Health effects research and regulation of diesel exhaust: an historical overview focused on lung cancer risk.

The mutagenicity of organic solvent extracts from diesel exhaust particulate (DEP), first noted more than 55 years ago, initiated an avalanche of diesel exhaust (DE) health effects research that now totals more than 6000 published studies. Despite an extensive body of results, scientific debate continues regarding the nature of the lung cancer risk posed by inhalation of occupational and environmental DE, with much of the debate focused on DEP. Decades of scientific scrutiny and increasingly stringent regulation have resulted in major advances in diesel engine technologies. The changed particulate matter (PM) emissions in "New Technology Diesel Exhaust (NTDE)" from today's modern low-emission, advanced-technology on-road heavy-duty diesel engines now resemble the PM emissions in contemporary gasoline engine exhaust (GEE) and compressed natural gas engine exhaust more than those in the "traditional diesel exhaust" (TDE) characteristic of older diesel engines. Even with the continued publication of epidemiologic analyses of TDE-exposed populations, this database remains characterized by findings of small increased lung cancer risks and inconsistent evidence of exposure-response trends, both within occupational cohorts and across occupational groups considered to have markedly different exposures (e.g. truckers versus railroad shopworkers versus underground miners). The recently published National Institute for Occupational Safety and Health (NIOSH)-National Cancer Institute (NCI) epidemiologic studies of miners provide some of the strongest findings to date regarding a DE-lung cancer association, but some inconsistent exposure-response findings and possible effects of bias and exposure misclassification raise questions regarding their interpretation. Laboratory animal studies are negative for lung tumors in all species, except for rats under lifetime TDE-exposure conditions with durations and concentrations that lead to "lung overload." The species specificity of the rat lung response to overload, and its occurrence with other particle types, is now well-understood. It is thus generally accepted that the rat bioassay for inhaled particles under conditions of lung overload is not predictive of human lung cancer hazard. Overall, despite an abundance of epidemiologic and experimental data, there remain questions as to whether TDE exposure causes increased lung cancers in humans. An abundance of emissions characterization data, as well as preliminary toxicological data, support NTDE as being toxicologically distinct from TDE. Currently, neither epidemiologic data nor animal bioassay data yet exist that directly bear on NTDE carcinogenic potential. A chronic bioassay of NTDE currently in progress will provide data on whether NTDE poses a carcinogenic hazard, but based on the significant reductions in PM mass emissions and the major changes in PM composition, it has been hypothesized that NTDE has a low carcinogenic potential. When the International Agency for Research on Cancer (IARC) reevaluates DE (along with GEE and nitroarenes) in June 2012, it will be the first authoritative body to assess DE carcinogenic health hazards since the emergence of NTDE and the accumulation of data differentiating NTDE from TDE.

Product stewardship and science: safe manufacture and use of fiber glass.

This paper describes a proactive product stewardship program for glass fibers. That effort included epidemiological studies of workers, establishment of stringent workplace exposure limits, liaison with customers on safe use of products and, most importantly, a research program to evaluate the safety of existing glass fiber products and guide development of new even safer products. Chronic inhalation exposure bioassays were conducted with rodents and hamsters. Amosite and crocidolite asbestos produced respiratory tract cancers as did exposure to "biopersistent" synthetic vitreous fibers. "less biopersistent" glass fibers did not cause respiratory tract cancers. Corollary studies demonstrated the role of slow fiber dissolution rates and biopersistence in cancer induction. These results guided development of safer glass fiber products and have been used in Europe to regulate fibers and by IARC and NTP in classifying fibers. IARC concluded special purpose fibers and refractory ceramic fibers are "possibly carcinogenic to humans" and insulation glass wool, continuous glass filament, rock wool and slag wool are "not classifiable as to their carcinogenicity to human." The NTP's 12th report on carcinogens lists "Certain Glass Wool Fibers (Inhalable)" as "reasonably anticipated to be a human carcinogen." "Certain" in the descriptor refers to "biopersistent" glass fibers and excludes "less biopersistent" glass fibers.

Particulate matter in new technology diesel exhaust (NTDE) is quantitatively and qualitatively very different from that found in traditional diesel exhaust (TDE).

Diesel exhaust (DE) characteristic of pre-1988 engines is classified as a "probable" human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC), and the U.S. Environmental Protection Agency has classified DE as "likely to be carcinogenic to humans." These classifications were based on the large body of health effect studies conducted on DE over the past 30 or so years. However, increasingly stringent U.S. emissions standards (1988-2010) for particulate matter (PM) and nitrogen oxides (NOx) in diesel exhaust have helped stimulate major technological advances in diesel engine technology and diesel fuel/lubricant composition, resulting in the emergence of what has been termed New Technology Diesel Exhaust, or NTDE. NTDE is defined as DE from post-2006 and older retrofit diesel engines that incorporate a variety of technological advancements, including electronic controls, ultra-low-sulfur diesel fuel, oxidation catalysts, and wall-flow diesel particulate filters (DPFs). As discussed in a prior review (T. W. Hesterberg et al.; Environ. Sci. Technol. 2008, 42, 6437-6445), numerous emissions characterization studies have demonstrated marked differences in regulated and unregulated emissions between NTDE and "traditional diesel exhaust" (TDE) from pre-1988 diesel engines. Now there exist even more data demonstrating significant chemical and physical distinctions between the diesel exhaust particulate (DEP) in NTDE versus DEP from pre-2007 diesel technology, and its greater resemblance to particulate emissions from compressed natural gas (CNG) or gasoline engines. Furthermore, preliminary toxicological data suggest that the changes to the physical and chemical composition of NTDE lead to differences in biological responses between NTDE versus TDE exposure. Ongoing studies are expected to address some of the remaining data gaps in the understanding of possible NTDE health effects, but there is now sufficient evidence to conclude that health effects studies of pre-2007 DE likely have little relevance in assessing the potential health risks of NTDE exposures.

Non-cancer health effects of diesel exhaust: a critical assessment of recent human and animal toxicological literature.

We reviewed laboratory and clinical studies bearing on the non-cancer health effects of diesel exhaust (DE) published since the 2002 release of the US EPA Health Assessment Document for Diesel Engine Exhaust. We critically evaluated over 100 published articles on experimental research, focusing on their value for predicting the risk of non-cancer health effects in humans exposed to DE. Human controlled-exposure studies provide new evidence of lung inflammatory effects and thrombogenic and ischemic effects of inhaled DE, albeit for older-model diesel engines and concentrations that are much higher (approximately 300 microg/m(3)) than typical ambient or even occupational levels. Recent animal studies provide insight into the potential mechanisms underlying observed respiratory and cardiovascular health responses; however, because of unrealistically high DE concentrations, the mechanisms elucidated in these studies may not be relevant at lower DE exposure levels. Although larger in number, and suggestive of possible mechanisms for non-cancer health effects at elevated DE levels, interpretation of this recent group of clinical-study findings and laboratory-animal results remains hindered by inconsistencies and variability in outcomes, potentially irrelevant DE-exposure compositions, limitations in exposure protocols and pathways, and uncertainties in extrapolation and generalization. A mechanism of action that allows reliable prediction of adverse health effects at DE-exposure levels typical of the present-day ambient and occupational environment has not emerged. Because of changing diesel-engine technology, inhalation studies using realistic environmental and occupational exposures of new-technology diesel exhaust are of critical importance.

Critical review of the human data on short-term nitrogen dioxide (NO2) exposures: evidence for NO2 no-effect levels.

Nitrogen dioxide (NO2) is a ubiquitous atmospheric pollutant due to the widespread prevalence of both natural and anthropogenic sources, and it can be a respiratory irritant when inhaled at elevated concentrations. Evidence for health effects of ambient NO2 derives from three types of studies: observational epidemiology, human clinical exposures, and animal toxicology. Our review focuses on the human clinical studies of adverse health effects of short-term NO2 exposures, given the substantial uncertainties and limitations in interpretation of the other lines of evidence. We examined more than 50 experimental studies of humans inhaling NO2, finding notably that the reporting of statistically significant changes in lung function and bronchial sensitivity did not show a consistent trend with increasing NO2 concentrations. Functional changes were generally mild and transient, the reported effects were not uniformly adverse, and they were not usually accompanied by NO2-dependent increases in symptoms. The available human clinical results do not establish a mechanistic pathway leading to adverse health impacts for short-term NO2 exposures at levels typical of maximum 1-h concentrations in the present-day ambient environment (i.e., below 0.2 ppm). Our review of these data indicates that a health-protective, short-term NO2 guideline level for susceptible (and healthy) populations would reflect a policy choice between 0.2 and 0.6 ppm. EXTENDED ABSTRACT: Nitrogen dioxide (NO2) is a ubiquitous atmospheric pollutant due to the widespread prevalence of both natural and anthropogenic sources, and it can be a respiratory irritant when inhaled at elevated concentrations. Natural NO2 sources include volcanic action, forest fires, lightning, and the stratosphere; man-made NO2 emissions derive from fossil fuel combustion and incineration. The current National Ambient Air Quality Standard (NAAQS) for NO2, initially established in 1971, is 0.053 ppm (annual average). Ambient concentrations monitored in urban areas in the United States are approximately 0.015 ppm, as an annual mean, i.e., below the current NAAQS. Short-term (1-h peak) NO2 concentrations outdoors are not likely to exceed 0.2 ppm, and even 1-h periods exceeding 0.1 ppm are infrequent. Inside homes, 1-h NO2 peaks, typically arising from gas cooking, can range between 0.4 and 1.5 ppm. The health effects evidence of relevance to ambient NO2 derives from three lines of investigation: epidemiology studies, human clinical studies, and animal toxicology studies. The NO2 epidemiology remains inconsistent and uncertain due to the potential for exposure misclassification, residual confounding, and co-pollutant effects, whereas animal toxicology findings using high levels of NO2 exposure require extrapolation to humans exposed at low ambient NO2 levels. Given the limitations and uncertainties in the other lines of health effects evidence, our review thus focused on clinical studies where human volunteers (including asthmatics, children, and elderly) inhaled NO2 at levels from 0.1 to 3.5 ppm during short-term ((1/2)-6-h) exposures, often combined with exercise, and occasionally combined with co-pollutants. We examined the reported biological effects and classified them into (a) lung immune responses and inflammation, (b) lung function changes and airway hyperresponsiveness (AHR), and (c) health effects outside the lungs (extrapulmonary). We examined more than 50 experimental studies of humans inhaling NO2, finding that such clinical data on short-term exposure allowed discrimination of NO2 no-effect levels versus lowest-adverse-effects levels. Our conclusions are summarized by these six points: For lung immune responses and inflammation: (1) healthy subjects exposed to NO2 below 1 ppm do not show pulmonary inflammation; (2) at 2 ppm for 4 h, neutrophils and cytokines in lung-lavage fluid can increase, but these changes do not necessarily correlate with significant or sustained changes in lung function; (3) there is no consistent evidence that NO2 concentrations below 2 ppm increase susceptibility to viral infection; (4) for asthmatics and individuals having chronic obstructive pulmonary disease (COPD), NO2-induced lung inflammation is not expected below 0.6 ppm, although one research group reported enhancement of proinflammatory processes at 0.26 ppm. With regard to NO2-induced AHR: (5) studies of responses to specific or nonspecific airway challenges (e.g., ragweed, methacholine) suggest that asthmatic individuals were not affected by NO2 up to about 0.6 ppm, although some sensitive subsets may respond to levels as low as 0.2 ppm. And finally, for extra-pulmonary effects: (6) such effects (e.g., changes in blood chemistry) generally required NO2 concentrations above 1-2 ppm. Overall, our review of data from experiments with humans indicates that a health-protective, short-term-average NO2 guideline level for susceptible populations (and healthy populations) would reflect a policy choice between 0.2 and 0.6 ppm. The available human clinical results do not establish a mechanistic pathway leading to adverse health impacts for short-term NO2 exposures at levels typical of maximum 1-h concentrations in the present-day ambient environment (i.e., below 0.2 ppm).

Analysis of the Full Economic Cost for Japanese Encephalitis Under Different Risk Scenarios for Business Travelers to Asia.

OBJECTIVE: Methods for assessing the costs and benefits of administering vaccines to international business/occupational travelers, assignees, and expatriates have neglected the impact of health and treatment on work productivity. The research objective is to evaluate the benefit to cost ratio of the Japanese encephalitis (JE) vaccine for international business/occupational travelers to Asia and other endemic areas incorporating a health and productivity approach. METHODS: Costs and benefits were estimated using actuarial methods with data obtained from secondary sources describing prevalence of infection risk and health outcomes, and business traveler demographic and travel characteristics. Results assumed 2018 salaries and prices, with employee time valued according to total compensation. RESULTS: Risks contracting JE vary widely on the basis of length of trip, season, and destination. The productivity benefits of vaccinating a traveler outweigh the vaccination costs for those staying 30 days or longer in endemic areas during one or more transmission seasons ($2009 vs $750 per traveler), and for business travelers to endemic areas during the transmission season with outdoor activities for the average 2-week/15.4-day international business trip ($502 to $815 vs $500). Vaccination costs outweigh the productivity benefits for short-term travelers who remain in urban areas or travel outside of the transmission season ($10 vs $500). CONCLUSION: JE Vaccination for business travelers in the active transmission season has a net benefit under certain conditions that are not commonly considered risky, such as average-length trips to peri-urban areas, in situations where contracting disease would result in significant business disruption, or when multiple trips are anticipated over several years.

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.

The changing epidemiology of Japanese encephalitis and New data: the implications for New recommendations for Japanese encephalitis vaccine.

The epidemiology of Japanese Encephalitis and risk to the traveler has changed and continues to evolve. The spread of Japanese Encephalitis virus into new environments, changes in agricultural practice and animal vectors, climate change, peri-urban growth, changes in international travel to Asia, personal risk factors, mosquito vector free transmission, interactions with other flaviviruses and better information on infections without encephalitis and other factors make Japanese Encephalitis an underappreciated risk. There has also been a change in the incidence of Japanese Encephalitis cases that questions the current travel duration and geographic based recommendations. A safe, effective vaccine (Ixiaro) that may be administered in a short course regimen is now available in the United States without the risks of the previous vaccine. However, the vaccine is significantly underutilized. These changes in the epidemiology and new data on the risks of the Japanese Encephalitis virus require a review of the practice guidelines and expert recommendations that do not reflect the current state of knowledge.

Impact of a musculoskeletal disability management program on medical costs and productivity in a large manufacturing company.

OBJECTIVE: To evaluate a program to reduce musculoskeletal disability-related absenteeism at a North American manufacturing facility. STUDY DESIGN: Staged communication and educational interventions targeting physicians to improve care of musculoskeletal conditions and reduce related absenteeism. METHODS: The program was implemented in three 1-year stages. The first stage required physicians to complete assessment forms for employees claiming disability because of musculoskeletal injuries. The second stage added physician education programs focusing on current clinical guidelines. The third stage incorporated local physician education about the facility's onsite physical therapy program. Annual number of work-related injuries, days lost per injury and per scheduled full-time-equivalent (FTE) employee, light-duty days per injury, average annual indemnity per FTE, indemnity per injury, medical costs per FTE, and medical costs per injury were examined to determine the program's effectiveness. RESULTS: Overall productivity improved by a mean of 12.5 days per injured employee. Mean days lost per work-related injury decreased from 35.1 to 27.6. Number of light-duty days increased from 6.1 to 11.1 per work-related injury. Mean annual indemnity per work-related injury decreased from $9327 to $4493; mean annual medical costs per work-related injury decreased from $4848 to $2679. The annual incidence of musculoskeletal injuries declined by up to 50%. CONCLUSIONS: This intervention was associated with reduced musculoskeletal disability-related absenteeism and increased productivity. The program reduced medical costs per work-related injury and improved the company's communications and relationship with local physicians.

Effect of smoking status on productivity loss.

OBJECTIVE: The objective of this study was to describe health-related productivity losses in nonsmokers, former smokers, and current smokers using a large, cross-sectional database of U.S. employees. METHODS: Volunteers completed the Wellness Inventory, an instrument measuring productivity losses related to 11 health conditions affecting employee health. Results are aggregated, dollarized, and reported by smoking group. RESULTS: Current smokers missed more days of work and experienced more unproductive time at work compared with former smokers and nonsmokers. The average annual cost for lost productivity for nonsmokers was 2623 dollars/year compared with 3246 dollars/year for former smokers and 4430 dollars/year for current smokers. More than half the costs were due to unproductive time at work. CONCLUSION: Current smokers incurred the highest productivity losses, which translated into higher costs to employers for current smokers. Costs were lower for former smokers and nonsmokers.

A focus on the asthma HEDIS measure and its implications for clinical practice.

With more than $16.1 billion in annual costs, the asthma management system is inadequate and needs revision to improve health and financial outcomes. Solutions may be found in the National Committee for Quality Assurance's guidelines and in such programs as Pay for Performance that financially reward providers for adherence to standards of practice based on Health Plan Employer Data and Information Set measures.

An Update on Travel Vaccines and Issues in Travel and International Medicine.

The fields of travel and international medicine are rapidly changing and growing. The role of occupational and travel health nurses is expanding and should be a focus for the future. At the American Association of Occupational Health Nurses Annual meeting on March 24, 2015, in Boston, five presentations were included in the session, An Update on Travel Vaccines and Issues in Travel and International Medicine. This article summarizes three of the presentations and includes a portion of the information generated by the Centers for Disease Control and Prevention (CDC) included in the fourth presentation. The first section focuses on the Essential Elements of Travel Medicine Programs including the pre-travel care assessment, trip research and risk identification, medication intervention review, non-pharmaceutical and prevention strategies, and post-travel care. The next section is an overview of key issues for business travelers. The growth in the number of international business travelers and unique aspects of business travel are emphasized in a comprehensive travel health program. This section also includes a discussion of expatriates and their special risks identified in recent literature (e.g., an assessment of the significant costs of health events and productivity losses by both business travelers and expatriates). The final section offers a specific example of a vaccine-preventable disease, namely, Japanese encephalitis (JE) virus, and needed changes in JE vaccine recommendations.

The Changing Risk of Japanese Encephalitis for Business Travelers.

Japanese Encephalitis is an often fatal and vaccine preventable disease. New vaccine recommendations are needed due to changes in travel and disease patterns.

Integrating health and safety in the workplace: how closely aligning health and safety strategies can yield measurable benefits.

OBJECTIVE: To better understand how integrating health and safety strategies in the workplace has evolved and establish a replicable, scalable framework for advancing the concept with a system of health and safety metrics, modeled after the Dow Jones Sustainability Index. METHODS: Seven leading national and international programs aimed at creating a culture of health and safety in the workplace were compared and contrasted. RESULTS: A list of forty variables was selected, making it clear there is a wide variety of approaches to integration of health and safety in the workplace. CONCLUSION: Depending on how well developed the culture of health and safety is within a company, there are unique routes to operationalize and institutionalize the integration of health and safety strategies to achieve measurable benefits to enhance the overall health and well-being of workers, their families, and the community.

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.

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.

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.