EPA/630/P-02/003A
June 2002
External Review Draft
Draft Action Plan
Development of a
Framework for Metals Assessment
and
Guidance for Characterizing and
Ranking Metals
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Metals Action Plan Workgroup
Bill Wood, ORD
Chair
Vanessa Vu, OPPTS
Past Chair
Ed Bender
Charles Delos
Steve DeVito
Chuck French
Alex McBride
Dave Mount
Kevin Minoli
ORD
OW
OKI
OAR
OSWER
ORD
OGC
Ed Ohanian
Keith Sappington
Marc Stifelman
Suhair Shallal
Randy Wentsel
John Whalan
OW
ORD
Region 10
OPPTS
ORD
OPPTS
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Executive Summary
Many EPA programs are faced with deciding whether and how to regulate toxic metals. These
decisions range from setting regulatory standards for environmental releases, to establishing safe
levels in different environmental media, to setting priorities for regulatory or voluntary efforts. A
basic input to the decision-making process for most EPA programs is an assessment of the
potential hazards and risks posed by the metal(s) to human health and the environment.
For the purpose of this document, the term "metals" refers to elements that have generally been
classified as metals or semi-metals (metalloids) based on their physical and chemical properties
in addition to inorganic and organic (organometallic) compounds of these elements. While in
concept the range of elements and compounds encompassed by this definition is broad, in
practice this action plan is focused on metals and metal compounds that are of most regulatory
concern to the Agency, such as selected transition metals and semi-metals.
Assessments of potential risk incorporate different levels of detail across EPA, from site-specific
analyses done to support individual permit decisions to broad national assessments which cover a
large range of possible exposure situations. The level of detail can vary from simplified hazard
screening analyses using default assumptions about various parameters to complex assessments
relying on large amounts of data and the use of sophisticated modeling procedures.
Hazard and risk assessments of metals and metal compounds raise issues not generally
encountered with organic chemicals. For example, metals are neither created nor destroyed by
biological and chemical processes, rather they are transformed from one chemical species to
another. Metal elements and some inorganic metal compounds are not readily soluble and as a
result toxicity tests based on soluble salts may overestimate the bioavailability and the potential
for toxicity for these substances. Some metals are essential elements at low levels (e.g., copper,
chromium, and zinc) but toxic at higher levels; while others which are non-essential (e.g. lead,
arsenic, and mercury) bioaccumulate and are toxic. Many organisms have developed
mechanisms to regulate accumulation of some metals to some extent, especially for essential
metals. In addition, each environmental form of the metal has its unique fate/transport,
bioavailability, bioaccumulation, and toxicity characteristics. These complexities put limits on
the generalizations that can be made about the hazard and risk that a metal and its compounds
pose to humans and ecological systems.
In recognition of the unique assessment issues raised by metals and the complexity of addressing
these issues consistently across the Agency's various programs, the Agency's Science Policy
Council (SPC) tasked an Agency work group to devise an Action Plan. The goal of this Action
Plan is to establish a process for developing guidance that will assure 1.) a consistent application
of scientific principles for assessing hazard and risk for metals, 2.) state-of-the-science
application of methods and data, 3.) A transparent process (i.e. articulating assumptions and
uncertainties), and 4.) the flexibility to address program-specific issues. It includes brief
descriptions of the Agency's metals assessment activities, and identifies the following critical
assessment issues that need to be addressed by this cross-agency guidance:
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Chemical speciation
Bioavailability
Bioaccumulation
Persistence
Toxicity
The work group recommends the development of two cross-Agency guidance documents:
A Framework for Metals Assessment
Guidance for Characterizing and Ranking Metals
The first document will be a Framework for Metals Assessment, to be completed by the end of
2003. This Framework will offer general guidance for EPA programs to use when considering
the various properties of metals in assessing the hazards and risks of metals and metal
compounds, such as speciation, bioavailability, bioaccumulation, persistence, and toxicity. The
Framework can serve as a basis for future Agency actions.
Whereas the Framework will consider issues and principles applicable across EPA's regulatory
activities, the Agency recognizes the need to take the next essential step of providing cross-
Agency guidance for applying these principles. Thus, the second document will be a Guidance
for Characterizing and Ranking Metals. It will provide the tools and specific guidance for
characterizing and assessing the hazards and risks of metals, and it will address critical needs
identified by the stakeholders. This guidance will specifically focus on delineating an assessment
approach for metals and metal compounds that can differentiate when appropriate among metals
and metal compounds, and can be applied in situations of priority setting, categorization, and
similar activities. This document will be developed in parallel with the Framework and will
follow the principles laid out in the Framework. It is anticipated that the Guidance for
Characterization and Ranking of Metals will be completed within five months of completing the
Framework. Together these documents should provide a reasonable, consistent, transparent, and
flexible approach for assessing metals and metal compounds that can help guide Agency risk
assessors and those conducting assessments for the Agency, and also provide a basis for planning
future research efforts to improve the Agency's assessment methodologies for metals.
Finally, this Action Plan sets out a process that will culminate in the production of the
Framework and the related Guidance for Characterization and Ranking of Metals. Public
involvement and peer review are a fundamental part of this process.
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Table of Contents
1. Background 1
2. Overview of Major Science Issues for the Framework 7
2.1 Chemical Speciation 7
2.2 Bioavailability 13
2.3 Bioaccumulation 17
2.4 Persistence 29
2.5 Toxicity 31
3. Description of the Framework 34
4. Description of the Guidance for Characterization and Ranking of Metals 38
5. Overall Approach and Schedule for Development of the Framework and Guidance 38
6. Outreach Activities 42
References 44
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1. Background
The goal of this Action Plan is to establish a process that will assure a consistent application of
scientific principles for assessing hazard and risk for metals, state-of-the-science application of
methods and data, a transparent process (i.e. articulating assumptions/uncertainties), and the
flexibility to address program-specific issues. For the purpose of this document, the term
"metals" refers to elements that have generally been classified as metals or semi-metals
(metalloids) based on their physical and chemical properties in addition to inorganic and organic
(organometallic) compounds of these elements. While in concept the range of elements and
compounds encompassed by this definition is broad, in practice this action plan is focused on
metals and metal compounds that are of most regulatory concern to the Agency, such as selected
transition metals and semi-metals.
Releases of metals and metal compounds to the environment pose concerns for many EPA
programs and cause these programs to take action. These actions can range from setting
regulatory standards for environmental releases, to establishing safe levels in different
environmental media, to setting priorities for regulatory or voluntary efforts. A basic input to the
decision-making process for most EPA programs is an assessment of the potential hazards and
risks posed by the metal(s) to human health and the environment.
There has been considerable interest in the scientific assessments that the Agency conducts on
metals and metal compounds as illustrated by recent events surrounding promulgation of the
Toxics Release Inventory (TRI) lead rulemaking (Lead and Lead Compounds; Lowering of
Reporting Thresholds; Community Right-to-Know Toxic Chemical Release Reporting; Final
Rule. 66 Federal Register, 4499-4547; January 17, 2001). During the drafting of a "White
Paper" by a technical panel of the Risk Assessment Forum for use in the Science Advisory Board
(SAB) review of the bioaccumulation potential of lead, it became clear that the development of
cross-agency guidance for assessing the hazards and risks of metal and metal compounds should
be a priority for EPA. Discussions between EPA and external stakeholders as well as concerns
expressed formally from the Congress, have led the Agency to develop a more comprehensive
approach to metals assessments that could be the basis for future Agency actions. Therefore the
Agency's Science Policy Council (SPC) has initiated a process to address the issues associated
with metals that will include opportunities for external input, peer review and cross-agency
involvement.
Problem Formulation - Establishing the Context for Evaluating Hazards and Risks of Metals
Assessments of hazard and risk can vary widely, from site-specific analyses to support decisions
regarding hazardous waste site remediation to very broad national assessments which cover a
large range of possible exposure situations. Within any particular type of assessment, the level of
detail can vary from simplified screening analyses using default assumptions about various
parameters to complex assessments relying on large amounts of data and the use of sophisticated
modeling procedures.
The first critical step for any evaluation of potential hazards and risks is Problem Formulation.
For the purpose of establishing a context for this Action Plan, three different regulatory examples
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are presented, namely: 1) Site-Specific Assessments, 2) National Regulatory Assessments, and 3)
National Hazard/Risk Ranking and Characterization. These scenarios illustrate the range of
assessment scenarios which require special attention when metals are involved. We will use
these examples to illustrate how technical issues may affect metal assessments. The issues
summaries identify questions to address in the Framework and the Guidance for Characterization
and Ranking of Metals.
Site-Specific Assessments
Site-specific assessments are typically done to inform a decision concerning a particular location.
An example is an assessment to determine appropriate soil cleanup levels at a Superfund site.
An accurate site-specific assessment for a metal requires knowledge of the form of the metal as it
enters the environment, the environmental conditions affecting the metal (climatological
conditions, soil geochemistry, water temperature and chemistry, etc.), the existence of plants
and/or animals which might accumulate the metal as well as the uptake factors for whatever
form(s) the metal may be in, plausible pathways and routes of exposures of organisms to the
metal, and the effect the metal will have on target organisms in whatever form it reaches that
organism. While many of these same factors also affect the risk potential of organic chemicals,
models for predicting fate, transport, and toxic properties are generally more robust for organic
chemicals than for metals.
As with any type of assessment, it may be appropriate to start with a screening level analysis
where variables are set to conservative default values to determine whether there is enough of a
potential problem to justify proceeding with a larger data collection and analysis effort. If the
screening level analysis indicates potential for unreasonable risk, a more detailed analysis might
be required to support decision making.
National Regulatory Assessments
National level assessments are typically done when the Agency is setting media standards or
guidelines for chemicals or other various risk-based regulations (e.g. Maximum Contaminant
Levels [MCLs], National Ambient Air Quality Standards [NAAQS], Residual Risk standards for
air toxics, ambient water quality criteria, Superfund soil screening levels, pesticide registrations)
or when the Agency is establishing national release and/or treatment standards for industrial
categories (e.g. Maximum Achievable Control Technologies [MACT] standards, effluent
guidelines, hazardous waste listings). The Clean Air Act list of hazardous air pollutants includes
numerous toxic metals that EPA must address through regulations and assessments. While many
of these latter standards have a large technical engineering component to them, risk evaluations
are sometimes conducted to ensure that the standards are appropriately protective and/or to assist
in selecting cost-effective alternatives.
While differing environmental conditions among specific locations can affect the risks posed by
metals or organic substances released in these locations, this variability may more significantly
affect the risk estimates for metals than for organic compounds. [Note: National standards
which apply at the point of exposure, such as MCLs, are less affected by these factors.] In order
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to do such assessments, there are several approaches the Agency commonly undertakes. One is
to define one or more exposure scenarios and to conduct a relatively detailed analysis. The
difficulty in this approach is in selecting the appropriate scenario; typically the Agency tries to
ensure that the scenario is conservative enough to be protective of the population at highest risk
(such as populations exposed above the 90th percentile) without being so conservative that the
standards are protective of hypothetical individuals whose calculated risks are above the real risk
distribution. In selecting the appropriate scenario, the Agency needs to consider all of the factors
which may affect potential risk, including environmental factors affecting the fate, transport,
exposure potential, and toxicity of the chemicals released. As has been mentioned before, these
factors may have greater impacts on the estimates of risks for metals than for organic
compounds.
Another common approach for a national assessment is to conduct a probabilistic analysis (such
as a Monte Carlo analysis) wherein the variability of the key factors is described by parameter
distributions which are used as inputs to a probability analysis procedure. The result is typically
an integrated distribution of potential risk levels. The difficulties in conducting this kind of
analysis are in developing appropriate distributions for each of the parameters, and in ensuring
that adequate attention is paid to potential correlations among key parameters. These correlations
are often more complex and difficult to describe for metals than for organic compounds.
National Hazard/Risk Ranking and Characterization
A third regulatory example for assessing potential hazard or risk is often used by the Agency
when it is attempting to set priorities or rank chemicals for different reasons, either for regulatory
activities or for other activities such as targeting voluntary pollution reduction efforts. This
includes programs which look at large numbers of chemicals as well as programs that focus
primarily on the inherent hazard of the chemical rather than on risk. In these cases, it is often not
feasible or it is outside the scope of the program to develop quantitative risk estimates across a
wide variety of potential releases as well as across the country. Therefore, the Agency may
choose to identify certain attributes of chemicals which it can then use as indicators of potential
risk.
Some attributes commonly used as indicators of hazard are 1) persistence, 2) bioaccumulation
potential, and 3) toxicity. The reasoning behind using these indicators is that toxic chemicals
that also persist and bioaccumulate are of particular concern because these properties may
increase the likelihood and extent of exposure of sensitive organisms to the chemical and thus the
likelihood of the chemical causing harm to the organism, or to consumers of the organism.
These indicators can be useful if they can be consistently estimated across chemicals. While the
Agency recognizes that there are always exceptions, the estimation process is generally more
straightforward for organics than for metals. The discussion of stakeholder comments that
follows identifies several issues in applying these attributes to assessments of metals and metal
compounds. Technical aspects of these and other issues are discussed in section 2.
Organic chemicals typically degrade in the environment (although the rates at which they degrade
vary tremendously), so persistence is measured or estimated as the chemical's half-life in
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different environmental media. When metals are viewed as elements, they are considered
persistent.
These programs often consider bioaccumulation because accumulation can result in significant
exposure to consumers of the organism which accumulated the chemical, or to the organism
itself. While these programs use measured bioaccumulation data, they may also rely on
estimation tools. Bioaccumulation potential for organic compounds in plants and animals can
often be estimated using a measured or calculated octanol/water partitioning coefficient, which is
an indicator of the degree to which a chemical can be absorbed by, and accumulated in, lipid
tissue.
Toxicity can be based on measured values for different types of animal or plant species, or can be
estimated based on structure-activity relationships. One factor that makes it comparatively
straightforward to determine these properties for an organic chemical is that, if the structure of
the chemical changes in the environment, then it no longer exists as that chemical and the
resulting compound is evaluated as a different chemical. In fact, persistence is the indicator of
the time that elapses before that process occurs.
For metals, the assignment of indicator values is more complex. A metal can exist in the
environment as an element or as a compound with other inorganic or organic elements. The
different metallic compounds can have significantly different properties from the element and
from each other. While the element itself is infinitely persistent in the environment, its chemical
form can change, and the different chemical forms can persist for different amounts of time.
Different chemical forms of a metal can interchange from one form to another. This process can
go on indefinitely. The specific form(s) which predominates is governed largely by prevailing
environmental conditions. Also, the chemical form of a metal can affect its toxicity and its
ability to bioaccumulate in the food chain. Thus, a particular chemical form that is not toxic or
capable of bioaccumulating may convert to a form that can bioaccumulate or cause toxicity, and
vice-versa. The ability of a metal to interconvert to different forms and the corresponding
influence that the interconversion has on exposure potential and toxicity poses significant
problems in ranking and characterizing metals.
Stakeholder Input
On February 20, 2002, EPA convened a one-day meeting to gather stakeholder input to help EPA
formulate an Action Plan for developing the Metals Assessment Framework. Specifically, EPA
solicited input on the following questions:
1. What organizing principles should the Framework follow?
2. What scientific issues should the Framework address?
3. What methods and models should be considered for inclusion in the Framework?
4. What specific steps should be taken to further involve the public and the scientific
community in the development of the Framework?
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Approximately forty stakeholders representing both industry and regulatory agencies attended the
meeting. With regards to Question 1 - What organizing principles should the Framework
follow?, organizing principles for the Framework suggested by the stakeholders included the
following:
• The Framework should provide a basis for identifying and prioritizing risks to the
environment that may be posed by some metals and metals species that is capable
of discriminating among metals, metal alloys, and other metal compounds with
respect to hazard and risk.
• The Framework should be developed using sound science, and be sufficiently
flexible to accommodate new methods and models as the understanding of the
factors that affect the fate, transport, bioavailability, and toxicity of metal
substances increases.
The Framework should allow for a tiered approach to accommodate differences in
purpose and availability of data.
• The Framework should recognize that consideration of "inherent toxicity" alone
has limited meaning with respect to metals and metal compounds, because
whether an inherently toxic metal will actually induce toxicity depends on the
extent of bioavailability.
• The Framework should focus initially on hazard assessment as a screening
mechanism while more detailed assessments for metals and metal compounds,
identified in the screening process, might include life cycle and uses of metals as
well as release and exposure data.
With regard to Question 2 - What scientific issues should the Framework address? and Question
3 - What methods and models should be considered for inclusion in the Framework?, the
stakeholders' suggestions included the following:
• Criteria and models properly incorporated into the Framework should reflect the
critical importance of speciation, transformation and bioavailability;
Valid approaches for assessing persistence should be incorporated;
Alternative approaches for assessing bioaccumulation should be considered;
• Determine what is considered significant bioaccumulation of metals in human
beings; and
• Differentiate between substances and elements.
With regard to Question 4 - What specific steps should be taken to further involve the public and
the scientific community in the development of the Framework?, the stakeholders suggested that
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EPA employ a variety of formal and informal mechanisms to further involve the public and the
scientific community in the development of the Framework. Mechanisms suggested include:
scientific workshops, Federal Register Notices, a website, and formation of cross-organizational
work groups.
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2. Overview of Major Science Issues for the Framework
As described earlier, the assessment of metals and metal compounds presents unique challenges
not generally encountered with organics in the development of an assessment framework. Based
on extensive public comment during the development of the TRI Lead Rule, publications in the
scientific literature, and discussions at the February 2002 stakeholder meeting, the EPA work
group has identified a set of interlocking issues that will need to be addressed in developing the
Framework. The following is a brief discussion of each issue. It is not the intent of this Action
Plan to provide a detailed review of the science underlying each issue (that will be done in
developing the Framework), rather this discussion is intended to identify the issues that must be
addressed by the Framework, to frame them in the context of the scientific debate and uncertainty
surrounding each issue, and to describe briefly how each issue is currently being addressed in
current Agency assessments.
2.1 Chemical Speciation
As elements, metals are infinitely persistent (i.e., they are never destroyed), but can exist
in different forms in the environment, transform from one form into another, or exist in
different forms simultaneously. The form, or "chemical speciation" of metals can vary
widely depending on the environmental conditions, and can be described in terms of
valence (oxidation) state, chemical formulation, physical composition at various scales,
and complexation with other chemicals or materials. These differences in chemical
speciation affect the environmental fate, bioavailability, and environmental risk of metals.
Compared to organic compounds, metals and metalloids exist in a much wider range of
physical and chemical forms, and can change reversibly or irreversibly from one form to
another under conditions found in the environment, or within organisms. Examples of
these various forms include different valence states (e.g., Cu°, Cu1+, or Cu2+), different
physical states (e.g., solid CuSO4 versus free Cu2+ in water; or gaseous elemental mercury
versus oxidized mercury), in association with different ions within a physical state (e.g.,
solid CuSO4 versus solid CuS), in different complexes (e.g., free aqueous Cu2+ versus
Cu2+ complexes with dissolved or colloidal organic carbon), or even in different
thermodynamic states within the same compound (e.g., amorphous FeS versus pyrite).
For purposes of this discussion, this entire range of chemical forms will be referred to
collectively under the term "chemical speciation."
Each of these forms can have unique physical, chemical, and toxicological properties,
which greatly complicate the assessment of environmental risk. For example, chemical
form influences the fate of metals in the environment. Emissions of elemental mercury
disperse great distances, becoming part of the global atmospheric pool, but oxidized
mercury (e.g., mercuric chloride) dissolves in cloud water and can deposit close to an
emissions source. Free Cu2+ ion in the water column is likely to disperse from the site of
release through diffusion and through physical movement such as currents, while solid
CuS is likely to fall to the sediment and may remain within the sediment for long periods
of time. Speciation also affects the potential for uptake by organisms; free Cu2+ in water
binds more readily to fish gills than does CuS. Finally, speciation affects the toxicity of
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metals; free Cu2+ in water disrupts ion regulation in fish gills, while CuS does not. Also,
atmospheric Cr6+ is a known human carcinogen, but Cr3+ is not. While differences in
these properties are clear, it must be remembered that chemical speciation can be dynamic
in the environment. For example, Cr6+ emissions can transform into Cr3+ in the
atmosphere and in soils Cr3+ can transform to Cr6+. Also, a free Cu2+ ion exposed to free
sulfide will quickly precipitate as CuS. Alternatively, if anoxic sediment containing CuS
is resuspended into the oxygenated water column, the compound may experience
oxidation of the sulfide to sulfate, with concurrent release of the copper as free Cu2+.
Rates of such transformations vary widely as well; formation of CuS from aqueous Cu2+
and S2" is very rapid (seconds), while oxidation/dissolution of amorphous CuS is much
slower (hours to days) and even slower for mineralized CuS (covellite; years and
beyond). While the above discussion focuses on copper, all metals generally show this
kind of variety in chemical speciation, though the details may vary from metal to metal.
For many metals, it is believed that the free ion is the primary metal species that affects
toxicity to aquatic organisms. Accordingly, the key parameters that affect toxicity to
aquatic organisms for these metals are those that affect speciation, such as pH and
binding to inorganic and organic ligands (e.g., dissolved organic carbon). In addition to
factors that directly affect speciation, metal toxicity to aquatic organisms is also affected
by other dissolved ions (e.g., Na1+, Ca2+) which compete with metals for binding sites on
the gills or other respiratory surfaces of aquatic organisms. The combined effects of
chemical speciation and competition for binding have been described in a modeling
Framework known as the "Biotic Ligand Model" (BLM) as described by DiToro et al.
(2001) and Santore et al. (2001).
While the water column is perhaps the most studied route of metal exposure for aquatic
organisms, metals can also be taken up by aquatic organisms via the diet. While
accumulation of metal by aquatic organisms via the diet is well documented, it is less
clear what role dietary metals may play in actually causing toxicity. For metals such as
Hg (in the methyl form) and Se, dietary exposure has critical importance in determining
toxicity. For metals such as Cu, Cd, Zn, and Pb, however, the significance of dietary
exposure is much less clear (e.g., compare Woodward et al., 1994 and Mount et al.,
1995). Some models for the accumulation of metal by aquatic organisms have been
developed (e.g., Fisher et al., 2000; Roditi et al., 2000). It does appear, however, that
whole body burdens of metals may not relate directly to toxicity (e.g., Lee et al., 2000),
presumably because of differences in effects occurring via dietary and waterborne
exposure.
In the terrestrial environment, the mobility and solubility of contaminants depends on
numerous factors including specific physical and geochemical binding mechanisms that
vary among contaminants and soil types. Metals interact with soil through interactions
with the surface of particulate material in soils (adsorption), by penetration through the
particulate surfaces where the contaminant becomes associated with the internal material
(absorption or partitioning), and through specific contaminant reactions sometimes
referred to as chemisorption. Also metals, can associate with inorganic and organic
ligands and precipitate. Metals can complex with inorganic soil constituents, e.g.,
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carbonates, sulfates, hydroxides, sulfides, to form either precipitates or positively charged
complexes. Both complexation and precipitation reactions are pH dependent. Therefore,
although these metals can form complexes with a net negative charge, under most
environmentally relevant scenarios (pH = 4 to 8.5), these metals either precipitate or
exist as cationic species. Contaminants can partition between soil and water media as
they are released from interactions with the soil and soil constituents, thus released into
the pore-water (EPA, 2000). Metals in their various forms can exist in the pore-water as
charged species, as soluble complexes, or precipitate out of solution. Retention by soil is
usually electrostatic with cationic species and anionic species being associated with
negatively and positively charged sites on the soil, respectively. Aging or weathering of
soils can also affect the availability of many contaminants in soil (Alexander, 1995; Loehr
and Webster, 1996). In many instances, chemisorption and precipitation reactions during
aging act to decrease the mobility and/or availability of chemicals. As a result, test
results obtained from freshly spiked soils may differ from those from aged soils.
Current Agency Practice
While the risk assessment issues introduced by metal speciation are broadly recognized,
the degree to which speciation is, or can be, incorporated into Agency assessments and
programs varies. This is because programs vary in the degree to which fate, transport,
and exposure information can be known or predicted for relevant scenarios. Examples
are described below. The greatest consideration of chemical speciation generally occurs
in the context of site-specific risk assessments, such as those conducted under the
Superfund program.
Site-Specific Risk Assessment
Site-Specific risk assessments are conducted in support of various programs including
developing cleanup alternatives on Comprehensive Environmental Response,
Compensation, and Liability Act (CERCLA) sites, and similar sites administered by
States, Tribes, or other programs across the country (Clay, 1991). Depending on the size
and scope of the anticipated response actions, metals speciation data may be collected to
provide information to refine estimates of toxicity, bioavailability, mobility, persistence,
and source apportionment. If the anticipated actions are of sufficient magnitude, it may
be appropriate to commit resources for more detailed investigations. Often, metals
speciation data are gathered in conjunction with animal or human tests to determine
bioavailability and to explore relationships between speciation and bioavailability
(Casteel et al., 1997; Maddaloni et al., 1998). Concern is warranted whenever the species
of the chemical of concern on the site (and the environmental and receptor characteristics)
differs from the chemical used in exposure and toxicity values used to estimate risk.
Many of the bioavailability/speciation studies of lead or arsenic were conducted at large
mining or smelting facilities where the extensive area of contamination warranted
additional studies (LaVelle et al., 1991; Davis et al., 1992, 1994; Freeman et al., 1994;
Casteel et al., 1997; Maddaloni et al., 1998). Currently, estimates of bioavailability rely
on empirical biological data rather than in vitro methods which are currently under
development (U.S. EPA Technical Review Workgroup for Lead, 1999). Reliance on
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animal models limits the applicability of many bioavailability studies because of the
requisite time, expertise, and expense.
National Regulatory Assessments
In other cases, the Agency conducts assessments that are intended to apply broadly, across
situations where site-specific conditions may vary. Examples in this category would
include national Ambient Water Quality Criteria (AWQC) intended to protect aquatic
organisms from waterborne contaminants. In this case, some parameters of exposure are
known (e.g., exposure is from waterborne chemical), but all site-specific factors that
could affect speciation of a metal (and therefore its toxicity) are not known and/or
measured.
One feature of AWQC is that they apply "instantaneously" to the chemical as it exists in
the receiving water. As such, they can be based on the toxic form(s) of a metal to the
extent that is known and can be measured/predicted. In this way, they do not have to
directly consider changes in chemical speciation that may happen over time; they simply
stipulate conditions that should not be exceeded more often than the designated
exceedance frequency. While this allows AWQC to be more explicitly focused on the
toxic form(s) of a metal, it does not completely sidestep the need to understand changes
in chemical speciation that may occur following release of a metal. To regulate the
release of metal to which the AWQC (or State standard) applies, such as in a municipal or
industrial effluent, some assumptions about chemical fate must be made to relate the form
and concentration of a metal in the effluent to the expected speciation in the receiving
water.
Expanded consideration of chemical speciation in environmental regulation is clearly
demonstrated in the evolution of AWQC for metals. When originally formulated in the
early 1980's, they were applied on the basis of "total recoverable" metal in water.
Although even these early criteria explicitly recognized that the toxicity of metal was
affected by chemical speciation, the Agency felt at that time that these effects could not
be adequately accounted for based on current science. In the early 1990's, the Agency
revised this approach, based on the growing evidence that the aquatic toxicity of most
metals was more directly related to the concentration of dissolved metal, rather than total
recoverable. This is not to say that non-dissolved metal could not become dissolved and
cause toxicity, but that the toxicity of ambient water was best assessed on the basis of
dissolved metal. Today, scientific understanding of the aquatic toxicity of metals has
brought the Agency to the point where AWQC for certain metals are expected to be
revised and expressed on the basis of a chemical/biological model (the so-called "Biotic
Ligand Model"; DiToro et al., 2001; Santore et al., 2001) that describes the expected
toxicity of metal in water based on its chemical speciation, calculated from the co-
occurring concentration of several organic and inorganic constituents of the water (e.g.,
Ca, Mg, K, Na, HCO3", pH, dissolved organic carbon).
As another example, EPA also evaluates potential risks from metals in order to identify
which solid wastes should be classified as hazardous under the Resource Conservation
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and Recovery Act (RCRA). One of the primary concerns from waste disposal is potential
leaching to groundwater, so the Agency models the movement of metals leaching from a
landfill environment into groundwater and then to potential drinking water wells. Since
the fate and transport of metals in the subsurface environment are largely dependent on
the speciation of those metals, EPA has developed models to predict changes in
speciation under different subsurface conditions. For a national assessment, EPA
evaluates the potential mobility of metals under a range of hydrogeological settings.
National Hazard/Risk Ranking and Characterization
One of the great challenges in national hazard and risk ranking and characterization of
metals is that the context of such an assessment is generally very broad. Unlike site-
specific assessments of a metal, which consider environmental conditions and speciation
at a particular site, national assessments consider the many different environmental
conditions that exist throughout the country, the effect these different conditions have on
the fate and speciation, and the corresponding influence on the metal's availability,
bioavailability and toxicity.
Some EPA programs regulate metal compounds as metal groups. One example is EPA's
Toxics Release Inventory (TRI) Program, which was established under section 313 of the
Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA). The TRI
Program is a national, multimedia, hazard-based program, not a site-specific or media
specific program. Listing of a substance onto the TRI list of toxic chemicals is generally
based on the hazards of the chemical; existence of risk is generally not a pre-requisite.
Under EPCRA, Congress established categories of metal compounds, such as lead
compounds, copper compounds, and chromium compounds. Thus, any compound that
contains lead, copper, or chromium is a listed chemical, unless it is specifically delisted
or exempted as explained below. The TRI Program's policy for listing metals by
category is based on the tenant that if a metal itself can cause, or reasonably can be
anticipated to cause, a toxic effect, any compound that contains the metal is deemed to
have satisfied the listing criteria if the EPA concludes that the metal can become available
under environmental or biological conditions. The Agency has delisted specific metal
compounds from EPCRA section 313 where available data show that the intact
compound does not meet the toxicity criteria for listing, and that the associated metal is
not available under environmental or biological (i.e., in vivo) conditions.
Risk assessments are also conducted for air toxics (including several metals) under the
authority of Clean Air Act and related air programs. These risk assessments include
residual risk assessments for specific source categories as well as various studies
evaluating exposures due to multiple source types. In each case, because of data
limitations, various assumptions need to be made about speciation. For example, the
EPA is currently using dispersion and exposure models to estimate exposures and risks
due to inhalation exposures to air toxics across the nation due to emissions from many
stationary and mobile source categories. This National Scale Assessment includes
several metals. Speciation is an important issue for several air toxic metals, but
especially for chromium and nickel. In the initial assessment, based on limited data from
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a few source categories, the EPA assumed that an average of 34 percent of the chromium
is in the hexavalent form. This 34% assumption was used for all sources. In the next
version of the assessment, EPA plans to develop a more refined approach whereby an
assumption will be made for each source category based on the limited available data for
that particular source category or similar source types as well as engineering judgement.
For nickel, the approach for the National Scale Assessment was based on trying to
determine the fraction that is in insoluble form versus soluble form because we think the
insoluble form is much more likely to be carcinogenic.
Issue Summary No. 2.1.1: The environmental fate and effects of metals are
heavily influenced by chemical speciation and, for that reason, explicit
consideration of speciation will reduce uncertainty. At the same time, data
availability will affect the degree to which Agency assessment can incorporate
chemical speciation What approaches for considering chemical speciation
are most appropriate for different assessment types (site-specific risk
assessment, national assessments, ranking/prioritization)? What are the data
needs for these approaches? To what degree can these approaches be
extrapolated across different environmental settings, across different metals,
or among different forms of the same metal?
Issue Summary No. 2.1.2: Because metals can be converted from one chemical
species to another in the environment, different compounds of the same metal are
sometimes grouped for the purposes of hazard or risk assessment. For example,
AWQC generally consider all forms of dissolved metal collectively. Hazard
ranking schemes used by multimedia EPA programs, such as the TRI Program,
consider all compounds of a particular metal collectively unless there is explicit
reason not to. Are there approaches that could be used to decide when
compounds of the same metal should or should not be grouped?
Issue Summary No. 2.1.3: In assessments such as those used for national
ranking and/or prioritization, an assessment may be required to span a wide
variety of potential environmental release and exposure scenarios, and consider
different media, different environmental conditions, and different types of
organisms, both terrestrial and aquatic. In these cases, broad generalizations
about environmental fate and effects may be necessary. In some programs, the
Agency addresses this challenge through the use of standardized scenarios under
which potential risk is judged and/or compared. What is the efficacy of creating
generalized assessment scenarios for metals and metal compounds under
other programs, such as ranking/prioritization? Under what circumstances
would this be effective? What additional uncertainties would be introduced?
What other approaches to evaluating chemical speciation might be applied
when assessments are required for environmental situations that are highly
variable or even unspecified?
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2.2 Bioavailability
Bioavailability is a measure of the potential for entry of a contaminant into ecological or
human receptors and is specific to the receptor, the route of entry, time of exposure, and
the environmental matrix containing the contaminant (Anderson et al., 1999). Several of
the issues relating to availability of metals to aquatic organisms are discussed in the
previous section on chemical speciation. To avoid duplication, this section will focus on
human health and terrestrial wildlife. In this document, for human health and terrestrial
wildlife, we will define bioavailability as the fraction of the oral dose that is absorbed.
Thus:
D. .; ..;- mass of chemical absorbed
Bioavailability
mass of chemical administered
Concern is warranted whenever the species of a metal in a regulatory or criteria setting
process (and the environmental and receptor characteristics) differs from the metal forms
used in exposure and toxicity values used to estimate risk. Bioavailability is an important
consideration for metals and metal compounds which are typically complexed or
precipitated in the environment. The behavior and bioavailability of contaminants are
greatly influenced by their interactions with environmental media, such that not all metal
and metal compounds are equally available to biota. Several authors have stressed the
importance of abiotic factors in aquatic and terrestrial systems on the bioavailability of
contaminants and the influence they have on exposure (Linz and Nakles, 1997;
Alexander, 1995; Allen et al., 1999; DiToro et al., 2001).
Relating aquatic, soil, food, and air chemistry parameters as important factors in
estimating the availability of ingested metals is not a straightforward process. The
percent of ingested or inhaled metal or metal compound that is absorbed is a complex
issue that requires metal-specific and organism-specific data to address. Dissolution and
subsequent absorption of metals in the gut or lung needs to be considered when
addressing metal bioavailability. Additionally, particulate metals may be absorbed by
phagocytosis. While the availability of a metal in the environment is an important factor
in determining its bioavailability in aquatic species, it appears to be considerably less
important in controlling its bioavailability in humans or other terrestrial species. The
bioavailability of lead in humans, for example, from seemingly nonbioavailable forms is
well documented. There are numerous unfortunate cases in which children have been
poisoned by lead from ingestion of plaster chips that contain lead-based paint, or soils
contaminated with lead from fugitive releases from nearby facilities. Lead in its neutral
form is also bioavailable in humans from the inhalation route as well as the oral route of
exposure. Metal compounds that have limited availability in aquatic environments may
have appreciable bioavailability in humans. The main reason why the metal portions of
many poorly soluble, environmentally non-dissociable metal compounds are bioavailable
in humans from the oral route is due to the acidic nature of the gastrointestinal tract.
Hydrochloric acid in the gastrointestinal tract of humans (and other mammals ) reacts
with the metal compound to form, in most cases, a metal chloride, which is usually more
soluble.
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From a geochemical perspective, factors affecting metal bioavailability include metal
speciation and biotransformation, availability of complexing ligands (e.g., organic carbon,
chloride, carbonate, sulfide, manganese and ferrous oxides), competition by other cations
for membrane adsorption sites (e.g., calcium, magnesium), pH, redox, particle sorption,
sediment and soil physicochemical properties and hydrology. The weathering or ageing
of metals over time also can reduce their bioavailability. Both adsorption and absorption
partitioning processes are considered reversible, although mass transfer from the particle
to the pore-water can be constrained. In the case of interactions within a particle, a
contaminant can become sequestered or trapped through various physical and
contaminant alterations that occur over time, such that contaminant release is completely
constrained (EPA, 2000).
Menzie and Little (2000) examined the variation in the ingestion of contaminants by
terrestrial wildlife. They found for some wildlife species, the accumulation of metals
from food is the primary route of exposure, while for other wildlife incidental ingestion of
soils is the most important exposure route for metals. In addition, the absorption of
contaminants bound to incidentally ingested soil particles in the gut, is influenced by
other parameters including residence time and physiology of the organism.
Another factor in evaluating the bioavailability and risk of metals to human health and
wildlife is the type and availability of laboratory toxicity studies. Often, soluble metals
salts are used in toxicity tests where they can maximize the bioavailability of the metal
tested. There is typically little data on the relationship between the toxicity of the metal
salts tested with the metals forms in environmental media or ingested by humans and
wildlife. Resolution of these issues may require adjusting toxicity testing methods to
address metal species, development of validated in vitro methods to estimate
bioavailability, use of adjustment factors to relate toxicity data to environmental media,
and the continued development of models addressing forms of metals in the environment
and their toxicity.
An issue has also been raised regarding metals detoxification by certain organisms
through complexation with metallothionein or formation of intra- and extracellular metal
granules and the bioavailability of metals stored in these forms. Formation of these
insoluble, mineralized deposits has been documented for various metals across phyla.
Their formation is believed to represent a detoxification mechanism that in some cases
becomes a precursor to metal excretion by the organism. Some organisms including
many bivalves can store extremely high metal concentrations in the form of these
intracellular metal-containing granules apparently without experiencing noticeable toxic
effects. Furthermore, metals detoxification may not be an exclusive process, as some
organisms apparently display a range of storage (detoxification) and regulation
mechanisms (Rainbow, 1996). Thus, mechanisms for regulating or storing metals in
organisms may still result in accumulation of metabolically active forms which can exert
toxicity, a hypothesis advanced by (Borgmann, 1998) for explaining the lack of
correlation between chronic toxicity and tissue residues of copper in the amphipod,
Hylella azteca. While some organisms may have an ability to store metals in a form that
is not toxic to the organism in which the metal is stored, it is possible that the detoxified
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form may be bioavailable in a consumer organism (e.g., humans) and toxic to the
consumer organism.
Current Agency Practice
The Agency addresses bioavailability through the use of default values and in some cases
through the development of site-specific values supported by laboratory studies.
Bioavailability is not incorporated to a greater degree due to the complexity of the issues,
their associated uncertainties and scientific data gaps.
Site-Specific Risk Assessments
The Office of Solid Waste and Emergency Response has published Risk Assessment
Guidance for Superfund (RAGS), which is also applicable to site-specific risk
assessments not prepared for Superfund (U.S. EPA, 1989). Other Agency publications
that address site-specific risk assessments include the Residual Risk Report to Congress
by the Office of Air Quality Planning and Standards. The most common treatment of
bioavailability for all chemicals, including metals, is to assume that the bioavailability of
the metal exposure on the site is the same as the bioavailability used to derive the toxicity
value used to estimate risk. This is typically accomplished by relying on laboratory
toxicity tests, which measure administered, rather than absorbed doses. Guidance for
making adjustments to ensure consistent treatment of bioavailability assumptions in
exposure and toxicity is included as Appendix A in RAGS. Adjustments to
bioavailability may be needed to account for differences in the exposure medium, the
speciation, or the route of exposure assessed at the site and the toxicity value used to
predict risks.
Site-specific values may be developed if sufficient data are available (U.S. EPA, 1999).
Usually, this entails conducting a well designed animal feeding study with juvenile swine
identified as the preferred animal model. This has been accomplished at several sites
across the country including the Murray Smelter in CO; Palmerton, PA; Jasper County,
MO; Smuggler Mountain, CO; and the Kennecott site in Salt Lake City, UT.
National Regulatory Assessments
Due to the complex issues presented above and the associated uncertainties and data gaps,
the application of bioavailability factors or mechanistic models in risk assessments are
frequently not supported by available scientific data. While it is commonly known that
bioavailability of metals in the environment may be substantially reduced due to a
number of factors (e.g. complexation, precipitation, competition with environmental
ligands, sorption onto soils and sediments, formation of insoluble metal compounds),
screening risk assessments often assume the bioavailability of the species of metal in the
assessment is the same as the bioavailability of the species of metal used to develop the
toxicity value. This occurs principally because of a lack of validated data and models for
assessing/predicting gut absorption of ingested metals, dissolution of ingested metals,
biota specific detoxification of metals, toxicity relationship between the metal forms
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tested in the laboratory and the metal forms ingested, and other assessment specific
factors.
Default values have been developed for some metals. For example, lead risks are
typically assessed by predicting blood lead levels using the Integrated Exposure Uptake
Biokinetic Model for Lead in Children (IEUBK) developed by USEPA (U.S. EPA,
200la). Risks protective of children are considered protective of adults, including
pregnant women. The IEUBK model assigns default bioavailability factors to all lead
exposure media. The default values for air, water, and soil are 32%, 50%, and 30%,
respectively (U.S. EPA, 200Ib).
The risk assessment to the Part 503 rule, addressing the land application of sludge,
utilized almost exclusively empirical metal from soil to plant uptake data. That is, data
from a variety of soils, crops, cationic exchange capacities of soils, soil pH, soil carbon,
soil moisture were used. Therefore, overall bioavailability of metals from soil to
crops/vegetation were automatically integrated into the exposure assessments.
National Hazard/Risk Ranking and Characterization
As was discussed in section 2.1, quantitative considerations of bioavailability are difficult
due to the varying environmental conditions across the country, the need to be protective
of many different types of organisms in different media, the lack of bioavailability data in
organisms, and the increased uncertainly due to the broad scope of national hazard or risk
characterizations. To be sufficiently protective, decisions about national hazard/risk
ranking and characterization are usually driven by available toxicity data and whether
there exists environmental conditions within the United States that would cause a metal
to become or remain available in the environment, or favor formation of bioavailable
forms of the metal.
Issue Summary No. 2.2.1: Metal bioavailability has long been recognized as
being a function of environmental chemistry. Recent research has advanced the
current level of understanding of metal bioavailability to aquatic life via aquatic
exposures, e.g., the Biotic Ligand Model. Likewise the equilibrium partitioning
approach is a way to incorporate bioavailability into the evaluation of sediment
bound metals and metal compounds. To date, these approaches have been applied
to site-specific assessments How can the Agency apply these approaches or
other variants to differentiate among metals for the purposes of national
regulatory standards setting or for hazard ranking and priority setting?
Issue Summary No. 2.2.2: Although approaches to assess the bioavailability of
metals in aquatic environments have been developed, the state of the science is
less developed in the case of humans and wildlife. What approaches/data
should be utilized for these receptors? In particular how can bioavailability
be used in hazard ranking and priority setting purposes?
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Issue Summary No. 2.2.3: Addressing bioavailability for most metals is limited
principally due to lack of validated data and models for assessing/predicting gut
absorption of ingested metals, dissolution of ingested metals, and biota-specific
detoxification of metals. Metal and metal compound specific issues and
physiological and sub-population variability of humans and terrestrial wildlife-
specific issues need to be addressed What methods should be applied or
developed to address these complex issues?
Issue Summary No. 2.2.4: The toxicology data base utilized to assess the
hazard or risk of many metals due to ingestion exposure in humans and terrestrial
wildlife is largely based on test animals exposed to soluble metal salts. Relating
metal speciation to toxicity in aquatic organisms is addressed in the chemical
speciation section. There are typically little data on the relationship between the
toxicity of the metal salts tested with the metals forms found in environmental
media or ingested by humans and wildlife. Resolution of these issues may require
adjusting toxicity testing methods to address metal species, use of adjustment
factors to relate toxicity data to environmental media, and the continued
development of models addressing forms of metals in the environment. What
methods or approaches should be applied or developed to reduce the
uncertainty resulting from current methods used in mammalian toxicity tests
(e.g. testing with metal forms common in the environment, development of
models to relate toxicity to environmental media, or measurement of
absorbed dose in toxicity tests)?
Issue Summary No. 2.2.5: The levels of metals that commonly occur in soils are
typically referred to as background. Background concentrations can vary due to
soil type, depth, and region of the country. Due to this variation, background
metal levels in soils are typically addressed on a site-specific basis. When doing
national level assessments, how should the Agency address background and
have criteria that are conservative and protective of human health and
wildlife?
2.3 Bioaccumulation
Plants and animals accumulate many chemicals in their tissues, including metals and
metal compounds, as a result of chemical exposure through external media such as water,
air, food, soil, and sediment. This process is called bioaccumulation. For aquatic
organisms, bioaccumulation has been defined as the net accumulation of a chemical in
tissue that results from exposure to all environmental sources including water and diet
(U.S. EPA, 1995; 2000a; Newman, 1998). This differs somewhat from the term
bioconcentration which refers to uptake and accumulation of a chemical from water
exposure only. For a given exposure condition, bioaccumulation and bioconcentration
can be viewed simply as the net result of the competing processes of chemical uptake and
elimination by an organism. Although simple in concept, many factors can affect the
magnitude of chemical bioaccumulation by an organism. Some of these factors include
the physicochemical properties of the chemical, the magnitude and duration of exposure,
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the biology, physiology and feeding ecology of the organism, and environmental factors
affecting the chemical's bioavailability. With respect to metals, chemical speciation is
one key determinant of bioavailability and bioaccumulation. Although the
aforementioned nomenclature has been more commonly applied to aquatic organisms, the
bioaccumulation process clearly applies to terrestrial organisms including humans.
Bioaccumulation itself is not a measure of an effect, adverse or otherwise. Rather, it
reflects a measure of a chemical's transfer between environmental and biological
compartments. For a number of chemicals and organisms, bioaccumulation is required to
sustain life (e.g., for essential trace elements such as zinc and copper). In other chemical
exposure situations, bioaccumulation produces residues in plants and animals that cause
direct toxicity to the exposed organism and/or indirect toxicity to those organisms which
consume it. Selenium is an example of an essential trace element that is both required at
low concentrations but harmful to aquatic and terrestrial organisms at higher
concentrations via direct and indirect (food chain) toxicity.
Some chemicals also biomagnify in aquatic food webs, a process whereby chemical
concentrations increase in aquatic organisms of each successive trophic level due to
increasing dietary exposures. Biomagnification appears to be restricted to certain types of
organic chemicals (e.g., highly hydrophobic, poorly eliminated organic compounds) and
also appears to be the exception rather than the rule for metals—with methylmercury
being one notable exception (Leland and Kuwabara, 1985; Beyer, 1986; Suedel et al.,
1994). In general, most inorganic forms of metals tend to biodilute in aquatic food webs,
a process where tissue concentrations decrease at higher trophic levels (Suedel et al.,
1994, Leland and Kuwabara, 1985). It should be noted, however, that lack of
biomagnification does not automatically imply a lack of exposure from trophic transfer.
Significant exposure through trophic transfer can occur in the absence of
biomagnification (i.e., biomagnification factors are simply one or lower). In the case of
selenium, such dietary exposures have been shown to have strong toxicological
significance. A number of cationic metals can be accumulated from the dietary exposure
pathway, but the toxicological significance of these exposures is still being investigated.
Bioaccumulation assessments have become integral components of many Agency
chemical assessment activities. Some of these activities include risk assessments of
mercury (U.S. EPA, 1997) and sewage sludge disposal practices (U.S. EPA, 1993),
derivation of water quality criteria to protect human health and wildlife (U.S. EPA, 1995,
2000a), development of ecological screening criteria for soils (U.S. EPA, 2000c) and
chemical hazard prioritization methodologies (U.S. EPA, 1999). Its growing importance
in the risk assessment and regulatory process has also led to considerable study of
bioaccumulation over the last few decades. For nonionic organic chemicals, substantial
progress has been made on identifying mechanisms and factors affecting the
bioaccumulation process. This research has led to the development of mechanistically-
based food web models which rely on assumptions of lipid and organic carbon
partitioning and measures of hydrophobicity to predict bioaccumulation across broad
classes of organic compounds (Gobas, 1993; Thomann, 1989). These models have been
used by EPA in the derivation of ambient water quality criteria (U.S. EPA, 1995, 2000a).
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For metals and metal compounds, such broadly applicable, mechanistically-based models
for assessing bioaccumulation across metal compounds have generally failed to gain
widespread regulatory application. The lack of broad application of mechanistically-
based models for metals largely results from the highly specific nature of the
bioaccumulation process with respect to different metal compounds, organisms and site
conditions. Some attempts have been made to generalize across metal compounds, such
as those quantifying the effect of body size on absorption and elimination rates for
inorganic substances (Hendriks and Heikens, 2001). For some specific metals,
mechanistically-based bioaccumulation models have been developed (e.g., Mercury
Cycling Model by Hudson et al., 1994; the Selenium Aquatic Toxicity Model by Bowie et
al., 1996; copper bioaccumulation in the amphipod, Hyalella azteca by Borgmann, 1998;
Thomann et al., 1997 for cadmium in rainbow trout). These models generally require a
substantial amount of site-specific or organism-specific data to accurately predict
bioaccumulation, and have yet to gain widespread regulatory application.
Current Agency Practice
The Agency currently relies on a variety of techniques to assess the bioaccumulation of
metals depending on the purpose of the assessment (e.g., site-specific risk assessment,
national risk assessment, national hazard/risk ranking and characterization). Common to
most of these bioaccumulation assessments for metals is a strong empirical basis.
Site-Specific Risk Assessments
For site-specific assessments, methods for assessing current condition of metals
bioaccumulation include direct measurement of metal residues in organisms at the study
site, in addition to in situ and ex situ methods, where organisms are exposed to
contaminated site media (water, sediment, soil) under field or laboratory conditions,
respectively. For example, standardized tests have been developed for evaluating
bioaccumulation of metals and other contaminants in sediments, including one for the
oligochaete, Lumbriculus variegatus (ASTM, 1997). Because some species are able to
regulate metals residues in their tissues and/or possess naturally high resides of certain
metals, the choice of species used to monitor metal bioaccumulation is critical.
In situations where bioaccumulation must be predicted under future conditions,
empirically-based accumulation factors (bioaccumulation factors, biota-sediment
accumulation factors, biota-soil accumulation factors) or site-specific regression
relationships (tissue residue vs. soil or sediment concentration) have been applied (e.g.,
Nan et al., 2002; Torres and Johnson, 2001a; Sample et al., 1999; 1998). Mechanistic
approaches including bioenergetic- or physiologically-based bioaccumulation models
have been used to describe and predict metals bioaccumulation, although their application
to site-specific risk assessments is less common compared to empirically-based
approaches. Some examples include Simas et al. (2001) for aquatic macrofauna, Saxe et
al. (2001) for earthworms, Ke and Wang (2001) for oysters, and Goree et al. (1995) for
cadmium bioaccumulation in terrestrial food webs.
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National Regulatory Assessments
By their very nature, national regulatory assessments often lack the data necessary to
incorporate all potentially important site-specific factors that can affect bioaccumulation.
This aspect, combined with the lack of generalizable constructs such as those commonly
used for organics (Kow, lipid and organic carbon partitioning), makes national metal
bioaccumulation assessments a challenging exercise. For national ambient water quality
criteria designed to protect human health and wildlife, EPA typically addresses
bioaccumulation of metals through the use of empirically-based bioconcentration factors
(BCFs) and bioaccumulation factors (BAFs). A BCF is determined from laboratory
exposures and accounts for uptake from water only. A BAF accounts for uptake from
water and diet and is usually determined in the field.
Various quality guidelines have been established for evaluating BCF data, most of which
are consistent with standard bioconcentration test protocols (e.g., ASTM, 1999). Because
a BCF or BAF for a given chemical and organism will vary depending on the exposure
duration up to the point where steady state is reached, BAF and BCF data are screened by
EPA to select those values which reflect longer-term accumulation in order to
approximate steady-state conditions. Since the protection goals of EPA water quality
criteria are known (i.e., protection of human health or wildlife), BAFs and BCFs are
selected for species and tissues that are most relevant to human and wildlife exposure.
Some limited guidance is provided for evaluating BAFs and BCFs for essential metals.
For example, EPA recommends that BCFs should be used only at exposure
concentrations that exceed the nutritional requirements of the organism, but below levels
causing adverse effects. Since bioavailability of metals (and for that matter, organic
compounds) may be a concern when applying national criteria to specific sites, EPA
water quality criteria encourages the development of site-specific BAFs to account for
bioavailability differences between the national BAF/BCF data set and the site(s) of
interest.
For establishing national ecological screening levels of metals in soil, empirically-based
soil-to-biota bioaccumulation factors and regression models have been developed and
applied (U.S. EPA, 2000c; Sample et al., 1999, 1998). Because variation in these factors
and regression models can be substantial (spanning several orders of magnitude),
conservative estimates of soil-to-biota BAFs have been used in screening applications. In
general, data for developing soil-to-biota accumulation factors are far more limited
compared to aquatic-based BAFs and BCFs.
National Hazard/Risk Ranking and Characterization
In the PBT frameworks used by several Agency programs, bioaccumulation is assessed
primarily through the evaluation of aquatic BCF and BAF data, although chemical
accumulation in humans has also been used for evaluating bioaccumulation potential.
Given the broad assessment goals of the PBT frameworks (i.e., ranking chemical hazard
based on all relevant exposure pathways, environmental media, and ecological and human
receptors), each species for which BCF data are available is given equal weight for
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comparison purposes. For example, for the final lead TRI rule, lead was classified as
bioaccumulative based on data from algal and bivalve species and on evidence of
bioaccumulation in humans (U.S. EPA, 2001a).
Bioaccumulation Issues
This section provides a discussion of several major issues confronting the Agency with
respect to interpreting and applying metals bioaccumulation data for various regulatory
purposes (metals categorization/ranking, water quality criteria derivation, national and
site-specific risk assessments). Several of these issues are centered on the use of BCF
and BAF data for metals because of their widespread regulatory application. The major
categories of metals bioaccumulation issues discussed below are:
1. Metals essentiality, regulation and interpretation of bioaccumulation data
2. Factors affecting metals bioaccumulation
3. Assessing bioaccumulation in terrestrial organisms
4. Selecting/weighting bioaccumulation data for different species
5. Interdependence of bioaccumulation and toxicity in characterizing metal hazard
Issue #1. Metals Essentiality, Regulation and Interpretation of Bioaccumulation Data
A number of metals are essential for maintaining proper biological function of terrestrial
and aquatic organisms. Some metals, including sodium, potassium, calcium, magnesium,
are required nutrients and serve important biological roles such as the maintenance of
chemiosmotic, electrophysiological, and structural (skeletal) function. These metals tend
not to be the focus of Agency regulatory and risk assessment activities. Other more
lexicologically relevant metals, such as copper, chromium, nickel, and zinc, are also
required micronutrients and are incorporated into various biologically important
macromolecules and metalloenzymes.
As a result of their direct role in cellular function and metabolism, organisms have
evolved strategies for regulating the accumulation of essential metals. One common type
of accumulation strategy has been documented for certain essential metals and species.
At low concentrations where organisms experience nutritional deficiency, greater uptake
and retention of metals occurs in order to achieve nutritional requirements. Above their
nutritional requirements, homeostasis of body burdens is maintained up to some
concentration limit in the organism. Beyond this point, metal detoxification and
elimination mechanisms can become saturated or disrupted thereby leading to increased
accumulation and toxicity to the organism or its consumers. Importantly, this
accumulation strategy is by no means universal across species (even for essential trace
metals). Closely related taxa can display widely differing accumulation strategies (e.g.,
regulation vs. storage) as reported by Rainbow and White (1989) and Borgmann (1998).
The regulation of metals by aquatic organisms (i.e., maintenance of constant or near
constant tissue concentrations over widely varying exposure concentrations) is thought to
be related to the mechanism of metal uptake. For metal ions, uptake into the organism is
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generally thought to occur through facilitated diffusion after binding of the metal ion to
membrane transport proteins or in some cases through active transport (Rainbow, 1996).
Organisms display other mechanisms for altering metal accumulation, including reducing
metal bioavailability via secretion of extracellular ligands, complexing metals via mucous
chelation, reducing the permeability of epithelial surfaces, reducing metals transport
across cell membranes, adopting behavioral modifications to avoid metal exposure and
altering metal elimination rates (Mason and Jenkins, 1995).
The regulation of metals accumulation by organisms leads to difficulties when
characterizing metals bioaccumulation based on simplified bioaccumulation indicators
(such as the BAF or BCF commonly used for aquatic organisms) and more complex
models (such as PBPK models and pharmacokinetic data commonly used for terrestrial
species including humans). For example, implicit with the use of BCFs and BAFs for
hazard ranking and criteria methodologies is the assumption that BCFs or BAFs are
independent of external exposure concentration, at least within typical ranges encountered
in the environment. This assumption essentially means that tissue residues are linearly
related to exposure concentration with a zero intercept, and that the same BCF can be
applied across different exposure concentrations for predicting tissue residues. For many
nonionic organic chemicals where chemical uptake is believed to occur primarily via
passive diffusion across biological membranes, the assumption of independence of
BCF/BAF with exposure concentration has generally been accepted, although theoretical
reasons exist to suggest it could be violated (e.g., when chemical metabolism is
important). For metals and metal compounds, departures from the assumption of
independence between the BCF (BAF) and exposure concentration have long been
recognized, particularly with essential trace elements for which accumulation is regulated
by many organisms (U.S. EPA, 1985; Spacie and Hamelink, 1985; Rainbow and White,
1989).
One complication associated with metals regulation is a dependency of BCFs on external
exposure concentration (e.g., declining BCFs with increasing exposure concentrations).
Thus, higher BCFs can be associated with lower tissue residues thereby reversing the
traditional concept that higher BCFs would lead to higher exposure and risk.
Observations of concentration dependency of BCFs are consistent with the notion of
metal uptake via facilitated diffusion, which would be expected to result in Michaelis-
Menton type saturation kinetics for metal uptake. Although BCF/concentration
dependency has commonly been described for essential trace elements, it has also been
documented for nonessential metals in some organisms (Brix and Deforest, 2000). This
and other information suggest that the mechanisms underlying metal regulation are not
necessarily specific to essential metals. Notably, concentration dependency and/or
similarity of tissue residues across varying exposure concentrations does not
automatically imply metal regulation. Such observations may result from artifacts of the
BCF or BAF study (e.g., short-term adsorption and growth dilution).
EPA has provided limited guidance on the BCF/concentration dependency issue for
deriving water quality criteria. In situations where BCFs vary with exposure
concentration, early guidance recommends using the BCF from the lowest exposure
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concentration above the control treatment (U.S. EPA, 1985; 1995). This same guidance
was adopted for hazard classification of metals, including lead under the TRI program
(U.S. EPA, 2001a). EPA's updated water quality criteria guidance recommends using
BCFs from concentrations that most closely align with the water quality criterion (U.S.
EPA, 2000a). The basis for this recommendation involves minimizing the uncertainty
when extrapolating BCFs and BAFs across different exposure concentrations between the
BCF study and its application for deriving a particular criterion. In theory, such an
approach might use an allowable dietary intake concentration (determined from the
toxicity and exposure data) and the concentration-tissue residue relationship derived from
the BCF test to identify the ambient concentration that is most suitable for estimating the
BCF. However, this guidance has not yet been applied for deriving criteria.
The existence of inverse relationships between BCF (BAF) and exposure concentrations
for certain metal/species combinations has led to recommendations by some to abandon
the current use of BCFs and BAFs for classifying metal hazards (Adams, 2000; Brix and
Deforest, 2000). The OECD has recently published guidance for classifying metals that
are hazardous to aquatic environments (OECD, 2001). The hazard classification schemes
presented in the guidance incorporate, among other parameters, evidence of
bioaccumulation as a basis for hazard ranking. The guidance advises, however, that in
situations in which there is an inverse relationship between BCF and external water
concentration the bioconcentration data should be used with care.
Issue Summary No. 2.3.1: Essentiality and subsequent regulation of metal
accumulation by organisms complicate the interpretation and application of metals
bioaccumulation data for aquatic and terrestrial organisms. What approaches for
considering essentiality of metals are appropriate for evaluating metals
bioaccumulation data for aquatic and terrestrial species? When BAF/BCF
values depend on exposure concentration, can such data be reliably
interpreted and applied in different regulatory scenarios (metal
characterization/ranking, criteria derivation, site-specific & national
assessments)? If so, what approaches are best for interpreting and applying
these data?
Issue #2. Factors Affecting Bioaccumulation
Besides the magnitude and duration of exposure, the bioaccumulation of a particular
metal by an aquatic or terrestrial organism can be affected by many factors. Most of these
factors relate to the biogeochemistry of the metal in the environment and the biological,
physiological or ecological characteristics of the organism of concern. From a
geochemical perspective, factors affecting metal bioaccumulation include metal
speciation and biotransformation, availability of complexing ligands (e.g., organic carbon,
chloride, carbonate, sulfide, manganese and ferrous oxides), competition by other cations
for membrane adsorption sites (e.g., calcium, magnesium), pH, redox, particle sorption,
sediment and soil physicochemical properties and hydrology. From an organism
perspective, some important factors include its age or size, life stage, feeding ecology,
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health or physiological condition, availability and/or induction of detoxification
mechanisms, exposure route and reproductive status.
Among these various factors affecting metals bioaccumulation, metal speciation is
particularly important because it defines the reactivity of chemical compound(s) involved
in the assessment. Because speciation and bioavailability can differ widely from the
laboratory to the field, concerns have been raised as to the applicability of laboratory-
based BCFs to field conditions. For example, laboratory studies of bioconcentration
typically use soluble metal salts in relatively clean water. In the field, metals may
transform into less soluble species or may be complexed with ligands thereby reducing
their bioaccumulation relative to laboratory tests. In the case of mercury,
bioaccumulation can be enhanced in the field relative to the laboratory due to the
biotransformation of inorganic mercury into methylmercury, which has significantly
higher bioavailability. Even with field-based BAFs, extrapolation of results from one site
to another involves uncertainty because of differences in bioavailability across sites and
ecosystems.
While much is known about various factors which can affect metals bioaccumulation, the
current ability to incorporate such factors into estimates or predictions of metal
bioaccumulation is limited, particularly in national or regional applications where site-
specific data are typically sparse. In site-specific applications, factors affecting
bioaccumulation can be incorporated directly through empirical approaches (i.e., site-
specific BAFs) or in some cases, through the calibration and application of
mechanistically-based models given sufficient resources. For national or regional
assessments, progress has been made in addressing bioavailability of metals for predicting
acute toxicity to aquatic organisms (e.g., development of the SEM/AVS and Biotic
Ligand Model (BLM) methodologies, U.S. EPA, 2000d, Di Toro et al., 2001). Although
these models do not explicitly predict bioaccumulation, they do represent critical
advancements in addressing metal bioavailability and toxicity, which are likely to be
applicable to bioaccumulation assessments.
Issue Summary No. 2.3.2: Numerous factors can affect the bioaccumulation of
metals by aquatic organisms. Unlike nonionic organic chemicals where certain
physicochemical parameters have been successfully applied for improving
predictions of chemical bioaccumulation (e.g., Kow, lipid content, organic carbon
fraction), analogous procedures for improving estimates of metals
bioaccumulation typically have not been developed or widely applied in most
EPA regulatory activities. In some cases, this limitation has led to substantial
uncertainty in the extrapolation of BAFs and BCFs across locations and species,
as illustrated by EPA's evaluation of BAFs for methylmercury (U.S. EPA, 2001b).
Given the present state of the science with respect to metals bioaccumulation,
to what extent can the Agency use current or emerging approaches to
incorporate factors affecting bioaccumulation by aquatic organisms for
improving the estimation and prediction of metals bioaccumulation? This
issue is particularly important in the context of regional or national-level
assessments where broad scale generalizations are necessary.
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Issue #3. Assessing Hazard from Bioaccumulation in Terrestrial Organisms
The U.S. EPA's PBT framework used by the TRI program currently relies on aquatic
bioaccumulation data (e.g., BCFs, BAFs) and human bioaccumulation data for classifying
chemicals according to their bioaccumulative properties (64 FR pages 58666-58753;
October 29, 1999 and 66 FR pages 4500-4547, January 17, 2001). Bioaccumulation
metrics analogous to the BCF or BAF are not available for mammals and humans, nor
might they be appropriate. The advantage of expressing bioaccumulation in terms of
BAF or BCF is that these terms serve as a simple and practical way of representing the
complex phenomena of bioaccumulation, just as octanol/water partition coefficient (log
Kow) is a practical and simple way of expressing a substance's lipophilicity. The reliance
on aquatic bioaccumulation data is due in part to the widespread use and availability of
BCFs and BAFs for toxic chemicals, including metals. The BCF and BAF descriptors
enable one to delineate or express more precisely the degree to which a chemical
bioaccumulates in an organism, and facilitates distinctions in ranking: e.g.,
"bioaccumulative versus highly bioaccumulative." Such delineations and distinctions
cannot be made as effectively by mental intuition or qualitative analysis of data.
Despite a strong focus on aquatic-based bioaccumulation data for hazard classification
purposes, the Agency clearly recognizes the importance of bioaccumulation in terrestrial
organisms, including humans. For some chemicals, bioaccumulation and subsequent
exposure of human and ecological receptors via the terrestrial food web may be of equal
or greater concern compared to the aquatic pathway. For example, human exposure via
dietary sources associated with the terrestrial food web is considered important for dioxin
and dioxin-like compounds (U.S. EPA, 2000b).
Various types of data and approaches have been used to characterize bioaccumulation by
terrestrial organisms. Some of these data include soil-to-biota concentration factors and
associated regression models for earthworms, plants, and small mammals. Recently, the
Agency has compiled such terrestrial bioaccumulation data for use in estimating
ecologically-based soil screening levels for organic and metal compounds (U.S. EPA,
2000c). Mechanistically-based models have also been developed and evaluated for
predicting bioaccumulation by terrestrial organisms (e.g., Saxe et al., 2001 for
earthworms; Torres and Johnson, 200Ib for small mammals). The earthworm
bioaccumulation model developed by Saxe et al (2001) appears promising, although
independent validation of the model was not possible due to lack of appropriate data. As
discussed by Torres and Johnson (200 Ib), many of the bioaccumulation models
developed for small mammals have achieved mixed success in terms of predictability.
Besides bioaccumulation data collected under natural exposures in the field, a large
pharmacokinetic data base exists for many specific types of mammals exposed under
laboratory conditions. Pertinent data are also available for humans from occupational or
clinical exposures. These data consist chiefly of organ or tissue concentrations of
chemicals that result from exposures of different routes, durations, sources and pathways.
Unlike bioaccumulation data measured in aquatic species, laboratory-based mammalian
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bioaccumulation data are not expressed in terms of BCF or BAF because these terms are
derived from exposure conditions that are generally not consistent with those used to
expose mammals (e.g., dietary, dermal, intravenous, inhalation, drinking water
exposures). While much data pertaining to the bioaccumulation of substances, including
metals, in humans and other mammals are available, there currently are no universally
accepted indices of these data. Interpretation and utilization of mammalian
bioaccumulation data during hazard assessments of substances are usually made
qualitatively. This makes the characterization of the bioaccumulative properties of a
substance in mammals more subjective, and ranking more difficult.
The lack of indices or a more descriptive approach for expressing bioaccumulation of
chemicals in mammals notwithstanding, mammals (including humans) can and do
bioaccumulate chemicals and EPA programs need to consider this when making
decisions regarding the bioaccumulative properties of a chemical. For example, in
selecting toxic endpoints for human health risk assessments of pesticides, EPA's Office
of Pesticide Programs (OPP) evaluates toxicity data measured in rodents and other
animals. As part of these hazard evaluations of pesticides, OPP toxicologists look for
evidence of bioaccumulation from pharmacokinetic studies, such as animal metabolism
studies. Evidence of bioaccumulation would include elevated tissue concentrations of
pesticide residues in tissues of test animals following exposure. Pesticide substances that
have, or appear to have bioaccumulative properties of concern may be assigned more
protective endpoints. The assessment of bioaccumulative properties of pesticides in
animals is done qualitatively, but a more descriptive method for assessing
pharmacokinetic data to draw conclusions regarding bioaccumulative properties of
pesticides would be preferable. For the TRI Lead Rule (U.S. EPA, 200la),
bioaccumulation of lead in humans was considered in the evaluation of lead as a PBT.
Issue Summary No. 2.3.3: EPA's current hazard evaluation methodologies
currently rely heavily on aquatic bioaccumulation data (e.g., BCFs, BAFs) to
classify chemicals according to their bioaccumulative properties. Bioaccumulation
of metals is also relevant to terrestrial organisms. Given the importance of
metal bioaccumulation in the terrestrial ecosystems, how can the Agency
apply existing and emerging tools used to quantify bioaccumulation in
terrestrial organisms for estimating and ranking bioaccumulation hazard
potential of metals? Specifically, how can the Agency better use and
interpret mammalian pharmacokinetic data, including human data, to
characterize bioaccumulation for hazard ranking purposes? Are there
reliable ways in which mammalian pharmacokinetic data can be represented
in the form of indices that are analogous to BCF and BAF for aquatic
species?
Issue #4. Selecting/Weighting Bioaccumulation Data for Different Species
Bioaccumulation of chemicals (including metals and metal compounds) is of concern
because it provides a mechanism to amplify the exposure of humans and other organisms
to chemicals released to the environment. Many bioaccumulation studies are conducted
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with fish and shellfish species, presumably because these organisms have clear
connectivity to consumption by humans, as well as aquatic and terrestrial-based
predators. For some chemicals, bioaccumulation data are available for other organisms,
such as algae, or benthic macroinvertebrates other than shellfish, which must be factored
into a decision regarding the bioaccumulative potential of a chemical. Some chemicals
show a propensity to accumulate in certain groups to a greater degree than in others.
When conducting a risk assessment and deriving chemical criteria, knowledge of the
receptor organism(s) and its prey base greatly informs the choice of species from which to
evaluate and assess bioaccumulation. For human health criteria derivations, choice of
species and tissues from which bioaccumulation is assessed includes consideration of
their representativeness of organisms consumed by humans. Similarly considerations are
made in the derivation of wildlife criteria, where whole-body residues are preferred over
other tissue types such as fillets. The scope of typical risk assessments and criteria
derivations also provides the opportunity to link bioaccumulation data with the most
appropriate metrics of exposure (e.g., consumption patterns and rates) and toxicity (e.g.,
ingestion-based toxicity values).
In the case of hazard assessment (e.g., EPA's PBT Framework), the broad assessment
goals (e.g., ranking hazard relative to all ecological and human receptors) render the
choice of species from which to evaluate bioaccumulation ambiguous. When few
bioaccumulation data are available, it would seem prudent to consider any high BCF as
evidence for bioaccumulation concern regardless of the organism, since in this case there
are no data for most organisms and the existence of bioaccumulation in one organism is
reason to presume its existence in others.
For chemicals having substantial bioaccumulation data, patterns in the bioaccumulation
data may be evident. For lead, bioaccumulation occurs to some degree in a variety of
aquatic organisms, but the highest BCFs occur in phytoplankton and algal species. In
determining whether high BCFs in a certain group of organisms are indicative of
increased hazard, it seems logical to consider whether there is reason to believe a pathway
exists between the organisms showing high bioaccumulation and those having sensitivity
to chemical exposure. In the case of lead, some algae are used by humans for food; this
then suggests that high BCFs for algae do indicate the potential for increased hazard to
humans and are therefore relevant to hazard ranking. A pathway to humans also exists
through incorporation of algae into a food chain leading to another organism ingested by
humans. In this instance, it is legitimate to consider whether this tropic transfer could
result in exposure comparable to that associated with high BCF values. For lead and
many other cationic metals, there is suggestion that concentrations decline with increasing
trophic level.
In the case of some other metals, toxicity of the metal to humans may be much lower
compared to lead. For example, copper shows substantial bioconcentration factors (even
at concentrations above nutritional sufficiency) in some organisms, but ingestion of
contaminated organisms by humans is of much lower concern than for a metal such as
lead. The best understood mechanism of copper toxicity to aquatic organisms is through
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disruption of ionoregulation at the respiratory surfaces (e.g., gills), which does not have a
connection to bioaccumulation/?er se. The evidence as to the toxicity of dietary copper
exposure within the aquatic food chain is mixed; it is clear that some degree of dietary
uptake of copper occurs, but the evidence is unclear as to whether this poses a toxicity
threat.
Assessing bioaccumulation hazard for non-human receptors is more complex. Essentially
all organisms are subject to predation by other organisms, so the plausible dietary
exposure always exists for some receptor. Unfortunately, it is not common to have
extensive data on the potency of dietary exposure for causing toxicity for non-human
receptors.
With respect to hazard ranking/assessment, questions have arisen whether or not
bioaccumulation data for some species should be excluded (or disproportionately
weighted) when classifying the hazards of metals according to their bioaccumulation
potential. It has also been suggested that such hazard evaluations be made in the context
of pre-defined exposure scenarios (e.g., human health, terrestrial and aquatic-dependent
wildlife). In theory, this practice might facilitate refinement of data used to indicate
hazard potential (e.g., toxicity, persistence, bioaccumulation, etc.) to align with the
constraints of the exposure scenario and protection goal. However, this benefit would
come at the cost of additional effort expended to define and implement such additional
analyses compared to the current hazard assessment approach.
Issue Summary No. 2.3.4: For a given chemical, bioaccumulation data may be
available from a number of different species (algae, zooplankton,
macroinvertebrates, fish). For some regulatory applications, data from certain
species (and tissue types) are preferred or excluded from consideration because
protection goals are narrowly defined. For assessing hazard using the PBT
framework under the TRI program, bioaccumulation data for each species are
given equal consideration due in part to the broad assessment goals of the program
(e.g., ranking hazard relative to all ecological and human receptors). When
classifying the hazards of metals according to their bioaccumulation
potential, should bioaccumulation data for some species be excluded (or
disproportionately weighted)? If so, which species should be weighted
differently? Should metals hazard evaluations be made in the context of
predefined exposure scenarios (e.g., human health, terrestrial and aquatic-
dependent wildlife) in an effort to reduce uncertainty associated with
combining independent indicators of hazard potential (e.g., toxicity,
persistence, bioaccumulation, etc.)?
Issue #5. Interdependence of Bioaccumulation and Toxicity in Characterizing Metal
Hazard
As discussed above and elsewhere in this document, consideration of the bioaccumulative
and toxic properties of a metal are among the important factors that need to be considered
when evaluating or ranking the hazard of the metal. There may be situations in which the
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organism of concern (i.e., the organism to which the metal is toxic) also bioaccumulates
the metal. In such situations it may be possible that the bioaccumulative properties of the
metal in the organism are represented in the metal's toxicity to the organism. That is, the
toxicity will only occur if the organism first bioaccumulates the metal. (This may be
most likely if the adversely affected tissue is the same tissue in which the
bioaccumulation has occurred; the bioaccumulation eventually leads to a tissue
concentration sufficient to cause toxicity.) In situations such as this, what is the
appropriateness of considering the bioaccumulation in making decisions regarding the
bioaccumulative properties of the metal?
There may be situations in which the organism of concern also bioaccumulates the metal,
and the bioaccumulative properties of the metal in the organism are not represented in the
metal's toxicity to the organism. That is, the toxicity of the metal to the organism is not
dependent upon or require prior bioaccumulation of the metal by the organism: they are
independent phenomena. In this situation, criteria based on toxicity might be inherently
underprotective, and it might then be appropriate to consider as part of the hazard
evaluation or hazard ranking of the metal the bioaccumulative properties of the metal in
the organism, in addition to the toxicity of the metal to the organism. Lead is an example
of a metal that is toxic to humans and bioaccumulates in humans. Specifically, lead
causes neurotoxicity and kidney toxicity to humans, and lead bioaccumulates in the
human skeleton. Neither the neurotoxicity or kidney toxicity caused by lead requires prior
bioaccumulation of lead in the human skeleton. Lead that has accumulated in skeletal
tissue can, however, serve as an endogenous source of exposure to lead during periods of
bone loss. It is well documented that under such physiological conditions lead that has
accumulated in the human skeletal tissue can remobilize from the skeleton and enter other
tissues. Consequently, if such exposure had not been considered in setting the toxicity
criteria, either the additional hazard could be considered by accounting for such
bioaccumulation independent of toxicity, or the toxicity criteria could be made more
stringent to account for the additional exposure during periods of bone loss.
Issue Summary No. 2.3.5: In situations in which the metal under review
causes toxicity to a certain organism (i.e., the target organism) and the metal
also bioaccumulates in the organism, should bioaccumulation be considered
independently of toxicity, and if so, what are the important factors that need
to be considered regarding the use of these data for hazard identification or
hazard ranking purposes?
2.4 Persistence
Persistence refers generally to the ability of a material to remain in the environment.
With respect to organic chemicals, it is generally characterized by the rate at which a
chemical is broken down in the environment (e.g., by bacterial degradation or photo
oxidation) into smaller compounds which are typically less hazardous than the original
compound. For example, DDT (along with DDE and DDD) is generally considered as
being persistent, because it is broken down to less toxic compounds very, very slowly
(years and beyond). In contrast, the herbicide glyphosate is typically broken down to
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innocuous materials relatively quickly (days). The concept of persistence becomes more
complicated when viewed in terms of metals. When metals are viewed as elements, they
are infinitely persistent; copper atoms are never changed to any other atom under
environmental conditions, but the speciation of the copper atom can change. The
"persistence" of a particular metal species may, however, be very low under certain
conditions (e.g., transformation ofaquo Cu2+ to solid CuS in the presence of sulfide),
which is not to say that it might not be transformed back to the original form when
environmental conditions change.
These two approaches to defining persistence (persistence of a metal atom versus
persistence of a physical/chemical form) are different in important ways, and discussions
about "persistence" of metals must be carefully framed. Alternative definitions have been
offered, e.g.,: "Persistence is a characteristic of a metal that is indicative of the constancy
and duration of exposure of the available metal forms in a particular medium." (DiToro et
al., 2001). This definition of persistence reflects the need to relate the exposure
concentration to the potential for adverse effects and leads to consideration of a metal's
rate and extent of transformation, it's complexation capacity, and the bioavailability of
the dominant species as discrimination tools to allow one to make differentiations among
metals and metal compounds. Proponents of this definition argue that, without specifying
the compound of concern and where it is of concern, the concept of persistence has little
meaning in the case of metals. In fact, for aquatic organisms the argument is made that,
for metals and metal compounds that are insoluble and therefore relatively persistent,
their persistency is a protective characteristic leading to less risk since toxicity is a
function of a metal's free ion concentration.
Current Agency Practices
Persistence is generally not considered as a separate factor when conducting typical site-
specific or national risk assessments. Instead, whatever information the risk assessor has
on environmental fate is applied within the risk assessment models to ultimately predict
exposure. For example, EPA has done extensive analyses of metals partitioning in soils
and groundwater to allow modeling of the impact of metals leaching from wastes or
contaminated soils into potential drinking water aquifers. The exception to this detailed
analytical approach is in prioritization or ranking analyses where persistence is used as
one of the surrogates for exposure. In these situations metals are generally considered
infinitely persistent, while persistence for organic chemicals is generally expressed in
terms of their half life in different environmental media.
Issue Summary No. 2.4.1: While metals are infinitely persistent as elements,
the "persistence" of specific metal compounds can vary with environmental
conditions. What approaches can be used to determine when and how
persistence should or should not be considered when conducting a
prioritization analysis? Is there an alternative way to define persistence of
metals and/or metal compounds that could be used in national prioritization
analyses that are designed to distinguish between metals?
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2.5 Toxicity
Toxicity is the potential of a substance to cause harm. Toxicity is commonly described in
terms of hazard identification and dose-response. Hazard identification is the review of
relevant toxicologic, biological, and chemical information to determine the nature and
potential to induce adverse health effects. Dose-response associates health effects with a
specified dose or exposure level. Toxicity is the link between dose and response, which
equates to dose (exposure) with response (risk). The dominance of dose is often
expressed emphatically as "The dose makes the poison" (paraphrased from Paracelsus
[1493-1541] in Klaassen, 2001). Many regulatory and public health actions are designed
to assure that exposures to humans and the environment will be at, or below, a given dose
(or exposure) level in order to minimize the risk of adverse effects.
Essentiality
Several metals are essential for maintaining good health. Low levels of any
essential metal can cause a nutritional deficiency that can lead to poor health, but
high levels are toxic. The essentiality and toxicity of these metals pose unique
challenges to their assessment and regulation in the environment. Essential metals
with potential for toxicity at excessive doses include cobalt, copper, iron,
magnesium, manganese, molybdenum, selenium, and zinc (Klaassen, 2001). As
commonly occurring natural elements, the metabolism of metals has played a role
in evolutionary development. The metabolism of an essential element, such as
calcium, can affect the metabolism of a non-essential toxic metal, such as lead
(Kern et al., 2000).
Speciation
As a defining characteristic of a metal, speciation controls toxicity, although some
generalizations can be made across metal compounds based on valence, solubility,
and covalent bonding with carbon and other elements. The valence state of a
metal can modify toxicity. For example, hexavalent chromium is a potent known
human carcinogen by the inhalation route of exposure, whereas trivalent
chromium is much less toxic, not considered a carcinogen, and is an essential
nutrient for humans. For other metals, solubility may act a surrogate for
bioavailability, and can modify risk by limiting the biologically relevant dose. For
example, insoluble nickel compounds (e.g., nickel subsulfide, nickel oxide) are
carcinogenic when inhaled, but soluble nickel forms (nickel sulfate, nickel
chloride) do not appear to be carcinogenic. Soluble forms of lead and arsenic are
generally assumed to be more bioavailable than insoluble forms. The toxicity,
mode of action, and exposure potential of organic mercury (methylmercury and
dimethylmercury) differs from inorganic mercury (e.g., elemental or mercuric
chloride). The fatality of a researcher handling dimethylmercury has underscored
its extreme toxicity (Siegler et al., 1999) relative to other forms of mercury. On a
national scale, combustion of organic tetraethyl lead proved to be an excellent
predictor of blood lead levels (National Research Council Committee on
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Measuring Lead in Critical Populations, 1993). Organic tin compounds are
generally more bioavailable than inorganic forms (Klaassen, 2001). Speciation
may also modify essentiality. For example, trivalent chromium is required for
glucose metabolism, but hexavalent chromium is not (Klaassen, 2001).
Metabolism and Mode of Action
The metabolism and mode of toxic action for metals may be quite different than
for organic pollutants. Metals adversely impact a wider array of target tissues.
Often, the targets for toxicity are biochemical processes that exist at multiple sites
throughout the organism and/or involve common cellular components such as
membranes of cells and organelles (Shumilla et al., 1998). For example,
chromium, cadmium, mercury, zinc, and arsenite inhibit thiol binding proteins.
Organs involved in the transport of metals, such as gastrointestinal tract, liver, or
renal tubular cells, are particularly susceptible to toxicity owing to the higher dose
received by these tissues. Metabolism of the toxic metal may be similar to that of
a related essential element (e.g. lead and calcium in the CNS; lead, iron, and zinc
in heme metabolism). For some metals, toxicity results from a mechanism of
action that is similar to the action of an essential element (e.g. lead activates
calcium ion receptors) (Kern et al., 2000). Moreover, metals are sometimes
metabolized to less toxic forms and stored in body tissues such as bones or liver,
and can be re-mobilized following pregnancy or menopause. For example, lead
stored in the bones of a woman may be released during nursing, thus becoming an
exposure and health issue for the nursing infant (Gulson et al., 2001).
Current Agency Practice
The Agency uses toxicity data to assess the hazards and risks of chemicals released in the
environment. Toxicity assessments and values for metals occur within the same data
bases as those for other compounds. The primary data base for human health toxicity
values is IRIS (http://www.epa.gov/iriswebp/iris/index.html). The diversity of ecological
receptors relative to the state of toxicological data means that ecological toxicity values
are less standardized and are often developed on a site-specific basis using newly-
generated data or data gathered from peer-reviewed literature. For non-cancer health
effects, estimated doses (or exposures) are compared to reference doses (RfDs), reference
concentrations (RfCs), or similar benchmarks to determine whether adverse effects are
likely. Cancer risks are described as incremental increases in the probability of
contracting cancer (cancer risks are usually assessed for human populations) per unit of
exposure (or dose). Adverse ecological effects are evaluated at the population level rather
than the individual level, unless the organism is a threatened, endangered, or otherwise
protected species.
One major challenge is that emissions (and exposure data) for metals are typically
reported as a total elemental metal (e.g., arsenic emissions) or as a compound class (e.g.,
arsenic and arsenic compounds). Occasionally, emissions data include some limited
information about the metal forms (e.g. sulfides of nickel). Emissions data are rarely
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available on specific species (e.g., nickel subsulfide). This lack of data on specific
species can be problematic for the risk assessment. Risk assessors are often faced with
making simplified assumptions when comparing exposure estimates with toxicity data
that are not concordant for the species (or route of exposure). For example, the inhalation
toxicity data for nickel subsulfide are quite good, but the data for nickel oxide are limited.
Likewise, substantial data exist on effects of methylmercury, but data on
dimethylmercury are more limited.
The selection of these assumptions and defaults should be based on good scientific
judgement, and should be as consistent between the exposure and toxicity data as
possible. In general, the data needs and the importance of considering these issues will
depend on how refined an assessment is needed and the relative significance of the
decision. For example, refined assessments being utilized to set costly regulatory levels
will require solid analyses and robust data, but a relative ranking analysis to determine
priorities, may have more modest needs.
Issue Summary No. 2.5.1: As described in previous sections, at issue is whether
the toxicity data and dose-response values for metals are adequate when metals
are known to occur as distinct compounds or species which can transform
dynamically (both spatially and temporally) in response to controlling
environmental conditions. What data gaps do you consider to be the key
limiting factors to performing robust hazard and risk assessments? What
methods could be used to account for limitations in the existence of
compound-specific toxicity values when assessing metals-related hazard/risk?
Issue Summary No. 2.5.2: Related to the adequacy of the toxicity data base, is
the availability of parallel sampling and analytical methods to collect, identify,
and quantify the relevant metal species in the environment. Parallel analytical
methods are needed for consistent and scientifically sound assessments to link
toxicity data with environmental concentrations of the relevant metal species. A
similar set of analytical questions follows from examination of the adequacy of
the toxicity data base What are the limitations of current analytical methods
to measure metal speciation in the environment? Which toxicity and
exposure issues create demands for new analytical methods?
Issue Summary No. 2.5.3: Understanding the biological significance of metals
in the environment often requires considering essentiality as well as exposure
levels that cause toxic effects. Essentiality should be considered in the
development and application of toxic dose-response reference levels such as
reference doses (RfDs) and reference concentrations (RfCs). For example,
appropriate uncertainty factors or modifying factors should be used such that an
RfD is not lower than the recommended intake level for adequate nutrition.
Should existing risk assessment methods be modified to account for
essentiality? If so, what options should be considered?
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3. Description of the Framework
The Framework will be patterned after the Agency's Ecological Risk Assessment Framework
(EPA/630/R-92/001; February, 1992). The Framework will lay out key scientific principles and
issues that need to be addressed in assessing metals; develop conceptual models for different
scenarios and types of environmental decisions; and identify the kinds of scientific information,
approaches, methods, and models that are available for differentiating among metals as to their
human health and ecological risk. The following is a proposed outline of the Framework:
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Outline of the Framework for Assessing Hazards and Risks of Metals and Metal Compounds
1. Introduction
1.1. Purpose and Scope of this Framework
1.1.1. Purpose and audience
The document will develop a cross-Agency framework describing basic principles that need to be
considered in assessing the hazards and risks posed by metals and it will present a consistent approach for
making these assessments. The audience of the framework is primarily risk assessors and the document will
also communicate principles of metal assessment to stakeholders and the public.
1.1.2. Scope
The framework is a science-based document that focuses on the special attributes and behavior of metals
and metal compounds affecting hazard and risk. It will supplement existing guidance and discuss key issues
with metal-specific information. The approach will include metal-by-metal considerations and it will vary
depending on level of scientific assessment needed and scope of regulatory activity.
1.1.3. Tiered Approach
A tiered approach will be developed which, as an initial approach, incorporates the regulatory context of the
assessment. The initial tier where the least amount of metal and metal compound-specific information
would likely be used would occur in National Hazard/Risk Ranking and Characterization. An intermediate
tier would include National Regulatory Assessments which set media standards or guidelines for chemicals.
The third tier, addressing primarily Site-Specific Assessments, would incorporate metal and metal
compound-specific data and environmental chemistry information to a greater degree due to the nature of
these assessments.
1.2. Overview of Key Issues.
An overview of key issues that expands upon what is discussed in section 2 of the Action Plan.
1. Appropriate application of chemical speciation data to assessments,
2. Addressing bioavailability in the assessments of metals,
3. Evaluating bioaccumulation in relation to metals,
4. Persistence as it relates to metals and metal compounds, and
5. Metal toxicity issues as affected by speciation, bioavailability, and routes of exposure.
2.0 Problem Formulation and Scope of the Analysis
Problem formulation is defined by considering laws and policies that apply to the sources of metals and
metal compounds, the nature of the problem, and the likely scale of the assessment (both temporal and
spatial). The goal of planning is to identify the context of the environmental decision, the risk management
objectives, the options under assessment, the type and level of analysis needed, and available resources, and
to resolve questions concerning scope and process.
2.1 Regulatory Context
This section describes three general groupings of regulatory actions where the metal issues may arise.
2.1.1 National Hazard/Risk Ranking and Characterization. These are used to set priorities or rank
chemicals in regulatory activities or activities such as voluntary pollution reduction efforts.
2.1.2. National Regulatory Assessments. These assessments are done when the Agency is setting media
standards or guidelines for chemicals.
2.1.3. Site-Specific Assessments. The environmental setting for the analysis is clearly defined and the
analysis is focused on evaluating data appropriate for that setting.
2.2 Metal Exposure Pathways and Ecosystem(s) Potentially at Risk
Issues to consider include: routes of exposure to be evaluated in the assessment or regulatory action; metals
and metal compounds; available information and data gaps; and pathways of exposure to ecological
systems.
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2.3 Mechanisms of Toxicity and Hazard Identification
This section will address the unique aspects of the toxicity of metal compounds to humans and ecological
endpoints. Within the regulatory context under consideration, methods to address data availability will be
presented.
2.4 Assessment Endpoint Selection
Processes will be presented to select the human health or ecological components to be protected. Principles
to determine sensitive subpopulations that receive significant exposure to the chemical of concern will be
developed.
2.5 Conceptual Models
The conceptual model shows the interrelationship between the metals and metal compounds and the
assessment endpoints. Endpoints are selected for their relevance to management goals, societal values and
laws, known adverse effects of metals, and the endpoint importance to stakeholders. The model depicts the
pathways from sources of metals to receptors and environmental processes, fate and transport routes which
affect the types of metal compounds and exposures that may occur. Conceptual models are case specific
and in this framework we will consider three categories: national hazard/risk ranking and characterization,
national regulatory assessments, and site-specific assessments.
3.0 Analysis Phase
3.1 Characterization of Exposure
3.1.1 Exposure pathway analysis. This section addresses the evaluation of the significant exposure
pathways and routes of exposure to the human health or ecological endpoints to be protected, e.g.
inhalation, ingestion, etc.
3.1.2 Metal speciation and distribution. Level of specification will depend on tier or regulatory context.
The development of principles to discuss metal speciation on a metal and metal compound basis will be
considered in this section. The identification of prevalent metal forms in the environment will support the
discussion.
3.1.3 Ecosystem(s) characterization. In the appropriate tiers or regulatory context, the development and
application of methods to evaluate the impact of ecosystem physical, chemical, and biological parameters
on the transport, transformation, and availability (or speciation) of metals is important in the assessment of
metals. Assess methods to incorporate natural background levels of metals and consider
adaptation/acclimation issues in wildlife.
3.1.4 Exposure distribution/ analysis. In the higher tiers, processes to estimate the concentration distribution
of metals and metal compounds are needed. Approaches will be considered to address these issues.
3.1.5 Bioavailability. Discuss issues for addressing within organism bioavailability issues from the various
routes of exposure in a tiered process. Approaches should be considered to further incorporate
bioavailability issues into regulatory processes.
3.2 Characterization of Human Health Effects
Issues to consider include: assessing the routes of exposure that are of most concern; identifying the
lexicological endpoints; utilization of a dose-response profile or a distribution that characterizes the effects
of the metal on the endpoints of concern; methods to relate the primary toxic forms of the metal and metal
compounds versus forms most common in the environment; and essentiality issues.
3.3 Characterization of Ecological Effects
Issues to consider include: metal toxicity and essentiality; processes for higher tiers to discuss metal
compounds tested and likely forms of the metal in the environmental media of concern; evaluation and
application of bioaccumulation methods; direct vs indirect toxicity; mobilization of stored metals;
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processes in higher tiers to utilize models to relate aquatic and soil chemistry information to toxicity;
depending on tier or regulatory context, application of dose-response profiles, species-toxicity
distributions, or probabilistic assessments.
4.0 Characterization of Exposure and Effects
4.1 Integration of dose-response with exposure pathways
Depending on the tier and regulatory context, what processes should be considered to assess the hazard or
risk assessed from major pathways of exposure (e.g., inhalation, ingestion, etc.)? Discuss approaches to
address bioavailability issues in a tiered process. What principles should be applied to metal
complexation/precipitation issues from physical and chemical characteristics of the environmental media
(water, soil, sediment)?
For a given regulatory tier, what processes should be used to assess sensitive human and ecological
endpoints? Discuss processes or calculations that should be used to determine sub-populations most at risk
4.2 Weight of Evidence
What levels of detail (tiers) are available for the evaluation of each aspect of hazard and risk? How can
background concentrations and weathering of metals be addressed? What approaches should be used to
evaluate metal speciation in the toxicity data base versus speciation of metals in the exposure pathways?
Are special data requirements needed for evaluating particular metals and metal compounds?
4.3 Uncertainty Analysis
What tiered process would be appropriate to evaluate uncertainty around risk estimates? When should
sensitivity analyses be applied? How should relating the value of additional information versus cost be
considered?
4.4 Case Studies.
For each regulatory tier, case studies should be developed to provide examples of how scientific data on
metals can be utilized in the assessment process. How does the nature of the management decision
presented in the case studies change the application of metal environmental chemistry?
5.0 Regulatory Applications and Implementation of the Framework
Discuss and compare practices among the statutes for assessing hazards and risks of metals and metal
compounds. Identify examples of the different tiers from statutes, regulatory guidance and criteria for risk
management. Discuss the handling of tiered approaches for addressing issues, information needs, and
research recommendations.
6.0 Research to Reduce Uncertainty
Within the tiered structure, discuss what research is required to enable assessors to apply increased levels of
metal-specific data on environmental chemistry, models, exposure and effects analysis, and
characterization. What process can be used to prioritize research topics that can reduce uncertainty in metal
assessments? What methods can effectively promote partnerships with the academic community and
Federal agencies to coordinate research to address high priority topics?
- End of proposed outline -
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4. Description of the Guidance for Characterization and Ranking of Metals
Whereas the Framework will consider issues and principles applicable across EPA's regulatory
activities, the Agency recognizes the need to take the next essential step of providing cross-
Agency guidance for applying these principles. The Guidance for Characterizing and Ranking
Metals will provide the tools and specific guidance for characterizing metals and assessing
hazard and risk, and it will address critical needs identified by the stakeholders.
Risk prioritization and ranking exercises typically involve relatively rapid evaluation and
comparison across a significant number of chemicals, either in a single media or across media.
The purpose of these exercises is generally to identify those chemicals which have a greater
potential to cause harm in the environment by looking at available indicators which are good
predictors of hazard and risk. The predictors which have been used by a number of Agency
programs are persistence, bioaccumulation potential, and toxicity. Chemicals having these
properties are of particular concern because they remain in the environment for long periods of
time, accumulate in organisms, can be transferred to other organisms within the food web, and
may cause a range of serious toxic effects such as neurological disorders, reproductive and
developmental problems, genetic damage, and cancer. In recent years there have been increasing
concerns both nationally and internationally over the hazards and risks posed by persistent,
bioaccumulative and toxic substances (PBTs). Over the years, PBT chemicals have gained a
great deal of public attention and concern due to the public health and environmental problems
they have caused. Many PBT chemicals are included in international agreements directed at
reduction or elimination of hazardous PBT pollutants.
There appears to be consensus among a number of organizations as to how to evaluate the
persistence, bioaccumulative, and toxicity of organic chemicals; however, such a consensus has
not been reached in the case of metals because of the various issues described earlier in this plan.
The controversy surrounding the recent decision (Lead and Lead Compounds; Lowering of
Reporting Thresholds; Community Right-to-Know Toxic Chemical Release Reporting; Final
Rule. 66 Federal Register, 4499-4547 (January 17, 2001) by the Agency that lead and lead
compounds are PBTs underscores the importance of developing guidance specific to metals that
can be applied for purposes of classification and priority setting.
The Guidance for Characterization and Ranking of Metals developed from this Action Plan will
build on the principles laid out in the Framework and will focus on how these principles and
available methods can be applied in a hazard ranking/characterization context. It will also take
into consideration on-going activities outside the Agency.
5. Overall Approach and Schedule for Development of the Framework and Guidance
This Action Plan will culminate in two guidance documents (the Framework and the Guidance
for Characterization and Ranking of Metals). The Agency sees these activities occurring in
parallel and being closely linked (see Figure 1). The Framework will provide the overarching
principles and methods for metals assessment that can be applied across EPA's programs to
assure consistency in addressing the various scientific issues described earlier. A peer
consultation review of this draft document is projected for April 2003 followed by SAB review
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in June 2003. The Guidance for Characterization and Ranking of Metals will address the
application of the principles and specific methods identified in the Framework to the issue of
how to differentiate among metals and metal compounds for purposes of setting priorities and
categorization. Activities that this Guidance will apply to include information gathering, testing,
and the like. A peer consultation review of this draft document is projected for September 2003
with SAB review in November 2003. At the time that the Agency brings the Guidance for
Characterization and Ranking of Metals to the SAB, it will also request the SAB to comment on
whether lead is highly bioaccumulative, an issue which arose in the earlier TRI Lead rulemaking.
The Office of Research and Development will lead the effort to develop the Framework, the
Office of Solid Waste and Emergency Response (OSWER) will lead the effort to develop the
Ranking and Categorization Guidance, and EPA's Risk Assessment Forum will be charged with
organizing the necessary peer involvement workshops and the development of white papers that
will allow the Agency to tap into the body of outside experts and coordinate its activities with
ongoing efforts nationally and internationally. A hallmark of this effort will be opportunities for
peer involvement and peer review.
Development of White Papers
As a first step, the Agency will develop white papers on the major scientific issues and sub-issues
described in this Action Plan. These white papers will summarize the state-of-the science of
each assessment issue and identify available approaches, models, and extant data that can be
applied to each of the three regulatory scenarios described earlier. The white papers will serve as
a major information source for the Framework and Categorization and Ranking Guidance, and
will help focus discussions at the first peer consultation workshop. An additional use of these
white papers will be to help guide EPA's future research efforts in the area of metals assessment.
A model for development of these white papers is a process that was effective in developing the
Agency's first Ecological Risk Assessment Framework. Teams consisting of EPA staff and
outside experts will be formed around each specific issue to develop the white papers. This
approach should facilitate consensus building and take advantage of related activities taking
place outside the Agency.
Peer Consultation Workshops
The Plan includes three peer consultation workshops which will provide an opportunity for the
scientific community and stakeholders to have input to the scope and direction of both the
Framework and the Ranking and Categorization Guidance.
Workshop 1 will be held in November 2002. Input to the workshop will be the recommendations
from the SAB Advisory on the Action Plan and the state-of-the science white papers. At the
workshop, participants will refine the scope and content for both the Framework and the Ranking
and Categorization Guidance based on the SAB's recommendations and the white papers. The
intended outcome of this workshop is consensus as to the annotated outlines for both documents.
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Workshop 2 is planned for April 2003 and will be an opportunity for the scientific community
and stakeholders to provide input on the draft Framework. This workshop will be held
sufficiently in advance of an SAB review of the Framework so that recommendations from the
workshop can be considered for inclusion/modifications of the draft before it goes to the SAB for
review.
Workshop 3 is planned for September 2003 and will be similar in organization to Workshop 2 but
will focus on the draft Ranking and Categorization Guidance. This workshop should benefit from
the June SAB review of the Framework. Recommendations coming out of this workshop will be
considered for inclusion/modifications of the draft before it goes to the SAB for review in
November 2003.
Science Advisory Board Review
In addition to the SAB Advisory on the Action Plan, two SAB reviews are anticipated. The first
review planned for June 2003 will review the draft Framework. The SAB meeting will also
provide another opportunity for public input. The second SAB review in November 2003 will
focus on the Ranking and Categorization Guidance and include review of the outstanding issue
from the TRI lead rulemaking as to whether lead can be considered to be highly bioaccumulative
under the TRI criteria. This review will take place after the review of the Framework to allow for
any needed adjustments based on the SAB's review of the Framework. Overall the Framework is
planned for completion in December 2003 and the Ranking and Categorization Guidance within
six months after completion of the Framework.
Figure 1 presents the overall process and schedule for the production of the Framework and
Ranking and Categorization Guidance.
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Figure 1. Development of Metals Assessment Framework and Metals
Characterization/Ranking Guidance
Metals Assessment \
Framework Workgroup Aj
Draft White Papers
Framework/ Guidance
Issues)
Metals Characterization/
Ranking Workgroup
Interim Draft
Framework
Workshop #1:
Framework/Guidance Scope &
State of the Science
(Nov02)
(Mar 03)
(Aug03)
Draft Characterization
Guidance
/Workshop #2:
Peer Input on Interim Draft
Framework
(Apr 03)
/Workshop #3:
(Sept 03) <^ Peer Input on Draft
>v Guidance
f SAB Review
vflnterim Draft Framework),
%^___
(June 03)
(Nov03)
Final Metals
Assessment Framework
SAB Review
(Draft Guidance &
TRI Lead Issues)
(Dec 03)
(May 04)
Final Metals
Characterization/
Ranking Guidance
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6. Outreach Activities
In carrying out this Action Plan, the Agency will involve the following groups to foster
consensus building:
The Scientific and Risk Assessment Communities
EPA will seek out opportunities to engage the scientific and risk assessment communities as it
develops the Framework and the Guidance for Characterization and Ranking of Metals. The
following examples are illustrative.
EPA staff are working jointly with scientists from academia, industry, and Environment Canada
to organize a Technical Workshop under the auspices of the Society for Environmental
Toxicology and Chemistry. The workshop is titled Hazard Identification Approach for Metals
and Inorganic Metal Substances and has been proposed to the SET AC Board of Directors. The
workshop will involve environmental regulatory agencies in North America and Europe, as well
as industry, academicians, and environmental organizations. Since the intent of the workshop is
to summarize the current state-of-the-knowledge and propose methodologies and criteria that
may be useful for hazard assessment of metals and inorganic metal compounds in a regulatory
context, we see direct relevance to our efforts. The information developed through this workshop
will complement our white paper development and contribute to the consensus building process.
Another avenue that is being explored is discussions with the Center for the Study of Metals in
the Environment. This is a consortium of eight universities funded by EPA that is addressing
questions concerned with the risks of metals in the environment through research, technology
transfer, outreach, and education. The Center is an outgrowth of a research consortium focused
on Bioavailability, Trophic Transfer and Fate of Pollutants in the Aquatic Environment
previously funded by EPA. Opportunities are being identified where complementary activities
would be beneficial.
Coordination with Other Federal Agencies
The Agency will coordinate its activities with other interested agencies as it moves forward in
developing the metals assessment guidance. For example, EPA staff are currently participating
in an interagency effort to characterize and distill the data needs for assessing the risks from
exposure to metals in various settings (e.g., occupational and environmental settings and
considering issues of route and speciation of the metal form(s) to be tested). The interagency
work group which is forming will work towards developing an overall strategy consisting of (1)
identification of key testing needs, (2) development of testing approaches for efficiently and
effectively meeting those needs, and (3) consideration of appropriate, available mechanisms for
meeting specific data needs for metals risk assessment (including, for example, federal research,
testing sponsored by the National Toxicology Program [NTP] or by industry (through voluntary
efforts or by regulations under the Toxic Substances Control Act [TSCA]), etc.).
Communication with Stakeholders
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EPA will take steps to ensure a broad range of stakeholders-including the regulated community,
the environmental community, and the public in general-are kept informed of and invited to
participate in the process. At the February 2002 workshop, stakeholders expressed a strong
interest in being kept informed as EPA moves forward in developing the metals assessment
guidance. One suggestion that is being pursued is a webpage (to be implemented within the Risk
Assessment Forum's website) where stakeholders can be kept abreast of progress, upcoming
workshops and reviews, and have access to external review drafts, i.e., white papers and
guidance documents. The three peer involvement workshops and two SAB reviews are other
opportunities for stakeholder input as the Agency moves forward.
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