Publications

This page is a list of publications in reverse chronological order. Please use search or the filters to browse by research areas, publication types, and content types.

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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.

Particulate Air Pollution and Daily Mortality: The Phase I Report of the Particle Epidemiology Evaluation Project. Phase I.A: Replication and Validation of Selected Studies

Health Effects Institute
August 1995
Special Report

The Phase I.A 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.A, Drs. Jonathan M. Samet and Scott L. Zeger and their colleagues at the Johns Hopkins University School of Hygiene and Public Health (1) reconstructed from original sources the data set for Philadelphia used in earlier studies and confirmed previous numerical results from analyzing these data; (2) developed an analytic approach (including new statistical methods) based on the Philadelphia data set; and (3) applied this approach to data sets for six locations: Philadelphia; Utah Valley; St. Louis, MO; Eastern Tennessee; Birmingham, AL; and Santa Clara County, CA.

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).