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RE: Abandon hope all ye target theory modelers..."Dose response"not linear?
Michael Brooks points us to a new issue of Mutation Research. Vol. 568
of Mutation Research is not online yet in my library, so I haven't seen
it.
But I wonder what he means by "dose response." A relationship predicting
a linear increase in detriment (as defined by the ICRP) with dose may be
a useful risk management concept, but as a scientific concept it's a
trifle simplistic!
Let's look as why it's simplistic. This is from my outline for the 2005
HPS Summer School in Spokane, updated from Strom (1998):
e) The Universe of Variables Needed to Predict Response: So-called
"Dose-Response" is a 14-Dimensional Problem
i) Dose
ii) Dose Rate
iii) Fractionation
iv) LET and Radiation Quality
v) Spatial Distribution of Energy Deposition
vi) Age at Beginning of Exposure
vii) Time Since Exposure Began
viii) Sex
ix) Species
x) Sub-species
(1) Genetic Predisposition
(2) Susceptible Subpopulations
(3) Biomarkers of Susceptibility
xi) Effect Modifiers (Other Risk or Protection Factors)
(1) Smoking
(2) Obesity
(3) Disease
(4) Nutrition and Malnutrition
(5) Combined Injury
xii) Endpoint
(1) Cancer
(a) Solid Tumors
(b) Cancers of the Blood-Forming Organs
(2) Heritable Ill-Health
(3) Tissue Effects
(4) Developmental Abnormalities (Teratogenic
Effects)
xiii) Morbidity and Mortality
xiv) Medical Care and Public Health
(1) Medical Care to Manage Dose
(a) Decontamination
(b) Amputation, Excision, and Debridement
(c) Chelation
(d) Forcing Fluids
(e) Blocking by Mass Action
(f) Lavage
(2) Medical Care to Manage Response
(a) Radioprotectant Drugs
(b) Infection Prevention and Management
(3) Progress in Medicine and Public Health
(a) Cancer prevention
(b) Cancer treatment
Bill Morgan gave a talk at CIRMS a couple of weeks ago that indicated
that there are huge gaps in what we know about carcinogenesis,
especially in vivo. Lots of stuff that happens in 2-D cell cultures or
even in 3-D liquid media does not happen in 3-D tissues, and vice versa.
So, if you're interested in the partial derivative (with respect to
dose) of the response of a particular health endpoint in a certain
genetic subset of a human population of a given age and sex with a
particular irradiation scheme of dose rate, fractionation, age at
exposure, radiation quality, uniformity of irradiation (partial or whole
body), in a particular nutritional state with a particular tobacco use
pattern and a particular pattern of disease and inflammation, within the
context of particular medical care situation and postulating exactly
what medical progress has been made with respect to cancer prevention
(e.g., by treating inflammation, now strongly implicated in many
cancers), we can talk about a "dose-response relationship."
Dose-response relationships for leukemia and bone cancer are most
assuredly not linear. The absence of excess leukemias around Chernobyl
is a very impressive null result that confirms the non-linearity of
leukemia with dose alone. Dose-response relationships for solid tumors
in the Japanese bomb survivors, the vast majority of whom received low
doses, are amazingly linear.
If you want to average over all dose rates, fractionations, radiation
qualities, ages, races, sexes, tobacco use, etc., you may have a
dose-response relationship that is of use in risk management, but may
not have a lot of scientific interest.
Science is but one input to radiation protection. None of the above
precludes the use of the linear nonthreshold dose-response model in risk
management and radiation protection.
Strom DJ. 1998. "Uses and Abuses of Models in Radiation Risk Management.
<http://www.pnl.gov/bayesian/strom/pdfs/Strom1998M_PNNL-SA-36701_Uses_&_
Abuses.PDF> PNNL-SA-36701. Radiation Protection Management 15(6):17-43.
- Dan Strom
The opinions expressed above, if any, are mine alone and have not been
reviewed or approved by Battelle, the Pacific Northwest National
Laboratory, or the U.S. Department of Energy.
Daniel J. Strom, Ph.D., CHP
Environmental Technology Directorate, Pacific Northwest National
Laboratory
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