[Federal Register: January 21, 2009 (Volume 74, Number 12)]
[Notices]
[Page 3615-3617]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr21ja09-88]
 
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
 
Food and Drug Administration
 
[Docket No. FDA-2009-N-0018]
 
 
Report of Quantitative Risk and Benefit Assessment of Commercial
Fish Consumption, Focusing on Fetal Neurodevelopmental Effects
(Measured by Verbal Development in Children) and on Coronary Heart
Disease and Stroke in the General Population, and Summary of Published
Research on the Beneficial Effects of Fish Consumption and Omega-3
Fatty Acids for Certain Neurodevelopmental and Cardiovascular
Endpoints; Availability
 
AGENCY:  Food and Drug Administration, HHS.
 
ACTION: Notice.
 
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SUMMARY:  The Food and Drug Administration (FDA) is announcing the
availability of two draft documents. The first is entitled ``Report of
Quantitative Risk and Benefit Assessment of Commercial Fish
Consumption, Focusing on Fetal Neurodevelopmental Effects (Measured by
Verbal Development in Children) and on Coronary Heart Disease and
Stroke in the General Population'' (draft risk and benefit assessment
report). The draft risk and benefit assessment report describes an
analysis done by FDA that results in quantitative estimates of the net
effect on fetal neurodevelopment in children of maternal consumption of
commercial fish, as measured by verbal development and the net effect
of eating commercial fish on coronary heart disease and stroke in the
general population. Effects with respect to each of these health
endpoints has been associated in the scientific literature with
methylmercury exposure (which primarily occurs through fish
consumption) and with the consumption of fish and of omega-3 fatty
acids, which are found in fish. The second draft document entitled
``Summary of Published Research on the Beneficial Effects of Fish
Consumption and Omega-3 Fatty Acids for Certain Neurodevelopmental and
Cardiovascular Endpoints'' (draft summary of published research) is a
compendium of research prepared by FDA for use in developing its
quantitative risk and benefit assessment. When peer and public review
are complete, the draft risk and benefit assessment report and the
draft summary of published research are intended to add to the growing
body of scientific literature investigating the
 
[[Page 3616]]
 
likelihood, magnitude, and direction of health impacts linked to
consumption of commercial fish. FDA is seeking public comment on the
draft risk and benefit assessment report and the draft summary of
published research.
 
DATES:  Comments on the draft risk and benefit assessment and on the
draft summary of published research must be submitted by April 21,
2009.
 
ADDRESSES: Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852. Submit electronic comments to
http://www.regulations.gov.
 
FOR FURTHER INFORMATION CONTACT:  Philip Spiller, Center for Food
Safety and Applied Nutrition (HFS-002), Food and Drug Administration,
5100 Paint Branch Pkwy., College Park, MD 20740-3835, 301-436-1428, FAX
301-436-2668, e-mail: Philip.Spiller@fda.hhs.gov.
 
SUPPLEMENTARY INFORMATION:
 
I. Background
 
    Fish provides protein, is low in saturated fat, and is rich in many
micronutrients; it also can be a source of certain omega-3 fatty acids.
As the Institute of Medicine of the National Academies of Science (IOM)
noted in a recent report, ``[i]n the past several years, research has
implicated seafood, particularly its contribution of EPA and DHA [two
omega-3 fatty acids], in various health benefits identified for the
developing fetus and infants, and also for adults, including those at
risk for cardiovascular disease.'' (Institute of Medicine, Committee on
Nutrient Relationships in Seafood: Selections to Balance Benefits and
Risks. Seafood Choices: Balancing Benefits and Risk. 2006, National
Academy of Sciences, at 1). However, as a result of natural processes
and human activity, aquatic food sources, including fish, can contain
methylmercury, which has been linked to adverse health consequences.
Because of the presence of methylmercury in fish, FDA and the U.S.
Environmental Protection Agency (EPA) issued an advisory to consumers,
``What You Need to Know About Mercury in Fish and Shellfish''
(http://www.cfsan.fda.gov/~dms/admehg3.html). The advisory, which was most
recently revised in 2004, recommends that women who may become
pregnant, pregnant women, nursing mothers, and young children avoid
some types of fish and eat fish and shellfish that are lower in
methylmercury, as specified in more detail in the advisory.
    Researchers in the United States and elsewhere have attempted in
recent years to develop approaches to better evaluate the net health
impacts of fish consumption; in other words, to understand the
relationship between the risk of not eating fish (and thus losing any
health benefits fish may provide) and the risk of eating fish that
contains methylmercury at the levels currently found in the commercial
fish available to consumers. As the IOM noted in its 2006 report, ``A
better way is needed to characterize the risks combined with the
benefits analysis.'' (IOM 2006 at 6). The draft summary of published
research and the draft risk and benefit assessment report were
developed by FDA to provide further scientific information to help
address this question for consumers of commercial seafood in the United
States (i.e., fish shipped or sold interstate, as opposed to fish
caught recreationally or for subsistence).
    The draft risk and benefit assessment report reflects an effort by
FDA to quantify the impact of eating commercial fish on three human
health endpoints: (1) Neurodevelopment, as measured by verbal
development in childhood as assessed by the effect of prenatal exposure
to methylmercury as passed from the mother to the developing fetus; (2)
risk of fatal coronary heart disease; and (3) risk of fatal stroke.
Each of these health endpoints has been associated in the scientific
literature both with adverse effects of methylmercury exposure
(including through fish consumption) and beneficial effects of regular
fish consumption. The draft risk and benefit assessment report provides
further scientific information about the likelihood and magnitude of
either beneficial or adverse net effects on health at current levels of
commercial fish consumption and exposure to methylmercury through fish
consumption in the United States. The draft risk and benefit assessment
report should not be construed as altering the existing fish advisory.
Moreover, because this assessment does not distinguish among types of
fish in terms of their beneficial constituents, it is not possible to
translate the results of this analysis into fish-specific advice to
consumers about maximizing benefits.
    The methodology used for the quantitative risk and benefit
assessment is novel for FDA in that, rather than attempting to quantify
the risk resulting from the presence of a particular hazard in a food,
it estimates that risk and the benefit from consumption of the food in
the same quantitative analysis. For fetal neurodevelopment, the
assessment estimates this net effect by separately estimating: (1) The
likelihood and size of an adverse contribution from methylmercury to
the net effect; (2) the likelihood and size of a beneficial
contribution to the net effect from fish; and (3) the likelihood, size,
and direction of the net effect. For the methylmercury contribution,
the assessment uses data to derive modeling estimates of the
association between methylmercury and early age verbal skills (as an
indicator of neurodevelopment) and then compares the results against
results developed elsewhere on methylmercury's effect on other aspects
of neurodevelopment, including intelligence quotient (IQ). For the fish
contribution, the assessment uses data to derive modeling estimates of
the association between fish consumption during pregnancy and early age
verbal skills. For the net effect, the assessment combines the results
from the methylmercury and fish contributions. This draft risk and
benefit assessment report builds on published work performed previously
by FDA scientists on the estimation of a methylmercury effect, as well
as recent articles by other investigators that have quantitatively
assessed this effect. For fatal coronary heart disease and stroke, the
assessment estimates the net effect on risk from fish consumption
without separately modeling a methylmercury contribution and a fish
contribution. Most data on this subject come from studies that measured
an association between fish consumption and these health endpoints
without measuring a methylmercury contribution. The modeling builds in
part on dose-response functions for these endpoints that have been
published in the scientific literature.
    The draft risk and benefit assessment report identifies and
discusses assumptions made for the scientific models and analyses and
sources of uncertainty with respect to each endpoint analyzed. Subject
to the limitations and assumptions set forth in the analysis, the risk
and benefit assessment estimated the net impact of consumption of
different amounts of fish. For example, with respect to fetal
neurodevelopment, we modeled various ``what if'' scenarios, in which we
estimated what would happen if women of child-bearing age ate more or
less fish, or if the amount of methylmercury in the fish they ate were
reduced.
    The results indicate that consumption of fish species that are low
in methylmercury has a significantly greater probability of resulting
in a net benefit, as measured by verbal development. The highest net
benefit
 
[[Page 3617]]
 
modeled in our risk and benefit analysis was modest. When we modeled
actual baseline consumption for the range of methylmercury
concentrations (low to high) the assessment indicated a significant
probability of a net adverse effect for 1/10 of 1 percent of children
for the central estimate. The highest estimated net adverse effect was
also quite modest. For fatal coronary heart disease and stroke,
commercial fish baseline consumption is averting a central estimate of
over 30,000 deaths per year from coronary heart disease and over 20,000
deaths per year from stroke. The results of our quantitative risk and
benefit assessment are generally consistent with research reported in
recent years in the scientific literature.
    The draft summary of published research identifies primarily
secondary analyses of the large body of scientific research on the
impact of fish and omega-3 fatty acids on cardiovascular and neurologic
endpoints, including research on both prenatal and post-natal
exposures. In addition to the IOM report, these secondary analyses
include reports by the American Heart Association, the European Food
Safety Authority, the International Society for the Study of Fatty
Acids and Lipids, the World Health Organization and a previous
investigation by FDA. This compendium of research was developed by FDA
for use in developing its quantitative risk benefit assessment and
provides background for that document. The draft summary of published
research identifies and delineates the lines of scientific evidence
that indicate the association of fish and omega-3 fatty acid
consumption with cardiovascular and neurodevelopmental health outcomes.
When available, the compendium of research also identifies reports of
quantitative dose-response relationships which may be relevant for risk
and benefit assessment modeling. The draft summary of published
research describes the context of the overall body of scientific
evidence currently available for potential application to the risk and
benefit assessment modeling and the draft risk and benefit assessment
report.
    The agency designated the draft risk and benefit assessment report
and the draft summary of published research as a ``highly influential
scientific assessment'' under the Office of Management and Budget's
(OMB) Final Information Quality Bulletin for Peer Review (the Bulletin)
(70 FR 2664, January 14, 2005). In August 2008, FDA submitted a draft
of the risk and benefit assessment report (which at the time also
incorporated the draft summary of published research) to seven
scientific experts outside the Federal Government, from a range of
scientific disciplines, for purposes of obtaining each expert's
independent, written peer review. The draft risk and benefit assessment
report and the draft summary of published research that are being made
available for public comment reflect revisions made to date in response
to the peer reviewers' comments and suggestions. The Information
Quality Act Bulletin for Peer Review requires FDA to post at its Web
site a report of the peer review that: (1) Contains the names and
credentials of the peer reviewers; (2) sets forth the ``charge,'' i.e.,
the scientific questions asked of the reviewers; (3) provides the
verbatim comments submitted by each reviewer (without attribution); and
(4) discusses what FDA has done to the documents in response to the
peer reviewers' comments. We have posted at our Web site an interim
draft of this report that provides this information at
http://www.cfsan.fda.gov/~dms/mehg109.html, although we expect and plan to
finalize this report after revising our draft risk and benefit
assessment report and the draft summary of published research, in
response to further expert and peer review comments.
    Separately, FDA solicited and received comments from scientists at
other Federal agencies, including EPA, the National Institutes of
Health, the Centers for Disease Control and Prevention, and the
National Oceanic and Atmospheric Administration during a review
coordinated by OMB. The draft risk and benefit assessment report and
the draft summary of published research being made available for
comment have been revised to reflect revisions made in response to the
inter-agency reviewers' comments.
    At the same time we are making these draft documents available for
public comment, we plan to provide a revised draft to the original peer
reviewers to enable them to submit any further comments. We will revise
the draft risk and benefit assessment report and the draft summary of
published research as necessary after considering the public comments
and any additional comments from the independent peer reviewers. We
also plan to provide the revised version of the documents, a summary of
the public comments that address significant scientific issues, and the
external peer review report to an FDA scientific advisory committee.
    After public and advisory committee review of these documents are
complete, appropriate risk management actions will then be considered
on the basis of currently available scientific information. The release
of these documents for public comment and peer review do not in any way
modify the recommendations set forth in the 2004 advisory on fish
consumption.
 
II. Comments
 
    Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified with the docket number found in brackets
in the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
 
III. Electronic Access
 
    The draft documents described in this notice are available
electronically at http://cfsan.fda.gov/~dms/mehg109.html.
 
IV. Access to Related Documents
 
    All references listed in the reports are available in FDA's
Division of Dockets Management (see ADDRESSES). Computer programs used
in the risk and benefit assessment modeling are available from Clark
Carrington, Center for Food Safety and Applied Nutrition (HFS-301),
Food and Drug Administration, 5100 Paint Branch Pkwy., College Park, MD
20740-3835, 301-436-1947, e-mail: Clark.Carrington@fda.hhs.gov.
 
    Dated: January 14, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-1081 Filed 1-15-09; 11:15 am]
 
BILLING CODE 4160-01-S

Draft Risk and Benefit Assessment Report and Draft Summary of Published Research January 15, 2009