Search

SummaryRecently reported dose responses in prenatally exposed Japanese bomb survivors for severe mental retardation (SMR), reduced intelligence, and reduced levels of school performance, are compared. The characteristics of, and differences between, severe and mild mental retardation in man are critically important for such comparisons. The meaning of linearity of dose response is not identical for these different forms of damage. When findings on tissue changes in the brain and in functional tests of irradiated experimental animals are taken into account, the dose response for SMR would be expected to have a threshold as is found using DS86 dosimetry. The dose responses for IQ and for school performance seem doubtfully valid: their underlying assumptions need re-examination.

Previously published estimates of the whole-body radiation dose expected to kill 50% of a normal human population, the LD50, have rarely been based explicitly on evidence. The difference which might result from medical treatment seems to have been markedly over-valued. The available and relevant evidence about severe haematopoietic damage in man uncomplicated by tissue necrosis is indeed very scanty. It comes from 20 cases of therapeutic whole-body exposure to gamma rays and from two criticality accidents involving nine subjects, one of whom died, and when exposure was to neutrons as well as gamma rays. The observations suggest a judgment that 4.5 Gy (450 rad) absorbed dose in the bone marrow for energetic and therefore penetrating gamma rays giving reasonably uniform irradiation of the marrow could be regarded as the LD50 in circumstances where those irradiated were protected from thermal radiation and blast damage and from neutrons and beta rays. Examination of all the available experimental data on acute lethality following whole-body exposure to low LET radiation shows a remarkably similar co-efficient of variation of the LD50 in five species of large animal. If the same value is adopted for the human species, a quantitative estimate of the human LD50 can be inferred from the human evidence discussed. This reinforces the judgement that it is about 4.5 Gy. The use of observations after criticality accidents is examined in detail in an Appendix. The Vinca accident does not clearly meet the criteria for relevancy but there is no other instance of death in man from an uncomplicated brief whole-body exposure to ionising radiation where the bone-marrow dose can be estimated, and a possible judgment made of the value for the LD50.

Besides their influence on the daily practice of radiology in medicine and dentistry, the Adrian Committee Reports must have a variety of administrative, economic, educational and forensic implications. But all the effects and the implications depend on the correctness of the initial assumption that exposures in the routine practice of medical radiology can possibly do harm. Only if this is so is it “essential to ensure that any unnecessary exposure from this source (medical radiology) is prevented”. As far as genetic effects are concerned it seems clear enough that any radiation exposure, however small, has a certain probability of causing point mutations in germ cells. Yet any natural species of organism, plant or animal, needs a steady supply of new mutations if it is to maintain its numbers and its qualities. An increase in mutations in fact does harm only if the supply of mutations is otherwise adequate. Our very real biological ignorance about the amount of genetic harm which medical radiology might...

1. Suggested causes of death after single doses of radiation are briefly reviewed. Species differences are prominent. 2. The dose-mortality relation for mammals killed by radiation shows less variability than mammalian responses to other toxic agents. Possible reasons for this are discussed and also its relevance to attempts to find substances which protect in vivo against irradiation. 3. Cell death after whole body irradiation seems to occur in two ways. Delayed death due to interference with cell division is well known, but probably more important in accounting for the immediate histological effects of radiation is some other mechanism responsible for the early death of cells which normally do not divide. 4. General principles of radiobiology are shown to need modification if they are to be applied to whole body irradiation of mammals.

Bone Tumour Production in Mice by Strontium-90: Further Experimental Support for a Two-Event Hypothesis

There seems to be a basic difference of approach between those who are trying to improve radiotherapy and those who are trying to understand the ways in which unwanted exposure to radiation can lead to harm. The aim of the therapist is often to destroy something selectively, be it a malignant tumour or some other pathological process, and what matters is how completely the pathological lesion can be eradicated. The basic mechanisms which are of fundamental importance are the mechanisms by which radiation kills cells or prevents their further division, whether by interfering with their ability to survive the ordeal of mitosis (Spear, 1953) or by changing their habit of growth in the direction of increasing differentiation (Glucksman, 1952). When considering the harmful effect of unwanted irradiation, however, it is not of primary importance what the mechanisms of cell death or of interference with cell division are, or how many cells are so affected, provided that some cells survive and can multiply to rep...

The first widespread application of the quantitative (Dreyer) Widal test during the 1914-18 war coincided with a thorough inoculation campaign against the enteric fevers. In an inoculated patient, the similar actions of antibodies produced by inoculation and by natural infection have often prevented a clear-cut interpretation of the results of the test, and claims for the test have had to be revised repeatedly in the light of further experience. For example Walker (1917) stated 'In every case proved bacteriologically...the diagnosis independently arrived at by means of agglutination tests... was proved to be correct'. Later it was found that the test material used in the 1914-18 war gave results dependent almost entirely on the 'H' agglutinin, and it is now accepted that, in inoculated persons, 'H'-type agglutinins are quite unreliable as a diagnostic test (Topley & Wilson, 1946). It was originally considered that 'a regular rise and subsequent fall of only 100 or 200 %' in titre at the appropriate period made it likely that the case was one of typhoid or paratyphoid infection (Dreyer, 1916). Later, 'a change in titre for one organism of not less than 200%' was usually accepted (Perry & Bensted, 1929), but now 'relatively large fluctuations in the titre of "0" agglutins' seem to be considered necessary (Topley & Wilson, 1946). The larger the rise in titre which is necessary for a 'positive' diagnosis, the smaller will be the percentage of diagnoses and the less the clinical value of the Widal as a diagnostic test. There are few published reports giving the actual titres of serial Widal tests in cases of enteric fever from which the frequency of positive tests can be discovered, even in the uninoculated. No such report has been found for tests in the inoculated so that the results on sixteen inoculated individuals are presented here. All were British Service personnel and had been inoculated during the 9 months preceding the onset of enteric fever, so that, as a group, they should have provided the least favourable material for the evaluation of the Widal test. The majority had received the alcohol-killed vaccine but many of these had also received the standard vaccine at one time or another. No special selection was made of the cases in which serial tests were done except for the inevitable exclusion of patients dying early in the course of the disease before the later tests could be carried out, and of others from whom no early blood sample was obtained.

The human evidence on radiation damage to the individual developing in utero is confined to mental impairment and carcinogenesis. New evidence is becoming available about levels of mental impairment of direct interest to radiological protection, but as yet no framework of understanding exists to allow quantitative predictions for the purposes of radiological protection. There is general agreement that malignant disease has been increased following antenatal radiography but no unanimity yet in concluding that irradiation was the main causal factor: reasons are given for accepting that radiography was the cause. Recent increases in biological understanding suggest why maldevelopment is not to be expected after irradiation of the conceptus. A clonal hypothesis for organogenesis provides a reasonable explanation for quantitative aspects of experimental observations on teratogenesis by ionising radiation, including the commonly found highly curvilinear dose-response relationship, the occurrence of so-called critical stages of sensitivity after exposures of a few hundred roentgens, and the reduction in frequency of induced abnormality with protraction of exposure. Clonal hypotheses predict that there will be a virtual threshold for polycystic (non-stochastic) forms of radiation damage. It may be misguided to adopt a linear dose-response relationship for deriving risk estimates for the practical purposes of radiological protection unless some mechanism for production of clinically evident harm can be advanced which provides a plausible reason for expecting linearity.

It is often difficult to accept that cancer induction by small doses of radiation is more than a theoretical possibility but actually happens. Indeed it is only quite recently that confirmatory evidence of considerable weight has become available to support the conclusion that the breast may be more sensitive to cancer induction by ionizing radiation than any other human tissue. Two groups of female patients have been followed up for ten to 44 years (mean follow-up each exceeding 25 years) (in Nova Scotia by Myrden and Hiltz, 1969; BEIR, 1972, and in Massachusetts by Boice and Monson, 1977). In the first series breast cancer incidence was five times, in the other twice, what would be expected in controls (tuberculous patients treated without pneumothorax, or regional population statistics). Other series may fail to show an increase but this is to be expected given the numbers of subjects, the magnitude of the breast doses and/or the use of mortality instead of incidence as the index of effect. In the two ...

When Professor Ellis (1979) provided his picture of the risk per rem for the irradiated human fetus it is a pity that he did just the opposite of what ICRP has consistently recommended over many years (ICRP 1977, paragraph 21; 1966, paragraph 21).