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Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part XI: Integrative Summary

Paul J Catalano
Ling-Yi Chang
Jack R Harkema
Debra A Kaden
Jerold A Last
Paul W Mellick
William C Parks
Kent E Pinkerton
Bhandaru Radhakrishnamurthy
Louise M Ryan
John L Szarek
April 1995
Research Report 65-XI

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. HEI funded eight independent research studies, including investigations of lung biochemical constituents, structural and cellular changes, lung function, and nasal structure and function.

Diesel Exhaust: Critical Analysis of Emissions, Exposure, and Health Effects

Health Effects Institute
April 1995
Special Report

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.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Parts VIII and IX

Ling-Yi Chang
Kent E Pinkerton
March 1995
Research Report 65-VIII & IX

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. In this report, two of studies and in the NTP/HEI Collaborative Ozone Project, were conducted to determine whether prolonged inhalation of ozone produces lasting effects on lung structure, potentially contributing to or aggravating chronic lung disease. Drs. Chang and Pinkerton and their respective colleagues investigated the effects of this prolonged ozone exposure on respiratory tract structure in healthy male and female F344/N rats. 

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part X: Robust Composite Scores Based on Median Polish Analysis

Paul J Catalano
John Rogus
Louise M Ryan
January 1994
Research Report 65-X

One major component of urban smog is ozone, a highly reactive gas that forms when emissions from mobile and industrial sources react chemically in the presence of sunlight.  One concern is that prolonged ozone exposure could cause noncancerous lung diseases such as fibrosis and emphysema. The NTP's bioassay project presented a unique opportunity for a collaboration between the HEI and the NTP.

Oxidant and Acid Aerosol Exposure in Healthy Subjects and Subjects with Asthma

Jane Koenig
Mark J Utell
November 1994
Research Report 70

In two separate studies, Drs. Koenig and Utell examined the effects of exposing healthy subjects and subjects with asthma to combined oxidant and acid pollutants. Each team of investigators conducted studies in which human volunteers received either combined or sequential exposures to oxidant gases and acid aerosols and standard pulmonary function tests were performed and symptoms were recorded. Dr. Koenig and colleagues exposed 28 adolescents with asthma to varying concentrations of ozone, nitrogen dioxide, and sulfuric acid. Dr. Utell and colleagues examined the effects of sequential exposures to sulfuric acid and ozone on pulmonary function in 30 subjects with asthma and 30 healthy subjects between the ages of 18 and 45. 

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part VII: Effects on the Nasal Mucociliary Apparatus

Jack R Harkema
Kevin T Morgan
Elizabeth A Gross
Paul J Catalano
William C Griffith
November 1994
Research Report 65-VII

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 nose is the first line of defense against inhaled pathogens, dusts, and irritant gases; thus, changes induced by ozone in the normal functions of the nose could result in an increased susceptibility to respiratory infections and other diseases. In one of eight studies in the NTP/HEI Collaborative Ozone Project, Drs.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part V: Effects on Pulmonary Function

Jack R Harkema
Joe L Mauderly
November 1994
Research Report 65-V

Ozone is the major pollutant in smog. It is formed by complex photochemical reactions between nitrogen oxides and volatile organic compounds in the presence of sunlight. Motor vehicle and industrial emissions are prominent sources of these compounds. Peak atmospheric ozone concentrations generally occur during the summer months because the photochemical reactions that produce ozone are enhanced by sunlight and high temperature.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part IV: Effects on Expression of Extracellular Matrix Genes

William C Parks
Jill D Roby
October 1994
Research Report 65-IV

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. Prolonged ozone exposure may injure respiratory tissue, leading to the development or exacerbation of chronic lung diseases such as fibrosis or emphysema. An excess of connective tissue can lead to fibrosis and changes in connective tissue are believed to be an underlying cause of emphysema. Dr.

Pulmonary Toxicity of Inhaled Diesel Exhaust and Carbon Black in Chronically Exposed Rats. Part I: Neoplastic and Nonneoplastic Lung Lesions

Joe L Mauderly
M Burton Snipes
Edward Barr
Steven A Belinsky
James A Bond
Antone L Brooks
I-Yiin Chang
Yung S Cheng
Nancy A Gillett
William C Griffith
Rogene F Henderson
Charles E Mitchell
Kristen J Nikula
October 1994
Research Report 68-I

Dr. Mauderly and coworkers exposed F344/N rats to clean air or to one of two levels (2.5 or 6.5 mg of particles/m3 of diesel exhaust or air) of either emissions from a light-duty diesel engine or carbon black particles. The exposures lasted for 16 hours/day, 5 days/week, for 24 months. The carbon black particles were similar to the soot particles in the diesel engine exhaust; however, they contained markedly lower amounts of adsorbed organic compounds.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part III: Effects on Complex Carbohydrates of Lung Connective Tissue

Bhandaru Radhakrishnamurthy
September 1994
Research Report 65-XIII

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 study of the effects of long-term ozone exposure on lung complex carbohydrates, described in this report, was one of eight laboratory studies supported by the NTP/HEI collaborative agreement. In addition to studying lung and nasal structure and function, investigators studied other constituents of lung connective tissue. Dr.

Noninvasive Determination of Respiratory Ozone Absorption: The Bolus-Response Method

James S Ultman
Abdellaziz Ben-Jebria
Shu-Chieh Hu
August 1994
Research Report 69

Dr. James Ultman and colleagues at Pennsylvania State University used a fast-responding ozone measurement system, which they had developed with previous HEI support, to noninvasively measure the absorption of inhaled ozone in different regions of the respiratory tract of healthy adult men. While the subject was breathing through the measurement apparatus, a narrow 10-mL bolus of ozone was introduced into the inhaled air at a predetermined point.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part II: Mechanical Properties, Responses to Bronchoactive Stimuli, and Eicosanoid Release in Isolated Large and Small Airways

John L Szarek
August 1994
Research Report 65-II

Ozone is a major outdoor air pollutant and short term inhalation can produce temporary chest discomfort, and transient changes in breathing patterns and lung function. Because a large number of people are exposed to levels of ozone sufficient to cause effects on breathing, it is important to understand the short- and long-term consequences of these exposures for human health. Dr.

Nitrogen Dioxide and Respiratory Illness in Children. Part III: Quality Assurance in an Epidemiologic Study

William E Lambert
Jonathan M Samet
Betty J Skipper
Alice H Cushing
William C Hunt
Stephen A Young
Leroy C McLaren
Margo Schwab
John Spengler
July 1994
Research Report 58-III

This report describes the quality assurance and quality control program developed for the previously reported epidemiologic study of nitrogen dioxide (NO2) and respiratory illness in children (Health Effects Institute Research Report 58, Parts I and II). The specific aims of the program were to make certain that data were sufficiently accurate, complete, verifiable, and retrievable.

Development of Methods for Measuring Biological Markers of Formaldehyde Exposure

Timothy R Fennell
June 1994
Research Report 67

Dr. Fennell at the Chemical Industry Institute of Toxicology sought to develop new methods for improving the detection of formaldehyde-DNA adducts in exposed cells and tissues. The investigator treated formaldehyde-DNA adducts with sodium bisulfite, a compound that reacts with these adducts and traps them as stable compounds, and then tested different analytical techniques for separating and detecting the adducts. He exposed pure DNA, cell nuclei, and cells in culture to formaldehyde and treated them with sodium bisulfite under a variety of experimental conditions.

The Effects of Copollutants on the Metabolism and DNA Binding of Carcinogens

Paul C Howard
Frederick A Beland
May 1994
Research Report 66

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.

Biomonitoring of Nitropolynuclear Aromatic Hydrocarbons via Protein and DNA Adducts

Karam El-Bayoumy
Bruce E Johnson
Ajit K Roy
Pramod Upadhyaya
Syrus J Partian
April 1994
Research Report 64

Exposure to polycyclic aromatic hydrocarbons (PAHs) and their nitro-substituted derivatives (nitro-PAHs), products of incomplete combustion, is widespread. This is of concern because individual PAHs and PAH-containing mixtures cause tumors in animals and they are suspected to contribute to human cancer. To asses their carcinogenic potential in humans, biomarkers of PAH exposure that measure the internal dose or the effective dose need to be developed. Dr.

Consequences of Prolonged Inhalation of Ozone on F344/N Rats: Collaborative Studies. Part I: Content and Cross-Linking of Lung Collagen

Jerold A Last
Thomas R Gelzleichter
Jack R Harkema
Susan Hawk
April 1994
Research Report 65-I

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 study of the effects of long-term ozone exposure on lung collagen, described in this report, was one of eight studies in a Collaborative Project supported by the NTP and the HEI. The others included studies of lung biochemistry, structure, and function, and one study of nasal structure and function. Dr.

Environmental Epidemiology Planning Project

Health Effects Institute
March 1994
Communication 3

HEI conducted the Environmental Epidemiology Planning Project in order to identify research needs and opportunities in selected areas of environmental epidemiology. Working groups in each selected area prepared documents composed of individually authored papers. The Planning Project documents were originally published in Environmental Health Perspectives (December 1993, Vol. 102).

Development of Samplers for Measuring Human Exposure to Ozone

Jack D Hackney
Petros Koutrakis
Yukio Yanagisawa
February 1994
Research Report 63

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. Assessing the risk of adverse health effects from such exposures is difficult because only limited data are available on the actual ozone concentrations that people experience. Under the HEI ozone sampler program, three studies were designed to advance the development and testing of personal ozone samplers. The studies were conducted by Dr. Hackney and colleagues at Rancho Los Amigos Medical Center (Part I), Dr. Koutrakis and colleagues at the Harvard School of Public Health (Part II), and Dr. Yanagisawa from the Harvard School of Public Health (Part III). 

Effects of Carbon Monoxide on Isolated Heart Muscle Cells

Beatrice A Wittenberg
Jonathan B Wittenberg
December 1993
Research Report 62

Human exposure to carbon monoxide can occur from automobile emissions, industrial processes, sidestream or mainstream cigarette smoke, and poorly ventilated appliances such as space heaters and gas stoves. Most researchers consider the major mechanism for the toxicity of carbon monoxide to be its ability to compete with oxygen for binding to hemoglobin, the protein that transports oxygen through the bloodstream and releases it to cells and tissues.

Methods Development Toward the Measurement of Polyaromatic Hydrocarbon–DNA Adducts by Mass Spectrometry

Roger W Giese
Paul Vouros
October 1993
Research Report 61

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.

Failure of Ozone and Nitrogen Dioxide to Enhance Lung Tumor Development in Hamsters

Hanspeter Witschi
Michael A Breider
Hildegard M Schuller
September 1993
Research Report 60

Ozone and nitrogen dioxide are highly reactive oxidant gases that are derived from the combustion of fossil fuels and the atmospheric transformation of these combustion products. A major unanswered question is whether or not exposure to oxidant air pollutants contributes to lung cancer. Dr. Witschi and colleagues at the University of California at Davis examined whether exposure to ozone or nitrogen dioxide enhances the development of tumors induced by the chemical carcinogen diethylnitrosamine (DEN), particularly neuroendocrine tumors, in the respiratory tract of hamsters.

Characterization of Particle- and Vapor-Phase Organic Fraction Emissions of a Heavy-Duty Diesel Engine Equipped with a Particle Trap and Regeneration Controls

Susan T Bagley
Linda D Gratz
David G Leddy
John H Johnson
July 1993
Research Report 56

Devices have been developed to reduce particle emissions from vehicles with diesel engines, such as a trap that filters the particles from the exhaust. Periodically, the trap is cleaned (regenerated) by electric heating, thereby burning the particles before they can clog the trap. There is concern that potentially harmful chemicals associated with the particles may be emitted from the trap during normal use and regeneration. Dr.

Nitrogen Dioxide and Respiratory Illness in Children, Part I: Health Outcomes, and Part II: Assessment of Exposure to Nitrogen Dioxide

Jonathan M Samet
William E Lambert
June 1993
Research Report 58-I & II

This publications contains two reports by Drs. Jonathan M. Samet, John D. Spengler, and colleagues, who conducted a prospective investigation of 1,205 healthy infants living in homes with gas or electric stoves in Albuquerque, NM. Nitrogen dioxide exposures were carefully estimated from repeated measurements in multiple locations in the subjects' homes throughout the entire 18-month observation period. Respiratory illnesses were monitored prospectively using a surveillance system based on daily parental diaries of respiratory signs and symptoms. Parental reports of illness episodes were validated in a subset of the population by comparison with clinical diagnoses and microbiological testing. Potential confounding factors that influence respiratory infections were reduced by selecting subjects whose parents did not smoke or intend to use day-care services outside the home.

Research Priorities for Mobile Air Toxics

Health Effects Institute
June 1993
Communication 2

Communication 2 provides information to decision makers on research that is potentially capable of narrowing uncertainties related to the health effects of specific air toxics. This report is based on the Mobile Air Toxics Workshop held in Monterey, CA, December 4–6 1992.

Do Electric or Magnetic Fields Cause Adverse Health Effects?

Health Effects Institute
June 1993
Special Report

HEI's Research Plan to Narrow the Uncertainties. This report of the HEI Electric and Magnetic Fields (EMF) Research Planning Committee presents a 5-7 year research program intended to clarify whether or not there are adverse health effects from exposure of the public to EMF from electric power transmission, machinery, or household appliances.

Determination of the Atherogenic Potential of Inhaled Carbon Monoxide

Arthur Penn
May 1993
Research Report 57

Carbon monoxide is a ubiquitous air pollutant. It is found in cigarette smoke and emissions from motor vehicles, industrial processes, and poorly ventilated combustion sources. Dr. Penn and his colleagues at New York University Medical Center sought to determine whether chronic exposure to ambient levels of carbon monoxide is also a risk factor for developing atherosclerosis because this disease is the leading contributor to deaths by heart attack and stroke in the United States.

Noninvasive Methods for Measuring Ventilation in Mobile Subjects

J Dennis McCool
Jonathan M Samet
May 1993
Research Report 59

This document contains two reports by Drs. McCool and Samet and their colleagues who were funded to develop and test methods for measuring ventilation in freely mobile subjects at home or at work. Drs. Dennis McCool and Domyung Paek at the Memorial Hospital in Rhode Island measured ventilation with a body surface displacement (BSD) model. Each subject wore wide elastic bands containing coated wire coils around the chest and abdomen and had special magnets affixed to the breastbone and navel, which yielded data about their breathing patterns, breath frequency, and ventilation. In the second study, Dr. Jonathan Samet and colleagues at Johns Hopkins University wanted to develop methods for estimating ventilation from heart rate for future epidemiologic studies. They used the Heartwatch, a portable, commercial device combining a small transmitter worn on the subject's chest with a wristwatch-style receiver that records heart rate.

Mutations Induced by 1-Nitrosopyrene and Related Compounds During DNA Recombination by These Compounds

Veronica M Maher
Nitai P Bhattacharyya
M Chia-Miao Mah
Janet Boldt
Jia-Ling Yang
J Justin McCormick
March 1993
Research Report 55

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.

Oxidant Injury to the Alveolar Epithelium: Biochemical and Pharmacologic Studies

Bruce A Freeman
Peter C Panus
Sadis Matalon
Barbara J Buckley
R Randall Baker
January 1992
Research Report 54

Ozone and nitrogen dioxide are significant outdoor and indoor air pollutants that can cause lung damage. Both are termed oxidant gases because the oxygen atoms they contain react with a variety of lung components and produce injury. Dr. Bruce Freeman and colleagues at the University of Alabama, Birmingham examined oxidant injury to alveolar epithelial cells and tested whether supplementing the levels of antioxidants would modify the cells' resistance to damage.

Use of Physical Chemistry and in Vivo Exposure to Investigate the Toxicity of Formaldehyde Bound to Carbonaceous Particles in the Murine Lung

George J Jakab
Terence H Risby
David R Hemenway
October 1992
Research Report 53

Dr. George Jakab and associates the Johns Hopkins University School of Public Health examined the effects of inhaled formaldehyde, an airway irritant that is part of motor vehicle emissions, on alveolar macrophages. The investigators exposed mice to varying levels of formaldehyde alone or to formaldehyde mixed with carbon black particles. Carbon black particles were chosen because of their similarity to combustion derived particles. Different alveolar macrophage functions were evaluated using two assays.

Carbon Monoxide Exposure of Subjects with Documented Cardiac Arrhythmias

Bernard R Chaitman
Thomas E Dahms
Sheila Byers
Lisa W Carroll
Liwa T Younis
Robert D Wiens
September 1992
Research Report 52

Drs. Chaitman and coworkers at the St. Louis University School of Medicine examined whether there is a link between carbon monoxide exposure and arrhythmias in subjects with coronary artery disease. Carbon monoxide is a ubiquitous air pollutant. It is found in cigarette smoke and emissions from motor vehicles, industrial processes, and poorly ventilated combustion sources. The investigators studied 25 men and 5 women, aged 45 to 77 years, all of whom were nonsmokers with stable coronary artery disease and who had moderate levels of ventricular arrhythmias.

Effects of Formaldehyde on Xenotransplanted Human Respiratory Epithelium

Andres JP Klein-Szanto
Hitoshi Ura
Shigeru Momiki
Daniel Bonfil
Samuel Litwin
July 1992
Research Report 51

Dr. Klein-Szanto and colleagues at the Fox Chase Cancer Center employed a novel exposure system to explore the capacity of formaldehyde to cause cancerous changes in human epithelial cells. Formaldehyde is classified as a toxic air pollutant and is emitted in exhaust of motor vehicles, but whether or not formaldehyde is injurious to human health is controversial. The investigators obtained autopsy samples from human infant airways and from adult nasal tissue.

New Methods in Ozone Toxicology: Abstracts of Six Pilot Studies

Health Effects Institute
April 1992
Communication 1

HEI Communications 1 contains abstracts for six feasibility studies that were funded under RFA 89-2: Health Effects of Chronic Ozone Inhalation: Collaborative National Toxicology Program–Health Effects Institute Studies: Pilot Studies.

The Role of Ozone in Tracheal Cell Transformation

David G Thomassen
Jack R Harkema
James D Sun
Nicole D Stephens
William C Griffith
April 1992
Research Report 50

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. When inhaled, ozone can cause cough, shortness of breath, and transient changes in breathing patterns; however the health significance of these effects is unknown. Dr. David Thomassen and coworkers examined the ability of ozone to alter the structure and growth characteristics of epithelial cells from rat tracheas in ways consistent with precancerous changes.

Mechanisms of Aldehyde-Induced Bronchial Reactivity: Role of Airway Epithelium

George D Leikauf
February 1992
Research Report 49

Dr. George Leikauf and coworkers at the University of Cincinnati Medical Center examined the mechanism by which aldehyde inhalation can alter breathing patterns and damage cells lining the airways. Emissions from motor vehicles using gasoline and diesel fuels add to the outdoor levels of aldehydes, including formaldehyde and acrolein, which are known irritants of the respiratory tract. The investigators prposed to examine whether airway constriction due to exposure to aldehydes is caused by damage to airway cells, by the entry of white blood cells into the lungs, or both.

Role of Ring Oxidation in the Metabolic Activation of 1-Nitropyrene

Frederick A Beland
December 1991
Research Report 46

Nitropyrenes are a class of chemicals found in diesel engine exhaust that can form DNA adducts and are suspected animal carcinogens. Dr. Beland at the University of Arkansas for Medical Sciences examined the relationship between DNA adducts and cancer in laboratory animals treated with 1-nitropyrene, the major nitropyrene present in diesel engine exhaust. The investigator used state-of-the-art techniques to study DNA adducts formed from 1-nitropyrene under different conditions of exposure, with an emphasis on identifying unique adducts that had not been recognized before.

Effects of Ozone Exposure on Airway Epithelial Permeability and Ion Transport

Philip A Bromberg
Venkatachalam Ranga
M Jackson Stutts
December 1991
Research Report 48

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. When inhaled, ozone can cause cough, shortness of breath, and transient changes in breathing patterns; however the health significance of these effects is unknown. Dr. Philip Bromberg and coworkers at the University of North Carolina, Chapel Hill examined whether exposure to ozone alters properties of the airway epithelium.

Murine Respiratory Mycoplasmosis: A Model to Study Effects of Oxidants

Jerry K Davis
Maureen Davidson
Trenton R Schoeb
December 1991
Research Report 47

Nitrogen dioxide is an ubiquitous air pollutant resulting from the combustion of fossil fuels. When inhaled at high levels, it reacts with and damages lung cells, including those cells that fight infection. This damage can affect breathing and may increase the risk of respiratory infections. Dr. J.K. Davis and his colleagues at the University of Alabama, Birmingham examined whether exposure to lower levels of nitrogen dioxide (less than 5 ppm) compromises mouse lung defense.

The Effects of Exercise on Dose and Dose Distribution of Inhaled Automotive Pollutants

Michael T Kleinman
William J Mautz
October 1991
Research Report 45

The human health effects that result from breathing air pollutants depend on the amount of pollutant inhaled from the air (exposure dose) and the amount of inhaled material that stays in the respiratory tract (retained dose). Because the retained dose of a pollutant may damage the respiratory tract and cause disease, it is a key factor for determining appropriate government regulations for air pollutants. Drs.

Leukocyte-Mediated Epithelial Injury in Ozone-Exposed Rat Lung

Kenneth Donaldson
Geraldine M Brown
David M Brown
Joan Slight
William M Maclaren
John MG Davis
October 1991
Research Report 44

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. When inhaled, ozone can cause cough, shortness of breath, and transient changes in breathing patterns; however the health significance of these effects is unknown. Drs. Kenneth Donaldson and coworkers at the Institute of Occupational Medicine examined whether exposure to ozone activates white blood cells to release substances that can damage lung tissue.

Effects of Methanol Vapor on Human Neurobehavioral Measures

Mary R Cook
Fred J Bergman
Harvey D Cohen
Mary M Gerkovich
Charles Graham
Roger K Harris
Linda G Siemann
August 1991
Research Report 42

In this pilot study, Dr. Mary Cook and colleagues at the Midwest Research Institute explored how exposure to methanol vapor might affect the human nervous system. Methanol could be used as an alternative fuel, but it may lead to increased levels of methanol and formaldehyde in the atmosphere. The investigators exposed 12 young male volunteers to either filtered air or methanol vapor and assessed their response using 20 commonly used tests of sensory, behavioral, and reasoning performance before, during, and after each exposure.

Mechanisms of Nitrogen Dioxide Toxicity in Humans

Mark J Utell
Mark W Frampton
Norbert J Roberts Jr
Jacob N Finkelstein
Christopher Cox
Paul E Morrow
August 1991
Research Report 43

Nitrogen dioxide is an ubiquitous air pollutant that can react with and damages lung cells when inhaled at high levels. Although outdoor and indoor levels of nitrogen dioxide are usually below the annual standard of 0.053 ppm, peaks can occur that reach up to 10 times this standard. Dr. Mark Utell and coworkers at the University of Rochester examined the human health impacts of higher (peak) levels of nitrogen dioxide that exceed the annual standard. The investigators exposed healthy, nonasthmatic, human volunteers to either nitrogen dioxide or filtered air for three hours.

Retention Modeling of Diesel Exhaust Particles in Rats and Humans

KJ Yoon
May 1991
Research Report 40

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.

Effects of 4 Percent and 6 Percent Carboxyhemoglobin on Arrhythmia Production in Patients with Coronary Artery Disease

David S Sheps
Margaret C Herbst
Alan L Hinderliter
Kirkwood F Adams
Lars G Ekelund
John J O'Neil
George M Goldstein
Philip A Bromberg
Martha Ballanger
Sonia M Davis
Gary Koch
May 1991
Research Report 41

Dr. Sheps and colleagues assessed the effect of exposure to carbon monoxide (CO) on ventricular arrhythmias in 41 nonsmoking human volunteers with coronary artery disease. On 3 consecutive days, volunteers were exposed in random order to air, 100 ppm CO (target 4% carboxyhemoglobin), and 200 ppm CO (target 6% carboxyhemoglobin), followed by a bicycle exercise test. Radionuclide cardiac ventriculography and ambulatory electrocardiogram were performed at rest and during exercise.

Noninvasive Determination of Respiratory Ozone Absorption: Development of a Fast-Responding Ozone Analyzer

James S Ultman
Abdellaziz Ben-Jebria
March 1991
Research Report 39

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.

Asbestos in Public and Commercial Buildings

Health Effects Institute
January 1991
Special Report

The Special Report Asbestos in Public and Commercial Buildings: A Literature Review and Synthesis of Current Knowledge (1991) describes the findings of the Asbestos Literature Review Panel, which was charged to determine what was known, not known, and uncertain about the risks of exposure to asbestos in public buildings.

Synergistic Effects of Air Pollutants: Ozone Plus a Respirable Aerosol

Jerold A Last
January 1991
Research Report 38

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.

Carbon Monoxide and Lethal Arrhythmias

Jay P Farber
Peter J Schwartz
Emilio Vanoli
Marco Stramba-Badiale
Gaetano M De Ferrari
December 1990
Research Report 36

This report describes a study by Dr. Farber and colleagues to investigate the effect of carbon monoxide (CO) exposure on cardiac parameters in dogs. They tested dogs that developed ventricular fibrillation during a test of exercise and acute myocardial ischemia (i.e. that were susceptible) and dogs that survived the test without fatal arrhythmias (i.e that were resistant). Susceptible and resistant dogs were exposed to a concentration of CO sufficient to raise carboxyhemoglobin levels to 5 – 15%.

Oxidant Effects on Rat and Human Lung Proteinase Inhibitors

David A Johnson
R Steve Winters
Kwan R Lee
Craig E Smith
December 1990
Research Report 37

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.

Markers of Exposure to Diesel Exhaust in Railroad Workers

Marc B Schenker
Steven J Samuels
Norman Y Kado
S Katharine Hammond
Thomas J Smith
Susan R Woskie
October 1990
Research Report 33

This report describes a study by Dr. Schenker and colleagues to investigate the usefulness of urinary mutagenicity as a biological marker of occupational diesel exhaust exposure. Personal exposure to diesel exhaust over 2 consecutive work shifts was monitored via personal air samplers in 87 railroad workers, with adjustment for first-hand and environmental tobacco smoke exposure. Urine samples collected at the end of shifts were evaluated for mutagenicity and analyzed for any correlation with diesel exhaust exposure.

Acute Effects of Carbon Monoxide on Cardiac Electrical Stability

Richard L Verrier
Alex K Mills
William A Skornik
October 1990
Research Report 35

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.

Metabolic Activation of Nitropyrenes and Diesel Particulate Extracts

Alan M Jeffrey
Regina M Santella
Diana Wong
Ling-Ling Hsieh
Volker Heisig
George Doskocil
Soraya Ghayourmanesh
July 1990
Research Report 34

This report describes a study by Dr. Jeffrey and colleagues to investigate the potential genotoxicity of components of diesel engine emissions using a variety of biological systems. In the first set of in vitro experiments, radiolabeled nitropyrenes were administered to DNA isolated from human bronchial tissue, mouse embryo fibroblasts, and rabbit tracheal tissue, and elution times were compared by high-pressure liquid chromatography. Antisera antibodies were also prepared against DNA modified by 1-nitrosopyrene to test for the presence of DNA adducts.

Respiratory Carcinogenesis of Nitroaromatics

Richard C Moon
Kandala VN Rao
Carol J Detrisac
April 1990
Research Report 32

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.

Acute Effects of Carbon Monoxide Exposure on Individuals with Coronary Artery Disease

Elizabeth N Allred
Eugene R Bleecker
Bernard R Chaitman
Thomas E Dahms
Sidney O Gottlieb
Jack D Hackney
Denise Hayes
Marcello Pagano
Ronald H Selvester
Sandra M Walden
Jane Warren
November 1989
Research Report 25

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.

DNA Binding by 1-Nitropyrene and Dinitropyrenes in Vitro and in Vivo: Effects of Nitroreductase Induction

Frederick A Beland
November 1989
Research Report 31

This report describes a study by Dr. Beland to investigate the extents to which 1-nitropyrene and 1,6-dinitropyrene, two PAHs found in diesel exhaust, bind DNA in order to better understand the higher relative mutagenicity of 1,6-Dinitropyrene. DNA binding was determined in rats by assay of tissue isolated from a variety of organs. A subset of rats was pretreated with 1-nitropyrene to determine any effect on induction of nitroreductases and subsequent DNA binding by both nitropyrenes.

Influence of Experimental Pulmonary Emphysema on Toxicological Effects from Inhaled Nitrogen Dioxide and Diesel Exhaust

Joe L Mauderly
David E Bice
Yung S Cheng
Nancy A Gillett
Rogene F Henderson
John A Pickrell
Ronald K Wolff
October 1989
Research Report 30

This report describes a study by Dr. Mauderly and colleagues to examine the influence of preexisting pulmonary emphysema on adverse health effects induced by chronic exposure of rats to diesel engine exhaust (DEE) or NO2. Rats were exposed 7 hours/day, 5 days/week for 24 months to 9.5 ppm NO2 or 3.5 mg soot/m3 DEE. Prior to exposure, a subset of rats was instilled with the proteolytic enzyme elastase to induce pulmonary emphysema.

Early Markers of Lung Injury

John N Evans
David R Hemenway
Jason Kelley
September 1989
Research Report 29

This report describes a study by Dr. Evans and colleagues to develop an early marker of lung injury that changes in response to exposure to NO2, which is an important component of mobile source emissions. Rats were exposed to NO2 in concentrations ranging from 0.5 to 30 ppm for 6 hours per day for periods ranging from 2 days to 4 weeks. Urine and bronchoalveloar lavage samples were collected and analyzed for the presence of the lung injury markers hydroxylysin, angiotensin-converting enzyme, and desmosine.

Nitrogen Dioxide and Respiratory Infection: Pilot Investigations

Jonathan M Samet
John Spengler
September 1989
Research Report 28

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.

Cardiovascular Effects of Chronic Carbon Monoxide and High-Altitude Exposure

James J McGrath
July 1989
Research Report 27

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.

Investigation of a Potential Cotumorigenic Effect of the Dioxides of Nitrogen and Sulfur, and of Diesel-Engine Exhaust, on the Respiratory Tract of Syrian Golden Hamsters

Uwe Heinrich
Ulrich Mohr
Rainer Fuhst
Carsten Brockmeyer
May 1989
Research Report 26

This report describes a study by Dr. Heinrich and colleagues to investigate the effects of exposure to NO2 and SO2 or diesel engine exhaust on tumor formation in hamsters. Hamsters were exposed for 6, 10.5, 15, or 18 months to whole diesel exhaust, diesel exhaust without particles, or a mixture of NO2 and SO2. Additional groups of animals exposed to each test atmosphere were also injected with 3 or 6 mg of diethylnitrosamine/kg body weight to evaluate any enhancing effect of diethylnitrosamine on exposure-related changes.

Altered Susceptibility to Viral Respiratory Infection During Short-Term Exposure to Nitrogen Dioxide

Richard M Rose
Paula Pinkston
William A Skornik
March 1989
Research Report 24

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.

Detection of Paracrine Factors in Oxidant Lung Injury

Keith A Tanswell
February 1989
Research Report 22

This report addressed the hypothesis that hypertrophy of the lung after oxidant injury with ozone or oxygen is due to local generation of lung-specific growth factors. Dr. Tanswell exposed rats to either 85% oxygen, 1 ppm ozone, or air for up to two weeks while samples of plasma, lung washings, and lung tissue were periodically collected. These samples were tested for their effect on the DNA synthesis of purified populations of three major lung cell types (pneumocyte, fibroblast, and endothelial cell) in culture.

Responses of Susceptible Subpopulations to Nitrogen Dioxide

Paul E Morrow
Mark J Utell
February 1989
Research Report 23

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.

Maximal Aerobic Capacity at Several Ambient Concentrations of Carbon Monoxide at Several Altitudes

Steven M Horvath
James W Agnew
Jeames A Wagner
John F Bedi
December 1988
Research Report 21

This report examined the interactive effects induced by exposure to altitude and carbon monoxide. Dr. Horvath and colleagues exposed 23 healthy young human volunteers living at sea level to concentrations of 0, 50, 100, or 150 ppm carbon monoxide in a hyperbaric chamber simulating altitudes of 55, 1,524, 2,134, or 3, 048 meters above sea level. Maximal aerobic capacity tests were performed under each exposure condition while respiratory and cardiac variables and blood levels of carboxyhemoglobin, hemoglobin, and lactate were monitored.

Modulation of Pulmonary Defense Mechanisms Against Viral and Bacterial Infections by Acute Exposures to Nitrogen Dioxide

George J Jakab
November 1988
Research Report 20

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.

Potential Health Effects of Manganese in Emissions from Trap-Equipped Diesel Vehicles

Health Effects Institute
September 1988
Special Report

The use of ceramic particulate traps, in conjunction with manganese fuel additives, has been viewed as a way to reduce emissions of particulate matter from diesel-fueled vehicles. This Special Report focuses on the potential health effects from increased public exposure to manganese emissions from such use.

Factors Affecting Possible Carcinogenicity of Inhaled Nitropyrene Aerosols

Ronald K Wolff
Edward Barr
James A Bond
Arthur F Eidson
William C Griffith
Fletcher F Hahn
Jack R Harkema
Rogene F Henderson
Charles E Mitchell
Simon J Rothenberg
George M Shopp
James D Sun
August 1988
Research Report 19

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.

Respiratory Infections in Coal Miners Exposed to Nitrogen Oxides

Michael Jacobsen
Tom A Smith
J Fintan Hurley
Alastair Robertson
Ralph Roscrow
July 1988
Research Report 18

This report investigated the association of occupational exposure to nitrogen oxides with respiratory infections in British coal miners. Dr. Jacobsen and colleagues leveraged data from the Pneumoconiosis Field Research Study, a long-term epidemiological study of British coal miners with information for the years 1953-1978.

Studies on the Metabolism and Biological Effects of Nitropyrene and Related Nitro-polycyclic Aromatic Compounds in Diploid Human Fibroblasts

Veronica M Maher
Joe Dale Patton
J Justin McCormick
March 1988
Research Report 17

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.

Metabolism and Biological Effects of Nitropyrene and Related Compounds

Charles M King
February 1988
Research Report 16

This report describes a study by Dr. King to investigate in rats the carcinogenetic properties of nitropyrene and related compounds and how these compounds are metabolically activated in target tissues. Nitropyrenes and related nitroaromatics are of interest because of their ubiquity in diesel emissions and reported carcinogenicity.

Susceptibility to Virus Infection with Exposure to Nitrogen Dioxide

Thomas J Kulle
Mary Lou Clements
January 1987
Research Report 15

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.

The Effects of Ozone and Nitrogen Dioxide on Lung Function in Healthy and Asthmatic Adolescents

Jane Koenig
William E Pierson
Susan Gayle Marshall
David S Covert
Michael S Morgan
Gerald van Belle
January 1987
Research Report 14

This report investigated whether asthmatic and healthy adolescents differ in their sensitivity to near-ambient concentrations of ozone and nitrogen dioxide. Dr. Koenig and colleagues exposed healthy and asthmatic participants to concentrations of 0.12 and 0.18 ppm ozone or 0.12 and 0.18 ppm nitrogen dioxide during rest or rest followed by moderate exercise.

Effects of Nitrogen Dioxide on Alveolar Epithelial Barrier Properties

Edward D Crandall
Jeffrey M Cheek
Marian E Shaw
Edward M Postlethwait
October 1987
Research Report 13

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.

Neurotoxicity of Prenatal Carbon Monoxide Exposure

Laurence D Fechter
September 1987
Research Report 12

This report describes a study by Dr. Fechter to investigate the effect of prenatal and neonatal exposure to low levels of carbon monoxide (CO) on the developing rat brain. Groups of rats were exposed prenatally, or prenatally plus 10 days neonatally to take into account the fact that the developing rat brain is considerably less mature at birth than the primate brain. Consequently, rats were exposed to CO concentrations ranging from 75-300 ppm through the period of neuronal proliferation and into the period of synapse formation.

Effects of Ozone and Nitrogen Dioxide on Human Lung Proteinase Inhibitors

David A Johnson
August 1987
Research Report 11

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.

Predictive Models for Disposition of Inhaled Diesel Exhaust Particles in Humans and Laboratory Species

July 1987
Research Report 10

Dr. Yu's project addressed several important issues regarding improved quantification of dose from known concentrations of atmospheric particulate matter. By focusing first on a specific category of automotive-derived particles, diesel exhaust particulate, Dr. Yu was able to characterize those aerosol properties (such as the mass medican aerodynamic diameter and size distribution) that influence regional deposition. After formulating a mathematical deposition model, Dr.

Biochemical and Metabolic Response to Nitrogen Dioxide-Induced Endothelial Injury

Jawaharlah M Patel
Edward R Block
June 1987
Research Report 9

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.

Automotive Methanol Vapors and Human Health: An Evaluation of Existing Scientific Information and Issues for Future Research

Health Effects Institute
May 1987
Special Report

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.

Effects of Inhaled Nitrogen Dioxide and Diesel Exhaust on Developing Lung

Joe L Mauderly
David E Bice
Robert L Carpenter
Nancy A Gillett
Rogene F Henderson
John A Pickrell
Ronald K Wolff
May 1987
Research Report 8

Previous research has reported that the lung development of animals exposed to oxidant gases early in life might be impaired, or that developing lungs might be more susceptible than adult lungs to inhaled toxicants. Dr. Mauderly and colleagues at the Lovelace Biomedical and Environmental Research Institute examined the age-related differences in the physiological responses of rats to inhaled automotive emissions. The younger group was exposed during gestation and through the age of six months, while the older group was exposed between the age of six and twelve months.

DNA Adducts of Nitropyrene Detected by Specific Antibodies

John D Groopman
April 1987
Research Report 7

Research Report 7 describes a study that attempted to produce monoclonal antibodies to DNA adducts of nitropyrene that could be used to study the mechanism of nitropyrene-induced carcinogenesis or develop analytical techniques for monitoring exposed populations. Dr. Groopman immunized mice against nitropolycyclic aromatic hydrocarbons conjugated with a carrier protein to study the progression of immune response. Dr. Groopman injected four antigens into groups of BALB/c, AJ, and NZB mice. Two of the antigens failed to produce any immune response.

Effect of Nitrogen Dioxide, Ozone, and Peroxyacetyl Nitrate on Metabolic and Pulmonary Function

Deborah M Drechsler-Parks
April 1987
Research Report 6

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).

An Investigation into the Effect of a Ceramic Particle Trap on the Chemical Mutagens in Diesel Exhaust

Susan T Bagley
Linda D Dorie
David G Leddy
John H Johnson
January 1987
Research Report 5

Dr. Bagley and colleagues at Michigan Technical University examined the chemical mutagenic effects of a ceramic particle trap on a medium-duty diesel engine. Diesel exhaust particles and vapor phase samples were collected from diluted (15:1) exhaust of a 10.4L displacement Caterpillar 3208 engine. The investigators compared uncontrolled (baseline) emissions with exhaust that had been modified by the use of an uncatalyzed monolithic ceramic trap.

The Metabolic Activation and DNA Adducts of Dinitropyrenes

Frederick A Beland
August 1986
Research Report 4

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.

Transport of Macromolecules and Particles at Target Sites for Deposition of Air Pollutants

TT Crocker
DK Bhalla
February 1986
Research Report 3

The pulmonary epithelium is a cellular, avascular layer of tissue that is the first point of contact between the lung and inhaled pollutants. Previous research has indicated that altered epithelial permeability may be an early marker of subsequent lung damage. Dr. Crocker and colleagues at the University of California, Irvine sought to study the study the sites of epithelial injury in rat airways following inhalation of formaldehyde, ozone, and nitrogen dioxide.

Disposition and Metabolism of Free and Particle-Associated Nitropyrenes After Inhalation

James A Bond
Michele A Medinsky
James D Sun
January 1986
Research Report 2

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.

Gasoline Vapor Exposure and Human Cancer: Evaluation of Existing Scientific Information and Recommendations for Future Research

Health Effects Institute
September 1985
Special Report

Report of the Institute's Health Review Comittee, September 1985. Supplement, January 1988. This report contains a review of data on the health effects of unburnt gasoline vapors, and evaluates the need for a research program to address major unresolved issues, especially in regard to the carcinogenicity of gasoline vapors. The supplement summarizes additional data published between 1985 and 1988 in response to a proposed regulatory strategy to reduce hydrocarbon emissions from mobile sources.

Estimation of Risk of Glucose 6-Phosphate Dehydrogenase Deficient Red Cells to Ozone and Nitrogen Dioxide

Marie A Amoruso
August 1985
Research Report 1

Acute hemolytic anemia is associated with a deficiency in glucose 6-phosphate dehydrogenase (G6PD), an X-linked inheritable characteristic. Hemolytic anemia is thought to be caused by a depletion of glutathione and other reducing compounds in red blood cells. Dr. Amoruso and colleagues sought to experimentally test the Calabrese hypothesis, which suggests that G6PD-deficient individuals may be at an increased risk of hemolysis during exposure to low levels of oxidants such as ozone.