Publications

This report describes a study by Drs. Yu and Yoon to mathematically predict the lung burden in rats and humans of diesel exhaust particles (DEP) from automobile emissions. Building on a previously constructed model describing DEP deposition, the present work focused on clearance and retention of DEPs deposited in the lung. The transport rates of each component of DEPs were derived using experimental data and mathematical approximations. The complete model was first developed for rats and then extrapolated to humans of different age groups.

This report describes a study by Drs. Ultman and Ben-Jebria to develop a chemiluminescent ozone analyzer and constructed an ozone bolus generator with the goal of using bolus concentration-response methods to noninvasively measure the longitudinal distribution of ozone absorption in human lungs. The analyzer was based on the chemiluminescent reaction between 2-methyl-2-butene and ozone. Validation of the system was performed in excised pig and sheep tracheas, and the resulting absorption coefficient was computed.

This report describes a study by Dr. Last to investigate possible synergistic effects of multiple air pollutants on pulmonary measures in rats. Rats were exposed for 1-9 days to mixtures of O₃ or NO₂ and aerosols of sulfuric acid, ammonium sulfate, or sodium chloride, and to each pollutant individually. Responses were evaluated by various biochemical and morphometric analyses of lung tissue and lavage fluid. An additional preliminary experiment treated exposed rats in vivo with various free-radical scavengers to elucidate possible protective properties.

This report describes a study by Dr. Johnson and colleagues to test the hypothesis that inhaled oxidants can cause lung damage by inactivating the proteinase inhibitors that normally protect the lung from proteolysis. In the first set of experiments, the functional activity of rat alpha-1-proteinase inhibitor (á1-PI) was measured in rat lung lavage fluid from rats exposed acutely or chronically to varying concentrations of NO₂, diesel exhaust, O₃, and O₃ in conjunction with CO₂.

This report describes a study by Dr. Verrier and colleagues to explore the effects of acute carbon monoxide (CO) exposure on cardiac electrical stability through a number of biological models. Experiments involved cardiac electrical testing of conscious and anesthetized dogs with normal and ischemic hearts who were exposed to CO for 2 or 24 hours. The experimental plan explored both the direct effects of CO exposure on the myocardium and possible indirect effects through alterations in the ability of platelets to aggregate or changes in nervous system activity.

This report describes a study by Dr. Moon and colleagues to investigate the carcinogenic potential of 1-nitropyrene, a mutagenic constituent of diesel exhaust particles, using a hamster respiratory-carcinogenesis model. Male hamsters were exposed to 1 or 2 mg of 1-nitropyrene via intratracheal administration either once or twice a week for 92 weeks. In order to study activity as a cocarcinogen, 1 or 2 mg of 1-nitropyrene was administered in combination with 0.25 mg of the known environmental carcinogen benzo[α]pyrene once per week for 92 weeks.

This report from the HEI Multicenter CO Study examined the effect of carbon monoxide (CO) exposure of male human participants with coronary artery disease, with a particular focus on myocardial ischemia onset during exercise. The participants were exposed to air or to CO concentrations sufficient to elevate blood carboxyhemoglobin (COHb) levels to 2% or 4% during exercise. The primary health endpoints examined were the time to onset of exercise-induced angina, and the time to a predefined ST-segment change.

This report describes two pilot investigations for a longitudinal study of infants designed to determine if NO₂ exposure from cooking stoves increases the incidence or severity of respiratory infections during the first 18 months of life. In the first study, Drs. Samet and Spengler selected 147 households with electric or gas stoves and infants for home indoor monitoring of NO₂ concentrations; the infants\' mothers completed a daily calendar-diary on respiratory symptoms and provided illness information every 2 weeks.

This report describes a study by Dr. McGrath to investigate the effect of chronic exposure of rats to CO at high altitude. Male rats were exposed for 6 weeks to CO ranging from 0 to 500 ppm at simulated altitudes ranging from 3,300 to 18,000 feet. The following weekly measurements were taken throughout the exposure period: weight, hematocrit, hemoglobin, and carboxyhemoglobin concentrations. Arterial pH, partial pressure of CO in the blood (PCO₂) and PO₂ were measured, as were blood pressure and ECG.

This report examined the effect of nitrogen dioxide exposure on the sensitivity of the lower respiratory tract to viral infection and reinfection. Dr. Rose and colleagues exposed mice to concentrations of nitrogen dioxide ranging from 1-10 ppm or to air prior to and after inoculation with varying doses of murine cytomegalovirus. A subset of mice was reinfected 30 days later. Infection status, macrophage phagocytic uptake, lymphocyte function, and virus-specific antibody levels were measured, and the results were compared by exposure condition.

This report investigated changes in pulmonary function, as well as the occurrence of symptoms, in potentially susceptible human subpopulations exposed to nitrogen dioxide. Drs. Morrow and Utell exposed healthy individuals and individuals with asthma, chronic obstructive pulmonary disease, and acute respiratory infection to air or 0.3 ppm nitrogen dioxide. The exposure period (four hours per day for five consecutive days) included defined periods of moderate exercise and pulmonary function measurements including spirometry, airway conductance, airway reactivity, and symptoms.

This report investigated the influence of acute exposure to nitrogen dioxide on susceptibility to and severity of viral and bacterial infection in mice. Dr. Jakab exposed normal and immunosuppressed mice to concentrations of nitrogen dioxide ranging from 1 to 30 ppm before or after bacterial or viral challenge and measured host resistance to infection by physiologic parameters.

This report assessed in rats the carcinogenicity of inhaled 1-nitropyrene, a compound frequently adsorbed to diesel particulate matter, and whether this effect is modified when 1-nitropyrene is associated with particles or irritant gases. Dr. Wolff and colleagues exposed rats to atmospheres containing 14C radiolabeled 1-nitropyrene alone or in combination with gallium oxide, sulfur dioxide, or both. After exposure, tissue samples were analyzed for radiolabel content to determine the tissue distribution of 1-nitropyrene and its metabolites.

This report describes a study by Dr. Maher and colleagues to investigate the biological effects of nitropyrene compounds, found in diesel emission particulate, on diploid human fibroblasts in culture in order to better evaluate potential health effects. Diploid human fibroblasts from normal individuals and individuals with a genetic predisposition to cancer were studied and compared through a series of experiments.

This report addressed the hypothesis that exposure to oxidant air pollutants enhances susceptibility to viral infection. Drs. Kulle and Clements exposed healthy human volunteers who were seronegative to cold-adapted influenza A virus to clean air or nitrogen dioxide concentrations of 1, 2, or 3 ppm for two hours a day for three consecutive days. Live influenza A virus was administered intranasally to all participants after the second day of exposure.

This report describes a study by Dr. Crandall and colleagues to investigate the ability of nitrogen dioxide (NO₂) to adversely alter the barrier and transport properties of mammalian alveolar epithelium and cause pulmonary edema. Rat type II alveolar cell monolayers cultured on non-porous and porous surfaces were used as models of isolated alveolar epithelium for in vitro exposure to NO₂.

Addressing the need for better assessment of human exposure to mobile source emissions, this report investigates proteinase inhibitor activity as a potential biomarker of oxidant exposure. In this study by Dr. Johnson, human participants were exposed to 0.5 ppm ozone for four hours on consecutive days and to concentrations ranging from 0.6-2 ppm nitrogen dioxide for three hours. Blood samples were obtained and the functional activity of the proteinase inhibitors, alpha-1-proteinase, and bronchial leukocyte proteinase was assessed.

Nitrogen dioxide is a ubiquitous air pollutant resulting from the combustion of fossil fuels. Since NO₂ is a reactive free radical, one postulated mechanism on NO₂ pulmonary injury involves peroxidation of membrane lipids. Dr. Patel and colleagues at the University of Florida evaluated the dose- and time-dependent effects of NO₂ exposure by measuring metabolic function, biochemical and biophysical parameters. The porcine pulmonary artery and aortic endothelial cells in monoculture cells were exposed to 3 or 5ppm of NO₂ or air for 3-24 hours.

Report of the Institute's Health Research Committee. This report summarizes what emissions-related health problems, if any, would emerge if methanol were to become more widely used as an automotive fuel. Methanol-fueled vehicles emit both formaldehyde and methanol vapors. in 1985, HEI started a research program to investigate the potential health effects of aldehydes, including formaldehyde. Before proceeding with research on methanol vapors, the HEI Health Research Committee decided to undertake additional analysis.

Dr. Drechsler-Parks and colleagues at the Institute of Environmental Stress sought to examine the effects of nitrogen dioxide, ozone, and peroxyacetyl nitrate on metabolic and pulmonary function. Because it is possible that two or more pollutants could interact in ambient air and cause effects that could not be predicted from the effects observed with the individual pollutants, the investigators examined varying levels of different pollutants in 32 non-smoking men and women (8 men and 8 women 18-26 years of age and 8 men and 8 women 51-76 years of age).

Nitrated polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants that often contain genotoxic activity. Dinitropyrenes are a class of PAHs that are associated with diesel exhaust. In this study, Dr. Beland and colleagues at the University of Arkansas for Medical Sciences sought to determine what factors contribute to the extreme genotoxicity of dinitropyrenes in bacteria and to establish if the same factors were important for the genotoxicity of dinitropyrenes in mammalian systems.

Nitro-polynuclear aromatic hydrocarbons, including 1-nitropyrene, are constituents of diesel exhaust. Previous fractionation research has suggested that 1-nitropyrene and various dinitropyrenes may account for 20-50% of the total mutagenicity in the diesel particle extract (DPE). Dr. Bond and colleagues at the Inhalation Toxicology Research Institute examined the biological fate of inhaled 14C-1-nitropyrene (NP) in Fischer-344 rats.