William B. Bunn

A Critical Assessment of Studies on the Carcinogenic Potential of Diesel Exhaust

After decades of research involving numerous epidemiologic studies and extensive investigations in laboratory animals, a causal relationship between diesel exhaust (DE) exposure and lung cancer has not been conclusively demonstrated. Epidemiologic studies of the transportation industry (trucking, busing, and railroad) show a small elevation in lung cancer incidence (relative risks [RRs] generally below 1.5), but a dose response for DE is lacking. The studies are also limited by a lack of quantitative concurrent exposure data and inadequate or lack of controls for potential confounders, particularly tobacco smoking. Furthermore, prior to dieselization, similar elevations in lung cancer incidence have been reported for truck drivers, and in-cab diesel particulate matter (DPM) exposures of truck drivers were comparable to ambient highway exposures. Taken together, these findings suggest that an unidentified occupational agent or lifestyle factor might be responsible for the low elevations in lung cancer reported in the transportation studies. In contrast, underground miners, many of whom experience the highest occupational DPM exposures, generally do not show elevations in lung cancer. Laboratory studies must be interpreted with caution with respect to predicting the carcinogenic potential of DE in humans. Tumors observed in rats following lifetime chronic inhalation of very high levels of DPM may be attributed to species-specific overload mechanisms that lack relevance to humans. Increased tumor incidence was not observed in other species (hamsters or mice) exposed to DPM at very high levels or in rats exposed at lower levels (≤2000 μg/m3). Although DPM contains mutagens, mutagenicity studies in which cells were exposed to concentrated extracts of DPM also have limited application to human risk assessment, because such extracts can be obtained from DPM only by using strong organic solvents, agitation, and heat. Most studies have shown that whole DPM itself is not mutagenic because the adsorbed organic compounds are minimally bioavailable in aqueous-based fluids. In the past two decades, dramatic changes in diesel engine technology (e.g., low-sulfur fuel and exhaust after-treatment) have resulted in >99% reduction in DPM and other quantitative and qualitative changes in the chemical and physical characteristics of diesel exhaust. Thus, the current database, which is focused almost entirely on the potential health effects of traditional diesel exhaust (TDE), has only limited utility in assessing the potential health risks of new-technology diesel exhaust (NTDE). To overcome some of the limitations of the historical epidemiologic database on TDE and to gain further insights into the potential health effects of NTDE, new studies are underway and more studies are planned.

Health, safety, and productivity in a manufacturing environment

The Health and Productivity Management model at International Truck and Engine Corporation includes the measurement, analysis, and management of the individual component programs affecting employee safety, health, and productivity. The key to the success of the program was the iterative approach used to identify the opportunities, develop interventions, and achieve targets through continuous measurement and management. In addition, the integration of multiple disciplines and the overall emphasis on employee productivity and its cost are key foci of the International Model. The program was instituted after economic and clinical services’ analyses of data on International employees showed significant excess costs and a high potential for health care cost reductions based on several modifiable health risk factors. The company also faced significant challenges in the safety, workers’ compensation, and disability areas. The program includes safety, workers’ compensation, short-term disability, long-term disability, health care, and absenteeism. Monthly reports/analyses are sent to senior management, and annual goals are set with the board of directors. Economic impact has been documented in the categories after intervention. For example, a comprehensive corporate wellness effort has had a significant impact in terms of reducing both direct health care cost and improving productivity, measured as absenteeism. Workers’ compensation and disability program interventions have had an impact on current costs, resulting in a significant reduction of financial liability. In the final phase of the program, all direct and indirect productivity costs will be quantified. The impact of the coordinated program on costs associated with employee health will be analyzed initially and compared with a “silo” approach.

Recent studies of man-made vitreous fibers. Chronic animal inhalation studies.

The history of asbestos use and asbestos-related disease is replete with comments that the public health would have been better protected if the results of laboratory investigation, epidemiologic surveys, and clinical studies were made available at appropriate intervals during the ongoing research, rather than in the generally accepted method of awaiting completion of studies prior to reporting medical and scientific findings. No substantive evidence of long-term adverse effects has been published in workers exposed to man-made vitreous fibers. Nevertheless, in an effort to preclude a repetition of this error of omission that occurred with asbestos exposure and use, the Thermal Insulation Manufacturers Association is regularly reporting interim and final data from ongoing animal studies. A significant segment of man-made vitreous fibers have now been tested in state-of-the-art chronic studies. This paper includes the recently completed animal inhalation studies on refractory ceramic fibers and fibrous glass. It also reviews interim data on mineral wool studies.

Carcinogenicity Studies of Diesel Engine Exhausts in Laboratory Animals: A Review of Past Studies and a Discussion of Future Research Needs

Diesel engines play a vital role in world economy, especially in transportation. Exhaust from traditional diesel engines using high-sulfur fuel contains high concentrations of respirable carbonaceous particles with absorbed organic compounds. Recognition that some of these compounds are mutagenic has raised concern for the cancer-causing potential of diesel exhaust exposure. Extensive research addressing this issue has been conducted during the last three decades. This critical review is offered to facilitate an updated assessment of the carcinogenicity of diesel exhaust and to provide a rationale for future animal research of new diesel technology. Life-span bioassays in rats, mice, and Syrian hamsters demonstrated that chronic inhalation of high concentrations of diesel exhaust caused lung tumors in rats but not in mice or Syrian hamsters. In 1989, the International Agency for Research on Cancer (IARC) characterized the rat findings as “sufficient evidence of animal carcinogenicity,” and, with “limited” evidence from epidemiological studies, classified diesel exhaust Category 2A, a “probable human carcinogen.” Subsequent research has shown that similar chronic high concentration exposure to particulate matter generally considered innocuous (such as carbon black and titanium dioxide) also caused lung tumors in rats. Thus, in 2002, the U.S. Environmental Protection Agency (EPA) concluded that the findings in the rats should not be used to characterize the cancer hazard or quantify the cancer risk of diesel exhaust. Concurrent with the conduct of the health effects studies, progressively more stringent standards have been promulgated for diesel exhaust particles and NOx. Engine manufacturers have responded with new technology diesel (improved engines, fuel injection, fuels, lubricants, and exhaust treatments) to meet the standards. This review concludes with an outline of research to evaluate the health effects of the new technology, research that is consistent with recommendations included in the U.S. EPA 2002 health assessment document. When this research has been completed, it will be appropriate for IARC to evaluate the potential cancer hazard of the new technology diesel.

The burden of allergies--and the capacity of medications to reduce this burden-in a heavy manufacturing environment.

This article addresses the observational findings of the first systematic study undertaken by a manufacturer to address the impact of allergies and use of allergy medications on health, safety, and productivity. It provides background for 3 other papers from the same project, including an evaluation of an intervention to promote appropriate medication use among affected employees, which appear in this issue. The observational data are developed on 10,714 employees from: 1) 2 employee surveys; 2) administrative databases monitoring employee absenteeism, workers compensation, short-term disability, and group health. The results show that health, productivity, absenteeism, workplace injury, and workers compensation measures register consistent declines as allergy severity levels increase. This pattern is present but less pronounced for the short-term disability and group health measures. In addition, among the 16 measures registering a significant allergy burden, 6 posted significant advantages for the use of nonsedating antihistamines relative to other medication regimens that included sedative antihistamines. These results document the burden of allergies and the capacity of medications to reduce this burden. Effective intervention programs that target this condition can achieve improved health, productivity, and related outcomes.

Validating self-reported measures of productivity at work: a case for their credibility in a heavy manufacturing setting.

The extent to which employee responses to productivity surveys assess what they are intended to assess has become a pivotal issue for employers and providers. Much work is now being devoted to the validity and reliability of these self-reports. Such issues will likely be resolved only over the long term. In the interim, the skepticism of business decision-makers who are unfamiliar with survey techniques needs to be addressed. This article taps the widespread acceptance that administrative adverse events have gained as indicators of productivity loss to address this issue. Joint analyses of adverse event measures and productivity self-reports on employees at International Truck and Engine Corporation are conducted to test 2 types of criterion validity: 1) concurrent validity; do prior/concurrent adverse events associate with self-reports as logic and common sense dictate? and 2) predictive validity; do self-reports distinguish the risk of subsequent adverse events? Self-reports are found to perform well in both sets of tests. The results are explored in light of: 1) concerns that users have with respect to how self-reports are now being applied, and 2) ways in which self-reports serve as a cornerstone for 3 articles that follow in this issue.

Do Long Workhours Impact Health, Safety, and Productivity at a Heavy Manufacturer?

Objectives: To test the health, safety, and productivity effects of long workhours. Methods: Secondary analyses of a longitudinal employee panel (n = 2746). Average hours worked during spring 2001 were assessed relative to health, safety, and productivity outcomes spanning summer 2001 through spring 2002. Results: Employees working overtime were no more likely to incur adverse physical or mental health, presenteeism, or disability outcomes. Those working 60+ hours were more likely to report new injuries and diagnoses, but these effects were overwhelmed by prior health, demographics, and compensation type. Conclusions: Much previous work has suggested that long workhours generate a wide range of adverse outcomes across the employee continuum. This study found no evidence for pervasive workhour effects. Rather, long workhours—especially weekly schedules at the 60 hour or above mark—can lead to problems in certain areas of health and safety. More research is needed that tests group differences across segmented characteristics (eg, poor versus good health) but keeps workhour impact in perspective.

A Reevaluation of the Literature Regarding the Health Assessment of Diesel Engine Exhaust

While the International Agency for Research on Cancer (IARC) classified diesel exhaust (DE) as a “probable” carcinogen in 1989 based primarily on “sufficient” animal data, other investigators have since concluded that the lung tumors found in the rat studies were a result of particle overloading. Subsequent health risk assessments of DE have not used the rat cancer data. The U.S. Environmental Protection Agency (EPA), in developing its 2002 Health Assessment Document (HAD) for DE, primarily considered the epidemiology studies of railroad workers and truck drivers to develop health risk assessments of DE. However, both sets of epidemiology studies have serious weaknesses that make them unsuitable for cancer risk assessment. Major shortcomings were the lack of contemporaneous measurements of exposures to DE, difficulties with exposure history reconstruction, and adequately accounting for other exposures such as gasoline exhaust and cigarette smoke. To compound these problems, there was not, and there is still not, a specific exposure marker for DE. Interestingly, in the underground mining industry, where diesel exposures are much higher than observed in railroad workers and truck drivers, there was no increase in lung cancer. These problems and concerns led the U.S. EPA to conclude that while DE was a “likely” carcinogen, a unit risk value or range of risk cannot be calculated from existing data and that the risk could be zero. In addition, the DE emissions have changed and continue to change with the implementation of new emission control technologies. The HAD recognized this fact and noted that further studies are needed to assess new diesel engine emissions. Recent chemical characterization studies on low-emitting diesel engines with catalyzed particulate filters have shown emissions rates for several chemicals of concern that are even lower than comparable compressed natural gas (CNG)-fueled engines. With lower emissions, better fire safety, and improved cost-effectiveness of new low-emitting diesels compared to CNG, current efforts to restrict use of low-emitting diesels seems misguided.

Using self-report and adverse event measures to track health's impact on productivity in known groups.

The use of survey data to measure and monitor health and productivity differences between groups is an issue of increasing importance. This article examines the capacity of productivity self-reports (derived from surveys) and adverse event measures (derived from administrative sources) to differentiate groups with a priori known characteristics. A replication strategy is used to test the contributions that productivity self-reports make, alone as well as above and beyond measures of adverse events, to the discrimination of 5 pairs of groups classified by clinical, job type, and demographic criteria. These tests are conducted on representative samples of the active, largely blue-collar employee population at International Truck and Engine Corporation. The results show that both productivity self-reports and adverse event measures differentiate and track known groups. Even in the presence of highly significant effects from adverse event measures, self-reports improve the assessment of productivity. We conclude that: 1) although the joint use of self-reports and adverse event measures is the better approach, practitioners can use self-reports with the expectation that this method will track group differences in health and productivity when adverse event measures are not available; and 2) survey self-reports make unique and independent contributions when adverse events measures are used.

Radiographic and spirometric findings in diatomaceous earth workers

Diatomaceous earth is a noncrystalline form of silica; in processing, calcining leads to formation of cristobalite, a form of crystalline silica. Four hundred ninety-two currently employed diatomaceous earth workers in a large mine and processing facility had chest radiographs performed and interpreted by the International Labour Office (ILO) system. Two hundred sixty-seven subjects underwent spirometry testing. Exposure indices for total dust (largely diatomaceous earth) and cristobalite were reconstructed for each individual based upon personnel records. Analysis demonstrated the following prevalences of radiographic findings: 5% had ILO scores > or = 1/0, and 25% had scores of 0/1 or higher. Regression analyses showed that there was a relationship between both total cristobalite exposure and total dust (largely diatomaceous earth) exposure and the ILO score. Radiographic patterns are not typical of those of classic silicosis. Linear regression analyses for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio did not demonstrate a relationship between cumulative exposure and lung function. Such analyses were performed using all subjects and stratified by smoking status. There were differences in spirometric data according to radiographic ILO category, but the results were inconsistent and did not permit determining if physiologic changes are associated with radiographic change or if this is due to confounding. Overall, the study suggests that diatomaceous earth pneumoconiosis (radiographically defined) is an entity distinct from silicosis. Recent exposure levels may produce radiographic abnormalities but do not lead to demonstrable physiologic effect. The prevalence of the disorder has diminished markedly in response to modern dust control measures. Ongoing medical surveillance is recommended in workers with potential exposure to significant quantity of material.