Research Reports

As part of the Health Effects Institute's air toxics research program, five independent studies were designed to advance our understanding of the roles of different metabolites in 1,3-butadiene (BD)-induced carcinogenesis and of the differences in sensitivity among species, and to develop methods for identifying and measuring biomarkers. The investigators focused on two BD metabolites (1,2-epoxy-3-butene [BDO] and 1,2,3,4-diepoxybutane [BDO₂]) that researchers had suspected may play a role in BD carcinogenesis. The studies were conducted by Dr. Rogene Henderson (Lovelace Respiratory Research Institute), Dr. Leslie Recio (CIIT), Dr. Vernon Walker (New York State Department of Health), Dr. Ian Blair (University of Pennsylvania), and Dr. James Swenberg (University of North Carolina at Chapel Hill).

Dr. Pryor and colleagues at Louisiana State University developed methods for measuring ozone reaction products in in vitro models of lung lining fluids exposed to ozone and in lung fluids from rats exposed to ozone. During the study, Dr. Mark Frampton of the University of Rochester provided Pryor with lung fluids from humans exposed to air or ozone under controlled conditions. Frampton and colleagues exposed exercising smokers and nonsmokers to filtered air or to 0.22 parts per million (ppm) ozone for four hours.

In a follow-up study to previous research, Dr. Mercer and colleagues at Duke University exposed three groups of rats continuously for six weeks to 2 or 6 ppm nitric oxide (NO) or to filtered air to learn more about the toxicity of NO so as to compare it with two other important oxidants, ozone and nitrogen dioxide (NO₂). At the end of the exposure period he used an electron microscope to measure the number of holes in the alveolar septa and to observe other structural changes, such as in the surface area and the number and type of other abnormalities in the alveolar septa.

Dr. Navidi and colleagues at the University of Southern California discussed the development of three sophisticated statistical methods that would improve the estimates of the health effects of air pollution obtained from epidemiologic studies. First, they took a standard case-crossover design and introduced a bidirectional element where control data were obtained both before and after the health event of interest.

Dr. Arey and colleagues of the University of California, Riverside, examined the genotoxic potential of two PAHs (naphthalene and phenanthrene) that are common air pollutants, and a subset of their atmospheric transformation products. The investigators evaluated the genotoxicity of these compounds using a variety of human cell lines with a range of metabolic capabilities. They examined the ability of these compounds to produce small-scale (damage to genes) and large-scale (damage to chromosomes) genetic damage.

Ozone, a common outdoor air pollutant, is a highly reactive gas and a major component of smog. A public health concern is that prolonged exposure to ozone might damage the airways and contribute to the development of noncancerous respiratory diseases. To examine this issue, the Health Effects Institute collaborated with the NTP to provide HEI-funded investigators access to animals that underwent the same rigorously controlled ozone exposure and quality assurance processes along with the animals used for NTP studies. One of the NTP/HEI investigator groups, Dr.

Dr. Ira Tager and colleagues at the University of California at Berkeley (UCB), and Dr. Patrick Kinney and colleagues at the School of Public Health, Columbia University objectives were to develop new methods for estimating an individual's past exposure to ozone.

Dr. Ultman and his colleagues at Pennsylvania State University redesigned their first-generation analyzer that measures the dose of inhaled ozone to reduce electronic noise (interference) and improve the signal's stability. To do so, they adjusted each parameter that influenced the analyzer's performance: the flow of the air sample into the instrument, the pressure in the chamber where the air sample and the reactant gas mixed, the relative amounts of the reactant gas and air sample, and electronic variables (frequency and voltage).