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Biomedical subjects

E S Gilbert

Publications and source records attributed to E S Gilbert.

At least 37 records · Page 2Linked to original sources

Plant compounds that induce polychlorinated biphenyl biodegradation by Arthrobacter sp. strain B1B.

Plant compounds that induced Arthrobacter sp. strain B1B to cometabolize polychlorinated biphenyls (PCBs) were identified by a screening assay based on the formation of a 4,4'-dichlorobiphenyl ring fission product. A chemical component of spearmint (Mentha spicata), l-carvone, induced Arthrobacter sp. strain B1B to cometabolize Aroclor 1242, resulting in significant degradation of 26 peaks in the mixture, including selected tetra- and pentachlorobiphenyls. Evidence for PCB biodegradation included peak disappearance, formation of a phenylhexdienoate ring fission product, and chlorobenzoate accumulation in the culture supernatant. Carvone was not utilized as a growth substrate and was toxic at concentrations of greater than 500 mg liter-1. Several compounds structurally related to l-carvone, including limonene, p-cymene, and isoprene, also induced cometabolism of PCBs by Arthrobacter sp. strain B1B. A structure-activity analysis showed that chemicals with an unsaturated p-menthane structural motif promoted the strongest cometabolism activity. These data suggest that certain plant-derived terpenoids may be useful for promoting enhanced rates of PCB biodegradation by soil bacteria.

Aroclors↗

An approach to evaluating bias and uncertainty in estimates of external dose obtained from personal dosimeters.

This paper describes an approach to quantifying errors in recorded estimates of external radiation dose obtained from personal dosimeters and applies the approach to dose estimates of workers at the Hanford site. Because a major objective of this evaluation is to provide the information needed for adjusting epidemiologic dose-response analyses of worker data for errors in dose estimates, the paper addresses the extent that errors for different workers are correlated, focuses on recorded doses as estimates of organ doses, and focuses on recorded doses as estimates of organ doses, and gives consideration to both annual and cumulative doses. The evaluation emphasizes errors resulting from the fact that dosimeters are limited in their ability to respond accurately to all radiation energies to which workers are exposed or to radiation coming from all directions. For each of several sources of error, systematic bias factors are estimated for two energy ranges (100--300 keV and 300--1,000 keV), two geometries (anterior-posterior and rotational), and four calendar year periods. These are then combined using information provided by health physicists on energies and geometries in Hanford exposure environments. Except for the period before 1958, deep dose, the objective of modern dosimetry systems, was found to be fairly accurately estimated. Lung dose was found to be overestimated by about 10%, and bone marrow dose was found to be overestimated by about 50%. However, many aspects of this evaluation relied heavily on subjective judgments, and, thus, these factors are subject to considerable uncertainty. Estimates of uncertainty in the bias factors and uncertainty reflecting random error are provided.

Bias↗

Analysis of lung tumor risks in rats exposed to radon.

Using data on 3117 rats exposed by inhalation to radon, radon progeny and uranium ore dust, the hazard function (or age-specific risk) for lung tumor incidence was modeled as a function of exposure, exposure rate and other factors. The overall estimate of lifetime risk was 237 cases per 10(6) rats per WLM (237 per 10(6) WLM), reasonably comparable to estimates obtained from data for humans. The data below 1000 WLM (20-640 WLM) were consistent with linearity with positive excess risks at all levels; however, evidence of statistically significant excess risk was limited to exposures of 80 WLM or greater. Evidence for an inverse exposure-rate effect was limited primarily to cumulative exposures exceeding 1000 WLM (1280-10,240 WLM) and to comparison of results at 100 and 1000 WL. Even at these levels, the possibility that the effect might be explained by time since last exposure or by heterogeneity across experiments could not be entirely excluded. The inverse exposure-rate effect was strongest for epidermoid and adenosquamous tumors, and the only indication of such an effect at exposures below 1000 WLM was modest evidence (P=0.024) in analyses limited to these tumors. When all lung tumors, or all malignant lung tumors, were included, there was no evidence of such an effect below 1000 WLM. These data support the viewpoint that the inverse exposure-rate effect is primarily a high-dose phenomenon.

Adenoma↗

Accounting for bias in dose estimates in analyses of data from nuclear worker mortality studies.

Although dose estimates used in epidemiologic studies of nuclear workers are far superior to exposure measures used in many epidemiologic studies, they are subject to several types of bias. These include bias resulting from practices used to measure and record very low doses and from underestimation of dose from neutrons. They also include bias resulting because available dose estimates do not include dose from internally deposited radionuclides, occupational dose received after workers have terminated employment at the facility of interest, or dose from background or medical exposures. These biases can potentially distort dose-response analyses and lead to biased risk estimates and confidence limits. This paper uses data on workers at the Hanford site to investigate the possible effects of these biases on dose-response analyses of leukemia and of all cancer except leukemia. This is accomplished by conducting analyses based on a variety of assumptions regarding the nature and magnitude of these biases. Results were not modified greatly (as compared to those based on the dose as recorded) for any of the 40 sensitivity analyses presented, including some based on fairly extreme assumptions. However, analyses that excluded workers with potential for dose from internal depositions and from neutrons did increase both the risk estimate and upper confidence limits; it may be desirable to emphasize this approach in future presentations. It is recommended that similar sensitivity analyses be performed with data from other worker studies, addressing the specific dosimetry problems that have been identified in those populations.

Bias↗

Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries.

Studies of the mortality among nuclear industry workforces have been carried out, and nationally combined analyses performed, in the U.S., the UK and Canada. This paper presents the results of internationally combined analyses of mortality data on 95,673 workers (85.4% men) monitored for external exposure to ionizing radiation and employed for 6 months or longer in the nuclear industry of one of the three countries. These analyses were undertaken to obtain a more precise direct assessment of the carcinogenic effects of protracted low-level exposure to external, predominantly gamma, radiation. The combination of the data from the various studies increases the power to study associations between radiation and specific cancers. The combined analyses covered a total of 2,124,526 person-years (PY) at risk and 15,825 deaths, 3,976 of which were due to cancer. There was no evidence of an association between radiation dose and mortality from all causes or from all cancers. Mortality from leukemia, excluding chronic lymphocytic leukemia (CLL)--the cause of death most strongly and consistently related to radiation dose in studies of atomic bomb survivors and other populations exposed at high dose rates--was significantly associated with cumulative external radiation dose (one-sided P value = 0.046; 119 deaths). Among the 31 other specific types of cancer studied, a significant association was observed only for multiple myeloma (one-sided P value = 0.037; 44 deaths), and this was attributable primarily to the associations reported previously between this disease and radiation dose in the Hanford (U.S.) and Sellafield (UK) cohorts. The excess relative risk (ERR) estimates for all cancers excluding leukemia, and leukemia excluding CLL, the two main groupings of causes of death for which risk estimates have been derived from studies of atomic bomb survivors, were -0.07 per Sv [90% confidence interval (CI): -0.4, 0.3] and 2.18 per Sv (90% CI: 0.1, 5.7), respectively. These values correspond to a relative risk of 0.99 for all cancers excluding leukemia and 1.22 for leukemia excluding CLL for a cumulative protracted dose of 100 mSv compared to 0 mSv. These estimates, which did not differ significantly across cohorts or between men and women, are the most comprehensive and precise direct estimates of cancer risk associated with low-dose protracted exposures obtained to date. Although they are lower than the linear estimates obtained from studies of atomic bomb survivors, they are compatible with a range of possibilities, from a reduction of risk at low doses, to risks twice those on which current radiation protection recommendations are based.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Mortality of workers at the Hanford site: 1945-1986.

Updated analyses of mortality of workers at the Hanford site provide little evidence of a positive correlation of cumulative occupational radiation dose and mortality from leukemia and from all cancer except leukemia. Estimates of the excess relative risk per 10 mSv were negative for both disease categories, but these estimates are consistent both with no risk and with estimates obtained through extrapolation from high-dose data. For all cancer except leukemia, the upper limit for a two-sided 90% confidence interval was about 1.5 times the prediction of the BEIR V model, but several times the estimate recommended by the ICRP 60 committee. For leukemia, the comparable upper limit was very close to that predicted by either BEIR V or ICRP 60. The all-cancer risk estimate, from a recent report on updated analyses of data for Oak Ridge National Laboratory workers, was strongly rejected based on the Hanford data. Of 24 specific cancer categories evaluated, only cancer of the pancreas and Hodgkin's disease showed positive correlations with radiation dose that approached statistical significance with one-tailed p values of 0.07 and 0.04, respectively; these correlations are interpreted as probably spurious. For multiple myeloma, for which a correlation was reported previously, the p value was 0.10. However, a significant correlation (p < .05) was obtained when analyses were expanded to include deaths with multiple myeloma listed on the death certificate but not considered to be the underlying cause, when analyses were expanded to include deaths occurring in Washington State during the time period 1987-1989, or when a 2-y latency period (instead of 10-y) was assumed.

Adult↗

Updated analyses of combined mortality data for workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Weapons Plant.

Updated analyses of mortality data on workers at the Hanford Site, Oak Ridge National Laboratory (ORNL), and Rocky Flats Weapons Plant are presented with the objective of providing a direct assessment of health risks resulting from protracted low-dose exposure to ionizing radiation. For leukemia, the combined excess relative risk estimate was negative (-1.0 per Sv), and confidence limits excluded risks that were more than slightly larger than those forming the basis of ICRP recommendations. For all cancer except leukemia, the excess relative risk estimate was 0.0 per Sv, but confidence limits indicated consistency with estimates several times those forming the basis of ICRP recommendations. Of 24 cancer types tested, 12 showed positive correlations with radiation dose and 12 showed negative correlations, as would be expected by chance fluctuation. Cancer of the esophagus, cancer of the larynx, and Hodgkin's disease showed statistically significant correlations with radiation dose (P < 0.05), but these correlations were interpreted as likely to have resulted from bias or chance fluctuation. Evidence of an increase in the excess relative risk with increasing age at risk was found for all cancer in both Hanford and ORNL, and both populations showed significant correlations of all cancer with radiation dose among those 75 years and older. Although this age effect may have resulted from bias in the data, its presence suggests that risk estimates based on nuclear worker data be interpreted cautiously.

Adult↗

Methods for analyzing combined data from studies of workers exposed to low doses of radiation.

Epidemiologic studies of workers exposed occupationally to protracted low doses of radiation provide a direct assessment of health effects resulting from such exposure and thus supplement information provided by studies of populations exposed at high doses of radiation and high dose rates. Analyses based on combined data from several studies can be expected to provide a more thorough assessment of low dose occupational studies and more precise risk estimates than can be obtained from any single study. Statistical methods for conducting such combined analyses are discussed, and different approaches, such as basing analyses on various levels of aggregation of exposure data, are compared and evaluated. Emphasis is given to methods for obtaining risk estimates and confidence limits that can be appropriately compared with estimates that form the basis for current radiation protection standards; these estimates have been obtained through extrapolation from high dose data. Methods are illustrated using combined data on workers at three US Department of Energy facilities: the Hanford Site, Richland, Washington; the Oak Ridge National Laboratory, Oak Ridge, Tennessee; and the Rocky Flats Nuclear Weapons Plant, Denver, Colorado.

Colorado↗

A case-cohort study of lung cancer, ionizing radiation, and tobacco smoking among males at the Hanford Site.

Results of several epidemiological studies of workers exposed occupationally to low levels of radiation have been reported but have not included data on smoking. The authors conducted a case-cohort study of male workers at the Hanford Site with an objective of investigating the association between lung-cancer risk and occupational radiation exposure with appropriate adjustment for tobacco use. Eighty-six lung-cancer deaths for the period 1965-1980 and a stratified random sample of 445 subcohort members were included in the study. Tobacco-use data were obtained from medical records collected over each subject's period of employment. Data from this study were analyzed using methods that took into account both the case-cohort design and changes over time in the quality of the tobacco-use data collected. Tobacco use was not strongly related to the level of radiation exposure, and adjustment for tobacco use did not greatly modify results of analyses assessing the association between lung-cancer risk and cumulative dose equivalent. With or without adjustment for tobacco use, the estimated risks per unit of cumulative dose equivalent were negative, but the 95% confidence intervals were wide and included values several times those estimated from populations with high levels of irradiation.

Cohort Studies↗

Issues in analysing the effects of occupational exposure to low levels of radiation.

A major objective of studying populations exposed to low levels of radiation is provision of direct assessment of the adequacy of estimates of health risks obtained by extrapolation of data on populations exposed at high levels. Meeting this objective requires the use of statistical methods that fully utilize available exposure measurements, and that consider the extensive body of prior knowledge regarding radiation-induced health effects. This paper describes various methods of analysis and illustrates the methods with data on workers at the Hanford Site. Special problems are discussed, with attention to comparability of estimates and confidence limits with those obtained from extrapolation.

Cohort Studies↗

Mortality of workers at the Hanford site: 1945-1981.

Analyses of mortality of workers at the Hanford Site were updated to include an additional three years of data (1979-81). Deaths occurring in the state of Washington in the years 1982-85 were also evaluated. Hanford workers continued to exhibit a strong healthy worker effect with death rates substantially below those of the general U.S. population. Comparisons by level of radiation exposure within the Hanford worker population provided no evidence of a positive correlation of radiation exposure and mortality from all cancers combined or of mortality from leukemia. Estimates of cancer risk due to radiation were negative, but confidence intervals were wide, indicating that the data were consistent with no risk and with risks several times larger than estimates provided by major groups concerned with risk assessment. Of 18 categories of cancer analyzed, a correlation of borderline statistical significance was identified for female genital cancers (p = 0.05), but was interpreted as probably spurious. The previously identified correlation for multiple myeloma persisted (p = 0.002).

Environmental Exposure↗

Time-related factors in the study of risks in animals and humans.

Data from epidemiological studies of humans exposed to potentially harmful substances are usually analyzed using methods that account for the dependence of risks on time-related factors such as age and follow-up period. Recently developed statistical procedures allow modeling of the age-specific risks as a function of dose as well as factors such as age at exposure, time since exposure, exposure duration, and dose rate. These procedures potentially allow more rigorous inferences and clearer understanding of the patterns of risk observed in epidemiological studies than has been available in the past. Statistical procedures that consider time-related factors can also be applied to laboratory animal data, providing information that is useful for the problems involved in extrapolating from animal studies to humans. By applying such procedures to data on exposure to the same substance in different species (including humans) or to different substances in the same species, better understanding of the relationship of risks across species and across substances can be achieved. In addition, such statistical procedures allow appropriate treatment of exposure that is accumulated over time and lead to improved understanding of patterns of risk over time. The approach is illustrated using data from a lifespan study of beagle dogs exposed to inhaled Pu.

Administration, Inhalation↗

Analyses of combined mortality data on workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Nuclear Weapons Plant.

An important objective of studies of workers exposed occupationally to chronic low doses of ionizing radiation is to provide a direct assessment of health risks resulting from this exposure. This objective is most effectively accomplished by conducting combined analyses that allow evaluation of the totality of evidence from all study populations. In this paper, combined analyses of mortality in workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Nuclear Weapons Plant are presented. These combined analyses provide no evidence of a correlation between radiation exposure and mortality from all cancer or from leukemia. Of 11 other specific types of cancer analyzed, multiple myeloma was the only cancer found to exhibit a statistically significant correlation with radiation exposure. Estimates of the excess risk of all cancer and of leukemia, based on the combined data, were negative. Upper confidence limits based on the combined data were lower than for any single population, and were similar to estimates obtained from recent analyses of A-bomb survivor data. These results strengthen support for the conclusion that estimates obtained through extrapolation from high-dose data do not seriously underestimate risks of low-dose exposure, but leave open the possibility that extrapolation may overestimate risks.

Adult↗

A case-control study of congenital malformations and occupational exposure to low-level ionizing radiation.

In a case-control study, the authors investigated the association of parental occupational exposure to low-level external whole-body penetrating ionizing radiation and risk of congenital malformations in their offspring. Cases and controls were ascertained from births in two counties in southeastern Washington State, where the Hanford Site has been a major employer. A unique feature of this study was the linking of quantitative individual measurement of external whole-body penetrating ionizing radiation exposure of employees at the Hanford Site, using personal dosimeters, and the disease outcome, congenital malformations. The study population included 672 malformation cases and 977 matched controls from births occurring from 1957 through 1980. Twelve specific malformation types were analyzed for evidence of association with employment of the parents at Hanford and with occupational exposure to ionizing radiation. Two defects, congenital dislocation of the hip and tracheoesophageal fistula, showed statistically significant associations with employment of the parents at Hanford, but not with parental radiation exposure. Neural tube defects showed a significant association with parental preconception exposure, on the basis of a small number of cases. Eleven other defects, including Down syndrome, for which an association with radiation was considered most likely, showed no evidence of such an association. When all malformations were analyzed as a group, there was no evidence of an association with employment of the parents at Hanford, but the relation of parental exposure to radiation before conception was in the positive direction (one-tailed p value between 0.05 and 0.10). Given the number of statistical tests conducted, some or all of the observed positive correlations are likely to represent false positive findings. In view of strong contradictory evidence, based on no demonstrated effects in genetic studies of atomic bomb survivors in Hiroshima and Nagasaki, it is unlikely that these correlations result from a cause and effect association with parental radiation exposure.

Abnormalities, Radiation-Induced↗