Executive Summary
(version française)
The assessment of carcinogenic risks associated with doses of ionizing
radiation from 0.2 Sv to 5 Sv is based on numerous epidemiological data.
However, the doses which are delivered during medical X-ray examinations
are much lower (from 0.1 mSv to 20 mSv). Doses close to or slightly higher
than, these can be received by workers or by populations in regions of
high natural background irradiation.
Epidemiological
studies have been carried out to determine the possible carcinogenic risk
of doses lower than 100 mSv, and they have not been able to detect statistically
significant risks even on large cohorts or populations. Therefore, these
risks are at worse low since the highest limit of the confidence interval
is relatively low. It is highly unlikely that putative carcinogenic risks
could be estimated or even established for such doses through casecontrol
studies or the follow-up of cohorts. Even for several hundred thousands
of subjects, the power of such epidemiological studies would not be sufficient
to demonstrate the existence of a very small excess in cancer incidence
or mortality adding to the natural cancer incidence which, in non-irradiated
populations, is already very high and fluctuates
Because of these epidemiological limitations, the only method for estimating the possible risks of low doses (< 100 mSv) is extrapolation from carcinogenic effects observed between 0.2 and 3 Sv. A linear no-threshold relationship (LNT) describes well the relation between the dose and the carcinogenic effect in this dose range where it could be tested. However, the use of this relationship to assess by extrapolation the risk of low and very low doses deserves great caution. Recent radiobiological data undermine the validity of estimations based on LNT in the range of doses lower than a few dozen mSv which leads to the questioning of the hypotheses on which LNT is implicitly based: 1) constancy
of the probability of mutation (per unit dose) whatever the dose or dose
rate,
Indeed,
At doses
of a few mSv (< 10 mSv), lesions are eliminated by disappearance of
the cells; at slightly higher doses damaging a large number of cells (therefore
capable of causing tissue lesions), repair systems are activated. They
permit cell survival but may generate misrepairs and irreversible lesions.
For low doses (< 100 mSv), the extent of mutagenic misrepairs is small
but its relative importance, per unit dose, increases with the dose and
dose rate. The duration of repair varies with the complexity of the damage
and its amount. Several enzymatic systems are involved
2) Moreover,
it was thought that radiocarcinogenesis was initiated by a lesion of the
genome affecting at random a few specific targets (proto-oncogenes, suppressor
genes, etc.). This relatively simple model, which provided a theoretical
framework for the use of LNT, has been replaced by a more complex one including
genetic and epigenetic lesions, and in which the relationship between the
initiated cells and their microenvironment plays an essential role. This
carcinogenic process is counteracted by effective defense mechanisms in
the cell, tissue and the organism. With regard to tissue, the mechanisms
which govern embryogenesis and direct tissue repair after injury appear
to play also an important role in the control of cell proliferation. This
is
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3) Immunosurveillance systems are able to eliminate clones of transformed cells, as is shown by tumor cell transplants. The effectiveness of immunosurveillance is also shown by the large increase in the incidence of several types of cancers among immunodepressed subjects (a link seems to exist between a defect in DNA repair (NHEJ) and immunodeficiency). All these
data suggest that the lower effectiveness of low doses, or the existence
of a practical threshold which could be related to either the failure of
a very low doses to sufficiently activate cellular signalling and thereafter
DNA repair mechanisms or to an association between apoptosis error-free
repair and immunosurveillance.. However on the basis of our present knowledge,
it is
These data show that it is not justified to use the linear no-threshold relationship to assess the carcinogenic risk of low doses observations made for doses from 0.2 to 5 Sv since for the same dose increment the biological effectiveness varies as a function of total dose and dose rate. The conclusion of this report is in fact in contradiction with those of other authors [43,118], which justify the use of LNT by the following arguments. 1. for
doses lower than 10 mGy, there is no interaction between the different
physical events initiated along the electron tracks through the DNA
or the cell;
The first
argument concerns the initial physico-chemical events which are proportional
to dose; however, the nature and efficiency of cellular defense reactions
that are activated vary with dose and dose rate. The second argument is
contradicted by recent radiobiological studies considered in the present
report. The third argument does not take into account recent findings on
the complexity of the carcinogenic process and the particular role of intercellular
relationships and the stroma.. Regarding the fourth argument, it can be
noted that besides LNT, other types of doseeffect relationships are also
compatible with data concerning solid tumors in atom bomb survivors, and
can also satisfactorily fit epidemiological data that are incompatible
with the LNT concept, notably the incidence of leukemia in these same A-bomb
survivors. Furthermore, taking into account the latest available data,
the dose-effect relationship for solid tumors in Hiroshima-Nagasaki survivors
is not linear but curvilinear between 0 and 2 Sv. Moreover, even if the
doseeffect
Finally,
with regard to in utero irradiation, whatever the value of the Oxford
study, some inconsistencies between the availbable data sets call for great
caution before concluding the existence of a causal relationship from data
showing simply an association. Furthermore, it is highly questionable to
extrapolate from the fetus to the child and adult, particularly, since
the developmental state, cellular interactions and immunological control
systems are very different.
In
conclusion,
this report raises doubts on the validity of using LNT for evaluating the
carcinogenic risk of low doses (< 100 mSv) and even more for very low
doses (< 10 mSv). The LNT concept can be a useful pragmatic tool for
assessing rules in radioprotection for doses above 10 mSv; however since
it is not based on biological concepts of our current knowledge, it should
not be used without precaution for assessing by extrapolation the risks
associated with low and even more so, with very low doses (< 10 mSv),
especially for benefit-risk assessments
Decision makers confronted with problems of radioactive waste or risk of contamination, should re-examine the methodology used for the evaluation of risks associated with very low doses and with doses delivered at a very low dose rate. This report confirms the inappropriateness of the collective dose concept to evaluate population irradiation risks. |