Publications

Dr. Eastmond and colleagures at the University of California, Riverside investigated whether chromosomal changes could be used as biomarkers of benzene exposure in mice and humans. The first part of the study involved detecting chromosomal alterations in cells using a modification of a molecular cytogenetic technique known as fluorescence in situ hybridization (FISH). Eastmond and colleagues evaluated the frequency of such chromosomal aberrations in the erythrocytes (red blood cells) from the bone marrow of mice exposed to various doses of benzene and for different exposure durations.

The three research projects contained in this report were initiated to increase our knowledge of the metabolism of ether oxygenates in humans and other species. Adding oxygenates, such as MTBE (methyl tert-butyl ether), to gasoline promotes more efficient combustion and reduces emission of carbon monoxide, ozone-forming hydrocarbons, and some air toxics, by increasing the oxygen content of the fuel. On the other hand, some oxygenates may increase emission of toxic compounds such as formaldehyde or acetaldehyde, and increased use of MTBE in fuel in the early 1990s led to complaints of unpleasant odor, headaches, and burning of eyes and throat. The studies were conducted by Dr Jun-Yan Hong (the University of Medicine and Dentistry of New Jersey – Robert Wood Johnson Medical School), Dr Wolfgang Dekant (University of Würzburg), and Dr Janet Benson (Lovelace Respiratory Research Institute).

Dr. Moss of CIIT evaluated the effects of rats exposed to ambient air in a highly polluted area in southwestern Mexico City. Pathologists have found evidence of cell damage and inflammation in nasal tissue from some human residents of this highly polluted area that was not present in people living in areas of the country with cleaner air and this study sought to determine if those effects could be replicated in rats.

Report of a workshop held November 29-30, 2000, sponsored by The H. John Heinz III Center for Science, Economics and the Environment, and the Health Effects Institute. 

Dr. Mark Goldberg and his colleagues at McGill University conducted a time-series study in Montreal using available data from the Quebec Health Insurance Plan and mortality and air pollution data to better the understanding of the mortality-particulate association. Because of the comprehensive nature of this health insurance database, the investigators were able to link individual deaths in Montreal to medical information up to 5 years before death.

A Special Report of the Institute's Particle Epidemiology Reanalysis Project. The overall objective of this project was to conduct a rigorous and independent assessment of the findings of the Harvard Six Cities and American Cancer Society Studies of air pollution and mortality. This objective was met in two parts. In Part I: Replication and Validation, the Reanalysis Team led by Dr. Daniel Krewski sought to replicate the original studies via a quality assurance audit of a sample of the original data and to validate the original numeric results.

In an effort to address the uncertainties regarding the association between PM and daily mortality, and to determine the effects of other pollutants on this association, HEI funded the National Morbidity, Mortality, and Air Pollution Study (NMMAPS). Dr Jonathan Samet and his colleagues at Johns Hopkins University, in collaboration with investigators at Harvard University, conducted this time-series study in large cities across the US where levels of PM and gaseous pollutants were varied.

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.

A Special Report of the Institute's Diesel Epidemiology Expert Panel. Although epidemiologic data have been used generally to identify the hazards associated with exposure to diesel exhaust, questions remain as to whether the human data can be used to develop reliable estimates of the magnitude of any risk for lung cancer (that is, through quantitative risk assessment [QRA]), and whether new research efforts could provide any additional data needed. In response to such issues, the Health Effects Institute initiated the Diesel Epidemiology Project in 1998.

Dr. Kleeberger and colleagues at Johns Hopkins University compared ozone-induced inflammation, epithelial cell injury, and epithelial cell proliferation (a marker of cell injury) in three types of mice: mice with a normal content of mast cells, mutant mice without mast cells, and mutant mice whose mast cells were repleted by a bone marrow transplant from normal mice. Each group of mice was exposed to clean air or to ozone for varying lengths of time.

Drs. Douglas Dockery at the Harvard School of Public Health and C. Arden Pope III at Brigham Young University speculated that exposure to PM might lead to a transient drop in blood oxygenation, which might have serious consequences in humans with heart or lung problems. The investigators designed a study to increase the possibility of observing PM effects by testing a potentially at-risk group (the elderly) at a time of year that historically had experienced relatively high levels of PM (the winter).

Daniel L. Albritton and Daniel S. Greenbaum, cochairs. Report of the PM Measurements Research Workshop, Chapel Hill NC, July 22 and 23, 1998. Aeronomy Laboratory of the National Oceanic and Atmospheric Administration, Boulder, CO, and Health Effects Institute, Cambridge, MA.

Dr. John Peters and colleagues of the University of Southern California School of Medicine compared the lung function, respiratory symptoms, activity levels, and bronchodilator use of 10- to 12-year-old healthy, asthmatic, and wheezy children. They conducted the study in Southern California during mid-spring (when ozone levels were expected to be low) and late summer (when ozone levels were expected to be high).

Dr. Thom and Dr. Ischiropoulos at the University of Pennsylvania Medical Center examined the effects of low concentrations of carbon monoxide on platelets and cells isolated from blood vessels. The investigators exposed blood platelets (taken from rats) and endothelial cells (isolated from bovine blood vessels) to varying concentrations of carbon monoxide and measured how much nitric oxide was released. To determine if exposure to carbon monoxide causes endothelial cells to produce peroxynitrite, the investigators looked for markers of its presence in the culture medium and in the cells.

Communication 5 contains proceedings of a workshop held in Cambridge, MA, December 3–4 1996. Presentations included: Current Understanding of the Health Effects of Particles and the Characteristics That Determine Dose or Effect; Particle Formation in Combustion; The EPA Particle Emissions Testing Procedure; Characterizing Particulate Matter in Motor Vehicle Exhaust; Atmospheric Aerosol Transformation; Generating Particles for Laboratory Studies; and Issues and Research Needs for Particle Characterization.

Dr. John Balmes and colleagues of the University of California, San Francisco, and Dr. Mark Frampton and associates of the University of Rochester characterized ozone-induced responses in two different study populations: normal and asthmatic men and women in the Balmes study (Part I), and male and female nonsmokers and smokers in the Frampton study (Part II). The investigators addressed three issues: (1) Is an individual's reactivity to inhaled methacholine related to changes in lung function after exposure to ozone? (2) What is the relation between ozone-induced airway inflammation and changes in lung function? and (3) Do the changes in lung function and markers of inflammation in response to ozone exposure differ between normal people and people with asthma?

The Phase I.B Report of the Particle Epidemiology Evaluation Project. The Health Effects Institute began the Particle Epidemiology Evaluation Project in 1994 to evaluate the emerging epidemiologic evidence of a relation between particulate air pollution and daily mortality. In Phase I.B, Drs. Jonathan M. Samet and Scott L. Zeger and their colleagues at the Johns Hopkins University School of Hygiene and Public Health (1) compared approaches for controlling the effects of weather variables when analyzing the connection between air pollution and daily mortality, primarily focusing on Synoptic Weather Categories, an approach newly proposed by Dr. Laurence S. Kalkstein of the University of Delaware; and (2) evaluated the association between particulate air pollution and daily mortality in the Philadelphia metropolitan area using statistical models that included data for five pollutants regulated under the Clean Air Act Amendments of 1990 (referred to as criteria pollutants).

Dr. Loomis and colleagues at the University of North Carolina and Dr. Víctor Borja-Aburto of the Instituto Nacional de Salud Pública in Cuernavaca, Mexico, collected mortality, air quality, and weather data from records and monitoring stations in Mexico City from 1990 through 1992. Using statistical techniques, the investigators evaluated the association between mortality and ambient levels of ozone, sulfur dioxide, and total suspended particles, both individually and in a model that included all three pollutants.

Drs. Pollack and Brouwer at the University of North Carolina determined the relationship between methanol exposure and its uptake into and elimination from the blood of nonpregnant and pregnant rodents. The investigators exposed rats and mice at several different stages of gestation to methanol intravenously or orally (doses ranged from 100 mg/kg of body weight to 2,500 mg/kg) or by inhalation (1,000 to 20,000 ppm for 8 hours). They measured blood, urine, and amniotic fluid concentrations of methanol and used the data to develop a model of methanol distribution in rodents.

A Special Report of the Institute's Oxygenates Evaluation Committee. Oxygenated fuel (usually referred to as oxyfuel) was formulated to reduce carbon monoxide emissions and contains at least 2.7% oxygen by adding methyl tert-butyl ether (MTBE) or ethanol. Reformulated gasoline was formulated to help reduce ground-level ozone concentrations and contains at least 2% oxygen, has a reduced content of benzene and other aromatic compounds, and produces limited emissions of total air toxics. The introduction of fuels containing oxygenates elicited concerns from workers and the general public in some areas, including reports of unpleasant odors, headaches, or other symptoms attributed to the fuels, and questions about their effects on the cost of gasoline, the performance of engines, and fuel economy. This Special Report summarizes an intensive review of (1) the existing science of the health effects of oxygenates, (2) the risk evaluations done by the EPA in 1993 and 1994, and (3) in a qualitative way, the health effects of exposure to the new additives as they relate to the health effects of other pollutants whose levels in emissions change when fuels containing oxygenates are used.

In Part III of this study, Dr. Belinsky and his associates at the Lovelace Biomedical and Environmental Research Institute examined lung tumors from rats that had inhaled high concentrations of diesel engine exhaust or carbon black particles (see Part I by Dr. Joe Mauderly). The investigators applied molecular biology techniques to measure mutations in selected genes in the DNA from the tumors.