UNSCEAR 1993 Report to the General Assembly, with Scientific Annexes
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SOURCES AND EFFECTS OF IONIZING RADIATION United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 1993 Report to the General Assembly, with Scientific Annexes UNITED NATIONS New York, 1993 NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Forty-eighth Session, Supplement No. 46 (N48/46). ll1e designation employed and the presentation of material in this publication do not imply tl1e expression of any opinion whatsoever on the part of tlie Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning tl1e delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those tliat were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where tliis was possible and appropriate, to reflect political changes. UNITED NATIONS PUBLICATION Sales No. E.94.IX.2 ISBN 92-1-142200-0 ANNEX F Influence of dose and dose rate on stochastic effects of radiation CONTENTS INTRODUCTION ..........................................620 DOSE RESPONSE FROM RADIATION EXPOSURE .............624 A . THEORETICAL CONSIDERATIONS ..................... 624 1. Single-hit target theory .............................625 2. Multi-track effects ................................ 626 3 . Low doses and low dose rates: miaodosimetric considerations ....................... 627 4. Radiation quality and relative biological effectiveness ........629 5 . Deviations from conventional expectations ............... 630 B. MULTI-STAGE MODELS OF CARCINOGENESIS ........... 630 1. Multi-stage models ................................630 2. Thresholds in the dose-effect relationships ................ 632 C. MECHANISMS OF DOSE-RATE EFFECTS IN MAMMALIAN CELLS ............................. 633 1. Repair of DNA damage ............................ 634 2 . Effect of dose rate ................................ 635 D. SUMMARY ........................................ 636 I1 . DOSE-RESPONSE RELATIONSHIPS IN EXPERIMENTAL SYSTEMS ............................ 637 A . TUMORIGENESIS IN EXPERIMENTAL ANIMALS .......... 639 1. Radiation-induced life shortening ...................... 639 2. Tumour induction .................................647 B. IN VITRO CELL TRANSFORMATION ....................662 1. Dose-response relationships .......................... 664 2. Dose rate and fractionation ..........................665 3 . High-LET radiation ...............................667 4 . Summary ......................................671 C. MUTAGENESlS ....................................671 1. Somatic mutations ................................ 672 2. Germ cell mutations ............................... 673 3 . Summary ...................................... 675 620 UNSCEAR 1993 REPORT 111. DOSE AND DOSE-RATE EFFECTS IN HUMAN CANCER .........676 A. LEUKAEMIA AND ALL OTHER CANCERS ............... 676 1. Survivors of thc atomic bombings ill Japan ...............676 2. Workers in the nuclear induslry .......................677 B. TllYROlD CANCER .................................678 C. BREAST CANCER ..................................679 D. SUMMARY ........................................679 IV. DESIGNATION OF LOW DOSES AND LOW DOSE RATES .......680 A. PHYSICAL FACTORS ................................680 B. BIOLOGICAL FACTORS .............................. 681 C. SUMMARY ........................................ 682 CONCLUSIONS ........................................... 682 Tables ................................................... 688 Figures .................................................. 697 References ................................................ 715 INTRODUCTION 1. Radiation-induced malignant disease is thc main which both total dose and dosc rate influcr~cecancer late sonlatic effect in human populations cxposcd to induction in exposed individuals. The two features of ionizing radiation and the only statistically detectable the dose response that are most important for evalua- cause of radiation-induced life shortening at inter- tion of the risk at low doscs arc the possible presence mediate to low doses. In this dose range the incidence of a lhrcshold dose, below which the cffccts could not of radiation-induced canccr appears to increase with occur, and the shape of the dose response. Both these increasing dosc, and the probabilistic nature of the factors have been considered in earlier reports of the relationship between dose and risk of the disease has Committee. led to the use of the tern1 "stochastic" for this type of effect. Quantitative information on the risk of cancer 3. Proving or disproving a threshold on the basis of in human populations exposcd to ionizing radiation at epidcrniological studies or studies on tumour induction present comes largely from infornlation available from in experimental animals is, for most tunlour types, populations that have been exposcd at intermediate to likely to be impossible due to statistical uncertainties high doses and dose rates. In general, however, for in both the spontaneous and induced incidences of the assessing the consequences of environmental and disease. Therefore, on the assumption that cellular occupational exposure to radiation, risks need to be targets can be altered by single ionizing events, that known for exposures to low doscs delivered at low such damage is u~~likelyto be error-free and that it dose rates. Some information is now starting to may ultiniatcly give rise to a tumour, it is normally bccomc available from epidemiological studics on assumed that thcre is no thrcshold for the neoplastic occupationally exposed groups, although at present the rcsponsc. This working hypothesis is consistent wiU~ results of such studies havc si~bstantial statistical many, but not all obscrvatior~sof induced callccr rates uncertair~tiesassociated with tl~cm.It is likely that for found in anirnal experinlcnts as well as with obscrva- the immediate future quantitative risk cstimatcs will tions in cpidcn~iologicalstutlics and is considered in continue to be based on the higher dosc/dose-rate some detail in Anr~exE, "Mcchanisnls of radiation studies, although increasingly low-dose studies will OIICO~CI~CS~S". provide support for these values. 4. Tumour induction resulting from exposures to 2. It has becn recognized by the Comrnittee for ionizing radiation has becn systematically examined in some time that infon~ialionis needed on the extent to studies with various species and strains of animals and ANN13 I.': INF1,UI~NCE 01: DOSE AND DOSE RA for specific tunlour typcs. Pl~ysical f;~ctors such as with decreasing dosc, approaching a maxin~un~ dosc, dose rate, dose fractioriatior~ and radiation at low doses. quality, as well as biological factors such as age, These patterns or dosc rcspoi~scfor low- and high- gender and species wliicli can modify the tunlour LET radiation are illustrated in Figurc 1. yield, havc been considered. In the rnajority of cases, tllc dose-cffcct rclatio~~sliipsobtained are complex, 7. It was gcricrally co~rcludcdin the UNSCEAR showing first a rise with increasing radiation doses, a 1977 Report ([U4], Ar111cx G, paragraph 31 1) that the peak or plaicau at intcrnlcdiatc doses and in marly risk per unit dosc of low-LET radiation at low doscs cascs a final decline in incidence at high doses. In a and/or dosc ratcs was unlikely to be higher but could few cascs the spontaneous iricidc~~ceof tumours chan- be subsrantially lower than tlic values dcrivcd by ges very little with incrcasilig radiation dose, and in linear extrapolatio~~to the range of a few tens of niilli- some studies where there is a high spontaneous inci- gray from observations niadc abovc 1 Gy. Reduction dence this has resulted in a negative correlation with factors froni 2 to 20 were reported between the highcst increasing dose at high doscs. and lowest dosc rates tested (1 to lo4 Gy min") and between single and extremely fractionated and protrac- 5. The Committee noted in the UNSCEAR 1977 ted doscs for various animal strains and tumour types. Report [U4] a considerable variability in the net incidence of various tumour types at intermcdiate to 8. It was specifically noted by the Committee that high doses, bolh between different species and, within the Life Span Study of the survivors of the atomic species, between inbred strains. In many cases a bombings in Japan followed to 1972 gave a risk of particular tumour could be induced by irradiation in leukaemia of 3.5 G~-'at a mean kcrma of 3.3 Gy only one or two strains of a given species, raising and 1.8 loJ G~-'at a mean kerma of 1 Gy, suggest- questions as to whether such tuniours represented ing a reduction factor of 2 for thc risk coefficient at adequatc models of the corresponding human diseases. the lower dose as compared with that at the higher Similar doubts also applied to some observed forms of dose ([U4], Annex G, paragraphs 317 and 318). The dose-response relationships that differed from species Committee in its final estimate of risk adopted a to species, although in other cases consistent patterns reduction factor of 2.5 for estimating risks at low were found. For thcse reasolls it was concluded that doses and low dosc ratcs when extrapolating from the absolute cxccss of radiation-induced tumours per high dose and dose-rate studies. The Co~nn~itteealso unit of dose could not, as a general rule, be extra- emphasized that this reductio~~factor was derived