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A Partnership to Examine Emerging Health Effects: EC/HEI Workshop on 1,3-Butadiene

Health Effects Institute
January 1998
Communication 6
Communication 6 contains proceedings from a workshop held in Brussels, Belgium, June 29–30 1998. Presentations focused on butadiene ambient concentrations, metabolism, mutagenicity, epidemiology, and a panel discussion on Butadiene Risk Assessment in the Regulatory Framework.

Daily Changes in Oxygen Saturation and Pulse Rate Associated with Particulate Air Pollution and Barometric Pressure

Douglas W Dockery
C Arden Pope III
Richard E Kanner
G Martin Villegas
Joel Schwartz
January 1998
Research Report 83

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).

Atmospheric Observations: Helping Build the Scientific Basis for Decisions Related to Airborne Particulate Matter

National Oceanic & Atmospheric Administration
Health Effects Institute
July 1998
Workshop Report

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.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part XIII: A Comparison of Changes in the Tracheobronchial Epithelium and Pulmonary Acinus in Male Rats at 3 and 20 Months

Kent E Pinkerton
Barbara L Weller
Margaret G Ménache
Charles G Plopper
June 1998
Research Report 65-XIII

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.

Acute Effects of Ambient Ozone on Asthmatic, Wheezy, and Healthy Children

Edward L Avol
William Navidi
Edward B Rappaport
John M Peters
May 1998
Research Report 82

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).

Methods Development for Epidemiologic Investigations of the Health Effects of Prolonged Ozone Exposure

Ira B Tager
Patrick L Kinney
March 1998
Research Report 81

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.

Mechanism of Oxidative Stress from Low Levels of Carbon Monoxide

Stephen R Thom
Harry Ischiropoulos
December 1997
Research Report 80

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.

Improvement of a Respiratory Ozone Analyzer

James S Ultman
Abdellaziz Ben-Jebria
Craig S MacDougall
Marc L Rigas
October 1997
Research Report 79

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).

Formation and Characterization of Particles: Report of the 1996 HEI Workshop

Health Effects Institute
September 1997
Communication 5

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.

Pharmacokinetics of Methanol and Formate in Female Cynomolgus Monkeys Exposed to Methanol Vapors

Michele A Medinsky
David C Dorman
James A Bond
Owen R Moss
Derek B Janszen
Jeffrey I Everitt
June 1997
Research Report 77

Dr. Medinsky and colleagues of the Chemical Industry Institute of Toxicology sought to determine how formate, a metabolite produced when methanol is broken down by the body, is formed and removed in monkeys after they have been exposed to methanol vapors. The investigators exposed female cynomolgus monkeys to environmentally relevant concentrations (10, 45, or 200 parts per million) of methanol vapors and to one high dose (900 ppm) for two hours.

Effects of Ozone on Normal and Potentially Sensitive Human Subjects

John R Balmes
Mark W Frampton
June 1997
Research Report 78

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?

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part XII: Atrophy of Bone in Nasal Turbinates

Jack R Harkema
Paul J Catalano
Jon Hotchkiss
April 1997
Research Report 65-XII

Ozone is a highly reactive gas that is a pervasive air pollutant at ground level. It is a major component of urban smog, forming when emissions from mobile and industrial sources interact with sunlight. The Health Effects Institute collaborated with the NTP to provide eight HEI-funded investigators access to animals that underwent the same rigorously controlled ozone inhalation protocol and quality assurance processes along with the NTP animals. HEI funded this follow-on study to allow Dr.

Particulate Air Pollution and Daily Mortality: The Phase I Report of the Particle Epidemiology Evaluation Project. Phase I.B: Analyses of the Effects of Weather and Multiple Air Pollutants

Health Effects Institute
March 1997
Special Report

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).

Nitrogen Dioxide and Respiratory Illness in Children. Part IV: Effects of Housing and Meteorologic Factors on Indoor Nitrogen Dioxide Concentrations

John Spengler
Margo Schwab
Aidan McDermott
William E Lambert
Jonathan M Samet
December 1996
Research Report 58-IV

Nitrogen dioxide is a ubiquitous air pollutant resulting from the combustion of fossil fuels. Indoor levels of nitrogen dioxide are often higher than outdoor concentrations, especially in homes where there are unvented heating and cooking appliances that utilize natural gas, kerosene, coal, or wood. Drs. John Spengler, Jonathan Samet, and their colleagues determined the impact of housing characteristics and the type and use of cooking ranges on nitrogen dioxide levels in infants' bedrooms in Albuquerque.

Ozone Exposure and Daily Mortality in Mexico City: A Time-Series Analysis

Dana P Loomis
Víctor H Borja-Aburto
Shrikant I Bangdiwala
Carl M Shy
October 1996
Research Report 75

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.

Characterization of Fuel and After-Treatment Device Effects on Diesel Emissions

Susan T Bagley
Kirby J Baumgard
Linda D Gratz
John H Johnson
David G Leddy
September 1996
Research Report 76

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.

Maternal-Fetal Pharmacokinetics of Methanol

Gary M Pollack
Kim LR Brouwer
June 1996
Research Report 74

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.

Developmental Neurotoxicity of Methanol Exposure in Rats

Bernard Weiss
Sander Stern
Sidney C Soderholm
Christopher Cox
Archana Sharma
Geoffrey B Inglis
Ray Preston
Marlene Balys
Kenneth R Reuhl
Robert Gelein
April 1996
Research Report 73

Dr. Weiss and his colleagues at the University of Rochester School of Medicine and Dentistry examined the effects of prenatal and early postnatal inhalation of methanol on selected measures of neurobehavior in rats. The investigators conducted a controlled series of experiments in which they exposed pregnant rats and their newborn offspring to 4,500 parts per million (ppm) methanol by inhalation, and then submitted them to tests of behavioral function.

The Potential Health Effects of Oxygenates Added to Gasoline. A Review of the Current Literature

Health Effects Institute
April 1996
Special Report

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.

Theoretical Approaches to Analyzing Complex Mixtures

Health Effects Institute
February 1996
Communication 4

Communication 4 contains four reports on analyzing complex mixtures. Three reports address analytical approaches to indentifying toxic compounds. One describes statistical approaches to analysis of interaction. (1) Immunoaffinity Chromatography in the Analysis of Toxic Effects of Complex Mixtures, William E. Bechtold (2) Stationary-Phase Programming for Liquid Chromatography: A New Concept for Separating Complex Mixtures, John G. Dorsey (3) Supercritical Separation and Molecular Bioassay Technologies Applied to Complex Mixtures, David L. Springer (4) Using the Parallel Coordinate Axis System to Analyze Complex Mixtures: Determining Biological Activity and Interactions Among Components, Chris Gennings.

Pulmonary Toxicity of Inhaled Diesel Exhaust and Carbon Black in Chronically Exposed Rats. Part II: DNA Damage

Kurt Randerath
Kim L Putnam
Joe L Mauderly
Paige L Williams
Erika Randerath
December 1995
Research Report 68-II

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.

Pulmonary Toxicity of Inhaled Diesel Exhaust and Carbon Black in Chronically Exposed Rats. Part III: Examination of Possible Target Genes

Steven A Belinsky
Charles E Mitchell
Kristen J Nikula
Deborah S Swafford
December 1995
Research Report 68-III

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.

DNA Adduct Formation and T-Lymphocyte Mutation Induction in F344 Rats Implanted with Tumorigenic Doses of 1,6-Dinitropyrene

Frederick A Beland
October 1995
Research Report 72

Dr. Beland and his associates at the University of Arkansas School of Medical Sciences developed an assay to measure mutations induced by dinitropyrenes, a class of diesel engine exhaust, in rats. The investigators analyzed the mutations in a selected gene in spleen T lymphocytes from rats treated with 1,6-dinitropyrene under conditions that induced lung tumors at the highest dose tested. They also examined DNA adduct levels in lung and liver tissues and in spleen lymphocytes and white blood cells.

Activation of Eicosanoid Metabolism in Human Airway Epithelial Cells by Products of Ozonolysis in Membrane Fatty Acids

George D Leikauf
Qiyu Zhao
Shaoying Zhou
Jeffrey Santrock
September 1995
Research Report 71

Dr. Leikauf and colleagues at the University of Cincinnati Medical Center examined the potential of the secondary products produced from the reaction of ozone with the fluids and the cell membrane of airway epithelial cells to cause biochemical effects. The investigators prepared aldehydes and hydroxyhydroperoxides of different carbon chain lengths. They tested these compounds and hydrogen peroxide in cultures of human airway epithelial cells grown from tissue explants.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part VI: Background and Study Design

Gary A Boorman
Paul J Catalano
Bernard J Jacobson
Debra A Kaden
Paul W Mellick
Kathleen M Nauss
Lousie M Ryan
August 1995
Research Report 65-VI

In 1987, the Health Effects Institute entered into a partnership with the National Toxicology Program (NTP) to evaluate the effects of prolonged ozone exposure on F344/N rats. The NTP studies focused on carcinogenicity, while HEI supported eight studies that addressed the biochemical, functional, and structural endpoints and a biostatistical study that developed a sample allocation design and helped to integrate the research findings.