Dose-response analyses of osteonecrosis in New Jersey radium workers point to roles for other alpha emitters.

A previous study of 25 radium workers reported radium osteonecrosis to be common down to that study's lower limit of detection of 226Ra. This paper reanalyzes those data using Poisson and linear regression to obtain quantitative dose-response estimates for radium osteonecrosis. A quadratic, supralinear response of the necrosis ratio to skeletal dose and preterminal 226Ra burden was observed at a high level of statistical significance. At low dose the response was linear. Clearly observable necrosis, that appearing in 4% of tissue blocks, was seen in femurs at approximately 0.8 Gy skeletal dose. Comparable effects from plutonium in spongy bone might therefore be expected in the 0.01-0.02 Gy dose range. Prediction equations are presented for preterminal 226Ra burden, for skeletal dose, and, at low doses where the response can be taken as linear, for dose from and uptakes of both 226Ra and 228Ra. Male New Jersey workers in the radium refinery were observed to have necrosis not explained by the 226Ra uptakes, but compatible with skeletal doses from other internal emitters, in the range 0.25-1.2 Gy lifetime dose acquired per year of employment. 210Po, inhaled directly or from inhaled 210Pb, is the most likely source of this dose.

Radium and leukemia: is current dogma valid?

Current reviews have concluded that internal 226Ra appears not to give rise to leukemia in humans, a conclusion based on incidence in U.S. female radium dial workers. In fact, leukemias have occurred significantly early in female dial workers; males occupationally exposed to radium show an excess of leukemias; and the rare erythrocytic leukemias appear in male workers as they do in Thorotrast case series. It appears more reasonable that Thorotrast data are suitable for projection of leukemogenic risk from radium and plutonium than that no concern for leukemogenic risk is warranted.

A case study of selected medical findings among plutonium injectees.

Available medical records of plutonium injectees exposed in experimental studies of plutonium biokinetics under Manhattan Engineer District auspices have been reviewed for subsequent medical findings potentially related to the plutonium exposures. Five subjects who had been injected with approximately 11 kBq 239Pu, and one injected with 3.5 kBq 238Pu, had useful follow-up medical data. Bone lesions dominated the findings: none of six subjects with follow-up for bone conditions lacked bone lesions clearly or potentially caused, or worsened, by plutonium. Roentgenograms of three subjects, read by a radiologist experienced reading films of radium cases, demonstrated possible to likely plutonium effects. Two cases of osteoporosis or non-specific degenerative changes were seen, associated with a hip fracture and vertebral fractures. Areas of increased bone density were seen, as well as numerous dystopic calcifications and one unusual case of widespread pathologic calcification on bone surfaces probably due to a plutonium-related calciphylactic reaction. Non-skeletal findings include labyrinthitis with inflammatory mastoid changes, conduction deafness, and a benign neurofibroma directly adjacent to bone. The radium literature contains similar observed findings, but interpretation of these limited clinical observations is hampered by lack of quantitative data on humans exposed to radium with respect to prevalence of non-specific ear, mastoid, and skeletal symptomatologies or x-ray findings, or cumulative incidence rates of bone fractures or of other physical disabilities related to ear, mastoid, or bone damage. Disability and invalidism late in life can be risk factors for earlier mortality.

Gamma distribution and house 222Rn measurements.

The statistical distribution of 222Rn measurements from basements and first floors of homes in northeastern Pennsylvania was investigated. The gamma distribution was statistically significantly superior to the normal distribution (p less than 0.005) in describing the frequency distribution of the logarithm of observed 222Rn levels. The fit to the data was closer both in the central portion and in the upper tail. The gamma distribution has certain characteristics that make it generally useful in the study of environmental toxic agents where several different exposures over a lifetime occur and must be combined, as for risk assessment or for statistical power calculations for epidemiologic studies.

Prediction of 222Rn from topography in Pennsylvania.

The relationships of Rn levels in basements and first floors of homes to topographic location in a northeastern ridge and valley section of Pennsylvania were investigated. Topographic variables relating to elevation and slope were quantified and related to house Rn levels using both conventional and classification and regression tree (CART) analyses. The original interest was in using topographic correlates to estimate missing values in epidemiologic studies. In this area, Rn levels are usefully predicted by relative and absolute elevations and nearness to hills and ridges. Three- to fourfold differences in geometric mean Rn levels can be obtained for categories representing significant portions of the population of houses. The relationship of first-floor to basement Rn levels was found to be curvilinear and modestly affected by topography.

A melanoma case-control study at the Los Alamos National Laboratory.

We conducted a melanoma case-control study at the Los Alamos National Laboratory to investigate whether related occupational exposures or personal characteristics of employees could be identified. This study was prompted by a recent report from the Lawrence Livermore National Laboratory that melanoma was much more frequent than expected among employees and that persons suffering from melanoma more often worked as chemists. Our investigation did not uncover an association with plutonium body burden, cumulative external radiation exposure, or employment as a chemist or a physicist. The major finding was that cases were more educated than controls. Melanoma risk was 2.11 among college-educated employees and increased to 3.17 among those with graduate degrees (Mantel-extension linear trend probability = 0.038). This finding is consistent with the often reported increased melanoma incidence among persons of higher social class. It points to personal characteristics, particular to persons of higher educational attainment, as risk factors for melanoma at the Los Alamos National Laboratory.

Contamination of individuals by radon daughters: a preliminary study.

Body radon daughter contamination reflects relative individual respiratory exposures to radon daughters; counts can be related both to household radon levels and to lung cancer risk factors such as sex and tobacco smoking. Radon daughters were counted by gamma spectroscopy from 180 adult residents of eastern Pennsylvania. A seven-position, 35-min scan was conducted in a mobile body counter, generally during afternoon or evening hours. Track-etch detectors for household radon were distributed, and were recovered from 80% of the subjects. Over 75% of the population had environmentally enhanced radon daughter contamination. House radon levels were strongly related, as anticipated, to radon daughter contamination in the 112 subjects for whom both sets of measurements were available (p less than .001); basement measurements were as strongly related to personal contamination as were living area measurements; bedroom measurements were slightly more strongly correlated. Both sex (p less than .02) and cigarette smoking (p less than .01) significantly modified the relationships, after nonlinear adjustment for travel times. Using a logarithmic model, a given house living-area radon level was associated in females with body contamination by radon daughters 2-3 times that in males. Nonsmokers had 2-4 times higher levels of contamination than smokers. Results are for the total of internal and external contamination, these being highly correlated in preliminary experiments. Time usage and activity patterns of the subjects are believed to be important in explaining these findings, and may become important variables in radon risk assessment.

Health risks from radium in workplaces: an unfinished story.

The classic health effects of occupational exposure to radium include osteosarcomas and fibrosarcomas of bone, carcinomas of paranasal sinuses and mastoid air cells, and microscopically and radiographically evident lesions of bone, along with fractures in highly exposed individuals. Among probable effects are breast cancer and acceleration of cataracts. Thyroid carcinoma is a possible high-dose effect. Leukemia is likely related to employment in the radium industry. Multiple myeloma and excess lung cancer may have resulted from high gamma radiation and radon exposures rather than from internal radium. At high doses, impairment of fertility has occurred. Further investigations of effects on the cardiovascular system and hearing, and on fracture-related disability very late in life, are needed.

Panel studies of acute health effects of air pollution. II. A methodologic study of linear regression analysis of asthma panel data.

Panel studies relating illness, such as asthma attacks, cardiopulmonary symptoms, and acute respiratory symptoms, to daily air pollution and weather are important in environmental epidemiology. A study of the practical robustness of multiple linear regression procedures, which have been the preferred statistical models in analyses, is presented. The study is based on data from three asthma panels in Chattanooga, Tennessee, collected in 1972-1973. Linear regression models, commonly used, which incorporate only minimum temperature and an air pollutant were found to be potentially misleading; such models are highly sensitive to reporting trends in the data and do not correct adequately for weather variables. Temporal and spatial control strategies were employed and proved to be useful in detecting problems in the data due to undiscovered intervening variables. True day-to-day relationships estimated by a pair-day analysis were frequently inconsistent with "daily" effects estimated by the usual regression models and suggested that, in fact, the asthma panel data contained no useful information concerning day-to-day relationships.

Identifying a susceptible subgroup: effects of the Pittsburgh air pollution episode upon schoolchildren.

Pulmonary function test results on 224 parochial schoolchildren collected during and after the Pittsburgh air pollution episode of November 1975 were reanalyzed to determine whether a small subgroup of susceptible children could be defined. Individual regressions of three-quarter second forced expiratory volumes (FEV.75) and forced vital capacities (FVC) on time over the six-day study period were calculated, and the distributions of individual slopes for the four exposed and two control schools were compared. Excesses of strong upward trends in the exposed areas would suggest effects of suspended particulate air pollution by indicating significant improvement following the episode. A highly statistically significant excess of strong upward trends in the FVC among exposed students was observed, and was consistent by sex and by school within sex. Approximately 10--15% of the students appear susceptible to an average impairment of about 20% of the FVC. The findings are limited by the small number of subjects with strong post-episode upward trends in the FVC, and by lack of validation by replication of the study design, but do suggest that episode levels of suspended particulates induce lung damage, and that this may occur only in a small susceptible subgroup. Children with low baseline pulmonary function values, histories of asthma, or with acute respiratory symptoms immediately following the episode were not found to be especially susceptible to these effects of suspended particulates.

Evaluation of Social Security follow-up of some southwestern populations.

A study of the completeness of death ascertainment through the Social Security Administration (SSA) was undertaken. Groups of subjects of known vital status were submitted by the Los Alamos National Laboratory to the SSA for a mortality record search. Correctly ascertained deaths ranged from 77% to 90% among males and from 53% to 76% among females. A duplicate record search one year later raised correct ascertainment to 88% to 94% of male deaths and to 73% to 87% of female deaths. Death ascertainment appeared to be independent of ethnicity (Anglo and Hispanic), cause of death, location of death, and year of death. Age at time of death was strongly related to death ascertainment. Individuals 65 years of age and over were identified much more accurately than persons less than 65 years of age. Lack of incentive to report deaths of persons under retirement age is believed to be responsible. The age of an industrial facility and of the work force may have a major influence on the adequacy of mortality ascertainment through social security.

Mortality from cancers of major sites in female radium dial workers.

The female radium dial workers have now experienced significant mortality from cancers other than the bone sarcomas and head carcinomas long known to be radium induced. The relationships of radium exposure to mortality from cancers of the stomach, pancreas, colon, rectum, liver, lung, breast, cervix, and corpus uteri, and from leukemia were studied in 1,285 pre-1930 dial workers. Mortality was compared with that expected from rates for US white females, with and without adjustment for local area mortality rates, and with mortality in dial workers exposed from 1930 to 1949. For the 693 cases whose body content of radium has been measured since 1955, dose-response relationships of cancer to systemic intake of radium and duration of employment were examined. Liver, pancreatic, cervical, and uterine cancers were clearly unrelated to radium exposure. Other cancers of the digestive tract appeared to be indirectly, if at all, associated with work in radium facilities. Lung cancer requires further investigation; inhalation exposures of the dial workers were reviewed. Analyses of the breast cancer data uncovered several observations inconsistent with the previously suggested causal association with radium exposure. Multiple myeloma was also reviewed. A threefold excess risk of death due to multiple myeloma has occurred, but is more closely correlated with duration of employment (a surrogate for external gamma radiation) than with radium intake.

Chronobiometry with pocket calculators and computer systems.

Selected methods for the study of biologic time series are reviewed and their relative merits are discussed in the light of underlying assumptions. Their potential applications are exemplified in several fields of biology and medicine. The monitoring of environmental integrity, notably of pollution, is investigated. The need for specifying optimal sampling requirements is underlined. An individualized and time-qualified definition of health by the establishment of reference intervals is required for increasingly rational individualized program for the prevention and/or treatment of disease. With these reference intervals and rhythm characteristics available, one can better interpret with single samples or time series an increased risk of a certain disease or the inception of the disease. For all of these aims the monitoring of environmental and/or personal marker rhythms is essential--to obtain large data bases from which information can be more easily derived for monitoring personal health, to recognize risk as well as to diagnose disease early and to optimize treatment by timing according to rhythms.