Review of Radon and Lung Cancer Risk

Radon, a long-established cause of lung cancer in uranium and other underground miners, has recently emerged as a potentially important cause of lung cancer in the general population. The evidence for widespread exposure of the population to radon and the well-documented excess of lung cancer among underground miners exposed to radon decay products have raised concern that exposure to radon progeny might also be a cause of lung cancer in the general population. To date, epidemiological data on the lung cancer risk associated with environmental exposure to radon have been limited. Consequently, the lung cancer hazard posed by radon exposure in indoor air has been addressed primarily through risk estimation procedures. The quantitative risks of lung cancer have been estimated using exposure-response relations derived from the epidemiological investigations of uranium and other underground miners. We review five of the more informative studies of miners and recent risk projection models for excess lung cancer associated with radon. The principal models differ substantially in their underlying assumptions and consequently in the resulting risk projections. The resulting diversity illustrates the substantial uncertainty that remains concerning the most appropriate model of the temporal pattern of radon-related lung cancer. Animal experiments, further follow-up of the miner cohorts, and well-designed epidemiological studies of indoor exposure should reduce this uncertainty.     

Assessment of the Effectiveness of Radon Screening Programs in Reducing Lung Cancer Mortality

The present study was aimed at assessing the health consequences of the presence of radon in Quebec homes and the possible impact of various screening programs on lung cancer mortality. Lung cancer risk due to this radioactive gas was estimated according to the cancer risk model developed by the Sixth Committee on Biological Effects of Ionizing Radiations. Objective data on residential radon exposure, population mobility, and tobacco use in the study population were integrated into a Monte‐Carlo‐type model. Participation rates to radon screening programs were estimated from published data. According to the model used, approximately 10% of deaths due to lung cancer are attributable to residential radon exposure on a yearly basis in Quebec. In the long term, the promotion of a universal screening program would prevent less than one death/year on a province‐wide scale (0.8 case; IC 99%: –3.6 to 5.2 cases/year), for an overall reduction of 0.19% in radon‐related mortality. Reductions in mortality due to radon by (1) the implementation of a targeted screening program in the region with the highest concentrations, (2) the promotion of screening on a local basis with financial support, or (3) the realization of systematic investigations in primary and secondary schools would increase to 1%, 14%, and 16.4%, respectively, in the each of the populations targeted by these scenarios. Other than the battle against tobacco use, radon screening in public buildings thus currently appears as the most promising screening policy for reducing radon‐related lung cancer.     

Reanalysis of the DEMS Nested Case‐Control Study of Lung Cancer and Diesel Exhaust: Suitability for Quantitative Risk Assessment

The International Agency for Research on Cancer (IARC) in 2012 upgraded its hazard characterization of diesel engine exhaust (DEE) to “carcinogenic to humans.” The Diesel Exhaust in Miners Study (DEMS) cohort and nested case‐control studies of lung cancer mortality in eight U.S. nonmetal mines were influential in IARC's determination. We conducted a reanalysis of the DEMS case‐control data to evaluate its suitability for quantitative risk assessment (QRA). Our reanalysis used conditional logistic regression and adjusted for cigarette smoking in a manner similar to the original DEMS analysis. However, we included additional estimates of DEE exposure and adjustment for radon exposure. In addition to applying three DEE exposure estimates developed by DEMS, we applied six alternative estimates. Without adjusting for radon, our results were similar to those in the original DEMS analysis: all but one of the nine DEE exposure estimates showed evidence of an association between DEE exposure and lung cancer mortality, with trend slopes differing only by about a factor of two. When exposure to radon was adjusted, the evidence for a DEE effect was greatly diminished, but was still present in some analyses that utilized the three original DEMS DEE exposure estimates. A DEE effect was not observed when the six alternative DEE exposure estimates were utilized and radon was adjusted. No consistent evidence of a DEE effect was found among miners who worked only underground. This article highlights some issues that should be addressed in any use of the DEMS data in developing a QRA for DEE.     

Lay Understanding of Synergistic Risk: The Case of Radon and Cigarette Smoking

The combination of radon and smoking produces a synergistic risk of lung cancer. Lay understanding of this risk was examined from the perspectives of mental models theory, the psychometric approach to risk perception, and optimistic bias. As assessed by interview, participants ( N = 50) had more extensive mental models for the risks of smoking than for the risks of radon or the combination of radon and smoking; 32% knew little or nothing about radon. Despite reading an informational brochure, their risk-perception ratings of the three hazards showed no perception of the synergy between smoking and radon risk, although the combined hazard was rated as less familiar but more controllable than the average of the single hazards ( p < .01). No evidence of optimistic bias for the health consequences of radon, or the combination of radon and smoking was observed. Participants appeared to be combining the single-hazard risks subadditively to arrive at their combined-hazard risk perceptions. Further research on the integration of perceived risks would be beneficial for designing optimal communications about synergistic risk.     

Multi-Stage Model Estimates of Lung Cancer Risk from Exposure to Diesel Exhaust, Based on a U.S. Railroad Worker Cohort

A California Environmental Protection Agency (Cal/EPA) report concluded that a reasonable and likely explanation for the increased lung cancer rates in numerous epidemiological studies is a causal association between diesel exhaust exposure and lung cancer. A version of the present analysis, based on a retrospective study of a U.S. railroad worker cohort, provided the Cal/EPA report with some of its estimates of lung cancer risk associated with diesel exhaust. The individual data for that cohort study furnish information on age, employment, and mortality for 56,000 workers over 22 years. Related studies provide information on exposure concentrations. Other analyses of the original cohort data reported finding no relation between measures of diesel exhaust and lung cancer mortality, while a Health Effects Institute report found the data unsuitable for quantitative risk assessment. None of those three works used multistage models, which this article uses in finding a likely quantitative, positive relations between lung cancer and diesel exhaust. A seven-stage model that has the last or next-to-last stage sensitive to diesel exhaust provides best estimates of increase in annual mortality rate due to each unit of concentration, for bracketing assumptions on exposure. Using relative increases of risk and multiplying by the background lung cancer mortality rates for California, the 95% upper confidence limit of the 70-year unit risks for lung cancer is estimated to be in the range 2.1 x 10(-4) (microg/m3)(-1) to 5.5 x 10(-4) (microg/m3)(-1). These risks constitute the low end of those in the Cal/EPA report and are below those reported by previous investigators whose estimates were positive using human data.     

Lung Cancer Risk from Radon in Marcellus Shale Gas in Northeast U.S. Homes

The amount of radon in natural gas varies with its source. Little has been published about the radon from shale gas to date, making estimates of its impact on radon‐induced lung cancer speculative. We measured radon in natural gas pipelines carrying gas from the Marcellus Shale in Pennsylvania and West Virginia. Radon concentrations ranged from 1,520 to 2,750 Bq/m³ (41–74 pCi/L), and the throughput‐weighted average was 1,983 Bq/m³ (54 pCi/L). Potential radon exposure due to the use of Marcellus Shale gas for cooking and space heating using vent‐free heaters or gas ranges in northeastern U.S. homes and apartments was assessed. Though the measured radon concentrations are higher than what has been previously reported, it is unlikely that exposure from natural gas cooking would exceed 1.2 Bq/m³ (<1% of the U.S. Environmental Protection Agency's action level). Using worst‐case assumptions, we estimate the excess lifetime (70 years) lung cancer risk associated with cooking to be 1.8×10^?4 (interval spanning 95% of simulation results: 8.5×10^?5, 3.4×10^?4). The risk profile for supplemental heating with unvented gas appliances is similar. Individuals using unvented gas appliances to provide primary heating may face lifetime risks as high as 3.9×10^?3. Under current housing stock and gas consumption assumptions, expected levels of residential radon exposure due to unvented combustion of Marcellus Shale natural gas in the Northeast United States do not result in a detectable change in the lung cancer death rates.     

Radon as a Tracer of Lung Changes Induced by Smoking

After smoking, exposure to radon and its progeny is the second leading cause of lung cancer. The probability of inducing lung carcinomas by inhaled radon progeny depends on the deposited radiation dose, and is significantly affected by physiological and morphometric changes induced by smoking. Due to irritation of the airways, the inhalation of cigarette smoke leads to the hyperproduction of mucus. Two concurrent processes occur: on one hand, increased production of mucus protects the target cells against radiation damage; on the other hand, in the case of long-term smokers, a chronic lung obstruction develops, causing an increase in the radiation dose to the lungs. Depending on the duration and intensity of smoking, these processes contribute to the final radiation dose with different weights. The primary objective of this study was to investigate to what extent these smoke-induced changes can modify the resulting absorbed dose of inhaled radon progeny relative to healthy nonsmokers. Since the bronchial dose depends on the degree of lung tissue damage, we have used this dose as a tool for detecting the effects of smoking on the lung epithelium. In other words, the biological effect of radon served as a tracer of changes induced by smoking.     

Diesel Engine Exhaust and Lung Cancer Mortality: Time‐Related Factors in Exposure and Risk

To develop a quantitative exposure‐response relationship between concentrations and durations of inhaled diesel engine exhaust (DEE) and increases in lung cancer risks, we examined the role of temporal factors in modifying the estimated effects of exposure to DEE on lung cancer mortality and characterized risk by mine type in the Diesel Exhaust in Miners Study (DEMS) cohort, which followed 12,315 workers through December 1997. We analyzed the data using parametric functions based on concepts of multistage carcinogenesis to directly estimate the hazard functions associated with estimated exposure to a surrogate marker of DEE, respirable elemental carbon (REC). The REC‐associated risk of lung cancer mortality in DEMS is driven by increased risk in only one of four mine types (limestone), with statistically significant heterogeneity by mine type and no significant exposure‐response relationship after removal of the limestone mine workers. Temporal factors, such as duration of exposure, play an important role in determining the risk of lung cancer mortality following exposure to REC, and the relative risk declines after exposure to REC stops. There is evidence of effect modification of risk by attained age. The modifying impact of temporal factors and effect modification by age should be addressed in any quantitative risk assessment (QRA) of DEE. Until there is a better understanding of why the risk appears to be confined to a single mine type, data from DEMS cannot reliably be used for QRA.     

Risk assessment methodologies for passive smoking-induced lung cancer

Risk assessment methodologies have been successfully applied to control societal risk from outdoor air pollutants. They are now being applied to indoor air pollutants such as environmental tobacco smoke (ETS) and radon. Nonsmokers' exposures to ETS have been assessed based on dosimetry of nicotine, its metabolite, continine, and on exposure to the particulate phase of ETS. Lung cancer responses have been based on both the epidemiology of active and of passive smoking. Nine risk assessments of nonsmokers' lung cancer risk from exposure to ETS have been performed. Some have estimated risks for lifelong nonsmokers only; others have included ex-smokers; still others have estimated total deaths from all causes. To facilitate interstudy comparison, in some cases lung cancers had to be interpolated from a total, or the authors' original estimate had to be adjusted to include ex-smokers. Further, all estimates were adjusted to 1988. Excluding one study whose estimate differs from the mean of the others by two orders of magnitude, the remaining risk assessments are in remarkable agreement. The mean estimate is approximately 5000 +/- 2400 nonsmokers' lung cancer deaths (LCDSs) per year. This is a 25% greater risk to nonsmokers than is indoor radon, and is about 57 times greater than the combined estimated cancer risk from all the hazardous outdoor air pollutants currently regulated by the Environmental Protection Agency: airborne radionuclides, asbestos, arsenic, benzene, coke oven emissions, and vinyl chloride.     

Modeling the Modification of the Risk of Radon-Induced Lung Cancer by Environmental Tobacco Smoke

The presence of environmental tobacco smoke (ETS) in homes has been implicated in the causation of lung cancer. While of interest in its own right, ETS also influences the risk imposed by radon and its decay products. The interaction between radon progeny and ETS alters the exposure, intake, uptake, biokinetics, dosimetry, and radiobiology of those progeny. The present paper details model predictions of the various influences of ETS on these factors in the U.S. population and provides estimates of the resulting change in the risk from average levels of radon progeny. It is predicted that the presence of ETS produces a very small (perhaps unmeasurable) increase in the risk of radiation-induced tracheobronchial cancer in homes with initially very high particle concentrations for both active and never-smokers, but significantly lowers the risk in homes with initially lower particle concentrations for both groups when generation 4 of the lung is considered the target site. For generation 16, the presence of ETS generally increases the radon-induced risk of lung cancer, although the increase should be unmeasurable at high initial particle concentrations. The net effect of ETS on human health is suggested to be a complicated function of the initial housing conditions, the concentration of particles introduced by smoking, the target generation considered, and the smoking status of exposed populations. This situation precludes any simple statements concerning the role of ETS in governing the incidence of lung cancer in a population.     

Residential Radon in Canada: An Uncertainty Analysis of Population and Individual Lung Cancer Risk

Following a comprehensive evaluation of the health risks of radon, the U.S. National Research Council (US-NRC) concluded that the radon inside the homes of U.S. residents is an important cause of lung cancer. To assess lung cancer risks associated with radon exposure in Canadian homes, we apply the new (US-NRC) techniques, tailoring assumptions to the Canadian context. A two-dimensional uncertainty analysis is used to provide both population-based (population attributable risk, PAR; excess lifetime risk ratio, ELRR; and life-years lost, LYL) and individual-based (ELRR and LYL) estimates. Our primary results obtained for the Canadian population reveal mean estimates for ELRR, PAR, and LYL are 0.08, 8%, and 0.10 years, respectively. Results are also available and stratified by smoking status (ever versus never). Conveniently, the three indices (ELRR, PAR, and LYL) reveal similar output uncertainty (geometric standard deviation, GSD approximately 1.3), and in the case of ELRR and LYL, comparable variability and uncertainty combined (GSD approximately 4.2). Simplifying relationships are identified between ELRR, LYL, PAR, and the age-specific excess rate ratio (ERR), which suggest a way to scale results from one population to another. This insight is applied in scaling our baseline results to obtain gender-specific estimates, as well as in simplifying and illuminating sensitivity analysis.     

Diesel Emissions and Lung Cancer1

This paper uses two different methods to assess the potential risk of human lung cancer from exposure to diesel engine emissions. One method analyzes the best available epidemiological evidence on the lung cancer risks of persons exposed in their occupations to diesel engine emissions. The second conducts a comparative analysis of laboratory and epidemiological data on diesel engine emissions and two chemically related environmental exposures–coke oven emissions and roofing tar emissions. The estimates of potential risk derived from these two distinct methods are compared. The sources of uncertainty in each method are explicitly characterized. The value of these estimates for comparing the potential lung cancer risks from exposure to diesel engine emissions with other personal and societal risks are discussed. Also considered are the limitations of these results in predicting the possible excess incidence of lung cancer from ambient exposure to diesel emissions.     

Environmental Tobacco Smoke Revisited: The Reliability of the Data Used for Risk Assessment

Several epidemiological studies have found a weak, but consistent association between lung cancer in nonsmokers and exposure to environmental tobacco smoke (ETS). In addition, a purported link between such exposure and coronary heart disease (CHD) has been of major concern. Although it is biologically plausible that ETS has a contributory role in the induction of lung cancer in nonsmoking individuals, dose-response extrapolation-supported by the more solid database for active smokers-gives an additional risk for lung cancer risk that is more than one order of magnitude lower than that indicated by major positive epidemiological studies. The discrepancy between available epidemiological data and dosimetric estimates seems, to a major part, to reflect certain systematic biases in the former that are difficult to control by statistical analysis when dealing with risks of such low magnitudes. These include, most importantly, misclassification of smoking status, followed by inappropriate selection of controls, as well as certain confounding factors mainly related to lifestyle, and possibly also hereditary disposition. A significant part of an association between lung cancer and exposure to ETS would disappear, if, on the average, 1 patient out of 20 nonsmoking cases had failed to tell the interviewer that he had, in fact, recently stopped smoking. In the large International Agency for Research on Cancer (IARC) multicenter study even lower misclassification rates would abolish the weak, statistically nonsignificant associations that were found. In the former study an apparent significant protective effect from exposure to ETS in childhood with respect to lung cancer later in life was reported, a most surprising finding. The fact that the mutation spectrum of the p53 tumor suppressor gene in lung tumors of ETS-exposed nonsmokers generally differs from that found in tumors of active smokers lends additional support to the notion that the majority of tumors found in ETS-exposed nonsmokers have nothing to do with tobacco smoke. The one-sided preoccupation with ETS as a causative factor of lung cancer in nonsmokers may seriously hinder the elucidation of the multifactorial etiology of these tumors. Due to the high prevalence of cardiovascular disease in the population, even a modest causal association with ETS would, if valid, constitute a serious public health problem. By pooling data from 20 published studies on ETS and heart disease, some of which reported higher risks than is known to be caused by active smoking, a statistically significant association with spousal smoking is obtained. However, in most of these studies, many of the most common confounding risk factors were ignored and there appears to be insufficient evidence to support an association between exposure to ETS and CHD. Further, it seems highly improbable that exposure to a concentration of tobacco smoke at a level that is generally much less than 1% of that inhaled by a smoker could result in an excess risk for CHD that-as has been claimed-is some 30% to 50% of that found in active smokers. There are certainly valid reasons to limit exposure to ETS as well as to other air pollutants in places such as offices and homes in order to improve indoor air quality. This goal can be achieved, however, without the introduction of an extremist legislation based on a negligible risk of lung cancer as well as an unsupported and highly hypothetical risk for CHD.     

Hexavalent Chromium and Lung Cancer in the Chromate Industry: A Quantitative Risk Assessment

The purpose of this investigation was to estimate excess lifetime risk of lung cancer death resulting from occupational exposure to hexavalent-chromium-containing dusts and mists. The mortality experience in a previously studied cohort of 2,357 chromate chemical production workers with 122 lung cancer deaths was analyzed with Poisson regression methods. Extensive records of air samples evaluated for water-soluble total hexavalent chromium were available for the entire employment history of this cohort. Six different models of exposure-response for hexavalent chromium were evaluated by comparing deviances and inspection of cubic splines. Smoking (pack-years) imputed from cigarette use at hire was included in the model. Lifetime risks of lung cancer death from exposure to hexavalent chromium (assuming up to 45 years of exposure) were estimated using an actuarial calculation that accounts for competing causes of death. A linear relative rate model gave a good and readily interpretable fit to the data. The estimated rate ratio for 1 mg/m3-yr of cumulative exposure to hexavalent chromium (as CrO3), with a lag of five years, was RR=2.44 (95% CI=1.54-3.83). The excess lifetime risk of lung cancer death from exposure to hexavalent chromium at the current OSHA permissible exposure limit (PEL) (0.10 mg/m3) was estimated to be 255 per 1,000 (95% CI: 109-416). This estimate is comparable to previous estimates by U.S. EPA, California EPA, and OSHA using different occupational data. Our analysis predicts that current occupational standards for hexavalent chromium permit a lifetime excess risk of dying of lung cancer that exceeds 1 in 10, which is consistent with previous risk assessments.     

Radon Testing Behavior in a Sample of Individuals with High Home Radon Screening Measurements

Although radon exposure has been identified as the second leading cause of lung cancer, fewer than 6% of U.S. homeowners test their homes for radon. This report examines participants'follow-up radon testing behavior subsequent to receiving an initial screening radon level greater than 20 pCi/L. Sixty-two participants in the Iowa State-Wide Rural Radon Screening Survey who had radon screening measurements over 20 pCi/L were questioned by phone survey 3 months after receipt of their radon screening result to assess: whether participants were aware of radon's health risk; if participants recalled the radon screening results; how participants perceived the relative health risk of radon and whether participants planned follow-up radon testing. Only 19% of the respondents specifically identified lung cancer as the possible adverse health outcome of high radon exposure, and the majority of participants underestimated the health risks high radon levels pose when compared to cigarettes and x-rays. In addition, less than one third (29%)of the participants actually remembered their radon screening level within 10 pCi/L 3 months after receiving their screening results. Only 53% of the individuals correctly interpreted their screening radon level as being in the high range, and only 39% of the participants planned follow-up radon measurements. Receipt of radon screening test results indicating high radon levels was not an adequate motivational factor in itself to stimulate further radon assessment or mitigation. Our findings suggest that free radon screening will not result in a dramatic increase in subsequent homeowner initiated remediation or further recommended radon testing.     

Cigarette Smoking and Multiple Health Risk Behaviors: A Latent Class Regression Model to Identify a Profile of Young Adolescents

Cigarette smoking is often established during adolescence when other health‐related risk behaviors tend to occur. The aim of the study was to further investigate the hypothesis that risky health behaviors tend to cluster together and to identify distinctive profiles of young adolescents based on their smoking habits. To explore the idea that smoking behavior can predict membership in a specific risk profile of adolescents, with heavy smokers being more likely to exhibit other risk behaviors, we reanalyzed the data from the 2014 Health Behaviour in School‐Aged Children Italian survey of about 60,000 first‐ and third‐grade junior high school (JHS) and second‐grade high school (HS) students. A Bayesian approach was adopted for selecting the manifest variables associated with smoking; a latent class regression model was employed to identify smoking behaviors among adolescents. Finally, a health‐related risk pattern associated with different types of smoking behaviors was found. Heavy smokers engaged in higher alcohol use and abuse and experienced school failure more often than their peers. Frequent smokers reported below‐average academic achievement and self‐rated their health as fair/poor more frequently than nonsmokers. Lifetime cannabis use and early sexual intercourse were more frequent among heavy smokers. Our findings provide elements for constructing a profile of frequent adolescent smokers and for identifying behavioral risk patterns during the transition from JHS to HS. This may provide an additional opportunity to devise interventions that could be more effective to improve smoking cessation among occasional smokers and to adequately address other risk behaviors among frequent smokers.     

Bounding Poorly Characterized Risks: A Lung Cancer Example

For diseases with more than one risk factor, the sum of probabilistic estimates of the number of cases caused by each individual factor may exceed the total number of cases observed, especially when uncertainties about exposure and dose response for some risk factors are high. In this study, we outline a method of bounding the fraction of lung cancer fatalities not due to specific well-studied causes. Such information serves as a "reality check" for estimates of the impacts of the minor risk factors, and, as such, complements the traditional risk analysis. With lung cancer as our example, we allocate portions of the observed lung cancer mortality to known causes (such as smoking, residential radon, and asbestos fibers) and describe the uncertainty surrounding those estimates. The interactions among the risk factors are also quantified, to the extent possible. We then infer an upper bound on the residual mortality due to "other" causes, using a consistency constraint on the total number of deaths, the maximum uncertainty principle, and the mathematics originally developed of imprecise probabilities.     

An Enforceable Indoor Air Quality Standard for Environmental Tobacco Smoke in the Workplace1

Environmental tobacco smoke (ETS)has recently been determined by U.S. environmental and occupational health authorities to be a human carcinogen. We develop a model which permits using atmospheric nicotine measurements to estimate nonsmokers’ETS lung cancer risks in individual workplaces for the first time. We estimate that during the 1980s, the U.S. nonsmoking adult population's median nicotine lung exposure (homes and workplaces combined)was 143 micrograms (μg)of nicotine daily, and that most-exposed adult nonsmokers inhaled 1430 μg/day. These exposure estimates are validated by pharmacokinetic modeling which yields the corresponding steady-state dose of the nicotine metabolite, cotinine. For U.S. adult nonsmokers of working age, we estimate median cotinine values of about 1.0 nanogram per milliliter (ng/ml)in plasma, and 6.2 ng/ml in urine; for most-exposed nonsmokers, we estimate cotinine concentrations of about 10 ng/ml in plasma and 62 ng/ml in urine. These values are consistent to within 15% of the cotinine values observed in contemporaneous clinical epidemiological studies. Corresponding median risk from ETS exposure in U.S. nonsmokers during the 1980s is estimated at about two lung cancer deaths (LCDs)per 1000 at risk, and for most-exposed nonsmokers, about two LCDs per 100. Risks abroad appear similar. Modeling of the lung cancer mortality risk from passive smoking suggests that de minimis [i.e., “acceptable” (10^-6)], risk occurs at an 8-hr time-weighted-average exposure concentration of 7.5 nanograms of ETS nicotine per cubic meter of workplace air for a working lifetime of 40 years. This model is based upon a linear exposure-response relationship validated by physical, clinical, and epidemiological data. From available data, it appears that workplaces without effective smoking policies considerably exceed this de minimis risk standard. For a substantial fraction of the 59 million nonsmoking workers in the U.S., current workplace exposure to ETS also appears to pose risks exceeding the de manifestos risk level above which carcinogens are strictly regulated by the federal government.     

Approximations for Estimating Change in Life Expectancy Attributable to Air Pollution in Relation to Multiple Causes of Death Using a Cause Modified Life Table

There is considerable debate as to the most appropriate metric for characterizing the mortality impacts of air pollution. Life expectancy has been advocated as an informative measure. Although the life‐table calculus is relatively straightforward, it becomes increasingly cumbersome when repeated over large numbers of geographic areas and for multiple causes of death. Two simplifying assumptions were evaluated: linearity of the relation between excess rate ratio and change in life expectancy, and additivity of cause‐specific life‐table calculations. We employed excess rate ratios linking PM_2.5 and mortality from cerebrovascular disease, chronic obstructive pulmonary disease, ischemic heart disease, and lung cancer derived from a meta‐analysis of worldwide cohort studies. As a sensitivity analysis, we employed an integrated exposure response function based on the observed risk of PM_2.5 over a wide range of concentrations from ambient exposure, indoor exposure, second‐hand smoke, and personal smoking. Impacts were estimated in relation to a change in PM_2.5 from 19.5 μg/m³ estimated for Toronto to an estimated natural background concentration of 1.8 μg/m³. Estimated changes in life expectancy varied linearly with excess rate ratios, but at higher values the relationship was more accurately represented as a nonlinear function. Changes in life expectancy attributed to specific causes of death were additive with maximum error of 10%. Results were sensitive to assumptions about the air pollution concentration below which effects on mortality were not quantified. We have demonstrated valid approximations comprising expression of change in life expectancy as a function of excess mortality and summation across multiple causes of death.     

Potency Factors for Risk Assessment at Libby,Montana

We reanalyzed the Libby vermiculite miners’ cohort assembled by Sullivan to estimate potency factors for lung cancer, mesothelioma, nonmalignant respiratory disease (NMRD), and all‐cause mortality associated with exposure to Libby fibers. Our principal statistical tool for analyses of lung cancer, NMRD, and total mortality in the cohort was the time‐dependent proportional hazards model. For mesothelioma, we used an extension of the Peto formula. For a cumulative exposure to Libby fiber of 100 f/mL‐yr, our estimates of relative risk (RR) are as follows: lung cancer, RR = 1.12, 95% confidence interval (CI) =[1.06, 1.17]; NMRD, RR = 1.14, 95% CI =[1.09, 1.18]; total mortality, RR = 1.06, 95% CI =[1.04, 1.08]. These estimates were virtually identical when analyses were restricted to the subcohort of workers who were employed for at least one year. For mesothelioma, our estimate of potency is K_M = 0.5 × 10^?8, 95% CI =[0.3 × 10^?8, 0.8 × 10^?8]. Finally, we estimated the mortality ratios standardized against the U.S. population for lung cancer, NMRD, and total mortality and obtained estimates that were in good agreement with those reported by Sullivan. The estimated potency factors form the basis for a quantitative risk assessment at Libby.