWER/OSW)zJohn Whalan (ORD/NCEA)zSarah Levinson (Region 1)zJennifer Hubbard (Region 3)zOfia Hodoh (Region 4)zKevin Koporec (Region 4)zArunas Draugelis (Region 5)zCheryl Overstreet (Region 6)zJeremy Johnson (Region 7)zBob Benson (Region 8)zSusan Griffin (Region 8)zDaniel Stralka (Region 9)zMarcia Bailey (Region 10)zTyra Gettleman (IEc)zHenry Roman (IEc)zEric Ruder (IEc)* Co-chairPrevious Approach Compared to UpdatedApproach: CarcinogensPrevious Approach (RAGS, Part A):Chronic Daily Intake = CA x(IR/BW) x (ET x EF x ED)/ATCancer Risk = Intake x CSFiUpdated Approach (1994 Guidance):Exposure Concentration (EC)= (CA x ET x EF x ED)/ATCancer Risk = EC x IURWhere: CA = concentration in air; IR = Inhalation Rate; BW = bodyweight; ET= exposure time; EF = exposure frequency; ED = exposure duration; AT =averaging time; CSFi= inhalation cancer slope factor; and IUR =inhalation unit risk.Previous Approach Compared to UpdatedApproach: Non-CarcinogensPrevious Approach (RAGS, Part A):Chronic Daily Intake = CA x(IR/BW) x (ET x EF x ED)/ATHazard Quotient (HQ) = Intake/RfDiUpdated Approach (1994 Guidance):*Exposure Concentration (EC)= (CA x ET x EF x ED)/ATHQ = EC/RfCWhere: CA = concentration in air; IR = Inhalation Rate; BW = bodyweight; ET= exposure time; EF = exposure frequency; ED = exposure duration; AT =averaging time; RfDi= inhalation reference dose; and RfC = referenceconcentration.* = this example assumesa chronic exposure scenarioExample Issues Discussed by WorkgroupzProtectiveness of the updated approach for children and sensitivesubpopulations;zCalculating cancer risks from high-level exposures;zCharacterizing inhalation exposure scenarios and selectingappropriate toxicity data;zIdentifying inhalation toxicity data for less-than chronic exposures;zUse of route-to-route extrapolation;zDevelopment of screening levels for inhalation exposures;zAggregating risk across multiple exposure routes and chemicals;zCalculating risk for occupational scenarios; andzKey uncertainties in the inhalation risk assessment approach.Protectiveness of the Updated Approachfor Children and Sensitive SubpopulationszWorkgroup discussed comments raised during theinhalation workshop about the protectiveness of theupdated methodology for exposures to children andother susceptible subgroups. Commenters wereconcerned that the risk equations do not allow foradjustments for these groups.ResolutionzDocument will indicate that the 10-fold uncertainty factor (UF) forintra-species variability considered when deriving an RfC isdesigned to address variation insusceptibility across the humanpopulation. Document willalso highlight conservativeassumptions in the derivation of IURs.zRisk Characterization section will encourage risk assessors todescribe sensitive populations orindividuals within a populationthat may exist at a site and discusspotential uncertainty in riskestimates for these groups.zAppendix to the guidance document presents comparisons ofHuman Equivalent Concentrations(HECs) calculated using EPAdefault parameters with HECs calculated using age- and activitygroup-specific parameters.Route-to-Route ExtrapolationzWorkgroup addressed the issue of whether ornot to use route-to-route extrapolation of oraltoxicity data to generate an RfC or IUR for acontaminant lacking inhalation toxicity data.ResolutionzGuidance will recommend against performing route-to-routeextrapolation using default bodyweight and inhalation rateparameters. Document will indicate potential errors associatedwith this approach.zGuidance will recommend that risk assessor contact NCEA’sSuperfund Health Risk TechnicalSupport Center (STSC) forassistance.zIf no alternate value is available, document recommendsperforming a qualitative risk assessment, and addressing theissue in the uncertainty section of the risk assessment.Next StepszFirst round of workgroup meetings completed. IEc isrevising the draft guidance document, incorporatingworkgroup recommendations.zEarly June 2006:Revised draft sent to workgroup forreview.zLate June 2006:Workgroup meetings to discusscomments on draft; IEc to revise.zAugust 2006:Revised draft document circulated forbroader internal EPA review.zLate 2006:Document submitted for external peer review.