Effects of inhaled α and β emitting radionuclides in lung tissues

RBE FOR DETERMINISTIC

39

EFFECTS

5. EFFECTS OF INHALED a AND fi EMITTING RADIONUCLIDES IN LUNG TISSUES 5.1. General Aspects of Dose Distributions from Radionuclides in Lung Tissue (148) The lung is a highly specialized organ containing more than 40 distinctive cell types. Dose-effect relationships for stochastic and deterministic effects from inhaled radionuclides have been reviewed in ICRP Publication 31 on Biological Eflects of Inhaled Radionuclides (ICRP, 1980). High concentrations of radionuclides deposited in the lung may cause early severe inflammation or late fibrosis. In the context of the present report on RBE for deterministic effects, it is important that some radionuclides that may be released in accidents, emit c( radiation, which has a high RBE relative to p/y radiation (Table 1). (149) A major problem in comparing lung damage from different inhaIed radionuclides arises from differences in the temporal and spatial distribution of dose and the relationship to the sensitive cells for early and late effects. This dose distribution depends on the types and energy of the radiations emitted, the rate of decay, the sizes of particles inhaled and their specific activities, their initial distribution in the lung tissues and factors influencing their subsequent movement, including the solubility of the material, and the overall rate of clearance of the radionuclide from the lung and the body. A theoretical example of the influence of particle size on dose distribution is given in Table 7. The influence of spatial and temporal distribution of dose on radiation damage to tissues has been reviewed for lung cancer induction following inhalation of /? emitters compared with a emitters; and an Equal Effectiveness Ratio of about 30 for a radiation was derived, which may be assumed to be close to RBE, (ICRP, 1980). More recently, Boecker et al. (1988) have reviewed data from life span studies in dogs exposed to “Y-labelled fused aluminosilicate particles (FAP) and 23QPu02 in micrometer sized particles. Preliminary results suggest that for lung cancer induction, a irradiation is about 20 times as effective as /? irradiation. This value is consistent with the quality factor of 20, adopted by ICRP (1977) for a radiation, related to cancer induction in man. In these studies the assumption was made that the dose was uniform throughout the lung tissue. (150) For deterministic effects including radiation pneumonitis and pulmonary fibrosis, the data on p emitting radionuclides were considered to be inadequate for determining doses for specified effects for comparison with effects of a radiation (ICRP, 1980). Since the publication of that report, limited data have become available on the consequences of inhalation of both a and fl emitting radionuclides which allow preliminary estimates to be made of their relative effectiveness in causing lung damage in accident situations. Table

7.

Relationship of particle size to number of cells at risk for a static lung burden of 600 Bq zs~Puo2~

Particle diameter (pm) 0.1 0.3 0.7 1.0

No. of particles 5.4 2.0 1.8. 5.4.

10’ lo6 lo5

lo4

Activity per particle (mBq) 0.01 0.4 3 11

Cells at risk 3. 1.3. 1.2. 3.6.

10”

10’0 109 lo*

Proportion of lung W) 30 1 0.1 0.03

’ Assuming static particlesin a structureless human lung of uniform density (0.2 gm cnm3 with an average cell volume of 103pm3). Cells at risk are taken to be those in a sphere of radius equal to the a particle range (200 pm at the assumed density). From Bair et at., 1974.

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REPORT OF A TASK GROUP OF COMMITTEE

1

5.2. Accidental Exposures (151) Any estimate of the effects of internally deposited radionuclides inhaled as a consequence of the release of radionuclides into the environment must depend upon a thorough knowledge of all the circumstances of the accident. The consequence of any release, from a nuclear plant for example, will depend upon the fraction of the core inventory of radionuclides that are released to the environment, the time dependence of the release, the size distribution of the aerosol, the elevation of the release, the time of containment, the atmospheric conditions during the release and the extent and timing of any evacuation. The important potential modes of exposure of the lungs following an accidental release are: external /?/y irradiation from activity in the release plume; -inhalation of /? and y emitting radionuclides from the release plume; external y irradiation from activity deposited on the ground. A small dose to the lung may also be contributed from the inhalation of activity resuspended following deposition on the ground. Thus, in accidents lung damage arises from inhaled radionuclides and from external radiation exposure. (152) In the U.S.A. reactor safety study, coded WASH 1400, the radionuclides likely to be of concern in any reactor accident assessment were identified (USNRC, 1975). A summary is given in Table 1. Whilst a large number of radionuclides may be involved in any accident situation, a small number will predominate with most of the dose to lungs coming from /?/y emitters. emitters. (153) Table 8 gives information on the percentage contribution to lung dose accumulated at 1 year after inhalation exposure arising as a result of a degraded core accident in a pressurized water reactor. Much of the lung dose from inhaled radionuclides arises from intakes of lo6Ru and 144Ce, with a smaller constribution from isotopes of iodine and caesium which are rapidly cleared from the lungs. Alpha emitting nuclides only make a small contribution to the total lung dose with 242Cm predominating. Thus, at 1 year the cumulative dose to the lungs from inhaled B/y emitting radionuclides is about 40% of the total lung dose; the rest of the dose largely arising from deposited y activity. In the case of an accident in which the population was promptly evacuated, the dose from deposited activity would be substantially reduced, but inhalation doses will be affected much less. The contribution to the total lung dose from inhaled a emitters is very small, but typical of those occurring in the case of accidents involving damage to, or melting of, the fuel. If no damage to fuel elements occurs, there would be no significant contribution of a activity to the total lung dose.

5.3. Effects of Inhaled Radionuclides in Accident Situations (154) Although substantial quantities of radionuclides have been produced and handled in the nuclear industry, there have been very few accidental human exposures in which the inhalation of radionuclides has resulted in the occurrence of deterministic effects. In the two known cases reported (Doenecke and Belt, 1931; Rajewski, 1939) it has not been possible to make an accurate assessment of the radiation doses received by the lungs. In reviews of data on USAEC contractors, no clinical evidence of pulmonary damage was reported in individuals who had inhaled a variety of radioactive materials, including enriched uranium, 23QPu, 210Po, 3H and a number of iodine isotopes (Ross, 1968). In a comprehensive review by the BEIR IV Committee of the health effects of radon and other a emitters, no acute effects on the human respiratory system were reported (BEIR IV, 1988).

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8. Contributions to the lung dose equivalent following an accidental release of radioactivity from a pressurized water reactor during a degraded core accident Table

Radionuclide

% contribution to lung dose at 1 yeaPb

Internal

j/y emitters 10.8 4.91 2.13 1.26 1.23 1.14 1.08 0.99

lo6Ru 14Ve 1331 ‘j2Te ‘29”Te l34CS 9’Y losRu ,351 1311

0.07 0.88 0.50

l3’CS Others

12.15

Total Bb)

38.1 memitters’

24lPu 23SPu 242Cm *39PU Other

0.02 0.27 1.23 0.09 0.14

Total c(

1.75

External

cloud y deposited y Total

1.85 58.3 loo.0

a At 5 km from the site. b No rain, which can significantly deposited y dose. c Assumes RBE for a’s of 10.

enhance

(Data input Jones and Williams (1988).)

(155) To assess the doses at which health effects are likely to occur in man, animal data must therefore be used. A series of animal studies in a number of laboratories have provided information on the effects of irradiation of the lung tissue by both a and /3emitting radionuclides that can be used for assessing the consequences of varying patterns of irradiation of lung tissue and for comparing the effects of radiations of different quality. 5.4. Mortality from Inhaled Radionuclides (156) The majority of studies in animals that are relevant to accident high dose conditions have reported on mortality resulting from radiation pneumonitis and fibrosis. Acute effects of p emitting radionuclides in animals have been reported after the inhalation of ‘44Ce dioxide (Stuart et al., 1964; Thomas et al., 1972), 9oY in fused clay particles (Hobbs et al., 1972) and the intratracheal injection of ‘44Ce chloride (Cember and Stemmer, 1964). (157) Extensive long term studies on the effects of inhaled p/y emitting radionuclides in dogs

42

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have been reported by McClellan et al. (1986). Beagle dogs were exposed to aerosols of a range of radionuclides with different half lives (“Y, tljz 64 h. ‘lY, t,,, 58.5 d; ‘44Ce t 285 d* “Sr, t,,, 28 yr) applied in insoluble FAP to give a range

time after

inhalation

exposure

( clay I

Fig. 10. Calculated absorbed p dose rate to the lungs of beagle dogs for various inhaled radionuclides normalized to 11 Gy d-’ initial dose rate. FAP: fused aluminosilicate particle (McClellan et al., 1986).

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EFFECTS

brief CFZp0S”t-e

protracted

I 100

200-365

14-200d.

O-l day

. .

..

102

103 to lung

Cy

)

Fig. 11. Relationships between mean low-LET radiation dose to lung and mortality from radiation pneumonitis pulmonary fibrosis as affected by dose protraction. Doses are to 1 year. 0 = human; n = rat; A =dog. Van Dyk et al. (1981), human thoracic irradiation; Dunjic et al. (1940), rats upper bodyirradiation;McClellan et ai. (1982) and Scott and Hahn (1989), dogs inhaled p emitting radionuclides, 9oY-FAP, “Y-FAP or ‘%e-FAP.

radiation pneumonitis than protracted irradiation from inhaled B emitting radionuclides that irradiated the lung over a period of a year or more. Even /? irradiation of the lung over a few weeks is about 5 times more effective than similar irradiation protracted over several years. (160) The early pulmonary effects of inhaled B emitting radionuclides and the influence of temporal radiation dose patterns have also been studied in rats (Scott et al., 1987). Groups of rats were exposed to aerosols of either 90Sr, 9oY + 25% 90Sr or 9oY + 2.3% 90Sr, incorporated in FAP, to give irradiation over short, intermediate or long periods of time. The rats were observed for 1.5 years and the number dying of radiation pneumonitis determined. Those rats dying of radiation pneumonitis after the brief irradiation (with 9oY + 2.3% 90Sr-FAP) did so at earlier times than the rats exposed to 90Sr-FAP. For examp le, over 80% of the rats exposed to 9oY + 2.3% 90Sr died within 100 days of inhalation. In contrast, over 80% of the rats exposed to 90Sr alone died between 140 days and 540 days after inhalation. (161) Protraction of the radiation dose in rats has a sparing effect. Thus, brief irradiation with 9oY +2.3% 90Sr (LD,, =230 Gy) was about 1.6 times more effective in producing death from pneumonitis than the protracted irradiation with 90Sr (LD,, =370 Gy). The LD,, for 9oY +25% 90Sr was intermediate between these two results (LD,,=330 Gy). The effect of protraction is much greater in the dog because of the longer life span and longer retention half time of particles in the dog lung (Snipes et al., 1984). (162) Radiation pneumonitis and pulmonary fibrosis, resulting in respiratory insufficiency have also been described in dogs after inhalation of insoluble OL emitting radionuclides (Park et al., 1972; Bair ef al., 1980; McClellan et al., 1986). The types of lesions are similar to those JAICAP 20:1-o

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REPORT OF A TASK GROUP OF COMMITTEE 1

et al., 1987). (163) A comparison ofthe dose-response relationships for 23gPu02 and “Sr-FAP inhaled by beagle dogs is shown in Fig. 12. A Weibull hazard function model, with the same shape as that used for analysis of all the response curves from the studies with inhaled /? emitting radionuclides in dogs, has been used to analyse the response to inhaled 23gPu02. The relationship departs from the data at the lower level of the curve, indicating that the relative effectiveness of a and /? irradiation of the lung may be a dose-dependent relationship. However, because errors in the data are quite large, further work is required to clarify this relationship. At the estimated LD,,‘s of 37 Gy and 400 Gy, the relative effectiveness of a versus B irradiation of the lung for inducing death from radiation pneumonitis and pulmonary fibrosis within 1.5 years is about 10. (164) The early pulmonary effects of inhaled a emitting radionuclides have also been studied in rats (Scott et al., 1988). Groups of rats were exposed to aerosols of 238P~-FAP. In this particulate form, the plutonium is highly insoluble and has a specific activity similar to 23gPu02. The rats were observed for 1.5 years and the number dying of radiation pneumonitis determined. The dose-response relationship described with a Weibull hazard function was steep with a median lethal dose of 45 Gy at 1 year. For rats exposed to “Sr-FAP, the mortality dose-response data (Scott et al., 1987) could be fitted with an identical shape factor giving an LD,, at 1 year of 320 Gy, corresponding to an equal effectiveness ratio for a and B irradiation of about 7. (165) Taken together, these data from dogs and rats indicate that the relative effectiveness ratio of a radiation compared to p radiation for death from radiation pneumonitis is in the range 100

/-

1 E 8

“Sr

FAP/

/

k 8 5

p 50 *

0I

I

.

.

.

.

.

.

,

10)

102 dossto one

yew

( cy )

Fig. 12. Comparison of dose responses for death from radiation pneumonitis/pulmonary fibrosis after inhalation of 2’gPu0, or gOSr-FAP by beagle dogs. Mean doses to 1 year and observation period for 1.5 years (Muggenburg et al., 1987; Scott and Hahn, 1988).

RBE FOR DETERMINISTIC

EFFECTS

45

of 7-10. The similarity in the results for the two species strengthens justification of extrapolation of these relative effectiveness ratios to human accident conditions. (166) One problem that is highlighted by the studies of inhaled a emitting radionuclides in dogs is the occurrence of death from radiation pneumonitis and pulmonary fibrosis several years after inhalation exposure, when neoplasia is also present. Deaths from radiation pneumonitis and pulmonary fibrosis that occur later than l-2 years after exposure may need to be regarded as a second category of late deterministic effect, related to inflammation of the lung. This second category would require a separate set of risk factors. Further work is needed to clarify the issue of deaths from “late” radiation pneumonitis and pulmonary fibrosis. 5.5. Morbidity from Inhaled Radionuclides (167) Some animal data are available on lung morbidity resulting from reduced lung function following radiation-induced progressive lung damage. The data, however, are not as extensive as those available on mortality from lung damage. The partial loss of lung function and other non-fatal effects resulting from inhalation of p emitting radionuclides have been examined in rats (Scott et al., 1987). Body weight, white blood cell count and pulmonary function were determined between 2 and 18 months after exposure in a group of rats after inhalation of 90Sr-FAP. Functional parameters determined were the breathing pattern, dynamic mechanics, diffusion capacity, maximum expiratory flow and lung volume. (168) Body weight and pulmonary function were reduced in those rats with lethal pulmonary injuries and could be used to predict the onset of death. However, the doses of B radiation required to produce impaired pulmonary function or weight loss were similar to those required for lethality. (169) A subsequent study of the acute mortality and morbidity of inhaled 14’Pm-FAP in rats did show a difference in the mean radiation doses required for mortality and morbidity as measured by pulmonary function (Scott et al., 1988). Promethium-147 is a low energy p emitter and, when incorporated in FAP, has a retention time in lung similar to that of inhaled 90Sr-FAP. In this study, survivors at 1.5 years after inhalation exposure were tested for pulmonary function. Reduced values were found for vital capacity and efficiency of gas exchange. This was associated with a less compliant lung and an altered intrapulmonary gas distribution. (170) These functional changes are consistent with the radiation pneumonitis and pulmonary fibrosis seen histologically in the affected rats. The radiation doses required to produce this effect were one-fourth of those required to produce death from radiation pneumonitis. (171) Respiratory impairment following inhalation of non-lethal amounts of /? emitting radionuclides has also been demonstrated by pulmonary function measurements in dogs. In one study, dogs were exposed by inhalation to aerosols of 90Y-FAP and functional measurements were made under stresses of treadmill exercise and added external respiratory dead space (Mauderly et al., 1973). Early functional impairment at 8 weeks after inhalation included defects in distribution of ventilation and in alveolar capillary gas exchange. The smallest dose to the lungs that caused alteration in lung function was 49 Gy, approximately one-half the median lethal dose. A similar relationship between the dose for morbidity and the dose for lethality was derived in a second study of dogs that inhaled ‘44Ce-FAP (Mauderly et al., 1980). Dogs were sacrificed after reaching various degrees of functional impairment. At cumulative doses of about one-half the median lethal dose, functional impairment was present and lesions of radiation pneumonitis were seen histologically. (172) Taken together, these studies of pulmonary function in dogs and rats that inhaled /1

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1

emitting radionuclides indicate that pulmonary injury can be detected with appropriate tests at one-half to one-fourth the median lethal dose. However, other indicators of illness, e.g. weight loss and altered blood cell profiles, are not affected at these doses. (173) Impairment of respiratory function has also been observed in dogs exposed to a emitters. A study of 10 dogs exposed to 23gPu0, showed increased respiratory frequency with a mild respiratory functional disorder 1 to 5.6 years after inhalation exposure, which persisted for 1.9 to 7.3 years with doses ranging from 2.4 to 3.2 Gy at 2600 days after inhalation (Muggenburg et al., 1988). The functional disorder consisted of smaller lung volume, reduced compliance, increased respiratory and minute volume, and reduced carbon monoxide diffusing capacity. The changes were seen in dogs with lung contents from 330 to 4 070 kBq 23gPu/kg. These changes were not, however, observed in all dogs exposed to 23gPu0,. In a second group of 10 dogs with initial lung contents between 100 and 1960 kBq 23gPu/kg-1, giving doses from 0.8 to 16 Gy, no changes in lung function, other than in carbon monoxide diffusing capacity, were observed over a similar follow-up time. (174) Insufficient data are available to adequately compare the relative effects ,of CLand /3 irradiation in beagle dogs for the induction of impaired lung function. Respiratory function tests have also been undertaken on rats exposed to 238Pu02. For 238Pu-a irradiation of the lung the average lung dose at 1.5 year to give an incidence of pulmonary morbidity of 50% was estimated to be about 11 Gy. For 14’Pm irradiation of the lung, the comparable dose was about 75 Gy to the lung. This suggests an RBE for lung morbidity of about 7 (Scott et al., 1988). 5.6. Summary of Information on Lung Damage by Inhaled Radionuclides (175) There are no human data that can be used for assessing the early effects on lung tissue of inhaled radionuclides. Limited data on the effects of acute external irradiation suggest that animal data can be applied to predict the consequences in man. The results of animal studies with inhaled radionuclides indicate that for /I irradiation, lung damage depends both on the total dose and on the dose rate. Thus, with radiation exposure from “Y protracted over days, the mean lethal dose in dogs is about 100 Gy, whereas for exposures from ‘44Ce over months and years it increases to about 550 Gy. Comparative information from animal studies on the effects of c1and /3/y irradiation of the lung indicate that for mortality from radiation-induced pneumonitis and fibrosis the equal effectiveness ratio is in the range 7-10. Very limited data on the effects of a and a/fly emitters on respiratory function indicate that functional impairment will occur at doses between about one-half and one-quarter of those resulting in mortality and that the equal effectiveness ratio is similar to that for mortality. The data described are summarized in Table 9.

6. DISCUSSION OF RBE VALUES FOR DETERMINISTIC AND THEIR RELATION TO Q VALUES

EFFECTS

6.1. Comparison of RBE Values for Different Doses and Dose Rates (176) From data reviewed in Sections 4 and 5, various general characteristics can be derived concerning the dependence of RBE on the deterministic end-points evaluated. A summary for fast neutrons and heavy ions is presented in Table 6. Assessment of ranges of RBE and mean values for various types of radiation, doses and effects is of interest in the context of radiation protection recommendations, but specific RBE values obtained from animal experiments or human experience are unlikely to be directly applicable in accident situations because of the