1. Anne Fairbrother, Randy Wentsel, Bill Wood, Keith Sappington, and Pam Noyes Office of Research and Development SETAC North America Annual Conference November 2006 Anne Fairbrother, Randy Wentsel, Bill Wood, Keith Sappington, and Pam Noyes Office of Research and Development SETAC North America Annual Conference November 2006 Framework for Inorganic Metals Risk Assessment

2. Background There has been considerable interest in the Agencys assessments on metals and metal compounds There has been considerable interest in the Agencys assessments on metals and metal compounds promulgation of the Toxics Release Inventory (TRI) lead rulemaking promulgation of the Toxics Release Inventory (TRI) lead rulemaking development of the Agencys Waste Minimization Prioritization Tool development of the Agencys Waste Minimization Prioritization Tool

3. PBT framework is based on principles developed for organic substances that do not apply to metals PBT framework is based on principles developed for organic substances that do not apply to metals PBT framework does not distinguish between metal elements, metal compounds, or particulate size PBT framework does not distinguish between metal elements, metal compounds, or particulate size There is a major disconnect between the forms selected for toxicity testing and those in the marketplace There is a major disconnect between the forms selected for toxicity testing and those in the marketplace Challenge to the PBT Framework as Applied to Metals

4. BCFs for metals BCFs for metals vary with species and environmental conditions vary with species and environmental conditions show an inverse relationship with concentration show an inverse relationship with concentration are not a predictor of toxicity are not a predictor of toxicity Speciation and bioavailability are more meaningful than persistence when evaluating hazard potential Speciation and bioavailability are more meaningful than persistence when evaluating hazard potential Challenge to the PBT Framework as Applied to Metals

5. PBT framework lacks discriminatory power for metals All metals would satisfy the criteria to be a PBT

6. Metals Framework Develop a cross-Agency guidance for assessing metal and metal compounds Develop a cross-Agency guidance for assessing metal and metal compounds discussions within the Agency, with external stakeholders and with Congress discussions within the Agency, with external stakeholders and with Congress provide opportunities for external input, peer review and cross- Agency involvement provide opportunities for external input, peer review and cross- Agency involvement

7. Metals Framework Develop a comprehensive framework that could be the basis of future Agency actions Develop a comprehensive framework that could be the basis of future Agency actions Provide a consistent set of key guiding principles to be considered in assessing risks posed by inorganic metals Provide a consistent set of key guiding principles to be considered in assessing risks posed by inorganic metals Identify available methods, models, and approaches for use in metals risk assessments Identify available methods, models, and approaches for use in metals risk assessments Foster consistency across EPA programs and regions Foster consistency across EPA programs and regions

8. Phase I: Metals Action Plan Dec 2002 Phase II: Issue Papers Aug 2004 Aug 2004ScheduleSABReview PeerReview EnvironChemistry HumanHealth EcoEffects Exposure Bioavail.Bioaccum.

9. Phase III: Draft Metals Framework June 2004 Phase IV: Final Document and Agency Implementation Jan 2007 Implementation Jan 2007Schedule Phase III: Draft Metals Framework Dec 2004 Peer Input Workshop July 2004 SAB Review Feb 2005 - 2006 InterAgency Review August 2006 IntraAgency Review July 2006

10. Metals and Metalloids of Primary Interest Aluminum Aluminum Antimony Antimony Arsenic Arsenic Barium Barium Beryllium Beryllium Boron Boron Cadmium Cadmium Chromium Chromium Cobalt Cobalt Copper Copper Iron Iron Lead Lead Manganese Manganese Mercury (inorganic) Mercury (inorganic) Molybdenum Molybdenum Nickel Nickel Selenium Selenium Silver Silver Strontium Strontium Tin Tin Thallium Thallium Vanadium Vanadium Zinc Zinc

11. Framework TOC Executive Summary Ch 1 – Intro Ch 2 – Framework overview Ch 3 – Environmental Chemistry, Transport, and Fate Ch 4 – Human Health Ch 5 – Aquatic EcoRisk Ch 6 – Terrestrial EcoRisk Ch 7 -- References

12. Ch 1. Introduction Purpose and audiences Purpose and audiences Metals Framework Scope Metals Framework Scope Metals Assessment Context Metals Assessment Context National ranking and categorization National ranking and categorization National risk assessments National risk assessments Regional and local risk assessments Regional and local risk assessments Key Principles to Consider Key Principles to Consider

13. Ch 1. Introduction Purpose and audiences Purpose and audiences Metals Framework Scope Metals Framework Scope Metals Assessment Context Metals Assessment Context National ranking and categorization National ranking and categorization National risk assessments National risk assessments Regional and local risk assessments Regional and local risk assessments Key Principles to Consider Key Principles to Consider

15. Principles Metals are naturally occurring constituents in the environment and vary in concentrations across geographic regions. Metals are naturally occurring constituents in the environment and vary in concentrations across geographic regions. All environmental media have naturally occurring mixtures of metals, and metals often are introduced into the environment as mixtures. All environmental media have naturally occurring mixtures of metals, and metals often are introduced into the environment as mixtures.

16. Natural occurrence of barite (USGS)

17. Principles Some metals are essential for maintaining proper health of humans, animals, plants, and microorganisms. Some metals are essential for maintaining proper health of humans, animals, plants, and microorganisms.

18. Principles Unlike organic chemicals, metals are neither created nor destroyed by biological or chemical processes Unlike organic chemicals, metals are neither created nor destroyed by biological or chemical processes They can transform from one species to another (valence states) and can convert them between inorganic and organic forms. They can transform from one species to another (valence states) and can convert them between inorganic and organic forms. The absorption, distribution, transformation, and excretion of a metal (toxicokinetics) within an organism depends on The absorption, distribution, transformation, and excretion of a metal (toxicokinetics) within an organism depends on the metal the metal the form of the metal or metal compound the form of the metal or metal compound the organisms ability to regulate and/or store the metal. the organisms ability to regulate and/or store the metal.

19. Ch 2. Framework Over view Human Health and Ecological Risk Assessment: Planning and Problem Formulation Human Health and Ecological Risk Assessment: Planning and Problem Formulation Metal Conceptual Model Metal Conceptual Model Assessment Phase Assessment Phase Bioavailability Bioavailability Characterization of Exposure Characterization of Exposure Characterization of Effects / Hazard Analysis Characterization of Effects / Hazard Analysis Risk Characterization Risk Characterization

20. Conceptual Model for Metal Risk Assessments

21. Assessment Questions Principles are translated into assessment questions to assist in their consideration Principles are translated into assessment questions to assist in their consideration Questions drafted for all phases of the risk assessment Questions drafted for all phases of the risk assessment

22. Example Assessment Questions BACKGROUND: How should background (natural and anthropogenic) levels for metals be characterized for the selected spatial scale of the assessment? BACKGROUND: How should background (natural and anthropogenic) levels for metals be characterized for the selected spatial scale of the assessment? MIXTURES: Are toxicological effects of metal mixtures being incorporated in the effects assessment? MIXTURES: Are toxicological effects of metal mixtures being incorporated in the effects assessment? ESSENTIALITY: How will both toxicity and deficiencies of essential metals be characterized? ESSENTIALITY: How will both toxicity and deficiencies of essential metals be characterized? METAL FORMS: Since environmental chemistry is a primary factor influencing metal speciation and subsequent transport, uptake, and toxicity, how will it be included in the risk assessment? METAL FORMS: Since environmental chemistry is a primary factor influencing metal speciation and subsequent transport, uptake, and toxicity, how will it be included in the risk assessment?

23. Ch 3. Environmental Chemistry, Transport, and Fate Introduction and Terminology Introduction and Terminology Hard and soft acids and bases Hard and soft acids and bases Transformations Transformations Aquatic chemistry Aquatic chemistry Ground water and metals mobility Ground water and metals mobility Sediment chemistry Sediment chemistry Soil chemistry Soil chemistry Atmospheric behavior / chemistry Atmospheric behavior / chemistry Metal Transport and Fate Metal Transport and Fate Aquatic and terrestrial transport pathways Aquatic and terrestrial transport pathways Atmospheric fate and transport Atmospheric fate and transport

24. Bioavailability Issues Bioavailability of metals varies widely according to the physical, chemical, and biological conditions under which an organism is exposed. Bioavailability of metals varies widely according to the physical, chemical, and biological conditions under which an organism is exposed. Bioavailability should be explicitly incorporated into all risk assessments Bioavailability should be explicitly incorporated into all risk assessments Trophic transfer can be an important route of exposure for metals Trophic transfer can be an important route of exposure for metals but biomagnification of inorganic forms of metals in food webs is generally not a concern in metals assessments but biomagnification of inorganic forms of metals in food webs is generally not a concern in metals assessments

25. BAF/BCF Issues Certain metal compounds are known to bioaccumulate in tissues and this bioaccumulation can be related to their toxicity. Certain metal compounds are known to bioaccumulate in tissues and this bioaccumulation can be related to their toxicity. The latest scientific data on bioaccumulation do not currently support the use of bioconcentration factor (BCF) or bioaccumulation factor (BAF) values when applied as generic threshold criteria for the hazard potential of inorganic metal The latest scientific data on bioaccumulation do not currently support the use of bioconcentration factor (BCF) or bioaccumulation factor (BAF) values when applied as generic threshold criteria for the hazard potential of inorganic metal

26. BAF/BCF Issues Single value BAF/BCFs hold the most value for site-specific assessments extrapolation across different exposure conditions is minimized For regional and national assessments, BAF/BCFs should be expressed as a function of media chemistry and metal concentration for particular species (or closely related organisms)

27. Environmental Chemistry Metal speciation affects Metal speciation affects toxicity, volatilization, photolysis, sorption, atmospheric deposition, acid/base equilibria, polymerization, complexation, electron-transfer reactions, solubility and precipitation equilibria, microbial transformations, and diffusivity toxicity, volatilization, photolysis, sorption, atmospheric deposition, acid/base equilibria, polymerization, complexation, electron-transfer reactions, solubility and precipitation equilibria, microbial transformations, and diffusivity Speciation includes Speciation includes free metal ions, metal complexes dissolved in solution and sorbed on solid surfaces, and metal species that have been co-precipitated in major metal solids or that occur in their own solids. free metal ions, metal complexes dissolved in solution and sorbed on solid surfaces, and metal species that have been co-precipitated in major metal solids or that occur in their own solids.

28. Environmental Chemistry pH and redox potential affect speciation pH and redox potential affect speciation Kd values Kd values limited use of single values limited use of single values Aging of metals in media reduces bioavailability Aging of metals in media reduces bioavailability Metal sorption behavior affects bioavailability Metal sorption behavior affects bioavailability

29. Ch 4. Human Health Risk Assessment for Metals Metals Principles Metals Principles Human Exposure Assessment Human Exposure Assessment Background Background Bioavailability Bioavailability Susceptible populations Susceptible populations Environmental release, transport and fate Environmental release, transport and fate Route-specific differences in effects Route-specific differences in effects Integrated exposures Integrated exposures Biomarkers Biomarkers Hazard Characterization Hazard Characterization Mixtures Mixtures Essentiality Essentiality Forms of metals Forms of metals Toxicokinetics / toxicodynamics Toxicokinetics / toxicodynamics Metal toxicity Metal toxicity Dose-response assessment Dose-response assessment Risk Characterization Risk Characterization

30. Human Health The organ or tissue in which metal toxicity occurs may differ from the organ or tissue(s) in which the metal bioaccumulates and may be affected by the metals kinetics The organ or tissue in which metal toxicity occurs may differ from the organ or tissue(s) in which the metal bioaccumulates and may be affected by the metals kinetics Both the exposure route and the form of a metal can affect the metals carcinogenic potential and its noncancer effects Both the exposure route and the form of a metal can affect the metals carcinogenic potential and its noncancer effects Sensitivity to metals varies with age, sex, pregnancy status, nutritional status, and genetics Sensitivity to metals varies with age, sex, pregnancy status, nutritional status, and genetics

31. Human Health Metals attached to small airborne particles are of primary importance for inhalation exposures. Metals attached to small airborne particles are of primary importance for inhalation exposures. Because the diets of humans and other animals are diverse, there may be wide variability in the dietary intake of some metals (e.g., in seafood) Because the diets of humans and other animals are diverse, there may be wide variability in the dietary intake of some metals (e.g., in seafood) results in temporal, geographic or cultural variability of responses results in temporal, geographic or cultural variability of responses

32. Essentiality should be viewed as part of the overall dose- response relationship for those metals shown to be essential Essentiality should be viewed as part of the overall dose- response relationship for those metals shown to be essential Zinc IRIS document is an example Zinc IRIS document is an example RFDs should not be below RDAs Human Health

33. Essentiality and Toxicity

34. Aquatic Ecological Risk Assessment for Metals Metals Principles Metals Principles Characterization of Exposure Characterization of Exposure Background Background Forms of metals Forms of metals Exposure pathway analysis Exposure pathway analysis Fate and transport of metals Fate and transport of metals Bioavailability and bioaccumulation Bioavailability and bioaccumulation Characterization of Effects Characterization of Effects Essentiality Essentiality Toxicokinetics / toxicodynamics Toxicokinetics / toxicodynamics Metal mixtures Metal mixtures Critical body residues Critical body residues Risk Characterization Risk Characterization

35. Terrestrial Ecological Risk Assessment for Metals Metals Principles Metals Principles Characterization of Exposure Characterization of Exposure Natural occurrence of metals Natural occurrence of metals Forms of metals Forms of metals Exposure routes Exposure routes Soil transport and fate models Soil transport and fate models Toxicokinetics / toxicodynamics Toxicokinetics / toxicodynamics Soil invertebrate exposure Soil invertebrate exposure Plant exposure Plant exposure Wildlife exposure Wildlife exposure Characterization of Effects Characterization of Effects Essentiality Essentiality Toxicity tests Toxicity tests Metal mixtures Metal mixtures Critical body residues Critical body residues Plant and invertebrate toxicity Plant and invertebrate toxicity Wildlife toxicity Wildlife toxicity Risk Characterization Risk Characterization

36. Ecological Background levels refers to those concentrations of metals that derive from natural as well as anthropogenic sources that are not the focus of the risk assessment Background levels refers to those concentrations of metals that derive from natural as well as anthropogenic sources that are not the focus of the risk assessment metal concentrations vary widely over space and time metal concentrations vary widely over space and time are partially responsible for distributions of plants and wildlife are partially responsible for distributions of plants and wildlife

37. Ecological For aquatic organisms, routes of exposure include For aquatic organisms, routes of exposure include absorption across respiratory organs, dermal absorption, sediment ingestion, and food ingestion absorption across respiratory organs, dermal absorption, sediment ingestion, and food ingestion For terrestrial organisms, routes of exposure include For terrestrial organisms, routes of exposure include binding to roots, foliar uptake, dermal absorption, food, water, and soil ingestion, or inhalation binding to roots, foliar uptake, dermal absorption, food, water, and soil ingestion, or inhalation

38. Ecological For most metals, the free ionic form is most responsible for toxicity For most metals, the free ionic form is most responsible for toxicity Free-ion activity models are useful for establishing relative toxicity among metals in different media Free-ion activity models are useful for establishing relative toxicity among metals in different media BLM BLM FIAM FIAM Sediment toxicity is reduced by acid volatile sulfides, organic carbon and other factors that bind free ions and decrease bioavailability Sediment toxicity is reduced by acid volatile sulfides, organic carbon and other factors that bind free ions and decrease bioavailability Soil toxicity is affected by pH, CEC, and % organic matter Soil toxicity is affected by pH, CEC, and % organic matter

39. Ecological Inorganic metal compounds rarely biomagnify across three or more trophic levels Inorganic metal compounds rarely biomagnify across three or more trophic levels Effects addition models are a useful first approximation of acute toxicity of metal mixtures Effects addition models are a useful first approximation of acute toxicity of metal mixtures Critical body or tissue residues can be used for effects estimations but few data are available for metals Critical body or tissue residues can be used for effects estimations but few data are available for metals

40. Metals Framework, January, 2007 Metals Framework, January, 2007http://? Issue papers August 2004 Issue papers August 2004 http://cfpub2.epa.gov/ncea/cfm/rec ordisplay.cfm?deid=86119 Web Sites

41. Core Technical Panel Co-leads: Anne Fairbrother ORD/NHEERL Randy Wentsel OW/OST Randy Wentsel OW/OST Steering Committee: Bill WoodORD/NCEA/RAF Steve DevitoOEI/OIAA Alec McBrideOSWER/OSW Dave MountORD/NHEERL Keith SappingtonORD/NCEA Pam Noyes ORD/NCEA/RAF Gary Bangs ORD/NCEA/RAF Gary Bangs ORD/NCEA/RAF