The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: study of errors in dosimetry.

To provide direct estimates of cancer risk after low-dose protracted exposure to ionizing radiation, a large-scale epidemiological study of nuclear industry workers was conducted in 15 countries. As part of this study, identification and quantification of errors in historical recorded doses was conducted based on a review of dosimetric practices and technologies in participating facilities. The main sources of errors on doses from "high-energy" photons (100-3000 keV) were identified as the response of dosimeters in workplace exposure conditions and historical calibration practices. Errors related to dosimetry technology and radiation fields were quantified to derive period- and facility-specific estimates of bias and uncertainties in recorded doses. This was based on (1) an evaluation of predominant workplace radiation from measurement studies and dosimetry expert assessment and (2) an estimation of the energy and geometry response of dosimeters used historically in study facilities. Coefficients were derived to convert recorded doses to H(p) (10) and organ dose, taking into account different aspects of the calibration procedures. A parametric, lognormal error structure model was developed to describe errors in doses as a function of facility and time period. Doses from other radiation types, particularly neutrons and radionuclide intake, could not be adequately reconstructed in the framework of the 15-Country Study. Workers with substantial doses from these radiation types were therefore identified and excluded from analyses. Doses from "lower-energy" photons (<100 keV) and from "higher-energy" photons (>3 MeV) were estimated to be small.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

Basis for the selective reduction of pulmonary vascular resistance in humans during infusion of adenosine.

The objective of this study was to demonstrate the basis for the selective reduction of pulmonary vascular resistance by intravenous infusion of adenosine. Secondary objectives of the study were to determine the rate of central infusion of adenosine at which the nucleoside appears in the systemic circulation and to relate this to hemodynamic events. Plasma concentrations of adenosine in the right and left atria were measured during peripheral (5 patients) and central (12 patients) infusions of adenosine in adults with normal pulmonary arterial pressures undergoing coronary artery bypass surgery. The hemodynamic effects of central (right ventricle) infusion of adenosine were also examined. The extraction of adenosine across the pulmonary vascular bed was found to be 73.6 +/- 4.8%. The mean maximal decrease in pulmonary vascular resistance index, 48.8 +/- 9.6%, occurred at an adenosine infusion rate of 30 micrograms.kg-1.min-1, whereas the systemic vascular resistance index remained unchanged. Thus, adenosine, administered centrally in anesthetized patients with normal pulmonary vascular resistances, selectively lower pulmonary vascular resistance. The basis for this selective effect is the substantial extraction of adenosine during passage through the pulmonary vascular bed.

Environmental emergency response team personnel protection plan guidelines.

Environmental emergency response teams are being established in local health departments throughout the country. A primary concern for these teams is personal protection from the hazardous materials at the response site. A set of guidelines is presented for establishing a personal protection plan for the environmental emergency response team which includes selection criteria for personal protective clothing and respirators as well as recommendations for ancillary components of the personal protection plan.

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Benzene exposure assessment in rubber hydrochloride workers: a critical evaluation of previous estimates.

Many risk assessments for leukemia associated with benzene exposure have been based on the mortality experience of the rubber hydrochloride worker cohort. Although there have been several different historical exposure assessments proposed for this cohort, Paustenbach et al. [1992, J Tox Environ Health], recently published a new historical characterization of benzene exposures based on data previously developed by Rinsky et al. [1981, Am J Ind Med] and further modified by Crump and Allen [1984: OSHA]. Adjustments by Paustenbach et al. in the Rinsky et al. data result in retrospective benzene exposure estimates far greater than those previously reported, by an order of magnitude in many cases. Judgments made on the significance of dermal contact and interpretation of historical measurement data led Paustenbach et al. to arrive at exposure estimates for this cohort that are in conflict with what is known about the adverse effects of benzene exposure. More reasonable estimates for dermal absorption are included in this report that do not substantially affect total estimates of benzene exposure for the cohort. The exposure estimates originally presented in the Rinsky et al. article appear in concordance with data not previously reported in any analyses.

Use of historical uranium air sampling data to estimate worker exposure potential to airborne radioactive particulate in a uranium processing facility.

Historical industrial hygiene monitoring records from a uranium processing plant were collected and analyzed to characterize exposure potential to airborne radioactive particulate. More than 2,100 samples were collected during the period of 1954-1968. The data was organized by job title, plant number, and year of measurement. Laboratory analysis of air samples indicated a wide range of potential exposures to the alpha-emitting particulate. Logarithmic transformation of the data was necessary to approximate Gaussian distributions. Geometric Mean (GM) values were used as the measure of central tendency within years. GM values ranged from 23-49 disintegrations per minute per cubic meter of air sampled (dpm/m3) with the years 1963 and 1964 being significantly higher than other years (ANOVA: p < 0.05). When comparing exposure potential across plants, GM ranged from 20-68 dpm/m3, with plants 5 and 8 being significantly higher than the others (ANOVA: p < 0.05). Exposure potential for specific job titles across the plants varied widely. GM for clerks was the lowest (11 dpm/m3) while furnace operators were the highest (235 dpm/m3). Other job titles with potentially high exposures were chemical operators, forklift operators, machine operators, and furnace operators. This analysis indicates the magnitude and distributions of worker exposure to alpha-emitting airborne particulate. Additional analysis and epidemiologic studies are planned for this facility.

Endogenous adenosine is an antiarrhythmic agent.

BACKGROUND: Adenosine administered intravenously terminates supraventricular tachycardias (SVT) involving the AV node as part of the reentrant circuit. Dipyridamole increases interstitial myocardial levels of this nucleoside. This study was designed to determine whether intravenous dipyridamole increases coronary sinus plasma adenosine concentrations ([Ado]cs) in humans to levels sufficient to alter electrophysiological parameters and terminate SVT. METHODS AND RESULTS: A custom-designed catheter and syringe for sampling blood for measurement of [Ado]cs was placed in the coronary sinuses of 7 patients. [Ado]cs and refractory periods and conduction characteristics of the atrium and AV node were determined after autonomic blockade and dipyridamole infusion (5 micrograms.kg-1.min-1 after a loading dose of 0.56 mg/kg). The atrial effective and functional refractory periods remained unchanged after dipyridamole infusion. In contrast, the AV nodal functional refractory period increased from 350 +/- 32 to 381 +/- 41 milliseconds (P = .03); the Wenckebach cycle length also increased from 309 +/- 47 to 350 +/- 57 milliseconds (P < .0001). Coincident with these changes, [ADO]cs increased from 0.18 +/- 0.11 to 0.31 +/- 0.12 mumol/L (P = .02). In another 10 patients with AV or AV nodal reentrant tachycardia, SVT was induced, and coronary sinus blood samples were drawn. Dipyridamole was infused, and coronary sinus blood samples were obtained after 15 minutes or coincident with termination of SVT. Mean [ADO]cs increased from 0.17 +/- 0.06 mumol/L during SVT to 0.38 +/- 0.21 mumol/L after dipyridamole (P = .02). Mean tachycardia cycle length increased from 334 +/- 132 to 375 +/- 139 milliseconds (P = .02); this effect was confined to the AV node, as demonstrated by an increase in AH interval from 171 +/- 144 to 214 +/- 140 milliseconds (P = .003). SVT terminated with the infusion of dipyridamole in 4 of the 10 patients. CONCLUSIONS: Administration of dipyridamole is associated with elevation of [ADO]cs, with coincident prolongation of the mean Wenckebach cycle length and AV nodal functional refractory period. During SVT, dipyridamole leads to prolongation of the AH interval and tachycardia cycle length and to an increase in [ADO]cs, with termination of SVT in four patients. These results support the hypothesis that adenosine may function as an endogenous antiarrhythmic metabolite.

An experimental design approach to retrospective exposure assessment.

There are several methods currently in use for retrospective estimation of quantitative exposure levels in occupational and environmental epidemiologic studies. The most popular is a job-exposure matrix approach using a combination of existing data and professional judgment. Another method is the use of statistical models based on available exposure data. The authors present an alternative approach using an experimental design in which several factors thought to affect exposure levels are identified and set at specific levels in a cross-classified design. This approach was used to estimate historical exposures to formaldehyde in a mortality study of embalmers. Exposures were estimated as a function of solution concentration, air exchange rate, and autopsied versus intact body. There were 12 combinations involving these 3 factors and a total of 25 embalming procedures (approximately 2 replicates of each combination) performed at a college of mortuary science. In addition to these design factors several covariates such as temperature, humidity, and the occurrence of spills were considered in an analysis of covariance statistical model. The results of the model prediction were validated against published measurements, and field samples were taken in several funeral homes. The overall accuracy of the model predictions was comparable to the variation found in replicate measurements of identical embalming procedures.