Diesel Exhaust

Stephen Holgate and his colleagues at the University of Southampton proposed that inflammatory changes in lung fluids and blood from humans exposed to PM were related to the chemical composition of the particles. He obtained samples from two human studies in which participants were exposed to diesel exhaust and concentrated ambient particles (CAPs). At a Swedish laboratory 25 healthy and 12 asthmatic participants were exposed to diesel exhaust or filtered air on separate days. At a US laboratory, 12 healthy participants were exposed to filtered air and 30 different healthy participants were exposed to a range of CAPs concentrations. All participants underwent bronchoscopy to obtain lung tissues and fluids to analyze inflammatory markers, including numbers of specific white blood cells, expression of activation markers, and levels of cytokines in addition to analysis of lung function, lung fluids, and blood.

A Special Report of the Institute's Diesel Epidemiology Working Group. The Diesel Epidemiology Working Group was formed in the fall of 2000 to (1) review reports from 6 diesel feasibility studies funded by HEI to provide information on potential study populations and on exposure assessment methods; and (2) consider the results of the feasibility studies and other ongoing research in order to develop a new research agenda to seek better information for quantitative risk assessment of lung cancer and other chronic diseases that may result from exposure to diesel exhaust. The 6 feasibility studies described in this report were funded by HEI to provide insight about whether a new retrospective or prospective epidemiologic study could provide data to improve estimates of cancer risk from exposure to diesel exhaust, and about whether new methods of exposure analysis would allow us to reevaluate older epidemiologic studies.

Dr. Susan Bagley and colleagues at Michigan Technological University conducted a laboratory study to characterize the physical and chemical composition, and the mutagenicity of emissions from a heavy-duty 1988 diesel engine equipped with a ceramic particle trap. This engine was operated with low-sulfur fuel at a constant speed under two different load conditions. They also studied the effects of an oxidation catalytic converter on emissions from a heavy-duty 1991 diesel engine using a low-sulfur fuel.

Dr. Randerath's study was part of a large cancer bioassay conducted by Dr. Joe Mauderly and colleagues of the Inhalation Toxicology Research Institute (ITRI). The investigators exposed F344/N rats by inhalation to clean (filtered) air or to one of two concentrations of either diesel exhaust or carbon (2.5 or 6.5 mg of particles/m³ of test atmosphere). Both Dr. Randerath and Dr. Mauderly measured DNA adducts in lung tissue samples from rats exposed at ITRI for different periods of time to the test atmospheres. Dr.

A Special Report of the Institute's Diesel Working Group. Diesel engine emissions have the potential to cause adverse health effects, including cancer and other pulmonary and cardiovascular diseases. However, it is difficult to distinguish the potential health risks attributable to exposure to diesel exhaust from those attributable to other air pollutants. For over a decade, HEI has supported a broad-based research program to evaluate the health risks of diesel emissions, including investigations of carcinogenesis, modeling studies, and emissions characterization. The purpose of this Special Report is to examine what is known, not known, and still uncertain about the health risks of exposure to diesel emissions.

High doses of inhaled diesel engine exhaust produce lung tumors in laboratory animals and may cause cancer in humans. Nitropyrenes are products of diesel engine exhaust and can be activated by the body\'s metabolism to form highly reactive products that interact with DNA to form DNA adducts. The adducts can interfere with the normal processes of DNA replication and can lead to genetic mutations that may result in carcinogenesis. Dr.

Both environmental and genetic factors are believed to contribute to the multistage process that results in carcinogenesis. Therefore, determining the health risks associated with exposure to known and suspected carcinogenic chemicals is essential for informed decision-making by regulatory agencies. Dr. Roger W. Giese and colleagues at Northeastern University developed sensitive and specific techniques for measuring polycyclic aromatic hydrocarbon (PAH)-DNA adducts, a class of DNA adducts associated with exposure to constituents of diesel emissions and other combustion products.

Nitropyrenes, which form during diesel fuel combustion, cause mutations and are carcinogenic in some animals. Dr. Veronica Maher and colleagues at Michigan State University studied the effect of nitropyrene-DNA adducts on gene mutation. The investigators exposed a specific gene, in culture, to each of two nitropyrene derivatives. They then (1) compared the number of adducts formed by each derivative, (2) analyzed the chemical structure of the adducts, and (3) determined in which region of the DNA the adducts formed.