Experimental Toxicology Division
Pulmonary Toxicology Branch Projects

Projects include: development and use of in vivo animal and in vitro models of human disease such as asthma, atherosclerosis, cardiac arrhythmias, hypertension and diabetes; characterization of the influence of lifestyle, dietary and genetic factors affecting susceptibility to air pollutants; dose response studies of air pollutants at different levels of organization (e.g., genome to target tissue); and development and validation of computational models for interspecies response extrapolation and prediction of human health risks from exposure to air pollutants.

This study looks at a validation of methods for comparing sources of air pollution against prototypic toxicants. Work involves literature search, standardization of methods, and identification and testing of standard materials. This project also includes a PI from the Immunotoxicology Branch, M. Ian Gilmour.

This study employs transgenic and genetic animal models of cardiovascular disease and diabetes, as well as cell and molecular biology approaches to characterize and ultimately predict the relative impact which specific combustion emission sources and nanomaterials have on the pulmonary and cardiovascular systems and associated disease progression.

The goal of this study is to determine if air pollutant exposure increases susceptibility to cardiopulmonary disease or worsens its progression. Our efforts involve modeling human disease, the search for electrophysiological and toxicological biomarkers, and the elucidation of mechanisms of action.

The goal of this study is to determine the role of neurophysiologic reflexes as a primary mode of action underlying air pollutant-induced cardiorespiratory dysfunction. Our efforts involve the characterization of the pathways and mechanisms by which pollutant-induced respiratory sensory irritation triggers altered cardiovascular function.

This study is an investigation into why asthmatics and individuals with pre-existing lung disease or allergies may be at increased risk for air pollutant exposure.

This study is Investigation into why individuals with pre-existing cardiovascular disease, i.e., coronary artery disease, may be at increased risk for air pollutant exposure.

This is a study of asbestos contamination of local sites around the country, especially in Libby, Montana, which has been associated with increased incidences of cancer and lung disease. Research is being conducted to relate the physical properties of different forms of asbestos from these sites with biological effects in rodents, which will inform dosimetry modeling and subsequent risk assessment to benefit the local communities.

In this study, animal models are used to identify genetic and biochemical factors responsible for air pollutant-induced lung and heart toxicity.

This is a project to develop a hierarchical computational model to describe dosimetry and delineate different tissue states due to oxidative stress from inhaled chlorine as a prototypical respiratory tract irritant. Work involves mechanistic experimental studies in several species and in vitro cell culture to quantify responses at different levels of organization, e.g. biochemical and pathology. Development of the computational model entails linking two components: 1) a hybrid computational fluid dynamics physiologically-based pharmacokinetic (PBPK) model to describe different dose metrics in tissues; and 2) a hierarchical biologically-based dose-response model of oxidative stress that distinguishes four different tissue states based on the degree of oxidative stress as the mode of action for chlorine toxicity: normal, adaptive, inflammatory, and toxicity.

The work in this project will extend existing multiple-path particle dosimetry model structure to address a larger range of fiber sizes. Supporting studies include asbestos fiber dissolution, intratracheal instillation, and inhalation. The model will be used to perform interspecies extrapolation and predict human dose-response for risk assessment applications.