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, 3615-3617 [E9-1081]
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<![CDATA[
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Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices
the agency must be accompanied by the
certification. On April 18, 2008, FDA
published a draft guidance on the
certification requirement. In the draft
guidance FDA provided a list of the
types of submissions and applications
that typically did not need to be
accompanied by a certification. We
received a number of comments to the
docket concerning whether a
certification should accompany the
types of submissions and applications
listed in the draft guidance, as well as
other types of documents and
information submitted to FDA. We also
received a number of comments on this
issue during the process for obtaining
clearance under the Paperwork
Reduction Act of 1995 (44 U.S.C. 3501–
3520) for the certification form itself. In
addition, FDA also has had more
experience with the submission of the
certification form since the form was
implemented.
The comments we received in
response to the draft guidance and the
development of the certification form,
the inquiries to the agency, and our
evolving experience caused us to
reconsider our initial approach of
identifying those documents and
information that did not need to be
accompanied by a certification. Instead,
we concluded that it was more useful to
identify those applications and
submissions that must be accompanied
by a certification. This approach is also
consistent with many of the comments,
which asked that we provide more
specific information than was included
in the draft guidance. Thus, we intend
to exercise enforcement discretion
concerning the submission of a
certification with certain categories of
applications and submissions to FDA, as
noted in the guidance.
This guidance describes FDA’s
current thinking, for purposes of
implementing Title VIII of FDAAA,
regarding specific types of applications
and submissions submitted to FDA
under section 505, 515, 520(m), or
510(k) of the act, or under section 351
of the PHS Act, and accompanying
certifications described in section
402(j)(5)(B) of the PHS Act, 42 U.S.C.
282(j)(5)(B). We note that the Agency’s
discussion of ‘‘applications’’ and
‘‘submissions’’ in this guidance is not
necessarily applicable to any other
provision of law. In determining how to
interpret the certification requirement,
FDA has focused on the plain language
of Title VIII of FDAAA, as well as
information that Title VIII is intended to
capture.
This guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
VerDate Nov<24>2008
18:54 Jan 16, 2009
Jkt 217001
The guidance represents the agency’s
current thinking regarding the
certification requirement in section
402(j)(5)(B) of the PHS Act (42 U.S.C.
282(j)(5)(B)). It does not create or confer
any rights for or on any person and does
not operate to bind FDA or the public.
An alternative approach may be used if
such approach satisfies the
requirements of applicable statutes and
regulations.
II. Comments
Interested persons may, at any time,
submit to the Division of Dockets
Management (see ADDRESSES) written or
electronic comments regarding the
guidance. 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. A copy of the guidance and
received comments are available for
public examination in the Division of
Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday.
III. Paperwork Reduction Act of 1995
This guidance refers to a previously
approved collection of information. This
collection of information is subject to
review by the Office of Management and
Budget (OMB) under the Paperwork
Reduction Act of 1995 (44 U.S.C. 3501–
3520). The collection of information has
been approved under OMB Control No.
0910–0616.
IV. Electronic Access
Persons with access to the Internet
may obtain the guidance document at
eitherhttps://www.fda.gov/oc/initiatives/
advance/fdaaa.html or https://
www.regulations.gov.
Dated: January 15, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and
Planning.
[FR Doc. E9–1183 Filed 1–15–09; 11:15 am]
BILLING CODE 4160–01–S
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3615
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.
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
E:\FR\FM\21JAN1.SGM
21JAN1
3616
Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices
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 https://
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:
mstockstill on PROD1PC66 with NOTICES
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’’ (https://
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.
VerDate Nov<24>2008
18:54 Jan 16, 2009
Jkt 217001
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
PO 00000
Frm 00076
Fmt 4703
Sfmt 4703
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 doseresponse 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
E:\FR\FM\21JAN1.SGM
21JAN1
mstockstill on PROD1PC66 with NOTICES
Federal Register / Vol. 74, No. 12 / Wednesday, January 21, 2009 / Notices
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
VerDate Nov<24>2008
18:54 Jan 16, 2009
Jkt 217001
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
https://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
PO 00000
Frm 00077
Fmt 4703
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3617
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
https://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]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2008–N–0658]
Risk Assessment of the Public Health
Impact From Foodborne Listeria
monocytogenes in Some Ready-to-Eat
Foods Sliced, Prepared, and/or
Packaged in Retail Facilities; Request
for Comments and for Scientific Data
and Information
AGENCY:
Food and Drug Administration,
HHS.
ACTION: Notice; request for comments
and for scientific data and information.
SUMMARY: The Food and Drug
Administration (FDA) is requesting
E:\FR\FM\21JAN1.SGM
21JAN1
]]>Agencies
[Federal Register Volume 74, Number 12 (Wednesday, January 21, 2009)]
[Notices]
[Pages 3615-3617]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-1081]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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 https://
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'' (https://
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 https://
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 https://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
