potential high-LET occupational dose may come from highly scattered low-energy neutrons.

Again, the lack of reference to primary sources is a concern here.

Page 7. The treatment of inverse dose rate effects seems inadequate and again does not seem to
consider the recent literature adequately. Both theory and experiment (e.g. Lubin ef al 1995)
strongly suggest that the inverse dose rate effect is relevant only for protracted high doses of
high-LET radiation. As the analysis nowhere uses risks or weighting factors that refer to
protracted high doses of high-LET radiation, it is hard to see why Eq. 5 contains an

“enhancement factor”.

Page 8. The use of Eq. 2 rather than Eq. 3 for photons, while welcome, makes for considerably
inconsistency within the report as a whole. The justification (page 9) that if one makes an
“arbitrary assumption”, the risks estimated using Eq. 3 would be about the same as the risks
estimated using Eq. 2, is itself not self consistent. If one forgets about Eq. 3, however (as the
authors do in this section), the analysis is quite reasonable and is the only part of the current
report which I found more satisfactory than the material in section IV-G of the accompanying
“Draft Report of the NCI-CDC Working Group” - specifically because the latter assumes a
radiation weighting factor of 1 for all photons.

Page 10. Again Eq. 2 is used rather than Eq. 3, this time without any comment or discussion. It is
hard to see how the authors can justify using a different risk model for neutrons compared with
that for alpha particles. The only practical explanation that I can see is that Edwards only

produced his analysis for neutron data.

Page 11. Similarly the treatment of the inverse dose-rate effect is inconsistent between neutrons

and alpha particles. No rationale is given for this difference.


COLUMBIA UNIVERSITY
CENTER FOR RADIOLOGICAL RESEARCH
630 WEST 168" STREET
New YORK, NY 10032

WORK: (212) 305-9930
FAX: (212) 305-3229
djb3@columbia.edu
Dec 13, 2001
Dr. James Neton

NIOSH
Dear Dr. Neton,
Attached is my review of “Proposed Radiation Weighting Factors for use in
Calculating Probability of Causation of Cancer”
FYI, I took about 3.5 days to do the review.

Yours Sincerely,
David Bremner

David J. Brenner, Ph.D., D.Sc.,

Director, Radiological Research Accelerator Facility
Professor of Radiation Oncology and Public Health,
Columbia University


Review of “Proposed Radiation Weighting Factors for Use in Calculating PC of Cancer”

The document under review would be quite appropriately submitted for journal
publication, but I do not see it as an appropriate basis for PC tables. The analysis techniques used
in it, particularly the use of Eq. 3, are highly non standard, and are inadequately justified,
particularly as there is not an established body of peer-reviewed literature to back them up. In
fact the only mention of the use of Eq. 3 that I know of in the peer-reviewed literature is in a
1999 paper by Alan Edwards at the UK NRPB; Edwards discusses the advantages of the
approach but finally opts for a completely different one. Nor is Eq. 3 applied uniformly, being

used only for neutrons, but not for other types of radiation.

In terms of the actual data analysis, the document relies heavily on the rather sparsely
documented analysis by Edwards (1999), and almost not at all on documented primary sources.
While this might be reasonable if a standard analysis technique was being used, the fact that this
is not the case makes the reliance on Edwards of considerable concern. Indeed Edwards (1999)
states “the values given ... result from my judgment of the basic data and other equally valid
values could be obtained by others considering the same data”. While this is perfectly acceptable
in the Edwards paper, it is not a good basis for the PC tables.

I did not find the treatment of uncertainly distributions satisfactory. In too many places
parameters were simply stated without adequate justification or documentation. Again the issue

of not being able to rely on past NCRP or ICRP analyses is a concern.

I note that in section IV-G of the accompanying material (Draft Report of the NCI-CDC
Working Group), there is a two page analysis of RBE. While it has aspects that can be criticized
and potentially improved (particularly, as discussed below, the rather implausible assumption
that photons of all energies have the same biological effectiveness), because it is so grounded in
the extensive prior analyses of the NCRP and ICRP, it makes for a more satisfactory basis for use

in PC tables than does the report under review.

Finally the use of terminology is somewhat sloppy throughout the paper. For example the
term “radiation weighting factor” (clearly defined by ICRP) is sometimes used to refer to W,,,

and sometimes to w;,, this latter also sometimes being referred to as the “RBE factor”.


In summary, not having the extensive analyses by the ICRP, nor those of the NCRP, as
background support, an expert witness would be hard-pressed to defend in court the proposed

radiation weighting factor.

Specific Comments follow:

Specific Comments:

Page 3. The argument applied in rejecting use of the standard Eq. 2 relates to the question of
whether high values of RBEmsx are associated with larger values of the DDREF than the factor of
2 used in analyzing low-LET A-bomb data. This may or may not be the case, but even if the
authors did make a strong case, there are simpler methods to overcome the problem than
rejecting the use of Eq. 2, and thus throwing away much of the accumulated analyses of the ICRP
and the NCRP.

Page 3. The use of the Eq. 3 is primarily designed to avoid problems associated with dose rate.
However the authors still need to add an ad-hoc correction for inverse dose rate effects. Again

this argues against changing the basic formalism used from the standard Eq. 2 to Eq. 3.

Page 4. The argument here that the use of Eq. 3 is necessary because the variability in their
derived weighting factor (wr,H) is “considerably less than the variability in RBEmax” is weak. In
the paper on which the current authors rely heavily (Edwards 1999), Edwards derives a
variability of a factor of 5 in derived RBEvax values, and a variability of a factor of 3% in

derived wry values.

Page 6. There are more recent data on the RBE of low-energy neutrons, published subsequent to
the Edwards (1999) analysis, which should have been considered (e.g. Miller et al Int. J. Radiat.
Biol. 2000). At this point the weight of evidence is probably that the cancer tisk does not

decrease with neutron energy from, say, 1 MeV to 50 keV — an important issue since much