5 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
^ WASHINGTON D.C. 20460
x«X
OFFICE OF THE ADMINISTRATOR
SCIENCE ADVISORY BOARD
January 5, 2010
EPA-SAB-10-001
The Honorable Lisa P. Jackson
Administrator
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue, N.W.
Washington, D.C. 20460
Subject: SAB Review of Draft "EPA Radiogenic Cancer Risk Models and Projections for the
U.S. Population"
Dear Administrator Jackson:
The Radiation Advisory Committee (RAC) of the Science Advisory Board (SAB) reviewed the
draft "EPA Radiogenic Cancer Risk Models and Projections for the U.S. Population, December 2008,"
also known as the draft revised "Blue Book," which was prepared by the EPA's Office of Radiation and
Indoor Air (ORIA). It describes proposed changes in methods for estimating radiogenic cancer risk, and
gives examples of risk estimates for individual radiogenic cancers that it derived mostly from advice and
methods based on the 2006 National Research Council Biological Effects of Ionizing Radiation (BEIR
VII) Report, which was sponsored by EPA and other federal agencies. The revised Blue Book will then
be used to obtain values of radionuclide risk coefficients for over 800 radionuclides in the revised Federal
Guidance Report 13 (FOR 13).
The SAB Committee, augmented with consultants for this specific review, found that the EPA's
draft revised Blue Book is impressively researched, based on carefully considered concepts, and well
written. We recommend the following in response to the three charge questions posed by EPA:
1) Appropriateness of models not taken directly from BEIR VII: The SAB agrees with the approaches
proposed by the EPA except for the following: (a) The discussion of a revised relative biological
effectiveness (RBE) value for low-energy beta particles, gamma rays, and x rays is unsuitably vague.
We recommend that the EPA select a value of the RBE after compiling and evaluating the pertinent
information and submitting it to peer review; the revised Blue Book publication need not be delayed
as long as the value of the RBE is decided before the revised FGR 13 is published; (b) We
recommend, in contrast to BEIR VII, using the arithmetic mean for combining information from each
pair of excess absolute risk value and excess relative risk value for transferring lifetime attributable
risk from the Japanese lifespan study to the U.S. population; use of the geometric mean recommended
by BEIR VII and accepted by the EPA has no preferred theoretical basis, can present difficulties in
further data processing, and results in unjustified lower mean values; and (c) We recommend that for
bone cancer, the EPA reconsider modeling the data base for the radium dial painter cohort with
consideration of the recently published data analyses. We compliment the EPA on developing an
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improved model that considers the survival rate of breast cancer patients. In the future, the EPA
should consider applying this model to other cancers with high rates of survival.
2) Adequacy and reasonableness of the uncertainty analysis by the EPA: The risk uncertainty analysis
in the draft revised Blue Book is reasonable and comprehensive for deriving overall estimate
uncertainty from sampling variation, model parameters, and data transfer to the U.S. population. We
recommend these improvements: (a) Increase the clarity and transparency in quantifying the sources
of uncertainty, notably in the selection of distributions chosen for the sources of uncertainty; (b)
Verify the uncertainty analysis by determining uncertainty intervals by a perturbation approach, i.e.,
varying the value of each major contributor to uncertainty over a reasonable range to calculate the
corresponding range of point estimates; and (c) Make Bayesian uncertainty analysis of confidence
intervals as consistent as possible with the point estimate of risk and justify use of these two distinct
approaches.
3) Presentation of overall information and application of BEIR VII: The draft revised Blue Book is
scientifically defensible and appropriate. We recommend that the EPA expand the presented
information by including: (a) studies of noncancer mortality; (b) brain cancer studies; (c) recent
reviews by the International Commission on Radiological Protection (ICRP) and United Nations
Scientific Committee on the Effects of Atomic Radiation (UNSCEAR); and (d) conclusions from the
National Council on Radiation Protection and Measurements (NCRP) Report #159 on the risks of
radiation-induced thyroid cancer.
The calculations and results in the draft revised Blue Book are readily understood. However, we
recommend that EPA clarify the purpose and application of the draft revised Blue Book contents in its
first Section by presenting in sufficient detail the path toward a revised FGR 13, and in its last Section by
listing sufficient FGR 13 values of radionuclide risk coefficients to demonstrate the impact - if any - on
them by the revised methods and updated data for estimated cancer risks proposed in the draft revised
Blue Book. The draft revised Blue Book has commendable accuracy and balance. We recommend that
the EPA enhance the level of detail by (a) reporting risk estimates associated with cohorts exposed to
protracted low doses of ionizing radiation, and (b) considering distinguishable types of cancer within a
given organ.
The SAB appreciates the opportunity to review this draft document and hopes that its
recommendations will support the EPA in implementing modifications in the current methods for
estimating radiogenic cancer risks and updating the Blue Book accordingly. We look forward to your
response to the recommendations contained in this review.
Sincerely,
/Signed/
Dr. Deborah L. Swackhamer, Chair,
Science Advisory Board
/Signed/
Dr. Bernd Kahn, Chair,
SAB Radiation Advisory Committee
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NOTICE
This report has been written as part of the activities of the Environmental Protection
Agency (EPA) Science Advisory Board (SAB), a public advisory group providing extramural
scientific information and advice to the Administrator and other officials of the EPA. The SAB
is structured to provide balanced, expert assessment of scientific matters related to problems
facing the Agency. This report has not been reviewed for approval by the Agency and, hence,
the contents of this report do not necessarily represent the views and policies of the EPA, nor of
other agencies in the Executive Branch of the Federal government, nor does mention of trade
names of commercial products constitute a recommendation for use. Reports and advisories of
the SAB are posted on the EPA website at http://www.epa.gov/sab.
in
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U.S. Environmental Protection Agency
Science Advisory Board (SAB)
Radiation Advisory Committee (RAC)
Augmented for the Review of EPA's Radiogenic
Cancer Risk Assessment
CHAIR
Dr. Bernd Kahn, Professor Emeritus, Nuclear and Radiological Engineering Program, and
Director, Environmental Radiation Center, Georgia Tech. Research Institute, Georgia Institute of
Technology, Atlanta, GA
MEMBERS
Dr. Susan M. Bailey, Associate Professor, Department of Environmental and Radiological
Health Sciences, Colorado State University, Fort Collins, CO
Dr. Thomas B. Borak, Professor, Department of Environmental and Radiological Health
Sciences, Colorado State University, Fort Collins, CO
Dr. Faith G. Davis, Senior Associate Dean and Director of Graduate Studies, Professor of
Epidemiology, Division of Epidemiology and Biostatistics, School of Public Health, University
of Illinois at Chicago, Chicago, IL
Dr. Brian Dodd, Independent Consultant, Las Vegas, NV
Dr. R. William Field, Professor, Department of Occupational and Environmental Health,
College of Public Health, University of Iowa, Iowa City, IA
Dr. Shirley A. Fry, Independent Consultant, Indianapolis, IN
Dr. William C. Griffith, Associate Director, Institute for Risk Analysis and Risk
Communication, Department of Environmental and Occupational Health Sciences, University of
Washington, Seattle, WA
Dr. Jonathan M. Links, Professor and Deputy Chair, Department of Environmental Health
Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
Dr. William F. Morgan, Director of Radiation Biology and Biophysics, Biological Sciences
Division, Fundamental & Computational Sciences Directorate, Pacific Northwest National
Laboratory, Richland, WA
Mr. Bruce A. Napier, Staff Scientist, Radiological Science & Engineering Group, Pacific
Northwest National Laboratory, Richland, WA
IV
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Dr. Daniel O. Stram, Professor, Department of Preventive Medicine, Division of Biostatistics
and Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los
Angeles, CA
CONSULTANTS
Dr. Ethel S. Gilbert, Staff Scientist, U.S. National Institutes of Health, National Cancer
Institute, Rockville, MD
Dr. Peter G. Groer, Professor Emeritus, University of Tennessee, Dept. of Nuclear
Engineering, Tampa, FL
Dr. David G. Hoel, Distinguished University Professor, Medical University of So. Carolina,
Department of Biometry & Epidemiology, Charleston, SC
Dr. Richard W. Hornung, Director of Biostatistics and Data Management, Division of General
& Community Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Dr. Genevieve Matanoski, Professor, Department of Epidemiology, Johns Hopkins University,
Baltimore, MD
Dr. Dale L. Preston, Principal Scientist, Hirosoft International, Eureka, CA
Dr. Genevieve S. Roessler, Professor Emerita and Radiation Consultant, Department of Nuclear
and Radiological Engineering, University of Florida, Elysian, MN
SCIENCE ADVISORY BOARD STAFF
Dr. K. Jack Kooyoomjian, Designated Federal Officer, US EPA, Science Advisory Board
(1400F), 1200 Pennsylvania Avenue, NW, Washington, DC, 20460
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U.S. Environmental Protection Agency
Science Advisory Board
FY 2009
CHAIR
Dr. Deborah L. Swackhamer, Professor and Co-Director, Environmental Health Sciences and
Water Resources Center, University of Minnesota, St. Paul, MN
MEMBERS
Dr. David T. Allen, Professor, Department of Chemical Engineering, University of Texas,
Austin, TX
Dr. John Balbus, Adjunct Associate Professor, George Washington University, School of
Public Health and Health Services, Washington, DC
Dr. Gregory Biddinger, Coordinator, Natural Land Management Programs, Toxicology and
Environmental Sciences, ExxonMobil Biomedical Sciences, Inc., Houston, TX
Dr. Timothy Buckley, Associate Professor and Chair, Division of Environmental Health
Sciences, College of Public Health, The Ohio State University, Columbus, OH
Dr. Thomas Burke, Professor, Department of Health Policy and Management, Johns Hopkins
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD
Dr. James Bus, Director of External Technology, Toxicology and Environmental Research and
Consulting, The Dow Chemical Company, Midland, MI
Dr. Deborah Cory-Slechta, Professor, Department of Environmental Medicine, School of
Medicine and Dentistry, University of Rochester, Rochester, NY
Dr. Terry Daniel, Professor of Psychology and Natural Resources, Department of Psychology,
School of Natural Resources, University of Arizona, Tucson, AZ
Dr. Otto C. Doering III, Professor, Department of Agricultural Economics, Purdue University,
W. Lafayette, IN
Dr. David A. Dzombak, Walter J. Blenko Sr. Professor of Environmental Engineering,
Department of Civil and Environmental Engineering, College of Engineering, Carnegie Mellon
University, Pittsburgh, PA
Dr. T. Taylor Eighmy, Vice President for Research, Office of the Vice President for Research,
Texas Tech University, Lubbock, TX
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Dr. Baruch Fischhoff, Howard Heinz University Professor, Department of Social and Decision
Sciences, Department of Engineering and Public Policy, Carnegie Mellon University, Pittsburgh,
PA
Dr. James Galloway, Sidman P. Poole Professor of Environmental Sciences
Associate Dean for the Sciences, College and Graduate School of Arts and Sciences, University
of Virginia, Charlottesville, VA
Dr. John P. Giesy, Professor and Canada Research Chair, Veterinary Biomedical Sciences and
Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Dr. James K. Hammitt, Professor, Center for Risk Analysis, Harvard University, Boston, MA
Dr. Rogene Henderson, Senior Scientist Emeritus, Lovelace Respiratory Research Institute,
Albuquerque, NM
Dr. James H. Johnson, Professor and Dean, College of Engineering, Architecture & Computer
Sciences, Howard University, Washington, DC
Dr. Bernd Kahn, Professor Emeritus, Nuclear and Radiological Engineering Program and
Director, Environmental Radiation Center, GTRI, Georgia Institute of Technology, Atlanta, GA
Dr. Agnes Kane, Professor and Chair, Department of Pathology and Laboratory Medicine,
Brown University, Providence, RI
Dr. Meryl Karol, Professor Emerita, Graduate School of Public Health, University of
Pittsburgh, Pittsburgh, PA
Dr. Catherine Kling, Professor, Department of Economics, Iowa State University, Ames, IA
Dr. George Lambert, Associate Professor of Pediatrics, Director, Center for Childhood
Neurotoxicology, Robert Wood Johnson Medical School-UMDNJ, Belle Mead, NJ
Dr. Jill Lipoti, Director, Division of Environmental Safety and Health, New Jersey Department
of Environmental Protection, Trenton, NJ
Dr. Lee D. McMullen, Water Resources Practice Leader, Snyder & Associates, Inc., Ankeny,
IA
Dr. Judith L. Meyer, Distinguished Research Professor Emeritus, University of Georgia, Lopez
Island, WA
Dr. Jana Milford, Professor, Department of Mechanical Engineering, University of Colorado,
Boulder, CO
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Dr. Christine Moe, Eugene J. Gangarosa Professor, Hubert Department of Global Health,
Rollins School of Public Health, Emory University, Atlanta, GA
Dr. M. Granger Morgan, Lord Chair Professor in Engineering, Department of Engineering and
Public Policy, Carnegie Mellon University, Pittsburgh, PA
Dr. Duncan Patten, Research Professor , Department of Land Resources and Environmental
Sciences, Montana State University, Bozeman, MT
Mr. David Rejeski, Director, Foresight and Governance Project, Woodrow Wilson
International Center for Scholars, Washington, DC
Dr. Stephen M. Roberts, Professor, Department of Physiological Sciences, Director, Center for
Environmental and Human Toxicology, University of Florida, Gainesville, FL
Dr. Joan B. Rose, Professor and Homer Nowlin Chair for Water Research, Department of
Fisheries and Wildlife, Michigan State University, East Lansing, MI
Dr. Jonathan M. Samet, Professor and Chair, Department of Preventive Medicine, University
of Southern California, Los Angeles, CA
Dr. James Sanders, Director and Professor, Skidaway Institute of Oceanography, Savannah,
GA
Dr. Jerald Schnoor, Allen S. Henry Chair Professor, Department of Civil and Environmental
Engineering, Co-Director, Center for Global and Regional Environmental Research, University
of Iowa, Iowa City, IA
Dr. Kathleen Segerson, Professor, Department of Economics, University of Connecticut, Storrs,
CT
Dr. Kristin Shrader-Frechette, O'Neil Professor of Philosophy, Department of Biological
Sciences and Philosophy Department, University of Notre Dame, Notre Dame, IN
Dr. V. Kerry Smith, W.P. Carey Professor of Economics , Department of Economics , W.P
Carey School of Business , Arizona State University, Tempe, AZ
Dr. Thomas L. Theis, Director, Institute for Environmental Science and Policy, University of
Illinois at Chicago, Chicago, IL
Dr. Valerie Thomas, Anderson Interface Associate Professor, School of Industrial and Systems
Engineering, Georgia Institute of Technology, Atlanta, GA
Vlll
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Dr. Barton H. (Buzz) Thompson, Jr., Robert E. Paradise Professor of Natural Resources Law
at the Stanford Law School and Perry L. McCarty Director, Woods Institute for the
Environment, Stanford University, Stanford, CA
Dr. Robert Twiss, Professor Emeritus, University of California-Berkeley, Ross, C A
Dr. Thomas S. Wallsten, Professor and Chair, Department of Psychology, University of
Maryland, College Park, MD
Dr. Lauren Zeise, Chief, Reproductive and Cancer Hazard Assessment Branch, Office of
Environmental Health Hazard Assessment, California Environmental Protection Agency,
Oakland, CA
SCIENCE ADVISORY BOARD STAFF
Mr. Thomas Miller, Designated Federal Officer, US EPA, Science Advisory Board (1400F),
1200 Pennsylvania Avenue, NW, Washington, DC, 20460
IX
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TABLE OF CONTENTS
1. EXECUTIVE SUMMARY 1
2. INTRODUCTION 4
2.1 BACKGROUND 4
2.2 REVIEW PROCESS AND ACKNOWLEDGEMENT 5
2.3 OVERVIEW OF EPA's DRAFT BLUE BOOK 5
3. RESPONSE TO CHARGE QUESTION 1: APPLICATION OF THE EXTENSIONS AND
MODIFICATIONS TO THE BEIR VII APPROACH IN THE DRAFT BLUE BOOK 8
3.1 CHARGE QUESTION # 1 8
3.2 RESPONSE TO CHARGE QUESTION # IA 8
3.2.1 ALPHA PARTICLE RADIATION 8
3.2.2 LOW-ENERGY ELECTRON AND PHOTON RADIATIONS 9
3.3 RESPONSE TO CHARGE QUESTION # IB 10
3.4 RESPONSE TO CHARGE QUESTION # Ic 11
3.4.1 KIDNEY 11
3.4.2 BONE 11
3.4.3 SKIN (FATAL AND NONFATAL NONMELANOMA CANCERS) 11
3.4.4 LIVER 12
3.4.5 LUNG 12
3.4.6 LEUKEMIA 13
3.5 RESPONSE TO CHARGE QUESTION # ID 13
3.6 RESPONSE TO CHARGE QUESTION # IE 14
3.6.1 NONFATAL SKIN CANCER 14
3.6.2 PRENATAL EXPOSURE CANCER RISK 14
4. RESPONSE TO CHARGE QUESTION 2: UNCERTAINTY ANALYSIS 16
4.1 CHARGE QUESTION # 2 16
4.2 RESPONSE TO CHARGE QUESTION # 2A 16
4.2.1 GENERAL COMMENTS 16
4.2.2 SPECIFIC COMMENTS 17
4.2.3 ADDITIONAL COMMENTS ON RISK TRANSFER 19
4.3 RESPONSE TO CHARGE QUESTION # 2B 20
5. RESPONSE TO CHARGE QUESTION 3: COMMENTS ON PRESENTATION OF OVERALL
INFORMATION AND APPLICATION OF BEIR VII IN THE DRAFT BLUE BOOK 21
5.1 CHARGE QUESTION # 3 21
5.2 RESPONSE TO CHARGE QUESTION # 3A 21
5.2.1 NONCANCER MORTALITY 21
5.2.2 INFORMATION FROM ICRP AND UNSCEARREPORTS 22
5.2.3 RADIOGENIC THYROID CANCER 22
5.2.4 RADIOGENIC BRAIN CANCER 22
5.3 RESPONSE TO CHARGE QUESTION # SB 22
5.3.1 TABULAR PRESENTATIONS 23
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5.3.2 TOPICAL ORGANIZATION AND CONTENT 23
5.3.3 RELATION OF INPUT INFORMATION TO PRESENTED RESULTS 23
5.3.4 APPLICATION OF DDREF 24
5.4 RESPONSE TO CHARGE QUESTION # 3c 24
5.4.1 LOW-DOSE PROTRACTED EXPOSURE 24
5.4.2 CANCER SITES WITH LIMITED DATA 24
5.4.3 CANCER SUBTYPES 24
5.4.4 PRESENTATION OF STEPWISE EPA DEVELOPMENT OF REVISED FOR 13 25
REFERENCES CITED 26
APPENDIX A - EDITORIAL COMMENTS 36
APPENDIX B-ACRONYMS 38
XI
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1. EXECUTIVE SUMMARY
The Radiation Advisory Committee (RAC) of the Science Advisory Board (SAB) has
completed its review of the Agency's draft titled "EPA Radiogenic Cancer Risk Models and
Projections for the U.S. Population" dated December 2008 (U.S. EPA/ORIA 2008). In this
draft "Blue Book", the EPA Office of Radiation and Indoor Air (ORIA) outlines proposed
changes in the Agency's methods for estimating radiogenic cancer risks and gives risk estimates
for individual radiogenic cancers that it derived by the proposed methods. The EPA sought the
RAC's advice on its draft Blue Book to assure reliable application of radiogenic cancer risk
assessment in EPA programs, notably updating Federal Guidance Report (FGR) 13, Health Risks
from Low-level Environmental Exposure to Radionuclides (U.S.EPA/ORIA 1999).
The RAC responded as follows to the EPA's itemized charge questions:
Charge Question 1 on appropriateness of models not directly taken from the National Research
Council BEIR VII Report:
la. The RAC agrees with the methods proposed by the EPA to estimate the cancer risks of alpha
particles that have greater linear energy transfer (LET) and relative biological effect (RBE)
values than beta particles, gamma rays and x rays. For low-energy beta particles (notably
tritium) and low-energy photons, on the other hand, the RAC finds that while the EPA review of
information is sufficient to conclude that the RBE exceeds 1, it is insufficient for selecting
appropriate RBE values. The RAC recommends that EPA staff publish, for review by the
scientific community, a compilation and evaluation of pertinent studies in a peer-reviewed
journal and then select an RBE value based on this document and professional responses to it.
This effort should not delay publication of the Blue Book, but its results should be available
before the EPA issues the revised FGR 13.
Ib. The RAC recommends — in contrast to BEIR VII — use of an arithmetic mean for each
pair of excess absolute risk (EAR) value and excess relative risk (ERR) value in transferring
lifetime attributable risk (EAR) to the U.S. population from the Japanese life span study (ESS)
population. The most important reason, in the absence of a theoretical basis for using either the
arithmetic or the geometric mean, is that the arithmetic mean results from a linear addition and
averaging of excess risk data, with equal emphasis on higher and lower values. The subsequent
choice of weighting factor then explicitly captures judgments about the relative importance of
the ERR- and EAR-based risk estimates. This approach has other benefits as well, such as
consistency with uncertainty estimates. Neither the EPA approach to calculating the geometric
mean (although supported in the RAC review of the EPA White Paper because of its
calculational consistency) nor the BEIR VII approach provides any calculational advantage
relative to the arithmetic mean.
Ic. The RAC agrees with the approaches proposed by the EPA to derive risk estimates not
specified in BEIR VII for solid cancers (kidney, skin) and for cancers associated with exposure
to alpha-particle emitters (lung, liver). With regard to the liver, the RAC cautions that the organ
1
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is subject to tumors with diverse histopathologies and possibly different outcomes. The RAC
recommends for bone cancer that the EPA reconsider utilizing the radium data for the dial
painter cohort (as asserted in the Blue Book, p. 64, but not done), and, most importantly, apply
recently published analyses of the data. For leukemia, the RAC notes the uncertainty related to
the EPA changing the RBE for alpha-particle radiation from 1 to 2 and suggests that the EPA
review the extent of these uncertainties before committing to the change.
Id. The RAC compliments the EPA on developing an improved model that considers the
survival rate of breast cancer patients. It suggests that the EPA consider in the future applying
this approach to derive risk estimates as sufficient data become available for other cancers (e.g.,
colon cancer) for which current survival rates are higher than previously observed.
le. The RAC agrees with the EPA approach for separating from its overall risk estimates the
nonfatal skin cancer risk estimates because of the dominance of spontaneous (nonradiogenic)
nonmelanoma skin cancers and the associated experience that most respond to treatment and are
not fatal. Their inclusion with cancers that result in a much higher mortality rate would greatly
distort the overall cancer morbidity and mortality risk estimates.
The RAC also agrees with the EPA that it is appropriate to use the same model to
estimate radiogenic cancer risk in adults whether the exposure occurs in utero or in childhood.
Differences in risk estimates between the two groups were not statistically significant.
Charge Question 2 on the adequacy of the uncertainty analysis:
2a. The RAC considers the approach to uncertainty analysis in the draft Blue Book to be
reasonable and comprehensive in deriving (1) overall risk estimate uncertainty from sampling
variation, (2) the various model parameters, and (3) transfer of data to the U.S. population. The
RAC recommends greater specificity, clarity, and transparency in identifying and quantifying
each source of uncertainty. One effective technique is to discuss each contributing uncertainty
to the LAR in the text and to summarize it in a table (in greater detail than is now in the Blue
Book) with emphasis on the major sources of uncertainty and how each is quantified.
The RAC recommends that the Blue Book make the Bayesian uncertainty analysis as
consistent as possible with the point estimates of risk. The EPA should justify use of these two
separate approaches to obtain best estimate values and confidence intervals.
The RAC recommends that the EPA verify the uncertainty analysis by obtaining
uncertainty intervals with a perturbation approach. The EPA should vary the value of each
major contributor to uncertainty over a reasonable range to recalculate the corresponding range
of the point estimate and demonstrate the validity of the recommended uncertainty.
2b. The RAC recommends that the EPA expand the text to clarify the reasoning behind the
selection of distributions chosen for the various sources of uncertainty. The discussion of
subjective priors listed partially in Table 4-1 of the draft Blue Book should justify the assigned
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distributions so that the reader can trace the basis of each decision concerning central value,
uncertainty, and distribution, and have confidence in these characteristics.
Charge Question 3 on presentation of overall information and application of BEIR VII:
3a. The RAC recognizes the scientific defensibility and appropriateness of the Blue Book.
However, the RAC recommends that EPA enhance Blue Book contents by reporting further
information on radiogenic cancer at low radiation doses from (1) studies ofnoncancer
mortality; (2) brain cancer studies; (3) recent ICRP and UNSCEAR reviews; and (4) NCRP
Report #159 on the risk of radiation-induced thyroid cancer (NCRP 2009).
3b. The RAC found that most of the calculations and results in the draft Blue Book are readily
understandable. The RAC recommends that the EPA clarify the purpose and application of
the Blue Book by presenting in detail, in its first Section, the contributions by Blue Book
contents in preparing Federal Guidance Report (FGR) 13 and, in its last Section, FGR 13
values ofradionuclide risk coefficients. This information should be sufficient to permit the
reader to attribute any significant changes in FGR 13 values to changes proposed in this Blue
Book, or to changes in the physiological models with which they will be combined, or to both, so
that such changes then can be examined in greater detail.
3c. The RAC considers the draft Blue Book to have the accuracy and balance appropriate to its
intended purpose, once the recommended revisions noted in this review are implemented. The
RAC recommends that EPA enhance the level of detail by expanding its discussion of the
following risk estimates: (1) those based on studies of cohorts exposed to low-dose protracted
radiation, and (2) those for distinguishable types of cancer within a given organ.
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2. INTRODUCTION
2.1 Background
In 1994, the U.S. Environmental Protection Agency (EPA) published the report
"Estimating Radiogenic Cancer Risks" (U.S. EPA 1994) often referred to as the "Blue Book,"
because of the blue cover on the document (http://epa.gov/radiation/docs/assessment/402-r-93-
076.pdf). The Blue Book presents EPA's current methodology for quantitatively estimating
radiogenic cancer risks. This EPA estimation of cancer risks due to low linear energy transfer
(LET) radiation exposures is based on information, mainly about the Japanese atomic bomb
survivors, that had become available since the publication of "The Effects on Populations
Exposed to Low Levels of Ionizing Radiation BEIR III" (NAS/NRC 1980) and the original Blue
Book (U.S. EPA 1984) that followed it. The incidence of fatal cancer in specified organs and
tissues per unit dose was estimated for a stationary U.S. population based on 1980 vital statistics.
The effect of high-LET alpha particles in terms of their RBE also was considered. The 1994
EPA report replaced the 1984 EPA report.
In an addendum to the 1994 report, the EPA published minor adjustments to the previous
values in terms of more recent vital statistics (U.S. EPA/ORIA 1999a). The addendum also
presented a partial analysis of the uncertainties in the values to provide a confidence interval for
the cancer risk per unit radiation dose (http://epa.gov/radiation/docs/assessment/402-r-99-
003.pdf).
Also in 1999, the Agency applied the 1994 Blue Book contents, metabolic models, and
usage patterns to publish Federal Guidance Report 13 (FGR 13), "Health Risks from Low-level
Environmental Exposure to Radionuclides" (U.S. EPA/ORIA 1999), with cancer risk estimates
for over 800 radionuclides by several exposure pathways, models, and U.S. usage patterns
(http://epa.gov/radiation/docs/federal/402-r-99-001.pdf). The risk estimates were later updated
(http://www.epa.gov/radiation/federal/techdocs.html#cd_supplement). Prior to their
publications, both the 1994 Blue Book and the addendum were reviewed by the Radiation
Advisory Committee (RAC) of the EPA Science Advisory Board (SAB) (U.S. EPA/SAB 1994,
1999).
In 2006, the National Research Council (NRC) of the National Academies of Sciences
(NAS) released "Health Risks from Exposure to Low Levels of Ionizing Radiation, BEIR VII
Phase 2 " (NAS/NRC 2006) (available at http://nap.edu/catalog/11340.htmltftoc) which
primarily addresses cancer and genetic risks from low doses of low energy transfer (LET)
radiation. This report was co-sponsored by the EPA and several other Federal agencies.
Also in 2006, the EPA prepared the draft "White Paper: Modifying EPA Radiation Risk
Models Based on BEIR VII" (U.S. EPA/ORIA 2006) in anticipation of issuing a revised Blue
Book (http://epa.gov/radiation/docs/assessment/white-paper8106.pdf). In the White Paper, the
Agency proposed changes to the EPA's methods for estimating radiogenic cancers, based on the
contents of BEIR VII and some ancillary information. The Agency expected to adopt the models
and methods recommended in BEIR VII, but believed that certain modifications and expansions
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were desirable or necessary for the EPA's purposes. The EPA Office of Radiation and Indoor
Air (ORIA) requested the SAB to review the Agency's draft White Paper and provide advice
regarding the proposed approach to dose-response assessment of radionuclides. The SAB/RAC
prepared an advisory, EPA-SAB-08-006 (U.S. EPA/SAB 2008)
(http://vosemite.epa.gov/sab/sabproduct.nsf/FD9963E56C66E4FF852573E200493359/$File/EP
A-SAB-08-006-unsigned.pdf). The SAB reviews responding to the above-cited EPA documents
can be found on the EPA SAB Web site at http://www.epa.gov/sab.
In December 2008, the ORIA issued the draft of the revised Blue Book, "EPA
Radiogenic Cancer Risk Models and Projections for the U.S. Population" (U.S. EPA/ORIA
2008), and asked the SAB to review it. The draft document contains specific methods and their
applications for estimating the risks of radiogenic cancer for many organs and tissues, with
uncertainty estimates. It utilizes the advice contained in the BEIR VII Phase 2 report, as well as
in the SAB's advisory for the White Paper and the earlier Blue Book addendum, both described
above.
2.2 Review Process and Acknowledgement
The SAB RAC met in a public teleconference on February 27, 2009, and conducted a
public meeting on March 23, 24, and 25, 2009, for this draft Blue Book review (see 74 Fed.
Reg., 5935, February 3, 2009). Additional public teleconferences took place on June 18, 2009
and July 22, 2009 (see 74 Fed. Reg., 25529, May 28, 2009). The notices, the charge to the RAC,
and supplemental information may be found at the SAB's Web site (http://www.epa.gov/sab).
The draft quality review dated August 20, 2009, was forwarded to the Chartered SAB for its
September 24, 2009, public teleconference (see 74 Fed. Reg., 42297, August 21, 2009). This
final report reflects the suggested editorial changes from the Chartered SAB.
The draft document "EPA Radiogenic Cancer Risk Models and Projections for the U.S.
Population, "December, 2008, is impressively researched, scientifically sound and well written.
Presentations by the EPA staff and the public commentary in the course of the public meetings
were helpful to the RAC in preparing this review. The EPA staff provided useful clarifications
of its approach to preparing the draft Blue Book, and conveyed information in response to
questions by the augmented RAC. The EPA/ORIA staff responded to all RAC requests and was
forthcoming in explanations and clarifications.
2.3 Overview of EPA's Draft Blue Book
The Agency is now requesting that the SAB review the draft document, "EPA
Radiogenic Cancer Risk Models and Projections for the U.S. Population, " dated December
2008, which was developed as a result of the previous White Paper advisory review. This draft
document presents the scientific basis for new EPA estimates of cancer incidence and mortality
risks due to low doses of ionizing radiation (IR) for the U.S. population. These estimates are
based on available information, and for the most part, are calculated using models recommended
in the NRC's BEIR VII Report. The three specific charge questions that follow (U.S. EPA/
ORIA 2009) are presented in Sections 3.1, 4.1, and 5.1 of this review. The revised Blue Book
will then serve as a basis for an updated version of FGR-13.
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The introductory Section 1 cites the earlier Blue Book (U.S. EPA 1994) and the BEIR
VII Report (NAS/NRC 2006). The BEIR VII Report is the major source of information, but
more-recently published information has also been considered. Major sources of uncertainty are
highlighted.
Section 2 presents the scientific basis for cancer risk. It briefly discusses biological
mechanisms that lead to radiogenic cancers. It describes a modified linear no-threshold
hypothesis and the extrapolation of low-LET risks from the measured results at relatively high
radiation doses to exposures at low doses and low dose rates. A Dose/Dose Rate Effectiveness
Factor (DDREF) is described for calculating the risk due to chronic low-dose and low-dose-rate
radiation exposure. Several effects that have been observed or proposed at low doses are
discussed, but are not invoked in subsequent calculations of risk. The authors present a survey
of the epidemiological evidence for radiogenic cancer risk, notably the LSS of atomic bomb
survivors at Hiroshima and Nagasaki, but also patients exposed to medical radiation.
Epidemiological studies of cohorts exposed to low levels of radiation over extended periods,
such as radiologists and nuclear workers, are cited.
The draft Blue Book presents revised estimates of cancer incidence and mortality risks
associated with low doses of ionizing radiation, defined as <0.1 Gray (Gy), for the U.S.
population. The risk estimates for solid cancers and leukemia following exposure to low doses
of low-LET radiations are derived exclusively from preferred models developed by the BEIR
VII committee. These models are applied to stationary year 2000 population mortality based on
survival rates in the U.S. to obtain an estimate of the LAR per person-Gy for the U.S. population.
The process for obtaining the LAR is described in Section 3. It is based on the mean of
each paired set of the ERR and EAR values derived from models in BEIR VII (Table 3-3). The
EPA uses a weighted geometric mean to combine the results from the ERR and EAR models to
obtain a point estimate of the excess risk, M (d,a,e), at an attained age a, following a single
exposure to dose d, at age e. This value is applied to the stationary population to obtain the "best
estimate" LAR. Section 3 also presents distinct approaches for breast cancer, leukemia, skin
cancer, and residual cancer sites. Each of these cancer types is treated with a separate risk
model.
Uncertainties in projections of the LAR for low-LET radiations are described in Section
4. The focus of the uncertainty analysis is on the calculation of LAR per person-Gy for the U.S.
population, based on the data for the LSS. An independent Bayesian assessment of uncertainty
is applied with a methodology quite different from that used to obtain point estimates in Section
O
Risk of radiogenic cancer associated with the high-LET radiation of alpha particles is
discussed in Section 5. Laboratory and epidemiological studies that provide data on RBEs for
alpha-particle radiation are presented. The latter include bone cancer associated with internal
exposure to radium isotopes by injection (224Ra) or ingestion (226Ra, 228Ra); liver cancer
associated with administration of diagnostic doses of Thorotrast to patients, and plutonium
intake by Russian nuclear workers; and lung cancer among underground miners exposed to alpha
particles from inhalation of radon gas and radon-daughter particles, and among Russian nuclear
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workers at risk of inhaling plutonium particles. The risk is evaluated in terms of the RBE values
based on contemporary data for alpha particles in specific organs or tissues.
Section 6 addresses risk from prenatal exposure to radiation. Induction of childhood
cancer due to fetal radiation has been shown in various case-control studies (Stewart et al. 1958;
MacMahon 1962; and other references in Section 6, p.96). While a causal link between in utero
radiation exposure and childhood cancer is generally accepted (Doll and Wakeford 1997), some
have termed the evidence for childhood cancers other than leukemia "equivocal" (Boice and
Miller 1999).
The atomic bomb survivors provide the only data on radiation effects of adult-onset
cancer risks among persons exposed in utero (Preston et al. 2008). The survivor data exhibit a
statistically significant radiation dose response for adult-onset cancers with levels of risk that are
considerably less than those reported for childhood cancers. There is also a weak suggestion that
the radiation effect for those exposed in utero may be less than what has been seen for atomic
bomb survivors exposed as children. The EPA decided to base risk estimates for childhood
cancers following in utero exposure on the summary risk estimates presented in Doll and
Wakeford (1997) and recommended by the International Commission on Radiological Protection
(ICRP 2000), and risk estimates for adult-onset cancers on the corresponding risk estimates for
childhood exposure.
In the very brief Section 7, application to calculating radionuclide risk coefficients is
considered. The EPA will combine the revised excess cancer morbidity and mortality risk per
person-Gy from this Blue Book with the latest available ICRP dose models to revise the risk for
each radionuclide per Bq intake or per unit exposure by external radiation. This information will
be reported in a revision of FOR 13. The ORIA expects some increases and some decreases,
depending on the radionuclide and target organ.
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3. RESPONSE TO CHARGE QUESTION 1: APPLICATION OF THE
EXTENSIONS AND MODIFICATIONS TO THE BEIR VII APPROACH IN
THE DRAFT BLUE BOOK
3.1 Charge Question # 1: As in BEIR VII, models are provided in the draft document for
estimating risk as a function of age at exposure, age at risk, gender, and cancer site, but a
number of extensions and modifications to the BEIR VII approach have been implemented.
First, BEIR VIIfocused on the risk from low-LET radiation only, whereas risks from higher LET
radiations are also addressed here. Second, this document presents a slightly modified
approach for combining BEIR VII models for projecting risks from Japanese A-bomb survivors
to the U.S. population. Third, this document goes beyond BEIR VII in providing estimates of risk
for certain other cancers. Fourth, a modified method is employed for estimating breast cancer
mortality risk, which corrects for temporal changes in breast cancer incidence and survival.
Finally, quantitative estimates of risks for skin cancers and from prenatal exposures are
included. Please comment on the appropriateness of the following either not specified in BEIR
VII or else otherwise modified by EPA from BEIR VII:
a. Approaches described for extending risk estimates to radiations of different LETs
- in particular, deriving site-specific risk estimates for alpha or low energy
electron and photon radiations based on models derived from the A-bomb
survivors, who were primarily exposed to higher energy gamma rays (see Section
5).
b. EPA 's adaptation of the BEIR VII weighted geometric mean approach for
combining the EAR and ERR models for projecting risk from the LSS to the U.S.
population (see Section 3.9).
c. Estimation of risks not specified in BEIR VII, including kidney, bone, and skin
cancers, as well as for alpha particle irradiation of the liver (see Sections 3.3 and
5.1).
a. Method for calculating breast cancer mortality risk, accounting for the relatively
long time from detection until death (see Section 3.10)
b. Approach for separating out nonfatal skin cancers and risks from prenatal
exposures from the overall risk estimates (see Sections 3.3 and 6).
3.2 Response to Charge Question # la
3.2.1 Alpha Particle Radiation
To derive risk estimates for site-specific alpha-particle induced cancers, the EPA
proposes to use the BEIR VII gamma-ray risk estimates, directly or with proposed modifications
as necessary, after applying an RBE of 20. Exceptions to this general approach are proposed for:
(1) Leukemia, for which an RBE of 2 will be applied to the BEIR VH-based gamma-ray
estimate;
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(2) Liver cancer with an RBE of 40;
(3) Lung cancer, for which the EPA proposes continuing to use models derived from BEIR VI
(NAS/NRC 1994) to estimate the lung cancer risk from inhaled radon progeny; and
(4) Bone cancer, for which the EPA obtains the alpha-particle exposure risk per Gy from patients
injected with 224Ra. This value is divided by an RBE of 10 to obtain the low-LET risk.
The RAC considers reasonable and generally acceptable the approach proposed by the
EPA for obtaining cancer risk estimates from alpha-particle emitters with the RBE values that
the EPA proposes. Specific advice is given in response to question #lc in Section 3.4 below.
3.2.2 Low-Energy Electron and Photon Radiations
Extensive discussion by RAC members regarding proposed changes by the EPA to the
RBE for low-energy electron and photon radiations identified the following questions that should
be addressed before a revised RBE is selected:
• Was this change recommended/suggested/implied in BEIR VII?
• Does ICRP, NCRP, or UNSCEAR have similar recommendations?
• Does the NIOSH Interactive Radioepidemiological Program (IREP) use an RBE > 1?
• Is the scientific rationale for this change suitably mature at present (Hunter and Muirhead
2009)?
• What will be the reference source (1 MeV electrons and/or 60Co)?
• Will this change be restricted only to radionuclides with beta-particle energies similar to
3H?
• How will "estimations" of "low energies" be determined in the case of mixed exposures
(e.g., photons and beta particles)?
• What is the rationale for using cutoffs at specific energies, i.e., 1, 3 or 5 keV?
• Which radionuclides will be included and/or excluded?
In previous comments (U.S. EPA/SAB 2008) on the EPA White Paper (U.S. EPA/ORIA
2006), the RAC supported EPA use of an RBE of 2 - 2.5 for photons of energies less than 30
keV and for 3H beta particles (0 to 18.6 keV). In light of this White Paper review and the current
discussion, the RAC recommends that the EPA prepare detailed justification to support a
proposed change in the RBE values for low-energy low-LET ionizing radiation. The EPA
should encourage preparation of a peer-reviewed publication that addresses these issues, consider
the responses by the scientific community, and then, before publishing the revised FGR 13,
decide the RBE value.
An important concern is the validity for diagnostic medical x rays of the proposed change
in the RBE (to ~ 1.4). The draft Blue Book notes (on pages 72 and 95) that risk coefficients
derived from studies of cohorts medically treated with x rays (at high but fractionated doses) in
some cases differ from those observed for A-bomb survivors (Hunter and Muirhead 2009; Little
2001). Given that medical radiation exposures make up the majority of the average U.S.
individual annual radiation dose (NCRP 2009a), the implications of a change in the RBE on the
reported dose for individuals can be significant in the long term.
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3.3 Response to Charge Question # Ib
The site-specific risk estimates in BEIR VII were computed as a weighted geometric
mean of ERR- and EAR-based LAR estimates for the year 2000 US population. The EPA has
proposed a method to compute an LAR as a weighted geometric mean of age- (and age-at-
exposure-) specific excess rates for the ERR and EAR models and then to apply this mean excess
rate function to a stationary US population. The EPA specifically asked the RAC about its
decision to use an average excess rate function rather than averaging the ERR- and EAR-based
LAR estimates. The EPA staff explained during the meeting that the primary motivation for
developing the average rate method was to insure additivity of age-specific risks.
The RAC recommends that the LAR computation makes use of the arithmetic mean
instead of the choice described by the EPA. The RAC considers the arithmetic mean preferable
even though this is a departure from the BEIR VII approach and even though the RAC endorsed
the average rate method in its Advisory on the White Paper (U.S. EPA/SAB 2008). The primary
reason for this current RAC recommendation is that the geometric mean results in a lower risk
estimate whereas the arithmetic mean equally balances the low and high risk estimates. It is the
selection of weights that explicitly captures judgments about the relative importance of the ERR-
and EAR-based risk estimates for weighted arithmetic means. Furthermore, use of arithmetic
means for risk estimates insures additivity of the age-specific risk estimates. The RAC
recommends that the Blue Book present both ERR- and EAR-based LAR estimates and then
compute the suggested risk estimate as a weighted arithmetic mean of the two estimates.
The BEIR VII report does not discuss these issues; geometric means may have been used
primarily because they simplified the analytical uncertainty assessment carried out for BEIR VII.
Because the EPA uses Bayesian Monte-Carlo methods to assess uncertainty, the complexity of
the uncertainty evaluation is not affected by how the risks are combined.
Arithmetic means have been used for the current (and earlier) ICRP recommendations.
The IREP also uses arithmetic means to combine relative-risk and absolute-risk based estimates
when computing probability of causation. Recent UNSCEAR reports (UNSCEAR 2000, 2008)
present ERR- and EAR-based estimates, but do not combine them.
Concerning the key issue of weighting results by the two models, the sense of the RAC is
that weighting should emphasize ERR models more than EAR models except for outcomes with
enough relevant data outside the LSS population (e.g., breast cancer) to indicate that EAR
models transfer risk information more accurately. This emphasis appears in the point estimation
process which, to the extent that it follows BEIR VII, places a weight of 0.7 on the ERR and 0.3
on the EAR results. Observations of tumor sites with different frequency of background
occurrence, and sometimes also over different strains of experimental animals, show that ERR
parameters tend to be more similar than EAR parameters (Storer et al. 1988). The RAC
recommends that the Blue Book include a brief discussion concerning the greater weight given to
the ERR-based risks than to the EAR-based risks in most cases, but not all (for example, lung
and breast cancer).
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Use of arithmetic instead of geometric means for averaging results based on ERR and
EAR models should improve consistency between the recommended point estimates and central
estimates from the uncertainty analysis. To resolve remaining discrepancies, the RAC suggests
that EPA make the prior distributions of weight parameters for the ERR and EAR models used in
the uncertainty analysis more compatible with the provided point estimates.
The question arises that if weighted arithmetic means are used in place of weighted
geometric means, do the site-specific ERR/EAR weights recommended by BEIR VII require
change? The RAC does not believe so because BEIR VII members apparently were thinking in
terms of linear (arithmetic) weights when they defined the weights used in their computations.
The RAC agrees with the EPA decision to use a stationary population rather than a
census-based population in LAR computations. The reasons for this change were cogently
described in the EPA staff presentation to the RAC. The RAC recommends that this discussion
(including presentation of gender-specific population pyramids or age-adjusted rates for selected
cancers) be included in the Blue Book to show the effect on solid cancer risk estimates of the
switch from a census based population to a stationary population.
3.4 Response to Charge Question # Ic
3.4.1 Kidney
In the absence of adequate epidemiological data for deriving a separate estimate for the
risk of radiogenic kidney cancer following exposure to low-LET radiation, the proposed EPA
kidney cancer risk calculation reasonably uses the BEIR VII residual cancers ERR model and the
EAR model with an adjustment factor.
3.4.2 Bone
The RAC notes that its Advisory on the Agency Draft White Paper (U.S. EPA/SAB
2008) (Section 5.7, page 19) supported the use of human data to derive estimates of the bone
cancer risk from 224Ra. The data from the study of radium dial painters who were exposed to
226Ra and 228Ra were recommended to derive directly the bone cancer risk from these
radionuclides. These approaches are outlined in the draft Blue Book (Section 4.2.2, page 64),
but radium dial painter data apparently were not used. The more detailed approach considered in
Section 5.1.2, pages 84-85, does not reflect attention to the Advisory's recommendation. The
RAC now reiterates this recommendation because the nature of the exposures (chronic, lifetime)
and the biokinetics of 226Ra and 228Ra are different from those of 224Ra.
When reconsidering the use of the radium dial painter data, the RAC recommends that
the EPA include the more recent analyses of the data for this population (Carnes et al. 1997;
Hoel and Carnes 2004).
3.4.3 Skin (Fatal and Nonfatal Nonmelanoma Cancers)
The EPA proposes, in draft Blue Book pages 31-32, to deviate from its previous approach
(U.S. EPA 1994) based on ICRP recommendations (ICRP 1991) for estimating the risk of
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radiation-induced nonmelanoma skin cancer (NMSC). This change reflects the findings of more
recent epidemiological analyses, changing disease patterns, and the conclusion that essentially all
NMSCs induced by low-to moderate doses of ionizing radiation are of the basal cell carcinoma
(BCC) type and nonfatal (Shore 2001, 2002; Preston et al. 2007; Karagas et al. 1999; Ron et al.
1991), as stated in the draft Blue Book (see also Section 3.6.1).
The RAC considers the proposed updated approach for deriving risk estimates for fatal
and nonfatal NMSC to be reasonable and acceptable. This EPA approach applies its new model
described in the Blue Book with age-specific baseline incidence rates to derive the ERR for the
nonfatal incidence of radiation-induced NMSC. More recent estimates of mortality due to BCC
in the general population (Lewis and Weinstock 2004) will be used as baseline data in estimating
the risk of fatal radiogenic NMSC. The NMSC risks for both incidence and mortality will be
estimated for males and females separately and in combination (sex-averaged). The EPA also
will use the revised DDREF value of 1.5 from BEIR VII to derive NMSC risk estimates in the
low-dose range in place of the value 2 used previously.
3.4.4 Liver
The liver is recognized as a target organ for certain alpha-particle emitters. The
relevance of the colloidal nature of Thorotrast should be considered and how this might impact
the radiogenic risks of liver cancer. Comparison of the liver cancer risk estimate for gamma
radiation derived by BEIR VII from the LSS data with that obtained from the follow-up study of
Danish Thorotrast patients suggested an RBE of 20 for alpha-particle radiation (Andersson et al.
1994). While recognizing the uncertainties inherent in both studies with respect to liver cancer
and the value of this RBE, the EPA initially proposed use of an RBE of 20 with the BEIR VII
liver cancer risk estimate to derive an estimate for alpha-particle-induced liver cancer (U.S.
EPA/ORIA 2006). The RAC supported this approach for liver and certain other cancers that
have been associated with alpha particle radiation (U.S. EPA/SAB 2008) with the
recommendation that any additional epidemiological data be taken into consideration.
Based on additional data from the follow-up study of German Thorotrast patients (Van
Kaick et al. 1999) and a reanalysis of the Danish patient data (Leenhouts et al. 2002) with an
empirical model and a lifetime risk projection, the EPA has revised its proposal to use a scaled
version of the BEIR VII model. The EPA now will use the BEIR VII low-LET age and gender-
specific liver cancer risk estimates and an RBE of 40 to provide risk estimates for alpha-particle-
induced liver cancer at environmental low doses. The RAC considers this approach reasonable,
and the use of an RBE of 40 as appropriate. However, because in the context of this report,
'liver cancer' (like 'cancer' in most other organs) is an all-embracing term that includes a diverse
number of histopathologies, the RAC cautions that the uncertainties associated with grouping
these different tumor histopathologies may outweigh any benefits gained by changing the RBE
to 40, and suggests that the EPA address this uncertainty before confirming this change to 40.
3.4.5 Lung
The draft Blue Book adopts an RBE of 20 for lung cancer by alpha-particle emitters other
than radon, baesd on BEIR VI (NAS/NRC 1994) models. A separate risk model for radon is the
suitable approach outlined in the draft Blue Book. The epidemiological evidence for other
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inhaled alpha-particle emitters comes primarily from the Mayak worker studies, because other
studies do not have sufficient power (i.e., precision) to estimate risks. As noted in the draft Blue
Book, the Mayak worker studies are in an early stage, but several reports are available. The lung
cancer risk estimates reported by the two most recent Mayak reports (Jacob et al. 2007;
Sokolnikov et al. 2008) were consistent with an RBE of 20. The EPA proposes to use an RBE of
20 which the RAC considers reasonable. The same value of 20 was recommended recently by
the ICRP (2003, 2005).
Animal studies show RBE values at, above, and below 20. Some animal studies of
radionuclides deposited in the lung obtained an RBE value of 20 or above (Gilbert et al. 1998;
Hahn et al. 1999; Lundgren et al. 1995, 1996, 1997; Muggenburg et al. 1996, 2006) by
comparing the effects of radionuclides that emit alpha particles with those that emit beta particles
and gamma rays. Other animal studies obtained a much lower RBE (Priest et al. 2006). The
RAC suggests caution in applying these values derived from animals that in many of these
groups were exposed to doses above 1 Gy, well above the low-dose range. Such elevated doses
can have a strong influence on the shape of the dose response curve and the calculated RBE.
3.4.6 Leukemia
The draft Blue Book recommends an RBE of 2 for alpha-particle-induced leukemia based
on epidemiological studies at low doses of 224Ra. This is a change from the value of 1 used in
past EPA reports. The RAC considers that the RBE of 2 may be reasonable, but recommends
that the EPA discuss in the Blue Book the uncertainties in this value that derive from estimating
doses from alpha-particle emitters and from different temporal patterns between the LSS and the
224Ra group for the appearance of leukemia. Animal studies have not been helpful in
understanding the RBE for alpha particles because of the variability in leukemia induction
among strains (Storer et al. 1990); moreover, they have not had sufficient power to estimate
leukemia risks from radiation (NAS-NRC 1990).
3.5 Response to Charge Question # Id
BEIR VII computed breast cancer mortality risk estimates by scaling age-specific
incidence risks for the ratio of the (age-specific) mortality-to-incidence rate ratios. The EPA
proposes replacing this simple ratio by a factor that allows for the relative survival of breast
cancer patients. The data presented to the RAC by EPA staff suggest that the modified method
leads to more realistic breast cancer mortality risk estimates. The RAC believes that the EPA
method is an improvement over that used by BEIR VII because the relative survival of breast
cancer patients is high and the excess risk estimates, including those derived by application of
ERR estimates used in the LAR computations, increase with attained age. The EPA should
consider in the future using a similar approach in computing mortality risks as sufficient data
become available for other types of cancer with relatively high survival rates, such as colon
cancer.
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3.6 Response to Charge Question # le
3.6.1 Nonfatal Skin Cancer
As noted in the response to Question #lc with regard to Skin (Fatal and Nonfatal
Nonmelanoma Cancers) in Section 3.4.3, the RAC supports the EPA proposal to update its
approach by deriving risk estimates for incidence and mortality associated with radiation-
induced NMSC from data for BCC in the light of more recent epidemiological data. In
particular, the RAC supports Shore's conclusion that essentially all NMSC induced by ionizing
radiation in the low to moderate dose range are of the BCC type with a very low mortality rate
(Shore 2001).
The RAC supports the EPA decision not to include NMSC risk estimates in estimating
total radiogenic cancer risk (see Tables in the draft Blue Book, Sections 3 and 4). The
dominance of NMSC incidence at the very low NMSC mortality would seriously distort the
summed incidence and mortality rates used for estimatng total radiogenic cancer rates.
3.6.2 Prenatal Exposure Cancer Risk
The RAC considers that estimation of cancer risks from prenatal radiation in the draft
Blue Book is appropriately based on the literature. Prenatal radiation exposure has been shown
in some studies to be causally associated with increases in childhood cancers and, in the LSS,
with increases in adult cancers. The recent ICRP Report 103 (ICRP 2007), however, concluded
that the DDREF value should remain at 2 and not be reduced to 1.5 as recommended by BEIR
VII. The EPA should justify its decision to disagree with the ICRP conclusion and follow BEIR
VII's recommendation.
In the draft Blue Book, the EPA accepts the absolute risk estimate of 0.06 Gy"1 of
prenatal exposure for death from cancer prior to age 16 that was suggested by Doll and
Wakeford (1997) and adopted by the ICRP (2000). Based on a review of the same studies
considered by Doll and Wakeford, Boice and Miller (1999) expressed some skepticism about this
estimate. However, the RAC considers it is reasonable to use the 0.06 Gy"1 risk estimate at this
time. This evidence is largely derived from exposure to 80 kVp medical x rays; hence, the risk
coefficient should be adjusted to 0.04 Gy"1 if the EPA adopts an RBE of 1.4 for diagnostic
medical x rays.
For estimating the risks of adult cancers among populations exposed in utero, EPA
proposes adopting the cancer risk models in draft Blue Book Section 3 with age set to zero.
Although an analysis of A-bomb survivors exposed in utero found a lower risk than those who
were irradiated as young children, the difference is not statistically significant (Preston et al.
2008). The RAC considers this a reasonable approach.
Caution should be expressed because some spontaneous abortions in women who received
the higher doses may have occurred in the periods immediately after the A-bombs. These
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possible abortions were unaccounted for in the LSS, would lower the risk estimates, and should
be mentioned by the EPA as an additional source of uncertainty for prenatal exposure effects.
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4. RESPONSE TO CHARGE QUESTION 2: UNCERTAINTY ANALYSIS
4.1 Charge Question # 2: BEIR VII 's approach to uncertainty is primarily based on data
from the Life Span Study (LSS). The LSS provides a great deal of information on risks for
many cancer sites; however precision is limited by errors in dosimetry and sampling errors.
The sampling errors are often quite large for specific cancer types, and the uncertainties are
even larger if one focuses on a specific gender, age at exposure, or time after exposure.
Another important uncertainty is the transfer of site-specific cancer risk estimates to the U.S.
population, based on results obtained on the LSS population, for sites with substantially
different baseline incidence rate. Compared to BEIR VII, this document provides a
somewhat altered and expanded analysis of the uncertainties in the cancer risk estimates^
Regarding the uncertainty analysis contained in Section 4,
a Please comment on the adequacy of the approach to uncertainty analysis.
b Are the distributions chosen for the various sources of uncertainty reasonable?
4.2 Response to Charge Question # 2a
The approach to obtaining quantitative estimates of uncertainty is reasonable and
comprehensive. The RAC has identified the specific issues, described below, related to the
uncertainty analysis that the EPA should address to clarify assumptions and processes.
4.2.1 General Comments
The methods used for the full uncertainty analysis of stomach, colon, liver, lung, and
bladder cancer are based on analysis of the data for the LSS. The LAR is a complex function of
parameters that can be classified into three types:
• Type I are the risk estimates obtained from models with parameters derived from the
LSS data.
• Type II are other parameters, such as RBE, DDREF, and population transfer, about which
little or no direct information comes from the LSS data.
• Type III is the age distribution obtained from a hypothetical (stationary) population that
mimics the US population.
The goal of the uncertainty analysis in the draft Blue Book is to combine sampling variation in
the estimates for Type I parameters with uncertainties in Type II parameters in order to provide
an overall uncertainty estimate for the LAR that is calculated either separately for individual
tumor types or for groupings of tumors (e.g. all solid tumors, leukemia).
A Bayesian analysis has been adopted by the EPA. It provides a consistent framework
for the treatment of unknown parameters as random variables and a formal method for updating
initial prior distributions for these random parameters with the information contained in the LSS
data about the parameters of Type I. The Bayesian nature of the uncertainty analysis rests on a
somewhat different statistical basis than a "frequentist" approach that yields the "best estimates"
of LAR for these cancers. It is not surprising that the LAR uncertainty bounds from the
Bayesian analysis are not symmetric around the best estimate.
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The Bayesian analysis for stomach and colon actually is a joint analysis of these cancers
and combines information about the linear ERR parameters across these cancer types. It
estimates a common mean (but separately by gender) and a common variance in the distribution
of these risk parameters. Doing this should have the useful property of reducing the uncertainty
in the posterior distribution of these risk estimates, especially for rarer cancers where the
information in the LSS is not large.
Because all Type I and Type II parameters are regarded as random variables, the LAR
itself is treated as a random variable that is a function of the other random variables in the
uncertainty analysis. While this general framework is sound, it is complicated, especially given
the need to provide prior distributions for all Type I and Type II parameters. Because of the
large amount of direct data from the LSS related to incidence and survival, the selection of prior
distributions for Type I parameters does not have a very strong effect on the final "posterior"
estimates of these parameters. However, prior distributions specified for Type II parameters tend
to dominate their posterior distributions because little or no information about these latter
parameters is in the LSS data.
4.2.2 Specific Comments
The Blue Book should clearly state and justify why one method is used to obtain a point
estimate of LAR and another method based on different assumptions is used for the uncertainty
analysis. The Bayesian approach provides a posterior density function for LAR that could be
used to obtain a "best estimate" (i.e., mean or median) as well as confidence limits for a
quantitative description of uncertainty. Thus, a Bayesian approach could provide a consistent
value for both the best estimate and uncertainty interval, to replace the existing frequentist
approach for the best estimate, accompanied by Bayesian methods to estimate the confidence
interval.
Presumably, the EPA used separate approaches to obtain a best estimate and confidence
intervals partly because the best estimate of a LAR for a specific cancer site does not impose the
constraint that the risk estimates for each cancer be similar. Thus, because such risk estimates
are not known a priori to be similar, it may be scientifically more sensible to use completely
different analyses of each cancer subtype to give the best estimate, even if an assumption of
commonality is necessary and reasonable to impose when evaluating uncertainty, especially for
relatively rare cancers.
An additional reason why Bayesian analysis might not be applied to generating the point
estimates is that Bayesian estimates depend greatly on the details of the priors used for Type II
parameters, which are inherently subjective. One also needs to utilize inherently subjective
choices to develop the point estimate, but the technical details and software (WinBUGS) used for
the Bayesian analysis are quite delicate. Although WinBUGS (Lunn et al. 2000) is preferred for
many Bayesian applications, convergence issues often arise. The Monte Carlo Markov Chain
(MCMC) methodology can be demanding. For example, minor changes in starting values used
in the simulations can have a large effect on the results. The RAC is sympathetic to the process
of using specific assumptions for Type II parameters to produce the point estimates, but then
allowing these to range widely when the uncertainty intervals are computed.
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In addition to concerns relating to prior distributions, the RAC notes an overall lack of
clarity concerning the likelihood function for the LSS data. The likelihood function for Poisson
regression analysis of grouped survival data may not be very familiar even to readers relatively
knowledgeable in statistics and should be described carefully. Moreover, because for the cancers
listed above (stomach, colon), a joint analysis is being performed (where tables of person years
and events are given for more than one outcome), the legitimacy of multiplying the likelihoods
for each outcome together should be affirmed, even though the same "denominator" values
(person years) are being used in each table.
The current description of LARs and corresponding uncertainty intervals are not
sufficiently detailed. No indication is given which parameters, either Type I or Type II, are the
most influential in controlling the uncertainty intervals for LAR. The RAC suggests that the
EPA create a table depicting the relative contribution of each source of uncertainty to the total
uncertainty for each LAR (i.e., site-specific and overall). The sources of uncertainty include (1)
incidence data (where 'incidence' includes both background and radiogenic incidence), (2)
DDREF, (3) risk transport model, and (4) other EPA data sources, including age and time
dependence, errors in dosimetry, and diagnostic misclassification. The relative contribution
could be expressed as a percent or as the squared correlation between LAR uncertainty and each
source of uncertainty, i.e. the correlations between the random parameters and the LAR in the
Monte-Carlo simulations used to evaluate the posterior distributions of these quantities.
Given the delicate nature of the MCMC calculations, verification of the uncertainty
intervals so obtained by a perturbation approach would be beneficial as a means of extending the
analysis. The RAC suggests the following: use the results of the current approach to the
uncertainty analysis to identify one or two key parameters for each point estimate (where 'key'
means most contributory to overall uncertainty). Then, in the model used to generate the point
estimate, vary the key parameters over their range in a parametric sensitivity analysis
(perturbation analysis) to generate a range of resulting risk estimates. This process should
indicate the operational range of the point estimate. In this way, one can verify whether the
results of the current uncertainty analyses are appropriate for a given point estimate, and observe
the width of the confidence interval for that point estimate.
As a general methodological comment on the usefulness of the posterior densities
resulting from a Bayesian approach, the RAC suggests considering in future risk predictions the
concept of the predictive density. It is well established in other applications of survival analysis,
e.g. reliability analysis, and takes all remaining parameter uncertainty into account for the
calculation of predicted quantities. Increased computing power and advances in numerical
integration (e.g., Quasi Monte Carlo Methods) make this feasible if the dimensionality of the
integrand is not too high (e.g. < 10) (c.f, Bolstad 2007).
When comparing the results of the draft Blue Book to previous estimates published in
FGR 13, the EPA stated that "The overall increase in LAR is not due to changes in the basic risk
models," but that".. .the increase in results is largely attributable to the use of the more recent
Surveillance, Epidemiology and End Results (SEER) incidence data as a primary basis for
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calculating incidence rates." The EPA should clarify how this information is reflected in the
distributions for sources of uncertainty in Table 4-2.
The prior distributions for Type I parameters in the ERR and EAR risk models are
formed by directly assigning probability density functions to each parameter as shown in Table
4-1. Uncertainty of the Type II parameters is based on a different methodology. For these, a
parameter is assumed to have a constant value (i.e., DDREF =1.5) and the uncertainty in the
parameter is quantified by a multiplicative factor that is assigned a probability density such as
LN (GM=1, GSD=1.35). The EPA should explain the reason for the two different approaches.
A multiplicative factor that is log-normally distributed would lead to a bias unless the mean
value for this multiplicative factor is equal to 1.0. This is not the case in Table 4-2 when LN
(0.95, 1.1) is used for systematic errors in dosimetry or LN (1.1, 1.1) is used for uncertainty in
selection bias.
4.2.3 Additional Comments on Risk Transfer
Risk due to radiation exposure may differ between populations for many reasons. The
EPA should consider commenting on the following topics in the Blue Book.
Important issues such as population differences in genetic susceptibility to cancer and
how such genetic differences would interact with radiation are only now beginning to be
understood. Risk assessments by UNSCEAR, ICRP, BEIR VII and the draft Blue Book make
the implicit assumption that, if the background rate of a particular cancer is similar in two
populations, then the excess radiogenic cancer risk also will be similar. In reality, this
assumption may be a simplification and as more is learned about genes (or environmental
exposures other than radiation) that interact with radiation, other differences in gene or exposure
frequency may be found between Japanese and U.S. populations. Nevertheless, a reasonable
assumption, given today's lack of knowledge, is that cancers with similar baseline rates will have
similar response to radiation exposure in the two populations. This forms the basis for risk
transfer models and the associated LAR calculations from the Japanese to U.S. populations.
For cancers with widely different baseline risks (e.g., stomach and prostate cancer)
between the Japan and U.S. populations, the choice of an ERR or EAR model can make a large
difference in the LAR when applying the Japanese risk estimates to the U.S. data. One key Type
II parameter is the weighting parameter that interpolates between the EAR and ERR models.
The LSS data provide no direct information about whether EAR or ERR models are more
reasonable because both models provide equivalent descriptions of the LSS data.
The uncertainty analysis gives only slight overall bias in favor of ERR compared to EAR
models in the MCMC calculations. The tendency for the EAR models to be stressed more in the
uncertainty analysis than in the point estimation may be the reason why in Table 3-11 the point
estimates for stomach cancer (31 cases per 10,000 person Gy) are so far from the midpoint of the
uncertainty interval (9-280 cases per 10,000 person Gy).
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4.3 Response to Charge Question # 2b
The RAC did not identify any specific issue with the selection of distributions to
characterize uncertainty in parameters used in the models to obtain LAR, but recommends that
the EPA clarify the reasoning for selecting the subjective priors used in the analysis (e.g., in
Table 4-1). This information would increase transparency in the draft Blue Book and facilitate
future scrutiny and verification of the assumptions used in the uncertainty analysis.
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5. RESPONSE TO CHARGE QUESTION 3: COMMENTS ON
PRESENTATION OF OVERALL INFORMATION AND APPLICATION
OF BEIR VII IN THE DRAFT BLUE BOOK
5.1 Charge Question # 3: Please comment on the presentation of the following overall
information and application of BEIR VII contained in the draft document:
a. Scientific defensibility and appropriateness of the models and assumptions employed
for estimating risk.
b. Presentations of the calculations and re suits.
c. Regarding the document's intended purpose, the accuracy, balance, and level of
detail of the scientific background material presented.
5.2 Response to Charge Question # 3a
The RAC finds that the models and assumptions for estimating risk presented in the draft
Blue Book are broadly applicable and scientifically defensible. The EPA effort in the draft Blue
Book to apply BEIR VII models is commendable. The draft Blue Book is one in a sequence of
EPA publications that apply various methods and models - especially those by BEIR VII for
low-dose, low-LET, radiation - and lead to FGR 13 as a basis for radiation protection programs.
The RAC suggests the following topics for additional consideration in the Blue Book.
5.2.1 Noncancer Mortality
The draft Blue Book focuses on cancer mortality and incidence, and does not address the
possibility of radiation-related noncancer mortality. Noncancer mortality, particularly mortality
from cardiovascular disease, has been linked with exposure to high therapeutic radiation doses
(NAS-NRC 2006), but it is not clear whether such effects are found at lower doses. Mortality
from most broad noncancer disease categories has been found to be related to radiation dose in
the LSS cohort (Preston et al. 2003). Because the identified radiation risks were small compared
to baseline risks, the shape of the dose-response function or age effects could not be evaluated
with any precision. For example, it was not possible to distinguish a linear dose response from a
dose response with a threshold as high as 0.5 Gy. Indications also exist of radiation-associated
increases in diseases of the circulatory system among nuclear workers in the United Kingdom
(McGeoghegan et al. 2008).
Lifetime risk estimates for radiation-related non-cancer mortality in the LSS cohort are
uncertain and range from zero to levels that approach those for cancer mortality estimates
(Preston et al. 2003). Due to the large uncertainties in the possible magnitude, or even existence,
of increased noncancer disease risk at low doses, the EPA decision not to provide lifetime risk
estimates for noncancer mortality is reasonable. The RAC recommends that noncancer mortality
be mentioned as a possible effect of radiation exposure even at low doses, and that the reasons be
stated for not providing risk estimates for this endpoint at the present time.
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5.2.2 Information from ICRP and UNSCEAR Reports
Since the publication of BEIR VII, both ICRP (2007) and UNSCEAR (2008) have
published reports that include lifetime risk estimates for radiation-related cancers. The ICRP
developed estimates for a world population defined as an average of risks for hypothetical Euro-
American and Asian populations, whereas UNSCEAR developed estimates for several different
countries, including the United States. The RAC recommends that the EPA add a brief
description of the methods used in the ICRP and UNSCEAR reports and a comparison with
those that are being used by the EPA. Tables showing comparisons of the EPA estimates not
only with BEIR VII but also with relevant estimates from ICRP and from UNSCEAR would be a
desirable addition to the Blue Book.
5.2.3 Radiogenic Thyroid Cancer
The draft Blue Book provides limited information regarding the risk of radiogenic thyroid
cancer as estimated by BEIR VII, although the EPA discussed this issue extensively in its draft
White Paper (U.S. EPA/ORIA 2006), where the EPA noted that "we now favor adoption of the
NCRP thyroid cancer model, assuming that we would have a proper reference that can be cited."
This reference is now available in National Council on Radiation Protection and
Measurements Report #159 (NCRP 2009). The RAC recommends that the EPA follow the
NCRP approach, but also consider in its modeling the latest epidemiological data on exposures
to the thyroid, published since the NCRP report was written in 2006, such as recent Chernobyl
thyroid studies (Zablotska et al. 2008).
5.2.4 Radiogenic Brain Cancer
Information on an association between ionizing radiation and brain cancer has been
generated from radiation-exposed cohorts that provide quantitative dose data and allow
estimation of radiogenic risks. Based on data from multiple cohorts including A- bomb
survivors, tinea capitiis, hemangiomas, and childhood cancer survivors, the brain-tumor
epidemiology literature has reached consensus that ionizing radiation is an established risk factor
for brain tumor development (Ohgaki 2009, Bondy et al. 2008, Davis 2007). While brain tumors
are complex histologically, radiation risk estimates for gliomas (the most common malignant
brain tumor) are available from several of these cohorts. The RAC recommends that the EPA
include the radiogenic risk to the brain in the context of the other cancer sites discussed in the
draft Blue Book. If the EPA does not wish to do so, it should present the rationale for excluding
radiogenic risks to the brain.
5.3 Response to Charge Question # 3b
The RAC found the presentation of calculations and results in the draft Blue Book to be
competent and comprehensible; it suggests the following for greater clarity and readability:
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5.3.1 Tabular Presentations
The RAC recommends that, in Table 4-2 on sources of uncertainty, a column listing
references for the source of the distribution parameters be added, and that these be discussed in
the text. It also recommends eliminating repetition in several tables of the same values of
lifetime risk estimates of cancer incidence or mortality.
5.3.2 Topical Organization and Content
The RAC recommends that the EPA clearly state the purpose and application of the Blue
Book in Section 1, notably the intended contributions of Blue Book cancer incidence and
mortality values to the contents of Federal Guidance Report 13.
The organization of the Blue Book can be improved by pulling together some scattered
topics. For example, in Section 3.3, pages 29-32 (U.S. EPA/ORIA 2008), risk models for
cancers not specified by BEIR VII (kidney, bone, NMSC, etc.) are discussed and conclusions
presented, but estimating cancer risks for these organs is discussed in detail in Section 5, pages
84-88.
The RAC found that the more detailed explanations and examples provided in the
materials orally presented by ORIA staff on March 23, 2009, and referred to above, clarified
draft Blue Book contents and suggests that they be included in the Blue Book.
5.3.3 Relation of Input Information to Presented Results
The RAC suggests that clarification of the changes based on updated SEER would be
helpful. The statement on page 55 that increased LAR estimates (compared to those of FGR 13)
are "largely attributable to the use of more recent SEER incidence [rates]" is confusing.
Similarly, on page 55 is a statement that "the LAR for all cancers combined is increased by about
20%" because of the new SEER incidence data, followed by a statement that the models
themselves would yield lower estimates of LAR than those published in FGR13 if the new
models were applied to comparable mortality and incidence rates. The EPA appears to be
making the point that for FGR 13 it uses poorly approximated incidence rates computed as
lethality-adjusted mortality risks but that the new estimates are based on actual age-specific
incidence rates.
The interplay between mathematical models and compiled incidence rates should be
explained clearly and simply in the Blue Book to address suspicion expressed by members of the
public at the meetings that the EPA will distort results to present falsely low risk values for
implementation in the revised FGR 13. The rationale and implications of calculating LAR based
on a life table for a hypothetical stationary population rather than the existing life tables for the
current US population also should be further explained to eliminate this approach as a cause of
distrust by the general reader.
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5.3.4 Application of DDREF
The recent ICRP Report 103 (ICRP 2007) concluded that the DDREF value should
remain at 2 and not be reduced to 1.5 as recommended by BEIR VII (U.S. NAS/NRC 2006).
The EPA should justify the decision to disagree with the ICRP conclusion and follow the BEIR
VII recommendation.
The RAC recommends that tables with LAR estimates indicate whether the estimates
include a DDREF adjustment.
5.4 Response to Charge Question # 3c
The RAC finds that the draft Blue Book presents the scientific background material with
appropriate accuracy and balance, but recommends that the scientific background can be
enhanced by including the following topics:
5.4.1 Low-Dose Protracted Exposure
The RAC realizes that much of the draft Blue Book relies on BEIR VII risk estimates
based primarily on LSS data, but suggests that the EPA compare the revised EPA estimates with
risk estimates from studies of persons exposed to low-level, protracted radiation exposure.
These include nuclear workers in the 15-country radiation worker study (Cardis et al. 2007) and
the study of United Kingdom National Registry of Radiation Workers (Muirhead et al. 2009).
The EPA is primarily interested in the health effects of low-dose protracted radiation exposure,
and acknowledges that risk estimates based on an acute exposure in a Japanese population carry
with them considerable uncertainty when applied to low-dose exposure of the U.S. population.
5.4.2 Cancer Sites with Limited Data
The RAC recommends that the EPA, in support for its rationale for estimating risk for
specific cancer sites, look to the expected summary of cancer sites that have limited or
inadequate data in the soon-to-be-published updated report by the International Agency for
Research on Cancer (IARC) on the cancer risks of ionizing radiation. Specifically, justification
should be given for estimating cancer risk for sites in which IARC concluded that the
epidemiological data are inadequate or limited. Conversely, the EPA needs to justify having
omitted any cancer sites for which IARC concluded that sufficient epidemiological evidence
exists.
5.4.3 Cancer Subtypes
The RAC encourages expanding the discussion of issues related to lympho-hematopoietic
cancers. For example, comment on: (1) recent discussions of whether chronic lymphocytic
leukemia (CLL) is radiogenic (Linet et al. 2007; Schubauer-Berigan 2007a, 2007b; Vrijhead et
24
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al. 2008; Silver et al. 2007), and appropriate references contained within; (2) absence of risk
estimates for leukemia subtypes; and (3) absence of risk estimates for non-Hodgkin's lymphoma
or multiple myeloma.
5.4.4 Presentation of Stepwise EPA Development of Revised FGR 13
The RAC recommends that the EPA include in Section 7 of the Blue Book specific
information concerning the anticipated radionuclide risk coefficient values in the revised FGR
13, based on currently available dosimetric models. Tables A4a and A4b in the 1994 Blue Book
can be taken as models. This information will enable the public and professionals to attribute
reasponsibility for changes in FGR 13 to revised cancer risk projections in the Blue Book or to
revised dosimetric models, or to both.
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REFERENCES CITED
Andersson, M., M. Vyberg, J. Visfeldt, B. Carstensen and H.H. Storm 1994. Primary liver
tumors among Danish patients exposed to Thorotrast. Radial Res 137: 262-273. 1994.
Boice, J.D. Jr., R.W. Miller 1999. Childhood and adult cancer after intrauterine exposure to
ionizing radiation. Teratol 59(4): 227-233. 1999.
Bolstad, William M. 2007. Introduction to Bayesian Statistics, 2nd ed., John Wiley & Sons,
Hoboken, NJ. 2007.
Bondy, M.L., M.E. Scheurer, B. Malmer, et al. 2008. Brain tumor epidemiology: consensus from
the Brain Tumor Epidemiology Consortiium, Cancer 2008; 113: 1953-68. 2008.
Cardis, E., M. Vrijheld, M. Blettner, E. Gilbert, M. Hakama, C. Hill et al. 2007. The 15-country
collaborative study of cancer risk among radiation workers in the nuclear industry: Estimates of
radiation related cancer risks. Radial Res 167: 396-416. 2007.
Carnes BA, Groer PG, Kotek TJ. 1997. Radium dial workers: issues concerning dose response
and modeling. Radial Res. 147(6):707-14. Jun 1997.
Davis, F.S., Epidemiology of brain tumors 2007. Expert Rev Anlicancer Ther 7:S3-6. 2007.
Doll, R. and Wakeford, R. 1997 Risk of childhood cancer from fetal irradiation. BritJ. Radiol
70: 130-139, 1997.
FR Citations:
FR Vol. 73, No. 76, Friday, April 18, 2008, pp. 21129-21130 (FRN solicitation to augment
expertise of RAC for the Blue Book Review. Hotlink is as follows:
http://www.epa.gov/fedrgstr/EPA-SAB/2008/April/Dav-18/sab8400.htm)
FR Vol. 74, No. 21, February 3, 2009, pp. 5935-5936 http://www.epa.gov/fedrgstr/EPA-
SAB/2009/February/Dav-03/sab2249.htm
FR Vol. 74, No. 101, May 28, 2009, pp. 25529 -25530 http://www.epa.gov/fedrgstr/EPA-
SAB/2009/Mav/Dav-28/sab 12480.htm
FR Vol 74, No. 161, pp. 42297-42298 http://www.epa.gov/fedrgstr/EPA-
S AB/2009/August/Dav-2 l/sab20171 .htm
Gilbert, E.S., W.C. Griffith, B.B. Boecker, G.E. Dagle, R.A. Guilmette, F.F. Hahn, B.A.
Muggenburg, J.F. Park, C.R. Watson 1998. Statistical modeling of carcinogenic risks in dogs
that inhaled (PuO2)-Pu-238, Radiation Research, 150(1): 66-92. July 1998.
26
-------
Hahn, F.F., B.A. Muggenburg, R.A. Guilmette, B.B. Boecker 1999. Comparative stochastic
effects of inhaled alpha- and beta-particle-emitting radionuclides in beagle dogs, Radiation
Research, 152(6): S19-S22 Supplement: Suppl S. 1999.
Hoel, D.G, and Carnes, B.A. 2004. Cancer Dose-Response Analysis of the Radium Dial Painters.
In: Proceedings of the 9th. International Conference on Health Effects of Incorporated
Radionuclides Emphasis on Radium, Thorium, Uranium and their Daughter Products.
Neuherberg, Germany. 2004.
Hunter N, Muirhead CR. 2009. Review of relative biological effectiveness dependence on linear
energy transfer for low-LET radiations. JRadiolProt. 2009 Mar; 29(1):5-21. Epub Feb 18,
2009.
ICRP 2007. ICRP Publication 103: The 2007 Recommendations of the International Commission
on Radiological Protection. Annals of the ICRP 37, 9-332. 2007.
ICRP 2005. International Commission on Radiological Protection (ICRP) Publication 99: Low
dose extrapolation of radiation-related cancer risk. Annals of the ICRP 35. 2005.
ICRP 2003. International Commission on Radiological Protection (ICRP) Publication 92:
Relative biological effectiveness (RBE), quality factor (Q), and radiation weighting factor (Wr).
Annals of the ICRP 33. 2003.
ICRP 2000. International Commission on Radiological Protection "(ICRP) Publication 84:
Pregnancy and Medical Radiation." Annals of the ICRP 30(1), Elsevier Science Ltd. New York.
2000.
ICRP 1991. International Commission on Radiological Protection (ICRP) The Biological Basis
for Dose Limitation in the Skin. ICRP Publication 59. Annals of the ICRP 22:2. 1991.
Jacob, P, R. Meckbach, M. Sokolnikov, V. V. Khokhryakov and E. Vasilenko 2007. Lung cancer
risk of Mayak workers: modelling of carcinogenesis and bystander effect. Radiat Environ
Biophys. 2007.
Karagas, M.R., E.R. Greenberg, S.K. Spencer, T.A. Stukel and L.A. Mott 1999. Increase in
incidence rates of basal cell and squamous cell skin cancer in New Hampshire, USA. New
Hampshire Skin Cancer Study Group. Int. JCancer 81(4): 555-559. May 17, 1999.
Leenhouts, H.P., M.J.P. Brugmans, M. Andersson, H.H. Storm 2002. A Reanalysis of liver
cancer in Danish patients administered Thorotrast using two-mutation carcinogenesis model.
Radiation Research 158:597-606. 2002.
Lewis, K.G., M.A. Weinstock 2004. Nonmelanoma skin cancer mortality (1988-2000). The
Rhode Island follow-back study. Arch Dermatol 140: 837-842. 2004.
27
-------
Linet, M.S., M. K. Schubauer-Berigan, D. D. Weisenburger, D. B. Richardson, O. Landgren, A.
Blair, S. Silver, R. W. Field, G. Caldwell, et al. 2007. Chronic lymphocytic leukemia: an
overview of etiology in light of recent developments in classification and pathogenesis. Br J
Haematol 139, 672-686. 2007.
Little, M. P. Comparison of the risks of cancer incidence and mortality following radiation
therapy for benign and malignant disease with the cancer risk observed in the Japanese A-bomb
survivors. J.Radiat.Biol.il, 431-464 (2001).
Lundgren, D.L., F.F. Hahn, W.W. Carlton, W.C. Griffith, R.A. Guilmette, N.A.GillettDose
responses from inhaled monodisperse aerosols of (Cm2O3)-244Cm in the lung, liver and skeleton
of F344 rats and comparison with (PuO2)-239Pu, Radiation Research, 147: Issue 5, 598-612.
1997.
Lundgren, D.L., F.F. Hahn, W.C. Griffith, A.F. Hubbs, K.J. Nikula, GJ. Newton, R.G. Cuddihy,
B.B. Boecker 1996. Pulmonary carcinogenicity of relatively low doses of beta-particle radiation
from inhaled (CeO2)-144Ce in rats, Radiation Research, 146: Issue 5, 525-535. 1996.
Lundgren, D.L., PJ. Haley, F.F. Hahn, J.H. Diel, W.C. Griffith, B.R. Scott 1995. Pulmonary
Carcinogenicity of Repeated Inhalation Exposure of Rats to Aerosols of (PuO2)-239Pu, Radiation
Research 142(1): 39-53. 1995.
Lunn, D.J., Thomas, A., BestN., and Spiegelhalter, D. 2000. WinBUGS - a Bayesian modelling
framework: concepts, structure, and extensibility, Statistics and Computing 10: 325-337. 2000.
MacMahon, B.1962. "Prenatal x-ray exposure and childhood cancer." J. Natl Cancer Inst 28:
1173-91. 1962.
McGeoghegan, D., K. Binks, M.Gillies, S. Jones and S. Whaley 2008. The non-cancer mortality
experience of male workers at British Nuclear Fuels pic, 1946-2005. Int JEpidemiol 37: 506-
518.2008.
Muggenburg, B.A., R.A. Guilmette, F.E. Hahn, J.H. Diel, J.L. Mauderly, S.K. Seilkop, B.B.
Boecker 2006. Radiotoxicity of Inhaled (PuO2)-Pu-239 in Dogs. 2003. Radiation Research,
170(6): 736-757. 2006.
Muggenburg, B.A., R.A. Guilmette, J.A. Mewhinney, N.A. Gillett, J.L. Mauderly, W.C. Griffith,
J.H. Diel, B.R. Scott, F.F. Hahn, B.B. Boecker 1996. Toxicity of inhaled plutonium dioxide in
beagle dogs, Radiation Research, 145(5): 525-612. 1996.
Muirhead CR, J.A. O'Hagan, R.G. Haylock, M.A. Phillipson, T. Willcock, G.L. Berridge, and
W. Zhang 2009. Mortality and cancer incidence following occupational radiation exposure: third
analysis of the National Registry for Radiation Workers. Br J Cancer. Jan 13;100(1):206-12.
2009.
28
-------
NAS/NRC 2006. Health Risks from Exposure to Low Levels of Ionizing Radiation, BEIR VII
Phase 2, National Academies of Sciences (NAS), National Research Council, Committee to
Assess Health Risks from Exposure to Low levels of Ionizing Radiation. 2006. 416 pages
http://nap.edu/catalog/11340.htmltftoc
NAS/NRC 1994. National Academy of Sciences Committee on the Biological Effects of
Ionizing Radiation, The Health Effects of Exposure to Indoor Radiation BEIR VI, National
Academy of Sciences Press, Washington, DC, National Academy Press, 1994.
http://nap.edu/openbook.php7record id=5499&page=20
NAS/NRC 1990. Health Effects to Exposure to Low Levels of Ionizing Radiation, BEIR V,
National Academy of Sciences Press. Washington, DC, National Academy Press, Washington,
DC, pp. 250-252. 1990. http://nap.edu/openbook.php7record id=1224&page
NAS/NRC 1980. National Academy of Sciences Committee on the Biological Effects of
Radiation, The Effects on Populations Exposed to Low Levels of Ionizing Radiation (BEIR III).
National Academy of Sciences Report BEIR III, National Academy of Sciences Press,
Washington, DC, National Academy Press, 1980.
NCRP 2009. "Risk to the Thyroid from Ionizing Radiation." National Council on Radiation
Protection and Measurements (NCRP); NCRP Report #159. Bethesda, MD. 2009.
NCRP 2009a. "ionizing Radiation Exposure of the Population of the United States," National
Council on Radiation Protection and Measurements (NCRP); NCRP Report #160, Bethesda,
MD. 2009.
Ohgaki, H. 2009. Epidemiology of brain tumors. Methods Mol Biol 472: 323-42. 2009.
Preston, D.L., H. Cullings, A. Suysama, S. Funamoto, N. Nishi, M. Soda, K. Mabuchi, K.
Kodama, F. Kasagi, and R.E. Shore 2008. "Solid cancer incidence in atomic bomb survivors
exposed in utero or as young children." J. Natl Cancer Inst 100(6), 428-436. 2008.
Preston, D.L., E. Ron, S. Tokuoka, S. Funamoto, N. Nishi, M. Soda, K. Mabuchi and K.
Kodama. 2007. Solid cancer incidence in atomic bomb survivors: 1958-1998. Radial Res 168, 1-
64. 2007.
Preston, D.L., Y. Shimizu, D.A. Pierce, A. Suyama and K. Mabuchi. 2003. Studies of mortality
of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997.
RadiatRes 160, 381-407. 2003.
Priest, N.D., D.G. Hoel, P.N. Brooks. 2006. Relative toxicity of chronic irradiation by Ca-45
beta particles and Cm-242 alpha particles with respect to the production of lung tumors in
CBA/Ca mice, Radiation Research, 166(5): 782-793, 2006.
29
-------
Ron, E., B. Modan, D. Preston, E. Alfandary, M. Stovall, JD Boice 1991. Radiation-induced
skin carcinomas of the head and neck. Radial Res 125; 318-325.1991.
Schubauer-Berigan M.K., R.D. Daniels, D.A. Fleming, A.M. Markey, J.R. Couch, S.H.
Ahrenholz, J.S. Burphy, J.L. Anderson, C.Y. Tseng 2007a. Chronic lymphocytic leukaemia and
radiation: findings among workers at five US nuclear facilities and a review of the recent
literature, British Journal ofHaematology, 139(5): 799-808, Dec. 2007.
Schubauer-Berigan M.K., R.D. Daniels, D.A. Fleming 2007b. Risk of leukemia at low doses:
TheNIOSH multi-site leukemia case-control study, Radiation Research, 167(3): 344-345, Mar.
2007.
Shore, R.E., M. Moseson, X. Xue, Y. Tse, N. Harley, B.S. Pasternack 2002. Skin cancer after x-
ray treatment for scalp ringworm. Radial Res 157: 410-418. 2002.
Shore, R.E. 2001. Radiation-induced skin cancer in humans. MedPediatr Oncol. 36(5):549-54,
May. 2001.
Silver S.R., S.L. Hiratzka, M.K. Schubauer-Berigan, R.D. Daniels 2007. Chronic lymphocytic
leukemia radiogenicity: a systematic review, Cancer Causes & Control., 18(10): 1077-1093, Dec.
2007.
Sokolnikov, M.E., E.S. Gilbert, D.L. Preston, N.S. Shilnikova, V.V. Khokhryakov, E.K.
Vasilenko, N.A. Koshurnikova 2008. Lung, liver, and bone cancer mortality in Mayak workers.
IntJ Cancer 123: 905-911. 2008.
Stewart, A., J. Webb, D. Hewitt 1958. A survey of childhood malignancies. Br. MedJ. 1(5086):
1495-1508. 1958.
Storer, J.B., TJ. Mitchell, and R.J.M. Fry 1988. Extrapolation of the relative risk of radiogenic
neoplasms across mouse species and to man. Radial.Res. 114: 331-353. 1988.
UNSCEAR. 2008. United Nations Scientific Committee on the Effects of Atomic Radiation,
Effects of Ionizing Radiation - - UNSCEAR 2006 Report to the General Assembly with Scientific
Annexes. Volume I. Effects of Ionizing Radiation. United Nations, New York. 2008.
UNSCEAR. 2000. United Nations Scientific Committee on the Effects of Atomic Radiation,
Sources, Effects, and Risks of Ionizing Radiation with Annexes, Volume II: Effects. United
Nations, New York. 2000.
U.S. EPA 1994. EstimatingRadiosenic Cancer Risks ("Blue Book"), Washington, DC (EPA
402-R-93-076), June 1994: http://epa.gov/radiation/docs/assessment/402-r-93-076.pdf
U.S. EPA. 1984. Radionuclides: Background Information Document for Final Rules, Vol. 1,
Washington, DC, EPA/1-84-022-1. 1984.
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U.S. EPA/ORIA 2009. Memorandum entitled "Advisory Review of the Draft Document: EPA
Radiogenic Cancer Risk Models and Projections for the U.S. Population, " from Elizabeth A.
Cotsworth, Director, Office of Radiation and Indoor Air to Vanessa Vu, Director, Science
Advisory Board Staff Office, January 26, 2009.
U.S. EPA/ORIA 2008. "EPA Radiogenic Cancer Risk Models and Projections for the U.S.
Population," U.S. Environmental Protection Agency (EPA), Office of Radiation and Indoor Air
(ORIA), Draft December 2008, 116 pages ("The Blue Book")
http://epa.gov/radiation/assessment/pubs.html
U.S. EPA/ORIA 2006. "Modifying EPA Radiation Risk Mode Is Based on BEIR VII, " Draft
White Paper, Prepared by Office of Radiation and Indoor Air, U.S. Environmental Protection
Agency, August 1, 2006, 36 pages
http://vosemite.epa.gov/sab/sabproduct.nsf/8097D8CE7070ClE4852571DA0005C605/$File/rac
oria white_paper 08-01 -06.pdf
U. S. EPA/ORIA 1999. "Cancer Risk Coefficients for Environmental Exposure to
Radionuclides, " Federal Guidance Report No. 13, EPA 402-R-99-001, September 1999, 335
pages http://epa.gov/radiation/docs/federal/402-r-99-001.pdf
U.S. EPA/ORIA 1999a. "Estimating Cancer Risks Addendum: Uncertainty Analysis, "U.S.
Environmental Protection Agency, Office of Radiation and Indoor Air (6608 J), Washington, DC,
May 1999, EPA 402-R-99-003. http://epa.gov/radiation/docs/assessment/402-r-99-003.pdf
U.S. EPA/SAB 2008. Advisory on Agency Draft White Paper Entitled "ModifyingEPA
Radiation Risk Models Based on BEIR VII, " EPA-SAB-08-006. January 31, 2008.
http://vosemite.epa.gov/sab/sabproduct.nsf/FD9963E56C66E4FF852573E200493359/$File/EPA
-SAB-08-006-unsigned.pdf
U.S. EPA/SAB 1999. "An SAB Report: Estimating Uncertainties in Radiogenic Cancer Risk, "
EPA-SAB-RAC-99-008, February 18, 1999.
http://vosemite.epa.gov/sab/sabproduct.nsf/D35 llCC996FB97098525718F0064DD44/$File/rac
9908.pdf
U.S. EPA/SAB 1994. "Evaluation ofEPA 's ProposedMethodology for Estimating Radiogenic
Cancer Risks, " EPA-SAB-RAC-LTR-93-004, December 9, 1992.
http://vosemite.epa.gov/sab/sabproduct.nsf/OAOE72B3E05BC892852573 lC007830F3/$File/RA
DIOGENIC+CANCER+RAC-LTR-93-004 93004 5-8-1995 68.pdf
Van Kaick, G., A. Dalheimer, S. Hornik, A. Kaul, D. Liebermann, H. Luhrs, A. Spiethoff, K.
Wegener, H. Welch 1999. The German Thorotrast study: Recent results and assessment of risks.
Radiation Research 152(6): S64-S71. 1999.
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Vrijhead, M., E. Cardis, P. Ashmore, A. Auvinen, E. Gilbert, R.R. Habib, H. Malker, C.R.
Muirhead, D.B. Richardson, A. Rogel, M. Schubauer-Berigan, H. Tardy, M. Telle-Lamberton
2008. Ionizing radiation and risk of chronic lymphocytic leukemia in the 15-country study of
nuclear industry workers. 15-Country Study Group. Radial. Res. 170(5): 661-5. 2008.
Zablotska LB, Bogdanova TI, Ron E, Epstein OV, Robbins J, Likhtarev IA, Hatch M, Markov
VV, Bouville AC, Olijnyk VA, McConnell RJ, Shpak VM, Brenner A, Terekhova GN,
Greenebaum E, Tereshchenko VP, Fink DJ, Brill AB, Zamotayeva GA, Masnyk IJ, Howe GR,
Tronko MD. A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl
accident: dose of thyroid follicular adenomas detected during first screening in Ukraine (1998-
2000). Am JEpidemiol. 2008 Feb 1; 167(3):305-12.
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WEB-BASED CITATIONS AND HOTLINKS
NAS/NRC. 2006. BEIR VII. Health Risks from Exposure to Low levels of Ionizing Radiation
BEIR VIIPhase 2, National Academies of Sciences (NAS), National Research Council,
Committee to Assess Health Risks from Exposure to Low levels of Ionizing Radiation,
http://nap.edu/catalog/11340.htmltftoc
U. S. EPA/ORIA. 1994. Estimating Radiosenic Cancer Risks ("Blue Book"), Washington, DC
(EPA 402-R-93-076), June, 1994: http://epa.gov/radiation/docs/assessment/402-r-93-076.pdf
U.S. EPA /ORIA. 1999. Federal Guidance Report (FGR)-13. Federal Guidance Report 13:
Cancer Risk Coefficients for Environmental Exposure to Radionuclides, Washington, DC (EPA
402-R-99-001), September, 1999 http://epa.gov/radiation/docs/federal/402-r-99-001.pdf
U. S. EPA/ORIA. 1999a. Estimating Radiogenic Cancer Risks Addendum: Uncertainty Analysis,
Washington, DC (EPA 402-R-99-003), May, 1999:
http://epa.gov/radiation/docs/assessment/402-r-99-003.pdf
U.S. EPA/ORIA. 1999b. Update to the Federal Guidance Report No. 13 and CD Supplement:
http://epa.gov/radiation/assessment/pubs.html (can also view pubs site for the April 2002 update:
CD Supplement)
U.S. EPA/ORIA. 2006. Office of Radiation and Indoor Air (ORIA), Draft White Paper:
Modifying EPA Radiation Risk Models Based on BEIR VII, August 1, 2006
http://vosemite.epa.gov/sab/sabproduct.nsf/8097D8CE7070ClE4852571DA0005C605/$File/rac
_oria_white_paper_08-01 -06.pdf
U.S. EPA/ORIA. 2008. "EPA Radiogenic Cancer Risk Models and Projections for the U.S.
Population, " U.S. Environmental Protection Agency (EPA), Office of Radiation and Indoor Air
(ORIA), Draft December 2008, 116 pages ("The Blue Book")
http://epa.gov/radiation/assessment/pubs.html
FEDERAL REGISTER SOLICITING NOMINATIONS TO AUGMENT EXPERTISE ON
THE RADIATION ADVISORY COMMITTEE (RAO:
Federal Register, Vol. 73, No. 76, Friday, April 18, 2008, pp. 21129-21130
http://www.epa.gov/fedrgstr/EPA-SAB/2008/April/Dav-18/sab8400.htm
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FEDERAL REGISTER ANNOUNCING MEETINGS OF THE AUGMENTED
RADIATION ADVISORY COMMITTEE (RAO:
Federal Register, 74, Tuesday, February 3, 2009, pp. 5935-5936
http://www.epa.gov/fedrgstr/EPA-SAB/2009/February/Dav-03/sab2249.httn
Federal Register, 74, Thursday, May 28, 2009, pp. 25529-25530
http://www.epa.gov/fedrgstr/EPA-SAB/2009/Mav/Dav-28/sabl2480.htm
FEDERAL REGISTER ANNOUNCING MEETING OF THE CHARTER SCIENCE
ADVISORY BOARD TO CONDUCT THE QUALITY REVIEW OF THE RAC'S
AUGUST 20, 2009 DRAFT REPORT
Federal Register. Volume 74, No. 161, Friday, August 21, 2009, pp. 42297-42298
http://www.epa.gov/fedrgstr/EPA-SAB/2009/August/Dav-21/sab20171.htm
BACKGROUND SAB REPORTS AND ADVISORIES:
U.S. EPA/SAB. 1992. "Evaluation ofEPA 's ProposedMethodology for Estimating Radiogenic
Cancer Risks, " EPA-SAB-RAC-LTR-93-004, December 9, 1992.
http://vosemite.epa.gov/sab/sabproduct.nsf/OAOE72B3E05BC892852573 lC007830F3/$File/RA
DIOGENIC+CANCER+RAC-LTR-93-004 93004 5-8-1995 68.pdf
U.S. EPA/SAB. 1998. "An SAB Report: Review of Health Risks from Low-Level Environmental
Exposures to Radionuclides (FRG-13 Report), " EPA-SAB-RAC-99-009, December 23, 1998
http://vosemite.epa.gov/sab/sabproduct.nsf/2EF0698AA08A29098525718F006532D8/$File/rac9
909.pdf
U.S. EPA/SAB. 1999. "An SAB Report: Estimating Uncertainties in Radiogenic Cancer Risk, "
EPA-SAB-RAC-99-008, February 18, 1999.
http://vosemite.epa.gov/sab/sabproduct.nsf/D35 llCC996FB97098525718F0064DD44/$File/rac
9908.pdf
U.S. EPA/SAB. 2008. Advisory on Agency Draft With Paper Entitled "ModifyingEPA
Radiation Risk Mode Is Based on BEIR VII, " EPA-SAB-08-006. January 31, 2008.
http://vosemite.epa.gov/sab/sabproduct.nsf/FD9963E56C66E4FF852573E200493359/$File/EPA
-SAB-08-006-unsigned.pdf
AGENCY AND OTHER DOCUMENTS (AND HOTLINKS) RELATED TO
ESTIMATING RADIOGENIC CANCER RISKS:
U.S. EP A/ORI A. 1994. Blue Book: Estimating Radiogenic Cancer Risks, EPA 402-R-93 -076,
June 1994 http://www.epa.gov/radiation/docs/assessment/402-r-93-076.pdf
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U.S. EPA/ORIA. 1999. Uncertainty Addendum: Estimating Radiogenic Cancer Risks
Addendum: Uncertainty Analysis, EPA 402-R-99-003, May 1999.
http://www.epa.gov/radiation/docs/assessment/402-r-99-003.pdf
The basis for the Blue Book SAB peer review is at:
U.S. EPA/SAB. 1992. "Evaluation ofEPA 's ProposedMethodology for Estimating Radiogenic
Cancer Risks, " EPA-SAB-RAC-LTR-93-004, December 9, 1992.
http://vosemite.epa.gov/sab%5Csabproduct.nsf/OAOE72B3E05BC892852573 lC007830F3/$File/
RADIOGENIC+CANCER+RAC-LTR-93-004 93004 5-8-1995 68.pdf
The Uncertainty Addendum SAB peer review is at:
U.S. EPA/SAB. 1999. "An SAB Report: Estimating Uncertainties in Radiogenic Cancer Risk, "
EPA-SAB-RAC-99-008, February 18, 1999.
http://vosemite.epa.gov/sab%5Csabproduct.nsf/D351 lCC996FB97098525718F0064DD44/$File
/rac9908.pdf
FEDERAL GUIDANCE REPORT 13:
U.S. EPA/OAR. 1999. "Cancer Risk Coefficients for Environmental Exposure to
Radionuclides, " Federal Guidance Report No. 13, EPA 402-R-99-001, September 1999, 335
pages http://epa.gov/radiation/docs/federal/402-r-99-001.pdf
NATIONAL ACADEMY OF SCIENCES BEIR VII REPORT:
NAS/NRC, 2006. Health Risks from Exposure to Low Levels of Ionizing Radiation, BEIR VII
Phase 2, National Academies of Sciences (NAS), National Research Council, Committee to
Assess Health Risks from Exposure to Low levels of Ionizing Radiation, 2006, 416 pages
http://nap.edu/catalog/11340.htmltftoc
AGENCY UPDATED DRAFT WHITE PAPER:
U.S. EPA/ORIA. 2006. Modifying EPA Radiation Risk Models Based on BEIR VII, Draft
White Paper, Prepared by Office of Radiation and Indoor Air, U.S. Environmental Protection
Agency, August 1, 2006, 36 pages
http://vosemite.epa.gov/sab/sabproduct.nsf/8097D8CE7070ClE4852571DA0005C605/$File/rac
oria white paper 08-01-06.pdf
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APPENDIX A - EDITORIAL COMMENTS
Minor (editorial) comments on the draft EPA document on Radiogenic Cancer Risk.
p.6: Insert acronyms:
UI Uncertainty interval
ICD ? (used on p.23)
p. 7, paragraph 2: This should mention the provision of estimates for alpha-emitters, X-rays etc.
Also, kidney cancer should be added to the list in the 3rd sentence.
p. 7, paragraph 4: Sentence "Nevertheless ... time after exposure." This is true, but for most
cancers the estimates are more precise than those from any other study. This point might be
worked into the paragraph. Another limitation that might be mentioned is the relevance for low
dose rate exposure.
p. 16, Section 2.1.5, line 2: Replace 'new' by 'recently observed'.
p. 20, 1st full paragraph: The study of British radiologists by Berrington et al. (Br. J. of
Radiology 2001) might also be cited.
p. 20, 2nd full paragraph: An important paper on workers that needs to be cited is the recent
update of the study of NRRW British nuclear workers (Muirhead et al. Brit. J. Cancer, 2009).
The most important limitations (in my opinion) are not mentioned. These are lack of statistical
power (imprecise risk estimates) and vulnerability to confounding when studying small risks.
There are also more recent Chernobyl papers that might be cited including 2 papers on thyroid
cancer (Cardis et al. JNCI 2005; Tronko et al. JNCI 2006) and 2 papers on leukemia incidence
(Romanenko et al. Radiat. Res. 2008; Kesminiene et al. Radiat. Res. 2008).
p. 21, line 1: Kidney cancer should be added here.
p. 23, last 2 lines: Suggest revising as following: "... the BEIR VII committee found that the
ERR per Gy decreased by about 25% per decade of age at exposure (for ages under 30) in the
model ...
p. 25, Table 3-2: For thyroid cancer, attained age (a) id not an effect modifier. The Ron et al.
pooled analysis should also be cited. For leukemia, the ERR and EAR were linear-quadratic
functions of dose.
p. 27, "Breast" paragraph: It would be helpful to indicate briefly the rationale for using only an
EAR model for this site.
p.27, Table 3-3: Last letter in heading should be Greek eta, not 'FT.
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p.28, Fig.3-2 and others: Always show units along axes.
p.41, Section 3.9.2: insert period after '9'.
p. 43: Line just below equation 3-21. The inequality is incorrect. When one multiplies the
expression in 3-21 by M^ -M^, the direction of the inequality will change when M^ -M^ is
negative.
p. 43, last paragraph: The wording here is confusing. Equation (3-20) seems to assume the
M(tme) that is between the EAR and ERR estimates.
p. 55, 3rd sentence: BEIR VII accounted for uncertainty in the age parameters for the all solid
cancer estimate.
p.57, Table 3-13: Do the 90% UI values refer to Kidney or to combined Residual + kidney as in
Table 3-11?
p. 59, paragraph 2: Another important difference is the approach to transport.
p. 62 ff: If there is sharing of the main effect parameters, there should be sharing of the age
parameters as well. Also, there should probably be allowance for correlation of the age at
exposure and attained age parameters. (I have no idea what the impact of the changes might be.)
p.63, Table 4-1: Replace 2nd parameter heading (it is the same as the 1st).
p.77, Table 4-4b: Insert 'age' in heading before '15'.
p.83, Table 4-5: Although heading says '95% uncertainty intervals', the values are similar to the
90% uncertainty intervals of Table 3-11. Check.
p. 88, 1st full paragraph: The more recent Sokolnikov et al. paper should also be cited here.
p. 90, 1st full paragraph: Provide confidence intervals for these estimates to remind readers of the
considerable uncertainty. This comment also applies to many other estimates presented in the
report.
p. 90, 2nd full paragraph: The Gilbert et al. 2004 paper argued that the estimates of the ERR per
Gy from plutonium and from radon were fairly comparable. You might want to check this paper
(beginning 2nd column on p. 514).
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APPENDIX B-ACRONYMS
A Atomic
AM Arithmetic Mean
BCC Basal Cell Carcinoma
BEIR Biological Effects of Ionizing Radiation (Pertains to committees of the Board of
Radiation Effects, National Research Council of the National Academy (now the
National Academies'), charged with assessing the Biological Effects of Ionizing
Radiation
BEIR VII The report entitled "Health Risks from Exposure to Low Levels of Ionizing
Radiation BEIR VII-Phase 2" published (2006) by the Committee to Assess
Health Risks from Exposure to Low levels of Ionizing Radiation of the Board on
Radiation Effects Research, National Research Council of the National
Academies
Bq Becguerel
CLL Chronic Lymphocyte Leukemia
Co Chemical symbol for Cobalt (60Co isotope)
CT scan Computed tomography scan
DDREF Dose and Dose-Rate Effectiveness Factor
EAR Excess Absolute Risk
EPA Environmental Protection Agency (U.S. EPA)
ERR Excess Relative Risk
eV Electron Volts
FOR Federal Guidance Report
FY Fiscal Year
GM Geometric Mean
GSD Geometric Standard Deviation
Gy Gray., SI unit of radiation absorbed dose (1 Gy is equivalent to 100 rad in
traditional units)
H Chemical symbol for Hydrogen (3H isotope)
IARC International Agency for Research on Cancer
ICRP International Commission on Radiological Protection
I Chemical Symbol for Iodine (131I isotope)
IR Ionizing Radiation
IREP Interactive Radio-epidemiology Program
k Kilo (thousands)
kVp Kilo Volt potential
LAR Lifetime Attributable Risk
LET Linear Energy Transfer
LN Linear Non-Threshold (also LNT)
LSS Life-Span Study
mGY Milli (one Thousandth) Gray
M Point estimate of the excess risk (d, a, e) [at an attained age, a, following a single
exposure to a dose, d, at age, e]
MCMC Markov Chain Monte Carlo methods
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NAS National Academy of Sciences
NCRP National Council on Radiation Protection and Measurements
NIOSH National Institute for Occupational Siafety and Health
NMSC Non-Melanoma Sikin Cancer
NRC National Research Council
OAR Office of Air and Radiation (U. S. EPA/OAR)
ORIA Office of Radiation and Indoor Air (U.S. EP A/O AR/ORIA)
Ra Chemical symbol for Radium (Isotopes include 224Ra,226 Ra, 228Ra, and 236Ra)
RAC Radiation Advisory Committee ((U.S. EPA/SAB/RAC)
RBE Relative Biological Effectiveness
SAB Science Advisory Board (U.S. EPA/SAB)
SEER Surveillance, Epidemiology and End Results
UNSCEAR United Nations .Scientific Committee on the Effects of Atomic Radiation
US United .States of America - used interchangeably with USA
WinBUGS Windows (for Microsoft windows programs) for Bayesian inference Using Gibbs
Sampling analysis software
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