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

• Published in: Critical reviews in toxicology Vol. 36; no. 9; pp. 727 - 776
• Main Authors: Hesterberg, Thomas W., Bunn III, William B., Chase, Gerald R., Valberg, Peter A., Slavin, Thomas J., Lapin, Charles A., Hart, Georgia A.
• Format: Journal Article
• Language: English
• Published: Colchester Informa UK Ltd 01.10.2006; Taylor & Francis; Informa Healthcare; Taylor & Francis Ltd
• Subjects: Air Pollutants - pharmacokinetics; Air Pollutants - toxicity; Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogenicity Tests; Carcinogens, Environmental - pharmacokinetics; Carcinogens, Environmental - toxicity; Chemical agents; Diesel; Engine Exhaust; Epidemiology; General aspects; Humans; Lung Cancer; Lung Neoplasms - epidemiology; Lung Neoplasms - etiology; Medical sciences; Meta-Analysis as Topic; Occupational Exposure; Pneumology; Public health. Hygiene; Public health. Hygiene-occupational medicine; Rats; Risk Assessment; Tumors; Tumors of the respiratory system and mediastinum; Vehicle Emissions - toxicity; Human; Lung disease; Risk Assessment; Respiratory disease; Diesel fuel; Toxicity; Engine Exhaust; Lung cancer; Diesel engine; Malignant tumor; Review; Occupational exposure; Epidemiology; Bronchopulmonary; Metaanalysis; Carcinogen; Animal; Risk factor; Bronchus disease; Critical study; Exhaust gas; Diesel; Occupational medicine
• ISSN: 1040-8444; 1547-6898
• DOI: 10.1080/10408440600908821

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.