[Federal Register Volume 74, Number 12 (Wednesday, January 21, 2009)]
[Notices]
[Pages 3615-3617]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-1081]


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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

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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: [email protected].

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

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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: [email protected].

    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