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Health Effects of Exposure to Radon: BEIR VI (1999)

Chapter: Appendix E Exposures of Miners to Radon Progeny

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Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
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E-ANNEX 1Exposures to Miner Cohorts: Review of Estimates for the Studies

Colorado Plateau Uranium Miners

Introduction

Uranium mining in the Colorado Plateau expanded rapidly in the post-World War II period to include more than 200 mines by 1950 (see Time Line E-1). The start of an industry and the boom times did not lead to orderly administration and record keeping, c.f. Czechoslovakia and Ontario below. Moreover, some of the miners who worked in the mines during the post-war uranium boom had previously worked the same ore bodies for radium and vanadium without any accounting of exposure to radon progeny. Most of the early mines were small and depended on natural ventilation so that ambient temperature change was the driving force for exchange of the mines' air with outside air. Until 1967, mining operations were regulated only by the states where mining was taking place, even though all ore was sold to the Atomic Energy Commission. There was no requirement in place for measurement of exposure and there was not a federal standard for exposure to radon progeny. Consequently adequate ventilation practices were not uniformly introduced from the outset and the extent of radon measurement was initially quite limited. As a result, estimates of cumulative exposures to uranium miners on the Colorado Plateau were largely based on various estimation procedures rather than direct measurements relating to a particular mine shaft or even the mine where a given worker was exposed.

The history of radon exposures to the miners was described by Holaday (1969) and the approaches followed by the U.S. Public Health Service for esti-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

mating exposures of individual participants in the epidemiologic study of Colorado uranium miners are described in National Institute for Occupational Safety and Health-National Institute for Environmental Sciences Joint Monograph No. 1 (Lundin and others 1971). A 1968 report of the Federal Radiation Council addressed the accuracy of the exposure estimates. SENES Consultants Limited of Ontario, Canada, has prepared a report entitled "Preliminary feasibility study into the re-evaluation of exposure data for the Colorado Plateau uranium miner cohort study" (SENES 1995). This report provides an extensive description of the calculation of the WLM values for the epidemiologic study and gives insights into the sources of variability and error in the estimates.

Estimation of WLM

The following description is taken largely from the 1971 monograph authored by Lundin and colleagues. The U.S. Public Health Service began surveying for radon in uranium mines in 1949. In 1950 they were joined by the Colorado State Department of Health and in 1951 by the U.S. Bureau of Mines for mines on Indian reservations. Coverage was far from complete; 1949 "a few measurements," 1950 "relatively few mines," 1951 "but again coverage was incomplete," (Lundin and others 1971). By 1952 an effort was made to survey all operating mines and radon progeny were sampled in 157 mines. This sampling may have examined most of the larger mines, but government records

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

indicate that over 450 mines shipped ore in 1951. Mining companies introduced radon surveys in 1956 and the state programs continued through 1960. Both company and state-sampling efforts were made in work areas for information purposes, not for control purposes, and "are considered to be representative of the areas in the mines in which miners were exposed" (Lundin and others 1971). This early data base is of primary importance in considering the adequacy and precision of miner's exposure estimates as utilized in epidemiology assessments of risks due to radon since a large portion of the cumulative exposure occurred in the 1950's.

By 1960, exposure levels had dropped precipitously in anticipation of Colorado's adoption of a 10 WL shutdown level in 1961. However, regulatory control probably reduced the validity of the measurements in mines for epidemiologic purposes. As outlined in Joint Monograph No. 1, the most complete description of the Colorado Plateau miner data (Lundin and others 1971) "Most radon daughter measurements available from Colorado, Utah, and Wyoming after 1960 were made by mine inspectors who measured air samples primarily for control purposes." This may have led to bias in the estimated exposures. As noted by Lundin and others (Lundin and others 1971), "Proportionately more measurements were made in sections of mines having high levels which tended to yield radon-progeny values greater than would have been obtained by sampling all work areas with equal frequency." In addition more measurements were concentrated in mines having high levels of radon. The U.S.P.H.S. investigators who assembled the data base for estimating cumulative exposures chose to exclude company measurements made after 1960 on the grounds that they might have been "minimized to avoid regulatory action." The aim was clearly ''to assure a consistent direction of bias, that is, over estimation of radon daughter levels" (Lundin and others 1971).

Even though the number of radon-progeny measurements increased during the 1960's, the number per mine increased only slowly from about six in 1960 to almost 12 in 1968 (Figure E Annex 1-1). Measurements of radon progeny in a particular mine were never extensive and, more importantly, were not made on even a once per year basis in the majority of mines. Only 341 miners, about 10% in the Colorado Plateau miner cohort, had their exposure assignments based on measured radon-progeny concentration. For the majority of the miners, information on measured levels was combined with estimates made using a variety of methods as described by Lundin and others (1971).

Many of the uranium miners were also employed as hardrock miners or previous to 1950 some had mined the same ore bodies, where uranium was found, for radium, vanadium etc., particularly in the Urivan Mineral Belt in Colorado. In the epidemiologic study, hardrock miners were assigned an exposure level of 1 WL for mining that occurred before 1935, 0.5 WL for 1935 through 1939, and 0.3 WL for later years (Lundin and others 1971). No information is given as to the basis of these estimates but a statement is included in Joint Monograph No. 1

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

FIGURE E ANNEX 1-1 Frequency of radon-progeny measurements on the Colorado Plateau in two-year intervals 1950–1969. Source: Presentation to the committee of analysis of the data tapes for the Colorado Plateau miners by Duncan Thomas and Dan Stram, September 1995.

(Lundin and others 1971) which indicates these estimates were thought to have been too high and that the average exposure was less.

A re-evaluation of a sample of the Colorado Plateau cohort for exposure during hardrock mining is described in Monograph 1. This reassessment indicates that the tabulation of hard rock mining duration was subject to error and that misclassification of exposure was fairly common for that portion of a cohort member's work experience. For example, for a sample of 101 cases and 202 controls, misclassification was only about 10% for cumulative exposures of less than 20 WLM but 50% or more at higher levels. Nevertheless, hard rock mining may be a relatively unimportant source of exposure compared to the mining of uranium-bearing ores for which exposure levels were often much higher than 1 WLM.

Because relatively few mines were initially monitored for radon or radon progeny, exposure estimates in uranium mines that occurred before 1951 were referred to as "guesstimates" in Joint Monograph No. 1 (Lundin and others 1971). According to that report, "guesstimates" were made on the basis of knowledge concerning ore bodies, ventilation practices, emission rates from different types of ores, and such radon or radon progeny measurements as were performed in 1951 and 1952.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

For mining that occurred after 1950, three other methods were used to estimate exposure levels. By far the most common was a process called area average estimation. This consisted of using the available, albeit often sparse, measured values to estimate concentrations in a given locality to obtain an "area average." In order to reduce sampling variability for these area averages it was required that three or more mines and ten or more samples had to be available for a locality in a year, otherwise the locality was assigned the average for the district in which it was located (Lundin and others 1971). If sufficient data for a district were not available, a state average was used or, in a few cases for which state data were insufficient, data for the state of Colorado were used. The degree to which area estimates were used to obtain exposure estimates is not often appreciated. Area estimates account for most of the exposure assignments throughout the study period of the Colorado Plateau cohort (Figure E Annex 1-2) Monograph 1 implies that when an individual mine was thought to differ appreciably from others in the same locality due to its ore quality or mining practices, guesstimation was substituted for an area average.

To complete gaps in the measurements in calculating individual WLM estimates, a system of extrapolation, interpolation, and expert judgment was used to estimate the exposure in mines monitored less frequently than once a year. For mines with actual measurements at least once every five years, working-level estimates were obtained by interpolation, that is, averaging the measured values

FIGURE E ANNEX 1-2 Bases for the assignment of exposure estimates by calendar year 1950–1969. Source: Presentation to the committee of analysis of the data tapes for the Colorado Plateau miners by Duncan Thomas and Dan Stram, September 1995.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

(Lundin and others 1971). Approximately 20% of the exposure assignments were made using this method (Figure E Annex 1-2). An assessment of this extrapolation procedure described in Monograph No. 1 indicates that it tended to overestimate exposures in the early years of mining but became more valid in the 1960s as information from more frequent measurements became available.

For mines with yearly monitoring information available, the measured concentration was used to assign a worker's cumulative exposure in a given year. Table IV-3 in the BEIR IV Report (NRC 1988) indicates that the number of measurements per year per mine surveyed was usually between 10 and 20 after 1959 so that the measured values provide a reasonably stable estimate of the average working levels in those areas monitored. However, the average number per mine was somewhat less, 8–9 as illustrated in Figure E Annex 1-1. Although nearly 43,000 measurements were obtained (Lundin and others 1971), there were about 2,500 mines and measured concentrations were not a frequent method of exposure assignment. Figure E Annex 1-2 indicates that from 1959 to 1969 only 10–20% of the exposure assignments in a given year were based on direct measurement of radon progeny concentration and that even fewer were made on such direct information prior to 1959, when exposure levels were, on the whole, much higher.

Assessment of Errors in the WLM Estimates

A comparison of exposure estimates in relation to calendar year is given in Figure E Annex 1-3 for each assignment method. Except for 1950, estimates based on the extrapolation procedures are in reasonable agreement with those based on direct measurement while area average estimates tend to be somewhat greater than obtained by other methods. This may in part be due to measurements having been made more frequently in large mines having more employees and because of larger capital investment in better ventilation.

The degree of variation in exposures among workers in a given mine was not well characterized. Before 1960 mechanical ventilation was not commonly used and a near equilibrium between radon and progeny was probably the rule under conditions of convective ventilation as indicated by the early data described by Holaday (1969). There appears to be no information on aerosol size distribution or even the unattached fraction in early mines. Even though diesel power was not common, compressed air or electricity was used to operate equipment including ore cars; dust was plentiful from drilling and hauling operations so that it is likely that the unattached fraction was low.

An extensive study of air quality in nine uranium mines was carried out by the AEC Health and Safety Laboratory (HASL), now the DoD Environmental Monitoring Laboratory, in 1967–1968. Mines were selected by the U.S. Bureau of Mines to represent a cross section of the uranium mining industry (Breslin and others 1969). This investigation was in response to the concerns expressed at the

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

FIGURE E ANNEX 1-3 Comparison of mean WL estimation by various methods in two year intervals 1950–1969. Source: Presentation to the committee of analysis of the data tapes for the Colorado Plateau miners by Duncan Thomas and Dan Stram, September 1995.

Joint Committee on Atomic Energy hearings in 1967 in which the validity of exposure and early risk estimates of increased lung-cancer in miners were questioned. A particular point in question was "the extreme variation of atmospheric characteristics within a mine and among mines"; the HASL study was directed at exploring this question (Breslin and others 1969).

The nine mines studied ranged in size from having two to 112 workers. Ore production varied from 150 to 11,000 tons per month. Mechanical ventilation rates varied from 5,600 to 100,000 cu. ft. per minute. Given this range of conditions, atmospheric conditions were surprisingly uniform, giving some credence to the validity of the estimation methods described above. In most of the mines the variation in radon-progeny concentration at different times and locations was only occasionally as large as a factor of two and 80% of the time had a coefficient of variation of 30% or less. The average WL ratio (pCi progeny to pCi radon) averaged 0.23 with a geometric standard deviation of 1.6 and showed limited variation with the absolute level of radon progeny. Equilibrium values F were also in a narrow range: about two-thirds were between 0.20 and 0.30; mode 0.25. Polonium-214 was most often at 16% of the equilibrium value, range 0.09 to 0.49.

Simultaneous measurements of radon progeny were made at various locations in stopes (mining chambers) and in drifts (tunnels). While drifts showed

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

greater variation than stopes, as indicated in Figure E Annex 1-4, the report's authors indicated that sampling location was not critical within a radius of 10 to 20 feet of the miners' location and that breathing-zone sampling was unnecessary. Similarly, the HASL study indicated that differences between various mining operations, for example, drilling, mucking, etc., had little effect on the measured working level (Figure E Annex 1-5). No measurements were taken immediately after blasting but such areas would not have been occupied because of other safety considerations. While the HASL study does indicate that mine-wide averaging probably provides a useful measure of worker exposure in the mines studies, this is probably less accurate for the high exposures which occurred before the introduction of mechanical ventilation in U.S. uranium mines.

The recent report from SENES Consultants Limited provides additional relevant information. Tables for several mines demonstrate substantial variation in WL values within a mine during a single visit by an inspector, typically one day. For example, U.S. Bureau of Mines data for one Utah mine in 1968 showed variation from 0.4 to 5.4 WL across the mine (Table-E Annex 1-1).

The Public Health Service investigators used self-reported mining history as the basis for estimating time spent underground in specific mines. This information was collected both retrospectively and prospectively during the annual miner censuses. The possibility of error in these histories has been acknowledged. The SENES report provides a series of case descriptions documenting inconsistencies in these histories and gives a compilation of exposure estimates for 78 miners for whom exposures have been calculated for both the epidemiologic study and for other purposes. Substantial variation is evident in these

FIGURE E ANNEX 1-4 Variation of radon concentration with distance in ventilated uranium mine drifts on the Colorado Plateau (Breslin and others 1969).

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

FIGURE E ANNEX 1-5 Variation of radon concentration with distance in ventilated uranium mine stopes on the Colorado Plateau (Breslin and others 1969).

estimates, largely reflecting various discrepancies in the alternative work histories used for the purpose of estimating the exposure.

New Mexico Uranium Miners

Large-scale uranium mining began in the early 1950s (see Time Line E-2) with the opening of the Jackpile mine, an open-pit mine. By the late 1950s, a number of large mines were operating at Ambrosia Lake and the Churchrock mining district became active in the late 1970s. The industry continued operating into the early 1990s, longer than in other U.S. locations, so that miners working after 1968 have individual exposure records (work location estimates and estimates of exposure) for this period of employment. These were calculated based on area measurements and work locations. For the most part, post-1968 employment was in very large industrial operations with state of the art ventilation. Mean annual exposures in 1968 were about 3.8 WLM and declined to 1.2 WLM or less by 1972 (Samet and others 1986b). Earlier exposures were not estimated as accurately, although the State Health Department and the State Mine Inspector had implemented active measurement programs by the late 1950s. The state implemented a progressively more stringent series of shut-down concentrations. As for the Colorado Plateau miners (see above), median annual exposures were considerably larger during the earlier years of the industry, about 30 WLM in the 1960's. Some members of the New Mexico cohort, who had also mined in the Colorado Plateau, had annual exposures as high as 300 WLM or more (Samet and others 1991).

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Investigators directed substantial effort at tracing employment histories for the purpose of estimating the cumulative exposures for those employed before exposure estimates were individualized (Samet and others 1991). The miners' underground employment and exposures in specific mines were traced by examining company personnel records and self-reported work histories taken at the time of periodic medical examinations. Estimated exposures for miners who had worked underground on the Colorado Plateau were supplied by the USPHS (Lundin and others 1971; Samet and others 1991). Contributions to the total mean exposure from various information sources are listed in Table E Annex 1-2 (Samet and others 1991).

With the notable exception of those members of the work force employed on the Colorado Plateau, this cohort probably has maintained the most extensively documented exposure estimates. In this regard, it should be noted that the state of New Mexico had more extensive and more frequent monitoring for radon then was common elsewhere in the early 1950's when exposures were very high (Lundin and others 1971). From 1957 to 1967 exposure estimates are based on 20,086 measurements taken during 1,886 visits. Most annual exposures were relatively low during this period, mean 4-5 WLM per year, so that this cohort has a large sub-cohort of miners exposed at low rates and relatively low cumulative exposures.

Beaverlodge Uranium Miners

The BEIR-IV report also includes a description of the exposure estimates for this cohort (NRC 1988). Exploratory uranium mining at Beaverlodge,

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE E ANNEX 1-1 U.S. Bureau of Mines February 1968 survey at North Alice Mine, Utaha

No. of Men

Location, Operation

Estimated Average Full Shift Exposure to Radon Daughtersb (WLc)

2 men, night shift

416 NE from 360 NW; mining

0.5

2 men, day shift

236 from 325 S; mining

1.7

1 man night shift

 

 

1 man day shift

240 W incline station and hoist

1.0

1 man night shift

 

 

1 man day shift

248 SE from 225 N; mining

5.4

2 men, night shift

242 S from 190 W; mining

3.6

1 man day shift

 

 

1 man night shift

240 W incline to main incline; tramming

2.2

2 men, night shift

100 S area; mining

0.6

2 men, day shift

147 N from 130 E; mining

2.8

3 men, day shift

 

 

2 men, night shift

128 S from 145 E; mining

1.5

1 man day shift

 

 

1 man night shift

main incline; trip rider

0.4

1 man day shift

all areas; electrician

1.4

2 men

all areas; mechanics

1.6

5 men

all areas; shift bosses

1.4

3 men

all areas; staff

1.0

3 men

all areas; bratticemen

2.6

a This table is from a February 1968 report on a Radiation Survey prepared by U.S. Bureau of Mines, obtained from SENES 1995.

b Average Levels are estimated from information gained by questioning the miners about where there time is spent and weighing the radon daughter concentrations in each place by the time spent in that place.

c NIOSH database: 1967 WL is 1.3, based on 39 measurements; 1968 WL is 3.3, based on 120 measurements.

Saskatchewan started in 1949 and commercial production began with a greatly expanded labor force in 1953 (see Time Line E-3). Radon monitoring was carried out in 1954 and 1956 but only sporadically until the end of 1961. A number of radon-progeny measurements were also made at this time but monitoring was mostly for radon and viewed as a check on ventilation rather than as a tool for exposure control. Nevertheless, the frequency of radon-progeny measurements increased and by 1961 exposure records were maintained for all full-time underground employees. These records listed each worker's occupancy time at each work place on a daily basis. In 1970 worker's exposure records were estimated retrospectively to 1 November 1966 and in 1971 part-time underground workers were included in the exposure assessment (SENES 1989).

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE E ANNEX 1-2

Source of Information on Underground Employment

Contributions To Mean Cumulative Exposure

Work outside New Mexico

24.9 WLM

New Mexico Employment records

59.5 WLM

Self reported work histories

11.8 WLM

Company individual records (1967 and later)

10.0 WLM

Other (1967 and later)

5.2 WLM

Two assessments of lung-cancer risk observed in Beaverlodge miners have been made by Howe and colleagues (Howe and others 1986; Howe and Stager 1996) using two related but differing exposure estimates. The first of these estimates was prepared by Frost (1983) who, observing a wide dispersal in the recorded concentrations in a given year, assigned the median of this quasi lognormal distribution as the best measure of exposure. Although, it was possible to assign work locations for service personnel, for miners, mine-wide medians were used in the cohort study reported by Howe and colleagues (1986).

A reassessment of the Beaverlodge exposure estimates was carried by SENES Consultants, Ltd. at the direction of the Atomic Energy Control Board (SENES 1989, 1991). This included a painstaking reconstruction of mining activity and its correlation with exposure information for the Beaverlodge mining complex. The revised exposure estimates were used by Howe as the basis for a recent case-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

control analysis of lung-cancer mortality (Howe and Stager 1996), which used cases and controls from a previous analysis that used the original exposure estimates (L'Abbe and others 1991). In the new analysis, averages rather than medians of the individual measurement data were used to estimate exposure levels in a given location. There was also a systematic consideration of the locations where mining took place at a given period of time and, in many cases, individual miners could be assigned to a given mine face, as recorded in bonus-pay information, removing in some measure the radon error inherent in using mine-wide averages.

The effects of these changes is illustrative of what an improved exposure assessment can accomplish. The exposure estimates for each of the miners in the case-control study were compared to those used in the original cohort and case-control studies. In general, the more recent exposure estimates were considerably higher than the original estimates, the mean exposure increasing from 50.6 WLM to 81.3 WLM. There is evidence that the new estimates reduced exposure misclassification. Table E Annex 1-3 compares the cumulative exposure estimates used in the original cohort study to the newer estimates for the case-control study.

Because of the wide intervals of grouped exposures, most workers remained in the same exposure category even though their estimated exposures were on the average considerable larger in the revised exposure estimates. However, there was a decrease in the number of workers receiving low exposures and a corresponding increase at higher levels. For example, the number of workers in the 200+ WLM group increased from 10 to 15 (Table E Annex 1-3). Because there is less misclassification of estimated exposures, the slope of the regression of risk on cumulative exposure is increased even though the estimated exposures increased. The original estimate of the excess relative risk from the case-control was an excess relative risk of 2.70% per 100 WLM while the revised exposure assessment was 3.25% (Howe and Stager 1996).

TABLE E ANNEX 1-3 Number of miners in each exposure category

Cumulative Exposure WLM

Cohort Study

Case-Control Study

0

43

42

1–24

90

80

25–49

15

18

50–99

15

17

100–199

18

19

200+

10

15

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×
Ontario Uranium Miners

Uranium mining in Ontario, Canada, started in 1953, somewhat later then in the United States and was conducted in relatively few mines in comparison to the United States (see Time Line E-4). A 12 WLM annual limit was adopted in 1954 with a concomitant decrease in annual exposure thereafter. Radon measurement and radon control programs were instituted within two years of the start of mining. Except for exposures occurring before 1958, exposure estimates are largely based on actual measurements (SENES 1989). However, some Ontario uranium miners had worked earlier as gold miners and were exposed to both radon progeny and arsenic in those operations. These miners had an estimated average cumulative exposure 2 WLM due to gold mining (Kusiak and others 1991) compared to an average of 30 WLM in uranium mines (Kusiak and others 1993). Even for those with gold mining experience, the approximated exposures from gold mining are only a minor portion of the total exposure.

The BEIR IV report provides a complete description of the exposure estimates for their cohort (NRC 1988). The radon-progeny measurement program was extensive: 131,000 measurements in 15 mines. Exposures were estimated using different methods for 1967 and earlier years and for 1968 and later years for which WLM estimates made by the companies were used. For 1957–1967, WLM were calculated by combining WL data with work histories. Two separate sets of estimates were derived for these years: the ''standard" or lower WL values were

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

the averages of the four quarterly averages or three four-month averages for a particular year while the "special" or upper WL values were a weighted average of the four highest quarterly measurements or the three highest four-month measurements in headings, stoops, raises, and travel ways. The differences between these two sets of values varied by mine and by year, with the special values being up to four times as high as the standard values. The investigators considered that the true exposures were bounded by the two sets of values. For its analysis, the BEIR IV committee used the WLM values based on the standard WL values. Some estimation of exposures for the earliest years of the industry, before 1954, required extrapolation from measured values, taking into account such factors as ventilation. These years included the highest exposures and consequently 22 percent of the total WLM accumulated by the cohort was based on extrapolation of measured values.

Port Radium Uranium Miners

The approach for exposure estimation for the Port Radium miners is well documented in a 1996 report by SENES Consultants Limited (1996b). Underground uranium and/or pitchblende mining at Port Radium started in 1932 and continued, with a two-year interruption, until 1960 (see Time Line E-5). Because records of employment before 1940 were not available, exposures occurring before that date have not been accounted for (Howe and others 1987, SENES

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

1989). Exposures occurring after 1939 have been estimated on the basis of rather sparse monitoring data for radon. Between 1945 and 1957, 261 radon measurements were made in seven years of this period, with from nine to 71 samples in an individual year. A few radon-progeny measurements were made and only three paired measurements of radon and progeny were obtained.

Absent information on concentrations of radon progeny, the equilibrium between radon and its progeny was estimated on the basis of knowledge of mine operations and by analogy from the Beaverlodge mine and the radon concentrations were then converted to concentrations of progeny. Although ventilation was introduced in 1947, it apparently was used in limited fashion during the winter season because of the cold. Consequently, the approach to estimating the WL values considered seasonal variation in equilibrium factor. The SENES report provides detailed documentation of the assumptions made in estimating the WL values from the radon measurements.

Reported radon concentrations were extremely variable ranging from 50–300,000 pCiL-1 and it is thought that before ventilation was introduced, some exposures could have been as high as 1,000 WLM per year (SENES 1989). Unfortunately, such large annual exposures could not be assigned to the involved workers unless the exposures took place after 1940 because of the missing work-history information before 1940.

The potential limitations of the exposure data were acknowledged in the initial report on the findings of the epidemiologic study of Port Radium miners (Howe and others 1987). SENES Consultants Limited (1996b) have recently re-estimated exposures to radon progeny for 171 miners included in a case-control study (see Table E Annex 1-4). For the 171 miners, employment histories were reconstructed and used with revised WL estimates to calculate WLM. Substan

TABLE E ANNEX 1-4 Summary of differences between the SENES reevaluation of miner exposures and epidemiology exposures used by Howe and others (1987). Data from 171 minersa

Months Worked

Months Worked

WLM

Mean difference

-1.64b

-5.2d

Maximum

66.93

2908

75th percentile

0.26

69

Median

-0.23c

0d

25th percentile

-1.97

-12

Inter quartile range

2.24

80

Minimum

-38.04

2348

a Based on SENES 1989, table 4.1.

b Mean difference significantly different at 5% level.

c Median difference significantly different from 0 at 1% level.

d Median difference and mean difference not significantly different from 0.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

tial differences were found in individual estimates, although the mean WLM values were comparable for the two sets of estimates. There were large differences in employment duration for some of the men and changes in estimated exposure as large as 2900 WLM were found. The report comments on key sources of uncertainty in the exposure estimates for the Port Radium miners: incomplete employment histories for other employment; lack of employment information for years before 1940 when exposures were extremely high; and the numerous assumptions made in calculating the WL values from the radon measurements. Finally, the report also indicates that Port Radium ores contained "significant concentrations of various elements including for example arsenic, nickel, and cobalt."

Czechoslovakia Uranium Miners

A cohort of miners in Czechoslovakia, who started uranium mining between 1948 and 1957, has been described extensively in the literature by Sevc and Placek (1976), Sevc and others (1988), Kunz and others (1978, 1979), and more recently by Tomásek and others (1993, 1994a,b). This cohort is often designated as group S by the Czech authors (see Time Line E-6). Compared to miner studies in other countries, exposure information for group S is among the most extensive. Measurement of radon and other potentially hazardous materials had become routine in Czech mines before 1948 so that estimation was not necessary for periods of employment during which radon measurements were not made. Even so, exposure estimates for radon-progeny exposures prior to 1961 are based on radon concentrations as concentrations of progeny were not measured.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

These radon measurements were, however, extensive, the annual number varying from 100 to 700 per shaft (Sevc 1993). Estimates of WLM for years before 1961, during which radon measurements only were made, were based on F values taken during periods of ventilation failure which occurred in 1969 and 1973. These data indicated an F value of 0.86 for the earliest years 1948–1952. From 1961–1969 the mean number of annual radon-progeny measurements recorded per shaft was 952, about 3 per work day.

In 1953, natural ventilation was augmented by mechanical means and F values decreased to an estimated average value of 0.55 in 1953–1959 and to 0.36 thereafter. Czech investigators estimate the coefficient of variation in converting radon levels to working levels as 28%. The fraction of unattached plutonium-214 has been estimated by Czech investigators as 0.1 (Hamilton and others 1990).

Estimated exposures of these miners have recently been reevaluated (Tomásek and others 1994a,b). The principal change appears to have been a more thorough investigation of workers' employment histories to take account of prior mining experience and the assignment of exposure for each month based on the particular shaft in which the miner worked. In any event, the newest account given below is more complete than those published previously. Additional background can be found in a report of a WHO-sponsored trip to Czechoslovakia made in 1988 by L.D. Hamilton, L.W. Swent, and D. B. Chambers (published by SENES Consultants Limited—see Hamilton and others 1990).

"During 1949–1963 about 39,000 measurements of radon gas were made in the 19 mine shafts in Jachymov and Horoni Slakov in which the men were employed. Some men also worked, particularly after the closure of most shafts at Jachymov and Horoni Slakov in 1963, at other Czechoslovak uranium mines, and substantial numbers of measurements were also made in these mines. An initial review of exposure estimates used in previous reports found a considerable number of errors, and for some miners a part of their employment histories had not been taken into account. Therefore, exposure estimates have been completely revised for the present analysis, based on a review of all available information. The radon-gas measurements were converted into estimates in terms of working levels using equilibrium factors based on radon-progeny measurements made after 1960, and on data collected during two accidents in the uranium mines at Zadni Chodov in 1969 and at Pribram in 1973, when mechanical ventilation was stopped for at least a month. An estimate of each man's exposure in each month in terms of working months (WLM) was calculated from the time he spent in each mine shaft in conjunction with the year- and shaft-specific WL estimates. Men worked 6 days per week with 1-month of holiday each year. For most men underground work was assumed to last 8 hours per day, but for geologists, safety and ventilation technicians, and emergency workers, it was estimated that 70% of working time was spent underground, while for managers 50% was estimated. About 300 men were involved in exploratory work, which was normally carried out in shallow shafts near the surface. Explicit radon measurements are not

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

available for this work, but exposures are thought to have been low, and are estimated at 3.3 WLM per year" (Tomásek and others 1994a).

With regard to the magnitude of exposure error, it is of interest that less than 5% of the new exposure estimates differed by as much as 50% from those used in previous analyses of these data. The mean cumulative exposure in the new evaluation is 219 WLM compared with 227 WLM in the older work (Sevc 1993). Presumably, random error as well as systematic biases were reduced in the reevaluation. Using a simple model in which the estimated relative risk is linearly related to the cumulative exposure yields a relative risk of 0.37%/WLM (95% C.I. = 0.18–0.55) with the old exposure estimates. With the new ones the estimated relative risk is 0.61%/WLM (95% C.I. = 0.29–0.8) (Tomásek and others 1994), providing evidence that the dose-response was flattened by errors in the original exposure estimates.

French Uranium Miners

Uranium mining in France started in 1946 with exploratory operations that continued through 1948 when extensive commercial operations commenced (Tirmarche and others 1984, 1993) (see Time Line E-7). The first reported radon sampling occurred in 1953 when 40 measurements were taken, an average of 10 per mine. Large-scale radon monitoring began in 1956 when forced ventilation was introduced. Exposures prior to this date have been estimated retrospectively by an expert group which considered mine characteristics and type and duration of work. For this early period, before forced ventilation, exposures were relatively high and varied substantially between individuals. The estimated median annual exposure from 1947 through 1955 was 11 WLM and varied for the 3rd quartile up to 55 WLM per year.

Exposures declined rapidly after forced ventilation was introduced, median exposures averaging about 3 WLM per year from 1956 to 1975 with a further decline to 1 WLM by the early 1980's. About half of the French miners started their underground employment before 1956 but most of their person years of exposure occurred after monitoring became comprehensive, ventilation improved, and exposures were relatively low. Nevertheless, for a large number of the French miners, a major portion of their cumulative exposure was based on estimations by experts for the period when ventilation was poor and routine monitoring lacking. After sufficient monitoring data became available, worker-exposure assessments were individualized to some extent by considering the type and location of work performed. Recently, personal dosimeters, using track-etch dosimeters, have provided direct information on individual miners. This has allowed a comparison of exposure based on area monitoring in 1982 with direct personal measurements in 1983. The comparison indicated that annual exposures based on area monitoring and work locations were, on the average, underestimated by almost 30% (Bernhard and others 1984; Piechowski and others 1981). Con-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

sidering the year-to-year variation in the true levels and miner location, as well as the accuracy of the personal dosimeters, the reported difference may not be indicative of a significant bias in the exposure estimates.

Radium Hill Uranium Miners

The Radium Hill mine began operations in Australia in 1952 and radon monitoring began two years later (see Time Line E-8). In estimating exposures, exposure levels in the prior years were assumed to be the same as in early 1954 (Woodward and others 1991). A total of 56 samples were collected by 1 April 1955. Early radon concentrations were low (estimated 1.8 WL) even before forced ventilation was introduced and declined substantially thereafter—range 0. 10–0.55 WL. Apparently only radon concentrations were measured; WL concentrations were estimated by means of a calculated equilibrium factor based on ventilation rates and air volumes at various locations but such methods do not account for plateout and recirculation of progeny.

Enough radon measurements were made to allow exposure estimates by job category for work after 1 April 1955. The estimated exposures for workers show an exponential distribution with a median exposure of 3 WLM; a mean of 7 WLM and a 3rd quartile limit of 7.4 WLM. A few heavily exposed workers received about 80 WLM (Woodward and others 1991).

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×
Chinese Tin Miners

Exposure assessments of Chinese miners employed by the Yunnan Tin Corporation are largely retrospective as no measurements of either radon or radon progeny were made prior to 1972 when mechanical ventilation was introduced (see Time Line E-9). Exposure estimates for two periods prior to 1972 reflect changes in the mining industry that occurred after nationalization in 1949. Before nationalization, mining was conducted in small mines with back hauling performed manually, often by children (Xuan and others 1993). To estimate exposures under these conditions, 117 measurements were made in 13 local mine pits that had been in operation before the large-scale expansion of the tin mines that started in 1953.

Exposure estimates for miners employed between 1953 and 1972 were based on 413 measurements obtained in the 1990's by recreating conditions in tunnels and galleries in original areas or in similarly configured areas in nearby mines that used techniques similar to those in the index year (Xuan and others 1993). Evidently, there was little change in radon progeny concentration in the larger, post 1953 mines. The reported average mean WL before 1950 was 2.3 ± 0.8 and 2.2 ± 1.2 thereafter. Mechanical ventilation was introduced rather slowly with priority given to new tunnels. Working levels decreased moderately in 1971–1975 to 1.7 ± 1.1, to 1.2 ± 0.8 in 1980 and 0.9 ± 0.3 in 1985 (Xiang-Zhen and others 1993). Exposure estimates from experience since 1972 have been based on over 26,000 measurements of radon progeny.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Little information is available on other characteristics of the occupational environment. Equilibrium factors, F, were measured in 1977–1978 and found to vary from 20% to 84% with a mean of 72% in "small pit operations" and of 62% in "larger tunnels" (Lubin and others 1990b). Evidently the mean of 72% refers to conditions prior to 1953 and the mean of 62% to the expanded operations. In any event the mines were very dusty by contemporary standards. Airborne dust was first measured in the 1950's and maximum levels were between 20 and 192 mg/m3. Wet drilling was introduced in the late 1950's and became widespread in 1964 when dust levels fell to about 6.2 mg/m3 (Xiang-Zhen and others 1993). Given these levels of dust, it is probable that equilibrium levels remained rather high throughout and that the unattached fraction was small.

For the epidemiological studies, workers were assumed to be exposed to radon progeny seven hours per day. For exposures occurring after 1972, estimates of exposures were adjusted by the worker's job title to take account of those exposed intermittently (Lubin and others 1990b). Exposure to arsenic in airborne dust was also accounted for in these studies and shows a large decrease over time from 0.4 mg/m3 in the mid 1950's to .01 mg/m3 in 1985. The radon exposure estimates for the Yunnan tin miners are not very well documented but, given the apparently uniform level of exposure throughout the period of miner employment, about a factor of 2, the estimates may be less subject to errors in estimation then for those uranium mines where exposure levels varied over time by factors of ten or more due to changes in ventilation practices. Arsenic exposure, on the other hand, did decrease appreciably as wet drilling became standard practice.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×
Newfoundland Fluorspar Miners

Underground mining for fluorspar started in 1936 in Newfoundland, Canada, and continued for more than three decades before monitoring for radon and radon progeny was initiated in 1960 (see Time Line E-10). Radon levels were found to be highly variable, range 0–190 WL (Morrison and others 1988). Ventilation was immediately introduced and in 1960 levels declined to an average of 0.5 WL (1960–1967) and then to an average of 0.17 WL (1969–1978) (Morrison and others 1988). Therefore, an average worker for the entire period of radon control would have accumulated about 30 WL as opposed to an estimated average exposure for all cohort members of 382.8 WL.

Exposure estimates for epidemiological purposes have been developed by Dory and Cockill (1984) and are described in SENES 1989. Exposure estimates for the period before 1961 were based on maps of the various mines, reports by mine inspectors, and workers' recollections. Apparently experience gained when the mines were monitored was also taken into account as well as the entry of water, the source of the radon, into the mines. Eventually a computational model was developed to simulate the annual radon progeny concentration in each mine so as to yield "average workplace concentration for high, medium, and low areas" (SENES 1989). For epidemiological purposes, workers have on the basis of their jobs been assigned to approximate areas of radon concentration, high, medium, etc. for a particular year and cumulative exposures estimated on this basis.

For exposures occurring after 1960, worker job records and monitoring data have been used to assign individual exposure estimates. As noted above, this period of employment is likely to be relatively unimportant for risk estimation because of the relatively small exposures. It is impossible to estimate the accu-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

racy of the exposure estimates for before 1960. Radon concentrations in mine water varied form 300 to 1300 pCiL-1 in 1960 (Report of the Royal Commission 1969). Under such conditions, actual exposures must have been highly variable and in spite of the thorough assessment performed by Corkhill and Dory, the estimated cumulative exposures are guesstimates c.f. Colorado Plateau miners.

Swedish Iron Miners

The BEIR IV report provides an extensive description of exposure estimates for this cohort (NRC 1988). Additional description can be found in a report submitted to the BEIR IV committee, ''Comments to the U.S. Mine Safety and Health Administration for the American Mining Congress", prepared by L.W. Swent and D.B. Chambers. This report describes a visit to the mine by Swent and Chambers and their discussion with mine personnel. Much of the material is described in the 1989 report by SENES Consultants Limited (1989).

Exposure estimates for the Swedish iron miners are primarily retrospective. The cohort includes those who started work earlier but for the cohort as a whole the average year of first exposure was 1934 (see Time Line E-11). The first extensive measurements of radon in these mines were not made until 1968; radon-progeny measurements were initiated somewhat later. Most of the mine radon came from water seepage and there is limited evidence that this source was relatively constant in strength from 1915 to 1972. Comparison of radon measurements in water taken in 1915 with data from 1972 and 1975 indicated constant groundwater concentration of radon. Exposures have been estimated using the assumption that levels of radon progeny were constant until forced ventilation was introduced in 1972 (Radford and St. Clair Renard 1984). This assumption

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

was supported by consideration of the pattern of natural convection and by data on quartz dust concentrations that extended to the 1930s. On the basis of their visit, Swent and Chambers have questioned the assumption of stable ventilation and suggest that the estimates of exposure were low by a factor of two or more due to air recirculation and changing ventilation conditions as the mines became deeper (SENES 1989). Because there are no measurement data for years before 1968, it is a matter of speculation as to how much exposures varied with time. It is likely, however, that the estimated error of the exposure estimated initially made by Radford and St.Clair Renard (1984), about 30%, was unduly optimistic.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

E-ANNEX 2Workshop on Uncertainty in Estimating Exposures to Radon Progeny in Studies of Underground Miners

INTRODUCTION

The epidemiologic studies of underground miners have been the principal basis for estimating the risk of indoor radon (NCRP 1984; NRC 1988; USEPA 1992c).

To estimate exposure to radon progeny, information is needed on the concentrations to which the miners have been exposed as well as the time spent at these concentrations. There are now 12 studies that include estimates of exposure to radon progeny (Lubin and others 1995b; Darby and others 1995). The exposures received by the miners in these studies began as long ago as the end of the nineteenth century in the case of the Malmberget iron miners (Radford and St. Clair Renard 1984) and are continuing for some of the more contemporary groups, such as the Chinese tin miners (Qiao and others 1989) and the French uranium miners (Tirmarche and others 1993). The information available for estimating exposures varied among the cohorts and even within the cohorts by time period. The measurements tended to be more sparse during the initial years of mining operations, the same years during which exposures were generally highest. In some of the studies (Chinese tin miners, Czechoslovakian uranium miners, Colorado Plateau uranium miners, Ontario uranium miners, and Radium Hill uranium miners, and French uranium miners) concentrations of radon progeny were not measured in the early years of operations and it was necessary to estimate WL based on radon measurements, assuming a value for the equilibrium of radon with its progeny (Lubin and others 1994a). Information was also used on mining practices and measurements were made in the Chinese tin mines based on

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

re-created mine conditions of earlier years. Personnel records were generally used to document time underground, although the detail of the information available also varied among studies. Gaps in the information available for estimating exposures of the underground miners in these epidemiologic studies are an acknowledged source of exposure misclassification with attendant implications for uncertainty in the risk estimates derived from these studies.

The consequences for risk estimation of the errors in exposure estimates have been of concern to the BEIR VI committee. The committee recognizes that exposure misclassification is inevitable in the epidemiologic studies of miners. However, techniques are becoming available to account for these errors in estimating exposure-response relationships (Thomas and others 1994). Statistical approaches to measurement error, with the specific application to the underground miner studies, was a topic of a one-half day workshop held in 1994 by the BEIR VI committee.

To further address the issue of measurement error and its consequences of risk estimation, the BEIR VI committee convened a second workshop on January 23 and 24, 1995. The workshop was designed to bring together geologists and mining and ventilation engineers who had worked on exposure issues in the underground mines with statisticians and epidemiologists who are now contending with the measurement-error problem. The workshop's goal was to obtain additional documentation on approaches followed to assess exposures and to obtain historical insights that might lead to better quantification of the errors in the exposure estimates. The committee also invited statisticians engaged in investigation of approaches for correcting for the effect of measurement error on risk estimates.

The workshop participants selected were appropriate for these objectives. William Chenoweth, now a consulting geologist in Grand Junction, Colorado, worked for many years for the Atomic Energy Commission. He has written extensively on the history of the various uranium mining districts in the United States. James Cleveland, an engineer, worked for Kerr-McGee Corporation in New Mexico for many years, directing ventilation and safety for the Ambrosia Lake operations of Kerr McGee, by far the largest uranium producer in the Grants Mineral Belt. Andreas George, from the Environmental Measurement Laboratory of the U.S. Department of Energy, made measurements of the attached and unattached fractions of radon progeny during the late 1960s and early 1970s; these data represent the only published, historical information on the distribution of progeny between attached and unattached fractions. Douglas Chambers from SENES Consultants Limited in Ottawa, Canada, has had long-standing interest in the assessment of exposures to radon progeny and the consequences of error for risk estimation. Neal Nelson from the U.S. Environmental Protection Agency, also a participant, has followed the exposure assessment issue closely for many years.

The practical experience of these participants was complemented by the statistical expertise of Dan Stram and Duncan Thomas, both from the University

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

of Southern California. Stram and Thomas have been applying new statistical methods for errors-in-variables to data from the Colorado Plateau miners. Their models make adjustments to risk estimates for measurement error. The workshop was also attended by BEIR VI committee members and Jonathan Samet, the committee's chair, presented descriptive analyses of exposure data for the New Mexico cohort of uranium miners.

The workshop provided valuable and not-well-documented information concerning the U.S. and Canadian uranium mining industries. Consequently, the committee decided to publish portions of the workshop proceedings as an appendix to its report. We include the historical material presented and not the discussion of ongoing work on measurement error by Stram and Thomas.

Workshop Introduction

The workshop began with a welcome and introductions by Jonathan Samet and Evan Douple, the study director. Ethel Gilbert, the workshop chair, reviewed the goals of the workshop and called attention to questions to be considered throughout the workshop. Roger McClellan reminded participants to focus on "uncertainties," not just on "errors." Philip Hopke asked that participants try to recall details regarding the underground mining procedures, especially environmental conditions and the methods used for measuring radon and radon progeny. He asked participants to review those details that have not been previously published or documented. These committee members provided a reminder that the committee needs to characterize the uncertainties that affect different levels of exposure received by the miners.

William Chenoweth (Grand Junction, Colorado)

Chenoweth joined the Atomic Energy Commission (AEC) in 1953 as a geologist. His work initially involved the vanadium mines of the Colorado Plateau. Vanadium mining was initiated in the mid-1930s; he noted that the mines were not ventilated. He then reviewed the uranium mining operations across the years 1947–1981; approximately two-thirds of the mines were in the Colorado Plateau region. The peaks of uranium mining production were in the 1960's and the 1980's on the Colorado Plateau (Moab, Monticello, and Uravan areas and the Grants Mineral Belt). The peak number of mines in operation was around 750, a total reached in the mid-1950s. The AEC stopped buying ore in 1962. However, it continued to purchase concentrates (yellowcake) from the mills through 1970.

Most uranium ore was mined from sandstone. Mining involves drilling, blasting, and mucking, the extraction of the ore. The needs for mining include compressed air and water; powder, blasting caps, and fuses; and a shovel or machine to load the ore. Typically blasting was done at night and the miners would return the next morning without ventilation operative in the mine. In the

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

early mines, ventilation was used primarily to reduce blasting fumes. Chenoweth explained that the typical cut was made with a burn of multiple fuses. The miners used wheelbarrows in remote areas and the larger mines used compressed-air locomotives. There was no ventilation when the 1952 measurements were made. There were incentives for miners to be productive since the AEC needed the uranium.

Chenoweth showed the structure of a larger Grants mine with a central ventilation shaft. He also showed a map of the Uravan area near the Colorado-Utah border. Brenner asked whether some of the vanadium miners beginning in 1936 were also uranium miners later. The answer was "yes." The same mines were mined back in the 1920's for radium; there was a radium industry from 1910 through 1923. Douglas Chambers stressed that many of the miners worked their own mines on weekends and others were vanadium miners before they worked in uranium mines. Krewski asked whether there were houses in the area. The answer was "no," as the mines tended to be in very remote locations with just a few ranches nearby.

The mines were generally 400 to 800 feet below the surface, although some were as much as 2000 feet deep. Chenoweth provided definitions of various mining terms: a "stope," the site of mining, is an area at the end of a "drift," or passage; a "raise" is a passage up between drifts whereas a "winze" is a passage down between drifts. A map of one early mine showed that there was no ventilation as the rooms were interconnected and the open rooms had randomly placed pillars. The Deremo mine was the largest that Union Carbide mined in the Uravan area. Pictures taken by the U.S. Bureau of Mines in 1953–1955 do not show ventilation; one photo showed a fan that was not in use. Chenoweth surmised that it may have been used for venting blasting powder. Between 1948 and 1956, smaller mines probably had less ventilation. Ventilation rates are affected by temperature and recirculation of radon progeny could have been a problem.

There were various types of operations [U.S. Vanadium (USV) contractors, large mining companies like Walter Duncan, Climax Uranium, Kerr-McGee, Union Carbide, small mining companies, Vanadium Corporation of American (VCA) mines, VCA leasors, small independent operators, and one- or two-man operations]. Some of these mines probably had adequate ventilation, that is, about 500 cubic ft per minute, enough to keep oxygen concentration at about 20%. Early miners did not live in the mines but typically lived in boarding houses; they worked 12-hour shifts and worked 30 days and then spent four or five days in town.

Chenoweth presented a summary of the key events in the history of uranium mine ventilation. Diesel-powered trucks and loaders were introduced in the 1960s. Respirators were issued, but they were not necessarily worn. A Bureau of Mines report (IC07908) states that the Climax Uranium Co. Was the first to use rubber-tired diesel equipment in their mines in the Uranan area in the early 1950s.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Union Carbide adopted extensive air sampling in 1957; it began using diesel in 1958. A shut-down level of 10 WL was adopted in 1958. The U.S. Department of Labor proposed a 3.6 WLM exposure limit in 1969.

Samet asked whether there is any information on arsenic in these mines. Chenoweth explained that a few years ago the Bureau of Land Management asked for a sampling for trace metals in mine dumps. Arsenic was a constituent of some uranium ores. With respect to the question of how many total miners were employed, Chenoweth pointed out that 780 Native American miners were included in the Public Health Service's epidemiologic study, but the Navajo Tribe has registered approximately 2,500 former miners through its Office of Navajo Uranium Workers. There were about 75 miners in 1948 and 5,000 in 1960. Frank Lundin had advised Neal Nelson that 15,000 miners were identified in the Public Health Service surveys, beyond those included in the epidemiologic study (U.S. Bureau of Mines). The current number of miners worldwide is uncertain but underground uranium mining is no longer carried out in the U.S. Some of the current sites of active uranium mining include Canada, China, and Russia. Uranium production is down substantially since the early 1980s and there is now an oversupply of uranium. Countries producing uranium in 1995 were:

• Canada

32% (of world total)

• Australia

11%

•Niger

9%

•USA

7%

•Russia

6%

• Uzbekistan

6%

• Kazakstan

6%

• Namibia

9%

• South Africa

4%

• France

3%

• China

2%

• Gabon

2%

• Other

6%

(From the International Atomic Energy Agency)

James Cleveland (Edmond, Oklahoma)

From 1960 until 1985, Cleveland was with Kerr-McGee. He provided a historical perspective on uranium mining in New Mexico. Uranium mining in New Mexico began with small mines on the Navajo reservation, which operated from the 1948 to 1968. Most Kerr-McGee mines on the reservation were small, operated by less than 20 people and usually by only two or three. The Shiprock uranium mill operated by Kerr-McGee was closed in 1963. The Grants mineral belt, the principal site of uranium mining in the state, stretches 200 miles from the Arizona border to the city of Albuquerque; it is about 25 to 50 miles wide. The Ambrosia Lake and the Jackpill-Paguate districts were the first large-scale production mining areas in New Mexico. In 1980, Grants-area mines employed 4,500 to 5,000 people.

Cleveland described a four-day meeting in 1961 between Archer and Wagoner, from the Public Health Service, and the industry. A warning concerning the

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

health effects of radon and radon progeny was presented. Three aspects of exposure control were addressed: 1) instrumentation for making measurements, then lacking and very temperamental; 2) ventilation; and 3) record-keeping.

  1. Instrumentation for measurements initially involved off-site equipment. Evacuated flasks were opened underground and then shipped to the Massachusetts Institute of Technology or elsewhere for measurement of radon. The Kusnetz method was then developed for measuring radon progeny. The Working Level (WL) unit of concentration and the Working Level Month (WLM) unit of exposure were established by the U.S. Public Health Service. A joint survey with state health department officials and mine inspectors found high levels of radon. The findings were discussed with the industry in 1961. The Junod instrument was used universally until 1967 to measure WLs, but this instrument was very sensitive to environmental conditions. Gas- and battery-powered air samplers were used. The samples were frequently four-hours old before the measurements were made. A probe was then developed for alpha counting and used underground. One could then measure for 40 to 90 minutes using the Kuznetz method. Next, Eberline Instruments developed an instant WL meter which could provide readings after a 2.5 minute count. Several groups developed other instruments for measuring radon. Area monitors were then designed that would give warnings. Cleveland estimated accuracy of the early instruments as plus/minus about 50%.

    A discussion followed about the accuracy of the measurements. Andreas George indicated that the uncertainties associated with the measurements were in the range of 50%. Duncan Thomas asked what was reported--the highs, the lows or an average? Douglas Chambers indicated that if there is a bias it is probably small, but with a substantial uncertainty. Lubin asked a series of questions about the measurements: Where were the readings taken? The answer was "in the worker's area in a stope." Within a room the concentration tended to not vary substantially if the air was not very mobile. How much difference was there between measurements? The answer was the variation depended on where the miners were working, and was possibly up to 4 WLM. In the Public Health Service study, Archer assembled all of the measurements and then averaged them for a particular mine. That average was then multiplied by the number of months worked in the mine to obtain WLM.

  2. Ventilation was increased in 1962 in most of the mines and the mining companies started to develop and maintain records. New Mexico adopted a 10 WL cease and desist level. Up to that time, ventilation had been natural or used gas-powered fans. The large mines in Ambrosia Lake had 30-inch diameter fans. The major purpose of the fans was to remove powder smoke which contained nitrogen oxides. Simple ventilation was used before 1961. Specifications called for 500 cubic feet per man per minute and, if diesel was used, greater ventilation was called for. State officials had the authority to shut-down mines if ventilation

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

was not adequate. Eventually, large-diameter vent holes, up to 72-inch diameter, were installed to increase ventilation. The mines needed parallel ventilation to deliver fresh air to all parts of the mines. Secondary protection measures, such as filters, respiratory protection (a simple two-canister and air supply unit, or a self-supply unit, depending on levels), and electrostatic precipitators, were proscribed and the latter were used in isolated instances for short periods of time.

  1. Records of measurements taken once or twice a quarter were initiated by the companies in 1962. The records used the worker's time in travel, time in the stope, and in other locations, and assigned WLM values to each worker. In 1972, the work week was assumed to include 40 hours. When levels were particularly high, measurements were sometimes taken more than once per week. Total WL-hours for the day were then expanded to the work in a week and the exposure was developed for the month. From 1967 on, records became quite complete. Before 1962, however, records were generally of poor quality. Exposures were grossly underestimated in the early days of the industry, when the work week was longer than 40 hours. Ambrosia Lake mines worked a 48-hour week until 1966.

    Hopke asked whether there was smoking underground. Smoking was banned in Ambrosia Lake in about 1975. Standards for exposure to radon progeny were not in place until 1972 when MESA adopted a 4 WLM standard.

Andreas George (New York, New York)

George addressed sources of variation in the measurements made in mines. Sometimes measurements were not made in proximity to the miners. George provided tables showing some typical measurement values and the range of concentrations measured over three days in various locations in the mines (Note: the mines were not named). In the table (Table E Annex 2-1), the arrow indicates either downcast or upcast ventilation by its direction. The WL values relate to specific locations in the mines but not to individual miners. The measurements were made as often as every 30 minutes. The variation in WL values within a stope was generally not large. Ziemer asked whether there were WL values for samples taken at similar locations but at different times of the year. The answer was "no."

Methods were developed for measuring the unattached fraction and applied in the mining environment. George recalled that measurements were made in four different mines for one week. Polonium-218 was measured to determine the uncombined fraction, which was almost related to the unattached fraction (less than 0.2 %). The uncombined fraction tends to be inversely related to particle concentrations. In the Beaverlodge uranium mines, diesel was used infrequently and the vehicles were primarily powered by electricity. Blasting dust remained in the mine for long time intervals. Ventilation ducts were occasionally damaged during blasting.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE E ANNEX 2-1

Date

Mine

Location

Activity

T(°F)

9/26–28/67

A

1-stope

none (dry)

57

9/26–28/67

A

2-stope

track laying

50

9/26–28/67

A

3-drift

blasting — ore hauling

50

9/29–10/2/67

B

1-drift

none (wet)

52

9/29–10/2/67

B

2-stope

slushing/mucking

53

9/29–10/2/67

B

3-stope

drilling/slushing

53

10/3–4/67

C

1-stope

mucking/slushing (wet)

52

10/3–4/67

C

2-stope

blasting/slushing

52

10/3–4/67

C

3-drift

none

51

11/2/67

D

1-drift

mucking ore (dry)

57

11/2–4/67

D

2-drift

drilling/charging

55

11/3–4/67

D

3-drift

hauling ore

55

11/2–4/67

D

4-stope

drilling/mucking

58

11/6–8/67

E

1-drift

drilling/slushing (dry)

50

11/6–8/67

E

2-drift

hauling ore

50

11/6–8/67

E

3-drift

drilling/charging/slushing

50

11/10–15/67

F

1-stope

drilling/mucking (wet)

55

11

F

2-stope

drilling/mucking (wet)

60

11/10, 11/13/67

F

3-stope

drilling/mucking (wet)

59

11

F

4-stope

drilling/mucking (wet)

59

11/14, 11/15/67

F

5-drift

slushing/mucking (wet)

49

11/10, 11/13/67

F

6-stope

drilling/mucking (wet)

53

11/15/67

F

7-drift

drilling/hauling (wet)

60

1/24–26/68

G

1-drift

drilling/mucking/hauling

63

1/24–26/68

G

2-drift

drilling/mucking/hauling

53

1/24, 1/25/68

G

3-heading

mucking (dry)

67

1/26/68

G

4-heading

drilling/charging

69

2/1–2/68

H

1-drift

drilling/slushing

34

1/30–31/68

H

2-drift

slushing/mucking

39

1/30, 2/1/68

H

3-drift

drilling/slushing/hauling

45

2/1–2/68

H

4-drift

drilling/slushing

44

2/2/68

H

5-drift

none

40

1/30, 3/1/68

H

6-stope

drilling/slushing/mucking

42

2/6, 7/68

I

1-drift

near shaft/ore hauling

55

2/5/68

I

2-drift

blasting/slushing

55

2/5–7/68

I

3-heading

drilling/slushing

62

2/5–7/68

I

4-cross-cut

 

60

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

 

RH(%)

(Ft3/min)

Ventilation (pCiL-1)

Radon WL

Mines

9/26–28/67

79

5,500

ND

0.67–2.8

Beaver

9/26–28/67

93

2,200–4,400

ND

1.4–4.5

Mesa,

9/26–28/67

93

4,500–5,900

ND

1.9–4.5

Colorado

9/29–10/2/67

94

22,000–34,000

ND

0.95–1.4

Beaver

9/29–10/2/67

95

200

ND

2.1–2.4

Mesa,

9/29–10/2/67

97

1,000

ND

2.1–2.3

Colorado

10/3–4/67

96

2,000

ND

5.0–5.5

Uravan,

10/3–4/67

96

3,500

ND

3.8–4.1

Colorado

10/3–4/67

97

13,000

ND

(3.8)

 

11/2-67

47

27,000

(410)

(0.69)

Uravan,

11/2–4/67

78

900

190–380

0.66–1.13

Colorado

11/2–4/67

73

3,000

(260)

(1.1)

 

11/2–4/67

71

1,000

410–1000

0.41–0.78

 

11/6–8/67

81

500

460–1000

1.27–3.10

 

11/6–8/67

63

3,000

ND

1.15–2.0

 

11/6–8/67

82

3,000 (on/off)

180–270

0.36–0.67

 

11/10–15/67

57

1,500–3,000

(430)

0.35–2.13

Uranum,

11

84

none

(490)

(1.28)

Colorado

11/10, 11/13/67

95

none

(360)

(2.36)

 

11

92

none

(340)

(1.74)

 

11/14, 11/15/67

66

fresh air 5,000–9,000

88–110

0.22–0.27

 

11/10, 11/13/67

92

7,000–9,000

180–220

0.42–0.46

 

11/15/67

94

ND

(540)

(1.28)

 

1/24–26/68

81

14,000

380–420

0.8–1.0

Ambrosia Lake, NM

1/24–26/68

80

8,000

1350–1790

3.1–5.10

 

1/24–1/25/68

90

(convection)

1900–2300

(1.70)

 

1/26/68

92

ND

(680)

 

 

2/1-2/68

57

26,000–29,000

330–370

0.26–0.43

Ambrosia Lake, NM

1/30-31/68

66

4,000

830–1010

1.04–1.08

 

1/30, 2/1/68

71

3,000–6,000

780–1150

1.4–2.1

 

2/1-2/68

60

6,000

770–920

1.28–1.60

 

2/2/68

62

15,000 (exhaust)

(870)

(2.13)

 

1/30, 3/1/68

67

3,000

670–960

1.10–1.37

 

2/6, 7/68

84

(fresh air) 66,000–72,000

84–190

1.19–0.23

Ambrosia Lake, NM

2/5/68

84

3,000

(160)

(0.26)

 

2/5-7/68

94

3,000–5,000

640–900

2.2–2.7

 

2/5-7/68

95

1,000–2,000

1020–1440

3.0–3.8

 

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Measurements were made using diffusion batteries developed in his (George's) laboratory. A bimodal distribution of alpha activity was found in some mines, similar to more recent information from homes. The 5–6 nm size was critical because this size is relevant for the bronchial deposition. Classical, bimodal, or unimodal (diesel mines) distributions were obtained for activity-weighted sizes. Five nm is the critical size for the tracheal deposition. NCRP 1978 gives a number of about 1.7, which should be compared to 4 in the publication ''Summary of dose conversion factors from reanalysis of New Mexico uranium mine particle-size data." Most of the progeny are attached to the larger particles while the smaller particles are deposited in the lung. It is realistic to assume two-fold variation in measurements from mine to mine.

Douglas Chambers (Ottawa, Canada)

Chambers discussed the characteristics of several mines, beginning with the Newfoundland fluorspar mines. The Black Duck Mine opened in 1933 and there was not forced ventilation until the 1950s. For the Newfoundland fluorspar mines, uncertainties are quite high for data before 1967, perhaps as high as 300-fold. The miners smoked heavily and it was a very dusty environment. Chambers was not aware of other contaminants in the mines, such as arsenic. The reconstruction of exposures for these mines has been difficult and the approaches used have been as much as can reasonably be done.

The original client for uranium from the Ontario mines was the U.S. AEC. Two uranium mines were operational in Ontario in 1955; in 1958 there were 15 mines. Between 1955 and 1981, 131,000 radon-daughter measurements were made over 141 mine-years of operation, averaging 929 measurements per mine-year. Two sets of exposures were calculated, "standard" and "special" (see 1988 NRC BEIR IV Report for a description of these two sets of exposures). Exposure to aluminum powder was used in an attempt to prevent silicosis. The Canadian report on health and safety in mines is a potential source of information (Canadian Task Force on the Periodic Health Examination 1990).

A comparison was made between past and present exposure conditions. Pre-1958 conditions included radon progeny at 0.3 to 1.4 WL and mineral dust at approximately 1 to 9 mg/m3 and for 1990 conditions at 0.05 to 0.3 WL and 0.05 to 1 mg/m3, respectively. The lung-cancer experience of Ontario uranium miners with and without gold-mining history was provided. The observed to expected ratio was greater for those with gold-mining experience.

Chambers also provided information concerning the Port Radium uranium mine. In the Port Radium mine, the ventilation was frequently turned off in the winter months. Arsenic may have been 6–7% of the pitchblende ore. Exposures to radon progeny were estimated based on retrospective reconstruction. The ore grade was high and yielded high WLs (50–100 WL). The original estimates were

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

done by Frost with Eldorado Nuclear. Chambers indicated that he has all of the records for the Port Radium mine.

Chambers also discussed the Beaverlodge mines. There has recently been a reassessment of exposures for some of the miners in the epidemiologic cohort of Beaverlodge mines. He noted that at Beaverlodge, while the person running the drill would be expected to get the highest dose, this was not necessarily the case. In 1990, the Atomic Energy Control Board asked if exposures could be reconstructed from the records. The Schwartzwalter Mine in Colorado is similar to the Beaverlodge Mines.

Chambers then discussed the estimation of WLM for Beaverlodge miners. Exposure was estimated by year and type of workplace. Men tended to migrate from one mine to another in the Beaverlodge area and this was not accounted for in the exposure reconstructions. There were six or seven mine areas and nine work-type categories. The reconstructed exposures were compared to the original estimates used in the epidemiologic report of Howe and colleagues. The correlation was strong, although the original exposure estimates tended to be less than the revised exposure estimates. Means rather than medians of individual measurements were used in the new estimates. A summary of observations in the cohort was provided. Many of the miners lived in homes built on uranium-containing foundations. A positive correlation was found between WLMs and konimeter data for particle counts. The category of a miner at first work was a factor (miners needed previous work experience).

Finally, Chambers provided some remarks concerning the Colorado Plateau study. In the Colorado mines, exposures were deliberately overestimated (see Lundin and others 1971). For other hardrock mining, exposures at concentrations of 1.0, 0.5, or 0.3 WL were assigned. A crude trace of work histories of 29 people was presented from Archer, 1966. The uncertainties were related to the location of the miners and their work histories. Studies in the past have not sufficiently considered the uncertainties in the exposures. The exposures after 1969 were probably not that significant, particularly in comparison to earlier years.

Jonathan Samet (Baltimore, Maryland)

Samet began by recommending a book, Uranium Frenzy by Raye C. Ringholz (University of New Mexico Press), for a review of the early history of the uranium-mining industry. He reviewed the measurements made in the New Mexico mines. Measurements were first made in the 1950s and by 1961–1967, WL measurements were being made routinely by the State Mine Inspector, the State Health Department, and the industry. He showed examples of data sheets for the years through 1967. Person-weighted totals of the individual measurements were made. These were referred to as Total Mine Indexes; the data sheets also included measurements by the type of area. Samet showed the scatter in the

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

data and the substantial variation in the measurements made within individual visits. Jim Cleveland mentioned that inspections by the State Agencies were unannounced. Attention was not paid to ventilation if the inspection results were satisfactory. Exposures in the Colorado Plateau were grossly underestimated by small companies.

Discussion Of Exposure Estimates

Samet reminded the participants that time-dependent errors affect the exposure estimates with implications for the committee's modeling. Hopke commented that there is ample qualitative information on errors, but it is not clear what should be done quantitatively. Brenner indicated that the uncertainty appears to be more of a problem in the small mines. Can mine size be incorporated on the basis of the total number of miners? Gilbert mentioned that the committee may want to develop a questionnaire. Can we remove certain cohorts for which the uncertainty was largest? Can we rank cohorts? Can we obtain additional data? Chambers mentioned that the presence of other factors in the dust should be considered. Lubin mentioned that data on arsenic are available for the China and Ontario cohorts. The Swedish study has some information on silica and the Czech data have some additional information as well. Chambers mentioned that he had inquired about this issue (other contaminants) in the mines that he visited. Do higher levels of exposure to radon progeny entail higher exposures to other agents? Has there been consideration of parallel analyses of entire cohorts versus the group with exposure to uranium alone. Ziemer asked "How consistent are the ore forms"? There appears to be a difference from location to location. Bill Chenoweth has a report (PP-320) describing measurements made by the U.S. Geological Survey of trace metals in different mines. There are data available from Union Carbide in Grand Junction from retired ventilation engineers and state records (by engineers such as Vern Bishop, Bob Beverly, and Ben Kilgore). Umetro Minerals Corp. is now doing restoration. Lubin asked—How common was it that workers worked at their own mines on weekends and holidays? Hopke asked—What do we mean by "other hardrock"? Gold and silver mines were common, as opposed to vanadium (or copper mines). The Port Radium mine was reopened as a silver mine (Chambers). The participants were reminded that AMSA keeps records on other metals in mines (Nelson).

What fraction of mines used diesel? Jim Cleveland answered that Kerr-McGee was almost all electric until the last few years; United Nuclear was mostly diesel. The Ambrosia Lake mines were mostly diesel. Was the use of diesel always accompanied by better ventilation? Yes. Good ventilation was needed for the diesel. Diesel was used in the '60's. Typically the miners blasted at noon and at 8:00 pm. They could not leave the lunchroom until 30 minutes after blasting. There was no diesel used until 1958 on the Colorado Plateau. By 1971, diesel use was as much as 90% and reached 100% by 1980. What were other sources of

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

particles in the air of the mines? Drilling and diesel were the major causes. The drilling did not fracture sandstone sand grains and the rock was very wet (20% moisture) at Ambrosia Lake. Slushing created some dust. Colorado mines were mostly dry mines with substantial dust. Mucking, pushing ore out the haulway, dropping it down chutes, and like activities, all created dust. In the late 1970s and early 1980s, gravel was hauled in for building good roadways. Was the mineralogy about the same throughout the Colorado mines? No, the mines differed in vanadium and other metals.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Appendix F
Exposures Other Than Radon in Underground Mines

OVERVIEW

Underground miners are exposed to a number of agents, in addition to radon progeny which may adversely affect the lung. Several of these agents are known or suspect carcinogens (arsenic, diesel exhaust, and silica), and some may cause airways inflammation (blasting fumes and diesel exhaust). Silica exposure causes silicosis and several investigations have assessed modification of the effect of radon progeny by the presence of this fibrotic disorder.

These exposures of miners, in addition to radon progeny, are a source of uncertainty in extending risk estimates based on the epidemiologic studies of miners to the general population. Inflammatory changes in the epithelium might non-specifically affect the risk of lung-cancer from radon progeny and the additional exposure to other carcinogens might alter the risk of radon progeny as well. These other exposures were considered in the BEIR IV report (NRC 1988) and subsequently in the radon dose panel report (NRC 1991).

In this appendix, we update the earlier reviews for exposure to arsenic, silica, and diesel exhaust. Information on exposures of the miners to the agents is limited and only a few studies provide human information on arsenic and silica. None of the studies have direct information on exposure to diesel exhaust. The limited data available on these exposures are summarized by cohort in appendix D. Use of diesel engines in U.S. mines is described in the workshop summary that is part of appendix E annex 2. The more general topic of interactions between agents is addressed in appendix C in considering the combined effect of cigarette smoking and radon.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Arsenic

Although evidence in experimental animal studies of the carcinogenicity of arsenic is limited, there is substantial evidence that inorganic arsenic is a carcinogen in humans (Blot and Fraumeni 1994; IARC 1987). Neubauer (1947) reports that arsenic was suspect as being carcinogenic as early as 1879 as a result of high lung-cancer rates in German miners (Bates and others 1992; Furst 1983). The ingestion of arsenic in drinking water and in pharmaceuticals has been associated with a number of disease outcomes, such as liver angiosarcoma and meningioma, and cancers of the skin, bladder, kidney, and colon, as well as black-foot disease (IARC 1987). Studies have also clearly shown that inhaled arsenic (arsenic trioxide) is a human lung carcinogen (IARC 1987). The principal concern for this committee is the role of exposure to airborne arsenic in mine dusts as a primary risk factor for lung-cancer, and how its presence might affect the evaluation of the relationship between radon-progeny exposure and lung-cancer.

Occupational studies have been the main source of data on the effects of exposure to arsenic and risk of lung-cancer. These studies have included workers manufacturing and using arsenical-containing pesticides (Hill and Faning 1948; Roth 1957; Ott and others 1974; Mabuchi and others 1985), smelter workers and underground miners (for summaries, see Blot and Fraumeni 1994 and IARC 1987). Although the majority of occupational studies of arsenic exposure have been conducted in smelter workers, an increased risk of lung-cancer with arsenic exposure has been observed in several studies of miner populations (Taylor and others 1989; Kusiak and others 1993; Xuan and others 1993; Enterline and others 1987; Simonato and others 1994). However, among the studies of miners, only the investigations of Chinese tin miners (Xuan and others 1993) and Ontario uranium miners (Kusiak and others 1993) have included a quantitative evaluation of arsenic and of the joint association of arsenic and radon-progeny exposure.

Although studies have consistently shown an increasing risk of lung-cancer with greater cumulative exposure to arsenic, there have been few detailed analyses of the shape of the dose-response curve for arsenic exposure. The analysis by Enterline and others (1995) and a meta-analysis of published studies (Hertz-Picciotto and Smith 1993) suggested a curvilinear relationship with a decrease in the excess relative risk per unit exposure as exposure increases, that is, the exposure-response curve was concave from below. Analyses of the Ontario miners (Kusiak and others 1993) and Chinese miners (Lubin, communication to the committee) showed a similar concave relationship, even after adjustment for radon-progeny exposure.

The distribution of histological types of lung-cancer in arsenic-exposed populations has not been extensively studied. There have been several small investigations, with little consistency in their finding. Based on 25 cases, Newman and others (1976) reported a higher proportion of poorly differentiated epidemiod carcinoma, while Wichs and others (1981) studied 42 smelter workers and 42

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

matched controls and found an excess of adenocarcinomas. In contrast, in a larger study of 93 lung-cancer cases highly exposed to arsenic and 136 referent lung-cancer cases, Pershagen and others (1987) found no variation in the histological distribution of lung-cancer cases when data were classified by a measure of arsenic exposure. The distributions of histological type in underground miners have been reported, but are potentially confounded by smoking and radon-progeny exposure.

Mathematical models, based on the Armitage-Doll multistage theory for carcinogenesis (Armitage and Doll 1961), were applied to data on lung-cancer from two studies of copper-smelter workers in Tacoma (Mazumdar and others 1989) and in Montana (Brown and Chu 1983). Both analyses drew similar conclusions, namely, arsenic exposure acts primarily as a late-stage carcinogen, but that the possibility of an early-stage effect cannot be ruled out. However, one limitation of both analyses was the inability to directly incorporate cigarette-smoking into the modeling, a factor which is thought to act as both an early-and late-stage carcinogen.

In the miner pooled analysis by Lubin and others (1994a), adjustment for arsenic exposure reduced the ERR/WLM in the Chinese miners from 0.61% to 0.16%. Interpretation of the reductions is hampered by the high correlation coefficient, 0.48, between cumulative radon-progeny exposure and arsenic exposure among jointly exposed miners. This suggests that the best estimate of the ERR/WLM for the radon progeny exposure-lung-cancer relationship lies between 0.0061 and 0.0016. In the Ontario data, adjustment for arsenic exposure reduced the ERR/WLM from 0.0093 to 0.0084. The correlation coefficient between radon-progeny exposure and arsenic exposure was 0.02. After adjustment for arsenic exposure as a primary risk factor, the ERR/WLM did not vary significantly with level of arsenic exposure in either study (Lubin and others 1994a). This pattern is consistent with a multiplicative association between radon-progeny exposure and arsenic exposure. However, interpretation of these results is hampered by differences in definition of the arsenic-exposure measure, which was percent arsenic in rock multiplied by duration of exposure for the Ontario study and duration of arsenic exposures (mgm-3y) for the China study. The evidence appears to suggest a greater than additive (synergistic) association for the combined relative risks for cigarette use and airborne arsenic exposure (Hertz-Picciotto and others 1992). In miner populations, the joint association of the three factors, radon progeny, arsenic, and smoking, has not been evaluated.

Silica

Silica, a ubiquitous exposure in many types of underground mining, is of particular interest in that it not only causes silicosis but also has been identified as a suspect human carcinogen by the International Agency for Research on Cancer (IARC 1987). In classifying crystalline silica as carcinogenic, IARC indicated

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

that evidence of silica was sufficient in animals while limited in humans. For a detailed review of silica and lung-cancer, see Goldsmith and Samet (1994). Abelson (1991) has identified silica in mines as one of the key factors contributing to uncertainty in the use of radon-associated lung-cancers for miners to estimate population risks for radon. Silica might modify the risk of radon directly as an additional carcinogenic exposure or indirectly by causing fibrosis and airways damage.

With regard to this possible indirect mechanism, there have been several studies on respiratory disease patients that suggest a significant association between obstructive lung function and lung-cancer (Davis 1976; Skillrud and others 1986; Tockman and others 1987). Similar findings have been reported for pneumoconiotic workers by Harber and others (1986) and by Carta and others (1991). Carta and others (1994) suggest that "airways obstruction may be an independent risk factor for bronchogenic carcinoma." Accordingly, they studied the lung-cancer mortality in relation to airways obstruction among Sardinian metal miners exposed to silica and low levels of radon progeny. In one of the two mines studied, the quartz concentration in the respirable dust was between 0.2% and 2.0% while the radon exposures averaged 0.07 Jm-3 (0.13 WL) with the maximum cumulative exposure in the 0.28 to 0.42 Jhm-3 (80–120 WLM) range. In the second mine, the silica levels were much greater, ranging from 6.5% to 29%, while the radon levels were lower than in the first mine. The cohort included some 1,741 miners and a total of 25,842.5 person-years of exposure. Lung function tests, chest radiographs, and smoking histories were available for all subjects entering the cohort. A total of seventeen subjects from the first mine and seven from the second died of lung-cancer. The standardized mortality ratio (SMR) for lung-cancer was higher for the first mine. Furthermore, among miners with initial spirometric airways obstruction, those in the first mine showed the highest risk. Carta and others concluded that crystalline silica as such does not affect lung-cancer mortality. They further suggest that impaired pulmonary function may be an independent predictor of lung-cancer and may be an important risk factor because of enhancement of residence times for inhaled carcinogens.

An important investigation that considered silica dust and silicosis as risk factors for lung-cancer in underground miners was reported by Radford and St. Clair Renard (1984). They conducted a case-control study of silicosis in Swedish iron miners involving 50 lung-cancer cases in deceased miners and 100 controls matched on age, year mining began, and duration of time mining. Both the severity of silicosis and the frequency of radiographic evidence of silicosis were comparable for the cases and the controls, indicating no effect of this disease on lung-cancer risk.

Epidemiological evidence of increased lung-cancer risk in silicotic patients has been reported by Koskela and others (1990) as well as by Chiyotani and others (1990) and Merlo and others (1990). However, there have been a number of studies that present conflicting results on lung-cancer risks for workers with

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

and without silicosis exposed to dust that contained silica. These studies include: Hessel and others (1990), Meijers and others (1990), Ng and others (1990), Ahlman and others (1991), Amandus and Costello (1991), Carta and others (1991), Chen and others (1991), Chia and others (1991), Hnizdo and Sluis-Cremer (1991), Kusiak and others (1991), and McLaughlin and others (1992). Generally these studies demonstrate no clear dose-response relationship for silica exposure even though an overall association between lung-cancer and the presence of silicosis was observed in some of the studies.

Samet and coworkers (1994) conducted a case-control study in the cohort of underground uranium miners in New Mexico to assess the presence of radiographic silicosis as a risk factor for lung-cancer. This is one of the cohorts included in the pooled data set. The presence of silicosis as determined by chest radiographs taken at or near the beginning of employment was determined for 65 lung-cancer cases and 216 controls. Data on the individual exposures to silica were not available, but there are data available that demonstrate the presence of silica in mines in the region of the study. Also, silicosis is well documented in underground uranium miners in the southwestern states. The study showed that the presence of silicosis was not associated with lung-cancer risk after adjustment was made for cumulative exposure to radon. These investigators recognized that the findings were limited by the small number of subjects, but they were able to conclude nonetheless that there was a lack of association of silicosis with lung-cancer. They stated that "silica exposure should not be regarded as a major uncertainty in extrapolating radon risk estimates from miners to the general population."

Finkelstein (1995) examined the presence of radiographic silicosis as a lung-cancer risk-factor in miners from the Ontario Silicosis Surveillance Database. In contrast to the findings of Samet and others (1994), he found that silicosis was a highly significant risk factor for lung-cancer. Accordingly, he concluded that the radon lung-cancer risk decreased if an adjustment for the presence of silicosis was made. However, Archer (1996) has criticized Finkelstein's conclusion on the basis that early lung-cancer is very difficult to discern from radiographs of individuals whose lungs contain fibrotic abnormalities. Archer states that it is likely that at the time they were admitted into the study the silicotics in Finkelstein's cohort had more undetected cancers than did the controls. Archer also criticized Finkelstein's assumption that radon exposures for the nonuranium miners was zero.

Recently, Enderle and Friedrich (1995) published a review of the exposure conditions and the health consequences for the East German uranium miners in the Saxony and Thuringia regions. They point out that in the 1946 to 1955 period working conditions were extremely poor and the miners were exposed not only to radon progeny, but also to very high dust levels, and to toxic chemicals or elements including arsenic and crystalline silica. They offer no direct evidence relating silica and lung-cancer for these miners, but they do cite a study by Melhorn (1992) that reports a high rate of bronchial carcinoma occurring in

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

miners with known silicosis. They also cite the work by Tockman and Samet (1994) who describe silicosis as a risk factor for lung-cancer.

Goldsmith and coworkers (1995) have also shown that, in addition to having increased mortality from nonmalignant respiratory diseases and from tuberculosis, silicotics have a significantly elevated risk of death from cancers of the trachea, bronchus, and lung.

Diesel Engine Exhaust and Fumes

Exposure to diesel is also relevant to extrapolation of risks from miners to the population. Some uranium-mining operations used diesel engine-powered equipment resulting in the exposure of miners to diesel exhaust. As will be discussed below, the diesel soot particles are readily respirable. They are carbonaceous particles and have associated hydrocarbons some of which are mutagenic and also carcinogenic. This raises the potential for the diesel soot to be carcinogenic, and further raises the possibility that diesel exhaust may induce lung-cancer. In turn, this raises the possibility for diesel exhaust to be a confounding factor in evaluating the lung-cancer risks of exposure to radon.

In this section, the evidence is reviewed for diesel exhaust causing lung-cancer. This is followed by a discussion of the possible role of diesel exhaust as a causative factor in lung-cancers observed in uranium miners.

The diesel engine, patented by Rudolph Diesel in 1892, has found wide use in commerce, including use in mining operations and in railroad locomotives. The dieselization of railroads occurred principally after World War II, reached its midpoint in 1952, and by 1959, approximately 95% of the locomotives in the United States were diesel powered (U.S. Department of Labor 1972).

Concern for health effects of exposure to diesel exhaust has existed for some time. This concern relates to the readily inhalable size of diesel soot particles, 0.1 to 0.5 µ (Cheng and others 1984), giving concern for the development of lung-cancer. This concern is heightened by an awareness that a significant portion, typically 10 to 15%, of the diesel soot particles by weight consist of organic compounds readily extractable by organic solvents (Johnson 1988). The extracted material includes many polycyclic aromatic hydrocarbons including many that are mutagenic and some that are carcinogenic (Schuetzle and Jensen 1985; Schuetzle and Lewtas 1986). Kotin and others (1955) demonstrated that organic solvent extracts of diesel soot were carcinogenic when painted on mouse skin.

The prospect for increased use of diesel engines in light-duty vehicles in the late 1970s increased concern for the cancer risks of inhalation exposure to diesel soot. This concern stimulated the conduct of epidemiological investigations, bioassays in laboratory animals, and a wide range of mechanistic studies at all levels of biological organization from cells to populations of mammals.

The epidemiological studies have been recently reviewed by Cohen and Higgins (1995) and Nauss and others (1995) in a special report prepared by the

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
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Health Effects Institute (1995). Two figures from that report provide a summary of the currently available data on lung-cancer risks evaluated in railroad workers (Figure F-1), and truck drivers (Figure F-2). From these figures, it is clear that the relative risk of lung-cancer measured in the various studies is only elevated significantly if at all in a few studies. A major confounder in these studies, as is usually the case, is cigarette-smoking which is a dominant causative factor in lung-cancer. This is illustrated by considering Table F-1 taken from Garshick and others (1987). The slightly elevated lung-cancer risk (odds ratio = 1.41, 95% CE = 1.06, 1.88) contrasts sharply with the substantial risk measured for cigarette-smoking. Cigarette-smoking risk increased with amount of cigarette smoking and age to an odds ratio of 9.14, 59% CE = 6.11, 13.70 for cases age greater than 65 years and >50 pack-years of cigarette smoking. Crump and others (1991) reanalyzed the data used by Garshick and others (1987) as well as additional data on the same population and was unable to discern an exposure-related increase in lung-cancer risk.

In the late 1980s, results of a number of well-conducted laboratory animal bioassays of diesel exhaust became available. These results have been extensively reviewed (Mauderly 1992; Health Effects Institute 1995; McClellan 1987). The results, summarized in Figure F-3 taken from the HEI report (1995), clearly indicate that long-term high-level exposure to diesel exhaust increases an excess of lung-cancer in rats. Mice and Syrian hamsters similarly exposed have yielded negative or equivocal results. An excellent example of this contrasting result is apparent from the studies of rats (increased lung-cancer) and mice (no increase in

FIGURE F-1 Lung cancer and exposure to diesel exhaust in railroad workers. = RR adjusted for cigarette-smoking; = RR not adjusted for cigarette-smoking. For two studies (adapted from Nauss and The HEI Diesel Working Group, 1995).

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

FIGURE F-2 Lung-cancer and exposure to diesel exhaust in truck drivers. = RR adjusted for cigarette smoking; = RR not adjusted for cigarette smoking. For the study by Williams (William and others 1977), CLs were not reported and could not be calculated. For the Steenland study (Steenland and others 1992), the data were gathered from the union reports of long-haul truckers; for the 1988 Boffetta study (Boffetta and others 1988), the data were self-reported by diesel truck drivers; and for the Siemiatycki study (Siemiatycki 1991), they were self-reported by heavy-duty truck drivers (personal communication).

lung-cancer) reported by Mauderly and others (1996) to diesel exhaust from the same source.

As the significance of the diesel exhaust rat lung-cancer findings was discussed, it was noted that chronic inhalation exposure of other particulate materials (lacking in capability to directly damage DNA) also caused an increase in lung-cancer in rats (Vostal 1986). This raised questions as to the mechanisms by which diesel exhaust and these other materials might be acting. It was speculated that the effects of these materials might be related to their ability, when inhaled at high concentrations, to overload lung-clearance mechanisms and cause chronic inflammation and, ultimately, lung-cancer (Vostal 1986; Morrow 1988; McClellan 1990).

To test this hypothesis, studies were conducted in which rats were chronically exposed to carbon black particles, which were relatively devoid of mutagenic organic compounds. Two major laboratories found that carbon black had about the same effectiveness as diesel exhaust in producing lung-cancer in rats. Recently, Driscoll and others (1996) and Oberdörster (1996) have shown that exposure to high concentrations of carbon black produced persistent pulmonary inflammation, and an increase in mutations in lung epithelial cells. These results provide a plausible mechanism for the pathogenesis of the particle-induced lung-cancer in rats. This is illustrated schematically in Figure F-4.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE F-1 Regression results using diesel exhaust exposure as a single continuous variable (diesel-years) adjusted for cigarette-smoking and asbestos exposure

Exposure Category

Odds Coefficient

Ratio

95% Cl

p Values

Case age = 64

 

 

 

 

Diesel-years

0.01719

1.41a

1.06, 1.88

0.02

Asbestos, Y/N

0.18111

1.20

0.87, 9.65

0.27

= 50 pack-yearsb

1.19196

3.29

1.57, 6.93

<0.01

>50 pack-yearsb

1.73606

5.68

2.73, 11.80

<0.01

Pack-years missingb

1.37975

3.97

1.86, 8.51

<0.01

Case age = 65

 

 

 

 

Diesel-years

-0.00461

0.91a

0.71, 1.17

0.47

Asbestos, Y/N

-0.01807

0.98

0.81, 1.20

0.86

= 50 pack-yearsb

1.47641

4.38

2.90, 6.60

<0.01

>50 pack-yearsb

2.21321

9.14

6.11, 13.70

<0.01

Pack-years missingb

1.35379

3.87

2.56, 5.84

<0.01

a Calculated on the basis of 20 years of exposure.

b Reference category of zero pack-years (never-smokers).

From Garshick and others (1987).

FIGURE F-3 The relation between rat lung tumor incidence and exposure rates for diesel exhaust particulate matter. Data point code is: B = Brightwell and others 1989; H1 = Heinrich and others 1995; I1 = Ishinishi and others 1986; (exhaust from 1.8-L engine); I2 Ishinishi and others 1986 (exhaust from 11-L engine); Iw = Iwai and others 1986; M1 = Mauderly and others 1987; M2 = Mauderly and others 1994. = Includes lesions identified by the investigator as ''benign squamous tumors"; = excludes these lesions.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

FIGURE F-4 Schematic representation of the pathogenesis of lung-cancer in rats with prolonged exposure of high concentrations of diesel exhaust or carbon black particles. From Health Effects Institute (HEI 1995).

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

The recent cancer results from rats exposed to diesel exhaust raises questions as to the appropriateness of their use for defining the carcinogenic risk of diesel exhaust to humans (McClellan 1996). Thus, the human lung-cancer risk of diesel exhaust exposure should be based exclusively on the epidemiological data reviewed earlier.

With the above information as background, the potential interaction between radon and diesel exhaust can be considered. In the absence of either epidemiological studies of radon-exposed individuals that have included characterization of diesel exhaust exposure as a confounder or laboratory animal studies with controlled exposure to radon and diesel exhaust, it is only possible to speculate on the potential combined effects of radon and diesel exhaust. Some insight may be gained by considering the data in Table F-1 from the study of railroad workers exposed to diesel exhaust. The results of this study can be interpreted as identifying diesel exhaust as a potential low-potency carcinogen. The characterization of diesel exhaust as a low-potency carcinogen is made with reference to cigarette-smoking that was substantially more potent than diesel exhaust depending on the extent of smoking. It is unlikely that the uranium miners had smoking histories substantially different from the railroad workers. Compared to diesel exhaust, radon exposure may also be classed as a high-potency risk factor. It can be argued that in an exposure environment involving the two high-potency risk factors, radon and cigarette-smoking, the addition of a low-potency risk factor, diesel exhaust, would be unlikely to affect the combined risk from the two high-potency risk factors.

Muscat and Wynder (1995) conducted a case-control study to determine the effects of exposure to diesel engine exhaust and fumes. The subjects were truck drivers, mine workers, firefighters, and railroad workers, and included 235 male hospital patients with laryngeal cancer. These investigators showed that diesel engine exhaust is unrelated to laryngeal cancer risk. They offered no suggestion that lung-cancer would be directly related to diesel fume exposures.

Mycotoxins

Recently there has been speculation about the possible role of mycotoxins in the production of lung-cancers. In a letter to the editor of Lancet, Venitt and Biggs (1994) suggested that exposure of uranium miners to mycotoxins such as sterigmatocystin could account for the mutations in p53 at codon 249 that had been reported by Taylor and coworkers (1994). Taylor and others had suggested that the codon 249 mutation may be a marker for radon-induced lung-cancer, but Venitt and Biggs point out that the gross damage caused by a particles would be expected to produce gross damage to the DNA rather than a precise mutation at a specific codon. Likewise, Hei and others (1994b) suggest that although a point mutation could be induced by a particles, complete loss of the p53 gene would be more likely. Bartsch and others (1995) also assert that a radon-induced hotspot

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

mutation would be surprising since one would expect mainly random DNA strand breaks. They screened for the presence of the codon 249 mutation in lung-cancers from the Saxony, Germany uranium miners and found that none of the 50 lung tumors analyzed showed the hotspot mutation. Lo and others (1995) also raised the possibility that the results found by Taylor and colleagues could be related to mycotoxins.

Hypotheses concerning a possible role of mycotoxins are presently speculative and not supported by any observation data. Information on exposures is completely lacking.

Sram and coworkers (1993) have reported that Czech uranium miners are exposed to chemical mutagens as well as radon. They found molds in throat swabs from 27% of the miners studied as compared to only 5% in controls. Various mycotoxins were found in the swabs, including sterigmatocystin, a bisfuranoid mycotoxin that is structurally related to aflatoxins. Sterigmatocystin is reported by Gopalakrishnan and others (1992) to be a potent carcinogen and mutagen that produces squamous carcinomas and adenocarcinomas in animal lungs.

SUMMARY

Exposures other than radon progeny sustained by underground miners could plausibly modify the lung-cancer risk associated with exposure to radon progeny. The relevant data for assessing such modification in the miner cohorts are scant. Uncontrolled arsenic exposure may be a source of positive bias, as shown for example in the Chinese tin miners. The role of silica has not been directly assessed; the scant epidemiologic evidence indicates that the presence of silicosis is not a strong modification of the risk of radon. Diesel exhaust, present in some of the more recent miners, was also probably not a strong modifier of the risk of radon progeny.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Appendix G
Epidemiologic Studies in the Indoor Environment

This appendix examines the epidemiologic evidence of an association between indoor radon-progeny exposure and lung-cancer. Although data from indoor-radon studies are not yet sufficient to develop a general risk-assessment model or to estimate precisely the magnitude of risk posed by radon in houses, the data do support a small increase in lung-cancer risk due to indoor radon exposure and are consistent both with the extrapolation of lung-cancer risk using miner-based models and with relative risks among miners with cumulative exposures similar to exposures that might be experienced by long-term residents in houses that exceed the Environmental Protection Agency (EPA) action level. However, there are sufficient uncertainties in current epidemiologic studies that the residential data alone do not conclusively support a definable excess lung-cancer risk associated with radon-progeny exposure.

Ecologic studies and analytic case-control studies are the 2 types of epidemiologic studies that have considered the issue. In an ecologic study, regional rates of lung-cancer are related to a measure of regional radon concentration. The measures of radon concentration are regional mean radon concentrations obtained from direct measurement in a small number of houses and purported correlates of indoor-radon concentration, such as geologic formations and housing characteristics. In an analytic case-control study, data are obtained directly from lung-cancer cases and controls, or their surrogates, through personal interviews. Radon-progeny exposure is estimated for each person and is based on either direct data from indoor-radon measurement or surrogate measures, such as housing type.

The committee concludes that only analytic case-control studies that rely on

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

direct measurement of radon in houses are useful for evaluating the risk of lung-cancer posed by indoor-radon exposure. In contrast, because of the inability to control for confounding at the level of the individual, limitations in the use of a few radon measurements to represent exposures for an entire region, and the large risk associated with cigarette-smoking (an excess lung-cancer risk of 1,000–2,000%, with an estimated 20–30% for indoor radon-progeny exposure), the committee believes that ecologic studies of indoor-radon exposure and lung-cancer are essentially noninformative and shed little light on the association of indoor radon-progeny exposure and lung-cancer.

In this appendix, we review the sources of exposure to radon progeny in the general population and the epidemiologic studies of indoor exposure, and we consider the results of the epidemiologic studies and their design limitations.

SOURCES OF ENVIRONMENTAL RADON EXPOSURE AMONG NONMINERS

The principal source of radon-progeny exposure in buildings is emanation from soil and rock below ground. In a few special situations, well water or building materials can contribute substantially but they make relatively small contributions to the overall dose (NCRP 1984).

The most-complete survey of radon concentrations in U.S. dwellings, the National Residential Radon Study (NRRS), was performed by EPA in 125 counties in 50 states (Marcinowski and others 1994). The arithmetic mean radon concentration was 46.3 Bqm-3 (geometric standard deviation, 3.11); the EPA action level is 148 Bqm-3. Figure 1–4 from Marcinowski and others (1994) shows that single-family homes have a slightly higher radon concentration (arithmetic mean 54.0 Bqm-3; geometric standard deviation, 2.97) than all dwellings, whereas multi-family units (defined as attached single-family dwellings, townhouses, apartments, duplexes, and condominiums) have a markedly lower mean radon concentration (arithmetic mean, 24.1 Bqm-3; geometric standard deviation, 3.23). In the survey, 6.1% of houses exceeded the EPA action level; this confirms earlier estimates, which were based on smaller studies compiled by Nero and others (1986), but it is much lower than estimates from commercial test vendors of 19% (Cohen and others 1984; Cohen and Gromicko 1988) and 23% (Alter and Oswald 1987). Presumably, the latter higher estimates result from a selection bias of homeowners who suspect they have a radon problem and not from biased measurement. Also in agreement with the earlier findings of Nero and others (1986), the NRRS found that the distribution of radon concentrations in residences could be satisfactorily represented by a lognormal distribution.

The NRRS also confirmed earlier studies that indicated that basements have higher average radon concentrations than higher floors. Their data showed that average radon concentrations in first-floor rooms were about 40% of those in basements, average second-floor room concentrations were about 90% of those

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

of first floors, and average third-floor or higher room concentrations were about 84% of those of second floors.

There is no evidence that average radon concentrations in U.S. dwellings are significantly different from those in other nontropical countries. The most-comprehensive international survey was compiled in the 1988 UN Scientific Committee on Effects of Atomic Radiation (UNSCEAR) report (UNSCEAR 1988), which analyzed worldwide radon surveys. The population-weighted arithmetic mean in temperate and high-latitude countries was estimated to be about 50 Bqm-3, which was combined with a "guesstimate" of about 20 Bqm-3 in tropical countries to yield a worldwide population-weighted arithmetic mean of about 40 Bqm-3.

Within a given dwelling or building, the radon concentration is determined essentially by the ratio (Scott 1992) of the average radon concentration in soil gas near foundation openings (Csoil) to the airflow resistance of soil around the house foundation (Isoil). That ratio is often called the soil-radon potential (SRP), and much effort has been devoted to its characterization. Csoil depends on depth, soil radium concentration, and water content (Rogers and Nielson 1991), and it is not well correlated with radium or uranium concentrations in the underlying bedrock (the poor correlation makes SRP predictions based on gross geologic considerations rather inaccurate). Isoil depends essentially on the basement dimensions and the soil permeability to air, which varies widely from 10 to 18 m2 for well-graded gravel, from 10 to 11 m2 for sand and gravel, and from 10 to 15 m2 for clay (Tanner 1990).

The various methods that have been used for estimating SRP have been reviewed by Yokel (1989). However, as the number of screening measurements of radon concentrations in homes has increased dramatically in the last decade, the need for predictive methods has correspondingly decreased, and radon-prone areas can be identified simply by analyzing the home measurements (Scott 1992, 1993). For example, the International Commission on Radiological Protection (ICRP 1993) has proposed that areas in which more than 1% of buildings have radon concentrations that are more than 10 times the national average might be designated as radon-prone.

In contrast with earlier expectations (for example, Rundo and others 1979; Cohen and Gromicko 1988), it now appears that house design and weatherproofing (both determinants of the rate of exchange of indoor with outdoor air) are not strong determinants of domestic radon concentration. For example, in a study of 2,000 British homes, Gunby and others (1993) found that house design, building-material type, and amount of weatherproofing together accounted for less than 5% of the observed variation in radon concentration; the implication is that, on the average, SRP is the dominant determinant.

The occupancy factor of schools and workplaces is about 2/7 that of homes (ICRP 1993). Thus, radon in schools and workplaces is likely to be an important contributor to the overall dose. ICRP (1993) has suggested that action levels in these buildings should be the reciprocal of that fraction, or 7/2, as high as in

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

dwellings (and should be weighted by the relevant dose-conversion coefficients, if applicable), but this suggestion has not been implemented.

Relatively few studies of radon concentrations in the workplace have been undertaken (Cohen and others 1984; Saccomanno and others 1986; Turk and others 1986; Westin and others 1991). In general, concentrations have been lower than those in local dwellings, presumably because of the larger number of floors and the greater ventilation rates in workplaces (Nero and others 1988).

Radon concentrations in schools are of particular interest because of the possible variation in radon susceptibility of children, compared with adults (Probart 1989). During 1990 and 1991, EPA undertook a randomized national survey of radon concentrations in U.S. public schools (the National Schools Radon Survey, or NSRS, EPA 1993). Of a random sample consisting of 927 public schools, about 19% had at least 1 classroom with a radon concentration above 148 Bqm-3, and 2.7% of all schoolrooms had concentrations above 148 Bqm-3. The NSRS, however, is not useful for estimating the contribution of schools to total radon-progeny exposure of children, teachers, and others from time in schools, in that measurements were conducted continuously, including on weekends and vacations, and thus failed to account for the intermittent occupancy of schools by students, teachers, and others. Typically, heating, ventilating, and air-conditioning systems would not be in use when children and teachers were away from school, but the increased concentrations during those times would not contribute to personal exposure.

ECOLOGIC STUDIES

In ecologic studies, data are considered at the group level, rather than the individual level, as in other epidemiologic studies (Morgenstern 1995). Ecologic studies typically use existing information, such as vital-statistics data, and are therefore relatively easy to perform. Ecologic studies have been useful for generating hypothesis about environmental exposures and disease but have been used less to characterize risks. Because recognized limitations in data and approximations of the form of the regression model, ecologic analyses are not generally useful for confirmatory purposes, such as risk estimation and hypothesis-testing. Piantadosi and others (1988) present several examples from a national health and nutrition survey that showed that ecologic regression coefficients based on aggregated data are larger and smaller than regression coefficients based on individual data and have opposite signs. In the case of radon risk, limitations of ecologic studies are particularly serious because of the presence of smoking, which constitutes an overarching risk factor for lung-cancer; as noted above, cigarette-smoking causes a 1,000–2,000% excess risk of lung-cancer.

Soon after the potential hazard of indoor radon was first identified, a number of ecologic studies were performed and reported. The findings of these studies were mixed in their support of the hypothesized lung-cancer risk associated with

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

indoor radon (Stidley and Samet 1993). One particularly large on-going study of lung-cancer mortality by county in the United States, reported in several papers by Cohen (1990, 1995) and Cohen and Colditz (1990), even shows an unanticipated inverse association between lung-cancer mortality by county and estimated average radon exposure of residents of the counties. Stidley and Samet (1993) reviewed the ecologic approach to indoor radon and lung-cancer and considered 15 studies published as of 1992. This chapter extends their review and considers the general utility of information from ecologic studies.

The Ecologic Study Design

In ecologic studies, the relation between exposure (radon) and disease (lung-cancer) is assessed by examining the association between a measure of disease occurrence (generally the age-adjusted lung-cancer mortality) in a group of people, usually those residing in a defined geographic unit, and the extent of exposure estimated for the group. Ecologic studies have proved feasible for developing hypotheses for further testing in studies at the individual level. For example, an ecologic association between breast-cancer mortality in a number of western countries and estimates of average fat consumption led to the hypothesis that higher intakes of fat increase breast-cancer risk (Armstrong and Doll 1975). Ecologic studies may also be useful if there is general homogeneity of exposure in a population. Typically, the ecologic design has not been used to assess risks associated with exposures at the individual level.

Morgenstern (1995) has classified ecologic studies by method of exposure measurement and method of grouping. Studies are termed exploratory if the primary exposure of interest is not measured and the data are analyzed to identify patterns that could lead to more-specific hypotheses. Analytic studies incorporate the exposure of interest; studies of radon have been of this type. With regard to the method of grouping, the groups in a study may come from multiple locations (multiple-group design), from multiple periods (time-trend design), or from multiple locations and periods (mixed design). The multiple-group design has been the principal ecologic approach to the study of indoor radon and lung-cancer; in the application of this approach to indoor radon, lung-cancer mortality is compared across geographic groups assumed to have a range of associated exposures to indoor radon. Stidley and Samet (1993) further classified the studies of indoor radon and lung-cancer according to the primary analytic approach—comparison of disease rates in different groups classified by radon exposure or regression of disease rates on a continuous estimate of radon exposure for the group.

Ecologic Studies of Radon and Lung-Cancer

In their 1993 publication, Stidley and Samet (1993) summarized 15 ecologic studies on lung-cancer and residential radon exposure. Through 1995, 4 addi-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

tional studies were reported, including a study of lung-cancer mortality in U.S. counties by Cohen (1995). Details of those studies are provided in Tables G-1 through G-4: their approach to estimation of radon exposure in Table G-1, their outcome variables and controlled covariates in Table G-2, their handling of smoking in Table G-3, and their findings in Table G-4. Following the approach of Stidley and Samet (1993), we have broadly grouped the studies as "comparison" or "regression" studies on the basis of the primary analytic approach for assessing the effect of the radon exposure measure. In the comparison studies, disease rates and mortality are compared in 2 or more groups; in the regression studies, the outcome measure is modeled as a function of exposure.

Diverse approaches have been used to estimate the exposures of the groups (Table G-1). In the comparison studies, exposure rankings have been assigned to the groups on the basis of geology, measurements, or other factors. In most of the regression studies, data on indoor radon concentrations from population-based surveys or from less formally developed samples were used to assign quantitative exposures to geographic units. Background gamma radiation and radon concentration in well water were also used as surrogates.

The outcome measure in the studies was either the age-adjusted incidence or mortality from lung-cancer (Table G-2). The extent to which other factors were considered in the analyses was variable. Analyses were done separately by sex, with adjustment for sex, or with restriction to one sex. Socioeconomic factors and urbanization were incorporated in some studies.

A number of the studies included measures of smoking by the members of the analytic groups (Table G-3); these measures were based on cigarette-sales information and smoking surveys.

The finding of the studies vary widely, from positive and statistically significant associations between radon-exposure measures and lung-cancer rates to negative and statistically significant associations (Table G-4). A number of studies showed no evidence of association. The studies reported by Cohen have been particularly prominent because of the large number of U.S. counties included in the analyses and the strong negative association between estimated county-average radon exposure and lung-cancer mortality. We have cited two, representative reports based on Cohen's analyses, including the most recent report (1995).

In the most-recent report by Cohen (1995), data from 1,601 counties, representing most of the U.S. population, were used. Radon exposures were assigned to the counties by combining data from 3 sources: measurements made by the University of Pittsburgh, measurements made by EPA, and measurements compiled by individual states. Potential confounding by smoking was addressed by extending 1985 data on statewide prevalence to the county level with adjustment for the degree of urbanization of the county. The potential for confounding by sociodemographic factors or their correlates was explored by stratification on levels of 54 variables. Confounding by geography was assessed by stratification,

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-1 Characteristics of radon-exposure measures in 19 ecologic studies of lung-cancer and indoor radon

Study

Exposure Measure

Comparison studies

Archer (1987)

Proportion of county covered by Reading Prong granites

Bean and others (1982a,b)

Radium concentration in municipal well-water supply

Dousset and Jammet (1985)

Two regions differing by a factor of 3–4 in indoor radon concentrations

Fleischer (1981)

Proximity of phosphate mines, deposits, or processing plants

Fleischer (1986)

Proportion of county within Reading Prong

Forastiere and others (1985)

Characteristics of soil

Hofmann and others (1985)

Adjacent areas varying by radon and thoron concentrations

Vonstille and Sacarello (1990)

Indoor radon

Ennemoser and others (1994)

Indoor radon

Neuberger and others (1994)

Indoor radon

Regression studies

Cohen (1993)

Indoor radon concentration

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Group measure

Exposure grouping and number of groups

Comparison studies

Archer (1987)

Location

Reading Prong (7 counties)

Border (9 counties)

Control (17 counties)

Bean and others (1982a,b)

Averages based on average of 9 measurements per town taken between 1958 and 1979

0–74 Bqm-3 (2–5 pCiL-1) (10 towns)

74–185 Bqm-3 (2–5 pCiL-1) (9 towns)

>>185 Bqm-3 (2–5 pCiL-1) (9 towns)

Dousset and Jammet (1985)

Location and radon

Limousin (high)

Poitou-Charentes (control)

Fleischer (1981)

Location

Counties with phosphate mines (25), deposits, or processing plants (total of 316 counties)

Fleischer (1986)

Location

Mostly within (3 counties)

Less than half within (10 counties)

Adjacent counties (138 counties adjacent to counties with mines)

Forastiere and others (1985)

Lithology

Volcanic (27 municipalities)

Nonvolcanic (4 municipalities)

(Total population for both groups <200,000)

Hofmann and others (1990)

Location, radon, and thoron

High background (0.38 WLM/yr) (764,696 person-yr)

Control (0.16 WLM/yr) (777,482 person/yr)

Vonstille and Sacarello (1990)

Averages for U.S. Geological Survey quadrangles based on statewide survey of 6,500 homes commissioned in 1985

High (99 Zip-code areas)

Low (1,983 Zip-code areas)

None (918 Zip-code areas) commissioned in 1985

Ennemoser and others (1994)

Location

Austria Alp area (mean, 4,121 Bqm-3 in 178 homes), remainder of Tyrol

Neuberger and others (1994)

Location

«8pCiL-1, 8–10 pCiL-1, >>10 pCiL-1

Regression studies

Cohen (1993)

Geometric means based on several surveys (some nonrandom) of homes: 39,000 measurements in living areas and 29,000 measurements in basements

411 countries

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Exposure Measure

Edling and others (1982)

Background gamma radiation

Haynes(1988)

Indoor radon concentration

Hess and others (1983)

Radon concentration in well water

Letourneau and others (1983)

Indoor radon concentration

Ruosteenoja (1991)

Average annual indoor radon concentration

Stranden (1987)

Indoor radon concentration

Magnus and others (1994)

Indoor radon concentration

Cohen (1995)

Indoor radon concentration

 

Source: Samet and Stidley 1993.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Group measure

Exposure grouping and number of groups

Edling and others (1982)

Averages based on county random sample of 1,500 homes; published in 1987

24 counties

Haynes (1988)

Averages based on county survey of 2,309 homes; published in 1987

55 counties

Hess and others (1983)

Averages weighted by proportion of rock type; survey of 2,000 wells

16 counties

Letourneau and others (1983)

Geometric means from survey of 14,000 homes conducted in summers of 1978–1980

18 cities (total population about 11,000,000)

Ruosteenoja (1991)

Geometric means based on nonrandom survey of average of 120 homes per municipality conducted by end of 1985

18 municipalities (total population of 59,000 males in 1980)

Stranden (1987)

Averages based on nonrandom sample of 20 houses in each municipality during heating season, 2 locations per house

75 municipalities

Magnus and others (1994)

Average based on national sample of 7,500 homes

427 municipalities

Cohen (1995)

Average based on 3 data sets

1,601 counties

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-2 Outcome and controlled variables in 19 ecologic studies of lung-cancer and indoor radon

Study

Outcome variable

Controlled variable

Comments on controlled variables

Comparison studies

Archer (1987)

Lung-cancer mortality, 1950–1979

Age

Rates standardized to 1970 U.S. census population.

 

 

Sex

Both sexs combined; analyses by sex gave similar results.

 

 

Ethnicity

Analysis restricted to Caucasians.

 

 

Socioeconomic

Groups ''similar."

 

 

Urbanization

Counties with large cities omitted; groups "similar."

 

 

Population growth

No adjustment, but rates differed for groups.

Bean and others (1982a,b)

Lung-cancer incidence, 1969–1978 (1972 excluded)

Age

Rates standardized to 1970 Iowa age distribution.

 

 

Sex

Analyses done by sex.

 

 

Smoking

Not included in model, but groups checked for similarity.

 

 

Socioeconomic

Included in regression model.

 

 

Urbanization

Included towns had 1970 population of 1,000–10,000; towns categorized by size.

 

 

Water characteristics

Used as exclusion criteria or included in regression model.

Dousset and Jammet (1985)

Lung-cancer mortality, 1968–1975

Age

Rates standardized to 1968 population.

 

 

Sex

Analyses done by sex.

 

 

Smoking

Similar average tobacco consumption.

Fleischer (1981)

Lung-cancer incidence, 1950–1969

Age

Rates standardized to the 1960 U.S. population.

 

 

Sex

Analyses done by sex.

 

 

Ethnicity

Main analysis restricted to Caucasians.

 

 

Urbanization

Analysis included stratification by population size.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Outcome variable

Controlled variable

Comments on controlled variables

Fleischer (1986)

Lung-cancer incidence, 1950–1969

Age

Rates standardized to the 1960 U.S. population.

 

 

Sex

Analyses done by sex.

 

 

Ethnicity

Analysis restricted to Caucasians.

Forastiere and others (1985)

Lung-cancer mortality, 1969–1978

Age

Analyses done by age groups or used age-adjusted rates; only those 35–74 yr old included.

 

 

Sex

Analyses done by sex or used sex-adjusted rates.

 

 

Smoking

Stratified by per capita yearly cigarette sales.

 

 

Urbanization

Largest town excluded; remaining municipalities stratified by population size.

Hofmann and others (1985)

Lung-cancer mortality, 1970–1983

Age

Age-adjusted rates.

 

 

Sex

Sex-adjusted rates.

 

 

Smoking

Neighboring groups; assumed similar; women did not smoke.

 

 

Socioeconomic

Neighboring groups; assumed similar.

 

 

Urbanization

Both groups rural.

 

 

Mobility

Stable populations.

Vonstille and Sacarello (1990)

Percentage of serious illnesses that were malignant neoplasms

Age

Age-adjusted to 1985 Florida population.

 

 

Sex

Analyses done by sex.

 

 

Socioeconomic and mobility

Limited one analyses to the lower class in an attempt to reduce effect of mobility.

Ennemoser and others (1994)

Lung-cancer mortality, 1970–1991

Age

Age-adjusted rates.

 

 

Sex

Sex-adjusted rates

Neuberger and others (1994)

Lung-cancer incidence, 1973–1990

Age

Age-adjusted rates.

 

 

Sex

Women only

Regression studies

Cohen (1993)

Lung-cancer mortality, 1950–1969

Age

Age-adjusted rates.

 

 

Sex

Analyses done by sex.

 

 

Ethnicity

Analysis restricted to Caucasians.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Outcome variable

Controlled variable

Comments on controlled variables

 

 

Smoking

Included in regression model.

 

 

Socioeconomic

Several variables included in regression models.

 

 

Urbanization

Several variables included in regression models.

 

 

Mobility

In some analyses, radon exposures were adjusted to account for mobility; Blacks omitted to reduce effect of mobility.

Edling and others (1982)

Lung-cancer mortality, 1969–1978

Age

Rates standardized to 1974 Swedish population>>40 yr; restricted to people>>40 yr.

 

 

Sex

Analyses done by sex.

Haynes (1988)

Standardized mortality ratios for lung-cancer mortality, 1980–1983

Age

Age adjustment attempted through standardized rate ratios.

 

 

Sex

Analyses done by sex.

 

 

Smoking

Included in regression model.

 

 

Socioeconomic

Included in regression model.

 

 

Urbanization

Population density included in regression model.

 

 

Diet

Vitamin A consumption included in regression model.

Hess and others (1983)

Lung-cancer mortality, 1950–1969

Age

Age-adjusted rates from National Cancer Institute.

 

 

Sex

Analyses done by sex.

 

 

Smoking

Concluded that smoking did not account for observed differences.

 

 

Urbanization

Concluded that population density did not account for observed differences.

 

 

Mobility and growth

Acknowledged that mobility would diminish an effect, but observed that state population has been stable in 1900s.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Outcome variable

Controlled variable

Comments on controlled variables

Letourneau and others (1983)

Lung-cancer mortality, 1966–1979

Age

Rates age-adjusted to 1971 Canadian population; restricted to those 45–79 yr old.

 

 

Sex

Analyses done by sex.

 

 

Smoking

Included in regression model.

 

 

Socioeconomic

Correlated with rates.

 

 

Mobility

Study restricted to people>>45 yr old to restrict effect of mobility, but mobility still high.

Ruosteenoja (1991)

Lung-cancer incidence, 1973–1982

Age

Rates age-adjusted to world standard population.

 

 

Sex

Study restricted to males.

 

 

Smoking

Included in regression model.

 

 

Urbanization

All groups rural.

 

 

Mobility

Stable population.

Stranden (1987)

Lung-cancer incidence, 1966–1985

Age

Age-adjusted rates.

 

 

Sex

Analyses done by sex.

 

 

Smoking

Included in regression model.

 

 

Urbanization

Oslo, Norway excluded.

 

 

House characteristics

Examined, but not controlled.

Magnus and others (1994)

Lung-cancer incidence, 1979–1988

Age

Age-adjusted rates.

 

 

Sex

Analyses done by sex.

 

 

Smoking

Included in regression model.

 

 

Asbestos

Included in regression model.

Cohen (1995)

Lung-cancer mortality, 1970–1979

Age

Age-adjusted rates.

 

 

Sex

Sex-specific analyses.

 

 

Smoking

Included in regression model.

 

 

Socioeconomic

Included in regression model.

 

Source: Samet and Stidley 1993.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-3 Adjustments for cigarette-smoking in 19 ecologic studies of lung-cancer and indoor radon

Study

Adjustment for cigarette-smoking

Comparison studies

Archer (1987)

No adjustment, but concluded that average smoking behavior should not differ significantly among groups.

Bean and others (1982a,b)

By examining lung-cancer rates in neighboring towns, they concluded that neighboring towns were similar to each other with respect to smoking behavior; from analysis of controls in National Collaborative Case-Control Study, they concluded that smoking rates were lower in counties with study town with high radium concentration in water than in counties with "low"-radium town.

Dousset and Jammet (1985)

No adjustment, because groups did not differ in average tobacco consumption.

Fleischer (1981)

No adjustment, but noted that average smoking rates differ only slightly among states.

Fleischer (1986)

No adjustment.

Forastiere and others (11985)

Stratified by per capita yearly cigarette sales from 1971 survey (thus, used current smoking behavior).

Hofmann and others (16)

No adjustment, because groups were assumed to be similar and women generally did not smoke.

Vonstille and Sacarello (1990)

No adjustment.

Ennemoser and others (1994)

No adjustment.

Neuberger and others (1994)

Smoking as of 1960 estimated from data from case-control study

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Adjustment for cigarette-smoking

Regression studies

Cohen (1993)

Average state cigarette sales and information from state tax collections were included in regression model restricted to state averages.

Edling and others (1982)

No adjustment.

Haynes (1988)

Regression model included average weekly household expenditure on cigarettes for 1961–1963; information obtained from 1962 Ministry of Labor report, from about 20 yr before lung-cancer deaths.

Hess and others (1983)

No variable included in regression model, but concluded that smoking did not account observed differences in lung-cancer mortality rates.

Letourneau and others (1983)

Regression model included percentage of people>>45 yr old who were current smokers or ex-smokers; information obtained from Canadian Labour Force Surveys in 1977, 1979, and 1981, so current smoking behavior was considered.

Ruosteenoja (1991)

Regression model included percentage of smokers; information obtained from recent smoking survey of men 19–70-yr old in each municipality.

Stranden (1987)

Regression model included average number of cigarettes smoked/d; information obtained from a 1964–1965 study, 1–21 yr before considered lung-cancer cases.

Magnus and others (1994)

Smoking data from 1964–1965 mailed survey.

Cohen (1995)

1985 smoking survey by state, adjusted for time trend.

 

Source: Samet and Stidley 1993.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-4 Findings of 19 ecologic studies of lung-cancer and indoor radon

Study

Location of study

Findings

Comparison studies

Archer (1987)

Reading Prong and

Increase in lung-cancer mortality for counties containing Reading Prong (p < 0.01), with increase from annual rate of 23.9 per 100,000 (95% CIa, 23.4–24.4) for control to 31.3 per 100,000 (95% CI, 30.5–32.1) for Reading Prong counties (rate ratio of 1.3b)

Bean and others (1982a,b)

Towns in Iowa

Lung-cancer incidence for males increased with increasing average radium concentration in water (p<.002); relative risk of 1.68 for males with exposure >185 Bqm-3 (5 pCiL-1) to those with exposure «74 Bqm-3 (2 pCiL-1). Relative risk of 1.45 for females not statistically significant.

Dousset and Jammet (1985)

Two regions in France

No difference in lung-cancer mortality between 2 exposure groups (rate ratios, 0.97 for males and 1.00 for females).b

Fleischer (1981)

U.S. counties

More counties than expected with high lung-cancer rates in group with phosphate deposits or processing plants under assumption of no association between phosphate and lung-cancer rates (p < 0.0001).

Fleischer (1986)

Reading Prong counties

More counties than expected with high lung-cancer rates in group mostly within Reading Prong under hypothesis of no geographic association with lung-cancer rates (p = 0.017 for males and p = 0.038 for females).

Forastiere and others (1985)

Towns in central Italy

Nonsignificant increase in lung-cancer mortality in volcanic area over nonvolcanic area; standardized rate ratio of 1.22 for males (p = 0.22) with 95% CI, 0.89–1.68 and standardized rate ratio of 1.24 for females (p = 0.37) with 95% CI, 1.77–1.98.b

Hofmann and others (1985)

Two adjacent areas in China

No association between lung-cancer mortality and radon exposure; 2.7 deaths per 100,000 in high-exposure group and 2.9 per 100,000 in control (rate ratio, 0.93).b

Vonstille and Sacarello (1990)

Florida

No difference in percentage of total serious illnesses that were malignant neoplasms among 3 exposure groups, with 3.6%, 5.4%, and 3.9% for males in no-exposure, low-exposure, and high-exposure groups, respectively; percentage for females were lower and with no difference.

Ennemoser and others (1994)

Tyrol, Austria

SMR for lung-cancer increased for high-radon region vs. Tyrol total; SMR = 6.2; 95% confidence interval, 4.4–8.4.

Neuberger and others (1994)

Counties in Iowa

Effect of radon with smoking, radon, and histologic type.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Location of study

Findings

Regression studies

Cohen (1993)

US counties

Negative association between lung-cancer mortality and average indoor radon concentration were as follows: -0.45 (37 Bqm-3)-1 (1 pCiL-1) per 00,000 (95% CI, -0.57 to -0.33) for females; -3.38 (95% CI, -4.03 to -2.73) for males.b

Edling and others (1982)

Counties in Sweden

Positive association between lung-cancer mortality and average background gamma-radiation exposure; correlation, 0.46 (p = 0.12) for males and 0.55 (p = 0.03) for females.

Haynes (1988)

Counties in Great Britain

Negative association between lung-cancer mortality and average indoor radon concentration; partial correlation, -0.20 (p < 0.01) for males and -0. 16 (p < 0.01) for females after adjustment for population density, social class, smoking, and diet.

Hess and others (1983)

Counties in Maine

Positive association between lung-cancer mortality and average radon concentration in water; correlation 0.65 (p < 0.01) for females and 0.46 (p < 0.10) for males.

Letourneau and others (1983)

Cities in Canada

No significant association between lung-cancer mortality and average indoor radon exposure; correlation -0.34 for males and 0.13 for females; after adjustment for smoking, estimates of ß1E in Model IIa were -2.7 (95% CI, -12. to -7.5) and 0.9 (95% CI, -1.4 to -3.2) for males and females, respectively.

Ruosteenoja (1991)

Municipalities in Finland

No significant association between lung-cancer incidence and average indoor radon concentration; adjusted for smoking, relative risk, 1.08 for 100 Bqm-3 (95% CI, 0.92–1.27); weighted correlation, 0.36 (p = 0.14).

Stranden (1987)

Cities in Norway

Positive association between lung-cancer incidence and average radon exposure; 95% CI for lifetime relative risk, 0.001–0.003 (Bqm-3)-1 radon.

Magnus and others (1994)

Municipalities in Norway

No overall association with radon; significant increase for small-cell carcinoma in women.

Cohen (1995)

U.S. counties

Negative association between lung-cancer mortality and average indoor radon concentration; smoking-adjusted coefficients, -7.3 per pCiL-1 per 100,000 for men and -8.3 per pCiL-1 per 100,000 for women.

a CI = confidence interval/

b Some numeric results were calculated from information provided in the articles.

Source: Samet and Stidley 1993.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

and the sensitivity of the findings to outliers was examined. There was a strong negative association between 1970–1979 lung-cancer mortality and the county-average radon concentrations; the association could not be explained by confounding. In interpreting this finding, Cohen proposes that the negative association implies failure of the linear, nonthreshold theory for carcinogenesis from inhaled radon decay products.

Limitations of the Ecologic Design for Investigating Indoor Radon and Lung Cancer

Methodologic limitations of the ecologic design have received extensive treatment in recent publications in the epidemiologic literature (Greenland and Morgenstern 1989; Brenner and others 1992; Greenland and Robins 1994a; Morgenstern 1995). Morganstern's (1995) review provides a framework for considering the limitations of ecologic studies of indoor radon and lung-cancer. He notes that the goal of an epidemiologic study might be to draw biologic inferences about individual risks or ecologic inferences about group rates. In the ecologic studies of radon and lung-cancer, the goal is to make inferences about the radon-associated lung-cancer risk of individuals, so there is a potential for cross-level bias as observations made at the group level (such as, the county level) are extended to individuals (for example, the county residents). The extension of quantitative risk estimates from ecologic studies to the individual level is also problematic. Estimated risks depend strongly on the choice of model form (Morgenstern 1995). Control of confounding might be accomplished by regression modeling (which includes stratification) or standardization, as typically done for age. However, in the context of ecologic studies, regression modeling for control of confounding might be unsuccessful unless a series of conditions are met with regard to associations among predictors and disease rates (Greenland and others 1989; Morgenstern 1995). Standardization for control of confounding might be unsuccessful unless all predictors are mutually standardized for the same confounders—a condition that requires data misspecification (Brenner and others 1992; Morgenstern 1995). Effect modification, that is, interaction effects—further complicates interpretation of ecologic estimates of risk.

Ecologic bias has long been known to be a principal limitation of the ecologic study design. This bias refers to the difference between associations at the group and individual levels (Morgenstern 1995). Ecologic bias has been given quantitative definition (Greenland and others 1989). Greenland and Morgenstern (1989) have described sources of ecologic bias in using linear regression to estimate the exposure effect; these sources include biases acting within a group, confounding by group, and effect modification by group. Other forms of bias can affect ecologic studies, including inadequate control of confounding, model

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

misspecification, and misclassification. Morgenstern (1995) also lists a lack of adequate data, temporal ambiguity of the exposure-disease relationship, collinearity of predictor variables within groups, and migration across groups.

In their 1993 review, Stidley and Samet (1993) specifically addressed limitations of ecologic studies of indoor radon and lung-cancer, covering measurement error and model misspecification. Each of the 15 studies was reviewed for 14 potential limitations in those 3 broad categories. All studies were found to have multiple limitations.

Stidley and Samet noted 5 sources of measurement error: use of current exposure to represent the biologically relevant period of past exposure, the inherent error of the measurement devices, use of an indirect measure of indoor concentrations as an index of indoor radon exposure, use of sample rather than total-population information, and estimation of individual exposure by a group indicator, the ecologic fallacy.

Within a region, radon concentrations for houses are extremely variable (Piantadosi and others 1988) and estimates of regional mean concentrations are usually derived from relatively few measurements. Radon concentrations are derived from measurements in houses, which are occupied an average of 60–70% of the time; the remaining 30–40% of people's time spent in other houses, in workplaces, outside, and so on. Time spent in unmeasured areas increases exposure uncertainty. And current measurements might not accurately reflect radon exposures of individuals over the last 30 yr or more. The effects of exposure errors can bias results in many ways; trends can increase or decrease or even reverse direction.

With regard to the fourth source of measurement error (use of sample data), Stidley and Samet showed that there are substantial probabilities of misclassifying counties or other geographic units as to exposure if only a few measurements are available. In an expanded analysis, Stidley and Samet (1994) assessed the impact of measurement error on the estimated effect of radon and on the standard error of the regression coefficient describing the ecologic relationship between radon and lung-cancer risk. They found that the effect of radon and the standard error of the effect estimate were underestimated because of measurement error; the degree of bias was greater for smaller samples. The underestimation of the standard error would tend to overstate significance levels for tests on regression coefficients.

Model misspecification refers to a biologically incorrect formulation of the relationship between radon exposure and lung-cancer risk. Possible errors in model specification include omission of confounders (such as, age and smoking) or effect modifiers (such as smoking), the use of inappropriate functional forms (such as linear rather than loglinear increase in risk posed by an exposure if the latter were correct), and the use of an incorrect form of the model (such as an additive model for the joint association of radon exposure and smoking rather than a supra-additive model). Effect modification at the individual level is an intractable problem at the ecologic level (Stidley and Samet 1993, 1994).

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Miner data clearly indicate that the relationship of lung-cancer occurrence in a person, to cumulative exposure, is not simply linear, and that the joint relationship of radon and smoking is not additive. The ''best" models indicate that the regression relationship depends on cumulative radon progeny exposure and on attained age, time since exposure, and exposure rate, although at the concentrations of radon found in homes exposure rate might be of less importance. In addition, effects of smoking are greater than additive. Thus, for analyses of aggregated data, the model for age-specific rates is not a simple linear regression in exposure and smoking. Ecologic regressions typically fit linear models to age-adjusted rates and to estimates of radon concentration and smoking. The dependence of the radon-progeny exposure effects on the various factors implies that comparisons can be made only among regions that have the same population profile for age and past radon exposures, including exposure rates, or these factors must be age-standardized to a common population. Furthermore, regions must have a similar joint distribution for radon-progeny exposure and smoking.

When the exposure-response relationship is linear, there are no group-level effects, and regressor variables are measured without error, population cumulative exposure can be used to obtain an unbiased estimate of the exposure-response parameter. However, that simplification, which theoretically might arise when the true model for individuals is linear, does not apply for radon-progeny exposure and lung-cancer. The complexity of the risk model at the individual level (exposure-response effects with age-specific, time-since-exposure and exposure-rate variations and multiplicative or submultiplicative effects of smoking) does not lend itself to a simply linear approximation for aggregated data and guarantees that a linear model for age-adjusted disease rates is misspecified.

Statistical power of published reports was considered in the 1993 review of Stidley and Samet (1993). They found power to be limited for the reported studies; given the expected magnitude of effect of radon on lung-cancer risk at typical indoor concentrations, inadequate statistical power can lead to the incorrect conclusion that there is no association.

Stidley and Samet (1994) and Greenland and Robins (1994a) have further considered limitations of ecologic studies of radon and lung-cancer. Using simulation, Stidley and Samet (1994) assessed the sensitivity of the ecologic design to confounding by cigarette-smoking. The average estimate of the effect of radon was negative when the correlation between radon and smoking was between -0.17 and -1.00 (Figure G-1). In an additional series of simulations, they explored the consequences of model misspecification, assessing the findings of a simple linear-regression model when the underlying model is nonlinear. They showed that age-dependent risks and smoking-specific risks can be incorrectly estimated by simple regression methods.

Greenland and Robins (1994a) considered biases that affect ecologic studies, using a number of examples based on investigating radon and lung-cancer. They provide an informative example based on a multiplicative relationship between

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

FIGURE G-1 Relative risks from 8 lung-cancer case-control studies of indoor radon. Dashed line, extrapolation of risk from miners (Lubin and others 1994); dotted line; relative risk of 1.

lung-cancer and radon level and smoking that mimics the negative exposure-response results of Cohen (1995). The example is based on the following: lung-cancer occurrence is positively associated with radon concentration and cigarette-smoking rate, with the relationship linear in radon level and jointly multiplicative in radon concentration and cigarettes smoked per day; proportions of never-smokers, 1-pack/d smokers and 2-pack/d smokers vary by region; smoking rates vary by region (smoking rate is higher in regions with lower proportions of ever-smokers), so regional mean smoking rate is independent of region; and radon concentration is uniform within region but varies by region and is negatively correlated with the proportion of ever-smokers. Even though the "true" relationship specifies an increasing risk with radon concentration, and the ecologic regression of lung-cancer rates on mean regional smoking rate shows a positive exposure-response relationship, the regression of lung-cancer rates on regional radon concentration shows a negative exposure-response relationship.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

The example does not prove that confounding from smoking is causing the negative regression in Cohen's analysis, but it shows that results of an ecologic regression can be affected by a risk factor that is confounding at the level of the individual, but not at the level of region.

That example and others in the same paper make it clear that conditions for confounding at the individual and ecologic levels are distinct and that regression methods might not fully control confounding. Greenland and Robbins also note misconceptions concerning ecologic regression: the incorrect assumption that a linear model should approximate the true model because of Taylor's theorem; failure to recognize that nonlinearities at the individual level can lead to ecologic bias; an incorrect belief that important departures from linearity in the individual-level model will be detected by a test of fit of the ecologic linear model; an incorrect belief that having a large number of analytic groups, such as, regions, will ensure a random relationship between exposure and covariates; and an incorrect assumption that for ecologic bias to be present, region must be a confounder on the individual level with control of other factors.

Cohen (1994), in responding to Greenland and Robins, dismissed those limitations as not applicable to ecologic studies of radon and lung-cancer. He argued that his ecologic study has at least 4 advantages over an individual study: a large number of data points, the small degree of uncertainty affecting county mortality, the availability of "good" data on many potential confounding factors, and the size and diversity of the population being studied. However, Cohen's response did not specifically address the inherent limitations of ecologic studies and ecologic regression, as detailed by Stidley and Samet (1993) and Greenland and Robins (1994a). Greenland and Robins (1994b), in responding to Cohen, found little merit in his responses and disagreed with a principal assertion of his: that the ecologic fallacy does not affect a test of "linear-nonthreshold theory."

Piantadosi (1994), commenting on the exchange, suggested that Cohen's findings do "more to discredit the analysis than the theory." He elaborated: "The result of Cohen's analysis will seem biologically implausible to many investigators although it is probably theoretically possible at the individual level. Many epidemiologists will likely attribute the discrepancy between theory and result more to deficiencies in ecologic analyses than to failure of the dose-response theory ... Most of us would not be willing to discard a useful theory on the basis of such a test." Like Greenland and Robbins, Piantadosi is concerned by the limitations of ecologic analyses and the inability to determine whether bias is present and to estimate the direction and magnitude of its effect.

Uncontrolled confounding by smoking remains an explanation for the negative association between radon and lung-cancer reported by Cohen. Stidley and Samet (1994) noted that there might be confounding in Cohen's analysis reflecting the higher concentrations of radon in western states, where smoking tends to be lower than elsewhere in the country. Gilbert (1994) further noted that other

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

smoking-related cancers are also negatively associated with radon concentration in Cohen's data, possibly providing further evidence of confounding.

Conclusions

Although a number of ecologic studies have been published since the BEIR IV report, the present committee did not find the new evidence to be informative concerning the risks posed by radon. The finding of a statistically significant negative association between radon and lung-cancer in Cohen's analysis of lung-cancer mortality in the United States was considered to have resulted from inherent limitations of the ecologic method. That analysis has been widely cited as weighing against any risk of lung-cancer at typical indoor radon concentrations (White and others 1992; Marcinowski and others 1994). The finding was considered to be an inappropriate basis for concluding that indoor radon is not a potential cause of lung-cancer. We also note that the case-control studies reported to date, although limited in statistical power, have not yielded evidence of a negative association between exposure to radon progeny and lung-cancer risk. The ecologic studies were also not considered to be an appropriate basis for quantitatively estimating lung-cancer risk associated with radon exposure. Ecologic regression coefficients can be biased, and extensive individual-level data are available for estimating risk.

CASE-CONTROL STUDIES

The most-direct evidence of health consequences of radon-progeny exposure in homes is offered by case-control studies, in which characteristics of lung-cancer patients are compared with those of control subjects who do not have the disease. After age, smoking, and other factors are accounted for, if residential radon causes lung-cancer, it would be expected that the mean of a measure of exposure of cases would exceed the mean of controls, given proper assessment of statistical sampling variation. Exposure measures are usually based on a surrogate thought to be correlated with exposure, such as type of home construction, or on a more-direct correlate, such as measured radon in current and past homes.

Although straightforward in principle, case-control studies of residential radon are burdened with several limitations. These are discussed later in this chapter and include in particular an inability to measure radon in current and all past homes and thereby create an accurate measure of exposure, the lack of an estimate of radon exposure outside the home, and the relatively small relative risk (RR) that is expected even for long-term residents of higher-radon homes, which are not common. A small RR implies that mean exposures of cases and controls differ by only a small amount, thus limiting study power. The detection of an excess risk of lung-cancer is potentially complicated also by an inability to

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

control completely for other lung-cancer risk factors, particularly cigarette-smoking, which has an RR of 10–20.

In this section, we review case-control studies, first those which use surrogate measures of exposure and then those in which direct measurements of radon concentration in homes were used.

Studies Using Surrogate Measures of Exposure

Many of the earliest studies of the effects of residential radon exposure relied on surrogate measures of exposure, such as housing style, for example, the presence or absence of a basement, the type of construction materials, or the characteristics of the local geology. Investigators often supplemented their observational data on houses with direct measurements of radon concentration to validate their "exposure" classifications. Table G-5 adapted from Samet (1989), lists the principal studies that used surrogate measures as the primary source of exposure classification. In those studies, measured concentrations were generally positively correlated with housing characteristics thought to be related to high indoor radon concentrations. For example, in several studies conducted in Sweden, radon measurements were related with their classification scheme whereby wood houses without basements on normal ground were classified as low-radon houses; wood houses on alum shale (known to have high radiation emanation rates), stone houses with basements, and stone houses without basements on alum shale were classified as high-radon houses; and the remainder were classified as moderate-radon houses. But housing type was not always directly related to radon concentration. In the Stockholm County study by Svensson and others (1989), which was supplemented by direct radon measurements in houses and reported by Pershagen and others (1992), measured houses with ground contact classified by "type of ground" had geometric means of 99, 108 and 153 Bqm-3 for low, moderate and high categories, respectively.

Results of the studies varied, but, the overall pattern of RRs suggests a positive association between the surrogate measure of radon concentration and lung-cancer risk, with an RR for the high-radon houses about twice that for the low-radon houses. When data were available, results were not materially affected by controlling for smoking. Because the links between the radon potential of a house and actual radon concentration and between radon concentration and individual exposure are uncertain, it is difficult to interpret the RRs in relation to extrapolations from miners or to studies in which radon concentrations in houses were measured.

The agreement among the studies that used surrogate measures complicates their interpretability, in that the results appear more consistent than do results of studies in which indoor radon was measured directly. Classification of indoor radon concentrations based on housing type or building materials might be expected to be less accurate and to have greater random and systematic errors in

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-5 Epidemiologic studies of residential redon-progeny exposure and lung-cancer with surrogate measures of exposure

Location: Reference

Study Design

Subjects

Exposure

Resultsa

Southern Sweden: Axelson and others 1979

Case-control

37 cases deceased in 1965–1977 and 178 controls deceased at same time as cases, excluding cancers; rural residents only

Residence type: wood without basement, "mixed," or stone with basement

RR=1.8 [95% CI (1.0,3.2)] for stone and mixed, compared with wood

Oeland, Sweden:

Edling and others 1984

Case-control

23 cases deceased in 1960–1978 and 202 deceased controls

Residence type: wood without basement on normal ground, "mixed," or wood on alum shale, stone with basement and stone without basement on alum shale; 1 mo measurements in some homes

RRs of 1.2 [90% CI (0.5,3.1)] and 4.3 [90% CI (1.7,10.6)] for intermediate-and high- vs. low-exposure categories; p for trend <0.01.

Southern Sweden: Edling and others 1984

Case-control

23 cases and 202 controls

Measurement with a-sensitive film

RR increased for hightest- vs. lowest- exposure categories.

Northern Sweden: Pershagen and others 1984

Case-control (matched pairs)

15 never-smoker and 15 ever-smoker case-control pairs

Construction characteristics

Estimated mean exposure significantly higher for smoking cases than controls; exposure not different for nonsmokers.

Sweden:

Pershagen and others 1984

Case-control (matched pairs)

11 never-smoker and 12 ever-smoker case-control pairs

Construction characteristics

Estimated mean exposures similar for cases and controls, regardless of smoking status.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Location: Reference

Study Design

Subjects

Exposure

Resultsa

Northern Sweden: Damber and Larsson 1987

Case-control

589 male cases, 582 deceased controls, and 453 living controls

Residence type: wood or nonwood

RR not increased with or without smoking adjustment; RR increased for those never employed in non-lung-cancer-related occupations.

Stockholm, Sweden: Svensson and others 1987

Case-control

292 female cases diagnosed in 1972–1980 and 584 controls, resident in Stockholm for at least 28 of prior 30 yr

Geology and living near ground level; grab-sample measurements in some homes

RR=2.2 [95% CI (1.2,4.0)]; exposure-response trend not significant.

Southern Sweden: Axelson and others 1988

Case-control

177 cases deceased 1960–1981 and who lived in same house at least 30 yr before death and 677 controls deceased in same years of noncancer causes

Residence type: wood without basement on normal ground, "mixed," or wood on alum shale, stone with basement and stone without basement on alum shale; 2 mo measurements in some homes

RR=1.8 [90% CI (1.0,3.3)] for nonsmokers and light smokers in rural areas; no association for smokers in rural areas or for urban residents.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Location: Reference

Study Design

Subjects

Exposure

Resultsa

Stockholm County, Swedenb: Svensson and others, 1989

Case-control

187 female cases in 1983–1985, 160 "hospital" controls with suspect lung-cancer found not to have the disease, and 177 population-based controls

Geology and living near ground level; 2-w radon measurements during the heating season in a sample of homes

RRs of 1.8 [95% CI (1.2,2.9)] and 1.7 [95% CI (0.9,3.3)] for intermediate-and high- vs. low-exposure categories; p for trend 0.03. Slight variation of risk by cell type or smoking status; steeper RR trend at highest ages.

Washington County, Maryland, U.S.A.: Simpson and Comstock 1983

Cohort

298 cases over 12-yr period

Housing characteristics

No association of incidence with housing characteristics.

a Parentheses provide 95% confidence interval for RR.

b Initial study, which was later expanded to include indoor radon measurements and reported by Pershagen and others 1992.

Source: adapted from Samet (1989).

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

exposure assessment; as a result, there would likely be greater attenuation of the observed association and greater variability in the outcomes of the independent studies. However, one should not necessarily conclude that studies using surrogate measures will be more misclassified than those using actual measurements, because their error structures differ fundamentally. There is a possibility that such might have some advantages. The ideal study would include both measurements and surrogates, and both should be included in an analysis incorporating measurement errors.

Results of these studies should therefore be interpreted cautiously. In addition, several of the studies had few lung-cancer cases, that often precluded subgroup analyses, which would permit evaluation of both internal consistency and consistency among studies.

Studies with Direct Measurements of Indoor Radon

Potentially, the most important source of direct information on the consequences of exposure to indoor radon is epidemiologic studies in which long-term measurements of radon concentration were carried out. Several such studies have been done, and they are described below. All studies used a case-control design, in which estimates of radon or radon-progeny exposure of lung-cancer subjects are compared with estimates of exposure of controls selected from the same target population as the cases taking account of other factors that might influence the comparison—such as age, smoking status, and sex—are accounted for.

Case-control studies that incorporate direct measurement of indoor radon concentrations have several advantages over ecologic studies and over case-control studies that use surrogate exposure measures. Such case-control studies must be viewed as generally having greater validity for the identification and ultimately the quantification of an excess risk of lung-cancer. In contrast with an ecologic study, a case-control study offers a well-defined target population, and outcome status is assessed unambiguously. Direct, long-term measurement of radon in houses permits estimation of exposures specific to individuals, thereby reducing exposure errors, compared with ecologic studies and studies that define exposure in terms of house type. Direct measurement data permit the reconstruction of historical exposure profiles and the evaluation of biologically plausible exposure periods. With direct measurement data, it is possible to evaluate the consequences of missing data and the effects of various imputation approaches. In addition, measurements from track-etch devices are generally more comparable across countries than are crude classifications by house type and so allow more valid comparison among studies from different countries. Thus, results of ecologic studies are considered noninformative, results of case-control studies that use surrogate exposure measures are provocative, and case-control studies with direct, long-term radon

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

measurement offer the best opportunity for identifying an excess risk of lung-cancer associated with indoor radon.

New Jersey Case-Control Study of Females
Study Subjects

The radon component of this study was an add-on to a continuing lung-cancer case-control study of females in New Jersey (Schoenberg and others 1990; Klotz and others 1993). The original case group consisted of 1,306 female residents with histologically confirmed lung-cancer diagnosed from August 1982 through September 1983 (see Table G-6). They were identified from hospital pathology records and from the New Jersey State Cancer Registry and death-certificate files. Data were collected on 994 cases (76%) from 532 in-person interviews and 462 next-of-kin interviews.

Controls were selected from New Jersey drivers-license file, on those under age 65 and from Health Care Financing Administration file, on those 65 and over. For cases with next-of-kin respondents, controls were selected at random from death certificates, excluding deaths from respiratory disease. Controls were individually matched to cases by race, age, and, for deceased cases, closest date of death. A total of 1,449 controls were identified, and interview data were obtained on 995 women (69%).

Houses to be measured were defined in the study in 2 phases (Table G-7). In phase I, a single "index" residence per subject was chosen in which the subject lived for at least 10 yr in the period 10–30 yr before diagnosis or selection. In phase II, the residence criteria were broadened, to add subjects to the radon component of the study and houses for subjects selected in phase I. The eligibility period for the index residence was extended to cover the period 5–30 yr before diagnosis, and the study enrolled all houses in which a subject resided for 4 yr or more in the 6 New Jersey counties with high average radon concentrations, or for 7 yr or more in the rest of the state. Twelve subjects were excluded because their eligible residences represented less than 9 yr of coverage in the exposure-time window. Of the 994 cases and 995 controls with completed interviews in the original study, 661 cases (66%) and 667 controls (67%) had residences that were eligible under the expanded phase II criteria.

Data Collection

Subjects or surrogate respondents were interviewed by trained interviewers. Study subjects provided 53% of the interviews, spouses 17%, and other next-of-kin 29%. Information was obtained on lifetime smoking history, smoking by other household members, lifetime residential and occupational histories, and consumption of food high in vitamin A. Information on specific addresses of past residences was collected several years after the original interview through telephone contacts. During eligible residencies, information was obtained on house characteristics, including heat circulation and modifications to the structure or to heating and ventilation.

Methods of Radon Measurement

Long-term a-track detectors were deployed

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-6 Summary of results of New Jersey female case-control study

Factor

Comment

Principal references

Schoenberg and others 1990, 1992.

Design

Case-control study in females.

Study subjects

Cases: Cases were selected from 1,306 histologically confirmed lung-cancers in females diagnosed in August 1982 through September 1983 throughout the state. In original study, 994 women were interviewed: 532 subjects and 462 next-of-kin. Cases for the radon analysis were further restricted by measurement protocol Phases I and II.

 

Controls: For living cases, controls were selected randomly from New Jersey driver's license files (age < 65 yr) or Health Care Financing Administration files (age = 65 yr). For next-of-kin cases, controls were selected randomly from death certificates that did not mention respiratory disease. Controls were matched by race, age, and, for deceased cases, date of death.

 

Subjects in radon study: Phase I included subjects who had lived in a single residence = 10 yr in the period 10–30 yr before diagnosis or selection; phase II included subjects who had lived in one or more residences in the period 5–30 yr before. Phase II added subjects to phase I and added houses. Subjects restricted to those with 9 yr of coverage. Totals of 480 cases and 442 controls were included.

Lung-cancer histology

480 cases: squamous 25.8%; small cell 29.8%; adenocarcinoma 21.9%; other 22.5%.

Rn measurement protocol

Measurements: 1-yr a track in living area (76%), 1-yr a track in basement (5.4%), basement and upstairs charcoal canister (6.5%), upstairs charcoal canister (1.4%). Canister below minimal detectable concentrations assigned MDC concentration. Apartments above the 2nd floor assigned 0.4 pCiL-1. Regressions linked basement and canister measurements to long-term values for living areas.

 

Missing: Under phase II eligibility, 74% of cases and 72% of controls had measurements.

Rn measurements

Mean: Cases, 0.7 pCiL-1; controls 0.7 pCiL-1.

 

Median: Cases, 0.5 pCiL-1; controls 0.5 CiL-1.

Rn-exposure estimation

Exposure-time window: 5–30 yr before the date of case diagnosis or control selection.

 

Coverage: Median 22 yr for cases and for controls; 35% of subjects fully covered.

 

Imputation for gaps: None for TWA radon exposure; for cumulative exposure, 0.6 pCiL-1 (22 Bqm-3) was assigned for missing intervals.

Results

Overall: For categories <1, 1–1.9, 2–3.9, and = 4 pCiL-1, RRs were 1.0, 1.2, 1.1, and 8.7, with p value for 1-sided test of linear trend 0.04. Only 5 cases and 1 control in highest category.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Factor

Comment

 

Histology: Increasing RRs with pCiL-1 only for ''other" cell types; no trend with other histologic types (Lubin and others 1994).

 

Smoking: For RR with pCiL-1 no trend in never-smokers, increasing RRs for <15 and 15–24 cigarettes/d, and decreasing trend for =25 cigarettes/d.

TABLE G-7 Distribution of 944 cases and 955 controls in original New Jersey lung-cancer case-control study by status in radon substudy for Phase I only and Phase I and II

 

No. (%) Subjects

 

Phase I only

 

Phase II only

 

Status

Cases

Controls

Cases

Controls

Included in radon studya

433 (44)

402 (40)

480 (48)

442 (44)

No address-specific informationb

140 (14)

126 (13)

168 (17)

152 (15)

No address met residence criterionc

253 (25)

256 (26)

165 (17)

176 (18)

No radon testing at index addressd

168 (17)

211 (21)

181 (18)

255 (23)

a Index residence(s) tested for radon with a-track detectors or charcoal canisters. If index residence was apartments above the 2nd floor, radon exposure assumed to be < 1 pCiL-1. Seven cases and 5 controls with complete measurements in phase I or II were excluded because they represented 8 yr or less of 25 yr exposure history.

b Respondent refused further contact after initial interview, respondent lost to follow-up, respondent refused address-specific information, or inadequate address-specific information.

c Subject did not meet residence criterion for inclusion in phase I (phase I and phase II).

d Index residence demolished, refusal by current resident, or no contact with current resident. Source: Schoenberg and others 1992.

for 1-yr. In each dwelling, 1 detector was placed in the living area, usually the master bedroom, and another in the lowest habitable level, usually the basement. In addition, 4-d screening measurements were made with the house closed, during the heating season, with charcoal canister detectors. The screening measurements were used primarily as a backup if long-term measurements could not be completed and to identify homes that required immediate mitigation. The radon concentration used for the house was based on the nonbasement primary-living-area a-track measurement when available (76% of houses). When it was unavailable, the nonbasement radon concentrations were estimated from other measurements in descending order of priority: basement a-track (5.4%), basement charcoal canister with upstairs canister (6.5%), and upstairs charcoal canister (1.4%). The estimates were derived from regression equations based on complete sets of measurements which also took into account the heating system (forced air versus

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

other). Canister readings below the minimal detectable concentration (MDC) were assigned the MDC value. Apartments above the 2nd floor (10.6%) were assigned a value of 14.8 Bqm-3 (0.40 pCiL-1). Usable measurements were obtained for 480 cases and 422 controls or, 74% and 72%, respectively, of those eligible under the Phase II criteria.

For analysis, 2 measures of exposure were developed. The time-weighted average (TWA) radon concentration was the mean concentration for all houses measured weighted by the years of residence in the exposure-time window of 5–30 yr. Cumulative radon exposure was computed as the product of residence time within the 5–30 yr and measured radon concentration. Within the 5–30 yr, unmeasured houses were assigned a radon concentration of 22.2 Bqm-3 (0.6 pCiL-1), the median concentration of all phase I control houses.

Results

On the basis of phase II data, the mean residence time within the 5–30 yr was 22 yr for cases and for controls; 35% of the subjects had radon measurements for all their homes in the exposure period. The houses in the New Jersey study had the lowest radon concentration of any of the current case-control studies; most of the TWA concentrations were below 37 Bqm-3 (1 pCiL-1). The median radon concentration was 18.5 Bqm-3 (0.5 pCiL-1) and was the same for cases and controls.

Table G-8 shows the RRs for categories of TWA radon concentration adjusted for cigarettes per day, cessation of smoking, age, occupation, type of respondent, and interaction of type of respondent with cigarettes per day (Schoenberg and others 1992). RRs were flat and increased only in the highest category, 148 Bqm-3 (4.0 pCiL-1), which included 5 cases and 1 control. The p-value for linear trend was significant at p = 0.05 but was based on a 1-sided, rather than the traditional 2-sided, test of the null hypothesis. For this study, it should be pointed out that 90% Cls were used for RR rather than the more

TABLE G-8 Distribution of cases and controls and adjusted odds ratios a (OR) and confidence intervals (CI) by time weighted average (TWA) radon concentration for the New Jersey case-control study of females

 

TWA Rn concentration, pCiL-1

 

<1

1–1.9

2–3.9

=4

Total

P for trend

No. Cases

384

72

19

5

480

No. Controls

360

69

12

1

442

ORa

1.0

1.2

1.1

8.7

0.05b

90% CI

 

(0.8,1.7)

(0.6,2.3)

(1.3,57.8)

a Adjusted for lifetime average cigarettes/d, years since smoking cessation, age, occupation, respondent type, and interaction between respondent type and cigarettes/d.

b One-sided test of linear trend

Source: Schoenberg and others 1992.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

conventional 95% Cls. Results for cumulative radon exposure were similar to those for TWA radon concentration (Schoenberg and others 1992).

Shenyang China Case-Control Study of Females
Study Subjects

Like the New Jersey study, the radon component of this study was an add-on to an existing lung-cancer case-control study of woman in Shenyang China (Xu and others 1989; Blot and others 1990). Potential cases were female residents of Shenyang, who were 30–69 yr old and were listed in the Shenyang Cancer Registry with primary lung-cancer in September 1985 to September 1987 (Table G-9). In the full study, 75% of the diagnoses for the female lung-cancer cases were based on pathologic or cytologic material; histologic information was available on 73% of all female cases (Xu and others 1989).

A population-based, age-matched control group of women was selected from the Shenyang general population by using the system of area administrative units and neighborhood population lists. Controls were randomly selected in 5-year age groups to reflect the age distribution of the cases.

The radon component of the study was initiated 6 months after the start of the original study and, because of budgetary reasons, ended before completion of case acquisition in the full study. A total of 397 cases and 391 control subjects had detectors placed in their houses, representing 95% and 99% of eligible cases and controls, respectively.

Data Collection

Trained nurses sought personal interviews with the subjects, except for those who were too ill or deceased. Participation rates were 95% for cases and 97% for controls. For most patients, the time between diagnosis and interview was less than 1 month. A structured questionnaire was used in an interview to inquire about smoking by the subject and other household members, occupation, prior medical conditions, residential history, and housing characteristics, such as indoor air pollution. A time-weighted index of lifetime air-pollution exposure was determined from housing characteristics, including type of heating, fuel used for cooking, and whether cooking facilities were in a separate kitchen or combined with living room or bedroom (Xu and others 1989).

Methods of Radon Measurement

Two a-track detectors were placed for 1 yr in the current residence of each case and control; 1 detector was usually in the living room and 1 in the bedroom. Nearly all homes were single-story buildings. For persons who lived in the current house less than 5 years, a prior Shenyang residence was tested, provided that it was accessible and the subject had lived there at least 5 years. Detectors were collected for 308 cases (78%) and 356 controls (91%).

The maximum of the 2 measurements were used in analysis. Among the paired measurements, the correlation was 0.52, 77% were within 74 Bqm-3 (2 pCiL-1), and 78% of the ratios of the 2 measurements were less than a factor of 2.

Results

Among the subjects, the median number of reported residences was 3, the median residence time in the last home was 24 yr, and 76% lived in the

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-9 Summary of results for Shenyang, China female case-control study

Factor

Comment

Principal reference

Blot and others 1990.

Design

Case-control study of females.

Study subjects

Cases: Cases included all female residents of Shenyang, China, aged 30–69 yr with primary lung-cancer diagnosed in September 1985 to September 1987 and listed in the Shenyang Cancer Registry. All case diagnoses were reviewed.

 

Controls: Controls were randomly selected in 5-yr age groups from the general population.

 

Subjects in radon study: For the radon component, ascertainment was delayed 6 mo but included all subjects. A total of 308 cases and 356 controls had radon measurements.

Lung-cancer histology

308 cases: squamous, 23.4%; small cell, 12.7%; adenocarcinoma, 30.8%; other or unknown 31.1%.

Rn measurement protocol

Measurements: 1-yr a-track detectors in living room and in bedroom of current home. For those who had lived for < 5 yr in the current home, 1-yr a-track detectors were placed in the previous residence if it was in Shenyang and accessible and subject had lived there 5 yr.

 

Missing: Among those eligible, 79% of cases and 91% of controls had measurements.

Rn measurements

Median: Cases, 2.8 pCiL-1; controls, 2.9 pCiL-1.

Rn-exposure estimation

Exposure-time window: 5–30 yr before case diagnosis or control selection.

 

Coverage: Median residence in last home was 24 yr, and 76% lived in measured home = 10 yr.

 

Imputation for gaps: None; analyzed only measured radon concentration.

Results

Overall: For categories <2, 2–3.9, 4–7.9, and =8 pCiL-1, RRs were 1.0, 0.9, 0.9 and 0.7 and 1.0, 0.7, 1.2, and 0.7 when analyses were restricted to subjects who lived =25 yr in their last residence.

 

Histology: RRs for small cell for pCiL-1 categories were 1.0, 1.2, 1.7, and 1.4, but with nonsignificant trend.

 

Smoking: Little evidence of a trend in RRs with pCiL-1 in any smoking category.

 

Subgroup analyses: RR patterns were the same within levels of an index of indoor air pollution or after adjustment.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-10 Distribution of cases and controls and adjusted odds ratiosa (OR) and confidence intervals (CI) by radon concentration in Shenyang, China, case-control study of females

 

Radon concentration (pCiL-1)

 

< 2

2–3.9

4.0–7.9

= 8.0

Total

P for trend

Cases

91

131

60

26

308

 

Controls

95

148

77

36

356

 

OR

1.0

0.9

0.9

0.7

 

n.s.

95% CI

 

(0.6,1.3)

(0.5,1.4)

(0.4,1.3)

 

 

a ORs adjusted for age, education, smoking status, and an index of indoor air pollution.

Source: Blot and others 1990.

measured home for 10 or more. On the average, subjects lived 66% of their adult lives in the measured home (Blot and others 1990). Using the maximum of the 2 radon measurements, the medians were 103.6 Bqm-3 (2.8 pCiL-1) for cases and 107.3 Bqm-3 (2.9 pCiL-1) for controls.

Categories of radon concentration ranged from < 74 Bqm-3 (2 pCiL-1) to 296 Bqm-3 (8.0 pCiL-1) (Table G-10). The RR for lung-cancer adjusted for age, education, smoking status, and an index of indoor air pollution showed no increase with increasing radon concentration.

In the Shenyang data, cigarette-smoking and indoor air pollution were found to be significant risk factors for lung-cancer for males and females (Xu and others 1989). Among females, 55% of cases and 35% of controls smoked cigarettes. The risk was over 9 times as high in women who smoked more than 1 pack/d for at least 40 yr, as in never-smokers. For females in the radon component of the study, the RR pattern with radon concentration was similar, that is, it showed no increase in never-smokers, light smokers and heavy smokers.

Indoor air pollution was found to increase lung-cancer risk by a factor of 2–3, depending on the variable analyzed. The greatest risks were associated with the use of a coal-burning kang (a brick bed under which heated smoke is passed through pipes before venting to the outside through a chimney or other opening) or cooking in the same room as the sleeping quarters.

An air-pollution index was developed to incorporate the type of heating for the home, the type of cooking fuel, and whether the kitchen and the bedroom were the same room. For females, no positive association was found with radon concentration for low or high categories of the indoor air-pollution index (Blot and others 1990).

Stockholm, Sweden Case-Control Study of Females
Study Subjects

The methods of the Swedish investigation have been described (Pershagen and others 1992) and are summarized in Table G-11. Women

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

suspected of having lung-cancer on admission in 1983–1985 to the 3 clinical departments of pulmonary medicine and the only department of thoracic surgery in Stockholm County were interviewed. Those later diagnosed as having lung-cancer (210) were classified as cases.

Two control groups were selected. Hospital controls consisted of women suspected of having lung-cancer who were later found not to have it (191), and population-based controls (209) were obtained from Stockholm County population registers. Results were reported for both control groups combined.

Data Collection

Subjects were interviewed by physicians using a structured questionnaire. For cases and hospital controls, information was obtained on admission. Population controls were interviewed in visits or by telephone. Information

TABLE G-11 Summary of results of Stockholm female case-control study

Factor

Comment

Principal reference

Pershagen and others 1992.

Design

Case-control study of females.

Study subjects

Cases: Cases (210) included females admitted to the 3 pulmonary departments and the 1 thoracic-medicine department in Stockholm County in September 1983 to December 1985.

 

Controls: Two controls were selected: "hospital" controls (191) included females suspected to have had lung-cancer but found not to, and population controls (209) selected randomly from County population registers.

 

Subjects in radon study: For the radon analysis, 31 women (5%) could not be measured, leaving 201 cases and 378 controls with radon measurements.

Lung-cancer histology

201 cases: squamous, 26.9%; small cell, 25.4%; adenocarcinoma, 34.4%; other 13.4%.

Rn measurement protocol

Measurements: 1-yr a-track detectors in living room and in bedroom (85.1 %) or thermoluminescence detector (TLD) for 1 wk in living room followed by 1 wk in bedroom (14.9%) in all homes occupied 2 yr or more since 1945. TLD values were then adjusted empirically to link with a-track measurements.

 

Missing: 2,118 homes fulfilled criteria for measurement; a-track detectors retrieved from 1,339 homes (63%) and TLD from 234 homes (11%).

Rn measurements

Median: Cases, 3.1 pCiL-1; controls, 2.9 pCiL-1

 

Mean: Cases, 3.6 pCiL-1; controls, 3.7 pCiL-1 (Lubin and others 1994).

Rn-exposure estimation

Exposure-time window: From 1945 to 5 yr before interview.

 

Coverage: 26.3 yr and 25.3 yr of residence corresponding to 78% and 77% of the time window.

 

Imputation for gaps: None for TWA radon concentration; unclear for cumulative exposure-some analyses set missing to zero, and some replaced missing with estimates based on housing characteristics.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

was obtained on smoking, exposure to environmental tobacco smoke, occupational history, and consumption of foods rich in vitamins A and C. Also obtained was a history of all residences in which the subject lived for 2 yr or more since birth or arrival in Sweden. The residential history included information on type of house, building material, and year of construction. Data from parish registries on past residences were used to verify and supplement the residential histories.

Methods of Radon Measurement

Measurements were sought for all dwellings where the subject resided for 2 years or more between 1945 and the end of the observation period, 1983–1985. For cases and hospital controls, the end of the exposure observation period was 5 years before the date of the study interview; for the population controls, it was 5 years before the interview of the corresponding case. Of the 2,118 residences so identified, no measurements could be made in 27.4%—in 11.2% because the house no longer existed, in 4.4% because the house was abroad, in 3.2% because the current owner refused, and in 8.6% for various other reasons (Pershagen and others 1992).

Year-long radon-concentration measurements were made in 1,339 dwellings with 2 a-track detectors: one in the living room and the other in the bedroom. In 234 dwellings (15%), measurements were made for 2 weeks during the winter with thermoluminescence detectors (TLDs) designed by the Swedish Institute of Radiation Protection. A TLD was placed in the living room for 1 week, then moved to the bedroom for another week. The 2 methods gave readings that had correlations above 0.8, although the TLD values were higher on the average, reflecting decreased ventilation in the colder months and the greater likelihood of their placement in areas of high-radon ground emanation (Svennson and others 1989). For analyses, TLD values were adjusted empirically to reflect a-track detector concentrations (Svensson and others 1988). The radon concentration assigned to a house was either the mean of the 2 a-track readings or the adjusted TLD reading.

Two measures of exposure were developed for analysis. The TWA radon concentration was the mean concentration for all houses measured weighted by the years of residency in the exposure window from 1945 to 5 years before enrollment. Cumulative radon exposure was computed as the product of residency time in the exposure window and measured radon concentration. The handling of missing measurements in the calculation of cumulative radon exposure was unclear. It appears that missing measurements were sometime set to zero and that "in certain analyses, missing radon measurements were replaced by estimates based on dwellings actually measured and information from the interview questionnaire on type of house, building material, and year of construction" (Pershagen and others 1992). Specific details were not provided.

Results

For cases and controls, the mean times covered by measurement data were 26.3 years and 25.3 years and represented 78% and 77% of the relevant period, respectively. For the subjects, median radon concentrations were 114.70 Bqm-3 (3.1 pCiL-1) for cases and 107.3 Bqm-3 (2.9 pCiL-1) for controls.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Results show a significant increase in RRs with increasing TWA radon concentration (Table G-12). The p value for trend was 0.05. As indicated by Pershagen and others and expanded on in the pooled analysis by Lubin and others (1994a), the significance of the test for trend depended on the cut points and on the quantitative value used. The p value of 0.05 computed by Pershagen and others (1992) used the median for each category as the quantitative trend variable, whereas Lubin and others computed the p value as 0.46 by using the continuous value for radon concentration. The former approach minimized the impact of extreme values; the latter approach eliminates the arbitrariness of categorization. The trend of increasing RR was reduced when adjusted for occupancy or when exposure 15 years and more before was given half the weight in line with results of miner studies. These differences highlight the need to interpret the Stockholm results with caution.

Because of the small number of cases, the trends in the RR with level of radon concentration were probably statistically homogeneous by histological type, although no formal assessment was done. However, the gradient of increase appeared greater for squamous cell and small cell carcinomas (Pershagen and others 1992).

Similarly, there was no statistical evaluation of the joint association of radon concentration and smoking status; however, the trend appeared slightly greater in never-smokers than in ever-smokers.

TABLE G-12 Distribution of cases and controls and adjusted odds ratiosa (OR) and confidence intervals (CI) by radon concentration for the Stockholm case-control study of females

 

Radon concentration (pCiL-1)

 

< 2

2–2.9

3.0–4.0

= 4.1

Total

P for trend

Cases

43

59

38

61

201

 

Controls

89

113

76

100

378

 

OR

1.0

1.2

1.3

1.7

 

0.05b

95% CI

 

(0.7,2.1)

(0.7,2.3)

(1.0,2.9)

 

 

ORc

1.0

1.5

1.6

1.5

 

0.19

95% CI

 

(1.0,2.4)

(0.9,2.7)

(0.6,3,4)

 

 

ORd

1.0

1.4

1.2

1.3

 

0.65

95% CI

 

(0.9,2.3)

(0.7,2.1)

(0.6,3.1)

 

 

a ORs adjusted for age, smoking, and municipality of residence.

b For test of linear trend using category means, P = 0.05; using continuous exposure, P 0.46.

c Exposure adjusted for occupancy.

d Exposure adjusted for BEIR IV weighting, exposures 5–15 yr before given full weight, exposures =15 yr before given 0.5 weight

Source: Pershagen and others 1992.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×
Swedish National Case-Control Study
Study Subjects

This study, the largest to date, relied on various national data files for the identification of subjects for the study (Pershagen and others 1994). The study is summarized in Table G-13. The study base was defined as all subjects 35–74 years old who had lived in any of 109 municipalities in Sweden at some time from January 1980 through December 1984 and who had been living in Sweden on January 1, 1947. The municipalities were selected to include areas suspected of having homes with high and low radon concentrations on the basis of measurement data or geologic and other information. Municipalities with mining activities and the large cities of Stockholm, Göteborg and Malmö were not included.

Using Swedish Cancer Registry files, cases included subjects diagnosed with primary lung-cancer in 1980-1984. All 650 women and a radon sample of 850 men (about 40% of all men with lung-cancer) were identified. After excluding those not in the study base, a total of 1,360 cases were enrolled 586 females and 774 males.

Two control groups were defined by using the population registers of Statistics Sweden. One control series consisted of a radon sample of women frequency-matched in 5-year age categories and calendar year of residence to the case group and included 1,424 subjects—730 women and 694 men. A second control group was selected by matching on age and calendar year and on vital status. Deceased controls were ascertained from the Swedish Cause of Death Registry, excluding subjects who had died of smoking-related diseases (cancer of the mouth, esophagus, liver, pancreas, larynx, or uterine cervix or bladder; ischemic heart disease; aortic aneurysm; cirrhosis of the liver; chronic bronchitis and emphysema; gastric ulcer; violent causes; or intoxication). In the second control group, there were a total of 1,423 subjects—650 women and 773 men.

At the time of selection on December 31, 1986, about 90% of the cases and of the second control group had died; about 9% of subjects in the first control group had died.

Data Collection

All subjects or their next of kin were mailed a standardized questionnaire. Information was collected on smoking habits of the subject, and their spouses and parents and on lifetime occupational and residential histories since 1947. Residential history included information on type of house, building material, heating system, and time spent at home. For incomplete questionnaires or nonrespondents, telephone interviews were attempted. Data from parish registries on past residences were used to supplement residential histories from questionnaires.

Methods of Radon Measurement

Measurements were sought for all dwellings where a subject resided for 2 years or more between 1947 and 3 years before the end of the observation period, defined as year of diagnosis for the case and calendar year of selection for the controls. Of a total of 13,392 residences,

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-13 Summary of results of Swedish national case-control study

Factor

Comment

Principal reference

Pershagen and others 1994.

Design

Case-control study of females and males.

Study subjects

Cases: A total of 1,500 subjects 35–74 yr old with primary lung-cancer diagnosed in January 1980 to December 1984 were selected from the Swedish Cancer Registry, including all 650 females and 850 males. After various exclusions, 586 females and 774 males remained.

 

Controls: Two controls were selected: 1 control group (730 females and 694 males) derived from a randomly selected sample from population registers, frequency matched on age to the cases; and 1 control group (650 females and 773 males) similarly selected and matched by vital status against the Swedish Cause of Death Registry.

 

Subjects in radon study: For the radon analysis, measurements were not obtained on 27.4% of the homes. A total of 1,281 cases and 2,576 controls were included.

Lung-cancer histology

1,281 cases: squamous, 33.1%; small cell, 23.1%; adenocarcinoma, 26.9%; other or unknown 16.8%.

Rn measurement protocol

Measurements: 3-mo a-track detectors in living room and in bedroom in all homes occupied 2 or more years since 1947.

 

Missing: 12,394 homes fulfilled criteria for measurement; a-track detectors were retrieved from 8,992 homes (73%).

Rn measurements

Median: 1.5 pCiL-1.

Rn-exposure estimation

Exposure-time window: From 1947 to 3 yr before end of follow-up diagnosis for cases or matched date of selection for controls.

 

Coverage: 23.5 yr and 23.0 yr of residence corresponding to 72% and 71% of the exposure-time window.

 

Imputation for gaps: None for TWA radon concentration; unclear for cumulative exposure—some analyses set missing to median concentration, and some replaced missing with estimates based on housing characteristics.

Results

Overall: For categories < 1.4, 1.4–2.1, 2.2–3.8, 3.8–10.8, and = 10.8 pCiL-1, RRs were 1.0, 1.2, 1.0, 1.3, and 1.8, with a P value for test of trend < 0.05.

 

Histology: RR trends showed no difference by cell type.

 

Smoking: No difference in RR trend greatest by smoking status, in contrast with the authors' view.

 

Subgroup analyses: RR trend occurred only for subgroup that reportedly did not sleep near an open window; no trend was observed in those who sleep near an open window.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

addresses could not be identified for 7.5%. Of the remaining 12,394 residences, 27.4% could not be measured, usually because they no longer existed or because they were used only as summer houses (Pershagen and others 1994). In all, 73% of identified homes (8,992) were measured.

Three-month radon measurements were made during the heating season—from October 1 to April 30—with a-track detectors, which were processed by the Swedish Radiation Protection Institute. Two detectors were used: one in the living room and the other in the bedroom. For analyses, the mean of the 2 values was assigned to the residence. The authors estimate that the winter measurements might be 10–20% higher than yearly values, although the basis for this estimate is not provided.

Cumulative radon exposure since 1947 was estimated by multiplying the measured radon concentration concentration and the length of residency in each home. For each subject, TWA radon concentration was calculated by dividing cumulative radon exposure by the total residential time covered by radon measurements. Missing measurement time was not included; in effect the concentration and duration during those times were zero. For some analyses, imputation of missing measurement data was accomplished by replacing the missing data with the median radon concentration for all subjects or values adjusted to reflect residential characteristics (Pershagen and others 1994).

Results.

Results were presented for males and females combined. There were a totals of 1,281 cases and 2,576 controls.

Radon measurements covered 23.5 years and 23.0 years of the exposure-time for cases and controls, representing 72% and 71 % of the intended period, respectively. For individuals, the median TWA radon concentration was 55.5 Bqm-3 (1.5 pCiL-1).

Results show a significant increase in RR with increasing radon concentration (Table G-14). The RR patterns appeared similar by cell type. For the 5 categories shown in Table G-14 RRs were: 1.0, 1.2, 1.3, 1.5, and 1.7 for squa

TABLE G-14 Distribution of cases and controls (males and females combined) and adjusted odds ratiosa (OR) and confidence intervals (CI) by radon concentration for the Swedish national case-control study

 

Radon concentration (pCiL-1)

 

< 1.4

1.4–2.1

2.2–3.8

3.8–10.8

=310.8

Total

P for trend

Cases

452

268

272

246

43

1,281

 

Controls

952

561

568

436

59

2,576

 

OR

1.0

1.1

1.0

1.3

1.8

 

<0.05

95% CI

 

(0.9,1.3)

(0.8,1.3)

(1.1,1.6)

(1.1,2.9)

 

 

a ORs adjusted for age, occupation, sex, smoking status, and urban compared with nonurban residence.

Source: Pershagen and others 1992.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

mous cell carcinomas; 1.0, 0.9 1.1, 1.2, and 2.8 for small cell carcinomas; and 1.0, 1.1, 1.0, 1.4, and 2.3 for adenocarcinomas. Differences in RRs for the highest category could have arisen by chance, in as much as the category included only 11, 15, and 12 squamous, small cell, and adenocarcinoma cases, respectively.

RR patterns were also similar by smoking status. For categories of radon concentration shown in Table G-14, RRs were: 1.0, 1.1, 1.0, 1.5, and 1.2 for never-smokers; 1.0, 0.9, 1.2, 1.7, and 0.4 for ex-smokers; 1.0, 1.0, 1.0, 1.2, and 4.0 for current smokers consuming fewer than 10 cigarettes/d; and 1.0 0.9, 0.9, 1.2, and 2.6 for current smokers consuming at least 10 cigarettes/d. RRs in the highest radon concentration category were based on 5, 1, 12, and 16 lung-cancer cases for never-smokers, ex-smokers, and current smokers of fewer than 10 and at least 10 cigarettes/d, respectively.

Pershagen and others found that the RR trend with radon concentration increased for those who reportedly sleep with their bedroom windows closed, but the trend disappeared for subjects who reported sleeping next to an open window. Those patterns of risk are difficult to interpret. Sleeping next to an open window is not itself a risk factor for lung-cancer. Furthermore, the radon concentration of a bedroom with an open window will be reflected in a reduced radon measurement. Subjects or next of kin were interviewed about sleeping practices many years after disease occurrence. The relationship between the radon measurement, the current practice of sleeping with an open window, and whether the case or control subject slept with an open window at the time of enrollment is uncertain, particularly in homes that no longer were occupied by the subjects or their spouses. Effects of errors in exposure estimation might also play a role in the observed RR patterns. Control data suggest that in this age group about 70% of the population sleep with closed windows. Among subjects who sleep with an open window, measurements in homes, particularly former homes, are more likely to occur with owners who sleep with closed windows, thereby adding to error in exposure estimation and obscuring exposure-response effects. Among subjects who sleep with windows closed, measurements in former homes are more likely to occur with closed windows; however, for owners who sleep with open windows, there is a systematic (nondifferential) under estimation of exposure, a condition that can induce an increase in the trend of the exposure-response relation (Dosemeci and others 1990). No data on sleeping next to an open window were obtained at the time of the radon measurement. Further conclusions regarding sleeping with an open window are problematic, in that other studies have not considered the issue.

Winnipeg Case-Control Study
Study Subjects

This study, summarized in Table G-15, was a case-control study of lung-cancer in males and females in Winnipeg, Canada. In Létourneau

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-15 Summary of results of Winnipeg, Canada, case-control study

Factor

Comment

Principal reference

Létourneau and others 1994.

Design

Case-control study of males and females.

Study subjects

Cases: Cases included all residents of Winnipeg, Canada 35–80 yr old with histologically confirmed, primary lung-cancer diagnosed in September 1983 to September 1990 and listed with the provincial cancer-incidence registry.

 

Controls: Controls were randomly selected from the Winnipeg telephone directory and individually matched on age within 5 yr and sex.

 

Subjects in radon study: A total of 759 pairs were assembled. After exclusion for misdiagnosis or improper control selection, 738 case-control pairs were enrolled. 257 cases and 78 controls had proxy interviews.

Lung-cancer histology

738 cases: squamous, 31.4%; small cell, 15.9%; adenocarcinoma, 32.9%; other 19.8%.

Rn measurement protocol

Measurements: Two sequential 6-mo a-track detectors in the bedroom and two in the basement of up to 3 homes in the Winnipeg metropolitan area. For apartments, only bedroom measurements were made. Yearly values were taken as the mean of the 2 measurements.

 

Missing: Subjects had a mean of 5 homes in the Winnipeg area; attempts were made to measure 3 homes. 7,318 homes were eligible, and 4,448 were measured (61%).

Rn measurements

Mean: For bedrooms: cases, 3.1 pCiL-1; controls, 3.4 pCiL-1. For basements: cases, 5.1 pCiL-1; controls, 5.6 pCiL-1.

Rn-exposure estimation

Exposure-time window: Two windows defined: 5–30 yr and 5–15 yr before date of case diagnosis or control selection.

 

Coverage: About 67% of 5 to 30 yr window and 80% of 5 to 15 yr window.

 

Imputation for gaps: For cumulative exposure, used mean concentration for Winnipeg (3.3 in the living area and 5.3 in the basement).

Results

Overall: For categories (estimated from cumulative exposure) <1.9, 1.9–3.9, 3.9–7.8, and = 7.8 pCiL-1, RRs were 1.0, 1.0, 0.8, and 1.0 for the 5 to 30 yr window and 1.0, 1.0, 0.8, and 1.0 for the 5 to 15 yr window.

 

Histology: RRs similar and show no increased risk with exposure by cell type.

 

Smoking: Smoking patterns were used only for adjustment; no evaluation of effect modification of radon RRs was conducted.

 

Subgroup analyses: Data on occupational exposures were used only for adjustment; no evaluation of effect modification of radon RR was conducted.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

and others (1994), cases were histologically confirmed primary lung-cancer cases diagnosed between the ages of 35 and 80 years and, listed in the provincial cancer-incidence registry maintained by the Manitoba Cancer Treatment and Research Foundation for 1983–1990. All patients were residing in Winnipeg at the time of diagnosis. Controls were individually matched to cases on age within 5 years and on sex and were identified through the Winnipeg telephone directory.

A total of 759 matched pairs were initially identified. When cases that did not have primary lung-cancer or had improperly matched controls were excluded, a total of 738 pairs remained for analysis.

Data Collection

Information from in-person interviews was collected on demographic characteristics, education, and smoking practices and on detailed residential history. The questionnaire also incorporated a detailed occupational history, including information on specific job exposures.

Methods of Radon Measurement

There was a mean of 9 homes per subject, of which 5 were in the Winnipeg metropolitan area. It was not clear whether these means reflect lifetime residency or residencies in an exposure-time window. Radon was measured in 3 of these homes, although it was not clear precisely what criteria were used to select homes. The authors identified a total of 7,745 homes to be measured. This number was reduced for homes that had been occupied for less than 1 year (6%), for refusals (11%), for homes that no longer existed, were commercial institutions, or could not be located (24%), or where the dosimeter was lost or damaged (2%). Radon measurements were obtained for 4,448 homes (57%).

Year-long monitoring of the bedroom and, if there was one, the basement was undertaken. The basement was selected to provide the maximal possible residential exposure. Year-long monitoring was achieved through the sequential placement of two 6 mo detectors.

The detectors were developed and calibrated in house by laboratories of the Bureau of Radiation and Medical Devices in the Department of National Health and Welfare. Although the in-house calibration might affect comparisons with other studies in overall mean radon concentration, it should have no effect on the evaluation of trends in the exposure-response relation.

Two exposure windows were defined: 5–30 yr and 5–15 yr before the date of enrollment in the study. For estimation of cumulative radon exposure, imputation of missing measurements used the mean concentration in living areas [122.10 Bqm-3 (3.3 pCiL-1)] or in basements [196.10 Bqm-3 (5.3 pCiL-1)].

Results

Available radon measurements covered about 67% and 80% of the exposure windows of 5–30 yr and 5–15 yr, respectively. For cases and controls mean radon concentrations were 114.7 Bqm-3 (3.1 pCiL-1) and 125.8 Bqm-3 (3.4 pCiL-1) for bedrooms and 188.7 Bqm-3 (5.1 pCiL-1) and 207.2 Bqm-3 (5.6 pCiL-1) for basements, respectively.

Preliminary analysis revealed that cases were significantly less educated than controls and somewhat less likely to be born in Canada, although almost

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-16 Distribution of cases and controls and adjusted odds ratiosa (OR) and confidence intervals (CI) by radon concentration in Winnipeg, Canada, case-control study (concentration level estimated from cumulative exposure)

 

Radon concentration (pCiL-1)

 

< 1.9

1.9–3.9

3.9–7.8

=7.8

Total

P for trend

Cases

92

488

118

40

738

 

Controls

84

453

153

48

738

 

OR

1.0

1.0

0.8

1.0

 

n.s.

95% CI

 

(0.6,1.5)

(0.5,1.4)

(0.7,1.5)

 

 

a ORs adjusted for education and smoking with analyses matched on age and sex.

Source: Létourneau and others 1994.

80% of the subjects were born in Canada. All analyses were adjusted for education and smoking status; age and sex were adjusted through the study matching. Table G-16 shows that there was no trend in the RRs with increasing TWA radon concentration in the bedrooms. Similar results hold for basement measurements. The results were similar when cases were restricted by histologic type.

Missouri Case-Control Study of Nonsmoking Females
Study Subjects

The Missouri study was a population-based case-control study of white non-smoking woman, defined as lifelong never-smokers or former smokers who ceased 15 yr or more before interview (Alavanja and others 1994). The study is summarized in Table G-17. Among former smokers, the median time since smoking cessation was 24 yr. Cases were women 30–84 yr old with primary lung-cancer who were reported to the Missouri Cancer Registry from June 1, 1986, to June 1, 1991. After exclusion of ineligible cases, interviews were completed on 618 cases. Radon measurements were obtained for 538 cases (83%); measurements were not obtained for 80 cases because of refusal, homes that were out of state or destroyed, or other reasons. Although all cases were confirmed when diagnosis was reported to the registry, a separate panel of experts was established to review available slides; 409 of the 538 cases (76%) were reviewed.

A population-based control sample of white nonsmoking women was randomly selected by using Missouri state driver's license files (age 30–64 yr) or files of the Health Care Financing Administration (age 65–84 yr). The controls were selected to match the age distribution of cases in 5-yr categories. Of the 1,527 controls who satisfied enrollment criteria, 1,402 (92%) agreed to an interview and 1,183 (77%) had at least one valid year-long a-x97;-track measurement.

Data Collection

An initial telephone questionnaire was used to screen eligible subjects. If a subject agreed to participate, a telephone-interview survey

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-17 Summary of results of Missouri case-control study of female never-smokers

Factor

Comment

Principal reference

Alavanja and others 1994.

Design

Case-control study of female never-smokers and long-term former smokers.

Study subjects

Cases: 618 women 30–84 yr old with primary lung-cancer listed with the Missouri Cancer Registry an June 1, 1986, to June 1, 1991, who never smoked or were long-term former smokers.

 

Controls: Population-based controls (1,527) selected from state drivers-license files or files of the Health Care Finance Administration, frequency matched by age.

 

Subjects in radon study: After refusals and other exclusions, 538 cases (87%) and 1,183 controls (78%) had at least 1 home in the 5–30 yr before enrollment measured for radon.

Lung-cancer histology

A histologic review, separate from registry notification, was conducted. From 409 cases, there were 262 adenocarcinomas (53.5%); other cell types were not reported.

Rn measurement protocol

Measurements: 1-yr a-x97;-track detectors in kitchen and in bedroom in all homes in Missouri occupied 1 yr or more from 5–30 yr before date of enrollment.

 

Missing: Radon measurements available for 74% of identified dwellings.

Rn measurements

Mean and median: Case and control values were the same, 1.8 pCiL-1 (mean) and 1.4 pCiL-1 (median). About 7% had homes above 4 pCiL-1.

Rn-exposure estimation

Exposure-time window: 5–30 yr before to case incidence or control interview.

 

Coverage: Mean 20 yr of residence corresponding to 78% of the exposure-time window.

 

Imputation for gaps: None for TWA radon concentration; missing values for cases and controls replaced with means all cases and controls, respectively.

Results

Overall: For quintile categories < 0.8, 0.8–1.2, 1.2–1.7, 1.7–2.5, and = 2.5 pCiL-1, RRs were 1.0, 1.0, 0.8, 0.9, and 1.2, P value for trend, 0.99 with continuous value for test and 0.19 with category means.

 

Histology: RR showed a suggestive trend with adenocarcinoma cell type; P value for trend was 0.31 with continuous and 0.04 with categoric radon values.

 

Smoking: No difference in RR trend with radon concentration for never-smokers or former smokers.

 

Subgroup analyses: Suggestive RR trend (P = 0.06) for data restricted to in-person interview. Since measured quantity, reason for differences uncertain.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

obtained information on demographic factors, occupational history, lifetime passive smoking, previous active smoking, diet, and previous diseases, and a detailed residential history.

Methods of Radon Measurement

For each subject, radon was measured in all homes in the state of Missouri occupied for at least 1 yr during the 30 yr before enrollment. One year-long a-track detector was placed in the bedroom and one in the kitchen. Every 3 mo, subject's homes were checked to see whether the dosimeters were still in place. Quality control procedures—blind inclusion of blank and spiked dosimeters and duplicate detectors—suggested excellent validity in the measurement protocol. A small subsample of 3-mo winter measurements had a mean value twice the year-long readings.

The time-weighted radon concentration was computed for each subject by using all available measurement data; gaps in the exposure window were ignored. Cumulative radon exposure was estimated for an exposure window of 5–30 yr before lung-cancer incidence for cases and before interview for controls. Missing values for cases or controls were set to the mean radon concentration data for cases or controls, respectively.

Questionnaire data revealed that the subject occupancy factor was 84%. No special adjustment for occupancy was carried out.

Results

An average of about 20 yr of occupancy in the exposure period of 5–30 yr was covered by measurement data, 78% of the residency time. Mean and median radon concentrations were the same for cases and for controls: 66.6 Bqm-3 (1.8 pCiL-1) and 51.8 Bqm-3 (1.4 pCiL-1), respectively.

RR results were presented by categories defined by quintiles; the mean for the highest radon-concentration category was 151.7 Bqm-3 (4.1 pCiL-1). Table G-18 shows no increase in age-adjusted RR with increasing radon concentration. The RRs were adjusted only for age, but the pattern was unaffected by further adjustment of RRs for previous smoking, pack-years of smoking, previous lung disease, education, or intake of saturated fat.

TABLE G-18 Distribution of cases and controls (males and females combined) and adjusted odds ratiosa (OR) and confidence intervals (CI) by quintiles of radon concentration in Missouri case-control study of female never-smokers

 

Radon concentration (pCiL-1)

 

< 0.8

0.8-1.2

1.2-1.7

1.7-2.5

= 2.5

Total

P for trend

Cases

112

112

93

99

122

538

 

Controls

233

242

233

252

223

1,183

 

OR

1.0

1.0

0.8

0.9

1.2

 

0.19

95% CI

 

(0.7,1.4)

(0.6,1.2)

(0.6,1.2)

(0.9,1.7)

 

 

a ORs adjusted for age.

Source: Alavanja and others in review.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

There was no RR trend with exposure within age categories or smoking status. Limiting cases to the 262 women with an adenocarcinoma cell type resulted in a suggestive RR trend. RRs for the 5 radon-concentration categories of Table G-18 were 1.0, 1.4, 1.1, 1.2, and 1.7; the p value for the test of linear trend was 0.04 when mean values for each category were used and 0.31 when continuous radon concentration.

Finnish Case-Control Study (Finland I)
Study Subjects

A population-based case-control study (denoted Finland I) of lung-cancer in men was conducted in southern Finland in 19 municipalities. As of 1980, about 65,000 males lived in these areas (Ruosteenoja 1991). The study is summarized in Table G-19. Cases consisted of lung-cancers diagnosed in men in the designated municipalities in 1980–1985. In the period 1980–1982, cases were identified from the Finnish Cancer Registry; the more-recent cases were accrued directly from the records of hospital that diagnose and treat lung-cancer. A total of 291 cases were available for study.

Controls were a random sample of all men in the Finnish Population Registry files who were living in the designed area on January 1, 1980. Controls were frequency-matched to the age profile of the cases. Controls were then sent a mail questionnaire to obtain information on tobacco use. From the returned questionnaires (91%), controls were further selected to match the smoking proportions of the cases; 10% never-smokers, 10% ex-smokers who quit before 1979, and 80% current smokers or recent ex-smokers. A total of 495 controls were enrolled into the study: 50 never-smokers, 50 ex-smokers, and 395 current smokers.

Data Collection

In-person interviews were conducted for cases and controls or, if they were deceased, with their next of kin. Information was collected on residential history, house type, smoking, education, and occupation.

Methods of Radon Measurements

The Finnish Centre for Radiation and Nuclear Safety conducted measurements of indoor radon concentrations in all dwellings occupied for 1 yr or more since 1950; a-track detectors were placed for 2 mo in the winter between November 1, 1986 and April 30, 1987.

For analysis, an exposure window was defined as the 25-yr period from 1950 to 1975. For homes that could not be measured, a regression equation developed by Mäkeläinen and others (1987) that accounted for housing type and other factors was applied to estimate radon concentration. For dwellings higher than the ground floor, radon concentration was assigned the value 51.8 Bqm-3 (1.4 pCiL-1). Two radon measures were calculated: the TWA radon concentration based on available measurements and a TWA radon concentration for the entire 25-yr period based on measured and estimated concentrations.

Results

A total of 238 cases and 434 controls were available for analysis after exclusion for nonresponse to interview or inability to locate the subject. At the time of interview, 88% of cases and 21% of controls were deceased.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-19 Summary of results of the Finnish case-control study

Factor

Comment (1991)

Principal references

Ruosteenoja 1991, Ruosteenoja and others 1996.

Design

Case-control study of males.

Study subjects

Cases: 238 males with primary lung-cancer diagnosed in 19 municipalities in Finland 1980–1985. For 1980–82 cases obtained from the Finnish Cancer Registry; from 1983–1985 cases from records of treatment hospitals.

 

Controls: Population-based sample of mean living in 19 municipalities on January 1, 1980, frequency matched by age category. With information on smoking from a mail questionnaire, a random sample of 10 never-smokers, 10 ex-smokers and 395 current smokers was selected to serve as controls.

Lung-cancer histology

238 cases: 91 (38.2%) squamous cell, 61 (25.6%) small cell, 18 (7.6%) adenocarcinomas, and 68 (28.6%) other or unknown.

Rn measurement protocol

Measurements: 2-mo a-track detectors in the living room or bedroom in all homes occupied 1 yr or more 1950–1975.

 

Missing: Radon measurements available for 50% of identified dwellings; and at least 1 measurement available for 76% of subjects.

Rn measurements

Mean or median: Not provided, but quintile cut-points indicate that 40% and 20% have concentrations above 4.7 and 7.4 pCiL-3, respectively.

Rn-exposure estimation

Exposure-time window: 25 yr between 195 to 75 or 5-10 y prior to case incidence or control interview.

 

Coverage: Mean 20 yr of residence corresponding to 78% of the exposure-time window.

 

Imputation for gaps: For TWA radon concentration, missing values were estimated on basis of regression of housing type, municipality and other factors.

Results

Overall: For quintile categories < 2.2, 2.2–3.4, 3.4–4.7, 4.7–7.4, and = 7.4 pCiL-1, RRs were 1.0, 1.1, 1.7, 1.9, and 1.1; and the P value for trend was not significant.

 

Smoking: Little effect of adjustment in pattern of RRs with radon concentration.

Subjects resided in a total of 1,393 homes during the 1950–1975 period and indoor radon measurements were conducted in 696 homes (50%). Radon measurements in at least one house were obtained for 171 cases (72%) and 342 controls (79%); in this subgroup, the mean residency time covered by measurement data was about 20 yr or about 80% of the exposure window.

It was not entirely clear, but there seemed to be little difference in results between TWA radon-concentration measures. The distribution of cases and controls by category concentration was not provided by the author; however,

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

RRs, adjusted for age and smoking, for 5 categories based on quintiles were 1.0, 1.1, 1.7, 1.9, and 1.1 (Ruosteenoja 1991).

Finnish Case-Control Study (Finland II)
Study Subjects

Subjects for this case-control study, denoted Finland II, were selected from a subset of records of the Finnish Population Registry on persons living in the same single-family house (called the index dwelling) from January 1, 1967, or earlier to the end of 1985 (Auvinen and others 1996). Cases eligible for the study consisted of all persons with lung-cancer diagnosed from January 1, 1986, to March 31, 1992, that were listed with the Finnish Cancer Registry. A total of 1,973 cases were identified. One control for each case was selected, matched by birth year and sex. The control had to be alive at the time of the diagnosis of the case. The investigators selected additional controls when possible, and a total of 2,885 controls were identified. There were 1,644 (83%) deceased cases and 326 (11%) deceased controls. The study is summarized in Table G-20.

Data Collection

In September 1992, a mail questionnaire was sent to subjects or their next of kin. Information was obtained on residential history, smoking habits and occupational exposures. Information was also obtained on the daily number of hours spent indoors in the 1960s and 1970s. Response rates for the mail questionnaire were 55% for cases and 54% for controls.

Methods of Radon Measurement

One-year measurements with track-etch devices were undertaken for all subjects for their index dwelling. In the winter of 1992–1993, residents were mailed a detector and instructed to place it in a bedroom or living room. The detectors were returned the next winter. Houses were excluded for a number of reasons, the most common being the building of new houses on the same locations as index dwellings, uncertain dates of construction, measurements of less than 150 days, uninhabitation, and extensive renovation. About 20% of houses were excluded for those reasons.

The authors estimated the relative precision of the 1-yr measurements as ±20% for concentrations below 50 Bqm-3 and ±15% for concentrations above 400 Bqm-3, with a systematic bias of less than 10%.

Results

After exclusions for incomplete questionnaires and missing radon measurements, data were available on 1,055 cases and 1,544 controls. The study had originally been designed as an individually matched study, so results were presented only for analyses restricted to 517 case-control pairs. However, the authors state that unmatched results based on all available data were similar to the results from the matched analysis.

The mean radon concentrations were 103 Bqm-3 for cases and 96 Bqm-3 for controls; the median was 67 for both groups. The median occupancy times were similar, 11.5 h/d for cases and 11.7 h/d for controls.

Median residence times in the index house were 37 yr for cases and 35 yr for

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-20 Summary of results of Finland-II case-control study

Factor

Comment (1991)

Principal reference

Auvinen and others 1996.

Design

Case-control study of males and females.

Study-subjects

Subjects were selected from the Finnish Population Registry of persons living in the same single-family house from January 1, 1967, or earlier until the end of 1985.

 

Cases: All lung-cancers diagnosed from January 1, 1986, to March 31, 1992, listed with the Finnish Cancer Registry; 1,973 cases were identified.

 

Controls: For each case, subject was matched by birth year and sex and alive at the time of the diagnosis of the case. Additional controls were selected when possible, and a total of 2,885 controls were identified. For the matched analysis, 517 pairs were available.

Lung-cancer histology

Histologic or cytologic confirmation was available on 92% of cases. In the final series, the distribution was 36% squamous, 14% small cell, 13% adenocarcinoma, 9% other, and 28% undefined. Sex distribution was not provided.

Rn measurement protocol

Measurements: One a-track detector was mailed to each subject with instructions for it to be placed in the bedroom or the living room.

 

Missing: About 20% of houses (subjects) were excluded due because of missing information or other problems with the index dwelling.

Rn measurements

Mean: Cases, 103 Bqm-3; and controls, 96 Bqm-3.

 

Median: 67 Bqm-3 for cases and controls.

Rn-exposure estimation

Exposure-time window: Defined by study design; medians for years in the index house, 38 yr for cases and 35 yr for controls; median occupancy times, 11.5 hr/d for cases and 11.7 hr/d for controls.

Results

Overall: For categories < 50, 50–99, 100–199, 200–399, and = 400 Bqm-3, adjusted RRs (and 95% CIs) were 1.0, 1.03 (0.8–1.3), 1.00 (0.8–1.3), 0.91 (0.6–1.4), and 1.14 (0.7–1.9). RRs similar when radon levels weighted by occupancy.

 

Histology: RR similar by cell type.

 

Smoking: RR patterns were similar within smoking categories.

controls, and 70% of cases and 76% of controls lived more than 30 yr in the index house. Although the design indicated a minimum of 19 yr of residency in the index house, registry information appears not to reflect actual residency. A total of 26 cases (5%) and 36 controls (7%) had less than 16 yr residency in the index house.

For indoor-radon categories of less than 50, 50–99, 100–199, 200–399, and = 400 Bqm-3, RRs (and 95% confidence intervals) adjusted for age, sex, and smoking were 1.0, 1.03 (0.8–1.3), 1.00 (0.8–1.3), 0.91 (0.6–1.4), and 1.14 (0.7–

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

1.9). RRs were similar when radon concentrations were weighted by occupancy or when adjusted for occupational asbestos exposure.

RRs were also similar when data were analyzed by histologic type of lung-cancer.

Israeli Case-Control Study
Study Subjects

This was a small hospital-based case-control study at the Rambam Medical Center in Israel, summarized in Table G-21. Subjects were consecutive patients with primary lung-cancer seen in the oncology ward in 1985-

TABLE G-21 Summary of results of Israeli case-control study

Factor

Comment (1991)

Principal reference

Biberman and others 1993.

Design

Hospital-based case-control study.

Study subjects

Cases: Two case groups defined on the basis of consecutive patients with primary lung-cancer at an oncology ward of the Rambam Medical Center in 1985–1989:35 cases with small-cell carcinoma (SCC) (including ever-smokers and never-smokers) and 26 cases with non-small-cell carcinoma (16 adenocarcinomas) who were never-smokers (NS). Cases must have live in Israel for at least 10 yr before diagnosis.

 

Controls: Patients without lung-cancer matched by sex and 5-yr age group who were admitted to the same hospital immediately after case admission and lived in Israel 10 yr or more.

 

Subjects in radon study: After exclusions and refusals, 52 cases and 43 controls were eligible; however, only 35 matched pairs (20 SCC pairs and 15 NS pairs) were available for analysis.

Rn measurement protocol

Measurements: a-track detectors placed for an average of 9 mo from June or July 1990 through April 1991.

Rn measurements

Median: For cases and controls, 1.09 and 0.9 pCiL-1 for SCC pairs and 0.9 and 1.07 pCiL-1 for NS pairs, respectively. Differences were not statistically significant. Overall mean concentration was 1.0 pCiL-1.

Rn-exposure estimation

Exposure-time window: None defined; measurement in current house only.

 

Coverage: 28 (80%) cases and 19 (54%) controls lived 20 yr or more in measured house; 15 (43%) cases and 13 (37%) controls lived 30 yr or more in measured house.

Results

Overall: No significant differences in median radon concentrations between cases and controls. RR for = 1 pCiL-1 compared with <1 pCiL-1 was 1.5 with 90% CI (0.4,5.4) for SCC pairs and 0.5 with 90% CI (0.1,2.2) for NS pairs.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

1989 (Biberman and others 1993). Two case groups were defined: 35 patients with small cell carcinoma (denoted the SCC group), including ever-smokers and never-smokers, and 26 patients with non-small cell carcinoma who were never-smokers (denoted the NS group and including 16 patients with adenocarcinoma). All subjects had to have lived in Israel 10 yr or more before diagnosis.

Controls were matched by sex and age group within 5 yr from admissions to the same hospital immediately after case admission. Controls were also limited to those who had lived 10 yr or more in Israel before admission.

A total of 52 cases and 43 controls were eligible; however, after refusals or an inability to obtain radon measurements, a total of 35 pairs were available for analysis (20 SCC pairs and 15 NS pairs).

Data Collection

Personal interviews with subjects or next of kin yielded information on residential, occupational, and smoking histories.

Methods of Radon Measurement

One a-track detector was placed in the bedroom of each subject in June-July 1990 and collected starting in April 1991. The detectors remained in place for a mean of 9 mo (Biberman and others 1993). Of the 70 dwellings, 33 (47%) were single-story or ground-floor units of multi-unit apartments. The geometric mean was 37 Bqm-3 (1.0 pCiL-1), and the range was 7.4-262.7 Bqm-3 (0.2-7.1 pCiL-1). Seven measurements were at or above 74 Bqm-3 (2 pCiL-1).

Results

In the SCC group, 17 subjects were males and 3 females; 19 subjects and 14 controls were ever-smokers. In the NS group, 4 subjects were males and 11 females; no subjects were smokers, and 2 controls were ever-smokers.

There was no significant difference in radon concentration between cases and controls for the SCC or NS groups. For cases and controls, median concentrations were 40.33 and 33.3 Bqm-3 (1.09 and 0.9 pCiL-1) for the SCC pairs and 32.93 to 39.59 Bqm-3 (0.89 and 1.07 pCiL-1) for the NS pairs. After adjustment for pack-years of cigarette use, the RR for 37 Bqm-3 (1.0 pCiL-1) compared with 37 Bqm-3 (1.0 pCiL-1) was 1.5 with a 90% CI of 0.4-5.4 for the SCC pairs and 0.5 with a 90% CI of 0.1–2.2 for the NS pairs. RRs were significantly increased for long-term residency on a ground floor for both case groups, but the interpretation of this result is clouded by other possible case-control differences for which no adjustment could be made.

Port Hope Case-Control Study

One of the earliest case-control studies to estimate indoor radon from direct measurements is summarized in Table G-22. This study was conducted in Port Hope, a town of about 10,000 residents on the north shore of Lake Ontario. In 1932, mining operations included processing of ore and the recovery of radium; after 1939, operations shifted to the production of uranium. Disposal of residue from the operations occurred on the plant site and in other designated areas. In 1953, modification of the operations resulted in use of demolition rubble and

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-22 Summary of results for the Port Hope case-control study

Factor

Comment (1991)

Principal reference

Lees and others 1987.

Design

Case-control study of males and females living in Port Hope, Ontario.

Study subjects

Cases: 27 lung-cancer cases diagnosed in 1969–1979, in persons who lived 7 yr or more in Port Hope, and were never employed at the uranium-refining plant.

 

Controls: 49 subjects matched on sex and date of birth, who lived 7 yr or more in Port Hope, with at least 1 of these years during the 7-yr period before the date of diagnosis of the matched case. One dead and 1 live control were matched to each deceased case, and 2 live controls were matched to each live case.

Lung-cancer histology

Cell types included 11 squamous cell carcinomas, 6 adenocarcinoma, and 11 unknown.

Rn progeny protocol

Measurements: Precise protocol was not provided, but apparently measurements were of WL.

WL measurements

Mean or median: Not provided.

Rn progeny exposure estimation

Exposure-time window: Estimates of exposure based on all estimation homes occupied in Port Hope since 1933. Residences outside Port Hope area were ignored. Exposure estimates in WLM and adjusted by a background exposure of 0.229 WLM/yr. On basis of WLM distributions, it was estimated that for cases and controls mean WLMs were 2.7 and 0.5, including 33% and 49% with ''zero" WLM exposure (below estimated background exposure), respectively; among exposed, means were 4.1 and 1.0 WLM.

Results

Overall RR of 1.55 with 95% CI (0.6,4.1) and with adjustment for smoking RR of 2.36 with 95% CI (0.8,7.1).

reclaimed building materials throughout the town for various construction purposes (Lees and others 1987).

Study Subjects

Subjects were defined as persons who died of lung-cancer in 1969–1979 and who lived in Port Hope for 7 yr or more before the year of diagnosis. Cases were identified through the Provincial Cancer Registry and by contacting local physicians.

For each case, 2 controls, matched on sex and year of birth, were selected from among persons who had lived in Port Hope for 7 yr or more, with at least 1 yr during the 7-yr period before the date of diagnosis of the matched case.

Persons were excluded if they had worked in the uranium-refining plant or if they did not meet residency requirements. After exclusions, 27 lung-cancer cases and 57 matched controls were studied.

Data Collection

Data were collected by personal interviews with subjects or next of kin, including information on residential, occupational, and smoking histories.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×
Methods of Radon Measurement

The protocol used to measure radon or radon progeny in homes was not given in Lees and others (1987). However, the authors indicate that in 1976 a "complete survey of the town was undertaken to delineate radiation contaminated areas and measure radon levels." It was not stated what was measured, but for the analysis exposure of each subject was estimated in cumulative Jhm-3 (WLM), on the basis of all houses occupied in Port Hope from 1933. Estimated values were adjusted to exclude background exposures, on the basis of an estimate 0.0008015 Jhm-3/yr (0.229 WLM/yr) and the assumption that a "worker" and a "nonworker" spend 60% and 85% of the year, respectively, inside the house.

Results

After adjustment of exposures, 67% of cases and 51% of controls had "nonzero" exposures. Among the exposed, mean exposures were 0.01435 and 0.0035 Jhm-3 (4.1 and 1.0 WLM) for cases and controls, respectively. The matched RR estimate for exposure was 1.55 (95% CI, 0.6–4.1) without adjustment for smoking status and 2.36 (95% CI, 0.8–7.1) with adjustment for smoking status.

Case-Control Studies of Indoor Radon in Progress

Extrapolations from miner studies suggest that lung-cancer risk posed by indoor radon exposure may be a potentially important public-health problem. There have been substantial interest in obtaining direct evidence of harmful effects of indoor radon to validate miner-based extrapolations and to identify an upper bound of the risk. Few studies have been published, and difficult design issues remain in the conduct of the studies (Lubin and others 1990a, 1995c; Stidley and Samet 1993). To expand the base of information on the consequences of indoor radon exposure, several case-control studies are under way. Table G-23 lists these studies, which total some 13,000 lung-cancer cases.

SUMMARY OF STUDIES OF LUNG CANCER AND INDOOR RADON

In this section, we provide an overall perspective from the various studies of residential radon, including results of a meta-analysis of current indoor-radon studies.

Ecologic Studies

Ecologic studies are limited by the inability to estimate relevant exposures, by the presence of an extremely strong risk factor for lung-cancer (cigarette-smoking), and by the intrinsic confounding arising from regression analyses that use summary data and model misspecification We conclude that ecologic studies are noninformative for estimating risks posed by exposure to indoor radon or for evaluating a potential threshold exposure below which radon-progeny exposure would not be harmful.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-23 Summary of continuing studies of residential radon and lung-cancer risk

Country

Location

Cases

Controls

Estimated completion date

Comments

European studies:

Belgium-France

Ardennes-Eiffel

1,200

1996

France

Brittany

600

1,200

1996

Germany

Western

2,500

 

1996

 

Eastern

1,500

 

1997

 

Tyrol

250

 

1997

Sweden

 

480

 

1998

United Kingdom

Cornwall and Devon

986

 

1997

North American studies:

Canada

800

 

1998

Includes only never-smoking subjects

United States

Connecticut

960

 

1995

Jointly conducted with Utah

 

Iowa

450

 

1998

Includes subjects with at least 20 yr in current house

 

Missouri

700

 

1996

Extension of previous study, but includes ever-smoking and never-smoking women

 

New Jersey

787

 

1995

 

 

Utah

600

 

1997

Jointly conducted with Connecticut

Other:

China

Gansu Province

900

1,800

1997

About 50% of population live in homes built below ground level

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Case-Control Studies

Qualitative Summary of Results

Results of epidemiologic studies of indoor radon concentration and lung-cancer that used surrogate measures were generally consistent with increased risk at higher exposures. Their interpretation is complicated by the inability to link the surrogate measure directly to an estimate of exposure to radon progeny for the study participants. Thus, although the results of these studies are an important step in establishing a link between residential radon and lung-cancer risk, their direct relevance in assessing either the risk posed by indoor exposure or the validity of miner-based risk extrapolations is limited. The most relevant epidemiologic studies of lung-cancer are those which used in-home measurements of radon to estimate exposure, in that direct measurements provide the most accurate estimates of exposure. Eight major case-control studies have been reported that included direct radon measurements, along with a pooled analysis of 3 of the studies and a meta-analysis of the major studies.

Table G-24 summarizes the sizes of the various studies, the radon concentrations and overall results. The highest radon concentrations were found in the Finland's-I study [mean, 210.9 Bqm-3 (5.7 pCiL-1 )], and the next highest in the Stockholm study [mean, 129.5 Bqm-3 (3.5 pCiL-1)] and Winnipeg study (mean, 118.4 and 199.8 Bqm-3 (3.2 and 5.4 pCiL-1) in the living room and basement, respectively). Intermeditate radon concentrations were measured in the Swedish national study [mean, 107.3 Bqm-3 (2.9 pCiL-1)], the Finland-II study [mean, 99.9 Bqm-3 (2.7 pCiL-1)], and the Shenyang study [median, 85.1 Bqm-3 (2.3 pCiL-1)]; and the lowest concentrations were measured in the New Jersey study [median, 22.2 Bqm-3 (0.6 pCiL-1)]. The relationship of the measurement information for both the Swedish national study and the Finland-I study relative to the other studies is uncertain, inasmuch as radon was measured in winter, with detectors placed for 3 and 2 mo, respectively.

Comparisons of results from subgroup analyses provide an additional framework for evaluating consistency among studies. Variations of risk patterns within subgroups and inconsistencies between studies compel a cautious interpretation of results. Three studies—Shenyang, Winnipeg, and Finland-II—found no association with exposure overall and after intense subgroup analysis. Results of the other studies offer mixed support for a positive association. In Finland-I, RRs exceeded 1.0 for all radon categories, but there was no significant trend with increasing radon concentration and the highest category had a low RR. In New Jersey, there was a significant linear trend, but RRs for radon categories, of less than 1.0, 1.0–1.9, 2.0–3.9, and at least 4.0 pCiL-1. were, 1.2, 1.2, 1.3, and 8.7, indicating that the trend was strongly influenced by the highest category, which included 5 cases and 1 controls. In Stockholm, there was a significant trend with radon concentration; however, the trend was affected by occupancy or when

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-24 Summary of results from case-control studies of residential radon exposure

Study

Cases

Controls

Rn levl- pCiL-1 (med/mean)

Comment

Finland-I

238

415

40% > 4.7

20% > 7.4

Results show only a modest suggestion of an overall trend with increasing radon level, but all RRs exceeded 1.

Finland-II

517

517

cases, 103 Bqm-3 (mean); controls, 96 Bqm-3 (mean)

Results show no overall trend. Residential occupancy less than 12 h/d.

Israel

35

35

1.0 (mean)

Study has few cases; radon concentrations are very low; no conclusions can be drawn.

Missouri

538

1,183

cases, 1.8 (mean); controls, 1.8 (mean)

Results show no trend with increasing radon level; suggestive trends were found when analyses restricted to adenocarcinoma cases or in-person interviews.

New Jersey

480

442

cases, 0.5 (med) controls, 0.5 (med)

Significant exposure-response trend, but mean exposures very low and results influenced strongly by highest exposure category with 5 cases and 1 control.

Port Hope

27

49

cases, 2.7a (mean); controls, 0.5a (mean)

Nonsignificant excess relative risk with or without adjustment for smoking.

Shenyang

308

356

cases, 2.8 (med); controls, 2.9 (med)

Results show no increasing RR with increasing radon level, overall and within categories of indoor air pollution.

Stockholm

201

378

cases, 3.1 (med); controls, 2.9 (med)

Results suggest positive increase, but cautious interpretation indicated because trend depends on cut-points and disappears after adjustment for occupancy or with BEIR IV weighting.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Study

Cases

Controls

Rn levl- pCiL-1 (med/mean)

Comment

Sweden

1,281

2,576

1.5 (med)

RRs increase significantly with increasing radon level; RR patterns similar by histologic type and homogeneous across categories for never-smoker, ex-smoker, and number cigarettes per day.

Winnipeg

738

738

cases, 3.1 (mean); controls, 3.4 (mean)

Results show no increasing RR with increasing radon level, as measured in living area or in basement.

a Estimated cumulative radon-progeny exposure in WLM.

exposures more than 15 yr before were given half the weight. Furthermore, it was found that the p value for the test of trend differed when continuous Bqm-3 (pCiL-1) was used as the quantitative value in the test statistic, as opposed to category-specific means. The Swedish national study offered the clearest pattern of increasing RR trend with radon concentration.

Subgroup analyses revealed inconsistencies within and between studies. In New Jersey, there was no trend in the RRs with radon concentration among never-smokers, a positive trend in light smokers (under 25 cigarettes/d), and a negative trend in heavy smokers (at least 25 cigarettes/d); in Stockholm the trend was observed only in never-smokers and in heavy smokers (at least 20 cigarettes/ d); and in the Swedish national study trends, were the same for never-smokers, ex-smokers, and current smokers. In New Jersey, the RR trend was steepest when the case group was restricted to large cell carcinomas (a relatively rare histologic type); in Stockholm, trends were most apparent with small and squamous cell carcinoma; and in Sweden, there was no difference by histologic type. By way of comparison, in miners, there is suggestive evidence that radon-progeny exposure might be more closely associated with small cell carcinoma (Land and others 1993; Yao and others 1994) and adenocarcinoma (Yao and others 1994).

Quantitative Summary Based on Pooled Analysis of Pooled Data from 3 Studies

Results from studies of indoor radon and lung-cancer are quantitatively summarized by either pooling data (Chekoway 1991; Friedenreich 1993) or con-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

ducting meta-analysis (Greenland 1987; Thacker 1988). In the former approach, original, primary data from multiple studies are combined and analyzed jointly. In the latter approach, only data from published papers are used (Glass 1976); that is, the study is the unit of analysis (Greenland 1987). Both approaches have well-known limitations due to differences among the studies in design, type and method of data collection, source population, quality-control procedures, information on important confounding variables, and time (Friedenreich 1993; Thacker 1988). Meta-analysis have added burdens associated with the need to rely on information that is available only in the published papers; that limits flexibility to assess the exposure of interest, adjust for important confounders, and evaluate subtle effects (Greenland 1984; Oakes 1990; Petitti 1994; Shapiro 1994).

An analysis of pooled primary data from residential case-control studies in New Jersey, Shenyang, and Stockholm—including almost 1,000 cases—concluded that these 3 studies were consistent with each other and that any differences among them could have arisen by chance (Lubin and others 1994b). The study-specific estimates of RR and 95% CIs at 150 per Bqm-3 based on fitted linear excess-RR models were 1.7 (0.8–3.8), 0.9 (0.0–1.2), and 1.2 (0.8–2.4), respectively. The combined exposure-response relationship showed no trend, with a pooled RR estimate of 1.0 with 95% CI (0.8–1.3) at 150 per Bqm-3. Results suggest that RRs were consistent with no effect of exposure; however, results were also consistent with extrapolations from miners.

Quantitative Summary Based on Meta-Analysis of 8 Studies

A recent meta-analysis involved the 8 studies that had enrolled 200 or more lung-cancer cases is listed in Table G-24 (and shown in figure G-1) (Lubin and Boice 1997). Overall, 4,263 lung-cancer cases and 6,612 controls contributed to the meta-analysis. Figure G-1 suggests that RRs from indoor studies are consistent with the extrapolation based on miner studies, but also that RRs are quite variable. The Cls for the individual RRs are large, suggesting that results are also consistent with no effect of radon concentration. However, more of the RRs exceeded 1.0 than were less than 1.0, and there was a general tendency for higher RRs with higher radon concentrations.

Lubin and Boice (1997) obtained RR estimates and 95% Cls for categories of radon concentration in Bqm-3 from published results and carried out weighted linear-regression analyses of the natural logarithm of the RR estimates using inverse variances as weights (Draper and Smith 1966). For each study, a loglinear RR model that passed through the quantitative value for the baseline category was fitted. For exposure at concentration x, the regression model was

log[RR(x;x0)] = ß (x - x0), (1)

where x0 was the exposure for the referent category and ß the unknown exposure-response parameter. Model (1) was fitted to each study, and an esti-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

mate of ßi, denoted ßi, was obtained. A summary estimate for ß1,...,ß8 was obtained with the same 2-step approach used by the committee in its analysis of miners.

Except for the Finland-I study, loglinear models provided good fits to the RR from the individual studies (Figure G-2), and there were no significant deviations from linearity. The study-specific values for the exponential of the estimates in units of 150 Bqm-3, that is, exp(ßi×150), are shown in Table G-25. The fitted RRs at 150 Bqm -3 ranged from 0.8 to 1.8. A test of homogeneity of the estimates was rejected (p < 0.001). The fitted RR at 150 Bqm-3 was exp(0.0009×150)= 1.14 with 95% CI of (1.0–1.3).

The baseline categories for the RRs differed for the various studies. RRs for each category and for each study were adjusted to a baseline concentration of "zero" radon (that is, ambient concentrations) by multiplying each RR by exp(ßix0i), where x0i was the concentration for the baseline category and ßi the estimate for the ith study. With the adjusted RRs, 5 categories of radon concentration were created on the basis of quintiles, less than 55.4, 55.5–88.7, 88.8–142.2, 142.3–250.8, and at least 250.9 Bqm-3. Estimates of RR and 95% CIs for the 5 categories were 1.0, 1.05 (0.9–1.2), 1.05 (0.9–1.2), 1.25 (1.0–1.5), and 1.20 (1.0–1.4). Those RRs were in turn adjusted to a zero baseline by multiplying by exp(ßx0), where x0 was the mean concentration for the lowest radon category, 34.2 Bqm-3, and ß the parameter estimate. Figure 3-2 presented earlier in chapter 3 shows the adjusted RRs (solid squares). The figure also shows that the summary loglinear model, log[RR(x)]= 0.009x, provided a good fit to the data.

Mean cumulative exposure in the miner studies was over 20 times greater than living 30 yr in an average US house at the mean concentration of 46 Bqm-3. With data from the < 0.175 Jhm-3 (< 50 WLM) restricted analysis of miners (see page 3–15), RRs in miners were compared with RRs from the residential studies. A correspondence between exposures for miners in Jhm-3 (WLM) and radon concentrations in homes in Bqm-3 was made assuming 30 yr of exposure, standard residential occupancy assumptions [living for 1 yr in a house at 37 Bqm-3 and assuming 70% occupancy, and 0.4 equilibrium factor is approximately equal to 0.00014 Jhm-3 (0.4 WLM) of exposure], and a 1.0 K factor. For example, a miner exposed to 0.0875 Jhm-3 (25 WLM) was assumed to have about the same exposure as a person living 30 yr in a house with a radon concentration of 220 Bqm-3 [= 37 × 25 WLM/(30 yr × 0.14 × 1.0)]. For miners, RRs were calculated for 0, 1–9, 10–19, 20–29, 30–39, and 40–49 WLM. Figure 3-1 shows RRs and 95% CIs from the miner data (open squares).

The estimate for RR from a loglinear model fitted to the miner RRs under 0. 175 Jhm-3 (50 WLM) was 1.13 at 150 Bqm-3 with a 95 % CI of 1.0–1.2, essentially the same as the 1.14 (1.0, 1.3) estimate from the meta-analysis of residential studies. Thus, RRs for miner exposures under 0.175 Jhm-3 (50 WLM) were similar to extrapolations with the miner-based risk model (Figure G-1), devel-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

FIGURE G-2 Relative risks for radon-concentration categories and fitted exposure-response models for each case-control study. Fitted lines adjusted to pass through quantitative value for baseline category.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×
Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

oped from data with generally higher exposures, and similar to the RRs from the indoor studies.

Results from the indoor case-control studies do not provide direct information on lifetime risks posed by radon exposure. The excess risk of 14% at 150 Bqm-3 corresponds to only 30 years of exposure in a house at a constant radon concentration and hence does not reflect the risk of lung-cancer following lifetime exposure, where the estimated excess lifetime relative risk at 150 Bqm-3 based on the miner models is 40 to 50% (Table 3-6). Estimated relative risks from indoor studies and from miner-based models reflect a 30-year exposure period at 148 Bqm-3 and not lifetime exposures at this level. Thus, if exposures outside this 30-year period influence lung-cancer risk, as suggested by the miner data, then the 14% excess relative risk at 148 Bqm-3 from indoor studies is a

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-25 Estimates of relative risk (RR) at 150 Bqm-3 and the 95% confidence interval (CI) each study and for all studies combined

Study

RRa

95% CI

Reported in original paperb

Finland-Ic

1.30

(1.09,1.55)

N.A.

Finland-II

1.01

(0.94,1.09)

1.02

New Jersey

1.83

(1.15,2.90)

1.77

Shenyang

0.84

(0.78,0.91)

0.92d

Winnipeg

0.96

(0.86,1.08)

0.97

Stockholm

1.83

(1.34,2.50)

1.79

Sweden

1.20

(1.13,1.27)

1.15

Missouri

1.12

(0.92,1.36)

N.A.

Combinede

1.14

(1.01,1.30)

a Values shown are estimated RR at 150 Bqm-3 that is, exp(ß × 150), where ß was obtained from a weighted linear regression fitting the model log(RR) = ß(x - x0), where x0 is the quantitative value for the lowest radon category and x is the category-specific radon level.

b RR at 150 Bqm-3, on the basis of computed from exposure-response relationship provided in original reports. Exposure-response data not available (N.A.) in Finland-I and Missouri studies.

c For Finland-I, there was a significant departure from linearity (P = 0.03). Estimated RR for 150 Bqm-3 with linear-quadratic model was 1.71.

d Taken from results in pooled analysis (Lubin and others 1994a).

e Combined estimate and confidence interval based on random-effects model. Fixed effects estimate was 1.11 with 95% CI (1.07,1.15).

biased estimate of the lifetime relative risk at this concentration and therefore cannot be used to estimate attributable risks for a population.

In the meta-analysis, study-specific exposure-response estimates differed significantly. In an attempt to explain the differences, values for overall mean radon level, percentage of exposure interval covered by radon-measurement data, mean number of homes per subject, mean number of measured homes per subject, percent of cases who smoked, percentage of eligible subjects included in the radon analysis, percentage of homes with year-long radon measurements, percentage living subjects, and percentage female subjects were obtained for each study. None of those variables, individually or jointly, explained the heterogeneity in the study-specific exposure-response estimates.

For the meta-analysis an influence analysis, in which summary estimates were computed on the basis of 7 of 8 studies, indicated that the overall estimates change very little when any single study is omitted.

In summary, there was a significant exposure-response relationship in the meta-analysis by Lubin and Boice (1997) with an estimated RR at 150 Bqm-3 of 1.14, and results were generally confirmatory of miner-based extrapolations of risk and with RR among the least-exposed miners. However, meta-analysis are known to have numerous limitations, including an inability to explore adequately the consistency of results within and between studies and to control for poten-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

tially important confounding factors. Nonetheless, the results are consistent with a small effect on lung-cancer associated with exposure to indoor radon progeny.

Finally, the results of the ecologic analysis by Cohen (1995) can be compared with the results of the meta-analysis. In his analysis, Cohen fitted a linear model that resulted in a declining linear excess-RR trend of 0.002/Bqm-3. Figure 3-2 compares the ecologic regression line with RRs from residential studies and from miner studies. It is clear that the negative exposure-response relationship is contradicted by both the miner data and the data from the indoor radon studies.

DESIGN LIMITATIONS OF INDOOR-RADON STUDIES

If miner studies are so unequivocal in showing the carcinogenicity of radon, why are results from current studies of indoor radon, particularly those which include measurements of indoor radon, variable and relatively inconclusive? Case-control studies of lung-cancer and indoor radon are, of course, limited by factors that affect any epidemiologic study as summarized in Table G-26 (Lubin and others 1990a). Inadequate design elements might result in reduced power for a study to detect a significant effect and in biased or confounded estimates. However, studies of lung-cancer and indoor radon have unique features that place additional burdens on the accurate assessment of the effects of exposure and the attainment of sufficient study power (Table G-27):

  • The use of miner-based extrapolations provides uncertain estimates of the size of the RR in homes, although expected RRs are very small—an RR in the range of 1.1–1.3 for a 25-yr exposure at 148 Bqm-3 (4 pCiL -1). For a case-control study, this implies that the distribution of exposures for cases is very similar to the distribution of exposures for controls. As a consequence, substantial numbers of subjects are needed to establish a significant difference in the distributions and

TABLE G-26 Potential limiting factors of case-control studies of indoor radon and lung-cancer

Error in estimation of radon exposure

Errors in estimation of tobacco use and other potential confounders

Data missing because of nonresponse

To interview

To radon measurement

From use of surrogate responders

Misclassification of disease

Identification of appropriate target population for selection of controls

Inappropriate design assumptions for accurate assessment of sample size and power:

Incorrect specification of dose-response

Incorrect specification of true exposure distribution

Failure to consider consequences of residential mobility

Failure to consider effects of random error in exposure assessment

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-27 Sources of error in estimation of cumulative indoor radon progeny exposure

Errors related to measurement of radon:

Counting error for a-track device

Possible effects of airborne contaminants

Measurement at fixed location in room

Measurements limited to 1 or 2 rooms only

Diurnal and seasonal variation

Use of contemporary measurements to characterize past levels

Sources of errors in duration of exposure:

Variation in occupancy over time

Imprecision of estimate of occupancy time

Radon exposures occurring outside home

Measurement gaps for homes within exposure period

Exposure as duration times mean exposure rate as an approximation of time-integrated exposure rate

Conversion of radon concentration to WLa

a WL denotes working levels, the unit of radon progeny measured in studies of underground mines.

Conversion of radon to radon progeny is needed to estimate risk based on miner models.

to estimate effects precisely. In addition, because the distribution of radon concentrations is skewed, few homes exceed 148 Bqm-3 (4 pCiL-1); in the United States, only 5–7% of homes are estimated to exceed this level (EPA 1991; Marcinowski and others 1994).

  • Subjects usually live in many homes during their lifetimes, thereby narrowing the range of exposures in the target population and reducing study power. The consequences of residential mobility can be demonstrated with an extreme example: If every member of the population moved every day and radon levels in homes were statistically independent, the total exposure of each subject after, say, 25 yr would be about 25 times the mean exposure rate; thus, there would be little or no exposure variation in the population, and this would complicate the detection of any risk.

  • The use of contemporary measurements in current and past homes results in exposures estimated with great imprecision. Unless those formidable limitations can be addressed—with new measurement technologies, with studies in low-mobility or high-exposure populations, or with the pooling of data—it is uncertain whether definitive results can ever be achieved.

EFFECTS OF ERROR, MOBILITY, AND MISSING DATA ON INDOOR-RADON STUDIES

The pattern of lung-cancer risk in miners suggests that exposures in the preceding 5–30 yr are the most relevant for estimating radon-associated lung-

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

cancer risk (NRC 1988; Lubin and others 1994). That permits exposure-assessment efforts in residential studies to focus on more-recent years, which is fortunate because it is often impossible to locate residences and measure radon concentrations for homes in which subjects lived previously. However, the extent to which exposures before to the defined exposure-time window contribute to lung-cancer risk, then omitting them by design adds imprecision to the exposure estimates (Lubin and others 1990).

There is an important distinction between error in a measurement device and error in assessment of individual exposure. The most-common area dosimeter used in epidemiologic studies is the a-track detector; radon concentration is determined by counting the number of etched tracks made on plastic film by alpha particles, and the number of tracks is proportional to concentration (Alter and Fleischer 1981; Lovett 1969). Both the counting and measurement processes are subject to error, which has been estimated to be about 15–25% (Létourneau and others 1994; Yeager and others 1991). The error in the measurement process defines the absolute lower bound of the accuracy of any exposure assessment based on a-track devices.

Many other factors contribute to error in the estimation of personal exposure (Table G-27). Total exposure to radon progeny is the sum of exposures received in all environments, including the home, the workplace, and outdoors. a-track detectors are usually left in place for several months to a year. In some studies, concentration measurements from short-term devices (3–7 days) supplemented those from long-term devices that might have been lost or unusable. Residential radon concentrations vary daily and seasonally (Swedjemark 1985), and short-term measurements or single-season measurements might not provide an accurate characterization of year-long radon levels.

For analysis, radon exposure in a defined time window is often computed as the time-weighted average concentration (TWA) or cumulative exposure in Bqm-3-yr (or pCiL-1-yr). For TWA, gaps in the measurement data for previous homes are often ignored when there is more than 1 residence. That can induce bias. Suppose that 1 subject lived for 30 yr in a home measured at 150 Bqm-3 and a second subject lived for 15 yr in a home measured at the same level and 15 yr in an unmeasured home. If one ignores the missing data from the unmeasured home, each subject would have a computed TWA of 150 Bqm-3. However, because of regression toward the mean, the TWA for the latter subject is likely an overestimate. If coverage of the exposure-time window is related to case status, ignoring measurement gaps is potentially biasing. To minimize such biases, an imputation procedure for missing data with adjustment for the variance estimates of parameters would be the preferred approach (Weinberg and others 1996).

In indoor-radon studies, only current radon levels can be measured, and they might not accurately reflect those of 15–30 yr earlier because of tightening of homes for energy conservation or other modifications (Kendall and others 1994). In addition, measurements are typically made only in a few rooms of a house.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

Simulation Studies

The effects of errors in exposure, residential mobility, and the inability to measure radon concentrations in all homes in the exposure-time window were illustrated in a series of simulation studies by Lubin and others (1995), expanding earlier analyses of Lubin and others (1990).

Steps in the simulation of data are shown in Table G-28. Case-control studies with M = 700 cases and N = 700 controls were selected from independently generated populations of 10,000 persons, with an overall lung-cancer rate of 10%. Initially, it was assumed that each person lived in only 1 house. The lognormal distribution of US radon concentrations was used, with a geometric mean (GM) of 24.8 Bqm-3 and a geometric standard deviation (GSD) of 3.11 (Marcinowski and others 1994).

A multiplicative error (U) was assumed; In(U) was assumed to be normally distributed with a mean of 0 and a variance of t2. Measurement error was specified by exp(t) as 1.0 (no error), 1.50, 2.0, and 3.0, which roughly correspond to exposure errors of zero, ±50%, ±100%, and ±200%, respectively. For example, exp(t) = 2.0 implies that a true exposure of 0.07 Jhm-3 (20 WLM) will be estimated as 0.035–0.14 Jhm-3 (10–40 WLM). For comparison with current case-control studies, radon progeny exposures were rescaled on the basis 25 yr of exposure to radon concentration, and RRs were computed by categories of Bqm-3.

Simulations were also conducted to illustrate the effects of error, mobility, and missing radon-measurement data from past residences (Lubin and others 1995). Table G-29 provides an empirical calculation of study power for case-control studies with 700 cases and 700 controls and with 2,000 cases and 2,000

TABLE G-28 Steps in simulation study conducted by Lubin and others (1995)

1. For each individual, generate a true radon concentration by randomly sampling from a lognormal distribution with geometric mean 24.8 Bqm-3 and GSD 3.11. Convert to radon progeny exposure in WLM on the basis of 25 yr of exposurea (X), multiplying by (0.18/37)25yr, where the first factor represents the conversion under standard assumptions of 1 yr residence in a house at 1 Bqm-3 to exposure in WLM/yr.a

2. Compute the probability of lung-cancer, on the basis of P(D = 1|X) = ea(1+bX){1+ea(1+bX)}-1, with a and b specified. Randomly sample from a uniform 0-1 distribution to determine disease status D.

3. Include a multiplicative error, U, by randomly sampling from a lognormal distribution, where ln(U) is normal with mean 0 and variance t2, and create an observed exposure Z = XU.

4. Repeat steps 1–3 10,000 times to generate a population.

5. Select M disease cases and N controls, categorize radon concentration, and compute RRs and test statistics, using continuous radon concentration as the quantitative variable.

6. Repeat steps 1–5 to generate each simulated case-control data set.

a Initial assumption was 25 yr of occupancy in a single house. This assumption was later relaxed.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-29 The percentage of times P value for score test of no linear trend in relative risk with exposure is less than 0.05, based on 1,000 simulated case-control studiesa

 

Number of homes occupied in 5 to 30 yr exposure windowb

 

1

2

 

3

 

 

Error distributionc: exp(t)

Percent coverage of exposure-time window

100%

100%

50%

100%

67%

33%

 

Study size: 700 cases and 700 controls

1.0

45.0

30.6

17.1

28.2

24.2

11.5

1.5

41.4

26.6

16.6

24.9

16.4

10.8

2.0

29.4

18.8

12.7

9.4

9.2

6.8

3.0

17.1

11.8

7.2

6.4

8.6

5.8

 

Study size: 2,000 cases and 2,000 controls

1.0

89.8

73.6

46.0

60.8

52.6

32.1

1.5

84.8

66.8

44.1

55.1

42.1

29.4

2.0

71.0

54.0

35.6

34.4

26.6

23.5

3.0

40.8

32.9

22.0

23.6

14.6

13.0

a Risk is based on a 0.10 background rate of lung-cancer and an excess relative risk of 0.015 per working level month. Exposure is based on 25 yr of residence and a lognormal radon concentration distribution with geometric mean 24.8 Bqm-3 and geometric standard deviation 3.11.

b For multiple homes, it is assumed that equal numbers of years are spent in each home. Thus, for 2 homes, 50% indicates that 12.5 yr of the exposure-time window was covered by radon-measurement data, for 3 homes, 33% and 67% indicate that 8.3 and 16.7 yr of the exposure window were covered by measurement data, respectively.

c The multiplicative error distribution is assumed to be lognormal, with the logarithm of the error having mean 0 and variance t2. The row with exp(t) = 1 shows results when exposure is measured without error.

controls, that is, the percentage of 1,000 simulated studies that rejected the null hypothesis of a radon effect. The table shows that a study with 700 cases and 700 controls, in which all subjects lived in a single residence for 30 yr and exposure is measured without error, has a power of 0.45 of rejecting a hypothesis test of no exposure effect when the true trend is 0.015/WLM. With 2,000 cases and 2,000 controls, the study has a power of 0.90. The table also illustrates the marked decline in power with increasing exposure error and mobility and with decreasing coverage of the exposure-time window.

Sample Sizes for Case-Control Studies

Table G-30 shows the number of cases required for a study designed to have 90% power to reject a null hypothesis based on a 2-sided 0.05-level test if the alternative, b = 0.015 WLM, were true (Lubin and others 1995). This table updates the sample sizes provided in Lubin and others (1990a). With typical

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

TABLE G-30 The effects of measurement error, exp(t), and mobility on sample sizea (entries are number of lung-cancer cases required)

 

Mobility pattern

Exp(t)b

1 × 25 yr

2 × 12.5 yr

3 × 8.3 yr

 

Control-to-case ratio = 1:1

1.0

2,033

2,447

3,408

1.5

2,521

3,292

4,879

2.0

3,716

5,365

8,484

3.0

8,429

13,530

22,694

 

Control-to-case ratio 2:1

1.0

1,488

1,810

2,530

1.5

1,846

2,437

3,626

2.0

2,724

3,974

6,311

3.0

6,183

10,034

16,895

a Study required to have 90% power to reject a trend in radon exposure, b = 0, when the true trend is b = 0.015, using a 2-sided 0.05-level test. Exposure based on 25 yr of exposure and occupancy in 1, 2, or 3 houses.

b It is assumed that error is multiplicative and the logarithm of the error is normally distributed with mean 0 and variance t2.

mobility and with exp(t) about 1.5–3.0, about 5,000–18,000 lung-cancer cases and an equal number of controls would be needed, or about 4,000–13,000 cases and twice the number of controls. Those numbers should be interpreted cautiously, perhaps as a lower bound, because calculations do not account for unmeasured houses and adjustment of other risk factors.

CONCLUSIONS

Accurate exposure estimation is essential for any study of lung-cancer and indoor radon. Estimating past exposures is a formidable task, and a present-day measurement, even if made for an entire year, might not accurately reflect radon concentrations of 30 yr ago or earlier. Exposure assessment is further burdened by subject mobility, which decreases the range of exposures in a population and thereby decreases study power. Mobility also creates the potential for gaps in the reconstruction of exposure histories because of an inability to measure all previous houses. When reasonable assumptions are made about measurement errors, mobility and gaps in the exposure-time window, any calculated dose-response relationship will probably be consistent with no exposure effect unless there are substantial numbers of cases and controls. On the basis of those observations, the committee concludes that the seeming inconsistency among case-control studies to date is in large part an inherent consequence of errors in dosimetry and residential mobility.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

In recent years, new statistical techniques have been developed for analyses of case-control data that attempt to take errors in exposure assessment into account. The validity of the techniques and a resulting ''corrected" risk estimate require direct information on the form of the error distribution. Thus, the estimation of the true effects of residential radon exposure could be enhanced by the collection of data that allows an evaluation of exposure errors.

The ability to estimate lung-cancer risk from indoor-radon studies is much more complex than the simple computer simulations, which were based only on measurement errors, considered only simple residential mobility patterns, and were defined by an ideal situation: occupancy known exactly, no variation in the equilibrium of radon with its decay products, and no misspecification of disease status. In reality, radon studies suffer from further uncertainties arising from a variable relationship between exposure and dose and from the potential confounding and potentiating effect of tobacco smoke, both active and passive, and the possible presence of other factors, such as indoor air quality or occupational exposures, which may also be measured only imprecisely.

Computer simulations document that small predicted levels of risk and misspecification of radon exposures contribute to the mixed results of current radon case-control studies. The public is perplexed by the seemingly conflicting results and uncertain as to the existence of an adverse effect. Although many of the newer studies are larger than published studies, the marked reduction in study power from (random) errors in exposure suggests that results from the newer studies might also be mixed (Samet 1994).

In the long term, several steps can help to address problems caused by extensive exposure-assessment errors. The most obvious is improvement in estimating exposures, which can be accomplished by selection of a stable target population so that the potential for gaps in exposure measurements is minimized or by using of improved technology for the measurement of radon concentrations.

The power of an indoor-radon study to detect an excess risk could also be enhanced by targeting special populations, such as a population with high exposures, a broad range of exposures, and low residential mobility.

Case-control studies of residential radon are limited by the generally low dose of alpha energy delivered to the lung, which reflects the low radon concentrations to which most of us are exposed every day. The anticipated excess risk is small and not readily measured, because of errors that affect estimation of exposure. On the basis of results of the simulations, the committee concludes the following:

  • Because of error intrinsic in the measurement and estimation of prior radon exposures, a single study cannot be expected to provide sufficiently precise lung-cancer risk estimates.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×
  • The inconsistencies in existing indoor radon concentrations are not surprising and are probably the consequence of mobility and errors in dosimetry related to missing radon measurements and poor exposure assessment.

  • With increased residential mobility and errors in dosimetry, it is virtually impossible practically to distinguish between studies for which an underlying radon effect is assumed and studies for which no radon risk exists.

  • Investigators are encouraged to include procedures to estimate the distribution of exposure errors in the design of indoor-radon studies, and analyses of studies should adjust for exposure errors.

  • Additional studies of the consequences of missing exposure data within the exposure-time window, of ignoring the roughly 30% of time exposed to nonhome sources of radon progeny, and of incomplete coverage of radon concentrations in prior homes are needed.

  • Improved technologies are needed for the accurate estimation of prior radon-progeny exposure.

Combining data from prior and current studies should be encouraged. However, even with a large sample size a clear picture of lung-cancer risk posed by residential radon exposure might not arise, because the substantial influence of errors in radon-exposure assessment.

Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
×

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Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
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Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
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Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
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Suggested Citation:"Appendix E Exposures of Miners to Radon Progeny." National Research Council. 1999. Health Effects of Exposure to Radon: BEIR VI. Washington, DC: The National Academies Press. doi: 10.17226/5499.
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