Progeny Exposure Research Articles

Health risk evaluation of radon progeny exposure in Nigerian traditional mud houses

Health risk evaluation of radon progeny exposure in Nigerian traditional mud houses

Computational analysis of radon progeny deposition patterns in the human respiratory system

In the last year, the use of computational fluid dynamics (CFD) techniques has gained prominence as a powerful tool for modeling biological phenomena and influencing the design of biomedical devices. In this study, we utilized a computational fluid dynamics (CFD) model to simulate airflow and the deposition of aerosol particles within the human respiratory tract. To achieve this, we meticulously constructed a 3D model of the human tracheobronchial airways using SolidWorks software. Our computational analyses encompassed a range of breathing conditions, ranging from 15 to 60 (L/min). Through the application of discrete phase modeling (DPM), we investigate the behavior of two-phase flow dynamics. Our focus lies in the examination of aerosol particles, with diameters ranging from 1 to 10 (μm), in order to evaluate the influence of aerosol particle size on deposition rates. Our findings encompass velocity contour maps, deposition rates of aerosol particles, and insights into the process of aerosol particle entrapment at various locations within the respiratory tract. Our study reveals a direct correlation between higher inhalation rates and larger aerosol particle sizes, resulting in increased deposition rates. Additionally, we observe a heightened deposition of aerosol-particles at bronchi region. These computational results hold significant value in estimating the distribution of doses resulting from radon progeny exposure in distinct anatomical regions of the respiratory tract.

Changes induced in the human respiratory tract by chronic cigarette smoking can reduce the dose to the lungs from exposure to radon progeny

Chronic cigarette smoking leads to changes in the respiratory tract that might affect the dose received from exposure to radon progeny. In this study, changes induced by cigarette smoking in the respiratory tract were collected from the literature and used for calculation of the dose received by the lungs and organs outside the respiratory tract. Morphological and physiological parameters affected by chronic smoking were implemented in the human respiratory tract model (HRTM) used by the International Commission of Radiological Protection (ICRP). Smokers were found to receive lung doses 3% smaller than the ICRP reference worker (non-smoking reference adult male) in mines and 14% smaller in indoor workplaces and tourist caves. A similar dose reduction was found for the extrathoracic region of the HRTM. Conversely, kidneys, brain, and bone marrow of smokers were found to receive from 2.3- up to 3-fold of the dose received by the respective organ in the ICRP reference worker, although they remained at least two orders of magnitude smaller than the lung dose. These results indicate that the differences in the lung dose from radon progeny exposure in cigarette smokers and non-smokers are smaller than 15%.

Circulatory system disease mortality and occupational exposure to radon progeny in the cohort of Newfoundland Fluorspar Miners between 1950 and 2016

ObjectivesExposure to ionizing radiation may increase the risk of circulatory diseases, including heart disease. A limited number of cohort studies of underground miners have investigated these associations. We previously reported a positive but non-statistically significant association between radon progeny and heart disease in a cohort of Newfoundland fluorspar miners. In this study, we report updated findings that incorporate 15 additional years of follow-up.MethodsThe cohort included 2050 miners who worked in the fluorspar mines from 1933 to 1978. Statistics Canada linked the personal identifying data of the miners to Canadian mortality data to identify deaths from 1950 to 2016. We used previously derived individual-level estimates of annual radon progeny exposure in working-level months. Cumulative exposure was categorized into quantiles. We estimated relative risks and their 95% confidence intervals using Poisson regression for deaths from circulatory, ischemic heart disease and acute myocardial infarction. Relative risks were adjusted for attained age, calendar year, and the average number of cigarettes smoked daily.ResultsRelative to the Newfoundland male population, the standardized mortality ratio for circulatory disease in this cohort was 0.82 (95% CI 0.74–0.91). Those in the highest quantile of cumulative radon progeny exposure had a relative risk of circulatory disease mortality of 1.03 (95% CI 0.76–1.40) compared to those in the lowest quantile. The corresponding estimates for ischemic disease and acute myocardial infarction were 0.99 (95% CI 0.66–1.48), and 1.39 (95% CI 0.84–2.30), respectively.ConclusionsOur findings do not support the hypothesis that occupational exposure to radon progeny increases the risk of circulatory disease.

Lung cancer and radon: Pooled analysis of uranium miners hired in 1960 or later

BACKGROUND Despite reductions in exposure for workers and the general public, radon remains a leading cause of lung cancer. Prior studies of underground miners depended heavily upon information on deaths among miners employed in the early years of mine operations when exposures were high and tended to be poorly estimated. To strengthen the basis for radiation protection, we report on follow-up of workers employed in later periods of mine operations for whom we have more accurate exposure information and for whom exposures tended to be accrued at intensities that are more comparable to contemporary settings. METHODS We conducted a pooled analysis of cohort studies of lung cancer mortality among 57,873 male uranium miners in Canada, Czech Republic, France, Germany, and the United States, who were first employed in 1960 or later (thereby excluding miners employed during the periods of highest exposure and focusing on miners who tend to have higher quality assessments of radon progeny exposures). We derived estimates of excess relative rate per 100 working level months (ERR/100 WLM) for mortality from lung cancer. RESULTS The analysis included 1.9 million person-years of observation and 1217 deaths due to lung cancer. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny (ERR/100 WLM=1.33; 95% CI: 0.89, 1.88). The association was modified by attained age, age at exposure, and annual exposure rate; for attained ages <55 years, the ERR/100 WLM was 8.38 (95% CI: 3.30, 18.99) among miners who were exposed at ages >=35 years and at annual exposure rates <0.5 working levels. This association decreased with older attained ages, younger ages at exposure, and higher exposure rates. CONCLUSIONS Estimates of association between radon progeny exposure and lung cancer mortality among relatively contemporary miners are coherent with estimates used to inform current protection guidelines.

Nonmalignant respiratory disease mortality in male Colorado Plateau uranium miners, 1960-2016.

To evaluate trends of nonmalignant respiratory disease (NMRD) mortality among US underground uranium miners on the Colorado Plateau, and to estimate the exposure-response association between cumulative radon progeny exposure and NMRD subtype mortality. Standardized mortality ratios (SMRs) and excess relative rates per 100 working level months (excess relative rate[ERR]/100 WLM) were estimated in a cohort of 4021 male underground uranium miners who were followed from 1960 through 2016. We observed elevated SMRs for all NMRD subtypes. Silicosis had the largest SMR (n = 52, SMR = 41.4; 95% confidence interval [CI]: 30.9, 54.3), followed by other pneumoconiosis (n = 49, SMR = 39.6; 95%CI: 29.6, 52.3) and idiopathic pulmonary fibrosis (IPF) (n = 64, SMR = 4.77; 95%CI 3.67, 6.09). SMRs for silicosis increased with duration of employment; SMRs for IPF increased with duration of employment and calendar period. There was a positive association between cumulative radon exposure and silicosis with evidence of modification by smoking (ERR/100 WLM≥10 pack-years = 0.78; 95%CI: 0.05, 24.6 and ERR/100 WLM<10 pack-years = 0.01; 95%CI: -0.03, 0.52), as well as a small positive association between radon and IPF (ERR/100 WLM = 0.06, 95%CI: 0.00, 0.24); these associations were driven by workers with prior employment in hard rock mining. Uranium mining workers had excess NMRD mortality compared with the general population; this excess persisted throughout follow-up. Exposure-response analyses indicated a positive association between radon exposure and IPF and silicosis, but these analyses have limitations due to outcome misclassification and missing information on occupational co-exposures such as silica dust.

Lung Cancer and Radon: Pooled Analysis of Uranium Miners Hired in 1960 or Later.

Background:Despite reductions in exposure for workers and the general public, radon remains a leading cause of lung cancer. Prior studies of underground miners depended heavily upon information on deaths among miners employed in the early years of mine operations when exposures were high and tended to be poorly estimated.Objectives:To strengthen the basis for radiation protection, we report on the follow-up of workers employed in the later periods of mine operations for whom we have more accurate exposure information and for whom exposures tended to be accrued at intensities that are more comparable to contemporary settings.Methods:We conducted a pooled analysis of cohort studies of lung cancer mortality among 57,873 male uranium miners in Canada, Czech Republic, France, Germany, and the United States, who were first employed in 1960 or later (thereby excluding miners employed during the periods of highest exposure and focusing on miners who tend to have higher quality assessments of radon progeny exposures). We derived estimates of excess relative rate per 100 working level months (ERR/100 WLM) for mortality from lung cancer.Results:The analysis included person-years of observation and 1,217 deaths due to lung cancer. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny (ERR/100 ; 95% CI: 0.89, 1.88). The association was modified by attained age, age at exposure, and annual exposure rate; for attained ages , the ERR/100 WLM was 8.38 (95% CI: 3.30, 18.99) among miners who were exposed at of age and at annual exposure rates of working levels. This association decreased with older attained ages, younger ages at exposure, and higher exposure rates.Discussion:Estimates of association between radon progeny exposure and lung cancer mortality among relatively contemporary miners are coherent with estimates used to inform current protection guidelines. https://doi.org/10.1289/EHP10669

Early postnatal exposure of rat pups to methylglyoxal induces oxidative stress, inflammation and dysmetabolism at adulthood.

This work aimed to investigate the effects of early progeny exposure to methylglyoxal (MG), programming for metabolic dysfunction and diabetes-like complications later in life. At delivery (PN1), the animals were separated into two groups: control group (CO), treated with saline, and MG group, treated with MG (20 mg/kg of BW; i.p.) during the first 2 weeks of the lactation period. In vivo experiments and tissue collection were done at PN90. Early MG exposure decreased body weight, adipose tissue, liver and kidney weight at adulthood. On the other hand, MG group showed increased relative food intake, blood fructosamine, blood insulin and HOMA-IR, which is correlated with insulin resistance. Besides, MG-treated animals presented dyslipidaemia, increased oxidative stress and inflammation. Likewise, MG group showed steatosis and perivascular fibrosis in the liver, pancreatic islet hypertrophy, increased glomerular area and pericapsular fibrosis, but reduced capsular space. This study shows that early postnatal exposure to MG induces oxidative stress, inflammation and fibrosis markers in pancreas, liver and kidney, which are related to metabolic dysfunction features. Thus, nutritional disruptors during lactation period may be an important risk factor for metabolic alterations at adulthood.

Low-level radon exposure and lung cancer in the Pooled Uranium Miners Analysis (PUMA)

BACKGROUND AND AIM: Radon, a ubiquitous gas, and its progeny are a leading environmental and occupational cause of lung cancer. To better inform radiation protection standards by estimating risk, we assembled an international cohort study of workers employed in uranium mining in Canada, the Czech Republic, France, Germany, and the United States. METHODS: We focus on miners employed during the more contemporary period of the uranium mining industry when radon exposures tended to be comparatively low, and individual exposure data are available. A cohort of 56,614 male uranium miners first employed in 1960 or later was assembled and followed to ascertain causes of death. Estimates of excess relative rate (ERR) per working level month (WLM) of cumulative radon progeny exposure for mortality from lung cancer were derived by internal Poisson regression. RESULTS:In the follow-up period a total of 1217 lung cancer deaths occurred, accumulating 1.9 million person-years at risk. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny, lagged 5 years (ERR/100 WLM=1.34; 95% CI: 0.89, 1.89). Attained age was a clear modifier of this association, showing a decrease in ERR/WLM with increasing attained age. Further potential modifiers are age at exposure or time since exposure and exposure rate. CONCLUSIONS:PUMA provides the most precise and informative estimates to-date of the association between low-level exposure to radon progeny and lung cancer mortality. The results strengthen the basis for radiation protection standards for radon and its progeny. KEYWORDS: Ionizing radiation, Occupational exposures, Risk assessment,International collaboration

Lung cancer risk and effective dose coefficients for radon: UNSCEAR review and ICRP conclusions

The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has provided a detailed and authoritative update of its reviews of the epidemiology and dosimetry of radon and progeny. Lifetime risk of lung cancer calculated using data for several miner cohorts were 2.4–7.5 × 10−4 per working level month (WLM) of radon-222 progeny exposure for a mixed male/female population and 3.0–9.6 × 10−4 per WLM for a male population. Dosimetric models gave mean values of effective dose coefficients from radon-222 progeny of 12 mSv per WLM for mines, 16 mSv per WLM for indoor workplaces and 11 mSv per WLM for homes. The lifetime risk coefficient used by the International Commission on Radiological Protection (ICRP) is 5 × 10−4 per WLM and it has recently recommended an effective dose coefficient for radon-222 and progeny of 3 mSv per mJ h m−3 (about 10 mSv per WLM) for most circumstances of exposure. The ICRP risk and dose coefficients are supported by the UNSCEAR review and provide a clear and firm basis for current international advice and standards for protection from radon. Notwithstanding this evidence and the ICRP advice, UNSCEAR will continue to use a lower value of effective dose coefficient of 5.7 mSv per WLM for assessments of population exposures.

Comparison of Approaches to Ensuring the Radon Safety of Designed Buildings in Russia and USA

Indoor radon and its progeny exposure poses a significant threat to the population collective health of most countries in the world. Modern construction technologies make it possible to regulate the radon entry from the soil within a wide range, but at present there is no universal approach to ensuring the radon safety of buildings. This situation is partly explained by the multifactorial nature of the process of the radon situation formation in the lower floor premises, which does not allow to unambiguously establishing the dominant mechanism of radon entry. The article discusses technologies for ensuring the radon safety of buildings in Russia and the United States, shows their fundamental differences, advantages and disadvantages.

Temporal effect modifiers of the radon-associated excess relative rate of lung cancer in the Pooled Uranium Miners Analysis (PUMA) study

Aim: The Pooled Uranium Miners Analysis (PUMA) is the largest pooled study of uranium miners to date. Here we report initial observations on temporal patterns of variation in the association between cumulative exposure to radon decay products and lung cancer mortality in this large multinational pooled study. Methods: PUMA combines cohorts of uranium miners from Canada, the Czech Republic, France, Germany, and the United States. PUMA includes approximately 120,000 males followed for lung cancer deaths between 1946 and 2014. Associations between occupational radon progeny exposure and lung cancer mortality were estimated using internal Poisson regression with background stratification by cohort, attained age, calendar period, and race. This analysis focuses on windows of age at exposure and time since exposure modeled simultaneously and separately as modifiers. Results: In this study with 7,774 lung cancer deaths and 4.4 million person-years, there was statistically significant evidence of a positive association between cumulative exposure to radon decay products, under a 5-year lag assumption, and lung cancer mortality. There was statistically significant evidence of variation by age at exposure in the association between cumulative exposure to radon decay products, under a 5-year lag assumption, and lung cancer mortality. There also was statistically significant evidence of variation in the association between cumulative exposure to radon decay products and lung cancer mortality with time since exposure; the estimated excess relative rate (ERR) per working level month (WLM) tended to diminish across windows defined by increasing time since exposure; however, estimated ERR per WLM remained above the null even 35+ years after exposure. Conclusion: Preliminary analyses yield estimates with substantial statistical precision of the radon-lung cancer association and its variation with age at exposure and time since exposure. Further analyses will investigate additional effect modification by exposure rate and heterogeneity between individual studies.

Innovations in applied decision theory for health and safety

ObjectivesThere are established methods for occupational epidemiological cohort analysis, such as proportional hazards regression, that are well suited to aetiological research and yield parameter estimates that allow for succinct communication...

Renal Oxidative Stress and Inflammatory Response in Perinatal Cyclosporine-A Exposed Rat Progeny and its Relation to Gender.

Background and Aim of the Work:The current study postulated that cyclosporine A (CSA) could induce gender-specific renal damage. Hence, the current study aims to investigate the nephrotoxic effect of perinatal exposure of male and female rat progeny to CSA. Moreover, it aims to evaluate the oxidative stress and inflammation as a possible pathophysiologic mechanism.Materials and Methods:Female rats were randomly allocated to two groups of four and assigned to undergo either CSA (15 mg/kg/day; the 6th day after conception and continuing until the progeny were weaned) or vehicle treatment as control groups. At the age of 6 weeks, the progeny were divided into the following four groups: male progeny of control-group mothers (M-vehicle, 7); male progeny of CSA-treated mothers (M-CSA, 9); female progeny of control-group mothers (F-vehicle, 7); and female progeny of CSA-treated mothers (F-CSA, 6). Serum adiponectin, tumor necrosis factor-α (TNF-α) and creatinine, creatinine clearance, and urinary 8-isoprostane were measured. Histopathological examination by hematoxylin and eosin stain of Kidney was carried out.Results:Proteinuria and decreased creatinine clearance are significant in M-CSA than M-vehicle and F-CSA. 8-isoprostane is lower in F-CSA than F-vehicle. Increased TNF-α and decreased adiponectin levels in M-CSA than M-vehicle were observed. No significant differences were found in female rat groups.Conclusion:From the current study, it could be concluded that CSA could induce renal inflammation as well as oxidative stress that may explain the impaired renal function. The sex difference was a prominent finding in their vulnerability to CSA effects.

The use of gamma-survey measurements to better understand radon potential in urban areas

Accounting for as much as 14% of all lung cancers worldwide, cumulative radon progeny exposure is the leading cause of lung cancer among never-smokers both internationally and in the United States. To understand the risk of radon progeny exposure, studies have mapped radon potential using aircraft-based measurements of gamma emissions. However, these efforts are hampered in urban areas where the built environment obstructs aerial data collection. To address part of this limitation, this study aimed to evaluate the effectiveness of using in situ gamma readings (taken with a scintillation probe attached to a ratemeter) to assess radon potential in an urban environment: DeKalb County, part of the Atlanta metropolitan area, Georgia, USA. After taking gamma measurements at 402 survey sites, empirical Bayesian kriging was used to create a continuous surface of predicted gamma readings for the county. We paired these predicted gamma readings with indoor radon concentration data from 1351 residential locations. Statistical tests showed the interpolated gamma values were significantly but weakly positively related with indoor radon concentrations, though this relationship is decreasingly informative at finer geographic scales. Geology, gamma readings, and indoor radon were interrelated, with granitic gneiss generally having the highest gamma readings and highest radon concentrations and ultramafic rock having the lowest of each. Our findings indicate the highest geogenic radon potential may exists in the relatively undeveloped southeastern part of the county. It is possible that in situ gamma, in concert with other variables, could offer an alternative to aerial radioactivity measurements when determining radon potential, though future work will be needed to address this project's limitations.

Radon and Thoron In-air Occupational Exposure Study within Selected Wine Cellars of the Western Cape (South Africa) and Associated Annual Effective Doses.

This is the first known study of exposure of Rn (radon) and secondarily Rn (thoron) in-air activity concentrations assessed within nine selected wine cellars in four wine districts of the Western Cape (South Africa) and the associated annual occupational effective doses. E-PERM electret ion chambers (EIC) and RAD-7 α-detectors were used to perform these measurements. The radon in-air levels ranged from 12 ± 4 Bq m to 770 ± 40 Bq m within the nine selected wine cellars. Eight of the nine wine cellars (excluding results from cellar w-6) had a median radon in-air activity concentration of 48 ± 8 Bq m. Continuous thoron in-air activity concentration levels were also measured near an internal granite wall of the wine cellar w-6 (barrel room), where peak levels of up to 1,520 ± 190 Bq m and an average of 680 ± 30 Bq m were observed. The occupational annual effective dose due to radon and decay progeny exposure in-air within the selected wine cellars ranged from 0.08 ± 0.03 mSv to 4.9 ± 0.3 mSv with a median of 0.32 ± 0.04 mSv (Tmax = 2,000 h). The annual effective dose within the wine cellar (w-6) ranged up to a maximum of 2.5 ± 0.4 mSv (Tmax = 2000 h) due to exposure to thoron and decay progeny. In general, most of the wines cellars pose negligible associated health risk to personnel due to ionizing radiation exposure from the inhalation of radon and progeny. Under certain conditions (proximity and exposure time), caution should be exercised at wine cellar w-6 because of elevated thoron in-air levels.

γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes.

The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans.

Dose estimation derived from the exposure to radon, thoron and their progeny in the indoor environment.

The annual exposure to indoor radon, thoron and their progeny imparts a major contribution to inhalation doses received by the public. In this study, we report results of time integrated passive measurements of indoor radon, thoron and their progeny concentrations that were carried out in Garhwal Himalaya with the aim of investigating significant health risk to the dwellers in the region. The measurements were performed using recently developed LR-115 detector based techniques. The experimentally determined values of radon, thoron and their progeny concentrations were used to estimate total annual inhalation dose and annual effective doses. The equilibrium factors for radon and thoron were also determined from the observed data. The estimated value of total annual inhalation dose was found to be 1.8 ± 0.7 mSv/y. The estimated values of the annual effective dose were found to be 1.2 ± 0.5 mSv/y and 0.5 ± 0.3 mSv/y, respectively. The estimated values of radiation doses suggest no important health risk due to exposure of radon, thoron and progeny in the study area. The contribution of indoor thoron and its progeny to total inhalation dose ranges between 13–52% with mean value of 30%. Thus thoron cannot be neglected when assessing radiation doses.

Fetal oxidative stress mechanisms of neurodevelopmental deficits and exacerbation by ethanol and methamphetamine.

In utero exposure of mouse progeny to alcohol (ethanol, EtOH) and methamphetamine (METH) causes substantial postnatal neurodevelopmental deficits. One emerging pathogenic mechanism underlying these deficits involves fetal brain production of reactive oxygen species (ROS) that alter signal transduction, and/or oxidatively damage cellular macromolecules like lipids, proteins, and DNA, the latter leading to altered gene expression, likely via non-mutagenic mechanisms. Even physiological levels of fetal ROS production can be pathogenic in biochemically predisposed progeny, and ROS formation can be enhanced by drugs like EtOH and METH, via activation/induction of ROS-producing NADPH oxidases (NOX), drug bioactivation to free radical intermediates by prostaglandin H synthases (PHS), and other mechanisms. Antioxidative enzymes, like catalase in the fetal brain, while low, provide critical protection. Oxidatively damaged DNA is normally rapidly repaired, and fetal deficiencies in several DNA repair proteins, including oxoguanine glycosylase 1 (OGG1) and breast cancer protein 1 (BRCA1), enhance the risk of drug-initiated postnatal neurodevelopmental deficits, and in some cases deficits in untreated progeny, the latter of which may be relevant to conditions like autism spectrum disorders (ASD). Risk is further regulated by fetal nuclear factor erythroid 2-related factor 2 (Nrf2), a ROS-sensing protein that upregulates an array of proteins, including antioxidative enzymes and DNA repair proteins. Imbalances between conceptal pathways for ROS formation, versus those for ROS detoxification and DNA repair, are important determinants of risk. Birth Defects Research (Part C) 108:108-130, 2016. © 2016 Wiley Periodicals, Inc.

Analyses of local dose distributions in the lungs for the determination of risk apportionment factors.

For radiation protection purposes, the relative contributions of bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) doses to lung cancer risk are represented by their corresponding apportionment factors. The current assumption of equal apportionment factors can be tested by comparing different radon and thoron progeny exposures, which produce different regional dose distributions, with the pathologically observed regional cancer distributions: (1) radon progeny inhalation, (2) thoron progeny inhalation, (3) thoron and thoron progeny exhalation (Thorotrast patients) and (4) RP inhalation in rats, and cigarette smoke inhalation as smoking is the dominant cause of lung cancer. Comparison with the pathologically observed regional cancer distributions suggests (1) a smaller apportionment factor for the AI region as compared with BB and bb regions and (2) a higher value for the BB region relative to that for the bb region.