DRAFT June 17, 2002

In the assumed lognormal distributions of REFs for fission neutrons, there is only a small
probability of values less than 1.0, and all values in the assumed piece-wise uniform distributions
at other neutron energies are greater than 1.0. Thus, the distributions incorporate an assumption
that the biological effectiveness of neutrons is greater than that of high-energy gamma rays.
Nonetheless, we acknowledge that the REF could be less than 1.0 when most of the dose is
delivered by 2.2-MeV gamma rays emitted following capture of thermalized neutrons by 'H
nuclei. This situation could occur when the incident neutron energy is less than about 10 keV,
but should not be important at higher energies (NCRP, 1971). The possibility of an REF less
than 1.0 at low neutron energies is based on the consideration that the biological effectiveness of
2.2-MeV gamma rays could be somewhat less than that of the reference Co gamma rays of
lower energies (1.2 and 1.3 MeV) used in radiobiological studies to estimate RBEs (Straume,
1995). However, we do not believe that this difference needs to be taken into account in
estimating REFs for neutrons. The reduction in the biological effectiveness of 2.2-MeV gamma
rays relative to Co gamma rays presumably is less than a factor of 2 (Straume, 1995). This
difference should be small compared with possible errors in estimating cancer risks that result
from an assumption that the spectrum of photons to which the Japanese atomic-bomb survivors
were exposed has the same biological effectiveness as “Co gamma rays. This assumption is
implicit in the REFs for neutrons, and other radiations, developed in this report.

We also acknowledge that the assumed probability distributions of REFs for neutrons
could tend to overestimate cancer risks in humans at energies greater than about 0.1 MeV (ICRP,
1997), In studies in small mammals used to estimate RBEs for fission neutrons, a substantial
fraction of the dose to target tissues was delivered by high-LET radiations (e.g., recoil protons).
In humans, however, more of the dose to deep-lying organs and tissues would be delivered by
gamma rays produced by neutron interactions in tissue. Therefore, RBEs obtained from studies
in small mammals should tend to overestimate the biological effectiveness of incident fission
neutrons in many organs and tissues of humans (ICRP, 1997; Edwards, 1997; Edwards, 1999).
We have not adjusted the probability distributions of REFs for neutrons to account for possible
differences in biological effectiveness in humans compared with small mammals, mainly because
calculations indicate that this difference depends in a complicated way on the neutron energy, the
target tissue of concern, and the irradiation geometry (ICRP, 1997).

ALPHA PARTICLES

Approach to Estimating RBEs

Like neutrons, alpha particles are high-LET radiations that have been shown to be
considerably more effective than low-LET radiations in inducing stochastic responses in
biological systems. Alpha particles also are presumed to have linear dose-response relationships
for any endpoints at doses below those where significant cel! killing occurs. Thus, in principle, it
would be desirable to estimate cancer risks in humans exposed to alpha particles based on
estimates of RBE at high acute doses of high-energy gamma rays, RBE,, in accordance with the

29


DRAFT June 17, 2002

23r
4ON
y 20- 4 .
gS
at] L i \
2
2 ash \
B1 ; \
z \
2 / \
= / \
sob 4 .
s / \
3 4 x
8 5 2 L >
1 z i L L 7 L z 1 7 Ls 1 i 3
we w? 10° ww Ww 10 10 10 ~—10

Incident neutron energy { MeV)

Fig. 7. Radiation weighting factor, wg, vs. neutron energy given in Fig. A.1 of ICRP (1991). Dashed
curve is approximation given by eq. (6).

Table 6. Quality factors for neutrons currently used by U.S. Nuclear
Regulatory Commission and U.S. Department of Energy*

Neutron energy Mean quality Neutron energy Mean quality
(MeV) factor (MeV) quality
<0.001 2 10 6.5
0.01 2.5 14 75
0.1 75 20 8
0.5 Bt 40 7
1 11 60 5.5

2.5 9 100 4
5 8 2200 3.5
7 7

*Values given in NRC (1991) and DOE (1993) are based on calculations and recommendations
by the NCRP (1971).

20


DRAFT June 17, 2002

Relative Probabili

1.00 10.75 20.50 30.25 40.00

Fig. 10. Assumed piece-wise uniform probability distribution of radiation effectiveness factor at low
doses and low dose rates of reference high-energy gamma rays, REF,, for induction of leukemias
by neutrons of energy 10-100 keV or 2-20 MeV. Other probability distributions of REFs for
solid tumors and leukemias at neutron energies other than 0.1-2 MeV are similar.

Correction for Inverse Dose-Rate Effect

An additional consideration in estimating cancer risks from exposure to neutrons is the
possibility that the biological effectiveness of neutrons and other high-LET radiations increases
as the dose rate decreases. This phenomenon is referred to as the inverse dose-rate effect. Some
studies of life-shortening and tumor induction in small mammals at relatively high doses of
fission neutrons reviewed by the NCRP (1990), the ICRP (1991), and CIRRPC (1995) show an
enhancement in biological effectiveness by as much as a factor of about 3 when the same dose is
delivered at lower dose rates. However, this effect is not seen in all studies of these endpoints at
high doses, and it usually is not seen at lower doses.

Although it is not clear whether the mechanisms responsible for the observed inverse
dose-rate effect for fission neutrons in some studies would apply in estimating cancer risks in
humans, especially at low doses (CIRRPC, 1995), we apply a small correction to account for this
effect. This correction, which we refer to as an enhancement factor, is applied only in cases of
chronic exposure to neutrons of any energy; it does not apply to acute exposures.

Based on discussions and summaries of data on life-shortening and tumor induction in
mice given in Sections 6 and 8 and Tables 6.2 and 8.2 of NCRP (1990), we assume a probability
distribution for the enhancement factor representing an inverse dose-rate effect under conditions
of chronic exposure to neutrons that ranges from 1 to 3 and is weighted toward lower values.
Specifically, we assume a discrete probability distribution with 50% of the values at 1.0, 30% at
1.5, 15% at 2.0, and 5% at 3.0. The arithmetic mean of this distribution is 1.4. Assigning the

25


DRAFT June 17, 2002

RP
a
1
o
Oo

°

T
_
o

a
T
—o—

o

Transformations per surviving cell, Gy*, x 10~

0 n 1 " }
0.01 0.4 1 10 100
Neutron energy, MeV

Fig. 9. Variation of RBE,, with neutron energy for transformation of C3H10T% mouse cells given in
Fig. 7 of Edwards (1997). Solid circles are data of Miller et al. (1989), and open squares are data
of Coppola (1993); error bars represent one standard error.

[3] The upper 97.5% confidence limit of each distribution should be less than the
upper confidence limit of the appropriate distribution for fission neutrons, but by
less than a factor of 2 or 4 to take into account that there is substantial uncertainty
in the reductions in REFs compared with fission neutrons. Thus, the upper
confidence limit relative to the median should increase compared with the ratio of
these quantities in the lognormal probability distributions for fission neutrons.

In general, probability distributions of REFs that have these properties must be highly skewed
toward values at the low end of an assumed range of values. Only a highly skewed distribution
has a fixed lower bound and a decreased median and upper confidence limit but an increased
upper confidence limit relative to the median compared with an assumed lognormal distribution
for fission neutrons.

There are many probability distributions that can be constructed to represent REFs based
on the three properties described above. In the interest of simplicity, we represent the REFs in all

22


DRAFT

June 17, 2002

15
Oo
%
O 1.0
8
z ° °
8 e
Fa e
S OSPF e
3 ia)
Oo
co
fe) L J 1 J
0.01 O4 4 10 100

Neutron energy, MeV

Fig. 8. Variation of RBE,, with neutron energy for induction of dicentric chromosomes in human
lymphocytes given in Fig. 6 of Edwards (1997; 1999). Solid circles are data of Edwards et al.
(1985; 1990), and open squares are data of Sevan’kaev et al. (1979).

Given the paucity of data on the energy dependence of RBEs for neutrons, we develop
subjective probability distributions of REFs for solid tumors and leukemias at energies other than
0.1-2 MeV based on the probability distributions for fission neutrons developed previously and
an assumption that the ICRP’s step function representation of the radiation weighting factor
shown in Fig. 7 provides a general indication of the energy dependence of REFs. We then
assume that the probability distributions of REFs for neutrons at energies other than 0.1-2 MeV
should have the following three properties:

(1]

[2]

The lower bound of each distribution should be at 1.0, based on an assumption
that neutrons of any energy should not be less effective than high-energy gamma
tays in inducing cancers in humans.

The median (50" percentile) of each distribution should be less than the geometric
mean of the appropriate lognormal probability distribution for fission neutrons by
a factor of about 2 or 4, based on the ICRP’s step function representation of the
radiation weighting factor (see Table 1 and Fig. 7).

21


DRAFT June 17, 2002

Leukemias (REF,) —

30% weight to uniform distribution from 1.0 to 2.3;
50% weight to uniform distribution from 2.3 to 3.5;
20% weight to uniform distribution from 3.5 to 25;
Median of 2.8 and upper 97.5% confidence limit of 22.

The assumed probability distribution of REF, for leukemias at neutron energies of 10-100 keV or
2-20 MeV is shown in Fig. 10. The distributions in the other cases are similar, the differences
being in the assumed widths of each interval in a piece-wise uniform distribution.

The probability distributions of REFs for neutrons of energy other than 0.1-2 MeV
described above illustrate the important point discussed in the Introduction that the assumed
distributions represent states of knowledge about the biological effectiveness of different
radiation types. These distributions are defined by the assumed properties of the lower bound,
median, and upper confidence limit and the assumption of a particular form of the distribution
(piece-wise uniform), but many other plausible distributions that are consistent with the limited
data on RBEs could be developed. The assumed piece-wise uniform distributions clearly do not
represent frequency distributions of RBEs that would be obtained if repeated radiobiological
experiments were performed, nor are they intended to.

In the piece-wise uniform probability distributions described above, some weight is given
to the possibility that the REF for a particular cancer type at energies of 10-100 keV or 2-20 MeV
is higher than the corresponding REF for fission neutrons (energies of 0.1-2 MeV), and similarly
for the REF for a particular cancer type at energies less than 10 keV or greater than 20 MeV
compared with the corresponding REF at 10-100 keV or 2-20 MeV. This possibility is supported
by the data shown in Figs. 8 and 9, and by the results of a recent study which indicated that the
biological effectiveness of 70-keV and 350-keV neutrons was not significantly different (Miller
et al., 2000).

In comparing the assumed probability distributions of REFs for solid tumors and
leukemias that apply at particular neutron energies, it is important to bear in mind that the REFs
for solid tumors apply at high doses and high dose rates of the reference high-energy gamma
rays, whereas the REFs for leukemias apply at low doses and dose rates. Consequently, the
probability distribution of REF, for leukemias at a given energy has higher values than the
corresponding distribution of REF,, for solid tumors even though, as noted previously, RBEs for
leukemias induced by fission neutrons tend to be lower than RBEs for solid tumors. To provide
a better comparison, the assumed distributions of REF, for solid tumors could be increased by a
factor of about 2 to yield equivalent distributions of REF,, based on the DDREF for the reference
radiation generally used in radiation protection (ICRP, 1991; NCRP, 1993).

24


DRAFT

June 17, 2002

Table 5, Estimates of RBE, and RBE,, of fission neutrons for tumor induction in
B6CF1 mice derived from analysis of selected study by Edwards (1999)*

Times of death

(days after

Tumor irradiation) Sex RBE,? RBE,,’
Lymphocytic 600-799 Male 6.6 +18
2.040.3 20+5
5.7+0.9 12#4
36+ 13
Female 5.4+0.6 8.4+0.7
11.4406 17.8 4 1.5
800-999 Male 2.5 +0.5 9.7215
6.5% 1.1 25.2 + 3.2
Female 8.5 + 3.0 8.5 41.8
17+5 15.8 + 2.6
Vascular tissue 600-799 Male 4.7+0.6 13.9+2.6
Female 3.7410 7243.2
800-999 Male 4.8 + 1.0 13.74 1.6
Female 64+ 14 8.9 + 2.0
All epithelial 600-799 Male 5.541.0 2345
tissue or ovary 11.0415 4547
Female 10.5 41.5 2344
800-999 Male 6.2413 14.4%2.9
13.442.2 31+5
Female 9.7419 19+6

“See Table 5 of Edwards (1999). RBE, is RBE at high doses and high dose rates of reference

high-energy gamma rays, and RBEy is RBE at low doses and low dose rates obtained by extrapolation of

data on dose-response for neutrons and the reference radiation. Analysis was based on data given in

Grahn et al. (1992). When two sets of values are given, they represent alternative interpretations that are
consistent with the data.
Uncertainties are one standard error.

16


DRAFT June 17, 2002

.060

04. Bernese

030—""~

Probabili

-015"

.006 > ° y , f , ' . 4

0.00 15.00 30.00 45.00 60.00

Fig. 12. Assumed probability distribution of REF, for fission neutrons and leukemias shown in Fig. 10
modified by enhancement factor representing inverse dose-rate effect under conditions of chronic
exposure. Median of distribution is at 7, and 95% confidence interval lies between 1.5 and 55;
about 1.4% of values lie between 60 and 120.

where REF,,,, and REF,,, are the radiation effectiveness factors at high doses and high dose rates
and at low doses and dose rates of high-energy gamma rays, respectively, EF, is the enhancement
factor representing an inverse dose-rate effect under conditions of chronic exposure, R,,, is the
risk coefficient (ERR per Gy) at high acute doses of high-energy gamma rays for the solid tumor
of concern, a is the coefficient of the linear term in the linear-quadratic dose-response
relationship for leukemias at high acute doses of high-energy gamma rays, and D, is the absorbed
dose of neutrons in the organ or tissue of concern.

In addition to the distinction between solid tumors and leukemias, which is based on
differences in RBEs for the two cancer types as well as the different assumptions about the form
of the dose-response relationships at high acute doses of high-energy gamma rays, the REFs for
neutrons are assumed to be energy dependent. REFs for five energy ranges are defined, and the
energy ranges are those used by the ICRP to define the energy dependence of the radiation
weighting factor for neutrons (see Fig. 7). When neutron energies are unknown, the REFs for
fission neutrons (0.1-2 MeV) should be used.

The assumed probability distributions of REFs for neutrons and the enhancement factor

representing the inverse dose-rate effect under conditions of chronic exposure to neutrons are
summarized in Table 7.

27


DRAFT June 17, 2002

highest weight to the value 1.0 (i.e., an assumption of no inverse dose-rate effect) takes into
account that the effect is not seen in all studies at high doses and usually is not seen at low doses
of greatest interest in routine exposures of workers and the public.

Applying the assumed probability distribution representing the inverse dose-rate effect to

the distributions of REFs shown in Figs. 6 and 10 results in the probability distributions under
conditions of chronic exposure to neutrons shown in Figs. 11 and 12.

Summary

At any dose and dose rate of neutrons (7), cancer risks in humans are estimated using the
following equations:

Solid tumors —
%, = REF,y x EF, x Ry x D, O)
Leukemias —

R, = a x REF,, x EF, x D, (8)

n

.03:
025+ |
a .017
oo
3
© cod . |
| | hasta
.000 - M i ! : L
> 4
0.00 11.25 22.50 33.75 45.00

Fig. 11. Assumed probability distribution of REF, for fission neutrons and solid tumors shown in Fig. 6
modified by enhancement factor representing inverse dose-rate effect under conditions of chronic
exposure. Median of distribution is at 10, and 95% confidence interval lies between 2.4 and 47;
about 3% of values lie beyond 45.

26


DRAFT June 17, 2002

cases by piece-wise uniform (step-function) probability distributions. We assume that each
probability distribution has three steps (intervals), and we assign probabilities (weights) of 30%
to the first interval, 50% to the second interval, and 20% to the third interval in all cases. The
width of each interval in the piece-wise uniform distribution then is adjusted to obtain a
distribution in which the median and upper 97.5% confidence limit approximate the desired
values. Again, the median is assumed to be about a factor of 2 or 4 less than the median of the
appropriate lognormal distribution for fission neutrons, and the reduction in the upper confidence
limit is assumed to be less than a factor of 2 or 4. We assume that the upper confidence limit
should be reduced by a factor of about 1.7-1.8 when the median is reduced by a factor of 2, and
that the reduction should be a factor of (1.7-1.8)’, or about 3, when the median is reduced by a
factor of 4. We believe that reducing the upper confidence limit by a substantially lower factor
(e.g., a factor of 1.5 when the median is reduced by a factor of 2) would give too much weight to
the uncertainty in the reduction of the median compared with the uncertainty in the appropriate
REF for fission neutrons.

The assumed piecewise-uniform probability distributions of REFs for neutrons of energy
other than 0.1-2 MeV that have the properties described above are summarized as follows:

E= 10-100 keV or 2-20 MeV (factor of 2 reduction in median) —
Solid tumors (REF,) -
30% weight to interval from 1.0 to 3.0,
50% weight to interval from 3.0 to 5.0;
20% weight to interval from 5.0 to 20;
Median of 3.8 and upper 97.5% confidence limit of 18.
Leukemias (REF,) -
30% weight to interval from 1.0 to 4.0;
50% weight to interval from 4.0 to 8.0;
20% weight to interval from 8.0 to 40;
Median of 5.6 and upper 97.5% confidence limit of 36.
E<10 keV or > 20 MeV (factor of 4 reduction in median) -
Solid tumors (REF) —
30% weight to interval from 1.0 to 1.6;
50% weight to interval from 1.6 to 2.4;

20% weight to interval from 2.4 to 12;
Median of 1.9 and upper 97.5% confidence limit of 11.

23


DRAFT June 17, 2002

REFs at Other Neutron Energies

Estimation of cancer risks in humans from exposure to neutrons is complicated by the
apparent dependence of RBEs on neutron energy. This energy dependence is represented by the
radiation weighting factors currently recommended by the ICRP (1991) and the NCRP (1993) for
use in radiation protection (see Table | and Fig. 7). In comparison, quality factors at different
neutron energies currently used by the U.S. Nuclear Regulatory Commission (NRC, 1991) and
the U.S. Department of Energy (DOE, 1993) are given in Table 6. These quality factors were
developed by the NCRP (1971) based on calculated depth-dose distributions in a cylindrical
phantom or tissue slab at incident neutron energies of 0.025 eV to 400 MeV. The recommended
radiation weighting factors and the quality factors used by regulatory authorities in the U.S.
indicate that the probability distributions of REFs for fission neutrons described above apply at
energies where the biological effectiveness is the highest.

The reductions in the radiation weighting factor by a factor of 2 or 4 at neutron energies
outside the range of 0.1-2 MeV recommended by the ICRP (1991) and the NCRP (1993) are
based mainly on limited data on the energy dependence of RBE,, obtained from studies in
animals and cell cultures, which are reviewed by the NCRP (1990) and the NRPB (Edwards,
1997), and calculations of the energy dependence of the neutron quality factor, such as those
shown in Fig. 2 (ICRU, 1986) and given in Table 6 (NCRP, 1971). The variation of RBE,, with
neutron energy is illustrated by the data shown in Figs. 8 and 9 (Edwards, 1997; 1999),

The ICRP (1991) also suggested that its recommended step function for the radiation
weighting factor given in Table 1 can be represented by a smooth function of the form

Wa = 5 + 17exp[-(in(2E))*/6} , (6)

where E is the neutron energy in MeV. This relationship is not intended to imply any biological
significance, but it does provide a convenient calculational tool when incident neutron energies
are well known. The smooth function in eq. (6) is shown with the recommended step function
for the radiation weighting factor in Fig. 7.

As indicated by the data shown in Figs. 8 and 9, experimental information on the energy
dependence of RBEs for neutrons is sparse. There are a few studies at energies of 10-100 keV or
2-20 MeV. However, reviews by the NRPB (Edwards, 1997) and the NCRP (1990) did not
provide any data on RBEs at energies less than 10 keV or greater than 20 MeV. Thus, based on
available data, there is considerable uncertainty in REFs that would represent the biological
effectiveness of neutrons in these energy ranges relative to fission neutrons.

19


DRAFT June 17, 2002

model in eq. (3), for example, as we have done for neutrons, to lessen the influence of variations
in DDREFs of the reference radiations. The importance of DDREF is indicated by the
pronounced increase in RBEs with decreasing dose of alpha particles in the studies summarized
in Fig. 13. As is the case with neutrons, high estimates of RBE at low doses, RBE,,, may be due,
at least in part, to high values of DDREF for the reference radiation.

As discussed below, however, most studies of the biological effectiveness of alpha
particles did not use high acute doses of gamma rays as the reference radiation. Furthermore, an
analysis to estimate RBEs of alpha particles at high acute doses of the reference radiation, similar
to the analysis for neutrons by Edwards (1997; 1999), has not, to our knowledge, been
performed. Such an analysis is not straightforward, due to the dependence of DDREF of the
reference radiation on the chosen value of a high dose (see Fig. 5). Therefore, for alpha particles,
we developed probability distributions of REFs at low doses and low dose rates of the reference
radiation, REF,, based on estimates of RBEy obtained from various studies. As is the case with
neutrons, the available data for alpha particles indicate that RBEs for leukemias are less than
RBEs for solid tumors, and we have developed separate probability distributions of REF, for
solid tumors and leukemias based on RBEs for the two types of cancers.

Alpha particles are somewhat simpler than neutrons in that the range of energies that
occur in radioactive decay is limited. A calculation of the energy dependence of the effective
quality factor by the ICRU (1986), shown in Fig. 14, indicates that the biological effectiveness of
alpha particles is nearly independent of energy over the energy range of concern. Therefore, we
have assumed that the probability distributions of REF, for solid tumors and leukemias can be
applied to all alpha particles that occur in radioactive decay.

3

5

po il [an en ee ee a ot
01 1 10 100
AVERAGE SKELETAL DOSE IN GY FROM RA o-PARTICLES

RELATIVE BIOLOGICAL EFFECTIVENESS

Fig, 13. Biological effectiveness of alpha particles emitted by ”*Ra, relative to beta particles emitted by
Sr and *Y, for induction of bone tumors in mammals given in Fig. 7.3 of NCRP (1990); curves
show pronounced dependence of RBE on dose.

30


DRAFT June 17, 2002

Propabiity

-000 > oO . , , |

0.00 7.50 15.00 22.50 30.00
Fig. 6. Assumed lognormal probability distribution of radiation effectiveness factor at high doses and
high dose rates of reference high-energy gamma rays, REF), for induction of solid tumors by

fission neutrons having a 95% confidence interval between 2.0 and 30. Median (50" percentile)
of distribution is at 7.7, and 2.5% of values lie beyond 30.

Comparison of REFs for Fission Neutrons with Radiation Protection Quantities

The probability distributions of REFs for fission neutrons described above can be
compared with the effective quality factor, Q, for neutrons of unknown energy recommended by
the ICRU (1986) and the radiation weighting factor, wg, for neutrons of energy 0.1-2 MeV
recommended by the ICRP (1991) and the NCRP (1993); see Table 1. The point values of OQ
and Wp are based on estimates of RBE,, and, thus, are directly comparable to the probability
distribution of REF, for leukemias, If we use a DDREF, of 2 as normally assumed in radiation
protection (ICRP, 1991; NCRP, 1993), the probability distribution of REF, for solid tumors
corresponds to a distribution of REF, having a 95% confidence interval between 4.0 and 60."5
Therefore, the assumed probability distributions of REFs for fission neutrons encompass the
point values of the recommended radiation protection quantities.'°

This confidence interval does not represent the range of estimates of RBE,, for fission neutrons
obtained from analyses of radiobiological studies, because DDREF for the reference radiation often
differed greatly from the value of 2 assumed here. As illustrated in Tables 3-5, upper confidence limits
of RBE,, considerably greater than 60 are obtained in some studies (see also Table 2).

‘6The point values wz = 20 and Q = 25 in Table 1 are at about the 70" and 80" percentiles,
respectively, of the inferred probability distribution of REF, for solid tumors, and are at about the 75"
and 85" percentiles of the probability distribution of REF, for leukemias, respectively.

18


DRAFT June 17, 2002

REF for Fission Neutrons and Solid Tumors

Risks of solid tumors from exposure to neutrons are estimated using eq. (3). The
probability distribution of REF, at high doses and high dose rates of reference high-energy
gamma rays is developed based on estimates of RBE, for solid tumors given in Tables 3-5. The
televant data are those for BALB/c and B6CF1 mice in Tabie 3, since life-shortening in these
mice was due primarily to solid tumors, the various tumors and adenocarcinomas in Table 4, and
the non-lymphocytic tumors in Table 5. Based on these data, we assume a lognormal probability
distribution of REF, for fission neutrons and solid tumors having a 95% confidence interval
between 2.0 and 30. This distribution, which is shown in Fig. 6, has a geometric mean (median
or 50" percentile) and geometric standard deviation of 7.7 and 2.0, respectively. A lognormal
distribution was selected based mainly on the variability in estimates of RBE, and the difficulty
in judging a credible upper bound of possible values. Lognormal probability distributions are
assumed for several other REFs developed in this report.

Data obtained from studies of tumor induction in other animals are consistent with the
probability distribution of REF, for fission neutrons and solid tumors described above. For
example, Wolf et al, (2000) deduced an RBE of about 20-25 for lethal tumors in Sprague-Dawley
rats at an acute dose of fission neutrons of 0.1 Gy. In a study in which monkeys were given
average doses of 6.7 Gy of X rays and 3.4 Gy of fission neutrons, Broerse et al. (1991) derived an
RBE for tumor induction of about 4-5. When this RBE is adjusted to account for the difference
of about a factor of 2 in the biological effectiveness of X rays and gamma rays, as discussed in a
later section, an RBE relative to gamma rays of about 8-10 is obtained. Other studies of tumor
induction in animals are discussed by the NCRP (1990).

The assumed probability distribution of REF, for fission neutrons and solid tumors
applies to a continuous spectrum of energies that normally ranges from 0.1 to 15 MeV. This
spectrum has a most probable energy of 0.8 MeV and an average energy of 2.0 MeV (Shleien et
al., 1998). As described later in this section, probability distributions of REFs based on RBEs for
fission neutrons are assumed to apply at energies of 0.1-2 MeV.

REF for Fission Neutrons and Leukemias

Risks of leukemias and related diseases, including lymphomas and lymphocytic cancers,
from exposure to neutrons are estimated using eq. (2). The probability distribution of REF, at
low doses and low dose rates of reference high-energy gamma rays is developed based on
estimates of RBE,, for leukemias given in Tables 3-5. The relevant data are those for RF/Un and
RFM mice in Table 3, since life-shortening in these mice was due primarily to leukemias,
lymphoma and the various leukemias in Table 4, and lymphocytic tumors in Table 5. Based on
these data, we assume a lognormal probability distribution of REF, for fission neutrons and
leukemias having a 95% confidence interval between 2.0 and 60. This distribution has a
geometric mean and geometric standard deviation of 11 and 2.4, respectively; it resembles the
distribution shown in Fig. 6, except it is more highly skewed toward lower values.

17


DRAFT June 17, 2002

Table 7. Summary of probability distributions of radiation effectiveness factors and
enhancement factor for neutrons to be used in estimating cancer risks
and probability of causation in accordance with eq. (7) or (8)

Cancer type/

Probability distribution of radiation effectiveness factor (REF)
Neutron energy

Solid tumors

0.1-2 Mev“ Lognormal distribution of REF,, having a 95% confidence interval
between 2.0 and 30

10-100 keV; Piece-wise uniform distribution of REF, with —

2-20 MeV 30% weight to interval from 1.0 to 3.0;

50% weight to interval from 3.0 to 5.0;
20% weight to interval from 5.0 to 20

<10keV; Piece-wise uniform distribution of REF, with —
> 20 MeV 30% weight to interval from 1.0 to 1.6;
50% weight to interval from 1.6 to 2.4;

Leukemias

0.1-2 Mev“ Lognormal distribution of REF, having a 95% confidence interval
between 2.0 and 60

10-100 keV; Piece-wise uniform distribution of REF, with —

2-20 MeV 30% weight to interval from 1.0 to 4.0;
50% weight to interval from 4.0 to 8.
20% weight to interval from 8.0 to 40

< 10 keV; Piece-wise uniform distribution of REF,, with —

> 20 MeV 30% weight to interval from 1.0 to 2.3;

50% weight to interval from 2.3 to 3.5,
20% weight to interval from 3.5 to 25

Enhancement factor representing inverse dose-rate effect under conditions of chronic exposure

Discrete distribution with —
50% weight to value 1.0;
30% weight to value 1.5;
15% weight to value 2.0;
5% weight to value 3.0

“Energy range also applies to spectrum of fission neutrons. Distributions of REFs at energies of
0.1-2 MeV should be used when neutron energies are unknown.

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