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.     

Air Nicotine and Saliva Cotinine as Indicators of Workplace Passive Smoking Exposure and Risk1

We model nicotine from environmental tobacco smoke (ETS) in office air and salivary cotinine in nonsmoking U.S. workers. We estimate that: an average salivary cotinine level of 0.4 ng/ml corresponds to an increased lifetime mortality risk of 1/1000 for lung cancer, and 1/100 for heart disease; >95% of ETS-exposed office workers exceed OSHA's significant risk level for heart disease mortality, and 60% exceed significant risk for lung cancer mortality; 4000 heart disease deaths and 400 lung cancer deaths occur annually among office workers from passive smoking in the workplace, at the current 28% prevalence of unrestricted smoking in the office workplace.     

Could Removing Arsenic from Tobacco Smoke Significantly Reduce Smoker Risks of Lung Cancer?

If a specific biological mechanism could be determined by which a carcinogen increases lung cancer risk, how might this knowledge be used to improve risk assessment? To explore this issue, we assume (perhaps incorrectly) that arsenic in cigarette smoke increases lung cancer risk by hypermethylating the promoter region of gene p16INK4a, leading to a more rapid entry of altered (initiated) cells into a clonal expansion phase. The potential impact on lung cancer of removing arsenic is then quantified using a three‐stage version of a multistage clonal expansion (MSCE) model. This refines the usual two‐stage clonal expansion (TSCE) model of carcinogenesis by resolving its intermediate or “initiated” cell compartment into two subcompartments, representing experimentally observed “patch” and “field” cells. This refinement allows p16 methylation effects to be represented as speeding transitions of cells from the patch state to the clonally expanding field state. Given these assumptions, removing arsenic might greatly reduce the number of nonsmall cell lung cancer cells (NSCLCs) produced in smokers, by up to two‐thirds, depending on the fraction (between 0 and 1) of the smoking‐induced increase in the patch‐to‐field transition rate prevented if arsenic were removed. At present, this fraction is unknown (and could be as low as zero), but the possibility that it could be high (close to 1) cannot be ruled out without further data.     

Physical injury risks associated with drinking water arsenic treatment.

We estimated the number of transportation deaths that would be associated with water treatment in Albuquerque to meet the EPA's recently proposed revisions of the Maximum Contaminant Level (MCL) for arsenic. Vehicle mileage was estimated for ion exchange, activated alumina, and iron coagulation/microfiltration water treatment processes to meet an MCL of 0.020 mg/L, 0.010 mg/L, 0.005 mg/L, and 0.003 mg/L. Local crash, injury, and death rates per million vehicle miles were used to estimate the number of injuries and deaths. Depending on the water treatment options chosen, we estimate that meeting an arsenic MCL of 0.005 mg/L will result in 143 to 237 crashes, 58 to 98 injuries, and 0.6 to 2.6 deaths in Albuquerque over a 70-year period, resulting in 26 to 113 years of life lost. The anticipated health benefits for Albuquerque residents from a 0.005 mg/L arsenic MCL, estimated using either a multistage Weibull or Poisson model, ranged from 3 to 80 arsenic-related bladder and lung cancer deaths prevented over a 70-year period, adding between 43 and 1,123 years of life. Whether a revised arsenic MCL increases or reduces overall loss of life in Albuquerque depends on the accuracy of EPA's cancer risk assessment. If the multistage Weibull model accurately estimates the benefits, the years of life added is comparable or lower than the anticipated years lost due to transportation associated with the delivery of chemicals, disposal of treatment waste, and operation of the water treatment system. Coagulation/microfiltration treatment will result in substantially fewer transportation deaths than either ion exchange or activated alumina.     

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.     

Estimated Cancer Risk Associated with Occupational Asbestos Exposure

This paper estimates the number of workers in the United States who were occupationally exposed to asbestos during and after World War II and assesses the impact of this exposure on overall cancer mortality. The results suggest that over half of the estimated 7–8 million potentially exposed workers employed between 1940 and 1970 may still be alive and at risk of dying from some form of asbestos-related cancer. While the maximum number of excess cancer deaths associated with this occupational exposure is likely to occur sometime in this decade, such deaths will continue to be seen for many years thereafter. At their peak, these deaths may account for an estimated 3% of the annual cancer death toll, with an associated range of 1.4–4.4%.     

Significance of Exposure Assessment to Analysis of Cancer Risk from Inorganic Arsenic in Drinking Water in Taiwan

The primary source of evidence that inorganic arsenic in drinking water is associated with increased mortality from cancer at internal sites (bladder, liver, lung, and other organs) is a large ecologic study conducted in regions of Southwest Taiwan endemic to Blackfoot disease. The dose-response patterns for lung, liver, and bladder cancers display a nonlinear dose-response relationship with arsenic exposure. The data do not appear suitable, however, for the more refined task of dose-response assessment, particularly for inference of risk at the low arsenic concentrations found in some U.S. water supplies. The problem lies in variable arsenic concentrations between the wells within a village, largely due to a mix of shallow wells and deep artesian wells, and in having only one well test for 24 (40%) of the 60 villages. The current analysis identifies 14 villages where the exposure appears most questionable, based on criteria described in the text. The exposure values were then changed for seven of the villages, from the median well test being used as a default to some other point in the village's range of well tests that would contribute to smoothing the appearance of a dose-response curve. The remaining seven villages, six of which had only one well test, were deleted as outliers. The resultant dose-response patterns showed no evidence of excess risk below arsenic concentrations of 0.1 mg/l. Of course, that outcome is dependent on manipulation of the data, as described. Inclusion of the seven deleted villages would make estimates of risk much higher at low doses. In those seven villages, the cancer mortality rates are significantly high for their exposure levels, suggesting that their exposure values may be too low or that other etiological factors need to be taken into account.     

Estimation of Unit Risk for Coke Oven Emissions

In 1984, based on epidemiological data on cohorts of coke oven workers, USEPA estimated a unit risk for lung cancer associated with continuous exposure from birth to 1 pg/m3 of coke oven emissions, of 6.2 × This risk assessment was based on information on the cohorts available through 1966. Follow-up of these cohorts has now been extended to 1982 and, moreover, individual job histories, which were not available in 1984, have been constructed. In this study, lung cancer mortality in these cohorts of coke oven workers with extended follow-up was analyzed using standard techniques of survival analysis and a new approach based on the two stage clonal expansion model of carcinogenesis. The latter approach allows the explicit consideration of detailed patterns of exposure of each individual in the cohort. The analyses used the extended follow-up data through 1982 and the detailed job histories now available. Based on these analyses, the best estimate of unit risk is 1.5 × with 95% confidence interval = 1.2 × 10-"1.8 X     

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.     

Comparative Potency Method for Cancer Risk Assessment: Application to Diesel Particulate Emissions1

An estimation of the human lung cancer “unit risk” from diesel engine particulate emissions has been made using a comparative potency approach. This approach involves evaluating the tumorigenic and mutagenic potencies of the particulates from four diesel and one gasoline engine in relation to other combustion and pyrolysis products (coke oven, roofing tar, and cigarette smoke) that cause lung cancer in humans. The unit cancer risk is predicated on the linear nonthreshold extrapolation model and is the individual lifetime excess lung cancer risk from continuous exposure to 1 μg carcinogen per m³ inhaled air. The human lung cancer unit risks obtained from the epidemiologic data for coke oven workers, roofing tar applicators, and cigarette smokers were, respectively, 9.3 × 10^?4, 3.6 × 10^?4, and 2.2 × 10^?6 per μg particulate organics per m³ air. The comparative potencies of these three materials and the diesel and gasoline engine exhaust particulates (as organic extracts) were evaluated by in vivo tumorigenicity bioassays involving skin initiation and skin carcinogenicity in SENCAR mice and by the in vitro bioassays that proved suitable for this analysis: Ames Salmonella microsome bioassay, L5178Y mouse lymphoma cell mutagenesis bioassay, and sister chromatid exchange bioassay in Chinese hamster ovary cells. The relative potencies of the coke oven, roofing tar, and cigarette smoke emissions, as determined by the mouse skin initiation assay, were within a factor of 2 of those determined using the epidemiologic data. The relative potencies, from the in vitro bioassays as compared to the human data, were similar for coke oven and roofing tar, but for the cigarette smoke condensate the in vitro tests predicted a higher relative potency. The mouse skin initiation bioassay was used to determine the unit lung cancer risk for the most potent of the diesel emissions. Based on comparisons with coke oven, roofing tar, and cigarette smoke, the unit cancer risk averaged 4.4 × 10^?4. The unit lung cancer risks for the other, less potent motor-vehicle emissions were determined from their comparative potencies relative to the most potent diesel using three in vitro bioassays. There was a high correlation between the in vitro and in vivo bioassays in their responses to the engine exhaust particulate extracts. The unit lung cancer risk per μg particulates per m³ for the automotive diesel and gasoline exhaust particulates ranged from 0.20 × 10^?4 to 0.60 × 10^?4; that for the heavy-duty diesel engine was 0.02 × 10^?4. These unit risks provide the basis for a future assessment of human lung cancer risks when combined with human population exposure to automotive emissions.     

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.     

Comparing Toxicologic and Epidemiologic Studies: Methylene Chloride-A Case Study

Exposure to methylene chloride induces lung and liver cancers in mice. The mouse bioassay data have been used as the basis for several cancer risk assessments. ^(1,2) The results from epidemiologic studies of workers exposed to methylene chloride have been mixed with respect to demonstrating an increased cancer risk. The results from a negative epidemiologic study of Kodak workers have been used by two groups of investigators to test the predictions from the EPA risk assessment models.^(3,4) These two groups used very different approaches to this problem, which resulted in opposite conclusions regarding the consistency between the animal model predictions and the Kodak study results. The results from the Kodak study are used to test the predictions from OSHA's multistage models of liver and lung cancer risk. Confidence intervals for the standardized mortality ratios (SMRs) from the Kodak study are compared with the predicted confidence intervals derived from OSHA's risk assessment models. Adjustments for the "healthy worker effect," differences in length of follow-up, and dosimetry between animals and humans were incorporated into these comparisons. Based on these comparisons, we conclude that the negative results from the Kodak study are not inconsistent with the predictions from OSHA's risk assessment model.     

Complicated grief symptoms in caregivers of persons with lung cancer: the role of family conflict, intrapsychic strains, and hospice utilization

Guided by a stress process conceptual model, this study examines social and psychological determinants of complicated grief symptoms focusing on family conflict, intrapsychic strains, and the potential moderating effect of care quality and hospice utilization. Relying on data from 152 spouse and adult child lung cancer caregiver survey respondents, drawn from an ancillary study of the Assessment of Cancer CarE and SatiSfaction (ACCESS) in Wisconsin, hierarchical multiple regression analysis was used to examine determinants of complicated grief. After controlling for contextual factors and time since death, complicated grief symptoms were higher among caregivers with less education, among families with lower prior conflict but higher conflict at the end-of-life, who had family members who had difficulty accepting the illness, and who were caring for patients with greater fear of death. Additionally, hospice utilization moderated the effect of fear of death on complicated grief. Findings suggest that family conflict, intrapsychic strains, and hospice utilization may help to explain the variability found in complicated grief symptoms among bereaved caregivers. Implications for enhancing complicated grief assessment tools and preventative interventions across the continuum of cancer care are highlighted.     

Quantitative Links Between Arsenic Exposure and Influenza A (H1N1) Infection‐Associated Lung Function Exacerbations Risk

The objective of this study was to link arsenic exposure and influenza A (H1N1) infection‐induced respiratory effects to assess the impact of arsenic‐contaminated drinking water on exacerbation risk of A (H1N1)‐associated lung function. The homogeneous Poisson process was used to approximate the related processes between arsenic exposure and influenza‐associated lung function exacerbation risk. We found that (i) estimated arsenic‐induced forced expiratory volume in 1 second (FEV₁) reducing rates ranged from 0.116 to 0.179 mL/μg for age 15–85 years, (ii) estimated arsenic‐induced A (H1N1) viral load increasing rate was 0.5 mL/μg, (iii) estimated A (H1N1) virus‐induced FEV₁ reducing rate was 0.10 mL/logTCID50, and (iv) the relationship between arsenic exposure and A (H1N1)‐associated respiratory symptoms scores (RSS) can be described by a Hill model. Here we showed that maximum RSS at day 2 postinfection for Taiwan, West Bengal (India), and the United States were estimated to be in the severe range of 0.83, 0.89, and 0.81, respectively, indicating that chronic arsenic exposure and A (H1N1) infection together are most likely to pose potential exacerbations risk of lung function, although a 50% probability of lung function exacerbations risk induced by arsenic and influenza infection was within the mild and moderate ranges of RSS at day 1 and 2 postinfection. We concluded that avoidance of drinking arsenic‐containing water could significantly reduce influenza respiratory illness and that need will become increasingly urgent as the novel H1N1 pandemic influenza virus infects people worldwide.     

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.     

Shiftwork tolerance and 24-h variations in moods

Abstract

The objective of the study was to identify the differences in 24-h variations in moods between three groups of oil-refinery workers: tolerant shiftworkers, intolerant shiftworkers and workers who had never worked in shifts. Each group comprised 29 workers matched by age. The mood measurements were taken during a 24-h period every 2 h starting from 08:00 h. Results were scored for three scales: positive moods, negative moods and fatigue. The two-factor ANOVA revealed the significant main effect of groups for all three moods indicating differences at the average level of 24-h variations in all moods between workers who differed in the degree of tolerance to shiftwork. The significant main effect of time of day was also found for all moods while the reliable interaction between groups and time of day was observed for negative moods only, indicating a different shape of 24-h variations for non-shiftworkers in comparison to shiftworkers.     

A Risk Assessment for Occupational Acrylonitrile Exposure Using Epidemiology Data

The extensive data from the Blair et al.((1)) epidemiology study of occupational acrylonitrile exposure among 25460 workers in eight plants in the United States provide an excellent opportunity to update quantitative risk assessments for this widely used commodity chemical. We employ the semiparametric Cox relative risk (RR) regression model with a cumulative exposure metric to model cause-specific mortality from lung cancer and all other causes. The separately estimated cause-specific cumulative hazards are then combined to provide an overall estimate of age-specific mortality risk. Age-specific estimates of the additional risk of lung cancer mortality associated with several plausible occupational exposure scenarios are obtained. For age 70, these estimates are all markedly lower than those generated with the cancer potency estimate provided in the USEPA acrylonitrile risk assessment.((2)) This result is consistent with the failure of recent occupational studies to confirm elevated lung cancer mortality among acrylonitrile-exposed workers as was originally reported by O'Berg,((3)) and it calls attention to the importance of using high-quality epidemiology data in the risk assessment process.     

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.     

Dose-Response and Risk Assessment of Airborne Hexavalent Chromium and Lung Cancer Mortality

This study evaluates the dose-response relationship for inhalation exposure to hexavalent chromium [Cr(VI)] and lung cancer mortality for workers of a chromate production facility, and provides estimates of the carcinogenic potency. The data were analyzed using relative risk and additive risk dose-response models implemented with both Poisson and Cox regression. Potential confounding by birth cohort and smoking prevalence were also assessed. Lifetime cumulative exposure and highest monthly exposure were the dose metrics evaluated. The estimated lifetime additional risk of lung cancer mortality associated with 45 years of occupational exposure to 1 microg/m3 Cr(VI) (occupational exposure unit risk) was 0.00205 (90%CI: 0.00134, 0.00291) for the relative risk model and 0.00216 (90%CI: 0.00143, 0.00302) for the additive risk model assuming a linear dose response for cumulative exposure with a five-year lag. Extrapolating these findings to a continuous (e.g., environmental) exposure scenario yielded an environmental unit risk of 0.00978 (90%CI: 0.00640, 0.0138) for the relative risk model [e.g., a cancer slope factor of 34 (mg/kg-day)-1] and 0.0125 (90%CI: 0.00833, 0.0175) for the additive risk model. The relative risk model is preferred because it is more consistent with the expected trend for lung cancer risk with age. Based on statistical tests for exposure-related trend, there was no statistically significant increased lung cancer risk below lifetime cumulative occupational exposures of 1.0 mg-yr/m3, and no excess risk for workers whose highest average monthly exposure did not exceed the current Permissible Exposure Limit (52 microg/m3). It is acknowledged that this study had limited power to detect increases at these low exposure levels. These cancer potency estimates are comparable to those developed by U.S. regulatory agencies and should be useful for assessing the potential cancer hazard associated with inhaled Cr(VI).     

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.