Genetic Effects from Internally Deposited Radionuclides (N C R P Report)

NCRP REPORT No. 89

Genetic Effects From Internally Deposited Radionuclides Recommendations of the NATIONAL COUNCIL O N RADIATION PROTECTION A N D MEASUREMENTS

Issued August 15,1987 National Council on Radiation Protection and Measurements 7910 WOODMONT AVENUE / BETHESDA, MD. 20814

LEGAL NOTICE This report was prepared by the National Council on Radiation Protection and Measurements (NCRP). The Council strives to provide accurate, complete and useful informationin its reports. However, neither the NCRP, the members of NCRP, other persons contributing to or assisting in the preparation of this report, nor any person acting on the behalf of any of these parties (a) makes any warranty or representation, express or implied, with respect to the accuracy, completeness or usefulness of the information contained in this report, or that the use of any information, method or process disclosed in this report may not infringe on privately owned rights; or (b) assumes any liability with respect to the use of, or for damages resulting from the use of, any information, method or process disclosed in this report, under the Civil Rights Act of 1964, Section 701 et seq. as amended 42 U.S.C. Section 24lOOe et seq. (Title VZI) or any other statutory or common law theory governing liability.

Library of Congress Cataloging-in-PublicationData National Council on Radiation Protection and Measurements Genetic effects from internally deposited radionuclides. (NCRP report; no. 89) Prepared by Task Group 11 on Genetic Risk of Scientific Committee 57 on Internal Emitter Standards. "Issued July 15, 1987." Bibliography: p. Includes index. 1. Radioisotopes in the body. 2. Genetic toxicology. 3. Ionizing radiation-Toxicology. I. National Council on Radiation Protection and Measurements. Task Group 11 on Genetic Risk. 11. Title. 111. Series. [DNLM: 1. Genetics, Medical. 2. Radioisotopesadverse effects. WN 620 N2745gl RA1224.4.R34N38 1987 ISBN 0-913392-86-3

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Copyright 0 National Council on Radiation Protection and Measurements 1987 All rights resewed. This publication is ~rotectedby copyright. No part of this publication may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotation in critical articles or reviews.

Preface It was learned in the late 1920's that ionizing radiation could produce genetic effects such as gene mutations and chromosome aberrations. However, at least until 1945, the focus of interest in radiation protection was primarily on somatic effects manifested in the individual exposed. Studies of the genetic effects of radiation using drosophila, however, refocused attention on effects transmitted to the exposed individuals offspring and concern over fallout in the 1950's resulted in efforts to estimate the genetic effects from exposure of human populations to internally deposited radionuclides. No human populations have been identified with burdens of internally deposited radioactive materials which have been shown to produce evidence of transmissible genetic damage. As a result, the research approach has been one in which macromolecular, cellular, and whole animal genetic studies have been combined to estimate genetic effects on humans following the deposition of radioactive materials in the body. The purpose of this report is to update the information available from animal and cellular experiments that relates genetic effects to deposited activity and dose from internally deposited radioactive materials. For the various radiation types, genetic data for internally deposited radioactive materials are compared with those derived from exposure to external acute or protracted radiation to estimate the relative genetic hazard. The units used in this report are those of the Systeme International d'Unites (SI) but they are followed by the conventional units in parenthesis in accordance with the procedure set forth in NCRP Report No. 82, SI Units in Radiation Protection and Measurements.

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Preface

The present report was prepared by Task Group 11on Genetic Risk of Scientific Committee 57 on Internal Emitter Standards. Sewing on the Task Group were: Antone L. Brooks, Choirman Lovelace Biomedical and Environmental Research Institute Albuquerque, New Mexico Douglas Grahn Argonne National Laboratory Argonne, Illinois

William L. Russell Oak Ridge National Laboratory Oak Ridge, Tennessee

Paul B. Selby Oak Ridge National Laboratory Oak Ridge, Tennessee

Sewing on Scientific Committee 57 on Internal Emitter Standards were: J. Newel1 Stannard, Choirman University of California at San Diego San Diego, California John A. Auxier Evaluation Research Corporation Oak Ridge, Tennessee

Roger 0. McClellan Lovelace Biomedical and Environmental Research Institute Albuquerque, New Mexico

William J. Bair Battelle Pacific Northwest Laboratory Richland, Washington

Chester R. Richmond Oak Ridge National Laboratory Oak Ridge, Tennessee

Bruce B. Boecker Lovelace Biomedical and Environmental Research Institute Albuquerque, New Mexico

Robert A. Scblenker Argonne National Laboratory Argonne, Illinois

Keith J. Eckerman Oak Ridge National Laboratory Oak Ridge, Tennessee

Roy C. Thompson Battelle Pacific Northwest Laboratory Richland, Washington

NCRP Seeretariot-E. Ivan White

The Council wishes to express its gratitude to the members of the Task Group and Scientific Committee for the time and effort devoted to the preparation of this report. Warren K. Sinclair President, NCRP Bethesda, Maryland April 15, 1986

Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Low-Energy Beta Emitters . . . . . . . . . . . . . . . . . . . . . . . . . .. 2.1 Tritium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Carbon-14 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. High-Energy Beta-Gamma-Emitting Radionuclides . . 4 Alpha-Emitting Radionuclides . . . . . . . . . . . . . . . . . . . . . . 4.1 Retention. Dose. and Distribution in Reproductive Organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.1 Testes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.2 Ovary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Genetic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.1 In- Vitro Studies on Alpha Irradiation . . . . . . . . . 4.2.2 Cytogenetic Damage in Somatic Tissue . . . . . . . . 4.2.3 Cytogenetic Damage in Reproductive Tissue . . . 4.2.4 Dominant Lethal Mutations (Males) . . . . . . . . . . 4.2.5 Specific-locus Mutations (Males) . . . . . . . . . . . . . 4.2.6 Dominant Skeletal Mutations . . . . . . . . . . . . . . . . 4.2.7 Mutations Induced in Female Mice . . . . . . . . . . . 4.3 Summary for Alpha-Emitting Radionuclides . . . . . . . . . . 5. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NCRP Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction The effects of radiation on humans can be manifested in the individual exposed, or can be undetectable in that individual but become evident in his descendants. In the latter case, the effects are termed genetic effects. Those which result from the incorporation of radioactive materials into the human body are the subject of this report. Much effort has been devoted to the estimation of the risk of genetic effects that can be attributed to a given level of radiation exposure, that is the risk per unit of radiation dose. The Committee on Biological Effects of Ionizing Radiation (BEIR) of the National Academy of Sciences has directed particular attention to this (NAS, 1972, 1980) as have the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) (UNSCEAR, 1972,1977,1982,1986), the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP). These organizations have provided a useful framework from which an understanding and definition of the genetic hazards of internally deposited radioactive materials can be developed. No human population has been identified with a burden of internally deposited radioactive materials that has been shown to produce evidence of transmissible genetic damage. Even if a population existed that had body burdens that would result in significant dose, reconstructing dose and dose rate histories to the human reproductive tissue would involve large uncertainties, making the dose hard to define. The response is equally difficult to define because it would be necessary to conduct long-term follow-up of human families in which one or both parents were exposed to radionuclides. The research approach dictated has been one in which macromolecular, cellular and whole animal genetic studies have been combined to predict the genetic response in man following the deposition of radioactive materials in the body. Thus, animal and cellular experimentation are the only sources of data available that relate genetic changes to radiation dose from internally deposited radioactive material. Therefore, risk assessment for genetic disorders induced by internally deposited radioactive material can only be developed through comparisons with disorders caused by external radiation exposure. Data are available from external exposure in a wide variety of experi1

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1. INTRODUCTION

mental systems that have been used to predict the upper boundary of genetic risk in humans. We have to ask: What is the level of genetic damage produced in animals or cellular systems per unit of radiation dose from internally deposited radioactive material relative to the level of injury produced by protracted or acute external x-ray, gamma-ray or neutron exposure? The answer to this question helps establish an upper bound on the genetic risk from internally deposited radioactive materials. It is not recommended that the spectrum of genetic endpoints used for evaluation of the effects of external radiation sources be experimentally reanalyzed for each radionuclide of concern. The dose-response functions, which have been defined for low dose-rate external radiation exposure, are assumed to be acceptable for internally deposited radioactive materials if proper account is taken of the retention, micro- and macro-distribution of each radionuclide and the LET and energy type of each radiation emitted. Exceptions to this or possible uncertainties that result from differences will be noted in the analyses presented below. This report is organized according to the characteristics of the radiation types and the radionuclides that produce these emissions. For each radiation type, genetic data that have been derived both in uitro and in uiuo for internal emitters will be compared with those derived after exposure to external acute or protracted radiation. These genetic responses are evaluated to estimate the relative genetic hazard of each emission type.

2. Low-Energy Beta Emitters 2.1 Tritium

Tritium (3H) moves readily through the environment and has the potential for uptake and incorporation into biologically important molecules (NCRP, 1979a). The low energy of tritium beta particle emissions (18 keV max) results in a limited range in tissue and in a unique radiation dose pattern. The energy of the tritium decay is deposited, for the most part, in the cellular and subcellular location containing the radionuclide. When tritium is incorporated into biologically important molecular sites such as the DNA, its production of genetic damage per unit of energy deposited has been measured to be higher than a similar dose from a protracted exposure from most (lowLET) external radiation (Burki et al., 1975). This may be related to the increase in LET near the end of the @-particlerange and the short range of the @-particlefrom 3H. This would result in much of the energy being deposited in the nucleus with a higher LET and effectiveness. The potential genetic hazard of tritium has been studied in a variety of systems using both prokaryotes and eukaryotes. This research was summarized in a "Workshop on Tritium Radiobiology and Health Physics" (Matsudaira et al., 1985) in NCRP Report No. 63 (NCRP, 1979b), and has also been reviewed by others (Searle, 1983; Sankaranarayanan, 1982). The position or transmutational effects of tritium decay have been reviewed (Person and Brockrath, 1965; IAEA, 1968) and updated (Person et al., 1976). Each of the stable positions of thymidine, cytosine, adenosine, and guanine has been evaluated in Escherichia coli and T-4 phage. Tritium labeling work indicated that when cytosine-5, thymidine-6, and adenosine-:! positions are involved, there is increased mutation production compared to other positions. In Drosophila melanogaster, when the tritium label involves carbon-5 of cytosine, the yield of mutations was higher for sex-linked recessive lethals than when there is a general tritiated cytosine label (Stromnaes, 1962). Mammalian cells in vitro also show evidence that positional effects can increase DNA damage and mutation frequency (Burki et al., 1975; Krasin et al., 1973). Bateman and Chandley (1962) demon3

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2. LOW-ENERGY BETA EMITTERS

strated that injected tritiated thymidine produced both dominant lethal mutations and labeling of DNA in sperm. The existence of transmutational or positional effects of tritium on DNA in mammals were demonstrated (Carr and Nolan, 1979); however, the extent of these effects on total genetic risk for internally deposited tritium including that from ingestion of tritiated water (HTO) seems to be minimal. Chromosome aberrations in mouse liver (Brooks et al., 1976) and dominant lethal mutation induction were evaluated in male and female mice drinking HTO over their lifetime at levels up to 1.1x lo3 Bq/ml (3 &i/ml) (Carsten and Commerford, 1976; Carsten et al., 1977,1982). These data indicated that the relative effectiveness of tritium compared to protracted gamma-ray exposure was between one and two. Specific-locus mutations were studied after single intraperitoneal injections of tritiated water (Cumming et al., 1974; Russell et al., 1979). The RBE for the induction of point mutations for post spermatogonial germ cell stages was close to 1, with fairly wide confidence intervals. The point mutation estimate of RBE for spermatogonia was slightly above 2 with confidence intervals that include 1. Although not involving mutations, research demonstrating a depletion of developing oocytes by tritium exposure was also considered because oocyte depletion may influence the reproductive capability of an exposed population. The oocytes in monkeys (Dobson et al., 1978) and mice (Dobson and Cooper, 1974) are very sensitive to cell killing from tritium and from external radiation exposure during embryonic development. The oocyte cell killing after tritium exposure, relative to the killing of these critical cells by chronic gamma ray exposure, resulted in RBE values of 2 to 3 in both mice and primates. The concentration for continuous exposure to tritium that kills half of the oocytes that ranges from 1.85 x lo4 Bq/ml (0.5 rCi/ml) for monkeys (Dobson et al., 1978) to 7.4 x lo4 Bq/ml (2 ~ C i / m l )for mice (Dobson and Cooper, 1974). Although transmutational effects exist in both whole animals and in vitro cell systems, their effects in the whole animal relative to the effect from the beta particle dose from tritium are small. They should receive only minor consideration in estimating genetic risks from deposition of tritium. However, in consideration of the experimental evidence that tritium in the form of tritiated water should be considered to be twice as effective as low levels of exposure to gamma rays for genetic damage.

Carbon-14 Carbon-14 (14C)produced in atmospheric testing of nuclear weapons contributed some population dose that has been postulated to have 2.2

produced a significant genetic hazard (Brent, 1954; Pauling, 1958). Research on the radiation effects of 14C in Drosophila, however, indicated that there was no enhanced mutagenic effect of incorporated 14Cabove that predicted on the basis of the beta dose alone (Lee, 1970; Stromnaes, 1962; Lee et al., 1972). Information on the genetic effects of I4Cin mammalian cells is difficult to obtain. Goud et al. (1981) and Shevchenko et al. (1981) demonstrated that 14Ccould induce dominant lethal mutations and that the effectiveness was very similar to that predicted from chronic exposure to external gamma irradiation. Studies have also indicated that the concentration of 14Cin reproductive tissue is not enhanced above that found in other tissues (UNSCEAR, 1972; ERDA, 1975; Snyder et al., 1974), suggesting that ingested or inhaled 14C will make only a minor contribution to the genetically significant dose from both fallout and nuclear qower production. The NCRP (197913) concluded that transmutdtional effects from 14C would be minor compared to the radiation effedts. The 1972 report of the BEIR Committee (NAS, 1972) also indicatetl that "Carbon-14 can cause effects from chemical transmutations to nitrogen and these effects should be added to the radiation effects fkom the beta particles. Nonetheless, when there are many 14C decay( per cell nucleus, the radiation effects would again far outweigh the donsequences of transmutations. This situation is deemed to be similar to that which occurs I with tritium." The genetic effects from 14C should be calchlated on the basis of absorbed dose with an effectiveness relative to protracted low-LET radiation of 1.

3. High-Energy Beta-GammaEmitting Radionuclides Many fission products may be released into the environment as the result of nuclear weapons detonations, reactor accidents or the use of nuclear power. The movement of many beta- and gamma-emitting fission products through ecological systems, their incorporation into the body, and their retention and distribution in mammalian tissues have been well characterized. However, because of the physical characteristics of these emissions and because their interaction with cells and molecules is very similar to those observed for low-dose-rate exposure to x- or gamma-rays from external sources, studies on their genetic effects have been limited. Studies have been conducted on the impact of 22Naon the testes (Harrison and Moore, 1980a, 1980b). They demonstrated changes in testes weight and a change in the frequency of abnormal sperm. Liining et al. (1963) and Frolen (1970) induced dominant lethal mutations by injecting mice intraperitoneally with O ' Sr and its daughter product '"Y. The route of administration caused some concern as to the dose that the reproductive organs received because the 'OSr was preferentially retained within the peritoneal cavity with the migrating through the inguinal canal to the scrotum. This would result in a very high dose to the testes which was not related to the activity in the blood stream. Internally deposited 'OSr or '"Ce produces the same level of chromosome damage per rad in cells from rapidly dividing tissue like bone marrow, or in cells from slowly dividing tissue like liver, as did protracted external exposure to "Co gamma rays (Brooks et aL, 1972; Brooks and McClellan, 1969). The existing evidence, though limited, suggests that for internally deposited high-energy beta-and gamma-emitting radionuclides, the effectiveness for the production of genetic damage relative to protracted external low-LET radiation is 1. This is supported by data indicating that for several endpoints there are no unique genetic effects from internally deposited high-energy beta or gamma emitters, compared with those effects measured from similar doses of protracted external x- or gamma-ray exposures. 6

4. Alpha-Emitting Radionuclides Although alpha-emitting radionuclides have been recognized as carcinogens and extensive research has been conducted on their carcinogenic potency, there has, until recently, been limited research on the genetic hazards of internally deposited alpha-emitting radionuclides. The genetic risk was considered to be small because the short range of alpha particles limits the dose from external sources and most a-emitting radionuclides do not concentrate in the ovaries or testes which limits the dose to the reproductive organs. Research on the genetic effects of alpha irradiation has been directed toward studies ~ of its importance in the production of nuclear using 2 3 9 Pbecause weapons and in nuclear waste from the nuclear power industry. Data on transmitted genetic effects of internally deposited alpha-emitting isotopes are thus limited almost exclusively to this radionuclide which has been used in this report as a model to predict the hazards from other internally deposited alpha-emitting radioactive materials. Most ~ of the genetic endpoints measured to define the effects of 2 3 9 Phave also been evaluated after exposure to either gamma rays or neutrons. Those evaluations provide a good background against which the genetic hazard of alpha irradiation can be assessed.

4.1 Retention, Dose, and Dose Distribution in Reproductive Organs 4.1.1 Testes The fraction of the initial systemic burden of plutonium retained in the interstitial tissue of mammalian gonads is from to lod5 (Richmond and Thomas, 1975). The plutonium activity in the gonads of several species remains rather constant with time after deposition. Thus, the radiation dose rate is also relatively constant as a function of time after deposition (Brooks et al., 1983; Richmond and Thomas, 1975; Lyaginskaya et al., 1985). There is enhanced deposition in the interstitial tissue around the spermatogenic tubules that results in an increased dose to germinal tissue, including the genetically important 7

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4. ALPHA-EMI'M'ING RADIONUCLIDES

spermatogonia (Miller, 1982; Miller et al., 1985). The calculated dose to these cells in the mouse is about 2 to 4 times greater than the calculated average dose to the organ, assuming a uniform distribution of activity (Brooks et al., 1979; Green et al., 1975; Russell and Lindenbaum, 1979). To determine if non-uniform distribution exists in primates, measurements have been made of the distribution of plutonium in the testes of the Cynomolgus monkey (Brooks et al., 1983) and morphometric measurements have been made in testes of men of different ages (Brooks et al., 1979). The fraction of the activity retained in the testes of monkeys 1200 days after inhalation exposure to 2 3 9 Pnitrate ~ was of the initial body burden. Plutonium concentrated from 3 - 5 x in the interstitial tissue of monkey testes in a manner similar to that of rodents (Green et al., 1980; Brooks et al., 1979; Taylor, 1977). However, because of the greater ratio of interstitial tissue to reproductive tissue and the larger separation between spermatogenic tubules in primate testes, it was calculated that the concentration of plutonium in the interstitial tissue resulted in no enhancement of the dose to the spermatogonia. The rather large doses of plutonium used in many experimental studies caused cell killing and a decrease in testis size. The dose rate to the testes slowly increased throughout the life of the animals because of the decrease in testes mass, while the activity in the testes remained constant. If the higher estimates of dose to testes from either nonuniform distribution of plutonium or decrease in testes size were used for calculating dose-response coefficients for genetic damage, the slopes of the curves would decrease. This would result in a decrease in slope of the alpha irradiation dose-response curves and would result in a decreased effectiveness ratio when alpha irradiation was compared to chronic external low-LET exposure. TO place genetic risk from internally deposited alpha emitters in perspective, it is useful to relate genetic risk to somatic risk from internally deposited radioactivity. Since plutonium is the primary radionuclide for which genetic damage has been measured, the dose to the testes is compared to that received by other somatic tissues following inhalation of this nuclide. ICRP Publication 26 (ICRP, 1977) suggested that the genetic risk is about lh of the somatic risk per unit radiation dose following uniform total body irradiation. Two examples are given to place genetic dose and risks from plutonium in perspective relative to somatic risks. First, the level of plutonium injected into the mice to induce measured genetic damage as expressed in specific locus mutation, dominant skeletal mutation and heritable translocation tests, can be related to the maximum permis-

4.1 RETENTION, DOSE, DOSE DISTRIBUTION

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sible body burden for plutonium in adult humans. The mice were injected with 0.37 MBq/kg (10 pCi/kg) body weight. For a 70 kg man, this level of injected plutonium would result in an initial body burden of 25.9 MBq (700 &i). This is 17,500 times the .0015 MBq (40 nCi) body burden allowed for workers and illustrates the very high body burdens that have to be used to produce detectable genetic damage. The second example involves determination of the dose that the testes would receive relative to the doses to other organs of the body. In this example, a worker is postulated to start in the nuclear industry at 20 years of age and to work in an environment where the air concentration of plutonium was always equal to one tenth of the maximum derived air concentration (DAC) of 0.2 Bq/m3 (5.4 pCi/m3). In this case, it was further assumed that the plutonium was in the oxide form, and that the particles had an activity mean aerodynamic diameter of 1pm or a real diameter of 0.32 pm. With this particle size, of the total amount inhaled, respiratory tract deposition was estimated to be 30% in the nose, 25% in the pulmonary region and 8% in the tracheal-bronchial (TB) region (ICRP Publication 30 assumptions; ICRP, 1979). Plutonium dioxide is a class Y compound so that the fraction absorbed directly into blood was calculated to be 1% of the amount deposited in the TB region, 1% of the amount deposited in the nose and 5% of the amount deposited in the pulmonary region. Of the material in the pulmonary region, 15% was translocated to the lymph nodes. Of the material translocated to lymph nodes, 90% was translocated to the blood (ICRP Publication 30 assumptions; ICRP, 1979). From this information, we can estimate that the blood would receive 0.0006 Bq/day (0.016 pCi/day) from plutonium deposited in the nose. The T B region would contribute 0.00016 Bq/day (0.0043 pCi/day) and the pulmonary region 0.0093 Bqlday (0.25 pCi/day). The sum of these would result in about 0.01 Bq (0.266 pCi) being translocated to the blood per day. Of the amount that reaches the blood, the fraction (Richmond and Thomas, 1975). translocated to the testes is 3.5 x If the retention time in the testes is assumed to be infinite, in one year the testes would accumulate 0.0013 Bq (0.035 pCi) and in a twenty-year reproductive life 0.026 Bq (0.69 pCi). This burden would result in a total cummulative dose of 0.2 mGy (0.02 rad) or an average dose of 0.1 mGy (0.01 rad) accumulated to the male gonad over 20 years of work history. Similar calculations were done for the lung, liver and bone. The dose they would accumulate over the 20 years would be 0.01, 0.07 and 0.005 Gy (1.1, 7.0, and 0.5 rad) for the lung, bone and liver, respectively. Thus, the testes dose is 50 to 700 times less than the dose to somatic tissues and indicates that if the effec-

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4. ALPHA-EMITTING RADIONUCLIDES

tiveness per unit dose is similar that genetic damage should be less than that for somatic damage following the inhalation and deposition of a given amount of plutonium. 4.1.2

Ovary

Less 2 3 9 Pis~ retained in the ovaries than in the testes, that is, of the initial systemic burden (Richmond and Thomas, 1975). The retention half-life is long in mice, rats, Chinese hamsters, and Cynomolgus monkeys; thus, it is reasonable to assume that it is also long in humans. Green et al. (1977, 1979) noted that, at early times after injection, 2 3 9 Pconcentrated ~ near the atretic follicles, thus lowering the genetically significant dose. At later times, there is an accumulation of plutonium in the medullary stroma. Searle et al., (1982) also found that plutonium distribution was nonuniform throughout the ovaries of mice. They noted little activity in the corpora lutea, with high concentrations in the stromal tissue. The "clustering" of tracks was associated with macrophages in the stromal tissue. There is some internal redistribution in the ovary. They also noted that initially the distribution is random with some collection in atretic follicles. As time passes, there is increased aggregation caused by macrophage activity which results in a more nonuniform distribution of the plutonium and a decrease in the effective genetic dose relative to the average dose to the organ.

4.2 Genetic Effects 4.2.1

In- Vitro Studies on Alpha Irradiation

There is little genetic information available from studies with bacteria or drosophila after exposure to alpha-emitting radionuclides. However, mutation frequency has been determined for mammalian cell cultures using CHO cells (Barnhart and Cox, 1979) and V-79 cells (Thacker et al., 1982). These studies used 2 3 8 Pas ~ a source of alpha particles and measured cell killing and mutations at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) gene locus as biological indicators of damage. For cell killing Thacker et al. (1982) determined that the RBE for alpha irradiation compared to acute high dose-rate x rays was between 3.5 and 6.0, depending on the level of survival and dose a t which the comparison was being made. Several research groups (Thacker et al., 1982; Cox et al., 1977; Barnhart and Cox, 1979)

4.2 GENETIC EFFECTS

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determined that if a quadric model Y = aD + /3DZwas fit to mutation data the range of the linear or alpha term was between 0.35-3.1 x mutations/cell/Gy (0.35-3.1 x mutations/cell/rad). The slope of the dose-response curves for the induction of mutations by chronic mutations/cell/Gy (1.0 x exposure to x rays was about 1.0 x mutations/cell/rad) (Nakamura and 07Kada, 1981). However, the slope of the dose-response curve after plutonium exposure, as measmutations/cell/Gy ured by Barnhart and Cox (1979) was 4.5 x mutations/cell/rad), while Thacker et al. (1982) found 8.6 (4.5 X X mutations/cell/Gy (8.6 x mutations/cell/rad). Thus, alpha particles in this in-uitro system are between 4 and 10 times as effective as acute x rays in producing mutation. The range of responses observed between the studies was thought to be caused by differences in experimental protocol and dose to the cells (Thacker et al., 1982). 4.2.2

Cytogenetic Damage in Somatic Tissue

Chromosome aberrations are an indication of genetic damage. Aberrations have been measured in liver cells after internal deposition of different alpha-, beta-, or gamma-emitting radionuclides (Brooks, 1975; Brooks and McClellan, 1969; Brooks et al., 1972, 1976). These studies indicated that alpha particles from 2 3 9 P ~2,* P ~ ,241Amand 252 Cf produce similar linear dose-response relationships for chromosome aberrations. The level of chromosome damage for 252Cfper unit of alpha-particle-dose was similar to that observed for 2 3 9 P ~This . suggests that the 252Cffission fragments, which deposit almost onehalf the total energy for 252Cfin a very small tissue volume, were not effective in producing chromosome aberrations. The slopes of the dose-response curves for alpha emitters were compared to those determined after exposure to protracted 60Co gamma rays or internally deposited 144Ce-144Pr,a beta-gamma emitter. The RBE from this comparison ranged from 15 to 20 (Brooks, 1975). Purrott et al. (1980), Edwards et al. (1980a, 1980b), Dufrain et al. (1979) have made measurements of chromosome aberrations in human blood lymphocytes using 2 3 9 P ~ 238Pu, , or 241Amas a radiation source and demonstrated a wide range (10 to 40) of RBE relative to the values derived by Brewen and Luippold (1971) for chronic gamma-ray exposure. The difference in the chromosome aberration frequency between the observations of Dufrain et al. (1979) and those of Purrott et al. (1980) were postulated to be related to the distribution of the radioactive material within the cells during the culture period. It was postulated by Fisher and Hanly (1982) that some alpha emitting radionuclide in the Dufrain et al.

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4. ALPHA-EMITTING RADIONUCLIDES

(1979) study was retained during cell culture which would increase the dose delivered to the cells. This would produce an error in the dose term and an increase in the effectiveness calculated for the alpha emitter. The literature suggests that alpha radiation is less effective than neutron irradiation (Purrott et al., 1980) in the production of chromosome aberrations and that effectiveness factors for alpha radiation compared to chronic beta-gamma emitting radionuclides are from 10 to 20 for aberrations produced in somatic cells (Brooks, 1975; Brooks and McClellan, 1969; Brooks et al., 1972, 1976; Purrott et al., 1980; Brewen and Luippold, 1971).

4.2.3

Cytogenetic Damage in Reproductive Tissue

The frequency of translocations, measured by the heritable translocation test, induced in mouse spermatogonia after exposure to internally deposited 2 3 9 P is ~ ,increased as a function of exposure t i e and dose above the level seen in the controls. Among the offspring of mice exposed to 0.038 Gy/week (3.8 rad/week) to the spermatagonia from 239pU (assuming a radionuclide distribution factor of 2.5 which was measured in mouse testes), the frequencies of heritable translocations were measured a t 23 to 24,28 to 30,52 to 53 and 55 to 58 weeks after plutonium injection. The translocation frequency increased as a function of time and dose (Generoso et al., 1985). When the frequency of translocations was divided by the estimated dose to the testes, the translocations/gamete was similar, suggesting a linear dose-response relationship. The study was, thus, conducted a t four different doses translocations/gamete/Gy (1.4 and had a response of 1.4-2.9 x translocations/gamete/rad). to 2.9 x In sharp contrast, for reciprocal translocations scored cytologically in descendant meiocytes of irradiated spermatogonial stem cells, the dose-response relationship is not monotonic. During the first several ~ there months after a single large intravenous injection of 2 3 9 Pcitrate, is an increase in the translocation frequency that generally conforms to that seen after fission neutron exposure. Beyond about 30 weeks of accumulated exposure, no further increase in the frequency of these aberrations is observed. The neutron/gamma effectiveness ratio for the responses determined after protracted exposures may be as high as 45 and the alphalgamma ratio for reciprocal translocations is initially the same. With increasing time, there seems to be a steady decline in the alphalgamma ratio (Searle, 1979; Grahn et al., 1983). At 60 weeks after 2 3 9 Pinjection, ~ the cytogenetic damage decreased until the alpha to gamma effectiveness ratio has returned to almost

'

4.2

GENETIC EFFECTS

/

13

unity. Pacchierotti et al. (1983) have also reported that a long-term (about 800 days) burden of 2 3 9 Pin~ mice has little or no effect upon the frequency of translocations. Their summary of all the available data has clearly shown that the frequency of translocations/cell/~~ from internally deposited plutonium peaks at about 100 days of retention, then drops to near control value by 300 days, regardless of the initial level of gonadal burden. The explanation for the difference in the shape of the dose-response curves obtained for heritable translocations and translocations observed cytologically is not yet known. The studies'were conducted in different strains of mice and with different methods of measuring the endpoints. Both of these factors may be involved in the observed differences. However, in view of the increase in the frequency of heritable translocations observed at one year, it seems prudent to assume that there is no decrease of radiation induced translocations over time. Primary spermatocytes, during the resting stage and those stages before the first meiotic metaphase, are sensitive to the induction of isochromatid and chromatid fragments that are scored at the first metaphase. This sensitive period extends for about 2 weeks in the mouse, so the relevant dose is accumulated only over that period. The frequency of fragments increases in the spermatocytes of animals ~ particles, neutrons, or 60Cogamma rays. exposed to either 2 3 9 Palpha The high-LET radiations have RBE values in the range of 20 to 35 for this endpoint (Searle et al., 1976; Grahn et al., 1983).

4.2.4

Dominant Lethal Mutations (Males)

Fission neutrons and 2 3 9 Palpha ~ particles have about the same efficiency for the induction of dominant lethal mutations in meiotic and post-meiotic cell stages per Gy to the male gonads (Grahn et al., 1979). Liining et al., (1976a, 1976b) and Liining and Frolen (1982) injected animals with either 2 3 9 Pcitrate ~ or 2 3 9 Pnitrate ~ and evaluated the frequency of dominant lethal mutations. The animals injected with 239 Pu nitrate had no increase in dominant lethals whereas those with plutonium citrate showed a marked response. When the alpha emissions are compared to continuous low-intensity 60Cogamma irradiation, the mutagenic efficiency is 10 to 15 times greater for the alpha radiation. The response to alpha radiation is similar to that for neutrons delivered in small weekly increments for up to one year. An important point is that the dominant Iethal mutation rate remains nearly constant for a given dose level of neutrons or alpha particles in

14

/

4. ALPHA-EMITTING RADIONUCLIDES

this long-term exposure. The dominant lethal mutation rate for lethals induced in post-spermatogonial cell stages does not decline as seen for translocation frequencies (Grahn et al., 1979,1983). The latter is more likely to have been induced in the spermatogonia.

4.2.5

Specific-locw Mutations (Males)

Two experiments at Oak Ridge National Laboratory (ORNL) measured the frequency of specific-locus mutations in male (101 x C3H) F1, mice after injection with 0.37 MBq of 239P~/kg body weight (10 &i/kg) (W. L. Russell, personal communication). The animals were first mated at 7 weeks after plutonium injection and matings continued for a total of 73 weeks. Thus, each weekly mating represented a population exposed to a different radiation dose. A small proportion of the animals were sacrificed for dosimetry from 6 through 354 days, and the total dose and dose rate were estimated from these animals. The average dose rate to the testes was rather constant at all the times of sacrifice with a mean of 0.22 x lo-' Gy/d (0.22 rads/d) or about 1.5 x Gy/week (1.5 rad/week). If plutonium were uniformly distributed throughout the volume of the testes, this would be an appropriate dose rate to use in calculating dose-response relationships. However, because plutonium is non-uniformly distributed in the testes of mice (Green et al., 1975), it is appropriate to multiply the dose by a distribution factor to estimate the dose to the genetically important stem-cell spermatagonia. Using autoradiographic techniques, the degree of non-uniformity or distribution factor was calculated by measuring the number of alpha tracks in the testicular tubules, in the intertubular spaces, and over the spermatogonial cells. The higher the distribution factor, the higher the relative dose to the genetically important spermatogonial cells. Distribution factors have been estimated for mice as 1.9 (Brooks et al., 1979), 2.4 (Green et al., 1975), and 3.7 (Russell and Lindenbaum, 1979). If the distribution factor of 2.5 is applied to the dose-response studies at ORNL, for which the average dose rate to the testes was calculated to be 1.5 x lo-' Gy/ week (1.5 rad/week), then the calculated dose rate to the spermatogonial stem cell population would be 3.75 x lop2Gy/week (3.75 rad/ week) during the breeding life of the male mice. Combining the two experiments, which gave similar results, yielded a total of 37 mutations in 186,275 offspring. The parents of these offspring had spermatogonial stem cells exposed to a calculated dose rate of 3.75 x low2Gy/week (3.75 radlweek). There were no clusters of identical mutations observed among these 37 mutations. The dose

4.2 GENETIC EFFECTS

/

15

at the time of breeding was estimated to range from about 0.25 to 2.75 Gy (25 to 275 rad) with a mean dose to the spermatogonia of 1.2 Gy (120 rads). When the mutation frequency was divided by the mean radiation dose, an induced mutation rate for 2 3 9 Palpha ~ exposure of 18.0 X 10-6/locus/Gy (18.0 x 10-8/locus/rad) was derived. After chronic gamma irradiation at dose rates of 2.1 x C/kg/min (0.8 R/min) or lower (Russell and Kelly, 1982a), the mutation rate was 3 X locus/C/kg (7.3 x 10-8/locus/R). Protracted gamma-ray exposure was about one third as effective as acute x-ray exposures (Russell and Kelly, 1982b). Using the value derived from the chronic exposure as the basis for comparison, plutonium is 2 to 3 times as effective in producing specific-locus mutations as protracted gamma-ray exposures. Russell calculated that the RBE for alpha particles compared C/kg/min (0.8 R/ to gamma rays delivered at dose rates 2.1 x min) or lower was 2.5. For neutron exposures, the mutation rate was 125 X 10-6/Gy/locus (125 x 10-8/rad/locus) (Batchelor et al., 1966; Searle, 1967). Thus, alpha radiation was much less effective than neutrons in producing mutations. These effectiveness factors assume that the type and severity of the genetic damage from low- and highLET radiation are similar. As shown below, there is some indication that this may not be the case, as genetic damage induced by alpha particles may be qualitatively more serious than that induced by gamma rays (W. L. Russell, personal communication). The following lines of evidence exist for these qualitative differences in alpha induced mutations. First, of the 28 mutations that were fully tested for genetic effects, only 3 proved to be viable in the homozygous condition, whereas with x and gamma irradiation, approximately one third is viable. Furthermore, in the large total number of offspring required to obtain the 239Pu-inducedmutations, one would have expected between 7 and 10 of the 28 mutations to be of spontaneous origin, and spontaneous mutations have a higher proportion of viables than do radiation-induced mutations. Therefore, the 3 viables observed in the offspring of animals injected with plutonium might well have been of spontaneous origin. If that were the case, then all the 2 3 9 P ~ induced mutations might have been lethals. Second, for 8 of the 37 mutations obtained, it was not possible to complete the genetic tests to determine the effect of the gene in the homozygous condition and one mutation is still being tested. In each of the mutant individuals, genetic testing was hampered by poor viability or fertility of the mutants themselves, or of their offspring, indicating a marked deleterious effect of these mutations in the heterozygous condition, and that they probably would have been lethal in the homozygous condition.

16

/

4. ALPHA-EMITTING RADIONUCLIDES

Third, in these plutonium experiments, the animals were scored for specific-locus-mutationsat birth, or shortly after, as well as at 3 weeks of age. At birth only some of the mutations at three of the seven loci can be detected. However, it was of interest to find out what proportion of the 24 mutants scored a t birth were already dead or failed to survive to 3 weeks of age. The number of mutants at 3 weeks of age in this category was 12. Thus, 50% of the mutants scored a t birth were dead by 3 weeks after birth. In an experiment with x irradiation scored in comparable fashion, only 23% of the mutants died before 3 weeks of age. The normal loss (i.e., in the non-mutant offspring) in this period is approximately 10%. The three lines of evidence outlined above indicate: (a) that because of early deaths the 239Pu-inducedspecific-locus mutation frequency scored in the usual way a t 3 weeks of age may represent a considerable underestimate of the true mutation frequency, and that this underestimate is greater than that obtained with x- or gamma-irradiation where early deaths are less frequent. This would increase the effective RBE for plutonium if the data were corrected for survival. (b) Mutations induced by 2 3 9 Pare, ~ on the average, qualitatively more serious than those induced by low-LET radiation since almost all (if not all) are lethal in the homozygous condition and many have marked deleterious effects in heterozygotes. These effects suggest that a high proportion of the mutations induced by 2 3 9 Pare ~ multi-locus deficiencies. Many of the mutations induced by neutrons are also multi-locus deficiencies. This supports the hypothesis that alpha radiation from 2 3 9 Pis~ less effective than neutron radiation (Batchelor et al., 1966) in inducing specific-locus mutations. As was mentioned earlier, translocation induction results differ greatly depending on how the translocations were studied. The data on the induction of reciprocal chromosome translocations as scored in descendent meiocytes of irradiated spermatogonial stem cells (Grahn et al., 1983; Pacchierotti et al., 1983) demonstrate a reduction in effect at long retention periods (20 weeks or more). The specific-locus results, like those for heritable translocations, do not follow the same pattern. Since there were not enough offspring to report the frequency for each week and relate it to the accumulated dose over that period, the numbers of mutations were summed in two time groups, early and late, and the mutation frequency was related to the cumulative dose in each group. If the dose-response relationship for specific locus mutation induction was non-linear, that is if the dose was high enough to cause excessive cell killing or selection which would result in a dose-response curve that increased at low doses then decreased as the dose got higher,

4.2 GENETIC EFFECTS

/

17

as has been reported for higher doses of x rays, then the response at the early times when the dose was low should have been higher per unit dose than at the later times. This was not observed. The cause of the humped dose-response curve observed following x-ray exposure was postulated to be excessive cell killing, followed by repopulation with normal cells. Three observations suggest that the dose-response relationship for specific locus mutations and heritable translocations induced by injected plutonium are not humped. These include: 1)the observation of an increase in the frequency of heritable translocations and specific locus mutations with time and dose; 2) a measured low rate of cell killing by the plutonium injection; and 3) no large increase in heritable translocations or specific locus mutations at early times. All these observations suggest that the dose-response relationship for plutonium-induced heritable translocations and specific locus mutations may be linear over the dose range studied. Using data from the first experiment and dividing offspring obtained during the total 73 weeks of breeding into two approximately equal periods, 67,708 offspring were obtained during the earlier period and 39,554 in the later period. The number of mutations in the two periods was 10 and 11, respectively. The predicted number derived from calculated dose over the two time periods would be 9.4 and 11.4, respectively. Thus, specific locus mutations increased rather linearly as a function of dose and exposure time.

4.2.6

Dominant Skeletal Mutations

The main reason for studying induction of dominant skeletal mucitrate ~ exposure was to determine if the effectations following 2 3 9 P ~ was tiveness factor for skeletal dominants is greater for 2 3 9 Pthan observed for specific locus recessive mutations. This question acquired more importance as the evidence accumulated showing that specificlocus mutations induced by plutonium alpha particles might be more severe than those induced by low-LET radiation. An experiment to measure the frequency of dominant skeletal mutations was carried out (P. B. Selby, personal communication) in which male mice were injected intravenously with 0.37 MBq/kg (10 pCi of 2 3 9 P citrate/kg ~ body weight). Based on (1) the ratio of specific-locus mutations to dominant skeletal mutations following exposure to low-LET radiation, and (2) the specific locus mutation frequency in the experiment on plutonium, the expected induced frequency of dominant skeletal mutations, following the mean alpha dose of 0.58 Gy (58 rad), was only 0.0005 mutations/gamete. The calculation of such a small expected

18

/

4. ALPHA-EMITTING RADIONUCLIDES

frequency shows that it would be extremely difficult to detect any induction of dominant skeletal mutations for such an exposure unless the ratio of skeletal mutations to specific-locus mutations is much higher for alpha radiation than predicted from low-LET exposure data. Two different endpoints for scoring dominant skeletal damage were used (the frequency of presumed dominant skeletal mutations and the index of mutation), and there was no evidence of induction of dominant skeletal mutations in the sample of 3322 offspring scored. This experiment is not in disagreement with the hypothesis that using the specific-locus mutation frequency induced by plutonium to estimate the extent of dominant damage induced by alpha emitters is reasonable.

4.2.7

Mutations Induced in Female Mice

Searle et al. (1980, 1982) conducted research on the genetic effects of plutonium deposited in female mice. However, estimates of genetic damage from plutonium in the female are complicated by the potential interaction of direct damage to the parent with genetic damage. After ~ injection of female mice with 0.74 MBq/kg (20 pCi 2 " 9 Pcitratelkg) body weight, there was marked oocyte killing, and the number of exposed females that became pregnant fell below the level observed in the control group. Both pre- and post-implantation dominant lethals were induced at long periods after exposure (12 weeks). The index of dominant lethality based on post-implantation death seems to be the most reliable one to use under conditions such as these where there was evidence of germ-cell killing. From this research and that of Russell (1977), a general picture has emerged of a high sensitivity to cell killing of the oocytes by radiation and a low sensitivity of female mice to the induction of genetic damage by protracted h'igh- or lowLET irradiation.

4.3 Summary for Alpha-Emitting Radionuclides There are several possible explanations for the observation that the effectiveness of alpha particles in producing mutations in the stem cell population in testes is below that predicted from the level observed with neutron exposure. One of these may be that microdistribution measu,rementsmay not reflect the true dose because of the changes in target distances and migration of the radioactivity. Second, the activity

4.3 SUMMARY FOR ALPHA-EMITTING RADIONUCLIDES

/

19

in the interstitial tissue seems to be concentrated in phagocytic cells to form "hot spots," resulting in very high local doses which may cause excessive cell killing. The formation of clones of cells in comparatively unexposed areas could lead to a progressive dilution of the irradiated germ-cell population by an essentially unirradiated germ-cell population and effectively reduce the observed level of genetic damage below that expected on the basis of estimated total dose to the gonad. Third, cells containing multiple mutations or chromosome aberrations produced by non-uniform alpha exposure may be more effectively selected out of the dividing and differentiating spermatogonial cell population than would be the case after uniform exposure to neutrons or gamma rays. Finally, protons from neutron irradiations have an LET that is more or less optimal for the induction of mutations, while that of alphas is higher, resulting in more overkill and wasted dose. The risk for alpha irradiation vs. beta-gamma exposure ranges between 10 and 40 for cytogenetic damage based on rather high doses of alpha radiation. Many cytogenetic events result in cell killing but not transmitted genetic change. This may help explain the lower effectiveness factors, 2.5 to 10, for specific-locus mutations and dominant lethals. These data indicate that the usual Quality Factor of 20 applied for alpha particle effects compared to low-LET radiation may be high for the induction of transmitted genetic damage by alpha irradiation relative to beta-gamma irradiation. Because there is evidence that the specific-locus mutations induced by alpha irradiation may be qualitatively more severe than those induced by gamma rays, it is especially useful to have data on the induction by alpha irradiation of dominant skeletal mutations. Because these data provided no evidence of induction of dominant skeletal mutations by 58 rad (0.58 Gy) of exposure in a sample of 3322 F1 offspring, they provide no basis for rejecting the application to genetic risk estimation of the effectiveness factor of 2.5 that is based on specific-locus mutations. Thus, it appears that the usual effectiveness factor of 20 applied for alpha irradiation overestimate genetic risk by a factor of 2 to 8 times in the case of 2 3 9 Pdeposited ~ in the testes. In view of the data derived from transmitted genetic damage, it would seem sufficiently cautious to use the factor of 20 for the potential genetic hazards from internally deposited alpha-emitting radioactive materials suggested in systems that directly measure damage. This factor may be several times too conservative, but it seems best to allow for a higher effectiveness factor than the 2.5 demonstrated from the specific-locus results. Research on the transmitted genetic effects from alpha-emitting radionuclides has been limited to 2 3 9 Pcitrate. ~ Since most of the

20

/

4. ALPHA-EMITTING RADIONUCLIDES

alpha-emitting radionuclides emit particles of similar energies and since dose-response relationships for the induction of cytogenetic damage by a range of alpha emitting radionuclides were similar, the research on transmitted genetic damage from 2 3 9 Pmay ~ be extrapolated to other alpha emitting radionuclides. However, 2 3 9 Pis~ very non-uniformily distributed in the reproductive tissue so that any extrapolation will depend on retention and local distribution of other alpha-emitting radionuclides. It is important to conduct additional research using a radionuclide which is more uniformily distributed throughout the reproductive tissue. Such research would provide data that would strengthen the extrapolation of alpha induced genetic damage to other radionuclides.

5. Summary A. Information on inherited genetic events that are expressed in the generation after irradiation of cells or animals is set out in Table 5.1. The data derived from cytogenetic evaluations are presented in Table 5.2 which includes information derived from exposed animals that have retained body burdens. These tables are not exhaustive, but they present the best estimates for all data in the field of genetic effects of internally deposited radionuclides. These tables include effectiveness ratios for high-LET radiation from internally deposited radioactive material or external exposure to neutrons compared to protracted low-LET external radiation exposure. These ratios are similar to the Relative Biological Effectiveness (RBE) as outlined by the RBE Committee of the International Commissions (ICRP-ICRU, 1963). RBE was defined as the dose of a standard radiation, with average LET in water of 3.5 keV per pm or less, required to result in a defined level of biological damage, divided by the .dose of high-LET radiation which produced the same level of damage. As the dose-rate or total dose decreases the slope of dose-response relationship becomes linear and can be used in this ratio. The dose-rate for internally deposited radionuclides treated in this report is low, and most of the standard radiations used for comparison were also delivered a t low dose-rates. Thus, the ratios of the slopes of dose-response relationships compared in Tables 5.1 and 5.2 are similar to the maximum relative biological effectiveness (RBE,) achieved at minimal dose, as defined by the RBE Committee (ICRP-ICRU, 1963). Using these ratios of genetic damage produced by internally deposited radioactive materials and external low- or high-LET radiation, RBE values have been derived. Recommendations are made on effectiveness factors needed to provide adequate radiation protection against genetic damage resulting from internally deposited radioactive materials. The radiation dose rates that result from internally deposited radioactive materials are typically low. The level of activitylgram deposited in the reproductive tract is also low, especially in human populations which are of concern in risk calculations. Accordingly, the report makes a linear comparison 1) of the slopes of response data from external low-dose rate exposure to the slopes of dose-response from internally deposited radioactive materials, and 2) of higher doses observed in the animal 21

22 /

^

^

5. SUMMARY

^

" 1 x g A d K N N N

X X X X X

555kb

woo-rhl

drrj,(jm.+

X X X X

-r

wzy

^

-

6 5 e4 N

4bb n-z x x

.n

D

2 5

z x x

n3-

t b b

TABLE5.2-The

indution of chromosome damage in vitro and in vivo by ionizing radiation Aberrations Spermatogonia Spemabcytes Heritable translocations translocations fragments Lymphocytes %lr~/cell/Cy' Fragments/cell/Gy' Tmnslocation/gamete/Cyl Rings and Dic/ceU/Cyl

External Chronic low LET

2.4 x

4.7 x 2.8 X

NDA

6.8 x

NDA

84 x

NDA

5.3 x 10-2'0 NDA 37 x 10-2(g)

Aberrations Liver

Abermtions/cell/Gy' 3.3 x 10-2'h)

1.8 X 10"'"'

High LET Internal 3H Other Low LET High LET

57.7 x

lo-3("

NDA NDA 39.3 x lo-3(''

Ratio High LET (Internal) Low LET (External)

16

41 x NDA NDA 78 x lo-""' 93 x 10-~'~' 120 x

NDA 1.5-2.95 x 10-3(C'

17-67

NDA

NDA

High LET (Internal) High LET (External)

f. g. h. i. j.

a Grahn et al. (1983) b. Searle et al. (1976) c. Generoso et al. (1985) d. Brewen and Luippold (1971) e. Edwards et al. (1980a)

' S.I. conversion, 1rad = lo-'

Gy.

Prosser et al. (1983) Purrott et al. (1980) Brooks (1975) Brooks et al. (1976) Brooks et al. (1972)

5.4

NDA 4-5 x 10-2") 3.1 x 50-70 x 10-2'h)

15-21

NDA

%

z

F 2

\

R and Dic = Rings and Dicentric chromosomes. NDA-No

data available.

~3 W

24

/

5. SUMMARY

studies to the low dose region of interest for estimates of potential genetic damage in humans. If there are differences in the shape of the dose-response relationships for internally deposited radioactive material relative to the damage observed following exposure to external radiation, the ratios used in this report may require modification or correction. B. Transmutational, chemical or positional effects exist for tritiated DNAprecursors; however, they seem to play a minor role in production of genetic damage. The effectiveness of tritium relative to protracted x- or gamma-ray exposure for the production of genetic effects is estimated as 2.0. C. Exposure of genetic material t o beta radiation from 14C is similar in effectiveness to that of chronic gamma-ray exposure so the effectiveness factor should be taken as 1.0. D. Relative to genetic effects of protracted x- or gamma-ray exposure, the effectiveness of high-energy beta-gamma emissions from internally deposited radionuclides is 1.0. E. Chronic beta or gamma irradiation from internally deposited beta-gamma emitting radionuclides is less effective per unit dose for producing genetic effects than acute x- or gamma-ray exposures. F. Chronic alpha irradiation is about 15 to 20 times as effective as protracted beta-gamma exposures for producing somatic chromosome damage in blood lymphocytes and liver and translocations in spermatogonia of the testes. G. Chronic alpha irradiation from internally deposited radionuclides such as 2 3 9 Pis ~ between 2.5 and 10 times as effective as protracted beta-gamma exposures in producing either specific-locus mutations in mice or mutations in vitro. H. When based on the average dose to gonads, alpha irradiation is approximately equal to neutrons in its ability to produce dominant lethal mutations in maturing or post-meiotic germ cells, but is much less effective than neutrons in producing specific-locus mutations and reciprocal translocations in the stem cells. I. The dose to reproductive tissues following plutonium inhalation is much less than that to lung, liver, and bone suggesting a lower genetic than a somatic risk from internally deposited plutonium. J. Distributional factors for 2 3 9 Pdo ~ not augment or increase the genetic response beyond that estimated by assumption of uniform distribution of dose; indeed non-uniform irradiation from 2 3 9 Pmay ~ have a sparing effect on genetic response. K. The specific-locus mutations induced by alpha irradiation appear to be qualitatively more severe than those induced by gamma rays. The dominant skeletal mutation test addressed the question of

whether overall induced damage might be much greater than expected from specific-locus results. No evidence of induction of dominant skeletal mutations by plutonium was found. L. In light of the wide range of effectiveness observed for alpha particles for the different measures of genetic damage, it is recommended that a conservative approach be used and that an overall quality factor of 20 is appropriate for genetic damage produced by alpha irradiation relative to protracted low-LET radiation. M. All the data seem to suggest that there is little evidence for a unique genetic hazard from internally deposited radioactive material which would not be predicted by external exposure studies.

References BARNHART, B. J. AND COX,S. H. (1979). "Mutagenicity and cytotoxicity of 4.4 MeV alpha particles emitted by plutonium-238," Radiat. Res. 80, 542. A. C. (1962). "Mutations induced in mouse BATEMAN, A. J. AND CHANDLEY, with tritiated thymidine," Nature 193, 705. BATCHELOR, A. L., PHILLIPS,R. J. S. AND SEARLE,A. G. (1966). "A comparison of the mutagenic effectiveness of chronic neutron and gamma irradiation of mouse spermatogonia," Mutation Res. 3,219. BRENT,R. L. (1954).Another Possible Cause of Spontaneous Mutation, Report USAEC UR-313 (U.S. Atomic Energy Commission, Washington, DC). BREWEN,J. G. AND LUIPPOLD,H. E. (1971). "Radiation-induced human chromosome aberrations in vitro dose rate studies," Mutation Res. 12,305. H. C., HAHN,F. F., MEWHINNEY, J. A., SMITH, BROOKS,A. L., REDMAN, J. A. AND MCCLELLAN, R. 0. (1983). "The retention, distribution, dose and cytogenetic effects of inhaled 2 3 9 P ~ 0or2 2 3 9 P ~ in nonhuman primates," page B4-04 in Proceedings of the Seventh Znternutwnal Congress of Radiation Research, Broerse, J. J., Barendsen, G. W. and van der Kagel, A. J., Eds. (Martinus Nijhoff, Amsterdam). R. 0. (1979). "The influence of BROOKS,A. L., DIEL,J. H. AND MCCLELLAN, testicular microanatomy on the potential genetic dose from internally deposited 2 3 9 Pcitrate ~ in Chinese hamster, mouse and man," Radiat. Res. 77, 292. C. AND CRAIN, BROOKS,A. L. CARSTEN, A. L., MEAD,D. K., RETHERFORD,J. C. R. (1976). "The effect of continuous intake of tritiated water (HTO) in the liver chromosomes of mice," Radiat. Res. 68, 480. R. 0.AND BENJAMIN, S. A. (1972). "The effects BROOKS,A. L., MCCLELLAN, of '44Ce-144Pron the metaphase chromosomes of the Chinese hamster liver cells in vivo," Radiat. Res. 52, 481. BROOKS,A. L. AND MCCLELLAN, R. 0. (1969). "Chromosome aberrations and other effects produced by 90Sr-mY in Chinese hamsters," Int. J. Radiat. Biol. 16, 545. BROOKS,A. L. (1975). "Chromosome damage in liver cells from low dose rate alpha, beta and gamma irradiation: Derivation of RBE," Sci. 190,1090. J. E. (1975). "DNA BURKI,H. J., BUNKER,S., RIT~ER,M. AND CLEAVER, damage from incorporated radioisotopes: influence of the 3H location in the cell," Radiat. Res. 6 2 , 299. CARR,T. E. F. AND NOLAN,J. (1979). "Testis mass loss in the mouse induced by injected tritiated thymidine, tritiated water or external irradiation by 60Cogamma rays," Health Phys. 36, 135. CARSTEN,A. L., BROOKS,A. L.,COMMERFORD, S. L. AND CRONKITE,E. P. 26

REFERENCES

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(1982). "Genetic and somatic effects in animals maintained on tritiated water (Special consideration of tritium distribution, turnover and microdosimetry)," page 101 in Proceedings of the Workshop on Tritium Radiobiology and Health Physics, Matsudaira, H., Yamaguchi, T., Nakazawa, T. and Saito, C., Eds. (National Institute of Radiological Sciences Anagawa, Chiba-shi, Japan). CARSTEN, A. L. AND COMMERFORD, S. L. (1976). "Dominant lethal mutations in mice resulting from chronic tritiated water (HTO) ingestion," Radiat. Res. 66,609. S. L. AND CRONKITE, E. P. (1977). "The CARSTEN, A. L., COMMERFORD, genetic and late somatic effects of chronic tritium ingestion in mice," Current Topics in Radiat. Res. 12,212. J., GOODHEAD, D. T. AND MUNSON R. J. (1977). "MutaCox, R., THACKER, tion and inactivation of mammalian cells by various ionizing radiations," Nature 267, 425. CUMMING, R. B., RUSSELL,W. L. AND SEGA,G. A. (1974). "Tritium-induced specific-locus mutations and radiation dose in the male mouse from injected tritiated water," page 128 in Biology Division Annual Progress Report, Report No. ORNL 4993 (Oak Ridge National Laboratory, Oak Ridge. Tennessee). DOBSON,R. L. AND COOPER,M. F. (1974). "Tritium toxicity: Effect of lowlevel 3HOHexposure on developing female germ cells in the mouse," Radiat. Res. 58,91. DOBSON,R. L., KOEHLER, C. G., FELTON,J. S., KWAN,T. C., WUEBBLES, B. C. AND JONES,P. C. L. (1978). "Vulnerability of female germ cells in developing mice and monkey to tritium, gamma rays and polycylic aromatic hydrocarbons," page 1 in Developmental Toxicology of Energy-Related Pollutions Report No. CONF-771017, Mahlum, D. D., Sikov, M. R., Hacket, P. L., Andrew, F. D., Eds. (U.S. Department of Energy, Washington, DC). DUFRAIN, R. L., LIITLEFIELD, L. C., JOINER,E. E. AND FROME,E. L. (1979). "Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am,"Health Phys. 37, 279. EDWARDS, J. S. AND LLOYD,D.C. (1980a). A. A., PURROTT, R. J., PROSSER, "The induction of chromosome aberrations in human lymphocytes by alpharadiation," Int. J. Radiat. Biol. 38,83. R., J. (1980b). "Dicentric EDWARDS, A. A., LLOYD,D. C. AND P U R R O ~ chromosome aberration yield in human lymphocytes and radiation quality; a resume including recent results using alpha-particles," page 1263 in Proceedings of Seventh Symposium on Microdosimetry, Booz, J., Ebert, H. G., and Hartfiel, H. D., Eds (Harwood Academic Publishers Ltd, London). ERDA (1975). Final Environmental Statement Liquid Metal Fast Breeder Reactor Program. Vol. 1. Summary and Supplemental Material, Report ERDA 1535 (United States Energy Research and Development Agency, Washington, D.C.) FISHER,D. R. AND HARTY,R. (1982). "The microdosimetry of lymphocytes irradiated by alpha-particles," Int. J. Radiat. Biol. 41, 315. FROLEN, H. (1970). "Genetic effects of mSr on various stages of spermatogen-

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esis in mice," Acta Radiologica (ther) 9, 596. W., CAIN,K. T., CACHEIRO, N. L. A. AND CORNETT, C. V. (1985). GENEROSO, "239Pu-inducedheritable translocations in male mice," Mutation Res. 152, 49. GRAHN,D., FRYSTAK,B. H., LEE, C. H., RUSSELL,J. J. AND LINDENBAUM, A. (1979). "Dominant lethal mutations and chromosome aberrations induced and by external fission neutron and in male mice by incorporated 239Pu gamma irradiation," page 163 in Biological Implications of Radionuclides Rekased from Nuclear Industries, Report IAEA-SM-237150 (International Atomic Energy Agency, Vienna). B. F. (1983). "Interpretation of GRAHN,D., LEE, C. H. AND FARRINGTON, cytogenetic damage induced in the germ line of male mice exposed for over 1 year to 2 3 9 Palpha ~ particles, fission neutrons, or 60Co gamma rays,'' Radiat. Res. 95,566. GREEN,D., HOWELLS,G. R., VENNART,J. AND WATTS, R. (1977). "The distribution of plutonium in the mouse ovary," Int. J. Appl Radiat. Isotopes 28,497. G. R. AND WATTS,R. (1979). "Plutonium in the tissues GREEN,D., HOWELLS, of foetal, neonatal and suckling mice after plutonium administration to their dams," Int. J. Radiat. Biol. 35, 417. J. (1975). GREEN,D., HOWELLS,G. R., HUMPHREYS, E. R. AND VENNART, "Localization of plutonium in mouse testes," Nature 255, 77. GREEN,D., HOWELLS, G. AND VENNART, J. (1980). Wadiation dose to mouse testes from 239P~," Health Phys. 38, 242. GOUD,S. N., REDDY,0.S. AND REDDY,P. P. (1981). "Dominant lethal mutations induced by 14C in mice," Experimenta 37,448. HARRISON, A. AND MOORE,P. C. (1980a). "Loss of mouse testis weight after x-irradiation or injection of "Na," Health Phys. 38, 1. HARRISON, A. AND MOORE,P. C. (1980b). "Reduction in sperm count and increase in abnormal sperm in the mouse following x-irradiation or injection of 22Na,"Health Phys. 39, 216. IAEA (1968). International Atomic Energy Agency, BiologicalEffects of Transmutation and Decay of Incorporated Radioisotopes, Report STI/PUB/183 (International Atomic Energy Agency, Vienna). ICRP (1977). International Commission on Radiological Protection, Recommendations of the ICRP, ICRP Publication 26. Annals of the ICRP 1, No. 3 (Pergamon Press, New York, New York). ICRP (1979). International Commission on Radiological Protection, Limits for Intakes of Radionuclides by Workers, ICRP Publication 30, Part 1, Annals of the ICRP 3, Nos. 1-4 (Pergamon Press, New York, New York). ICRP-ICRU (1963). International Commission on Radiological Protection, and the International Commission on Radiation Units and Measurements. Report of the RBE Committee to the International Commission on Radiological Protection and on Radiological Units and Measurements, Health Phys. 9,357. KRASIN,F., PERSON,S. AND SNIPES,W. (1973). "DNA strand breaks from tritium decay: a local effect for ~ ~ t o s i n e - 6 - ~ H Int. , " J. Radiat. Biol. 23,417.

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LEE, W. R. (1970). "Stability of the eukaryotic chromosome to transmutation of carbon-14 to nitrogen-14 within the DNA molecule," page 128 in Livre des Resumes IV erne Cong. Int. de Radiobiologie et de Physics Chimic des Rayonnements, Evian. LEE, W. R., SEGA,G. A. AND BENSON,E. S. (1972). "Transmutation of carbon-14 within DNA of Drosophila melanogaster spermatozoa," Mutation Res. 1 6 , 195. LUNING,K. G., FROLEN,H., NELSON,A. AND RONNBACK, C. (1963). "Genetic effects of strontium-90 injected into male mice," Nature 197,304. LONING,K. G., FROLEN,H. AND NILSSON,A. (1976a). "Dominant lethal tests o f male mice given 2 3 0 Psalt ~ injections," page 39 in Bological and Enuironmental Effects of Low-Leuel Radiation, Report IAEA STI/PUB/409 (International Atomic Energy Agency, Geneva). L~JNING, K. G., FROLEN,H. AND NILSSON,A. (1976b). "Genetic effects of 2 3 9 Psalt ~ injections in male mice," Mutation Res. 34, 539. H. (1982). "Genetic effects of 2 3 9 p salt ~ injections LONING,K. G. AND FROLEN, in male mice," Mutation Res. 92, 169. LYAGINSKAYA, A. M., MOSKALEV, Y. I., FILYUSHKIN, I. V., PONERANTSEVA, M. D., RAMAIYA, L. K., DEMENTYEV, S. I. AND SHEVCHENKO, V. A. (1985). Biological Grounds for Clarification of Safety Standards for Internal Exposure of the Gonads (Institute of Biophysics, Ministry of Health, Moscow, USSR). MATSUDAIRA, H., YAMAGUCHI, T. AND ETOH, H. (1985). Proceedings of the Second Workshop on Tritium Radwhgy and Health Physics, National Institute of Radiobiological Sciences NIRS-M-52, 9-1, 4-chome, Anagawa, Chibanshi, Japan. MILLER,S. C. (1982). "Localization of plutonium-241 in the testis: An interspecies comparison using light and electron microscope autoradiography," Int. J. Radiat. Biol. 41,633. H. G. AND BOWMAN, B. M. (1985). "Distribution MILLER,S. C., ROWLAND, of cell populations within alpha range of plutonium deposits in the rat and beagle testis," Radiat. Res. 101, 102. NAKAMURA, N. AND OKADA,S. (1981). "Dose rate effects of gamma-rayinduced mutations in cultured mammalian cells," Mutation Res. 83, 127. NAS (1972). National Academy of Sciences, The Effects on Populutwn of Exposure to Low Levels of Ionizing Radiation, (BEIR I Report) (Government Printing Office, Washington, DC). NAS (1980). National Academy of Sciences, The Effects on Population of Low Levels of Ionizing Radiation, BEIR I11 Report (U.S. Government Printing Office, Washington, D.C.). NCRP (1979a). National Council on Radiation Protection and Measurements, Tritium in the Environment, NCRP Report No. 62 (National Council on Radiation Protection and Measurements, Bethesda, Maryland). NCRP (1979b). National Council on Radiation Protection and Measurements, Tritium and Other Radionuclide Labeled Organic Compounds Incorporated in Genetic Material, NCRP Report No. 63 (National Council on Radiation Protection and Measurements, Bethesda, Maryland). P A C C H I E R OF., ~ I ,RUSO,A. AND METALLI,P. (1983). "Reciprocal transloca-

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The NCRP The National Council on Radiation Protection and Measurements is a nonprofit corporation chartered by Congress in 1964 to: 1. Collect, analyze, develop, and disseminate in the public interest information and recommendations about (a) protection against radiation and (b) radiation measurements, quantities, and units, particularly those concerned with radiation protection; 2. Provide a means by which organizations concerned with the scientific and related aspects of radiation protection and of radiation quantities, units, and measurements may cooperate for effective utilization of their combined resources, and to stimulate the work of such organizations. 3. Develop basic concepts about radiation quantities, units, and measurements, about the application of these concepts, and about radiation protection; 4. Cooperate with the International Commission on Radiological Protection, the International Commission on Radiation Units and Measurements, and other national and international organizations, governmental and private, concerned with radiation quantities, units, and measurements and with radiation protection. The Council is the successor to the unincorporated association of scientists known as the National Committee on Radiation Protection and Measurements and was formed to carry on the work begun by the Committee. The Council is made up of the members and the participants who serve on the eighty-two scientific committees of the Council. The scientific committees, composed of experts having detailed knowledge and competence in the particular area of the committee's interest, draft proposed recommendations. These are then submitted to the full membership of the Council for careful review and approval before being published. The following comprise the current officers and membership of the Council: Officers President Vice President Secretary and Treasurer AssGtunt Secretary Assistant Treasurer

THE NCRP Members ARTHURC. LUCAS CHARLES W. MAYS ROGER0. MCCLELLAN JAMES E. MCLAUGHLIN BARBARA J. MCNEIL THOMAS F. MEANEY B. MEINHOLD CHARLES MORTIMER L. MENDELSOHN FREDA. MET~LER WILLIAME. MILLS DADEW. MOELLER A. ALANMOGHISSI WESLEYNYBORG MARYELLENOICONNOR ANDREW K. POZNANSKI NORMAN C. RASMUSSEN WILIAMC. REINIG CHESTERR. RICHMOND JAMES S. ROBERTSON LAWRENCE N. ROTHENBERG LEONARD A. SAGAN J. SCHULL WILLIAM GLENNE. SHELINE ROYE. SHORE WARREN K. SINCLAIR PAULSLOVIC LEWISV. SPENCER WILLIAML. TEMPLETON J. W. THIESSEN ROYC. THOMPSON JOHN E. TILL ARTHURC. UPTON GEORGEL. VOELZ EDWARD W. WEBSTER GEORGEM. WILKENING H. RODNEY WITHERS MARVIN ZISKIN

Honorary Members LAURISTON S. TAYLOR, Honorary President

*Elected posthumously

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THE NCRP

Currently, the following subgroups are actively engaged in formulating recommendations: Basic Radiation Protection Criteria Medical X-Ray, Electron Beam and Gamma-Ray Protection for Energies Up to 50 MeV (Equipment Performance and Use) X-Ray Protection in Dental Offices Standards and Measurements of Radioactivity for Radiological Use Radiation Exposure from Consumer Products Biological Aspects of Radiation Protection Criteria Task Group on Atomic Bomb Survivor Dosimetry Subgroup on Biological Aspects of Dosimetry of Atomic Bomb Survivors Natural Background Radiation Radiation Associated with Medical Examination Radiation Received by Radiation Employees Operational Radiation Safety Task Group 2 on Uranium Mining and Milling-Radiation Safety Programs Task Group 3 on ALARA for Occupationally Exposed Individuals in Clinical Radiology Task Group 4 on Calibration of Instrumentation Task Group 5 on Maintaining Radiation Protection Records Task Group 6 on Radiation Protection for Allied Health Personnel Task Group 7 on Emergency Planning Task Group 8 on Radiation Protection Design Guidelines for Particle Accelerators Task Group 9 on ALARA at Nuclear Power Plants Instrumentation for the Determination of Dose Equivalent Assessment of Exposure of the Population Conceptual Basis of Calculations of Dose Distributions Internal Emitter Standards Task Group 2 on Respiratory Tract Model Task Group 5 on Gastrointestinal Models Task Group 6 on Bone Problems Task Group 8 on Leukemia Risk Task Group 9 on Lung Cancer Risk Task Group 10 on Liver Cancer Risk Task Group 12 on Strontium Task Group 13 on Neptunium Task Group 14 on Placental Transfer Task Group 15 on Uranium Human Radiation Exposure Experience Radon Measurements Radiation Exposure Control in a Nuclear Emergency Task Group on Public Knowledge About Radiation Task Group on Exposure Criteria for Specialized Categories of the Public Radionuclides in the Environment Task Group 5 on Public Exposure from Nuclear Power Task Group 6 on Screening Models Task Group 7 on Contaminated Soil as a Source of Radiation Exposure

THE NCRP

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Task Group 8 on Ocean Disposal of Radioactive Waste Task Group 9 on Biological Effects on Aquatic Organisms Task Group 10 on Low Level Waste Task Group 11on Xenon Quality Assurance and Accuracy in Radiation Protection Measurements Biological Effects and Exposure Criteria for Ultrasound Biological Effects of Magnetic Fields Microprocessors in Dosimetry Efficacy of Radiographic Procedures Quality Assurance and Measurement in Diagnostic Radiology Radiation Exposure and Potentially Related Injury Radiation Received in the Decontamination of Nuclear Facilities Guidance on Radiation Received in Space Activities Effects of Radiation on the Embryo-Fetus Guidance on Occupational and Public Exposure Resulting from Diagnostic Nuclear Medicine Procedures Practical Guidance on the Evaluation of Human Exposures in Radiofrequency Radiation Extremely Low-Frequency Electric and Magnetic Fields Radiation Biology of the Skin (Beta-Ray Dosimetry) Assessment of Exposure from Therapy Control of Indoor Radon Study Group on Comparative Risk Task Group on Comparative Carcinogenicity of Pollutant Chemicals Ad Hoc Group on Medical Evaluation of Radiation Workers Ad Hoc Group on Video Display Terminals Task Force on Occupational Exposure Levels

In recognition of its responsibility to facilitate and stimulate cooperation among organizations concerned with the scientific and related aspects of radiation protection and measurement, the Council has created a category of NCRP Collaborating Organizations. Organizations or groups of organizations that are national or international in scope and are concerned with scientific problems involving radiation quantities, units, measurements, and effects, or radiation protection may be admitted to collaborating status by the Council. The present Collaborating Organizations with which the NCRP maintains liaison are as follows: American Academy of Dermatology American Association of Physicists in Medicine American College of Nuclea; Physicians American College of Radiology American Dental Association American Industrial Hygiene Association American Institute of Ultrasound in Medicine American Insurance Association American Medical Association American Nuclear Society

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THE NCRP

American Occupational Medical Association American Podiatric Medical Association American Public Health Association American Radium Society American Roentgen Ray Society American Society of Radiologic Technologists American Society for Therapeutic Radiology and Oncology Association of University Radiologists Atomic Industrial Forum Bioelectromagnetics Society College of American Pathologists Conference on Radiation Control Program Directors Federal Communications Commission Federal Emergency Management Agency Genetics Society of America Health Physics Society National Bureau of Standards National Electrical Manufacturers Association Radiation Research Society Radiological Society of North America Society of Nuclear Medicine United States Air Force United States Army United States Department of Energy United States Department of Housing and Urban Development United States Department of Labor United States Environmental Protection Agency United States Navy United States Nuclear Regulatory Commission United States Public Health Service

The NCRP has found its relationships with these organizations to be extremely valuable to continued progress in its program. Another aspect of the cooperative efforts of the NCRP relates to the special liaison relationships established with various governmental organizations that have an interest in radiation protection and measurements. This liaison relationship provides: (1) an opportunity for participating organizations to designate an individual to provide liaison between the organization and the NCRP; (2) that the individual designated will receive copies of draft NCRP reports (at the time that these are submitted to the members of the Council) with an invitation to comment, but not vote; and (3) that new NCRP efforts might be discussed with liaison individuals as appropriate, so that they might have an opportunity to make suggestions on new studies and related matters. The following organizations participate in the special liaison program: Commission of the European Communities Commisariat a 1'Energie Atomique (France)

THE NCRP

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Defense Nuclear Agency Federal Emergency Management Agency Japan Radiation Council National Bureau of Standards National Radiological Protection Board (United Kingdom) National Research Council (Canada) Office of Science and Technology Policy Office of Technology Assessment United States Air Force U n i t d States Army United States Coast Guard United States Department of Energy United States De~artmentof Health and Human Services United States ~ e i a r t m e n of t Labor United States Department of Transportation United States Environmental Protection Agency United States Navy United States Nuclear Regulatory Commission

The NCRP values highly the participation of these organizations in the liaison program. The Council's activities are made possible by the voluntary contribution of time and effort by its members and participants and the generous support of the following organizations: Alfred P. Sloan Foundation Alliance of American Insurers American Academy of Dental Radiology American Academy of Dermatology American Association of Physicists in Medicine American College of Nuclear Physicians American College of Radiology American College of Radiology Foundation American Dental Association American Hospital Radiology Administrators American Industrial Hygiene Association American Insurance Association American Medical Association American Nuclear Society American Occupational Medical Association American Osteopathic College of Radiology American Pediatric Medical Association American Public Health Association American Radium Society American Roentgen Ray Society American Society of Radiologic Technologists American Society for Therapeutic Radiology and 0ncolog)l American Veterinary Medical Association American Veterinary Radiology Society Association of University Radiologists

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THE NCRP

Atomic Industrial Forum Battelle Memorial Institute Center for Devices and Radiological Health College of American Pathologists Commonwealth of Pennsylvania Defense Nuclear Agency Edison Electric Institute Edward Mallinckrodt, Jr. Foundation Electric Power Research Institute Federal Emergency Management Agency Florida Institute of Phosuhate Research Genetics Society of America Health Physics Society Institute of Nuclear Power Operations James Picker Foundation National Aeronautics and Space Administration National Association of Photographic Manufacturers National Bureau of Standards National Cancer Institute National Electrical Manufacturers Association Radiation Research Society Radiological Society of North America Societv of Nuclear Medicine united States Department of Energy United States De~artmentof Labor United States Environmental Protection Agency United States Navy United States Nuclear Regulatory Commission

To all of these organizations the Council expresses its profound appreciation for their support. Initial funds for publication of NCRP reports were provided by a grant from the James Picker Foundation and for this the Council wishes to express its deep appreciation. The NCRP seeks to promulgate information and recommendations based on leading scientific judgment on matters of radiation protection and measurement and to foster cooperation among organizations concerned with these matters. These efforts are intended to serve the public interest and the Council welcomes comments and suggestions on its reports or activities from those interested in its work.

NCRP Publications NCRP publications are distributed by the NCRP Publications' office. Information on prices and how to order may be obtained by directing an inquiry to: NCRP Publications 7910 Woodmont Ave., Suite 1016 Bethesda, MD 20814 The currently available publications are listed below.

Proceedings of the Annual Meeting No. 1

2 3

4

5 6

7

Title Perceptions of Risk, Proceedings of the Fifteenth Annual Meeting, Held on March 14-15, 1979 (Including Taylor Lecture No. 3) (1980) Quantitative Risk in Standards Setting, Proceedings of the Sixteenth Annual Meeting, Held on April 2-3, 1980 (Including Taylor Lecture No. 4) (1981) Critical Issues in Setting Radiation Dose Limits, Proceedings of the Seventeenth Annual Meeting, Held on April 8-9, 1981 (Including Taylor Lecture No. 5) (1982) Radiation Protection and New Medical Diagnostic Procedures, Proceedings of the Eighteenth Annual Meeting, Held on April 6-7, 1982 (Including Taylor Lecture No. 6) (1983) Environmental Radioactivity, Proceedings of the Nineteenth Annual Meeting, Held on April 6-7, 1983 (Including Taylor Lecture No. 7) (1984) Some Issues Important in Developing Basic Radiation Protection Recommendations, Proceedings of the Twentieth Annual Meeting, Held on April 4-5, 1984 (Including Taylor Lecture No. 8) (1985) Radioactive Waste, Proceedings of the Twenty-First Annual Meeting, Held on April 3-4,1985 (Including Taylor Lecture No. 9) (1986) 39

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NCRP PUBLICATIONS

Symposium Proceedings The Control of Exposure of the Public to Ionizing Radiation in the Event of Accident or Attack, Proceedings of a Symposium held April 27-29, 1981 (1982)

Lauriston S. Taylor Lectures No.

Title and Author

The Squares of the Natural Numbers i n Radiation Protection by Herbert M . Parker (1977) W h y be Quantitative About Radiation Risk Estimates? by Sir Edward Pochin (1978) Radiation Protection-Concepts and Trade Offs by Hymer L. Friedell (1979) [Available also in Perceptions of Risk, see above] Prom "Quantity of Radiation" and "Dose" to "Exposure" and "Absorbed Dose1'-An Historical Review by Harold 0.Wyckoff (1980) [Available also in Quantitative Risks i n Standards Setting, see above] How Well Can W e Assess Genetic Risk? Not Very by James F. Crow (1981) [Available also in Critical Issues in Setting Radiation Dose Limits, see above] Ethics, Trade-offs and Medical Radiation by Eugene L. Saenger (1982) [Available also in Radiation Protection and New Medical Diagnostic Approaches, see above] The Human Environment-Past, Present and Future by Merril Eisenbud (1983) [Available also in Environmental Radioactivity, see above] Limitation and Assessment i n Radiation Protl,ction by Harald H . Rossi (1984) [Available also in Some Issues Important in Developing Basic Radiation Protection Recommendations, see above] Truth (and Beauty) i n Radiation Measurement by John H. Harley (1985)

NCRP Commentaries No. 1

Commentary Title

Krypton-85 in the Atmosphere- With Specific Reference to the Public Health Significance of the Proposed Controled Release at Three Mile Island (1980)

NCRP PUBLICATIONS

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Preliminary Evaluation of Criteria for the Disposal of Transuranic Contaminated Waste (1982) Screening Techniques for Determining Compliance with Environmental Standards (1986) Guidelines for the Release of Waste Water from Nuclear Facilities with Special Reference to the Public Health Significance of the Proposed Release of Treated Waste Waters at Three Mile Island (1987)

NCRP Reports No.

Title

Control and Removal of Radioactive Contamination i n Laboratories (1951) Recommendations for Waste Disposal of Phosphorus-32 and Iodine-131 for Medical Users (1951) Radioactive Waste Disposal in the Ocean (1954) Maximum Permissible Body Burdens and Maximum Permissible Concentrations of Radionuclides i n Air and i n Water for Occupational Exposure (1959) [Includes Addendum 1 issued in August 19631 Measurement of Neutron Flux and Spectra for Physical and Biological Applications (1960) Measurement of Absorbed Dose of Neutrons and'Mixtures of Neutrons and Gamma Rays (1961) Stopping Powers for Use with Cavity Chambers (1961) Safe Handling of Radioactive Materials (1964) Radiation Protection in Educational Institutions (1966) Medical X-Ray and Gamma-Ray Protection for Energies Up to 10 MeV-Equipment Design and Use (1968) Dental X-Ray Protection (1970) Radiation Protection in Veterinary Medicine (197b) Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides (1970) Protection against Neutron Radiation (1971) Basic Radiation Protection Criteria (1971) Protection Against Radiation from Brachytherapy Sources (1972)

Specification of Gamma-Ray Brachytherapy Sources (1974) Radiological Factors Affecting Decision-Making in a Nuclear Attaclz (1974)

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NCRP PURLICA'rlONS

Review of the Current State of Radiation Protection Philosophy (1975) Krypton-85 in the Atmosphere-Accumulation, Biological Significance, and Control Technology (1975) Natural Background Radiation i n the United States (1975) Alpha-Emitting Particles in Lungs (1975) Tritium Measurement Techniques (1976) Radiation Protection for Medical and Allied Health Personnel (1976) Structural Shielding Design and Evaluation for Medical Use of X Rays and Gamma Rays of Energies Up to 10 MeV (1976) Environmental Radiation Measurements (1976) Radiation Protection Design Guidelines for 0.1-100 MeV Particle Accelerator Facilities (1977) Cesium-I37 From the Envircnment to Man: Metabolism and Dose (1977) Review of NCRP RadioZion Dose Limit for Embryo and Fetus in Occupationally Exposed Women (1977) Medical Radiation Exposure of Pregnant and Potentially Pregnant Women ( i977) Protection of the Thyroid Gland in the Event of Releases of Radioiodine (1977) Radiation Exposure 7ronz Consumer Products and Miscellaneous Sources (1977) Instrumentation and Monitoring Methods for Radiation Protection (1978) A Handbook of Radioactii.ity Measurements Procedures, 2nd ed. (1985) Operational Radiation Safety Program (1978) Physical, Chemical, and Biological Properties of Radiocerium Relevant to Radiation Protection Guidelines (1978) Radiation Safety Training Criteria for Industrial Radii~graphy (1978) Tritium in the Environment (1979) Tritium and Other Radionuclide Labeled Organic Compounds Incorporated in Genetic Material (1979) Influence of Dose and Its Distribution in Time on DoseResponse Relationships for Low-LET Radiations (1980) Management of Persons Accidentally Contaminated with Radionuclides (1980) Mammography (1980) Radiofrequency Electromagnetic Fields-Properties, Quan-

NCRP PUBLICATIONS

68 69 70 71 72 73 74 75 76

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tities and Units, Biophysical Interaction, and Measurements (1981) Radiation Protection in Pediatric Radiology (1981) Dosimetry of X-Ray and Gamma-Ray Beams for Radiation Therapy in the Energy Range 10 keV to 50 MeV (1981) Nuclear Medicine-Factors Influencing the Choice and Use of Radionuclides in Diagnosis and Therapy (1982) Operational Radiation Safety-Training (1983) Radiation Protection and Measurement for Low Voltage Neu.tron Generators (1983) Protection in Nuclear Medicine and Ultrasound Diagnostic Procedures in Children (1983) Biological Effects of Ultrasound: Mechanisms and Clinical Implications (1983) Iodine-129: Evaluation of Releases from Nuclear Power Generation (1983) Radiological Assessment: Predicting the Transport, Bioaccumulation, and Uptake by Man of Radionuclides Released to the Environment (1984) Exposures from the Uranium Series with Emphasis on Radon and its Daughters (1984) Evaluation of Occupational and Environmental Exposures to Radon and Radon Daughters in the United States (1984)

79 80 81 82 83 84 85 86 87 88 89

Neutron Contamination from Medical Electron Accelerators (1984) Induction of Thyroid Cancer by Ionizing Radiation (1985) Carbon-14 in the Environment (1985) SZ Units in Radiation Protection and Measurements (1985) The Experimental Basis for Absorbed Dose-Calculations in Medical uses of Radionuclides (1985) General Concepts for the Dosimetry of Internally Deposited Radionuclides (1985) Mammography-A User's Guide ( 1986) Biological Effects and Exposure Criteria for Radiofrequefrcy Electromagnetic Fields (1986) Use of Bioassay Procedures for Assessment of Internal Radionuclide Deposition Radiation Alarms and Access-Control Systems (1987) Genetic Effects of Internally Deposited Radionuclides (1987)

Binders for NCRP Reports are available. Two sizes make it possible to collect into small binders the "old series" of reports (NCRP Reports

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NCRP PUBLICATIONS

Nos. 8-30) and into large binders the more recent publications (NCRP Reports Nos. 32-88). Each binder will accommodate from five to seven reports. The binders carry the identification "NCRP Reports" and come with label holders which permit the user to attach labels showing the reports contained in each binder. The following bound sets of NCRP Reports are also available: Volume I. NCRP Reports Nos. 8,9, 12, 16, 22 Volume 11. NCRP Reports Nos. 23, 25, 27, 30 Volume 111. NCRP Reports Nos. 32, 33, 35,36, 37 Volume IV. NCRP Reports Nos. 38,39,40,41 Volume V. NCRP Reports Nos. 42,43,44,45,46 Volume VI. NCRP Reports Nos. 47,48,49,50,51 Volume VII. NCRP Reports Nos. 52, 53, 54,55, 56, 57 Volume VIII. NCRP Reports No. 58 Volume IX. NCRP Reports Nos. 59,60,61,62,63 Volume X. NCRP Reports Nos. 64,65,66,67 Volume XI. NCRP Reports Nos. 68, 69, 70, 71, 72 Volume XII. NCRP Reports Nos. 73,74,75,76 Volume XIII. NCRP Reports Nos. 77, 78, 79,80 Volume XIV. NCRP Reports Nos. 81,82, 83, 84,85. Titles of the individual reports contained in each volume are given above). The following NCRP Reports are now superseded and/or out of print: No. 1

Title X-Ray Protection (1931). [Superseded by NCRP Report No. 31 Radium Protection (1934). [Superseded by NCRP Report No. 41 X-Ray Protection (1936). [Superseded by NCRP Report No. 61 Radium Protection (1938). [Superseded by NCRP Report No. 131 Safe Handling of Radioactive Luminous Compounds (1941). [Out of Print] Medical X-Ray Protection Up to Two Million Volts (1949). [Superseded by NCRP Report No. 181 Safe Handling of Radioactive Isotopes (1949). [Superseded by NCRP Report No. 301 Radiological Monitoring Methods and Instruments (1952). [Superseded by NCRP Report No. 571

NCRP PUBLICATIONS

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Maximum Permissible Amounts of Radioisotopes in the Human Body and Maximum Permissible Concentrations i n Air and Water (1953). [Superseded by NCRP Report No. 221 Recommendations for the Disposal of Carbon-14 Wastes (1953). [Superseded by NCRP Report No. 811 Protection Against Radiations from Radium, Cobalt-60 and Cesium-137 (1954). [Superseded by NCRP Report No. 241 Protection Against Betatron-Synchrotron Radiations Up to 100 Million Electron Volts (1954). [Superseded by NCRP Report No. 511 Safe Handling of Cadavers Containing Radioactive Isotopes (1953). [Superseded by NCRP Report No. 211 Permissible Dose from External Sources of Ionizing Radiation (1954) including Maximum Permissible Exposure to Man, Addendum to National Bureau of Standards Handbook 59 (1958). [Superseded by NCRP Report No. 391 X-Ray Protection (1955). [Superseded by NCRP Report No. 261 Regulation of Radiation Exposure by Legislative Means (1955). [Out o f Print] Protection Against Neutron Radiation Up to 30 Million Electron Volts (1957). [Superseded by NCRP Report No. 381 Safe Handling of Bodies Containing Radioactive Isotopes (1958). [Superseded by NCRP Report No. 371 Protection Against Radiations from Sealed Gamma Sources (1960). [Superseded by NCRP Report Nos. 33, 34, and 401 Medical X-Ray Protection Up to Three Million Volts (1961). [Superseded by NCRP Report Nos. 33, 34, 35, and 361 A Manual of Radioactivity Procedures (1961). [Superseded by NCRP Report No. 581 Exposure to Radiation in an Emergency (1962). [Superseded by NCRP Report No. 421 Shielding for High Energy Electron Accelerator Installations (1964). [Superseded by NCRP Report No. 511 Medical X-Ray and Gamma-Ray Protection for Energies Up to 10 MeV-Structural Shielding Design and Evaluation (1970). [Superseded by NCRP Report No. 491

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Other Documents The following documents of the NCRP were published outside of the NCRP Reports series: "Blood Counts, Statement of the National Committee on Radiation Protection," Radiology 63, 428 (1954) "Statements on Maximum Permissible Dose from Television Receivers and Maximum Permissible Dose to the Skin of the Whole Body," Am. J. Roentgenol., Radium Ther. and Nucl. Med. 84, 152 (1960) and Radiology 75, 122 (1960) X-Ray Protection Standards for Home Television Receivers, Interim Statement of the National Council on Radiation Protection and Measurements (National Council on Radiation Protection and Measurements, Washington, 1968) Specification of Units of Natural Uranium and Natural Thorium (National Council on Radiation Protection and Measurements, Washington, 1973) NCRP Statement on Dose Limit for Neutrons (National Council on Radiation Protection and Measurements, Washington, 1980) Control of Air Emissions of Radionuclides (National Council on Radiation Protection and Measurements, Bethesda, Maryland, 1984)

Copies of the statements published in journals may be consulted in libraries. A limited number of copies of the remaining documents listed above are available for distribution by NCRP Publications.

Index Abnormal sperm, 6 Alpha-Emitting Radionuclides, 7-20 %'Am, 11 252Cf,11 '"h, 7-19.24 '"h, 11 Blood Lymphocytes, 11, 23,24 Bone Marrow, 6,11 "C, 4,5, 24 Dominant lethal mutations, 4 , s Effectiveness factor, 5 Cell killing, 3.4, 8, 10, 16-18 Chromosome Aberrations, 3,6, 11-13, 19, 23,24 '"Am, 11 Blood lymphocytes, 11, 23-24 Bone Marrow, 6.11 '"Cf, 11 chromatid fragments, 13 isochromatid fragments, 13 liver, 6, 11, 24 238h,11 '"Pu, 11,24 testes, 12, 13 tritium induced, 3,4 Cytogenetic damage in Reproductive tissue, 11,17, 23 heritable translocations, 11, 23 reciprocal translocation, 11, 17, 23 Cytogenetic damage in somatic cells liver, 3-5, 11-13, 19, 23-24 bone marrow, 6,11 blood lymphocytes, 11,23, 24 Derived Air concentration, 9 Distribution factor, 14, 24 Dominant lethal mutations, 4, 5, 13, 14, 18-20,22, 24,25 %o, 13 ovaries, 18 post-meiotic spermatogonial cells, 13 -Pu, 13, 17 Dominant skeletal mutations, 17, 18, 25 47

Dose-response relationships, 10,11,16,17 humped, 17 mutations in vitro, 10, 11 specific locus mutations, 16,17 Drosophila melanogaster, 3, 4, 10 Effectiveness factor, 6, 7, 12, 15, 19-20, 24-25 '%, 4,5,24 High energy Beta-gamma, 6, 24 Plutonium, 18, 19, 20,24 3H,3,4,24 Fallout, 4 , 5 Fractional Activity in Tissue, 7-10 Bone, 9 liver, 9 lung, 9 ovaries, 10 testes, 7-10 Gamma ray exposure, 3-6, 11,15,24 Genetic dose, 7-10, 14 ovaries, 10 testes, 7-9, 14 Genetic risk, 1, 2, 4,5,8, 24, 25 Heritable translocations, 12,13, 16, 22 plutonium, 12 High energy beta-gamma, 6,23 lace, 6 lnCs, 6 Dominant lethal mutations, 6 Fission products. 6 "Na, 6 '"Sr, 6 Hot-Spots, 19 Index of Mutation. 18 In Vitro Studies, 10, 22 cell killing, 8, 10 HGPRT mutations, 10, 22 LET, 2,5,6,14-20,24 Low energy Beta Emitters, 2,5,6, 24 14C,4, 5, 24 3H, 2,3,24 Liver, 4,6,9, 11, 23, 24

Maximum permissible body burden, 8.9 Mutations in vitro, 3, 10, 22 Neutrons; 7, 12, 13 Non-Uniform Distribution of isotopes, 8, 10, 14, 20, 24 Ovaries, 10 Plutonium, 10, 24 Testes, 8, 14,24 Nuclear Power, 5 Oocytes, 4.18 Ovary, 10,18 cell killing, 18 direct damage, 18 dominant lethals, 4, 18 non-uniform distribution of Pu, 10 retention of plutonium, 10,18 "VU,7-20, 24 Quality Factor, 19 Qualitative differences in alpha induced mutations, 15, 16 fertility, 15 heterozygous, 15,16 homozygous, 15, 16 multi-locus deficiencies, 15 survival, 15 RBE, 4 1 1 , 13-16.19-20 Reciprocal Translocations, 12, 16, 23, 24 Respiratory tract deposition, 9

Respiratory tract deposition (Continued) lymph nodes, 9 nose, 9 pulmonary region, 9 tracheal-bronchial region, 9 Somatic dose, 8, 9, 24 Somatic risk, 8, 9, 24 Specific Locus Mutations, 4,14-17,19,22, 24,25 gamma ray induced, 4,15 multi-locus deficiencies, 16 Plutonium induced, 14-17 Tritium induced, 4 Spermatocyte fragments, 23 Spermatogonial stem cells, 16 Testes, 7-10, 12-14,24 Transmutational effects, 4, 5, 24 "C,4, 5, 24 aH, 3,4,24 Tritium, 3 4 , 22-24 Chromosome aberrations, 3,4,23 DNA damage from, 3,4,22 Dominant lethal mutations from, 3, 4, 22 mutation induced by, 3,4, 22 RBE of, 4 specific locus mutations from, 4, 22 X-rays, 3, 6, 15, 16,24