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

Abstract

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.

Spatial and seasonal distribution of aerosol chemical components in New York City: (2) Road dust and other tracers of traffic-generated air pollution

“…In both studies, they were able to produce acute pulmonary changes and increases in blood fibrinogen with both concentrated ambient particles (CAPs) and concentrated DEP, but it took far higher concentrations of DEP than CAPs to do so. Others (USEPA, 2002;Hesterberg et al, 2005;Mills et al, 2005Mills et al, , 2007Li et al, 2007;Spira-Cohen et al, 2008;Cherng et al, 2009;Quan et al, 2010) have shown associations between human exposure to DEP and oxidative stress, proinflammatory cytokines, asthma aggravation, atherosclerotic disease, and a large number of other important health end points. In order words, exposure to DEP is widely understood to have significant effects on human health.…”

Particulate Matter in New Technology Diesel Exhaust (NTDE) is Quantitatively and Qualitatively Very Different from that Found in Traditional Diesel Exhaust (TDE)

“…Despite some major uncertainties and limitations in both the human epidemiologic and laboratory animal evidence from the historical DE studies, [7][8][9][10] these agencies have generally concluded that sufficiently high DE exposures can increase the risk of cancer (e.g., lung cancer) and noncancer health effects. Specifically, in 1989, IARC classified DE as a "probable" human carcinogen (Group 2A) based on "limited" evidence in humans but "sufficient" evidence in rats.…”

“…These advances resulted in the emergence of what has been termed "New Technology Diesel Exhaust", or NTDE. 1,7,8 As discussed further in the next section, NTDE has been defined as emissions from post-2006 diesel engines and earlier-model diesel vehicles retrofitted with aftertreatment devices. It is a product of the innovative development of integrated, multicomponent emissions reduction systems (engines, fuel injection systems, ultra-low-sulfur fuels, lubricants, and exhaust aftertreatment devices) to meet the tightened U.S. EPA emissions standards.…”

Assessment of Workplace Diesel Exhaust Exposure and Health Effects

“…Figure 1. Proposed pathway of the health effects of diesel exhausts [18,25]. Two main pathways have been identified, the 'dominant pathway' indicates the effects related to particulate exposure, and the alternate pathway relates to gas phase components such as PAHs.…”

“…Chronic-exposure, animal inhalation studies show a spectrum of dose-dependent inflammation and histopathological changes in the lung in several animal species, including rats, mice, hamsters, and monkeys [3,[25][26]. Human studies have demonstrated exacerbations of chronic bronchitis and chronic obstructive pulmonary disease [17].…”