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.     

Evaluation of Take‐Home Exposure and Risk Associated with the Handling of Clothing Contaminated with Chrysotile Asbestos

The potential for para‐occupational (or take‐home) exposures from contaminated clothing has been recognized for the past 60 years. To better characterize the take‐home asbestos exposure pathway, a study was performed to measure the relationship between airborne chrysotile concentrations in the workplace, the contamination of work clothing, and take‐home exposures and risks. The study included air sampling during two activities: (1) contamination of work clothing by airborne chrysotile (i.e., loading the clothing), and (2) handling and shaking out of the clothes. The clothes were contaminated at three different target airborne chrysotile concentrations (0–0.1 fibers per cubic centimeter [f/cc], 1–2 f/cc, and 2–4 f/cc; two events each for 31–43 minutes; six events total). Arithmetic mean concentrations for the three target loading levels were 0.01 f/cc, 1.65 f/cc, and 2.84 f/cc (National Institute of Occupational Health and Safety [NIOSH] 7402). Following the loading events, six matched 30‐minute clothes‐handling and shake‐out events were conducted, each including 15 minutes of active handling (15‐minute means; 0.014–0.097 f/cc) and 15 additional minutes of no handling (30‐minute means; 0.006–0.063 f/cc). Percentages of personal clothes‐handling TWAs relative to clothes‐loading TWAs were calculated for event pairs to characterize exposure potential during daily versus weekly clothes‐handling activity. Airborne concentrations for the clothes handler were 0.2–1.4% (eight‐hour TWA or daily ratio) and 0.03–0.27% (40‐hour TWA or weekly ratio) of loading TWAs. Cumulative chrysotile doses for clothes handling at airborne concentrations tested were estimated to be consistent with lifetime cumulative chrysotile doses associated with ambient air exposure (range for take‐home or ambient doses: 0.00044–0.105 f/cc year).     

Mesothelioma: Risk Apportionment Among Asbestos Exposure Sources

The mesothelioma epidemic in the United States, which peaked during the 2000–2004 period, can be traced to high‐level asbestos exposures experienced by males in occupational settings prior to the full recognition of the disease‐causing potential of asbestos and the establishment of enforceable asbestos exposure limits by the Occupational Safety and Health Administration (OSHA) in 1971. Many individuals diagnosed with mesothelioma where asbestos has been identified as a contributing cause of the disease have filed claims seeking compensation from asbestos settlement trusts or through the court system. An individual with mesothelioma typically has been exposed to asbestos in more than one setting and from more than one asbestos product. Apportioning risk for mesothelioma among contributing factors is an ongoing problem faced by occupational disease compensation boards, juries, parties responsible for paying damages, and currently by the U.S. Senate in its efforts to formulate a bill establishing an asbestos settlement trust. In this article we address the following question: If an individual with mesothelioma where asbestos has been identified as a contributing cause were to be compensated for his or her disease, how should that compensation be apportioned among those responsible for the asbestos exposures? For the purposes of apportionment, we assume that asbestos is the only cause of mesothelioma and that every asbestos exposure contributes, albeit differentially, to the risk. We use an extension of the mesothelioma risk model initially proposed in the early 1980s to quantify the contribution to risk of each exposure as a percentage of the total risk. The percentage for each specific discrete asbestos exposure depends on the start and end dates, the intensity, and the asbestos fiber type for the exposure. We provide justification for the use of the mesothelioma risk model for apportioning risk and discuss how to assess uncertainty associated with its application.     

Human Health Risks Associated with Asbestos Abatement

Upperbound lifetime excess cancer risks were calculated for activities associated with asbestos abatement using a risk assessment framework developed for EPA's Superfund program. It was found that removals were associated with cancer risks to workers which were often greater than the commonly accepted cancer risk of 1 x 10(-6), although lower than occupational exposure limits associated with risks of 1 x 10(-3). Removals had little effect in reducing risk to school populations. Risks to teachers and students in school buildings containing asbestos were approximately the same as risks associated with exposure to ambient asbestos by the general public and were below the levels typically of concern to regulatory agencies. During abatement, however, there were increased risks to both workers and nearby individuals. Careless, everyday building maintenance generated the greatest risk to workers followed by removals and encapsulation. If asbestos abatement was judged by the risk criteria applied to EPA's Superfund program, the no-action alternative would likely be selected in preference to removal in a majority of cases. These conclusions should only be interpreted within the context of an overall asbestos risk management program, which includes consideration of specific fiber types and sizes, sampling and analytical limitations, physical condition of asbestos-containing material, episodic peak exposures, and the number of people potentially exposed.     

A Quantitative Estimate of Leukemia Mortality Associated with Occupational Exposure to Benzene3

In 1980, the U.S. Supreme Court vacated a revised occupational standard for benzene, stating that the Occupational Safety and Health Administration (OSHA) had failed to demonstrate that significant health risks existed under the current standard. This decision has been interpreted by OSHA as requiring the consideration of quantitative risk assessments, whenever possible, in the development of regulations for occupational carcinogens. In light of this decision, the available epidemiologic evidence was used to generate a quantitative risk assessment for benzene. Uncertainties regarding the levels and lengths of benzene exposure for the studied cohorts were incorporated into the analysis. Based on the one-hit model, the assessment indicates that a working lifetime exposure to benzene at the current permissible exposure level (10 ppm) poses a substantial excess risk of death from leukemia. This report discusses the calculation of the risk estimates, the basis for relying on certain assumptions, and the inherent limitations of using epidemiologic studies to quantify cancer risks.     

Potential Airborne Asbestos Exposure and Risk Associated with the Historical Use of Cosmetic Talcum Powder Products

Over time, concerns have been raised regarding the potential for human exposure and risk from asbestos in cosmetic‐talc–containing consumer products. In 1985, the U.S. Food and Drug Administration (FDA) conducted a risk assessment evaluating the potential inhalation asbestos exposure associated with the cosmetic talc consumer use scenario of powdering an infant during diapering, and found that risks were below levels associated with background asbestos exposures and risk. However, given the scope and age of the FDA's assessment, it was unknown whether the agency's conclusions remained relevant to current risk assessment practices, talc application scenarios, and exposure data. This analysis updates the previous FDA assessment by incorporating the current published exposure literature associated with consumer use of talcum powder and using the current U.S. Environmental Protection Agency's (EPA) nonoccupational asbestos risk assessment approach to estimate potential cumulative asbestos exposure and risk for four use scenarios: (1) infant exposure during diapering; (2) adult exposure from infant diapering; (3) adult exposure from face powdering; and (4) adult exposure from body powdering. The estimated range of cumulative asbestos exposure potential for all scenarios (assuming an asbestos content of 0.1%) ranged from 0.0000021 to 0.0096 f/cc‐yr and resulted in risk estimates that were within or below EPA's acceptable target risk levels. Consistent with the original FDA findings, exposure and corresponding health risk in this range were orders of magnitude below upper‐bound estimates of cumulative asbestos exposure and risk at ambient levels, which have not been associated with increased incidence of asbestos‐related disease.     

Cancer Risk Assessment with Intermittent Exposure

Applications of methods for carcinogenic risk assessment often focus on estimating lifetime cancer risk. With intermittent or time-dependent exposures, lifetime risk is often approximated on the basis of a lifetime average daily dose (LADD). In this article, we show that there exists a lifetime equivalent constant dose (LECD) which leads to the same lifetime risk as the actual time-dependent exposure pattern. The ratio C = LECD/LADD then provides a measure of accuracy of risk estimates based on the LADD, as well as a basis for correcting such estimates. Theoretical results derived under the classical multistage model and the two-stage birth-death-mutation model suggest that the maximum value of C, which represents the factor by which the LADD may lead to underestimates of risk, will often lie in the range of 2- to 5-fold. The practical application of these results is illustrated in the case of astronauts subjected to relatively short-term exposure to volatile organics in a closed space station environment, and in the case of the ingestion of pesticide residues in food where consumption patterns vary with age.     

Estimated Risk of Occupational Fatalities Associated with Hazardous Waste Site Remediation

This study presents a method to assess short term traumatic fatality risks for workers involved in hazardous waste site remediation to provide a quantitative, rather than qualitative, basis for evaluating occupational exposures in remediation feasibility studies. Occupational employment and fatality data for the years 1979–1981 and 1983 were compiled from Bureau of Labor Statistics data for 11 states. These data were analyzed for 17 occupations associated with three common remediation alternatives: excavation and landfill, capping, and capping plus slurry wall. The two occupations with the highest death rates, truck driver and laborer, contributed most to total exposure hours in each alternative. Weighted average death rates were produced for each alternative and multiplied by respective total person-years of exposure. The resultant expected number of fatalities was converted, using the Poisson distribution, to the risk of experiencing at least one fatality, as follows: 0.149 for excavation and landfill, 0.012 for capping, and 0.014 for capping plus slurry wall. These risks were discussed in light of the need to obtain more reliable and comprehensive data than are currently available on the occupational safety and health risks associated with hazardous waste site remediation and the need for a more scientific, quantitative approach to remediation decisions involving risks to workers.     

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.     

Quantitative Assessment of the Risk of Lung Cancer Associated with Occupational Exposure to Refractory Ceramic Fibers

We present the results of a quantitative assessment of the lung cancer risk associated with occupational exposure to refractory ceramic fibers (RCF). The primary sources of data for our risk assessment were two long-term oncogenicity studies in male Fischer rats conducted to assess the potential pathogenic effects associated with prolonged inhalation of RCF. An interesting feature of the data was the availability of the temporal profile of fiber burden in the lungs of experimental animals. Because of this information, we were able to conduct both exposure–response and dose–response analyses. Our risk assessment was conducted within the framework of a biologically based model for carcinogenesis, the two-stage clonal expansion model, which allows for the explicit incorporation of the concepts of initiation and promotion in the analyses. We found that a model positing that RCF was an initiator had the highest likelihood. We proposed an approach based on biological considerations for the extrapolation of risk to humans. This approach requires estimation of human lung burdens for specific exposure scenarios, which we did by using an extension of a model due to Yu. Our approach acknowledges that the risk associated with exposure to RCF depends on exposure to other lung carcinogens. We present estimates of risk in two populations: (1) a population of nonsmokers and (2) an occupational cohort of steelworkers not exposed to coke oven emissions, a mixed population that includes both smokers and nonsmokers.     

Projections of Cancer Risks Attributable to Future Exposure to Asbestos

To assess the maximum possible impact of further government regulation of asbestos exposure, projections were made of the use of asbestos in nine product categories for the years 1985-2000. A life table risk assessment model was then developed to estimate the excess cases of cancer and lost person-years of life likely to occur among those occupationally and nonoccupationally exposed to the nine asbestos product categories manufactured in 1985-2000. These estimates were made under the assumption that government regulation remains at its 1985 level. Use of asbestos in the nine product categories was predicted to decline in all cases except for friction products. The risk assessment results show that, although the cancer risks from future exposure to asbestos are significantly less than those from past exposures, in the absence of more stringent regulations, a health risk remains.     

Leukemia Risk Associated with Benzene Exposure in the Pliofilm Cohort: I. Mortality Update and Exposure Distribution

The National Institute of Occupational Safety and Health (NIOSH) recently completed a vital status update adding 6 years of observation on the rubber workers known as the Pliofilm cohort. Using traditional standardized mortality ratio (SMR) analysis, we investigate the impact of the additional information gathered in the NIOSH update. We also compare the effect of using three sets of job-, plant-, and year-specific exposure estimates on the evaluation of benzene's leukemogenicity. The lack of any additional cases of multiple myeloma does not support trends toward elevated risks for this endpoint (as had been observed earlier), and there is no indication of increased incidences of solid tumors (as predicted by animal studies). Qualitatively, which exposure estimates are used does not alter the conclusions. The data added in the update did not greatly modify the estimated relative risk of leukemia associated with benzene exposure, but did confirm previous findings that occupational exposure to high concentrations had leukemogenic potential. The fact that leukemia has not been observed in any individual who started employment in Pliofilm production after 1950 suggests that the observed leukemia cases could be a response to very high levels of benzene exposure that occurred during the early years of this manufacturing process.     

Computerized Estimates of Potential Occupational Health Risk Due to Chemical Exposure

Estimating the potential health risk encountered by workers due to their exposure to various chemicals is enormously complex, since many chemicals may be involved and each may have multiple toxic effects. As an aid to this estimation process, a computer program, or model, which computes index numbers expressing the relative health risk of occupational groups due to their potential chemical exposures was developed at the National Institute for Occupational Safety and Health (NIOSH). This model considers an inventory of the chemicals to which specific occupational groups are potentially exposed, the published information regarding the toxic effects of each chemical, and the conditions of occupational exposure. The system then develops indices of potential occupational group health risk by considering weighted combinations of eight distinct health effects. No direct comparison with external occupational risk indices is currently possible, but internal testing of the model reveals no obvious inconsistencies.     

Computerized Estimates of Potential Occupational Health Risk Due to Chemical Exposure

Estimating the potential health risk encountered by workers due to their exposure to various chemicals is enormously complex, since many chemicals be involved and each may have multiple toxic effects. As an aid to this estimation process, a computer program, or model, which computes index numbers expressing the relative health risk of occupational groups due to their potential chemical exposures was developed at the National Institute for Occupational Safety and Health (NIOSH). This model considers an inventory of the chemicals to which specific occupational groups are potentially exposed, the published information regarding the toxic effects of each chemical, and the conditions of occupational exposure. The system then develops indices of potential occupational group health risk by considering weighted combinations of eight distinct health effects. No direct comparison with external occupational risk indices is currently possible, but internal testing of the model reveals no obvious inconsistencies.     

Leukemia Risk Associated with Benzene Exposure in the Pliofilm Cohort. II. Risk Estimates

The detailed work histories of the individual workers composing the Pliofilm cohort represent a unique resource for estimating the dose-respoonse for leukemia that may follow occupational exposure to benzene. In this paper, we report the results of analyzing the updated Pliofilm cohort using the proportional hazards model, a more sophisticated technique that uses more of the available exposure data than the conditional logistic model used by Rinsky et al. The more rigorously defined exposure estimates derived by Paustenbach et al. are consistent with those of Crump and Allen in giving estimates of the slope of the leukemogenic dose-response that are not as steep as the slope resulting from the exposure estimates of Rinsky et al. We consider estimates of 0.3-0.5 additional leukemia deaths per thousand workers with 45 ppm-years of cumulative benzene exposure to be the best estimates currently available of leukemia risk from occupational exposure to benzene. These risks were estimated in the proportional hazards model when the exposure estimates of Crump and Allen or of Paustenbach et al. were used to derive a cumulative concentration-by-time metric.     

Comparative Risks of Cancer from Drywall Finishing Based on Stochastic Modeling of Cumulative Exposures to Respirable Dusts and Chrysotile Asbestos Fibers

Sanding joint compounds is a dusty activity and exposures are not well characterized. Until the mid 1970s, asbestos‐containing joint compounds were used by some people such that sanding could emit dust and asbestos fibers. We estimated the distribution of 8‐h TWA concentrations and cumulative exposures to respirable dusts and chrysotile asbestos fibers for four worker groups: (1) drywall specialists, (2) generalists, (3) tradespersons who are bystanders to drywall finishing, and (4) do‐it‐yourselfers (DIYers). Data collected through a survey of experienced contractors, direct field observations, and literature were used to develop prototypical exposure scenarios for each worker group. To these exposure scenarios, we applied a previously developed semi‐empirical mathematical model that predicts area as well as personal breathing zone respirable dust concentrations. An empirical factor was used to estimate chrysotile fiber concentrations from respirable dust concentrations. On a task basis, we found mean 8‐h TWA concentrations of respirable dust and chrysotile fibers are numerically highest for specialists, followed by generalists, DIYers, and bystander tradespersons; these concentrations are estimated to be in excess of the respective current but not historical Threshold Limit Values. Due to differences in frequency of activities, annual cumulative exposures are highest for specialists, followed by generalists, bystander tradespersons, and DIYers. Cumulative exposure estimates for chrysotile fibers from drywall finishing are expected to result in few, if any, mesothelioma or excess lung cancer deaths according to recently published risk assessments. Given the dustiness of drywall finishing, we recommend diligence in the use of readily available source controls.     

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.     

How Do Cancer Risks Predicted From Animal Bioassays Compare with the Epidemiologic Evidence? The Case of Ethylene Dibromide

Cancer risks for ethylene dibromide (EDB) were estimated by fitting several linear non-threshold additive models to data from a gavage bioassay. Risks predicted by these models were compared to the observed cancer mortality among a cohort of workers occupationally exposed to the same chemical. Models that accounted for the shortened latency period in the gavaged rats predicted upper bound risks that were within a factor of 3 of the observed cancer deaths. Data from an animal inhalation study of EDB also were compatible with the epidemiologic data. These findings contradict those of Ramsey et al. (1978), who reported that extrapolation from animal data produced highly exaggerated risk estimates for EDB-exposed workers. This paper explores the reasons for these discrepant findings.     

The Cancer Risk Associated with Residential Exposure to Soil Containing Radioactive Coal Combustion Residuals

Coal combustion residuals (CCRs) are composed of various constituents, including radioactive materials. The objective of this study was to utilize methodology on radionuclide risk assessment from the Environmental Protection Agency (EPA) to estimate the potential cancer risks associated with residential exposure to CCR‐containing soil. We evaluated potential radionuclide exposure via soil ingestion, inhalation of soil particulates, and external exposure to ionizing radiation using published CCR radioactivity values for ²³²Th, ²²⁸Ra, ²³⁸U, and ²²⁶Ra from the Appalachia, Illinois, and Powder River coal basins. Mean and upper‐bound cancer risks were estimated individually for each radionuclide, exposure pathway, and coal basin. For each radionuclide at each coal basin, external exposure to ionizing radiation contributed the greatest to the overall risk estimate, followed by incidental ingestion of soil and inhalation of soil particulates. The mean cancer risks by route of exposure were 2.01 × 10⁻⁶ (ingestion), 6.80 × 10⁻⁹ (inhalation), and 3.66 × 10⁻⁵ (external), while the upper bound cancer risks were 3.70 × 10⁻⁶ (ingestion), 1.18 × 10⁻⁸ (inhalation), and 6.15 × 10⁻⁵ (external), using summed radionuclide‐specific data from all locations. The upper bound cancer risk from all routes of exposure was 6.52 × 10⁻⁵. These estimated cancer risks were within the EPA's acceptable cancer risk range of 1 × 10⁻⁶ to 1 × 10⁻⁴. If the CCR radioactivity values used in this analysis are generally representative of CCR waste streams, then our findings suggest that CCRs would not be expected to pose a significant radiological risk to residents living in areas where contact with CCR‐containing soils might occur.     

Science Policy Choices and the Estimation of Cancer Risk Associated with Exposure to TCDD

United States regulatory agencies use no-threshold models for estimating carcinogenic risks. Other countries use no-threshold models for carcinogens that are genotoxic and threshold models for carcinogens that are not genotoxic, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD or "dioxin"). The U.S. Environmental Protection Agency has proposed a revision of the carcinogenic potency estimate for TCDD that is based on neither a threshold nor a no-threshold model; instead, it is a compromise between risk numbers generated by the two irreconcilably different models. This paper discusses the revision and its implications.