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

Abstract

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 mug/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.

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

“…In vitro studies can offer some insight on the relative toxicity of NTDE versus TDE, although they are also limited in this regard due to the numerous differences from the in vivo situation that affect the interpretation of their findings for DEP, including (1) absence of the normal lung-defense mechanisms (e.g., macrophage mediated and mucocilliary clearance); (2) absence of cellular protective mechanisms such as antioxidants and DNA repair that act to prevent the expression of intracellular damage or DNA mutations; (3) extremely high doses compared to what is deposited in the alveolar regions of the lung after inhalation, thus eliciting high-dose responses not mechanistically relevant to lower doses; (4) dosing with compounds concentrated from DEP by high-temperature, organic solvent extraction, that is, compounds that appear to be much less bioavailable from inhaled and lung-retained DEP; and (5) possible dosing with reactive artifacts-for example, nitrated organic compounds-formed on filters due to the extended collection times needed to obtain enough DEP mass. 7,8 Recognizing their inherent limitations, we briefly review findings from in vitro studies of NTDE below.…”

“…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. 8 NTDE is distinct from, and contrasts in many ways from, "traditional" DE (TDE), which refers to emissions from pre-1988 diesel engines sold and in use prior to the U.S. EPA HDDE particulate standards, and "transitional" DE, which consists of DE from 1988 to 2006 diesel engines manufactured during a time period of continuous improvements to the internal design of the diesel engine, but prior to the fullscale implementation of multicomponent aftertreatment systems.…”

“…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.…”

“…U.S. EPA standards for particulate emissions from heavyduty diesel trucks (t) or urban buses (ub), calculated as grams particulate matter emitted per brake-horsepower-hour (g/bhpÁhr) and adjusted relative to pre-1988 unregulated engine emissions. From Hesterberg et al 8 and U.S. EPA Health Assessment Document for Diesel Engine Exhaust 3 ( Table 2-4, p. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”