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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON D.C. 20460
OFFICE OF THE ADMINISTRATOR
SCIENCE ADVISORY BOARD
Working Review Draft
EPA-SAB-RAC-ADV-07-xxx
The Honorable Stephen L. Johnson
Administrator
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue, N.W.
Washington, DC 20460
Subject: Advisory on Agency Draft White Paper entitled "ModifyingRadiation Risk
Models Based on BEIR VII, "
Dear Administrator Johnson:
The Radiation Advisory Committee (RAC) of the Science Advisory Board has completed
its review of the Agency's draft white paper entitled 'Modifying EPA Radiation Risk Models
Based on BEIR VII, " dated August 1, 2006. In this white paper, the Agency's Office of
Radiation and Indoor Air (ORIA) outlined proposed changes in the EPA's methodology for
estimating radiogenic cancers. The EPA sought the RAC's advice on the application of BEIR
VII's cancer risk estimates and on issues relating to the proposed modifications and expansions
desirable or necessary for EPA's purposes.
In providing advice to the Agency, the RAC had to consider the important distinction
between the current state of scientific knowledge and the need for a practical, operational public
health approach to radiation protection and standards setting. The RAC endorses EPA's
proposal to base its approach to low dose risk estimation on BEIR VII. Specifically, for
purposes of establishing radiation protection policy, the RAC endorses the EPA's use of a Linear
Non-Threshold (LNT) model combined with the Dose and Dose Rate Effectiveness Factor
(DDREF) for estimating risks following low dose exposures. By low dose, the RAC follows
BEIR VII's definition; that is, doses below 100 mSv (0.1 Sv), in the context of low Linear Energy
Transfer (LET) radiation. In endorsing the use of an LNT model for low dose risk estimation,
the RAC wishes to emphasize that BEIR VII does not use a linear extrapolation of the risk
derived from high doses to estimate the risk following low doses or low dose-rate exposures.
The slope of the dose-response relationship at lower doses and dose rates is less than the slope in
the high dose region. The ratio of slopes derived in the high and low dose regions is the DDREF.
The RAC endorses the concept of using DDREF factors for estimating the risk in the low dose
region.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
The RAC agrees with the EPA that the BEIR VII methodologies using incidence models
and data should be used wherever possible. The RAC accepts the EPA's use of BEIR VII
methodologies for deriving risk estimates for cancers of the stomach, colon, liver, prostate,
uterus, ovary, bladder, and other solid tumors. The RAC did not find compelling evidence to
suggest the use of the alternative lung cancer model discussed by EPA and recommends that the
EPA use the BEIR VII methodologies for deriving risk estimates for radiogenic lung cancer risk.
However, the RAC finds that the EPA is warranted in modifying the BEIR VII methodologies in
several specific areas.
The RAC agrees that the proposed estimation of radiogenic cancer risks for the U.S.A.
population for a standard stationary population based on the year 2000 death rate, or fixed cohort
is a reasonable adaptation of the BEIR VII approach. The RAC agrees that the EPA's proposed
use of the most current cancer-specific incidence and mortality rates available is an appropriate
and scientifically valid adaptation of the BEIR VII approach.
The RAC agrees with the EPA's proposed approach for projecting risk estimates from the
Japanese A-bomb survivors to the U.S.A. population by combining the age-specific results from
the Excess Absolute Risk (EAR) and Excess Relative Risk (ERR) models using the weighted
geometric mean before calculating the lifetime attributable risk.
The RAC concurs with EPA's exploration of alternative methods for estimating the
relative risk for radiogenic breast cancer. In particular, the RAC concurs with the EPA's
proposal to relate current breast cancer mortality rates to retrospective incidence rates rather than
current incidence rates to better reflect the influence of life style changes, earlier breast cancer
detection and treatment that could influence survival and hence mortality rates over an extended
period.
The RAC understands that EPA requires a rationale to estimate risks from exposures to
higher LET radiation, especially alpha particles and lower energy photons and beta particles, but
this subject was beyond the scope of BEIR VII. For alpha particles, the RAC is supportive of the
use of a generally accepted Maximum Relative Biological Effectiveness (RBEM) value, such as
20 which is currently being used. The RAC recommends using data specific to particular
radionuclides where such human cancer risk data are available (e.g., lung, liver, bone, or bone
marrow). For other organs and tissues, the RAC is supportive of the general approach of using
the low-LET cancer risk from BEIR VII multiplied by RBEm. The RAC concurs that an
effectiveness factor in the range of 2 to 2.5 seems reasonable for low-energy photons and
electrons for purposes of setting radiation protection standards.
The RAC recognizes that although the BEIR VII committee chose not to provide risk
estimates for non-melanoma skin cancer (NMSC) induced by ionizing radiation, EPA has an
operational need for such estimates. The RAC supports EPA's proposed use of the 1991
International Commission on Radiological Protection (ICRP) model to estimate the incidence
and mortality risks of radiogenic NMSC. The RAC concurs with EPA that because of the high
background incidence rates and low mortality due to NMSC, it is inappropriate to include risk
estimates for radiogenic NMSC in the estimate of the total risk for radiogenic cancer.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
The risk of bone cancer from low-LET radiation is not specified in the BEIR VII report
but such information is required to consider the cancer risk from a bone-seeking beta-emitting
radionuclide such as 90Sr. The EPA proposes to divide the bone cancer risk observed in humans
224 90
exposed to alpha particles from Ra by an RBE to estimate the bone cancer risk from Sr. The
RAC concurs with this practical, operational approach to radiation protection.
BEIR VII does not provide risk estimates for in utero exposure to radiation, but the EPA
requires an estimate for its guidance documents. The RAC concludes that it would be reasonable
for the EPA to base its risk estimates for in utero radiation exposure on those recommended by
the ICRP for internally-deposited radionuclides.
The RAC considers that it is premature for RAC to offer any advice to ORIA on thyroid
cancer. A major review of radiogenic thyroid cancer is being completed by the National Council
on Radiation Protection and Measurements (NCRP). This information should be considered by
ORIA as it will reflect more recent or more relevant data that could improve the risk estimates
provided by BEIR VII.
The RAC strongly endorses the EPA-ORIA's desire to estimate uncertainty bounds for its
radiogenic cancer risk estimates. The uncertainty bound estimates should incorporate, to the
extent possible, all sources of error and/or uncertainty, including the three main sources
identified in BEIR VII (sampling variability in the Life Span Study (LSS) data, transport of risk
from LSS to the U.S.A. population, and the appropriate value for DDREF at both high and low
doses of low-LET radiation (or, equivalently, the appropriate use of the LNT dose-response
model used for low dose extrapolation). Other sources of error and/or uncertainty identified by
the EPA-ORIA (including dosimetry (of which neutron RBE is a factor), disease detection,
disease classification, temporal patterns, and appropriate RBE values) should also be considered.
The RAC considered several additional complications that could influence uncertainty.
The significant biological responses from the LSS and other epidemiological data cover a limited
range of individual doses. The uncertainties associated with risk estimates are smallest for doses
where cancer rates are significantly elevated. At doses below this range, risk estimates are based
on an assumed LNT dose-response model and method of extrapolation from higher-dose/higher-
response data. In such a situation, lower-dose risk estimates may have larger relative
uncertainties than higher-dose risk estimates because of this extrapolation. In BEIR VII and the
EPA-ORIA's proposed approach to uncertainty estimation, this "additional" uncertainty is
contained within the uncertainty in the value for DDREF, since DDREF is only invoked at lower
doses. The RAC thus strongly endorses the EPA-ORIA's intention to include uncertainty in
DDREF in the overall uncertainty analysis.
BEIR VII specifically considered adaptive response, genomic instability, and bystander
effects, and concluded that currently there is insufficient evidence to explicitly add these effects
to the dose-response model. In the absence of compelling scientific evidence to do otherwise,
the RAC endorses the EPA-ORIA's plan to follow BEIR VII and use the LNT for calculation of
radiation risk. The RAC does recommend, however, that the EPA-ORIA include a (qualitative)
discussion of modern cellular and molecular biological concepts in its final report. As a
cautionary note, the RAC recommends that the EPA discuss potential problems associated with
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
the use of LNT risk estimates in very low dose settings where currently statistically significant
differences are not observed between the cancer rates among exposed populations relative to
those among non-exposed populations and where the doses are a fraction of those associated
with exposure to background radiation.
Uncertainties in risk estimates also change as a function of time into the future, being
smallest in the near time frame. This is due to several factors, including changes in future
(actual) populations (as opposed to a 'stationary population'), future background cancer
incidence, and future medical advances (since the case fatality rate may decrease as a result of
better treatment interventions in the future). Uncertainties thus become greater as the risk
estimates are applied further into the future. The RAC recommends that EPA-ORIA include a
(qualitative) discussion of these concepts in its final report.
An additional source of uncertainty in risk estimates is associated with the mechanistic
biophysical model that is used in BEIR VII to support the LNT in the low dose region. In
Appendix A, the RAC provides a brief review of current research and recommends that ORIA
remain aware of the research, continuously updating the biophysical model used to support the
estimates of radiation risk following low dose radiation exposure.
In summary, the SAB finds that the draft dated August 1, 2006 and entitled "Modifying
EPA Radiation Risk Models Based on BEIR VII, " is an important document to provide the basis
for EPA's update of radiogenic cancer risk estimates. The RAC appreciates the opportunity to
review this draft document and hopes that the recommendations contained herein will enable
EPA to implement changes in the methodology for estimating radiogenic cancers and revise the
"Blue Book". We look forward to your response to the recommendations contained in this
Advisory.
Sincerely,
Dr. M. Granger Morgan
Chair
Science Advisory Board
Dr. Jill Lipoti
Chair, Radiation Advisory Committee
Science Advisory Board
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
NOTICE
This advisory has been written as part of the activities of the EPA Science Advisory
Board (SAB), a public advisory group providing extramural scientific information and advice to
the Administrator and other officials of the Environmental Protection Agency. The SAB is
structured to provide balanced, expert assessment of scientific matters related to problems facing
the Agency. This advisory has not been reviewed for approval by the Agency and, hence, the
contents of this advisory do not necessarily represent the views and policies of the
Environmental Protection Agency, 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.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
FY 06 Roster
U.S. Environmental Protection Agency (EPA)
Science Advisory Board (SAB)
Radiation Advisory Committee (RAC)
CHAIR
Dr. Jill Lipoti, Director, Division of Environmental Safety and Health, New Jersey Department
of Environmental Protection, Trenton, NJ
MEMBERS
Dr. Bruce Boecker, Scientist Emeritus, Lovelace Respiratory Research Institute, Albuquerque,
NM
Dr. Antone L. Brooks, Professor, Radiation Toxicology, Washington State University Tri-
Cities, Richland, WA
Dr. Brian Dodd, Consultant, Las Vegas, NV
Dr. Shirley A. Fry, 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. Helen A. Grogan, Cascade Scientific, Inc., Bend, OR
Dr. Richard W. Hornung, Director of Biostatistics and Data Management, Cincinnati
Children's Hospital Medical Center, Division of General and Community Pediatrics, Cincinnati,
OH
Dr. Jonathan M. Links, Professor, Department of Environmental Health Sciences, Bloomberg
School of Public Health, Johns Hopkins University, Baltimore, MD
Dr. Richard J. Vetter, Radiation Safety Officer, Professor of Biophysics, Mayo Clinic,
Rochester, 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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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
FY 07 Roster
U.S. Environmental Protection Agency (EPA)
Science Advisory Board (SAB)
Radiation Advisory Committee (RAC)
CHAIR
Dr. Jill Lipoti, Director, Division of Environmental Safety and Health, New Jersey Department
of Environmental Protection, Trenton, NJ
MEMBERS
Dr. Thomas B. Borak, Professor, Department of Environmental and Radiological Health
Sciences, Colorado State University, Fort Collins, CA
Dr. Antone L. Brooks, Professor, Radiation Toxicology, Washington State University Tri-
Cities, Richland, WA
Dr. Brian Dodd, Consultant, Las Vegas, NV
Dr. Shirley A. Fry, 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. Helen A. Grogan, Cascade Scientific, Inc., Bend, OR
Dr. Jonathan M. Links, Professor, Department of Environmental Health Sciences, Bloomberg
School of Public Health, Johns Hopkins University, Baltimore, MD
Mr. Bruce A. Napier, Staff Scientist, Radiological Science & Engineering Group, Pacific
Northwest National Laboratory, Richland, WA
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
Dr. Richard J. Vetter, Radiation Safety Officer, Professor of Biophysics, Mayo Clinic,
Rochester, 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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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
U.S. Environmental Protection Agency
Science Advisory Board
(Roster to be Inserted in Later Drafts)
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
2 — (Outline to be Refined in Later Drafts — KJK)
3
4 1. EXECUTIVE SUMMARY 1
5
6 2. INTRODUCTION 5
7 2.1 Background 5
8 2.1.1 Request for EPA Science Advisory Board (SAB) Review 5
9
10 2.2 Proposed EPA Adjustments and Extensions to BEIR VII Models 6
11 2.2.1 Current EPA Cancer Risk Models 6
12 2.2.2 BEIR VII Models 6
13 2.2.3 Proposed EPA Adjustments and Extensions to BEIR VII Models 7
14 2.2.4 Uncertainty Estimates 8
15 2.2.5 Level of Review 8
16 2.2.6 Specific Charge to the Committee 8
17
18 3. PHILOSOPHY OF APPROACH TO THE CHARGE 10
19 3.1 Responding to the Agency's Specific Request 10
20 3.2 Acknowledgement 10
21
22 4. RESPONSE TO CHARGE QUESTION 1: APPLICATION OF THE OVERALL APPROACH AS
23 DESCRIBED IN THE DRAFT WHITE PAPER 12
24 4.1 Response to Charge Question #1 12
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26 5. RESPONSE TO CHARGE QUESTION 2: WHITE PAPER MODIFICATIONS & EXTENSIONS 13
27 5.1 Response to Charge Question #2 13
28 5.2 Response to Charge Question # 2a 14
29 5.3 Response to Charge Question # 2b 14
30 5.4 Response to Charge Question #2c 14
31 5.5 Response to Charge Question #2d 15
32 5.6 Response to Charge Question #2e 17
33 5.7 Response to Charge Question #2f. 17
34 5.8 Response to Charge Question #2g 20
35 5.9 Response to Charge Question #2h 20
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37 6. RESPONSE TO CHARGE QUESTION 3: UNCERTAINTIES NOT QUANTIFIED IN BEIR VII 22
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39 7. RESPONSE TO CHARGE QUESTION 4: ISSUES RELATING TO RADIOGENIC THYROID
40 CANCER NOT QUANTIFIED IN BEIR VII 25
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42 8. ISSUES BEYOND THE CHARGE 26
43
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
1 TABLE 1 - COMPARISON OF THE WHITE PAPER (WP) and BEIR VII METHOD FOR COMBINING
2 EAR and ERR LAR PROJECTIONS FOR LUNG CANCER INCIDENCE 16
3 REFERENCES CITED 27
4 Web-based Citations and Hotlinks 33
5 APPENDIX A - ON-GOING RESEARCH AND PARADIGMS ASSOCIATED WITH BIOLOGICAL
6 RESPONSES TO LOW DOSES OF RADIATION 34
7 APPENDIX B - BIOSKETCHES 37
8 APPENDIX C-ACRONYMS 38
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
1. EXECUTIVE SUMMARY
The Radiation Advisory Committee (RAC) of the Science Advisory Board (SAB) has
completed its review of the Agency's draft white paper entitled "Modifying EPA Radiation Risk
Models Based on BEIR VII, " dated August 1, 2006 (U.S. EPA. ORIA. 2006a). In this white
paper, the Agency's Office of Radiation and Indoor Air (ORIA) outlined proposed changes in
the EPA's methodology for estimating radiogenic cancers. The EPA sought the RAC's advice on
the application of BEIR VII's (U.S. NAS/NRC 2006) cancer risk estimates and on issues relating
to proposed modifications and expansions desirable or necessary for EPA's purposes.
In providing advice to the Agency, the RAC had to consider the important distinction
between the current state of scientific knowledge and the need for a practical, operational public
health approach to radiation protection and standards setting. The RAC endorses EPA's
proposal to base its approach to low dose risk estimation on BEIR VII. Specifically, for the
purposes of establishing radiation protection policy, the RAC endorses the EPA's use of a Linear
Non-Threshold (LNT) model combined with the Dose and Dose Rate Effectivenesss Factor
(DDREF) for estimating risks following low dose exposures. By low dose, the RAC follows
BEIR VII's definition; that is, doses below 100 mSv (0.1 Sv), in the context of low Linear Energy
Transfer (LET) radiation. In endorsing the use of an LNT model for low dose risk estimation,
the RAC wishes to emphasize that BEIR VII does not use a linear extrapolation of the risk
derived from high doses to estimate the risk following low dose or low dose-rate exposures. The
slope of the dose response relationship at lower doses and dose rates is less than the slope in the
high dose region. The ratio of slopes derived in the high and low dose regions is the DDREF.
The RAC endorses the concept of using DDREF factors for estimating the risk in the low dose
region.
With respect to recent advances in the scientific knowledge of radiation biology and
carcinogenesis, the RAC wishes to emphasize that considerable uncertainties remain in the risk
estimates for radiation-induced cancers, especially at low doses and low dose rates. The
epidemiological data below 100 mSv are not sufficient by themselves for risk estimation and
considerable cellular and animal data suggest complexities beyond the application of a simplified
deoxyribonucleic acid (DNA) damage model which historically has been used as support for an
LNT dose-response model. The RAC also emphasizes the additional complexities introduced
with varying RBE and dose-rate. Thus, while the RAC endorses EPA's use of the LNT model,
the Agency is advised to continue to monitor the scientific basis of the relationship between low
dose effects and cancer risk.
The RAC agrees with the EPA that the BEIR VII methodologies using incidence models
and data should be used wherever possible. The RAC accepts the EPA's use of BEIR VII
methodologies for deriving risk estimates for cancers of the stomach, colon, liver, prostate,
uterus, ovary, bladder, and other solid tumors. The RAC did not find compelling evidence to
suggest the use of the alternative lung cancer model discussed by EPA and recommends that the
EPA use the BEIR VII methodologies for deriving risk estimates for radiogenic lung cancer risk.
However, the RAC finds that the EPA is warranted in modifying the BEIR VII methodologies in
several specific areas as discussed below.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
The RAC agrees that the proposed estimation of radiogenic cancer risks for the U.S.A.
population for a standard stationary population based on the year 2000 death rate, or fixed cohort
is a reasonable adaptation of the BEIR VII approach. It is consistent with the EPA's established
approach to cancer risk estimation from exposures to chemicals.
The RAC agrees that the EPA's proposed use of the most current cancer-specific
incidence and mortality rates available is an appropriate and scientifically valid adaptation of the
BEIR VII approach.
The RAC agrees with the EPA's proposed approach for projecting risk estimates from the
Japanese A-bomb survivors to the U.S.A. population by combining the age-specific results from
the Excess Absolute Risk (EAR) and Excess Relative Risk (ERR) models using the weighted
geometric mean before calculating the lifetime attributable risk. This approach is a modification
of that used in BEIR VII, but it has the advantage of allowing the risk results from multiple
exposures to be integrated, enabling the risk from chronic lifetime exposure to be calculated.
Additionally, this method was previously used by the EPA in FGR 13.
The RAC concurs with EPA's exploration of alternative methods for estimating the
relative risk for radiogenic breast cancer. In particular, the RAC concurs with the EPA's
proposal to relate current breast cancer mortality rates to retrospective incidence rates rather than
current incidence rates to better reflect the influence of life style changes, earlier breast cancer
detection and treatment that could influence survival and hence mortality rates over an extended
period.
The RAC understands that EPA requires a rationale to estimate risks from exposures to
higher LET radiation, especially alpha particles and lower energy photons and beta particles, but
this subject was beyond the scope of BEIR VII. For alpha particles, the RAC is supportive of the
use of a generally accepted Maximum Relative Biological Effectiveness (RBEM) value, such as
20 which is currently being used. For those radionuclides for which human cancer risk data are
available (lung, liver, bone, or bone marrow), the RAC recommends that this information be
used directly whenever possible. For other organs and tissues, the RAC is supportive of the
general approach of using the low-LET cancer risk from BEIR VII multiplied by RBEM.
For low-energy photons and electrons, the EPA white paper suggests that the Relative
Biological Effectiveness (RBE) for medical x-rays is about 2 to 2.5. X-rays are not uniquely
different from gamma rays, so the RAC recommends that any risk estimate association with
exposure to photons should be correlated with energy rather than the method of production. The
RAC concurs that an effectiveness factor in the range of 2 to 2.5 seems reasonable for low-
energy photons and electrons for purposes of setting radiation protection standards.
The RAC recognizes that although the BEIR VII committee chose not to provide risk
estimates for non-melanoma skin cancer (NMSC) induced by ionizing radiation, EPA has an
operational need for such estimates. The RAC supports EPA's proposed use of the 1991
International Commission on Radiological Protection (ICRP) model to estimate the incidence
and mortality risks of radiogenic NMSC taking into account more recent findings that most of
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
the NMSCs attributable to low to moderate doses of LET ionizing radiation are of the basal cell
carcinoma (BCC) type (Shore .2001.), and that the incidence rates of BCC have been increasing
substantially in recent decades among the general population (Karagas et al. .1999.). However,
the RAC concurs with EPA that because of the high background incidence rates and low
mortality due to NMSC, it is inappropriate to include risk estimates for radiogenic NMSC in the
estimate of the total risk for radiogenic cancer.
The risk of bone cancer from low-LET radiation is not specified in the BEIR VII report
but such information is required to consider the cancer risk from a bone-seeking beta-emitting
radionuclide such as 90Sr. The EPA proposes to divide the bone cancer risk observed in humans
224 90
exposed to alpha particles from Ra by an RBE to estimate the bone cancer risk from Sr. The
RAC concurs with this practical, operational approach to radiation protection.
BEIR VII does not provide risk estimates for in utero exposure to radiation, but the EPA requires
an estimate for its guidance documents. The RAC concludes that it would be reasonable for the
EPA to base its risk estimates for in utero radiation exposure on those recommended by the
ICRP for internally-deposited radionuclides.
The RAC considers that it is premature for RAC to offer any advice to ORIA on thyroid
cancer. A major review of radiogenic thyroid cancer is being completed by the National Council
on Radiation Protection and Measurements (NCRP). This information should be considered by
ORIA as it will reflect more recent or more relevant data that could improve the risk estimates
provided by BEIR VII.
The RAC strongly endorses the EPA-ORIA's desire to estimate uncertainty bounds for its
radiogenic cancer risk estimates. The uncertainty bound estimates should incorporate, to the
extent possible, all sources of error and/or uncertainty, including the three main sources
identified in BEIR VII (sampling variability in the Life Span Study (LSS) data, transport of risk
from LSS to the U.S.A. population, and the appropriate value for DDREF at both high and low
doses of low-LET radiation (or, equivalently, the appropriate use of the LNT dose-response
model used for low dose extrapolation). Other sources of error and/or uncertainty identified by
the EPA-ORIA (including dosimetry of which neutron RBE is a factor), disease detection,
disease classification, temporal patterns, and appropriate RBE values) should also be considered.
The RAC considered several additional complications that could influence uncertainty.
To begin with, the significant biological responses from the LSS and other epidemiological data
cover a limited range of individual doses. The uncertainties associated with risk estimates are
smallest for doses where cancer rates currently are statistically significantly different from the
spontaneous cancer rates. At doses below this range, risk estimates are based on an assumed
LNT dose-response model and method of extrapolation from higher-dose/higher-response data.
In such a situation, lower-dose risk estimates may have larger relative uncertainties than higher-
dose risk estimates because of this extrapolation.
BEIR VII specifically considered adaptive response, genomic instability, and bystander
effects, and concluded that currently there is insufficient evidence to explicitly add these effects
to the dose-response model. The EPA-ORIA proposes at the present time to follow BEIR VII
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reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
and use the LNT combined with a DDREF for calculation of radiation risk. In the absence of
compelling scientific evidence to do otherwise, the RAC endorses the EPA-ORIA's plan in this
regard. The RAC does recommend, however, that the EPA-ORIA include a (qualitative)
discussion of modern cellular and molecular biological concepts in its final report. As a
cautionary note, we recommend that the EPA discuss potential problems associated with the use
of LNT risk estimates in very low dose settings where cancer rates currently are not statistically
significantly different from spontaneous cancer rates and where the doses are a fraction of those
associated with exposure to background radiation.
It is important to note that there is indeed opportunity to include uncertainties in the
model - that is, uncertainties in high-dose versus low dose behavior - in the overall uncertainty
analysis. In BEIR VII and the EPA-ORIA's proposed approach to uncertainty estimation, this
"additional" uncertainty is contained within the uncertainty in the value for DDREF, since
DDREF is only invoked at lower doses. The RAC thus strongly endorses the EPA-ORIA's
intention to include uncertainty in DDREF in the overall uncertainty analysis.
Uncertainties in risk estimates also change as a function of time into the future, being
smallest in the near time frame. This is due to several factors, including changes in future
(actual) populations (as opposed to a 'stationary population'), future background cancer
incidence, and future medical advances (since the case fatality rate may decrease as a result of
better treatment interventions in the future). Uncertainties thus become greater as the risk
estimates are applied further into the future. The RAC recommends that EPA-ORIA include a
(qualitative) discussion of these concepts in its final report.
An additional source of uncertainty in risk estimates is associated with the mechanistic
biophysical model that is used in BEIR VII to support the LNT in the low dose region. In
Appendix A, the RAC provides a brief review of current research and recommends that ORIA
remain aware of the research continuously updating the biophysical model used to support the
estimates of radiation risk following low dose radiation exposure.
These recent advances provide a scientific basis for the observed non-linear dose-
response relationships seen in many biological systems (BEIR VII, Ko et al. 2006, Mitchel et al.
2004). They suggest that the mechanism of action of radiation-induced damage is different
following exposure to high doses than it is after low radiation doses. It becomes important to
consider new paradigms associated with the biological responses to low doses of radiation and to
modify and further develop the models used to support the extrapolation of dose-response
relationships into dose regions where it is not possible to measure changes in radiation-induced
cancer incidence/mortality in human populations.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
2. INTRODUCTION
2.1 Background
In 1994, the EPA published a report, referred to as the "Blue Book," which lays out the
EPA's methodology for quantitatively estimating radiogenic cancer risks (U.S. EPA. 1994)
http://epa.gov/radiation/docs/assessment/402-r-93-076.pdf. A follow-on report made minor
adjustments to the previous estimates and presented a partial analysis of the uncertainties in the
numerical estimates (U.S. EPA. 1999a) http://epa.gov/radiation/docs/assessment/402-r-99-
003.pdf. Finally, the Agency published Federal Guidance Report 13 (U.S. EPA. 1999)
http://epa.gov/radiation/docs/federal/402-r-99-Q01.pdf which utilized the previously published
cancer risk models, in conjunction with International Commission on Radiological Protection
(ICRP) dosimetric models and the U.S.A. usage patterns, to obtain cancer risk estimates for over
800 radionuclides, and for several exposure pathways. These were later updated (U.S. EPA.
1999b) http://epa.gOv/radiation/federal/techdocs.htm#reportl3.
The National Research Council (NAS/NRC) recently released Health Risks from
Exposure to Low levels of Ionizing Radiation BEIR VII Phase 2 which primarily addresses
cancer and genetic risks from low doses of low-LET radiation (BEIR VII) (U.S. NAS/NRC.
2006) http://newton.nap.edu/catalog/11340.html#toc). In the EPA draft White Paper: Modifying
EPA Radiation Risk Models Based on BEIR VII, the Agency proposes changes to the EPA's
methodology for estimating radiogenic cancers, based on the contents of BEIR VII (U.S. EPA.
2006a). The Agency expects to adopt the models and methodology recommended in BEIR VII,
but believes that certain modifications and expansions are desirable or necessary for the EPA's
purposes.
2.1.1 Request for EPA Science Advisory Board (SAB) Review
The Radiation Advisory Committee (RAC) was initially briefed on the draft White Paper
topic at its public planning meeting of December 21, 2005 which was held at the National Air
and Environmental Radiation Laboratory (NAERL) in Montgomery, Alabama (see 70 Fed. Reg.
69550, November 16, 2005). ORIA issued its external draft White Paper entitled "Modifying
EPA Radiation Risk Models Based on BEIR VII, " on August 1, 2006 (U.S. EPA. 2006a). The
charge questions to the SAB were formally submitted on August 31, 2006 (U.S. EPA. 2006b).
The SAB RAC met in a public teleconference meeting on September 6, 2006 and
conducted a face-to-face public meeting on September 26, 27 and 28, 2006 for this advisory (see
71 Fed. Reg. 45545, August 9, 2006). Additional public conference calls took place on
November 28, 2006, December 18, 2006, and March 9, 2007 (see 71 Fed. Reg., 62590, October
26, 2006 and add additional meetings as appropriate — KJK). These notices, the charge to the
RAC and other supplemental information may be found at the SAB's Web site
(http ://www. sab. gov/ sab).
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
2.2 Proposed EPA Adjustments and Extensions to BEIR VII Models
2.2.1 Current EPA Cancer Risk Models
For most cancer sites, radiation risk models are derived primarily from epidemiologic
data from the Life Span Study (LSS) of the atomic bomb survivors. The EPA's models for
esophageal, stomach, colon, lung, ovarian, bladder and "residual" cancers and leukemia were
adapted from the models published by Land and Sinclair based on a fit to the linear non-
threshold (LNT) fit to the LSS data (Land and Sinclair. 1991.).
For each solid tumor site, gender, and age-at-exposure interval, there is a model
providing a coefficient for the excess relative risk (ERR) per gray (Gy) for cancer mortality,
which is assumed to be constant beginning at the end of a minimum latency period until the end
of life. Land and Sinclair present two sets of models known as the "multiplicative" and the
"National Institutes of Health (NIH)" models that differ in how one "transports" risk from the
Japanese LSS population to the United States population. In the multiplicative model, it is
assumed that the ERR/Gy is the same in all populations, whereas, in the NIH model, it is
assumed that the excess absolute risk (EAR) is the same in different populations for the limited
period of epidemiological follow-up. Given the scarcity of information on how radiogenic
cancer risk varies between populations having differing baseline cancer rates, the EPA
previously adopted an intermediate geometric mean coefficient "GMC" model for each site,
where the risk coefficients were taken to be the weighted geometric mean of the corresponding
ERR and EAR coefficients for both the multiplicative and the NIH models (U.S. EPA. 1994).
For leukemia, the treatment of the temporal response in the models was more complex,
but the approach for transporting risk to the U.S.A. population was analogous. Following the
approach of Land and Sinclair, the EPA also developed a GMC model for kidney cancer from
the LSS data. The EPA's models for other site- or type-specific cancers, including breast, liver,
thyroid, bone, and skin were based on various authoritative reports (NCRP. 1980.; NRC. 1988.;
ICRP. 1991a, b; Gilbert. 1991.). Based primarily on ICRP recommendations at that time (ICRP
1991a), for low doses and dose rates, each coefficient was reduced by a factor of two, dose and
dose-rate effectiveness factor (DDREF), from that which would be obtained from a LNT fit to
the LSS data.
2.2.2 BEIR VII Models
BEIR VII cancer site-specific models derived from the LSS differ from those of Land and
Sinclair in several notable ways: (1) they are derived primarily from cancer incidence rather than
cancer mortality data; (2) mathematical fitting is performed to better reflect the functional
dependence of solid cancer risk on age at exposure and attained age, (i.e., age at diagnosis of a
cancer or age at death due to cancer depending on the end-point of interest); (3) a weighted
average of risk projection models is used to transport risk from the LSS to the U.S.A. population;
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
(4) a value for the DDREF of 1.5 is estimated from the LSS and laboratory data; (5) quantitative
uncertainty bounds are provided for the site-specific risk estimates in BEIR VII.
For breast cancer and thyroid cancer, BEIR VII risk models are based on pooled analyses
of data from the LSS cohort, together with data from epidemiologic studies of medically
irradiated cohorts (Preston et al. 2002; Ron et al. 1995).
2.2.3 Proposed EPA adjustments and Extensions to BEIR VII Models
In the draft White Paper: Modifying EPA Radiation Risk Models Based on BEIR VII
(U.S. EPA. ORIA ,2006a.), the Agency's Office of Radiation and Indoor Air (ORIA) outlined
proposed changes in the EPA's methodology for estimating radiogenic cancers, based on the
contents of BEIR VII and some ancillary information. For the most part, the Agency expects to
adopt the models and methodology recommended in BEIR VII; however, the Agency believes
that certain modifications and expansions are desirable or necessary for the EPA's purposes.
The objective of BEIR VII was to derive/update cancer risk estimates for radiation exposures of
100 mSv or less, primarily from external photon radiation based on the most current valid
epidemiological and experimental data available. In order to satisfy EPA's broader mission, the
EPA needs to have a basis for estimation of cancer risks outside BEIR VII's scope.
One significant extension to be considered is the estimation of cancer risks from
exposures to higher Linear Energy Transfer (LET) radiations, especially to alpha particles, and
also to lower energy photons and beta particles. An important expansion proposed by EPA to be
considered is the estimation of risks from exposures to alpha particles, and also to alpha emitters
deposited in the lung and the bone. BEIR VII does not present any risk estimates for radiogenic
bone cancer. The EPA proposes to estimate bone cancer risk from data on radium injected
patients and to multiply that risk by a quality factor to estimate the risk from internally deposited
beta-gamma emitting radioactive materials.
BEIR VII does not provide quantitative estimates of risk for skin cancer. It does not fully
address prenatal exposures. BEIR VII presents a model for estimating the risk of the radiogenic
thyroid cancer incidence, but not of mortality due to radiogenic thyroid cancer.
The EPA proposes to use somewhat different population statistics from BEIR VII.
Consideration is given to an alternative model for estimating radiogenic lung cancer. For breast
cancer, the EPA proposes an alternative method for estimating mortality, which takes into
account changes in incidence rates and survival rates over time.
At this point in its activity on this topic, the EPA is seeking advice from the Agency's
Science Advisory Board's (SAB) Radiation Advisory Committee (RAC) on the application of
BEIR VII's cancer risk estimates and on issues relating to these modifications and expansions.
After receiving the advisory review, the Agency plans to implement changes in their
methodology through the publication of a revised Blue Book, which it would expect to submit to
the SAB's RAC or a specialty panel supplementing the RAC for final review. The revised Blue
Book could then serve as a basis for an updated version of FGR-13.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
2.2.4 Uncertainty Estimates
BEIR VII provides quantitative uncertainty bounds for each of its risk coefficients,
however, no uncertainty was assigned to the form of the dose-response relationship. It was
implicitly assumed that the dose-response relationship followed the hypothetical dose-response
curve depicted in Figure 10-1. This shows a progression of linear approximations, with different
slopes within different dose ranges. The relationship between these different slopes provides the
definition of the DDREF. This progression allowed the BEIR VII Committee to place
uncertainty on bounds of the DDREF. Mechanisms pertaining to the biological effects of low-
level ionizing radiation are being investigated. This could eventually mandate a different dose-
response model, potentially resulting in changes in estimates of risk at low doses. Assigning
probabilities to alternative models would be highly subjective at this time. The EPA does not
propose to quantify the uncertainty pertaining to low-dose extrapolation, but it would provide a
brief discussion of the issue.
2.2.5 Level of Review
There are various levels of reviews which EPA can request from the SAB. These include
reviews, advisories, and commentaries. The request from EPA-ORIA was for an "advisory"
review of the draft White Paper. ORIA was interested in vetting ideas with a group of scientific
experts on how to incorporate the changes in cancer risk models described by BEIR VII and to
extend the BEIR VII models to areas not specifically addressed by the BEIR VII committee.
ORIA described it as a "mid-course correction" which would allow the RAC to provide advice
on a series of questions which would guide the Agency in incorporating the latest scientific
thinking into their risk estimates. The RAC was not asked to provide policy direction,
therefore the RAC did not consider the implications to EPA standards which may be an outcome
of the changes to the risk estimates.
2.2.6 Specific Charge to the Committee
1) BEIR VII provides incidence models for many cancer sites as a basis for calculating the
risk from low-dose, low-LET radiation. Please comment on EPA's application of this overall
approach as described in the draft White Paper.
2) In addition to the overall approach described in BEIR VII, the draft White Paper presents
specific modifications and extensions. Please comment on the soundness of the following
proposals:
a. Calculation of the risk to the life table (stationary) population instead of the actual
U.S. population (see Sections II.A.-C.); this is consistent with our current approach.
b. Use of more recent incidence and mortality data from SEER and/or other sources
(see Section II.D.); BEIR VII used a previous version of SEER data for the years
1995-1999.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
c. Methodfor combining BEIR VII's models for projecting risk from Japanese A-bomb
survivors to U.S. population (see Section HE.). In contrast to BEIR VII, we propose
to combine the two risk models before integration to calculate the lifetime
attributable risk.
d. Adoption of an alternative model for radiogenic lung cancer risk which may better
account for the effects of smoking than the BEIR VII approach (see Section II.G.).
e. Methodfor calculating breast cancer mortality risk, accounting for the relatively long
time from detection until death (see Section II.H.).
f. Proposed approaches for extending risk estimates to radiations of different LET's - in
particular, deriving site-specific risk estimates for alpha or x radiations based on
models derived from the A-bomb survivors, who were primarily exposed to gamma
rays (see Section III).
g. Estimation of risks for sites not specified in BEIR VII, specifically bone and skin, for
which we propose to update our current approaches (see Sections III.A. and V,
respectively).
h. Estimation of risk due to prenatal exposure. EPA 's current lifetime risk estimates do
not include risk from prenatal exposure, and BEIR VII does not provide them. The
draft White Paper uses ICRP recommendations to project its risks of childhood
cancers induced by in utero exposure. Please comment on the soundness of the
approach described in the draft White Paper to apply ICRP as described in Section
IV.
3) BEIR VII provides quantitative uncertainty bounds for each of its risk coefficients. EPA
proposes to adopt this methodology with some additional discussion of the uncertainties not
quantified in BEIR VII. Please comment on the adequacy of this approach (see Section U.K.).
4) In Section VI, the draft White Paper discusses some issues relating to radiogenic thyroid
cancer. Does the RAC have any specific suggestions for dealing with this risk; e.g., does the
RAC have any advice on gender specificity, effectiveness of iodine -131 compared to gamma
rays, or estimation of thyroid cancer mortality?
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
3. PHILOSOPHY OF APPROACH TO THE CHARGE
3.1 Responding to the Agency's Specific Request
In providing advice to the Agency, the RAC had to consider the important distinction
between the current state of scientific knowledge and the need for a practical, operational public
health approach to radiation protection and standards setting. In this Advisory, the RAC wishes
to comment on both issues.
For the purposes of providing estimates of the risks of radiation-induced cancers as a
basis for setting radiation protection standards, the RAC endorses EPA's proposal to base its
approach to low dose risk estimation on BEIR VII. Specifically, for purposes of establishing
radiation protection policy, the RAC endorses the use of an LNT model combined with the
DDREF for estimating risks following low dose exposures.. By "low dose," the RAC follows
BEIR VII's definition; that is, doses below 100 mSv (0.1 Sv), in the context of low-LET
radiation. In endorsing the use of an LNT model for low dose risk estimation, the RAC wishes
to emphasize that BEIR VII does not use a linear extrapolation of the risk derived from high
doses to estimate the risk following low doses or low dose-rate exposures. The slope of the
dose-response relationship at lower doses and dose rates is less than the slope in the high dose
region. The ratio of slopes derived in the high and low dose regions is the DDREF. The RAC
endorses the concept of using DDREF factors for estimating the risk in the low dose region
With respect to recent advances in the scientific knowledge of radiation biology and
carcinogenesis, the RAC wishes to emphasize that considerable uncertainties remain in the risk
estimates for radiation-induced cancers, especially at low doses and low dose rates. As BEIR
VII acknowledges, the epidemiological data below 100 mSv (0.1 Sv) are not sufficient by
themselves for risk estimation, and considerable cellular and animal data suggest complexities
beyond the application of a simplified DNA damage model which historically has been used as
support for an LNT dose-response model. The RAC also wishes to emphasize the additional
complexities introduced with varying RBE and dose rate. Thus, while the RAC endorses EPA's
use of the LNT model, the Agency is advised to continue to monitor the science relating to low
dose effects and cancer induction.
Additional discussion of the biophysical models of radiation effects in the low dose
region is in Appendix A.
3.2 Acknowledgement
The document "Modifying EPA Radiation Risk Models Based on BEIR VII, " August 1,
2006 was well written and provided much needed background. Similarly, with the BEIR VII
report, presentations by the ORIA staff and other information provided to the RAC in the course
of the public meetings were found to be helpful. During the meetings, the ORIA staff worked
diligently to augment their draft White Paper with additional pieces of information that the RAC
felt were necessary to assist with the advisory. The staff took care to honor all the RAC's
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
1 requests and demonstrated their patience as members sought to understand all that went into the
2 modified procedures being proposed.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
4. RESPONSE TO CHARGE QUESTION 1: APPLICATION OF THE
OVERALL APPROACH AS DESCRIBED IN THE DRAFT WHITE PAPER
4.1 Response to Charge Question 1:
BEIR VII provides incidence models for many cancer sites as a basis for calculating the risk
from low-dose, low-LET radiation. Please comment on EPA's application of this overall
approach as described in the draft White Paper.
The Radiation Advisory Committee (RAC) agrees with the EPA that the BEIR VII
methodologies using incidence models and data should be used wherever possible. The RAC
accepts the EPA's use of BEIR VII methodologies for deriving risk estimates for cancers of the
stomach, colon, liver, prostate, uterus, ovary, bladder, and other solid tumors. Furthermore, if
one of the four following conditions applies, then the RAC agrees that the EPA is warranted in
modifying the BEIR VII methodologies. The four possible conditions are:
1) Information and data are needed about subject matter not addressed in BEIR VII;
2) More recent or more relevant data exist which could improve or otherwise
influence the risk estimates;
3) Compelling evidence suggests the use of a more appropriate scientific method; or
4) The EPA's implementation requirements for practicality or applicability
necessitate an adaptation or other alternative to BEIR VII methodologies.
The RAC grouped all of the charge issues according to these conditions. For example,
under condition one, the RAC considered prenatal exposures, bone and skin cancers, x- and
alpha-particle radiations and tritium as areas not addressed by BEIR VII, and for which the EPA
has a need to derive a basis for risk estimates. An example of applying condition two is that the
use of the most recent Surveillance, Epidemiology, and End Results (SEER) data would improve
the risk estimate. Examples of condition three are issues where a more appropriate scientific
method was considered, i.e. in development of breast cancer risk estimates and the estimation of
uncertainty. An example of condition four is the use of a stationary or a standard population.
The RAC concludes that the EPA's use of the gray (Gy) as the unit of radiation absorbed
dose is appropriate and agrees that modifying factors should be applied to the risk rather than
dose.
The RAC's approach to giving advice to the EPA is predicated on the basic premise that
the risk estimates are for use in assessing population risk, rather than risk to a specific individual.
This is because specific individuals may be more or less susceptible to radiation-induced cancer
than the average for the population. Furthermore, at present there is little known about either the
degree of or the causes of variation in individual susceptibility to the effects of radiation.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
5. RESPONSE TO CHARGE QUESTION 2: WHITE PAPER
MODIFICATIONS AND EXTENSIONS
5.1 Response to Charge Question # 2
In addition to the overall approach described in BEIR VII, the draft White Paper presents
specific modifications and extensions. Please comment on the soundness of the following
proposals:
a. Calculation of the risk to the life table (stationary) population instead of the actual U.S.
population (see Sections II.A.-C.); this is consistent with our current approach.
b. Use of more recent incidence and mortality data from SEER and/or other sources (see
Section II.D.); BEIR VII used a previous version of SEER data for the years 1995-1999.
c. Methodfor combining BEIR VII 's models for projecting risk from Japanese A-bomb
survivors to U.S. population (see Section HE.). In contrast to BEIR VII, we propose to
combine the two risk models before integration to calculate the lifetime attributable risk.
d. Adoption of an alternative model for radiogenic lung cancer risk which may better
account for the effects of smoking than the BEIR VII approach (see Section II. G.).
e. Methodfor calculating breast cancer mortality risk, accounting for the relatively long
time from detection until death (see Section II.H.).
f. Proposed approaches for extending risk estimates to radiations of different LET's - in
particular, deriving site-specific risk estimates for alpha or x radiations based on models
derivedfrom the A-bomb survivors, who were primarily exposed to gamma rays (see
Section III).
g. Estimation of risks for sites not specified in BEIR VII, specifically bone and skin, for
which we propose to update our current approaches (see Sections III.A. and V,
respectively).
h. Estimation of risk due to prenatal exposure. EPA 's current lifetime risk estimates do not
include risk from prenatal exposure, and BEIR VII does not provide them. The draft
White Paper uses ICRP recommendations to project its risks of childhood cancers
induced by in utero exposure. Please comment on the soundness of the approach
described in the draft White Paper to apply ICRP as described in Section IV.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
5.2 Response to Charge Question # 2a
Calculation of the risk to the life table (stationary) population instead of the actual U.S.
population (see Sections II.A.-C.); this is consistent with our current approach.
The RAC agrees that the proposed estimation of radiogenic cancer risks for the U.S.A.
population using a standard stationary population based on the year 2000 death rate, or fixed
cohort is a reasonable adaptation of the BEIR VII approach. Specifically, it avoids the potential
for changes over time in the baseline cancer rates among the actual U.S.A. population that may
be associated with changes in its racial, ethnic, cultural or other characteristics known to
influence population disease rates. It also is consistent with the EPA's established approach to
cancer risk estimation from exposures to chemicals (U.S. EPA. 2005a, U.S. EPA. 2005b, Also
FR Vol 70, No. 66, pp 17765, April 7, 2005)
5.3 Response to Charge Question #2b
Use of more recent incidence and mortality data from SEER and/or other sources (see
Section II.D.); BEIR VII used a previous version of SEER data for the years 1995-1999.
The RAC agrees that the EPA's proposed use of the most current cancer-specific
incidence and mortality rates available is an appropriate and scientifically valid adaptation of the
BEIR VII approach.
It is anticipated that incidence or mortality data for the years 1998-2002 will be available
for the final calculations of radiogenic cancer incidence risk estimates from NCI's SEER
program. In contrast, only data from this program for 1995-1999 were available to BEIR VII.
Although other potential sources of valid, nationally representative data will be
considered by the EPA, the RAC considers that the most current SEER data are adequate and
preferred for consistency with the BEIR VII approach. The EPA may want to consider the latest
vital statistics report produced from the 2000 census for mortality rates if they become available
before the final report is produced.
5.4 Response to Charge Question #2c
Methodfor combining BEIR VII 's models for projecting risk from Japanese A-bomb
survivors to U.S. population (see Section HE.). In contrast to BEIR VII, we propose to
combine the two risk models before integration to calculate the lifetime attributable risk.
The RAC notes that there is considerable uncertainty in the application of risk estimates
developed from the Japanese atomic bomb survivors to the U.S.A. population. This uncertainty
results from different genetic and lifestyle characteristics of the two populations and differences
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
in the baseline cancer risks. The RAC agrees with the EPA's proposed approach for projecting
risk estimates from the Japanese A-bomb survivors to the U.S.A. population by combining the
age-specific results from the Excess Absolute Risk (EAR) and Excess Relative Risk (ERR)
models using the weighted geometric mean before calculating the lifetime attributable risk. This
approach is a modification of that used in BEIR VII but is consistent with the method used
previously by the EPA in FGR13. The RAC notes that the EPA method has the advantage of
allowing the risk results from multiple exposures to be integrated, thereby enabling the risk from
chronic lifetime exposure to be calculated.
5.5 Response to Charge Question #2d
Adoption of an alternative model for radiogenic lung cancer risk which may better account
for the effects of smoking than the BEIR VII approach (see Section II.G.).
The RAC recommends that the EPA use the BEIR VII methodologies for deriving risk
estimates for radiogenic lung cancer risk. The RAC does not find compelling evidence to
suggest the use of the alternative model discussed by EPA.
The lung cancer risk estimates reported by BEIR VII are primarily based on analyses of
the LSS data. These estimates were not adjusted for cigarette smoking which is potentially an
important confounder and/or effect modifier. This problem of lack of adjustment for cigarette
smoking is further compounded by the fact that lung cancer incidence rates are lower in Japan
than the U.S.A. and the lung cancer incidence rate ratio of males to females is considerably
higher in Japan than in the U.SA. The BEIR VII Committee was aware of this problem and
chose to deal with it by using a risk transport model that more heavily weighted the EAR
estimates relative to ERR estimates, i.e. assigning the weight of 0.7 for EAR and 0.3 for ERR.
The BEIR VII Committee justified this approach based on mechanistic arguments and the
finding reported by Pierce (Pierce el al. 2003), that in the LSS population of Japanese atomic
bomb survivors the interaction between low LET radiation and smoking was consistent with an
additive effect. This weighting scheme results in a Lifetime Attributable Risk (LAR) that is
roughly twice as great among females as among males.
The EPA white paper provided an alternative model to the BEIR VII lung cancer risk
estimates. EPA was concerned that the lack of adjustment for cigarette smoking and birth cohort
effects would result in an overestimate of risk in the U.S.A. population as well as female to male
incidence rate ratio that was too high. EPA proposed to use a pure EAR model for lung cancer,
equivalent to a weighting of 1.0 for EAR and 0.0 for ERR risk models.
The RAC requested additional work on this problem from the EPA consisting of the
following tasks:
• Compare results of the calculation of LAR using BEIR VII weighting to 100% EAR model
and to alternative weighting schemes and/or the use of arithmetic, AM, or geometric, GM,
means.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
1 • Consider how the additive ERR model for smoking and radiation provides evidence for the
2 appropriate weighting scheme.
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4 • Consider papers additional to Pierce (2003) on the nature of the smoking /radiation
5 interaction.
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8 Based upon EPA's response to these requests, Table 1 below illustrates the effect upon
9 LAR estimates for lung cancer incidence of several different weighting schemes for the EAR and
10 ERR risk models. The columns labeled White Paper (WP) and BEIR VII reflect differences in
11 how the weighting was applied. BEIR VII used a weighted average of the final age-adjusted
12 ERR and EAR estimates on a log scale, while EPA first weighted each age-specific stratum and
13 then combined the weighted age-specific risk estimates. Inspection of the table reveals that the
14 difference in application of the weights produced very small changes in the WP and BEIR VII
15 LAR estimates. The weighting of 0.0 for ERR proposed by EPA produces LAR estimates that
16 are somewhat smaller than the weight of 0.3 for ERR chosen by BEIR VII, most notably for
17 females. The RAC also notes that the evidence for a purely additive model is not compelling
18 based upon the literature review performed by EPA. There is some support for an interaction
19 between radiation exposure and cigarette smoking that is intermediate between additive and
20 multiplicative, similar to the weighting scheme selected by BEIR VII.
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22 Accordingly, due to a lack of compelling evidence to depart from the weighting approach
23 used by BEIR VII, the RAC recommends that EPA should not employ alternative weighting
24 schemes.
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Table 1:
Comparison of the EPA White Paper (WP) and BEIR VII Method for Combining
EAR and ERR LAR Projections for Lung Cancer Incidence.1
Combination
Method
RR weight2 = 0.0
Combination
Method
RR weight3 = 0.3
Combination
Method
RR weight = 0.5
Combination
Method
RR weight = 0.7
Combination
Method
RR = 1.0
Sex
WP
BEIR VII
WP
BEIR VII
WP
BEIR VII
WP
BEIR
VII
WP
BEIR VII
Male
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186
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213
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230
Female
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344
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428
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495
541
573
714
714
NOTE: Number of cases per 100,000 persons exposed to 0.1 Gy. Results do not incorporate DDREF adjustment.
Results are shown for stationary populations and SEER incidence data for the years 1998-2002.
2Weight for projection based on EPA proposal
3Weight for projection using BEIR VII
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
5.6 Response to Charge Question #2e
Methodfor calculating breast cancer mortality risk, accounting for the relatively long time
from detection until death (see Section II.H.).
The RAC notes that the EPA adopts BEIR VII's approach to estimating the risk of breast
cancer in females that differs from that used by BEIR VII to estimate the risks for the majority of
other solid cancers. However, the EPA identified issues relative particularly to the changing
clinical course of breast cancer in conjunction with a relatively long survival period, and
questions some aspects of BEIR VII's risk estimation method for this site-specific cancer. The
EPA thus has identified several alternative methods for estimating the relative risk for radiogenic
breast cancer in an effort to take into account some of the temporal features that can influence
the cancer's clinical course and hence the risk estimates. The RAC concurs with the EPA's
decision to explore these alternative methods.
Specifically, the RAC concurs with the EPA's proposal to relate current breast cancer
mortality rates to retrospective incidence rates rather than current incidence rates to better reflect
the influence of life style changes, earlier breast cancer detection and treatment that could
influence survival and hence mortality rates over an extended period.
The RAC notes the potential for development of second cancers during the cancer
survival period. Such an event could be spontaneous or related to treatment of the initial cancer.
In the case of breast cancer, it could impact mortality reporting and loss of deaths attributed to
breast cancer.
The RAC suggests that the EPA explore the feasibility of using the BEIR VII approach
with the proposed method (above) with retrospective lagging incidence rates relative to current
mortality rates.
5.7 Response to Charge Question #2f
Proposed approaches for extending risk estimates to radiations of different LET's - in
particular, deriving site-specific risk estimates for alpha or x radiations based on models
derivedfrom the A-bomb survivors, who were primarily exposed to gamma rays (see Section
III).
A significant extension requiring subject matter not addressed in BEIR VII is guidance
on how to deal with the estimation of risks from exposures to different LET radiation, especially
alpha particles and lower energy photons and beta particles. Knowledge of these risks is
required particularly for dealing with the possible health risks from chronic irradiation from
alpha, beta, or gamma emissions from internally deposited radionuclides. A key feature of the
low-LET radiation exposures used in the analyses available in the BEIR VII report, especially
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
those based on the Japanese atomic bomb survivors, is that they involved a very brief, whole-
body exposure to radiation from an external source. In such a situation, all of the organs and
tissues of the body were irradiated and the long-term risks to these organs and tissues have been
studied directly. When dealing with internally deposited radionuclides, the situation is different
because the radionuclide is likely to be distributed non-uniformly in the body, with only a few
organs and tissues receiving most of the dose. This can change the spectrum of cancers
produced. Also, because of the possible long-term retention of some long-lived radionuclides,
the dose can continue to accumulate at a low dose rate over months or years. Dealing with these
differences is important but not necessarily straightforward as discussed below.
Higher LET Radiation
The RAC noted that the white paper only considered alpha particles for radionuclides
inhaled or ingested.
A. Alpha Particles
The EPA white paper discusses three possible approaches to estimating the lifetime
health risks from internally deposited alpha-emitting radionuclides. These three approaches are
discussed below:
a) Data from human populations exposed to alpha-emitting radionuclides.
Good risk data are available for the following organs and tissues (U.S. NAS/NRC. 1988:
U.S. NAS/NRC. 1999; Koshurnikova et al. 2000; Gilbert et al. 2004):
226 228
- Bone cancer from radium dial painters and radium chemists exposed to ' Ra;
- Bone Cancer from ankylosing spondylitis patients exposed to 224Ra;
- Liver cancer from patients given Thorotrast (232Th) as an imaging agent;
- Leukemia from patients given Thorotrast (232Th) as an imaging agent;
- Lung cancer from uranium miners who inhaled 222Rn and progeny; and
- Lung cancer from Mayak Russian workers who inhaled 239Pu.
Since the lung, liver, bone and bone marrow are the major organs at risk for internally
deposited, alpha-emitting radionuclides, these populations provide important information on
carcinogenic risk for alpha-emitting radionuclides. The RAC notes that this information is based
on site-specific cancer mortality among groups whose total doses are generally well above the
low-dose region.
b) Data from life-span studies of laboratory animals exposed via various routes of exposure
to graded activity levels of alpha-emitting radionuclides.
There are sizeable data bases available for different species of laboratory animals
exposed to different beta-, gamma- or alpha-emitting radionuclides by various routes and studied
for their lifetimes. These studies provide much information on the life-span health effects but the
number of variables involved including species, route of exposure, animal husbandry and other
factors make it difficult to extrapolate the risk results directly to human populations in a
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
consistent manner. However, they do provide useful information on radionuclides for which no
human data are available. Such studies also help define the influence of dose distribution and the
relative effectiveness of high- and low-LET radiations in those cases where studies of the high
and low-LET emissions were examined in a parallel manner under similar conditions.
c) The most recent cancer risk data from the RERF studies of atomic bomb survivors
exposed to low-LET radiation multiplied by a general RBEm factor for alpha particles.
This third, more general, approach assumes that an appropriate value for RBEM is known
and that it is appropriate to use this value with the cancer risk seen after a brief, high dose-rate
exposure received by the atomic bomb survivors to estimate cancers risks in a broad range of
organs and tissues for which no data are available for alpha-particle exposure.
As discussed in Section III. A. 3, Summary and Recommendations of the White Paper, the
EPA proposes to multiply site-specific gamma-ray cancer risk estimates by an RBE of 20 to
derive corresponding estimates of cancer risk from alpha radiation, with two exceptions:
a) An RBE =1-3 for leukemia induced by alpha emitters deposited in bone; and
b) Continued use of models derived from BEIR VI to estimate lung cancer risk from
inhaled radon progeny.
The RAC recognizes the problems that the EPA has to deal with in adding consideration
of alpha-emitting radionuclides to the information already provided for low-LET radiation in the
BEIR VII report. This particular issue is one example of the need for a practical, operational
public health approach to radiation protection and standards setting mentioned earlier in this
Advisory. On this basis, the RAC is supportive of the use of a generally accepted RBEM value
such as the 20 that they are using currently. For those radionuclides for which human cancer risk
data are available for the lung, liver, bone, or bone marrow, the RAC recommends that this
information be used directly whenever possible. For other organs and tissues, the RAC is
supportive of the general approach (except for bone cancer as discussed in Section 5.8) of using
the low-LET cancer risk from BEIR VII multiplied by RBEm.
B. Low-energy Photons and Electrons
The EPA White Paper suggests that the relative biological effectiveness (RBE) for
medical x rays is about 2 - 2.5. However, x-rays are not uniquely different from gamma-rays
except for their production. Any risk estimate associated with exposure to photons needs to be
correlated with the energy of the photon rather than the method of production.
Reviews by ICRU (1986) and Kocher et al. (2005) show that RBEs for low energy
photons, < 30 keV, and low energy electrons, <15 keV, are higher than one when compared to
higher energy x-rays and ^Co gamma-rays. A probability distribution by Kocher et al. (2005)
showed a median radiation effectiveness factor of approximately 2.4 for photons less than 30
keV and for ^H beta particles. Thus, an effectiveness factor for these low energy radiations in
the range of 2 to 2.5 seems reasonable.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
5.8 Response to Charge Question #2g
Estimation of risks for sites not specified in BEIR VII, specifically bone and skin, for which we
propose to update our current approaches (see Sections III.A. and V, respectively).
The risk of bone cancer from low-LET radiation is not specified in the BEIR VII report
but such information is required to consider the cancer risk from a bone-seeking beta-emitting
radionuclide such as 90Sr. In this case, the EPA proposes to do the reverse of what is discussed
above in Section 2f. Instead of multiplying a low-LET cancer risk by an RBE to estimate a high-
LET cancer risk, it proposes to divide the bone cancer risk observed in humans exposed to alpha
224 90
particles from Ra by an RBE to estimate the bone cancer risk from Sr (NCRP 1991). Once
again, this practical, operational approach to radiation protection and standards setting seems
appropriate and conservative for the task at hand.
The RAC recognizes that although the BEIR VII committee chose not to provide risk
estimates for non-melanoma skin cancer (NMSC) induced by ionizing radiation, EPA has an
operational need for such estimates. This presents ORIA with certain methodological challenges
given the high incidence and low mortality rates of NMSC among the US general population and
the limitations of available data.
The RAC supports EPA's proposed use of the 1991 ICRP model to estimate the incidence
and mortality risks of radiogenic NMSC taking into account more recent findings that most of
the NMSCs attributable to low to moderate doses of LET ionizing radiation are of the basal cell
carcinoma (BCC) type (Shore. 2001.), and that the incidence rates of BCC have been increasing
substantially in recent decades among the general population (Karagas et al. .1999.).
However, the RAC concurs with EPA that because of the high background incidence
rates and low mortality due to NMSC, it is inappropriate to include risk estimates for radiogenic
NMSC in the estimate of the total risk for radiogenic cancer. The RAC also notes that as ionizing
radiation is not considered to be a risk factor for melanoma skin cancer there is no rationale for
risk estimation in this instance.
5.9 Response to Charge Question #2h
Estimation of risk due to prenatal exposure. EPA 's current lifetime risk estimates do not
include risk from prenatal exposure, and BEIR VII does not provide them. The draft White
Paper uses ICRP recommendations to project its risks of childhood cancers induced by in
utero exposure. Please comment on the soundness of the approach described in the draft
White Paper to apply ICRP as described in Section IV.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
BEIR VII does not provide risk estimates for in utero exposure to radiation. Even though
the risk from in utero exposure is a minor component of the overall radiogenic cancer risk, the
EPA requires an estimate for radiation protection and standard setting purposes.
Few human data exist on which to base an estimate of radiogenic cancer risk for in utero
exposure to radiation from either external sources or internally deposited radioactive materials.
The primary sources of data for external exposures are the Oxford Survey of Childhood
Cancer (Stewart et al., 1958.; Mole, 1990) and as reviewed by Mettler and Upton, (1995) and by
Doll and Wakefield, (1997) and the studies of Japanese atomic bomb survivors exposed in utero
(Delongchamp et al., 1997). When all sources of uncertainty are taken into account, the risk
estimates from these studies are not incompatible with each other (Wakeford & Little, 2002).
The dose to the embryo/fetus from internally-deposited radionuclides has been reviewed
(NCRP, 1998; ICRP 2000) and ICRP (2001) provides organ/tissue dose coefficients (Sv/Bq) to
the embryo/fetus from chronic intake of individual radionuclides by the mother. These data can
be used to develop cancer risk estimates for the embryo/fetus exposed coincidentally to radiation
delivered at low dose rates from the same sources
The RAC concludes that it would be reasonable for the EPA to use the dose coefficients
provided by ICRP as a basis for developing its estimates risk estimates for in utero radiation
exposure from internally-deposited radionuclides.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
6. RESPONSE TO CHARGE QUESTION 3: UNCERTAINTIES NOT
QUANTIFIED IN BEIR VII
Charge Question 3: BEIR VII provides quantitative uncertainty bounds for each of its risk
coefficients. EPA proposes to adopt this methodology with some additional discussion of the
uncertainties not quantified in BEIR VII. Please comment on the adequacy of this approach (see
Section U.K.).
The RAC strongly endorses the EPA-ORIA's desire to estimate uncertainty bounds for its
radiogenic cancer risk estimates. Indeed, given the range of possible operational uses of the risk
estimates, as much effort should go into estimating the uncertainty bounds as into producing the
central or point risk estimates themselves.
Ideally, the uncertainty analysis would involve the development of a probability density
function for (site-specific) estimated risk, rather than bounds around a central or point risk
estimate. Such an approach, which has previously been considered by other national and
international committees, would facilitate risk estimation based on other than the average risk.
For example, such an approach might facilitate the identification of a minimum cost-of-errors (or
'loss') risk estimate for operational use (e.g., in risk-informed regulation). However, the RAC
believes that such an approach is not likely to be practically achievable, and endorses the EPA-
ORIA's approach (central risk estimate with uncertainty bounds, following BEIR VII).
The uncertainty bound estimates should incorporate, to the extent possible, all sources of
error and/or uncertainty, including the three main sources identified in BEIR VII (sampling
variability in the LSS data, transport of risk from LSS to the U.S.A. population, and the
appropriate value for DDREF at both high and low doses of low-LET radiation (or, equivalently,
the appropriate use of the LNT dose-response model used for low dose extrapolation)). Other
sources of error and/or uncertainty identified by the EPA-ORIA (including dosimetry (of which
neutron RBE is a factor), disease detection, disease classification, temporal patterns, and
appropriate RBE values) should also be considered.
By "consider," the RAC means that the EPA-ORIA should attempt to estimate, in a
preliminary fashion, the relative magnitude of the contribution of the additional known sources
of error or uncertainty they identified to the overall uncertainty. Of importance, it is useful to try
to estimate the independent contribution of these additional sources, most of which are likely
partially correlated with those sources identified in BEIR VII. One possible way of estimating
the magnitudes is via some modest simulation studies. Only if the independent contribution of
any of these additional sources of error is potentially significant in magnitude should that source
be included in the uncertainty analysis. In any event, the methods of uncertainty analysis should
follow BEIR VII.
There is some value to producing two sets of uncertainty bounds, one representing the
bounds on the (site-specific) central or point risk estimate for the method of combining the RR
and AR that the EPA finally chooses to use, the other representing combinations ranging from
100% RR through 100% AR. The former gives a measure of the uncertainty of the central risk
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
estimate derived from the method specifically used, and the latter gives an indication of the range
in which the true value (independent of method) likely resides.
In coming to these recommendations, the RAC considered several additional
complications that could influence uncertainty. One such complication arises because the
uncertainties associated with the current risk estimates for radiogenic cancers are smallest for the
doses at which statistically significant increases in cancer mortality or incidence have been
observed in the LSS and other epidemiological studies of exposed populations. However, such
increases have been observed over a limited range of individual doses. At doses below this
range, risk estimates are based, on an assumed LNT dose-response model and method of
extrapolation from higher-dose/higher-response data. This extrapolation may result in the risk
estimates associated with doses in the low-dose range having larger relative uncertainties than
those in the higher dose range.
Having said that, BEIR VII specifically considered adaptive response, genomic
instability, and bystander effects, and concluded that there is insufficient evidence to explicitly
add these effects to the dose-response model. The EPA-ORIA proposes at the present time to
follow BEIR VII and use the LNT combined with the DDREF for calculation of radiation risk.
In the absence of compelling scientific evidence to do otherwise, the RAC endorses the EPA-
ORIA's plan in this regard. The RAC does recommend, however, that the EPA-ORIA include a
(qualitative) discussion of modern cellular and molecular biological concepts in its final report.
As a cautionary note, the RAC recommends that the EPA discuss the application of its LNT risk
estimates in very low dose settings where currently cancer risks are not significantly elevated
above background cancer rates and where the doses are a fraction of the background radiation
exposure.
It is important to note that there is indeed opportunity to include uncertainties in the
model - that is, uncertainties in high-dose versus low dose behavior - in the overall uncertainty
analysis. In BEIR VII and the EPA-ORIA's proposed approach to uncertainty estimation, this
"additional" uncertainty is contained within the uncertainty in the value for DDREF, since
DDREF is only invoked at lower doses. The RAC thus strongly endorses the EPA-ORIA's
intention to include uncertainty in DDREF in the overall uncertainty analysis.
There is also a need to evaluate uncertainty following exposure to high doses delivered at
low dose rates. In addition to the DDREF it may be necessary to have a dose rate effectiveness
factor for high doses delivered at low dose rates. Low dose rate exposure causes minimal life
shortening even when the total doses are very large. The cancer risk estimates derived for acute
exposure even with a DDREF do not result in an accurate prediction of risk to populations
exposed to high doses delivered at a low dose rate.
Uncertainties in the estimates are also a function of time into the future, being smallest in
the near time frame. This is due to several factors, including changes in future (actual)
populations (as opposed to a 'stationary population'), future background cancer incidence, and
future medical advances (since the case fatality rate may decrease as a result of better treatment
interventions in the future). Uncertainties thus become greater as the risk estimates are applied
23
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
1 further into the future. The RAC recommends that EPA-ORIA include a (qualitative) discussion
2 of these concepts in its final report.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
7. RESPONSE TO CHARGE QUESTION 4: ISSUES RELATING TO
RADIOGENIC THRYOID CANCER NOT QUANTIFIED IN BEIR VII
Charge Question 4: In Section VI, the draft White Paper discusses some issues relating to
radiogenic thyroid cancer. Does the RAC have any specific suggestions for dealing with this
risk; e.g., does the RAC have any advice on gender specificity, effectiveness of iodine -131
compared to gamma rays, or estimation of thyroid cancer mortality?
The RAC believes that it is premature to offer any advice to ORIA on this issue. A major
review of radiogenic thyroid cancer is being completed by the National Council on Radiation
Protection and Measurements. This information should be considered by ORIA as more recent
or more relevant data which could improve the risk estimates provided by BEIR VII.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
1
2 8. ISSUES BEYOND THE CHARGE
3
4 The RAC received information from the public on the use of "Reference Man" for setting
5 radiation protection standards. The RAC recommends the EPA consider the concept described
6 in ICRP Publication 89 (ICRP. .2002.). In ICRP 89, this concept has been expanded into what
7 might be thought of as a Reference Family because it contains reference information on persons
8 at ages from newborns to adults and both genders. It also looks at results from studies of Asian
9 reference persons.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
REFERENCES CITED
(Format citation will be finalized in later draft KJK)
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
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of human exposure to ionizing radiation. International Journal of Radiation Biology 82(9): 605-
639, 2006.
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NRC 1999. BEIR VI. Health Effects of Exposure to Radon. National Research Council,
Committee on Health Risks of Exposure to Radon.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
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Radiation effects on breast cancer risk: a pooled analysis of eight cohorts. Radiation Research
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U.S. Environmental Protection Agency (EPA), Office of Air and Radiation (OAR). 1999.
"Federal Guidance Report 13. Cancer Risk Coefficients for Environmental Exposure to
Radionuclides, " Washington, DC (EPA-402-R-99-001),
http://www.epa.gov/radiation/docs/federal/402-r-00-Q01.pdf
U.S. EPA/OAR. 1999. Federal Guidance Report (FGR)-13. Federal Guidance Report 13:
Cancer Risk Coefficients for Environmental Exposure to Radionuclides:
http://epa.gov/radiation/docs/federal/402-r-99-Q01.pdf
U. S. EPA (Environmental Protection Agency) 1999a. Addendum: Uncertainty Analysis:
http://epa.gov/radiation/docs/assessment/402-r-99-0Q3.pdf
U.S. EPA. (Environmental Protection Agency) 1999b. Update to the Federal Guidance Report
No. 13 and CD Supplement: http://epa.gOv/radiation/federal/techdocs.htm#reportl3
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
U.S. EPA SAB. 2002. "PanelFormation Process: Immediate Steps to Improve Policies and
Procedures: An SAB Commentary, " EPA-SAB-EC-COM-02-003, May 17, 2002.
U.S. EPA. 2005a. Guidelines for Carcinogen Risk Assessment, EPA/630/P-03/001F, March 29,
2005
U.S. EPA. 2005b. Supplemental Guidance for Assessing Susceptability from Early-Life Exposure
to Carcinogens. EPA/630/R-03/003F, March29, 2005
U.S. Environmental Protection Agency, Office of Radiation and Indoor Air (ORIA). 2006a
"Modifying EPA Radiation Risk Models based on BEIR VII, " Draft White Paper, Prepared by:
ORIA, U.S. Environmental Protection Agency, August 1, 2006
http: //epa. gov/radi ati on/news/recentadditi ons. htm
U.S. EPA, Office of Radiation and Indoor Air (ORIA). 2006b. Memorandum from Elizabeth A.
Cotsworth, Director, ORIA to Vanessa Vu, Director, Science Advisory Board Staff Office,
entitled "Advisory Review of the Draft White Paper: Modifying EPA Radiation Risk Models
Based on BEIR VII, August 31, 2006
U.S. 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: //newton. nap. edu/catal og/11340. html#toc
Wakeford R, Little MP. .2003. Risk coefficients for childhood cancer after intrauterine
irradiation: a review. Int JRadiat Biol. May;79(5):293-309, 2003.
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Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
Web-based Citations and Hotlinks
U. S. EPA (Environmental Protection Agency). 1994. Estimating Radiogenic Cancer Risks
("Blue Book"): http://epa.gov/radiation/docs/assessment/402-r-93-076.pdf
U. S. EPA (Environmental Protection Agency) 1999a. Addendum: Uncertainty Analysis:
http://epa.gov/radiation/docs/assessment/402-r-99-0Q3.pdf
U.S. EPA. (Environmental Protection Agency) 1999b. Update to the Federal Guidance Report
No. 13 and CD Supplement: http://epa.gOv/radiation/federal/techdocs.htm#reportl3
FGR-13. Federal Guidance Report 13: Cancer Risk Coefficients for Environmental Exposure to
Radionuclides:
http://epa.gov/radiation/docs/federal/402-r-99-Q01.pdf
U.S. 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: //newton. nap. edu/catal og/11340. html#toc
U.S. EPA. 2006. Office of Radiation and Indoor Air (ORIA), Draft White Paper: Modifying EPA
Radiation Risk Models Based on BEIR VII, August 1, 2006
http: //epa. gov/radi ati on/news/recentadditi ons. htm
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
APPENDIX A -ON-GOING RESEARCH AND PARADIGMS
ASSOCIATED WITH BIOLOGICAL RESPONSES TO LOW DOSES OF
RADIATION
According to the BEIR VII report, "Atomic bomb data for solid tumors combined
provide statistical evidence of a radiation-associated excess at doses down to around 100 mSv;
these combined data are well described by a linear no-threshold dose-response, although some
low dose nonlinearity is not excluded (US NAS/NRC. 2006. BEIR VII, p. 245)." "It is
abundantly clear that direct epidemiological and animal approaches to low dose cancer risk are
intrinsically limited in their capacity to define possible curvilinearity or dose thresholds for risk
in the range of 0-100 mSv. For this reason the present report has placed much emphasis on the
mechanistic data that can underpin such judgments (US NAS/NRC. 2006. BEIR VII, p.245)."
The uncertainty associated with the use of the epidemiological data to estimate risk in the
low dose range has been covered in detail in Charge Question 3: Uncertainties not Quantified in
BEIR VII. An additional source of uncertainty in risk estimates is associated with the
mechanistic biophysical model that is used in BEIR VII to support the LNT in the low dose
region. Although the BEIR VII committee conducted an extensive review of the cell and
molecular literature relative to biological responses at low doses and discussed the recent
advances, they concluded that the mechanistic cell and molecular biological research supported
the current biophysical model that they use (US NAS/NRC. 2006. BEIR VII, pp. 63-64).
However, the rapid increase in information on the biological responses to low doses of radiation
suggest new paradigms in radiation biology (Brooks 2005) that may modify the biophysical
model used in the BEIR VII report.
BEIR VII uses a biophysical model that suggests that each and every ionization increases
the probability of a DNA breakage (Burma et al. 2001) and that this results in a linear increase in
the risk for mutations and therefore in the risk for cancer (US NAS/NRC. 2006. BEIR VII, pp.
10-11). This model assumes independent action of cells and a lack of cell communication. The
model suggests that there is no change in response as a function of previous radiation exposure
and that there is a linear link between unrepaired DNA damage, rare mutational events and the
development of cancer. Recent research has been conducted to provide a solid data base on the
response of molecules, cells, tissues and organisms to very low doses and dose rates of radiation
(Ko et al. .2004.; Azzam and Little .2004.; Little .2006.; Brooks .2005.; Mitchel et al. .2004.).
This research has suggested that several of the assumptions used in the BEIR VII biophysical
model may no longer be valid (Tubiana 2005). The data base that questions the assumptions
used by BEIR VII include information on dose dependent changes in gene expression, radiation
induced changes in redox status of the cells, apoptosis, bystander effects, adaptive responses, and
genomic instability (Spitz et al. .2004; Di Masi et al. .2006.; Coleman et al. .2005.; Azzam and
Little .2004.; Little .2006.; Brooks .2004.). The BEIR VII report has discussed each of these
effects and concluded that until molecular mechanisms of action involved in the induction of low
dose biological effects are elucidated, they cannot be utilized in modification of dose-response
relationships. This appendix provides a brief review on the mechanistic research being
conducted and to suggest the need for continuously updating the biophysical model used to
support the estimates of radiation risk following low dose radiation exposure.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
It is well known that cells communicate by a variety of direct and indirect mechanisms.
Many new radio-biological observations indicate that cells do not respond to radiation
independently. This communication results in modification of responses to low dose and dose
rate radiation.
Using recently developed microbeams and other technology to expose individual cells
and study the response of the "hit" cells and the response of neighboring cells demonstrated the
presence of "bystander effects." These effects demonstrate that a cell traversed by an alpha
particle or "hit" by a focused low LET beam communicate with neighboring cells and can
produce changes in "non-hit" cells. These changes have been shown to be both "harmful" and
"protective" and are most marked following exposure to high-LET radiation (Little 2006.).
Bystander effects impact the current use of "hit-theory" in defining radiation risk since the
radiation target is much larger than the individual cell. The research demonstrates that cells
communicate within each tissue making the assumption of independence of action of individual
cells used in the BEIR VII biophysical model inappropriate. Since non-hit cells show biological
responses, it may not be appropriate to calculate radiation dose to individual cells or cell types in
tissues. (US NAS/NRC. 2006. BEIR VII page 54) Bystander effects also make it more difficult
to define the biological target for the interaction of radiation with cells and the induction of
cancer. The data suggest that tissues and organs respond as a whole and that the biological
response is related to the dose to the whole organ/tissue which is the metric used by BEIR VII in
all the human studies rather than to the dose to individual cells (Barcellos-Hoff and Brooks
.2001.).
It has been demonstrated that following exposures to low doses of radiation there are
unique dose-dependent changes in gene and protein expression which were not recognized or
identified when the BEIR VII biophysical models were developed (Ding et al. 2005.; Coleman
and Wyrobek 2006.; Marchetti et al. 2006.). Low dose activation of such mechanisms supports
the existence of non-linear dose-response relationships for low-LET radiation. Identification of
these genes is providing a scientific basis for defining metabolic pathways activated by radiation
and determining mechanisms of action.
Previous radiation exposure can alter the response producing diminished biological
effects. This is called the "adaptive response". Two different types of adaptive responses have
been identified (Azzam and Little 2004.). The first is where low doses of radiation decrease the
amount of damage observed relative to background levels (Ko et al. 2006.). The second is where
a small "priming dose" of radiation given before a high acute "challenge dose" results in a
decreased response relative to the high dose alone (Olivieri et al .1984.). The ability to produce
an adaptive response is dependent on genetic background of the cells. Different sets of genes
are up and down regulated in cells capable of adaptation compared to cells that cannot adapt to
radiation exposure. Cells and tissues that demonstrate an adaptive response following low dose
exposures have repair and stress genes up regulated (Coleman et al. 2005.).
Research has been conducted to understand cell/cell and cell/tissue interactions and how
they modify cancer frequency (Barcellos-Hoff 2005.). Tissue interactions have been shown to
modify the expression of cellular and molecular damage and to be critical in the expression of
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
cancer. There is evidence that under certain experimental conditions, radiation damage can be
modified in vitro (Kennedy et al. 2006). Also administration of stable iodine considerably later
than the period normally prescribed to block exposure to radioactive iodine was unexpectedly
associated with a decreased risk of thyroid cancer incidence among a population at risk of
exposure as a result of the Chernobyl accident. The authors suggested that this finding may be
related to a modification of radiation-induced cellular or molecular damage in the presence of
stable iodine (Cardis et al. 2005). Data from this research verified that the initial DNA damage
increases linearly with radiation dose, that DNA damage triggers many molecular responses and
that even the initial DNA damage and repair is modified by radiation type, dose and dose-rate
(Ishizaki et al. 2004.). Importantly, it has shown that biological repair of this damage as well as
the other cellular and organ responses are very non-linear over the low dose region. These new
findings may have significance in quantifying the safety margins associated with regulatory
standards.
Genomic instability suggests that, in addition to rare mutational events, frequent
radiation-induced changes following exposure may play an important role in cancer induction.
Radiation-induced genomic instability is seen at a high frequency in cells many cell divisions
after the radiation exposure (Morgan 2003.; Ponnaiya et al. 1997.). The instability results in
increased frequency of mutations, chromosome aberrations, and cell killing. Radiation-induced
genomic instability seems to be one of the early stages in the carcinogenesis process and has
been seen both in vitro and in vivo. These observations challenge the relative importance that
initial mutations play in radiation-induced cancer (Kadhim et al. 2004.). The BEIR VII
biophysical model suggests that since DNA damage increases as a linear function of acute
radiation dose that there must be a linear increase in cancer risk (page reference). Genomic
instability and the ability to modify responses after the radiation exposure both challenge the
linear relationship between initial DNA damage and cancer frequency.
The magnitude of the response for all of these phenomena has been shown to be
dependent on the genetic background of the cells, tissues and organisms in which they are being
measured (Coleman et al. 2005.; Ponnaiya et al. 1997.; Azzam and Little 2004.; Little 2006.). A
better definition of the range of inter-individual variability and the development of analytical
methods and tools may make it possible to identify individuals that are either sensitive or
resistant to either the early or late effects of radiation or both. However, currently it is not
possible to identify either radiation resistant or radiation sensitive individuals, or to use this
information in a regulatory framework.
These recent advances provide a scientific basis for the observed non-linear dose-
response relationships seen in many biological systems (US NAS/NRC. 2006. BEIR VII; Ko et
al. 2006.; Mitchel et al. 2004.). They suggest that the mechanism of action of radiation-induced
damage is different following exposure to high doses than it is after low radiation doses. It
becomes important to consider new paradigms associated with the biological responses to low
doses of radiation and to modify and further develop the models used to support the
extrapolation of dose-response relationships into dose regions where it is not possible to measure
changes in radiation-induced cancer incidence/mortality in human populations.
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
APPENDIX B - BIOSKETCHES
U.S. ENVIRONMENTAL PROTECTION AGENCY
SCIENCE ADVISORY BOARD
RADIATION ADVISORY COMMITTEE (RAC)
(To be Added in Quality Review Draft)
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
APPENDIX C-ACRONYMS
A-Bomb
Atomic Bomb
AM
Arithmetic Mean
AR
Absolute Risk
BCC
Basal Cell Carcinoma
BEIR
Biological Effects of Ionizing Radiation
BEIR VII
Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII
Phase 2
CDC
Centers for Disease Control and Prevention
CFR
Code of Federal Regulations
Co
Chemical symbol for cobalt (60Co isotope)
DDREF
Dose and Dose-Rate Effectiveness Factor
DFO
Designated Federal Officer
DNA
Deoxyribonucleic Acid
EAR
Excess Absolute Risk
EPA
Environmental Protection Agency (U.S. EPA)
ERR
Excess Relative Risk
FR
Federal Register
FGR-13
Federal Guidance Report 13
GM
Geometric Mean
GMC
Geometric Mean Coefficient
GSD
Geometric Standard Deviation
Gy
gray
H
Chemical symbol for Hydrogen (3H isotope)
I
Chemical symbol for Iodine (131I isotope)
ICRP
International Commission on Radiological Protection
ICRU
International Commission on Radiation Units and Measurements, Inc.
IREP
Interactive RadioEpidemiological Program
keV
kiloelectron Volts
LAR
Lifetime Attributible Risk
LET
Linear Energy Transfer
LNT
Linear Non Threshold
LSS
Life Span Study
mSv
milli-Sievert
NAS
National Academy of Sciences (U.S. NAS)
NCHS
National Center for Health Statistics
NCI
National Cancer Institute
NCRP
National Council on Radiation Protection and Measurements
NIH
National Institutes of Health
NIOSH
National Institute for Occupational Safety and Health
NMSC
Non-Melanoma Skin Cancer
NRC
National Research Council
OAR
Office of Air and Radiation (U.S. EPA/OAR)
ORIA
Office of Radiation and Indoor Air (U.S. EPA/OAR/ORIA)
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SAB Working Review Draft Advisory dated February 23, 2007 for Radiation Advisory Committee Edits - Do Not Cite or
Quote. This review draft is a work in progress, does not reflect consensus advice or recommendations, has not been
reviewed or approved by the Science Advisory Board's Charter Board, and does not represent EPA policy.
PAG
Protective Action Guide
Pu
Chemical symbol for Plutonium (239Pu Isotope)
QA
Quality Assurance
QC
Quality Control
QA/QC
Quality Assurance/Quality Control
R
roentgen
Ra
Chemical symbol for Radium (Isotopes include 224Ra, 226Ra, 228Ra, and 236Ra)
RAC
Radiation Advisory Committee (U.S. EPA/SAB/RAC)
rad
Traditional unit of radiation absorbed dose in tissue (a dose of 100 rad is
equivalent to 1 gray (Gy) in SI units)
RBE
Relative Biological Effectiveness
RBEm
Maximum Relative Biological Effectiveness
REF
Radiation Effectiveness Factor
rem
Radiation equivalent in man; traditional unit of effective dose equivalent (equals
rad x tissue weighting factor) (100 rem is equivalent to 1 Sievert (Sv))
RERF
Radiation Effects Research Foundation
R/h
Roentgen per hour; traditional measure of exposure rate
Rn
Chemical symbol for Radon (222Rn Isotope)
RR
Relative Risk
SAB
Science Advisory Board (U.S. EPA/SAB)
see
Squamous Cell Carcinoma
SEER
Surveillance, Epidemiology, and End Results
SI
International System of Units (from NIST, as defined by the General Conference
of Weights & Measures in 1960)
Sr
Chemical Symbol for Strontium (90Sr Isotope)
Sv
sievert, SI unit of effective dose equivalent in man (1 Sv is equivalent tolOO rem
in traditional units)
Th
Thorotrast (232Th Isotope)
UNSCEAR
United Nations Scientific Committee on the Effects of Atomic Radiation
US
United States
WLM
Working Level Months
End of Document
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