The matter has been discussed in some detail since 1998 by the independent European Committee on Radiation Risk (ECRR) whose reports [ 4 , 5 ] provide a methodology for assessing health effects through a system of weighting factors based on available data. As more and more evidence emerged after 1995 that something was very wrong with the ICRP absorbed dose approach to internal radiation, the UK government set up a Committee Examining Radiation Risk from Internal Emitters (CERRIE). Since there were (and are) political dimensions to the issue, the committee was composed of scientists and experts from the nuclear industry and the official radiation protection organisations in the UK. Unfortunately the 4-years process ended in acrimony, legal threats to member of the committee, and failure to agree a final report. Two reports were issued [ 6 , 7 ]. However, there was agreement that there were reasonable concerns about the safety of employing “absorbed dose” for certain internal radionuclide situations, and similar concerns about the safety of the ICRP model were made in 2005 by the French IRSN [ 8 ]. The error factor that these discussions led to was believed by different ends of the CERRIE process to be between 10-fold and 1000-fold. More recently, the value put on this error factor by the retired Scientific Secretary of the ICRP at a meeting in Stockholm in 2009 was “two orders of magnitude”. What this means, in our Strontium-90 case above, is that the dose from 100Bq contamination to the whole body is no longer 0.056μSv but may now be between 0.56μSv and 56μSv and the risk of fatal cancer is proportionately increased. To put this in perspective, the mean Sr-90 dose over the period 1959-1963 to individuals in the northern hemisphere was given as about 1 mSv [ 9 ]. The ICRP risk model gives a 0.45% per Sievert excess lifetime cancer risk. Epidemiological studies suggest that the cancer “epidemic” which began in the 1980s in areas of high rainfall and fallout is a consequence of the earlier fallout exposures [ 10 ]. The weighting of dose necessary to explain this is greater than 300 if calculated from the ICRP absolute risk factor of 0.05/Sv [ 5 , 11 ]. Many other instances of anomalous health effects from exposure to internal radionuclides require hazard weighting factors of between 100-fold and more than 1000-fold, and these are consequences of mechanisms which will be presented.

Thus, in the historic and also the current system of radiation protection, those experts who assess radiation risk, who are termed Health Physicists, calculate the cumulative absorbed dose in Grays, i.e. in terms of the total energy in Joules imparted by the beta electron or alpha particle decays of the internal radionuclide contamination to one kilogram of tissue. For this calculation, the tissue is modelled as water. For example, those whose body contains 100 Bq of Strontium-90 are assessed, for the purposes of radiation protection, as having received a cumulative absorbed dose of 100 x w where w is the “cumulative (absorbed) dose coefficient”, obtained from measurements of the biological half life of the Strontium in the body and the decay energy of each decay in Joules. This number w is to be found in a Table published by the ICRP. In the case of the Strontium-90 contaminated individual, if the person weighed 50 kg, then the mean activity concentration would be 2 Bq/kg. The resulting absorbed dose would then be 2 x 2.8 x 10 -8 (this is the ICRP 72 dose coefficient [ 3 ]). In other words, the committed dose is 5.6 x 10 -8 Sv (0.056 μSv). But can this be safely compared with a dose from a chest X-ray (40 μSv ) or from natural background radiation (2500 μSv) or from a high dose acute exposure to gamma rays from an atomic bomb linearly scaled to zero dose (the current way of modelling radiation effects)? This chapter explores this question. It is one which has become increasingly necessary as serious health effects, including cancer and leukemia, have been reported in those exposed to internal radioactivity in areas contaminated by radionuclides released from nuclear sites, weapons testing fallout and accidents like Chernobyl and Fukushima, at very low conventionally calculated “absorbed doses”.

In this bag of water model, illustrated in Fig 1 , the total energy transferred by the radiation to living tissue is diluted into a large mass, greater than a kilogram, as if the effects were uniform throughout the tissue being considered. In Fig 1 the tissue mass A represents an external irradiation by X-rays or gamma rays and here the effects are uniform across the tissue. But in the case B, for internal irradiation, it is clear that it is possible, for certain kinds of exposure, for tissue local to the source to receive very large amounts of radiation energy at the same overall energy transfer to the tissue mass.

Soviet scientists were more interested in internal radiation effects from fission-product radionuclides, but unfortunately their valuable studies have been difficult to access since they are published in Russian. In 1977 Gracheva and Korolev published a book summarising work in this area which was translated in India in 1980 as Genetic Effects of the Decay of Radionuclides in Cells [ 2 ]. This presented a wealth of interesting data relating to beta emitter genetic effects in various systems and drew attention to the distinction that must be made between external and internal radiation. This is important since the whole assessment of radiation in terms of health has been through the quantity “absorbed dose” and what can be called the bag-of-water model.

The question of the health effects of internal radionuclide exposures began to be asked in the early 1950s when there was widespread fallout contamination of food and milk from atmospheric nuclear tests. It quickly became the subject of disagreements between two committees of the newly formed International Commission on Radiological Protection (ICRP)[ 1 ]. The questions of the equivalence of internal and external radiation exposure, which were the basis of these disagreements, have still not been resolved. In the West, up to very recently, the whole spectrum of health effects from internal incorporated radionuclides has focused on animal studies of Radium, Plutonium and Strontium-90 and human retrospective studies of those individuals exposed to Radium-226 and Thorium-232 in the contrast medium “Thorotrast”. These studies suffer from a number of problems which will be discussed.

In this chapter, there is insufficient space to exhaustively review the research which has been carried out on internal radionuclide effects. I hope only to highlight evidence which shows that internal radionuclides cannot be assessed by the current radiation risk model, and to suggest some research directions that may enable a new model to be developed, one which more accurately quantifies the real effects of such exposures. The biological effects of exposure to ionizing radiation have been studied extensively in the last 70 years and yet very little effort has gone into examining the health effects of exposure to internal incorporated radionuclides. This is curious, since the biosphere has been increasingly contaminated with novel man-made radioactive versions of naturally occurring elements which living creatures have adapted to over evolutionary timescales, and intuition might suggest that these substances could represent a significant hazard to health, one not easily or accurately modelled by analogy with external photon radiation (X-rays and gamma rays).

2. Fundamental principles

Ionising radiation, however it is delivered, creates harmful effects by causing mutations in genetic material both at the somatic level (cellular DNA) and germ cell level (heritable mutations). The mutations are caused by alterations in the cellular DNA in the nucleus and in mitochondria. These are brought about by three mechanisms:

Direct ionisation of the DNA and subsequent chemical alteration of the bases to molecules which are not recognised as a coding signal. Indirect ionisation of the DNA by reactive species produced by ionisation of water (called Reactive Oxygen Species ROS). A mechanism termed “Genomic Instability” which is an inducible cell-cell signal consequence of the production of ROS in the cytoplasm (non-DNA region) of an irradiated cell. This process is communicable between cells in some way and even between individuals and has been termed the “bystander effect”.

These mechanisms are well described in the literature and in textbooks, and the processes described here can be found in the reports of radiation protection agencies e.g. [12].

Ionising radiation always transfers its energy to matter in the form of structured tracks of charged particles. Photon radiation (gamma and X-radiation) is absorbed by matter mainly through Compton Effect, Photoelectron, and Pair-production. All these cause the creation of tracks of energetic electrons which carry the energy of the original photon and collide with molecules in the absorbing medium causing ionisation. The ionised fragments (in the case of living tissue mainly of water) then recombine or react with local molecular entities causing chemical changes in the molecular structure. Various chemical reactions take place e.g.

H 2 O ( radiation ) → H 2 O + + e -

H 2 O + + H 2 O → OH* + H 3 O +

The free radical OH* has an unpaired electron and is highly reactive; it will combine with local species including DNA if that is close to the track. If it reacts again with water species the result is a range of highly reactive fragments which are collectively described as Reactive Oxygen Species. The process can be written:

H 2 O ( radiation ) → e aq , H*, H 2 O 2 , H 2 , OH* .

The relative concentrations of the main ROS are [12]:

e aq (hydrated electron) 45%

OH* (hydroxyl radical) 45%

H* (hydrogen radical) 10%

These reactive species attack molecules in the cell and cause damage; because it is an oxidising agent the OH* radical is likely to be the most effective DNA damaging agent, abstracting a hydrogen atom from the deoxyribose moiety of DNA yielding a highly reactive DNA radical. This will then rearrange or react with local molecules to produce a new molecule in the DNA coding sequence, the gene, a molecule which is unrecognizable to the coding transfer process and alters the message of the gene.

It seems that evolution has recognised the dangers of high levels of cellular ROS and has developed a process to deal with the threat to the species or to the organism. At the organism level the process involves firstly the existence of double strands of DNA which permit repair of ionisation damage to a base located on one strand by copying from the opposite strand. This type of lesion, termed a “point mutation” is a more likely result for chemical mutagenesis or random attack by ROS species present in the cell at some background concentration (as a by product of other chemical processes in the cell). In some cells, the result of DNA damage is programmed cell suicide, termed apoptosis. But at the organism level, one response is the induction of genomic instability, whereby a signal is switched on in the DNA resulting in increased levels of random mutagenesis built into cell replication of the damaged cell and also bystander cells. The exact purpose of this process, which is well documented, is uncertain [13]. If the damage is more extensive, involving locally multiply damaged sites (LMDS) or both strands, it becomes more difficult to accurately repair the material and either a fixed mutation or cell death results.

Internal exposure results from the radioactive decay of radionuclides incorporated into tissue through inhalation or ingestion. There are three principle types of decay which represent the majority of all internal exposures. Gamma decay, which produces fast electron tracks, β decay which also produces fast electron tracks, and alpha decay. In addition there are also short range electron tracks from Auger decays. The main internal nuclides of environmental and radiobiological importance are listed in Table 1.

Apart from effects at the nuclide (recoil, transmutation) β decay is indistinguishable from the fast (photoelectron) electron tracks produced from gamma and X-ray interactions. With β-decay, unstable elements change into elements with one greater atomic number Z and emit an electron in the process; they may also emit a gamma ray. Sometimes the daughter nuclide is also unstable and may further decay. An example is Strontium-90 which emits a β-particle of endpoint energy 546 keV (kiloelectron volts) and transmutes into Yttrium-90 which further emits a β−particle of endpoint energy 2280 keV and transmutes into stable Zirconium-90. There are several series decay sequences in which ten or more unstable nuclides are formed, one from another. An example is the natural α-emitter Uranium-238 which decays through twelve sequential unstable radionuclides until the sequence stops at stable Lead-206. Transmutation involving α-decay involves the change of the chemical element to one with Atomic Number Z four places lower on the Periodic Table. Thus U-238 emits an α-particle and decays to Thorium-234.

There is strong evidence that damage to DNA is the cause of the effects of ionising radiation. For example, experiments have been carried out with nuclides which have short range electron emissions (Auger emissions) or Tritium chemically incorporated into DNA precursors so that these elements become covalently bonded to the DNA. The measured harmful effects are up to 100-times greater than would be predicted from the “absorbed dose” showing that it is the ionisation in the DNA that is key to the destruction of the cell [14, 15]. Another argument is based on the effects of the weak β-emitter Tritium, as tritiated water HTO. The measured effects of Tritium exposure are not too different from that expected on the basis of the absorbed dose (although it may be higher, see below). But clearly the Tritium will be evenly distributed throughout the cell. Since the beta energy of Tritium is only 6 keV the electron track range will be less than 0.5 μ and the ionisations will occur in clusters, uniformly distributed in the cell but with no overlap. It is clear that only those clusters which are close to the DNA will have an effect on the DNA, and the great majority of the energy will be “wasted” in the cytoplasm. Thus for a Tritium dose modelled by ICRP as 1 mSv, only a very small fraction of the Tritium decays will contribute to the effect.

The main target DNA, in the cell nucleus, represents a very small fraction of the total material in the cell. In a 10 μ diameter cell (mass 520 pg) there is 6 pg of DNA made up of 2.4 pg bases, 2.3 pg deoxyribose, 1.2 pg phosphate. In addition, associated with this macromolecule are 3.1 pg of bound water and 4.2 pg of inner hydration water [16]. Since absorbed dose is given as Joules per kilogram, if it were possible to accurately target the DNA complex alone, a dose to the cell (mass 520 pg) of 1 milliJoule per kilogram (one milliGray, one milliSievert) would, if absorbed only by the DNA complex (6 pg), represent a dose of 520/6 = 87 mSv to the DNA. It is possible to imagine the DNA as an organ of the body, like the thyroid gland or the breast. If this is done, then there should be a weighting factor for its radiobiological sensitivity of 87 which would be based on spatial distribution of dose alone. Of course, for external photon irradiation, to a first approximation, tracks are generated at random in tissue. Therefore only a small proportion of these tracks will intercept the DNA but the interception will be mainly uniform, and the health effects from such external exposure may be assumed to be described by the averaging approach of “absorbed dose”. This is not the case for internal exposures from radionuclide decays in a number of quite specific circumstances which will be described below (see [5]).

The calculations of “absorbed dose” also assume that the medium irradiated has uniform isotropic qualities with an absorption coefficient roughly equivalent to that of water. However the absorption of gamma radiation is proportional to the 4th power of the atomic number Z. It follows that the probability of absorption of gamma radiation will be location specific, and this is highly relevant to a number of high Z elements, either biologically necessary (Iodine, Z=53) or as contaminants (Uranium Z=92) [17].

Radionuclides are primarily chemical elements with the affinities and reactivities of the non-radioactive forms of these elements. They will therefore have quite specific biochemical pathways in the body and may accumulate at positions in cells as a result of their chemical group, valency, ionic volumes, charge etc. This will result in high local doses at sites where they accumulate. In addition, the decay of a nuclide attached to some cell structure or macromolecule will result in the alteration of the radionuclide into a different element with a different charge, with resultant recoil energy. This will always break the chemical bond and result in ionisation. Thus there will be local ionisation and this may be on some critical macromolecule like DNA. These localisation and transmutation effects were studied in the 1960s but no attempt has been made to incorporate them for radiation protection purposes.

The decay of a radionuclide attached chemically to the DNA is illustrated schematically in Fig 2.

Cells have two phases of activity during their lifespan. They are mostly in a quiescent phase where DNA is not localised spatially. For a short period at the end of their lifespan, when they replicate, they are in a cell cycle phase. In this phase they are much more sensitive to irradiation. Therefore this repair replication phase represents a critical window for mutagenesis if it can be engineered. The radiation sensitivity of the repair replication phase has been studied extensively and it was suggested [18, 19] that two irradiation events separated by about 10-12 hours could represent an enhanced hazard since the first pushed quiescent cells into repair replication and the second damaged them during the sensitive 12 hour period. The idea is termed the Second Event theory. There is some evidence for it from work with split doses of X-rays. It will be discussed below.