oEPA
EPA/635/R-18/292
IRIS Assessment Plan
www.epa.gov/iris
IRIS Assessment Plan for Methylmercury
(Scoping and Problem Formulation Materials)
CASRN 22967-92-6
April 2019
Integrated Risk Information System
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency

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IRIS Assessment Plan for Methylmercury
DISCLAIMER
This document is a public comment draft for review purposes only. This information is
distributed solely for the purpose of public comment It has not been formally disseminated by
EPA. It does not represent and should not be construed to represent any Agency determination or
policy. Mention of trade names or commercial products does not constitute endorsement or
recommendation for use.
This document is a draft for review purposes only and does not constitute Agency policy.
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IRIS Assessment Plan for Methylmercury
CONTENTS
AUTHORS | CONTRIBUTORS | REVIEWERS	vi
1.	INTRODUCTION	1
2.	SCOPING AND INITIAL PROBLEM FORMULATION	2
2.1. BACKGROUND	2
2.2.SCOPING SUMMARY	4
2.3.	PROBLEM FORMULATION	5
2.4.	ASSESSMENT APPROACH	6
2.5.	KEY SCIENCE ISSUES	7
3.	OVERALL OBJECTIVE, SPECIFIC AIMS, AND DRAFT POPULATIONS, EXPOSURES,
COMPARATORS, AND OUTCOMES (PECO) CRITERIA	8
3.1.	SPECIFIC AIMS	9
3.2.	DRAFT PECO CRITERIA	10
REFERENCES	11
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IRIS Assessment Plan for Methylmercury
TABLES
Table 1. EPA program and regional office interest in a methylmercury assessment	5
Table 2. Draft PECO criteria for the methylmercury assessment	10
FIGURES
Figure 1. IRIS systematic review problem formulation and method documents	2
Figure 2. Simplified conceptual model of the reassessment of DNT resulting from exposure to
methylmercury	9
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IRIS Assessment Plan for Methylmercury
ABBREVIATIONS
ATSDR	Agency for Toxic Substances and Disease Registry
CAA	Clean Air Act
CDC	Centers for Disease Control and Prevention
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
CWA	Clean Water Act
DNT	developmental neurotoxicity
EICG	Effects Identification and Characterization Group
EPA	U.S. Environmental Protection Agency
HAP	hazardous air pollutant
HERO	Health and Environmental Research Online
IAP	IRIS Assessment Plan
IRIS	Integrated Risk Information System
NAS	National Academy of Sciences
NCEA	National Center for Environmental Assessment
NRC	National Research Council
OAR	Office of Air and Radiation
OLEM	Office of Land and Emergency Management
PBPK	physiologically based pharmacokinetic
PECO	Populations, Exposures, Comparators, and Outcomes
QRMG	Quantitative Risk Methods Group
RCRA	Resource Conservation and Recovery Act
RfD	reference dose
UNEP	United Nations Environment Programme
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AUTHORS | CONTRIBUTORS | REVIEWERS
Assessment Team
Leonid Kopylev (co-Assessment Manager)	U.S. EPA/ORD/NCEA
Deborah Segal (co-Assessment Manager)
Johanna Congleton
Yu-Sheng Lin
Rebecca Nachman
Elizabeth Radke-Farabaugh
Michele Taylor
Amina Wilkins
Executive Direction
Tina Bahadori
Mary Ross
Emma Lavoie
Samantha Jones
Kristina Thayer
James Avery
Andrew Kraft
David Bussard
Viktor Morozov
Santhini Ramasamy
Norman Birchfield
NCEA Center Director
NCEA Deputy Center Director
NCEA Assistant Center Director for Scientific Support
NCEA Associate Director
NCEA/IRIS Division Director
NCEA/IRIS Deputy Director (acting)
NCEA/IRIS Associate Director for Science
NCEA-W Division Director
NCEA/QMRG Branch Chief
NCEA/EICG Branch Chief
Former NCEA/EICG Branch Chief
Contributors and Production Team
Hillary Hollinger
Ryan Jones
Samuel Thacker
Erin Vining
Vicki Soto
Dahnish Shams
Maureen Johnson
HERO Librarian
HERO Director
HERO Technical Information Specialist
HERO Data Specialist/ORAU Student Contractor
Project Management Team
Project Management Team
NCEA Webmaster
This document is a draft for review purposes only and does not constitute Agency policy.
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1. INTRODUCTION
The Integrated Risk Information System (IRIS) Program is undertaking a reassessment of
the health effects of methylmercury.1 Methylmercury was included in the December 2015 IRIS
Program multiyear agenda (https://www.epa.gov/iris/iris-agenda) as a chemical having high
priority for assessment development In December 2018, it was reconfirmed as a priority chemical.
IRIS assessments provide high-quality, publicly available information on the toxicity of
chemicals to which the public might be exposed. These assessments are not regulations but can
provide a critical part of the scientific foundation for decisions made in U.S. Environmental
Protection Agency (EPA) program and regional offices to protect public health.
As part of the initial steps in assessment development, the IRIS Program undertakes scoping
and initial problem formulation activities. During scoping activities, the IRIS Program consults with
EPA program and regional offices to identify the nature of the hazard characterization needed, the
most important exposure pathways, and the level of detail required to inform Agency decisions. A
broad, preliminary literature survey also will be conducted to assist in identifying the extent of the
evidence and health effects that have been studied for the chemical of interest Based on the
preliminary literature survey and the scope defined by EPA, the IRIS Program undertakes problem
formulation activities to frame the scientific questions that will be the focus of the assessment A
summary of the IRIS Program's scoping and problem formulation conclusions is contained in the
IRIS Assessment Plan (IAP).
The IAP is followed by development of a Systematic Review Protocol, which presents
detailed methods for conducting the full systematic review and dose-response analysis, including
any adjustments made to the IAP in response to public input. The IAP describes what will be
assessed, and the chemical-specific protocol describes how the assessment will be conducted.
Figure 1 graphically displays the context of the IAP and Systematic Review Protocol in the
systematic review process.
This document presents the draft IAP for methylmercury* a summary of the IRIS
Program's scoping and initial problem formulation conclusions. It describes the Agency need for
the assessment; objectives and specific aims of the assessment; draft Populations, Exposures,
Comparators, and Outcomes (PECO) criteria that outline the evidence considered most pertinent to
address the specific aims of the assessment; and identification of key areas of scientific complexity.
Brief background information on uses and potential for human exposure is provided for context.
iThis assessment evaluates methylmercury only. An IAP for inorganic mercury (i.e., mercury salts) is
currently in development. Elemental mercury might be considered at a later date for an additional
assessment.
This document is a draft for review purposes only and does not constitute Agency policy.
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Assessment
Initiated
IRIS Handbook: Standard operating procedures and consider;
Identify Studies with
Systematic Sufficient Details of Study Select Studies for Use in Derive Toxicity
Scoping Review Protocol Quantitative Modeling Evaluation Deriving Toxicity Values Values
itions
Assessment






Developed
lducted
Initial Problen
Formulation
Assessment
Plans:
What the
assessment
will cover
4
Literature Refined Summarize Informative Extract data
Search Analysis Plan studies and Consider
Susceptibility
Protocols: How the assessment will be cor
Figure 1. Methylmercury IRIS systematic review problem formulation and method
documents.
2.1. BACKGROUND
Multiple health agencies CHealth Canada. 2007: IJNEP. 2002: U.S. EPA. 2001: ATSDR. 1999:
U.S. EPA. 19971 and the National Academy of Sciences' (NAS) National Research Council fNRC.
2000) have established that prenatal oral exposure to methylmercury in humans causes
developmental neurotoxicity (DNT). An existing IRIS reference dose (RfD) for methylmercury was
published in 2001 (U.S. EPA. 20011 and was based on an NAS assessment from 2000 fNRC. 20001.
The outcomes described by the NAS included impaired cognitive function, motor function,
visuospatial performance, and abnormal (increased or decreased) muscle tone following in utero
methylmercury exposure fNRC. 20001. The RfD of 0.1 [ig/kg-day2 was derived from maternal daily
intakes of methylmercury of 0.86-1.47 [ig/kg-day, estimated to result in cord blood concentrations
of 46-79 |ig/L associated with multiple DNT measures (specifically, developmental
neuropsychological3 impairment) in a Faroe Island cohort described by Grandjean etal. (1997).
This epidemiological study found impaired cognitive function in 7-year-old children from the Faroe
Islands who were prenatally exposed to methylmercury fBudtz-Targensen etal.. 1999: Grandiean et
al.. 1997). IRIS's previous 1995 RfD for methylmercury was the same as the 2001 RfD and was also
based on DNT outcomes from in utero exposure using data from a 1971 Iraqi poisoning incident
2Expressed as a concentration in whole maternal blood, the RfD is approximately 3.5 |.ig/L fMahaffev et al..
20091.
3In the 2001 IRIS Assessment of methylmercury, the term developmental neuropsychological impairment was
used to describe the adverse effects on the nervous system that were identified in humans following
exposures to methylmercury during developmental life stages. Developmental neuropsychological
impairment is a type of DNT, the former terminology being used in many epidemiological studies.
This document is a draft for review purposes only and does not constitute Agency policy.
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[derivation described in	7)]. In both previous IRIS assessments, DNT outcomes were
concluded to be the most sensitive.
Methylmercury is formed when inorganic mercury is methylated by biota in water and soil.
Gaseous elemental mercury is released into the atmosphere from natural (e.g., volcanoes) and
anthropogenic (e.g., fossil-fuel combustion) sources. Elemental mercury can be converted to
inorganic mercury, which then can be transported to land or water through wet or dry deposition
processes. Combustion processes can also release inorganic ionic mercury, which can adsorb to
particulate matter (Srivastava et al, 2006). Inorganic divalent mercury adsorbed to particulates
can deposit after relatively short distances, compared to elemental mercury vapor that can travel
long distances. Once deposited, microorganisms convert inorganic mercury to methylmercury,
which then bioaccumulates in fish tissue. Concentrations of methylmercury in fish tissue,
particularly predatory fish higher on the food chain (e.g., swordfish), can be much greater than
methylmercury concentrations found in ambient water (U.S. EPA. 2010).
Consumption of contaminated fish and other seafood is the major pathway for exposure to
methylmercury in humans (NRC. 2000). Between 2011 and 2014, average blood methylmercury
levels in the U.S. population ranged from 0.434 to 0.498 |ig/L fCDC. 20171 and average total blood
mercury levels, which often are used as a basis for determining methylmercury blood levels, ranged
from 0.678 to 0.703 |ig/L between 2011 and 2016 fCDC. 20181. Males had slightly higher
methylmercury blood levels than females. For example, the average for males in 2013-2014 was
0.448 |ig/L and, for females, it was 0.422 |ig/L. Blood methylmercury levels were also found to
increase with age. In 2011 and 2012, the most recent years that methylmercury blood levels were
available for several age groups, the average for children 6 to 11 years of age was 0.209 |ig/L; for 12
to 19 year-olds, it was 0.276 |ig/L; and for adults over 19, it was 0.624 |ig/L fCDC. 20181. The
estimated mean daily intake of total mercury for women older than 20 years in the United States is
approximately 1 [ig/day4 fCDC. 2016a: Birch et al. 20141.
Methylmercury readily crosses the placenta and concentrates in cord blood at
approximately 1.7 times the levels in maternal blood (Straka etal. 2016: Stern and Smith. 2003:
Yang et al. 1997). It is also transferred from mothers to children via breastmilk (CDC. 2009:
ATSDR. 1999). As noted earlier, the developing nervous system is particularly sensitive to
methylmercury, so these gestational, lactational, and other postnatal exposures are of great
concern. Methylmercury exposures to women of childbearing age who could become pregnant
might be harmful as well, as studies have reported an average half-life of methylmercury in the
body of 50 days, which might then result in fetal exposure early in pregnancy (CDC. 2016b). A one-
compartment toxicokinetic model estimated a longer half-life for methylmercury, 80 days, based on
blood samples from an adult population (lo et al. 2015). The half-life of methylmercury varies
4Based on the calculated average monthly mercury intake using 2009-2010 NHANES (National Health and
Nutrition Examination Survey) data reported by Birch et al. and CDC's anthropometric reference values for
2011-2014 (CDC. 2016a: Birch et al.. 20141.
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among individuals, as some individuals have longer clearance times than others. For example,
EPA's 2001 assessment reported half-lives for methylmercury ranging from 32 to 189 days after
evaluating data from five studies fSmith etal. 1994: Sherlock etal. 1984: Kershaw et al. 1980: Al-
Shahristani and Shihab. 1974: Miettinen et al. 19711.
Subsistence fishing communities and other populations with high dietary intakes of
predatory fish species could be exposed to higher-than-average levels of methylmercury.
Therefore, women of childbearing age and children in these communities could have high
methylmercury exposures during susceptible life stages. People who consume fish from habitats
with high methylmercury concentrations due to large microbial populations that convert inorganic
mercury to methylmercury also might have particularly high exposures. This includes people
eating fish from certain types of wetlands, rivers with a high proportion of wetlands in their
watersheds, dilute and low-pH lakes in the Northeast and Northcentral United States, parts of the
Florida Everglades, newly flooded reservoirs, and coastal wetlands particularly along the Gulf of
Mexico, Atlantic Ocean, and San Francisco Bay (U.S. Department of the Interior. 20001. In some
regions of the world, consumption of fish from waters polluted by mercury from small-scale and
artisanal gold mining also might result in high methylmercury exposures. Contaminated rice and
rice-based food products, such as infant cereals, also can be a source of methylmercury exposure
fCui et al. 2017: Rothenberg et al. i ; othenberg et al. 20161.
2.2. SCOPING SUMMARY
During the scoping process, the IRIS Program met with EPA program and regional offices
that had an interest in an IRIS reassessment of methylmercury to discuss specific needs. Table 1
provides a summary of input from this outreach.
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IRIS Assessment Plan for Methylmercury
Table 1. EPA program and regional office interest in a methylmercury assessment
EPA
program or
regional
office
Oral
Inhalation
Statute/Regulation
Anticipated uses/interest
OLEM
EPA Regions
1-10
V
V
Comprehensive
Environmental
Response,
Compensation and
Liability Act (CERCLA)
Resource Conservation
and Recovery Act
(RCRA)
Clean Water Act (CWA)
CERCLA authorizes EPA to conduct short- or long-
term cleanups at Superfund sites and later recover
cleanup costs from potentially responsible parties
under section 107. Methylmercury toxicological
information may be used to make risk
determinations for such response actions (e.g.,
short-term removals, long-term remedial response
actions).
Mercury is listed under RCRA as a characteristic (40
CFR 261.24) and hazardous waste (40 CFR 261.33).
Methylmercury toxicological information may be
used to evaluate mercury toxicity from releases of
elemental mercury and mercury compounds as
environmental sources of methylmercury.
CWA requires EPA to develop water quality criteria
for states and tribes to use in developing water
quality standards, requires states and tribes to
adopt water quality criteria that protect designated
uses such as fish consumption, and requires states
and authorized tribes to review water quality
standards every three years and modify them based
on updated health effects studies derived by EPA.
1	2.3. PROBLEM FORMULATION
2	Based on a preliminary survey of the methylmercury literature, including review of
3	assessments conducted by other agencies, potential health outcomes identified other than DNT
4	include the following:
5	 Nervous system outcomes (non-developmental)
6	 Developmental outcomes (other than nervous system effects)
7	 Cardiovascular outcomes
8	 Immune system outcomes
9	 Reproductive outcomes
10	This assessment will only reassess and update the existing dose response for DNT
11	outcomes. It will not reevaluate whether methylmercury causes DNT outcomes because DNT is a
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well-established human hazard (as discussed in Section 2.1, Background). Also, it will not assess
the potential for methylmercury exposure to cause the other possible health outcomes of interest
described above, which might be the focus of subsequent analyses (see Section 2.4).
Because ingestion is the primary route of exposure for methylmercury fNRC. 20001.
inhalation and dermal routes of exposure are not addressed in this assessment OLEM expressed
the need for an inhalation reference concentration (RfC) for methylmercury; however, at this time,
sufficient data to derive an RfC are not available.
The reassessment of DNT dose response will focus on human studies because the
availability of a large epidemiological database on methylmercury exposure and DNT outcomes
[see review by Karagas et al. (20121] eliminates uncertainties associated with interspecies
extrapolation. During this reassessment, IRIS will evaluate epidemiological evidence for all types of
DNT outcomes resulting from exposure to the fetus, infants, children, or adolescents. Mechanistic
studies that address uncertainties in deriving reference values (e.g., by filling data gaps on
susceptibility) will be considered.
A reassessment of DNT dose response is justified by recent epidemiological studies that
analyzed effects at lower methylmercury exposure levels than those in studies used to derive the
existing RfD flJ.S. EPA. 2001: NRC. 20001. Many of these recent studies provide exposure-response
information, which enables reevaluation of the 2001RfD. Several studies investigated cognitive
function [e.g., Goldingetal. (20161: lacobson et al. (20151: Orenstein et c	; Sagiv et al.
(20121: Lederman etal. (20081: Oken et al. (20081: Oken etal. (20051] and motor function [e.g.,
Prpic et a	; ioldingetal. (20161: Suzuki (20161: Lederman et al. (20081: Pespres et al.
(20051: Daniels et al. (20041] at various ages following prenatal or postnatal exposures to
methylmercury. Other DNT outcomes (e.g., behavioral, structural, and electrophysiological)
following methylmercury exposures also have been evaluated [e.g., lin et al. (2016): Ng et al.
(20151: Boucher et al. f20101],
2.4. ASSESSMENT APPROACH
This assessment will use a modular approach. A "modular approach" means EPA will first
evaluate the most important route(s) of exposure (based on scoping) and the associated selected
health outcome(s). DNT resulting from oral exposure was selected as the focus of this first module
because it is a well-established hazard and the two previous RfDs for methylmercury were derived
for oral exposure DNT outcomes (see Section 2.1). Once completed, an assessment addressing the
DNT dose-response relationship for oral exposure will be released, rather than waiting until all
outcomes have been evaluated. This approach will expedite the release of important findings.
While completing this module, EPA also will survey the available hazard information for
other adverse health outcomes (see Section 2.3 for list), primarily by reviewing methylmercury
assessments by other agencies and organizations, and recent epidemiological studies. For health
effects for which hazard has not been well-established, animal and mechanistic studies will also be
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1	surveyed. Because there is insufficient data for all health effects following inhalation exposure to
2	methylmercury, only oral exposure studies will be evaluated.
3	EPA will use this survey to determine whether there is sufficient evidence to develop new
4	modules that assess hazard and/or derive reference values for these other adverse health outcomes
5	and whether they are likely to occur at environmental exposure levels such that they would be
6	important to consider for EPA decision making. If so, these new modules will have their own IAPs
7	that will be released separately. Consequently, the remainder of this IAP focuses only on the first
8	module, which is a methylmercury dose-response analysis of DNT outcomes in humans.
9 2.5. KEY SCIENCE ISSUES
10	Based on the preliminary literature survey, the following key scientific issues were
11	identified that warrant evaluation in this assessment.
12	 Consider the accuracy of the different types of biomarkers (e.g., hair, maternal blood, cord
13	blood) to measure methylmercury exposure. Consider the reliability and utility of these
14	different measures, including whether different biomarkers provide useful information for
15	developing a dose-response relationship for methylmercury exposure and
16	neurodevelopmental effects.
17	 Some epidemiological studies will measure methylmercury directly in human blood, hair or
18	nails. Other studies rely on measures of total mercury to estimate methylmercury exposure.
19	Consider how best to use all of the different biomarkers that were used in PECO-relevant
20	epidemiology studies to inform estimates of the relationship between methylmercury
21	exposure and neurodevelopmental effects.
22	 Consider how potential confounding [e.g., Budtz-lorgerisen etal. [20071] in studies is
23	accounted for in the analysis. For example, many fish species that contain methylmercury
24	also have beneficial nutrients, such as selenium and polyunsaturated fatty acids, which are
25	important to brain development In addition, fish could contain other contaminants that
26	might be harmful to brain development, such as polychlorinated biphenyls.
27	 Consider the differences in DNT evaluation methods, and how their results may be utilized
28	in this assessment For example, developmental scores are consistently higher for both
29	term and preterm infants when using the Bayley III test versus the Bayley II test, and some
30	suggest using an adjustment factor to compare the two scores (Lowe et al. 2012).
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3. OVERALL OBJECTIVE, SPECIFIC AIMS, AND
DRAFT POPULATIONS, EXPOSURES,
COMPARATORS, AND OUTCOMES (PECO)
CRITERIA
The overall objective of this assessment is to characterize the dose-response relationship
between methylmercury exposure and DNT outcomes and then use this information to update the
existing RfD. Because the current RfD for methylmercury was posted by IRIS in 2001 and was
based on an NAS fNRC. 20001 assessment, evaluation of studies since 1998 is expected to capture
literature that was not considered in the earlier assessments. The relevant dose-response analyses
included in these previous assessments will also be considered in this reassessment. Studies that
evaluated the relationships between methylmercury exposures to women of childbearing age and
the developing child and DNT outcomes that become apparent at any life stage (infancy through the
elderly) will be considered. A conceptual model is presented below to illustrate the focus of the
planned assessment (Figure 2).
Systematic review methods will be used to evaluate the epidemiological literature on DNT
outcomes, and the analysis conducted will be consistent with all relevant EPA guidance.5 As a part
of this systematic review, potential susceptible populations and life stages will be considered. The
Systematic Review Protocol will be disseminated after review of the draft assessment plan and will
reflect changes made to the specific aims and PECO criteria in response to public input
5EPA guidance documents: http://www.epa.gov/iris/basic-information-about-integrated-risk-information-
svstem#guidance/.
This document is a draft for review purposes only and does not constitute Agency policy.
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Exposure Pathway
Diet
[based on biomonitoring (hair, nails,
blood) or seafood consumption]
Exposed
Populations
Outcomes
Developmental Neurotoxicity
(neuropsychological outcomes such as cognition and
motor function; other DNT outcomes evaluated as well;
outcomes measured in infants through adulthood)
Response Metrics
Test scores (e.g., Bayley Scales of Infant Development,
Wechsler Scales) and other measures of nervous
system function
Figure 2. Simplified conceptual model of the reassessment of DNT resulting
from exposure to methylmercury.
3.1. SPECIFIC AIMS
	Identify epidemiological literature examining effects of exposure to methylmercury as
outlined in the PECO criteria (Section 3.2, Table 2). Develop and execute a literature search
strategy to broadly capture data from methylmercury epidemiological studies published
since 1998, and screen results for relevance.
	Use predefined criteria to identify epidemiological studies from the screened results that
provide exposure-response information for DNT outcomes.
	Conduct study evaluations (risk of bias and sensitivity) for identified epidemiological
studies. Studies with critical deficiencies generally will be considered uninformative and
not considered further.
	Summarize study methods and results from epidemiological studies on DNT outcomes,
including explicit identification and discussion of issues concerning potentially susceptible
populations and life stages.
	Evaluate whether dose conversion [i.e., physiologically based pharmacokinetic (PBPK)
modeling] is needed. Depending on the biomarker (e.g., cord blood), conduct a search and
review of the relevant literature as needed to determine if calculations used in the previous
assessment (to convert from cord blood to oral exposure) need to be updated. If necessary,
individual PBPK models will be evaluated using predefined criteria, and their strengths and
uncertainties will be summarized.
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1	 Derive a toxicity value (e.g., RfD) for DNT outcomes as supported by the available data.
2	 Characterize uncertainties and identify key data gaps and research needs, such as
3	limitations of the evidence base and the systematic review.
4	 Determine if the available data would also support the derivation of a dose-response
5	relationship for DNT outcomes that would be useful for benefit analyses to quantify the
6	health benefits of actions to reduce exposures to methylmercury.
7	3.2. DRAFT PECO CRITERIA
8	The PECO criteria are used to identify the evidence that addresses the specific aims of the
9	assessment and to focus the search terms and inclusion/exclusion criteria in a systematic review.
10	The draft PECO criteria for this methylmercury assessment (Table 2) were based on (1) basis for
11	the chemical's prioritization for assessment, (2) discussions with scientists in EPA program and
12	regional offices to determine the scope of the assessment that will best meet Agency needs, and (3)
13	preliminary review of the DNT literature for methylmercury (primarily reviews and authoritative
14	health assessment documents).
Table 2. Draft PECO criteria for the methylmercury assessment
PECO element
Evidence
Populations
Human populations exposed during life stages ranging from the fetus through adolescence.
Exposures
Any quantitative exposure to methylmercury based on biomonitoring data (e.g., hair, nails,
blood), or, possibly, food consumption (e.g., fish and seafood, rice) expressed as a daily intake
(e.g., mg/kg/d). Measurements must be either direct methylmercury measurements or
measurements of total mercury (not other forms of mercury, e.g., mercury salts).
Comparators
Referent populations exposed to lower (within the study) levels of methylmercury will be used
to examine specific effects. The results of the comparisons must be presented with sufficient
detail of quantitative modeling (e.g., regression coefficients presented with statistical measure
of variation).
Outcomes
DNT outcomes measured at any age including, but not limited to, tests or measures of
cognition, motor function, behavior, vision, and hearing.
This document is a draft for review purposes only and does not constitute Agency policy.
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This document is a draft for review purposes only and does not constitute Agency policy.
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This document is a draft for review purposes only and does not constitute Agency policy.
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This document is a draft for review purposes only and does not constitute Agency policy.
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This document is a draft for review purposes only and does not constitute Agency policy.
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