SCA-TR-TASK3-0008, Rev. 3 

DRAFT 

NATIONAL INSTITUTE FOR 

OCCUPATIONAL SAFETY AND HEALTH 

ADVISORY BOARD ON RADIATION AND WORKER HEALTH 

TASK 3: REVIEW OF NIOSH/ORAUT PROCEDURES AND METHODS 

USED FOR DOSE RECONSTRUCTION 

A PRELIMINARY REVIEW OF NIOSH’S PROGRAM EVALUATION REPORT 

OCAS-PER-009, “TARGET ORGANS FOR LYMPHOMAS” 

Contract No. 200-2004-03805 

SCA-TR-TASK3-0008, Rev. 3 

Prepared by 

SC&A, Inc. 

S. Cohen & Associates 

1608 Spring Hill Road, Suite 400 

Vienna, VA 22182 

June 2008 

Disclaimer 

This document is made available in accordance with the unanimous desire of the Advisory Board on 

Radiation and Worker Health (ABRWH) to maintain all possible openness in its deliberations. However, 

the ABRWH and its contractor, SC&A, caution the reader that at the time of its release, this report is predecisional and has not been reviewed by the Board for factual accuracy or applicability within the 

requirements of 42 CFR 82. This implies that once reviewed by the ABRWH, the Board’s position may 

differ from the report’s conclusions. Thus, the reader should be cautioned that this report is for 

information only and that premature interpretations regarding its conclusions are unwarranted.

 
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Document No. 

SCA-TR-TASK3-0008 

Effective Date: 

Draft — June 20, 2008 

S. COHEN & ASSOCIATES: 

Technical Support for the Advisory Board on

Radiation & Worker Health Review of 

NIOSH Dose Reconstruction Program Revision No. 3 – (Draft) 

Task 3: Review of NIOSH/ORAUT Procedures 

And Methods Used For Dose Reconstruction 

A PRELIMINARY REVIEW OF NIOSH’S 

PROGRAM EVALUATION REPORT 

OCAS-PER-009, “TARGET ORGANS FOR 

LYMPHOMAS” 

Page 2 of 44 

Co-Task Managers: 

________________________ Date: ___________ 

U. Hans Behling, PhD, MPH 

________________________ Date: ___________ 

John J. Mauro, PhD, CHP 

Project Manager: 

________________________ Date: ___________ 

John J. Mauro, PhD, CHP 

Supersedes: 

Rev. 2 
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TABLE OF CONTENTS 

Executive Summary.........................................................................................................................5 

1.0 Statement of Purpose ...........................................................................................................7 

2.0 Subtask 1: Conduct a Critical Review and Analysis of the “Issue” that Served as 

the Basis for OCAS-PER-009 and Assess the Circumstance under which SC&A 

First Became Aware of the Issue .........................................................................................8 

3.0 Subtask 2: Assess NIOSH’s Evaluation / Characterization of the Issue and Its 

Potential Impacts on Dose Reconstruction ..........................................................................9 

3.1 Regulatory Basis for OCAS-PER-009.....................................................................9 

3.2 Relevant Background Information...........................................................................9 

3.3 Overview of the ICRP Respiratory Model...............................................................9 

3.3.1 Deposition Fractions within Respiratory Tract..........................................10 

3.3.2 The ICRP Respiratory Tract Clearance Model..........................................12 

3.3.3 Radiological Impacts to Lymph Nodes......................................................14 

3.4 NIOSH’s Response to the Issue.............................................................................15 

4.0 Subtask 3: Assess NIOSH’s Specific Sources of Information to Ensure the 

Credibility of the Corrective Action and Its Consistency with Current/Consensus 

Science ...............................................................................................................................16 

4.1 Excerpts from Section Seven, § 500 – Lymphoreticular Neoplasms (Beeson 

et al., 1979) ............................................................................................................16 

4.2 Excerpts from § 501 – Non-Hodgkin’s Lymphomas (Beeson et al., 1979) ..........18 

4.3 Summary Conclusions Regarding the Reliability of ICD-9 Codes for Dose 

Reconstruction of Lymphomas..............................................................................18 

5.0 Subtask 4: Evaluate the PER’s Stated Approach for Identifying the Universe of 

Potentially Affected Dose Reconstructions; or Assess the Criteria by which a 

Subset of Potentially Affected Dose Reconstructions was Selected for Re-Evalution .....20 

5.1 Preliminary Conclusions and Recommendations ..................................................20 

5.2 Smoking as Modifying Agent that May Require Further Consideration...............23 

6.0 Subtask 5: Conduct Audits of Dose Reconstructions Selected by the Advisory 

Board, which were Affected by OCAS-PER-009..............................................................24 

6.1 Audit of Dose Reconstructions Involving Lymphomas.........................................24 

7.0 References..........................................................................................................................26 

Appendix A-1: NIOSH Memorandum Dated April 18, 2008.....................................................27 

Appendix A-2: NIOSH E-mail Dated May 1, 2008 ...................................................................36 

Appendix B: NIOSH White Paper..............................................................................................37 

Appendix C: Dr. Crowther Report..............................................................................................39 

Appendix D: Dr. Eckerman Report ............................................................................................41 
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LIST OF TABLES 

Table 1. Compartmental Deposition Fractions ..........................................................................10 

Table 2. ICRP Respiratory Tract Reference Clearance Rates for Insoluble Particulates ..........14 

Table 3. Regional Committed Dose Equivalents for Intake of 1 Bq of a Long-Lived, 

Type S Alpha-Emitter..................................................................................................14 

Table 4. Classification of Lymphoreticular Neoplasms* ...........................................................17 

Table 5. Sample Information .....................................................................................................22 

Table 6. Dose Distribution for a Single Acute Intake of Pu-239...............................................25 

LIST OF FIGURES 

Figure 1. Respiratory Tract Compartment for which Inhaled Particles May Be Deposited .......10 

Figure 2. Fractional Deposition in Each Region of Respiratory Tract for Reference 

Worker (Normal Nose Breather) .................................................................................11 

Figure 3. Fractional Deposition in Each Region of Respiratory Tract for Reference 

Worker (Mouth Breather) ............................................................................................12 

Figure 4. Compartment Model to Represent Time-Dependent Particle Transport 

from Each Region ........................................................................................................13 
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EXECUTIVE SUMMARY 

During the Advisory Board on Radiation and Worker Health (Advisory Board or Board) 

conference call held on November 27, 2007, SC&A was directed to perform a review of Program 

Evaluation Report (PER)-009. The purpose of a PER is to establish a formal process for 

evaluating the effects of new information on previously adjudicated claims that have been 

denied. The PER process was developed by the National Institute for Occupational Safety and 

Health (NIOSH) in recognition that our scientific understanding of the factors that bear on a dose 

reconstruction is continually improving. In addition, new information could also come to light 

regarding the nature and types of exposures that a given worker might have experienced. When 

such new information becomes available, it is incumbent upon NIOSH to re-evaluate worker 

dose reconstructions that might be impacted by the new information. 

As a result of ongoing reviews, it became apparent to NIOSH that the methods being used to 

reconstruct the doses to workers that contracted lymphoreticular neoplasms (cancer of the lymph 

nodes) required revision, revisions that could result in very large increases in the derived doses to 

the organs of concern and the possible reversal of previously denied claims. 

The need for a revision to the dose reconstruction methodology became apparent when NIOSH 

recognized that its standard method for reconstructing the doses to workers with cancer of the 

lymph nodes, which made use of a surrogate organ, could substantially underestimate the doses 

to the affected lymph nodes. NIOSH’s standard procedure for deriving doses to lymph nodes 

was based on the assumption that an upper bound on the doses to the organ of concern could be 

derived by using the colon (or the highest non-metabolic organ) as a surrogate organ. For 

reasons that are described in the main body of this report, this assumption could result in doses 

that are low by 2 to 3 orders of magnitude. 

In order to address this issue, NIOSH implemented PER-009, which establishes a new protocol 

for reconstructing the doses to the organ of concern for workers with cancer of the lymph nodes. 

NIOSH used this new methodology to reconstruct the doses to all workers whose reconstructed 

doses could be impacted by this new procedure and whose claims were previously denied. The 

outcome of this process was the re-evaluation of 528 claims. Of these 528 claims, 152 

previously denied claims were now granted compensation, 23 claims were returned to NIOSH 

for rework, and 348 claims remained denied. 

Under Task Order 3, the Advisory Board requested that SC&A review the entire process under 

which the 528 lymphoma claims were reviewed. Our review process was divided into five 

subtasks, which are individually discussed in the main body of this report. 

Our review concluded that OCAS-PER-009 reflects revisions to OCAS-TIB-012 and ORAUTOTIB-0005, which correct previous deficiencies for the reconstruction of radiation doses to 

lymphatic tissues associated with the respiratory system. SC&A found that NIOSH was 

extremely thorough in ensuring that all cases that might be affected by the change in protocol 

were explicitly addressed. 
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Our review also identified two issues with potential significance to lymphoreticular neoplasms, 

but which may be outside of NIOSH’s mandate under the Energy Employee Occupational Illness 

Compensation Program Act (EEOICPA) and its implementing regulations. Our primary concern 

pertains to the uncertainty associated with the assignment of a definitive International 

Classification of Diseases (ICD-9) code to a claimant’s lymphoma, which in turn directs NIOSH 

to reconstruct radiation doses to a specific internal and external target organ. It is SC&A’s 

understanding that this concern is outside the purview of NIOSH and may be more appropriately 

addressed by other agencies. 

It is SC&A’s opinion that, for various classes of lymphomas and/or stage of the neoplasm, there 

remains a substantial level of uncertainty regarding (1) the cell-line of origin for the neoplasm, 

and (2) the anatomical location where the neoplastic transformation and/or clonal expansion took 

place. While significant refinements in diagnostic methods have reduced the uncertainty in the 

classification of lymphomas in recent years, of greatest concern are claims in which the cancer 

diagnosis was made at a time when clinical data were inadequate for the assignment of an ICD-9 

code. Uncertainties representing the assignment of ICD-9 codes are discussed in Section 4.3 of 

this report. As pointed out by NIOSH, the assignment of the ICD-9 code to a claimant’s cancer 

is the sole responsibility of the Department of Labor (DOL). Hence, many of the findings 

provided in this report may pertain more to those aspects of the PER process under the purview 

of the DOL than under NIOSH. 

A second concern raised by SC&A relates to smoking and its potential impacts on lymphomas 

associated with lymph nodes of the respiratory tract (LNTH and LNET). The potential impact of 

smoking was not addressed in PER-009 and is briefly summarized in Section 5.2 of our report. 

Regarding the impact of smoking, NIOSH concluded that this is a highly technical issue that 

cannot be resolved by NIOSH at this time and may require a formal review by an ad hoc 

committee of scientific experts. 
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1.0 STATEMENT OF PURPOSE 

 

To support dose reconstruction, the National Institute for Occupational Safety and Health 

(NIOSH) and the Oak Ridge Associated Universities Team (ORAUT) have assembled a large 

body of guidance documents, workbooks, computer codes, and tools. In recognition of the fact 

that all of these supporting elements in dose reconstruction may be subject to revisions, 

provisions exist for evaluating the effect of such programmatic revisions on the outcome of 

previously completed dose reconstructions. Such revisions may be prompted by document 

revisions due to new information, misinterpretation of guidance, changes in policy, and/or 

programmatic improvements. 

The process for evaluating potential impacts of programmatic changes on previously completed 

dose reconstructions has been proceduralized in OCAS-PR-008, Preparation of Program 

Evaluation Reports and Program Evaluation Plans, (OCAS 2006a), Revision 2, dated December 

6, 2006. This procedure describes the format and methodology to be employed in preparing a 

Program Evaluation Report (PER) and a Program Evaluation Plan (PEP). 

A PER provides a critical evaluation of the effect(s) that a given issue/programmatic change may 

have on previously completed dose reconstructions. This includes a qualitative and quantitative 

assessment of potential impacts. Most important in this assessment is the potential impacts on 

the probability of causation (POC) of previously completed dose reconstructions with POCs of 

<50%. 

As needed, a PEP may be issued that serves as a formal notification of an impending PER. The 

PEP provides a preliminary description of the issue(s) that will be addressed in the PER, and 

summarizes the likely scope of the effort required to complete the PER. 

Under the existing Task Order 3 project, SC&A has been tasked by the Advisory Board to 

conduct a review of OCAS-PER-009, Target Organs for Lymphoma (OCAS 2007). In behalf of 

the PER review, SC&A performed five subtasks as authorized by the Board, each of which is 

discussed below.
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2.0 SUBTASK 1: CONDUCT A CRITICAL REVIEW AND ANALYSIS 

OF THE “ISSUE” THAT SERVED AS THE BASIS FOR OCAS-PER-009 

AND ASSESS THE CIRCUMSTANCE UNDER WHICH SC&A FIRST 

BECAME AWARE OF THE ISSUE 

On April 2, 2008, the Procedures Review Work Group held a teleconference that specifically 

assessed Revision 0 of this draft report. Participants in this teleconference included persons 

representing NIOSH. It was during the teleconference that SC&A was first informed that 

NIOSH had initiated a formal technical review of issues leading up to PER-009 on or before 

November 2004. NIOSH explained that on or about July 2004, several members of the NIOSH 

team discussed the possible need to revise the protocol for reconstructing doses to lymph nodes. 

Coincidentally, in November 2004, SC&A completed and delivered a draft review of a dose 

reconstruction for a worker with cancer of the lymph nodes, and discussed the results with 

NIOSH and the Board. In that report, and during those discussions, SC&A was critical of the 

protocol and suggested strategies to improve the methods used to reconstruct doses to lymphatic 

tissue. In the original draft of this report, SC&A was under the impression that it was this review 

that was the genesis of the PER. However, SC&A was subsequently informed by NIOSH that 

SC&A’s review apparently played no significant role in the genesis of the PER (see 

Attachment A-1, memorandum from NIOSH to the working group dated April 18, 2008, and 

Attachment A-2, NIOSH e-mail dated May 1, 2008). As further support for the need for this 

PER and as part of the PER process, NIOSH had several consultants prepare special reports on 

this subject, which are reproduced in Attachments B, C, and D. These attachments are discussed 

below. 
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3.0 SUBTASK 2: ASSESS NIOSH’S EVALUATION / 

CHARACTERIZATION OF THE ISSUE AND ITS POTENTIAL IMPACTS 

ON DOSE RECONSTRUCTION 

3.1 REGULATORY BASIS FOR OCAS-PER-009 

Section § 82.18(b) of Title 42 Part 82 of the Code of Federal Regulations (42 CFR 82) states 

that, “. . . NIOSH will calculate the dose to the organ or tissue of concern using the appropriate 

current metabolic models published by ICRP.” 

Specifically, Section I.G. of the Preamble to the Final Rule for 42 CFR 82 states that, “. . . at this 

time NIOSH will use the new ICRP respiratory tract model for assessing doses due to the 

inhalation of radioactive particles1” [emphasis added]. [Note: Footnote 1 in this citation 

identifies ICRP Publication 66: Human Respiratory Tract Model for Radiological Protection

(ICRP 1993).] 

3.2 RELEVANT BACKGROUND INFORMATION 

For energy employees, inhalation is likely the dominant route for radionuclides to enter the body. 

Once inhaled, the fate and radiological consequence for a given radionuclide is determined by 

numerous physical, chemical, and biological factors. Important factors include particle size of 

the airborne contaminant, its solubility in aqueous media, and its biochemical/metabolic role in 

human physiology. Collectively, these variables will determine the initial distribution of the 

airborne contaminant within the respiratory tract, and subsequently the rate(s) of clearance from 

the respiratory tract, absorption into blood, and/or translocation to and retention by other 

organs/tissues. All of these factors, as well as the unique radiological properties of the inhaled 

radionuclides, will determine the radiation dose to individual tissues. 

A comprehensive discussion of the complex variables that may affect the radiological 

consequences of an inhalation exposure is beyond the scope of this review. Instead, the 

discussion that follows will focus only on those aspects of the inhalation exposure pathway that 

may impact the radiation dose to lymphatic/hematopoietic tissues and affect their risk to cancer 

induction. 

3.3 OVERVIEW OF THE ICRP RESPIRATORY MODEL 

A model for the deposition behavior of airborne particulates in the respiratory tract is 

characterized in ICRP Publication 66 (ICRP 1993). Figure 1 identifies those compartments in 

which inhaled particulates may be initially deposited. Inspection of Figure 1 identifies the 

following compartments: 

• Extrathoracic Airways – The extrathoracic airways consist of two distinct regions 

designated as ET1 and ET2. For this discussion, tissues associated with ET1 are not 

considered relevant. ET2 represents the posterior nasal passages, nasopharynx, 

oropharynx, and larynx. 
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• Thoracic Airways – Particulates that enter the thoracic airways may be deposited in the 

bronchi (BB), bronchioles (bb), and the alveolar interstitium (AI). 

 

Figure 1. Respiratory Tract Compartment for which Inhaled Particles May Be 

Deposited 

(Source: ICRP 1993) 

3.3.1 Deposition Fractions within Respiratory Tract 

Particle deposition within the respiratory tract is heavily affected by the particle size distribution, 

with larger particles differentially depositing in the upper airways. Additional factors affecting 

the fractional deposition include the age and, therefore, the anatomical dimensions of the 

individual’s airways, and the individual’s breathing rate, breathing style (nasal or oro-nasal), and 

other factors that influence inertial impaction and Brownian diffusion. 

Table 1 identifies initial deposition fractions in each of the major regions of the respiratory tract 

for 5-micrometer (μm) AMAD aerosol inhaled by an adult male nose breather. 

Table 1. Compartmental Deposition Fractions 

(Source: ICRP 1993, Table F-1) 

Region Deposition Fraction 

ET1 0.34 

ET2 0.40 

BB 0.018 

Bb 0.011 

AI 0.053 

Total 0.82 
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Figures 2 and 3 graphically illustrate reference deposition values for each major compartment as 

a function of particle size. Reference values are for the adult male nose or mouth breather with a 

respiration rate of 1.2 cubic meters (m3) per hour. Important to note are the variable and 

oscillating deposition fractions for ET1 and ET2. For very small particles (i.e., 0.001 μm), the 

deposition fractions for ET1 and ET2 are about 0.4 each (or 0.8 for both). With increased particle 

size, the deposition fractions decrease and reach a low point for particle sizes of about 0.1 μm 

before rising again to a plateau of about 0.4 fraction for particle sizes of a few microns. 

Figure 2. Fractional Deposition in Each Region of Respiratory Tract for Reference 

Worker (Normal Nose Breather) 

(Source: ICRP 1993)
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Figure 3. Fractional Deposition in Each Region of Respiratory Tract for Reference 

Worker (Mouth Breather) 

(Source: ICRP 1993) 

3.3.2 The ICRP Respiratory Tract Clearance Model 

When inhaled particles deposit onto the epithelial lining of the respiratory tract, their rate of 

removal by absorption and/or mechanical means is highly variable. The ICRP model assumes 

that particles deposited within the anterior nasal passages (i.e., ET1 region) are removed by 

extrinsic means (nose blowing, wiping, etc.) and will, therefore, not be considered within the 

context of this report. 

Material deposited in the nasopharynx, oropharynx, and larynx (or ET2 region) is subject to rapid 

clearance in the layer of fluid/mucus that covers this portion of the respiratory tract. 

Particles deposited in the thoracic airways representing the BB and bb regions are subject to 

modest ciliary clearance rates, while materials deposited in the AI region (which is further 

subdivided among compartments AI1, AI2, and AI3) are successively cleared more slowly. 

Figure 4 depicts the various compartments of the respiratory tract and provides reference/ 

clearance rates expressed in terms of the fraction of the material cleared from a given 

compartment per day (d-1) for completely insoluble material. Heavy solid lines define the 

directional transport over airway surfaces towards the ET2 compartments, where such particles 

are swallowed and enter the GI tract. Besides ciliary clearance, a secondary clearance 

mechanism of insoluble particles involves alveolar macrophages (AM) that have phagocytized 

particulate matter and subsequently migrate to regional lymph nodes, where these phagocytic 

cells may stay for long periods of time. For the ET2 region, removal by phagocytic alveolar 

macrophages relocate particulates to extrathoracic lymph nodes (LNET), while macrophages in 
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thoracic compartments transfer particles to thoracic lymph nodes (LNTH). Table 2 provides 

summary data for the clearance rates between individual compartments and their corresponding 

half-times. Inspection of Table 2 indicates that particles directly deposited in the ET2

compartment have a rapid clearance rate of 100 d-1, which corresponds to a half-time of 

10 minutes. Thus, following an acute exposure, nearly all insoluble materials initially deposited 

in ET2 are transferred to the GI tract within the first hour of exposure. 

Of interest here, however, are clearance rates from AI3 to LNTH, bbseq to LNTH, BBseq to LNTH, 

and ETseq to LNET. Once macrophages bearing radioactive microparticulates enter a lymph node, 

the particulates are likely to be released and sequestered within the node for long periods of time. 

The mean residence time of microparticulates in LNTH/LNET is estimated at 10,000 days. 

Histologically, lymph nodes are dense, encapsulated bundles of cells, which, in addition to 

macrophages, include bone marrow-derived or B-lymphocytes, and thymus-derived or 

T-lymphocytes. It is estimated that there are more than 600 lymph nodes in the human body, and 

their size varies from a few millimeters to more than a centimeter. Collectively, the weight of 

lymph nodes in the adult is estimated between 400 g and 800 g. 

Figure 4. Compartment Model to Represent Time-Dependent Particle Transport 

from Each Region 

(Source: ICRP 1993) 
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Table 2. ICRP Respiratory Tract Reference Clearance Rates for Insoluble 

Particulates 

Clearance Rates 

From To Rate (d-1) Half-Time 

AI1 bb1 0.002 35 d 

AI2 bb1 0.001 700 d 

AI3 bb1 0.0001 7000 d 

AI3 LNTH 0.00002 — 

bb1 BB1 2 8 h 

bb2 BB1 0.03 23d 

bbseq LNTH 0.01 70 d 

BB1 ET2 10 100 min 

BB2 ET2 0.03 23 d 

BBseq LNTH 0.01 70 d 

ET2 GI tract 100 10 min 

ETseq LNET 0.001 700 d 

3.3.3 Radiological Impacts to Lymph Nodes 

Radiation exposure to lymph nodes associated with the respiratory tract are maximized when the 

inhaled radio-contaminant (1) emits an alpha particle, (2) is highly insoluble, and (3) has a long 

physical half-life. Thus, lung clearance of microparticulates to regional lymph nodes with small 

tissue mass results in large time-integrated doses that are well above those of lung tissues. For 

illustration, ICRP 66 derived 50-year committed effective dose equivalent (CEDE) values for a 

1-Bq intake of a long-lived Type S radionuclide emitting a 5.15 MeV alpha particle (Table 3). 

Inspection of Table 3 shows that in time, LNTH and LNET will experience doses that are well 

above those of the lung. 

Table 3. Regional Committed Dose Equivalents for Intake of 1 Bq of a Long-Lived, 

Type S Alpha-Emitter 

(Source: ICRP 1993) 

Respiratory Tract Region CEDE (rem) 

Extra Thoracic: 

 - ET2 7.94E-03 

 - LNET 1.45E-02 

Thoracic: 

 - BBbsal 5.90E-04 

 - BBsecretory 6.44E-03 

 - bb 3.24E-03 

 - AI 3.96E-03 

 - LNTH 5.36E-02 
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3.4 NIOSH’S RESPONSE TO THE ISSUE 

On October 24, 2005, NIOSH issued a white paper entitled, NIOSH Re-examination of 

Lymphoma Target Organ Selection (Ulsh 2005). The White Paper acknowledged that, in the 

past, dose reconstruction for cancers of the lymphatic and hematopoietic tissues may have been 

improperly based on the “highest nonmetabolic organ [HNMO].” NIOSH concluded that the use 

of the HNMO as surrogate tissue for thoracic and extra-thoracic lymph nodes for dose 

reconstruction may have resulted in dose estimates that were far below those involving select 

lymphatic tissues. 

During technical discussions with NIOSH on April 29, 2008, NIOSH explained that they used 

the HNMO approach because that approach served them well for other non-metabolic cancers. 

In addition, NIOSH recognized that the risk coefficients for cancer of the lymph nodes were 

derived primarily based on epidemiological investigations of Hiroshima and Nagasake 

exposures, where the populations experienced uniform whole-body exposure to penetrating 

radiation. Hence, the risk coefficients for cancer of lymphatic tissues were originally derived 

based on data where all of the lymphatic tissue was acutely exposed. For the purpose of dose 

reconstruction of workers who might have inhaled highly insoluble alpha emitters, only a small 

fraction of the lymphatic tissue would have been exposed. Hence, at the time of the development 

of the original protocol, NIOSH judged that there were off-setting factors (i.e., though the dose 

to selected lymph nodes might be substantially higher than those derived using the HNMO 

approach, the risk coefficient cancer of lymphatic tissue, as derived from data associated with 

uniform whole-body exposures, would tend to overestimate the risk.) However, upon further 

reflection (see Attachments A, B, and C), NIOSH determined that there was a need to revise the 

protocol for reconstructing these to lymphatic tissue. 

Enclosed herein as Appendices A, B, and C are the full text of the NIOSH White Paper and the 

supporting documents by Drs. M. Crowther1

 and K. Eckerman,2 respectively. Revision 0 of 

OCAS-TIB-012 (OCAS 2005), issued August 15, 2005, reflects recommendations by Dr. 

Crowther. Subsequently, as a result of comments and suggestions provided by Dr. Eckerman, 

additional revisions were incorporated in Revision 1 of OCAS-TIB-012 (OCAS 2006b), issued 

on February 10, 2006. Concurrently, on February 10, 2006, Internal Dosimetry Organ, External 

Dosimetry Organ, and IREP Model Selection by ICD-9 Code, ORAUT-OTIB-0005, Revision 02 

PC-1 (ORAUT 2006) was issued, which incorporated organ selections identified in OCAS-TIB012. 

Our review of these documents confirms that NIOSH fully understood the need and technical 

basis for developing OCAS-TIB-012 and revising ORAUT-OTIB-0005. 

 1

 Mark Crowther, M.D., MSc., FRCPC, McMaster University, Canada, was hired as a NIOSH consultant. 

2

 Keith Eckerman, Ph.D., Oak Ridge National Laboratory, Oak Ridge, Tennessee, was hired as a NIOSH 

consultant. 
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4.0 SUBTASK 3: ASSESS NIOSH’S SPECIFIC SOURCES OF INFORMATION TO 

ENSURE THE CREDIBILITY OF THE CORRECTIVE ACTION AND ITS 

CONSISTENCY WITH CURRENT/CONSENSUS SCIENCE 

It is SC&A’s opinion that the core technical issue of OCAS-PER-009 is complex and multidisciplinary. Corrective action, therefore, not only requires a thorough understanding of 

radiological models used to quantify the transfer of radio-particulates from the respiratory tract 

to regional lymph nodes, but also requires a keen understanding of the immunological, 

cytological, and oncological features that characterize cells and tissues of the lymphatic system. 

Lastly, it is equally important to recognize clinical limitations that surround the detection, 

diagnosis, and classification of lymphomas. This is especially true for claims in which the 

diagnosis was made decades ago. 

To provide a level of scientific/clinical expertise, NIOSH enlisted the advice of two outside 

experts. The first, Mark Crowther, MD, is board certified in internal medicine and hematology. 

As a result of personal communications with Dr. Crowther that include his consultant report (see 

Appendix B), NIOSH drafted and issued OCAS-TIB-012, Revision 0 on August 15, 2005. 

As acknowledged in NIOSH’s White Paper, OCAS-TIB-012 Revision 0 was subsequently 

forwarded to Dr. Keith Eckerman, an internationally recognized health physicist, who authored 

extensive publications related to internal dosimetry and biokinetic modeling. Dr. Eckerman 

recommended substantial changes, which were incorporated in Revision 1 of OCAS-TIB-012 

(OCAS 2006b). As explained by NIOSH in its commentary dated April 18, 2008, the majority 

of Dr. Eckerman’s recommendations were concerned primarily with internal dosimetry issues 

related to the classification of lymph nodes as LN(TH) and LN(ET), and the magnitude of the 

resulting doses to those organs. 

A review of Dr. Crowther’s report (see Appendix B) suggests that even today, a substantial level 

of ambiguity exists in defining the specific cell-line of origin, as well as the primary anatomical 

location that gave rise to a cancer associated with lymphatic and hematopoietic tissues. Under 

the Energy Employee Occupational Illness Compensation Program Act of 2000 (EEOICPA), the 

need to assign a highly definitive International Classification of Diseases (ICD-9) code for 

cancers diagnosed many years ago is even further hampered by diagnostic/clinical methods that 

by today’s standards are crude at best. 

Presented below are excerpts from a standard medical reference text published nearly 30 years 

ago that further illustrates the difficulties/ambiguities that surround the diagnosis and 

classification of lymphoreticular neoplasms over time (Beeson et al. 1979). 

4.1 EXCERPTS FROM SECTION SEVEN, § 500 – LYMPHORETICULAR 

NEOPLASMS (BEESON ET AL., 1979) 

Lymphoreticular neoplasms arise in lymphocytic cells, reticulum cells, or 

primitive precursor cells... The lymphoreticular cells are located primarily in 

lymph nodes, thymus, spleen, and liver, but components of the lymphoreticular 
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system are also found in the submucosal areas of the respiratory and 

gastrointestinal tracts as well as the marrow. . . 

Lymphoreticular tumors may become clinically apparent as single or multiple 

tumors in the lymph nodes, spleen, or gastrointestinal tract and may or may not 

involve the bone marrow. Since lymphocytes and macrophages also normally 

occur in the peripheral blood, lymphoreticular tumor cells may circulate . . . 

The term malignant lymphoma commonly refers to patients who present 

predominately with solid tumors and must be further classified as to cell type, i.e., 

histiocytic, lymphocytic, or Hodgekin’s... When the marrow and peripheral blood 

manifestations are prominent as contrasted to tumor or nodal enlargement, the 

term leukemia or leukemic phase is applied. Thus, in patients with 

lumphoreticular neoplasms, one sees a complete spectrum from localized tumors 

only to multiple tumors, leukemias, and mixtures. The presentation at time of 

diagnosis reflects only a point in time, and the natural progression – untreated 

or after ineffective therapy – is toward dissemination... 

The current approach to classification of lymphoreticular neoplasms, as well as 

the previously applied terms, is shown in the accompanying table [reproduced as 

Table 4 below]. The use of this classification and the appreciation of chronologic 

changes in cell type should clear up many of the previous difficulties with 

confusing names that encompassed grossly different prognostic categories. 

The diagnosis of lymphoreticular neoplasms must always be based on adequate 

tissue biopsy. Occasionally, multiple biopsies may be needed before the decision 

as to pathologic classification can be definitively made... cytochemical studies 

will help clarify the specific cell type and degree of differentiation. 

More recently, specific markers of the cell surface such as immunoglobulin 

receptors, complement receptors, immunoglobulin fluorescence, or rosette cell 

formation have classified cell variants that heretofore were difficult or 

impossible to categorize. [Emphasis added.] 

Table 4. Classification of Lymphoreticular Neoplasms*

Proposed Name Old Name 

Lymphoma, Lymphocytic type, well differentiated Lymphosarcoma 

Lymphoma, Lymphocytic type, poorly differentiated Lymphosarcoma 

Lymphoma, histiocytic type Reticulum cell sarcoma 

Lymphoma, mixed lymphocytic-histocytic type Mixed lymphoma 

Lymphoma, undifferentiated pleomorphic type Stem cell lymphoma 

Lymphoma, undifferentiated Burkitt type Stem cell lymphoma 

 * From Beeson et al., 1979
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4.2 EXCERPTS FROM § 501 – NON-HODGKIN’S LYMPHOMAS (BEESON et al., 

1979) 

The diagnosis and classification of a lymphoma must be based on careful 

evaluation of biopsy material. However, in certain instances it may be difficult to 

distinguish benign from malignant disorders. Misinterpretation with respect to 

histopathologic subclassification are also common. Frequently the distinction 

between leukemia and lymphoma cannot be made on the basis of biopsy alone... 

The non-Hodgekin’s lymphomas have traditionally been classified according to 

their morphology under the light microscope. Most of the terminologies used to 

describe and classify these disorders were proposed long before the remarkable 

developments in immunology of recent years. ... As newer techniques in 

immunology have been applied to the study of the non-Hodgekin’s lymphomas, 

several new classification systems have been suggested. [Emphasis added.] 

4.3 SUMMARY CONCLUSIONS REGARDING THE RELIABILITY OF ICD-9 

CODES FOR DOSE RECONSTRUCTION OF LYMPHOMAS 

From these statements, it is only fair to conclude that past and even present-day methods for the 

classification of neoplasms of the reticuloendothelial tissues were/are inconsistent and subject to 

a high degree of uncertainty. Contributing factors include (1) changes in cancer nomenclature, 

(2) improved diagnostic equipment and methods for the detection and staging of the cancer, and 

(3) changes in clinical protocols used to identify the origin of the neoplastic cell lines. Of special 

concern for some claimants is the time of cancer diagnosis and classification of their cancer that 

may pre-date the ICD-9 codes, which were first introduced in 1977. 

Even when the assignment of an ICD-9 code is regarded with absolute accuracy, the site of 

exposure/cell-transformation is not absolute, as acknowledged by NIOSH in OCAS-TIB-012. 

For Tables 1, 3, 4, 8, 11, 13, and 14 of OCAS-TIB-012, a significant number of cancers are 

identified for which the internal target organ is either HNMO or bone marrow, along with either 

of the following cautionary statements: 

• The site of occurrence is the most likely site of the original injury.

[Emphasis added.] 

• Therefore, the most plausible site of original radiation injury is the bone 

marrow. [Emphasis added.] 

While SC&A does not question NIOSH’s conclusion of a “most likely” or “most plausible” site 

of the original radiation injury, the need to give the claimant the benefit of doubt must be 

considered, as specified under 42 CFR 82. Uncertainty regarding the site of the original injury 

may even include acute lymphocytic leukemia (ICD-9 code 204), which, according to OCASTIB-012, consistently identifies the bone marrow as the only potential internal target organ. For 

example, § 497 in Beeson et al. 1979 states the following: 
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Acute lymphocytic leukemia arises in lymphoid tissue and is ordinarily first 

manifest by its presence in marrow. In some instances thymic infiltration 

precedes overt marrow disease, but it is not known whether the initial 

leukemogenic event in man is usually extramedullary [i.e., outside the bone 

marrow]. Many instances of lymphosarcoma of various cell types culminate in 

an acute leukemic phase which bears some resemblance to acute lymphocytic 

leukemia. [Emphasis added] 

Thus, a derived internal dose for an alpha-emitting Type S radionuclide (that is falsely based on 

the red bone marrow as its internal organ when, in fact, the site of injury may have involved 

LNET or LNTH) would underestimate the real dose by about 2 orders of magnitude. 

As acknowledged in the Executive Summary of this report, assignment of an ICD-9 code is the 

exclusive responsibility of the DOL and is, therefore, outside of NIOSH’s purview. Regardless 

of which federal agency bears responsibility, SC&A believes that we have an obligation to 

communicate these concerns to the Board.
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5.0 SUBTASK 4: EVALUATE THE PER’S STATED APPROACH FOR 

IDENTIFYING THE UNIVERSE OF POTENTIALLY AFFECTED DOSE 

RECONSTRUCTIONS; OR ASSESS THE CRITERIA BY WHICH A SUBSET OF 

POTENTIALLY AFFECTED DOSE RECONSTRUCTIONS WAS SELECTED FOR REEVALUTION 

As previously noted, internal doses to lymph nodes versus HNMO may differ by as much as 2 

or even 3 orders of magnitude. In addition, the issuance of OCAS-TIB-012 Revision 1 changed 

the external target organ from bone marrow to various other organs for many forms of 

lymphoma. This, too, increased the dose and the resulting POC. 

As part of the plan for resolution and corrective action, NIOSH issued OCAS-PEP-009 (OCAS 

2006c) on December 8, 2006. In behalf of OCAS-PEP-009, a query of the NIOSH OCAS 

Claims Tracking System (NOCTS) database identified that prior to February 10, 2006, a total of 

528 lymphoma claims had been processed with POCs less than 50% and were, therefore, subject 

to re-evaluation under OCAS-PER-009. 

NIOSH re-evaluated the dose reconstructions for all 528 affected lymphoma claims using the 

revised guidance documents. The following conclusions for the re-evaluation were reported by 

NIOSH in OCAS-PER-009 on March 8, 2007: 

This report is issued indicating a resolution to each of the 528 claims reevaluated. Of the 528 claims, 23 had been returned to NIOSH for rework for 

various reasons. These claims were updated using the current dose 

reconstruction methods so no evaluation under this PER was necessary. Five 

claims have no current method of dose reconstruction. NIOSH will ask that these 

claims be returned for rework based on the revision to the lymphoma target 

organ. Of the remaining 500 claims, 152 claims were found to now result in a 

probability of causation of greater than 50%, while the remaining 348 claims 

resulted in the probability of causation remaining below 50%. 

5.1 PRELIMINARY CONCLUSIONS AND RECOMMENDATIONS 

Under Subtask 5, SC&A is required to conduct audits of dose reconstructions selected by the 

Advisory Board that were affected by OCAS-PER-009. At this time, the Board’s Work Group 

on Procedures Review has not selected dose reconstructions for SC&A’s review. Thus, the final 

subtask will not commence until the Work Group presents SC&A with its selection of dose 

reconstructions. 

We believe that the audits of these cases should have two objectives. The first pertains to 

confirming that, given the ICD-9 code assigned by NIOSH, SC&A would confirm that the dose 

reconstructions were performed in accordance with the current procedures. The second objective 

would be to assess the degree to which the benefit of the doubt was given to the claimant when 

assigning ICD-9 codes, taking into consideration the uncertainties and challenges associated with 

the diagnosis of these types of cancers. SC&A recognizes that this second objective is concerned 
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NOTICE:

with matters that might be outside the purview of NIOSH. Hence, we look to the Board for 

guidance on whether it is appropriate for the audit to look into this particular issue. 

If the Board elects to limit the audit to the first objective, we believe a random sample of three 

dose reconstructions from the re-evaluated claims will fulfill the objectives of this assignment. 

If the Board judges that the audit should try to achieve both objectives, it is SC&A’s opinion that 

a meaningful selection process will require additional information that characterizes a subset of 

perhaps 10 dose reconstructions from among the 348 dose reconstructions from which 3 dose 

reconstructions will be selected for audit. This could be accomplished as follows: 

• Classify re-evaluated claims based on their original approach used for dose 

reconstruction, i.e., maximized or best estimate 

• Classify re-evaluated claims based on (1) change to the internal target organ, (2) change 

to the external target organ, and (3) change to both internal and external organs 

• Identify the POC of the individual re-evaluated claim

• Identify those re-evaluated claims for which internal exposures included (or should have 

included) in-vivo/in-vitro bioassay data for U, Pu, Am, and/or Th 

This information can be readily summarized for each of the 10 dose reconstructions in a 

spreadsheet, as illustrated in Table 5.
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Table 5. Sample Information 

Target Organ DR Method POC (%) DR ID # ICD-9 Code Internal External Original New Original New Year of Cancer Diagnosis 

Claim 001 200.84 LNTH Lung Maximized Best Estimate 18% 46% 1976 

↓

Claim 348 
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5.2 SMOKING AS MODIFYING AGENT THAT MAY REQUIRE FURTHER 

CONSIDERATION 

Smoking causes histological and cytological alterations within the respiratory tract. Most 

relevant to this discussion is the impairment of the tracheobronchial mucociliary 

transport/clearance mechanism. The impaired ciliary clearance mechanism of a smoker implies 

a longer residency time of particulates in the lung and a likely shift towards lung clearance by 

alveolar macrophages that involve LNTH and LNET. ICRP (1993) notes the following: 

. . . A major cytologic feature in smokers is a considerable increased alveolar 

macrophages population . . . Whereas a nonsmoker usually has about 5 billion 

macrophages, a smoker might have as many as 70 billion or more.

[Emphasis added.] 

It is safe to assume that the more than 14-fold increase in alveolar macrophages among smokers 

will profoundly increase the transfer of activity to LNTH and LNET. The ICRP, however, offers 

no further discussion on the radiological impacts of smoking. In the absence of information, a 

reasonable approach might assume that the increased number of alveolar macrophages would 

proportionately increase the fractional amount of radioactivity transferred to and concentrated in 

the regional lymph modes. 

On the basis of first principles, it is only reasonable to conclude that the elevated number of 

alveolar macrophages would significantly enhance the relocation of respired radioparticulates to 

LNTH and LNET and proportionately raise their radiation exposure. In brief, for a common 

inhalation intake, smokers are likely to be at greater risk for lymphoma than non-smokers. 

During the procedures review work group teleconference on April 2, 2008, NIOSH stated that 

there are many uncertainties associated with modeling the biokinetics of the clearance of 

particles deposited in the deep lung and transferred to thoracic lymph nodes for smokers. In 

addition, due to changes in the morphology of the lymph nodes of smokers and the radiation 

doses that lymph nodes of smokers experience due to natural radioactivity in tobacco, along with 

other confounding factors, it is not possible at this time to explicitly address this issue, given the 

state of the scientific understanding of this subject. SC&A agrees with this perspective and 

suggests that this subject might best be addressed by NIOSH as a global scientific issue. 
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6.0 SUBTASK 5: CONDUCT AUDITS OF DOSE RECONSTRUCTIONS 

SELECTED BY THE ADVISORY BOARD, WHICH WERE AFFECTED BY 

OCAS-PER-009 

Before reviewing specific dose reconstructions for compliance with OCAS-TIB-012, SC&A also 

assessed the Integrated Modules for Bioassay Analysis (IMBA) software (ACJ 2002) in order to 

verify its consistency with the ICRP Publication 66 (ICRP 1993) for deriving dose estimates for 

select tissues. Specifically, SC&A assessed dose ratios among tissues as given in Table 24 of 

ICRP Publication 66 and compared these to dose ratios calculated by IMBA. For this 

comparison, SC&A ran IMBA using the following arbitrary input parameters: 

(1) A 24-hour urine sample yielded an excretion of 1 dpm/day for Pu-239, Type S 

(2) The inhalation intake was confined to a single acute exposure that occurred 30 days prior 

to the date of urine collection 

(3) CEDE values were calculated for 5 μm and 1 μm particles 

Table 6 provides the corresponding CEDE values for various regions of the respiratory tract, 

lymph nodes (LNTH and LNET), and other organs/tissues. Important to note is that the two 

highest doses correspond to LNTH and LNET. For example, the dose to LNTH is more than 

10 times the dose to the lung and more than 100 times that of the red bone marrow. A 

comparison of IMBA dose ratios with ratios defined in Table 24 of ICRP Publication 66 shows 

nearly identical values (small differences can be attributed to the fact that ICRP values are based 

on a hypothetical alpha emitter of 5.15 MeV particles with no beta/gamma emission). 

6.1 AUDIT OF DOSE RECONSTRUCTIONS INVOLVING LYMPHOMAS 

This section will be completed following receipt of dose reconstructions selected by the Work 

Group.
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Table 6. Dose Distribution for a Single Acute Intake of Pu-239 

IMBA Generated CEDE Values 

5 μm Particles 1 μm Particles 

Target Organs Equivalent Dose (rem) Target Organs Equivalent Dose (rem) 

Adrenals 1.52E+00 Adrenals 1.73E+00 

Urinary Bladder 1.52E+00 Urinary Bladder 1.73E+00 

Brain 1.52E+00 Brain 1.73E+00 

Breast 1.52E+00 Breast 1.73E+00 

Gall Bladder 1.52E+00 Gall Bladder 1.73E+00 

Heart Wall 1.52E+00 Heart Wall 1.73E+00 

Kidneys 3.81E+00 Kidneys 4.34E+00 

Liver 1.87E+02 Liver 2.13E+02 

Muscle 1.52E+00 Muscle 1.73E+00 

Ovaries 1.16E+01 Ovaries 1.33E+01 

Pancreas 1.52E+00 Pancreas 1.73E+00 

Testes 1.19E+01 Testes 1.35E+01 

Thyroid 1.52E+00 Thyroid 1.73E+00 

R.B.M. 4.37E+01 R.B.M. 4.98E+01 

Bone Surface 8.81E+02 Bone Surface 1.00E+03 

Stomach 1.53E+00 Stomach 1.74E+00 

S.I. 1.53E+00 S.I. 1.74E+00 

U.L.I. 1.60E+00 U.L.I. 1.77E+00 

L.L.I. 1.76E+00 L.L.I. 1.84E+00 

Skin 1.52E+00 Skin 1.73E+00 

Spleen 1.52E+00 Spleen 1.73E+00 

Thymus 1.52E+00 Thymus 1.73E+00 

Uterus 1.52E+00 Uterus 1.73E+00 

ET 7.75E+02 ET 2.49E+02 

Lung 4.55E+02 Lung 4.70E+02 

Colon 1.67E+00 Colon 1.80E+00 

ET1 1.56E+01 ET1 5.88E+00 

ET2 7.75E+02 ET2 2.49E+02 

LN(ET) 1.40E+03 LN(ET) 4.48E+02 

BBsec 6.32E+02 BBsec 3.82E+02 

BBbas 5.78E+01 BBbas 2.61E+01 

bb 3.23E+02 bb 3.64E+02 

AI 6.85E+02 AI 8.28E+02 

LN(TH) 4.82E+03 LN(TH) 4.89E+03 

Esophagus 1.52E+00 Esophagus 1.73E+00 

Gonads 1.19E+01 Gonads 1.35E+01 

Spare 0.00E+00 Spare 0.00E+00 

Remainder 1.92E+00 Remainder 1.88E+00 
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7.0 REFERENCES 

42 CFR 82, 2002. Methods for Radiation Dose Reconstruction Under the Energy Employees 

Occupational Illness Compensation Program Act of 2000; Final Rule, Federal 

Register/Vol.67, No. 85/Thursday, May 2, 2002, p. 22314. 

ACJ 2002. Integrated Modules for Bioassay Analysis, (IMBA), Phase 1, ACJ & Associates and 

the UK National Radiological Protection Board, Software produced for NIOSH-OCAS as part of 

the EEOICPA Program, Version 1.0.42, UK.

Beeson, P.B., M.D., W. McDermott, M.D., and J.B. Wyngaarden, M.D. (Editors), 1979. Cecil 

Textbook of Medicine, W.B. Saunders Co., Philadelphia, Pennsylvania. 

ICRP (International Commission on Radiological Protection) 1993. “Human Respiratory Tract 

Model for Radiological Protection,” ICRP Publication 66, Annals of ICRP 24/1-2, Oxford: 

Pergamon Press. 

OCAS 2005. Selection for Internal and External Dosimetry Target Organs for 

Lymphatic/Hematopoietic Cancers, OCAS-TIB-012, Revision 0, NIOSH’s Office of 

Compensation Analysis and Support, Cincinnati, Ohio. August 15, 2005 

OCAS 2006a. Preparation of Program Evaluation Reports and Program Evaluation Plans, 

OCAS-PR-008, Revision 2, NIOSH’s Office of Compensation Analysis and Support, 

Cincinnati, Ohio. December 6, 2006 

OCAS 2006b. Selection for Internal and External Dosimetry Target Organs for 

Lymphatic/Hematopoietic Cancer, OCAS-TIB-012, Revision 1, NIOSH’s Office of 

Compensation Analysis and Support, Cincinnati, Ohio. February 10, 2006. 

OCAS 2006c. Evaluation of the Changes in Target Organs for Dose Reconstruction Involving 

Lymphoma, OCAS-PEP-009, Revision 0, NIOSH’s Office of Compensation Analysis and 

Support, Cincinnati, Ohio. December 8, 2006. 

OCAS 2007. Target Organs for Lymphoma, OCAS-PER-009, Revision 0, NIOSH’s Office of 

Compensation Analysis and Support, Cincinnati, Ohio. March 8, 2007. 

ORAUT 2006. Internal Dosimetry Organ, External Dosimetry Organ, and IREP Model 

Selection by ICD-9 Code, ORAUT-OTIB-0005, Revision 02 PC-1, Oak Ridge Associated 

Universities Team: Cincinnati, Ohio. February 10, 2006. 

Ulsh, B. 2005. NIOSH Re-examination of Lymphoma Target Organ Selection. National 

Institute for Occupational Safety and Health. October 24, 2005
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APPENDIX A-1: NIOSH MEMORANDUM DATED APRIL 18, 2008 

April 18, 2008 

NIOSH Comments on SC&A’s Draft of SCA-TR-Task3-0008, Rev. 1 

A Preliminary Review of NIOSH’s Program Evaluation Report OCAS-PER_009 

Target Organs for Lymphomas

SCA-TR-TASK3-0008, Rev. 1, Page 5:

As a result of ongoing internal reviews, including the review of dose reconstructions 

performed by SC&A, it became apparent to NIOSH that the methods being used to 

reconstruct the doses to workers that contracted lymphoreticular neoplasms (cancer of the 

lymph nodes) required revision; revisions that could result in very large increases in the 

derived doses to the organs of concern and the possible reversal of previously denied claims. 

NIOSH comment:

As discussed during the April 2, 2008 conference call, the SC&A review of dose 

reconstructions was not a contributor to NIOSH’s decision to review target organ selection 

for cancers of the lymphatic/hematopoietic system. The review comment made by SC&A 

(see exhibit #1 on page 10) referred to a case of Hodgkin’s lymphoma. The revision to our 

approach in selecting organs for Hodgkin’s lymphoma remains unchanged from the time that 

this case was completed. That is, the site of diagnosis is considered to be the site of origin 

for Hodgkin’s lymphoma. Thus, our response to the review comment is still valid. 

NIOSH’s decision to review our approach to dealing with lymphomas was initiated by 

informal oral comments made to NIOSH by members of the public, which preceded SC&A’s 

dose reconstruction review. 

SCA-TR-TASK3-0008, Rev. 1, Page 5:

The need for a revision to the dose reconstruction methodology became apparent when 

NIOSH recognized that its standard method for reconstructing the doses to workers with 

cancer of the lymph nodes was fundamentally flawed. NIOSH’s standard procedure for 

deriving doses to lymph nodes was based on the erroneous assumption that an upper bound 

on the doses to the organ of concern could be derived by using the colon (or the highest nonmetabolic organ) as a surrogate organ. 

NIOSH comment:

NIOSH has never stated or concluded that our previous dose reconstruction methodology 

was “fundamentally flawed”. The previous methodology accurately reflected our scientific 

understanding of the issue at the time. Subsequently, new information became available and 

NIOSH revised our dose-reconstruction methodology accordingly. This is an example of 

NIOSH seriously considering comments received from members of the public, and our 

commitment that dose reconstruction methodology be based on the best available scientific 

information. 
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SCA-TR-TASK3-0008, Rev. 1, Page 5:

Our review concluded that OCAS-PER-009 reflects revisions to OCAS-TIB-012 and ORAUTOTIB-0005, which correct previous deficiencies for the reconstruction of radiation doses to 

lymphatic tissues associated with the respiratory system. 

NIOSH comment:

In other instances in SC&A’s report, this issue is characterized as a “problem” with NIOSH’s 

previous dose-reconstruction methodology. NIOSH does not concur with the implication 

that this issue represents a “problem” or “deficiency” in the previous dose reconstruction 

methodology. The previous methodology accurately reflected our scientific understanding of 

the issue at the time. The methodology was revised to reflect the latest scientific 

information. 

SCA-TR-TASK3-0008, Rev. 1, Page 6:

It is SC&A’s opinion that for various classes of lymphomas and/or stage of the neoplasm, 

there remains a substantial level of uncertainty regarding (1) the cell-line of origin for the 

neoplasm, and (2) the anatomical location where the neoplastic transformation and/or clonal 

expansion took place. While significant refinements in diagnostic methods have reduced the 

uncertainty in the classification of lymphomas in recent years, of greatest concern are claims 

in which the cancer diagnosis was made at a time when clinical data were inadequate for the 

assignment of an ICD-9 code. 

NIOSH comment:

NIOSH agrees that there are certain classes of lymphomas for which there exist current and 

historic uncertainties regarding the cells of origin, and where in the body radiation might 

interact with these cells to subsequently form a neoplasm. This uncertainty is the reason 

NIOSH has chosen to make the very claimant-favorable assumption that these interactions 

may have occurred, for example, in the thoracic lymph nodes for non-Hodgkin’s lymphomas. 

NIOSH, however, disagrees with SC&A’s opinion that these uncertainties apply to 

Hodgkin’s lymphoma and a few other classes of lymphoma which involve immobile cells 

forming the lymphatic system. The ability to accurately distinguish between Hodgkin’s and 

non-Hodgkin’s lymphoma has existed for close to a hundred years. While understanding of 

the origins of these diseases has certainly evolved over the years, the contemporary 

assignment of the ICD-9 code reflects this accumulated knowledge. That is, the ICD 9 codes 

are assigned by DOL to each cancer at the time the application is received from the claimant. 

For situations where the medical files are unclear or contain ambiguity, DOL has the ability 

to provide NIOSH with codes that reflect this uncertainty. NIOSH strongly disagrees with 

SC&A’s argument that the described historical uncertainties of the origins and etiology of 

certain lymphomas impacts the reliability of ICD-9 code assignment, which occurs when the 

claim is filed. 

SCA-TR-TASK3-0008, Rev. 1, Page 6:

Regarding the impact of smoking, NIOSH concluded that this is a highly technical issue that 

cannot be resolved by NIOSH and may require a formal review by an ad hoc committee of 

scientific experts. 
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NIOSH comment:

NIOSH does not recall stating this conclusion. Rather, it is NIOSH’s opinion that SC&A’s 

arguments regarding the potential impact of smoking are speculative in nature, and the 

current scientific evidence is not sufficient to justify the adoption of SC&A’s position. 

NIOSH believes that a general increase in macrophage activity due to smoking must be 

considered in the context of a number of factors, including: 1) the concomitant intake of 

natural radioactivity in cigarette smoke; 2) the increase in the mass of the lymph nodes due to 

accumulation of deposited smoke particles; and 3) the sequestering of dozens of known 

chemical carcinogens in the lymph nodes by the macrophages. 

SCA-TR-TASK3-0008, Rev. 1, Page 8:

On April 2, 2008, the Procedures Review Work Group held a teleconference that specifically 

assessed Revision 0 of this draft report. Participants in this teleconference included persons 

representing NIOSH. It was during the teleconference that SC&A was first informed that 

NIOSH had initiated a formal technical review of issues leading up to PER-009 on or before 

November 2004. Specific dates and details surrounding the circumstances, which may have 

served as the initial trigger for OCAS-PER-009 were neither discussed during the 

teleconference nor provided in a white paper enclosed herein as Appendix A. Therefore, 

what follows below is only a partial and incomplete assessment of the circumstances that 

may have served as the basis for OCAS-PER-009. 

NIOSH comment:

NIOSH responded to specific inquiries from SC&A regarding the date the NIOSH white 

paper was issued. SC&A never consulted NIOSH regarding our motivation for initiating our 

investigation of the target organ selection issue for lymphatic/hematopoietic cancers. NIOSH 

was unaware that this was an issue upon which SC&A was reporting until we received 

SC&A’s draft report. Revision 0 of this report stated that SC&A’s review of a dosereconstruction contributed to NIOSH’s decision to review this issue. NIOSH addressed 

SC&A’s statement during the April 2, 2008 Working Group meeting, yet Revision 1 of 

SC&A’s report (page 5) still makes this claim. 

It is NIOSH’s opinion that our motivation for investigating this issue is not germane to the 

technical adequacy of our resulting revisions to target organ selection. If this is an issue that 

SC&A feels the need to discuss in their report, then the reported timeline and motivations for 

our investigation should be accurate. 

SCA-TR-TASK3-0008, Rev. 1, Page 17:

Enclosed herein as Appendices A, B, and C are the full text of the NIOSH White Paper and 

the supporting documents by Drs. M. Crowther1

 and K. Eckerman,2 respectively. Revision 0 

of OCAS-TIB-012 (OCAS 2005), issued August 15, 2005, reflects recommendations by Dr. 

Crowther. Subsequently, as a result of comments and suggestions provided by Dr. 

Eckerman, substantial revisions were incorporated in Revision 1 of OCAS-TIB-012 (OCAS 

2006b), issued on February 10, 2006. 
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NIOSH comment:

SC&A’s statement can be interpreted as implying that the recommendations of Dr. Eckerman 

conflicted with those of Dr. Crowther, and that this necessitated revision of OCAS-TIB-012. 

While it is understandable how SC&A could have come to this conclusion, it is not entirely 

accurate. Revision 0 of OCAS-TIB-012 reflected NIOSH’s discussions with Dr. Crowther 

regarding the possible origins of various classes of lymphoma. Dr. Crowther does not have 

expertise in internal modeling of radionuclide transport and deposition. The classification of 

lymph nodes as LN(TH) and LN(ET), and the magnitude of the resulting doses to those 

organs, is a health physics designation, specific to internal modeling. To cover this aspect of 

the issue, we solicited Dr. Eckerman’s review. As SC&A notes, and as discussed in 

NIOSH’s white paper, Dr. Eckerman recommended that we select LN(TH) rather than 

LN(ET) if our criteria was claimant favorability. We accepted Dr. Eckerman’s 

recommendation and revised OCAS-TIB-012 accordingly. 

SCA-TR-TASK3-0008, Rev. 1, Page 18:

Dr. Eckerman recommended substantial changes, which were incorporated in Revision 1 of 

OCAS-TIB-012 (OCAS 2006). 

NIOSH comment:

As discussed in NIOSH’s white paper, the most substantial change recommended by Dr. 

Eckerman was the selection of LN(TH) rather than LN(ET), because the former is claimantfavorable. 

SCA-TR-TASK3-0008, Rev. 1, Page 18:

A review of Dr. Crowther’s report (see Appendix B) suggests that even today, there exists a 

substantial level of ambiguity for defining the specific cell-line of origin, as well as the 

primary anatomical location that gave rise to a cancer associated with lymphatic and 

hematopoietic tissues. Under Energy Employee Occupational Illness Compensation 

Program Act of 2000 (EEOICPA), the need to assign a highly definitive International 

Classification of Diseases (ICD-9) code for cancers diagnosed many years ago is even 

further hampered by diagnostic/clinical methods that by today’s standard are crude at best. 

NIOSH comment:

NIOSH questions SC&A’s interpretation of Dr. Crowther’s report. Dr. Crowther, who is a 

highly qualified hematologist, reviewed our revised target organ selections and concurred 

with our revisions. 

NIOSH agrees that there are certain classes of lymphomas for which there exist current and 

historic uncertainties regarding the cells of origin, and where in the body radiation might 

interact with these cells to subsequently form a neoplasm. This uncertainty is the reason 

NIOSH has chosen to make the very claimant-favorable assumption that these interactions 

may have occurred, for example, in the thoracic lymph nodes for non-Hodgkin’s lymphomas. 

However, NIOSH disagrees with SC&A’s application of these uncertainties to Hodgkin’s 

lymphoma and a few other classes of lymphoma which involve immobile cells forming the 

lymphatic system. The ability to accurately distinguish between Hodgkin’s and nonHodgkin’s lymphoma has existed for close to a hundred years. While understanding of the 
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origins of these diseases has certainly evolved over the years, the contemporary assignment 

of the ICD-9 code reflects this accumulated knowledge. NIOSH strongly disagrees with 

SC&A’s argument that the described historical uncertainties of the origins and etiology of 

certain lymphomas in any way impacts the reliability of ICD-9 code assignment, which 

occurs when the claim is filed. 

The EEOICPA prescribes that the benefit of the doubt be given to the claimant when science 

alone is insufficient to choose between multiple plausible alternatives. However, the 

alternatives must be plausible. The very radiogenicity of Hodgkin’s disease (and similar 

lymphomas) is questionable, as no consistent relationship between ionizing radiation 

exposure and Hodgkin’s disease has been observed in the many radioepidemiological studies 

conducted to date. If SC&A’s recommendations were accepted, it would result in Hodgkin’s 

disease being one of the most compensated cancers in the EEOICPA program. This is 

inconsistent with the epidemiological evidence. Combined with the opinion of a wellqualified hematologist, this suggests that SC&A’s recommendations are not scientifically 

plausible. 

SCA-TR-TASK3-0008, Rev. 1, Pages 18-19:

EXCERPTS FROM SECTION SEVEN, § 500 LYMPHORETICULAR NEOPLASMS 

(BEESON ET AL., 1979) 

Lymphoreticular neoplasms arise in lymphocytic cells, reticulum cells, or primitive 

precursor cells . . . The lymphoreticular cells are located primarily in lymph nodes, 

thymus, spleen, and liver, but components of the lymphoreticular system are also 

found in the submucosal areas of the respiratory and gastrointestinal tracts as well as 

the marrow. . . 

Lymphoreticular tumors may become clinically apparent as single or multiple tumors 

in the lymph nodes, spleen, or gastrointestinal tract and may or may not involve the 

bone marrow. Since lymphocytes and macrophages also normally occur in the 

peripheral blood, lymphoreticular tumor cells may circulate . . . The term malignant 

lymphoma commonly refers to patients who present predominately with solid tumors 

and must be further classified as to cell type, i.e., histiocytic, lymphocytic, or 

Hodgekin’s . . . When the marrow and peripheral blood manifestations are 

prominent as contrasted to tumor or nodal enlargement, the term leukemia or 

leukemic phase is applied. Thus, in patients with lumphoreticular neoplasms, one 

sees a complete spectrum from localized tumors only to multiple tumors, leukemias, 

and mixtures. The presentation at time of diagnosis reflects only a point in time, 

and the natural progression – untreated or after ineffective therapy is toward 

dissemination. . . 

The current approach to classification of lymphoreticular neoplasms, as well as the 

previously applied terms, is shown in the accompanying table [reproduced as Table 4 

below]. The use of this classification and the appreciation of chronologic changes in 

cell type should clear up many of the previous difficulties with confusing names that 

encompassed grossly different prognostic categories. 
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The diagnosis of lymphoreticular neoplasms must always be based on adequate 

tissue biopsy. Occasionally, multiple biopsies may be needed before the decision as 

to pathologic classification can be definitively made . . . . cytochemical studies will 

help clarify the specific cell type and degree of differentiation. 

More recently, specific markers of the cell surface such as immunoglobulin receptors, 

complement receptors, immunoglobulin fluorescence, or rosette cell formation have 

classified cell variants that heretofore were difficult or impossible to categorize. [Emphasis 

added.] 

NIOSH comment:

NIOSH has not reviewed the textbook cited by SC&A, however, we note that the quoted 

section speaks generally about lymphoreticular neoplasms, which would include all 

lymphomas. There is nothing in the quoted text which suggests that there is ambiguity 

differentiating between Hodgkin’s and non-Hodgkin’s lymphoma, which is the relevant 

question for target organ selection. 

SCA-TR-TASK3-0008, Rev. 1, Page 19-20:

EXCERPTS FROM § 501 – NON-HODGKIN’S LYMPHOMAS (BEESON ET AL., 

1979) 

The diagnosis and classification of a lymphoma must be based on careful evaluation 

of biopsy material. However, in certain instances it may be difficult to distinguish 

benign from malignant disorders. Misinterpretation with respect to histopathologic 

subclassification is also common. Frequently the distinction between leukemia and 

lymphoma cannot be made on the basis of biopsy alone.... 

The non-Hodgekin’s lymphomas have traditionally been classified according to their 

morphology under the light microscope. Most of the terminologies used to describe 

and classify these disorders were proposed long before the remarkable developments 

in immunology of recent years. . . . As newer techniques in immunology have been 

applied to the study of the non-Hodgekin’s lymphomas, several new classification

systems have been suggested. [Emphasis added.] 

NIOSH comment:

It is unclear why SC&A quoted the 29-year old Beeson text regarding uncertainties relevant 

to non-Hodgkin’s lymphoma. NIOSH has already addressed this uncertainty. NIOSH agrees 

that there are current and historic uncertainties regarding the cells of origin, and where in the 

body radiation might interact with these cells to subsequently form a neoplasm in the case of 

non-Hodgkin’s lymphoma. This uncertainty is the reason NIOSH has chosen to make the 

very claimant-favorable assumption that these interactions may have occurred, for example, 

in the thoracic lymph nodes. However, NIOSH disagrees with SC&A’s opinion that these 

uncertainties apply to Hodgkin’s lymphoma and a few other classes of lymphoma which 

involve immobile cells forming the lymphatic system. The ability to accurately distinguish 

between Hodgkin’s and non-Hodgkin’s lymphoma has existed for close to a hundred years. 

While understanding of the origins of these diseases has certainly evolved over the years, the 
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contemporary assignment of the ICD-9 code reflects this accumulated knowledge. NIOSH 

strongly disagrees with SC&A’s argument that the described historical uncertainties of the 

origins and etiology of certain lymphomas in any way impacts the reliability of ICD-9 code 

assignment, which occurs when the claim is filed. 

SCA-TR-TASK3-0008, Rev. 1, Page 20:

From these statements, it is only fair to conclude that past and even present-day methods for 

the classification of neoplasms of the reticuloendothelial tissues were/are inconsistent and 

subject to a high degree of uncertainty. 

NIOSH comment:

NIOSH agrees that there are current and historic uncertainties regarding the cells of origin, 

and where in the body radiation might interact with these cells to subsequently form a 

neoplasm in the case of non-Hodgkin’s lymphoma. This uncertainty is the reason NIOSH 

has chosen to make the very claimant-favorable assumption that these interactions may have 

occurred, for example, in the thoracic lymph nodes. However, NIOSH disagrees with 

SC&A’s opinion that these uncertainties apply to Hodgkin’s lymphoma and a few other 

classes of lymphoma which involve immobile cells forming the lymphatic system. The 

ability to accurately distinguish between Hodgkin’s and non-Hodgkin’s lymphoma has 

existed for close to a hundred years. While understanding of the origins of these diseases has 

certainly evolved over the years, the contemporary assignment of the ICD-9 code reflects this 

accumulated knowledge. NIOSH strongly disagrees with SC&A’s argument that the 

described historical uncertainties of the origins and etiology of certain lymphomas in any 

way impacts the reliability of ICD-9 code assignment, which occurs when the claim is filed. 

SCA-TR-TASK3-0008, Rev. 1, Page :

Even when the assignment of an ICD-9 code is regarded with absolute accuracy, the site of 

exposure/cell-transformation is not absolute, as acknowledged by NIOSH in OCAS-TIB-012. 

For Tables 1, 3, 4, 8, 11, 13, and 14 of OCAS-TIB-012, a significant number of cancers are 

identified for which the internal target organ is either HNMO or bone marrow, along with 

either of the following cautionary statements: 

• The site of occurrence is the most likely site of the original injury. 

[Emphasis added.] 

• Therefore, the most plausible site of original radiation injury is the bone 

marrow. [Emphasis added.] 

While SC&A does not question NIOSH’s conclusion of a “most likely” or “most plausible” 

site of the original radiation injury, the need to give the claimant the benefit of doubt must be 

considered, as specified under 42 CFR 82. 

NIOSH comment:

The need to give the benefit of the doubt to the claimant is exactly what motivated NIOSH to 

revise the target organ assignment for non-Hodgkin’s lymphoma. However, EEOICPA does 

not prescribe that NIOSH ignore scientific plausibility. SC&A’s recommendations regarding 

Hodgkin’s lymphoma are not scientifically plausible. 
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The text from OCAS-TIB-012 quoted by SC&A reflects prudent scientific caution. The 

weight of the current scientific evidence suggests that it is plausible that non-Hodgkin’s 

lymphoma could have originated anywhere in the body, and benefit of the doubt dictates that 

NIOSH make claimant-favorable assumptions for target organ selection for this disease. The 

weight of the current scientific evidence also indicates that for Hodgkin’s disease (and 

similar lymphomas), the site of occurrence is the most likely site of original radiation injury, 

and this is also reflected in OCAS-TIB-012. 

Of course NIOSH cannot guarantee with absolute certainty that future scientific evidence 

won’t indicate changes from the procedures in OCAS-TIB-012, and it is unreasonable for 

SC&A to predicate its recommendations upon such a demand. If future scientific evidence 

reverses current understanding on this issue, NIOSH will revise our procedures accordingly. 

SCA-TR-TASK3-0008, Rev. 1, Page 20:

Uncertainty regarding the site of the original injury may even include acute lymphocytic 

leukemia (ICD-9 code 204), which, according to OCAS-TIB-012, consistently identifies the 

bone marrow as the only potential internal target organ. For example, § 497 in Beeson et al. 

1979 states the following: 

Acute lymphocytic leukemia arises in lymphoid tissue and is ordinarily first 

manifest by its presence in marrow. In some instances thymic infiltration 

precedes overt marrow disease, but it is not known whether the initial 

leukemogenic event in man is usually extramedullary [i.e. outside the bone 

marrow]. Many instances of lymphosarcoma of various cell types culminate in 

an acute leukemic phase which bears some resemblance to acute lymphocytic 

leukemia. [Emphasis added] 

NIOSH comment:

The report by Dr. Crowther clearly states, “In general, anything currently classified as a 

Leukemia (including those discussed below that I feel should be reclassified as leukemia) 

should be classified as red bone marrow under IMBA applicable organ”. Dr. Crowther does 

not make an exception for ALL. Dr. Crowther’s report describes that semantic arguments 

could probably be made about whether every single case fits this description, however the 

weight of the current scientific evidence suggests bone marrow as the appropriate target 

organ for ALL. It is NIOSH’s opinion that ignoring the advice of a highly qualified 

hematologist on the basis of a 29-year old textbook is not prudent. 

SCA-TR-TASK3-0008, Rev. 1, Page 23:

It is safe to assume that the more than 14-fold increase in alveolar macrophages among 

smokers will profoundly increase the transfer of activity to LNTH and LNET. The ICRP, 

however, offers no further discussion on the radiological impacts of smoking. In the absence 

of information, a reasonable approach might assume that the increased number of alveolar 

macrophages would proportionately increase the fractional amount of radioactivity 

transferred to and concentrated in the regional lymph modes. 
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NIOSH comment:

SC&A has presented no evidence that there is any correlation whatsoever between the 

number of alveolar macrophages and additional incorporation of radioactivity in the thoracic 

or extrathoracic lymph nodes. Even if such a correlation could be made, the overall increase 

in risk associated with this activity would have to be modeled, as previously described, in the 

context of all relevant information. To our knowledge, this information does not exist. The 

ICRP apparently did not feel that the scientific evidence justified making any 

recommendations on this issue. If SC&A has any evidence in this regard, NIOSH would be 

very interested in reviewing it. 

SCA-TR-TASK3-0008, Rev. 1, Page 23:

On the basis of first principles, it is only reasonable to conclude that the elevated number of 

alveolar macrophages would significantly enhance the relocation of respired 

radioparticulates to LNTH and LNET and proportionately raise their radiation exposure. 

NIOSH comment:

History is replete with reasonable-sounding speculations that are nonetheless wrong. NIOSH 

cannot base dose-reconstructions on unproven speculation. If SC&A has any evidence to 

back up these arguments, NIOSH would be very interested in reviewing it. 

SCA-TR-TASK3-0008, Rev. 1, Page 23:

During the Procedures Review Work Group teleconference on April 2, 2008, NIOSH stated 

that “. . . Due to the technical nature of this issue, a credible/quantitative assessment may be 

outside the scope of NIOSH’s responsibility.” 

NIOSH comment:

NIOSH does not recall making this statement as it is written. We did state that this is a 

highly technical issue; however, we do not recall asserting that an issue being highly 

technical puts it outside NIOSH’s responsibility. We also stated our position that SC&A was 

inappropriately selecting factors which might increase the dose, but neglecting factors which 

might decrease the dose (such as increased mass of the thoracic lymph nodes). We 

concluded the current scientific evidence does not support making the adjustments for 

smoking that SC&A is recommending. 
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APPENDIX A-2: NIOSH E-MAIL DATED MAY 1, 2008 
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APPENDIX B: NIOSH WHITE PAPER 

White Paper: 

NIOSH Re-examination of Lymphoma Target Organ Selection 

Questions have arisen regarding target organ selection for cancers of the lymphatic and 

hematopoietic systems. Current NIOSH guidance is for a medical review to be conducted for 

cases of lymphoma. In the past, these reviews have relied on the listed biopsy location for 

determination of appropriate target organs and this determination has frequently been “highest 

nonmetabolic organ” for internal target organ, and a nearby organ has been used as a surrogate 

for external target organ. NIOSH has re-examined the appropriateness of this strategy of target 

organ selection in light of the current scientific literature on the diagnosis and etiology of the 

various forms of lymphoma. 

To assist in its review, NIOSH sought the expert advice of Dr. Mark Crowther, Associate 

Professor of Medicine at McMaster University in Hamilton, Ontario. Dr. Crowther has boardcertifications in internal medicine and hematology. 

This re-examination has revealed that for many non-Hodgkin’s lymphomas, there are two 

problems in selecting target organs for organ-specific radiation dose reconstruction. First, the 

site of occurrence of the tumor is not necessarily the site of original radiation injury. NonHodgkin’s lymphoma is a disease involving malignant lymphocytes. Unlike the case for most 

primary solid tumors, where the tumor results from the interaction of radiation with immobile 

cells, radiation could have interacted with these lymphocytes anywhere in the lymphatic system, 

and then formed a tumor elsewhere. 

The second problem is that the site listed in the diagnosis may not actually be the site of 

primary involvement. Rather, it is common to list the site of the biopsy, which is selected based 

primarily on convenience, that is, as indicated by clinical symptoms and ease of surgical access. 

In such cases, selection of target organs will be based on claimant-favorable assumptions 

(i.e., assumptions that result in higher organ doses) and professional judgment about plausible 

sites of original radiation injury. In many cases, the thoracic lymph nodes associated with the 

lungs will be selected for two reasons: (1) due to the insoluble nature of many of the 

radionuclides energy employees could inhale, the dose to these organs is typically higher than 

the dose to other organs. (2) a significant fraction of the total lymphoid organ mass occurs in the 

thoracic cavity, in close proximity to the lungs, making this selection plausible. For the subset of 

lymphomas where tumor location is informative about the probable site of original radiation 

injury (e.g., Hodgkin’s disease, lymphosarcoma, etc.), this information will be considered in 

target organ selection. 

Note that this guidance pertains only to the selection of appropriate target organ as the 

site of radiation injury (i.e., for calculation of effective radiation dose during the dose 

reconstruction process.) It has no bearing on the selection of the appropriate IREP cancer risk 

model, nor does it impact the risk models themselves. 

Following extensive telephone and email consultations with Dr. Crowther, NIOSH 

prepared OCAS-TIB-012: Selection of internal and external dosimetry target organs for 

lymphatic/hematopoietic cancers. This technical information bulletin reviewed current NIOSH 

procedure regarding the target organ selection for lymphatic/hematopoietic cancers, as specified 

in ORAUT-OTIB-0005: IMBA organ, external dosimetry organ, and IREP model selection by 

ICD-9 code. 
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OCAS-TIB-012 was then subjected to further review by Dr. Keith Eckerman of Oak 

Ridge National Laboratory (ORNL). Dr. Eckerman, a recognized expert in internal dosimetry 

and a member of the International Commission on Radiological Protection (ICRP), provided 

several suggestions, the most significant of which was to select the thoracic lymph nodes 

[LN(TH)], rather than the extrathoracic lymph nodes [LN(ET)], for internal target organs in 

situations where the site of original radiation injury is unknown. Dr. Eckerman’s proposal, as 

noted in his attached review, was based on the fact that it is a plausible choice and that it is also 

claimant-favorable, as doses to LN(TH) are typically higher than doses to LN(ET). This 

suggestion was incorporated into Revision 1 of OCAS-TIB-012. 

Concurrent with preparation of OCAS-TIB-012, NIOSH began a program evaluation 

report to identify completed lymphoma dose-reconstructions with a probability of causation 

<50% at the upper 99th percentile credibility limit which may be affected by the revised organ 

selection guidance. Approximately 500 cases requiring re-examination have been identified. 

Further action on this re-examination, as well as implementation of OCAS-TIB-012 for currently 

uncompleted cases, is pending review by the Advisory Board on Radiation Worker Health, as 

requested by the Board at its meeting on October 19, 2005. 
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APPENDIX C: DR. CROWTHER REPORT 

Consultant’s Report 

Dose Reconstruction Project 

Dr Mark Crowther, MD, MSc, FRCPC 

General comments: 

In general, anything currently classified as a Leukemia (including those discussed below that I 

feel should be reclassified as leukemia) should be classified as red bone marrow under IMBA 

applicable organ, rather than “medical review.” Thus, in my opinion, all of the "leukemias" 

should be classified similarly to the classification currently used for acute myeloid leukemia 

(ICD9 205) and others. One could have a complicated semantic argument about whether all 

leukemias originate in the marrow; clearly, some do not but we presume that the majority do. 

Presumably the exposure causing the leukemia occurred in the marrow although again one could 

probably find examples where this is not true. Similarly, non-marrow exposures are probably 

responsible for the "lymphomas" and other non-leukemic hematologic malignancies. However, 

again, one would have a hard time finding good quality scientific evidence to back this up and 

there is no doubt that there are examples of non-leukemic hematologic malignancies where the 

exposure occurred in the marrow (early in leukocyte development) or in other non-marrow and 

non-lymphatic sites. 

For the purposes of this proposal I would include organs such as the thymus within the 

"lymphatic system" since it would be difficult to pin down any particular diseases which 

occurred within or outside the thymus. The lymphatic system can be assumed to spread widely 

throughout the body and although concentrated in the chest and abdomen it has components 

throughout the body. It is my understanding that the lymphatic system is classified within the 

"remainder" category. 

All forms of hematological malignancy (with the possible exception of limited stage Hodgkin’s 

disease) are assumed to be widely disseminated at presentation; thus they are treated with 

systemic therapy. Hodgkin’s disease is assumed to start at a single location and spread to 

contiguous lymph node groups. Thus, classifying a specific site of exposure for non-Hodgkin’s 

hematological malignancies is illogical; even if the bulk of disease is confined to a single 

location (for example massive lymphadenopathy in the left cervical region) it cannot be assumed 

that this was the site of original exposure. Similarly, if a patient had a limited exposure (for 

example, radiation exposure confined to a limb) and later presented with a lymphoma at a remote 

site, it cannot be assumed that they are unrelated, since the exposed organ (in this case the 

lymphoreticular system) is not confined to a discrete body section or organ. 

I presume that the classification "leukemia, less CLL" is a carryover from the concept that CLL 

is not a radiation related disease. As noted, many disorders (for example Sezary syndrome and 

hairy cell leukemia as well as some forms of indolent lymphomas such as small lymphocytic 

lymphoma) behave very similarly to CLL and would best be classified as a CLL like disorder. 

However, it appears to me this would require the generation of a new IREP model since it is not 

included in this document. 
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I realize that you are confined to ICD codes however many of the diseases presented are 

illogical; for example, I'm not sure what "subacute leukemia" is and many of the disorders (such 

as leukemias limited to body cavities) are also illogical. 

Specific review comments: 

202.2 SEZARY DISEASE AND ALL SUBTYPES (202.20 TO 202.28) 

This would generally be regarded as a form of leukemia and thus probably is better classified as 

a “red bone marrow” disorder, rather than “Remainder.” Under IREP model I would suggest 

that they should be classified as a leukemia, although it would difficult to classify them as 

“leukemia, less CLL” since they all behave like CLL. 

202.4 LEUKEMIA RETICULENDOTHELIAL AND HAIRY CELL LEUKEMIA (202.4 TO 

202.48) 

These would generally be regarded as a form of leukemia and thus probably is better classified as 

a “red bone marrow” disorder, rather than “Remainder.” Under IREP model I would suggest 

that they should be classified as a leukemia, although it would be difficult to classify them as 

“leukemia, less CLL” since they all behave like CLL. 

204.1 TO 204.11 CHRONIC LYMPHOID LEUKEMIA 

These are regarded as a form of leukemia and thus should be classified as a “red bone marrow” 

disorder, rather than “NA”. Under IREP model I would suggest that they should be classified as 

a leukemia, (cannot, logically, be classified as “leukemia, less CLL” ; see comments above ). 

205.0 TO 205.11 ACUTE MYELOID LEUKEMIA 

Not clear to me why they are classified as “Leukemia, less CLL AND Acute Myeloid Leukemia” 

– this classification is illogical since they are acute myeloid leukemia.
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APPENDIX D: DR. ECKERMAN REPORT 

Target Organs for Lymphatic and Hematopoietic Cancers 

Comments/Suggestions by K. F. Eckerman 

Introduction 

The lymphatic system consists of bone marrow, spleen, tonsils, nodes, and thymus. The only

nodes explicitly addressed in dosimetric models are those associated with the respiratory system 

in the head (ET) and thorax (TH). The number of nodes in the body has been indicated to be 

between 600 – 700; 8-37 in the arm pits, at least 50-60 in the lung, and 200-500 in the mesentery 

(ICRP 1975). The same mass has been estimated for the extrathoracic lymph nodes [LN(ET)] 

and thoracic lymph nodes (LN(TH)} in adults; the value being 12 and 15 g in the female and 

male, respectively (ICRP 1994). If the 60 nodes in the lung have a mass of 15 g, then the mass 

of the 600 nodes of the body would be 150 g. ICRP publications do not indicate a mass for the 

body’s lymph nodes. 

General Comment 

The following statement appears frequently in the proposed technical information bulletin. 

 

Due to the insoluble nature of many of the radionuclides ...the dose to the 

extrathoracic lymph nodes [LN(ET)] is typically higher than the dose to HNMO. 

While the statement is true, the thoracic lymph nodes [LN(TH)] are generally more highly 

irradiated that the extrathoracic nodes, at least in ICRP’s calculations. This is typically the case 

for in most radionuclides of U, Th, Pu, Am, and Cm. Apparently IMBA differs for the standard 

calculations on this matter? Furthermore the LN(TH) are present in the thoracic not LN(ET) as 

apparently assumed here. 

Specific Comments: 

Table 1: ICD 200 – 200.18 

Below are my suggested changes by ICD for the internal – all externals accepted. 

a. 200.00 LN(TH) 

b. 200.01 LN(ET) 

c. 200.02 LN(TH) 

d. 200.04 LN(TH) 

e. 200.05 Colon 

f. 200.06 Colon 

g. 200.08 LN(TH) 

h. 200.10 LN(TH) 

i. 200.11 LN(ET) 

j. 200.12 LN(TH) 

k. 200.14 LN(TH) 

l. 200.15 Colon 
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m. 200.16 Colon 

n. 200.18 LN(TH) 

Table 2: ICD 200.2-200.28 

Change all the internals target organs to LN(TH). Note the last sentence of the discussion 

following the table suggest that a large fraction of the lymph mass is in the thorax and yet the 

extrathoracic lymph was cited in the table. From the introduction the thoracic lymph is probably 

only about 1/10 of the total lymph node mass. 

Table 3: ICRP 200.8 – 200.08 

Below are my suggested changes by ICD for the internal – all externals accepted. 

a. 200.8 LN(TH) 

b. 200.80 LN(TH) 

c. 200.81 LN(ET) 

d. 200.82 LN(TH) 

e. 200.84 LN(TH) 

f. 200.85 Colon 

g. 200.86 Colon 

h. 200.88 LN(TH) 

Here again the discussion following the table associated LN(ET) with the thorax! Also the 

statement that the HNMO is the “claimant-favorable choice” is not clear since it rules out a 

metabolic organ. For insoluble materials the target of 200.85 and 200.86 is suggested above to 

be the colon rather than HNMO. Maybe these should be HNMO or Colon to be claimant 

favorable. 

Table 4: ICD 201-201.98 

Below are my suggested changes by ICD for the internal – all externals accepted. 

a. 201 LN(TH) 

b. 201.0 LN(TH) 

c. 201.00 LN(TH) 

d. 201.01 LN(ET) 

e. 201.02 LN(TH) 

f. 201.04 LN(TH) 

g. 201.05 Colon 

h. 201.06 Colon 

i. 201.08 LN(TH) 

j. 201.1 LN(TH) 

k. 201.10 LN(TH) 

l. 201.11 LN(ET) 

m. 201.12 LN(TH) 

n. 201.14 LN(TH) 

o. 201.15 Colon 

p. 201.16 Colon 

q. 201.18 LN(TH) 

r. 201.2 LN(TH) 

s. 201.20 LN(TH) 
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t. 201.21 LN(ET) 

u. 201.22 LN(TH) 

v. 201.24 LN(TH) 

w. 201.25 (Colon) 

x. 201.26 (Colon) 

y. 201.28 LN(Th) 

z. 201.4 LN(TH) 

aa. 201.40 LN(TH) 

bb. 201.41 LN(ET) 

cc. 201.42 LN(TH) 

dd. 201.44 LN(TH) 

ee. 201.45 Colon 

ff. 201.46 Colon 

gg. 201.48 LN(TH) 

hh. 201.5 LN(TH) 

ii. 201.50 LN(TH) 

jj. 201.51 LN(ET) 

kk. 201.52 LN(TH) 

ll. 201.54 LN(TH) 

mm. 201.55 Colon 

nn. 201.56 Colon 

oo. 201.58 LN(TH) 

pp. 201.6 LN(TH) 

qq. 201.60 LN(TH) 

rr. 201.61 LN(ET) 

ss. 201.62 LN(TH) 

tt. 201.64 LN(TH) 

uu. 201.65 Colon 

vv. 201.66 Colon 

ww. 210.68 LN(TH) 

xx. 201.70 LN(TH) 

yy. 201.71 LN(ET) 

zz. 201.72 LN(TH) 

aaa. 201.74 LN(TH) 

bbb. 201.75 Colon 

ccc. 201.76 Colon 

ddd. 201.78 LN(TH) 

eee. 201.9 LN(TH) 

fff. 201.90 LN(TH) 

ggg. 201.91 LN(ET) 

hhh. 201.92 LN(TH) 

iii. 201.94 LN(TH) 

jjj. 201.95 Colon 

kkk. 201.96 Colon 

lll. 201.98 LN(TH) 
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Table 5: ICD 202-202.08 

Change all internal target organs to LN(TH). Externals look OK. 

Table 6: ICD 202.1 – 202.18 

Use skin for the internal targets since it is explicit in the calculations. 

Table 7: ICD 202.2 – 202.28 

Same treatment as in Table 6 is suggested. 

Table 8: ICD 202.3- 202.38 

Since these cancers are found in connective tissue, which is a component of all solid organs, why 

not use the highest dose to a solid organ as the estimate for internal exposure. I would exclude 

bone surface from this list. 

Table 9: ICD 202.4 – 202.48 

OK 

Table 10: ICD 202.5-202.58 

Same comment at for Table 6 and 7. 

Table 11: ICD 202.6-202.68 

a. 202.6 LN(TH) 

b. 202.60 LN(TH) 

c. 202.61 LN(ET) 

d. 202.62 LN(TH) 

e. 202.64 LN(TH) 

f. 202.65 Colon 

g. 202.66 Colon 

h. 202.68 LN(TH) 

Table 11: ICD 202.8 – 202.98 

Change all internal targets to LN(TH). 

Table 13: ICD 203-203.01 

OK 

Table 14: ICD 203.1 -208.91 

OK 

References 

ICRP 1975. Report of the Task Group on Reference Man. ICRP Publication 23, Pergamon 

Press, Oxford, United Kingdom. 

ICRP 1994. Human Respiratory Tract Model for Radiological Protection. ICRP Publication 66, 

Ann. ICRP 24(1-3).