Effects of exposures to two types of ionizing radiation on cancer mortality among Rocketdyne Atomics International workers
<-- LA Rocketdyne Nuclear Meltdown
Download: UCLA Final Report (PDF)
To the Public Health Institute
(Formerly the California Public Health Foundation)
Subcontract No. 324A-8701-S0163
Epidemiologic Study to Determine Possible Adverse
Effects to Rocketdyne/Atomics International Workers
from Exposure to Ionizing Radiation
Principal Investigator Hal Morgenstern, Ph.D.
Professor of Epidemiology
UCLA School of Public Health
Co-Principal Investigator John Froines, Ph.D.
Professor of Toxicology
UCLA School of Public Health
Co-Investigator & Study Coordinator Beate Ritz, M.D., Ph.D.
Assistant Professor of Epidemiology
UCLA School of Public Health
Co-Investigator Bambi Young, Ph.D., M.P.H.
UCLA School of Public Health
Background and Objective. In the early 1990s, a worker health study--discussed in this report--was initiated in response to strong concerns voiced by area residents about the use of radioactive and toxic substances at the Santa Susana Field Laboratory (SSFL) of Rocketdyne/Atomics International (AI), a Department of Energy contractor. Starting in the early 1950s, SSFL activities included the operation of nuclear reactors, handling of plutonium, and rocket-engine testing. This report will focus on the possible effects of exposures to two types of ionizing radiation on cancer mortality among Rocketdyne/AI workers: penetration of the body by gamma and X rays (external radiation); and the ingestion, inhalation, or absorption of alpha-emitting radionuclides such as uranium (internal radiation). Possible effects of selected chemical exposures on cancer mortality will be addressed in a future addendum report.
Health effects of radiation have been widely studied among nuclear workers in the past two decades, but much controversy remains concerning the extent to which chronic exposure to low-level ionizing radiation encountered in the workplace increases the risk of specific cancers. Despite the biologic plausibility of carcinogenic effects on several ("radiosensitive") organs and tissues, the results for most types of cancers are rather inconsistent across studies. The only type of cancer that has been found in most studies to be associated with occupational radiation exposures is leukemia.
Methods. We conducted a retrospective cohort study among employees of Rocketdyne/AI, who were monitored for low-level ionizing-radiation exposure between 1950 and 1993. The study population consisted of 4,563 employees monitored for external radiation and 2,297 employees monitored for internal radiation, with the second group being mostly a subset of the first.
Historical radiation information was abstracted from company records and used to measure cumulative doses (in millisieverts [mSv]) of both types of radiation. (The radiation dose from one chest x-ray, for example, is approximately 0.1 mSv.) Personnel records provided us with information about age, gender, employment history, pay type (salaried professional/managerial, salaried technical/administrative, or hourly), and some limited information on work location. Crude measures of asbestos and monomethyl-hydrazine exposures were based on job titles during selected periods of employment and, for asbestos, on selected work locations. Medical records allowed us to obtain smoking information for a subset of our cohort. Three sources of vital-status information plus Rocketdyne/AI beneficiary files were used to identify deaths occurring by December 31, 1994. We collected information about underlying and contributing causes of death from death certificates obtained for deceased cohort members.
Two analytic approaches were used in this study for different purposes: internal comparisons of monitored workers according to measured level of cumulative radiation dose (dose-response analyses); and external comparisons of monitored Rocketdyne/AI workers with two other (external) reference populations. We relied on the internal comparisons to estimate radiation effects in this study. External comparisons were used solely to describe the study population, to assess the net influence of "healthy-worker" effects operating in this study population, and to identify types of cancers with elevated mortality rates that might be explained by radiation (or other) effects estimated from the internal comparisons.
In the internal-comparison approach, conditional logistic regression was used to estimate the effects (rate ratios) of external- and internal-radiation exposures on cancer mortality among monitored workers. Externally monitored workers were used to estimate the effects of external radiation, and internally monitored workers were used to estimate the effects of internal radiation. Cumulative (total) radiation doses were treated as time-dependent predictors and lagged by zero to 20 years to account for varying periods of induction/latency. To estimate each radiation effect, we controlled analytically for the other type of radiation exposure (internal or external dose), age at risk (time dependent), time since first radiation monitoring (time dependent), pay type, and in certain analyses, other variables such as asbestos and hydrazine exposures.
Because there were not enough deaths from most specific cancer sites to conduct separate dose-response analyses, we grouped cancers on the basis of a priori information. For analyses of the effects of external radiation, the outcome events of interest were deaths from all cancers, solid cancers of "radiosensitive" organs (according to BEIR V, 1990), hemato- and lymphopoietic cancers (blood and lymph system, excluding chronic lymphocytic leukemia), and lung cancer (the most common radiosensitive solid cancer). In analyses of the effects of internal radiation, the outcome events of interest were deaths from all cancers, hemato- and lymphopoietic cancers (excluding chronic lymphocytic leukemia), lung cancer, upper-aerodigestive-tract cancers (oral cavity, pharynx, esophagus, and stomach), and urinary-tract cancers (bladder and kidneys).
Since the results of other occupational studies suggest that the effect of low-level radiation may depend on the ages at which workers are exposed, we used several methods to examine possible interaction effects between radiation dose and age at exposure. The principal method was to estimate simultaneously the separate effects of cumulative radiation dose received during three age intervals: before age 40, between ages 40 and 49, and after age 49.
In the external-comparison approach, we estimated standardized mortality ratios (SMRs), comparing the mortality experience of monitored Rocketdyne/AI workers with the mortality experience of two external populations: the general U.S. population, and a population of workers assembled by the National Institute for Occupational Safety and Health (NIOSH) from other occupational studies. SMRs were based on stratification by age, sex, and calendar year; in addition, comparisons with the NIOSH population were stratified by pay type (salaried vs. hourly).
Results. Among externally monitored workers, we identified 875 total deaths, of which 258 (29.5%) were due to cancer as the underlying cause. Among internally monitored workers, we identified 441 total deaths, of which 134 (30.4%) were due to cancer as the underlying cause. By comparing different sources of vital-status information, we established that the identification of deaths before 1995 was nearly complete.
In the dose-response analyses of monitored workers, external-radiation dose was positively associated with the rate of dying from hemato- and lymphopoietic cancers and from lung cancer; the mortality rates for both types of cancer were especially elevated for dose levels greater than 200 mSv. We also observed increasing trends in mortality rates with increasing external-radiation dose for all cancers and for radiosensitive solid cancers. No external-radiation effects were observed for cancers of nonradiosensitive organs.
Among workers monitored for internal radiation, we found increasing trends in mortality rates with increasing internal-radiation dose for upper-aerodigestive-tract cancers and for hemato- and lymphopoietic cancers. No appreciable internal-radiation effects were observed for cancers of the lung or urinary tract.
The estimated external- and internal-radiation effects did not change when adjusting for our measures of asbestos and hydrazine exposures. Furthermore, smoking status was not systematically associated with cumulative external-radiation dose in three subgroups of monitored workers sampled at different times.
Our analyses of external-radiation effects at different ages of exposure yielded contrasting results for different cancer outcomes. For total cancers, radiosensitive solid cancers and lung cancer, we found that the effect of external radiation was relatively greater for doses received after age 50; but for hemato- and lymphopoietic cancers, we found the effect was relatively greater for doses received before age 50.
Compared with the general U.S. population, Rocketdyne/AI workers monitored for external- or internal-radiation exposure experienced lower mortality rates from all causes, all cancers, and heart disease. Comparisons of monitored Rocketdyne/AI workers with NIOSH-cohort members of comparable pay type showed lower mortality rates for all causes and heart disease, but similar mortality rates for total cancers. Compared with either reference population, monitored Rocketdyne/AI workers also experienced a higher mortality rate from leukemias.
Conclusions. All available evidence from this study indicates that occupational exposure to ionizing radiation among nuclear workers at Rocketdyne/AI has increased the risk of dying from cancers of the blood and lymph system. Despite the small numbers of deaths from these cancers in workers with relatively high doses, we observed associations for both external and internal radiation, and these associations are not likely to be chance findings; furthermore, these findings are consistent with the results of our external comparisons with two reference populations. In addition, these findings are consistent with results previously reported for several other nuclear cohorts.
Exposure to external radiation appears to have increased the risk of dying from lung cancer. Although this effect has not been observed consistently in other studies of nuclear workers, it does not appear to be due to the confounding effects of smoking, asbestos, or hydrazine exposures. Nevertheless, we cannot rule out residual confounding by these factors or by unmeasured risk factors such as other chemical carcinogens, but such potential bias could be in either direction.
Results of this study strongly suggest that exposure to internal radiation has increased the risk of dying from cancers of the upper-aerodigestive tract. We observed a strong dose-response relationship that is not likely to be a chance finding. Although there were limitations in measuring internal-radiation doses among workers, we would expect such measurement errors to result in an effect estimate that is smaller than the true effect (i.e., bias toward the null).
Nevertheless, we cannot rule out confounding (in either direction) by alcohol consumption, dietary factors, and other unmeasured risk factors. Upper-aerodigestive-tract cancers have not been analyzed as a single group in previous radiation studies, and we did not have enough deaths of each cancer type in this group to conduct separate dose-response analyses; thus, our finding needs to be replicated in other populations. In contrast to findings reported for several other epidemiologic studies of radiation effects, we observed an association between cumulative external-radiation dose and total-cancer mortality. Indeed, the estimated excess rate ratio (rate ratio minus one) corresponding to the effect of 100 mSv was at least 6 to 8 times greater in our study than comparable estimates extrapolated from the study of A-bomb survivors. Our results, however, are consistent with those of two previous studies of nuclear workers.
We estimated that 9 cancer deaths observed in the externally monitored cohort were attributable to external-radiation doses of 10 mSv or more; this attributable number represents 3.5% of all observed cancer deaths and 11.1% of "exposed" cancer deaths with cumulative doses of 10 mSv or more. We also estimated that 15 cancer deaths observed in the internally monitored cohort were attributable to internal-radiation doses greater than 0 mSv; this attributable number represents 11.2% of all observed cancer deaths and 27.3% of "exposed" cancer deaths with cumulative doses greater than 0 mSv. Since we were not able to provide confidence limits for these estimates, their precision cannot be assessed. Nevertheless, the estimated numbers of attributable deaths may be conservative for several reasons: e.g., they ignore deaths possibly due to external doses less than 10 mSv; they ignore possible radiation-induced cancer deaths after 1994; and they ignore radiation-induced cases of cancer that are not fatal.
The results of this study also suggest that the effect of low-level ionizing radiation may vary by age at exposure and that the pattern of this effect modification by exposure age may differ by type of cancer. While the estimated effects of external radiation on total cancers, radiosensitive solid cancers, and lung cancer were largest for doses received after age 50, the estimated effect on hemato- and lymphopoietic cancers was largest for doses received before age 50. Despite the low statistical power for testing the effects of age-specific radiation doses in our analyses, these results are consistent with findings from other studies. We therefore recommend that other researchers
consider exposure age when estimating the effects of ionizing radiation.
Results of the external comparisons suggest that the mortality rates for all causes and, in particular, heart disease were lower for monitored Rocketdyne/AI workers than for either the general U.S. population or the NIOSH population of other worker cohorts. These findings do not mean that being employed at Rocketdyne/AI decreases the risk of dying from heart disease or other causes, but rather that healthier individuals are more likely to get employed at Rocketdyne/AI and stay in the radiation-monitoring program than are less healthy individuals. This latter phenomenon is known as the "healthy-worker effect."
Although we cannot rule out all forms of error in our estimates of radiation effects, we believe the direction of possible bias is no more likely to be away from the null (exaggerating effects) than toward the null (underestimating effects). Moreover, the positive findings observed in our study, in contrast to many previous studies, may be due in part to the extended follow-up period. Longer follow-up allows time for the development of radiation-induced cancers that are characterized by long induction/latency periods or that tend to occur more frequently after exposures late in life. It should be noted that only 20% of monitored workers had died by the end of the follow-up period. On the basis of this consideration, plus other methodologic issues that cannot be resolved by the present study, we recommend continued follow-up of the Rocketdyne/AI cohort in the coming decades. Future surveillance should include the detection of cancer incidence as well as mortality.
Download: Final Report (PDF)
<-- LA Rocketdyne Nuclear Meltdown
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