PNNL-13501 - Pacific Northwest National Laboratory

(species, sub-species, and sex), space-and-time-course of
irradiation, space-and-time-course of modifying factors,
time-course of biological change, and damage. The
species (human, animal, plant, cells in vitro), sub-species
(racial makeup, ethnicity), genetic predisposition
(DNA repair), susceptibility, and sex (e.g., in humans,
thyroid cancer risk is proportional to the number of
X-chromosomes, and breast cancer risk is proportional to
[the number of X-chromosomes] 10 ) all affect radiation
risk. The stage of development as a function of age
(embryo, fetus, infant, child, adult, elderly adult),
reproductive status, and hormonal status must be
accounted for. The space-and-time-course of irradiation,
the instantaneous spatial distributions of ionizations and
excitations throughout existence of organism, the dose,
the dose rate, the fractionation, the “quality” or (linear
energy transfer, or lineal energy) all must be known as a
function of time (age) and as a function of tissue or body
part. The space-and-time-course of modifying factors
include diet, temperature, infectious agents, combined
injury (trauma, burns), the state of organ function, the
state of adaptive response (DNA repair stimulation), the
presence or absence of other initiators, promoters, tumor
progressors (smoking), oxygen, dehydration, exogenous
chemicals (antioxidants, free radical scavengers), drugs,
and medical interventions such as surgery, and all must be
know as a function of time (age) and location in an
organism.
The dependent variable for such a radiation-detriment
model is the time-course of biologic change and damage.
The model must predict biomarkers, initiated cells,
tumors, dermatitis, cataracts, etc., as a function of time
(age) and location in organism. The same factors must be
considered when calibrating the model from existing data.
Given this very ambitions project, what is knowable?
What radiation measurements would be sufficiently
predictive? For external irradiation, tissue-equivalent
proportional counters to record lineal energy spectra as a
function of time for the entire body for the entire life are
externally used to infer that which is occurring inside the
body. For internal irradiation, it is difficult to imagine
precise enough measurements of emissions from
radionuclides in the body to compare with external
measurements, so one must model the dose-related
quantities.
If thresholds exist, then only the irradiation that occurs
above a certain dose rate matters (as shown below).
Dose, especially committed dose, alone does not predict
risk in this case. One must model the entire time course
of irradiation in each tissue, and such models do not
follow strictly linear dose-response relationships.
Enhancement of GENII Code
The GENII computer code for calculating 50-year
committed effective dose equivalent (Napier et al.
1988a-c) has been modified to calculate instantaneous
dose rates to each organ and tissue, as well as
radioactivity contents as a function of time. This
capability permits the examination of thresholds in dose
rate as suggested by generalizing the Ames and Gold
(1990) “mitogenesis increases mutagenesis” assertion
(Figure 1).
Figure 1. Fraction of 50-year committed effective dose
equivalent due to Pu content of various organs and tissues
calculated by enhanced GENII code. With threshold
responses for osteosarcoma and liver cancer, only 25% of
dose leads to any risk at low doses.
Thresholds
An unexpected discovery was that many simplistic and
incorrect inferences of dose thresholds result from
plotting incidence or mortality data on a logarithmic dose
scale (Strom 2000). A number of representative examples
are listed below.
Human Radium Exposure and Bone Cancer
Analysis of human data for exposure to radium (Rowland
1994) using new methods (Chomentowski et al. 1990)
unequivocally indicates an alpha radiation dose threshold
for osteosarcoma at about 8 Gy (Figure 2).
Human Thorium Exposure and Liver Cancer
The Advisory Committee on Radiological Protection
(ACRP 1996) stated that there “appears to be a practical
threshold of about 2 Gy to liver tissue for induction of
liver cancer” by Thorotrast (p. E-9) based on
epidemiology of Danish patients as reported in 1992
(Andersson and Storm 1992). Thorotrast-exposed
patients are the fourth largest human population
Human Health and Safety 279