# F 

# E 

# o TL 

# Lu E J 

# C)

I 

# z I 

# o lU 

# F Defense

Threat Reduction

Agency 8725 John J. Kingman

Road, MSC 6201 Fort Belvoir.

VA 22060-6201

DTRA-TR.O74 

# Screening

Doses for Induction

of Cancers Calculated

with the Interactive

RadioEpidemiological Program (IREP)

Approved

for public release;

distribution

is unlimited.



## March 2007

DTRA01-03-C-0064

David C. Kocher

and Julian A. Apostoaei Prepared

by:
SENES Oak Ridge,

lnc. 102 Donner Drive Oak Ridge,

TN 37830 

# WSTANDARD FORM 298 (Rev. 8/98) Form Approved 

### REPORT DOCUMENTATION PAGE OMB No. 0704-0188
Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Service, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Manag ent and Budget, em PLEASE DO NOT RETURN YOUR ORM TO THE ABOVE DDRESS. Paperwork Reduction Project (0704-0188) Washington, DC 20503. F A 1. REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE Technical Report 3. DATES COVERED (From - To) 31-03-2007
5a. CONTRACT NUMBER DTRA01-03-C-0064

5b. GRANT NUMBER 4. TITLE AND SUBTITLE Screening Doses for Induction of Cancers Calculated with the Interactive RadioEpidemiological Program (IREP)

5c. PROGRAM ELEMENT NUMBER 139D

5d. PROJECT NUMBER CS 6. AUTHOR(S)

5e. TASK NUMBER AH Kocher, David C. and Apostoaei, A. Iulian

5f. WORK UNIT NUMBER DH11146
7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER SENES Oak Ridge, Inc. DTRA-TR-07-4 102 Donner Drive Oak Ridge, TN 37830

10. SPONSOR/MONITOR'S ACRONYM(S) DTRA RD-NTSN 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) Defense Threat Reduction Agency Nuclear Technologies Directorate 8725 John J. Kingman Road, Stop 6201 Fort Belvoir, VA 22060-6201 11. SPONSORING/MONITORING AGENCY REPORT NUMBER DTRA-TR-07-4

12. DISTRIBUTION AVAILABILITY STATEMENT Approved for public release; distribution is unlimited.

13. SUPPLEMENTARY NOTES This work was sponsored by the Defense Threat Reduction Agency under RDT&E RMSS Code B 139D D K113 CS AH 111 46 25 04D. 9
14. ABSTRACT This report presents tabulations of equivalent doses of i onizing radiation, referred to as screening doses, that correspond to an estimated probability of causation of sp ecific cancers of approximately 50% at the upper 99% credibility limit. Screening doses for 32 cancer types were calculated with the Interactive RadioEpidemiological Program, which is used by the Department of Veterans Affa irs in adjudicating claims for compensation for cancer by veterans of military services.

15. SUBJECT TERMS Nuclear Test Personnel Review, NTPR, Veteran, Atmosp heric Nuclear Testing, Hiroshima Nagasaki Occupation, Cancer, Probability of Causation, PC, IREP

16. SECURITY CLASSIFICATION OF: 19a. NAME OF RESPONSIBLE PERSON Dr. Paul K. Blake 17. IMITATION OF BSTRACT

L A UU 18. NUMBER OF PAGES 83 a. EPORT

R U b. A TRACT

BS U c. THIS P E 19b. TELEPONE UMBER ( Include area code) N 703 767-2407 AG Uiii ABSTRACT

This report presents tabulations of equivalent doses of ionizing radi ation, referred to as screening doses, that correspond to an estimated probability of causation (PC) of specific cancers of approximately 50% at the upper 99% credib ility limit. A PC of 50% at the upper 99% credibility limit is often used in evaluating whethe r it is at least as lik ely as not that a given cancer in an individual was caused by exposure to ionizing radiation for purposes of adjudicating claims for compensation. Screening doses fo r 32 cancer types were calculated with the Interactive RadioEpidemiological Program (IREP), which is used by the Department of Veterans Affairs (VA) in adjudicating claims for compensation for cancer by veterans of military services. Screening doses calculated with IREP take into account uncertainties in estimating cancer risk and PC associated with given e quivalent doses to organs or ti ssues in which cancers occur. Except for cancers that occur only in females a nd breast cancer in females, tabulated screening doses apply to males. Screening doses for most cancer types depend on an individual’s age at exposure and age at the time of diagnosis of cance r. Screening doses for lung cancer also depend on an individual’s smoking history, and screen ing doses for skin cancers depend on an individual’s race or ethnicity. Screening doses calculated with IREP are compared with screening doses for a limited number of cancer types calculated previously by the Committee on Interagency Radiation Research and Policy Coor dination (CIRRPC), which were used by VA for many years in adjudicating claims for compensati on. Screening doses calcu lated with IREP are higher than the corresponding values obtained from the CIRRPC table for most combinations of cancer type, age at exposure, and age at diagnosi s. An analysis of the accuracy of screening
doses calculated with IREP and ta bulated in this report indicate s that they could differ from equivalent doses that correspond to an upper 99% credibility limit of PC of exactly 50% by less than ±10% for most cancer types, ages at expos ure, and ages at diagnosis of concern in VA radiation claims. Inaccuracies in screening doses are due to the randomness of statistical sampling in the method of uncerta inty analysis used in IREP.iv TABLE OF CONTENTS

ABSTRACT....................................................................................................................... ............ iii

LIST OF TABLES................................................................................................................. ..........v

LIST OF FIGURES ................................................................................................................ ..... viii

1. INTRODUCTION ............................................................................................................... .......1

2. APPROACHES TO EVALUATI NG CAUSATION OF CANCERS .......................................4 2.1 Description and Estimation of Probability of Causation ..............................................4 2.2 Evaluation of Causation of Cancers Using CIRRPC Table..........................................6 2.3 Evaluation of Causation of Cancers Using IREP .........................................................7

3. CANCER RISK MODELS INCORPORATED IN IREP........................................................11 3.1 Categories of Cancer Risk Models .............................................................................11 3.1.1 Group 1 Cancers ........................................................................................12 3.1.2 Group 2 Cancers ........................................................................................12 3.1.3 Group 3 Cancers ........................................................................................13 3.1.4 Risk Models for Lung Cancer ....................................................................13 3.1.5 Group 4 Cancers ........................................................................................14 3.2 Minimum Latency Period fo r Different Cancer Types...............................................15

4. SCREENING DOSES CA LCULATED WITH IREP..............................................................19 4.1 Tabulation and Discussion of Screening Doses..........................................................19 4.1.1 Calculation of Screening Doses .................................................................19 4.1.2 Accuracy of Calculated Screening Doses ..................................................21 4.1.3 Discussion of Screening Doses ..................................................................25 4.2 Comparison with Screening Doses in CIRRPC Table................................................27 4.3 Application of Screening Doses..................................................................................29 4.3.1 Exposure to Multiple Radiation Types .......................................................29 4.3.2 Exposures in More Than One Year ............................................................31 4.4 Summary Discussion of Ca lculated Screening Doses ................................................33

REFERENCES ..................................................................................................................... .........71

DISTRIBUTION LIST......................................................................................73v LIST OF TABLES

Table 2-1. Screening doses (rem) for specific cancer types calculate d by CIRRPC (1988) and used by VA in adjudicating claims for co mpensation for radiation-induced cancer...........9
Table 3-1. Categories of cancer risk models incorporated in IREP..............................................17
Table 4-1. Screening doses (rem) calculated wi th IREP: Cancers of oral cavity and pharynx (including lip)................................................................................................................ .....35
Table 4-2. Screening doses (rem) calcula ted with IREP: Cancer of esophagus...........................36
Table 4-3. Screening doses (rem) calcu lated with IREP: Cancer of stomach ..............................37
Table 4-4. Screening doses (rem) calcu lated with IREP: Cancer of colon...................................38
Table 4-5. Screening doses (rem) calculated with IREP: Cancer of rectum (including anus and anal canal) ............................................................................................................... ....39
Table 4-6. Screening doses (rem) calculated wi th IREP: Cancers of digestive tract other than stomach, colon, and rectum........................................................................................40
Table 4-7. Screening doses (rem) calculated wi th IREP: Cancer of liv er (including biliary system) ....................................................................................................................... ........41
Table 4-8. Screening doses (rem) calculated with IREP: Cancer of gallbladder (including bile ducts)................................................................................................................... ........42
Table 4-9. Screening doses (rem) calcula ted with IREP: Cancer of pancreas..............................43
Table 4-10. Screening doses (rem) calculated wi th IREP: Cancer of lung (including trachea and bronchus) – I ............................................................................................................. ..44
Table 4-11. Screening doses (rem) calculated wi th IREP: Cancer of lung (including trachea and bronchus) – II ............................................................................................................ ..45
Table 4-12. Screening doses (rem) calculated wi th IREP: Cancers of re spiratory tract other than lung..................................................................................................................... ........46
Table 4-13. Screening doses (rem) cal culated with IREP: Cancer of bone..................................47vi LIST OF TABLES (continued)

Table 4-14. Screening doses (rem) calculate d with IREP: Cancers of connective tissue (including soft tissue not listed).........................................................................................48
Table 4-15. Screening doses (rem) calculated with IREP: Malignant melanoma of skin ............49
Table 4-16. Screening doses (rem) calculated with IREP: Basal cell carcinoma of skin.............50
Table 4-17. Screening doses (rem) calculated with IREP: Squamous cell carcinoma of skin .....51
Table 4-18. Screening doses (rem) calculated with IREP: Cancer of breast (female) .................52
Table 4-19. Screening doses (rem) calculate d with IREP: Cancer of breast (male).....................53
Table 4-20. Screening doses (rem) calcu lated with IREP: Cancer of ovary ................................54
Table 4-21. Screening doses (rem) calculated wi th IREP: Cancers of all female genitalia other than ovary .............................................................................................................. ...55
Table 4-22. Screening doses (rem) calculated with IREP: Cancers of all male genitalia (including prostate) .......................................................................................................... ..56
Table 4-23. Screening doses (rem) calcula ted with IREP: Cancer of bladder..............................57
Table 4-24. Screening doses (rem) calculated with IREP: Cancers of kidney and other urinary organs except bladder............................................................................................58
Table 4-25. Screening doses (rem) calcu lated with IREP: Cancer of eye....................................59
Table 4-26. Screening doses (rem) calculate d with IREP: Cancers of nervous system (including brain)............................................................................................................. ....60
Table 4-27. Screening doses (rem) calcula ted with IREP: Cancer of thyroid..............................61
Table 4-28. Screening doses (rem) calculated with IREP: Cancers of endocrine glands other than thyroid............................................................................................................ ...62
Table 4-29. Screening doses (rem) calculated wi th IREP: Cancers of other and ill-defined sites ......................................................................................................................... ...........63vii LIST OF TABLES (continued)

Table 4-30. Screening doses (rem) calcula ted with IREP: Lymphoma and multiple myeloma....................................................................................................................... ......64
Table 4-31. Screening doses (rem) calculate d with IREP: All leukemia excluding chronic lymphocytic leukemia (CLL).............................................................................................65
Table 4-32. Screening doses (rem) calcula ted with IREP: Chronic myeloid leukemia (CML) ......................................................................................................................... .......66
Table 4-33. Screening doses (rem) calculate d with IREP: Acute lymphocytic leukemia (ALL) ......................................................................................................................... ........67
Table 4-34. Screening doses (rem) calculated with IREP: Acute myeloid leukemia (AML) ......68
Table 4-35. Lowest screening doses (rem) for any age at exposure and time since exposure when cancer is diagnosed for all cancer types calcul ated with IREP................................69viii LIST OF FIGURES

Figure 3-1. S-shaped (sigmoid) function assume d in IREP to represen t effect of minimum latency period on reducing risks of all solid cancers except thyroi d and bone cancer at early times since exposure and its uncertainty...................................................................181 1. INTRODUCTION

The Department of Veterans Affairs (VA) is responsible for adjudicating claims for compensation for cancers that occur in veterans of military services who were exposed to ionizing radiation. 1 In some cases, adjudication of a claim takes into account estimates of radiation dose to an organ or tissue in which a cancer occurred that are developed by the Defense Threat Reduction Agency (DTRA). In all su ch cases, VA uses estimated upper bounds of equivalent doses 2 provided by DTRA and other informa tion to develop a medical opinion on whether a veteran’s cancer was caused by ionizing radiation. Upper bounds of equivalent doses are intended to be at least uppe r 95% credibility limits when uncertainties in estimating equivalent doses to an organ or tissue of con cern are taken into account . Compensation usually
is awarded if VA concludes that it is at least as likely as not that a veteran’s cancer was caused by radiation (i.e., the probability is at least 50%). VA gives clai mants the benefit of the doubt by interpreting “at least as likely as not” to mean that the probability of causation (PC) should be at least 50% at the upper 99% credibility limit when uncertainties in estimating cancer risk and PC associated with upper-bound estimates of equiva lent doses are taken in to account. Thus, VA usually awards compensation when there is at leas t a 1% chance that PC is 50% or greater. An upper 99% credibility limit of PC of at least 50% also is used in evaluating causation of cancers in the Department of Labor’s compensation pr ogram for workers at Department of Energy facilities (EEOICPA 2000; DHHS 2002). The most common circumstance that require s VA to use estimates of radiation dose provided by DTRA in adjudicating claims for compensation involve s cancers that ar e not one of

1 Radiation-exposed veterans of concern to this report are specified in VA regulations [38 CFR 3.309(d)(3)]. They include participants in the atmospheric nuclear-weapons testing program between 1945 and 1962 and occupation forces or prisoners of war in Hiroshima or Nagasaki, Japan, after the atomic bombings in 1945. Diseases other than can cer that could be caused by exposure to ionizing radiation (e.g., cataract of the lens of the eye) are not considered in this report.

2 As defined by the International Commission on Ra diological Protection (ICRP 1991), equivalent dose is an average absorbed dose to an organ or tissue of concern modified by a prescribed radiation weighting factor ( w R ) for the radiation type that delivers the dose. Equivalent dose was previously called “dose equivalent” by DTRA.2 21 cancers that are specified as “presumptive” diseases in VA regul ations [38 CFR 3.309(d)(2)]. A presumptive disease is assumed to be service- connected, without regard for the dose received, if adequate proof of particip ation in a radiation-risk activ ity is provided. Claims for compensation for cancers that are not presumptiv e diseases are adjudicated under VA regulations for “nonpresumptive” diseases [ 38 CFR 3.311]. In all such cases, VA uses estimated upper bounds of equivalent doses provided by DTRA in developing a medical opinion on whether it is at least as likely as not that a veteran’s cancer was caused by radiation. 3 Skin and prostate cancer are the most common nonpresumptive cancers in claims of concern to this report. VA currently uses computer software cal led the Interactive RadioEpidemiological Program (IREP) (Land et al. 2003; NIOSH 2002) wh en it is necessary to evaluate whether a veteran’s cancer was caused by exposure to ioni zing radiation (Mansfield 2005). VA uses IREP to calculate a probability distribution of PC associated with a veteran’s upper-bound estimates of equivalent doses, ages at times of exposure, and age at the time of diagnosis of cancer. Probability distributions of PC calculated by IREP take into acc ount uncertainties in estimating
an individual’s risk of cancer due to radiation exposure and as sociated PC. VA then compares the upper 99% credibility limit of the probability distributi on of PC with the value 50% in evaluating whether it is at least as likely as not that the vetera n’s cancer was cause d by radiation. VA’s current policy of using an upper 99% cred ibility limit of PC calculated with IREP in evaluating causation of cancers superseded a policy adopted in the late 1980s of using a table of equivalent doses that also corresponded to an estimated upper 99% cred ibility limit of PC of 50% for a limited number of cancer types. That table was deve loped by the Committee on Interagency Radiation Research and Policy Coor dination (CIRRPC 1988) on the basis of data on
risks of cancers that were considered to be radi ogenic at the time (NIH 1985). Equivalent doses in the CIRRPC table were referred to as “screening doses,” and the same terminology is used in this report to denote equivalent doses that correspond to an esti mated upper 99% credibility limit

3 In other, less common circumstances, VA is required to use estimates of radiation dose in adjudicating claims for compensation for any of the 21 cancers that are presumptive diseases. Estimates of dose must be used if adequate proof of participa tion in a radiation-risk activity while in service is not available, or if a claimant is seeking compensation to cover a time period prior to the time the veteran’s cancer was declared to be presumptive in VA regulations . In all such cases, a claim is adjudicated under the regulations for nonpresumptive diseases.3 of PC of approximately 50%. For more than a year prior to adopting a policy of using IREP exclusively, VA evaluated causation of cancers usi ng the CIRRPC table and IREP in parallel
when a cancer of concern was included in the CI RRPC table. In all such cases, the method that
was more favorable to the claimant was used in adjudicating a cl aim (VHA/OPHEH 2003; Mather and Otchin 2004). The primary purpose of this report is to pr esent tabulations of sc reening doses for many cancer types that we calculated with IREP. Agai n, a screening dose is an equivalent dose that corresponds to an estimated uppe r 99% credibility lim it of PC of approximately 50% when uncertainties in estimating cancer risk and PC asso ciated with given equivalent doses to an organ
or tissue in which a cancer occurred are taken in to account. Screening doses calculated with IREP also are compared with screening doses for the limited number of can cer types given in the CIRRPC table, as used previously by VA. The following section describes how PC is estimated, and it discusses VA’s use of the
CIRRPC table and IREP to evaluate causation of cancers on the basis of es timates of equivalent dose to an organ or tissue in which a cancer occu rred. Section 3 describes models incorporated
in IREP to estimate risks of different cancer t ypes due to exposure to ionizing radiation.
Information on risk models is intended to be helpful in understandi ng how screening doses calculated with IREP depend on an individual’s age at exposure a nd age at the time of diagnosis of cancer. Section 4 describes the assumptions us ed to calculate screening doses and presents
tabulations and discussions of sc reening doses, as well as compar isons with screening doses in the CIRRPC table. An evaluation of the accuracy of screening doses tabulated in this report also is presented. This evaluation is based on the consideration that screening doses calculated with IREP generally do not correspond to an upper 99% cred ibility limit of PC of exactly 50%. Inaccuracies in screening doses calculated with IREP are due to the randomness of statistical sampling in the method used to estimate uncertainty in cancer risk and PC.4 2. APPROACHES TO EVALUA TING CAUSATION OF CANCERS

This section presents an overview of appr oaches to evaluating causation of cancers in individuals who were exposed to ionizing radiation. Section 2.1 describes how PC is estimated and how PC depends on dose. Sections 2.2 a nd 2.3 discuss the two approaches (i.e., the CIRRPC table and IREP) that have been used by VA in evaluating causation of cancers in veterans who were exposed to radiation.

2.1 Description and Estimation of Probability of Causation

The term “probability of causation” refers to the probability that a diagnosed cancer in an individual was caused by prior exposure to ionizing radiation. 4 PC is defined as:

B R R PC + = , (1)

where R is the risk (probability ) of the cancer of concern due to radiation exposure and B is the baseline (background) risk of that cancer due to all other causes . Risks of most cancers due to radiation exposure are assumed to depend on sex, age at exposure, and attained age (age at a given time); baseline risks generally depend on se x and attained age. Although PC is related to risk and is also a probability, there is an essential difference: whereas risk is the probability that a
radiation-induced cancer will occur at some time afte r an exposure in an individual who is free of that cancer, PC is conditiona l on the occurrence of cancer. In IREP, PC is calculated on the basis of an estimate of the excess relative risk (ERR) associated with a given radiation dose to an organ or tissue in which a cancer occurred (Land et al. 2003). ERR is calculated as:

4 PC is referred to as “assigned share” by Land et al . (2003) to indicate that it is calculated on the basis of estimates of cancer risks obtained in epidemiological studies of exposed populations. Thus, PC is a property of a group to which an individual belongs that is assigned to that individual; it may not be the true PC for that individual.5 ERR = RR – 1 , (2)

where RR is the relative risk, defi ned as the risk in an exposed popul ation relative to the risk in a similar unexposed population, given by:

R B R RR +

= , (3)

Thus, using the definition in eq. (1) and the relations in eqs. (2 ) and (3), PC is estimated as:

1 ERR

ERR PC + = . (4)

Although PC is a probability and, thus, has a valu e between 0 and 1, we express PC in percent (e.g., a PC of 0.5 is expressed as 50%) to be consistent w ith output from IREP. For any cancer type, ERR is assumed to be an increasing functi on of dose, without threshold. Risk models for all cancer types incorporated in IREP, except for leukemia under conditions of acute exposure to low-LET radiations (photons or electrons), assume that ERR is a linear function of dose (Land et al. 2003). Thus, in most cases, PC is estimated as:

1 ) α ( α PC + × ×

= D D , (5)

where α is the ERR per unit equivalent dos e for a cancer type of concern and D is the equivalent dose to the organ or tissue where that cancer occurs. Risk models for all types of leukemia under conditions of acute exposure to low-LET radia tions assume that ERR is a linear-quadratic function of dose given by α ( D + D 2 ) (Land et al. 2003), and PC in these cases is estimated as:

1 )] ( α [( ) ( α PC 2 2

+ + × +

×

= D D D

D . (6)6 Thus, for any cancer type, PC is a nonlinear f unction of dose, and the dose corresponding to a given PC increases nonlinearly as the risk, R, and ERR associat ed with radiation exposure decrease, and vice versa.

2.2 Evaluation of Causation of Cancers Using CIRRPC Table

From the late 1980s until April 2005, VA evaluated causation of some cancers in veterans who were exposed to ionizing radiati on using a table of scr eening doses that was developed by CIRRPC (1988); the CIRRPC table of screening doses, which correspond to an estimated upper 99% credibility limit of PC of 50%, is reproduced in Table 2-1. If an estimated upper bound of the total equivalent dose to an or gan or tissue in which a cancer occurred, as provided by DTRA, equaled or ex ceeded the screening dose obtained from the CIRRPC table that applied to the veteran of concern, VA usually rendered a favorable medical opinion. 5 Screening doses in the CIRRPC table were calculat ed on the basis of estimat es of PC at various equivalent doses obtained from the 1985 Radioepidemiological Tables (NIH 1985) 6 and estimates of uncertainty in cancer risks associated with given equivalent doses in each organ or tissue of concern (CIRRPC 1988). Cancer types for which screening doses were given in the
CIRRPC table are those that were considered to be radiogenic on the ba sis of a statistically significant dose-response in Japanese atomic- bomb survivors and other study populations (NIH 1985). It should be noted that VA did not actua lly estimate PC when screening doses obtained from the CIRRPC table were used in evaluating causation of cancer.

5 Comparison of an estimated upper bound of the total equivalent dose with the applicable screening dose obtained from the CIRRPC table was not th e only factor that could be considered by VA in formulating a medical opinion on causation of a veteran’s cancer. For example, information on a veteran’s history of exposure to ionizing radia tion and other carcinogens at times other than during participation in a radiation-risk activity also could be considered. Similar c onsiderations apply to VA’s use of IREP. However, VA has rarely based its medical opinions on causation of cancer on factors other than screening doses obtained from Table 2-1 or est imates of upper 99% credibility limits of PC calculated with IREP (N. Otchin, Department of Veterans Affairs, personal communication).

6 The 1985 Radioepidemiological Tables were based on cancer risk models that were developed in the BEIR III report (NRC, 1980) on the basis of data obtained from studies of Japanese atomic-bomb survivors and medical patients who had been exposed mainly to x rays or high-energy gamma rays.7 The following points about screening doses in th e CIRRPC table are of interest. First, for all cancer types considered, sc reening doses increased with in creasing age at exposure from age 20 to 40 and remained constant thereafter. Those increases were based on data which
indicated that risks due to radi ation exposure rela tive to baseline risks d eclined with increasing age at exposure (NRC 1980). Second, for all cancer types except leukemia, screening doses were independent of the time since exposure when cancer was diagnosed, provided the time between exposure and diagnosis exceeded an assumed minimum latenc y period. Finally, screening doses for the various types of leukemia were higher at times since exposure when cancer was diagnosed of 20 years or more than at times between exposure and diagnosis less than 20 years. The assumed dependencies on time since exposure were based on data which
indicated that risks of radiation-induced leukemia declined n early to baseline levels at times beyond a few decades after exposure (NRC 1980).
The CIRRPC table did not incl ude screening doses for some cancer types for which an estimate of radiation dose was required in adju dicating claims for comp ensation. Important examples include skin and prostate cancer. Prior to 2003, VA formulated a medical opinion on
causation of such cancers on the basis of information obtained from the medical or epidemiological literature or information prov ided by the physician who diagnosed the cancer. For example, beginning in the late 1990s, VA ev aluated causation of basa l cell carcinoma (the most common type of skin cancer) on the basis of an estimate of the lowest equivalent dose at which an excess of that cancer type had been ob served in epidemiological studies. That dose was about 9 rem (NRC 1990).

2.3 Evaluation of Causation of Cancers Using IREP

In 2003, VA began using IREP in parallel w ith the CIRRPC table when an evaluation of causation of cancers was required (VHA/OPHEH 2003; Mather and Otchin 2004), and a policy of using IREP exclusively was adopted in Apri l 2005 (Mansfield 2005). IREP was developed to update and replace the 1985 Radi oepidemiological Tables, which provided the basis for screening doses in the CIRRPC table.8 In contrast to the CIRRPC table, IREP assumes that all cancers except chronic lymphocytic leukemia (CLL) are radiogenic, including cancers that show only a weak association with exposure to ioni zing radiation in Ja panese atomic-bomb survivors (Land et al. 2003). IREP also incorporates more recent da ta on cancer risks due to exposure to ionizing
radiation and revised models to es timate ERRs associated with given equivalent doses to specific organs or tissues (Land et al. 2003 ). IREP calculates a probability distribution of PC associated with given equivalent doses to an organ or tissue in which a cancer occurred. Probability
distributions of PC take into account several sources of uncertainty in estimating ERR associated with an individual’s radiation exposure, as well as uncertainties in estimated equivalent doses if they are included in input to a calculation. 7 Probability distributions of PC calculated with IREP include an upper 99% credibility limit, which VA compares with the value 50% for the purpose of evaluating causation of cancer in veterans who were exposed to ionizing radiation.

7 VA does not use uncertainties in estimated equi valent doses provided by DTRA in evaluating causation of cancers. Rather, in accordance with VA regulations [38 CFR 3.31 1(a)(1)], only estimated upper bounds of equivalent doses, wh ich are intended to be at least upper 95% credibility limits, are used in adjudicating claims for compensation. This appr oach usually results in a higher estimate of the upper 99% credibility limit of PC than would be obtained by using probability distribu tions of equivalent doses as input to a calculation. Exceptions could occur onl y when the uncertainty in the dose is larger than other uncertainties in estimating ERR associated w ith an individual’s given doses. Statistical uncertainties in estimating ERRs in Japanese atomic-b omb survivors and other study populations on the basis of fits to data on dose-response are always important, and uncertainties in transferring ERRs in atomic-bomb survivors to the U.S. population are important for many cancers.9 Table 2-1. Screening doses (rem) for specific ca ncer types calculate d by CIRRPC (1988)

and used by VA in adjudicating claims for compensation for radiation-induced cancer a Age at exposure (y) Type of cancer < 20 30 > 40 Chronic granulocytic leukemia b Within 20 years of exposure c 0.9 1.3 1.4 20 or more years post-exposure c 2.7 3.2 5.9
Acute leukemia b Within 20 years of exposure c 1.1 1.8 4.1 20 or more years post-exposure c 3.5 4.1 5.5 Leukemia (excluding chronic lymphatic) b , d Within 20 years of exposure c 1.1 1.7 3.3 20 or more years post-exposure c 3.3 3.9 5.5
Colon cancer 17.0 33.1 58.1 Esophageal cancer 3.9 9.9 16.7
Female breast cancer 18.8 37.0 78.6 Kidney and bladder cancer 13.4 23.1 34.7
Liver cancer 1.0 3.3 8.2 Lung cancer
Known smokers e 25.5 48.8 72.1
Others f 4.3 9.3 15.0
Pancreatic cancer 5.8 13.7 24.3
Stomach cancer 6.9 13.8 23.2 Thyroid cancer 3.3 7.4 8.8 See following page for footnotes to table.10 Footnotes to Table 2-1

____________________

a Adapted from Table 3 of CIRRPC (1988). Screenin g doses were developed on the basis of the 1985 Radioepidemiological Tables (NIH 1985) for cancer ty pes that were considered to be radiogenic. Screening doses corresponded to an estimated uppe r 99% credibility limit of PC of 50% when uncertainties in estimating cancer risks associated with given equivalent doses in each organ or tissue of concern were taken into account. Screening doses for ages at exposure between 20 and 30 years or 30 and 40 years should be obtained by linear interpolation. b Dose to active bone marrow.

c Time since exposure when cancer was diagnosed. d Cancer type refers to all leukemia as a gr oup and was assumed when the diagnosed leukemia was not a particular type listed separately.

e Category applied when the veteran was known to have been a regular smoker (10 or more cigarettes per day) within five years of diagnosis. Screening doses were calculated by assuming that the veteran was a member of an average U.S. pop ulation that included smokers and nonsmokers. f Category applied when the veteran’s smoking habits were unknown, th e veteran was known to have stopped smoking five years or more before diagno sis, or the veteran was known to be a nonsmoker. Screening doses were calculated by assu ming that the veteran was a nonsmoker.11 3. CANCER RISK MODELS INCORPORATED IN IREP

This section describes models incorporated in IREP to estimate ERRs for specific cancers that are associated with given doses of ionizing radiat ion to organs or tissues in which those
cancers occur. These discussions are intended to be helpful in understanding how screening doses calculated with IREP depend on an individual ’s age at exposure and ag e at diagnosis. Risk models for all cancer types are described in de tail elsewhere (Land et al. 2003; NIOSH 2002). Except as noted, risk models discussed in this se ction are incorporated in versions of IREP that were developed by the National Institute for Occ upational Safety and Health (NIOSH) for use in the Department of Labor’s compensation prog ram for workers at Department of Energy facilities. Versions of IREP developed by NI OSH have been used by VA in evaluating causation
of cancers in veterans who were exposed to ionizing radiation.

3.1 Categories of Cancer Risk Models

Cancer risk models incorporat ed in IREP are categorized in to four groups, as summarized in Table 3-1. Use of a variety of risk models for cancer types ot her than leukemia contrasts with models for those cancer types incorporated in CIRRPC screening doses, which assumed that risks decrease with increasing age at exposure from age 20 to 40 but are independent of attained age (NIH 1985). Another differen ce involves assumed dependencies of cancer risks on dose. In IREP, a linear relationship between dose and risk is assumed, except a linear-quadratic relationship is assumed for all types of leuke mia under conditions of acute exposure to low-LET radiations (Land et al. 2003). In risk models that were used to calculate screen ing doses in the CIRRPC table, a linear dose-response relationshi p was assumed for breast and thyroid cancer but a linear-quadratic relationship was assu med for all other can cer types (NIH 1985). Risk models for cancer types in each categ ory are discussed in the following sections, except the model for lung cancer due to exposure to radon (Group 4) is not discussed because exposure to radon is not a concer n in VA radiation claims. An implicit assumption in these
discussions is that the time sin ce exposure is sufficiently long that the minimum latency period12 does not have a significant effect on estimated ri sks. Assumptions in IREP about the minimum latency period for each cancer type are discussed in Section 3.2.

3.1.1 Group 1 Cancers

For cancer types in Group 1, ERR is assume d to depend on age at exposure and attained age. For a given age at exposure, ERR decreases linearly with increasing attained age to age 50 and remains constant thereafter. For a given a ttained age, ERR decreases exponentially between ages at exposure of 15 and 30 and remains consta nt outside that interval. The model includes a cancer-specific parameter to modify the a ssumed linear dose-respons e relationship, and dependencies of ERR on age at exposure and atta ined age are modified by parameters that also are assumed to be cancer-specific. The various model parameters are a ssumed to be strongly
correlated on the basis of data for the relativel y large number of cases of these cancer types in Japanese atomic-bomb survivors. The model for br east cancer is based on data in females and is assumed to apply to males as well. In modeling the dose-response for cancer ty pes in Group 1 in Japanese atomic-bomb survivors, only ERRs for all digestive cancers other than stomach, colon, and rectum are assumed to depend on sex; ERRs for liver cancer ar e the same in males and females. However, in applying estimated ERRs for liver cancer, as well as breast cancer in females, to the U.S. population, sex-specific base line risks were taken into account (Land et al. 2003).

3.1.2 Group 2 Cancers

The risk model for cancer types in Group 2 is similar to the model for Group 1 cancers. Specifically, ERR for a given age at exposure decreases linearly w ith increasing attained age to age 50 and remains constant thereafter, and ERR for a given attained ag e decreases exponentially between ages at exposure of 15 and 30 and remain s constant outside that interval. However, because there have been fewer cases of Group 2 cancers in Japanese atomic-bomb survivors, the cancer-specific parameter that modifies the as sumed linear dose-response relationship was found13 to be practically independent of cancer-spe cific parameters that modify the assumed dependencies of ERR on age at exposure and atta ined age (Land et al. 2003). Therefore, the model for Group 1 cancers is replaced by an appr oximation in which the parameters that modify the dependencies of ERR on age at exposure and atta ined age are assumed to be the same for all cancer types. The model for lung cancer in Gr oup 2 also depends on an individual’s smoking history. 8 As discussed in the following two sectio ns, an alternative model for lung cancer in Group 3 is included in the version of IREP currently used by NIOSH. For all cancer types in Group 2 that occur in males and females, ERRs in Japanese atomic-bomb survivors are assumed to depend on sex (Land et al. 2003). As with all cancer types in Group 1, sex-specific baseline risks we re taken into account in transferring ERRs in atomic-bomb survivors to the U.S. population.

3.1.3 Group 3 Cancers

For cancer types in Group 3, ERR is assume d to be independent of age at exposure and attained age. A dependence of ERR on sex simila r to the sex-dependence in the risk model for cancer types in Group 2 is assumed in the model for lung cancer in Group 3.

3.1.4 Risk Models for Lung Cancer

As indicated in Table 3-1, two different risk models for lung cancer are incorporated in the version of IREP currently used by VA. In the model described by NIOSH (2002), ERR for lung cancer is assumed to be independent of age at exposure and attained age, and lung cancer is included in Group 3. In the model developed more recently by the National Institutes of Health (NIH), ERR for lung cancer is assumed to depend on age at exposure and attained age (Land et al. 2003), and lung cancer is included in Group 2. In addition, although both models use the

8 In cases of exposure to sources other than radon, IREP calculates ERRs for lung cancer for the following smoking categories: never-smokers, former smokers, current smokers with an unspecified consumption rate of cigarettes, and four categories of current smokers defined by the number of cigarettes smoked per day.14 same categories of smoking history for an expos ed individual, the two models use somewhat different approaches to calculati ng ERR in the different categories. 9 The version of IREP currently used by VA calculates PC using both models for lung cancer, and the higher estimate of PC at the upp er 99% credibility limit is emphasized in the output from IREP. As indicated by screening doses tabulated in th is report, the model that gives the higher upper 99% credibility limit of PC depends on smoking history and the time since exposure when cancer was diagnosed (see Section 4.1.3).

3.1.5 Group 4 Cancers

Cancer types in Group 4 each have a unique ri sk model. The model for each cancer type in this group is described in the following paragraphs.
Two models are assumed for skin cancers. ERRs for basal cell carcinoma decrease exponentially with increasing age at exposure to age 40 and remain constant thereafter, but are independent of attained age; the model for basa l cell carcinoma also is applied to malignant melanoma, for which there were too few cases in Japanese atomic-bomb survivors to establish a dose-response relationship (Land et al. 2003). ERRs for non-melanoma skin cancers other than basal cell carcinoma (e.g., squamous cell carcino ma) are independent of age at exposure and attained age. ERRs for all sk in cancers are independent of se x but depend on race or ethnicity. 10
Differences in baseline risks of skin cancers in different racial and ethnic groups are taken into account in the transfer of ERRs in Japanese atomic-bomb survivors to the U.S. population. ERR for thyroid cancer decrea ses exponentially with increasing age at exposure to age 50 and remains constant thereafter, but is independent of attained age and sex.

9 The two models estimate ERR for lung cancer using the same smoking-related adjustment factors but apply them differently. In the model for lung cancer in Group 3, adjustments for smoking history are applied to an estimated ERR that is an average over all smoking categories. In the model for lung cancer in Group 2, those adjustments are applie d to an estimated ERR in never-smokers only.

10 IREP calculates ERRs for skin cancers for the following racial or ethnic groups: American Indians or Alaska natives; Asians, native Hawaiians, or other Pacific islanders; blacks; white Hispanics; and white non-Hispanics. ERRs for all other cancer types are assumed to be independent of race or ethnicity.15 ERR for all leukemia as a group, excluding CLL, 11 decreases expone ntially with increasing age at exposure to age 55 and increasi ng time since exposure to 50 years, and remains
constant thereafter. The effect of time since e xposure on ERR is similar to the effect that is incorporated in screening doses for various types of leukemia in the CIRRPC table (see Section 2.2). Modifications of this model are used for specific types of leukemia. ERRs for acute myeloid leukemia (AML) and chronic myeloi d leukemia (CML) are independent of age at exposure, and the exponential d ecrease in ERR for CML with increasing time since exposure is
faster in males than in females. ERR fo r acute lymphocytic leukemia (ALL) decreases exponentially with increasing time since exposure when exposure occurs before age 20, but is independent of time since exposure when exposure occurs at age 20 or beyond. ERRs for AML, ALL, and all leukemia as a group are independent of sex.

3.2 Minimum Latency Period for Different Cancer Types

Descriptions of risk models for different cancer types in Section 3.1 presume that the time between exposure and diagnosis of cancer exceeds the minimum latency period for each cancer type. The minimum late ncy period is the elapsed time between exposure to a hazardous agent and the earliest occurrence of detectable dis ease caused by that agent. In IREP, the effect of the minimum latency period on cancer risks due to radiati on exposure is assumed to be represented by an S-shaped (sigmoid) function of time that increases from 0 shortly after exposure to 1 at a time when la tency no longer has an effect on es timated risks (Land et al. 2003; NIOSH 2002). 12 The value of this function is 0.5 at the midpoint between the two times. Thus, the effect of the minimum latency period is to rapidly decrease estimates of cancer risk as the time since exposure decreases below times at whic h the S-shaped function has values near 1.

11 Although CLL is not considered to be a radioge nic cancer in IREP, VA estimates PC in cases of CLL by assuming that CLL is a form of non-Hodgkin’s lymphoma and uses the risk model for lymphoma and multiple myeloma in Group 2 (N. Otchin, Departme nt of Veterans Affairs, personal communication; April 18, 2006).

12 The assumption of an S-shaped function takes in to account that the minimum time required for radiation exposure to result in an increase in cancer risk is difficult to estimate, and it avoids an assumption of an abrupt increase in risk at some time after exposure.16 One of three parameterizations of the S-shaped function is assumed to represent the effect of latency on risk, depending on the cancer type (Land et al. 2003). For all solid tumors except thyroid and bone cancer, the mini mum and maximum values of 0 a nd 1 in the S-shaped function are essentially attained at times after exposure less than 4 years and greater than 11 years, respectively (i.e., the values at 4 and 11 years are 0.01 and 0.99), and the midpoint is at 7.5 years. This function is given by the solid curve in Fig. 3-1; it is also used to represent the minimum latency period for lymphoma and multiple myeloma. For thyroid and bone cancer, which have a shorter minimum latency period than other solid tumors, the minimum and maximum values in the S-shaped function are essentially attained at times after exposur e less than 2 years and greater than 7 years, respectively, and the midpoint is at 4.5 years. For all types of leukemia, which have a shorter minimum latency period than all other cancer types, the minimum and maximum values in the S-shaped function ar e essentially attained at times after exposure less than 1 year and about 5 years, respectively, a nd the midpoint is at 2.25 years. To represent uncertainty in the assumed e ffects of the minimum latency period on cancer risks, the midpoint of each S-shaped function described above is repr esented by a triangular probability distribution that has a maximum value at 7.5, 4.5, or 2.25 years and ranges from 5 to 10 years, 4 to 5.5 years, or 2 to 2.5 years, resp ectively (Land et al. 2003 ). The effect of the assumed uncertainty in the midpoint of the S-shap ed function for all solid cancers except thyroid
and bone cancer is also shown in Fig. 3-1. For all cancer type s, this uncertainty results in
substantial increases in estimates of ERR and PC at times after exposure less than the midpoints of the triangular distributions , compared with estimates obtai ned by assuming no uncertainty in the S-shaped function (Land et al. 2003). Effects of this uncertainty on estimates of ERR and PC are less at times after exposure beyond the midpoints of the triangular distributions.17 Table 3-1. Categories of cancer risk models incorporated in IREP a Category Cancer types Description of risk model Group 1 All digestive cance rs other than stomach, colon, and rectum; stomach (female only); liver; breast Risk depends on age at exposure, attained age, and sex (all digestive cancers other than stomach, colon, and rectum only). Group 2 Oral cavity and pharynx; esophagus; stomach (male only); colon; rectum; gallbladder; pancreas; lung (including trachea and bronchus) b ; respiratory other than lung (e.g., nasal cavity, larynx); bone; all connective tissue; ovary; all male genitalia (including prostate); bladder; kidney and other urinary organs except bladder; eye; nervous system (including brain); endoc rine glands other than thyroid; other and ill-defined sites; lymphoma and multiple myeloma Risk depends on age at exposure, attained age, and sex, but model structure describing dependencies on age at exposure and attained age is different from model for cancer types in Group 1; risk of lung cancer also depends on smoking history.

Group 3 Lung (including trachea and bronchus) b ; all female genitalia except ovary Risk is independent of age at exposure and attained age; risk of lung cancer depends on sex and smoking history. Group 4 Malignant melano ma and non-melanoma skin cancers (basal cell carcinoma and others including squamous cell carcinoma) c ; thyroid; leukemia (other than chronic lymphocytic leukemia, CLL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and acute lymphocytic leukemia (ALL); lung cancer due to exposure to radon Unique risk model for each cancer type.

a Risk models, excluding model for lung cancer due to exposure to radon, are discussed in Section 3.1. All cancers except CLL are considered to be radiogenic in IREP. b Risk model for lung cancer in Group 2 was devel oped by Land et al. (2003), whereas a different model in Group 3 was used originally by NIOSH (2002). Both risk models for lung cancer are incorporated in the version of IREP currently used by VA.

c Risks of skin cancers depend on race or ethnicity.18 Figure 3-1. S-shaped (sigmoid) function assume d in IREP to represent effect of minimum latency period on reducing risks of all solid cancers except thyroi d and bone cancer at early times since exposur e and its uncertainty. 

### 0.0 0.2 0.4 0.6 0.8 1.0

0 5 10 15 1st %-ile 5th %-ile 50th %-ile 95th %-ile 99th %-ile

L a t e n c y a d j u s t m e n t



### Time since exposure (y)19 4. SCREENING DOSES CALCULATED WITH IREP

This section presents screening doses for di fferent cancer types that were calculated with IREP. These screening doses ar e tabulated and discussed in S ection 4.1. In Section 4.2, screening doses calculated with IREP are compared with previous screening doses in the CIRRPC table (see Table 2-1). Us e of tabulated screening doses in cases of exposure to multiple radiation types or exposures in more than one y ear is discussed in Section 4.3. A summary of important points about screening doses tabulated in this report is given in Section 4.4.

4.1 Tabulation and Discussion of Screening Doses

Screening doses for different cancer types that were calculat ed with IREP are given in Tables 4-1 through 4-34. 13 Screening doses were calculated fo r selected ages at exposure and times since exposure when cancer is diagnosed. The latter quantity is given by the difference between the age at diagnosis and age at exposur e. Screening doses were estimated by iteration using constant equivalent doses, with no uncertainty , as input to IREP. For reasons discussed in Section 4.1.2, all screening doses are given to two significant figures. Sections 4.1.1 and 4.1.2 discuss assumptions used in calculating sc reening doses and the accuracy of the results. Secti on 4.1.3 then discusses screening doses for specific cancer types.

4.1.1 Calculation of Screening Doses

With one exception, screening doses in Ta bles 4-1 through 4-34 were calculated with
versions of IREP that we re developed by NIOSH (2002); 1 3 versions developed by NIOSH have been used by VA in evaluating causation of cancer s in veterans who were exposed to ionizing radiation. Screening doses for lung cancer in Table 4-11 were cal culated with a ve rsion of IREP

13 Most calculations were performed using Version 5.4 of NIOSH-IREP. Screening doses for thyroid and bone cancer were calculated using Version 5.5, which incorporated recent changes in models used to estimate ERRs for those cancer types.20 that was developed by NIH (Land et al. 2003). 1 4 As discussed in Sect ion 3.1.4, the current version of NIOSH-IREP incorporates both risk models for lung cancer. IREP calculates probability distributions of PC by repeated random sampling of probability distributions that represent uncertain ties in all parameters and propagation of the randomly selected parameter values through th e models used to estimate ERR and PC. 1 5 Probability distributions of PC generated in IREP include an upper 99% credibility limit, which is used to estimate the screening dose in each ca se. All screening doses were calculated using 2000 iterations per run, and the random seed to initiate the sampling proc ess was set to 99. These are the default settings in NIOS H-IREP and are generally used by VA.
All calculations of screeni ng doses assumed acute exposure to high-energy (> 250 keV) photons or, in cases of skin cancer, acute e xposure to higher-energy (>15 keV) electrons; the latter assumption gives the same PC as an assumption of acute exposure to high-energy photons. 1 6 An assumption of acute exposure to photons or electrons results in a higher estimate of PC than an assumption of chronic exposure, 1 7 due to the influence of a dose and dose-rate

14 Calculations were performed us ing Version 5.3 of NIH-IREP.

15 The technique of random sampling used in IREP is a form of Monte Carlo sampling referred to as midpoint Latin hypercube sampling. In this method, probability distributions of model parameters are divided into N intervals of equal probability, where N is the number of iterations per run, and values at the midpoints of each of the N intervals are selected in random order. Use of Latin hypercube sampling assures that the entire range of probabili ty distributions of all parameters is sampled. This technique thus gives a more robust probability distribution of PC fo r a given number of iterations, especially at an upper credibility limit, than conventional Monte Carlo sa mpling in which parameter values are selected at random in each iteration without rega rd for previously sampled values.

16 It is intended that doses will be entered into IREP by radiation type. Equivalent doses for the following radiation types can be entered: photons of energy < 30 keV, 30-250 keV, and > 250 keV; electrons of energy < 15 keV and > 15 keV; neutr ons of energy < 10 keV, 10-100 keV, 0.1-2 MeV (including spectra of fission neutrons), 2-20 MeV, and > 20 MeV; and alpha particles of any energy emitted in radioactive decay (Land et al. 2003). When equivalent doses are entered by radiation type, the biological effectiveness of each radiation type rela tive to reference high-energy (> 250 keV) photons and its uncertainty are taken into account in calculating probability distributions of PC.

17 To follow guidance by NIOSH (2002), VA assumes that all external exposures to photons or electrons are acute, because that assumption is more fa vorable to claimants than an assumption of chronic exposure (N. Otchin, Department of Veterans A ffairs, personal communication; April 26, 2006).21 effectiveness factor (DDREF) in reducing risks from chronic exposure to those radiation types (Land et al. 2003). 1 8 Use of screening doses in cases of exposure to other radiation types is
discussed in Section 4.3.1. Screening doses for ages at exposure or ti mes since exposure when cancer was diagnosed
that are not included in the tabl es can be estimated by interpolat ion. Two-dimensional linear interpolation should be adequate wh en screening doses are not changi ng rapidly. In the tables of screening doses, this condition is met when the ti me since exposure is more than 3 years for all types of leukemia, 5 years for thyroid and bone ca ncer, and 10 years for all other cancer types. Of course, the more precise option of running IREP for specific cases is always available. This option is recommended when the time since e xposure is sufficiently sh ort that the minimum latency period has an effect on reducing estimat es of ERR and increasing screening doses. Except for cancers of the female breast, ova ry, and all female genitalia except ovary, tabulated screening doses apply to males only. For cancer types in Groups 1, 2, or 3 that occur in males and females and for chronic myeloid le ukemia (CML) in Group 4 (see Table 3-1), ERRs are assumed to depend on sex, and screening dos es for females differ from values for males. 1 9

4.1.2 Accuracy of Calculated Screening Doses

As noted previously, all screening doses in Tables 4-1 through 4-34 are presented to two significant figures only. More sp ecifically, each screening dose is the lowest equivalent dose to two significant figures at which the calculated upper 99% credibility limit of PC is 50% or greater. Thus, a screening dose is not necessarily the equivalent dose at which the calculated

18 Probability distributions of DDREF with mean values greater than 1.0 are used in IREP to estimate ERRs for all cancer types, except leukemia, from chronic exposure to photons or electrons. For acute exposure to those radiation types, DDREF is phased in as the dose decr eases below an uncertain reference dose between 3 and 20 rem and appro aches the assumed DDREF for chronic exposure as the dose decreases toward zero (Land et al. 2003). A DDR EF also is implicit in the assumed linear-quadratic dose-response relationship for leuke mia under conditions of acute expos ure to photons or electrons.

19 Screening doses for males and females may diffe r even when ERRs in Japanese atomic-bomb survivors are independent of sex, because baseline risks u sed in modeling the transfer of ERRs to the U.S. population may be sex-specific (Land et al. 2003).22 upper 99% credibility limit of PC is closest to 50%. 2 0 By using this approach, an equivalent dose (to two significant figures) less than an applicable screening dose corresponds to a calculated upper 99% credibility limit of PC le ss than 50% when the default settings of 2000 iterations per run and a random seed of 99 are used. Reporting of screening doses to no more than two significant figures can be justified by considering the accuracy of the calculations. If the number of iterations pe r run is fixed at the default setting of 2000, a change in the random seed can have a substantial effect on the calculated upper 99% credibility limit of PC. Th is effect is illustrated by calculations we performed with Version 5.5 of NIOSH-IREP, in which an equivalent dose that gave an upper 99% credibility limit of PC close to 50% for part icular combinations of cancer type, age at exposure, and attained age were assumed; some of these combinat ions were selected with the intent of maximizing the effect of a change in the random seed. 2 1 By performing calculations at the same equivalent dose but using up to 50 diffe rent random seeds, the maximum variation in

20 If, for example, an equivalent dose (to two significant figures) of 110 rem gives an upper 99% credibility limit of PC of 49.96% and an equivale nt dose of 120 rem gives a value of 51.23%, the tabulated screening dose would be 120 rem.

21 Calculations were performed for the following co mbinations of cancer type, age at exposure (ae), and age at diagnosis of cancer (ad): (1) liver cancer, ae = 18 and ad = 28; (2) cancers of the respiratory tract other than lung cancer, ae = 18 and ad = 28; (3) non-melanoma basal cell carcinoma (white, non-Hispanics), ae = 18 and ad = 70; (4) b asal cell carcinoma (white, non-Hispanics), ae = 40 and ad = 70; (5) cancers of all male genitalia (includi ng prostate), ae = 20 and ad = 70; (6) thyroid cancer, ae = 18 and ad = 60; and (7) all leukemia excluding CLL, ae = 18 and ad = 70. The first two calculations apply to the cancer types in Group 1 and Group 2 (see Section 3.1 and Table 3-1) for which uncertainties in the estimated ERR per unit equivalent dose are th e highest (Land et al. 2003) and, thus, calculated upper 99% credibility limits of PC at a fixed dose ar e among the most sensitive to changes in the random seed. The age at exposure and age at diagnosis in those two calculations were chosen to maximize the effect of changes in the random seed. Calculati ons for basal cell carcinoma and prostate cancer were included because these are the most common types of nonpresumptive cancers in VA radiation claims of concern to this report. The ages at exposure and ages at diagnosis in the calculations for those two cancer types were selected to represent a variety of likely comb inations and, in the first calculations for basal cell carcinoma, to maximize the effect of changes in th e random seed. Calculations for thyroid cancer and leukemia were included to investigate the effect for cancer types other than skin cancer with unique risk models (see Section 3.1.5). In all calculations, the equivalent dose was fixed at the applicable screening dose given in Table 4-7, 4-12, 4-16, 4-22, 4-27, or 4-31.23 the upper 99% credibility limit of PC about the nominal value of 50% was ±3.0 percentage points, or ±6.0% of th e nominal value of 50%. 2 2,2 3 For the purpose of estimating screening doses, we are interested in the variation in the dose that gives a calculated uppe r 99% credibility limit of PC of 50% due to a change in the random seed in IREP, rather than the variation in an upper 99% credibilit y limit of PC of about
50% at a fixed dose. Since PC is a nonlin ear function of dose (see Section 2.1), the two
variations are not the sa me. Our analysis of the variation of interest is described as follows.
We define the variation in PC due to a change in the random seed as Δ (PC)/PC and the corresponding variation in dose as Δ D / D . When ERR is a linear functi on of dose, as in all risk models incorporated in IREP except the model for all types of leukemia under conditions of acute exposure to photons and el ectrons (Land et al. 2003), PC is estimated using eq. (5). By differentiating eq. (5) with respect to dose and taking into account that α × D = 1 at a PC of 50%,
we find that when PC is about 50%, a variation in PC of x at a fixed dose corresponds to a
variation in dose of 2 x at a fixed PC of 50%. This result means that a screeni ng dose is twice as sensitive to a change in the random seed as the upper 99% credibility limit of PC of about 50% at
a fixed dose. 2 4 Thus, in the example calculations discussed above, in which the maximum variation in the upper 99 % credibility limit of PC was ±6.0% of the nominal value of 50% at a fixed dose, the corresponding variation in the equi valent dose that gives an upper 99% credibility

22 The maximum variation was obtained in the calcula tions for liver cancer. In all calculations for basal cell carcinoma and prostate cancer, the variatio n in PC was no more than about ±2.2 percentage points, or ±4.4% of the nominal value of 50%.

23 The variation in the upper 99% credibility limit of PC at a fixed dose due to a change in the random seed is reduced by increasing the number of itera tions per run. When the number of iterations per run was increased to 10,000, which is the maximum no rmally allowed in IREP, the maximum variation in the upper 99% credibility limit of PC was about ±1 per centage point, or about ±2% of the nominal value of 50%. We used 2000 iterations per run in all cal culations to conform to the default used by VA.

24 When ERR is assumed to be a linear-quadratic function of dose, as in the risk models incorporated in IREP for various types of leukemi a under conditions of acute exposure to photons and electrons (Land et al. 2003), the same method can be u sed to show that a screening dose is less than twice as sensitive to a change in the random seed as an upper 99% credibility limit of PC of about 50% at a fixed dose. Thus, a linear dose-response relationshi p provides the bounding case for the sensitivity of a screening dose to a change in the random seed.24 limit of PC of 50% (i.e., the maximum variation in the screening dose) is ±12%. This result applies to the cancer type, age at exposure, and age at time of di agnosis for which the effect is expected to be the greatest. The maximum variat ion in a screening dose due to a change in the random seed is less for other cancer types, ages at exposure, and ages at diagnosis. 2 5
The choice of a random seed to be used as a default in IREP is ar bitrary. Therefore, results of the analysis described above indicate that re porting of screening doses calculated with IREP to more than two significant figures when the default number of iterations per run and random seed are used would imply an accuracy in the calculations that is unwarranted. An important implication of the analysis described above is that screening doses tabulated in this report should be interpreted with caution. Although the tabulated screening doses are intended to correspond to an upper 99% credibility limit of PC of 50%, this correspondence clearly is not exact. Thus, it is not necessarily the case that an estimated equivalent dose (to two significan t figures) equal to or greater th an a screening dose tabulated in this report corresponds to an actual upper 99% credib ility limit of PC of 50% or greater, nor is it necessarily the case that an estimated equivale nt dose less than a scre ening dose corresponds to an actual upper 99% credibility limit of PC less than 50%. 2 6 Results of our analysis of the sensitivity of sc reening doses to the choice of a random
seed also indicate the extent to which a screening dose tabulated in this report could differ from the equivalent dose that correspond s to an actual upper 99% credib ility limit of PC of 50%. As

25 The maximum variation in a calculated upper 99% cr edibility limit of PC due to a change in the random seed in IREP can be much higher than obtained in our analysis if the equivalent dose is assumed to be uncertain, rather than fixed at a single value. For example, in a calculation in which the uncertainty in an estimated dose was represented by a geometric st andard deviation (GSD) of 3 and the median dose was set at a value that gave an upper 99% credibility limit of PC close to 50%, the maximum variation in the upper 99% credibility limit of PC due to changes in the random seed was nearly ±10% of the nominal value of 50% (B.A. Thomas, SENES Oak Ridge, Inc. , personal communication; March 9, 2006). An assumption of a fixed dose is appropriate for our anal ysis when VA uses point estimates of equivalent dose in evaluating causation of cancer (see Section 2.3, footnote 6).

26 An actual upper 99% credibility limit of PC woul d only be obtained by specifying a very large (essentially infinite) number of iterations per run. When the number of iterations is very large, the choice of a random seed no longer has an effect on the calculated probability distribution of PC, essentially because nearly all possible combinations of para meter values are selected by random sampling.25 derived above, the largest difference between a calculated screening dose and its actual value should be no more than ±12%. Furthermore, the greatest effect of a chan ge in the random seed
was obtained in the calculations for liver cancer that assumed a very young age at the time of diagnosis of cancer (see footnote 21 ). Such a young age at diagnosis should rarely, if ever, occur in VA radiation claims of concern to this repor t. For more common ages at diagnosis, the difference between a calculated screening dose and the equivalent dose that corresponds to an actual upper 99% credibility limit of PC of 50% should be less than ±10%. 2 7

4.1.3 Discussion of Screening Doses

Screening doses in Tables 4-1 through 4-34 show certain de pendencies on age at exposure and time since exposure when cancer was diagnosed (i.e., difference between age at diagnosis and age at exposure). The following di scussion of these dependen cies assumes that the time since exposure when cancer was diagnosed is sufficiently long that assumptions about the minimum latency period described in Section 3.2 do not have a significant effect on estimates of ERR and PC. When the time since exposure is shor t (e.g., less than the mi dpoint of the S-shaped function that is assumed to represent the effect of the minimum latency period on risk), screening doses increase rapidly with decreasing time since exposure. For all cancer types in Groups 1 and 2 (see Ta ble 3-1), which are th e majority of cancer types considered in IREP, screening doses incr ease with increasing ag e at exposure and time since exposure when cancer was diagnosed until a plateau region is reached, where screening doses are constant. These depe ndencies are the result of assump tions about the dependence of ERRs on age at exposure and attained age, as descri bed in Section 3.1. In most such cases, the minimum screening dose for any age at exposure occurs at a time since exposure when cancer

27 When more common ages at diagnosis that appl y to recent or future VA radiation claims are considered (e.g., an age at diagnosis of at least 50), additional calculations indicated that the largest difference between a screening dose tabulated in this report and the equivalent dose that corresponds to an actual upper 99% credibility limit of PC of 50% is grea tly reduced for cancer types in Groups 1 and 2 (see Section 3.1 and Table 3-1), including liver cancer. The calculation that gives the largest difference then becomes basal cell carcinoma for an age at expos ure of 18, and the maximum difference between a screening dose and its actual value for that cancer type should not exceed about ±9%.26 was diagnosed of about 10 years or less, depe nding on the assumption about the effect of the minimum latency period on risk (see Section 3.2) . Further discussion of screening doses for selected cancer types is provide d in the following paragraphs. Lung cancer . Screening doses for lung cancer in Ta bles 4-10 and 4-11 were calculated using different risk models (see Section 3.1.4) . For younger ages at exposure and earlier times since exposure when cancer was di agnosed, screening doses in Tabl e 4-11 often are substantially lower than the corresponding values in Table 4-10. This differen ce is explained by the following: screening doses in Ta ble 4-10 were calculated on the basis of an estimate of the average ERR associated with radiation exposure in a population of all ages, and that ERR is substantially lower than estimated ERRs for younger ages at expos ure and earlier attained ages that were used in calculating screening doses at those ages in Table 4-11. For never-smokers, however, screening doses in Table 4-11 are substa ntially higher than th e corresponding screening doses in Table 4-10 for ages at exposure be yond about 25 and times since exposure beyond about 15 years. At those ages and tim es, age-specific ERRs used to calculate screening doses for
never-smokers in Table 4-11 are lower than th e average ERR for never-smokers in a population of all ages.
Skin cancer . Skin cancers are the only cancer ty pes for which risks due to radiation exposure are assumed to depend on race or ethnic ity. Screening doses for basal cell carcinoma (Table 4-16) and squamous cell carcinoma (Table 4-17) are about a factor of 2 higher in white, non-hispanics than in blacks. For malignant me lanoma, however, screening doses (Table 4-15) are less dependent on race or ethnicity.
Breast cancer . Screening doses for breast cancer in males (Table 4-19) are slightly lower than the corresponding values for females (Table 4-18). Even though the risk model for breast cancer is the same for both sexes, there are differe nces in uncertainties in baseline risks in the two sexes that affect upper 99% cr edibility limits of PC for an i ndividual in the U.S. population. Thyroid cancer . Screening doses for thyroid cancer (Table 4-27) increase more slowly with increasing age at exposure than screening do ses for other solid tumors. In this case, an increase in uncertainty in ERR with increas ing age at exposure (Land et al. 2003) has a substantial effect on upper 99% credibility limits of PC. In addition, screening doses are27 constant for ages at exposure beyond 50, even though ERR for thyroid can cer is expected to decrease with increasing age at exposure be yond age 50. However, the number of thyroid cancers in this age group in Ja panese atomic-bomb survivors wa s judged to be too small to establish a dependence of ERR on age at exposure, and ERR for thyroid cancer is assumed to be independent of age at exposure beyond age 50 (Land et al. 2003).
Leukemia . A noteworthy characteri stic of screening doses for all leukemia excluding CLL (Table 4-31) is that values in the lower-ri ght portion of the table d ecrease with increasing age at exposure and time since exposure when can cer was diagnosed. This behavior is seen even though ERR associated with radi ation exposure is assumed to decrease exponentially with increasing age at exposure to age 55 and time si nce exposure to 50 years. In the portion of
Table 4-31 where this behavior is seen, the uncertainty in the estimated ERR is increasing more rapidly with increasing age at exposure and time since exposure than the corresponding decrease in the central estimate of ERR (Land et al. 2003), resulting in increases in upper 99% credibility
limits of PC. Screening doses for acute lymphocytic leukemia (ALL) (Table 4-33) show a pronounced increase as the age at exposure increases from 18 to 20, provided the time since exposure when cancer was diagnosed is about 20 years or less. Those large in creases do not result from an assumption that the ERR for ALL associated with radiation exposure decr eases greatly when the age at exposure increases by only 2 years. Rather, screening doses for an age at exposure of 18 were calculated on the basis of an average ERR fo r all ages at exposure up to age 20, and that ERR is determined primarily by the high ERRs in infants and children when ERR is assumed to decrease exponentially with increasing age at exposure.

4.2 Comparison with Screening Doses in CIRRPC Table

For cancer types included in the CIRRPC ta ble (Table 2-1), the corresponding screening doses calculated with IREP usually are higher. T hose increases are due in part to reductions in uncertainties in estimated ERRs in exposed populations, mainly Japanese atomic-bomb survivors, as the number of cancers on those popula tions has increased over time. A decrease in28 uncertainty in an estimated ERR results in a decr ease in uncertainty in PC and, therefore, an increase in the equivalent dose corresponding to an upper 99% credibility limit of PC. In a few cases, a lower screening dose was calculated with IREP compared with the corresponding screening dose obtained from the CIRRPC table. These cases include: colon cancer and breast cancer for ages at exposure of about 20 years or less and times since exposure when cancer was diagnosed of about 10-15 year s, and acute lymphocytic leukemia (ALL) for ages at exposure less than 20 y ears and times since exposure less th an about 10 years. In those cases, changes in data and assumptions used to estimate ERRs other than reductions in uncertainties in estimated ERRs in Japanese atomic-bomb survivors are important. Depending on the cancer type, important changes may include: (a) increases in central estimates of ERR, (b) differences in assumptions about the transfer of ERRs in atomic-bomb survivors to the U.S. population to account for differences in baseline risks in the two populations, and (c) a change from a linear-quadratic dose-respon se relationship, as used to calculate screening doses for most cancers in the CIRRPC table, to a linear relati onship and a DDREF at low doses and low dose rates in IREP (Land et al. 2003; NIH 1985). However, a change in the dose-response relationship is not relevant for breast cancer, since a linear relati onship was assumed previously. Furthermore, a change from a linear-quadratic re lationship to a linear re lationship with a DDREF for solid tumors does not apply to any type of leukemia (excluding CLL), since a linear-quadratic dose-response relationship for t hose cancer types was assumed pr eviously and is assumed in
IREP under conditions of acute e xposure to low-LET radiations. Although screening doses calcu lated with IREP are higher in most cases than the corresponding screening doses obtained from the CIRRPC table, increases in screening doses should affect compensation decisions in only a small fraction of VA claims. All cancers
included in the CIRRPC table are presumptive diseases in VA regul ations [38 CFR 3.309(d)(2)]. Therefore, except as noted in Section 1 (see foot note 2), adjudication of claims for compensation for those cancers does not require an evaluation of causation. Screening doses for the most common cancers in VA radiation claims (basal cell carcinoma and prostate cancer) are not included in the CIRRPC table. However, the lo west screening doses fo r basal cell carcinoma29 calculated with IREP (Table 4-16) are similar to or less than the screen ing dose of about 9 rem used previously by VA (see Section 2.2). Another difference between screening doses cal culated with IREP and screening doses in the CIRRPC table concerns their dependen ce on time since exposure when cancer was diagnosed. Screening doses for many cancer types calculated with IREP increase with increasing time since exposure when that time is sufficiently long that an assumption about the minimum latency period (see Section 3.2) does not have a significant effect on estimated ERRs. However, with the exception of the various types of leukemia, screening doses in the CIRRPC table are independent of time since exposure when cancer was diagnosed.

4.3 Application of Screening Doses

Comparisons of estimated equivalent doses to individuals with scr eening doses tabulated in this report may be straightfo rward in some cases. However, additional consideration needs to be given to cases in which an individual was ex posed to multiple radiation types or exposures occurred in more than one year. These situ ations are discussed in the following sections.

4.3.1 Exposure to Multiple Radiation Types

Screening doses in Tables 4-1 through 4-34 ar e equivalent doses to organs or tissues in which each cancer type occurs. Th erefore, the dose to an indi vidual that should be compared with a screening dose is a total equivalent dose from all radiation types combined that takes into account the biological effectiveness of different radiation types. Alpha particles a nd neutrons are the high-LET radiations of concer n for which the biological effectiv eness is considerably greater than for high-energy photons. As noted in Section 1, estimates of equiva lent dose that are pr ovided by DTRA for use by VA in adjudicating claims are intended to be at least upper 95% credibility limits of uncertain doses. Therefore, upper cr edibility limits of total equivalent do ses to be compared with tabulated screening doses should take into account uncertainties in the biological eff ectiveness of alpha30 particles and neutrons when exposure to those ra diation types occurred, as well as uncertainties
in absorbed doses. 2 8 Uncertainties in the biological effec tiveness of alpha part icles and neutrons that can be used in estimating upper bounds of e quivalent dose from these radiation types are represented by probability distri butions of radiation effectiven ess factors (REFs) that were developed by Kocher et al. (2002; 2005) for use in IREP (Land et al. 2003). 2 9,3 0 Uncertainties in the biological effectiveness of al pha particles and neutrons should also take into account a small correction to probability distributions of REFs to represent an assumed inverse dose-rate effect and its uncertainty. 3 1

28 These considerations also apply to the use of screening doses in the CIRRPC table (Table 2-1).

29 It is important to emphasize that uncertainties in the biological effectiveness of alpha particles and neutrons should not be taken into account when estimating equivalent doses from those radiation types to be used as input to IREP. Since uncertainti es in REFs are incorporated in IREP, they are taken into account when IREP is used to calculated an upper 99% credibility limit of PC. Therefore, when IREP is used, equivalent doses from alpha particles a nd neutrons (including upper bounds used by VA in adjudicating claims for compensation) should be es timated using point values of radiation weighting factors ( w R ) recommended by ICRP (1991), without uncertainty; the recommended w R is 20 for alpha particles and fission neutrons. The need to account for uncertainty in the biological effectiveness of alpha particles and neutrons in estima ting equivalent doses arises only when an estimated upper bound of the total equivalent dose from all radiation types combin ed is compared with a tabulated screening dose.

30 Caution is advised when estimated total equi valent doses to be compared with tabulated screening doses for various types of leukemia include significant contributions fr om alpha particles or neutrons. Such comparisons are difficult when th e dose-response relationship for acute exposure to photons assumed in calculating screening doses is linear- quadratic, but the dose-response relationship for alpha particles and neutrons is linear. This diffe rence is not a concern for cancer types other than leukemia.

31 This correction represents an assumption that the biological effectiveness of high-LET radiations increases with decreasing dose rate and, t hus, that the risk from chronic exposure at a given dose is higher than the risk from acute exposure at the same dose. In using IREP, VA assumes that all exposures to alpha particles are chronic and, to fo llow guidance provided by NIOSH (2002), VA uses the same assumption for external exposure to neutrons becau se it is more favorable to claimants. Therefore, when using tabulated screening doses in cases of exposur e to those radiation types, an inverse dose-rate effect should be taken into account in estimating upper bounds of equivalent doses, to be consistent with VA’s assumptions. If VA were to change its policy a nd assume that all exposures of service personnel to neutrons at atmospheric nuclear-weapons tests were acute, an REF for neutrons uncorrected for an inverse dose-rate effect should be used in estim ating upper bounds of equivalent doses.31 4.3.2 Exposures in More Than One Year

Another complicating factor in using tabulated screening doses arises when exposures occurred in more than one year (i .e., at more than one age). Expos ures in more than one year can affect comparisons of estimated equivalent dose s with screening doses when the screening dose depends on age at exposure and time since exposur e when cancer was diagnosed. This situation occurs for most cancer types. As described be low, suitable approaches to addressing exposures in more than one year depend on wh ether the intent is to use a screening dose to show that the upper 99% credibility limit of PC associated with estimated equivalent doses is clearly less than 50% or clearly greater than 50%. All suitable approaches discussed below involve comparisons of the total equivalent dose from all years of exposure with an applicable screening dose for the cancer type of concern. If a screening dose is used to determine wh ether estimated equivalent doses correspond to an upper 99% credibility limit of PC that is clearly less th an 50%, the simplest approach to accounting for exposures in multiple years is to compare the total equivalent dose with the lowest screening dose for the cancer type of conc ern that applies to any age at exposure and time since exposure when cancer was diagnosed. In ma king such comparisons, it is important to take into account the accuracy of screening doses cal culated with IREP (i.e., potential differences between tabulated screening doses and the equivale nt dose that correspon ds to an actual upper 99% credibility limit of PC of 50%), as discus sed in Section 4.1.2. The lowest tabulated screening dose for each cancer type is given in Table 4-35. If the estim ated upper bound (at least an upper 95% credibility lim it) of the total equivalent dose from exposure in all years is less than the lowest screening dose that applies to the can cer type of concern, the upper 99% credibility
limit of PC is less than 50%. This conclusion applies without regard for the distribution of equivalent dose with age at exposure or the age at the time of diagnosis. For all cancer types except leukemia, an alte rnative approach can be used to demonstrate that estimated equivalent doses correspond to an upper 99% credibility limit of PC that is clearly less than 50%. In this approach, the total equivalent dose is compared with the screening dose (again with due consideration of its accuracy) that applies to the youngest age at exposure and a32 time since exposure given by the difference between the age at diagnosis and the oldest age at exposure (age during the year of last exposure). This alternativ e is valid when screening doses do not decrease with increasing age at expos ure or time since exposure when cancer was diagnosed. However, it should be used only when the difference between the age at diagnosis and oldest age at exposure exceeds the time ove r which the minimum latency period for the cancer type of concern has a signific ant effect on estimated risks. The alternative approach described above al so is valid for specific types of leukemia (CML, ALL, and AML) in many cases, given the dependence of screening doses (Tables 4-32, 4-33, and 4-34) on age at exposure and time si nce exposure when cancer was diagnosed. However, as indicated by the dependence of screening doses for all leukemia as a group (Table 4-31) on age at exposure and time si nce exposure when cancer was diagnosed (see Section 4.1.3), this alternative may not be valid when using screening dose s in that table. For example, it may not be valid if significant external doses were received in di fferent years, or if a
substantial fraction of th e total equivalent dose resulted from intakes of long-lived radionuclides that are tenaciously retained in the body and deli ver a dose over many years. In both examples, an assumption that a total equivalent dose wa s received at the youngest age at exposure could
result in a substantial underestim ate of ERR and PC in some cases. We now consider the use of screening doses to demonstrate that estimated equivalent doses correspond to an upper 99% credibility limit of PC that is clearly greater than 50%. One of two approaches to comparing the total equivalent dose with a screening dose (again with due
consideration of its accuracy) can be used. 3 2 The first approach, which can be used for all cancer types, is to use only the highest equivalent dose in any year. This approach is particularly

32 The approaches described here apply only if acu te exposure is assumed, because an assumption of acute exposure to photons or electrons was used in calculating all screening doses. If chronic exposure were assumed, in which case the full DDREF in IREP w ould be applied, the estimated PC at a given dose would be less and, therefore, the applicable screening dose would be greater than values tabulated in this report. As noted previously, VA assumes that all exte rnal exposures to photons or electrons are acute in using IREP to calculate an upper 99% credibility limit of PC, in order to be more favorable to claimants; only internal exposures to those radiation types are assumed to be chronic. The restriction to an assumption of acute exposure does not apply when a scr eening dose is used to demonstrate that estimated equivalent doses correspond to an upper 99% credibility limit of PC that is clearly less than 50%.33 appropriate when the total dose is dominated by the dose in a single year. If the highest equivalent dose in any year equals or exceeds th e screening dose for that age at exposure and time since exposure when cancer was diagnosed, the upper 99% credibility limit of PC would clearly be greater than 50%. The second approach is to compare the tota l equivalent dose with the screening dose that applies to the oldest age at exposure and a time since exposure given by the difference between the age at diagnosis and the youngest age at exposure (age during the year of first exposure). This appro ach is valid except when using sc reening doses for all leukemia as a group (Table 4-31) or ALL (Table 4-33) for so me ages at exposure and times since exposure.

4.4 Summary Discussion of Calculated Screening Doses

In considering and using screening doses ta bulated in this report, certain assumptions
embodied in the calculations with IREP and th e implications of thos e assumptions should be borne in mind. Important points about sc reening doses are summarized as follows:

• All screening doses were calcu lated using the default number of iterations per run (2000) and random seed (99) in IREP; these defaults are assumed by VA when IREP is used to calculate an upper 99% credibili ty limit of PC for the purpose of evaluating causation of cancer in veterans who were exposed to ioni zing radiation. Since calculated screening doses can vary substantially with changes in the number of iterations per run and the random seed, screening doses should not be in terpreted as giving e quivalent doses that correspond to an upper 99% credibility limit of PC of exactly 50% (see Section 4.1.2).

• All screening doses were cal culated by assuming acute e xposure to high-energy photons (> 250 keV) or higher-energy electrons (> 15 keV) to be consistent with assumptions used by VA in using IREP to calculate an uppe r 99% credibility limit of PC in cases of external exposure to those ra diation types. Screening doses that would be obtained by assuming chronic exposure to those radiati on types are higher (see Section 4.1.1.).

• Screening doses can be used when exposure to alpha particles or neutrons occurred. However, uncertainties in the biological eff ectiveness of those radi ations (including an34 inverse dose-rate effect) need to be taken into account when an estimated equivalent dose to be used in comparisons w ith a screening dose is intended to be an upper bound (at least an upper 95% credibility limit). Caution is also advised in using screening doses for various types of leukemia when doses from al pha particles or neutr ons are a significant contributor to the total equiva lent dose (see Section 4.3.1).

• All screening doses are presen ted to two significant figures . This is an important consideration when a screening dose is 100 rem or greater. Each screening dose is the lowest equivalent dose (to two significan t figures) at which the calculated upper 99% credibility limit of PC is 50% or greater ; a screening dose is not necessarily the equivalent dose that gives a calculated upper 99% credibility limit of PC closest to 50%.

• On the basis of an analysis of the variati on in calculated screening doses due only to a change in the random seed in IREP when the number of iterations per run is fixed at the default value (see Section 4.1.2) , the equivalent dose that corresponds to an actual upper 99% credibility limit of PC of 50% could diffe r from a screening dose tabulated in this report by no more than ±12% in the worst case. This di fference should be less than ±10% in almost all cases of practical interest in VA radiation claims.

Screening doses tabulated in this report are potentially useful in several ways. When due consideration is given to thei r accuracy, screening doses can be used to indicate whether the upper 99% credibility limit of PC associated with estimated equivalent doses is clearly less than 50% or clearly greater th an 50%. Thus, for example, they can be used to provide a check of the validity of calculated upper 99% credibility limits of PC and the resulting decision on granting a claim for compensation for cancer in specific cases. More generally, we believe that the most important use of screening doses is to give a genera l indication of the ma gnitude of radiation doses that are required to warrant a favorable compensation decision.35 Table 4-1. Screening doses (rem) calculated with IREP: Cancers of oral cavity and pharynx (including lip) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 110 32 45 61 77 93 (98) d

20 160 43 59 76 95 120
25 300 82 110 140 160 160
30 530 150 170 210 210 210
35 740 190 210 210 210 210

≥ 40 890 210 210 210 210 210

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).36 Table 4-2. Screening doses (rem) calculated with IREP: Cancer of esophagus a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 41 12 16 22 28 33 (35) d

20 56 15 21 28 34 40
25 120 28 37 47 56 56
30 210 50 61 72 72 72
35 270 64 72 72 72 72

≥ 40 340 77 72 72 72 72

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).37 Table 4-3. Screening doses (rem) calculated with IREP: Cancer of stomach a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 40 9.0 13 17 22 26 (27) d

20 54 12 16 21 27 32
25 110 22 29 37 44 44
30 210 40 48 58 58 58
35 270 50 58 58 58 58

≥ 40 330 61 58 58 58 58

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).38 Table 4-4. Screening doses (rem) calculated with IREP: Cancer of colon a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 40 12 17 24 31 37 (39) d

20 54 16 23 31 38 45
25 110 33 41 54 64 64
30 210 57 70 85 85 85
35 280 74 85 85 85 85

≥ 40 330 89 85 85 85 85

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).39 Table 4-5. Screening doses (rem) calculated with IREP: Cancer of rectum (including anus and anal canal) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 150 36 50 66 83 100 (110) d

20 190 48 63 83 110 130
25 370 91 120 150 180 180
30 650 160 200 230 230 230
35 880 210 230 230 230 230

≥ 40 1100 240 230 230 230 230

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).40 Table 4-6. Screening doses (rem) calculated with IREP: Cancers of digestive tract other than stomach, colon, and rectum a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 76 22 30 42 53 63 (66) d

20 110 28 38 51 64 75
25 190 49 63 81 96 96
30 310 79 96 120 120 120
35 410 110 120 120 120 120

≥ 40 510 130 120 120 120 120

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific organs and tissues to which this cancer type applies are liste d in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.1.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).41 Table 4-7. Screening doses (rem) calculated with IREP: Cancer of liver (including biliary system) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 15 4.0 5.3 7.3 8.8 11 (11) d

20 19 5.2 6.7 8.5 11 13
25 35 8.5 11 14 16 16
30 60 14 17 20 20 20
35 78 18 20 20 20 20

≥ 40 96 22 20 20 20 20

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.1.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).42 Table 4-8. Screening doses (rem) calculated with IREP: Cancer of gallbladder (including bile ducts) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 24 6.0 7.8 11 13 16 (17) d

20 33 7.6 9.8 13 16 18
25 68 14 17 21 24 24
30 130 24 27 33 33 33
35 160 30 33 33 33 33

≥ 40 190 34 33 33 33 33

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).43 Table 4-9. Screening doses (rem) calculated with IREP: Cancer of pancreas a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 120 31 42 55 70 84 (89) d

20 150 40 53 70 86 110
25 310 74 93 130 150 150
30 540 140 160 200 200 200
35 710 170 200 200 200 200

≥ 40 900 200 200 200 200 200

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).44 Table 4-10. Screening doses (rem) calculated with IREP: Cancer of lung (including trachea and bronchus) – I a , b Time since exposure when cancer was diagnosed (y) c Smoking status Age at exposure (y) 5 10 ≥ 15 Never smoker Any 220 46 44 Former smoker Any 530 130 130
Current smoker d Any 720 160 150

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Sections 3.1.3 and 3.1.4.

c Difference between age at diagnosis and age at exposure. d Screening doses apply when the number of ciga rettes smoked per day is unknown. IREP also calculates PC for separate smoking categories of < 10, 10-19, 20-40, and ≥ 40 cigarettes per day; screening doses for these smoking categories are simila r to values for former smokers and current smokers with an unknown number of cigarettes smoked per day.45 Table 4-11. Screening doses (rem) calculated with IREP:

Cancer of lung (including trachea and bronchus) – II a , b , c Time since exposure when cancer was diagnosed (y) d Age at exposure (y) 5 10 15 20 25 ≥ 30

18 58 95 100 18 23 23 26 32 33 35 43 44 44 54 54 52 (54) e 63 (66) 64 (68)
20 76 120 140 24 30 31 33 41 42 44 54 54 55 65 67 63 76 78
25 150 250 250 45 56 57 60 71 73 77 89 91 90 110 110 90 110 110
30 270 420 440 80 95 97 100 120 120 120 140 140 120 140 140 120 140 140
35 360 550 570 100 120 120 120 140 140 120 140 140 120 140 140 120 140 140

≥ 40 450 680 720 130 150 150 120 140 140 120 140 140 120 140 140 120 140 140

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed with Version 5.3 of NIH-IREP (Land et al., 2003). The risk model for this cancer type is described in Sections 3.1.2 and 3.1.4.

c For each age at exposure and time since exposure when cancer was diagnosed, first entry gives the screening dose for never smokers, second entry giv es the screening dose for former smokers, and third entry gives the screening dose for current smokers that applies when the number of cigarettes smoked per day is unknown. IREP also calculates PC for separate smoking categories of < 10, 10-19, 20-40, and ≥ 40 cigarettes per day; screening doses for these smok ing categories are similar to values for former smokers and current smokers with an unknow n number of cigarettes smoked per day. d

Difference between age at diagnosis and age at exposure.

e First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).46 Table 4-12. Screening doses (rem) calculated with IREP: Cancers of respiratory tract other than lung a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 150 34 47 62 79 94 (100) d

20 210 45 59 78 95 120
25 360 83 110 130 160 160
30 630 150 170 210 210 210
35 840 190 210 210 210 210

≥ 40 1100 220 210 210 210 210

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific organs and tissues to which this cancer type applies are liste d in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).47 Table 4-13. Screening doses (rem) calculated with IREP: Cancer of bone a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 3 5 10 15 20 25 ≥ 30
18 33 10 14 21 30 38 45 (48) d

20 47 14 19 28 37 47 55
25 96 32 37 51 64 76 76
30 190 61 66 84 110 110 110
35 270 83 84 110 110 110 110

≥ 40 320 110 110 110 110 110 110

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed with Vers ion 5.5 of NIOSH-IREP (NIOSH, 2002); see Section 4.1.1, footnote 13. The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).48 Table 4-14. Screening doses (rem) calculated with IREP: Cancers of connective tissue (inc luding other soft tissue not listed) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 48 16 23 31 39 47 (50) d

20 69 21 29 39 49 58
25 140 41 53 67 80 80
30 260 72 87 110 110 110
35 330 92 110 110 110 110

≥ 40 410 120 110 110 110 110

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer types occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).49 Table 4-15. Screening doses (rem) calculated with IREP: Malignant melanoma of skin a , b Time since exposure when cancer was diagnosed (y) c White, non-hispanic d Black d Age at exposure (y) 5 10 ≥ 15 5 10 ≥ 15
18 35 6.3 5.9 28 5.6 5.3
20 49 8.4 7.9 37 7.7 7.3
25 94 17 16 72 15 15
30 190 33 31 140 30 29
35 310 55 51 250 49 47

≥ 40 550 91 86 440 80 77

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.5.

c Difference between age at diagnosis and age at exposure. d

IREP also calculates risks of skin cancers for the following racial or ethnic groups: American Indians or Alaska natives; Asians, native Hawaiians, or other Pacific islanders; and white Hispanics.50 Table 4-16. Screening doses (rem) calculated with IREP: Basal cell carcinoma of skin a , b Time since exposure when cancer was diagnosed (y) c White, non-hispanic d Black d Age at exposure (y) 5 10 ≥ 15 5 10 ≥ 15
18 36 6.2 5.9 18 3.2 3.1
20 48 8.5 7.9 24 4.3 4.0
25 94 17 16 46 7.9 7.4
30 190 33 31 89 15 15
35 320 54 51 160 26 24

≥ 40 550 89 87 270 44 42

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.5.

c Difference between age at diagnosis and age at exposure. d IREP also calculates risks of skin cancers for th e following racial and ethnic groups: American Indians or Alaska natives; Asians, native Hawaiians, or other Pacific islanders; and white Hispanics.51 Table 4-17. Screening doses (rem) calculated with IREP: Squamous cell carcinoma of skin a , b Time since exposure when cancer was diagnosed (y) c White, non-hispanic d Black d Age at exposure (y) 5 10 ≥ 15 5 10 ≥ 15
All 2500 310 300 1100 160 150

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.5.

c Difference between age at diagnosis and age at exposure. d IREP also calculates risks of skin cancers for th e following racial and ethnic groups: American Indians or Alaska natives; Asians, native Hawaiians, or other Pacific islanders; and white Hispanics.52 Table 4-18. Screening doses (rem) calculated with IREP: Cancer of breast (female) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 49 14 22 33 43 53 (57) d

20 64 18 27 39 51 62
25 130 32 45 60 75 75
30 230 51 66 84 84 84
35 300 69 84 84 84 84

≥ 40 380 89 84 84 84 84

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.1.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).53 Table 4-19. Screening doses (rem) calculated with IREP: Cancer of breast (male) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 38 12 20 30 41 50 (53) d

20 51 16 25 37 49 58
25 94 29 41 56 70 70
30 160 46 61 78 78 78
35 210 63 78 78 78 78

≥ 40 270 80 78 78 78 78

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.1.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).54 Table 4-20. Screening doses (rem) calculated with IREP: Cancer of ovary a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 42 14 19 25 32 38 (41) d

20 60 17 23 32 39 46
25 120 33 42 53 63 63
30 220 57 69 82 82 82
35 290 73 82 82 82 82

≥ 40 350 87 82 82 82 82

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).55 Table 4-21. Screening doses (rem) calculated with IREP: Cancers of all female genitalia other than ovary a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 ≥ 15
All 26000 1600 1500

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.3.

c Difference between age at diagnosis and age at exposure.56 Table 4-22. Screening doses (rem) calculated with IREP: Cancers of all male geni talia (including prostate) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 89 21 28 38 47 56 (60) d

20 120 27 36 47 57 68
25 250 50 61 77 91 91
30 420 85 99 120 120 120
35 490 110 120 120 120 120

≥ 40 650 130 120 120 120 120

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).57 Table 4-23. Screening doses (rem) calculated with IREP: Cancer of bladder a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 48 16 22 31 38 46 (49) d

20 64 21 29 38 47 56
25 140 40 51 64 77 77
30 260 69 84 100 100 100
35 330 88 100 100 100 100

≥ 40 400 110 100 100 100 100

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).58 Table 4-24. Screening doses (rem) calculated with IREP: Cancers of kidney and other ur inary organs except bladder a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 41 14 21 29 36 44 (46) d

20 57 19 27 36 45 53
25 120 38 49 63 75 75
30 220 67 83 100 100 100
35 290 87 100 100 100 100

≥ 40 370 110 100 100 100 100

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific organs and tissues to which this cancer type applies are liste d in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).59 Table 4-25. Screening doses (rem) calculated with IREP: Cancer of eye a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 51 16 23 30 39 47 (49) d

20 71 21 29 39 48 57
25 150 41 52 67 78 78
30 270 73 87 110 110 110
35 360 92 110 110 110 110

≥ 40 430 120 110 110 110 110

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).60 Table 4-26. Screening doses (rem) calculated with IREP: Cancers of nervous syst em (including brain) a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 120 32 44 60 74 89 (95) d

20 170 42 57 73 92 110
25 350 78 100 130 150 150
30 570 140 160 190 190 190
35 760 170 190 190 190 190

≥ 40 960 200 190 190 190 190

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific organs and tissues to which this cancer type applies are liste d in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).61 Table 4-27. Screening doses (rem) calculated with IREP: Cancer of thyroid a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 3 5 ≥ 10
18 44 9.4 7.5

20 51 11 8.3
25 71 15 12
30 110 23 18
35 160 34 26
40 180 36 29
45 220 39 31

≥ 50 250 43 34

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed with Vers ion 5.5 of NIOSH-IREP (NIOSH, 2002); see Section 4.1.1, footnote 13. The risk model for this cancer type is described in Section 3.1.5.

c Difference between age at diagnosis and age at exposure.62 Table 4-28. Screening doses (rem) calculated with IREP: Cancers of endocrine gla nds other than thyroid a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 42 14 20 28 36 42 (45) d

20 58 19 27 35 44 51
25 130 37 47 61 74 74
30 230 66 81 96 96 96
35 290 83 96 96 96 96

≥ 40 360 99 96 96 96 96

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).63 Table 4-29. Screening doses (rem) calculated with IREP: Cancers of other and ill-defined sites a , b Time since exposure when cancer was diagnosed (y) c Age at exposure (y) 5 10 15 20 25 ≥ 30
18 52 16 23 31 40 48 (50) d

20 72 21 29 39 49 58
25 150 42 53 68 81 81
30 280 74 88 110 110 110
35 360 93 110 110 110 110

≥ 40 430 120 110 110 110 110

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed w ith Version 5.4 of NIOSH-IREP (NIOSH, 2002). The risk model for this cancer type is described in Section 3.1.2.

c Difference between age at diagnosis and age at exposure. d

First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).64 Table 4-30. Screening doses (rem) calculated with IREP: Lymphoma and multiple myeloma a , b , c Time since exposure when cancer was diagnosed (y) d Age at exposure (y) 5 10 15 20 25 ≥ 30
18 96 22 30 38 48 57 (61) e
20 120 29 37 47 59 70
25 230 50 64 78 93 93
30 420 88 110 130 130 130
35 520 110 130 130 130 130

≥ 40 690 140 130 130 130 130

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Calculations were performed with Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific diseases to which this cancer type applies are listed in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.2.

c VA assumes that chronic lymphocytic leukemia (CLL) is a form of non-Hodgkin’s lymphoma. d

Difference between age at diagnosis and age at exposure.

e First entry applies at time since exposure of 30 years; second entry in parentheses applies at time since exposure of 32 years or greater (age at diagnosis of 50 years or greater).65 Table 4-31. Screening doses (rem) calculated with IREP: All leukemia excluding chronic lymphocytic leukemia (CLL) a , b , c Time since exposure when cancer was diagnosed (y) d Age at exposure (y) 3 5 10 15 20 25 30 35 40 45 ≥ 50

18 2.2 1.9 4.4 9.1 17 28 41 58 78 110 140
20 2.5 2.2 4.8 9.8 18 29 42 59 79 110 140
25 3.4 3.0 6.1 12 20 31 44 59 78 100 130
30 4.5 3.9 7.4 14 22 32 44 57 73 92 120
35 5.7 5.0 8.8 15 23 32 42 53 65 78 94
40 6.9 6.0 11 16 24 31 38 46 53 61 69
45 8.0 7.0 12 17 23 29 34 37 40 43 46
50 9.2 8.0 12 18 23 26 28 29 29 28 27

≥ 55 11 8.8 13 19 22 24 23 21 19 17 15

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b The corresponding cancer type in the CIRRPC tabl e (Table 2-1) is leukemia (excluding chronic lymphatic).

c Calculations were performed with Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific diseases to which this cancer type applies are listed in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.5. d

Difference between age at diagnosis and age at exposure.66 Table 4-32. Screening doses (rem) calculated with IREP: Chronic myeloid leukemia (CML) a , b , c Time since exposure when cancer was diagnosed (y) d Age at exposure (y) 3 5 10 15 20 25 30 35 40 45 50

All 1.6 1.4 5.0 12 22 37 57 86 130 180 240

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b The corresponding cancer type in the CIRRPC table (Table 2-1) is chronic granulocytic leukemia.

c Calculations were performed with Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific diseases to which this cancer type applies are listed in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.5. d

Difference between age at diagnosis and age at exposure.67 Table 4-33. Screening doses (rem) calculated with IREP: Acute lymphocytic leukemia (ALL) a , b , c Time since exposure when cancer was diagnosed (y) d Age at exposure (y) 3 5 10 15 20 25 30 35 40 45 50

18 0.28 0.24 0.91 2.7 6.5 13 24 40 64 110 160

≥ 20 19 16 e

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Acute leukemia of unspecified type is included in the CIRRPC table (Table 2-1).

c Calculations were performed with Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific diseases to which this cancer type applies are listed in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.5. d

Difference between age at diagnosis and age at exposure.

e Entry applies at all times since exposure when cancer was diagnosed of 5 years or greater.68 Table 4-34. Screening doses (rem) calculated with IREP: Acute myeloid leukemia (AML) a , b , c Time since exposure when cancer was diagnosed (y) d Age at exposure (y) 3 5 10 15 20 25 30 35 40 45 50

All 6.7 5.8 9.1 14 19 25 29 33 35 38 39

a Screening doses are equivalent doses, to two signi ficant figures, to the organ or tissue in which cancer type occurs that are intended to correspond to an upper 99% credibility limit of PC of 50%. Calculations are described in Section 4.1.1 a nd the accuracy of screening doses is discussed in Section 4.1.2. b Acute leukemia of unspecified type is included in the CIRRPC table (Table 2-1).

c Calculations were performed with Version 5.4 of NIOSH-IREP (NIOSH, 2002). Specific diseases to which this cancer type applies are listed in Table 4 of NIOSH (2002), and the risk model for this cancer type is described in Section 3.1.5. d

Difference between age at diagnosis and age at exposure.69 Table 4-35. Lowest screening doses for any ag e at exposure and time since exposure when cancer was diagnosed for all cancer types calculated with IREP a
Cancer type Screening dose (rem) Cancer type Screening dose (rem) Oral cavity and pharynx (including lip) 32 Non-melanoma basal cell carcinoma of skin 3.1 (5.9) c

Esophagus 12 Non-melanoma squamous cell carcinoma of skin 150 (300) c

Stomach 9.0 Breast (female) 14 Colon 12 Breast (male) 12 Rectum (including anus and anal canal) 36 Ovary 14

Digestive tract other than stomach, colon, and rectum 22 All female genitalia other than ovary 1500

Liver (including biliary system) 4.0 All male genitalia (including prostate) 21

Gallbladder (including bile ducts) 6.0 Bladder 16

Pancreas 31 Kidney and other urinary organs except bladder 14

Lung (including trachea and bronchus) b 18 Eye 16

Respiratory tract other than lung 34 Nervous system (including brain) 32

Bone 10 Thyroid 7.5
Connective tissue (including other soft tissues not listed) 16 Endocrine glands other than thyroid 14

Malignant melanoma of skin 5.3 (5.9) c Other and ill-defined sites 16

Table is continued on following page.70 Table 4-35. (continued)
Cancer type Screening dose (rem) Cancer type Screening dose (rem) Lymphoma and multiple myeloma 22 Acute lymphocytic leukemia (ALL) 0.24

Leukemia excluding chronic lymphocytic leukemia (CLL) 1.9 Acute myeloid leukemia (AML) 5.8

Chronic myeloid leukemia (CML) 1.4

a Lowest screening dose for each cancer type is obtained from Tables 4-1 through 4-34. Values apply to age at exposure of 18 and shortest time since exposure when cancer was diagnosed at which assumption about minimum latency period does not have significant effect on estimated risk (see Section 3.2). b Lowest screening dose for never smokers calculated with NIH-IREP (Land et al., 2003) and obtained from Table 4-11. Lowest screening dose calculated with NIOSH-IREP (NIOSH, 2002) and given in Table 4-12 is higher.

c First entry applies to blacks; second entry in parentheses applies to white, non-Hispanics.71 REFERENCES

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ICRP 21(1-3) (Pergamon Press, New York, NY). Kocher, D.C., Apostoaei, A.I., and Hoffman, F.O., 2002. Radiation Effectiveness Factors (REFs) for Use in Calculating Probability of Causation of Radiogenic Cancers (SENES Oak Ridge, Inc., Oak Ridge, TN). Available at: http://www.cdc.gov/niosh/ocas /pdfs/irep/irepref.pdf. Kocher, D.C., Apostoaei, A.I., and Hoffman, F. O., 2005. “Radiation Effectiveness Factors for Use in Calculating Probability of Causation of Radiogenic Cancers,” Health Phys. 89(1),
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2003. Report of the NCI-CDC Working Group to Revise the 1985 NIH Radioepidemiological Tables (U.S. Department of H ealth and Human Services, Washington, DC).72 Mansfield, G.H., 2005. Letter to M. Strehlow an d H.D. Royal, Veterans Advisory Committee on Environmental Hazards (The Deputy Secretar y of Veterans Affairs, Washington, DC) (April 22). Mather, S.H., and Otchin, N.S., 2004. Letter to M. Strehlow and H.D. Royal, Veterans Advisory Committee on Environmental Hazards (Office of Public Health and Environmental Hazards, Department of Veterans Affa irs, Washington, DC) (February 2). NIH (National Institutes of Health), 1985. Report of the National Inst itutes of Health Ad Hoc Working Group to Develop Radioepidemiological Tables , NIH Publication No. 85-2748 (National Institutes of Health, Washington, DC). NIOSH (National Institute for Occupa tional Safety and Health), 2002. NIOSH-Interactive RadioEpidemiological Progr am (IREP) Technical Documentation; Final Report

. Available at: http://www.cdc.gov/niosh/o cas/pdfs/irep/i repfnl.pdf. NRC (National Research Council), 1980. The Effects on Populations of Exposure to Low Levels of Ionizing Radiation , BEIR III Report (National Academy of Sciences, Washington, DC). NRC (National Research Council), 1990. Health Effects of Exposure to Low Levels of Ionizing
Radiation—BEIR V (National Academy Press, Washington, DC). VHA/OPHEH (Veterans Health Administration, Office of Public Health and Environmental Hazards), 2003. “Standard Operating Procedures—Use of the ‘Interactive RadioEpidemiological Program’ (IREP) for Form ulating Medical Opinions to Assist in Adjudication of Some VA Radi ation Compensation Claims” (Off ice of Public Health and Environmental Hazards, Department of Veterans Affairs, Washington, DC) (December 17).73 DISTRIBUTION LIST DTRA-TR-07-4
Additional copies are available at: http://www.dtra.mil/rd/programs /nuclear_personnel/pubs.cfm

DEPARTMENT OF DEFENSE

Defense Technical Information Center 8725 John J. Kingman Road, Suite 0944 Fort Belvoir, VA 22060-6201 2 CYS ATTN: DTIC/OCA
Defense Threat Reduction Agency 8725 John J. Kingman Road, RD-NTSN Fort Belvoir, VA 22060-6201
United States Army Director, Proponency Office for Preventive Medicine 2050 Worth Road, Suite 25 San Antonio, TX 78234-6025
US Army Radiation Standa rds & Dosimetry Laboratory ATTN: AMSAM-TMD-SR-D Bldg. 5417 Redstone Arsenal, AL 35898-5000
United States Navy Head, Ionizing Radiation Branch M342 Bureau of Medicine and Surgery 2300 E. Street NW Washington, DC 20372-5300
United States Navy Naval Dosimetry Center Bethesda, MD 20889-5614

United States Air Force AFMOA/SGZR 110 Luke Ave., Suite 405 Bolling AFB, DC 20332-7050

United States Air Force AFIOH/SDRR/Radiatio n Dosimetry Lab. 2350 Gillingham Drive Brooks City - Base, TX 78235-510374 Armed Forces Radiobiology Research Institute 8901 Wisconsin Avenue Bethesda, MD 20889-5603

DEPARTMENT OF VETERANS AFFAIRS
Department of Veterans Affairs Chief, Public Health & Environmental Hazards VA Central Office (13) 810 Vermont Ave., NW Washington, DC 20420
Department of Veterans Affairs Director, Compensation and Pension Service VA Central Office (210A) 810 Vermont Ave., NW Washington, DC 20420

DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institute of Occupational Safety and Health Director, Compensation Analysis and Support Robert A. Taft Laboratories 4676 Columbia Parkway Cincinnati, OH 45226-1998

DEPARTMENT OF LABOR
U. S. Department of Labor, DEEOIC 200 Constitution Avenue NW, Room C-3321 Washington, DC 20210

DEPARTMENT OF JUSTICE
Department of Justice Civil Division - Radiation E xposure Compensation Program Ben Franklin Station PO Box 146 Washington, DC 20044-0146

FEDERAL AGENCY ADVISORY BOARDS
Veterans’ Advisory Board on Dose Reconstruction 7910 Woodmont Avenue, Suite 400 Bethesda, MD 20814-309575 Veterans’ Advisory Committ ee on Environmental Hazards Department of Veterans Affairs Compensation and Pension Service VA Central Office (210A) 810 Vermont Ave., NW Washington, DC 20420
Advisory Board on Radiation and Worker Health 4676 Columbia Parkway, MS: C-46 Cincinnati, OH 45226

DEPARTMENT OF DEFENSE CONTRACTORS

ITT Industries ITT Systems Corporation 1680 Texas Street, SE Kirtland AFB, NM 87117-5669 2 CYS ATTN: DTRIAC ATTN: DARE

L3 Communications 11410 Isaac Newton Square North, Suite 103 Reston, VA 20190-5005
Senes Oak Ridge, Inc. 102 Donner Drive Oak Ridge, TN 37830

SAIC 8301 Greensboro Drive, M/S E-5-5 McLean, VA 22102
Oak Ridge Associated Universities 4850 Smith Road, Suite 200 Cincinnati, OH 45212

S. Cohen and Associates 6858 Old Dominion Drive, Suite 301 McLean, VA 22101