ML20099J503
| ML20099J503 | |
| Person / Time | |
|---|---|
| Site: | Limerick  |
| Issue date: | 05/22/1984 |
| From: | AFFILIATION NOT ASSIGNED |
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| References | |
| OL-A-148, NUDOCS 8411290088 | |
| Download: ML20099J503 (5) | |
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769.' Finally, for the class of diseases which b rumeri - progeny per millico births per 10-2 Gy who will suffer cally most frequent among spontaneously-arising ; from the effects ofinduced mutations h:ving dominant.
Am namely, the irregularly. inherited ones, it is- effects. He data on the induction of dominant skeletal.
difficult to make the. kind of estimates (in terms of mutations in mice were1: sed to make this estimate. For-impatred life, life loss, etc.,).which Carter has made for ~ structural aberrations of chromosomes-giredominantly .
other classes. He figures for those fiven in columns t reciprocal translocations-the risk was estimated to lie r 3-7 of Table 50 are no more than crude guesses and between 2 and 10 per million livebirths per 10-2 cy
- may be zssociated with considerable errors. This under similar radiation conditions. The cytogenetic
) ~ limitatioa doubtless applies also to estimates of data on radiation-induction of reciprocal translocations I r s detriment associated with radiation-induced irregu- in marmoset and human males were used for this f
t larly-inherited diseases. purpose.
( en t' t 770. In spite of these problems and difficulties, the 775. He risk for irradiation of human females, both f : Committee considers it worthwhile to attempt some from the induction of mutations having domint.nt
- estimates of detnment for radiation-induced genetic effects and from the induction of reciprocal transloca.
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dis, cases,,f i
only to illustrate a possible method and to tions was considered low, but no quantitative estimates 6 .
gain some rough idea of the impact of these relative to were given.
? E. that for spontaneously. arising ones. Such estimates are
)- le given in Table 55. It is worth reiterating that the
" W numerical values are only approximate and must be 776. He risk from the induction of sex-chromosome 5 viewed in the light of the numt:r of reservations losses in either sex was also considered low, for the
'i mentioned earlier. radiadon conditions applicable to humans.
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1- 771. It snay be noted that the numerical figures given 777. He risk estimate arrived at using the doubling o'- in column 2 of Table 55 (induced cases yer 106 births) dose method was that, under conditiors of continuous are those from Tabic 44, but the donninant and X - radiation exposure to low-LET, low dose rate irradi.
y@i linked categories are shown separately. Furthermore, ation at a rate of 10 2 Gy/ generation, the additional
~ following Childs (C68], the first generation incidence number of cases of genetic disease will be about 63 per l & for dominant and X-linked diseases is assumed to be million births in the first generation and about three (4 ,i 14% and 25%, respectively, of the equilibrium times this frequency at equilibrium (over and above the d A; incidence. For chromosomal and irregularly inherited 105 200 per million births occurring spontaneously).
W 3 diseases, the figures given in column 2 are the same as He doubling dose assumed was 1 Gy.
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those given in Table 44. For impaired life and life loss, J h the figures used are the sar- as,those given in Table 50, except that for chromosomal diseases, the figures given 778. Since the publication of the 1977 report, new
( i in Table 49 for autosomal structural aneuploidy are data have become available. Among these are those j'
t which confirm and further document the Committee's g-employed. earlier conclusions; those that help to shed light on the validity of the assumptions and tentative conclusions
,4, 772. The general conclusions to be drawn from Table (arrived at on the basis oflimited data) or controversial 55 can be stated as follows,: if a population is exposed view. points; those that are relevant in a qualitative to low dose rate, low-LET irradiation at a rate of 1 Gy sense, but which as yet cannot be used in quantitative'
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per generation, the expected increment in genetic risk assessments; and those that are of relevance for g disease ts of the order of about 2000 cases,per 106 births quantitative risk assessments. Rese have been briefly in the first generatio,n; this frequency is about one- reviewed in this chapter. He new data pertain to the seventh of that at equilibnum. Rese diseases are likely induction of dominant cataract mutations in mice and g;- to cause about 50 000 years of impaired life per 106 to the induction of reciprocal translocations in the l g births and an equal amount oflife loss per 106 births in rhesus monkey. Use was made of these data (in
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the first generation. At equilibnum, the figures are about 6 to 7 times higher. A comparison of these figures addition to those that were used in the UNSCEAR 1977 report) in quantitative hazard evaluations.
3 with the magmtude of detriment associated with m; spontaneously-arising genetic diseases (Table 50) will show that the former are relatively small for the stated 779. New publications on quantitative estimation of A
radiation conditions. He Committee wishes to stress genetic hazards in humans (those ofindividual authors again that these figures (Tables 50 and 55) are crude, and of scientific bodies) have appeared since the i
j but may be useful .in the comparison of detriment UNSCEAR 1977 report. Brief summaries of the,mam associated with spontaneously-arising and radiation. . conclusions reached in these are given, m addition to induced cancers. some detailed discussions on the similarities and differ-
- ences between the conclusions reached by the
? UNSCEAR in 1977, an ICRP Task Group and the J < BEIR Committee in its 1980 report. It is pointed out that, the conclusions reached by all three scientific E.
SUMMARY
AND CONCLUSIONS bodies are similar and where differences exist, they stem from the different assumpticas used (the basic Nje 773. In its 1977 report, the Committee made use of data for all three are the same).
4, both the " direct" and -doubling dose" methods to f %, obtain quantitative estimates of genetic radiation 730. The Committee's current estimates of genetic hazards in humans. He main conclusions were the hazards have also been made using the direct and e'
r 3 doubling dose methods. With the former method, the following.
M $ $ risk from the induction of mutations having dominant h'
774. Using the direct method, the Committee effects in the progeny has now been estimated 'o lie in
, estimated that following low.LET, low dose rate irradi- the range of 1000 - 2000 cases of affected indniduals ation of males, there will be about 20 cases of affected per million born per Gy of low.LET, low dose rate 8411290088 840522
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VIII. SUGGESTIONS FOR FUTURE rough estimate of risk nder similar conditicar b 0-900 . RESEARCH -
cases per million births. %3 Itwer limit cf this estimate . s assumes that the mutational, sensitivity of the human 784. In this Annex, the progress that has been m 7 immature oocytes will be sirplar to that of mouse mammalian and human genetics, cytogenetics, ';
immature oocytes whereas the upper estimate assumes 4
g that the human oocyte will respond in a manner similar cell genetics and in other areas pertinent to the ation of genetic radiation hazards in man has i y%y to that of maturin,g mouse oocytes under conditions of reviewed, and revised estimates of genetic risks ;
chrome low.LET trradiation. been presented. He Committee feels thst, in orde-increase our precision in risk assessment, more r 781. He n. sk from the induction of effort along the following lines will be useful (the 4 cations has now been estimated to the e in h, reciprocal region of translo-o in which these are listed do not reflect the order about 30 to 1000 cases of affected individuals per importance).
million births per Gy oflow-LET, low dose rate irradi- y' -
ation of males; for irradiation of females, the very N""#" ##" '#
indirectly estimated risks are lower (range of 0-300 q h~
cases of affected individuals per 106 births). Continuation of surveys on hereditary dise 782. As in the 1977 report, the Committee has used a human populations chromosomal defects; studiesand correlation of clinical data auf on the contribu t
doubling dose of 1 Gy to estimate risks using the ' mutations to irregularly-i. herited disorders; :
I doubling dose method (the argument that the doubling atiori of studies on genetic disorders such as ~ fe, dose is likely to be higher than 1 Gy was considered, telangiectasia in which the cells derived from p 6 but it was decided to keep the figure of 1 Gy for this suffering from the disorders show enhanced sensitig' I l
4 Annex until more data on this aspect accumulates). ne to damage induced by radiation and by other m quantitative estimates of risk arrived at in this Annex using all possible approaches and comparisons.- -
l are slightly different from those arrived at in the 1977 I
- report. It is,now estimated that under conditions of (b) Studies with mammals and other higher J contmuous irradiation at a rate of one Gy per L-
' generation (low-LET, low dose rate), the expected total Continuation of studies on the nature of ra i increment in the frequency of genetic diseases is about induced dominant and recessive mutations at i 2000 cases per million births in the first generation gene loci; studies on the induction of mutations in"
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(instead an estimated 6300 cases per million) and about cells and somatic cells at low doses and low dose ~n <[
15 000 cases of affected individuals per million births at studies on factors modifying radiation-induced damage and on mutational assay systems in h
equilibrium (instead of Ig 000 cases per million). He p
reasoning for this change has been: recent calculations cells; studies on the possible influence of ^
indicate that for dominant and X-linked diseases, the background on the induced frequency of do g l p '
first generation increment is 15% of that at equilibrium mutations in higher eukaryotes. ?' 7 l \ (thus lowering the number of cases from 2000 per million to 1000 per million); the conclusion of the (c) Studies at the chromosociallevel a i
i Committee (arrived at on the basis of all avadable r-l cvidence) that the assumption of a doubling dose of 1 Studies on the induction of reciprocal trans! $
l Gy for all chromosomal disorders (most of which are (including primates and human testis material. e.
a numerical anomalies of chromosomes) rests on particu- possible) using cytogenetic techniques, especia!!y l larly uncertain grounds; the Committee's current dose rates and low doses of radiation; studies ca 1 assessments relate only to the structural component of induction of structural aberrations in m ~ d;. -
chromosomal disorders; the risk from the induction of oocytes; studies on factors influencing the in #
numerical anomalies is considered to be very small. and recovery of chromosome aberrations in germ and somatic cells in suitable mammalian syst +
7T,3. In this Annex, the Committee has reviewed data 4 3 that bear on severity or detriment associated with (d) Blochemicalstudies using suitablepro T~
genetic diseases and, has also made a first attempt to crdaryoticsystems give some crude estimates of genetic detriment based ,
on a number of assumptions, for spontaneously-arising On: the relationships between DNA damage,iti f, and radiation. induced genetic diseases. Under the and assumption that the average life expectancy at birth is tions;the origin of mutations mechanisms of constitutive andand chromosome induced DIGabes ' y(;
70 years (and thus, for a million liveborn,70106 years), repair by physical and chemical agents andAk e it has been estimated that overall, sponta::cously- relevance for mutagenesis; mechanisms of regulatioH % . .
arising genetic diseases cause about 2 300 000 years of DNA repair and of genetic recombination (poaR 4 impaired life per million livebirths and about 3 000 000 role of hormones and growth factors) and their years oflife loss per million livebirths. For a population differentiation and carcinogenesis; DNA repair exposed to low-LET low dose rate irradiatior at a rate gametogenesis; relationship of DNA lesions to. .
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of one Gy per generation, the additional cases of in DNA sequences. Q b genetic disease induced, would cause about 50000 J !
' 1 years of impaired life per million livebirths and,an (c) Researeh on biologicaldosimeters to ' Y' approximately equal amount of life loss per milhon livebirths in the first generation following the radiation radiation aposures 1[s f exposure. At equilibrium, the comparable figures are, New approaches on the use of chrom l O
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340 000 years of impaired life per million livebirths and , biological dosimeters; development of bi
. about 286 000 years of life loss per million livebirths. immunological techniques for monitoring,e De Cogunittee wishes to reiterate that these estimates DNA sequences and their applic:gon;lo (
'. are very crude ones, but are illustrative of at least one cumulative doses arising from exposure to ph method to estimate genetic detriment. . chemical agents. of
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"' e .er"assumptiins arid risk estimites remain essen- 2. Somatic effects at tially valid. Rese estimates hav2 been compared with -
1' spontaneously-arising hereditary defects which affect, 49. One of the conclusions of the present report is that nt with differen'- grades of severity, roughly 10% of all at low doses and dose rates the induction of non-
. liveborn children. Physical agents such as ionizing neoplastic effects is not observed. His conclusion holds
/? radiation, as well as some noxious chemicals, may true for both whole-body and specific organ irradi-C/i 2" interac' with the genetic material of the germinal cells ation. At comparable doses and dose rates cancer is in the testes or in the ovary by altering the genes, the induction may be the only somatic consequence of
.w elementary units of heredity (thus causing gene irradiation in animals and man.
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" mutadons or with the structure or number of chromo-O somes on),which the genes are carried (thus 50. causingIn its 1977 report the Committee discussed factors r ". chromosomal aberrations). Changes in the genetic which make any accurate assessment of risk of cancer induction in man very difficult. In spite of such diffi-S m #yf material defects, may some be of associated which have with a variety severe of hereditary clinical conse- culties, the Committee provided at that time an analysis f quences. of the human data and of the risk estimates to be derived therefrom, to be used as a necessary starting
.ygpc 44. Using gene mutations and chromosomal aberra- point for decisions of practical value, particularly as f
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tions as end points of experimental observations, data on dose-effect relationships have been compared in a scientific criteria for radiation protection policies.
- 51. In view of the limited amount of.new epidemi.
t C variety of organisms. These comparisons have streng-ological evidence, there would have been no merit in I '2]., thened the assumption that one may expect a propor-repeating the same analysis in a short time interval. De tionality between the rates of spontaneous and of
~@i ',,t induced mutations of particular genes. His basic Committee undertook instead to review whatever infor-3:N' assumption has been applied in the indirect method of mation might be of interest, in experimental animals and in man,in the light of some basic models of tumour Ih. risk estimation.
'MQ g. 45. Using the indirect. method, the Committee induction. He scope was to assess the possible errors that might affect the estimates if one or another model estimated in 1977 that when a population is continu- of radiation action applied. Such a study might be j regarded as an indirect way of estimating risk ranges at
, y Q,ig,,.p4 ously exposed to low doses of low.LET radiation at a rate of 0.01 Gy per generation (1 generation - 30 the low doses and dose rates where direct evidence is
' p1. . years),63 new cases of hereditary diseases per million not available.
AE first generation progeny would be expected. A substantial part of the hereditary diseases included in 52. The Committee decided, however, to postpone the ded.--- this estimate is related to those arising from numerical publication of a document based on this study when it
,5 Q 'p6:.c anomalies of chromosomes. However, data on experi- became known that revisions had been proposed to the dosimetric estimates for the survivors of the atomic ,
ijd ' .h r mental animals and man point to the possibility that the (v) estimate for diseases falling under the category of bombs at Hiroshima and Nagasaki on which some of
&( 9;wm chromosomal diseases may be lower than previouslythe Committee's analyses had been based. Not only the ,
- V - estimated. In view of this, the Committee has now total doses received by the exposed populations, but
@- estimated that when a populatiort is exposed under the also the relative contributions of the neutron and c" conditions specified above, the increment in genetic gamma-ray components in de presently used T65D b diseases is likely to be of the order of 20 (instead of 63). (Tentative 1965 Dose) were called into question. He 3 e cases per million births in the first generation and about effect of the proposed revisions is to reduce the neutron dose component at both cities and to increase the h b 150 (instead of 185) cases per million births at N equilibrium (or about 2000 and 15 000 cases in the first gamma component at Hiroshima substantially, while
& reducing the gamma component at Nagasaki slightly. ;
I bNY generation and at equilibrium, respectively, when the
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N In addition, many more factors must be examined and
>:]M {<F exposure is at a rate of 1 Gy per generation). taken into account before reliable revised estimates of 7* N 46. As in the 1977 report, an estimate of risk for individual organ doses can be determined for the h N hereditary disorders has also been made using the T. '+ pP' direct method. He estimated values using these two survivors. His matter is technically complex, and it appears unlikely that the proposed revisions can be !
l#j 9' ' different methods (i.e., indirect and direct methods) are thoroughly investigated and agreed upon within a short 3
time.
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W S' 47. He risk from the induction of a particular type of $3. The Committee awaits with interest the results of U .,h chromosomal effect of radiation (reciprocal transloca- further studies in this field, as they would form one of W g' tions) has been re-evaluated on the basis of results from the bases on which radiation risk estimates in man must C9 d studies in marmosets, rhesus monkeys and man. be founded. In the meantime the Committee wishes to i lh However, the health consequences to the individuals emphasize that it does not expect a significant impact j S$
Q4 4b carrying such translocations cannot be reliably assessed at present.
of these revisions on the risk estimates contained in the 1977 report of the Committee, namely, that the risk of fatal cancer induction for x and gamma rays is of the i
I Tf;gi order of 210-5 for an effective dose equivalent corre-
- 48. Further advances have been made in our
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knowledge of the dose-response relationships and other sponding to one year of natural background, as an
? j. aspects of some of the more important types of genetic average for both sexes and all ages. His is so for two reasons. First, while it is impossible yet to say exactly 8 +.Z changes which can be induced by radiation in experi-l l k. ,& tg i mental mammals. Extensive use of experimental data what influence the revisions, if accepted, will have on the risk estimates, it is unlikely that this influence will r
r for genetic risk assessment is still considered essential l J. '8 in the absence of significant results with respect to exceed a factor of 2. Indeed, improved agreement 4'; hereditary efTects after human exposures. Suggestions between data from Hiroshima and Nagasaki may tend 3 d e- have also been formulated for more detailed analyses of ultimately to strengthen confidence in the estimates.
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- genetic effects with respect to detriment. Secondly, the information derived from the survivors of
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