Framework for Inorganic
Metals Risk Assessment
Anne Fairbrother, Randy Wentsel, Bill
Wood, Keith Sappington, and Pam Noyes
Office of Research and Development
SETAC North America Annual Conference
November 2006
Background
 There
has been considerable
interest in the Agency’s
assessments on metals and
metal compounds
 promulgation of the Toxics
Release Inventory (TRI) lead
rulemaking
 development of the Agency’s
Waste Minimization Prioritization
Tool
Challenge to the PBT Framework as
Applied to Metals



PBT framework is based on
principles developed for organic
substances that do not apply to
metals
PBT framework does not distinguish
between metal elements, metal
compounds, or particulate size
There is a major disconnect between
the forms selected for toxicity testing
and those in the marketplace
Challenge to the PBT Framework as
Applied to Metals
 BCFs
for metals
 vary with species and
environmental conditions
 show an inverse relationship with
concentration
 are not a predictor of toxicity
 Speciation
and bioavailability
are more meaningful than
persistence when evaluating
hazard potential
Challenge to the PBT Framework as
Applied to Metals
 PBT
framework lacks
discriminatory power for
metals
All metals would satisfy the
criteria to be a PBT
Metals Framework
 Develop
a cross-Agency
guidance for assessing metal
and metal compounds
 discussions within the Agency,
with external stakeholders and
with Congress
 provide opportunities for external
input, peer review and crossAgency involvement
Metals Framework

Develop a comprehensive
framework that could be the
basis of future Agency actions

Provide a consistent set of key
guiding principles to be
considered in assessing risks
posed by inorganic metals

Identify available methods,
models, and approaches for use
in metals risk assessments

Foster consistency across EPA
programs and regions
Schedule
Environ
Chemistry
Phase I: Metals
Action Plan Dec 2002
SAB
Review
Phase II: Issue Papers
Aug 2004
Peer
Review
Exposure
Bioavail.
Bioaccum.
Human
Health
Eco
Effects
Schedule
Phase III: Draft Metals
Framework June 2004
Peer Input Workshop
July 2004
Phase III: Draft Metals
Framework Dec 2004
SAB Review Feb 2005 - 2006
IntraAgency Review July 2006
InterAgency Review August 2006
Phase IV: Final Document and Agency
Implementation Jan 2007
Metals and Metalloids of
Primary Interest

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Aluminum
Antimony
Arsenic
Barium
Beryllium
Boron
Cadmium
Chromium
Cobalt
Copper
Iron
Lead
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Manganese
Mercury
(inorganic)
Molybdenum
Nickel
Selenium
Silver
Strontium
Tin
Thallium
Vanadium
Zinc
Framework TOC
Executive Summary
Ch 1 – Intro
Ch 2 – Framework overview
Ch 3 – Environmental Chemistry,
Transport, and Fate
Ch 4 – Human Health
Ch 5 – Aquatic EcoRisk
Ch 6 – Terrestrial EcoRisk
Ch 7 -- References
Ch 1. Introduction
 Purpose
and audiences
 Metals Framework Scope
 Metals Assessment Context
 National ranking and
categorization
 National risk assessments
 Regional and local risk
assessments
 Key
Principles to Consider
Ch 1. Introduction
 Purpose
and audiences
 Metals Framework Scope
 Metals Assessment Context
 National ranking and
categorization
 National risk assessments
 Regional and local risk
assessments
 Key
Principles to Consider
Categories of Metals Assessments and Applicable
EPA Statutory Framework
Site-Specific Assessments
National-Scale Assessments
[CWA, CAA, CERCLA, RCRA]
Screening-Level
Analyses
Criteria/
Standards Development
[CAA, CWA, SDWA,
CERCLA, RCRA]
Chemical Reviews
[TSCA, FIFRA,
CAA, EPCRA]
Screening-Level
Analyses
Complex Analyses
Complex Analyses
Ranking/
Categorization
[EPCRA, CERCLA, RCRA
TSCA, FIFRA,
SDWA, CAA, CWA]
Principles
 Metals
are naturally occurring
constituents in the environment
and vary in concentrations
across geographic regions.
 All
environmental media have
naturally occurring mixtures of
metals, and metals often are
introduced into the
environment as mixtures.
Natural occurrence of barite
(USGS)
Natural occurrence of
barite
Principles

Some metals are essential for
maintaining proper health of
humans, animals, plants, and
microorganisms.
Principles

Unlike organic chemicals, metals are
neither created nor destroyed by
biological or chemical processes
 They can transform from one species to
another (valence states) and can convert
them between inorganic and organic forms.

The absorption, distribution,
transformation, and excretion of a
metal (toxicokinetics) within an
organism depends on
 the metal
 the form of the metal or metal compound
 the organism’s ability to regulate and/or
store the metal.
Ch 2. Framework Over view
 Human
Health and Ecological
Risk Assessment: Planning and
Problem Formulation
 Metal Conceptual Model
 Assessment Phase
 Bioavailability
 Characterization of Exposure
 Characterization of Effects /
Hazard Analysis
 Risk
Characterization
Media-based
Toxicity Models
Dose-based
Toxicity Models
(M8)
soil, seds., air
ground water
surface water
Metal
Loadings
to Media
diet
soil, seds., air
ground water
surface water
soil, seds., air
ground water
surface water
Fate & Transport
Models
Metal
Distribution
in Media
(M1)
Media-based
Exposure
Models
(M2)
Exposure
to Metal
(M7)
Bioaccumulation
/TK Models
(e.g., mg/kg/d)
(M3)
fur, feather etc.
kidney, gill
liver, lung,
Metal
Distribution
in
Tissues
other endpoints
growth, repro.
mortality
Residue-based
Toxicity Models
(M4)
Population,
Habitat, Ecosystem
Models
Dietary Exposure
Models
(M6)
2o consumers
1o consumers
producers
Bioaccumulation
Food Web Model
Metal
Distribution
in
Diet
Risk
(Toxicity)
to
Organism /
Individual
(M9)
ecosystem
community
population
Risks at
Higher
Levels of
Biological
Organization
(M5)
Conceptual Model for Metal Risk Assessments
Assessment Questions
 Principles
are translated into
assessment questions to assist
in their consideration
 Questions
drafted for all
phases of the risk assessment
Example Assessment
Questions

BACKGROUND: How should background
(natural and anthropogenic) levels for
metals be characterized for the selected
spatial scale of the assessment?

MIXTURES: Are toxicological effects of
metal mixtures being incorporated in the
effects assessment?

ESSENTIALITY: How will both toxicity and
deficiencies of essential metals be
characterized?

METAL FORMS: Since environmental
chemistry is a primary factor influencing
metal speciation and subsequent
transport, uptake, and toxicity, how will it
be included in the risk assessment?
Ch 3. Environmental Chemistry,
Transport, and Fate

Introduction and Terminology
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Hard and soft acids and bases
Transformations
Aquatic chemistry
Ground water and metals mobility
Sediment chemistry
Soil chemistry
Atmospheric behavior / chemistry
Metal Transport and Fate
 Aquatic and terrestrial transport
pathways
 Atmospheric fate and transport
Bioavailability Issues
Bioavailability of metals varies widely
according to the physical, chemical,
and biological conditions under which
an organism is exposed.
 Bioavailability should be explicitly
incorporated into all risk assessments
 Trophic transfer can be an important
route of exposure for metals

 but biomagnification of inorganic forms of
metals in food webs is generally not a
concern in metals assessments
BAF/BCF Issues

Certain metal compounds are
known to bioaccumulate in tissues
and this bioaccumulation can be
related to their toxicity.

The latest scientific data on
bioaccumulation do not currently
support the use of bioconcentration
factor (BCF) or bioaccumulation
factor (BAF) values when applied as
generic threshold criteria for the
hazard potential of inorganic metal
BAF/BCF Issues

Single value BAF/BCFs hold the
most value for site-specific
assessments
 extrapolation across different exposure
conditions is minimized

For regional and national
assessments, BAF/BCFs should be
expressed as a function of media
chemistry and metal concentration
for particular species (or closely
related organisms)
Environmental Chemistry

Metal speciation affects
 toxicity, volatilization, photolysis,
sorption, atmospheric deposition,
acid/base equilibria, polymerization,
complexation, electron-transfer
reactions, solubility and precipitation
equilibria, microbial transformations,
and diffusivity

Speciation includes
 free metal ions, metal complexes
dissolved in solution and sorbed on
solid surfaces, and metal species that
have been co-precipitated in major
metal solids or that occur in their own
solids.
Environmental Chemistry

pH and redox potential affect
speciation

Kd values
 limited use of single values

Aging of metals in media reduces
bioavailability

Metal sorption behavior affects
bioavailability
Ch 4. Human Health Risk
Assessment for Metals


Metals Principles
Human Exposure Assessment
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Hazard Characterization
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Background
Bioavailability
Susceptible populations
Environmental release, transport and fate
Route-specific differences in effects
Integrated exposures
Biomarkers
Mixtures
Essentiality
Forms of metals
Toxicokinetics / toxicodynamics
Metal toxicity
Dose-response assessment
Risk Characterization
Human Health

The organ or tissue in which metal
toxicity occurs may differ from the
organ or tissue(s) in which the
metal bioaccumulates and may be
affected by the metal’s kinetics

Both the exposure route and the
form of a metal can affect the
metal’s carcinogenic potential and
its noncancer effects

Sensitivity to metals varies with
age, sex, pregnancy status,
nutritional status, and genetics
Human Health

Metals attached to small airborne
particles are of primary
importance for inhalation
exposures.

Because the diets of humans and
other animals are diverse, there
may be wide variability in the
dietary intake of some metals
(e.g., in seafood)
 results in temporal, geographic or
cultural variability of responses
Human Health
 Essentiality
should be viewed
as part of the overall doseresponse relationship for
those metals shown to be
essential
 Zinc IRIS document is an
example
RFDs should not be below
RDAs
Essentiality and Toxicity
Nutritionally
Essential Metals
with Potential Toxic
Effects at Higher
Doses
Cobalt
Chromium III
Copper
Iron
Manganese
Molybdenum
Selenium
Zinc
Toxic Metals With
Possible Beneficial
Effects
Arsenic
Boron
Nickel
Silicon
Vanadium
Toxic Metals With
no Known
Beneficial Effects
Aluminum
Antimony
Barium
Beryllium
Cadmium
Chromium VI
Lead
Mercury
Silver
Strontium
Thallium
Tin
Aquatic Ecological Risk
Assessment for Metals
Metals Principles
 Characterization of Exposure
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Characterization of Effects
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Background
Forms of metals
Exposure pathway analysis
Fate and transport of metals
Bioavailability and bioaccumulation
Essentiality
Toxicokinetics / toxicodynamics
Metal mixtures
Critical body residues
Risk Characterization
Terrestrial Ecological Risk
Assessment for Metals

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Metals Principles
Characterization of Exposure
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Characterization of Effects
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Natural occurrence of metals
Forms of metals
Exposure routes
Soil transport and fate models
Toxicokinetics / toxicodynamics
Soil invertebrate exposure
Plant exposure
Wildlife exposure
Essentiality
Toxicity tests
Metal mixtures
Critical body residues
Plant and invertebrate toxicity
Wildlife toxicity
Risk Characterization
Ecological

Background levels refers to those
concentrations of metals that derive
from natural as well as anthropogenic
sources that are not the focus of the
risk assessment
 metal concentrations vary widely over
space and time
 are partially responsible for distributions
of plants and wildlife
Ecological

For aquatic organisms, routes of
exposure include
 absorption across respiratory organs,
dermal absorption, sediment ingestion,
and food ingestion

For terrestrial organisms, routes of
exposure include
 binding to roots, foliar uptake, dermal
absorption, food, water, and soil
ingestion, or inhalation
Ecological
For most metals, the free ionic form
is most responsible for toxicity
 Free-ion activity models are useful
for establishing relative toxicity
among metals in different media

 BLM
 FIAM
Sediment toxicity is reduced by acid
volatile sulfides, organic carbon and
other factors that bind free ions and
decrease bioavailability
 Soil toxicity is affected by pH, CEC,
and % organic matter

Ecological

Inorganic metal compounds rarely
biomagnify across three or more
trophic levels

Effects addition models are a
useful first approximation of acute
toxicity of metal mixtures

Critical body or tissue residues
can be used for effects
estimations but few data are
available for metals
Web Sites

Metals Framework, January, 2007
http://?

Issue papers August 2004
http://cfpub2.epa.gov/ncea/cfm/rec
ordisplay.cfm?deid=86119
Core Technical Panel
Co-leads:
Anne Fairbrother ORD/NHEERL
Randy Wentsel OW/OST
Steering Committee:
Bill Wood
Steve Devito
Alec McBride
Dave Mount
Keith Sappington
Pam Noyes
Gary Bangs
ORD/NCEA/RAF
OEI/OIAA
OSWER/OSW
ORD/NHEERL
ORD/NCEA
ORD/NCEA/RAF
ORD/NCEA/RAF